Medical Hypotheses[JOURNAL]
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200 papers
Acoustic reflex preshoot: A sign of contraction of the tensor tympani muscle?
Barozzi S, Zanetti D, Di Berardino F … +2 more , Aldè M, Cantarella G
Med Hypotheses · 2021 Oct · PMID 34412022 · Publisher ↗
Two tiny muscles are attached to the ossicles of the middle ear: the stapedius, whose role as a protector of the inner ear against loud noise has been widely accepted, and the tensor tympani, which remains a mystery sinc...
Two tiny muscles are attached to the ossicles of the middle ear: the stapedius, whose role as a protector of the inner ear against loud noise has been widely accepted, and the tensor tympani, which remains a mystery since no valid method of detecting its contraction has yet been developed. However, tonic contraction of the tensor tympani has been associated with a number of otological conditions including fullness, tinnitus, slight hearing loss, and Menière-like findings. Our hypothesis is that an easily recognizable sign in the acoustic immittance testing that is part of almost every basic audiological evaluation indicates the contraction of the tensor tympani. During acoustic reflex assessment, a loud stimulus causes a bilateral contraction of the stapedial muscles and an increase in impedance which appears as a deflection in the tracing of the immittance test results. In the case of a contracted tensor tympani, when an intense sound is sent to provoke the acoustic reflex, the stapedius must overcome its resistance which would otherwise have the opposite effect on the footplate. This effort can be seen as a small peak or "preshoot" preceding the greater negative deflection of the impedance. We report the cases of ten patients with unilateral aural symptoms such as tinnitus, impaired noise tolerance, fullness, ear pressure and/or ear discomfort during chewing; the preshoot was present only in the symptomatic ear. If further studies confirm our hypothesis, this could give rise to new therapeutical strategies aimed at reducing contraction of the tensor tympani and balancing its function.
Can interruption of innate immune recognition-mediated emergency myelopoiesis impede tumor progression?
Mallick R, Duttaroy AK
Med Hypotheses · 2021 Oct · PMID 34403869 · Publisher ↗
Cancer cells survive and grow despite various advanced anti-cancer therapy. To overcome this antineoplastic resistance, adjuvant therapy is often required to prevent cancer cells' immunoescape capacity. Established tumor...
Cancer cells survive and grow despite various advanced anti-cancer therapy. To overcome this antineoplastic resistance, adjuvant therapy is often required to prevent cancer cells' immunoescape capacity. Established tumors build a stressful and hostile microenvironment in order to escape protective innate and adaptive immune responses. Specific conditions and factors within tumors, including hypoxia, nutrient starvation, acidic pH, and increased levels of free radicals, provoke a state of "endoplasmic reticulum stress" in both malignant cells and infiltrating myeloid cells. The stimulated endoplasmic reticulum stress can affect cancer progression via cross-talks with the innate immune system. Recently, the immunosuppressive activities of myeloid cells in the development of antineoplastic resistance are gaining more attention. Based on all these available data, we hypothesize that interruption of innate-immune recognition-mediated emergency myelopoiesis may be beneficial in halting cancer progression.
Prediction of obstructive sleep apnea using ensemble of recurrence plot convolutional neural networks (RPCNNs) from polysomnography signals.
Taghizadegan Y, Jafarnia Dabanloo N, Maghooli K … +1 more , Sheikhani A
Med Hypotheses · 2021 Sep · PMID 34399170 · Publisher ↗
Obstructive Sleep Apnea (OSA) is a common disorder characterized by periodic cessation of breathing during sleep. OSA affects daily life and poses a severe threat to human health. The standard clinical method for identif...
Obstructive Sleep Apnea (OSA) is a common disorder characterized by periodic cessation of breathing during sleep. OSA affects daily life and poses a severe threat to human health. The standard clinical method for identifying and predicting OSA events is the use of Polysomnography signals. In this paper, a novel scheme based on an ensemble of recurrence plots (RPs) and pre-trained convolutional neural networks (RPCNNs) is proposed to improve the prediction rate of OSA. First, RPs were used to represent the dynamic behavior of single electroencephalogram (EEG) and electrocardiogram (ECG) signals for 60 s before and during OSA events. Then, using RPs, three prompt CNNs named ResNet-50 were fine-tuned, and their classification results were fused via the Majority Voting (MV) method to produce a final result concerning prediction. Next, the subject-independent Leave-One-Subject-Out Cross-Validation (LOSO-CV) and subject-dependent 10-fold Cross-Validation (10-fold CV) methods were used to validate the prediction rate from signals derived from the University College Dublin Sleep Apnea Database. Finally, the highest achieved average accuracy for the fusion level was 91.74% and 89.45% at the 10-fold CV and LOSO-CV. Additionally, our results outperformed state-of-the-art findings and could be recommended to predict and detect other biomedical signals. As a result, this predictive system can also be used to adjust the air pressure in sleep apnea patients' Automatic Positive Airway Pressure (APAP) devices.
Drug-repurposing against COVID-19 by targeting a key signaling pathway: An in silico study.
Oh KK, Adnan M, Cho DH
Med Hypotheses · 2021 Oct · PMID 34399157 · Full text
Currently, a plethora of information has been accumulated concerning COVID-19, including the transmission pathway of SARs-CoV-2. Thus, we retrieved targets associated with the development of COVID-19 via PubChem. A total...
Currently, a plethora of information has been accumulated concerning COVID-19, including the transmission pathway of SARs-CoV-2. Thus, we retrieved targets associated with the development of COVID-19 via PubChem. A total of 517 targets were identified, and signaling pathways responded after infection of SARs-CoV-2 in humans constructed a bubble chart using RPackage. The bubble chart result suggested that the key signaling pathway against COVID-19 was the estrogen signaling pathway associated with AKT1, HSP90AB1, BCL2 targets. The three targets have the strongest affinity with three ligands-Akti-1/2, HSP990, S55746, respectively. In conclusion, this work provides three key elements to alleviate COVID-19 symptoms might be anti-inflammatory effects on SARs-CoV-2-infected lung cells.
Age, obesity and hyperglycaemia: Activation of innate immunity initiates a series of molecular interactions involving anionic surfaces leading to COVID-19 morbidity and mortality.
Birts CN, Wilton DC
Med Hypotheses · 2021 Oct · PMID 34392108 · Full text
Obesity and type 2 diabetes are major factors in COVID-19 causing a progression to excessive morbidity and mortality. An important characteristic of these conditions is poor glycaemic control leading to inappropriate che...
Obesity and type 2 diabetes are major factors in COVID-19 causing a progression to excessive morbidity and mortality. An important characteristic of these conditions is poor glycaemic control leading to inappropriate chemical reactions and the production of glycated proteins in which positively charged lysine and arginine residues are neutralised. We propose that this protein glycation primes the inflammatory system as the presence of aspartate and glutamate residues in any glycated zwitterionic protein will thus increase its anionic characteristics. As a result, these macromolecules will be recognised by the innate immune system and identified as originating from infection or cell damage (sterile inflammation). Many proteins in the body exist to non-specifically target these anionic macromolecules and rely heavily on positively charged (cationic) binding-sites to produce a relatively non-specific interaction as the first step in the body's response. Proteins involved in this innate immunity are collectively referred to as damage associated molecular pattern molecules or pathogen associated molecular pattern molecules. A crucial player in this process is RAGE (Receptor for Advanced Glycation End products). RAGE plays a central role in the inflammatory response and on ligand binding stimulates many aspects of inflammation including the production of the key inflammatory mediator NF-κB, and the subsequent production of inflammatory cytokines. This process has the potential to show a positive feedback loop resulting in a dramatic response within the tissue. We propose that protein glycation primes the inflammatory system by generating negatively charged surfaces so that when a SARS-Cov-2 infection occurs within the lung the further release of negatively-charged macromolecules due to cell damage results in a potentially catastrophic inflammatory response resulting in the cytokine storm associated with COVID-19 morbidity and mortality. That part of the population who do not suffer from inflammatory priming (Phase 1), such as the young and the non-obese, should not be subjected to the catastrophic inflammatory response seen in others (Phase 2). This hypothesis further highlights the need for improved dietary intake to minimise the inflammatory priming resulting from poor glycaemic control.
Possible influence of neurosteroids in the anxiolytic effects of alpha-casozepine.
Manna SSS
Med Hypotheses · 2021 Oct · PMID 34392107 · Publisher ↗
Alpha-casozepine (α CZP), a tryptic hydrolysate of milk casein is a decapeptide shown to promote sleep and produce anxiolytic or anticonvulsant activity. Intriguingly, studies indicate structural similarities to benzodia...
Alpha-casozepine (α CZP), a tryptic hydrolysate of milk casein is a decapeptide shown to promote sleep and produce anxiolytic or anticonvulsant activity. Intriguingly, studies indicate structural similarities to benzodiazepine (BZD)-like molecules (e.g., diazepam), resulting in positive modulation of γ-aminobutyric acid A type (GABA) receptors. However, some unexplained anomalous behaviour of α-CZP includes 1) 1000 times less affinity for BZD site on GABA receptor in vitro conditions, whereas in vivo it showed 10-fold increased affinity when compared to diazepam; 2) anxiolytic effects were observed only in stressed conditions and 3) unlike diazepam, it failed to exhibit dependence or habituation. Interestingly, neurosteroids like allopregnanolone or its analogues that are synthesized de novo have both genomic and non-genomic actions. The rapid nongenomic neuronal inhibition of these compounds is mediated by GABA receptors through autocrine and paracrine actions. Studies have shown that changes in the levels of neurosteroids during acute (rise) and chronic stress (decreased), consequently, altering the senetivity of GABA receptor subunits. Neurosteroids even at low concentration (nanomolar range) potentiate the response of GABA indirectly, while at higher concentrations they directly activate the receptor-channel complex. Interestingly, coadministration of neurosteroids and BZPs has shown not only to prevent the development of tolerance of BZP and augmented recovery from BZP withdrawal anxiety and hyperactivity in mice. The combination also produced synergetic anxiolytic effects. Taken together, the evidence suggests possible implications of neurosteroids in the actions of CZP via BZD receptors. The present hypothesis brings out the possible role of neurosteroids and the various factors that might participate in CZP-induce anxiolytic effects.
The use of negative oxygen ion clusters [O(HO)] and bicarbonate ions [HCO] as the supportive treatment of COVID-19 infections: A possibility.
Badhe RV, Nipate SS
Med Hypotheses · 2021 Sep · PMID 34390895 · Full text
The COVID-19 or novel coronavirus SARS-CoV-2 pandemic is challenging worldwide healthcare system and severely affecting global economy. Furious efforts to end the pandemic including prevention of spread of SARS-CoV-2, us...
The COVID-19 or novel coronavirus SARS-CoV-2 pandemic is challenging worldwide healthcare system and severely affecting global economy. Furious efforts to end the pandemic including prevention of spread of SARS-CoV-2, use of antiviral drugs, symptomatic treatments and vaccination are underway. But there are no effective treatments available to save the dying patient in stage 2 (pulmonary) and stage 3 (hyperinflammation) of the infection. The detailed genetic and phenotypical analysis of SARS-CoV-2 revealed that the spike protein (S1) has increased positive charges (compared to SARS-CoV) on them and are responsible for attachment to human angiotensin-converting enzyme 2 (ACE2) receptor and infection by the virus. In addition, it was also reported that the inflammation in the tissue rendered the lung environment more acidic supporting the fusion of SARS-CoV-2 with the cells. We hypothesize that the intermittent use of the oxygen ionizer generating negative oxygen ion clusters [O(HO)] and sodium bicarbonate nebulizer (generating HCO); when connected to ventilator inlet or oxygen concentrator will neutralize the spike protein of the virus in respiratory tract and lungs and change the lung environment to neutral/alkaline condition respectively facilitating improved oxygen pressure in blood. These physical changes can effectively reduce the viral burden and help the patient recover from the infection faster.
Nerve plane: An optimal surgical plane for laparoscopic rectal cancer surgery?
Li K, He X, Tong S … +1 more , Zheng Y
Med Hypotheses · 2021 Sep · PMID 34388537 · Publisher ↗
Radical resection for rectal cancer with total mesorectal excision has been widely recognized in mid-low rectal cancer. Although such surgery reduced the tumor recurrence rate and improved the survival rate of patients,...
Radical resection for rectal cancer with total mesorectal excision has been widely recognized in mid-low rectal cancer. Although such surgery reduced the tumor recurrence rate and improved the survival rate of patients, the rate of urinary and sexual dysfunction was high after rectal cancer surgery, which might be attributed to pelvic autonomic nerve injury. The present study found that the pelvic autonomic nerves never exist alone. These are always surrounded by tiny capillaries and adipose tissue and covered by a thin layer of membranous tissue, leading to a continuous plane that should be preserved pelvic autonomic nerve from thermal damage, ischemic injury, nerve stretching, and chemical factors produced by local inflammatory effects. However, the completeness of the continuous plane is easily damaged intraoperatively in routine total mesorectal excision in rectal cancer. Postoperative urinary and sexual dysfunction might be closely associated with the injury of continuous plane. Therefore, the continuous plane should be protected and considered as the optimal surgical plane for rectal cancer surgery.
Supportive therapy during COVID-19: The proposed mechanism of short-chain fatty acids to prevent cytokine storm and multi-organ failure.
Jardou M, Lawson R
Med Hypotheses · 2021 Sep · PMID 34385045 · Full text
The world is currently facing the COVID-19 pandemic that is taking a heavy toll on several countries. While many infected patients have a good prognosis, in some cases the progression can be serious and even lead to deat...
The world is currently facing the COVID-19 pandemic that is taking a heavy toll on several countries. While many infected patients have a good prognosis, in some cases the progression can be serious and even lead to death. The commonly seen complications are a cytokine storm and multi-organ failure that require intensive care. The mortality of critically ill patients depends on age, sex, immune state or co-morbidities. There is an urgent need to discover a biomarker to identify early on patients at risk of developing serious complications and to find an effective treatment that could prevent disease progression and critical states. Recent investigations have pointed to the possible contribution of intestinal dysbiosis to the pathophysiology of COVID-19. Herein, we hypothesize that butyrate, a short-chain fatty acid initially produced by the gut microbiota, could be administered as supportive therapy to prevent immune system activation and disease progression.
Radiation exposure and mitochondrial insufficiency in chronic fatigue and immune dysfunction syndrome.
Rusin A, Li M, Cocchetto A … +2 more , Seymour C, Mothersill C
Med Hypotheses · 2021 Sep · PMID 34358921 · Publisher ↗
Chronic fatigue and Immune Dysfunction Syndrome (CFIDS) is a heterogeneous disease that may be promoted by various environmental stressors, including viral infection, toxin uptake, and ionizing radiation exposure. Previo...
Chronic fatigue and Immune Dysfunction Syndrome (CFIDS) is a heterogeneous disease that may be promoted by various environmental stressors, including viral infection, toxin uptake, and ionizing radiation exposure. Previous studies have identified mitochondrial dysfunction in CFIDS patients, including modulation of mitochondrial respiratory chain activity, deletions in the mitochondrial genome, and upregulation of reactive oxygen species (ROS). This paper focuses on radiation effects and hypothesizes that CFIDS is primarily caused by stressor-induced mitochondrial metabolic insufficiency, which results in decreased energy production and anabolic metabolites required for normal cellular metabolism. Furthermore, tissues neighbouring or distant from directly perturbed tissues compensate for this dysfunction, which causes symptoms associated with CFIDS. This hypothesis is justified by reviewing the links between radiation exposure and CFIDS, cancer, immune dysfunction, and induction of oxidative stress. Moreover, the relevance of mitochondria in cellular responses to radiation and metabolism are discussed and putative mitochondrial biomarkers for CFIDS are introduced. Implications for diagnosis are then described, including a potential urine assay and PCR test for mitochondrial genome mutations. Finally, future research needs are offered with an emphasis on where rapid progress may be made to assist the afflicted.
Barrier resuscitation by lay rescuers during COVID-19 pandemic.
Lederer W, Isser M
Med Hypotheses · 2021 Sep · PMID 34358920 · Full text
Aerosols generated from chest compressions and ventilation attempts in patients with cardiac arrest may cause airborne infections. Accordingly, the interim international resuscitation guidelines have restricted basic lif...
Aerosols generated from chest compressions and ventilation attempts in patients with cardiac arrest may cause airborne infections. Accordingly, the interim international resuscitation guidelines have restricted basic life support by lay rescuers to compression only and the use of an automated external defibrillator during the COVID-19 pandemic. Although these measures may diminish the risk of infection for laypersons, the missing respiratory support can be detrimental for patients with hypoxia-related cardiac arrest. To overcome this shortcoming we want to introduce a special tool that allows ventilation during barrier resuscitation by laypersons. We hypothesize that the application of a device made of a polyvinyl chloride shield with a centrally installed S-shaped ventilation pipe with integrated filter can provide adequate ventilation while concurrently protecting patient and rescuer from airborne agents. Aerosols from air leakage are removed by adhesion and drainage below the barrier. No specific training other than basic life support is needed. We suggest that a tool of this kind be considered essential equipment and stored together with disposable gloves in public access locations.
Combination therapy of curcumin and fecal microbiota transplant: Potential treatment of polycystic ovarian syndrome.
Corrie L, Gulati M, Vishwas S … +4 more , Kapoor B, Singh SK, Awasthi A, Khursheed R
Med Hypotheses · 2021 Sep · PMID 34332209 · Publisher ↗
Polycystic ovarian syndrome (PCOS) is a combination of various symptoms like anovulation, hirsutism, chronic amenorrhea, infertility, obesity and polycystic ovaries. It affects over 7 million women worldwide. The current...
Polycystic ovarian syndrome (PCOS) is a combination of various symptoms like anovulation, hirsutism, chronic amenorrhea, infertility, obesity and polycystic ovaries. It affects over 7 million women worldwide. The current strategy to treat this disorder is based on the use of drugs that provide symptomatic relief. Most of these, however, exhibit numerous side effects and are not able to ameliorate all the signs and symptoms of PCOS. As dysbiosis is considered as one of the prime underlying causes of PCOS, restoration of eubiosis was considered as a plausible way to treat it. Bacteriotherpeutics like probiotics, synbiotics and even fecal microbiota transplant (FMT) have shown considerable effectiveness in PCOS. Of these baceteriotherapeutic options, FMT is considered to be the most holistic as it encompasses the bacteriome, virome, fungome, archaeome and even parasitome while both probiotics as well as synbiotics mainly comprise bacteria. Repeated FMT, however, is not a pragmatic option because of its inconvenience, lack of standardization, involved risk and scepticism amongst patients and physicians. If the eubiosis ushered by FMT is sustained for a long time, the repeated administrations of FMT can be avoided and maintenance therapy with any agent that can maintain the eubiotic condition can be adopted. Role of curcumin on gut microbiota is widely known. It is largely attributed to the ability of certain microbes to consume polyphenols as substrates and its positive effect on bacterial consumption of nutrients such as sugars. Based on various mechanisms and studies, a new hypothesis is being proposed wherein FMT and curcumin combination is predicted to be an effective and sustained treatment of PCOS with much lower rates of remission.
On the prevention and treatment of Alzheimer's disease: Control the promoters and look beyond the brain.
Goldstein MR, Cheslock M
Med Hypotheses · 2021 Sep · PMID 34315048 · Publisher ↗
Alzheimer's disease (AD) is a progressive incurable neurodegenerative disease of the brain afflicting a third of the population aged 85 and older. Pathologic hallmarks include extracellular plaques of amyloid-beta (Aß),...
Alzheimer's disease (AD) is a progressive incurable neurodegenerative disease of the brain afflicting a third of the population aged 85 and older. Pathologic hallmarks include extracellular plaques of amyloid-beta (Aß), intraneuronal neurofibrillary tangles of hyperphosphorylated tau protein, synaptic destruction, neuronal death, and brain atrophy. Neuroinflammation, mediated by microglia, is a central component of the disease, and is intricately connected with peripheral inflammation. The clinical manifestations include progressive memory loss and eventual death. The present treatment of AD is largely ineffective. Nearly all AD is late-onset and presents age 65 or older, and the most common genetic risk factor is carriage of an apolipoprotein (APO) E4 allele, seen in about 25% of the general population. Individuals carrying an APOE4 allele produce more Aß and clear it less efficiently from the brain throughout life. There has been accumulating pathologic and clinical evidence that microbes, particularly the herpes simplex virus (HSV), is a causative factor for AD, most notable in carriers of the APOE4 allele. Eighty percent of the adult population harbors HSV and it resides in the trigeminal ganglion in latent state throughout life, but periodically reactivates, traveling antegrade resulting in herpes labialis and traveling retrograde into the brain leading to neuroinflammation. Functioning as an antimicrobial peptide, Aß inactivates HSV and the recurring process culminates in a buildup of Aß plaque and other hallmarks of AD over time. Periodontal disease exists in 20-50% of the adult population and is also a causative factor for AD. Accordingly, bacteria causing periodontal disease and their byproducts can enter the brain directly via the trigeminal nerve or indirectly through the bloodstream, resulting in AD pathology over time. There are many other promoters of AD, particularly inflammatory conditions outside of the brain, that can be mitigated. Small trials are finally in progress testing antimicrobial drugs for the prevention and treatment of AD. In the meantime, a more proactive approach to the prevention and treatment of AD is posited, with an emphasis on prevention, since the pathologic underpinnings of the disease start decades before the clinical manifestations. Individuals can be stratified in risk categories using family history, periodontal disease presence, APOE4 carriage, and HSV IgG positivity. Moderate- and high-risk individuals can be treated safely with various preventive measures and appropriate antimicrobial agents as discussed. Importantly, the proposed treatments are concordant with the accepted practice of medicine, and if utilized, could significantly decrease AD prevalence.
TLR4 involvement in COVID-19 predicts a seasonal risk of Aspergillus superinfection: A call for vigilance.
Retzinger AC, Retzinger GS
Med Hypotheses · 2021 Sep · PMID 34280838 · Full text
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Hemorrhagic areas as a histological prognosticator in oral cancer: A novel proposition.
Sarode GS, Sarode SC, Sengupta N … +3 more , Ghone U, Sharma NK, Patil S
Med Hypotheses · 2021 Sep · PMID 34274885 · Publisher ↗
Determination of prognosis in oncology practice is a major challenge and many histological prognosticators have been applied because of the ease and simplicity of using them in day-to-day practice. Our histopathologic ob...
Determination of prognosis in oncology practice is a major challenge and many histological prognosticators have been applied because of the ease and simplicity of using them in day-to-day practice. Our histopathologic observation on 96 oral squamous cell carcinoma (OSCC) specimens revealed 34 cases associated with frank hemorrhagic areas, which were close to tumor cells. Hence, we propose that there could be a cross-talk between tumor cells and RBCs which can modulate the biological behavior of the tumor and prognosis of the patient. In the present paper, a scientific foundation is provided for this proposition. Furthermore, an experimental approach is recommended which will facilitate the identification of extracellular metabolites within the tumor microenvironment near RBCs. Such studies may pave the way for a better understanding of the clinical heterogeneity of oral cancer due to differential heme content of red blood cells (RBCs) in the tumor microenvironment (TME).
B cell receptor (BCR) guided mechanotransduction: Critical hypothesis to instruct SARS-CoV-2 specific B cells to trigger proximal signalling and antibody reshaping.
Haneef K, Ghaffar Memon A, Saleem R … +2 more , Batool F, Sadeeq M
Med Hypotheses · 2021 Aug · PMID 34271511 · Full text
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, has spread around the globe with remarkable consequences for the health of millions of people. Despite the approval of mRNA vaccines to...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, has spread around the globe with remarkable consequences for the health of millions of people. Despite the approval of mRNA vaccines to prevent the spread of infection, long-term immunity must still be monitored. Targeting and modifying virus receptor binding regions to activate B cell receptors (BCRs) is a promising way to develop long-term immunity against SARS-CoV-2. After the interaction of antigens, BCRs undergo series of signal transduction events through phosphorylation of immune receptor tyrosine activation motifs (ITAMs) to produce neutralizing antibodies against pathogens. BCRs intricate entity displays remarkable capability to translate the external mechanosensing cues to reshape the immune mechanism. However, potential investigations suggesting how SARS-CoV-2 specific B cells respond to mechanosensing cues remain obscure. This study proposes a sophisticated hypothesis explaining how B cells isolated from the CP of SARS-CoV-2 infected patients may undergo a triggered series of B cell activation, BCR dynamics, proximal signalling, and antibody production on PDMS-embedded in-vitro antigen-presenting structures (APCs). These studies could provide detailed insights in the future for the development of structural and therapeutic entanglements to fight against pathogens.
Highly expressed ACE-2 receptors during pregnancy: A protective factor for SARS-COV-2 infection?
Figueiro-Filho EA, Hobson SR, Farine D … +1 more , Yudin MH
Med Hypotheses · 2021 Aug · PMID 34256245 · Full text
While previous viral pandemics showed that pregnancy was a risk factor for susceptibility and adverse outcomes, current evidence is conflicting whether SARS-CoV-2 infection during pregnancy is more severe than in the gen...
While previous viral pandemics showed that pregnancy was a risk factor for susceptibility and adverse outcomes, current evidence is conflicting whether SARS-CoV-2 infection during pregnancy is more severe than in the general population, with relatively low maternal and fetal/neonatal mortality rates. SARS-CoV-2 is known to enter host cells via the ACE-2 receptors, competitively occupying their binding sites. In theory, viral invasion can lead to a reduction in available ACE-2 receptors and consequently an unbalanced regulation between the ACE-AngII-AT1 axis and the ACE-2-Ang-(1-7)-MAS axis, thus enhancing pathological vasoconstriction, fibrosis, inflammation and thrombotic processes. We hypothesize that the normal pregnant state of highly expressed ACE-2 receptors leads to higher Ang-(1-7) levels and consequently more vasodilation and anti-inflammatory response to SARS-COV-2 infection. We suggest that this up-regulation of ACE-2 receptors in human gestation may actually be clinically protective and propose a potential research line to investigate this hypothesis, which may lead to future novel therapeutics.
Demethyleneberberine: A possible treatment for Huntington's disease.
Gupta S, Khan A, Vishwas S … +8 more , Gulati M, Gurjeet Singh T, Dua K, Kumar Singh S, Najda A, Sayed AA, Almeer R, Abdel-Daim MM
Med Hypotheses · 2021 Aug · PMID 34229236 · Publisher ↗
Huntington disease (HD) is a type of neurodegenerative disease that is characterized by presence of multiple repeats (more than 36) of cytosine-adenine-guanine (CAG) trinucleotides and mutated huntingtin (mHtt). This can...
Huntington disease (HD) is a type of neurodegenerative disease that is characterized by presence of multiple repeats (more than 36) of cytosine-adenine-guanine (CAG) trinucleotides and mutated huntingtin (mHtt). This can further lead to oxidative stress, enhancement in level of ROS/RNS, mitochondrial dysfunction and neuroinflammations. Many clinical and preclinical trials have been conducted so far for the effective treatment of HD however, none of the drugs has shown complete relief. The regeneration of neurons is a very complicated process and associated with multiple pathological pathways. Hence, finding a unique solution using single drug that could act on multiple pathological pathways is really cumbersome. In the proposed hypothesis the use of demethyleneberberine (DMB) as a potential anti-HD agent has been explained. It is a metabolite of berberine and reported to act on multiple mechanistic pathways that are responsible for HD. Present article highlights new mechanistic insights through which DMB inhibits ROS/RNS, oxidative stress, mitochondrial dysfunctions and neuroinflammation such as NFκB, TNF-α, IL-6 and IL-8, cytokinin. Further its action on cellular apoptosis and neuronal cell death are also reported.
Carpal, cubital or tarsal tunnel syndrome after SARS-CoV-2 infection: A causal link?
Roncati L, Gianotti G, Gravina D … +4 more , Attolini G, Zanelli G, Rosa ND, Adani R
Med Hypotheses · 2021 Aug · PMID 34217126 · Full text
COVID-19 is a complex disease with many clinicopathological issues, including respiratory, gastrointestinal, neurological, renal, cutaneous, and coagulative ones; in addition, reactive arthritis has been reported by diff...
COVID-19 is a complex disease with many clinicopathological issues, including respiratory, gastrointestinal, neurological, renal, cutaneous, and coagulative ones; in addition, reactive arthritis has been reported by different authors. Here, we hypothesize that a peripheral microangiopathy involving nerve supply, a viral demyelination, or an immune-mediated irritating antigenic stimulus on synovial sheaths after SARS-CoV-2 infection may all induce a carpal, cubital or tarsal tunnel syndrome of variable entity in genetically predisposed subjects associated with myxoid nerve degeneration.
Glial cells have more important role in tDCS-induced brain activities rather than neurons.
Saidi M, Firoozabadi SM
Med Hypotheses · 2021 Aug · PMID 34214759 · Publisher ↗
Transcranial Direct Current Stimulation (tDCS) is a non-invasive and sub-threshold method for altering the excitability of neurons to achieve target conditions. Many clinical applications of tDCS are in progress includin...
Transcranial Direct Current Stimulation (tDCS) is a non-invasive and sub-threshold method for altering the excitability of neurons to achieve target conditions. Many clinical applications of tDCS are in progress including treatment of neurological disease. Despite the therapeutic and practical potentials of tDCS, the precise mechanism of its impact is still unclear to a large extent. The initial perspective about the effect of tDCS on synaptic plasticity was that electric stimulation of the brain degrades the threshold of neural firing, thus facilitating electrical transmission and improving conductivity between neurons and ultimately leading to changes in the processing of information. However, new results of some experimental studies have changed the initial perspective. Recently, calcium imaging has shown sudden calcium fluctuations, followed by a change in cortical metaplasticity under tDCS. These pieces of evidence pinpoint the important role of astrocytes in describing the effect of tDCS. Astrocytes are glial cells that are traditionally viewed with only a supportive and nutritional role, but recent research expresses that they are active and contribute to processing and regulating synaptic information. We hypothesize that considering astrocytes as an important player in tDCS effect instead of the direct effect on voltage membrane of neurons is closer to the reality of tDCS effect mechanism. This hypothesis is examined here based on the experimental evidence published so far, which indicates astroglia involvement in tDCS-induced activities and results of our proposed computational model.
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