Medical hypotheses最新文献

{"title":"Muscle fatigue and interference phenomenon during concurrent aerobic and strength training: An alternative hypothetical model","authors":"Benedito Sérgio Denadai,&nbsp;Camila Coelho Greco","doi":"10.1016/j.mehy.2025.111614","DOIUrl":"10.1016/j.mehy.2025.111614","url":null,"abstract":"<div><div>Concurrent training, defined as the combination of strength and aerobic exercise in a periodized program, has been shown to be important in both health and athletic performance contexts. Prescribing concurrent training is challenging because some studies have shown that improvements in strength and muscle mass may be attenuated when compared to strength training alone (i.e., the interference phenomenon). In a previous theoretical model, primarily based on manipulating training intensity, training zones were proposed to either maximize (aerobic training: 95–100 % VO₂max + resistance training: 3–4 sets of &gt; 10 maximal repetitions; RM) or minimize (30 to 60 min of moderate-intensity continuous training; MICT + resistance training performed at different % RM) the interference phenomenon. The model proposes that the primary location of adaptations promoted by MICT (i.e., central − cardiovascular) differs from those promoted by strength training protocols (neural and/or peripheral adaptations), thereby attenuating the interference effect on muscle strength. However, there is substantial evidence that the peripheral adaptations (muscle oxidative capacity) from endurance training are not dependent on exercise intensity. In this paper, we propose an alternative hypothetical model of the concurrent training interference phenomenon based on the acute hypothesis (i.e., residual fatigue). We discuss the strengths of the model, considering moderator variables (sex, within-session exercise order, between-mode recovery, endurance training volume, intensity, and modality), which can maximize or minimize the interference phenomenon.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"198 ","pages":"Article 111614"},"PeriodicalIF":2.1,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747925","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":"Gut microbiota as a potential mechanism besides ketone bodies in Ameliorating Parkinson’s disease symptoms with the ketogenic diet","authors":"Xian-Mu Luo ,&nbsp;Jun Luo ,&nbsp;Ling-Yong Zeng ,&nbsp;Chun-Ling Chi","doi":"10.1016/j.mehy.2025.111609","DOIUrl":"10.1016/j.mehy.2025.111609","url":null,"abstract":"<div><div>Current research indicates that the ketogenic diet effectively alleviates symptoms in Parkinson’s disease (PD) patients, presenting a promising novel therapy. The prevailing view attributes the ketogenic diet’s efficacy in PD improvement to ketone bodies. Studies in epilepsy have demonstrated that the ketogenic diet improves epilepsy by modulating gut microbiota. Inspired by this, we hypothesize that the gut microbiota mediates the ketogenic diet’s alleviation of PD symptoms. On one hand, evidence from epilepsy and Alzheimer’s research supports the ketogenic diet’s influence on gut microbiota. On the other hand, PD studies indicate that gut microbiota can influence PD progression. Potential mechanisms may involve the production of neuroprotective metabolites, the modulation of the brain-gut microbiota axis, and the reduction of pathological protein aggregation. This hypothesis can be tested through animal models or clinical experiments. If validated, it could strongly support the widespread application of ketogenic diet therapy in PD and signify gut microbiota as a target for PD treatment, fostering simple and effective therapeutic approaches.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"198 ","pages":"Article 111609"},"PeriodicalIF":2.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759194","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":"Cholinergic eubiosis: A hypothesis on Ivermectin-upregulated Bifidobacterium","authors":"Sabine Hazan ,&nbsp;Adriana C. Vidal ,&nbsp;Adonis Sfera","doi":"10.1016/j.mehy.2025.111613","DOIUrl":"10.1016/j.mehy.2025.111613","url":null,"abstract":"<div><div>Ivermectin, an anti-parasitic agent extracted from <em>Streptomyces avermitilis</em>, has drawn attention during the COVID-19 pandemic by stirring a controversy regarding its efficacy against the SARS-CoV-2 virus. Some studies supported the use of this drug against SARS-CoV-2, while others demonstrated poor antiviral effect or even detrimental action. However, the controversy aside, whether Ivermectin can restore the depleted levels of beneficial gut microbiota, including <em>Bifidobacterium</em>, remains unanswered. It was established that Ivermectin is a positive allosteric regulator of alpha7 nicotinic acetylcholine receptors, active participants in the cholinergic anti-inflammatory pathway, a component of the gut-brain axis. Alpha7 nicotinic acetylcholine receptors activate gut immunosuppressive CD4 + CD25 + regulatory T cells, increasing the abundance of commensals, including <em>Bifidobacterium and Lactobacillus</em>. Intestinal regulatory T cells are crucial for oral and gastrointestinal tolerance, a physiological mechanism of immune unresponsiveness to food proteins and gut commensal flora. <em>Bifidobacterium</em> upregulates intestinal regulatory T cells, while the latter augments the former in a bidirectional manner, maintaining gut homeostasis. We hypothesize that Ivermectin enhances the cholinergic anti-inflammatory pathway and influences gut immunity and barrier integrity. At the subcellular level, this is accomplished by phosphorylation of signal transducer and activator of transcription 3 (STAT3)/ aryl hydrocarbon receptor (AhR) complex, which increases interleukin 22 and the abundance of beneficial gut microbes, including <em>Bifidobacterium.</em> In return<em>,</em> interleukin 22 and <em>Bifidobacterium-</em>generated interleukin 10 induce STAT3/AhR phosphorylation, producing more interleukin 22 and further upregulation of gut <em>Bifidobacterium</em>. This article uses the term “cholinergic eubiosis” to denote parasympathetic system-mediated increase in commensal levels and restoration of beneficial gut microbes’ immune tolerance. As intestinal inflammations are recorded in the Insular Cortex, a brain area responsible for interoception, this hypothesis may explain some beneficial effects of probiotics on neuropathology.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"198 ","pages":"Article 111613"},"PeriodicalIF":2.1,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738453","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":"Comment on “The prostatic urethra as a Venturi effect urine-jet pump to drain prostatic fluid”","authors":"P. Deepu","doi":"10.1016/j.mehy.2025.111611","DOIUrl":"10.1016/j.mehy.2025.111611","url":null,"abstract":"","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"197 ","pages":"Article 111611"},"PeriodicalIF":2.1,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143714666","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":"Time and the body: A new approach to disease","authors":"Alethea Black","doi":"10.1016/j.mehy.2025.111610","DOIUrl":"10.1016/j.mehy.2025.111610","url":null,"abstract":"<div><div>A better understanding of the nature of reality could lead to a better understanding of disease. Typically, the body has been viewed through a materialist lens. Yet materialism has been challenged, with compelling evidence, from cognitive and neuroscientists, who describe the way the brain creates the images we perceive; and from physicists, who have been investigating alternate models of reality, such as a holographic universe, for over twenty-five years. If the universe functions like a quantum computer, there would be something more fundamental than matter: information. Space is not the appropriate medium when considering information. This model will look at the human body as it exists against a different “fabric”: time. In an accelerating, expanding universe, time can be expressed in terms of density. Perhaps we should consider the background density when we make our observations.</div><div>The human body continuously responds to its perception of time, which is processed through sensory inputs. Time can be conceptualized as a dynamic continuum, analogous to a cone, with a dense, constricted “pit” at one end and an expansive “mouth” at the other. Between these extremes is the present or baseline. Mathematically, the baseline can be derived from the values for pit and mouth; however, for this to be physiologically accurate, the scale of these temporal boundaries must be correctly understood. This hypothesis proposes that a misinterpretation of temporal scale and the subsequent maladaptive responses to these forces contribute to the pathophysiology of various disease states.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"198 ","pages":"Article 111610"},"PeriodicalIF":2.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737866","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":"Exploring the role of gut microbiota in the pathogenesis of Kashin-Beck Disease: A Focus on selenium deficiency and T-2 toxin exposure","authors":"Lian Liu ,&nbsp;Lulu Bai ,&nbsp;Yifan Wu ,&nbsp;Yu Zhang ,&nbsp;Chaowei Wang ,&nbsp;Shujin Li ,&nbsp;Yuequan Yuan ,&nbsp;Xi Lv ,&nbsp;Hui Wang ,&nbsp;Yirong Qin ,&nbsp;Xiong Guo ,&nbsp;Xi Wang ,&nbsp;Yujie Ning","doi":"10.1016/j.mehy.2025.111606","DOIUrl":"10.1016/j.mehy.2025.111606","url":null,"abstract":"<div><div>Kashin-Beck disease (KBD) is a chronic degenerative osteochondral condition endemic to certain regions, with its etiology and pathogenesis yet to be fully understood. Research indicates that low selenium levels and exposure to T-2 toxin are recognized environmental risk factors associated with KBD. The gut microbiota, a complex assemblage of microorganisms residing in the human gastrointestinal tract, engages in intricate interactions with its metabolites and the host organism, which can have either beneficial or harmful impacts on host health. These interactions may contribute to or influence the development and progression of various diseases. Clinical investigations into osteoarthritis (OA) have demonstrated alterations in the gut microbiota of patients, which are closely associated with the onset of OA. Notably, KBD exhibits clinical and pathological similarities to OA. In light of the relationship between gut microbiota and bone-related diseases, we propose the hypothesis that selenium deficiency and T-2 toxin exposure induce dysbiosis of the gut microbiota, thereby contributing to the pathogenesis of KBD. We hypothesize that the gut microbiota and its metabolites may play a role in the injury or necrosis of chondrocytes induced by inflammatory responses, as well as in the degradation of the chondrocyte extracellular matrix (ECM), via the “cartilage-gut-microbiome” axis. This interaction could result in pathological changes in chondrocytes. Understanding this mechanism may offer novel insights for the treatment and management of KBD.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"197 ","pages":"Article 111606"},"PeriodicalIF":2.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600776","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":"Cardiac power and the magical number 451","authors":"Enrique Monares-Zepeda ,&nbsp;Christopher Barrera-Hoffmann","doi":"10.1016/j.mehy.2025.111607","DOIUrl":"10.1016/j.mehy.2025.111607","url":null,"abstract":"","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"197 ","pages":"Article 111607"},"PeriodicalIF":2.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679795","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":"Sinoatrial node rod cells transplantation into the injured spinal cord as a novel therapeutic approach to improve proper information transmission","authors":"Mohammad Saleh Ranaiy ,&nbsp;Dina Rajabi Zadeh ,&nbsp;Mozhgan Abasi ,&nbsp;Hamed Ghazvini ,&nbsp;Misagh Shafizad ,&nbsp;Seyedeh Masoumeh Seyedhosseini Tamijani ,&nbsp;Raheleh Rafaiee","doi":"10.1016/j.mehy.2025.111608","DOIUrl":"10.1016/j.mehy.2025.111608","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a devastating condition that disrupts neural circuits, leading to severe motor, sensory, and autonomic dysfunction. Despite extensive research, no effective treatment has been established to restore proper information transmission across the injury site. Current therapeutic strategies, including cell therapy and electrical stimulation, have shown promise but remain limited in their ability to fully re-establish functional connectivity. This study proposes a novel therapeutic approach for SCI by implanting sinoatrial node (SAN) rod cells into the injured spinal cord to facilitate electrical signal transmission and restore neural communication. Given their intrinsic ability to conduct electrical impulses in the heart, we hypothesize that SAN rod cells can serve as bioelectrical bridges, reconnecting the severed. We discuss the pathophysiology of SCI, barriers to axonal regeneration, and existing treatment modalities, highlighting the limitations of current interventions. We propose a transplantation strategy involving SAN rod cells and evaluate their potential for integration into the spinal cord. The hypothesis is supported by the role of gap junctions, particularly connexins, in neuronal electrical coupling, which may enable functional interaction between rod cells and spinal neurons. Furthermore, we outline experimental approaches, including in vivo spinal cord transection models and potential methods for generating SAN rod cells from induced pluripotent stem cells. Rod cells, known for their ability to conduct electrical signals without generating action potentials, could theoretically facilitate neural communication across SCI lesions. Their integration into spinal networks via gap junctions may re-establish lost connectivity, potentially improving motor and sensory function.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"197 ","pages":"Article 111608"},"PeriodicalIF":2.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610317","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":"DPP4 inhibitors and the matters of metaflammation!","authors":"Rohan Magoon","doi":"10.1016/j.mehy.2025.111605","DOIUrl":"10.1016/j.mehy.2025.111605","url":null,"abstract":"","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"197 ","pages":"Article 111605"},"PeriodicalIF":2.1,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549725","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":"“Idiopathic” adhesive capsulitis is caused by reactivation of latent neurotrophic virus involving peripheral nerves around the shoulder capsule: A hypothesis","authors":"William Zhan Xia ,&nbsp;Rosa Ezquerro Cortes ,&nbsp;Kuen Foo Chin ,&nbsp;Carlos Cobiella ,&nbsp;Simon Lambert","doi":"10.1016/j.mehy.2025.111604","DOIUrl":"10.1016/j.mehy.2025.111604","url":null,"abstract":"<div><div>The aetiology and pathogenesis of so-called “idiopathic” adhesive capsulitis (IAC), otherwise known as “frozen shoulder” is not well understood. The condition has been compared to the contracture of Dupuytren’s disease, but this appears to be unlikely, and the many modalities of treatment appear to incompletely address the associated symptoms while not affecting the underlying course of the disorder. It is a debilitating and intrusive condition with a characteristic lengthy duration, sharing features with other conditions characterized by initial hyperaemia with subsequent fibrosis. We hypothesize that IAC is caused by reactivation of latent neurotrophic viruses involving peripheral nerves in the shoulder capsule and synovium, predominantly affecting the distribution of branches of the lateral pectoral nerve in which sympathetic efferents from the stellate ganglion pass to the rotator interval of the shoulder. We postulate that IAC is a low-grade infection from reactivation of latent neurotropic herpesvirus or other viruses with similar biological behaviors. This is based on the observations of increased expression of neural markers in shoulder capsule in early IAC, the epidemiological and clinical similarities between IAC and herpes zoster, the recognition of diverse clinical presentations of herpes zoster induced brachial plexopathy, and finally the significant association between herpesvirus infection and idiopathic pulmonary fibrosis and fibrogenic cancers. An improved understanding on the aetiology of IAC may guide future research on identifying the exact pathogen(s), revealing the pathogenesis, facilitate early diagnosis and prognostication of the disease, and more importantly may potentially improve treatment outcomes (and cure the disease) with antiviral therapy or immunomodulation and possibly decrease the incidence of the condition with antiviral vaccine in susceptible subjects.</div></div>","PeriodicalId":18425,"journal":{"name":"Medical hypotheses","volume":"197 ","pages":"Article 111604"},"PeriodicalIF":2.1,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520569","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}