The Effects of Sleep Quality and Resilience on Perceived Stress,Dietary Behaviors,and Alcohol Misuse: A Mediation-Moderation Analysis of Higher Education Students from Asia,Europe, and North America during the COVID-19 Pandemic

Background: The coronavirus disease 2019 (COVID-19) pandemic has increased the already high levels of stress that higher education students experience. Stress influences health behaviors, including those related to dietary behaviors, alcohol, and sleep; yet the effects of stress can be mitigated by resilience. To date, past research studying the connections between dietary behaviors, alcohol misuse, sleep, and resilience commonly investigated singular relationships between two of the constructs. The aim of the current study was to explore the relationships between these constructs in a more holistic manner using mediation and moderation analyses. Methods: Higher education students from China, Ireland, Malaysia, South Korea, Taiwan, the Netherlands, and the United States were enrolled in a cross-sectional study from April to May 2020, which was during the beginning of the COVID-19 pandemic for most participants. An online survey, using validated tools, was distributed to assess perceived stress, dietary behaviors, alcohol misuse, sleep quality and duration, and resilience. Results: 2254 students completed the study. Results indicated that sleep quality mediated the relationship between perceived stress and dietary behaviors as well as the relationship between perceived stress and alcohol misuse. Further, increased resilience reduced the strength of the relationship between perceived stress and dietary behaviors but not alcohol misuse. Conclusion: Based on these results, higher education students are likely to benefit from sleep education and resilience training, especially during stressful events.     

Gender Differences in the Relationships between Perceived Stress,Eating Behaviors,Sleep, Dietary Risk,and Body Mass Index

Background: Obesity is a growing epidemic among university students, and the high levels of stress reported by this population could contribute to this issue. Singular relationships between perceived stress; engagement in restrained, uncontrolled, and emotional eating; sleep; dietary risk; and body mass index (BMI) have been reported in the current body of literature; however, these constructs interact with each other, and the complex relationships among them are infrequently examined. Therefore, the aim of the present study was to explore the complex relationships between these constructs using mediation and moderation analyses stratified by gender. Methods: A cross-sectional study, enrolling university students from the United States (U.S.), the Netherlands, South Korea, Malaysia, Ireland, Ghana, and China, was conducted between October 2020 and January 2021 during the COVID-19 pandemic. Perceived stress; maladaptive eating behaviors including restrained, uncontrolled, and emotional eating; sleep duration and quality; dietary risk; and BMI were assessed using validated questionnaires, which were distributed through an online platform. Results: A total of 1392 students completed the online survey (379 male, 973 female, and 40 who self-identified as “other”). Uncontrolled and emotional eating mediated the relationship between perceived stress and dietary risk for both males and females; higher sleep quality weakened this relationship among female students but not males. Emotional eating mediated the relationship between perceived stress and BMI for both males and females, but higher sleep quality weakened this relationship only among females. Conclusions: Our findings suggest that students in higher education are likely to benefit from interventions to reduce uncontrolled and emotional eating. Programs that improve sleep quality, especially during highly stressful periods, may be helpful.     

Cell contact guidance via sensing anisotropy of network mechanical resistance

Despite the ubiquitous importance of cell contact guidance, the signal-inducing contact guidance of mammalian cells in an aligned fibril network has defied elucidation. This is due to multiple interdependent signals that an aligned fibril network presents to cells, including, at least, anisotropy of adhesion, porosity, and mechanical resistance. By forming aligned fibrin gels with the same alignment strength, but cross-linked to different extents, the anisotropic mechanical resistance hypothesis of contact guidance was tested for human dermal fibroblasts. The cross-linking was shown to increase the mechanical resistance anisotropy, without detectable change in network microstructure and without change in cell adhesion to the cross-linked fibrin gel. This methodology thus isolated anisotropic mechanical resistance as a variable for fixed anisotropy of adhesion and porosity. The mechanical resistance anisotropy |Y*|⁻¹ − |X*|⁻¹ increased over fourfold in terms of the Fourier magnitudes of microbead displacement |X*| and |Y*| at the drive frequency with respect to alignment direction Y obtained by optical forces in active microrheology. Cells were found to exhibit stronger contact guidance in the cross-linked gels possessing greater mechanical resistance anisotropy: the cell anisotropy index based on the tensor of cell orientation, which has a range 0 to 1, increased by 18% with the fourfold increase in mechanical resistance anisotropy. We also show that modulation of adhesion via function-blocking antibodies can modulate the guidance response, suggesting a concomitant role of cell adhesion. These results indicate that fibroblasts can exhibit contact guidance in aligned fibril networks by sensing anisotropy of network mechanical resistance.

Contact guidance refers to the tendency of a cell to orient and migrate bidirectionally in response to anisotropic topographical features, such as parallel grooves on a two-dimensional (2D) substratum or aligned fibrils in a three-dimensional (3D) collagen or fibrin gel. Contact guidance has been ascribed importance in a number of physiological processes since Weiss first identified and investigated its role in development (1). More recently, the role of contact guidance in cancer metastasis (2) as well as tissue engineering scaffold design (3) has been described.Contact guidance on 2D substrata like parallel grooves or adhesive ligand stripes has been intensively studied (recent examples include refs. 4–6) because in these experiments, the guidance field can be precisely defined and easily manipulated. However, it is the case of aligned fibrils that has the preponderance of physiological relevance. Contact guidance is also vital to the success of engineered connective tissues that mimic native alignment (and thereby function) by harnessing mechanically constrained fibrin gel compaction by fibroblasts and the associated contact guidance response (7–9). Unfortunately, even for the case of collagen and fibrin gels, not to mention tissues, the guidance field generally cannot be precisely defined or controllably manipulated. This is because of the inherent biophysical complexities of an aligned fibril network, resulting in multiple interdependent and simultaneous signals presented to cells. These signals include anisotropy of adhesion, porosity, and mechanical resistance (a combination of elastic stiffness and viscous friction, in general), at least. In a recent publication on this topic (10), for example, a correlation was suggested between protrusion activity with respect to alignment direction and contact guidance. This study made use of varied gel concentrations (typical for contact guidance studies), a method that confounds easy interpretation because all potential anisotropies are almost certainly altered simultaneously.While there are phenomenological studies reporting the contact guidance response of cells in aligned collagen and fibrin gels (11–14), the signal-inducing contact guidance in aligned fibrils has thus far defied elucidation since Dunn first proposed contact guidance in response to these anisotropies nearly 40 y ago (15), illustrated in Fig. 1. The main reason for the lack of progress in distinguishing between these anisotropies is the intrinsic difficulty in changing just one of them in an aligned fibril network—in Dunn’s terms: chemical anisotropy, mechanical anisotropy, or steric anisotropy—without changing the others. This stands in stark contrast to almost every other form of directed cell migration in which the signal is absolutely clear, for example, a chemotactic factor concentration gradient in chemotaxis, an adhesion gradient in haptotaxis, an electric potential gradient in galvanotaxis, and a stiffness gradient in durotaxis.Open in a separate windowFig. 1.Illustration of Dunn’s hypotheses for the signal-inducing cell contact guidance in aligned fibrils. A cell with four pseudopods is depicted. (A) Chemical (adhesion) anisotropy. Cell-binding sites are indicated by blue dots. (B) Mechanical (stiffness/friction) anisotropy. Fibrils presenting a high local modulus to the pseudopod because of their coalignment are colored red, and fibrils presenting a local low modulus to the pseudopods because of their anti-alignment are colored blue. The colored segments are also thickened for visualization. (C) Steric (porosity) anisotropy. Note this figure is not drawn to scale for clarity; as we (59) and others (e.g., ref. 60) have shown with electron microscopy, a pseudopod is much larger than the typical pore size in the standard in vitro models (collagen and fibrin gels) and interacts with many interconnected fibrils simultaneously, not single fibrils.Despite its ubiquitous and powerful role, the signal contained in an aligned fibril network that induces contact guidance remains unknown. The entire mechanism of contact guidance entails many events beyond signal sensing, for example, mechanotransduction pathways and spatial regulation of cell pseudopods. However, before the entire mechanism of contact guidance in response to aligned fibril networks can be understood, the signal(s) contained in aligned fibrils that induce contact guidance must be identified. Thus, in this study, we isolated anisotropic mechanical resistance as a variable, for fixed anisotropy of adhesion and porosity. If contact guidance is shown to depend on varied anisotropic mechanical resistance, for fixed anisotropy of adhesion and porosity, anisotropic mechanical resistance is established as a sufficient signal (not necessarily the only signal or the dominant signal).By combining key technologies—magnetic alignment of fibrin gels during fibrillogenesis, active microrheology (AMR) for local network mechanical resistance measurement, cell-compatible cross-linking of fibrin via dityrosine formation, and adhesion blocking antibodies—and ascertaining the effects of cross-linking on fibrin network mechanical resistance anisotropy, fibrin network microstructure, and fibroblast adhesion to fibrin, we established isolation of mechanical resistance anisotropy as the sole variable when cross-linking an aligned fibrin gel. In addition to quantifying variation in mechanical resistance anisotropy with cross-linking using AMR, absence of network microstructure changes was concluded from morphometric analysis of 3D reconstructed confocal reflectance images, and absence of changes in cell adhesion to the fibrin gel was concluded from a centrifugation assay. Altered contact guidance response in the cross-linked aligned gels was ascertained from the cell anisotropy index (AI) based on the tensor of cell orientation, defined by the orientation of the long axis for each cell. Finally, the same contact guidance experiment performed with cells pretreated with a combination of antibodies against α_vβ₃ integrin and β₁ integrin, which are shown to substantially inhibit cell adhesion in these gels based on the centrifugation assay, was performed to assess whether adhesion is contributing to the contact guidance response when mechanical resistance anisotropy is an operative signal; the same contact guidance experiment was also performed in the presence of a fibrinolysis inhibitor to assess whether fibrinolysis must be considered to interpret the findings. The data show that fibroblasts exhibit contact guidance in a network of aligned fibrin fibrils via sensing anisotropy of mechanical resistance, modulated by integrin-mediated adhesion.     

Relationship between diabetic retinopathy and diabetic peripheral neuropathy - Neurodegenerative and microvascular changes

Purpose:To determine the relationship between diabetic retinopathy (DR) and diabetic peripheral neuropathy (DPN), and their associated risk factors.Methods:We conducted a cross-sectional analysis on 500 patients who attended the Endocrinology department at a quaternary health care center in Kerala between November 2017 and April 2018. Patients above the age of 30 years with type 2 diabetes mellitus (DM) were included. They underwent a detailed medical history, dilated fundus examination for DR, assessment and grading of DPN, and blood investigations. Among these, 49 randomly selected patients without DR had peripapillary retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) assessed by optical coherence tomogram. RNFL and GCIPL changes in different grades of neuropathy were evaluated.Results:Out of 500 patients, 303 (60.6%) were males and 197 (39.4%) were females. Prevalence of DR was 48% and DPN 71.8%. Risk factors for the development of DR included duration of DM >15 years, HbA1c (glycated hemoglobin) greater than 6.5%, serum creatinine more than 1.5 mg/dl, and the presence of DPN. There was a statistically significant association between DR and DPN. There was significant thinning of GCIPL in patients with moderate to severe neuropathy without DR.Conclusion:There is a significant association between DR and DPN and their severities. There are early changes in inner retinal layers of diabetic patients without microvascular changes of DR. These neurodegenerative changes parallel DPN in the course of DM. Our study stresses the importance of multidisciplinary approach in the management of diabetes and its complications.     

Efficacy of Tranexamic Acid in Reducing Blood Loss in Lower Segment Cesearean Section: A Randomised Controlled Study

ObjectivesTo determine the efficacy of tranexamic acid in decreasing blood loss in elective/emergency LSCS.Materials and MethodsA prospective randomised case control study was done in 200 pregnant women undergoing elective/emergency LSCS in the Department of Obstetrics and Gynaecology, at a tertiary care teaching hospital in Mysuru, from December 2018 to September 2019. Women in the age group of 18–35 years were included in the study. Those with anaemia (Hb < 10 gm%), hypertension in pregnancy, bleeding diathesis, GDM on insulin, polyhydramnios, oligohydramnios, cardiac and chronic liver disorders were excluded from the study. Two hundred women undergoing emergency/elective LSCS were divided into case (group 1) or control (group 2) groups using a computer-generated random number table. Tranexamic acid (10 mg/Kg) was given in 100 ml Normal Saline 10 mins prior to skin incision to women in the first group, along with routine care (10 Units of Oxytocin IM soon after extraction of the baby). Routine care, as per institutional protocol, was followed in the second group. The primary outcome was to estimate the intraoperative blood loss. Blood loss was measured by weighing pads, mops, drapes before and after surgery and blood in the suction container after surgery. Two separate suction catheters and containers were used, in order to minimise mixing of blood and amniotic fluid. Total blood loss was calculated as the difference in the weight of the pads, mops and drapes before and after surgery and the sum of the amount of blood in suction container. The difference between the pre-operative and post-operative haemoglobin and haematocrit was compared. The pre-operative, intra-operative and post-operative hemodynamics were also compared.ResultsStatistical analysis was done using MS Excel and R-3.5.1 software. Unpaired and paired t test were used. In our study, there was a significant decrease in intraoperative bleeding in women receiving tranexamic acid. Women in the control group had a significant fall in the postoperative hemoglobin when compared to women who received tranexamic acid. Also, women who received tranexamic acid did not develop any significant hemodynamic changes during or immediately after the surgery.ConclusionTranexamic acid can be safely used as a prophylactic agent to reduce bleeding during elective and emergency LSCS.     

Genomic classification of betanodavirus by molecular phylogenetic analysis of the coat protein gene

The classification of betanodavirus into four species was reviewed including newer and well-characterised isolates. Six major clusters were identified, four of which were similar to the classic species. Two single isolate clusters were worth consideration as new species.     

Differential neuroendocrine responses to chronic variable stress in adult Long Evans rats exposed to handling-maternal separation as neonates

Burgeoning evidence supports a preeminent role for early- and late-life stressors in the development of physio- and psychopathology. Handling-maternal separation (HMS) in neonatal Long Evans hooded rats leads to stable phenotypes ranging from resilient to vulnerable to later stressor exposure. Handling with 180 min of maternal separation yields a phenotype of stress hyper-responsiveness associated with facilitation of regional CRF neurocircuits and glucocorticoid resistance. This study assessed whether or not prolonged HMS (180 min/day, HMS180) on post-natal days 2-14 sensitizes the adult limbic hypothalamo-pituitary-adrenal (LHPA) axis to chronic variable stress (CS) compared to brief HMS (15 min/day, HMS15). We examined regional mRNA densities of corticotropin-releasing factor (CRF), its receptor CRF1, glucocorticoid receptor (GR), and mineralocorticoid receptor (MR); regional CRF1 and CRF2alpha binding, and pituitary-adrenal responses to an acute air-puff startle (APS) stressor in four groups: HMS15, nonstressed; HMS15, stressed; HMS180, nonstressed; HMS180, stressed. As expected we observed exaggerated pituitary-adrenal responses to APS, increased regional CRF mRNA density, decreased regional CRF1 binding, and decreased cortical GR mRNA density in nonstressed HMS180 vs. HMS15 animals. However, in contrast to our hypothesis, CS decreased pituitary-adrenal reactivity and central amygdala CRF mRNA density in HMS180 rats, while increasing cortical GR mRNA density and CRF1 binding. CS had no effect on the pituitary-adrenal response to APS in HMS15 rats, despite tripling hypothalamic paraventricular CRF mRNA density. The data suggest that many effects of prolonged HMS are reversible in adulthood by CS, while the neuroendocrine adaptations imbued by brief HMS are sufficiently stable to restrain pituitary-adrenal stress responses even following CS.