Search

The aim of this paper is to provide sufficient and necessary conditions under which the linear combination $\alpha A + \beta B$, for given operators $A,B \in {\cal B}({\cal H})$ and $\alpha, \beta \in \mathbb{C}\setminus \lbrace 0 \rbrace$, is injective. Using these results, necessary and sufficient conditions for left (right) invertibility are given. Some special cases will be studied as well.

Objective This study conducted exploratory metabolomic and lipidomic profiling of plasma samples from the DASH (Dietary Approaches to Stop Hypertension) Sodium Trial to identify unique plasma biomarkers to identify salt-sensitive versus salt-resistant participants. Methods Utilizing plasma samples from the DASH-Sodium Trial, we conducted untargeted metabolomic and lipidomic profiling on plasma from salt-sensitive and salt-resistant DASH-Sodium Trial participants. Study 1 analyzed plasma from 106 salt-sensitive and 85 salt-resistant participants obtained during screening when participants consumed their regular diet. Study 2 examined paired within-participant plasma samples in 20 salt-sensitive and 20 salt-resistant participants during a high-salt and low-salt dietary intervention. To investigate differences in metabolites or lipidomes that could discriminate between salt-sensitive and salt-resistant participants or the response to a dietary sodium intervention Principal Component Analysis and Orthogonal Partial Least Square Discriminant Analysis was conducted. Differential expression analysis was performed to validate observed variance and to determine the statistical significance. Results Differential expression analysis between salt-sensitive and salt-resistant participants at screening revealed no difference in plasma metabolites or lipidomes. In contrast, three annotated plasma metabolites, tocopherol alpha, 2-ketoisocaproic acid, and citramalic acid, differed significantly between high-sodium and low-sodium dietary interventions in salt-sensitive participants. Conclusion In DASH-Sodium Trial participants on a regular diet, plasma metabolomic or lipidomic signatures were not different between salt-sensitive and salt-resistant participants. High-sodium intake was associated with changes in specific circulating metabolites in salt-sensitive participants. Further studies are needed to validate the identified metabolites as potential biomarkers that are associated with the salt sensitivity of blood pressure.

Objectives The pain related to spinal cord injury (SCI) is difficult to treat, and it is associated with significant morbidity. One aspect to improve therapeutics is to explore markers of pain and its correlates in SCI. Methods In this cross-sectional neurophysiological analysis of a randomized, double-blind controlled trial, 39 patients with SCI were included. We analyzed conditioned pain modulation (CPM) efficiency as the index of the descending pain inhibitory system, EEG variables, and clinical pain levels as measured by the Visual Analogue Scale. Regression analyses were performed to assess the relationship among EEG variables, pain levels, and CPM. Results We included 39 SCI patients, 74% reported SCI-related pain. We found that (1) less alpha and beta power are related to pain presence, (2) less alpha and beta power are associated with higher pain levels among patients with pain, (3) patients with pain have decreased peak alpha-theta frequency compared to no-pain group, (4) more relative theta power are related to the presence of low CPM efficiency, (5) higher relative theta power is associated with lower CPM efficiency. Conclusions Our results confirm and provide additional data on the relationship between decreased alpha and beta frequencies and higher pain levels. One important finding, though, was a specific and different EEG signature for the descending inhibitory pain system, as we showed that increased theta EEG power is related to decreased CPM efficiency; suggesting that, although low CPM efficiency plays a major role in pain in these participants, it does seem to be associated with a specific oscillatory brain rhythm different from clinical pain. These findings have significant implications for future research on EEG-based biomarkers of pain in post-SCI and new interventions as neurofeedback to manage pain in this population.

Despite its increased application in pancreatic ductal adenocarcinoma (PDAC), complete response to neoadjuvant therapy (NAT) is rare. Given the critical role of host immunity in regulating cancer, we sought to correlate baseline inflammatory profiles to significant response to NAT. PDAC patients receiving NAT were classified as responders (R) or nonresponders (NR) by carbohydrate antigen 19-9 response, pathologic tumor size, and lymph node status in the resected specimen. Baseline (treatment-naive) plasma was analyzed to determine levels of 27 inflammatory mediators. Logistic regression was used to correlate individual mediators with response. Network analysis and Pearson correlation maps were derived to determine baseline inflammatory mediator profiles. Forty patients (20R and 20NR) met study criteria. The R showed significantly higher overall survival (59.4 vs. 21.25 mo, P=0.002) and disease-free survival (50.97 vs. 10.60 mo, P=0.005), compared with NR. soluble interleukin-2 receptor alpha was a significant predictor of no response to NAT (P=0.045). Analysis of inflammatory profiles using the Pearson heat map analysis followed by network analysis depicted increased inflammatory network complexity in NR compared with R (1.69 vs. 1), signifying a more robust baseline inflammatory status of NR. A panel of inflammatory mediators identified by logistic regression and Fischer score analysis was used to create a potential decision tree to predict NAT response. We demonstrate that baseline inflammatory profiles are associated with response to NAT in PDAC, and that an upregulated inflammatory status is associated with a poor response to NAT. Further analysis into the role of inflammatory mediators as predictors of chemotherapy response is warranted.

Background and aims: Age-related kidney function decline is accelerated in patients with coronary heart disease (CHD). CHD and chronic kidney disease may share common etiologies. We examined plasma fatty acids (FAs) as novel biomarkers of kidney function decline after myocardial infarction (MI). Methods and results: The analysis included 2329 Dutch post–MI patients aged 60-80y (Alpha Omega Cohort) most receiving state-of-the-art medications. Plasma FAs (% total FAs) in cholesteryl esters were assessed at baseline (2002–2006), and ∼40 months change in creatinine-cystatin C based glomerular filtration rate was estimated (eGFR, in ml/min per 1.73 m2). Beta coefficients for annual eGFR change in relation to plasma linoleic acid (LA; 50.1% of total FAs in CE), omega-3 FAs (EPA + DHA; 1.7%), odd-chain FAs (C15:0 and C17:0; 0.2%), and C14:0 (0.7%) were obtained from linear regression analyses adjusted for age, sex, smoking, and alcohol intake. Mean baseline eGFR ±SD was 78.5 ± 18.7, which declined by 4.7 ± 13.1 during follow-up, or 1.4 ± 3.9 per year. The annual decline in eGFR was less in patients with higher plasma LA (adjusted beta: 0.40 for LA >47 vs ≤ 47%, 95% CI: 0.01; 0.78; p = 0.046). Associations of plasma LA with annual eGFR decline were stronger in 437 patients with diabetes (1.21, 0.24; 2.19) and in 402 patients with CKD (eGFR

Background Simvastatin, a drug for lowering serum cholesterol, has been shown to enhance bone regeneration, but few studies have qualitatively and quantitatively tested its effect when used topically in different animal models. This study aims to investigate topical administration of simvastatin as a bone regeneration inducer by testing its effect on bone formation in both long tubular bone and flat bone defect, and the mechanism involved. Methods Two animal models were used for testing the effect of simvastatin on entochondrostosis and intramembranous ossification respectively. Simvastatin of different dosages combined with poly lactic acid were implanted in extreme radial defects of 12 adult male New Zealand rabbits. Bone formation was monitored using x-ray and CT-scan and measured using x-ray scales, pixel values and spiral CT-scan for 16 weeks before being subject to histological and immunohistochemistry examination. The result was compared with that of autograft and blank control groups. Simvastatin with thrombin and fibrin sealant were implanted in calvarial defects of three Rhesus monkeys and monitored for 18 weeks. Bone formation was compared between the simvastatin and the blank control group using spiral CT-scan and histological examination. Results Both visual and quantitative measurements by x-ray and spiral CT-scan indicated significant bone formation in radial defects in all simvastatin groups and the autograft group whereas no bone formation was found in control groups. There was no significant difference in bone formation quantity between 100 ​mg simvastatin and autograft. Histological and immunohistochemistry examination indicated entochondrostosis in association with positive expression of BMP-2 and HIF-1 alpha. Spiral CT-scan and histological examination of calvarial defects of monkeys showed intramembranous ossification after simvastatin implantation. No change was found in the control group. Conclusions Topical administration of simvastatin induces entochondrostosis and intramembranous ossification by enhancing expression of BMP-2 and HIF-1 alpha. The effect of simvastatin on bone regeneration is comparable to autograft. The translational potential of this article Topical administration of simvastatin can repair bone defect in both long tubular bones and flat bones of rabbits and monkeys as effectively as autograft. Given that it is cheap, safe and already in clinical use, simvastatin might be considered as a bone regeneration inducer with great potential.

The influence of thermal cycling treatment of pseudo-α-titanium alloys OT4 and VT20 on their structural and substructural characteristics, as well as their mechanical properties is considered. A significant change in structural characteristics is established. This contributes to an increase in the strength properties of alloys with satisfactory ductility and high-temperature strength.

Response errors often cause individuals to slow down their subsequent reactions (posterror slowing [PES]). Despite intensive investigations on PES, the adaptive nature of PES remains unresolved. Here, we systematically examined this issue by manipulating response-stimulus intervals (RSIs) and examining their influence on behaviors and neural dynamics of PES. Behavioral and electrophysiological (EEG) measures were recorded while male and female human participants performed a four-choice flanker task as RSIs were manipulated. Behaviorally, PES showed maladaptive features at short RSIs but some adaptive features at long RSIs. EEG results indicated that RSIs did not affect basic error-related processing, indexed by the same pattern in the contrasts between flanker errors and correct responses on the error-related negativity (ERN), error positivity (Pe), or theta band, no matter at short or long RSIs. However, RSIs significantly influenced postflanker error attentional adjustment, motor inhibition, and sensory sensitivity. At short RSIs, compared with postcorrect trials, postflanker error trials elicited larger beta band power and smaller P1 amplitude but did not affect alpha band power, suggesting that motor processing was inhibited, and subsequent sensory processing was impaired, but no attentional adjustment occurred. By contrast, at long RSIs, postflanker error trials led to smaller alpha and beta band power but did not affect P1 amplitude, indicating that attentional adjustment but not motor inhibition occurred, and sensory processing was not impaired. Together with behavioral results, the current study demonstrated that PES was adaptive at long RSIs but maladaptive at short RSIs. We further discuss the role of central resources in the adaptability of PES. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background To date, the genetic contribution to Parkinson’s disease (PD) remains unclear. Mutations in the collagen type VI alpha 3 (COL6A3) gene were recently identified as a cause of isolated dystonia. Since PD and dystonia are closely related disorders with shared clinical and genetic characteristics, we explored the association between COL6A3 and PD in a Chinese cohort. Methods We performed genetic screening of COL6A3 in a Chinese cohort of 173 patients with sporadic PD and 200 healthy controls. We identified variants that are likely to have pathogenic effects based on: 1) a minor allele frequency of COL6A3 on PD via SKAT-O analysis. Results First, we found compound heterozygous COL6A3 gene mutations in one early-onset PD patients. Then, we explored whether COL6A3 variants contributed to increased risk of developing PD in a Chinese population. We detected 21 rare non-synonymous variants. Pathogenicity predictions identified 7 novel non-synonymous variants as likely to be pathogenic. SKAT-O analysis further revealed that an aggregate burden of variants in COL6A3 contributes to PD (p = 0.038). Conclusion An increased aggregate burden of the COL6A3 gene was detected in patients with PD.

Several measures of ecological diversity have been defined at alpha, beta, and gamma levels and less attention has been paid to characterise their ecological dominance. In this paper, we extend the concept of negative entropy (negentropy) for the measurement of ecological dominance and diversity at the three hierarchical levels of community characterization. Negentropy is a measure of energy, and gives a convex curve for binary negentropy function, whereas Shannon’s entropy gives a typical concave curve. Similarly, we have defined indices for Simpson’s and Brillouin’s dominance functions at alpha, beta and gamma levels. The results of diversity indices followed a trend for different sites as: Harike > Beas > Goindwal Sahib, while trend obtained for dominance is Goindwal Sahib > Beas > Harike. The pooled results of both indicated that Harike showed maximum ecological information by the application of Shannon’s diversity and Simpson’s inverse diversity, while results of Simpson’s diversity remain same for all sites.

The objective of our work is to study the influence of nature and the shape of the insulating materials on the mechanical performance of composites based on plaster. The study aims to increase the thermal performance of the building envelope and the same time maintains sufficient mechanical properties of the composites studied. Plaster was combined with two additives (alpha fiber and granular cork). A physical and mechanical characterization of the composites plaster-fiber alpha and plaster-cork was carried on. Authors obtained an important gain in term of lightness 27 % concerning the composite plaster-fiber alpha, however for the composite plaster-cork, the value is 34 %. Concerning the mechanical properties, authors found a decrease in flexural strength of 60 % for the plaster-cork, and an increase of 33 % for the plaster-alpha fiber. For the compressive strength, a reduce of 87 % for the plaster-alpha fiber and 80% for the plaster-cork was observed. Those finding are justified by the scanning microscopic electron tests which show the distribution of the two insulators and adhesion within the plaster matrix.

Background Combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) is emerging as a powerful technique for interrogating neural circuit dysfunction in psychiatric disorders. Here, we utilized time-frequency analyses to characterize differences in neural oscillatory dynamics between subjects with major depressive disorder (MDD) and healthy controls (HC). We further examined changes in TMS-related oscillatory power following convulsive therapy. Methods Oscillatory power was examined following TMS over the dorsolateral prefrontal and motor cortices (DLPFC and M1) in 38 MDD subjects, and 22 HCs. We further investigated how these responses changed in the MDD group following an acute course of convulsive therapy (either magnetic seizure therapy [MST, n = 24] or electroconvulsive therapy [ECT, n = 14]). Results Prior to treatment, MDD subjects exhibited increased oscillatory power within delta, theta, and alpha frequency bands with TMS-EEG over the DLPFC, but showed no differences to HCs with stimulation over M1. Following MST, DLPFC stimulation revealed attenuated baseline-normalized power in the delta and theta bands, with reductions in the delta, theta, and alpha power following ECT. TMS over M1 revealed reduced delta and theta power following ECT, with no changes observed following MST. An association was also observed between the treatment- induced change in alpha power and depression severity score. Limitations Limitations include the modest sample size, open-label MST and ECT treatment designs, and lack of a placebo condition. Conclusions These results provide evidence of alterations in TMS-related oscillatory activity in MDD, and further suggest modulation of oscillatory power following ECT and MST.

The contribution of glucagon to type 1 and type 2 diabetes has long been known, but the underlying defects in alpha cell function are not well-described. During both disease states, alpha cells respond inappropriately to stimuli, leading to dysregulated glucagon secretion, impaired glucose tolerance and hypoglycaemia. The mechanisms involved in this dysfunction are complex, but possibly include changes in alpha cell glucose-sensing, alpha cell de-differentiation, paracrine feedback, as well as alpha cell mass. However, the molecular underpinnings of alpha cell failure are still poorly understood. Recent transcriptomic analyses have identified vitamin D binding protein (DBP), encoded by GC/Gc, as an alpha cell signature gene. DBP is highly localized to the liver and alpha cells and is virtually absent from other tissues and cell types under non-pathological conditions. While the vitamin D transportation role of DBP is well characterized in the liver and circulation, its function in alpha cells remains more enigmatic. Recent work reveals that loss of DBP leads to smaller and hyperplastic alpha cells, which secrete less glucagon in response to low glucose concentration, despite vitamin D sufficiency. Alpha cells lacking DBP display impaired Ca2+ fluxes and Na+ conductance, as well as changes in glucagon granule distribution. Underlying these defects is an increase in the ratio of cytoskeletal F-actin to G-actin, highlighting a novel intracellular actin scavenging role for DBP in islets.

It is known that the alpha isoform of heat shock protein 90 (HSP90α) plays an important role in wound healing. HSP90α has a stimulating effect on migration and invasion of cells in the wound area. The role of beta isoform of HSP90 (HSP90β) in wound healing has not been fully determined. Recombinant human HSP90β expressed in E. coli has been obtained and characterized in the present work. By using an excision model of wound healing in mice, it was shown that purified recombinant human HSP90β introduced into the wound area increases the rate of wound healing by 28% compared to the control. This fact allows HSP90β to be considered a promising drug for wound healing.

Chronic obstructive pulmonary usually is subcategorized into 2 groups: chronic bronchitis and emphysema. The main cause of chronic bronchitis and emphysema is smoking; however, alpha1-antitrypsin also has been seen to cause emphysema in patients who are deficient. As symptoms and lung function decline, treatment modalities, such as lung volume reduction surgery, have been used in individuals with chronic obstructive pulmonary disease and upper lobe predominant emphysema. This article analyzes multiple published series where lung volume reduction surgery has been used in individuals with alpha1-antitrypsin deficiency and their overall outcomes.

Introduction: Triclosan [TCS] is a broad-spectrum antibacterial xenoestrogencommonly used in cosmetics, soap and various products. Exposure to Triclosancreates a disruption between reactive oxygen species (ROS) and antioxidant defenses.Oxymatrine [OMT] has potent anti-cancer, anti-fibrosis, and anti-oxidant effects. Aimof work: To study the effect of Oxymatrine on Triclosan-induced ovarian toxicity.Material and Methods: The studied rats have been divided into five groups formeasurement of total antioxidant capacity, Caspase-3, the levels of Tumor NecrosisFactor –alpha[TNF- α], Estrogen and Progesterone levels , and Liposaccharide BindingProtein [LBP] gene expression in response to Triclosan-induced ovarian toxicity by realtimePolymerase Chain Reaction [PCR]. Results: Triclolsan [TCS] caused statisticallysignificant reduction in total antioxidant capacity, with statistically significant elevationin TNF-α and Caspase-3 activity compared to the control group. Oxymatrine inducedstatistically significant elevation in total antioxidant capacity, statistically significantdecrease in the level of TNF-α, Caspase-3 activity with increased levels of Estrogenand Progesterone compared to the Triclosan group. Histopathological and electronmicroscope examination revealed vacuolar degeneration and atretic follicles in ratstreated with Triclosan, and significant improvement after Oxymatrine intake. In theTriclolsan + Oxymatrine [TCS+OMT] group, gene expression levels of TNF‑α,Caspase 3, Mitogen-activated protein kinase [MAPK], Nuclear Factor-kappa [NF-KB], and Liposaccharide Binding Protein [LBP] were statistically significant reduced comparedto the Triclolsan group. Conclusion: The use of Oxymatrine [OMT] as anti-oxidant leadto decrease in genetic expression of Tumor Necrosis Factor –alpha [TNF‑α] , Caspase 3,p38-MAPK, [NF-KB], and LBP, in Triclosan-induced ovarian injuries.

Schizophrenia is among the most debilitating neuropsychiatric disorders. However, clear neurophysiological markers that would identify at-risk individuals represent still an unknown. The aim of this study was to investigate possible alterations in the resting alpha oscillatory activity in normal population high on schizotypy trait, a physiological condition known to be severely altered in patients with schizophrenia. Direct comparison of resting-state EEG oscillatory activity between Low and High Schizotypy Group (LSG and HSG) has revealed a clear right hemisphere alteration in alpha activity of the HSG. Specifically, HSG shows a significant slowing down of right hemisphere posterior alpha frequency and an altered distribution of its amplitude, with a tendency towards a reduction in the right hemisphere in comparison to LSG. Furthermore, altered and reduced connectivity in the right fronto-parietal network within the alpha range was found in the HSG. Crucially, a trained pattern classifier based on these indices of alpha activity was able to successfully differentiate HSG from LSG on tested participants further confirming the specific importance of right hemispheric alpha activity and intrahemispheric functional connectivity. By combining alpha activity and connectivity measures with a machine learning predictive model optimized in a nested stratified cross-validation loop, current research offers a promising clinical tool able to identify individuals at-risk of developing psychosis (i.e., high schizotypy individuals).

Aim: to determine the nature of the cytokine response in patients with measles infection of varying severity, both with and without complications. Materials and methods. 65 patients who were treated in the Kharkiv regional infectious hospital from 2017 to 2019 were included in the study. All patients were divided into 4 groups depending on the severity of the disease and the presence of complications. All patients included in the study on the day of admission to the hospital and on the 10th day of hospital stay were examined for serum concentrations of pro- and anti-inflammatory cytokines as well as interferons alpha and gamma, which was carried out by solid-phase enzyme immunoassay using kits manufactured by “Vector-best” company (RF) according to the manufacturer’s instructions. Statistical processing of the obtained data was carried out using the IBM SPSS Statistics 22.0 software package. Results. The study of the levels of pro- and anti-inflammatory cytokines in dynamics showed a decrease in their levels on the 10th day of hospital stay in patients who did not have complications, and their increase in patients whose illness was accompanied by the development of pneumonia. Levels of INFα and INFγ in dynamics increased in all groups of patients. Significant changes in relation to the control group in the ratio of pro- and anti-inflammatory cytokines in the dynamics were observed only in patients with a dissociative type of cytokine response. In patients of this group on the 1st and 10th days of hospital stay the ratio index of IL-6/IL-10 was shifted towards a significant predominance of proinflammatory cytokines. Conclusions. The study demonstrates the presence of three possible types of cytokine response in patients with measles infection of varying severity: normoreactive, dissociative and hyporeactive. Each type was typical to a specific group of patients and influenced the clinical course of the disease and the development of complications, which is associated with the dynamics of increasing levels of pro- and anti-inflammatory cytokines and increasing levels of INFα and INFγ. The dynamics of increase in levels of these factors in severe disease is lower than in moderate disease. Taking into account the obtained data it can be assumed that in process of anti-infectious immunity formation in response to measles infection the prevalence of the Th-1 immune response over the Th-2 response becomes important.

Since the COVID-19 pandemic alarm was made by the severe acute respiratory syndrome (SARS)-coronavirus (CoV) 2, several institutions and agencies have pursued to clarify the viral virulence and infectivity. The fast propagation of this virus leads to an unprecedented rise in the number of cases worldwide. COVID-19 virus is exceptionally contagious that spreads through droplets, respiratory secretions, and direct contact. The enveloped, single-stranded RNA virus has a specific envelop region called (S) region encoding (S protein) that specifically binds to the host cell receptor. Viral infection requires receptors' participation on the host cell membrane's surface, a key- step for the viral invasion of susceptible cells. Recently, the Italian alpha 1 antitrypsin Registry results showed a close geographic distribution of positive cases like the one recorded for SARS -CoV-2 infection. AAT deficient patients presented with the highest infection rates. They were giving attention to alpha 1 antitrypsin AAT's role in COVID-19 infection. Alpha 1 antitrypsin deficiency (AATD) is undoubtedly the most common genetic condition in adults. AATD is characterized by decreased serum levels or impaired AAT action, raising the risk of developing many diseases, particularly pulmonary emphysema cirrhosis of the liver. This review will discuss the main immunological properties that AAT has as a protective agent against the infection and possible therapeutic application.

To quantitatively analyze α-zone and β-zone peripapillary atrophy (PPA) in patients having early primary open-angle glaucoma (POAG) using fundus autofluorescence (FAF) in conjunction with spectral domain optical coherence tomography, colored photography and perimetry. This is an observational cross-sectional case–control study. This study included 100 eyes (54 patients) of early to moderate POAG and 100 normal eyes (50 subjects). Ophthalmological examination, OCT for the optic nerve and FAF were performed. The extent of α-PPA and β-PPA was measured. The extent of α-PPA and β-PPA as measured by FAF had higher values in POAG group as compared to control group (p values 0.003 and ≤ 0.001 for the total nasal and temporal extents, respectively). However, the nasal alpha and temporal beta zones showed more values in POAG patients as compared to normal controls (p values 0.002 and 0.024). The difference between the total extents of either zones alone was not significant. B-scan OCT was able to positively detect both zones. Detecting the alpha zone was significantly higher in the control group, while beta zone detection was significantly higher in the POAG group (p values ≤ 0.001). The sensitivity of alpha zone detection was equal using colored photographs, FAF and B-scan OCT. FAF showed superior results in estimating the beta zone extent although OCT was more accurate in the anatomical delineation of Bruch’s membrane and RPE termination. The nasal alpha and temporal beta zone extents could be taken as early indices for evaluating early glaucomatous optic neuropathy.

We report a non-consanguineous family from North-west India in which 3 siblings succumbed to a rare variant of combined immunodeficiency. All three had similar clinical and immunological profiles. However, the youngest child also developed Non-Hodgkin lymphoma in infancy. Genetic analysis revealed a previously reported variant in the T cell receptor alpha constant (TRAC) gene.

A variety of evidence supports the dominance of the right hemisphere in perceptual and visuo-spatial processing. Although growing evidence shows a strong link between alpha oscillations and the functionality of the visual system, asymmetries in alpha oscillatory patterns still need to be investigated. Converging findings indicate that the typical alpha desynchronization occurring in the transition from the eyes-closed to the eyes-open resting state might represent an index of reactivity of the visual system. Thus, investigating hemispheric asymmetries in EEG reactivity at the opening of the eyes in brain-lesioned patients may shed light on the contribution of specific cortical sites and each hemisphere in regulating the oscillatory patterns reflecting the functionality of the visual system. To this aim, EEG signal was recorded during eyes-closed and eyes-open resting state in hemianopic patients with posterior left or right lesions, patients without hemianopia with anterior lesions and healthy controls. Hemianopics with both left and right posterior lesions showed a reduced alpha reactivity at the opening of the eyes, suggesting that posterior cortices have a pivotal role in the functionality of alpha oscillations. However, right-lesioned hemianopics showed a greater dysfunction, demonstrated by a reactivity reduction more distributed over the scalp, compared to left-lesioned hemianopics. Moreover, they also revealed impaired reactivity in the theta range. This favors the hypothesis of a specialized role of the right hemisphere in orchestrating oscillatory patterns, both coordinating widespread alpha oscillatory activity and organizing focal processing in the theta range, to support visual processing at the opening of the eyes.

This study sought to determine whether chronic exposure to khat (Catha Edulis, Forsk) increases the vulnerability to the toxic effects of manganese (Mn2+), when co-exposed. Three (3)-week-old forty (40) Swiss albino mice were randomly divided into four groups (n = 10). The various groups received khat and manganese separately or both. The experiment was conducted for 132 days to mimic chronic exposure to khat, with manganese administration in the last twelve days. Khat-induced neurological deficits were markedly pronounced on co-exposure with manganese. Notably, deficits in motor performance, touch escape and aggression were deepened by manganese. Co-exposure (khat + Mn2+) induced more profound changes in hematological indices such as suppression of RBCs, low hematocrit and hemoglobin levels. Manganese enhanced khat-induced depletion of a very powerful antioxidant, glutathione (GSH) in the brain, liver, heart and lung tissues. Exposure to khat and/or manganese led to significant elevations in the pro-inflammatory cytokines—tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-ϒ), with a concomitant suppression of the anti-inflammatory cytokine and interleukin 10 (IL-10). Similarly, there was enhanced suppression of IL-10 following co-exposure (khat + Mn). Khat-induced hepatotoxicity and nephrotoxicity were exacerbated by co-exposure. In conclusion, acute exposure to manganese appears to aggravate neurological deficits and other multiple organ toxicities driven by chronic exposure to khat.

Objective Astatine (211At) is a promising alpha emitter as an alternative to iodine (131I). We are preparing the first-in-human (FIH) clinical trial of targeted alpha therapy for differentiated thyroid cancer in consultation with Pharmaceuticals and Medical Devices Agency. Here, we performed an extended single-dose toxicity examination under a reliability standard, as a preclinical safety assessment of [211At]NaAt to determine the FIH dose. Methods [211At]NaAt solution was injected into normal 6-week-old mice (male (n = 50) and female (n = 50), body weight: male 33.2 ± 1.7 g, female 27.3 ± 1.5 g), which were then divided into four groups: 5 MBq/kg (n = 20), 20 MBq/kg (n = 20), 50 MBq/kg (n = 30), saline control (n = 30). The mice were followed up for 5 days (primary evaluation point for acute toxicity: n = 80) or 14 days (n = 20: evaluation point for recovery) to monitor general condition and body weight change. At the end of the observation period, necropsy, blood test, organ weight measurement, and histopathological examination were performed. For body weight, blood test, and organ weight, statistical analyses were performed to compare data between the control and injected groups. Results No abnormal findings were observed in the general condition of mice. In the 50 MBq/kg group, males (days 3 and 5) showed a significant decrease in body weight compared with the control. However, necropsy did not differ significantly beyond the range of spontaneous lesions. In the blood test, males (50 MBq/kg) and females (50 MBq/kg) showed a decrease in white blood cell and platelet counts on day 5, and recovery on day 14. In the testis, a considerable weight decrease was observed on day 14 (50 MBq/kg), and multinucleated giant cells were observed in all mice, indicating a significant change related to the administration of [211At]NaAt. Conclusions In the extended single-dose toxicity study of [211At]NaAt, administration of high doses resulted in weight loss, transient bone marrow suppression, and pathological changes in the testis, which require consideration in the FIH clinical trial.

In this manuscript, we initiate the concept of rectangular $\alpha$-$G$-admissible mappings with respect to $\beta$ and we consider related type contractions in the setting of $G$-metric spaces. We provide some fixed point results. Also, some examples are given to support the obtained results.

In this paper, we will continue our investigation on the new recently introduced $(\alpha, \beta)$-metric $F=\beta+\frac{a\alpha^{2}+\beta^{2}}{\alpha}$ in \cite{Pis}; where $\alpha$ is a Riemannian metric; $\beta$ is a 1-form, and $a\in \left(\frac{1}{4},+\infty\right)$ is a real positive scalar. We will investigate the deformation of this metric, and we will investigate its properties.

Our aim in this work is to prove an analogue of Titchmarsh’s theorem [19, Theorem 84] and Younis’s theorem [20, Theorem 3.3] on the image under the q-Dunkl transform of a class functions satisfying the q-Dunkl–Lipschitz condition in the space $$L^{p}_{q,\alpha }({\mathbb {R}}_{q},|x|^{2\alpha +1}d_{q}x)$$ , where $$1

Early diagnosis of the neurodegenerative disorder Parkinson’s disease (PD) and Scan without Evidence of Dopaminergic Deficit (SWEDD) is essential for effective patient management in neurodisorders,...

Currently, the main method of treatment for hemophilia A is replacement therapy with drugs of blood coagulation factors VIII (FVIII). As a result of the development of new production technologies, recombinant FVIII are increasingly used for the treatment of hemophilia A. The justification for the use of new drugs in pediatric clinical practice requires careful preparation and clinical research studies of their efficacy and safety. The aim of this study was to evaluate the efficacy, safety and pharmacokinetics (PK) of domestic B-domain deleted recombinant factor VIII of Moroctocog alpha (Octofactor, GENERIUM JSC) in a cohort of children with hemophilia A aged 6 to 12 years in the framework of phase III clinical study of moroktocoga alpha in children 2 to 12 years old with hemophilia A. Materials and methods of the research: the age cohort of 6 to 12 years olds of an open multicenter prospective noncomparative study included 27 male children with severe hemophilia A (mean age 8,3±1,9 years). The study was carried out sequentially in 2 stages. Stage I included the study of PK parameters in 22 patients after a single study drug dose of 50 IU/kg. At stage II, the efficacy and safety of the drug was assessed in patients of stage I, as well as in additionally included 5 patients who received the study drug dose of 30±10 IU/kg per day every 2–3 days for 22±1 weeks of treatment. To assess the efficacy, we analyzed the incidence of spontaneous bleeding that occurred within 48–72 h after drug administration; the number of injections and the dose of FVIII used for prophylaxis, as well as for treatment on demand of one episode of bleeding, taking into account its severity; number of patients with severe hemophilia A with residual FVIII activity >/=1% 48–72 h after drug administration; the investigator's overall assessment of response to therapy on the acute hemarthrosis response scale. The main indicators for the analysis of PK properties were the area under the «concentration-time» curve, the half-life, the elimination constant, the increase in activity, and the degree of recovery of activity. To assess safety, the frequency of formation of an inhibitor to FVIII, the dynamics of vital and laboratory parameters, the frequency and characteristics of adverse events (AEs) associated with the administration of the drug were taken into account. Results: the area under the FVIII-time activity curve in the region of 0–48 h (AUC0-48) and with exponential extrapolation to infinity (AUC0-inf) was 731,82±264,94%*h and 756,11±270,16%*h, respectively. The half-life (T1/2) was 10,32±2,27 hours. In the examined age group, 78 bleeding were recorded, of which only 27 (35%) were spontaneous, including 24 (30%) episodes that occurred during 48–72 hours after the administration of drug under investigation. Haemorrhage within 48–72 hours after administration of the Octofactor drug was absent or was observed rarely (1–3 times) against the background of prophylactic treatment in most patients (88%), the median number of bleeding within 48–72 hours after administration of the study drug was 2 episodes per observation period. The proportion of spontaneous bleeding was the smallest in patients receiving a single prophylactic doses of the study drug 2000–3000 IU (7% of all bleeding), the largest proportion of spontaneous bleeding was observed in patients receiving a single prophylactic doses of the study drug 1000–2000 IU (70% of bleeding). The average single dose of Octofactor for preventive treatment was 1290,4±458,6 IU or 39,12±7,79 IU/kg, for on-demand treatment – 1641,7±722,4 IU per single injection. Of the 78 reported bleeding episodes, 68 (87%) required the study drug administration for relief, while the remaining 10 bleedings were selfcontained. On average, to stop bleeding, it took 1,5±0,8 injections of the drug on demand, median doses were 1 [1; 2], and average doses were 2434,3±1501,7 IU. During the study, 37 AEs were recorded in 15 (56%) patients. At the same time, 36 AEs (97%) were not associated with the drug under investigation, and one AE (allergic reaction), according to the researchers, was associated with the use of the drug. Thus, the analysis of data indicates the efficacy and safety of the Octofactor drug both the prophylactic treatment and treatment of on-demand bleeding in 6 to 12 year old patients with severe hemophilia A.

Long noncoding RNA (lncRNA) Cancer Susceptibility 2 (CASC2) has been proved to contribute to the development of cancers. However, the mechanism behind the action of CASC2 in thyroid cancer is not quite clear. We demonstrated that CASC2 was downregulated in thyroid cancer. We noted that CASC2 overexpression restrained the growth, migration, and invasion of thyroid cancer cells, whereas CASC2 depletion caused opposite trends. Bioinformatics analysis predicted that hypoxia inducible factor 1 subunit alpha inhibitor (FIH‐1) was potentially targeted by miR‐18a‐5p, which was confirmed by luciferase reporter assay. Upregulation of FIH‐1 abrogated the promotive effect of miR‐18a‐5p on the growth and invasion of thyroid cancer cells. In addition, CASC2 serves as a competing endogenous RNA (ceRNA) and a ''sponge'' for miR‐18a‐5p, thereby regulating the expression of FIH‐1. These data elucidated the CASC2/miR‐18a‐5p ceRNA network in thyroid cancer pathogenesis.

Objectives To investigate the role of hypoxia-inducible factor 1 alpha (HIF-1 alpha) signaling, the expression profile of M1 and M2 macrophages, and the role of the sphingosine 1-phosphate (S1P)/S1P receptor system in palatal wound healing of heterozygous HIF-1 alpha-deficient (HIF-1 alpha HET) mice. Materials and methods HIF-1 alpha HET and wild-type (WT) littermates underwent palatal tissue excision at the mid-hard palate. Histological analysis, immunostaining, real-time PCR, Western blotting (WB), and cellular migration assays were performed to analyze wound closure and macrophage infiltration. Results DMOG pretreatment showed an acceleration of palatal wound closure in WT mice. In contrast, the delayed palatal wound closure was observed in HIF-1 alpha HET mice with diminished production of Col1a1, MCP-1, and MIP-1 alpha, compared with WT mice. Decreased infiltration of M1 macrophage (F4/80(+)TNF-alpha(+), F4/80(+)iNOS(+)) and M2 macrophage (F4/80(+)Arginase-1(+), F4/80(+)CD163(+)) was observed. The numbers of F4/80(+)S1P(1)(+) macrophages of HIF-1 alpha HET wounded tissues were significantly lower compared with WT tissues. S1P treatment of bone marrow macrophages (BMMs) significantly upregulated expression of S1P(1) in WT mice compared with HIF-1 alpha HET. Phosphorylation of MAPK rapidly decreased in BMMs of HIF-1 alpha HET mice than in BMMs of WT mice by S1P stimulation. Moreover, S1P enhanced HIF-1 alpha expression via S1P(1) receptors to affect macrophage migration. Conclusions HIF-1 alpha deficiency aggravates M1 and M2 macrophage infiltration and controls macrophage motility via S1P/S1P(1) signaling. These results suggest that HIF-1 alpha signaling may contribute to the regulation of palatal wound healing.

Ovarian hypofunction is one of the reproductive disorders that occur due to a decrease in ovarian function that causes animals to not experience heat. The purpose of this study was to determine the effect of GnRH antagonist hormone interventions on ovarian hypofunction model rats by looking at the expression of alpha ERs (ERs α) and the profile of folliculogenesis in the ovaries. This study used two groups of female Wistar strain rats, aged 8-10 weeks, bodyweight 150-180 grams and each group contained 10 animals. Intervention gave control group, without cetrorelix acetate intervention (placebo aqua dest sterile), treatment group with the induction of cetrorelix acetate 0.0135 mg/kg BW for 17 days. Observation of α ERs expression in the ovary was analyzed by immunohistochemical methods, and data were analyzed using T-Test analysis (α

Goal: Idiopathic generalized epilepsy (IGE) represents generalized spike-wave discharges (GSWD) and distributed changes in thalamocortical circuit. The purpose of this study is to investigate how the ongoing alpha oscillation acts upon the local temporal dynamics and spatial hyperconnectivity in epilepsy. Methods: We evaluated the spatiotemporal regulation of alpha oscillations in epileptic state based on simultaneous EEG-fMRI recordings in 45 IGE patients. The alpha-BOLD temporal consistency, as well as the effect of alpha power windows on dynamic functional connectivity strength (dFCS) was analyzed. Then, stable synchronization networks during GSWD were constructed, and the spatial covariation with alpha-based network integration was investigated. Results: Increased temporal covariation was demonstrated between alpha power and BOLD fluctuations in thalamus and distributed cortical regions in IGE. High alpha power had inhibition effect on dFCS in healthy controls, while in epilepsy, high alpha windows arose along with the enhancement of dFCS in thalamus, caudate and some default mode network (DMN) regions. Moreover, synchronization networks in GSWD-before, GSWD-onset and GSWD-after stages were constructed, and the connectivity strength in prominent hub nodes (precuneus, thalamus) was associated with the spatially disturbed alpha-based network integration. Conclusion: The results indicated spatiotemporal regulation of alpha in epilepsy by means of the increased power and decreased coherence communication. It provided links between alpha rhythm and the altered temporal dynamics, as well as the hyperconnectivity in thalamus-default mode circuit. Significance: The combination between neural oscillations and epileptic representations may be of clinical importance in terms of seizure prediction and non-invasive interventions.

Abstract Glioblastoma is the most common and malignant primary brain tumour, with a poor prognosis. Introduction of new treatment options is critically important. The study aimed to assess the appropriateness of escalation doses and toxicity of [225Ac]Ac-DOTA-SP therapy. Material and methods A total of 21 patients (age of 43.0 ± 9.5 years), with histologically confirmed recurrent or conversion glioblastoma grade 4 following a standard therapy, have been included in the study. One to 2 intracavitary port-a-cath systems were stereotactically inserted. Patients were treated with escalation dose protocol with 10, 20 and 30 MBq per cycle totally 1–6 doses of [225Ac]Ac-DOTA-SP in 2-month intervals. Therapeutic response was monitored by clinical performance status and MRI imaging. Results Treatment was well tolerated with mostly mild temporary adverse effects (oedema, epileptic seizures, aphasia, hemiparesis) mainly in the group of patients treated with 30 MBq of [225Ac]Ac-DOTA-SP. Only one patient treated with 30 MBq revealed thrombopenia grade 3. There was no other grade 3 and 4 toxicity related to [225Ac]Ac-DOTA-treatment in all groups. The median overall survival time from the primary diagnosis (OS-d) was 35.0 months and from the diagnosis of the recurrence/conversion (OS-r/c) was 13.2 months. From the start of treatment with [225Ac]Ac-DOTA-SP, the median PFS was 2.4 months, and the OS-t was 9.0 months. There were no statistically significant differences between the investigated dose escalation groups. Conclusions Treatment of recurrent glioblastoma with [225Ac]Ac-DOTA-SP is safe and well tolerated up to 30 MBq per cycle. The escalation dose protocol showed good tolerability. Only mild temporary adverse effects were observed. No remarkable haematological, kidney and liver toxicity was seen.

"non-alcoholic fatty liver disease" starts with hepatic lipid accumulation and is a dangerous factor for disease development. Thus, we aimed to determine the serum levels of haptoglobin,alpha2 macroglobulin, apolipoprotein A1, gamma-glutamyl transferase, hemoglobin A1c, Total bilirubin, Triglyceride, cholesterol, low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, urea, and creatinine among patients with nonalcoholic fatty liver disease and healthy individuals. This study was carried out on 60 patients with NAFLD and 30 healthy subjects who were attending the Gastroenterology and Hepatology Teaching Hospital/Baghdad from August /2019 to March /2020. Patients data included age, sex, BMI, and abdominal ultrasound with other medical information. Serum samples were collected and then some biochemical tests were done by an Autoanalyzer, while serum apolipoprotein A1, haptoglobin, and Alpha 2maacroglobulin were measured by ELISA technique. The study found that obesity (70%) and dyslipidemia (50%) are more common in NAFLD patients than another metabolic disease such as hypertension (20%) and diabetes mellitus (type 1 and 2) (3% and 30%) respectively. Also, the results showed a significant difference among the age group (p=0.006). NAFLD subjects had a highly significant elevation (p=0.000) in the mean ± SD of BMI, FBS, HbA1c, AST, ALP, cholesterol, triglyceride, LDL, VLDL, and Alpha 2 macroglobulin compared with the healthy control. Serum ALT and total bilirubin (mean ± SD) were significantly elevated (p=0.001) in NAFLD subjects (54.28±23.05IU/L and 14.47±9.65 µmole/l respectively) when compared with the mean± SD of healthy control. In addition, the results revealed a significant elevation (P=0.027) in the mean ± SD of serum albumin in NAFLD patients when compared with mean ± SD of healthy control and a significant elevation (P=0.002)in the mean ± SD of the LDL of the NAFLD patients as compared to the healthy control. However, the results showed a highly significant decrease (P=0.000) in the mean ± SD of serum HDL, Apolipoprotein, and haptoglobin. Furthermore, the present study observed that the optimal cut-off value was ≤67.13ng/ml for haptoglobin with a sensitivity and specificity of 80% and 93.33% respectively. In addition, the results revealed that the optimal cut-off value was >257ng/ml for Alpha 2Macroglobulin with a sensitivity and specificity of 73.33% and 86.67% respectively. The study found an optimal cut-off value of ≤86 ng/ml for Apolipoprotein A1 with a sensitivity and specificity of 85% and 90% respectively.

Chronic high salt intake is well known to be linked to cause an increase in the blood pressure and one of the pathogenic effects of high salt on blood pressure is vascular functional impairment. The effect of sodium on vasculature involves an increase in the vascular resistance that could triggers a rise in the blood pressure. Sodium-induced increase in vascular resistance is primarily independent of any change in blood pressure; however, it could be an initiating factor for increase in the blood pressure. Salt induced increase in the vascular resistance involves alterations in several vasoregulatory mechanisms as evidenced in various vascular beds. A mechanism exhibiting a substantial effect on vascular function is the alpha (α1)-adrenergic system that significantly influences vascular resistance, thereby affecting peripheral vascular resistance and blood pressure. This review focused on the effects of increase dietary sodium intake on the α1-adrenergic system in renal vascular beds under normotensive and hypertensive conditions. Because the α1-adrenergic regulations of renal vascular function and renal hemodynamics affect blood pressure to a great extent, renal vascular assessment was performed. Study reports enhanced renal vascular sensitivity to α1-adrenergic agonist in high sodium normotensive and hypertensive condition, this could be due to functional alterations in the renal α1-adrenoreceptor density. This provide additional evidence on the underlying vascular pathology in salt-induced hypertension.

We examined gut microbiome (GM) profiles in relation to mammographic breast density (BD) and body mass index (BMI) in healthy postmenopausal women. Eligible women were postmenopausal, had a BMI ≤ 35 kg/m2, and had not recently taken oral/IV antibiotics. All women provided a fecal sample and information on breast cancer risk factors. Mammographic BD was classified with the American College of Radiology’s BI-RADS BD classification system. Bacterial DNA was isolated from fecal samples and the V1–V2 hypervariable regions of 16S rRNA were sequenced on the Illumina MiSeq platform. We examined associations of GM with indices of within-sample (alpha) diversity and the ratio of the two main phyla (Firmicutes and Bacteroidetes; F/B ratio) with BD and BMI. Among 69 women with BD data, 39 had low BD (BI-RADS I/II) and 30 had high BD (BI-RADS III/IV). BMI was inversely associated with BD (mean BMI = 23.8 and 28.0 in women with high and low BD, respectively, p = 1.07 × 10–5). Similar levels of GM diversity were found across weight groups according to Shannon (p = 0.83); Inverse Simpson (p = 0.97); and Chao1 (p = 0.31) indices. F/B ratio and microbiota diversity were suggestively greater in women with high vs. low BD (p = 0.35, 0.14, 0.15, and 0.17 for F/B ratio, Shannon, Inverse Simpson and Chao1, respectively). Suggestive differences observed in women with high and low BD with respect to GM alpha diversity and prevalence of specific GM taxa need to be confirmed in larger studies.

AimsThe mechanisms that drive breast cancer (BC) progression and poor outcome are not fully understood. The human heat shock protein 90 alpha family class A member 1 (HSP90α) encoded by the HSP90ΑA1 gene has a vital role in cellular responses to stress and is implicated in the development and progression of many cancers. The current study aims to explore the clinical and prognostic importance of HSP90α in BC.MethodsThe Molecular Taxonomy of Breast Cancer International Consortium (n=1980); The Cancer Genome Atlas (n=1097) and the Breast Cancer Gene-Expression Miner (Bc-GenExMiner) BC datasets (n=5056) were used to evaluate HSP90ΑA1 mRNA expression. HSP90α protein expression was further assessed using immunohistochemistry in a large (n=911) well-characterised BC series. The association between mRNA and protein expressions with other clinicopathological parameters and outcome was analysed.ResultsHigh expression of HSP90ΑA1 both at the mRNA and protein levels was significantly associated with characteristics of BC poor prognosis, including high grade, lymphovascular invasion, poor Nottingham Prognostic Index and positive expression of p53 and PIK3CA. Outcome analysis revealed that high HSP90α protein expression is an independent predictor of shorter BC-specific survival.ConclusionHSP90α can be used as a potential prognostic marker in BC. Further mechanistic studies are warranted to determine the underlying molecular mechanisms mediated by HSP90α in BC.

We obtained the asymptotic equalities for the least upper bounds of the approximation of functions from the classes $$ {W}_{\beta}^r{H}^{\alpha } $$ by three-harmonic Poisson integrals in the case r + α ≤ 3 in the uniform metric.

Background Pain empathy enables a person to experience and understand other's pain state by observing others in pain condition. Such prosocial ability is deficient in many psychopathological disorders. Somatosensory alpha suppression is considered as neural correlates of pain empathy and is hypothesized as a target for enhancement of pain empathy. Researches demonstrated that alpha suppression could be enhanced by transcranial alternating current stimulation (tACS) at alpha frequency non‐invasively. Aims We applied alpha tACS over the primary somatosensory cortex of healthy subjects to investigate whether alpha tACS is able to enhance the pain empathy performance. Results The results showed that there was no difference of pain empathy performance between alpha tACS and sham tACS either when tACS was applied during the task or before task. While in the alpha tACS group, the pain empathy performance was positively correlated with empathic concern of male subjects, the sub‐component of personal trait empathy. Conclusions Alpha tACS cannot alter the empathy performance overall, but the modulation effect of alpha tACS on pain empathy is dependent on the gender and trait empathy of subjects., We tested whether alpha tACS could enhance the empathy ability, which is deficit in many psychopathological disorders such as autism and alexithymia. We did not find overall modulation effect of alpha tACS on pain empathy performance either online or offline. While the pain empathy was positively correlated with empathy concern of male subjects indicating the gender and trait empathy‐dependent characteristics of alpha tACS on pain empathy.

Occipital oscillations in the alpha band are closely related to visual perception and attention. In multiple studies, increased alpha power has been shown to reduce detection rates of hard-to-detect visual stimuli. Recent studies explain this finding by a shift in perceptual bias. Moreover, the phase of alpha oscillations prior to stimulus onset appears to be critical for the detection of visual stimuli. This is explained by a shift in cortical excitability over the course of each alpha cycle. However, prior studies often used short presentation times of visual stimuli at the perceptual threshold. Here, we use longer presentation times to elucidate whether the same mechanisms hold for the perception of salient but challenging visual stimuli presented for up to 1,500 ms. To this end, we presented participants with hard to distinguish but salient upright or tilted Gaussian gratings in a two-alternative forced choice task, while recording occipital electroencephalographic activity. Previous reports link alpha power to stimulus detection hit rates, and we found that low prestimulus power at the individual alpha frequency relates to higher perceptual accuracy. Contrary to recent findings, we neither found an influence of alpha power on criterion, nor an influence of alpha phase on perception or response speed. We argue that longer presentation times might attenuate a possible response bias, and increased excitability might sharpen the discrimination ability, thereby leading to increased perceptual accuracy and unaffected response criterion.

Objectives: To find the association of single nucleotide polymorphism of hypoxia-inducible factor-1 alpha, rs11549465 (1772 Cytosine > Thymine) with metabolic syndrome, and to compare the anthropometric and biochemical variables in different genotypes of hypoxia-inducible factor-1 alpha. Methods: The cross-sectional comparative study was conducted at the University of Health Sciences, Lahore, Pakistan, from July 2016 to April 2019, and comprised patients of metabolic syndrome selected from the Sheikh Zayed Hospital, Lahore. Healthy controls were also enrolled. Fasting venous sample was taken for the determination of study parameters. The genetic variant of hypoxia-inducible factor-1 alpha was analysed by restriction fragment length polymorphism polymerase chain reaction. Data was analysed using SPSS 22. Results: Out of 400 subjects, 200(50%) each were patients and controls. The frequency of CC genotype of hypoxia-inducible factor-1 alpha Cytosine > Thymine in patients was 166(83%) and in controls 147(73.5%); CT genotype was 34(17%) and 53(26.5%) respectively, while TT genotype was not observed. There was a significant association of the C allele and CC genotype (p=0.03) with the increased risk of metabolic syndrome (p=0.02). On comparison of study variables in the two genotypes, systolic blood pressure, anthropometric and lipid parameters were significantly higher in the wild CC genotype compared to CT in the control group (p0.05). Conclusion: Major allele C of hypoxia-inducible factor-1 alpha 1772 Cytosine > Thymine was found to be associated with increased risk of metabolic syndrome. Continuous...

Background: Dementia due to Alzheimer’s disease (AD) is a complex neurodegenerative disorder, which much of heritability remains unexplained. At the clinical level, one of the most common physiological alterations is the slowing of oscillatory brain activity, measurable by electroencephalography (EEG). Relative power (RP) at the conventional frequency bands (i.e., delta, theta, alpha, beta-1, and beta-2) can be considered as AD endophenotypes. Objective: The aim of this work is to analyze the association between sixteen genes previously related with AD: APOE, PICALM, CLU, BCHE, CETP, CR1, SLC6A3, GRIN2 β, SORL1, TOMM40, GSK3 β, UNC5C, OPRD1, NAV2, HOMER2, and IL1RAP, and the slowing of the brain activity, assessed by means of RP at the aforementioned frequency bands. Methods: An Iberian cohort of 45 elderly controls, 45 individuals with mild cognitive impairment, and 109 AD patients in the three stages of the disease was considered. Genomic information and brain activity of each subject were analyzed. Results: The slowing of brain activity was observed in carriers of risk alleles in IL1RAP (rs10212109, rs9823517, rs4687150), UNC5C (rs17024131), and NAV2 (rs1425227, rs862785) genes, regardless of the disease status and situation towards the strongest risk factors: age, sex, and APOE ɛ4 presence. Conclusion: Endophenotypes reduce the complexity of the general phenotype and genetic variants with a major effect on those specific traits may be then identified. The found associations in this work are novel and may contribute to the comprehension of AD pathogenesis, each with a different biological role, and influencing multiple factors involved in brain physiology.

Background: Human coronaviruses (CoV) are significant causes etiological factors of respiratory tract infections. There are four major subgroups of CoVs, known as alpha, beta, gamma and delta. Four types of endemic human CoVs are 229E, OC43, NL63 and HKU1. Aims and Objectives: In this retrospective study, we aimed to analyze the results of the respiratory samples of hospitalized patients by Real-Time(RT) PCR for CoVs 229E, NL63,OC43 and HKU1. Methodology: Hospitalized patients with respiratory symptoms, including nasal congestion, rhinorrhea, nasal discharge, sneezing, sore throat and cough, were tested by RT PCR between April 2018 and March 2020. We retrospectively investigated the results of 1422 respiratory samples including 1245 nasopharyngeal swabs and 177 BAL samples. Detection rate and subtypes of CoV among upper and lower respiratory samples were retrospectively analyzed from patient records. Results: Patients were between 0-93 years with a mean age of 26 years. We detected 142 (11,4%) CoVs in 1245 nasopharyngeal samples and 21 CoVs (11,9%) in 177 BAL samples. Most common CoV was OC43 (n=72, 44,2%) in overall samples. Conclusion: Although CoV infections are predominant in the winter season, they are diagnosed throughout the year with lower incidence in summer and are identified in individuals of all ages. Understanding the epidemiological and virological features of CoV infections is important to effectively control their burden.

Ongoing oscillatory neural activity before stimulus onset influences subsequent visual perception. Specifically, both the power and the phase of oscillations in the alpha-frequency band (9-13 Hz) have been reported to predict the detection of visual stimuli. Up to now, the functional mechanisms underlying pre-stimulus power and phase effects on upcoming visual percepts are debated. Here, we used magnetoencephalography recordings together with a near-threshold visual detection task to investigate the neural generators of pre-stimulus power and phase and their impact on subsequent visual-evoked responses. Pre-stimulus alpha-band power and phase opposition effects were found consistent with previous reports. Source localization suggested clearly distinct neural generators for these pre-stimulus effects: Power effects were mainly found in occipital-temporal regions, whereas phase effects also involved prefrontal areas. In order to be functionally relevant, the pre-stimulus correlates should influence post-stimulus processing. Using a trial-sorting approach, we observed that only pre-stimulus power modulated the Hits versus Misses difference in the evoked response, a well-established post-stimulus neural correlate of near-threshold perception, such that trials with stronger pre-stimulus power effect showed greater post-stimulus difference. By contrast, no influence of pre-stimulus phase effects were found. In sum, our study shows distinct generators for two pre-stimulus neural patterns predicting visual perception, and that only alpha power impacts the post-stimulus correlate of conscious access. This underlines the functional relevance of prestimulus alpha power on perceptual awareness, while questioning the role of alpha phase.