Hypertension as an Independent Risk Factor for In-Patient Mortality in Hospitalized COVID-19 Patients: A Multicenter Study.

Despite the lack of direct evidence that hypertension increases the likelihood of new infections, hypertension is known to be the most common comorbid condition in COVID-19 patients and also a major risk factor for severe COVID-19 infection. The literature review suggests that data is heterogeneous in terms of the association of hypertension with mortality. Hence, it remains a topic of interest whether hypertension is associated with COVID-19 disease severity and mortality. Herein, we perform a multicenter retrospective analysis to study hypertension as an independent risk for in-hospital mortality in hospitalized COVID-19 patients. This multicenter retrospective analysis included 515 COVID-19 patients hospitalized from March 1, 2020 to May 31, 2020. Patients were divided into two groups: hypertensive and normotensive. Demographic characteristics and laboratory data were collected, and in-hospital mortality was calculated in both groups. The overall mortality of the study population was 25.3% (130 of 514 patients) with 96 (73.8%) being hypertensive and 34 (26.2%) being normotensive (p-value of 0.01, statistically non-significant association). The mortality rate among the hypertensive was higher as compared to non-hypertensive; however, hypertensive patients were more likely to be old and have underlying comorbidities including obesity, diabetes mellitus, coronary artery disease, congestive heart failure, stroke, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and cancer. Therefore, multivariable logistic regression failed to show any significant association between hypertension and COVID-19 mortality. To our knowledge, few studies have shown an association between hypertension and COVID-19 mortality after adjusting confounding variables. Our study provides further evidence that hypertension is not an independent risk factor for in-hospital mortality when adjusted for other comorbidities in hospitalized COVID-19 patients.

Comparison of Outcomes for Non-ST Elevation Acute Myocardial Infarction in Weekday vs Weekend Admissions: The Weekend Effect.

Background: Recent literature shows that reduced staffing over the weekends in hospitals may compromise patient care with acute conditions like acute coronary syndrome (ACS). Objective: Our study evaluated differences in the outcomes between patients presenting with non-ST segment elevation acute coronary syndrome (NSTE-ACS) on weekends versus those coming on weekdays. Methods: A single-center retrospective study was performed on NSTE-ACS patients. Data were analyzed using SPSS version 22 to calculate an independent sample t-test value for significance between the two groups. Results: The mean DTB time for patients admitted over the weekend was significantly higher than those admitted over weekdays (p = 0.000). The mean peak troponin level and length of stay (LOS) for patients admitted over the weekends vs. weekdays was significantly higher by 5 ng/dL (9.71 ± 5.23 vs. 4.194 ± 2.60, p = 0.0001) and 24 h (72 ± 10 vs. 48 ± 6 h, p = 0.003), respectively. While the mean left ventricular ejection fraction (EF) of patients on discharge was lower by 5% for patients admitted over the weekend compared to patients admitted on weekdays (p = 0.001). Conclusion: NSTE-ACS patients admitted over the weekends have a significantly higher myocardial injury evidenced by an increased LOS, higher peak troponin levels, and reduced EF due to delayed PCI compared to weekday admissions.

Computational Modeling of Mitochondria to Understand the Dynamics of Oxidative Stress.

Mitochondria are complex organelles that use catabolic metabolism to produce ATP which is the critical energy source for cell function. Oxidative phosphorylation by the electron transport chain, which receives reducing equivalents (NADH and FADH2) from the tricarboxylic acid cycle, also produces reactive oxygen species (ROS) as a by-product at complex I and III. ROS play a significant role in health and disease. In order to better understand this process, a computational model of mitochondrial energy metabolism and the production of ROS has been developed. The model demonstrates the process regulating ROS production and removal and how different energy substrates can affect ROS production.

Gender Differences in Smoking Attitude among Saudi Medical Students.

BACKGROUND: Smoking is a growing public health problem throughout the world. However, the attitude of males and females toward smoking may differ. Therefore, this study examines gender differences in smoking behavior and attitude among Saudi medical students. METHODS: From January 2020 to August 2020, a snowball cross-sectional online survey was conducted in five major regions of Saudi Arabia. Medical students (18 years or older) were invited to respond to the questionnaire. RESULTS: Out of the 421 respondents, 255 (60.6%) were female, 243 (57.7%) were between 18 and-24-year-old, and 164 (39%) were from the Eastern Province. The overall prevalence of smoking was 25.4% and was higher among males than females [(44% and 13.3%, respectively), P < 0.001]. However, there was no significant difference in the mean score of the overall attitude towards smoking between males and females [(3.02±0.44 and 3.00±0.34), respectively, P=0.64]. However, more female students believed e-cigarettes were harmful to health than male students [(4.19±1.04 and 4.45±0.9), respectively, P=0.002]. CONCLUSION: The study showed that male students smoke more than female students, and there were no significant differences in the overall attitudes score towards smoking. Therefore, campaigns are needed to decrease smoking rate, especially among male students.

Contemporary trends in the incidence of spontaneous coronary artery dissection (SCAD) - ethnic and household income disparities.

OBJECTIVES: Spontaneous coronary artery dissection (SCAD) may contribute to 35% of acute coronary syndrome among women ≤50 years of age. We aimed to investigate the overall incidence, as well as the trends of SCAD incidence based on race, household income, and the U.S. census regions utilizing the National Inpatient Sample. METHODS: In this retrospective cohort study the discharge data were extracted from the NIS using 9th and 10th revisions of the International Classification Disease for SCAD. RESULTS: We found that the incidence of SCAD is rising in all U.S. census regions, and patients were predominantly females. Overall crude incidence of SCAD per 1,000,000 discharges per year was found to be 4.95 (2010), 5.73 (2011), 5.34 (2012), 6.18 (2013), 7.64 (2014), 8.11 (2015), 14.58 (2016), and 14.81 (2017). There was a higher incidence of SCAD in white population and higher-income groups. Among U.S. census regions, West has had the highest incidence followed by the Northeast, Midwest, and South. Statistically significant differences were observed in year-to-year SCAD incidence among racial groups, household income quintiles, and U.S. census regions (P < 0.0001). CONCLUSION: Recent trends indicate that the incidence is highest among White race, highest household income quintile, and in U.S. CENS-R4 (Census Region 4: West). These findings defy classic racial trends in cardiovascular disease burden which need further discovery.

Local feedback inhibition tightly controls rapid formation of hippocampal place fields.

Hippocampal place cells underlie spatial navigation and memory. Remarkably, CA1 pyramidal neurons can form new place fields within a single trial by undergoing rapid plasticity. However, local feedback circuits likely restrict the rapid recruitment of individual neurons into ensemble representations. This interaction between circuit dynamics and rapid feature coding remains unexplored. Here, we developed "all-optical" approaches combining novel optogenetic induction of rapidly forming place fields with 2-photon activity imaging during spatial navigation in mice. We find that induction efficacy depends strongly on the density of co-activated neurons. Place fields can be reliably induced in single cells, but induction fails during co-activation of larger subpopulations due to local circuit constraints imposed by recurrent inhibition. Temporary relief of local inhibition permits the simultaneous induction of place fields in larger ensembles. We demonstrate the behavioral implications of these dynamics, showing that our ensemble place field induction protocol can enhance subsequent spatial association learning.

A Review of Left Ventricular Non-compaction Cardiomyopathy (LVNC).

Left ventricular non-compaction (LVNC) is a rare congenital phenotype defined by the presence of prominent left ventricular trabeculae, deep intertrabecular recesses (continuous with the ventricular cavity), and a thin compacted layer. The most common presentation of LVNC is dyspnea (60%), followed by palpitations (18%), chest pain (15%), syncope (9%), and prior stroke (3%). LVNC presenting with acute myocardial infarction (MI) has rarely been reported in the literature. A forty-one-years old female presented with substernal chest pain and exertional dyspnea. On physical examination, she was alert without any distress, her lungs and heart examination were within normal limits. Peripheral pulses were palpable and regular, and +1 peripheral pitting edema was noted. EKG showed normal sinus rhythm with premature atrial contractions (PACs), left axis deviation, and ST-segment and T wave changes suggestive of inferior wall ischemia. Troponin I level was found to be elevated, which peaked within 24 hours, Troponinmax 110.08 ng/ml. Transthoracic echocardiography showed moderate LV dilatation with severely reduced EF (15-20%), and diffuse LV hypokinesis with a grade III restrictive pattern. There was heavy trabeculation of LV involving 2/3rd LV endocardium and wall thickness with sinusoidal tunnels perpendicular to LV wall. These morphological findings met the diagnostic criteria of LVNC/NCM. LVNC presenting with acute myocardial infarction (MI) can be related to poor outcomes, however, more data is needed to establish the clinical implication of this presentation. Asymptomatic LVNC can be observed while symptomatic LVNC should be treated with standard guidelines of HF.

Heart Failure Patients and Implications of Obesity: A Single-Center Retrospective Study.

Background and objective The prevalence of heart failure (HF) is on the rise; currently, it affects around five million people in the United States (US) and the prevalence is expected to rise from 2.42% in 2012 to 2.97% in 2030. HF is a leading cause of hospitalizations and readmissions, accounting for a major economic burden to the US healthcare system. Obesity is a widely accepted risk factor of HF; however, data regarding its independent association with HF mortality and morbidity is heterogeneous. Globally, more than two-thirds of deaths attributable to high body mass index (BMI) are due to cardiovascular diseases (CVD). This study aimed to investigate the potential role of obesity (BMI >30 Kg/m2) in HF patients in terms of 30-day readmissions, in-hospital mortality, and the use of noninvasive positive pressure ventilation (NIPPV). Methods In this single-center, retrospective study, all adult (age: >18 years) patients who were hospitalized with a primary diagnosis of HF at the Abington Jefferson Hospital from January 2015 to January 2018 were included. Demographic characteristics were collected manually from electronic medical records. Outcomes were 30-day readmission due to HF, all-cause in-hospital mortality, and requirement for NIPPV. Multivariable logistic regression analysis was conducted to investigate the association of obesity with HF outcomes. Results A total of 1,000 patients were initially studied, of these 800 patients were included in the final analysis based on the inclusion criteria. Obese patients showed higher odds for 30-day readmissions and the use of NIPPV compared to non-obese patients. There was no significant difference in in-hospital mortality in obese vs. non-obese patients. Conclusions Based on our findings, BMI >30 Kg/m2 is an independent risk factor for HF readmissions. Additionally, our results highlight the importance of guidelines-directed medical therapy (GDMT) for HF exacerbation, a low threshold for use of NIPPV in obese patients, promotion of lifestyle modifications including weight loss, and early follow-up after discharge to prevent HF readmissions in the obese population.

In Silico Prediction of the Phosphorylation of NS3 as an Essential Mechanism for Dengue Virus Replication and the Antiviral Activity of Quercetin.

Dengue virus infection is a global health problem for which there have been challenges to obtaining a cure. Current vaccines and anti-viral drugs can only be narrowly applied in ongoing clinical trials. We employed computational methods based on structure-function relationships between human host kinases and viral nonstructural protein 3 (NS3) to understand viral replication inhibitors' therapeutic effect. Phosphorylation at each of the two most evolutionarily conserved sites of NS3, serine 137 and threonine 189, compared to the unphosphorylated state were studied with molecular dynamics and docking simulations. The simulations suggested that phosphorylation at serine 137 caused a more remarkable structural change than phosphorylation at threonine 189, specifically located at amino acid residues 49-95. Docking studies supported the idea that phosphorylation at serine 137 increased the binding affinity between NS3 and nonstructural Protein 5 (NS5), whereas phosphorylation at threonine 189 decreased it. The interaction between NS3 and NS5 is essential for viral replication. Docking studies with the antiviral plant flavonoid Quercetin with NS3 indicated that Quercetin physically occluded the serine 137 phosphorylation site. Taken together, these findings suggested a specific site and mechanism by which Quercetin inhibits dengue and possible other flaviviruses.

Investigation of Cyber-Security and Cyber-Crimes in Oil and Gas Sectors Using the Innovative Structures of Complex Intuitionistic Fuzzy Relations.

Recently, there has been enormous development due to advancements in technology. Industries and enterprises are moving towards a digital system, and the oil and gas industries are no exception. There are several threats and risks in digital systems, which are controlled through cyber-security. For the first time in the theory of fuzzy sets, this research analyzes the relationships between cyber-security and cyber-crimes in the oil and gas sectors. The novel concepts of complex intuitionistic fuzzy relations (CIFRs) are introduced. Moreover, the types of CIFRs are defined and their properties are discussed. In addition, an application is presented that uses the Hasse diagram to make a decision regarding the most suitable cyber-security techniques to implement in an industry. Furthermore, the omnipotence of the proposed methods is explained by a comparative study.

Hard Palate Perforation in an Elderly Man With Dementia.

A 74-year-old male with a history of mild cognitive impairment presented to the emergency department with failure to thrive and generalized weakness. He was having difficulty swallowing leading to 30 pounds of unintentional weight loss in the last three months. His social history was significant for 12.5 pack-year smoking and drinking (two to three glasses of wine/day). The oral cavity examination revealed a large (3 × 2 cm2) defect with the erythematous border that encompassed the mid-palatal structures and emanated from the hard palate into his nasal cavity. Auto-immune work-up was negative. Palatal biopsy showed squamous cell carcinoma (SCC; well-differentiated). A diagnosis of locally advanced (stage IVa) oral cavity squamous cell carcinoma (OSCC) was made based on PET scan findings. A palatal obturator (prosthesis) was placed to improve his eating, prevent regurgitation. The patient opted for palliative care and did not want to pursue further treatment. He was discharged home with a regular follow-up visit.

X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin.

The stretching of a cardiomyocyte leads to the increased production of reactive oxygen species that increases ryanodine receptor open probability through a process termed X-ROS signaling. The stretching of the myocyte also increases the calcium affinity of myofilament Troponin C, which increases its calcium buffering capacity. Here, an integrative experimental and modeling study is pursued to explain the interplay of length-dependent changes in calcium buffering by troponin and stretch-activated X-ROS calcium signaling. Using this combination, we show that the troponin C-dependent increase in myoplasmic calcium buffering during myocyte stretching largely offsets the X-ROS-dependent increase in calcium release from the sarcoplasmic reticulum. The combination of modeling and experiment are further informed by the elimination of length-dependent changes to troponin C calcium binding in the presence of blebbistatin. Here, the model suggests that it is the X-ROS signaling-dependent Ca2+ release increase that serves to maintain free myoplasmic calcium concentrations during a change in myocyte length. Together, our experimental and modeling approaches have further defined the relative contributions of X-ROS signaling and the length-dependent calcium buffering by troponin in shaping the myoplasmic calcium transient.

Wrapped Left Anterior Descending Artery Presenting As Inferior Myocardial Infarction: Case Report and Review of the Literature.

Acute occlusion of the left anterior descending (LAD) coronary artery generally results in ST-segment elevation in the anterior leads of the electrocardiogram and reciprocal ST-segment depression in the inferior leads. We present a case of LAD occlusion presenting as inferior wall ST-segment elevation myocardial infarction.

Coumarin improves tomato plant tolerance to salinity by enhancing antioxidant defence, glyoxalase system and ion homeostasis.

Salinity is a severe threat to crop growth, development and even to world food sustainability. Plant possess natural antioxidant defense tactics to mitigate salinity-induced oxidative stress. Phenolic compounds are non-enzymatic antioxidants with specific roles in protecting plant cells against stress-mediated reactive oxygen species (ROS) generation. Coumarin (COU) is one of these compounds, however, to date, little is known about antioxidative roles of exogenous COU in enhancing plant tolerance mechanisms under salt stress. The involvement of COU in increasing tomato salt tolerance was examined in the present study using COU as a pre-treatment at 20 or 30 µM for 2 days against salt stress (100 or 160  NaCl; 5 days). The COU-mediated stimulation of plant antioxidant defence and glyoxalase systems to suppress salt-induced ROS and methylglyoxal (MG) toxicity, respectively, were the main hypotheses examined in the present study. Addition of COU suppressed salt-induced excess accumulation of ROS and MG, and significantly reduced membrane damage, lipid peroxidation and Na+ toxicity. These results demonstrate COU-improved plant growth, biomass content, photosynthetic pigment content, water retention and mineral homeostasis upon imposition of salinity. Finally, this present study suggests that COU has potential roles as a phytoprotectant in stimulating plant antioxidative mechanisms and improving glyoxalase enzyme activity under salinity stress.

Hippocampal Network Reorganization Underlies the Formation of a Temporal Association Memory.

Episodic memory requires linking events in time, a function dependent on the hippocampus. In "trace" fear conditioning, animals learn to associate a neutral cue with an aversive stimulus despite their separation in time by a delay period on the order of tens of seconds. But how this temporal association forms remains unclear. Here we use two-photon calcium imaging of neural population dynamics throughout the course of learning and show that, in contrast to previous theories, hippocampal CA1 does not generate persistent activity to bridge the delay. Instead, learning is concomitant with broad changes in the active neural population. Although neural responses were stochastic in time, cue identity could be read out from population activity over longer timescales after learning. These results question the ubiquity of seconds-long neural sequences during temporal association learning and suggest that trace fear conditioning relies on mechanisms that differ from persistent activity accounts of working memory.

Management of Atopic Eczema in primary care.

Introduction : Atopic eczema (AE) is a common inflammatory skin dermatosis that is increasing in prevalence. However, it can present in various clinical presentations, which leads to challenges in the diagnosis and treatment of the condition, especially in a primary care setting. The Clinical Practice Guidelines on the Management of Atopic Eczema was developed by a multidisciplinary development group and approved by the Ministry of Health Malaysia in 2018. It covers the aspects of diagnosis, severity assessment, treatment, and referral.

Fatigue Increases Dynamic Knee Valgus in Youth Athletes: Results From a Field-Based Drop-Jump Test.

PURPOSE: To determine whether fatigue increases dynamic knee valgus in adolescent athletes, as measured after a standardized exercise protocol and video-based drop-jump test. A secondary aim was to determine whether individual risk factors place certain athletes at increased risk for dynamic knee valgus. METHODS: Athletes aged 14 to 18 years were recruited for this video analysis study. Athletes were recorded performing a standard drop-jump to assess dynamic valgus. Participants then completed a standardized exercise protocol. Fatigue was quantified using a maximum vertical jump, which was compared with pre-exercise values. The drop-jump was repeated postexercise. All drop-jump recordings were randomized and scored for dynamic valgus by 11 blinded reviewers. Univariate analysis was performed to identify characteristics that predisposed athletes to increased dynamic valgus. RESULTS: Eighty-five (47 female, 38 male) athletes with an average age of 15.4 years were included in this study. Forty-nine percent of athletes demonstrated an increase in dynamic valgus determined by drop-jump assessment after exercise. A significantly greater percentage of athletes were graded "medium or high risk" in jumps recorded after the exercise protocol (68%) as compared with before the exercise protocol (44%; P < .01). Female athletes (P < .01) and those older than 15 years of age (P < .01) were the most affected by fatigue. CONCLUSIONS: In conclusion, our study found that exercise increases dynamic knee valgus in youth athletes. Female athletes and those older than 15 years of age were most significantly affected by exercise. Greater fatigue levels were found to correlate with an increase in dynamic knee valgus, which may place athletes at greater anterior cruciate ligament injury risk. The field-based exercise drop-jump test is a low-cost and reproducible screening tool to identify at-risk athletes who could possibly benefit from anterior cruciate ligament injury-prevention strategies. LEVEL OF EVIDENCE: III, Comparative trial.

Is There any Additional Benefit of Multiple Doses of Tocilizumab in COVID-19 Patients?

Many patients with coronavirus disease 2019 (COVID-19) have a hyperactive immune response (cytokine storm) which has been incriminated in multiorgan dysfunction (MOD). Interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are the key cytokines involved in mediating systemic inflammation and triggering endothelial dysfunction. To limit these effects, IL-6 receptor inhibitors (IL6ri) have been used in COVID-19 patients. The best approach regarding the total number of doses in COVID-19 patients is still unclear. In this single-center retrospective study, we investigated if multiple doses of tocilizumab (TCZ) prevented deterioration of COVID-19 patients. Patients were divided into two cohorts based on the number of TCZ doses; cohort 1 (received one dose) and cohort 2 (received ≥ two doses). In both cohorts, all-cause-mortality was the primary outcome. Of 270 hospitalized patients with COVID-19, 81 patients received TCZ. Fifty patients received one dose of TCZ and 31 received ≥ two doses. All-cause-mortality in cohort 2 remained higher (41.9%) suggesting that there was no additional benefit of multiple doses of TCZ to prevent the primary outcome. In addition, multiple doses of TCZ did not change any other secondary outcome [(ICU admission, acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), acute cardiac injury (ACI), thrombotic events, septic shock, and total hospital stay].

Mental Health and Tobacco Use Are Correlated With Physical Function Outcomes in Patients With Knee Pain and Injury.

PURPOSE: To examine the relation between the Patient-Reported Outcomes Measurement Information System (PROMIS) domains of Pain Interference (PROMIS-PI), Depression (PROMIS-D), and Physical Function (PROMIS-PF) for nonoperative patients presenting to our ambulatory sports orthopaedic clinic with knee complaints and to determine whether patient demographic characteristics influence PROMIS scores, particularly tobacco use. METHODS: All patients treated nonoperatively for a primary complaint of knee pain were recruited for participation. Patients were included if they completed all 3 PROMIS questionnaires prior to their clinical evaluation. Patients were excluded if their treatment plan determined that surgical intervention was warranted. Survey results were compiled, and statistical correlations were run between PROMIS domains and patient demographic characteristics. RESULTS: A total of 527 PROMIS questionnaire sets were included. PROMIS-PF had a strong negative correlation with PROMIS-PI (R = -0.75, P < .001) and a nearly moderate negative correlation with PROMIS-D (R = -0.47, P < .001). When evaluating patient demographic characteristics, we found a significant decrease in physical function scores and increases in pain and depression scores in both current and former tobacco users compared with nonsmokers. Differences in all PROMIS domains between smokers and nonsmokers exceeded minimal clinically important differences. CONCLUSIONS: Our study showed an inverse correlation between PROMIS-PI and PROMIS-PF, as well as between PROMIS-D and PROMIS-PI, in patients seen in the ambulatory setting for knee complaints treated nonoperatively. A positive correlation was found between PROMIS-PI and PROMIS-D. Tobacco use was a patient demographic factor found to significantly impact PROMIS scores leading to minimal clinically important differences across all 3 PROMIS domains. The findings of this study may be used to identify patients at high risk of poor outcomes. LEVEL OF EVIDENCE: Level III, observational study.

Diagnostic accuracy of ultrasound for rotator cuff tears.

Ultrasonography (US) is an inexpensive, convenient, and effective tool that can be used to evaluate the shoulder. It does not expose the patient to harmful radiation and can be used to evaluate the musculoskeletal system dynamically. Additionally, US is not subject to metal artifacts when evaluating patients with previously placed hardware. Over the years, US has been found to be reliable and accurate for diagnosing rotator cuff tears (RCTs), despite its operatordependence. The usage of US for diagnosing RCTs in orthopedic practice varies depending on practitioners' familiarity with the exam and the availability of experienced technicians. The purpose of this article is to review the diagnostic accuracy of US for identifying RCTs.