Medical hypotheses最新文献

{"title":"Interpretation of subjective ratings within pain research: What about context effects? an induced secondary hyperalgesia example","authors":"Niels Jansen,&nbsp;Marie-Laure A.H.C. Snijders,&nbsp;Jan R. Buitenweg","doi":"10.1016/j.mehy.2025.111571","DOIUrl":"10.1016/j.mehy.2025.111571","url":null,"abstract":"<div><div>In many experimental and clinical studies, subjective ratings of experimentally induced pain experiences are used to evaluate the nociceptive function. However, our understanding of how these subjective ratings are produced and influenced is limited. Not taking into account variability in how the subjective responses are produced, e.g. due to experience with (experimental) pain, might lead to biased, underpowered or even misinterpreted studies or clinical decisions. Here, we illustrate such variability in the case of studying secondary hyperalgesia using High Frequency Stimulation (HFS) as a conditioning stimulus. Recently, different findings have been reported related to the effect of HFS on single electrical stimuli. While most studies report an increased pain rating at the test electrode after HFS relative to the control site, in some studies this difference between test and control ratings is the result of a decrease in pain ratings at the control site. In these reports, the observations are explained by nociceptive mechanisms like habituation or descending inhibition. In our view these mechanisms do not (fully) explain the observable event, nor the differences between the studies. Here, we provide a phenomenological analysis of the observable event and based on this analysis hypothesize that ratings can be affected by prior experience with experimental stimuli (i.e. familiarization with HFS). Acceptance of the hypothesis suggests the (co–)existence of alternative mechanisms at experiments with HFS, as earlier suggested underlying mechanisms are unable to explain these observations. We argue that both the observable event and the differences between the studies can be explained by mechanisms underlying so-called context effects, i.e. well-known phenomena in other sensory modalities whereby the participant’s response is altered based on earlier provided stimuli. Importantly, from a theoretical perspective context effects could (have) play(ed) a role in (many) more experimental procedures within pain research than only when HFS is used, but seemingly to date have not received attention. Consequently, with some experimental procedures within pain research, observed variation might be wrongly attributed to changes in nociceptive function due to an explanatory focus on nociceptive mechanisms. On the short-term, acceptance of the hypothesis highlights an urgent need to perform research in which the effect and magnitude of context effects are evaluated in commonly performed procedures within pain research. On the long-term, dependent on the findings of these studies, this might lead to revisiting not only experimental (familiarization) procedures, but also revising the way earlier results from these experimental procedures have been interpreted.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111571"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A quantum mechanical explanation for auditory-visual hallucinations","authors":"Liam Greenacre","doi":"10.1016/j.mehy.2024.111554","DOIUrl":"10.1016/j.mehy.2024.111554","url":null,"abstract":"<div><div>Auditory-visual hallucinations might be caused by Quantum Mechanics. The Many-Worlds Interpretation suggests those who have hallucinations might be experiencing alternate realities due to the unique nature of the quantum. Hallucinations, in part to their quantum nature, are neither biological or social-environmental. On the other hand, the scholarship on the origin of Auditory-Visual Hallucinations usually focuses on either the biological or the social-environmental. There is a range of evidence to suggest that quantum mechanics operates in the brain, like EEGs and the nature of mental states, but the social dynamic is introduced via the Many-Worlds Interpretation. The hypothesis that hallucinations are the result of the Many-Worlds Interpretation is reached through a consideration of quantum biology, optics and acoustics. The proposed hypothesis allows us to consider potential therapeutic and medical benefits of the theory, potentially improving the lives of patients via potential technologies or through reducing the trivialisation of their experiences.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111554"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise-induced intraventricular pressure gradient may be the cause of sudden cardiac death in patients with unknown cardiac disease","authors":"Nuno Cotrim ,&nbsp;Hugo Café ,&nbsp;Pedro Cordeiro ,&nbsp;Jorge Guardado ,&nbsp;Luís Baquero ,&nbsp;Carlos Cotrim","doi":"10.1016/j.mehy.2024.111552","DOIUrl":"10.1016/j.mehy.2024.111552","url":null,"abstract":"<div><div>Sudden cardiac death (SCD) is a tragedy at any age and under any circumstances, but it is especially poignant, and fortunately very rare, when it takes the life of an athlete, a person who represents health and a healthy lifestyle. Sports cardiologists worldwide have worked to quantify the incidence of SCD in athletes, identify risk factors, develop pre-participation screening tools, and formulate plans to address on-field SCD. While progress has been made, there is still much to do to make both competitive and recreational sports safer for individuals with known cardiac disease and athletes without known or suspected cardiac abnormalities.</div><div>We recently published the case of an athlete who practices triathlon and underwent medical evaluation after an episode of aborted sudden death. The complete diagnostic workup including a complete genetic study for myocardiopathy had normal results. An exercise stress echocardiogram (ESE) was finally performed during which he developed a significant intraventricular pressure gradient (IVPG) − a possible cause of ischemia − over 100 mmHg with an end-systolic peak at the end of exercise that was associated with frequent premature ventricular complexes.</div><div>We hypothesize the possible role of ESE for IVPG assessment in athletes who have unexplained symptoms related to exercise or aborted sudden death. In our opinion, it should be considered useful and used by routine to improve the clinical approach of this group of patients, detecting possible high-risk athletes.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111552"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148409","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":"Activation of resident immune cells induces enteric neuronal death","authors":"João Janilson da Silva Sousa ,&nbsp;Vanessa de Sousa do Vale ,&nbsp;Rafael da Silva Prudêncio ,&nbsp;Diva de Aguiar Magalhães ,&nbsp;Viviane Pinheiro Alves de Almeida ,&nbsp;Antônio Kleiton de Sousa ,&nbsp;Tino Marcos Lino da Silva ,&nbsp;Kaique Aguiar Souza ,&nbsp;Vanderlene Oliveira Rodrigues ,&nbsp;André Luiz dos Reis Barbosa","doi":"10.1016/j.mehy.2024.111555","DOIUrl":"10.1016/j.mehy.2024.111555","url":null,"abstract":"<div><div>Resident immune cells are involved in the pathogenesis of inflammatory bowel diseases (IBDs). Studies have already demonstrated that these cells, mainly mast cells and macrophages, are close to and in communication with neurons of the enteric nervous system (ENS). Enteric neurons organized in ganglions participate in processes such as control of motility, secretory functions, absorption and blood flow. Morphological and functional changes in these neurons can cause intestinal damage, such as changes in intestinal motility and diarrhea, common features of IBD. Uncontrolled or unregulated activation of mast cells can also interfere with intestinal homeostasis and generate tissue dysfunction and promote inflammation in various gastrointestinal diseases. These cells can also act by releasing mediators that activate enteric glial cells (EGC), leading to reactive gliosis. Despite being recognized as essential regulators of neuronal function in the ENS, when activated by injuries and inflammatory processes, these cells can proliferate and undergo broad activation that, in association with other cells of the external muscular layer of the intestine (neutrophils, monocytes, resident macrophages and smooth muscles) produces and releases pro-inflammatory mediators. This pro-inflammatory action also involves the participation of the beta fraction of the calcium-binding protein S100 (S100β), which despite being found in other cells, in the intestine its expression is limited to EGC. The increase in the expression of this protein may be responsible for the death of neurons, through the activation of receptors for advanced glycation end products (RAGE) and consequent activation of the nuclear transcription factor-κB (NFκB). RAGE-type receptors are expressed in several cells, including their presence in macrophages. It is known that interactions between macrophages and the ENS interfere with intestinal motility, serve as a protective mechanism during injuries and infections, but can also contribute to tissue damage and other gastrointestinal disorders. Therefore, our hypothesis suggests that mast cells and macrophages, resident immune cells, are involved in enteric neuronal death, through the activation of EGCs and the release of pro-inflammatory factors.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111555"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148417","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":"Heart rate variability may serve as an intermediate indicator for limiting atrial fibrillation in hypertensive patients","authors":"Hao Yang ,&nbsp;Mi He ,&nbsp;Yi He ,&nbsp;Tao Liu ,&nbsp;Houyuan Hu","doi":"10.1016/j.mehy.2024.111553","DOIUrl":"10.1016/j.mehy.2024.111553","url":null,"abstract":"<div><div>Hypertension（HT） is a common disease and, if uncontrolled, may lead to atrial fibrillation (AF). Current research has revealed that the autonomic nervous system dysfunction (ANSD) and body fluid imbalance are important factors in the progression of HT. Hence, we hypothesize that by improving ANSD via intermittent monitoring of heart rate variability (HRV) in conjunction with effective blood-pressure control, anti-HT treatment may reduce AF events more successfully. This hypothesis presents a novel direction and perspective for further research into early interventions and ambulatory management for HT patients to limit the risk of AF.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111553"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148418","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":"Deep cervical lymphovenous bypass for Parkinson’s disease: A hypothesis","authors":"Guanyu Yang ,&nbsp;Gaiqing Yang ,&nbsp;Feiyun Wang ,&nbsp;Qinjun Chu","doi":"10.1016/j.mehy.2024.111559","DOIUrl":"10.1016/j.mehy.2024.111559","url":null,"abstract":"<div><div>As the population ages, the incidence of Parkinson’s disease has been progressively increasing, becoming a significant global public health concern. This disease is closely associated with the abnormal accumulation of α-synuclein, which adversely affects neuronal function and exacerbates symptoms. Recent studies have indicated that the lymphatic system plays a crucial role in clearing metabolic waste from the brain. However, patients with Parkinson’s disease often exhibit dysfunction of the brain’s lymphatic system, resulting in impaired clearance of α-synuclein. Therefore, reducing the accumulation of α-synuclein in the brain has emerged as a therapeutic target for Parkinson’s disease. In this context, a hypothesis is proposed regarding the use of deep cervical lymphovenous bypass surgery. This procedure aims to create a pathway for the drainage of cerebrospinal lymph by anastomosing the deep cervical lymphatic vessels with the cervical veins, thereby accelerating lymphatic drainage and improving the drainage function of the brain’s lymphatic system. If this hypothesis is validated, it could provide new solution into the treatment of Parkinson’s disease, potentially halting disease progression and possibly being applicable to other neurodegenerative disorders.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111559"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical exercises can alleviate harmine toxicity in the case of oncological treatments","authors":"Bogdan-Alexandru Hagiu","doi":"10.1016/j.mehy.2025.111579","DOIUrl":"10.1016/j.mehy.2025.111579","url":null,"abstract":"<div><div>Research conducted on experimental animals has shown remarkable antitumor effects of harmine. However, the doses at which therapeutic effects are observed show toxic effects on hepatic and neuronal mitochondria. A possible way to mitigate these adverse effects is to practice physical exercises that stimulate the functionality, regeneration, and even biogenesis of mitochondria in the liver and nervous system. Drugs that stimulate mitochondrial biogenesis are also being researched, but they are either not effective enough, have long-term effects that can worsen cancer, or interfere pharmacologically with harmine.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"196 ","pages":"Article 111579"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143158748","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":"Potential role of bacterial extracellular vesicles in the pathophysiology of systemic lupus erythematosus","authors":"Khianne Ed Miguel P. Orteza ,&nbsp;Marc Erickson G. Mosqueda ,&nbsp;Jericho V. Carena ,&nbsp;Ourlad Alzeus G. Tantengco","doi":"10.1016/j.mehy.2024.111545","DOIUrl":"10.1016/j.mehy.2024.111545","url":null,"abstract":"<div><div>Systemic Lupus Erythematosus (SLE) is a rare autoimmune disorder influenced by various factors, including infections. Following bacterial or viral infections, there is an increase in IFN-I production, primarily by plasmacytoid dendritic cells (pDCs). Overproduction of IFN-I has been shown to drive the progression of SLE. Recent findings indicate that the gene expression signature of IFN-I in lupus nephritis patients does not co-occur with pDCs as expected; instead, it is localized in glomerular regions with anastomosing capillaries, suggesting a potential source from the blood. T cells, natural killer cells, and myeloid lineage cells may also secrete IFN in the bloodstream. Bacterial presence in the bloodstream challenges the concept of blood sterility, raising the possibility that cell-free microbial components, such as bacterial extracellular vesicles (BEVs), could trigger excessive IFN production through systemic circulation. While existing studies suggest a role for BEVs in human SLE, experimental evidence has yet to establish a direct association between the entire BEV nanoparticle and the disease. Research has primarily focused on (1) mammalian EVs and (2) purified eDNA and other specific cargoes as contributors to SLE progression. It remains unproven whether these bacterial molecules exert their effects while associated with vesicular membranes, i.e., BEVs. We hypothesize that BEVs, which carry diverse cargoes including nucleic acids, may enter systemic circulation, induce cellular responses leading to IFN overproduction, and exacerbate SLE severity. Clinical studies could investigate the association of BEVs with SLE progression by monitoring their presence and quantity in blood samples and correlating these factors with disease outcomes. Furthermore, understanding the involvement of BEVs may aid in identifying SLE biomarkers, inform infection prevention strategies, and inspire the development of BEV-neutralizing agents.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111545"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148410","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":"Dysfunction of the Gut-Brain-Axis in delayed encephalopathy after carbon monoxide poisoning","authors":"Kexin Xiong ,&nbsp;Yuehong Ma ,&nbsp;Wenying Lv ,&nbsp;Dazhi Guo","doi":"10.1016/j.mehy.2024.111550","DOIUrl":"10.1016/j.mehy.2024.111550","url":null,"abstract":"<div><div>Carbon monoxide (CO) poisoning usually causes brain lesions and delayed encephalopathy, also known as delayed neurological sequelae (DNS). The mechanism of direct brain damage caused by CO poisoning is extremely complicated which is mainly focused on the hypoxia, disorder of energy metabolism, failure of the cellular mitochondrial respiration, oxidative stress, inflammation, auto-immunological attack, excitatory amino acid toxicity, etc. However, the etiology for neurological deficits that arise from days to weeks after poisoning remains unclear. In recent years, more and more studies have shown that the intestinal flora and their gene expression products communicate directly with the brain and transmit information to each other through the complex enteric nervous system, also called Gut-Brain-Axis (GBA), and the<!--> <!-->mismatch<!--> <!-->between<!--> <!-->the<!--> <!-->metabolism and<!--> <!-->the<!--> <!-->gut microbiota<!--> <!-->is thought to be important<!--> <!-->for many neurological disorders, such as multiple sclerosis, mood and anxiety disorders, Alzheimer disease, etc. Therefore, we propose a hypothesis that CO poisoning leads to dysbiosis of the gut microbiota, affects neuroendocrine system, neuroimmnue system, autonomic system and enternic nervous system, causes disruption of symbiotic microbial populations in the gut and increases intestinal permeability, leading to “leaky out” of intestinal microorganisms and metabolites from the gut into the bloodstream, disrupts the homeostatic state of brain tissues and induces neuroinflammation, thus contributing to “persistent and worsening” brain damage and leading to the development of DNS. We believe that the combination therapies to remodel gut microbiota and regulate host metabolism may be important for the prevention and treatment of DNS after CO poisoning.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111550"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcitonin gene-related peptide-induced central sensitization: A hypothesis for long COVID symptoms","authors":"Ella J. Lee ,&nbsp;Cynthia Tsang ,&nbsp;Martha Lucía Gutiérrez Pérez ,&nbsp;Mehdi Abouzari ,&nbsp;Hamid R. Djalilian","doi":"10.1016/j.mehy.2025.111570","DOIUrl":"10.1016/j.mehy.2025.111570","url":null,"abstract":"<div><div>Central sensitization (CS) denotes aberrant processing of sensory stimuli within the central nervous system, wherein innocuous inputs activate pain pathways, leading to pain hypersensitivity. Features observed in CS conditions are often present in patients with long COVID, suggesting a potentially shared pathophysiological mechanism. We hypothesize that elevated levels of calcitonin gene-related peptide (CGRP), a neuropeptide known to play an integral role in the development of CS, may contribute to the persistent symptoms observed in long COVID. This article explores the role of CGRP within the context of CS and proposes its potential relationship to long COVID.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"195 ","pages":"Article 111570"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148430","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}