查看更多>>摘要：Statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors interfere with several pathophysiological pathways of coronavirus disease 2019 (COVID-19)。
查看更多>>摘要：Group B streptococcus (Streptococcus agalactiae) is proposed as causative agent for the development of the sporadic form of Alzheimer`s disease。 Using a fibrinogen binding protein， aggregates are formed including A-beta。 After triggering Alzheimer`s disease by the bacterium， the next down-stream events mainly follow the well known so called A-beta hypothesis。 The combination of the two hypotheses is able to explain a number of epidemiological and biochemial aspects of Alzheimer's disease。
查看更多>>摘要：Takotsubo cardiomyopathy (TTS)， known as stress cardiomyopathy， is a rare disorder characterized by acute and transient left ventricular systolic and diastolic dysfunction， often associated with a stressful， emotional or physical event。 TTS may be closely related to SARS-CoV-2 infection and the ongoing pandemic。 The enormous emotional stress caused by the pandemic and respiratory infections caused by SARS-CoV-2 could be potential triggers for TTS。 The case series cited above implicates that TTS should be considered in the differential diagnosis across the entire spectrum of myocardial injury in SARS-CoV-2 infected patients。 Myocardial damage associated with SARS-CoV-2 infection is usually attributed to sepsis， hypoxemia， coronary artery disease， and myocarditis。 We hypothesize that TTS may also play a role among these lesions。
查看更多>>摘要：SARS-CoV-2 infection generally begins in the respiratory tract where it can cause bilateral pneumonia。 The disease can evolve into acute respiratory distress syndrome and multi-organ failure， due to viral spread in the blood and an excessive inflammatory reaction including cytokine storm。 Antiviral and anti-cytokine drugs have proven to be poorly or in-effective in stopping disease progression， and mortality or serious chronic damage is common in severely ill cases。 The low efficacy of antiviral drugs is probably due to late administration， when the virus has triggered the inflammatory reaction and is no longer the main protagonist。 The relatively poor efficacy of anti-cytokine drugs is explained by the fact that they act on one or a few of the dozens of cytokines involved， and because other mediators of inflammation - reactive oxygen and nitrogen species - are not targeted。 When produced in excess， reactive species cause extensive cell and tissue damage。 The only drug known to inhibit the excessive production of reactive species and cytokines is methylene blue， a low-cost dye with antiseptic properties used effectively to treat malaria， urinary tract infections， septic shock， and methaemoglobinaemia。 We propose testing methylene blue to contrast Covid-related acute respiratory distress syndrome， but particularly suggest testing it early in Covid infections to prevent the hyper-inflammatory reaction responsible for the serious complications of the disease。
查看更多>>摘要：The prevalence of autism has increased dramatically over the last 60 years， and the cause of this increase is unclear。 In this paradigm-shift paper， I propose an explanatory paradigm for the cause of autism and its increased prevalence in the general population。 I also discuss how social and historical contexts may have influenced the evolution and manifestation of specific traits in the autism population。 These traits expand the characterization of the broader autism phenotype to include a constellation of socially valued traits， termed Broader Autism Phenotype Constellations (BAPCO)。 The frequency of these traits may have increased due to assortative mating opportunities that occurred alongside social changes in education and occupational opportunities over the last 100 years。 I propose that assortative mating can lead to both positive and negative developmental consequences affecting social and language development。 I also propose that BAPCO traits， which are not intrinsically disabilities， could interact with co-occurring conditions in a new model called the BAPCO-Disability Matrix Paradigm (BAPCO-DMAP)。 In this paradigm， autism is located at the intersection of BAPCO traits and at least one co-occurring condition。 These proposed models support the need to create a more comprehensive definition of autism that includes constellations of BAPCO traits。 The BAPCO-DMAP paves the way to testable predictions of autism prevalence and provides a framework to better understand the foundational traits of autism。 Finally， this paradigm radically redefines the broader autism phenotype with characteristics that can inform therapy and child development。
查看更多>>摘要：A ubiquitous finding on MRI in older individuals， age-related cerebral white matter hyperintensities (WMHs) are associated with cognitive decline， dementia， disability， and death。 Currently， these findings are thought to represent small infarcts secondary to lipohyalinotic arteriosclerosis。 Commonly though， the anatomic distribution of WMHs is often non-arterial， and parallel the deep venous system。 Furthermore， there is discrepant evidence for the role of conventional vascular risk factors such as hypertension， carotid atherosclerosis and diabetes for the development and progression of these。 Interventions targeting conventional vascular risk factors lack consistency in preventing the progression of WMHs。 There is evidence for age-related hemodynamic cervical venous dysfunction resulting in reduced internal jugular vein venous compliance， venous dilatation， and venous reflux。 Similarly， venous collagenosis increases with age。 Increased blood-brain barrier (BBB) permeability is also noted with aging。 Both hemodynamic venous dysfunction， venous sclerosis， and increased BBB permeability are associated with WMHs。 We propose that age-related WMHs are a sequalae of venous dysfunction。 Venous dysfunction results initially in increased transmission of venous pressures to the brain。 Subsequent BBB disruption leads to increased permeability with progression to end-stage findings of age-related WMHs。
查看更多>>摘要：Little attention has been paid to the anatomopathological factors and pathophysiologic mechanisms involved in CRC perforation。 Perforation is one of the most serious complications occurring up to 11% of the cases and may also be the first manifestation of the tumor。 Differentiation and angiogenesis have an important role in the tumor perforation mechanism。 On the one hand， a greater expression of vascularization optimizes the supply of oxygen to the tumor and thus entails a lower necrotic wall rate and thus of perforation， on the other it is associated with a lower rate of differentiation and hence to a more aggressive cancer cells。
查看更多>>摘要：Introduction: Migraine is a common neurological disease and is listed second among the most disabling health conditions worldwide。 Refractory migraine (RM) is a term used to emphasize the unresponsiveness of migraine to various treatment options， encompassing both episodic refractory and chronic refractory migraine。 In this paper we discuss various known and possible mechanisms of pharmacological refractoriness in RM， such as possible involvement of the gut microbiome， the blood-brain barrier， migraine genetics and various mechanisms of pharmacokinetic and pharmacodynamic tolerance。 Development of medication-overuse headache as a secondary disorder following migraine is also considered。 We argue that the available literature is insufficient to fully explain the mechanisms of refractoriness and we present our hypothesis。
查看更多>>摘要：Laryngopharyngeal reflux (LPR) is a prevalent disease associated with non-specific symptoms and findings。 Many gray areas persist in the pathogenesis of LPR， the diagnosis and the treatment。 Symptoms are poorly correlated with fiberoptic signs or hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring findings。 The therapeutic response remains uncertain with some resistant patients to medical or surgical treatment。 The development of LPR-symptoms and findings may be related to the refluxate of a myriad of gastroduodenal enzymes， which may modify the laryngopharyngeal and oral microbiome leading to mucosa maintenance and recovery impairments。 The diet of patient is important because it may impact the microbiome composition and some foods are known to increase the number of hypopharyngeal reflux events。 The number of hypopharyngeal reflux events may be increased by autonomic nerve dysfunction that may have an important role in the persistence of LPR-symptoms。
查看更多>>摘要：Gout is the most common inflammatory arthritis in adults。 It is causally associated with intraarticular deposition of monosodium urate crystals in hyperuricemia。 The commonest pathogenesis is renal under-excretion of urate in metabolic syndrome。 Despite being the commonest type， the exact etiology of hyperuricemia in metabolic syndrome remains unclear。 Historically， common gout was found at increased rates in affluent men， earning its name the 'disease of kings'。 It is also rare in premenopausal women。
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Elsevier