Vascular endothelial growth factor ameliorated palmitate-induced cardiomyocyte injury via JNK pathway

Enhanced apoptosis of cardiomyocytes in suffering overloaded saturated fatty acids (SFAs) can result in myocardial infarction and cardiac dysfunction. The function of vascular endothelial growth factor (VEGF) in cardiomyocyte protection was not clearly described. To investigate the preservative effects of VEGF sensitization on ceramide-mediated programmed cell death of cardiomyocytes, palmitate-induced injury in H9c2 cells was established as an in vitro model. Results revealed that 0.5 mM palmitate application effectively led to debased viability and activated apoptotic factors. A significant time-dependent relation between PAL and cardiomyocyte injury was observed. The apoptosis rate was increased greatly after 16 h of treatment with 0.5 mM PAL. In addition, cell viability was restored by VEGF overexpression during treatment with 0.5 mM PAL. Reduced apoptosis rate and expression of caspase 3, Bax, and NF-κB p65 were observed in this process, while boosted Bcl-2, p-JNK/JNK expression and activity of caspase 3 were checked. However, p-ERK/ERK levels did not exhibit a significant change. These findings indicated the protective effects of VEGF in confronting the ceramide-induced cardiomyocyte apoptosis, and would devote therapeutic targets for cardiovascular safeguard in dealing with fatty acid stress.

Clinical Profile of Alcoholic Liver Disease in Saveetha Medical College and Hospital and Its Association with Type, Amount and duration of Alcohol Consumption

Introduction: Alcoholic liver disease is a caused as a result of overconsuming alcohol that damages the liver, leading to inflammation, and scarring. It is often fatal with mortality and morbidity worldwide. Many studies in various countries show contradictory results about the role of amount, type and duration of alcohol exposure in determining the risk to develop ALD. This study aims to evaluate clinical profile of ALD in south Indian population and to correlation of disease severity with alcohol intake. Material and Methods: A total of 50 patients of ALD were evaluated to correlate their clinical findings, biochemical parameters, prognostic markers (Discriminant function [DF] score, Model for end-stage liver disease [MELD] score and Child-Pugh score) and with their alcohol intake data in form of type, amount and duration of alcohol intake. Results: Hepatic encephalopathy, neutrophil to lymphocyte ratio (NLR) and all three prognostic scores showed a dose-dependent relation with the amount of alcohol intake (p <0.05). The results showed that the duration of alcohol had a positive impact on the results. NLR correlates well with all prognostic markers (p <0.05 for NLR's Spearman correlation with DF score and Child-Pugh Score), more so with MELD score (p <0.0001); and complications like hepatic encephalopathy and hepato-renal syndrome. Conclusion: In this study we conclude that there is significant dose dependent relation of ALD along with its complications, prognostic markers and NLR with the amount, type and duration of alcohol consumption. Although the type of alcohol consumption didn’t have much influence on the results, amount of intake had a correlation with NLR.

Neck Chamber Technique Revisited: Low-Noise Device Delivering Negative and Positive Pressure and Enabling Concomitant Carotid Artery Imaging With Ultrasonography

Background and Objectives: Recently, novel noiseless device for the assessment of baroreceptor function with the neck suction (NS) has been presented. In this study, we present another in-house approach to the variable-pressure neck chamber method. Our device offers further critical improvements. First, it enables delivery of negative (NS) as well as positive pressure (neck pressurizing, NP) in a noiseless manner. Second, we used small, 3D-printed cups positioned over the carotid sinuses instead of cumbersome neck collar to improve subject comfort and to test feasibility of tracking the pressure-induced changes in carotid artery with ultrasonography.Methods: Five healthy, non-smoking, normal-weight subjects aged 29 ± 3 years (mean ± SD) volunteered for the study. Heart rate (HR, bpm) and mean arterial pressure (MAP, mmHg) responses to short, 7-s long episodes of NS and NP were recorded. Each trial consisted of 12 episodes of variable-pressure: six episodes of NS (suction ranging between -10 and -80 mmHg) and six episodes of NP (pressure ranging between + 10 and + 80 mmHg). Carotid artery sonography was performed during the NS and NP in four subjects, on another occasion.Results: The variable-pressure episodes resulted consistently in the expected pattern of hemodynamic alterations: HR and MAP increases or decreases following the NP and NS, respectively, as evidenced by the coefficient of determination (R2) of ≥0.78 for the carotid-HR response curve (for all five participants) and the carotid-MAP response curve (for four out of five participants; the curve cannot be calculated for one subject). We found a linear, dose-dependent relation between the applied pressure and the systolic-diastolic difference in carotid artery diameter.Conclusion: The novel device enables noiseless stimulation and unloading of the carotid baroreceptors with the negative and positive pressure, respectively, applied on the subject’s neck via small, asymmetric and one-side flattened, 3D-printed cups. The unique design of the cups enables concomitant visualizing of the carotid artery during the NS or NP administration, and thereby direct monitoring of the intensity of mechanical stimulus targeting the carotid baroreceptors.

Immunogenicity and Safety Analysis of Inactivated Virus Vaccine against SARS-CoV-2: A Systematic Review of Phase 1/2 Clinical Trials

Introduction: The lingering Severe Acute Respiratory System-Coronavirus-2 (SARS-CoV-2) pandemic worldwide has called scientists to accelerate vaccine production and reduce the spread of the virus. The inactivated virus vaccine has been administered widely due to its potency. Following its recent public use, we aim to summarize the efficacy and safety of the inactivated vaccine, especially following Indonesia’s settlement on the SinoVac vaccine. Materials and Methods: A systematic review was performed, searching for randomized controlled trials, according to the PRISMA statement throughout four online databases with studies published up to 2 February 2021. Critical appraisal was further conducted utilizing the Cochrane Risk of Bias Tool 2.0. Results and Discussions: The search yielded six phase ½ clinical trials with a total of 3251 subjects. The outcome was obtained in seroconversion rates (%) after two doses of vaccine. Four studies administered the CoronaVac inactivated vaccine and resulted in a high seroconversion rate, ranging from 89—90%. The other two studies administered the BBV152 and BBIBP-CorV inactivated vaccine and showed similar results. Furthermore, a dose dependent relation is shown with higher doses showing higher seroconversion rates. The safety analysis reported injection site pain as an insignificant but most prevalent local adverse reaction, with other adverse reactions being mild to moderate respiratory tract infections Conclusion: The inactivated vaccine’s efficacy has been proven to stimulate antibody response regardless of dosage, period of administration, and age, with insignificant adverse effects. Further phase 3 clinical trials and widespread administration with the help of non-governmental and medical student organizations are recommended

Disaggregating between- and within-person relations for depression and burnout symptoms with cumulative hair cortisol and endocannabinoid concentrations: A multilevel analysis of four annual assessment waves

Background: The endocannabinoid system (ECS) is increasingly being recognized as key regulatory system coupled with the glucocorticoid system implicated in the pathophysiology of stress-related mental disorders. However, prior studies examining the ECS in depression or burnout have been inconclusive, of small sample size or of cross-sectional nature limiting interpretations of causal inferences or time-dependent effects.Methods: In a prospective community based cohort study including 128 individuals (women: 108), depression (PHQ-9) and burnout symptoms (MBI-GS) as well as hair cortisol and endocannabinoids were measured annually over four years. Cortisol, arachidonylethanolamide (AEA) and 2-arachidonyl-sn-glycerol/1-arachidonyl-sn-glycerol (2-AG/1-AG) were extracted from 3 cm hair segments reflecting cumulative concentrations of the last 3 months prior hair sampling.Results: Cross sectional group comparisons at baseline revealed reduced cortisol and AEA levels in the group with a positive major depressive disorder screening compared to individuals with low depression symptomatology (both p &lt; .05). Cortisol was also reduced in the group with a positive burnout screening compared to individuals with a negative screening at baseline (p &lt; .05). Longitudinal multilevel analysis, showed for the total sample that a within-person increase in burnout symptoms was associated with a decrease in cortisol levels over time (p &lt; .05). In the male subsample, a between-person increase in AEA levels across time was associated with a decrease in depression symptoms and vice versa. However, a within-person increase of AEA levels across time was associated with an increase in depression symptoms and vice versa (both p &lt; .05). Further, a within-person increase in burnout symptoms lead to a significant increase in AEA levels in the male subsample (p &lt; .05).Conclusions: While cross-sectional analyses suggest higher depression or burnout symptomatology to be associated with reduced cortisol and AEA release, longitudinal analyses disaggregating between- and within-person effects reveal a complex pattern. A within-person increase in burnout symptoms precedes a decrease in cortisol secretion suggesting an exhaustion of the HPA axis. Between-person analysis show only for men a negative association between depression symptoms and AEA levels over time. However, within-person effects, indicate an increase in depression symptoms to preced and to follow an increase in AEA levels, suggesting a dynamic counterregulatory mechanism between the EC and depression in men differing on the between- and within-person levels. These longitudinal associations further elucidate the time and sex dependent relation between depression, burnout, glucocorticoid and endocannabinoid secretion.

Time Course of Redox Biomarkers in COVID-19 Pneumonia: Relation with Inflammatory, Multiorgan Impairment Biomarkers and CT Findings

Although the original data on systemic oxidative stress in COVID-19 patients have recently started to emerge, we are still far from a complete profile of changes in patients’ redox homeostasis. We aimed to assess the extent of oxidative damage of proteins, lipids and DNA during the course of acute disease, as well as their association with CT pulmonary patterns. In order to obtain more insight into the origin of the systemic oxidative stress, the observed parameters were correlated with inflammatory biomarkers and biomarkers of multiorgan impairment. In this prospective study, we included 58 patients admitted between July and October 2020 with COVID-19 pneumonia. Significant changes in malondialdehyde, 8-hydroxy-2’-deoxyguanosine and advanced oxidation protein products levels exist during the course of COVID-19. Special emphasis should be placed on the fact that the pattern of changes differs between non-hospitalized and hospitalized individuals. Our results point to the time-dependent relation of oxidative stress parameters with inflammatory and multiorgan impairment biomarkers, as well as pulmonary patterns in COVID-19 pneumonia patients. Correlation between redox biomarkers and immunological or multiorgan impairment biomarkers, as well as pulmonary CT pattern, confirms the suggested involvement of neutrophils networks, IL-6 production, along with different organ/tissue involvement in systemic oxidative stress in COVID-19.

Three-dimensional shear-wave quality factor, Qs(f), model for south-central Gulf of California, Mexico obtained from inversion of broadband data

We apply an iterative inversion scheme, initially developed by Hashida and Shimazaki (1984) and later modified by Joshi et al., (2010), to estimate three - dimensional shear - wave quality factor, Qs(f), of south-central Gulf of California, Mexico. An area of 230 km x 288 km in this region is divided into 108 rectangular blocks of different Qs(f). We use 25 well-located earthquakes recorded at three broadband stations of the regional network RESBAN operated by CICESE (Centro de Investigación Científica y de Educación Superior de Ensenada, Baja California) and three Ocean Bottom Seismographs (OBS) of the Sea of Cortez Ocean Bottom Array (SCOOBA) experiment. This dataset permits us to obtain Qs(f) estimates of different blocks using the modified inversion algorithm. Qs(f) is obtained at various frequencies in 0.16 - 7.94 Hz range. We found that the estimated Qs structure correlates with geological and tectonic models of the region proposed in previous studies. A regional frequency-dependent relation using all 1944 values of shear-wave quality factor is obtained at 18 different frequencies in all blocks can be approximated by a function of the form Qs(f) = 20 f 1.2. This relation is typical in a tectonically active region with high S-wave attenuation and is similar to attenuation relations reported by other authors for the Imperial Valley, California region.

Modification of the k-epsilon scheme and its application for describing turbulence in inland water bodies

&lt;p&gt;A parameterization of the Prandtl number as a function of the gradient Richardson number is proposed in order to correctly take into account stratification when calculating the thermohydrodynamic regime of inland water bodies. This parameterization allows the existence of turbulence at any values &amp;#8203;&amp;#8203;of the Richardson number.&lt;/p&gt;&lt;p&gt;The proposed function is used to calculate the turbulent thermal conductivity coefficient in a k-epsilon mixing scheme. Modification is implemented in the three-dimensional hydrostatic model developed at the Research Computing Center of Moscow State University.&lt;/p&gt;&lt;p&gt;It is demonstrated that the proposed modification (in contrast to the standard scheme with a constant Prandtl number) leads to smoothing all sharp changes in vertical distributions of turbulent mixing parameters (turbulent kinetic energy, temperature and thickness of the shock layer) and imposes a Richardson number-dependent relation on the empirical constants of k-epsilon turbulent mixing scheme.&lt;/p&gt;&lt;p&gt;The work was supported by grants of the RF President&amp;#8217;s Grant for Young Scientists (MK-1867.2020.5) and by the RFBR (19-05-00249, 20-05-00776).&amp;#160;&lt;/p&gt;