Yaqinuddin, AhmedAmbia, Ayesha RahmanElgazzar, Tasnim AtefAlSaud, Maha Bint Mishari...
7页
查看更多>>摘要：COVID-19 is an airway disease that has affected -125 million people worldwide， caused by a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)， spread through respiratory droplets， direct contact， and aerosol transmission。 Although most patients presenting with absent or mild symptoms recover completely， the highest morbidity and mortality rates are seen in the elderly， and patients with comorbidities such as cardiovascular diseases， cancer， immunosuppressive diseases， diabetes， and pre-existing respiratory illnesses。 Several therapeutic strategies have been examined， but a wide-ranging therapeutic option for particularly severe cases of COVID-19 remains to be elucidated。 Considering the indications presented by COVID-19 patients who present similarly with inflammatory conditions， intravenous immunoglobulin (IVIG) administration has been examined as a possible route to reduce proinflammatory markers such as ESR， CRP and ferritin by reducing inflammation， based on its anti-inflammatory effects as indicated by utilisation of IVIG for numerous other inflammatory conditions。 Herein， summarising the recent key clinical evaluations of IVIG administration， we present our hypothesis that administration of IVIG within a specific dosage would be extremely beneficial towards reducing mortality and perhaps even the length of hospitalisation of patients exhibiting severe COVID-19 symptoms。
查看更多>>摘要：Over the past century autoimmune disease incidence has increased rapidly in (post-) industrialised， affluent societies， suggesting that changes in ecology and lifestyle are driving this development。 Epidemiological studies show that (i) 80% of autoimmune disease patients are female， (ii) autoimmune diseases co-occur more often in women， and (iii) the incidence of some autoimmune diseases is increasing faster in women than in men。 The female preponderance in autoimmunity is most pronounced between puberty and menopause， suggesting that diverging sex hormone levels during the reproductive years are implicated in autoimmune disease development。 Using an evolutionary perspective， we build on the hypotheses that female immunity is cyclical in menstruating species and that natural selection shaped the female immune system to optimise the implantation and gestation of a semi-allogeneic foetus。 We propose that cyclical immunomodulation and female immune tolerance mechanisms are currently out of balance because of a mismatch between the conditions under which they evolved and (post-)industrialised， affluent lifestyles。 We suggest that current changes in autoimmune disease prevalence may be caused by increases in lifetime exposure to cyclical immunomodulation and ovarian hormone exposure， reduced immune challenges， increased reproductive lifespan， changed reproductive patterns， and enhanced positive energy balance associated with (post-)industrialised， affluent lifestyles。 We discuss proximate mechanisms by which oestrogen and progesterone influence tolerance induction and immunomodulation， and review the effect of the menstrual cycle， pregnancy， and contraceptive use on autoimmune disease incidence and symptoms。
Zaydman, Alla M.Strokova, Elena L.Pahomova, Nataliya Y.Gusev, Arkady F....
22页
查看更多>>摘要：Adolescent idiopathic scoliosis (AIS) affects 2-3% of children。 Numerous hypotheses on etiologic/causal factors of AIS were investigated， but all failed to identify therapeutic targets and hence failed to offer a cure。 Therefore， currently there are only two options to minimize morbidity of the patients suffering AIS: bracing and spinal surgery。 From the beginning of 1960th， spinal surgery， both fusion and rod placement， became the standard of management for progressive adolescent idiopathic spine deformity。 However， spinal surgery is often associated with complications。 These circumstances motivate AIS scientific community to continue the search for new etiologic and causal factors of AIS。 While the role of the genetic factors in AIS pathogenesis was investigated intensively and universally recognized， these studies failed to nominate mutation of a particular gene or genes combination responsible for AIS development。 More recently epigenetic factors were suggested to play causal role in AIS pathogenesis。 Sharing this new approach， we investigated scoliotic vertebral growth plates removed during vertebral fusion (anterior surgery) for AIS correction。 In recent publications we showed that cells from the convex side of human scoliotic deformities undergo normal chondrogenic/osteogenic differentiation， while cells from the concave side acquire a neuronal phenotype。 Based on these facts we hypothesized that altered neural crest cell migration in early embryogenesis can be the etiological factor of AIS。 In particular， we suggested that neural crest cells failed to migrate through the anterior half of somites and became deposited in sclerotome， which in turn produced chondrogenic/osteogenic-insufficient vertebral growth plates。 To test this hypothesis we conducted experiments on chicken embryos with arrest neural crest cell migration by inhibiting expression of Paired-box 3 (Pax3) gene， a known enhancer and promoter of neural crest cells migration and differentiation。 The results showed that chicken embryos treated with Pax3 siRNA (microinjection into the neural tube， 44 h post-fertilization) progressively developed scoliotic deformity during maturation。 Therefore， this analysis suggests that although adolescent idiopathic scoliosis manifests in children around puberty， the real onset of the disease is of epigenetic nature and takes place in early embryogenesis and involves altered neural crest cells migration。 If these results confirmed and further elaborated， the hypothesis may shed new light on the etiology and pathogenesis of AIS。
Yamada, YujiroFrith, Emily M.Wong, VickieSpitz, Robert W....
6页
查看更多>>摘要：Blood flow restriction， in combination with low load/intensity exercise， has consistently been shown to increase both muscle size and strength。 In contrast， the effects of blood flow restricted exercise on cognition have not been well studied。 Therefore， the purpose of this paper is 1) to review the currently available literature investigating the impact of blood flow restricted exercise on cognition and 2) to provide some hypotheses for how blood flow restriction might provide an additive stimulus for augmenting specific cognitive domains above exercise alone。 Given the lack of research in this area， the effects of blood flow restricted exercise on cognition are still unclear。 We hypothesize that blood flow restricted exercise could potentially enhance several cognitive domains (such as attention， executive functioning， and memory) through increases in lactate production， catecholamine concentration， and PGC-1 alpha expression。 We review work that suggests that blood flow restriction is not only a beneficial strategy to improve musculoskeletal function but could also be a favorable method for enhancing multiple domains of cognition。 Nonetheless， it must be emphasized this is a hypothesis that currently has only minimal experimental support， and further investigations in the future are necessary to test the hypothesis。
Katerndahl, DavidBurge, SandraVillacampa, Maria del Pilar MontanezBecho, Johanna...
11页
查看更多>>摘要：Intimate partner violence (IPV) is a blight on society。 Our traditional understanding suggests that interventions should be straightforward， leading to predictable positive results。 However， these assumptions do not reflect the reality of IPV， which continues to frustrate physicians。 While IPV research has thoroughly described the developmental risks and impacts of IPV， the violent incident itself remains largely unstudied and poorly understood。 Although this lack of research may partially explain physician frustration and the limitations of our interventions， the greater problem may be our reliance upon the wrong paradigm in guiding our understanding。 Complexity science says that systems are globally understandable， but not completely knowable。 Our hypothesis is that IPV needs to be viewed as a complex adaptive system if we are to understand the phenomenon， identify expectations and appropriately intervene。 When viewed through the lens of complexity science， IPV becomes less knowable and predictable， suggesting that interventionists should expect variable response。 Research has indeed demonstrated that partner violence is a complex phenomenon with multiple， interdependent factors and a nonlinear trajectory。 This nonlinearity/unpredictability can impact outcomes in IPV， often more so than the frequency or severity of the violence。 Similarly， women's decision-making concerning the violence is also a nonlinear process dependent upon multiple factors and catastrophic influences。 Once recognized， complexity science offers a novel approach to explain IPV's obfuscation and resistance to predictable change。 Using the tempered expectations of a systems lens， the violent interdependencies can be clarified， the obscure causes of events can be visualized， and the temporal irregularities can be mapped。 Not only can the disruptive tipping points， system feedforward propagations， powerful attractors and discontinuities compromise reasoned intervention， but these same factors， if understood， can be harnessed to foster and magnify circumstances that enable positive change。
查看更多>>摘要：Coronavirus disease 2019 (COVID-19) is an inflammatory process with complex pathophysiology and by affecting the cardiovascular system directly or indirectly that causes life threatening cardiac injuries。 Therefore， clarifying the effects of this infection on the cardiovascular system is of importance in terms of the clinical course of the disease。 The increases in cardiac and inflammatory biomarkers in COVID-19 have been associated with poor prognosis and mortality。 However， there are no specific laboratory markers yet to assess the severity of the disease。 In this context， the combination of available biomarkers is needed to better define the clinical course of this disease。 Carbohydrate antigen 125 (CA-125) has become a remarkable marker in recent years as a result of the correlation of increasing levels in cardiovascular diseases with clinical， hemodynamic， echocardiographic parameters and its relation with mortality or re-hospitalization due to heart failure。 These findings suggest that CA-125 might be useful biomarker to identify the damage mechanisms of COVID-19， monitoring the prognosis of the disease and the course of the treatment。
Sehirli, Ahmet OzerAksoy, UmutKoca-Unsal, Revan BirkeSayiner, Serkan...
4页
查看更多>>摘要：Daily new information emerges regarding the COVID-19， infection of SARS-CoV-2， which is considered a global pandemic。 Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) are required to complete the viral invasion pathway and are present in the oral mucosa， gingiva and periodontal pocket。 Thus， increasing the likelihood of periodontitis and gingivitis caused by COVID-19。 The cytokine storm during COVID-19 similarly arises during periodontal inflammation。 Studies have reported that NOD-Like Receptor family pyrin domain-containing 3 (NLRP3) inflammasome is significant in the cytokine storm。 Recently， the course of the COVID-19 has been related to the melatonin levels in both COVID-19 and periodontal diseases。 It is known that melatonin prevents the activation of NLRP3 inflammasome。 In light of these findings， we think that melatonin treatment during COVID-19 or periodontal diseases may prevent the damage seen in periodontal tissues by preventing the activation of NLRP3 inflammasome。
查看更多>>摘要：The origin of post-ictal malfunctions is debatable。 We want to propose a novel idea of a cause of these adverse results occurring following epileptic seizures and anesthesia。 Previously we have put forward the idea that epileptic seizures termination is caused by the function of the glymphatic system in the brain。 A new measurement shows that this system can be much faster than what was estimated before。 Moreover， the method enabling this speeding was actually measured in brains of epilepsy subjects。 So， the main objection to our model is relegated。 As a possible consequence of the glymphatic process， there can be an excess cleaning of the brain's interstitial fluid。 We discuss possible adverse results of this process。 This over-cleaning (that can， to a lower extent， occur also during anesthesia) which results post-ictally from the previous overexpression of fluid materials by the neurons during their seizure operation， can reduce ingredients essential for regular neuronal functioning， thereby leading to function reduction and EEG suppression which last until those materials are replenished。 We argue that this ingredients' scarcity is the cause of post-ictal generalized EEG suppression (PGES)， of post-ictal immobility (PI) and possibly of Sudden Unexpected Death in Epilepsy Patients (SUDEP)。 Similarly， such cleaning can lead to morbidity and even mortality problems following anesthesia。 If our assumption is correct， this understanding of the process of the problems' origin can lead to a method to remedy them by judicial supplement of the lost materials。
查看更多>>摘要：SARS-CoV-2 is the causal agent of COVID-19 disease。 Currently， infection with SARS-CoV-2 has been the cause of death of over 2。5 million people globally， and there is still no effective curative treatment。 Clinically， the severe symptoms caused by COVID-19， in addition to pneumonia， are associated with the development of hyperinflammatory syndrome and thrombosis。 It is urgent to expand our understanding of the molecular mechanisms involved in the pathophysiology of COVID-19。 This article discusses the potential role that the chemokine CX3CL1 could have in the development of COVID-19-associated thrombosis。 CX3CL1 is abundantly expressed by activated endothelium and is an important regulator of many aspects of endothelial function and dysfunction， including thrombosis。 The generation of hypotheses about molecules that could be relevant in well-defined aspects of the pathophysiology of COVID-19 encourages the development of basic and clinical studies， that could help find effective and much needed treatments。
NSTL
Elsevier