Medical hypotheses最新文献

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Sickle Cell Crisis – Home Oxygen in the Golden Half Hour, can prevent or stop a crisis, prevent complications and change the trajectory of disease 镰状细胞危机-家庭氧气在黄金半小时，可以预防或停止危机，防止并发症和改变疾病的轨迹

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-12-24 DOI: 10.1016/j.mehy.2025.111869

Sota Omoigui

Reversible sickle cells (RSC) can become irreversible sickle cells (ISC) after repeated episodes of sickling. The reversible sickle cells can revert to their original flexible discoid shape when reoxygenated, but repeated or prolonged sickling can damage the cell membrane and make it impossible for the cells to return to their normal shape, becoming irreversible sickle cells. In-hospital oxygen therapy administered when patients are in a sickle cell crisis does not stop a crisis and does not reduce the pain. This is because patients are already in an irreversible sickle cell crisis; the cells have undergone cell damage and can no longer be resuscitated with oxygen. These sickle cells obstruct blood flow and have to be destroyed by the body in a process of hemolysis or phagocytosis. Such process leads to the known complications of sickle cell crisis including organ damage and severe anemia. However if oxygen is administered at home in the early stages of a crisis, preferably the golden half hour (30 mins), when the sickle cells are still reversible, it can restore the sickle cells to their normal discoid shape and prevents them from progressing to a critical mass of irreversible sickle cells, wherein the sickle cell crisis becomes established and intractable. The efficacy of home oxygen therapy in preventing and aborting a crisis in the golden half hour is very promising. Aborting a crisis would reduce ischemic and hemolytic complications, therefore lowering disability and mortality rates. In addition, it will reduce health care costs associated with SCD.

可逆镰状细胞（RSC）可成为不可逆镰状细胞（ISC）反复发作后。可逆镰状细胞在复氧后可恢复到原来的柔韧性盘状，但反复或长时间的镰状细胞会损伤细胞膜，使细胞无法恢复到正常形状，成为不可逆镰状细胞。当病人处于镰状细胞危象时，在医院内进行氧气治疗并不能阻止危象，也不能减轻疼痛。这是因为患者已经处于不可逆转的镰状细胞危象中；这些细胞已经受损，不能再用氧气使其复苏。这些镰状细胞阻碍血液流动，必须在溶血或吞噬过程中被身体消灭。这一过程导致镰状细胞危象的已知并发症，包括器官损伤和严重贫血。然而，如果在危机的早期阶段，最好是黄金半小时（30分钟），当镰状细胞仍然可逆时，在家中给予氧气，它可以使镰状细胞恢复到正常的盘状形状，并防止它们发展到不可逆转的镰状细胞的临界质量，此时镰状细胞危机变得确定和难以控制。家庭氧疗在黄金半小时内预防和终止危机的效果是非常有希望的。中止危机将减少缺血性和溶血性并发症，从而降低致残率和死亡率。此外，它还将降低与SCD相关的卫生保健费用。

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引用次数: 0

Creatine insufficiency as an energetic amplifier of brainstem dysfunction in ME/CFS and long COVID 肌酸不足是ME/CFS和长COVID患者脑干功能障碍的能量放大器

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-12-24 DOI: 10.1016/j.mehy.2025.111868

Nikola Todorovic

引用次数: 0

DNA as life’s archive: unraveling the molecular storage of memories and information DNA是生命的档案：解开记忆和信息的分子存储

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-12-23 DOI: 10.1016/j.mehy.2025.111856

Akeel Abed Yasseen , Alaa Salah Jumaah , Hussein Nafakhi

The traditional view of DNA as merely a blueprint for protein synthesis is being challenged by emerging evidence suggesting that the genome, particularly its non-coding regions, may carry subtle imprints of life experiences. Epigenetic mechanisms, including DNA methylation, histone modifications, and the regulatory actions of non-coding RNAs, are increasingly recognized as mediators of memory formation, maintenance, and potentially even intergenerational transmission of stress and trauma. These molecular processes can alter gene expression without changing the underlying DNA sequence, providing a plausible framework for how experiences might leave lasting biological marks.

This manuscript hypothesizes that the non-coding genome, coupled with epigenetic machinery, could serve as a biological record of emotionally significant events. Evidence from animal and human studies demonstrates that epigenetic changes can persist across cell divisions and, in some cases, may influence offspring through germline transmission. While robust mechanistic proof in humans remains limited, the convergence of neuroscience, molecular biology, and epigenetics suggests a tantalizing possibility: that life experiences, emotions, and even aspects of behavior could be encoded within our molecular framework.

Understanding such mechanisms would not only expand our conception of DNA function but also open new avenues for research into memory, psychological resilience, and the biological inheritance of experience. If confirmed, this hypothesis could transform approaches to mental health, trauma, and cognitive disorders, providing a molecular lens through which the imprint of life’s experiences might one day be read.

DNA仅仅是蛋白质合成的蓝图的传统观点正受到新的证据的挑战，这些证据表明，基因组，特别是其非编码区域，可能携带着生命经历的微妙印记。表观遗传机制，包括DNA甲基化、组蛋白修饰和非编码rna的调节作用，越来越多地被认为是记忆形成、维持甚至可能是压力和创伤代际传递的介质。这些分子过程可以在不改变潜在DNA序列的情况下改变基因表达，为经历如何留下持久的生物印记提供了一个合理的框架。这篇论文假设非编码基因组，加上表观遗传机制，可以作为情感重大事件的生物学记录。来自动物和人类研究的证据表明，表观遗传变化可以在细胞分裂期间持续存在，在某些情况下，可能通过种系传播影响后代。虽然在人类身上强有力的机制证据仍然有限，但神经科学、分子生物学和表观遗传学的结合表明了一种诱人的可能性：生活经历、情感，甚至行为的各个方面都可以在我们的分子框架内编码。了解这种机制不仅可以扩展我们对DNA功能的概念，还可以为研究记忆、心理弹性和经验的生物遗传开辟新的途径。如果得到证实，这一假设可能会改变心理健康、创伤和认知障碍的研究方法，提供一个分子透镜，有朝一日，人们可能会通过它来解读生活经历的印记。

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引用次数: 0

Long COVID may be treatable with noradrenergic transmission reducing drugs 长期COVID可通过降肾上腺素能传播药物治疗

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-12-23 DOI: 10.1016/j.mehy.2025.111867

Paul J. Fitzgerald

Long COVID remains a major public health problem throughout the world, even as cases of acute COVID infection have declined. With no well-established pharmacological treatments for long COVID, new approaches are urgently needed. This condition is associated with a wide range of deleterious symptoms, including: fatigue, post-exertional malaise, cognitive dysfunction, cardiovascular abnormalities such as tachycardia and hypertension, neurological abnormalities, and others. A unifying theme may be that norepinephrine and sympathetic nervous system signaling are systemically elevated in the condition, consistent with recent reports of autonomic abnormalities and systemic inflammation in long COVID. Further, many of the symptoms of long COVID, including neurological sequelae, may surprisingly be a consequence of elevated systemic noradrenergic signaling and could be treatable with existing noradrenergic transmission reducing drugs such as clonidine, guanfacine, propranolol, and prazosin. Since serotonin may counteract some of the physiological effects of norepinephrine, SSRIs (fluvoxamine, fluoxetine, citalopram, sertraline, paroxetine) may also be therapeutic in long COVID, where fluvoxamine has already shown therapeutic effects against acute COVID. Since acetylcholine may also counteract physiological effects of norepinephrine, the acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) may also have therapeutic properties in long COVID. If the above different classes of pharmacological agents can alone treat long COVID, then perhaps pairs of these drugs may have even greater therapeutic effects, if such pairs do not have significant metabolic interactions or side effects.

尽管急性COVID感染病例有所下降，但COVID仍然是世界各地的一个重大公共卫生问题。由于长期COVID没有成熟的药物治疗方法，迫切需要新的方法。这种情况与多种有害症状相关，包括：疲劳、运动后不适、认知功能障碍、心血管异常（如心动过速和高血压）、神经异常等。一个统一的主题可能是，在这种情况下，去甲肾上腺素和交感神经系统信号全身性升高，这与最近关于长期COVID的自主神经异常和全身性炎症的报道一致。此外，长期COVID的许多症状，包括神经系统后遗症，可能是全身性去甲肾上腺素能信号传导升高的结果，并且可以用现有的减少去甲肾上腺素能传递的药物（如可乐定、胍法辛、心得安和哌唑嗪）治疗。由于血清素可能抵消去甲肾上腺素的一些生理作用，SSRIs（氟伏沙明、氟西汀、西酞普兰、舍曲林、帕罗西汀）也可能治疗长期COVID，其中氟伏沙明已经显示出对急性COVID的治疗效果。由于乙酰胆碱还可以抵消去甲肾上腺素的生理作用，因此乙酰胆碱酯酶抑制剂（多奈哌齐、加兰他明、利瓦斯替明）也可能在长期COVID中具有治疗特性。如果上述不同类别的药理学药物可以单独治疗长期COVID，那么如果这些药物对没有显着的代谢相互作用或副作用，那么这些药物对可能具有更大的治疗效果。

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引用次数: 0

Climate change and the decline in human core body temperature: A hypothesis of physiological adaptation 气候变化与人体核心体温下降：一种生理适应假说

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-12-22 DOI: 10.1016/j.mehy.2025.111866

Nina Mehta , Andy Goren

Average human core body temperature has decreased over the past two centuries. While reduced infections and modern lifestyles have likely contributed to this observation, we hypothesize that increasing global temperatures as a result of human activity are driving a physiological adaptation by resetting thermoregulatory set points. This shift may reflect short-term plasticity rather than genetic evolution. Understanding these changes requires considering metabolic, immune, and demographic factors, as well as acknowledging limitations in historical temperature measurements. Recognizing this trend could reshape our understanding of human health in the context of climate change.

在过去的两个世纪里，人类的平均体温一直在下降。虽然减少感染和现代生活方式可能促成了这一观察结果，但我们假设，人类活动导致的全球气温升高正在通过重置体温调节设定值来推动生理适应。这种转变可能反映了短期的可塑性，而不是遗传进化。了解这些变化需要考虑代谢、免疫和人口统计学因素，并承认历史温度测量的局限性。认识到这一趋势可以重塑我们对气候变化背景下人类健康的理解。

引用次数: 0

Reinterpreting autism through the analogy of inflammation: a hypothesis of non-specific neurodevelopmental response 通过炎症的类比重新解释自闭症：非特异性神经发育反应的假设

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-12-22 DOI: 10.1016/j.mehy.2025.111865

Zhengbing Zhou , Saralah Devi Mariamdaran Chetiyar , Beiyong Cui

Autism Spectrum Disorder (ASD) is conventionally viewed as a discrete disease. This paper proposes an alternative hypothesis: ASD traits may represent the brain’s adaptive responses to early neurodevelopmental divergence rather than markers of a unified pathology. Drawing an analogy with inflammation, we suggest ASD symptoms are non-specific, stable outcomes of early Central Nervous System (CNS) perturbations, some impairing, others benign or advantageous. This hypothesis emphasizes multifactorial etiology involving genetic susceptibility, environmental exposure, and immune factors. Just as inflammation varies in severity and function, so too do ASD traits. By reframing autism as a symptom complex, not a singular disease, we support a shift away from causal reductionism and toward individualized care. This perspective offers a more integrative framework for understanding ASD and reduces stigma by recognizing neurodiversity. It also highlights implications for clinical practice and early intervention strategies.

自闭症谱系障碍（ASD）通常被视为一种独立的疾病。本文提出了另一种假设：ASD特征可能代表大脑对早期神经发育差异的适应性反应，而不是统一病理的标志。与炎症类似，我们认为ASD症状是非特异性的，是早期中枢神经系统（CNS）扰动的稳定结果，有些是受损的，有些是良性的或有利的。该假说强调多因素病因，包括遗传易感性、环境暴露和免疫因素。正如炎症的严重程度和功能各不相同，ASD的特征也是如此。通过将自闭症重新定义为一种复杂的症状，而不是一种单一的疾病，我们支持从因果还原论转向个性化护理。这一观点为理解ASD提供了一个更综合的框架，并通过认识神经多样性来减少耻辱感。它还强调了临床实践和早期干预策略的含义。

引用次数: 0

From perinatal thiamine insufficiency to growth-phase airway phenotypes: A developmental hypothesis on craniofacial growth, functional oral tongue space, and collapsibility 从围产期硫胺素不足到生长阶段气道表型：颅面生长、功能性口腔舌空间和可折叠性的发育假说

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-12-21 DOI: 10.1016/j.mehy.2025.111864

Björn U. Winter

Craniofacial growth, oral posture, and airway collapsibility arise from interacting developmental, metabolic, and biomechanical factors, yet the potential contribution of perinatal micronutrient status remains underexplored. It is hypothesized that perinatal thiamine (vitamin B1) insufficiency, by constraining thiamine-dependent flux through pyruvate/α-ketoglutarate dehydrogenases and transketolase in the pentose phosphate pathway, creates a bio-energetic/redox bottleneck in cranial neural crest cells during critical windows of craniofacial morphogenesis and palatogenesis. The developmental phenotype is expected to include subtle maxillo-mandibular undergrowth and palatal shape changes that reduce functional oral tongue space, favor mouth breathing, and promote a downward resting position of the hyoid bone, thereby increasing upper airway collapsibility and sleep-disordered breathing (SDB) risk. Perinatal thiamine status is both measurable and modifiable. The model can be tested using biomarker-anchored cohorts, organoid/animal systems, and finite element simulations. Modern, highly processed diets may induce functional thiamine scarcity via increased demand, reduced availability, and increased losses, thereby priming early developmental risks even without frank deficiency. If corroborated, perinatal micronutrition plus interceptive functional/orthopedic care may lessen the burden of a hyoid-descent-prone airway phenotype while respecting SDB heterogeneity.

颅面生长、口腔姿势和气道塌陷是由发育、代谢和生物力学因素相互作用引起的，但围产期微量营养素状况的潜在影响仍未得到充分探讨。假设围产期硫胺素（维生素B1）不足，通过限制硫胺素依赖的通量通过丙酮酸/α-酮戊二酸脱氢酶和戊糖磷酸转酮醇酶途径，在颅面形态发生和腭发育的关键窗口期在颅神经嵴细胞中产生生物能/氧化还原瓶颈。发育表型预计包括轻微的上颌下颌生长不足和腭形改变，减少功能性口腔舌空间，有利于口腔呼吸，促进舌骨向下休息位置，从而增加上呼吸道塌陷和睡眠呼吸障碍（SDB）的风险。围产期硫胺素状态是可测量和可改变的。该模型可以使用生物标志物锚定队列、类器官/动物系统和有限元模拟进行测试。现代高度加工的饮食可能通过增加需求、减少供应和增加损失而导致功能性硫胺素短缺，从而引发早期发育风险，即使没有明显的缺乏。如果得到证实，围产期微量营养加上阻断功能/矫形护理可以减轻舌骨下降倾向气道表型的负担，同时尊重SDB的异质性。

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引用次数: 0

Phospholipid nanoparticles for adsorptive sequestration of cocaine: a modeling hypothesis 用于吸附可卡因的磷脂纳米颗粒：一个模型假设

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-12-17 DOI: 10.1016/j.mehy.2025.111857

Ryan Sasse

This hypothesis presents a simple, design-level mass-balance estimate for anionic phospholipid nanoparticles engineered to capture small-molecule drugs, particularly cocaine, via surface binding. Using a Langmuir-type adsorption relation combined with a bulk mass-balance calculation, we obtain estimates linking liposome structural parameters to the nanoparticle dose required for a desired reduction in circulating cocaine. In an illustrative case, a suspension of 25 nm anionic liposomes can achieve a 95 % reduction in plasma cocaine if each square meter of liposome surface binds only ∼0.21 mg of cocaine. The model is intentionally minimal and does not attempt to account for detailed transport kinetics, metabolism, or multi-compartment pharmacokinetics, but instead provides an order-of-magnitude feasibility check for adsorption-based detoxification.

这一假设为阴离子磷脂纳米颗粒提供了一个简单的设计级质量平衡估计，通过表面结合来捕获小分子药物，特别是可卡因。使用langmuir型吸附关系结合体积质量平衡计算，我们获得了脂质体结构参数与减少循环可卡因所需的纳米颗粒剂量之间的估计。在一个说明性的案例中，如果每平方米的脂质体表面仅结合~ 0.21 mg的可卡因，25 nm阴离子脂质体的悬浮液可以使血浆可卡因减少95%。该模型是最小的，并且不试图解释详细的运输动力学，代谢或多室药代动力学，而是为基于吸附的解毒提供了一个数量级的可行性检查。

引用次数: 0

Dysregulation of mitochondrial dynamics as a central mechanism driving diabetic peripheral neuropathy and a target for disease-modifying therapy 线粒体动力学失调作为驱动糖尿病周围神经病变的中心机制和疾病修饰治疗的靶标

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-12-15 DOI: 10.1016/j.mehy.2025.111855

M.D. Pandareesh , H.S. Bhumika

Diabetic peripheral neuropathy (DPN) is among the most prevalent and disabling complications of diabetes mellitus, characterized by chronic pain, sensory loss, and neurodegeneration. Despite significant advances in diabetes care, DPN remains without disease-modifying therapy, as current treatments address only symptoms rather than underlying mechanisms. Mounting evidence implicates mitochondrial dysfunction as the central pathogenic event linking metabolic stress to neuronal injury. We hypothesize that dysregulation of mitochondrial dynamics, such as excessive fission, impaired fusion, defective mitophagy, and suppressed biogenesis, constitutes the key molecular driver of DPN. This imbalance results in mitochondrial fragmentation, oxidative stress, and energy failure within peripheral neurons. Mitochondrial balance restoration through modulation of the AMPK-SIRT1-PGC-1α signaling axis, normalization of fission–fusion balance, and enhancement of antioxidant capacity may therefore modify disease progression. This hypothesis is supported by various experimental and clinical data demonstrating altered mitochondrial morphology, reduced ATP production, and increased ROS generation in diabetic nerves. The hypothesis predicts that interventions targeting mitochondrial dynamics will preserve axonal integrity and restore bioenergetic function. Validation of this concept would shift DPN therapy from symptomatic relief toward mechanism-based, disease-modifying strategies.

糖尿病周围神经病变（DPN）是糖尿病最常见和致残的并发症之一，以慢性疼痛、感觉丧失和神经变性为特征。尽管糖尿病护理取得了重大进展，但DPN仍然没有改善疾病的治疗，因为目前的治疗只针对症状，而不是潜在的机制。越来越多的证据表明，线粒体功能障碍是将代谢应激与神经元损伤联系起来的中心致病事件。我们假设线粒体动力学失调，如过度裂变、融合受损、线粒体自噬缺陷和生物发生抑制，构成了DPN的关键分子驱动因素。这种不平衡导致线粒体断裂、氧化应激和周围神经元的能量衰竭。因此，通过调节AMPK-SIRT1-PGC-1α信号轴恢复线粒体平衡、恢复裂变融合平衡和增强抗氧化能力可能会改变疾病进展。这一假设得到了各种实验和临床数据的支持，这些数据表明糖尿病神经中线粒体形态改变，ATP产生减少，ROS生成增加。该假说预测，针对线粒体动力学的干预将保持轴突完整性并恢复生物能量功能。这一概念的验证将使DPN治疗从症状缓解转向基于机制的疾病改善策略。

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引用次数: 0

Can severe anaemia limit carbon dioxide clearance under acute carbon dioxide load 急性二氧化碳负荷下严重贫血会限制二氧化碳清除吗

IF 0.8 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Medical hypotheses

Pub Date : 2025-12-14 DOI: 10.1016/j.mehy.2025.111854

Sampath Gnanarathne , Ashani Ratnayake , U.A. Isurindi

Carbon dioxide (CO₂) transport in blood is often underemphasized in clinical discussions compared to oxygen transport. Red blood cells and haemoglobin are integral to CO₂ carriage, especially via carbaminohaemoglobin and buffering systems. This hypothesis is based on delayed hypercapnic encephalopathy observed in anaemic patients after laparoscopic surgery using carbon dioxide pneumoperitoneum. We hypothesize that severe anaemia reduces the blood’s CO₂ carrying capacity, predisposing to hypercarbia under acute CO₂ loading conditions. The body has a large capacity to handle excretion of CO₂. This capacity may be significantly reduced in severe anaemia, but can be clinically apparent in acute exogenous CO₂ loads, such as the creation and maintenance of CO₂ pneumoperitoneum. This can lead to delayed clearance of CO₂ and hypercapnic encephalopathy. This hypothesis highlights the need for alternative perioperative strategies such as revising transfusion triggers and considering delayed extubation in vulnerable individuals.

在临床讨论中，与氧运输相比，血液中的二氧化碳运输往往被低估。红细胞和血红蛋白是二氧化碳运输不可或缺的一部分，特别是通过碳氨血红蛋白和缓冲系统。这一假设是基于在使用二氧化碳气腹的腹腔镜手术后贫血患者中观察到的迟发性高碳酸血症脑病。我们假设严重贫血降低了血液的二氧化碳承载能力，在急性二氧化碳负荷条件下易发生高碳血症。身体有很大的能力来处理二氧化碳的排泄。这种能力在严重贫血时可能会显著降低，但在急性外源性CO2负荷（如CO2气腹的产生和维持）中可能在临床上表现明显。这可能导致二氧化碳清除延迟和高碳酸血症脑病。这一假设强调了围手术期替代策略的必要性，如修改输血触发因素，并考虑在易感个体中延迟拔管。

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