#Clinical case reports

[cryptdfish]

“white mourning.”

[jcsmicasereports]

Obsessive Compulsive Disorder in Palestine: A Literature Review by Israa M.Sawalha in Journal of Clinical Case Reports Medical Images and Health Sciences

Abstract

Methods A computerized literature searches (Google Scholar, PubMed, Science Direct, Springer Link, Elsevier, Semantic Scholar, and HINARI) was used to collect studies addressing the OCD in Palestine.

Results and Conclusion OCD in Palestine is widely presented in adolescence and children at a young age. The most common type of OCD in Palestine is checking type. Set of risk factors increases developing OCD, including sexual abuse at any age as well as anxiety, depression, phobia and somatization disorders. In addition, the family incomes play a big role in presenting OCD, especially low income families. Most of the patients who have OCD were depressed and complaining of stigma and ignorance. Recommendations include getting rid of the stigma, creating a chance for low income families, further studies into OCD in Palestine, ending of the occupation and preventing children from following TV programs and war results.

Key words OCD, Obsessive compulsive disorder, Palestinians Mental Health, Palestine, Gaza Strip, West Bank

Background

In this section the researchers highlighted the meaning of health, mental health and mental illness. Also, they showed the impact of Israeli occupation on Palestinians people since 1948 and lastly in 2019. Besides, the state of mental health services in Palestine. A complete condition of physical, social and mental well-being and not purely disability or disease absence are the definition of the health, according to World Health Organization (WHO)(1). According to American Psychiatric Association (APA) the mental health is the foundation for learning, communication, emotions, thinking, self-esteem and resilience, also, it is the key to personal and emotional well-being, relationships, personal and contributing to the community or society(2). Therefore, the combination of behavioral, emotional or thinking process changes, or involving a change in one of them is called a mental health illness which is common and can be treatable(3). Historically, Palestinians health affected because of the Israeli occupation of Palestine, which was divided into two areas (West Bank and Gaza Strip)(4). Those two areas were occupied by Israel in 1948, related to that about 60 percent of the Palestinians living in villages with 27 percent of them in refugee camps(5). Accordingly, Israel attacks the civilians in their places and they experience infringement of their human rights which impact their health(6). Because of affection on the civilian health, especially the mental health, there is a need to develop mental health services(7). Therefore, in 2004 the mental health policy officially adopted for West Bank and Gaza Strip by Palestinian Ministry of Health (MoH) and in 2002-2003 it was formulated(5). As a result, Palestinians need to meet them human rights and develop the mental health policies and services(8). In summary, the history that the researchers mentioned above about Palestine’s political condition, clearly showed that there are major challenges faced the civilians’ mental health, as well as, their social and economic state.

Methodology

A computerized literature searches (Google Scholar, PubMed, Science Direct, Springer Link, Elsevier, Semantic Scholar, and HINARI) was used to collect studies addressing the OCD in Palestine. Search terms included “obsessive-compulsive disorder,” “obsessive compulsive” “OCD Palestine” “Palestinians mental health” “Health in Palestine” “Mental health Palestine” in both Arabic and English languages. Additional papers, which did not appear clearly in the electronic database while searching, were obtained via an examination of reference lists of published papers. Relevant empirical studies are summarized and presented hither. This study included all studies about OCD in Palestine and excluded the studies talked about anxiety, PTSD, or other disorders. The search identified 33 articles. Duplicates and irrelevant articles were removed. Nine articles related to OCD in a Worldwide, fifteen in Arabic countries and nine articles related to OCD in West Bank and Gaza Strip in Palestine. Also the researcher used some Arabic studies and translated them to English language. Studies selected after critically appraised.

An overview of OCD

In this following section the researchers explained the origin of Obsessive Compulsive Disorder (OCD) by writing its definition and clarified main class of OCD and from where it came. Also, this review showed studies about mental health in a worldwide then Arabic world later in Palestine. Moreover, the following sections focused on OCD in Palestine.

Definition of Obsessive Compulsive Disorder This part of the study focused on the definition of Obsessive Compulsive Disorder as both of the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) defined it. According to ICD-10, the essential feature of OCD is recurrent Obsessional thoughts and Compulsive act(9), but according to DSM-5, OCD is the presence of obsessions, compulsions, or both of them(10). Obsessional thoughts are images, impulses, or ideas that enter the patient's mind repeatedly in a vulgar form. They are almost fixedly distressing and the patient often tries, unsuccessfully, to endure them, this definition according to ICD-10(9). But DSM-5 defined the Obsessional thoughts as an intruder, unwanted and recurrent thoughts or impulses that most patients cause marked anxiety or distress and the patient trials to ignore such thoughts or images by performing a Compulsion(10). Additionally, ICD-10 about Compulsive, an acts or rituals are stereotyped behaviors that are repeated over and over, these acts are not enjoyable, nor do they result in the completion of useful tasks(9). Also, the repetitive behaviors (e.g., hand washing, ordering, checking) or mental acts (e.g., praying, counting, repeating words silently) is aimed at preventing or reducing anxiety or distress, or preventing some dreaded event or situation, this definition according to DSM-5(10). As the researchers mentioned above, the OCD is a mental health disorder associated with a change in behaviors and acts, as well as with thoughts changes.

History of Obsessive Compulsive Disorder

In this part the researchers showed the historical sequence of Obsessive Compulsive Disorder. Al-Balakhi was the first one in the world mentioned a mental illness and he put the differentiation of OCD from other forms of mental illnesses nearly a millennium earlier(11). Historically, as with any mental health condition, over time the conceptualization and treatment of OCD has changed(12). In the centuries sixteenth, seventeenth, eighteenth, nineteenth and the first half of the twentieth century the OCD passed through different conceptualizations. Religious melancholy was in seventeenth century the description of Obsession and Compulsion(13), but they have likely been around since humans first roved the earth(12). OCD was associated with moral and spiritual issue in the seventeenth century. Later, in eighteenth century many doctors saw that the Obsessions and Compulsions were caused by intellectual disordered(12).After this view, in the nineteenth century a modern concepts of OCD began to evolved(14),which is ‘neurosis’ implied a neuropathological condition. In the last quarter of the nineteenth century OCD was engulfed along with numerous other disorders(13). Supplementally, in the twentieth century the OCD became with a new concept. Sigmund Freud (1856-1939) and Pierre Janet (1859-1947) isolated OCD from neurasthenia(14).Freud’s view highlighted that this mental health disorder related to subconscious problems, and he sawed that both of obsessions and compulsions were often treated via psychoanalysis(14). Throughout the first half of the twentieth century Freud’s view dominated the mental health field(13). Finally, the researchers back in the time since the appearance of Obsessive Compulsive Disorder until the new concept were appeared.

OCD in a worldwide

In this section the researchers showed a review of OCD from the worldwide view by showing the prevalence of OCD in a worldwide, also the effect of it on the patient’s life, as well as its types and the prevalence of each one. Later the researchers showed risk factors. In the world, at some points in peoples’ lives, they have obsessive thoughts with or without compulsive behaviors, but that does not mean that all of them suffer from Obsessive Compulsive Disorder(15). Approximately 2% is the prevalence of in the general population in a worldwide(16). During the past year, OCD in the U.S affected 1.2% of adults. But now it affects approximately 1 in 40 adults and 1 in 100 children in the U.S. According to the National Institute of Mental Health (NIMH)(17). In Australia around 2% of people have OCD(18). But in the UK population, OCD affects about 12 in every 1,000 people (1.2% of the population) from young children to adults, regardless of social, cultural background or gender(19). In China the prevalence of OCD is 3.17%, according to a study done by Guo et al., its title is “Meta-analysis of the prevalence of anxiety disorders in mainland China from 2000 to 2015”(20). In this condition the patient has an obsessive need to repeatedly do certain things and may have unwanted ideas, impulses or images(21). People with OCD are usually aware that their symptoms are illogical and excessive, but they find the obsessions ungovernable and the compulsions unattainable to resist(18). There are many forms of OCD, Checking, Contamination/Mental Contamination, Symmetry and ordering, Ruminations/Intrusive thoughts and Hording(22). About the prevalence of each type the checking obsessive has the highest prevalence which is 79.3%, the second high prevalence is Hoarding obsessive which has 62.3%, later Ordering 3%, Morality 5%, Sexual/Religious 2%, Contamination/Washing 3%, Harming/Aggression 5% and Illness ratios 8% to 10% (23). A study done by J. Henderson and C. Pollard in greater ST. Louis showed that the overall prevalence rate of OCD was 2.8%. The most prevalent type of Obsessive Compulsive Disorder involved checking (1.6%), followed by a multiple category that included counting, repeating and collecting rituals (1.0%) and, finally, washing compulsions (0.8%)(24) According to National Comorbidity Survey Replication (NCS-R), many people with Obsessive Compulsive Disorder have more than one OCD form(23). The risk factors which may increase the incidence of getting an OCD are divided into three ranks, factors that the person born with, factors outside human control and modifiable risk factors(25). Factors person born with like genetics 50%, gender male at more risk to develop childhood OCD than female, brain structure and socioeconomic status as a study showed that there is an association between OCD and low socioeconomic status(25). But about the factors outside human control are included age life events and mental illness. The risk of OCD drops with age and the late adolescence has the greater risk(25). Those who have stressful life and suffer from physical or sexual abuse are a major risk factor to get OCD, also having another mental illness such as anxiety or depression increase the risk of having OCD (26). According to Owen and Adrian, the third rank is the modifiable risk factors such as drugs, marital status and employment. Drug uses cans causing a neurotransmitter changes in the brain, which create a chance for developing OCD, and being unmarried increase the risk too as well as being unemployed. However, there are many risk factors may increase the incidence to develop an OCD. OCD at higher risk to present comorbid major depression or another anxiety disorder across all areas(27). Peoples suffering from OCD also end up suffering from a lack of self-esteem and self-confidence, relationship problems, very weak willpower, and social withdrawal(28).

OCD in the Arabic countries

In this section the researchers showed a review about OCD in Arabic countries. From one hand, they pointed out that the first one highlighted the OCD was an Arabian psychiatrist and he wrote about it since 1000 years ago. And from other hand, they reviewed different studies about OCD prevalence, Islamic view, culture view and stigma in the Arabic world. Statistics mentioned that the frequency of most mental disorders does not have much difference from country to country around the world(32). The prevalence of OCD in Egyptian adolescent population is 2.2%(33). Also, 0.1 % in Lebanon(34). In Iraq, the peak age for OCD was from 21 to 30 years old, females were predominating (63.2%), singles were (47.3%) and the family history of OCD and any mental illness was observed in 20.5% and 52.9%, respectively(35). The few statistics coming out of certain Arab countries assert the reality of having no difference from country to country in the frequency of mental disorders specially OCD(32). The issue in the Arab world is more to do with stigma and ignorance than it is lack of mental health problems(32). Despite the complication and the importance of the mental health problems, the Arab world still shows a lack of awareness; patients in Arab countries tend to express their psychological issues in terms of physical symptoms, thereby avoiding the stigma attached to mental illness(36). A study done by Mohamed et al., 2015 in Egypt showed the following result: “Religious patients receiving religious psychotherapy showed significantly more rapid improvement and required lower dosage of medications and for periods less than others. The role of religion as CBT could be significant in the Islamic culture.”(37). Recently, the relationship between mental health, religiosity, and personal beliefs (Such as magical ideation) has been studied Psychiatry is depending on culture more than any other medical discipline, therefore, it is not well known in developing countries the frequency of mental illness such as anxiety, OCD or depression, even doctors themselves may not know the problem size, on the contrary of the developed countries which are well characterized in determining mental diseases(32).

An overview of OCD in Palestine

In this section the researchers showed a review of OCD in Palestine. They mentioned the prevalence of OCD in Palestine, and showed the all available studies about OCD. A 15.3% is the prevalence of Obsessive Compulsive Disorder among Palestinian university students in Gaza Strip, in assessing OCD and sociodemographic variables such as family income and type of college, study showed that the OCD is more in students coming from families earning 250$ and leases more than students from families earning 500-750$ and there is no statistical significant in OCD and type of college. In addition to that, this study showed there is no statistically significant correlation between OCD and age and grade average of the students. Also, this study clarifies that the OCD correlate with anxiety (R=0.63), with depression (R=0.66, P=0.001), with Phobic anxiety (R=0.44) and with Somatization (R=0.51). However, in assessing the OCD statue with sex, the T independent test according to the same study showed statistically significant in female than in male (Mean 15.39 vs. 15.20) (T= -50)(39). Additionally, a descriptive study done by Amira Abu Shaban in Jerusalem zone by using self-reported questionnaire and the Yale-Brown Obsessive Compulsive Scale (CY-BOCS) among Palestinian school children grade 11 (public and private), this study showed that the prevalence of OCD among Palestinian school students is 15.6%: 19.1 for females and 10.2 for males. Also, the study showed significant associations among OCD and females, students with low academic level, school achievements and less educated parents. Moreover, this study showed a strong relationship between OCD and social-demographic variables and a weak relationship with social environmental factors(40). 20.6%, according to Spence anxiety scale reported Obsessive Compulsive Disorder problems among children working due to low family income. This study, which was done by Mater et al (2007), aimed to identify the impact of work on children general mental health and anxiety in a total number of 789 children in the Gaza Strip. Also, it showed that 79.2% of children rating themselves as a psychiatric patient(42). The study sample included 99 women and their ages ranged between 16 years to 42 years with mean age 25.5. In this study pre and post assessment for women who got counseling and vocational training. Accordingly, the study showed that there was improvement in Obsessive Compulsive Disorder for the women(45). In the summary for the OCD in Palestine, the OCD is higher in women than men, in adolescent and children than older ages. The risk factors that increase the OCD separation between Palestinians are low income families, stigma, and Israeli occupation, and violence, sexual abuse of the children, depression disorder and anxiety disorder.

Discussion

In this section the researchers discussed the reviewed studies about OCD worldwide, in Arabic countries, and in Palestine by showing the differences in prevalence, stigma, and risk factors.

Prevalence

The studies showed that the prevalence of OCD in a worldwide is 2%-3% (16) Convergent to the prevalence in Arabic countries 2.2% (32), but there is no general prevalence of OCD in Palestine because of lack in studies. But some studies showed 15.3% the prevalence of Obsessive Compulsive Disorder among Palestinian university students in Gaza Strip (16, 32). Checking Obsessive is the most common type in the world, 79.3% of the OCD patients are checking obsessively and 62.3% suffer from Hording Obsessive (23). The studies in Arabic countries also support this prevalence of checking obsessive 1.6%, then hording then contamination obsessions (23, 22), after that the contamination obsessions in Arabic countries and in Palestine (22, 34).

Stigma

The issue in the Arab world is more to do with stigma and ignorance than it is lack of mental health problems and the stigma attached to the illness (34, 35). Also the Palestinians studies showed that the patients suffer from community view to them and their mental health (38). The Arab world still shows a lack of awareness; patients in Arab countries tend to express their psychological issues in terms of physical symptoms, thereby avoiding the stigma attached to mental illness (36).

The risk factors

The risk factor which may increase the incidence of getting an OCD are divided into three ranks, factors that the person born with, factors outside human control and modifiable risk factors (26). The genetic factor prevalence is 50% and the male more than female in childhood (25, 28) in the world view, but in comparison with Arabic countries view the risk factors were in female more than in male in ages between 21 to 30 years old (34, 31) . Finally, in Palestine the low family income earning 250$ and less were the basis for having an OCD among Palestinians, also the studies in Palestine showed that the female more than male with mean age 15.39 for female Verses 15.20 for male(38, 31). In addition to the OCD risk factor in Palestine the sexual abuse at any age play a major role in having OCD as well as Anxiety, depression, Phobic anxiety and Somatization disorders (31, 38, 40, 44).

Definition

They are almost fixedly distressing and the patient often tries, unsuccessfully, to endure them while DSM-5 defined the Obsessional thoughts as an intruder, unwanted and recurrent thoughts or impulses that most patients cause marked anxiety or distress and the patient trials to ignore such thoughts or images by performing a Compulsion (15).

Results and Conclusion

In this section, the researchers conclude the results of this review. According to the studies that the researchers reviewed and discussed above, they found that there is a difference between the prevalence of OCD in Palestine in comparing with Arabic countries as well as with a worldwide. Also, they discovered that there is a lack of studies about OCD in Palestine especially in West Bank. The most common type of OCD in Palestine is checking type; in addition to that, OCD patients suffer from the stigma so the prevalence of it was significantly high related to fear from the community. However, there is a religious view about OCD as well as cultural view. Palestinians because of Israel occupation faced a lot of barriers standing in front of their mental health status. OCD in Palestine is widely presented in adolescence and children at a young age. The family incomes play a big role in present of OCD, especially low income families as well as a stigma. In concluding, Palestinians with OCD have a related disorder, the most common one is depressed. Also the researchers found that there was a lack in studies about OCD in Palestine and other mental health disorders, and they discovered that there is a study in specific areas of Palestine such as Gaza Strip

Recommendations

Recommendations include get rid of the stigma and create a work chances for a low income family, apply more and more studies about OCD in Palestine, ending of the occupation and prevent the children from following TV programs and war.

Limitations

The literature review has discussed an Obsessive Compulsive Disorder in Palestine. Palestine is a state that is seeking independence with a scare of resources; therefore, the research is underdeveloped. As a result, there is a lack of detailed data regarding Obsessive Compulsive Disorder in Palestine. Due to lack the complete data, all literature that was found, including a thesis study done in Al-Quds Open University about the OCD among school students in 11 grade was included.

Acknowledgments

Special thanks to all authors in the field of mental health in Palestine who equipped us with the relevant information for this literature.

This case represents an unusual example of extrinsic esophageal compression due to lymphoma1,2 leading to severe pill- induced esophagitis3.

[myrawjcsmicasereports]

 Movement is life proper movement is active longevity by Gusyev Valentyn in Journal of Clinical Case Reports Medical Images and Health Sciences

The increase in human life expectancy is usually attributed to the achievements of medicine. At the same time, it is not mentioned that Peter 1 fought with 300-year-old elders, that age in those days was measured in circles at 145 years. Gerontology even today says that the resource of the heart is determined by 300 years, and the liver by 600 years. Medicine is also silent about the fact that in the part by which life expectancy has increased, most people are no longer able to work, they cannot move independently. But it is precisely the movement, the work of the venous-muscular pumps of the legs that maintains blood circulation in the system of small and large blood circulation in the human body. Our alleged monkey ancestors do not have such a pump. Their life expectancy is limited to only tens of years. They can't even think like humans. After all, brain cells develop from muscles tired during the day, 80% of which are leg muscles. The activity of people in recent years has decreased by 200 times. Previously, a rural worker walked 17 kilometers a day, but today it is less than a kilometer. It is obvious that the mental abilities of people who lived in previous centuries were higher. Modern scientists cannot explain how people used to build pyramids, underground cities, process stone, create statues and flying machines. Today we have come to a situation where people, like robots, are taught to perform only certain actions. The doctor sells drugs and does not suspect that diseases arise due to poor nutrition and the removal of cell decay products. What are the skeletal muscles responsible for these processes, the work of which is limited by improperly made shoes, leading to deformations in the system of the most powerful leg pumps. These are the gastrocnemius and soleus muscles, which reduce their activity with improper walking. Stores sell over 90% of improperly made shoes. The fulcrum in which the position of the thumb does not correspond to the reference points of the skeleton (1-2-3).

But medicine does not pay attention to this, because it is engaged in business. In the first place in terms of mortality are violations of arterial blood flow. This is ischemia of the heart, lower extremities and the naked brain. But no one sees that the cause is a violation of the outflow of venous blood - the biomechanics of walking. Violation of the sequence of muscle contraction also leads to overload of the central nervous system, which began to be noted as chronic fatigue syndrome.

The process of walking upright, maintaining a stable position of the body is carried out according to the addition of inherent, unconditioned reflexes independent of our desires. Therefore, a violation of walking in the case of deformities of the feet leads to a change in the position of the bones in all the higher lying joints of the skeleton and a violation of the contractile pumping function of the muscles. The body perceives changes in walking for a dance, which leads to overloads of the Central Nervous System. You just stood on your heel, and the signal from the mechanoreceptors under your fingers says you are already pushing, jumping.

All the knowledge of the world cannot make a person a doctor of a self-regulating organism. Therefore, not to treat, but to restore the pumping function of the musculoskeletal frame of the body should be the primary task of the body's therapy. But how can a specialist of a narrow profile understand this, who was taught the wrong way and for whom everything new is incomprehensible and frightening.

[jcmcri]

Journal of Clinical & Medical Case Reports, Images (JCMCRI)

Welcome to the Journal of Clinical & Medical Case Reports, Images (JCMCRI) where innovation meets exploration in the realm of peer-reviewed open access publishing. Our journal serves as a dynamic platform for showcasing ground-breaking research across various formats including Case Reports, Clinical Images, Case Studies, Short Communications, Commentaries, Technical Notes, Review Opinions, and Brief Notes. Spanning a broad spectrum of Scientific, Clinical, and Medical Sciences, we pride ourselves on fostering a diverse array of scholarly contributions.

At the heart of our mission are Case Reports, the cornerstone of medical literature. These meticulously documented single clinical observations embody a venerable tradition in scientific discourse. They serve as invaluable reservoirs of uncommon insights, often catalysing new avenues of research and innovation in clinical and medical practice. Additionally, Case Studies offer illuminating glimpses into the decision-making process, empowering fellow physicians with the tools of lateral thinking to navigate their own clinical challenges. Particularly in the context of rare diseases, these studies assume paramount significance, enriching our collective understanding of complex medical phenomena.

Our commitment extends to nurturing a collaborative environment that transcends geographical boundaries. We actively encourage clinical and medical professionals, scientists, doctors, professors, and academicians to contribute their latest findings and emerging insights. By providing a dedicated platform for the dissemination of unique, unusual, and rare cases, we aspire to elevate the discourse surrounding disease processes, diagnostics, and management on a global scale.

Join us in our quest to illuminate the frontiers of medical knowledge and make a lasting impact on the landscape of clinical and medical sciences worldwide.

Submit your research here: https://jcmcrimages.org/submit-manuscript/

For more information, regarding our Journal please visit: https://jcmcrimages.org/journal-aims-and-scope/

[cockatude]

According to the report only two of the pregnancy related reports are specifically unplanned pregnancy.

Another doctor also suggests it could be the result of ozempic fixing issues with womens fertility.

Ozempic and its siblings can make contraceptive meds less effective, on top of everything else

[drsauravarora]

Enhancing Homeopathy Through Quality Case Reports: Insights from Dr. Saurav Arora's Webinar

Recently, Dr. Saurav Arora, an internationally acclaimed medical homeopath, conducted a webinar titled “The Art of Writing Scientific Cases in Homeopathy“. This enlightening session, available on this channel, delved into the critical need for high-quality, evidence-based case reports in homeopathy. (Link – https://youtu.be/399HlkzIGAo ) ##The Importance of Good Case Reports There is a…

[barnesonly]

Obsession

possessive!bucky barnes x reader

summary: You don’t even really like Bucky Barnes — he’s grumpy, kinda mean, and totally clueless about how you feel. But damn, he’s so hot it’s driving you crazy. Every time he walks in, all you can think about is what it’d be like if he just took you right there. You try to play it cool… but yeah, that’s not happening.

word count: 6021

WARNINGS: 18+ explicit content, MDNI. curse words, masturbation, dirty talk, degrading, praising, desperation, fingering, teasing, PiV, unprotected sex, rough sex and he talks through it, breeding, overstimulation, oral (m receiving), possessive behavior.

A/N: i’m horny, okay?…

You don’t have a crush on Bucky Barnes.

That would imply affection. Admiration. Maybe even a little emotional investment.

You don’t have any of that.

What you do have is a deeply inconvenient, soul-destroying case of lust. A constant, throbbing ache between your legs every time he walks past. A full-body reaction to the way he stretches, or leans on the counter, or wears those fucking grey sweatpants like a goddamn weapon.

It’s chemical. It’s hormonal. It’s not personal.

Because Bucky Barnes is grumpy. Bucky Barnes is quiet. And Bucky Barnes has absolutely no idea that he’s the reason you can’t go three days without needing to fuck yourself stupid.

Like right now.

He’s just standing there in the kitchen, back to you, broad shoulders stretching that worn black Henley like it’s a second skin. His hair’s short now, freshly trimmed at the nape, the kind of cut that shows off the sharp line of his jaw, the back of his neck.

You’re staring. Again.

You don’t mean to. But he makes a little grunt when he stretches — just a tired noise, nothing sexual — and you nearly whimper like a kicked dog. Instinct. Pavlovian response.

And he doesn’t notice. Not even a flicker of awareness as he pours his coffee and walks out, oblivious, muttering something about the mission report.

You just stand there, holding a spoon, clenched thighs and flushed cheeks like you’ve just been fucked by the idea of him.

It’s getting worse.

Like, medically worse.

You’ve gone from horny to feral to clinically unwell, and it’s all because of one man.

One grumpy, emotionally constipated, vein-poppingly hot man who can’t say a sentence without sounding mildly irritated. Who barely even looks at you unless you’re in the way. Who definitely doesn’t like you — and yet somehow owns your nervous system like a fucking landlord.

And it’s not fair.

Because he’s not even nice to you.

He’s short with you in meetings. Scoffs when you crack jokes. Gives you that look when you say something mildly reckless on a mission — like you’re exhausting. Like you’re annoying.

But then he’ll do something that ruins you completely. Like grunt your name low and gravelly when tossing you your gear. Or casually push you out of the line of fire with one big, rough hand and say, “Watch it, sweetheart,” like you’re some dainty little thing.

You pace your room that night, ranting to no one.

“I don’t even like him,” you mutter, folding laundry with violent purpose. “He’s so rude. He never smiles. Doesn’t talk to anyone unless he has to.”

Your shirt gets yanked onto a hanger too hard. You nearly snap it.

“And he doesn’t even like me. Not even a little. I’m just some girl who laughs too loud and gets in his way and—oh my god, I would let him ruin me.”

That’s probably the most honest thing you said all week. You’d let him manhandle you. Throw you over his shoulder. Rail you into the mattress like a war crime. That arm? The metal one? You’ve thought about it. God, you’ve thought about it so much it’s starting to feel like a sin.

You can’t help it.

You collapse onto your bed, still in your T-shirt and underwear, legs kicking uselessly against the sheets. Your body is hot — too hot. Your skin prickles, stomach twisting tight with the sheer need of it.

You shouldn’t do it.

But fuck it — you do.

Your hand slips beneath the waistband of your panties like second nature, no hesitation. You’re already soaked — of course you are. One fucking grunt from Bucky in the kitchen and you’ve been like this all day, wound tight and throbbing.

Your fingers slide through the slick heat of your folds, and your hips twitch. You let out a soft, breathless whimper, biting your lip like it’ll help.

It doesn’t.

He’s all you can think about.

Bucky, with that low rasp of a voice. Bucky, sweat-slicked and panting, muscles straining above you. Bucky, staring down at you like you’re a mess he likes making.

You rub lazy circles around your clit, teasing yourself, letting it build slow. Letting the images crawl behind your eyes:

His hands gripping your thighs, spreading them open.

That cold metal arm wrapped around your throat, holding you in place while he pounds into you, relentless and filthy.

His voice in your ear, rough and possessive —“You been thinkin’ about this, sweetheart? Been touching yourself like a needy little thing?”

Your fingers move faster.

You arch into the mattress, breath stuttering, hips chasing the pressure. Your other hand slides up under your shirt, finds your breast and squeezes hard, tugging at your nipple.

“Fuck,” you whisper, squirming, already so close it’s pathetic.

You imagine his hand — that hand — between your legs. Imagine him shoving your panties to the side with those cool, precise fingers and just… watching you squirm. Watching you come undone with that unreadable expression of his, like he’s filing it away for later.

You imagine him making you come like this. Telling you you’re not allowed to stop. That you’re gonna do it again, and again, until you’re crying.

Your thighs start to shake.

You gasp, pressing harder, grinding down. Your toes curl, muscles tensing, pleasure tearing through you like lightning — sharp, wet, overwhelming.

You come hard, moaning into your pillow, breathless and ruined, hand still trembling between your thighs.

And then?

You lie there. Sticky. Hot. Unsatisfied.

Because no matter how many times you make yourself come, it’s never enough.

Not when it’s him you want.

Not when it’s Bucky fucking Barnes.

———

You’re minding your business. Truly. Peacefully. Drinking your stupid little smoothie, scrolling through intel reports on your tablet, trying so hard not to think about last night and the shame spiral that followed.

You’re in the common room, feet tucked under you, hair up, living a clean and quiet life.

The front door hisses open. Voices filter in—Sam laughing, Nat muttering something dry, Steve’s boots heavy on the floor.

And him.

Bucky.

You don’t look up at first. You don’t need to. You can feel him. Like some sixth sense activated just by his presence, like the air itself is different when he walks into it.

But then you do look up and you regret it immediately.

He’s just back from the field. Tactical gear still clinging to him, black shirt soaked through with sweat in that way that makes it stick to every hard line of muscle underneath. The sleeves are tight around his biceps—dangerously tight—making it look like the fabric’s seconds from giving out under the strain of his arms.

His hair’s damp, just messy enough to be criminal, a few strands sticking to his forehead. Dog tags resting against his chest. Black cargo pants slung low on his hips, clinging to his thighs like they were custom-made by someone with your exact problem.

He’s flushed from exertion, a little dirty, jaw tight like he’s still coming down from combat.

And he doesn’t notice you. He just walks past, arm flexing as he drags his glove off with his teeth.

You actually—physically—have to grip the edge of the couch.

You squeeze your thighs together so tight your eyes almost roll back. Your smoothie is sweating in your hand, condensation dripping onto your leg, and it’s the least of your problems right now.

Because that man?

That man could rail you into next week with the anger he carries in his shoulders alone. You’d let him wreck you in the debriefing room, up against the wall, still wearing that gear and not saying a word.

You’d tear those tactical pants off with your teeth.

And he just keeps walking. Oblivious. Like he’s not singlehandedly dragging you through the gates of horny hell.

“God,” you mutter under your breath, heart hammering. “You’re gonna kill me.”

He pauses for half a second like he might’ve heard you. Glances over his shoulder—just once.

And then he’s gone, down the hall.

You stare at the door for a long time, smoothie forgotten, thighs still clenched like your life depends on it.

You need help. You need prayer. Exorcism. A cold shower.

Or maybe you just need him to ruin your entire existence.

You barely make it back to your room.

Your legs are shaking. Your mind’s a blur. All you can see is him—sweaty, panting, muscles strained beneath that black t-shirt. His arm flexing, the curve of his jaw, those goddamn tactical pants hugging every inch of thigh like a threat.

You lock the door behind you with trembling fingers.

You don’t even bother taking your clothes off properly—just shove your hand down your shorts as you collapse back onto your bed, legs spread, head spinning.

He looked so good.

Your fingers slide through your folds, already wet, your body acting like it’s been starving for him. Like it’s been waiting all day, all year, for a glimpse of that man so it can break down on command.

You rub your clit in tight, needy circles, moaning quietly.

Your eyes flutter shut.

You picture him over you, sweaty and still in gear, that black shirt pushed up just enough to show the cut of his stomach. You imagine his voice, low and rough, right next to your ear—“Couldn’t even wait, huh? Needed me that bad?”

Your hips buck, thighs shaking, pleasure building fast and desperate.

“Fuck—Bucky,” you gasp, breath catching.

You don’t hear the quiet footfalls in the hall.

Don’t hear the door next to yours click shut.

Don’t know he’s just gotten back to his room.

But he hears you.

Bucky stops with one boot halfway unlaced.

He frowns—still half in mission mode—until he hears it again: a faint whimper through the wall. A soft gasp. Then��his name. Muffled. Almost whispered.

His blood goes still.

He steps closer to the wall, heart suddenly pounding, every nerve pulled tight.

Another moan. Higher this time. Desperate.

He can hear the rhythm now—quiet, wet sounds, a bed creaking slightly with every movement. You’re touching yourself. Saying his name. Whimpering like it’s been torturing you.

His mouth goes dry. Something low in his stomach twists.

He shouldn’t listen.

But he doesn’t move. Doesn’t even breathe.

You don’t know he’s there—don’t know you’ve already ruined him. That he’s standing on the other side of the wall, jaw clenched, cock straining against his pants, while you moan into your pillow and come with his name on your lips.

———

The next day, you tell yourself you’re fine.

You look fine. You act fine. You sit in the common area with your laptop open and a mug in your hands like a picture of peace. The night before? Never happened. The hand between your thighs? The breathy moans into your pillow? The orgasm that left you limp and half-ashamed?

A delusion. A private, pathetic delusion.

Until he walks in.

And your entire body remembers.

Bucky enters like it’s nothing. Like he’s nothing. Joggers low on his hips, black T-shirt riding up in the back, hair damp from a shower and curling just slightly around his ears.

You look up instinctively.

And he looks right at you.

Your breath catches. Your stomach drops. He holds your gaze for half a second—half a second too long—then nods, casual as ever, and heads to the kitchen.

No hello. No smirk. Nothing to suggest he heard the way you moaned his name with your fingers stuffed between your thighs like you were starving for him.

He doesn’t say a word.

You try to refocus, try to look at your screen and breathe, but your eyes keep flicking back.

He’s moving around the kitchen now, calm, quiet, efficient. Forearms flexing with every movement. The joggers cling when he crouches to grab something from a low cabinet, and your mouth actually goes dry.

Your thighs squeeze together.

He knows.

He has to know.

But he’s pretending like he doesn’t, and it’s driving you fucking insane.

You don’t even want to like him. He’s grumpy and rude and dismissive. He doesn’t flirt. He barely talks. He exists like a thundercloud with muscles and you still want to cry from how badly you want him.

And now he knows.

Now you’ve moaned his name with a hand between your legs, and he’s seen you since and said nothing.

You want to crawl into the floor.

You want to jump him.

You want him to ruin you until you can’t even say your own name.

He walks past you again with a cup of coffee, eyes flicking toward you—slow, heavy, unreadable.

And this time?

You swear there’s a hint of a smirk.

He leans against the counter, sipping his coffee, that black mug dwarfing in his gloved hand. The steam curls around his face, catching the light, and he’s just staring at nothing—completely unreadable.

Until he speaks. “Sleep okay last night?”

You freeze. Your heart flatlines. Then kicks into overdrive.

You glance up too fast, trying to act casual, but your grip on the mug betrays you—tight, white-knuckled.

“Yeah,” you say, blinking. “Why?”

Bucky shrugs. Sips again. His face is all calm, cold stillness. Like he’s discussing the weather. Not like he heard you moaning his name behind the paper-thin wall like your soul was leaving your body.

“Nothing,” he says, low and even.

You swallow hard. Try to hide the heat crawling up your neck.

You stare at him. Waiting for something. A look. A smirk. A single flicker of anything.

But he gives you nothing.

Just turns back toward the hallway, casual as ever, coffee in hand, like he didn’t just dangle a loaded gun over your head and walk away.

And as he disappears down the hall, your thighs press together again.

You’re so fucked.

———

You try to sleep.

You really, really do.

You toss. You turn. You fluff your pillow. You kick the blankets off and pull them back up. You stare at the ceiling and beg your brain to stop replaying the way he looked in that shirt. The way his voice dropped when he asked about your night. The nothing he gave you like a damn grenade and walked away.

It doesn’t stop.

It won’t stop.

You squeeze your thighs together for the fifth time in twenty minutes, but it only makes it worse. Your whole body’s aching—burning. Tight with the need that’s been building for the entire day.

You glance at the door. You know you should get up and lock it.

But you don’t. Because you’re tired. And turned on. And pathetic.

“Fuck it,” you whisper, dragging your hand under the sheets. “I’ll be quiet.”

You bite your lip as your fingers slide down, already warm, already soaked. You work slow at first, trying to stay silent—just enough to relieve the pressure. Just enough to breathe again.

But then your mind starts drifting.

To him.

Always him.

Bucky in the gym, sweat-slick and scowling. Bucky walking past you post-mission like a walking sin. Bucky pressing you into your mattress with that big metal hand wrapped around your throat, voice rough in your ear—“You’re so fucking loud for me, baby.”

You gasp. Then whimper. Soft. Barely audible.

But he hears it.

He’s in his room again. Reading. Trying to pretend like he didn’t spend all day imagining the look on your face when he asked about your sleep. Trying not to picture your hand between your thighs again.

And then he hears you.

Again.

A muffled moan, breathless and aching, like it’s being pulled out of you against your will.

He stands without thinking.

Crosses the hall with quiet, deliberate steps. His pulse is steady, but something low is stirring—something primal. Something possessive. The kind of heat that doesn’t burn—it consumes.

He stops outside your door.

Closed. Not locked.

He doesn’t even knock.

The handle turns with the softest click, and then—

He steps inside. The door shuts behind him with a quiet snick.

You don’t hear it.

You’re on your back, one knee bent, your hand buried under the hem of your shorts. Your head is tipped back against the pillow, mouth open in these soft, gasping little whimpers as you chase the edge, hips twitching, breath fogging in the dim light.

You have no idea he’s there.

Not until you hear him speak.

“Didn’t I just ask if you slept okay?” The voice—his voice—cracks through the quiet like a whip.

You bolt upright.

Everything inside you lurches, heart ramming against your ribs, a violent rush of heat and panic rising through your chest like you’ve been caught in a fire. Your hand yanks back from your shorts like it’s been scorched, and you scramble to pull the blanket up, dragging it over your thighs as your breath shatters.

Your eyes fly to the source of the voice.

And there he is. Leaning against the door like he’s got all the time in the world. Arms crossed. One brow slightly raised.

His expression is unreadable—casual, maybe—but there’s a flicker in his eyes. Something dark. Something hungry. Like he’s taking inventory of every inch of you in one glance.

You can’t move. Can’t think.

Your heart’s thudding like a drumline, and your cheeks go hot, burning as your stomach flips over itself in full-blown horror.

You can still feel your arousal—sticky, heat pressed between your thighs, your pulse fluttering in places he’s not even touched.

“Bucky—” you croak, throat tight. “I—what are you doing—how—”

“The door wasn’t locked,” he says flatly.

Matter-of-fact. Like that explains everything.

And it kind of does.

You just sit there, still clutching the blanket to your chest like it can undo what he saw. As if it can erase the sound of you moaning into your pillow while your fingers worked yourself over to the thought of him.

He doesn’t smirk. Doesn’t leer.

He just watches.

Like he’s curious. Patient. Like he’s giving you a chance to dig your own grave or shut up and let him lower you into it.

You look at him and it hits you how big he is. Broad and solid, filling the doorway like a wall. The black t-shirt is stretched across his shoulders, tucked into his pants just enough to show the lines of his waist, and that goddamn metal hand is flexing at his side like it’s already made its decision.

And still… he doesn’t leave.

Your voice breaks trying to fill the silence. “I didn’t mean— I thought I was quiet— I didn’t know—”

“I heard everything.”

That shuts you up.

His voice is calm. But it’s not soft. Not gentle. It sinks into your gut like a stone, and your thighs squeeze together before you can stop yourself—before your body betrays you again.

You look away. You can’t look at him. Not when you’re like this—hair messy, skin flushed, caught in the act like a filthy little secret with your want written all over your sheets.

He moves. Not quickly. Not harshly. Just decisively. Like this is inevitable. Like he knew the moment he opened that door that he wasn’t going to leave until you were ruined.

He crosses the room in two slow steps. Sits on the edge of your bed, right next to you. His thigh brushes yours, warm and solid, and your breath hitches—your entire body tensing as his presence crowds the air.

Then his hand—the metal one—reaches out.

He takes your wrist. Your fingers are still damp. Still twitching from where they were buried between your thighs. He stares at them for a second, then meets your eyes.

“Touch yourself.”

You blink. “What—”

“I said touch yourself,” he repeats, a little lower this time. “Show me.”

Your heart slams. His grip stays locked around your wrist, not forcing—but not letting go either. He doesn’t need to threaten. Doesn’t need to beg.

He’s already heard you fall apart for him.

Now he wants the show.

And fuck—your body obeys before your brain can stop it.

You shift beneath the covers, breath shaking, eyes wide as your hand slides back down, slipping under the waistband of your shorts.

Your skin’s hot. Everything throbs and you’re soaked.

Shame prickles in your chest, but it’s drowned by the way he watches—focused and still, his hand still gripping yours like he owns it.

You let your fingers find that spot again, slick and swollen, and you shudder.

“Fuck,” you whisper, breath catching.

His voice cuts through it. Soft. Direct. “You’ve been touching yourself thinking about me?”

You nod, cheeks burning.

“And now you can’t stop, can you?” he murmurs. “Poor thing. You want me this much, baby?”

You let out a tiny, broken sound—something between a gasp and a whimper—and press harder.

His metal thumb strokes over the inside of your wrist, slow and thoughtful, like he’s testing your pulse. You’re so wet your fingers glide without resistance, your hips moving on their own.

“Messy little thing,” he mutters. “God, you’re desperate. Didn’t even lock the door.”

His flesh hand moves too now—reaching up to push your hair from your face, tilting your chin toward him.

“You wanted to get caught, didn’t you?”

You shake your head, but your body betrays you—back arching, thighs tensing, rhythm faltering as your orgasm creeps up again, fast, tighter than before.

He sees it. Feels it. And he knows.

“You gonna come for me?” he whispers. “Right here, baby? With my hand around yours and your pussy soaking your sheets?”

You sob his name and he finally leans in—breath warm against your cheek.

“Good girl.”

Your fingers slip again—rhythm stuttering, body caught in that maddening edge.

He watches you falter. Watches your mouth fall open, brows pull together, your thighs start to shake with the pressure of holding yourself there. So close. Too close.

And that’s when he moves. His grip on your wrist tightens just enough to make you freeze.

“Let go,” he says.

You whimper. “But—”

“I said let go.” His voice leaves no room for argument.

You obey. Your hand slips from your shorts, fingers slick and trembling, and your chest rises in short, desperate breaths as he shifts closer.

“Bucky—” you gasp.

But he’s already there. His fingers slide between your folds—just one, at first, cool and unreal, brushing over your clit in a slow, torturous circle. Your hips jerk like you’ve been shocked.

“God,” you moan, clinging to the sheets, “fuck—”

“So sensitive,” he murmurs.

His eyes are locked on your face, hungry, focused—like he’s memorizing the way your mouth falls open for him, the way your lashes flutter when he presses a little harder.

You can’t stop the sounds you make.

You’re already too close—too much—your body wired tight from teasing yourself for nights and thinking of him, only him.

One metal finger dips lower—in now, slick and slow—and your breath punches from your chest.

Your hips grind into it, chasing it like you’re starving.

He fucks you with it slow at first. Deep. Deliberate. Watching you unravel inch by inch.

“You’ve been dreaming about this?” he says, voice like gravel. “Getting off to the thought of my hands on you?”

You nod helplessly, fingers clenching around the sheets.

Another finger slides in.

Your body wails for it—so full, so good, the metal stretching you just right—and your thighs tremble, back arching as your orgasm builds so fast it almost hurts.

“Then come for me,” he growls. “Right now. I want to feel how tight you get when you finish.”

You choke on a cry.

And then you fall apart.

Hard.

Your walls clamp down around his fingers, body convulsing as the wave hits you—sharp and electric—shaking through your entire frame with a loud, wrecked moan that echoes in your room.

His hand doesn’t stop. He fucks you through it—slower now, drawing it out, holding your body steady with his free hand while you tremble and sob and drip around him.

You don’t know how long it lasts. You just know you’ve never come like that before.

Not in your life.

Not until him.

You’re still gasping, thighs twitching, brain static from how hard you just came—but he’s not done with you. Not even close.

His fingers slip from you slow, drenched, and he brings them up to his mouth, sucking them clean without taking his eyes off you.

Then?

He smirks.

That low, dangerous smirk you’ve only ever imagined. Dreamed about. Touched yourself to. And now it’s real.

“You’ve been thinking about me so much,” he says, voice thick with heat, “I bet you want to feel my cock, huh?”

You don’t even answer. Can’t. Your mouth opens but nothing comes out but a broken moan.

He laughs. Dark. Rough. “You fucking slut.”

He stands. Hands go to the waistband of his pants.

Your breath catches, watching.

He doesn’t rush. He doesn’t need to.

The black tactical pants slide down slow over those solid thighs, revealing the outline of what’s beneath—thick, heavy, hard. You feel your whole body clench at the sight.

He steps out of them, shirt already discarded somewhere between your moans, and he’s standing there now in nothing but black briefs—soaked at the tip.

And holy fuck, he’s big.

Your lips part, staring. You want to drool.

He notices.

“Go ahead,” he murmurs. “Look at what you’ve been aching for every night.”

He pulls the briefs down—slow, shameless.

His cock springs free, thick and hard and flushed at the tip, veins running along the length like something out of a wet dream. You whimper, thighs pressing together reflexively.

“You wanted this inside you so bad you couldn’t keep quiet,” he says, climbing onto the bed again, crawling over you until his weight cages you in. “Moaning my name with the fucking door unlocked.”

Your body arches up to meet him.

“Please,” you whisper.

He fists his cock once, dragging his head through your soaked folds, teasing your entrance.

You’re still sensitive. Still pulsing.

“Is this what you want?” he growls, notching the tip right against you. “Want me to stretch you open and fuck the brains outta that filthy little head of yours?”

You nod, desperate.

His cock sits heavy in his hand, the flushed tip glistening as he slides it through your slick folds again. Over and over—up and down—until you’re squirming beneath him, hips chasing every motion like you can’t stand another second of not being filled.

But he doesn’t give in. Not yet.

He drags the thick head over your entrance, slow and deliberate, just barely nudging inside before pulling back again.

“Fuck—Bucky,” you whimper, body arching.

“You’re soaked again,” he growls, almost to himself. “You got this wet just thinking about my cock?”

You nod, but it’s not enough. Not for him. He taps your clit once—sharp and teasing—and your whole body jerks.

“Say it.”

Your breath catches. “I—I thought about it every night,” you gasp. “I wanted it so bad. I still want it. Please, Bucky—”

He groans, low and ragged. The tip of his cock presses at your entrance again. Just a little. Just enough to make you feel the burn of it—how thick he is, how your body tries to pull him in even as he holds himself back.

“You feel that?” he murmurs, circling your hole with maddening precision. “How much your pussy needs me?”

You moan, desperate. Hands clawing at his shoulders, his arms, anywhere you can hold onto.

He grins. “Needy little thing.”

Then he pushes. Just the tip—slow and thick, stretching you inch by inch.

Your mouth falls open. Breathless. Wide-eyed.

“Oh my—fuck,” you cry.

He pulls back.

You sob.

“Patience,” he mutters, teasing your entrance again. “Wanna feel you beg for it.”

“I’m begging,” you gasp. “Please, Bucky—please, I need it, I need you to fuck me—”

His mouth crashes over yours, swallowing your cry as he thrusts in deep—all the way—filling you to the hilt in one thick, devastating stroke.

Your back arches. Your vision whites out.

“So fucking tight,” he growls against your mouth, rolling his hips, grinding in deeper. “Fuck—you were made for this, weren’t you?”

He stays there for a moment—buried inside you—his cock stretching you open so wide it burns in the best way, hips pressed flush to yours. You can barely breathe, your body trembling with the shock of just how full you feel.

Then he moves. A slow pull out—just a few inches—before slamming right back in.

You scream. Not from pain. From everything. The pressure, the friction, the heat of his skin, the weight of his body pinning you down like he owns you.

“Goddamn,” he hisses, his jaw clenched tight. “You’re fucking dripping around me.”

Your nails dig into his back.

He starts thrusting—hard and fast, hips snapping against yours with brutal rhythm, the head of his cock dragging over every sensitive spot inside you like he knows exactly where to hit.

And all the while, he talks.

“Been thinking about this tight little cunt every night since I got here. Didn’t know it was mine to take.”

You moan—choked and desperate.

“You wanted it so bad, didn’t you? Wanted me to catch you with your legs spread and fuck you like the filthy little cock-drunk slut you are.”

“Y-Yes—please—” you’re a mess beneath him, eyes wet, mouth open.

He grabs your jaw, thumb pressing into your cheek, forcing you to look up at him.

“Look at me,” he growls. “Don’t you dare look away while I fuck your pussy.”

You blink up at him, dazed. And fuck—he looks insane. Hair a mess, sweat dripping down his temples, that metal hand gripping your thigh so hard you might bruise.

And still—he doesn’t stop. He fucks you like it’s punishment. Relentless. Ruthless.

Every thrust knocks the air out of your lungs, your body jerking with the force of it. The bed creaks beneath you, headboard slamming against the wall, your moans echoing like you’re meant to be heard.

“You gonna come again, baby?” he murmurs, lowering his mouth to your ear. “You gonna soak my cock just like you soaked your fingers last night?”

“Bucky—Bucky, I’m gonna—fuck, I can’t—”

“Yes, you can.”

His hand slips down between you, fingers rubbing fast circles over your clit as he keeps fucking you open with brutal thrusts.

“You’re gonna come with me inside you, sweetheart. You’re gonna come on my cock like a good little toy.”

And it snaps.

You cry out—loud and broken—as your orgasm slams into you hard enough to steal your breath, your pussy clenching around him like a vice.

“Fuck, yes,” he growls, grinding deep into you as you come, riding you through it. “That’s it. So fucking tight—so good for me—”

He’s close now too. You can feel it—his thrusts stuttering, muscles tensing.

“Gonna fill you up,” he groans. “You want that, baby? Want me to come inside this perfect little pussy?”

You’re still shaking, but you nod. Whimpering. Needy.

“Please—inside—want it so bad—”

He buries himself deep and groans loud—raw and wrecked—as he spills inside you, hips jerking, cock twitching as you feel every hot pulse of it.

You’re ruined.

His weight sinks down on top of you, breath ragged in your ear, and for a long moment, all you can hear is the sound of both of you panting.

The room’s heavy with heat and sweat, skin sticking where it meets, your body still twitching with the aftershocks of how hard he fucked you.

Then he lifts his head. Eyes drag down your flushed face. Your parted lips. Your chest rising and falling fast. Still dazed. Still ruined.

He shifts back onto his knees between your thighs, hands gripping your hips, keeping you spread open wide beneath him.

“Look at this,” he murmurs, almost to himself.

Then he pulls out—slow and thick, his cock dragging against your fluttering walls before slipping free with a wet sound that makes you whimper.

And fuck.

You feel it immediately. The warm spill of him leaking out of you—thick and hot and so much—trickling down your folds and onto the sheets in sticky, glistening streams.

Bucky groans under his breath, his eyes locked on your pussy like it’s the most perfect thing he’s ever seen.

“Goddamn,” he mutters. “You took it all. So fucking good for me.”

You try to close your legs on instinct, flushed and wrecked and so overstimulated—but he stops you with a firm grip, holding you open with his metal hand.

“Uh-uh. Keep ’em open. I wanna see it.”

His thumb slides down, spreads you further, letting him watch as more of his cum drips from your aching hole.

“Look at that mess,” he murmurs, gaze heavy-lidded, voice thick with pride and hunger. “You’re leaking all over the place, baby.”

You shiver under him.

He swipes his thumb through the slick, then presses it back in—just a little—pushing some of it inside again while your body jerks from the sensitivity.

“Fuck,” he growls. “You were made to be filled like this.”

He leans in close, lips brushing the shell of your ear, breath hot and uneven.

“You’re gonna clean me up, sweetheart,” he rasps, voice thick with command. “Gonna taste every drop.”

Your pulse spikes. You barely have the strength to move, still reeling from the wreck he’s made of you—but you obey, because you need it, because he told you to.

He shifts forward, settling between your thighs again. His metal hand spreads you open, keeping you wide for him, raw and messy. His other hand trails down, steadying his cock where it rests—still hard, still slick with both of you.

He throbs against your skin, flushed and glistening.

You lean forward without hesitation, tongue flicking out to catch the first salty bead that clings to the head. He lets out a quiet groan above you.

His eyes burn as you take your time, licking slowly around the tip—teasing, deliberate—before your lips part wider and you sink down, wrapping him in heat.

Your cheeks hollow as you draw him in deeper, your mouth soft and eager.

“Fuck,” Bucky grits, his hand sliding into your hair, curling tight. “You’re good at this.”

You moan around him, letting the praise sink in as you begin to move—slow, controlled bobs of your head. Your tongue swirls, tasting the mix of him and yourself, and it only makes you hungrier.

You’re not just cleaning him up. You’re savoring him and he knows it.

He pulls you up by your hair, not rough—controlled. Intentional. His mouth crashes onto yours in a kiss that’s all teeth and heat and claiming, like he’s branding you from the inside out. His metal hand clamps around your waist, anchoring you, holding you still as he devours you like he owns you.

And fuck, maybe he does.

When he finally breaks the kiss, his breath ghosts over your lips, low and ragged.

“That’s enough,” he murmurs, voice thick with something dark and satisfied. “You did so well. That’s my good girl.”

Your stomach twists, body still trembling, as you melt into him — breathless and soaked, the taste of him still slick on your tongue.

He doesn’t move for a while, just lets his weight settle into you, chest rising and falling against yours, heart still pounding beneath sweat-damp skin. His breath is warm where it fans over your cheek, his metal hand still possessively wrapped around your waist.

Then, gently, he shifts. His fingers slide up, brushing your hair back from your face with a tenderness that makes your throat tighten. He kisses your forehead—soft, slow—like he’s claiming you all over again, but quieter this time.

“My good girl,” he murmurs, the words husky but reverent now. “You were perfect.”

Your eyes flutter closed at the sound, overwhelmed, wrecked in the best way. His flesh hand strokes your cheek, soothing the heat from it, while the metal one trails lazy circles over your spine.

“Did so good for me,” he whispers again, like a secret meant only for your bones.

You don’t trust your voice, so you just nuzzle closer, tucking yourself into his chest.

Fuck, he did ruin you.

tags: @iamthatonefangirl

[clinionplatform]

Simplifying eCRF | GenAI eCRF Clinical Trial | Electronic Case Report (eCRF)

Electronic Case Report Forms (eCRF) 's evolution is remarkable progress in the clinical trials landscape. The transition from paper-based CRFs to eCRFs was driven by several factors, including the increasing complexity of clinical trial protocols, the need for greater efficiency in managing large volumes of trial data, and advancements in technology that supported digital solutions for data collection and management. The main objective of this shift was to obtain accuracy and speed in data collection, data validation, enhanced security, and the overall improvement of the clinical trials. As eCRFs have continued to advance, they have adapted to the evolving trial requirements and contributed to the standardization of the data collection process.

AI in Clinical Trials: Smarter eCRFs for Better Data Management

[reasonsforhope]

"For most people, a rat is at best an unwelcome guest, and at worst, the target of immediate extermination. But in a field clinic in Tanzania, rats are colleagues—heroes even.

Far from a trash bin-dwelling NYC street rat, the African giant pouched rat is docile, intelligent, easier to train than some dogs, and for East Africans, the performer of lifesaving tuberculosis diagnoses every day.

400,000 new cases of tuberculosis (TB) were estimated to have been prevented by these rats, whose sense of smell would make a bloodhound take notice. As [TB is] the number-one killer among infectious diseases worldwide, many of those 400,000 can be translated into lives saved.

“Not only are we saving people’s lives, but we’re also changing these perspectives and raising awareness and appreciation for something as lowly as a rat,” said Cindy Fast, a behavioral neuroscientist who coaches the rodents for the nonprofit APOPO.

“Because our rats are our colleagues, and we really do see them as heroes.”

APOPO uses giant pouched rats to sniff out traces of TB in the saliva of patients. In parts of Tanzania, a saliva smear test under a microscope by a human may only be 20-40% effective at detecting TB.

By contrast, a giant pouched rat like Ms. Carolina, a now-retired service rat who worked for APOPO for 7 years, raised the rates of detection on TB samples by 40% in the clinic where she worked.

Pictured: An APOPO employee with one of their trained rats

It would take 4 days for scientists to analyze the number of samples that Carolina could screen in 20 minutes. For that reason, when Carolina retired last November, a party was thrown at the clinic in her honor, and she was given a cake.

TB is sometimes thought of as a thing of the past—a disease for which doctors used to prescribe “dry air,” leading a modern sense of humor to muse at the antiquated, pre-antibiotic medical advice.

But it remains the number-one cause of death globally from a single infectious pathogen, and Tefera Agizew, a physician and APOPO’s head of tuberculosis, told National Geographic that once people see what the nonprofit’s rodents can do to slow the spread, they “fall in love with them.”

3,000 times in her career did Carolina detect one of the six volatile compounds that can be used to identify Mycobacterium tuberculosis, and she got a hero’s send-off to a special compound to live out the rest of her days with her closet friend and sniffer colleague Gilbert, in a shaded enclosure dubbed “Rat Florida.”

“We’ve made special little rat-friendly carrot cakes with little peanuts and things on it that the rat would enjoy,” Fast said. “Then we all stand around and we clap, and we give three cheers, hip hip hooray for the hero, and celebrate together. It’s really a touching moment.”

APOPO has made headlines for its use of these rats in other lifesaving tasks as well: landmine clearance.

One of the world’s great underreported scourges (a lot like TB, coincidentally) is landmine contamination. There are 110 million landmines or unexploded bombs in the ground right now in about 67 countries, covering thousands of square miles in potential danger. Thousands of civilians are killed or injured by these weapons every year.

GNN reported on APOPO’s demining efforts using pouched rats back in 2020. One rat named Magawa alone identified 39 landmines and 28 items of unexploded ordnance across an area the size of 20 football fields.

If at the start of this story you didn’t like rats, maybe Magawa and Carolina will have changed your mind."

-via Good News Network, March 31, 2025

[kaidatheghostdragon]

More, because im kind of sad that nobody else has added to this. (Btw all my ideas/prompts are free for anyone to take and make their own - even if its something ive massively fleshed out and you want to take it a different direction. All i ask is you drop a link so i can read whatever you did!)

Tim was the first of the bats to be hit by the strange weapon. The white suits had shown up in gotham a few weeks ago shooting up the place, and about one-fifth of the people they hit were instantly evaporated.

The bats were at their wits end trying to investigate, and nobody was allowed to patrol alone. The Justice League was also reporting that the suits had been spotted in a number of other cities, including Fawcett and Central City. However, the strange weapons seemed to be far more lethal in Gotham than anywhere else.

The suits loudly declared that anyone who was evaporated was a malevolent ghost pretending to be human. They had scanners that they used on *everyone,* and shot anyone who measured above a certain threshold without hesitation or remorse.

The bats had stolen one of the scanners pretty early on and found that every one of them measured above the threshold. Whatever logic the suits were using to justify their crusade was clearly nonsense.

Tim had found a lead, a rumor that one of the evaporated had reappeared. They lived in crime alley, and as per the buddy system currently in force, and Hood's rule that no bat enters his territory without his escort, Jason partnered with Tim to investigate.

White suits were already swarming the place, possibly catching wind of the same rumor. Hood and Red Red Robin booked it out as fast as they could, but as luck would have it, the scanners picked up their presence, and the suits gave chase, relentless in their pursuit.

Hood knew every inch of the alley and carefully led Red Robin through many narrow escape routes, forcing the suits to seperate and regroup, but none of it was enough to shake them when they could somehow track the bats' movements.

Tim was running the math as they escaped. Jason had died and came back, and was arguably closest to what the agents claimed of everyone over the scanner's threshold. There was no doubt in Tim's mind that it Hood was hit, he would be killed.

In fact, nearly everyone in the family had died at some point or another. Everyone except Tim. Yes, he was over the scanner's threshold, but only barely. There was still about an 80% chance that he would be unaffected. The agents would stop chasing him if the gun didn't affect him, and it would give jason a chance to escape.

Tim had worked with worse odds before. And if it did kill him? Better him than jason. Bruce wouldn't survive losing jason a second time, no matter how emotionally constipated they both were to each other. Tim had always been just a replacement.

So Red Robin lagged behind, waiting for an opportunity where Hood was far enough a way to get out of the scanner's range while the agents focused on Red Robin.

When Tim felt his entire body go numb from the shot, he knew his gamble had failed. He could only spend his last fraction of a second of critical thought, hoping that Jason wasn't dumb enough to turn around.

And then Tim woke up. Or maybe that wasn't the right description, as he wasn't fully convinced he had even lost consciousness. A quick self-check confirmed that he was whole and uninjured, laying on *extremely* soft carpeted floor.

Tim sat up, guaging his surroundings as quickly as possible. He was in an extremely large room, walls of stone like an old keep or castle. In the center of the room stood a piece of frankensteined tech that Tim *guessed* was some sort of antennae, by the overall shape of it. Covering most of the walls were shelves stacked to capacity with various medical supplies and emergency first aid equipment. There were a couple of prepped and ready--to-use gurneys, and a clear-doored fridge stocked with glass jars and iv bags filled with a lazarus green liquid.

In one corner of the room, sitting on two stools, was an enormous black knight cloaked in purple flames, and next to him, an honest-to-god yeti, one arm made of clear ice, even displaying the arm bones.

"Ah, another liminal," the yeti commented.

The knight sighed as they stood, "I'll go inform the prince," then promptly vanished into thin air in a whirl of purple flame.

Half an hour later, as Tim was asking a million questions of the ever-patient and delightfully friendly yeti, Red Hood showed up the same way Red Robin had, battered and bruised. As Tim and his new friend Frostbite gave Jason emergency medical care, Jason (after getting over the shock of still being alive and returning back to vigilante mode) informed Tim that he did, in fact, turn around ("WHAT in the GODDAMN FUCK were you THINKING, Tim?!?!") and the agents had attempted to live-capture Hood, but he had put up so much of a fight that they decided to shoot him instead when he had nearly escaped.

He had also called in back-up after Tim had been shot, and right on cue, Robin and Nightwing appeared in the room. More injured than Tim but less than Jason.

Great, Tim thought, Bruce is probably really going through it right now. So much for noble sacrifices.

Good reveal au, where after learning phantom's identity and realizing the atrocities that the GIW have committed (or alternatively, ethical science au, where they find out the GIW plagarized them), the fenton parents decided to create the 'ultimate ghost-ending weapon' and sell it to the agents.

They go absolutely overboard, describing to the agents in meticulous detail how it evaporates any ghost it hits near-instantly and describing it quite ruthlessly in the blueprints, and soon the GIW have raplaced all their main weapons with the new gun.

Except it doesn't actually kill ghosts. It's the Fenton Bazooka. You know, the one that creates a portable portal to suck the ghost back into the ghost zone? What they actually did was retool it slightly to make it look more grusome than it actually is. They even added a beacon in Phantom's Keep, which all Fenton Bazookas will target when they open a portal, so the ghosts are always delivered to the keep.

From there, Phantom stationed an emergency medical team at the keep to treat the many injured and ragged ghosts that the GIW 'destroyed,' and to explain what just happened.

What they didn't anticipate was that now that the GIW have a mass-produced weapon that they believed would effectively eradicate ghosts, they would go on the offensive. They have a number of cities they've been monitoring but didn't want to get involved in without better tools.

One of those cities is Gotham.

And the Bats are ectocontaminated enough to register as ghosts.

Batman witnessed several of his children get evaporated by green energy weapons within mere moments of each other. He's absolutely gutted. Devastated. They didn’t even stand a chance.

He'll get his revenge, and it's frighteningly easy to track the weapon to private subcontractors. The Doctors Fenton, in Illinois. Their research calls for the genocide of all ghost kind, and apparently, that war started by killing his own children.

His children will not die in vain.

He gets to Amity Park and finds the Engineer's Nightmare of a building that is Fentonworks, but that night, before he can hack through the security and break in, one of the windows opens.

It's one of his kids that he had watched evaporate before his very eyes. They give him a silent signal of one of their identifying security codes and gesture for him to come inside.

Is it a trap? A prank in poor taste? Utterly genuine?

He goes through the window.

All of his dead kids are there, wearing borrowed pajamas and only their dominoes to conceal their identities. Daniel Fenton (son of the Fentons, this is his bedroom, has voiced a few arguments against his parent's views, but still an unknown) is among the crowd of teens and young adults, twirling on an office chair and obnoxiously sipping a capri sun.

"First thing you need to know, Bats," Daniel says after finishing his drink, "is that my parents are absolutely NOT genocidal ectophobic scumbags, and that is the reason why your kids are still alive."

[myrawjcsmicasereports]

 Inhibition of EIF4E Downregulates VEGFA and CCND1 Expression to Suppress Ovarian Cancer Tumor Progression by Jing Wang in Journal of Clinical Case Reports Medical Images and Health Sciences

Abstract

This study investigates the role of EIF4E in ovarian cancer and its influence on the expression of VEGFA and CCND1. Differential expression analysis of VEGFA, CCND1, and EIF4E was conducted using SKOV3 cells in ovarian cancer patients and controls. Correlations between EIF4E and VEGFA/CCND1 were assessed, and three-dimensional cell culture experiments were performed. Comparisons of EIF4E, VEGFA, and CCND1 mRNA and protein expression between the EIF4E inhibitor 4EGI-1-treated group and controls were carried out through RT-PCR and Western blot. Our findings demonstrate elevated expression of EIF4E, VEGFA, and CCND1 in ovarian cancer patients, with positive correlations. The inhibition of EIF4E by 4EGI-1 led to decreased SKOV3 cell clustering and reduced mRNA and protein levels of VEGFA and CCND1. These results suggest that EIF4E plays a crucial role in ovarian cancer and its inhibition may modulate VEGFA and CCND1 expression, underscoring EIF4E as a potential therapeutic target for ovarian cancer treatment.

Keywords: Ovarian cancer; Eukaryotic translation initiation factor 4E; Vascular endothelial growth factor A; Cyclin D1

Introduction

Ovarian cancer ranks high among gynecological malignancies in terms of mortality, necessitating innovative therapeutic strategies [1]. Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis, influencing endothelial cell proliferation, migration, vascular permeability, and apoptosis regulation [2, 3]. While anti-VEGF therapies are prominent in malignancy treatment [4], the significance of cyclin D1 (CCND1) amplification in cancers, including ovarian, cannot be overlooked, as it disrupts the cell cycle, fostering tumorigenesis [5, 6]. Eukaryotic translation initiation factor 4E (EIF4E), central to translation initiation, correlates with poor prognoses in various cancers due to its dysregulated expression and activation, particularly in driving translation of growth-promoting genes like VEGF [7, 8]. Remarkably, elevated EIF4E protein levels have been observed in ovarian cancer tissue, suggesting a potential role in enhancing CCND1 translation, thereby facilitating cell cycle progression and proliferation [9]. Hence, a novel conjecture emerges: by modulating EIF4E expression, a dual impact on VEGF and CCND1 expression might be achieved. This approach introduces an innovative perspective to impede the onset and progression of ovarian cancer, distinct from existing literature, and potentially offering a unique therapeutic avenue.

Materials and Methods

Cell Culture

Human ovarian serous carcinoma cell line SKOV3 (obtained from the Cell Resource Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences) was cultured in DMEM medium containing 10% fetal bovine serum. Cells were maintained at 37°C with 5% CO2 in a cell culture incubator and subcultured every 2-3 days.

Three-Dimensional Spheroid Culture

SKOV3 cells were prepared as single-cell suspensions and adjusted to a concentration of 5×10^5 cells/mL. A volume of 0.5 mL of single-cell suspension was added to Corning Ultra-Low Attachment 24-well microplates and cultured at 37°C with 5% CO2 for 24 hours. Subsequently, 0.5 mL of culture medium or 0.5 mL of EIF4E inhibitor 4EGI-1 (Selleck, 40 μM) was added. After 48 hours, images were captured randomly from five different fields—upper, lower, left, right, and center—using an inverted phase-contrast microscope. The experiment was repeated three times.

GEPIA Online Analysis

The GEPIA online analysis tool (http://gepia.cancer-pku.cn/index.html) was utilized to assess the expression of VEGFA, CCND1, and EIF4E in ovarian cancer tumor samples from TCGA and normal samples from GTEx. Additionally, Pearson correlation coefficient analysis was employed to determine the correlation between VEGF and CCND1 with EIF4E.

RT-PCR

RT-PCR was employed to assess the mRNA expression levels of EIF4E, VEGF, and CCND1 in treatment and control group samples. Total RNA was extracted using the RNA extraction kit from Vazyme, followed by reverse transcription to obtain cDNA using their reverse transcription kit. Amplification was carried out using SYBR qPCR Master Mix as per the recommended conditions from Vazyme. GAPDH was used as an internal reference, and the primer sequences for PCR are shown in Table 1.

Amplification was carried out under the following conditions: an initial denaturation step at 95°C for 60 seconds, followed by cycling conditions of denaturation at 95°C for 10 seconds, annealing at 60°C for 30 seconds, repeated for a total of 40 cycles. Melting curves were determined under the corresponding conditions. Each sample was subjected to triplicate experiments. The reference gene GAPDH was used for normalization. The relative expression levels of the target genes were calculated using the 2-ΔΔCt method.

Western Blot

Western Blot technique was employed to assess the protein expression levels of EIF4E, VEGF, and CCND1 in the treatment and control groups. Initially, cell samples collected using RIPA lysis buffer were lysed, and the total protein concentration was determined using the BCA assay kit (Shanghai Biyuntian Biotechnology, Product No.: P0012S). Based on the detected concentration, 20 μg of total protein was loaded per well. Electrophoresis was carried out using 5% stacking gel and 10% separating gel. Subsequently, the following primary antibodies were used for immune reactions: rabbit anti-human polyclonal antibody against phospho-EIF4E (Beijing Boao Sen Biotechnology, Product No.: bs-2446R, dilution 1:1000), mouse anti-human monoclonal antibody against EIF4E (Wuhan Sanying Biotechnology, Product No.: 66655-1-Ig, dilution 1:5000), mouse anti-human monoclonal antibody against VEGFA (Wuhan Sanying Biotechnology, Product No.: 66828-1-Ig, dilution 1:1000), mouse anti-human monoclonal antibody against CCND1 (Wuhan Sanying Biotechnology, Product No.: 60186-1-Ig, dilution 1:5000), and mouse anti-human monoclonal antibody against GAPDH (Shanghai Biyuntian Biotechnology, Product No.: AF0006, dilution 1:1000). Subsequently, secondary antibodies conjugated with horseradish peroxidase (Shanghai Biyuntian Biotechnology, Product No.: A0216, dilution 1:1000) were used for immune reactions. Finally, super-sensitive ECL chemiluminescence reagent (Shanghai Biyuntian Biotechnology, Product No.: P0018S) was employed for visualization, and the ChemiDocTM Imaging System (Bio-Rad Laboratories, USA) was used for image analysis.

Statistical Analysis

GraphPad software was used for statistical analysis. Data were presented as (x ± s) and analyzed using the t-test for quantitative data. Pearson correlation analysis was performed for assessing correlations. A significance level of P < 0.05 was considered statistically significant.

Results

3D Cell Culture of SKOV3 Cells and Inhibitory Effect of 4EGI-1 on Aggregation

In this experiment, SKOV3 cells were subjected to 3D cell culture, and the impact of the EIF4E inhibitor 4EGI-1 on ovarian cancer cell aggregation was investigated. As depicted in Figure 1, compared to the control group (Figure 1A), the diameter of the SKOV3 cell spheres significantly decreased in the treatment group (Figure 1B) when exposed to 4EGI-1 under identical culture conditions. This observation indicates that inhibiting EIF4E expression effectively suppresses tumor aggregation.

Expression and Correlation Analysis of VEGFA, CCND1, and EIF4E in Ovarian Cancer Samples

To investigate the expression of VEGFA, CCND1, and EIF4E in ovarian cancer, we utilized the GEPIA online analysis tool and employed the Pearson correlation analysis method to compare expression differences between tumor and normal groups. As depicted in Figures 2A-C, the results indicate significantly elevated expression levels of VEGFA, CCND1, and EIF4E in the tumor group compared to the normal control group. Notably, the expression differences of VEGFA and CCND1 were statistically significant (p < 0.05). Furthermore, the correlation analysis revealed a positive correlation between VEGFA and CCND1 with EIF4E (Figures 2D-E), and this correlation exhibited significant statistical differences (p < 0.001). These findings suggest a potential pivotal role of VEGFA, CCND1, and EIF4E in the initiation and progression of ovarian cancer, indicating the presence of intricate interrelationships among them.

EIF4E, VEGFA, and CCND1 mRNA Expression in SKOV3 Cells

To investigate the function of EIF4E in SKOV3 cells, we conducted RT-PCR experiments comparing EIF4E inhibition group with the control group. As illustrated in Figure 3, treatment with 4EGI-1 significantly reduced EIF4E expression (0.58±0.09 vs. control, p < 0.01). Concurrently, mRNA expression of VEGFA (0.76±0.15 vs. control, p < 0.05) and CCND1 (0.81±0.11 vs. control, p < 0.05) also displayed a substantial decrease. These findings underscore the significant impact of EIF4E inhibition on the expression of VEGFA and CCND1, indicating statistically significant differences.

Protein Expression Profiles in SKOV3 Cells with EIF4E Inhibition and Control Group

Protein expression of EIF4E, VEGFA, and CCND1 was assessed using Western Blot in the 4EGI-1 treatment group and the control group. As presented in Figure 4, the expression of p-EIF4E was significantly lower in the 4EGI-1 treatment group compared to the control group (0.33±0.14 vs. control, p < 0.001). Simultaneously, the expression of VEGFA (0.53±0.18 vs. control, p < 0.01) and CCND1 (0.44±0.16 vs. control, p < 0.001) in the 4EGI-1 treatment group exhibited a marked reduction compared to the control group.

Discussion

EIF4E is a post-transcriptional modification factor that plays a pivotal role in protein synthesis. Recent studies have underscored its critical involvement in various cancers [10]. In the context of ovarian cancer research, elevated EIF4E expression has been observed in late-stage ovarian cancer tissues, with low EIF4E expression correlating to higher survival rates [9]. Suppression of EIF4E expression or function has been shown to inhibit ovarian cancer cell proliferation, invasion, and promote apoptosis. Various compounds and drugs that inhibit EIF4E have been identified, rendering them potential candidates for ovarian cancer treatment [11]. Based on the progressing understanding of EIF4E's role in ovarian cancer, inhibiting EIF4E has emerged as a novel therapeutic avenue for the disease. 4EGI-1, a cap-dependent translation small molecule inhibitor, has been suggested to disrupt the formation of the eIF4E complex [12]. In this study, our analysis of public databases revealed elevated EIF4E expression in ovarian cancer patients compared to normal controls. Furthermore, through treatment with 4EGI-1 in the SKOV3 ovarian cancer cell line, we observed a capacity for 4EGI-1 to inhibit SKOV3 cell spheroid formation. Concurrently, results from PCR and Western Blot analyses demonstrated effective EIF4E inhibition by 4EGI-1. Collectively, 4EGI-1 effectively suppresses EIF4E expression and may exert its effects on ovarian cancer therapy by modulating EIF4E.

Vascular Endothelial Growth Factor (VEGF) is a protein that stimulates angiogenesis and increases vascular permeability, playing a crucial role in tumor growth and metastasis [13]. In ovarian cancer, excessive release of VEGF by tumor cells leads to increased angiogenesis, forming a new vascular network to provide nutrients and oxygen to tumor cells. The formation of new blood vessels enables tumor growth, proliferation, and facilitates tumor cell dissemination into the bloodstream, contributing to distant metastasis [14]. As a significant member of the VEGF family, VEGFA has been extensively studied, and it has been reported that VEGFA expression is notably higher in ovarian cancer tumors [15], consistent with our public database analysis. Furthermore, elevated EIF4E levels have been associated with increased malignant tumor VEGF mRNA translation [16]. Through the use of the EIF4E inhibitor 4EGI-1 in ovarian cancer cell lines, we observed a downregulation in both mRNA and protein expression levels of VEGFA. This suggests that EIF4E inhibition might affect ovarian cancer cell angiogenesis capability through downregulation of VEGF expression.

Cyclin D1 (CCND1) is a cell cycle regulatory protein that participates in controlling cell entry into the S phase and the cell division process. In ovarian cancer, overexpression of CCND1 is associated with increased tumor proliferation activity and poor prognosis [17]. Elevated CCND1 levels promote cell cycle progression, leading to uncontrolled cell proliferation [18]. Additionally, CCND1 can activate cell cycle-related signaling pathways, promoting cancer cell growth and invasion capabilities [19]. Studies have shown that CCND1 gene expression is significantly higher in ovarian cancer tissues compared to normal ovarian tissues [20], potentially promoting proliferation and cell cycle progression through enhanced cyclin D1 translation [9]. Our public database analysis results confirm these observations. Furthermore, treatment with the EIF4E inhibitor 4EGI-1 in ovarian cancer cell lines resulted in varying degrees of downregulation in CCND1 mRNA and protein levels. This indicates that EIF4E inhibition might affect ovarian cancer cell proliferation and cell cycle progression through regulation of CCND1 expression.

In conclusion, overexpression of EIF4E appears to be closely associated with the clinical and pathological characteristics of ovarian cancer patients. In various tumors, EIF4E is significantly correlated with VEGF and cyclin D1, suggesting its role in the regulation of protein translation related to angiogenesis and growth [9, 21]. The correlation analysis results in our study further confirmed the positive correlation among EIF4E, VEGFA, and CCND1 in ovarian cancer. Simultaneous inhibition of EIF4E also led to downregulation of VEGFA and CCND1 expression, validating their interconnectedness. Thus, targeted therapy against EIF4E may prove to be an effective strategy for treating ovarian cancer. However, further research and clinical trials are necessary to assess the safety and efficacy of targeted EIF4E therapy, offering more effective treatment options for ovarian cancer patients.

Acknowledgments:

Funding: This study was supported by the Joint Project of Southwest Medical University and the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University (Grant No. 2020XYLH-043).

Conflict of Interest: The authors declare no conflicts of interest.

[jcmcri]

The Seesaw in Healthcare by Deane Waldman* in Journal of Clinical & Medical Case Reports, Images (JCMCRI) ISSN: 3064-8025

Introduction

Government insurance: The Affordable Care Act (ACA, colloquially Obamacare) was signed into law in 2010 but was not fully implemented until 2014. In 2010, the U.S. uninsured rate was 16 percent. [2] By 2017, nearly 20 million Americans had gained government coverage dropping the uninsured rate to 9 percent. Roughly 90 percent of the increased coverage was due to Medicaid expansion: the rest resulted from ACA subsidies. In 2017, Merritt Hawkins measured wait times to see a doctor and acceptance rates of Medicaid patients by physicians. [3] Patients’ maximum wait time for a primary care physician in a mid-sized city increased from 99 days in 2010 to 122 days in 2017. Since then, wait times have gotten longer. [4] In 2011, the Medicaid acceptance rate was 69 percent nationally [5] and has fallen since then. In nine of 14 major cities studied by Merritt Hawkins in 2017, less than 50 percent of physicians would accept new Medicaid patients into their practices. Doctors cited two reasons: [6] excessive regulatory/administrative burden [7] and low payment schedules, often below cost-of-doing-business. Association does not equal causation. Nonetheless, the fact that access to care has declined is alarming. The seesaw relationship – government coverage up, access down – is worrisome especially given data on death-by-queue. The phrase death-by-queue refers to people dying while waiting in line for technically possible medical care that is not provided in time to save them. This has been reported particularly in government-insured Americans in both Medicaid [9] and Tricare. [10] Death-by-queue is due to excessively long wait times and low Medicaid acceptance rates. If patients wait too long for care or don’t have a doctor at all, their health suffers. Even a four-week delay in a cancer diagnosis increases mortality. [11] Imagine what a four-month delay does to patient survival. [3]

Insurance profits: A 2023 Kaiser financial analysis showed that Medicare Advantage had the highest gross margin in the health insurance market. [12] Gross margin, often used as a proxy for profit, is defined as revenue retained after paying for goods sold and services provided. It does not include administrative costs or tax liabilities. Bottom line for non-economists: selling health insurance is highly profitable. Another metric of insurance profitability is stock price. People will pay higher prices for a stock when they anticipate higher returns (more personal profit) in the future. Between 2007 and 2017, stock prices of the seven largest health insurance companies rose 157 percent to 635 percent. [13] Over the same time, the S&P 50 index rose 82 percent.As noted previously, during the 2007 to 2017 period, wait times increased and Medicaid acceptance rates fell. Thus, access to medical care declined as profits increased. Keeping in mind that association isn’t causation, a Pearson chi square test (χ2=24.5582) of stock profits versus access to care indicates a very strong seesaw correlation, p < 0.0001. [13] Insurance premium rates are set by federal and state agencies. Thus, revenue for insurance companies is determined solely by how many people they sign up. They generate profits when they don’t spend money. Typically, they use a “three D” strategy to increase profits: delay, defer, and deny paying for patient care. [14] The economic incentive structure of insurance third-party payment in healthcare exposes another seesaw relationship: insurance profits increase when sellers reduce delivery of care. Federal regulations There is a common misconception that writing a federal regulation somehow directly causes the effect regulated. By this reasoning, passing a mandate for price transparency will immediately make health care price lists available to the public. Such magical thinking does not recognize the process called BARRCOME between passing a federal law and having an impact on the public. BARRCOME stands for bureaucracy, administration, rules, regulations, compliance, oversight, mandates, and enforcement. [15] After passing a law or issuing an executive order, Bureaucrats are hired to populate a new Agency. Lawyers are tasked with writing Rules to reflect the law’s intent. Then others are hired to create actionable Regulations (second R). Compliance must be assured requiring new Overseers. Mandates must be Enforced by additional new hires, including penalizing the non-compliant. BARRCOME costs money, particularly for the tens of thousands of new bureaucrats, administrators, agents, lawyers, and overseers. One look at the organizational chart of the ACA confirms the massive size of the non-clinical healthcare workforce. [16] Nationally, BARRCOME cost between 31 percent [17] and more than 50 percent [14] of all U.S. spending on its healthcare system, which totaled $4.5 trillion in 2023. Thus, Washington expended $1.4 trillion to $2.25 trillion healthcare dollars to pay people who provide no patient care. Where does all that money come from? It is diverted to pay bureaucrats stealing money intended for care providers. [14] To pay for ACA BARRCOME, former President Obama took $716 billion from the Medicare Trust, money intended to pay for seniors’ hospital care. [18] On the healthcare seesaw, as the BARRCOME money side goes up, the patient care side goes down.

Conclusion

Washington directly controls healthcare spending for 186 million Americans (56 percent of population) as their third-party insurer through Medicaid/CHIP, Medicare, Tricare, and EMTALA (for the uninsured). Federal government indirectly controls health expenditures for 147 million with private coverage as insurance sellers must strictly follow federal insurance regulations. Thus, Washington is the ultimate third-party controller of American healthcare dollars. The common element in seesaw relationships is money, specifically who does or does not control it. Whether it is an insurance company, a health plan, a pharmacy benefits manager, state or federal government, the one person who does not control his or her health care spending is the consumer, the patient. In market terms, this is called “microeconomic disconnection,” [19] where buyer and seller are disconnected by a third-party.

As the payer or controller of money, the third party becomes the decision-maker, both financial and medical.  [20, 21] “Disconnection” suppresses free market forces. Buyers (patients, who are not payers) have no incentive to economize, and sellers do not compete for buyers’ dollars. Without these forces, spending rises inexorably, and service (access to care) declines – the exact problems U.S. patients are experiencing. The solution stems directly from identification of the root cause. Since disconnection of buyer from seller is the central problem in healthcare, the answer is to reconnect them. Remove third parties from decision-making in healthcare. Allow patients and providers to interact (connect) directly. Patients would then control their own hard-earned dollars, medical autonomy would be restored, [22] and the seesaw would vanish.

For more Medical Case Reports: https://jcmcrimages.org/

[lisalicharles]

Recognizing CRF's Importance in Clinical Research

In order to further medical knowledge, enhance patient care, and provide novel treatments and cures, clinical research is essential. The gathering and management of data, which is made possible by the use of Case Report Forms (CRFs), is essential to the success of clinical trials. We examine the role, elements, and effects of CRFs on the drug development process as we examine the importance of CRFs in clinical research.

Fundamentally, a CRF is an organized instrument for gathering and documenting information gathered throughout a clinical study. It is intended to collect comprehensive data on all study participants, including demographics, medical histories, treatment plans, and adverse events. CRFs allow researchers to precisely assess the safety and efficacy of investigational medications or therapies by methodically recording this data.

The capacity of CRFs to guarantee the precision, consistency, and completeness of data gathered during the course of a clinical trial accounts for its significance. Every CRF is painstakingly created to capture particular data points pertinent to the study protocol, guaranteeing that no crucial information is missed or left out. This careful method of gathering data is necessary to preserve the accuracy and dependability of clinical trial results.

A standard CRF has multiple fields and sections, each intended to record certain data pertinent to the research goals. These could include personal information, medical history, test results from lab work, concurrent drugs, and adverse occurrences. To aid in data entry and interpretation, CRFs frequently have predetermined response options, consistent terminology, and unambiguous instructions.

The capacity of CRFs to be tailored and adjusted to the particular needs of any clinical trial is one of its main advantages. A Phase I safety study or a Phase III efficacy trial can have its CRF customized to include the information required by the study's goals and protocol. This adaptability guarantees that researchers can collect thorough and pertinent data to successfully support their research conclusions.

More importantly, CRFs are essential for guaranteeing adherence to GCP norms and regulatory requirements. Researchers can show stakeholders and regulatory bodies that their clinical trial data is legitimate and reliable by following established protocols for data collection and recording. In order to obtain approval and licensure for new medications and therapies, compliance with regulatory criteria is crucial.

The use of electronic CRFs (eCRFs) in clinical research has improved data-gathering accuracy and efficiency even more. eCRFs simplify and lower the risk of errors in data management by enabling automatic data validation, real-time data entry, and remote monitoring. Furthermore, eCRFs speed up data analysis and decision-making by facilitating smooth coordination between sponsors, research locations, and regulatory bodies.

To summarize, CRFs are essential tools in clinical research, serving as critical components of data collection, management, and analysis. Clinical trial data integrity, completeness, and correctness are guaranteed by CRFs, which helps to produce solid evidence for the efficacy and safety of novel medications. CRFs will continue to be crucial elements of the drug development process as clinical research develops, spurring innovation and enhancing patient outcomes.

[literaturepublishers22]

Where Can I Publish Clinical Case Reports

Clinical Images and Case Reports Journal publishes clinical case reports, medical case reports, clinical case series in medicine, medical case series, journal of clinical case reports etc. We want to publish Clinical Case Reports with valuable clinical lessons. Common Clinical Case Reports that present a diagnostic, ethical or management challenge, or that highlight aspects of mechanisms of injury, pharmacology or histopathology are deemed of particular educational value. It is essential that the learning outcomes of the articles are important and novel.

Journal Homepage: https://www.literaturepublishers.org/

In addition, we encourage Clinical Case Reports of global health cases and medicine practiced in unusual settings. Global Clinical Case Reports should focus on the causes of ill health and access to healthcare services, whether economic, social or political – global health issues as they impact on individual patient’s lives. These cases require a comprehensive review of the relevant global health literature and an in depth understanding of the anthropological background of the case you present.

Authors wishing to submit a Clinical Case Reports reporting adverse drug reactions and complications, novel treatment including a new drug/ lifestyle/treatment intervention or the use of an established drug or procedure in a new situation are advised to contact the Editor in Chief with a presubmission enquiry at editor.cicrj@literaturepublishers.org prior to taking out a fellowship. We do not publish case reports that assess the efficacy or effectiveness of interventions. This includes Clinical Case Reports of patients enrolled in phase II trials.

We want to publish cases worthy of discussion, particularly around aspects of differential diagnosis, decision making, management, clinical guidelines and pathology. The advantage is that we learn from real cases

Manuscript Submission

Authors may submit their manuscripts through the journal's online submission portal: https://www.literaturepublishers.org/submit.html

(or) Send an e-mail attachment to the Editorial Office E-mail Id: editor.cicrj@literaturepublishers.org

[makingsenseofwhathappened]

What Are My Options?

You’re being harassed at work. You know something’s not right. But you’re not sure what you’re allowed to do.

Here’s The Truth

You don’t have to:

Report it to your boss.

Start with HR.

Follow “the policy” if the policy is part of the problem.

You can:

Talk to a lawyer first, or a legal clinic or support org.

Start with a friend, a hotline, a notes app file.

Document it without reporting it.

Protect yourself before asking for help.

And no matter what they say, staying quiet isn’t the same as doing nothing. Sometimes it’s the smartest move you can make while you figure out what’s safe.

The system definitely isn’t built to protect you in many cases, but there are ways to protect yourself.

You have more options than they want you to think.

NOTE: This isn’t legal advice. It’s “you deserve to know your options” advice.

[literaturepublisher23]

Journal of Clinical and Medical Case Reports

Journals Accepting Clinical and Medical Case Reports publishes clinical case reports, medical case series, medical case studies, medical case reports and clinical images for publication that fall under the scope of all clinical and medical studies. Journal of Clinical and Medical Case Reports mainly focuses on symptoms, signs, diagnosis, treatment, and follow-up of patient disease in different areas of the journal in diagnostic case report and treatment.

Journal Homepage: https://www.literaturepublishers.org/

Journal of Clinical and Medical Case Reports is a peer-reviewed open access high impact factor indexed Journal that publishes highly cited research work conducted as case reports in the medical field on various types of diseases, covering their respective clinical journal case reports, medical journal case report, clinical reports, medical case reports, clinical images, clinical case reports, journal of medical case reports and diagnosis issues.

Scope and Keywords: Journal of Clinical and Medical Case Reports, Open Journal of Clinical and Medical Case Reports, Journal of Medical Case Reports, Clinical and Medical Case Reports, Journal of Clinical Images and Medical Case Reports, Journal of Clinical Studies & Medical Case Reports, Journal of Clinical and Medical Case Studies, International Journal of Clinical and Medical Cases, Journal of Clinical Medicine, Clinical Case Reports, International Medical Case Reports Journal, Archives of Clinical and Medical Case Reports, Case Reports - A journal for medical case reports, International Journal of Clinical Case Reports and Reviews, Japanese Journal of Clinical and Medical Case Reports etc.

Journal of Clinical and Medical Case Reports Journal publishes only high quality articles from all over the world. Journal of Clinical and Medical Case Reports follows double blinded peer review process. All Editors are active and Editorial Board Members belonging to reputed institutions from abroad. They are senior faculty members, doctors, scientist and research fellows etc. Journal regularly releasing issues with good number of articles in the form of clinical images and case reports.