•COVID-19 is caused by a highly pathogenic coronavirus named “SARS-CoV-2”.•COVID-19 pathophysiology is primarily defined by acute respiratory illness.•Several studies have revealed a possible ...neurological component to COVID-19.•Various neurological manifestations have also been reported for SARS and MERS.•Further research into the importance of neurological manifestations in COVID-19 is needed.
Central to COVID-19 pathophysiology is an acute respiratory infection primarily manifesting as pneumonia. Two months into the COVID-19 outbreak, however, a retrospective study in China involving more than 200 participants revealed a neurological component to COVID-19 in a subset of patients. The observed symptoms, the cause of which remains unclear, included impaired consciousness, skeletal muscle injury and acute cerebrovascular disease, and appeared more frequently in severe disease. Since then, findings from several studies have hinted at various possible neurological outcomes in COVID-19 patients. Here, we review the historical association between neurological complications and highly pathological coronaviruses including SARS-CoV, MERS-CoV and SARS-CoV-2. We draw from evidence derived from past coronavirus outbreaks, noting the similarities and differences between SARS and MERS, and the current COVID-19 pandemic. We end by briefly discussing possible mechanisms by which the coronavirus impacts on the human nervous system, as well as neurology-specific considerations that arise from the repercussions of COVID-19.
Interest has been focused on differentiating anatomical, molecular, and physiological characteristics of the types of mammalian adipose tissues. White adipose tissue (WAT) and brown adipose tissue ...(BAT) are the two main forms of adipose tissue in humans. WAT functions as an endocrine organ and serves as a reservoir of energy in the form of triglycerides. The hormones released by WAT are called adipokines. BAT consists of a group of specialized cells with abundant uncoupling protein 1 (UCP1) in the inner mitochondrial membrane and also fulfills endocrine functions. Following the identification of functional (BAT) in human adults, there has been a great deal of interest in finding out how it is induced, its localization, and the mechanisms by which it regulates thermogenesis. Fibroblast growth factor 21 (FGF21) is a key regulator of the differentiation to brown adipocytes. The main mechanisms occur through enhancing UCP1 expression. In addition, following exposure to cold or exercise, FGF21 induces upregulation of local peroxisome proliferator-activated receptor gamma co-activator (PGC)-1-alfa and thus promotes thermogenesis in adipose tissue and skeletal muscle. FGF21 integrates several pathways allowing the regulation of human energy balance, glucose levels, and lipid metabolism. Such mechanisms and their clinical relevance are summarized in this review.
Obesity and stress are independently associated with decrements in neuromuscular functions. The present study examined the interplay of obesity and stress on neuromuscular fatigue and associated ...heart rate variability (HRV).
Forty-eight non-obese (18.5<body mass index (BMI)<25 kg m(-2)) and obese (30⩽BMI) adults performed repetitive handgrip exertions at 30% of their maximum strength until exhaustion in the absence and presence of a mental arithmetic stressor. Dependent measures included gold standard fatigue indicators (endurance time and rate of strength loss), perceived effort and mental demand, heart rate and temporal (RMSSD: root mean square of successive differences between N-N intervals) and spectral (LF/HF: ratio of low to high frequency) indices of HRV.
Stress negatively affected endurance time (P<0.0001) and rate of strength loss (P=0.029). In addition, significant obesity × stress interactions were found on endurance time (P=0.0073), rate of strength loss (P=0.027) and perceived effort (P=0.026), indicating that stress increased fatigability, particularly in the obese group. Both obesity (P=0.001) and stress (P=0.033) independently lowered RMSSD. Finally, stress increased LF/HF ratio (P=0.028) and the interaction of stress and obesity (P=0.008) indicated that this was augmented in the obese group.
The present study provides the first evidence that stress-related neuromuscular fatigue development is accelerated in obese individuals. In addition, the stress condition resulted in poorer HRV indices, which is indicative of autonomic dysfunction, particularly in the obese group. These findings indicate that workers are more susceptible to fatigue in high-stress work environments, particularly those with higher BMI, which can increase the risk of musculoskeletal injuries as well as cardiovascular diseases in this population.
•We report two UK cases of cerebral venous sinus thrombosis and thrombocytopenia following first dose of the Vaxzevria vaccine (previously named COVID-19 Vaccine AstraZeneca).•The proposed ...pathophysiology is a vaccine-induced immune mechanism, supported by the detection of antibodies to platelet factor-4.•Neuroimaging revealed high clot burden with large amount of parenchymal and subarachnoid haemorrhage, leading to fatal outcomes.•Management of this condition differs from usual treatment of cerebral venous sinus thrombosis,in particular avoiding heparin and platelet transfusions.
Recent reports have highlighted rare, and sometimes fatal, cases of cerebral venous sinus thrombosis (CVST) and thrombocytopenia following the Vaxzevria vaccine. An underlying immunological mechanism similar to that of spontaneous heparin-induced thrombocytopenia (HIT) is suspected, with the identification of antibodies to platelet factor-4 (PF4), but without previous heparin exposure. This unusual mechanism has significant implications for the management approach used, which differs from usual treatment of CVST. We describe the cases of two young males, who developed severe thrombocytopenia and fatal CVST following the first dose of Vaxzevria. Both presented with a headache,with subsequent rapid neurological deterioration. One patient underwent PF4 antibody testing, which was positive. Arapid vaccinationprogramme is essential in helping to control the COVID-19 pandemic. Hence, it is vital that such COVID-19 vaccine-associated events, which at this stage appear to be very rare, are viewed through this lens.However, some cases have proved fatal. Itis critical that clinicians arealerted to the emergence of such eventstofacilitate appropriate management.Patients presenting with CVST features and thrombocytopenia post-vaccination should undergoPF4 antibody testing and be managed in a similar fashion to HIT,in particular avoiding heparin and platelet transfusions.
Background Small randomized trials have demonstrated that radial access reduces access site complications compared to a femoral approach. The objective of this meta-analysis was to determine if ...radial access reduces major bleeding and as a result can reduce death and ischemic events compared to femoral access. Methods MEDLINE, EMBASE, and CENTRAL were searched from 1980 to April 2008. Relevant conference abstracts from 2005 to April 2008 were searched. Randomized trials comparing radial versus femoral access coronary angiography or intervention that reported major bleeding, death, myocardial infarction, and procedural or fluoroscopy time were included. A fixed-effects model was used with a random effects for sensitivity analysis. Results Radial access reduced major bleeding by 73% compared to femoral access (0.05% vs 2.3%, OR 0.27 95% CI 0.16, 0.45, P < .001). There was a trend for reductions in the composite of death, myocardial infarction, or stroke (2.5% vs 3.8%, OR 0.71 95% CI 0.49-1.01, P = .058) as well as death (1.2% vs 1.8% OR 0.74 95% CI 0.42-1.30, P = .29). There was a trend for higher rate of inability to the cross lesion with wire, balloon, or stent during percutaneous coronary intervention with radial access (4.7% vs 3.4% OR 1.29 95% CI 0.87, 1.94, P = .21). Radial access reduced hospital stay by 0.4 days (95% CI 0.2-0.5, P = .0001). Conclusions Radial access reduced major bleeding and there was a corresponding trend for reduction in ischemic events compared to femoral access. Large randomized trials are needed to confirm the benefit of radial access on death and ischemic events.
The current-voltage and resistive switching properties of Cu2O and CuO based resistive random access memories in metal-oxide-metal structure with Cu as bottom electrode and different metals (Ti, Ag, ...Au and Pd) as top electrodes have been investigated. The observation of resistive switching in Cu2O and its absence in CuO based devices indicates that Ohmic nature of top and bottom metal–oxide contacts is favourable for resistive switching behaviour. The rectifying metal-oxide contact results in the applied voltage drop at the rectifying contact, resulting in the absence of electric field induced structural changes which are crucial for occurrence of resistive switching. The values of switching parameters, such as, electroforming, reset, set voltages and also the resistance ratio are also observed to depend upon the work function of the electrode materials and nature of metal-oxide interface.
•Growth condition optimization of phase pure copper oxide thin film for memory devices.•Electronic, structural and optical characterization of Cu2O and CuO thin films.•Effect of top electrode on resistive memory characteristics of MOM devices.•Ohmic contact is essential for observing resistive switching in copper oxide devices.
Successful spatial navigation is thought to employ a combination of at least two strategies: the following of landmark cues and path integration. Path integration requires that the brain use the ...speed and direction of movement in a meaningful way to continuously compute the position of the animal. Indeed, the running speed of rats modulates both the firing rate of neurons and the spectral properties of low frequency, theta oscillations seen in the local field potential (LFP) of the hippocampus, a region important for spatial memory formation. Higher frequency, gamma-band LFP oscillations are usually associated with decision-making, increased attention, and improved reaction times. Here, we show that increased running speed is accompanied by large, systematic increases in the frequency of hippocampal CA1 network oscillations spanning the entire gamma range (30-120 Hz) and beyond. These speed-dependent changes in frequency are seen on both linear tracks and two-dimensional platforms, and are thus independent of the behavioral task. Synchrony between anatomically distant CA1 regions also shifts to higher gamma frequencies as running speed increases. The changes in frequency are strongly correlated with changes in the firing rates of individual interneurons, consistent with models of gamma generation. Our results suggest that as a rat runs faster, there are faster gamma frequency transitions between sequential place cell-assemblies. This may help to preserve the spatial specificity of place cells and spatial memories at vastly different running speeds.
Summary Study objective To examine the efficacy and safety of the once-daily, inhaled, long-acting muscarinic antagonist/β2 -agonist combination umeclidinium/vilanterol (UMEC/VI) compared with UMEC ...and VI monotherapies in patients with chronic obstructive pulmonary disease (COPD). Methods In this 24-week, double-blind, placebo-controlled, parallel-group study ( ClinicalTrials.gov : NCT01313650 ) eligible patients were randomised 3:3:3:2 to treatment with UMEC/VI 62.5/25 mcg, UMEC 62.5 mcg, VI 25 mcg or placebo administered once daily via dry powder inhaler ( N = 1532; intent-to-treat population). Primary endpoint was trough forced expiratory volume in one second (FEV1 ) on Day 169 (23–24 h post-dose). Additional lung-function, symptomatic, and health-related quality-of-life endpoints were assessed, including 0–6 h weighted-mean FEV1 , rescue salbutamol use, Transition Dyspnoea Index (TDI), Shortness Of Breath With Daily Activity (SOBDA) and St. George's Respiratory Questionnaire (SGRQ) scores. Safety evaluations included adverse events (AEs), vital signs, 12-lead/24-h Holter electrocardiography parameters and clinical laboratory/haematology measurements. Results All active treatments produced statistically significant improvements in trough FEV1 compared with placebo on Day 169 (0.072–0.167 L, all p < 0.001); increases with UMEC/VI 62.5/25 mcg were significantly greater than monotherapies (0.052–0.095 L, p ≤ 0.004). Improvements were observed for UMEC/VI 62.5/25 mcg vs placebo for weighted-mean FEV1 on Day 168 (0.242 L, p < 0.001), rescue salbutamol use during Weeks 1–24 (−0.8 puffs/day, p = 0.001), TDI (1.2 units, p < 0.001), SOBDA (−0.17 units, p < 0.001) and SGRQ (−5.51 units, p < 0.001) scores. No clinically-significant changes in vital signs, electrocardiography, or laboratory parameters were observed. Conclusion Once-daily UMEC/VI 62.5/25 mcg was well tolerated and provided clinically-significant improvements in lung function and symptoms in patients with COPD.
Patients with stable coronary artery disease and diabetes were randomly assigned to receive either ticagrelor plus aspirin or placebo plus aspirin. At 40 months, the incidence of the composite ...efficacy outcome of cardiovascular death, myocardial infarction, or stroke was lower with ticagrelor than with placebo; the frequency of major bleeding was higher with ticagrelor.
PDF
