Medical hypotheses最新文献

{"title":"Fibroblast-to-myofibroblast differentiation in gut wall and abdominal soft tissue corrupts normal bowel function in “irritable bowel syndrome”: A hypothesis","authors":"Shiloh Plaut","doi":"10.1016/j.mehy.2026.111905","DOIUrl":"10.1016/j.mehy.2026.111905","url":null,"abstract":"<div><div>Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal discomfort, pain, and altered bowel habits, as well as extraintestinal manifestations such as fatigue, musculoskeletal pain, gastroesophageal reflux, depression, and anxiety. Despite prevalences of approximately 10% in the general population, its fundamental etiopathogenesis remains unclear. Current theories mainly point toward a multifactorial aetiology crediting psychological stress with a prominent role. The paradigms currently embraced for IBS are mainly based on, and emphasize, the gut-brain axis, visceral hypersensitivity, central sensitization, neuroendocrinology, dysbiosis, motility abnormalities, and post-infectious persistent low-grade mucosal inflammation. Yet, they don’t fully explain its diverse clinical presentations nor IBS’s symptomatic overlap with conditions such as fibrositis/fibromyalgia syndrome. Available treatments are mostly symptomatic and provide limited relief, indicating a still major gap in our mechanistic understanding. This paper proposes a hypothesis for IBS etiopathogenesis as an organic disease of the extracellular matrix driven by myofibroblast overactivity in the gut wall and abdominal soft tissue, along with downstream consequences stemming from tissue stiffness. This process is theorized to mechanically compress visceral structures and nerves, impair synchronized organ motility, and induce substrate stiffness-mediated visceral hypersensitivity. In this theoretical framework the extraintestinal manifestations reflect mechanistic overlap with fibromyalgia, which helps unify functional-psychosomatic syndromes as a medical entity with a shared organic mechanism. This mechanism, along with known mechanisms of gut dysbiosis and the gut-brain axis, helps explain “medically unexplained symptoms” of fibromyalgia-type syndromes and offers testable predictions for future research and suggests new avenues for IBS diagnosis and treatment.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111905"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Percutaneous pedicle screws may be one of the causes of intermuscular hematoma following minimally invasive percutaneous treatment for thoracolumbar fractures","authors":"Lei Wu,&nbsp;Yuda Xu,&nbsp;Jun Zhang,&nbsp;Yanli Zhu,&nbsp;Rongming Xu,&nbsp;Changming Zhao","doi":"10.1016/j.mehy.2026.111920","DOIUrl":"10.1016/j.mehy.2026.111920","url":null,"abstract":"<div><div>Percutaneous pedicle screw fixation has emerged as a minimally invasive surgical approach for the treatment of thoracolumbar fractures, presenting benefits like diminished tissue trauma, minimal blood loss, and accelerated recovery. Despite these benefits, a number of patients still suffer from the occurrence of intermuscular hematoma after undergoing surgery. This hypothesis proposes that the structural characteristics of percutaneous pedicle screws, especially their hollow design, might play a role in the development of intermuscular hematoma. We explore the underlying potential mechanisms of this phenomenon and provide evidence from existing literature to support our hypothesis.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111920"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuro-entero-cardiac bridge: could gut-derived catecholamine-loaded extracellular vesicles synchronize the pathogenesis of Parkinson’s disease, irritable bowel syndrome, and stress-triggered arrhythmias?","authors":"Okechukwu Paul-Chima Ugwu ,&nbsp;Mariam Basajja ,&nbsp;Fabian C. Ogenyi ,&nbsp;Chinyere N. Ugwu ,&nbsp;Michael Ben Okon ,&nbsp;Mustafa M. Mundu","doi":"10.1016/j.mehy.2026.111896","DOIUrl":"10.1016/j.mehy.2026.111896","url":null,"abstract":"<div><div>The gut–brain–heart axis is increasingly recognized as a clinically relevant interface in chronic and stress-responsive disorders. Parkinson’s disease (PD), irritable bowel syndrome (IBS), and stress-triggered arrhythmias show epidemiologic and mechanistic convergence through autonomic dysregulation, mucosal immune activation, barrier dysfunction, and systemic inflammatory signaling. However, the molecular messengers that could help “couple” these organ systems over time remain incompletely defined. Extracellular vesicles (EVs) represent a plausible integrative mechanism because they can transport regulatory cargo (RNAs, proteins, lipids) and influence distant tissues, including during inflammation and stress responses. We hypothesize that stress-responsive gut-linked EVs originating from intestinal epithelial, immune, enteroendocrine, and enteric neural compartments may contribute to shared vulnerability across PD, IBS, and arrhythmias by distributing inflammatory and neuroactive regulatory signals (especially microRNAs) systemically. Importantly, direct evidence that gut-derived EVs are “highly enriched” with catecholamines (dopamine, norepinephrine) in PD, IBS, or arrhythmia contexts is currently lacking; therefore, EV-mediated catecholamine transport is presented here as a testable sub-hypothesis rather than an established driver of pathology. Even if EV-associated catecholamines are detectable, they may constitute a minor fraction relative to synaptic/autonomic catecholamine signaling and could represent an epiphenomenon of stress biology rather than a dominant transport route. We outline falsifiable predictions and a rigorous experimental strategy that explicitly addresses EV heterogeneity, contamination by non-EV particles, and causality controls. If supported, gut-linked EV cargo profiles could provide biomarkers that stratify tri-system risk and point toward adjunctive therapeutic approaches that complement established gut–brain–heart pathways (vagus/autonomic signaling and microbiota-derived metabolites, including TMAO-related pathways).</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111896"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arm elevation as a compensatory neuromechanical strategy during smartphone use: a hypothesis on segmental reweighting for postural stability","authors":"Noppharath Sangkarit,&nbsp;Weerasak Tapanya,&nbsp;Saisunee Konsanit","doi":"10.1016/j.mehy.2026.111900","DOIUrl":"10.1016/j.mehy.2026.111900","url":null,"abstract":"<div><div>Contemporary smartphone interaction involves prolonged static postures and attentional diversion, both of which challenge sensorimotor regulation of balance. Yet, emerging evidence suggests that subtle changes in arm elevation may paradoxically enhance postural stability during smartphone use. We hypothesize that arm elevation constitutes a compensatory neuromechanical adaptation that improves whole-body equilibrium through dynamic segmental reweighting. By elevating the arms, users may shift the center of segmental mass upward, engaging tonic activation of scapular and trunk musculature, which in turn increases mechanical coupling and stabilizing stiffness across the axial chain. This redistribution may reduce uncontrolled trunk oscillations and enhance sensorimotor efficiency of balance control, despite concurrent cognitive loading. Preliminary smartphone-based accelerometry observations indicate lower center-of-mass sway magnitudes under elevated-arm conditions, consistent with this proposed stabilization mechanism. If validated, this hypothesis reframes arm elevation during smartphone use as an active, goal-directed stabilizing strategy—rather than a passive by-product of mechanical load—and highlights ergonomic interventions that leverage segmental mechanics to preserve postural stability during mobile multitasking.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111900"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146147506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of spinal cord pulsatility in the pathogenesis of Post-traumatic syringomyelia: A novel hypothesis","authors":"Feifan Xu ,&nbsp;Fengzeng Jian ,&nbsp;Jian Guan ,&nbsp;Zhiqiang Yi ,&nbsp;Xingwen Wang","doi":"10.1016/j.mehy.2026.111924","DOIUrl":"10.1016/j.mehy.2026.111924","url":null,"abstract":"<div><div>This paper proposes a novel hypothesis that impaired spinal cord pulsatility is a critical factor in the pathogenesis of post-traumatic syringomyelia (PTS). Beyond established theories on cerebrospinal fluid dynamics and intramedullary changes, we posit that post-traumatic adhesions and compression diminish spinal cord motion and compliance. This loss of normal kinematics disrupts fluid homeostasis, facilitating syrinx formation and progression. Supporting evidence includes consistent intraoperative observation of reduced pulsatility in PTS, which improves after decompression and adhesion release, correlating with syrinx collapse. Literature confirms pulsatility’s role in cord protection and cerebrospinal fluid dynamics. If validated, this hypothesis reframes PTS pathophysiology, suggesting spinal cord pulsatility as a biomarker for diagnosis, a real-time surgical guide for decompression, and a target for future therapies aimed at restoring mechanical homeostasis.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111924"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aquaporin dysregulation and persistent hyperosmolar microenvironments as a barrier to tissue recovery","authors":"Susie Sarkozy","doi":"10.1016/j.mehy.2026.111916","DOIUrl":"10.1016/j.mehy.2026.111916","url":null,"abstract":"<div><div>Chronic inflammatory conditions frequently persist despite anti-inflammatory treatment, suggesting that inflammation alone does not fully explain incomplete tissue recovery. Many affected tissues exhibit localized extracellular hyperosmolarity, which can impose sustained biophysical stress independent of inflammatory signaling. We hypothesize that persistent hyperosmolar microenvironments represent an underappreciated barrier to tissue recovery and that aquaporin-mediated water equilibration plays a critical role in resolving, but not initiating, this stress. When aquaporin function is dysregulated, compensatory water movement may be insufficient, permitting hyperosmolar stress to persist even as inflammatory markers improve. We hypothesize that persistent hyperosmolar microenvironments can represent an underappreciated barrier to tissue recovery and that aquaporin-mediated water equilibration may play a critical role in resolving this stress, while upstream initiators vary by condition and subtype.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111916"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A substrate-competition hypothesis for type 2 diabetes driven by nutrient excess rather than a primary insulin-signaling defect","authors":"John M. Poothullil","doi":"10.1016/j.mehy.2026.111926","DOIUrl":"10.1016/j.mehy.2026.111926","url":null,"abstract":"<div><div>Type 2 diabetes (T2D) is most commonly framed within a dominant insulin-resistance paradigm characterized by reduced insulin-stimulated glucose disposal and inadequate suppression of hepatic glucose output. While this framework describes reproducible physiological phenotypes, the causal status and temporal ordering of insulin-signaling–associated changes in the development of chronic hyperglycemia remain debated. Clinical observations—including variable diabetes risk across BMI strata and frequent glycemic improvement with dietary change—motivate consideration of alternative causal models.</div><div>This article proposes an alternative hypothesis for the pathogenesis of T2D with an explicit causal sequence that does not invoke a primary insulin-signaling defect. In this framework, chronic dietary substrate surplus—particularly refined-carbohydrate exposure—exceeds an individual’s capacity to buffer and safely store lipid in adipose tissue (“personal fat threshold”). As adipose buffering becomes constrained, lipid overflow into the circulation and non-adipose tissues increases, leading to ectopic lipid accumulation in liver and skeletal muscle. This metabolic state promotes a preferential shift toward fatty-acid oxidation via substrate competition (the Randle cycle), functionally displacing glucose utilization. Within this framework, reduced insulin effectiveness emerges as a context-dependent physiological phenotype rather than as evidence of a required insulin-signaling defect or a necessary causal mediator of dysglycemia.</div><div>The model yields falsifiable predictions regarding temporal ordering and measurable intermediates and outlines cohort and controlled feeding-trial designs that allow direct empirical adjudication between this framework and insulin-resistance–first models, with implications for dietary strategies in T2D prevention and treatment.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111926"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal coding instability in tinnitus: The temporal jitter hypothesis","authors":"Halime Sümeyra Sevmez","doi":"10.1016/j.mehy.2026.111913","DOIUrl":"10.1016/j.mehy.2026.111913","url":null,"abstract":"<div><div>Despite decades of investigation, the pathophysiological basis of tinnitus remains incompletely understood. Prevailing models have largely emphasized peripheral deafferentation, central hyperactivity, maladaptive plasticity, aberrant neural synchrony, and deficits in sensory gating. While these frameworks account for selected features of tinnitus, they do not fully explain several persistent observations, including the heterogeneity of electrophysiological findings, the occurrence of tinnitus in individuals with clinically normal audiograms, and the frequently inconsistent associations between tinnitus and conventional neural amplitude or latency measures. Against this background, the Temporal Jitter Hypothesis is proposed as a complementary conceptual framework that identifies temporal auditory coding fidelity as a potentially underrecognized dimension of tinnitus pathophysiology, particularly within a mechanistically coherent subgroup of individuals characterized by preserved audiometric thresholds yet disrupted temporal processing. The hypothesis posits that increased variability in neural spike timing and reduced phase locking across the auditory pathway may give rise to temporally unstable neural representations even in the absence of overt threshold elevation. Such instability may subsequently interact with central gain and predictive processes, increasing the likelihood that internally generated auditory activity attains perceptual salience and persistence. Rather than constituting a universal explanation, this framework is intended to complement existing models by providing a constrained and empirically testable account of tinnitus within this specific physiological context. By shifting the explanatory emphasis from neural response magnitude toward temporal precision, the Temporal Jitter Hypothesis integrates behavioral, electrophysiological, and computational evidence while establishing a structured foundation for future experimental and translational research.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111913"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An environmental–sensorimotor cascade hypothesis: Spatial and mechanical affordances shape segmental trunk control in preterm infants","authors":"Weerasak Tapanya,&nbsp;Noppharath Sangkarit","doi":"10.1016/j.mehy.2026.111918","DOIUrl":"10.1016/j.mehy.2026.111918","url":null,"abstract":"<div><div>Preterm infants frequently display delayed postural control and segmental instability, yet the environmental mechanisms influencing this neuromechanical development remain poorly understood. Conventional views emphasize intrinsic neuromuscular immaturity, overlooking how daily environments constrain sensorimotor calibration. Drawing from longitudinal observations of moderate-to-late preterm infants, we propose an environmental–sensorimotor cascade hypothesis. This framework posits that spatial and mechanical affordance within infant home containers (e.g., playpens, cribs/cots, and other bounded spaces)—specifically <em>usable play area</em> and <em>surface compliance</em>—may modulate the quality and frequency of postural perturbations, thereby shaping the maturation of segmental trunk control. Limited spatial area restricts center-of-mass excursions and reduces opportunities for anticipatory and reactive adjustments, while excessively firm surfaces may impose lower demands on proprioceptive reweighting. Conversely, moderately compliant surfaces stimulate multi-segment coordination and feedforward stabilization. Over time, these constraints produce distinct trajectories of static, active, and reactive trunk control, influencing upright locomotor milestones. We hypothesize that such affordance-dependent calibration operates through adaptive tuning of trunk muscle synergies and sensory feedback gain. If confirmed, this hypothesis redefines the environment as an active biomechanical teacher, offering new targets for early intervention in preterm infants.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111918"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel multilayered drug-releasing stent for actively accelerating thrombosis in aneurysm therapy","authors":"Peng Zhang ,&nbsp;Xiaoyan Deng ,&nbsp;Xiao Liu ,&nbsp;Fan Zhang ,&nbsp;Jun Li ,&nbsp;Chun Guo ,&nbsp;Shangming Liu","doi":"10.1016/j.mehy.2026.111930","DOIUrl":"10.1016/j.mehy.2026.111930","url":null,"abstract":"<div><div>Current endovascular treatments such as flow diverters promote aneurysm occlusion through passive changes in blood flow, but are limited by a high-risk transition period during which delayed thrombus formation may lead to sac enlargement and rupture. We hypothesize that engineering a porous stent with a localized, controlled-release system for pro-thrombotic agents can actively accelerate the formation of stable thrombus, thereby mitigating this risk. The proposed stent device combines flow stagnation via overlapping struts, a structural support for endothelialization, and targeted delivery of thrombotic agents into the aneurysm sac. If confirmed, this approach may introduce a new treatment strategy that combines device design with targeted drug therapy to improve occlusion effectiveness and patient safety.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"209 ","pages":"Article 111930"},"PeriodicalIF":0.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147386089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}