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Mipo - A Biological Method for Fixation of Complex Fractures of Tibia- Lupine Publishers

Surgery Open access journal| Lupine Publishers

Abstract

Introduction: Management of proximal and distal tibial fractures is challenging because of the complexity of injury, limited muscle coverage and poor vacularity. Surgical management of tibial fractures includes multiple options: external fixation, IM nailing, ORIF and minimally invasive plate osteosynthesis (MIPO). Open reduction and internal fixation with a plate may end in wide dissection and tissue devascularization. Fixation of tibial fractures with MIPO allows protection of soft tissue and blood supply. This is a report of a series of prospectively studied closed proximal and distal tibial fractures treated with MIPO.

Materials and Methods: A total of 20 patients with closed proximal or distal tibial or fractures were enrolled in the study between 2016 and 2017 and completed follow-up. Demographic characteristics, mechanism of injury, time required for union, range of motion and complications were recorded. Eleven patients had proximal tibial fractures and nine had distal tibial fractures. Patients were followed up to 2 and 6 weeks and then at intervals of 4 to 6 weeks until 12 months.

MResults: Mean age of the patients was 39.5 years (range 18-65 years). Thirteen cases were the consequence of high-energy trauma and seven were the result of low-energy trauma. The clinical and radiological outcome were excellent in 13 patients, good in 6 patients and fair in 1 patient. The average time for fracture union was 16.4 weeks, ranging from 16 to 20 weeks. None of our patients developed any complications.

Conclusion: MIPO is a reliable method of management for tibial fractures; it provides a high union rate and good functional outcome with minimal soft tissue problems.

Keywords: Tibial fractures, MIPO, Soft tissue, Locking plate, Osteointegration, Functional outcome, Clinical outcome

Abbreviations: MIPO: Minimally Invasive Plate Osteosynthesis, LCP: Locking Compression Plate

Introduction

Proximal tibial fractures are serious injuries and pose a treatment challenge. They usually result from high energy injuries, damage is usually extensive and open fractures, compartment syndromes, and vessel injuries are frequently related [1-4]. On the other hand, distal tibial fractures are typically the result of combined compressive and shear forces, and may end in instability of the metaphysis, with or without articular depression, and injury to the soft tissue [5]. The aim of fracture treatment is to obtain early fracture union in the most acceptable anatomical position with early and maximum functional return of activity. Conservative management of closed comminuted fractures with cast are associated with complications like prolonged immobilization, deformity, shortening, angulations, joint stiffness etc. Precise reduction by open reduction and internal fixation with conventional plate, frequently lead to complications like non-union, delayed union, infection, implant failure and need for bone grafting [6]. In addition, it also results in significant soft tissue stripping [3,7] The Minimally Invasive Plate Osteosynthesis (MIPO) is a technique which enables indirect reduction and stable fixation with minimal biological footprint and preserving vascular supply at the fracture site [3,8]. The aim of this prospective study was to evaluate clinical results and complications of MIPO in complex tibial fractures.

Materials and Methods

Case 1

Between 2016 and 2017, 20 patients with acute, closed proximal and distal tibial fractures were selected. Among them 11 had proximal tibial fractures and 9 had distal tibial fractures. The exclusion criteria included open fractures, tibial shaft fractures in which intramedullary nailing was done, fractures with neurovascular injury, and pathological fractures. There were 15 males and 5 females who consented to be a part of this study. Fractures were analysed preoperatively using radiographs and CT scans if there was any articular involvement (Figure 1). We prospectively gathered their data. Demographic characteristics, mechanism of injury, time required for union, range of motion and complications were recorded The Locking compression plate which are anatomically pre-contoured were used. Preoperative calculations were done on radiographs to ascertain the size of the plate, accurate size of locking, cortical and cancellous screws after subtraction of the magnification factor. Patients were operated on as soon as they were medically fit. Surgeries were performed under Spinal Anaesthesia. Patients were positioned supine on a radiolucent table. The involved leg was draped and a pneumatic tourniquet applied.

Figure 1:   X-Ray showing the fracture of tibia and fibula at junction of proximal two-third and distal one-third.

An incision of 2 to 3 cm over the proximal aspect of the tibia on the medial or lateral sides was made, according to the fracture site. For distal tibial fractures, a straight incision was made at the level of the medial malleolus or antero-laterally with preservation of the vessels and nerves depending on the fracture site. Fractures were reduced indirectly by a reduction forceps under fluoroscopic guidance and by ligamentotaxis using an external fixator. A sub muscular plane was made with a long hemostat and chisel without causing additional periosteal damage. The locking plate was applied sub muscularly to fix the fracture. The plate was fixed with screws, which were inserted percutaneously through the primary surgical incisions. Reduction and position of the plate was checked under a C-arm (Figure 2). Postoperatively, the limbs were protected using an above knee splint for 2 days. Active and passive range of motion exercises were permitted to avoid knee stiffness and to strengthen the quadriceps. Suture removal was done after 2 weeks and non-weight-bearing walking was allowed for 6 weeks. Partial weight bearing was allowed depending on fracture healing and patient compliance. At week 12, full weight bearing was permitted as tolerated. At each follow up patients was assessed for pain at the fracture site, tenderness, range of movement at knee and ankle, operative scar and radiological union at 6,10,14,18 and 22 weeks. Clinical and radiological assessments based on the criteria laid down by S.J.LAM9 were recorded using a proforma. The criteria are as follows:

Figure 2:   Post-operative AP and Lateral view showing the fracture with implant in situ.

a) Excellent: Range of movement of adjacent joints 80-100 % of normal. No pain in performing daily activities.

b) Good: Range of movement of adjacent joints 60-80% normal. Pain not enough to cause any modification of patient daily routine.

c) Fair: Range of movement of adjacent joints 30-60% normal. Pain enough to cause restriction patients daily activities.

d) Poor: Range of movement of adjacent joints less than 30% of normal. Pain enough to cause severe disability or non union.

Result

A total of 20 enrolled patients completed follow-up for one year and were included in the study; there were 15 males and 5 females. Mean age of the patients was 39.5 years (range 18-65 years). Thirteen cases were the consequence of high-energy trauma and seven were the result of low-energy trauma. Proximal tibial fracture was in eleven cases and distal tibial fractures in nine cases. Majority of the patients were operated within 3 days of injury. On S.J.LAM criteria, 13 patients showed excellent results, 6 patients had good results and 1 patient had fair result. The average time for fracture union was 16.4 weeks, ranging from 16 to 20 weeks (Figure 3). None of our patients developed any complications.

Figure 3:   X- Ray showing radiological union at the fracture site.

Discussion

MIPO allows indirect fracture reduction and percutaneous sub muscular implant placement [3]. The minimal-invasive method agrees in theory to combine the principles of a stable construct to a closed reduction with conservation of the haematoma [10]. Contrast to conventional plates, the locking compression plate (LCP) is anatomically pre-contoured; it does not depend on on friction and provides superior stability. Thus, it reduces the risk of loss of reduction through locking screws secured in the plate. The key aspect that led.com to use locking plates to treat fractures of the tibial shaft was the difficulty we would have faced in controlling the reduction of the proximal or distal fractures with intramedullary nailing. Indirect reduction and subcutaneously applied plates protects soft tissue and periosteal blood supply; hence, MIPO should provide undisturbed union and a low complication rate. In spite of the advantage of well-preserved blood supply, MIPO does not help in reduction. The fragments may not be anatomically reduced and interfragmentary compression may be inadequate, which consequences in delayed union. Barei DP et al. [11] demonstrated that after open reduction and internal fixation, 20% of the cases developed superficial or deep infections in spite of acceptable functional outcome. In this study, all patients had radiological union without any complications. In the present study, early surgical intervention was performed. Majority of patients were operated within 3 days because delay in intervention makes fracture reduction challenging. The time to consolidation reported in our study was to some extent less, when matched to the data known from the literature concerning plating osteosynthesis [4,5]. The average time for fracture union in our series was 16.4 weeks. MIPO decreases postoperative pain and aids early rehabilitation, which improves articular cartilage nutrition and healing. It is cosmetically more acceptable owing to less scar formation [3]. Uniqueness of this study was early mobilization, high mean time to fracture union, which was 16.4 weeks, no complications and majority of the patients having excellent outcome. The current study has some limitations. This is a non-randomized study with no control group. In addition, the sample size was small and the mean follow up was for 12 months. In conclusion, MIPO is a reliable method of treatment for distal tibial fractures; it provides a high union rate and good functional outcome with minimal soft tissue complications.

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Lupine Publishers | Breast Cancer awareness, knowledge and beliefs among Libyan women

Lupine Publishers |  Scholarly Journal Of Psychology And Behavioral Sciences

Abstract

Background: Breast cancer (BC) is the most frequent cancer of women. The high mortality in developing countries is associated with late detection, and lack of knowledge among women and adequate screening programmes.

Objectives: The objectives of this study are assess the current level and determinants of knowledge and beliefs regarding (BC), risk factors and various screening methods among Libyan women.

Methods: A cross-sectional descriptive study carried out between September and October 2016 among a sample of adult women in western Libya. Participants were asked to fill a validated questionnaire to investigate their knowledge about the risk factors as well as their awareness and screening behaviours of (BC). Data were collected from 1091 woman.

Results: The results of the study showed the majority of women participated in the study were aware of BC early warning signs and symptoms with over 90% of the women were able to list at least one symptom of breast cancer correctly. The most frequent warning sign identified was breast lump (91.0 %), followed by discharge from the nipples (80.6%). Also, 565 (52.7%) of those surveyed were aware that increasing age was associated with a higher incidence of breast cancer and 747 (68.3%) of the respondents identified positive family history as a risk factor for breast cancer. Moreover, 62% of female participants know how to perform SBE, and only 59% ever performed BSE. The majority of women in the study (92%) would seek medical advice if they discovered a mass in the breast whereas, about half of those (59%) would consult a male doctor.

Conclusions: Women participated in this study were fairly informed about BC risks and warning signs; the results appear to reflect growing awareness of women regarding BC screening methods. health education message should be presented and delivered in a culturally-sensitive manner and tailored to provide simple and clear information and avoid false beliefs and misconceptions about the disease, its screening methods and management options.

Keywords: Breast cancer; Breast cancer self-examination; awareness; Libya

Introduction

Breast cancer is the most common cancer in women both in the developed and less developed world. It is estimated that worldwide over 508 000 women died in 2011 due to breast cancer. Although breast cancer is thought to be a disease of the developed world, almost 50% of breast cancer cases and 58% of deaths occur in less developed countries [1]. Breast cancer (BC) represents 10% of all cancers diagnosed annually and the second principal cause of cancer deaths in women worldwide [2,3]. The incidence of new cases is expected to rise from 10 million in 2002-15 million by 2025, with 60% of those cases occurring in developing countries. Data from the Arab world have placed breast cancer at the number one position with almost half of cases occurs in women under the age of 50 [4]. In Libya, breast cancer is accounting for more than 25% of all cancer in females with age-standardised mortality rate of 10.9 per 100,000 [5]. Breast cancer survival rates vary greatly worldwide, ranging from 80% or over in North America, Sweden, Japan and Australia to around 60% in Brazil and Slovakia and below 40% in Algeria [6].

The low survival rates in less developed countries can be explained mainly by the lack of early detection programmes, resulting in a high proportion of women presenting with late-stage disease, as well as by the lack of adequate diagnosis and treatment facilities [1]. WHO promotes breast cancer control within the context of comprehensive national cancer control programmes that are integrated to non-communicable diseases and other related problems. Comprehensive cancer control involves prevention, early detection, diagnosis and treatment, rehabilitation and palliative care. Raising general public awareness on the breast cancer problem and the mechanisms to control as well as advocating for appropriate policies and programmes are key strategies of population-based breast cancer control [1].

Screening and early detection is widely recognized as being a principal factor in reducing the mortality from breast cancer [7]. However, previous studies reported that most breast cancer patients present at advanced stages of the disease which emphasise the need for increasing awareness and improved screening programmes including self-examination, clinical breast examination and mammography [8,9]. In 2011, a comparison of the clinic-pathological and epidemiological features of breast cancer in Libya to corresponding data from patients from Nigeria and Finland has reported that approximately 51% of Libyan patients were classified in stages 3 and 4 [10,11]. Also, research has shown poor levels of knowledge towards risk factors awareness and screening methods even among young and educated women [12-18].

Knowledge deficiency may lead to delayed presentation with advanced stages when little or no benefit is derived from any form of therapy. For presentation at an early stage, women must be “breast aware”; they must be capable of identifying symptoms of BC through routine practice of screening [19]. Assessment of the current level of breast cancer awareness and knowledge toward risk factors and screening methods is crucial for the development of awareness campaigns and programmes for women to decrease the burden of the disease and mortality. Therefore, the study will be conducted to assess the current level and determinants of knowledge and beliefs regarding breast cancer, risk factors and various screening methods among Libyan women.

Materials and Methods

A cross-sectional descriptive study carried out between September and October 2016 among a sample of adult women in western Libya. Women participating in the study were interviewed using pre-tested validated questionnaire. The questionnaire included 49 questions pertaining three sections:

I. socio demographic characteristics of women participating in the study;

.

II. knowledge of breast cancer risk factors and warning signs;

III. Knowledge and awareness of women towards breast cancer screening methods knowledge (BSE, CBE, and mammography).

Knowledge Scoring

The questionnaire consisted of 23 items that assessed students’ knowledge related to breast cancer (13 questions related to BC risk factors and 10 questions related to BC warning signs0 and 20 items that assessed students’ knowledge regarding breast cancer screening methods. These questions were then scored; each correct response was scored one (1) point and each wrong or “don’t know” was scored zero (0). A correct response was based on literature and current practice. The knowledge index was calculated for each participant by summing the number of correct answers. The total score of the participants’ knowledge regarding breast cancer is 23 (100%). The knowledge level was categorised as “low” for scores within 0-49%, “moderate” for scores within 50-79% and “high” for scores within 80-100% [20]. These scores were then used to assess the relationship between socio-demographic factors and level of breast cancer knowledge and warning signs.

Statistical Analysis

Data were translated to English and analysed using SPSS version 17 (SPSS Inc., Chicago, IL). Descriptive statistics including means, standard deviation, frequencies, and percentages were obtained for all continues and categorical variables as appropriate. Chi-square test was used to examine the association between the respondents’ socio-demographic variables and knowledge of breast cancer.

Ethical Considerations: Permissions were obtained from the local health directorate and prior orientation of participants was carried out. The data collection tools were anonymous, and data confidentiality was maintained throughout the study.

Results

The mean age of the 1091 women enrolled in the study was 33.2 (SD 9.6; age range: 18-61) years. Most participants (71.8%) were aged less than 40 years and there were 501 (45.8%) single respondents; 463 (42.2) were students; 996 (79.6%) had a university degree and 930 (93.4%) had no family history of breast cancer (Table 1).

Table 1: Socio-demographic Characteristics of the Participants.

Section A of Table 2 shows respondents’ knowledge of risk factors for breast cancer; The women surveyed had a fair knowledge of BC risk factors; 565 (52.7%) of those surveyed were aware that increasing age was associated with a higher incidence of breast cancer and 747 (68.3%) of the respondents identified positive family history as a risk factor for breast cancer. However, only third of the participants answered correctly about the effect of early menarche (31.9%) and late menopause (37.5%). The majority of women participated in the study were aware of BC early warning signs and symptoms with over 90% of the women were able to list at least one symptom of breast cancer correctly. The most frequent warning sign identified was breast lump (91.0 %), followed by discharge from the nipples (80.6%). Only 566 people (52.4%) acknowledged that weight loss could be a warning sign of breast cancer (Table 2).

Table 2: knowledge regarding Breast cancer risk factors and warning signs among study participants.

The results showed that 62% of female participants know how to perform SBE, and only 59%% ever performed BSE. The majority of women in the study (92%) would seek medical advice if they discovered a mass in the breast, whereas, about half of those (59%) would consult a male doctor. Regarding screening methods, women were more familiar with BSE. Only 20% of participants were not aware of BSE, compared to 40% of women who were not aware of ultrasound as a BC screening method. In total, women who didn’t know any screening methods constituted only 4%. While, 45% of women were familiar with the five screening methods [20].

Figure 1: Distribution of breast cancer risk factors and warning signs knowledge scores.

Table 3: Relationship between knowledge scores and demographic variables of the respondents.

Figure 1 shows the distribution of the knowledge scores amongst the respondents. The median score was 15 with 782 (71.5%) of women scoring >50% and 240 (22%) had a good score of o 80% or more. Age of the participants, marital status and their level of education did play a significant role in determining the knowledge attitude, while positive family history of breast cancer in a first degree relative as well as a history of breast problem were not significantly associated with BC knowledge (Table 3). Almost 50% of those with good knowledge score aged between 26-35 years and 75% had a university degree. Whereas only 8% of participants with good knowledge score had a positive family history breast cancer or a previous breast problem.

Discussion

Breast cancer is the most common of all female cancers in Libya [5]. In this study, the knowledge and practice among general population in western Libya was explored. The main findings were that level of awareness of risk factors and early warning signs of BC was moderate, with 71.5 % having good knowledge, also the study showed that 59.2% of women participated in the study perform BSE. The level of knowledge about breast cancer and the screening behaviour is generally poor in Arabic region compared to the developed world [6,10,17]. In the present study, respondents answered correctly that the commonest symptom of breast cancer is a breast mass. Our results are consistent with those of similar studies carried in Saudi Arabia [21,22] and Kuwait [23].

The present study showed that women demonstrated higher knowledge of breast cancer screening and risk factors and were more likely to perform BSE compared to other recent studies in neighbouring countries [24-26]. Similar to previous studies [23,25,27] the most familiar methods was BSE followed by CBE and mammography. As it was expected, satisfactory knowledge scores were more common among younger participants and those with higher educational levels. However, unlike other studies in the region [24-25] and worldwide [28], the anticipated fact that women who had a breast problem or positive family history of BC would have better knowledge scores could not be demonstrated in the present study. The study revealed that about two thirds of the participants shared a misconception that early menarche and late menopause were not risk factors for BC. This finding was supported by a previous study [29].

The results of this study may be influenced by the young age and the relatively high educational level of the surveyed women which may reflect selection bias. A second limitation of the current study is the use of convenience sampling to recruit participants which may limit the generalisability of the findings. Nevertheless, convenience sampling considered a valid data collection method and has been widely used in health education research [30]. In spite of these limitations, the study yielded significant findings that could have implications reorganise the national health education strategy.

Conclusion

women participated in this study were fairly informed about BC risks and warning signs; the results appear to reflect growing awareness of women regarding BC screening methods. However, health education message should be presented and delivered in a culturally-sensitive manner and tailored to provide simple and clear information and avoid false beliefs and misconceptions about the disease, its screening methods and management options

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Lupine Publishers | Ethnobotanical Survey and Identification of Potential Interactions of Plants Used in a City in Northeastern Brazil

Lupine Publishers | LOJ Pharmacology & Clinical Research

Abstract

The study of medicinal plants is currently one of the alternative sources of allopathic medicine for therapeutic purposes. Given the high consumption of medicinal plants and the risks of indiscriminate use, the objective of the study was the identification of potential plant-drug interactions in the pharmacotherapy of the Public Health System users in a Brazilian Northeastern city, from 2015 to 2017 regarding the plant species used, as well as their therapeutic properties. An ethnobotanical study was conducted with a questionnaire. For this purpose, 46 types of plants were used by the 402 interviewees, where 297 were women, with 279 adult participants, and 269 medicinal plants used. Only 199 people out of the total interviewed used some medication, of which 55 associated the use of the drug with medicinal plants. We analyzed associations between the use of 13 plants and 27 drugs, totaling 42 potential interactions. Lemon balm was the vegetal species that presented the most common interactions among the interviewees. Thus, it was possible to conclude that medicinal plants are quite used for therapeutic purposes. However, one must be cautious about its use since they can interact with drugs, reducing or potentiating their effects.

Keywords: Empirical knowledge; Interactions; Medicinal plants

Introduction

The use of medicinal plants (MPs) has been noted since the beginning of the civilization and this practice has been passed down through generations, drawing popular taste and leading to their planting in the houses, trade in free markets and popular market, as well as their use as a medicine [1]. According to the World Health Organization, almost 80% of the worldwide population uses medicinal plants to treat minor health problems and for several patients this is often the only available health resource [2]. In Brazil, it is estimated that there are between 350,000 and 550,000 plant species, where only 55,000 are cataloged and are distributed among different regions of the country. However, some of these species do not have studies about their therapeutic potential, although this is a process that has been evolving significantly [3]. In addition, Brazil also has a long tradition of using medicinal plants linked to popular knowledge transmitted through generation [4]. Because of their pharmacological properties, the use of MPs has been encouraged by health regulatory agencies in order to develop integrative/complementary methods for resolving health problems [5]. Besides, in 2009, the Ministry of Health made available a list of 71 medicinal plants, including the National Relation of Medicinal Plants of Interest to the Unified Health System (RENISUS), aiming at the development of herbal medicines and use in the Public Health System. Brazilians are also increasingly interested in “natural” ways to promote a healthier life. Approximately 82% of the population uses medicinal herbal products [6]. For many patients, the use of a single drug is not sufficient, and when two or more drugs are prescribed, the desired benefit is not always achieved, since they may interact negatively, increasing or reducing the therapeutic effect or the toxic effect of one or the other [7]. It should be noted that these interactions do not reduce to the universe of the synthesized chemical substances, but they can occur between those present in plants used in the form of teas, homemade syrups and phytotherapics [8]. Thus, this study aims to evaluate the use of medicinal plants by patients from a community in the Northeast of Brazil, aiming at tracing the profile of the plant species used, as well as its therapeutic properties and the risk of possible plant-drug interactions.

Methods

This is an ethnobotanical study with a questionnaire interview and collection of botanical material (when necessary). It was carried out in the municipality of Lagarto, comprising an area of approximately 968,921 km² situated in the southern portion of the state of Sergipe, Northeastern region of Brazil Figure 1, 78 km away from the capital, Aracaju. It presents a semi-arid transition climate dominating most of its lands on the western part of the municipality, where a local vegetative variety can be found [9]. It has about 103,188 inhabitants, with basically half of them residing in the rural area and the other half in the urban zone [10]. This research was carried out at the Maria do Carmo Nascimento Alves Health Center located in the municipality of Lagarto-SE. This unit targets 6 micro-regions comprising different neighborhoods and accompanied by 6 different community agents. Data collection was carried out in the region comprised by the Ademar de Carvalho neighborhood, which consists of 1,282 families accompanied by home visits of community health agents, in addition to consultations with physicians and nurses of the unit (Figure 1). In order to obtain the number of users to be interviewed, the sample calculation was performed considering a tolerable error of 5% (95% confidence), where after the calculation the minimum sample size was 296, but it was possible to apply the questionnaire to 406 users. For the calculation, the following equation was used:

N = population size e = margin of error (percentage in decimal format) z = z score

It is worth mentioning that the collection was initiated after the approval of the project by the Ethics Committee in Research with Human Beings of the Universidade Federal de Sergipe (protocol number 47369315.2.0000.5546). The collected material was pressed in the field, according to [11] and identified through specialized literature, specialist assistance and comparisons with pre-existing specimens in the ASE Herbarium-Federal University of Sergipe. All procedures for access to genetic patrimony and associated traditional knowledge were carried out and the project was registered in SISGEN (Sistema Nacional de Gestão do Patrimônio Genético e do Conhecimento Tradicional Associado) in accordance with Brazilian Law nº 13.123/2015 under registration number A894E5C. Some inclusion criteria were selected in this research: be a user of the Maria do Carmo Nascimento Alves Health Center; be older than 18 years and sign the TCLE - Free and Informed Consent Form specific to this research. A brief questionnaire was applied to the users of the Maria do Carmo Nascimento Alves Health Center regarding their purpose, frequency, conservation, obtaining and form of use. In addition, information was collected on the morbidities and socio-demographic profile of the interviewees. Some plant samples were collected in this community and submitted to identification of the species by a botanist of the Biology Department of the Federal University of Sergipe. Fidelity level was calculated to quantify their importance in treating a major disease, using the following

formula: FL = (Ip /Iu)×100 where Ip = Number of informants who suggested the use of a species for the same main objective (therapeutic use), (Iu) = Total number of informants who mentioned plant species for any use [2]. The identification of potential drug-plant interactions was carried out by means of a bibliographical survey of the plants used, in scientific articles indexed in national and international bases, being the bases used: Pubmed, Scielo, Lilacs, Science direct. In addition, it was consulted through the site, the Plant- Drug Interaction Observatory of the Faculty of Pharmacy of the University of Coimbra. Subsequently, interactions were classified on the pharmacodynamic or pharmacokinetic mechanism and on the risk: mild, moderate and severe. After the questionnaires were applied, the data were tabulated on the Microsoft Office Excel® 2007 spreadsheets, submitted to descriptive statistical analysis.

Results and Discussion

In this study, 406 people were interviewed, mostly women, all users of the Basic Health Unit in the study. The predominance of women can be justified because they are generally responsible for home and childcare, seeking knowledge about medicinal plants in order to obtain home treatments to cure or prevent diseases of family members (Lobler et al. 2013) (Table 1). Among those interviewed, the most prevalent level of schooling was the incomplete elementary school with 54%. This factor is associated with low income, which makes the use of plants a way of prevention and treatment of complications more accessible to these people.The origin of a considerable part of the plants is their own residences (Lobler et al. 2013). Socio-epidemiological profile of volunteers (Table 1) and of all the interviewees, 262 of them did not present any type of morbidity. The other 144 had morbidities such as hypertension (33%), cardiovascular problems (19%), diabetes (14%), psychological disorders (7%), respiratory problems (5%) and gastrointestinal problems (5%). In 2000, the prevalence of arterial hypertension in the world population was 25% and the estimate for the year 2025 is 29% [12].

The increase among individuals with blood pressure matches an increasing risk factor for cardiovascular diseases [13]. Of the 406 interviewees, 66% (269) stated that they used medicinal plants (MP) for therapeutic purposes, being 210 (78%) women and 59 (22%) men. Most of the interviewees use the plant species as tea. Besides, other forms of use were reported such as bath, inhalation, chewing, topical use, oral intake of the plant made as juice and syrup. The use of medicinal plants occurs over generations and the technique of preparation and conservation of these products, as well as their therapeutic purposes, are empirically passed on and generally by people who have a certain conviviality and affinity, usually relatives, friends and neighbors [14]. In fact, family members prevail with the highest number of indications, it was identified that 64% of the indications are made by one of the family (parents, grandparents, daughter-in-law and mother-in-law), 13% by self-knowledge, 8% by acquaintances, 4% by health professionals and 1% indicated by the media.

According to culture of medicinal plants was brought by the inhabitants of Brazil to be acquired by the Health System, with the purpose of providing a therapeutic alternative to the users of the system. However, for this idea to materialize, it will be necessary to implant this culture to the health professionals since the beginning of their academic formation, so that the prejudice of the use of medicinal plants for the treatment of medicinal plants can be demystified. This statement can be proven with the data obtained in this research, since only 4% of the indication of the use of medicinal plants was made by health professionals. On the other hand, 64 interviewees reported that they had already received guidance on the use of MP by health professionals, who are doctors (84%), nurses (11%), health workers (2%), nutritionists (2%) and social workers (1%). Many factors have contributed to increased use of plants as a medicinal resource, among them the high cost of industrialized medicines, the difficult access of the population to medical care, as well as the trend to use natural products. It is believed that care taken through medicinal plants is favorable to human health, provided the user has prior knowledge of its purpose, risks and benefits [15].

Participants who reported the use of medicinal plants mentioned 46 plant species (Table 2), whereby the 5 mostly used are lemon balm (213), boldo (130), holy grass (112), chamomile (58) and fennel (41). These plants are the most frequently used because they are the most popularly known and also because of their various pharmacological actions. Several studies conducted in Sergipe as well as in other northeastern regions report the use of these plants by the population. One instance is the research [15], where it is stated that the plants most frequently used by the participants were holy grass, boldo and lemon balm, corroborating with the data of this study. It made a survey of the medicinal plants used in the caatinga, where among the plants used for medicinal purposes are the ones cited in this work. Besides, it was verified that 93% of the medicinal plants reported used the leaves, 2% the stem, 3% the seed, 2% the fruit and bark and 1% the root. The predominance of leaf use can be attributed to the greater ease of collection and availability throughout the year, or also, depending on the species, due to the fact that the leaf is the organ of the plant with the highest amount of the desired metabolites [16].

Table 2: Relation between the use of the most frequent medicinal plants by the interviewees and the literature.

The samples of 21 plants were collected and submitted to botanical identification by a biologist. The plants were confirmed through the identification of the genus. It was not possible to identify the species because specific parts of the plants, such as roots and flowers, were needed and that was not possible at the time of collection. As it can be seen in Table 2, the popular use does not depart much from the literature, since 45 have shown use compatible with the pharmacological properties described in the literature. However, divergence or lack of scientific evidence was found. The interviewees reported that green tea Camellia sinensis has a sedative effect. However, this plant is rich in methylxanthines, such as caffeine, presenting SNC-stimulating effect [17]. Besides, this tea also has anti-inflammatory and immunomodulatory properties, which aid in the treatment of various atherosclerotic, dietetic and even carcinogenic diseases [4].

Similarly, eggplant (Solanum melongena L.) has been reported to lower cholesterol. Despite this, the literature shows that a deeper understanding of this therapeutic activity is necessary since it has not been fully elucidated [18]. Another plant that was also used with divergent purposes of the literature was the elderberry (Sambucus nigra L.) since in the literature there is still no scientific evidence to prove its action as anti-flu and to stop pruritus (Table 2) Relation between the use of the most frequent medicinal plants by the interviewees and the literature. The level of fidelity (FL) was calculated based on the number of users of a particular species of plant to treat a serious disease. The fidelity level (FL) shows the percentage of informants who use a plant species for the same disease, which is important for the total number of informants who mention the plant for any use (Table 2). Fidelity levels higher than 50% are considered as reliable for use, which was observed for most plant species, showing the importance of the use of these species in the treatment of the diseases mentioned in the study area. Peumus boldus and Equisetum sp were highly utilized plants that had the highest fidelity levels of 93.12% and 87.87% in the treatment of gastrointestinal discomforts and inflammations, respectively. Some plants had 100% fidelity level, yet these plants were little used by the interviewees, which accounts for the great index of level.

However, 55% (148) of the interviewees also use drugs and medicinal plants, presenting potential risks of interaction between MP and drugs. Therefore, we evaluated the potential interactions as shown in Table 3 and identified 42 potential interactions between MP and drugs. Of these, 90.5% (n = 38) were identified as pharmacodynamic interactions and modifications of the effector organ responses may occur, giving rise to synergistic, antagonistic, and potentiating events. Besides, 9.5% (n=4) were considered as pharmacokinetic interactions, since they are caused by a triggering drug on the absorption, distribution, biotransformation and excretion procedures of another drug, whose effect is modified (Table 3) Potential plant-drug interaction.

The lemon balm was the plant that presented the most common interactions among the interviewees since it was the most used by them. Their interaction with sedative and anxiolytic drugs such as fluoxetine, amitriptyline, clonazepam (medicines that the respondents reported use), cause increased sedative activity, and this may occur because the lemon balm exerts an additive effect when simultaneously with central nervous system depressant drugs due to their neurocognitive properties [19]. The clinical significance of drug interactions is related to their type (mechanism) and magnitude (severity). In fact, this information is useful to support the need and intensity of patient monitoring or changes in therapy to avoid possible adverse consequences [20-25], since of the 66 respondents who were advised by a health professional, 15 of these could have had potential plant-drug interactions. However, there are no data about the severity degree of plant-drug interactions, as well as the lack of a source that deals with plant-plant interactions.

In fact, plant-plant interactions are also important for their safe use. In our study, of the 406 interviewees, 67 mixed different medicinal plants in the same preparation, such as: sacred grass with lemon balm, lemongrass with chamomile, boldo with lemon balm, barberry with barbatimão, but studies on these interactions are scarce and there is no scientific evidence among these plants. However, it is worth mentioning that of the 406 participants, none reported intoxication or adverse effect related to the use of medicinal plants alone or in a mixture. In addition, 34 (8.3%) participants reported the use of phytotherapics, among whom 31 (91%) were female and 4 (9%) started use due to medical indication [26-31]. Among the phytotherapics used daily are Calmam® (Passiflora incarnata L., Propolis extract (tree resin, beeswax, flower pollen, essential oils), Vitro Naturals Noni Juice® Morinda citrifolia, Herbarium “Unha de gato”® Uncaria tomentosa, Seakalm® (Passiflora Incarnata), Calmix® (Passiflora Incarnata, Melissa officinalis, Valeriana officinalis, Erythrina verna, Cymbopogon citratus, Hypericum perforatum, Matricaria chamomilla), Valeriane® (Valeriana officinalis L.). Thus, the numbers of informants that make use of these phytotherapics are 16, 8, 2, 2, 2, 2, 2, respectively. The low consumption of phytotherapics can be strained to the little knowledge of the population since they have been recently inserted in the market because the National Policy on Integrative and Complementary Practices in the Public Health System was approved in 2006. Besides, since a great part of the interviewees is of low class, many are not able to acquire these medicines [32-38].

Conclusion

In summary, when tracing the epidemiological profile and the medicinal plants used, it was possible to conclude that the use of MPs is part of the popular culture of a city of Sergipe, a state of northeastern Brazil, and is frequently used to aid in the relief and/ or cure of symptoms or diseases, as it is also observed in other regions of the country [39-43]. It was also observed that despite advances in the production of medicines, people still use medicinal plants for therapeutic purposes, where the sociocultural aspect has a strong influence [44-47]. However, medicinal plants are not exempt from causing any harm to human health, since, in addition to toxicity, they may interact with some medicinal products [48-52], if used concomitantly with the plant, reducing or potentiating its effects, as presented in this study. In view of this, there is a need for a rational and safe use of alternative medicines and therapies, as well as the orientation of qualified health professionals and the awareness of the risks and benefits of the concomitant use of the therapies under study in order to prevent health problems [53-57].

 https://lupinepublishers.com/pharmacology-clinical-research-journal/pdf/LOJPCR.MS.ID.000131.pdf

https://lupinepublishers.com/pharmacology-clinical-research-journal/fulltext/ethnobotanical-survey-and-identification-of-potential-interactions-of-plants-used-in-a-city-in-northeastern-brazil.ID.000131.php

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[gethealthy18-blog]

Bee-Friendly Plants for Your Yard or Garden

New Post has been published on https://healingawerness.com/news/bee-friendly-plants-for-your-yard-or-garden/

Bee-Friendly Plants for Your Yard or Garden

Table of Contents[Hide][Show]

What would happen if one day 80% of flowering plants disappeared? If bees and pollinators die out, that’s exactly what would happen. Bee-friendly garden plants are a simple way to save the honey bees and make the world a better (and more beautiful) place.

Why Are Bees So Important?

In recent years there’s been more awareness to save the dying bee populations. But how important are bees really? Although they’re tiny, bees play a big role in our ecosystem.

According to the USDA Forest Service, over 80% of flowering plants need bees and pollinators to reproduce. This includes flowers, fruit trees, and many other fruits and vegetables. Bees also help pollinate flowers and plants other animals rely on for food.

Basically without bees… there is no us!

The Time to Act Is Yesterday

The USDA National Agricultural Statistics Service releases their honeybee surveys and reports every year. They’ve found bee colonies took a nosedive in the early 90s, but there’s been a slow uphill climb the past few years. While bees are still at risk of becoming endangered, it seems more people are addressing the issue. We need a whole lot more though!

We’re losing about 30% of bee colonies every single year. There’s only so much time before the clock runs out and we’ve lost our most important pollinators for good.

Build a Bee-Friendly Yard

One of the biggest changes we can make is to create a bee-friendly environment in our own backyards (and front yard, and side yard…). It may not seem like much, but the more people chip in the more of a difference we can make.

Here are some simple ways to create a haven for bees:

Get Lazy with the Lawnmower

Flowering “weeds” like dandelion and clover are food for hungry pollinators. A picture-perfect patch of green grass may look good in a magazine, but for a bee it’s like an empty buffet. Keeping grass higher and ditching the weed killer means more flowers and wild plants have a chance to grow.

Filling your yard with bee-friendly plants and not mowing wildflowers is a big first step. When a neighbor makes a comment about the “weeds,” that’s a golden opportunity to spread the bee-saving message.

Variety Show

Just like we don’t want to eat only broccoli all day every day, bees also need a variety of foods. Diverse plant life also makes for healthier soil and attracts beneficial insects that feed on the bad bugs.

GMO monocrops, like corn and soy, rely on pesticides that kill wildflowers and decimate friendly insects. Other farms rely on bees to pollinate, but unfortunately many of them still use bee damaging/killing pesticides. Almond groves are a prime example.

We can advocate for better forms of bug control by voting with our dollars and supporting organic farms. Some small farmers don’t use pesticides but aren’t certified organic. It’s worth asking around at the local farmer’s market!

We can also use natural, pollinator-friendly pest control methods in our home gardens.

Not All Plants Are Created Equal

There’s more to making a pollinator garden than setting out some flowers. Certain bees prefer certain plants, and some colors are more attractive than others. Bright colored flowers, especially purple, are more likely to bring bees.

Avoid Neonics

Aka neonicotinoids, this class of pesticides was developed in the 1990s and is widely used. Unfortunately there’s evidence neonics are harming our eco-system, including the bee population. Seeds are coated in the neonicotinoids and as the plant grows the pesticide becomes part of the plant. The pollen and nectar are then poisonous to bees and other pollinators.

Plants and seeds treated with neonics should be clearly marked, so be sure to carefully read any labels before purchase.

A Pollinator Garden for Every Season

While dandelions and purple dead nettle are great for spring and early summer bee food, there’s the rest of the year to think about. It helps to plant different flowers that will be in bloom throughout the summer and into the fall.

In the plant lists below, many are marked with when they’re in bloom. By planting a variety, bees can eat throughout the seasons before they go dormant in winter.

Plant by Zone

Many plants work in most growing zones, but if possible, native plants are the way to go. This website has details on native species for pollinators tailored to each area of the US.

Best Plants for Bees and Other Pollinators

Flowers usually come to mind when we think about food for bees. However, flowering trees are the biggest food source for pollinators. The Arbor Day Foundation recommends the following trees for a pollinator garden.

Trees

Maple

Serviceberry – prefers areas with cold winters

Koelreuteria – a popular variety is the goldenraintree

Fruit trees – plums, apples, crabapples, peaches, cherries, and pears are good options.

Crapemyrtle – Flowers late spring through summer

Liquidamber – a popular variety is American Sweetgum

Black tumelo – Native to eastern states and yields especially good honey for honey bees.

Sourwood – native to eastern states and produces seed capsules into winter.

Linden – Silver linden and littleleaf linden are popular species

Hawthorn

Tulip trees

Southern magnolia

Privets

Pollinator Garden Flowers

Here are some flowers bees, butterflies, and other pollinators rely on. Not every plant will grow in every area. Be sure to check which growing conditions a plant prefers before planting.

Columbine – blooms mid spring to early summer

Lupine – spring

Dandelion – spring through fall.

Clover – early spring through summer, depending on the variety

Irises – early summer

Milkweed – blooms throughout the summer

Marigold  –   blooms throughout the summer

Rocky mountain iris – summer

Aspen fleabane – summer through fall

Gentian – mid summer to fall

Sunflowers – summer and into fall

Wild bergamot (also known as bee balm) – blooms late summer through early fall

Rose – begins blooming in May. Depending on the variety it may only bloom once per season.

Goldenrod – end of summer through fall

Joe pye weed – blooms late summer through fall

Fruits and Vegetables

Blueberry

Eggplant

Legumes

Watermelon

Tomatoes

Pumpkin

Strawberry

Edible and Medicinal Herbs

Where to Buy Pollinator Plants

Check your local garden store, neighborhood plant swap, or grow them from seed!

Our pollinator friends still may be in danger, but there’s plenty we can do to help them out! You can read lots more about gardening and get tons of tips for how to grow and maintain a garden here. 

Sources:

Anderson, C. (2020, April, 21). 7 Flowering Herbs for Bees. Carolina Honey Bees. https://carolinahoneybees.com/best-herbs-for-bees-and-homesteading/

Arbor Day Foundation. (N.D.). Trees for Bees and Other Pollinators. Arbor Day. https://www.arborday.org/trees/health/pests/article-trees-for-bees.cfm

Kaplan, K. (2020, March 13). Fact Sheet: Survey of Bee Losses During Winter of 2012/2013. USDA. https://www.ars.usda.gov/oc/br/beelosses/index/

Pollinator Partnership. (N.D.). List of Pollinated Food. Pollinator. https://pollinator.org/list-of-pollinated-food

USDA. (2020, April, 4). Surveys. United States Department of Agriculture

National Agricultural Statistics Service. https://www.nass.usda.gov/Surveys/Guide_to_NASS_Surveys/Bee_and_Honey/

Source: https://wellnessmama.com/426197/bee-friendly-plants/

[frogoboggins]

Thank December ch. 1

Harry Potter AU if Ginny were Ron’s twin

warning:Draco has feelings and character development get over it

It was a cloudy afternoon in the early October of Hermione's fourth year. The Gryffindor/ Hufflepuff game had started about ten minutes ago. Somewhere in the Gryffindor stands, Hermione, Ginny, and Luna cheered on their team. As Hermione watched, the quaffle flew through the air narrowly missing the ring at the Hufflepuff end. It was retrieved and the game continued. Hermione glanced down at the red-haired boy sitting at her feet. Ron was scrambling to finish copying his potions homework for tomorrow. He wouldn't have time to bash on Cedric at the victory party that night if he didn't get it done by the end of the game. There wouldn't be time for much quidditch this year with the triwizard tournament; in fact there were no official games at all. Dumbledore wanted the whole school to feel united, so no quidditch, no house cup, and absolutely no house pride after parties. The wizard made some fair points but let's be honest, Gryffindors don't really believe in rules. The house after parties so far this year were the biggest and loudest Hermione had seen yet.

Hufflepuff was already up by 30 points but there was no way Gryffindor was going to lose. Something caught Hermione's eye not far above. It was Fred Weasley. He, of course, was showing off again. Hermione rolled her eyes. Fred looked down and winked at her, flipping on his broom. The poor idiot wasn't even paying attention to the small worn ball barreling toward him. The bludger smacked into his broom, breaking it and sending him to the ground. One of the teachers managed to slow him down, but that didn't stop him from hitting the ground with a thud.

Before she realized she had even moved, Hermione was on the field. George lifted Fred, pulling his arm over him. George laughed, “Well maybe if you werent too busy making eyes at Granger, you'd have hit the bloody ball at Diggory and won us the game.”

“Well I guess you could say he was falling for her, eh Georgie?” Dean Thomas cut in. Dean took Fred's other arm.

“Now don't look at me like that, Granger,” Fred laughed, “Madam Pomfrey and I have become close personal friends. She’ll fix me right up.” He winked again. “Ow ow ow! George I think I may have pulled ahead of you on this one.”

“What?” Hermione stared

“Don't worry about it sweetheart,” George smirked.

Later in the hospital wing

Hermione, Harry, and Ron approached Fred's bedside that evening surprised to see a cast on each leg and a massive bruise on his arm.

Seeing the shocked and slightly worried look on Hermione's face, Fred smiled. “Turns out Pomfrey and I aren't so close after all.”

“She didn't do anything?” Hermione gasped.

“Apparently if I want to be healthy, i need to ‘stop taking risks, grow up,and stop being such a flirtatious show off.’” He made finger quotes as he listed Madam Pomfrey's suggestions. “Whatever that means.”

“It means my older brother is a bloody idiot,” Ron scoffed

“Now there's no need to talk that way about Percy,” George said, walking up behind Ron.

“Yeah Ron, he’s just emotionally challenged,” Fred continued.

“Meaning he never had any,” George concluded.

“Well I hope you learn your lesson,” Hermione said, sounding a bit too happy about the outcome of their earlier interaction. “You really should pay attention to details. Next time it could be your neck.”

“Look everyone! Mudblood Granger’s crushing on a Weasley!” Draco's consistently irritating voice made Hermione flinch. “Should have known she’d settle for one of those embarrassments.”

“Shove off Malfoy,” Harry snapped

“Why don't you go fix your makeup Potter,” Draco countered. “You've got a little something just there.” He gestured to the center of his forehead. “Maybe your mum could get it. Oh wait.”

Harry lunged at him but George and Dean held him back. “MALFOY I SWEAR I'LL SKIN YOUR PATHETIC LITTLE-”

“Now Potter,” Draco drawled, “You should really get that violent streak under control. Wouldn't want to get anyone else killed now would we?” With that last sentence draco stepped forward and tapped harry's nose with his slender cold index finger. His face came so close to Harry's, he could feel the heat of his breath. It smelled slightly bitter, but also like his teeth were cleaned obsessively.

Harry froze for only about a half a second, staring straight into Draco's eyes. He was still just long enough for Dean's grip to loosen. As soon as his arm had the freedom to do so, Harry swung his fist up to collide with the face that hovered centimeters from his own. Draco hit the ground and sat back on his elbows. He touched his nose and looked at the blood on his fingers.

“Felt good didn't it?” Hermione smiled at Harry.

“Madam Pomfrey! Did you see that?! Potter hit me!”

“I don't recall that happening at all, Mr. Malfoy,” the old witch said calmly. “I only saw a clumsy boy trip over his own feet. Now you best go tend to that nose of yours.”

Draco stood, glaring at Harry with his trademark “I’ll get you Potter” look and left.

Passing him at the door, Luna came rushing in with a moaning Neville at her side. She was surprisingly calm, but that's just how Luna is.

“Madam P.,” Luna spoke softly, “I'm afraid Neville ingested a bit of his herbology project before it was quite perfected.”

“Again Longbottom? Well, better bring him to an open cot.” She moved over to the cupboard and searched around in it for a bit. “Well that's odd. Professor Snape just made up a fresh draught. I guess we'll have to use something else.” She shut the cupboard.

“Something else for what Madam P.?” Dean asked.

“To make Mr. Longbottom vomit up whatever creation he botched this time, Mr. Thomas.”

George grinned, “I've got something you could use.” He reached into his pocket and pulled out what looked like a piece of hard candy.

“Is that what's been sending me so many first years?”

“Not if you want it it isn't,” Fred said with a grin.

Madam Pomfrey hesitated, then what could have been a smile twitched at the corner of her mouth. “Fine Mr. Weasley. Hand it over, and the headmaster won't hear of it from me.”

George handed it to her but laughed, “That old geezer? He bought a whole box last week!”

“Yeah the old man loves a good joke, he gets all our stuff. I’d watch my pumpkin juice around him if i were you.”

The group all laughed, and the old witch’s mouth twitched again.

“Well we better be heading down for dinner now,” George announced. “I'll bring ya back somethin good, Freddy.”

And with that the group gathered their things and departed.

Hermione didn't eat much that evening. For some reason she couldn't get the image of Fred falling out of her head.

“Madam P. says he can leave the hospital wing day after tomorrow, but she says he won't be able to play quidditch for a few weeks,” George announced as he sat at the gryffindor table.

“Really? That’s awful! I was really looking forward to seeing him on the field again soon.” Cedric Diggory had run over from Hufflepuff.

Harry rolled his eyes and started piling food on his plate. He glanced up across the room to see Draco glaring at him with a bruised nose. But he wasn't looking directly at Harry. His gaze was slightly off like he could have been looking at Harry’s plate. He must have been zoning out, Harry thought. Malfoy was strange, but he didn't glare at food like it had punched him.

George and Cedric were still chatting it up when Harry came back to the conversation.

“Right, well, I was just about to bring the old boy a plate, if you wanna come.”

Cedric grinned like a child on Christmas. “I’d love to!”

George laughed and he and Cedric headed up to the hospital wing.

Harry turned back to his meal, but as he did he could have swore he saw Draco lick his lips. He was probably trying to make them stop hurting though. Harry had hit him pretty hard.

“So Harry, I heard Sirius finally got the house. How’s he doing?” Ron asked.

“Still pissed at the ministry for making it take so long with all the legal stuff, but the place is beautiful. He calls it his ‘two hundred acres of freedom.’ Buckbeak is loving it, too. He wants me to invite everyone for Christmas. Weasleys, Grangers, and anyone else who would like to come. He definitely has the room. The retribution money from the ministry for his twelve years in Azkaban, along with the book he published on his experience there have made him quite a wealthy man.”

“Yeah i heard What the Actual Bloody Hell was a huge hit in America,” Ron laughed.

“How the man managed to make experiencing your worst fears and slowly being driven mad everyday funny is beyond me,” Hermione added.

“Because he's a genius Hermione!” Ron shoved a huge bite of potatoes in his mouth.

“Yeah. I'm pretty excited about staying there. He even has a place for Lupin out there on his property.”

Harry looked up. Draco was still glaring. “Guys, I think I might have hit Malfoy a bit too hard.”

His friends turned around to catch Draco staring, and the blonde boy's face turned even redder than before. Draco stood to leave but his robe was caught on the edge of the table. As he struggled to free himself, his face only got brighter.

“Guys turn back around,” Harry ordered, “He knows you’re looking”.

“So?” Ron shrugged as he turned to face Harry. “The guy's a jerk.”

Harry wasn't sure why he cared either. Malfoy had always gone out of his way to torment them. Harry took the silence as a chance to change the subject. “So, Ron, are you gonna take Fred’s place on the team for a few weeks?”

“No way!” Ron replied. “I don't play Beater.”

“I’ll do it!” Ginny eagerly volunteered as she sat next to Harry. She smelled a bit like strawberries.

“Really? You sure?” Harry asked. “It's a difficult position. It's a lot harder to balance and-”

“Harry, I’ve got it,” she stopped him. “Believe it or not, I'm a much better flier that my brother.” She smiled.

“Alright,” Harry laughed. “Why don't you go get a broom and gear and meet us on the field in an hour?”

“Okay,” Ginny grinned and ran off to track down some beaters gear.

A bang and a puff of smoke went off just a little ways down the table.

“Mr. Finnigan.” Professor Snape stood behind Seamus.

“Yes professor?” Seamus turned and looked up, his hair on end and his face covered in soot.

“There is a reason your beverage will not transform into alcohol,” Snape sneered coldly. “We have rules here. I suggest you abide by them.”

“Yes Professor.”

“Mr. Finnigan.”

“Yes professor?”

“Detention.”

“Yes professor.”

Snape moved down the side of the table, noticing Harry and the others watching. “Ten points from Gryffindor.”

A collective sound of disappointment and irritation erupted from the table.

“Mental, that one,” Ron whispered as soon as Snape was gone.

“I think I’ll head out to the field now and get some practice in before Ginny gets there.”

“Tryin to impress someone, Harry?” Ron laughed. “Can’t be Ginny.”

“No it’s just been a long day, and flying sounds really great right now”

“Okay. Just don't look at Hermione while you’re in the air,” Ron joked. “I hear that's bad luck.”

Hermione punched his arm

“Ow, ‘Mione. That hurt!

Hermione grinned, “Then don't try to be clever”

“Wouldn't dream of it. We all know only the great Hermione Granger is allowed to do that”

Hermione glared for a moment until Ron was thoroughly uncomfortable.

“I'm going back to the common room to study,” she announced at last and left the table. Harry also got up to leave.

“You coming, Ron?” harry asked hopefully.

“No, I still need to finish copying my homework. Maybe next time”

“I hear Fred and George are gonna find a way to get George’s name in the goblet next week. That should be exciting”

“Yeah they're idiots.”

Harry laughed and made his way to the door. He stepped out into the corridor and down to the end.

Once he was outside with his broom, he bolted for the quidditch field at full speed. He was going so fast, he almost didn't stop before running straight into Victor Krum.

Harry's face went red and he couldn't think of what to say so it just came out, “oh... umm... Krum hi... umm…. sorry... i was just ….quidditch….Ginny...umm...sorry.

“You are… Harry Potter?” Krum had an intense look on his face that looked like he was thinking very hard about nothing at all. “Victor Krum,” he said as stuck his hand out for harry to shake. “I will join you for quidditch?”

“Uh sure, yeah,” Harry said in shock. He snapped out of it and remembered who else was coming. “Umm so my friend Ginny is gonna come out to practice to fill in for one of the Gryffindor beaters”

“Hmmm,” Krum held his chin in deep thought. “I will help this Ginny also. He will learn beater very well,” Krum nodded as if his statement had been somehow philosophical. His friends nodded with him all with the same intense look.

Harry held back a laugh, “Ginny is a girl, but she's a great flier”

“Well of course she is. Women are quite agile fliers and fierce competitors. I apologize.”

Just like that Harry Potter found himself leading one of the world’s best quidditch players to his home field.

[jimmiejcrochet]

Nifty Next 50–Same Bottoms for a Year.

Nifty Next50 has made an interesting formation for the last year. Almost bottoming out around the same base for 4 times in the last 1 year.

Nifty Next50 Technical Chart

Same bottoms for last 1 year.

Knocking at the last 2 months high.

This is still down 17% from the highs.

Also topped out in January 2018 like all other broader indices.

Did make an attempt to try all time highs in Sept 2018.

Now for the last 1 year even this index is diverging with the Nifty50.

Over a long period of time Nifty Next50 has generally outperformed Nifty50.

Nifty 50 and Nifty Next 50

1) Over the last 5 years the Nifty next 50 has outperformed nicely.

2) Over the max period also a strong outperformance.

If i were to run a long term large cap index fund strategy would be a mix of Nifty50 and Nifty Next 50 in some ratio say a 50-50 or rather just the Nifty next50. 

One of the major reasons to like the Nifty next50 index is that it is a lot more diversified and less top heavy.

3) Long periods of Underperformance too.

But there are long periods of underperformance too. A lil old snapshot from a post on capitalmind. Suppose the underperformance has continued and now this has lasted 300 plus trading sessions. Only time this did so was in 2008 fall and 2011-2012 fall.

Source – Capitalmind - 

Given the stretch and good formation it could well be the time for Nifty Next50 to outperform the Nifty50. Will it happen due to Nifty

The Top 20 names in the Index as per weight.

HDFCLIFE 3.98 DABUR 3.74 SBILIFE 3.71 GODREJCP 3.4 SHREECEM 3.34 PEL 3.16 PIDILITIND 3.1 DIVISLAB 3.05 MARICO 2.98 ICICIGI 2.95 PETRONET 2.95 HINDPETRO 2.86 MCDOWELL-N 2.76 LUPIN 2.62 COLPAL 2.5 HAVELLS 2.5 AUROPHARMA 2.49 DMART 2.46 BAJAJHLDNG 2.45 INDIGO 2.4

Very well diversified across stocks with nothing weight more than 4%.

At the same time Nifty50 has top 8 names above 4% weight and comprise 55% of the index. The Top 8 here comprise only 28%.

So even the bottom 10-20-30 stocks in Nifty next 50 can give a good impact to the performance.

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Nifty Next 50–Same Bottoms for a Year. published first on your-t1-blog-url

[lupine-publishers-ciacr]

Lupine Publishers | The Systems of Consumer Demand Analysis: A Review

Lupine Publishers |  Agriculture Open Access Journal

Abstract

For several decades both theoretical and empirical economist have shown interest in consumers behavior and regarding consumer's preferences has increased our understanding enormously. This paper is based on the comparative assessment of the demand system selected; the Linear Expenditure System fails to describe consumers demand behavior as specified by Engel's-Law. With the increasing expenditures, inferior commodities lean towards luxuries which are not plausible. So, for food demand analysis the LES is not appropriate. With utility maximizing behavior the Rotterdam is not consistent even if corresponds-to-generally- accepted-empirical-facts-and-is flexible (e.g. the substitutive or complementary relationship among goods and demand description for inferior commodities, necessities and luxuries). The parametric restrictions given by AIDS and Indirect Trans log System, theoretical properties of demand function can be imposed. Both systems depict generally empirical facts and are derived from flexible function from. However, estimation process may become difficult due to relatively high number of independent parameters the Indirect Tans log System. Linear Approximate Almost Ideal Demand System are much simpler in estimation and linear in parameters and therefore, LA/AIDS can be widely applied as basic model for empirical studies.

Introduction

For several decades both theoretical and empirical economist have shown interest in consumers behavior and regarding consumer's preferences has increased our understanding enormously Brown and Deaton, 1972. Due to increased computing capacities and well as availability of detailed dataset, recently renewed interest has been registered. In particular, empirical research has come up with more sophisticated models of consumer's behavior [1]. Modern consumer demand analysis is practiced by formulating and estimating demand system, which can be defined as given the prices of goods, income and with specific characteristics how consumers allocated their total expenditures to consumption of these goods or services is described by sets of equations. Thus, information on demand responses to change in prices of goods, income (expenditure) and other variables of interest is provided by complete demand system. In order to get meaningful information and justified outcomes, the conditions required by neoclassical microeconomic theory and fit the data well must be satisfied by such system [2].

Using a given dataset, among many of the available functional form for estimation of demand, the best model specification cannot be answered by any economic theory. Since the ambiguity of any model having finite number if parameters cannot be spanned by the space of the neoclassical functions. In literature, different approaches have been proposed for comparison. An elementary approach for estimation of different demand function is one having goodness of fit-statistics [3,4]. Another approach which possesses neoclassical preferences of the demand functions is known in the region where the function meet the theoretical regularity conditions. By knowing the location and size of the regular region superiority of one functional form over another can be supported [5,6].

According to Blanciforti [7] when we trying to estimate demand system two basic approached are used. The first which fulfills various axioms of choice starts with utility maximization. By utility maximization function subject to budget constraint demand functions are obtained. The second one starts by imposing restrictions on the system having an arbitrary demand system. As compared to the first approach, to a much closer extend the second approach corresponds with micro and macroeconomic theories. It is useful to know the meaning of utility in order to understand the general framework of consumer utility maximization. Utility is defined as an index of satisfaction from consuming goods and services and can be additive or comparable across consumers [8]. The use of duality allows a considerable increase in the flexibility with which empirical demand equations can be specified and permits much more intimate relationship between theory and practice [9]. The last but not the least approach to study a Monte Carlo study to explore the demand model accuracy is when the true elasticity's of substitution are known [10].

Partial Versus Complete Demand System

Partial demand system is still estimated to describe consumer behavior in empirical research due to results interpretation and ease of estimation. Among many of the advantages of partial demand model is that smaller number of observations are required than the complete demand models which enables estimation simpler having limited number of parameters. However, under special circumstances such as time, data constraint and theoretical consideration this should only be done. In recent decades, most of the researcher concentrated on complete demand system for estimation. To use and estimated the complete demand system in empirical studies few of its advantages are listed below [11].

1. Expenditures and own/cross price demand elasticity's (uncompensated and compensated) are usually generated by empirical estimation of a complete demand system.

2. The substitutive or complementary relationship among the commodities can be described by considering the interdependence already existed.

3. Many of the welfare indicators such as subsistence level of expenditures or consumption for a specific good and marginal propensity to consume are also provided by some of the system specification.

4. In addition, testing of hypothesis about restrictions derived from demand theory, information is provided by the complete demand system.

There are also some difficulties beside the above-mentioned advantages which are related to the use of complete demand system.

1. To estimate the number of parameters adequate large dataset is required. Therefore, in order to reduce the number of parameters restrictions of separability are imposed.

2. By applying the demand theoretical problems like "aggregation problem over individuals" of the neoclassical demand theory exists [11,12]. Individual’s decisions of consumption in the neoclassical demand theory, it is assumed restrictively and implicitly that all the individuals have same utility functions, if average expenditures and consumption data are used for empirical estimation. In empirical estimations household take decisions based on household data and not the individuals.

3. Similarly, aggregation over different commodities is another problem which need assumptions on preferences structure and the use of index theory to choose suitable values for quantities and prices for these aggregated commodities. Demand system categorized it into three sub groups:

First, the directly specified demand system like the Rotterdam System. Second, based on expenditures function or indirect utility, demand systems are derived such as the Linear Expenditures System (LES). Third, from a flexible functional form demand systems are estimated, for example the Indirect Trans log System (ITS) and The Almost Ideal Demand System (AIDS) as presented in the following section.

The linear expenditure system

The Linear Expenditure system was developed in 1954 by stone to begin with a simple expenditure model [13]. Form the stone Geary utility functions LES is derived and has previously been considered by Klein Rubin (1948). The stone Geary utility function is as follows:

LES does not allow for inferior goods as suggested by the coefficient βk in the Stone Geary function having positive marginal share. As the marginal utility foreachgood βk (qk - qk) is positive, qk is greater than the corresponding than γk .

The sum of individual expenditures for these goods is equal to the total expenditures which indicates that the above utility function is strongly additive or separable. In addition, thelevel ofconsumption ofall other goodsis independentof themarginal utilityof each good iv

Maximizing the Stone Gearyutility functionw.r.t thebudget constraint yields the expenditure on good i as:

The expenditure function on good i is interpreted for all positive γ_i as follows.

At the cost of piγi for good i, the consumer will purchase first the quantity γi representing subsistence consumption level of good i. Leaving supernumerary expenditures after the total consumption on all goods is Pkγk, which is allocated between the goods in the fixed proportion βi. The main features of the Linear Expenditures System can be summarized as:

Homogeneity, addingup and Slutsky symmetry restrictions of the demand system are satisfied by this system. The LES cannot be complemented using the linear estimation method because it is linear in parameter, but not linear in parameters. As indicated by the positive coefficient the description for inferior goods demand does not allowed by the Linear Expenditures System i.e. (0< βk <1).

1. For good i the expenditure elasticity.com defined as (0< βk <1) .

2. No two good may be substitutes which is implied by the strongly separable property and is justifiable only for large aggregates of goods.

3.The relationship between the expenditure elasticities and price is proportional as implied by the additive utility function, but this restrictive assumption cannot be justified.

4. Under LES all cross price elasticities are negative which means that all pairs of goods are complements, while the own price elasticities for positive γi , ranges between minus one and zero, implies that all goods are price inelastic.

5. The compensated ownprice elasticities (ε*ii) = εii +βi are positive, also the positive cross-price elasticities indicated that every commodity cannot be complements of each other and must be substituted for one another.

The Rotterdam System

The Rotterdam system was introduced by Theil [14] and Barten [15] which is similar to the Linear Expenditures system of stone (1954). Instead of level of logarithms it works in differentials [16,17].

The resultant demand functions as:

where εi represent the expenditure elasticity for commodity i, andthecross-priceelasticities are εij

The compensatedcrossprice elasticities ε*ij can be writtenas ε*ij =εi- wj (Slutsky decomposition), so that:

Where the budget constraint is followed by the second equality. For good i, the marginal propensity to spend on good is represented by the variable bi, the compensated cross price elasticity cij, weighted by the budget share such that

Where the Slutsky substitution matrix is composed of , i and j.

Theoretical consistency: The theoretical restriction can easily be related with the parameters of the Rotterdam system. The basic requirements of the adding-up property indicate that the net effect of change in price will be equal to zero and the marginal propensity to spend on all k will result in unity.

If the Slutsky matrix is semi definite then the substitution matrix will also be negative and semi definite as indicated by the negativity restriction. The Rotterdam system is although not derived from explicitly the expenditures or utility function but it is linear in parameter and easy to estimate. Using the marginal budget shares bi and ci. income elasticity's can be calculated and whether a good is luxury or necessity can also be concluded. All the substitutive or the complementary relation can be described among all the commodities. The Slutsky term and the marginal shares are supposed to be constant in the Rotterdam model.

The indirect translog system

Christensen, Jorgenson, Lau [18] developed the Indirect Trans log System and can be derived using the logarithmic second ordered Taylor series approximates from the indirect utility function. Which can be written as:

Under the symmetry restriction βij=βji, the parameters α0,γi,and 946;ij can be estimated. Symmetry and Homogeneity restriction imposition leaves independent parameters of which need to be estimated.

In budget share form application of Roy's identity will lead to the following demand system.

The following normalization is needed to ensure the nondecreasing in expenditures nature of the indirect utility function.

To estimate the system several parameters are needed which yield a high nonlinear demand function. If many goods are included, the demand system become very complex causing difficulties in estimation. The Trans log system may also yield problems in empirical estimation as it is nonlinear in parameters. The demand for necessity, luxury and inferior goods and substitutive or complementary relation can also be described by the Tans log system.

The almost ideal demand system (AIDS)

Deaton [19] introduced the Almost Ideal Demand System, which is derived from flexible expenditures function having many desirable and is extremely useful for demand system estimation. With simple parametric restrictions, such as symmetry and homogeneity, it automatically satisfies the aggregation restriction. In addition, this model is consistent with household budget data and has the ability to portray non-linear Engel curve. Due to its properties and simplicity in estimation the Linear Approximate Almost Ideal Demand System (LA/AIDA) is popular for empirical studies [16,20].

By applying the Shephard’s Lemma Hicksain demand function can be derived.

Hicksa in demand functions can be obtained by applying the Shephard's Lemma. The level of utility depends on total expenditures and prices are described by the indirect utility function when the cost function is inverted. By substituting the indirect utility function into the Hicksian demand function the Marshallian demand function can be obtained in its budget share form.

Where wi represents the budget share of good i, αi , 946;i and γij are the parametersneed to be estimated, pj is the price of good j, while x is the total expenditures and P is the aggregate price index that is defined by:

Simplicity of estimation: By using the above price index (24) will result in a non-linear relationship between price index and food prices and will appear in the form of a complicated nonlinear system. Deaton [19] proposed that by replacing the above mentioned price index (p) with Stone's price index the relationship can be linearized.

The AIDS model in which the stone price index is incorporated is called as the Linear Approximate Almost Ideal Demand system (LA/AIDS). It is widely cited that by using stone price index will introduce unit of measurement error [20]. The fundamental property of index number is not violated by the stone index because it is variant to changes in the unit if measurement for prices. The units of measurements error can be corrected if sample mean is used for prices. As suggested by Moschini 1995, to overcome the measurement error a Laspeyres price index can be used. If wi in Equation 58 is replaced by the log linear analogue can be obtained. Hence, the Laspeyres price index becomes a geometrically average of prices. As linear estimation procedure, can be used so its estimation is much simpler.

By incorporating Equation 61 into Equation 58 yields a Linear Approximate Almost Ideal Demand System having Laspeyres Price index as below:

Using the relationship proposed by Pollak, wales [21], equation 28 is augmented with household socioeconomic characteristics as follows:

Where δ_(ir ) is the vector of parameters and η_r is a matrix of socioeconomic variables. The socioeconomic characteristics included in Equation 88 become as follows:

that uses dummies and the demographic variables is the same as the single equation model.

Where the number of demographic and other dummies is represented by m.

When the property of additively is imposed, the expenditure function resulted in a singular matrix of variance and covariance. Thus, to estimate the LA/AIDS model one of the equations needed to be omitted. The expenditure equation for "other food" is omitted and by using the theoretical conditions imposed during the estimation process the coefficient for the omitted equation are derived. However, the coefficients estimated using the LAAIDS is invariant to omitted equation.

Derivation of demand elasticity's for the LA/AIDS model: For the LA/AIDS model elasticity derivation are extensively investigated and well documented. Following Green [20] and Buse [21] with respect to ln(x) taking the derivative of equation 64, the expenditure elasticity can be obtained as below:

Taking the derivatives w.r.t to ln (pj), uncompensated own price elasticities (j=1) and cross price elasticities (j ≠ i), eij LA/AIDS , becomes as follow

where δij is Kronecker delta that is 1 if i=j otherwise 0. Sample mean was used in this study for the point of normalization. The compensated price elasticities sij LA/AIDS,, become as follows:

Theoretical consistency: Restrictions can be imposed on the parameters in the LA/AIDS model as follows:

The negativity condition can be tested by estimation of the all compensated own-price elasticity's. By using LA/AIDS the βi parameter determines the effect of a change in real expenditures on the budget share of good i and whether the good is necessity, luxury or an inferior good [22-36]. βi < 0 for a necessity and the expenditure elasticity lies between 0 and 1 (0 < εi < 1). Decrease with increasing total expenditures and for luxury βi > l and the expenditure elasticity is greater than 1 (εi > 1 ), and increases with increasing total expenditures. The expenditure elasticity is less than 0 (εi < 0) for inferior good and βi < 1. It is also possible to examine the complementary and substitutive relations between pairs of goods by estimating the compensated price elasticity’s.

Conclusion

Theoretical consistency is required for specific demand function in any kind of empirical study. Moreover, the selected functional form should be sufficiently simple and flexible. The estimated preferences function has no restrictions on its free parameters to get the required flexibility, and can approximate the second order twice continuously differentiable preference function. On the other hand, for simplicity in the estimation procedure increase in the degree of freedom available can be used as a procedure if the numbers of parameters are limited and the functional form is limited. Furthermore, the complementary or substitution relationship between good is also described by the functional form which allows demand description for necessities, luxuries and inferior commodities [37-50]. A comparative assessment of the demand system selected, the Linear Expenditure System fails to describe consumers demand behavior as specified by Engel's-Law.

With the increasing expenditures, inferior commodities lean towards luxuries which are not plausible. So, for food demand analysis the LES is not appropriate. With utility maximizing behavior the Rotterdam is not consistent even if corresponds- to-generally-accepted-empirical-facts-and-is flexible (e.g.the substitutive or complementary relationship among goods and the description of demand for luxuries, necessities and inferior goods). The parametric restrictions given by AIDS and Indirect Trans log System, theoretical properties of demand function can be imposed. Both systems depict generally empirical facts and are derived from flexible function from. However, estimation process may become difficult due to relatively high number of independent parameters the Indirect Tans log System. Linear Approximate Almost Ideal Demand System is much simpler in estimation and linear in parameters and therefore, LA/AIDS can be widely applied as basic model for empirical studies [51-70].

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The T-R {Generalized Lambda V} Families of Distributions

Lupine Publishers- Biostatistics and Biometrics Open Access Journal

The four-parameter generalized lambda distribution (GLD) was proposed in [1]. We say the GLD is of type V, if the quantile function corresponds to Case(v) in of [2], that is,

where u 2 (0, 1) and a, b 2 (−1, 0). In this short note, we introduce the T-R {Generalized Lambda V} Families of Distributions and show a sub-model of this class of distributions is significant in modeling real life data, in particular the Wheaton river data, [2]. We conjecture the new class of distributions can be used to fit biological and health data.

Contents

a) The T – R {Y} Family of Distributions

b) The New Distribution

c) Practical Significance

d) Open Problem

The T – R {Y} Family of Distributions

This family of distributions was proposed in [3]. In particular, let T, R, Y be random variables with CDF’s FT (x) = P (T _ x), FR(x) = P (R _ x), and FY (x) = P (Y _ x), respectively. Let the corresponding quantile functions be denoted by QT (p), QR(p), and QY (p), respectively. Also, if the densities exist, let the corresponding PDF’s be denoted by fT (x), fR(x), and fY (x), respectively. Following this notation, the, the CDF of the T – R {Y} is given by

and the PDF of the T-R{Y} family is given by

The New Distribution

Theorem: The CDF of the T-R {Generalized Lambda V} Families of Distributions is given by

where the random variable R has CDF FR(x), the random variable T with support (0,1) has CDF FT, and a, b 2 (−1, 0) Proof. Consider the integral

and let Y follow the generalized lambda class of distributions of type V, where the quantile is as stated in the abstract

Remark: the PDF can be obtained by differentiating the CDF

Practical Significance

In this section, we show a sub-model of the new distribution defined in the previous section is significant in modeling real life data. We assume T is standard exponential so that FT (t) = 1 − e−t, t > 0 and R follows the two-parameter Weibull distribution, so that

Now from Theorem 2.1, we have the following

Theorem: The CDF of the Standard Exponential-Weibull {Generalized Lambda V}

Families of Distributions is given by

where c, d > 0 and a, b 2 (−1, 0)

By differentiating the CDF, we obtain the following

Theorem: the PDF of the Standard Exponential-Weibull {Generalized Lambda V} Families of Distributions is given by

where c, d > 0 and a, b 2 (−1, 0)

Remark: If a random variable B follows the Standard Exponential-Weibull {Generalized

Lambda V} Families of Distributions write

B _ SEWGLV (a, b, c, d)

Open Problem

Conjecture: The new class of distributions can be used in forecasting and modelingn of biological and health data. Related to the above conjecture is the following

Question: Is there a sub-model of the T-R {Generalized Lambda V} Families of Distributions that can fit? [3] (Appendix 1) and (Figures 1-3).

Appendix 1:

DataQ1 = Flatten Data11; Length DataQ1 72

Min DataQ1 0.1; Max DataQ1 64.

AX1 = Empirical Distribution DataQ1

Data Distribution «Empirical», { 58}

K1 = Discrete Plot [CDF [AX1, x ], {x, 0, 65, (65-0)/58} , Plot Style c {Black, Thick} , Plot Markers c {Automatic, Small} , Filling c None,

Plot Range c All]

(Figure 1)

F1 x_, a_, b: = 1 - 1 - x ^ ab

CDF Weibull Distribution c, d, x

I. Weibull. nb

D 1 - E^ - F1 M x, c, d, a, b, x

PLK1 = Sum Log MQ DataQ1, a, b, c, di, i,1, Length DataQ1;

JK=D [PLK, a];

JK1=D [PLK, b];

JK2=D [PLK, c];

JK3=D [PLK,d];

Find Root JK, JK1, JK2, JK3, a, - 0.11 ,b, - 0.12 , c, 0.9 , d, 11.6

a c – 7.2577, b c – 0.395297, c c 0.776499, d c 657.998

RR = Plot 1 - E^ - F1 M x, 0.776499, 657. 998, - 7.2577, - 0.395297, x, 0, 65, Plot Style c Thick, Blue, Plot Range c All

(Figure 2)

II. Weibull. nb

CMU = Show K1, RR, Plot Range c All

(Figure 3)

Export “CMU.jpg”, CMU CMU.jpg

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Lupine Publishers | The Current Status of Continuous Flow Left Ventricular Assist Devices

Abstract

In this review, we hope to give a perspective of the new realities of cardiac mechanical circulatory assist devices. New iterations of devices are providing greater durability and freedom of complications. Work is near to provide internal batteries and transcutaneous energy transfer systems for completely implantable systems, avoiding the need for an externalized drive line.

Keywords: Heart Failure; Transplantation; Mechanical Circulatory Support

Twine and Twine or Lose the Plug- Dislodged Left Atrial Appendage Closure Device

In patients with severe heart failure, cardiac transplantation has been shown to provide considerable benefit. Since 1967, in excess of 88,000 total heart transplants have been performed and 1-year survival is 81%, the annual mortality is 4% per year thereafter. The supply of donor hearts is incredibly limited and much research has focused on mechanical means of improving myocardial function, and several such left ventricular assist devices (LVADs) have been developed through the National Institutes of Health artificialheart program. Several devices have been previously approved by the Food and Drug Administration as bridging therapy to transplantation, though none have been studied as long-term alternatives to transplantation. The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) [1] trial explored whether a specific type of LVAD (a previous generation pulsatile device), when used in the long-term, would reduce mortality (Figure 1). The survival following severe heart failure was extremely poor in the optimally medically treated group in this trial (defined as End-stage heart failure was defined as New York Heart Association (NYHA) class IV symptoms for at least 90 days, left ventricular ejection fraction (LVEF) <25%, peak oxygen consumption <12 mL/kg/min or continued need for intravenous inotropes for symptomatic hypotension).

In the optimally medically treated control arm of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial [1] which evaluated an externalized pulsation ventricular assist device, survival at one year was 28% and 6% at two years, underlying the poor prognosis of this clinical entity (Figure 1). Driving the need for mechanical circulatory support (MCS) is the relative paucity of donors and the unmet need for orthotopic heart transplantation in the general population. There has also been an increase in the number of patients who require mechanical circulatory support (MCS) as a bridge to transplantation [2]. This has been driven, particularly in the UK by limitation of the number of hearts for donation, and also to buy time on the transplant waiting list. This is due to an increase in the numbers of non-heart beating donors (DCDs), whereby retrieval takes place in a circulation arrested donor, and the increased survival of head injury patients and those with intracranial bleeds who are treated by a decompressive craniotomy, reducing the pool of donors who have raised intracranial pressure and who have coned, resulting in brain stem death. The net result is a retrieval rate for heart transplantation of around 19%. The risk of having preformed antibodies directed against the donor heart (sensitised patients) is increasingly likely and is particularly challenging as it may increase the risk of rejection and allograft vasculopathy. There has also been an increase in the number of patients requiring MCS as a bridge to transplantation [3]. This allows many severely ill adults and paediatric patients to survive until a suitable donor heart is available. Patients with MCS are at increased risk for rejection, infection, stroke, and bleeding. The need for transfusions also increases the risk of pre-sensitization [3-5]. Survival at 1 and 5 years is decreased in patients requiring MCS prior to transplantation, but still higher than 80% and 70%, respectively (ISHLT database) [2].

Figure 1:  Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial (Rose et al N Engl J Med 2001; 345:1435-1443).

Advances in Donor Allocation and Selection

Recipient criteria for heart transplantation include, severe symptoms despite maximal medical management, the absence of reversible or surgically amenable heart disease, and where estimated 1-year survival is less than 50% [6]. An estimate of functional capacity in ambulatory patients can be best quantified by measurement of peak O2 consumption (VO2max). Patients with low VO2max (<12 ml/min/kg) have high mortality even if treated with beta blockers and transplantation should be considered for these patients. In addition, heart failure prognosis scores to estimate survival, such as the Heart Failure Severity Score may be used. This calculates a survival probability on the basis of the presence of ischaemic cardiomyopathy, resting heart rate, left ventricular ejection fraction, mean blood pressure, interventricular conduction delay, VO2max and serum sodium concentration [7].

Figure 2:  Competing outcomes for continuous flow LVADS (82% survival at 1 year, intention to treat).

Transplantation eligibility is always considered with regard to risk factors, especially, pulmonary hypertension (Figure 2). Right heart catheterization must be performed in all potential candidates for heart transplantation in order to quantify pulmonary vascular resistance [7]. Right heart failure is a substantial cause of mortality. Right ventricular failure is likely when post implant pulmonary artery pressures exceed 50 mmHg. Patients with chronic heart failure may develop pulmonary hypertension due to elevated left ventricular end diastolic pressure with elevated left atrial and pulmonary venous pressures. This is a reactive form of pulmonary hypertension and may fall when the cardiac output is increased with inotropes or unloaded with nitrate infusions [7]. The transpulmonary gradient is calculated by subtracting the left atrial filling pressure from the mean pulmonary artery pressure. A fixed transpulmonary gradient in excess of 14 mmHg is associated with greatly elevated risk, and thus this cut off is used in the UK [8]. In such patients a destination therapy strategy may be used with continuous flow LVADS.

Mechanical Circulatory Assist Devices

In recent years, the use of MCS device in treating patients with end-stage heart disease has increased significantly, as bridge to transplantation and as destination therapy for transplant ineligible candidates. This increase is based on the accumulated experience with new second-generation continuous-flow devices which show significant improvements in survival, functional capacity and quality of life [9,10]. On the basis of the Heart Mate II Registry experience (1300 patients), guidelines for the clinical management of patients treated with continuous-flow devices have been published [11]. Risk scoring systems, such as the Seattle Heart Failure Model [12] and the Cumulative Risk Score for 90-Day in-Hospital Mortality [13] and the Destination Therapy Risk Score have been investigated to stratify patients who might benefit from LVAD support [14].

Right ventricle failure is a leading cause of morbidity and death after LVAD implant (incidence of about 35%), and can be very difficult to predict [15,16]. Various means to assess right ventricle function both pre- and postoperatively have been assessed (10). Right ventricular failure risk scores have been created that stratify the risk of right ventricular failure (RVFRS) and death after LVAD implantation (Figure 3). One such RVFRS found independent predictors of right ventricular failure to include vasopressor requirement, aspartate aminotransferase >80 IU/L, bilirubin >2.0mg/dL and creatinine >2.3mg/dL [15]. Another study developed a score to predict RVAD need after LVAD placement, which included factors of cardiac index, right ventricular stroke work index, severe preoperative right ventricular dysfunction, creatinine, previous cardiac surgery and systolic blood pressure [16]. More recently the presence of severe TR and a tricuspid annulus of >43mm and right ventricular sphericity have been proposed as predictive of occult RV failure and need for biventricular support. The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry, which follows all long-term MCS systems in the United States, has defined patient profiles that can help identify risks associated with the timing of implant [17]. In the future, the INTERMACS patient profile would be a useful tool to improve management and outcomes of patients who need VAD implant and unify criteria for future clinical trials and devices (Figure 4). As more LVAD patients are listed for heart transplant, a competition has occurred for organs between stable LVAD supported registrants and less stable registrants listed UNOS status 1A or 1B (the highest categories and most at risk if not urgently transplanted). A recent study found that stable LVAD patients had significantly less 30-day risk of events compared to other status 1A patients concluding that allowance of 30 days of elective status 1A time should not be allocated to stable registrants with implanted LVADs [18]. As VAD technology improves, further revisions to the allocation system will need to be recommended.

Figure 3:  Heartmate 3, the latest centrifugal blood pump in comparison to Heartmate II an axial flow pump. Superior event free survival is seen with HM 3.

Figure 4:  Heart-mate 3 vs Heartmate II comparison of event free survival.

INTERMACS Profile and Description and Timescale to MCS

a) “Crashing and burning”—critical cardiogenic shock. Within hours b) “Progressive decline”—inotrope dependence with continuing deterioration. Within a few days c) “Stable but inotrope dependent”—describes clinical stability on mild-to-moderate doses of intravenous inotropes (patients stable on temporary circulatory support without inotropes are within this profile). Within a few weeks d) “Recurrent advanced heart failure”—“recurrent” rather than “refractory” decompensation. Within weeks to months e) “Exertion intolerant”—describes patients who are comfortable at rest but are exercise intolerant. Variable f) “Exertion limited”—describes a patient who is able to do some mild activity but fatigue results within a few minutes of any meaningful physical exertion. Variable g) “Advanced NYHA III”—describes patients who are clinically stable with a reasonable level of comfortable activity, despite history of previous decompensation that is not recent. Not a candidate for MCS

INTERMACS = Interagency Registry for Mechanically Assisted

Circulatory Support; MCS = mechanical circulatory support;

NYHA = New York Heart Association.

Figure 5:  Durability of HM 3 vs HM II, freedom from pump replacement due to pump thrombosis or haemolysis.

Temporary MCS are available that can be implanted quickly and simply to normalise cardiac output in patients with severe acutely decompensated heart failure. The CentriMag [19], Tandem Heart [20], Impella [21] and Circulite [22]. Clinical trials suggest that treatment of temporary VADs does not necessarily correlate with better survival, but merely comprise a component of treatment leading to recovery, upgrade to fully implantable systems as a bridge to transplant or destination therapy, or transplantation [23,24]. Device miniaturisation, without externalized drive-lines connecting the device to a console and longer endurance will be the future trend of mechanical design for long term support. Blood pumps with magnetically levitated rotors has shown satisfactory 1-year survival [25]. The smaller size and weight of the continuousflow devices has allowed an extension of the new VADs into smaller patients. Fully wireless resonant coupling power sources are currently undergoing evaluation, which if successful will greatly reduce the incidence of drive line infections (Figure 5), which is the weakest point of the technology of current fully implantable systems. There is some evidence that fully implantable systems will be available in the near future to greatly improve the quality of life and to reduce the frequency of severe infections with continuous flow LVADS.

Many recent studies have focused on the reversed molecular and cellular alterations, such as improved β-adrenergic responses and decreased calcium-regulating gene expression (Figure 6), in patients using LVAD as a bridge to recovery therapy [26]. Functional recovery has been observed in a subset of heart failure patients [26,27]. Recently, a clinical trial using clenbuterol (β-2 agonist and anabolic agent) and LVAD in refractory non-ischemic heart failure patients, reported recovery of heart function in 60% of patients (n=20) with non-ischemic cardiomyopathy that allows the pump to be explanted (Harefield Recovery Protocol Study for Patients with Refractory Chronic Heart Failure, HARPS) [28]. LVAD therapy is associated with decreased collagen turnover and crosslinking and increased tissue angiotensin II. LVAD combined with angiotensinconverting enzyme inhibition results in decreased tissue angiotensin II and collagen cross-linking, normalizes left ventricular end-diastolic pressure volume relationships and is associated with modestly higher rates of bridge to recovery [29]. Other adjunctive treatments including other medications, cell or gene therapy with over expression of SERCA2a might in conjunction with VAD support provide a meaningful alternative therapy in patients with severe heart disease [30].

Figure 6.  

Conclusion

Heart transplantation is associated with excellent long-term outcomes and is the gold standard solution for intractable end stage heart failure in eligible patients. What limits its impact, overall, is the limited availability of donor organs. The development of ventricular assist devices has mitigated against this, to some extent. Subsequent device iterations with further miniaturisation and continuous flow have resulted in effective bridge to transplant solutions. The presence of an externalized drive line exposes the VAD recipient to infections, however, which may precipitate urgent listing for heart transplant in the bridge to transplant candidate and may limit the life span of the destination therapy candidate. Fully implantable driveline free systems will definitely enhance the utility of these systems in these settings. As our knowledge of molecular medicine increases, manipulation of key proteins implicated in the pathophysiology of heart failure such as SERCA2a may allow some recovery of the myocardium in patients with heart failure to the extent that transplantation may be deferred or the LVAD explanted [31-35].

https://lupinepublishers.com/cardiology-journal/pdf/ACR.MS.ID.000125.pdf

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Lupine Publishers - Journal of Neurology & Neurosurgery

Ictal Asystole after Meningioma Resection: Case Report by  Adeel Ilyas

We report the first-ever case of left fronto temporal-onset seizures causing ictal a systole, within 24 hours of a left sphenoid wing meningioma resection. It reinforces the importance of close monitoring of neurosurgical patients with continuous EEG. Autonomic dysfunction in various forms, affecting the cardiovascular, respiratory, gastrointestinal and other systems, is commonly associated with seizures. Seizures frequently affect the heart rate and rhythm, often in a transient manner. An increase in heart rate is very common with various kinds of seizures, but ictal bradycardia and a systole are much less common [1]. Symptomatic ictal Brady arrhythmias occur in less than 0.5% of epilepsy patients, and the overwhelming majority have been reported in association with temporal lobe epilepsy. The common presentation is a patient who has complex partial seizures with or without secondary generalizations, who develops ictal a systole and syncope. It has been suggested that this is a seizure self-termination mechanism [2].We report here a case of a woman with new onset seizures caused by a meningioma, who had episodes of ictal a systole following tumor resection. To our knowledge, this is the first-ever report of ictal a systole that began after tumor resection - most cases in the literature noted this in the setting of long-standing temporal lobe epilepsy. While illustrating the importance of the central autonomic network in cardiac function, it also emphasizes the need for neurosurgical patients to be closely monitored following their procedure. To know more please click on below link https://lupinepublishers.com/neurology-brain-disorders-journal/fulltext/ictal-asystole-after-meningioma-resection-case-report.ID.000102.php

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Lupine Publishers | The Current Status of Continuous Flow Left Ventricular Assist Devices

Lupine Publishers | Cardiovascular Research

Abstract

In this review, we hope to give a perspective of the new realities of cardiac mechanical circulatory assist devices. New iterations of devices are providing greater durability and freedom of complications. Work is near to provide internal batteries and transcutaneous energy transfer systems for completely implantable systems, avoiding the need for an externalized drive line.

Keywords: Heart Failure; Transplantation; Mechanical Circulatory Support

Twine and Twine or Lose the Plug- Dislodged Left Atrial Appendage Closure Device

In patients with severe heart failure, cardiac transplantation has been shown to provide considerable benefit. Since 1967, in excess of 88,000 total heart transplants have been performed and 1-year survival is 81%, the annual mortality is 4% per year thereafter. The supply of donor hearts is incredibly limited and much research has focused on mechanical means of improving myocardial function, and several such left ventricular assist devices (LVADs) have been developed through the National Institutes of Health artificialheart program. Several devices have been previously approved by the Food and Drug Administration as bridging therapy to transplantation, though none have been studied as long-term alternatives to transplantation. The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) [1] trial explored whether a specific type of LVAD (a previous generation pulsatile device), when used in the long-term, would reduce mortality (Figure 1). The survival following severe heart failure was extremely poor in the optimally medically treated group in this trial (defined as End-stage heart failure was defined as New York Heart Association (NYHA) class IV symptoms for at least 90 days, left ventricular ejection fraction (LVEF) <25%, peak oxygen consumption <12 mL/kg/min or continued need for intravenous inotropes for symptomatic hypotension).

In the optimally medically treated control arm of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial [1] which evaluated an externalized pulsation ventricular assist device, survival at one year was 28% and 6% at two years, underlying the poor prognosis of this clinical entity (Figure 1). Driving the need for mechanical circulatory support (MCS) is the relative paucity of donors and the unmet need for orthotopic heart transplantation in the general population. There has also been an increase in the number of patients who require mechanical circulatory support (MCS) as a bridge to transplantation [2]. This has been driven, particularly in the UK by limitation of the number of hearts for donation, and also to buy time on the transplant waiting list. This is due to an increase in the numbers of non-heart beating donors (DCDs), whereby retrieval takes place in a circulation arrested donor, and the increased survival of head injury patients and those with intracranial bleeds who are treated by a decompressive craniotomy, reducing the pool of donors who have raised intracranial pressure and who have coned, resulting in brain stem death. The net result is a retrieval rate for heart transplantation of around 19%. The risk of having preformed antibodies directed against the donor heart (sensitised patients) is increasingly likely and is particularly challenging as it may increase the risk of rejection and allograft vasculopathy. There has also been an increase in the number of patients requiring MCS as a bridge to transplantation [3]. This allows many severely ill adults and paediatric patients to survive until a suitable donor heart is available. Patients with MCS are at increased risk for rejection, infection, stroke, and bleeding. The need for transfusions also increases the risk of pre-sensitization [3-5]. Survival at 1 and 5 years is decreased in patients requiring MCS prior to transplantation, but still higher than 80% and 70%, respectively (ISHLT database) [2].

Figure 1:  Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial (Rose et al N Engl J Med 2001; 345:1435-1443).

Advances in Donor Allocation and Selection

Recipient criteria for heart transplantation include, severe symptoms despite maximal medical management, the absence of reversible or surgically amenable heart disease, and where estimated 1-year survival is less than 50% [6]. An estimate of functional capacity in ambulatory patients can be best quantified by measurement of peak O2 consumption (VO2max). Patients with low VO2max (<12 ml/min/kg) have high mortality even if treated with beta blockers and transplantation should be considered for these patients. In addition, heart failure prognosis scores to estimate survival, such as the Heart Failure Severity Score may be used. This calculates a survival probability on the basis of the presence of ischaemic cardiomyopathy, resting heart rate, left ventricular ejection fraction, mean blood pressure, interventricular conduction delay, VO2max and serum sodium concentration [7].

Figure 2:  Competing outcomes for continuous flow LVADS (82% survival at 1 year, intention to treat).

Transplantation eligibility is always considered with regard to risk factors, especially, pulmonary hypertension (Figure 2). Right heart catheterization must be performed in all potential candidates for heart transplantation in order to quantify pulmonary vascular resistance [7]. Right heart failure is a substantial cause of mortality. Right ventricular failure is likely when post implant pulmonary artery pressures exceed 50 mmHg. Patients with chronic heart failure may develop pulmonary hypertension due to elevated left ventricular end diastolic pressure with elevated left atrial and pulmonary venous pressures. This is a reactive form of pulmonary hypertension and may fall when the cardiac output is increased with inotropes or unloaded with nitrate infusions [7]. The transpulmonary gradient is calculated by subtracting the left atrial filling pressure from the mean pulmonary artery pressure. A fixed transpulmonary gradient in excess of 14 mmHg is associated with greatly elevated risk, and thus this cut off is used in the UK [8]. In such patients a destination therapy strategy may be used with continuous flow LVADS.

Mechanical Circulatory Assist Devices

In recent years, the use of MCS device in treating patients with end-stage heart disease has increased significantly, as bridge to transplantation and as destination therapy for transplant ineligible candidates. This increase is based on the accumulated experience with new second-generation continuous-flow devices which show significant improvements in survival, functional capacity and quality of life [9,10]. On the basis of the Heart Mate II Registry experience (1300 patients), guidelines for the clinical management of patients treated with continuous-flow devices have been published [11]. Risk scoring systems, such as the Seattle Heart Failure Model [12] and the Cumulative Risk Score for 90-Day in-Hospital Mortality [13] and the Destination Therapy Risk Score have been investigated to stratify patients who might benefit from LVAD support [14].

Right ventricle failure is a leading cause of morbidity and death after LVAD implant (incidence of about 35%), and can be very difficult to predict [15,16]. Various means to assess right ventricle function both pre- and postoperatively have been assessed (10). Right ventricular failure risk scores have been created that stratify the risk of right ventricular failure (RVFRS) and death after LVAD implantation (Figure 3). One such RVFRS found independent predictors of right ventricular failure to include vasopressor requirement, aspartate aminotransferase >80 IU/L, bilirubin >2.0mg/dL and creatinine >2.3mg/dL [15]. Another study developed a score to predict RVAD need after LVAD placement, which included factors of cardiac index, right ventricular stroke work index, severe preoperative right ventricular dysfunction, creatinine, previous cardiac surgery and systolic blood pressure [16]. More recently the presence of severe TR and a tricuspid annulus of >43mm and right ventricular sphericity have been proposed as predictive of occult RV failure and need for biventricular support. The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry, which follows all long-term MCS systems in the United States, has defined patient profiles that can help identify risks associated with the timing of implant [17]. In the future, the INTERMACS patient profile would be a useful tool to improve management and outcomes of patients who need VAD implant and unify criteria for future clinical trials and devices (Figure 4). As more LVAD patients are listed for heart transplant, a competition has occurred for organs between stable LVAD supported registrants and less stable registrants listed UNOS status 1A or 1B (the highest categories and most at risk if not urgently transplanted). A recent study found that stable LVAD patients had significantly less 30-day risk of events compared to other status 1A patients concluding that allowance of 30 days of elective status 1A time should not be allocated to stable registrants with implanted LVADs [18]. As VAD technology improves, further revisions to the allocation system will need to be recommended.

Figure 3:  Heartmate 3, the latest centrifugal blood pump in comparison to Heartmate II an axial flow pump. Superior event free survival is seen with HM 3.

Figure 4:  Heart-mate 3 vs Heartmate II comparison of event free survival.

INTERMACS Profile and Description and Timescale to MCS

a) “Crashing and burning”—critical cardiogenic shock. Within hours b) “Progressive decline”—inotrope dependence with continuing deterioration. Within a few days c) “Stable but inotrope dependent”—describes clinical stability on mild-to-moderate doses of intravenous inotropes (patients stable on temporary circulatory support without inotropes are within this profile). Within a few weeks d) “Recurrent advanced heart failure”—“recurrent” rather than “refractory” decompensation. Within weeks to months e) “Exertion intolerant”—describes patients who are comfortable at rest but are exercise intolerant. Variable f) “Exertion limited”—describes a patient who is able to do some mild activity but fatigue results within a few minutes of any meaningful physical exertion. Variable g) “Advanced NYHA III”—describes patients who are clinically stable with a reasonable level of comfortable activity, despite history of previous decompensation that is not recent. Not a candidate for MCS

INTERMACS = Interagency Registry for Mechanically Assisted

Circulatory Support; MCS = mechanical circulatory support;

NYHA = New York Heart Association.

Figure 5:  Durability of HM 3 vs HM II, freedom from pump replacement due to pump thrombosis or haemolysis.

Temporary MCS are available that can be implanted quickly and simply to normalise cardiac output in patients with severe acutely decompensated heart failure. The CentriMag [19], Tandem Heart [20], Impella [21] and Circulite [22]. Clinical trials suggest that treatment of temporary VADs does not necessarily correlate with better survival, but merely comprise a component of treatment leading to recovery, upgrade to fully implantable systems as a bridge to transplant or destination therapy, or transplantation [23,24]. Device miniaturisation, without externalized drive-lines connecting the device to a console and longer endurance will be the future trend of mechanical design for long term support. Blood pumps with magnetically levitated rotors has shown satisfactory 1-year survival [25]. The smaller size and weight of the continuousflow devices has allowed an extension of the new VADs into smaller patients. Fully wireless resonant coupling power sources are currently undergoing evaluation, which if successful will greatly reduce the incidence of drive line infections (Figure 5), which is the weakest point of the technology of current fully implantable systems. There is some evidence that fully implantable systems will be available in the near future to greatly improve the quality of life and to reduce the frequency of severe infections with continuous flow LVADS.

Many recent studies have focused on the reversed molecular and cellular alterations, such as improved β-adrenergic responses and decreased calcium-regulating gene expression (Figure 6), in patients using LVAD as a bridge to recovery therapy [26]. Functional recovery has been observed in a subset of heart failure patients [26,27]. Recently, a clinical trial using clenbuterol (β-2 agonist and anabolic agent) and LVAD in refractory non-ischemic heart failure patients, reported recovery of heart function in 60% of patients (n=20) with non-ischemic cardiomyopathy that allows the pump to be explanted (Harefield Recovery Protocol Study for Patients with Refractory Chronic Heart Failure, HARPS) [28]. LVAD therapy is associated with decreased collagen turnover and crosslinking and increased tissue angiotensin II. LVAD combined with angiotensinconverting enzyme inhibition results in decreased tissue angiotensin II and collagen cross-linking, normalizes left ventricular end-diastolic pressure volume relationships and is associated with modestly higher rates of bridge to recovery [29]. Other adjunctive treatments including other medications, cell or gene therapy with over expression of SERCA2a might in conjunction with VAD support provide a meaningful alternative therapy in patients with severe heart disease [30].

Figure 6.  

Conclusion

Heart transplantation is associated with excellent long-term outcomes and is the gold standard solution for intractable end stage heart failure in eligible patients. What limits its impact, overall, is the limited availability of donor organs. The development of ventricular assist devices has mitigated against this, to some extent. Subsequent device iterations with further miniaturisation and continuous flow have resulted in effective bridge to transplant solutions. The presence of an externalized drive line exposes the VAD recipient to infections, however, which may precipitate urgent listing for heart transplant in the bridge to transplant candidate and may limit the life span of the destination therapy candidate. Fully implantable driveline free systems will definitely enhance the utility of these systems in these settings. As our knowledge of molecular medicine increases, manipulation of key proteins implicated in the pathophysiology of heart failure such as SERCA2a may allow some recovery of the myocardium in patients with heart failure to the extent that transplantation may be deferred or the LVAD explanted [31-35].

https://lupinepublishers.com/cardiology-journal/pdf/ACR.MS.ID.000125.pdf

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https://lupinepublishers.com/cardiology-journal/index.php

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