Risk and protective factors of depression in the general population during the COVID-19 epidemic in Korea

Background: The risk of depression has risen in the general population during the COVID-19 epidemic. This study was conducted to explore risk and protective factors associated with depression among the general population uninfected by COVID-19. Methods: A cross-sectional study was conducted with 1,500 representative South Korean citizens aged 19–65 years through an anonymous online survey. Depression was defined as a Patient Health Questionnaire-9 score of 10 or higher. Other questionnaires included one measuring psycho-behavioural and social changes, and stress, due to COVID-19, a six-item version of the Gratitude Questionnaire (GQ-6), and a three-item version of the UCLA loneliness scale. Results: Of the 1492 participants not infected by COVID-19, 312 (20.9%) exhibited depression. Multiple logistic regression analysis revealed that depression was positively associated with COVID-19-related stress and psycho-behavioural variables such as disturbances in eating and sleeping, younger age, smoking, underlying mental illness, and loneliness scale scores. In contrast, exercise three or more times per week and GQ-6 scale scores were inversely associated with depression. Conclusion: During the COVID-19 pandemic, maintaining daily routines including eating, sleeping, and regular exercise and focusing on gratitude may be important for the prevention of depression. In addition, more attention should be paid to vulnerable populations, including young people, those with mental illnesses, and smokers, who might be more susceptible to depression

THE ANTERIOR CRUCIATE LIGAMENT INURY PREVENTION PROGRAM: A META-ANALYSIS

The purpose of this study was to evaluate the effect of a neuromuscular protocol on the prevention of anterior cruciate ligament (ACL) injury by performing meta-analysis. An extensive literature review was conducted to identify relevant studies, and eventually, only seven randomized controlled trials or prospective cohort studies were included in the analysis. Subgroup analysis revealed that an age under 18, soccer rather than handball, pre- and in-season training rather than either pre or in-season training, and the plyometrics and strengthening components rather than balancing were significant. Metaanalysis showed that pre- and in-season neuromuscular training with an emphasis on plyometrics and strengthening exercises was effective at preventing ACL injury in female athletes, especially in those under 18 years of age

Prospective Validation of FibroTest in Comparison with Liver Stiffness for Predicting Liver Fibrosis in Asian Subjects with Chronic Hepatitis B

Liver stiffness measurement (LSM) and FibroTest (FT) are frequently used as non-invasive alternatives for fibrosis staging to liver biopsy. However, to date, diagnostic performances of Enhanced Liver Fibrosis (ELF) test, which consists of hyaluronic acid, aminoterminal propeptide of procollagen type-III, and tissue inhibitor of matrix metalloproteinases-1, have not been compared to those of LSM and FT in Asian chronic hepatitis B (CHB) patients.Between June 2010 and November 2011, we prospectively enrolled 170 CHB patients who underwent liver biopsies along with LSM, FT, and ELF. The Batts system was used to assess fibrosis stages.Areas under receiver operating characteristic curves (AUROCs) to predict significant fibrosis (F≥2), advanced fibrosis (F≥3), and cirrhosis (F = 4) were 0.901, 0.860, and 0.862 for ELF, respectively; 0.937, 0.956, and 0.963 for LSM; and 0.896, 0.921, and 0.881 for FT. AUROCs to predict F≥2 were similar between each other, whereas LSM and FT had better AUROCs than ELF for predicting F≥3 (both p<0.05), and LSM predicted F4 more accurately than ELF (p<0.05). Optimized cutoffs of ELF to maximize sum of sensitivity and specificity were 8.5, 9.4, and 10.1 for F≥2, F≥3, and F = 4, respectively. Using suggested ELF, LSM and FT cutoffs to diagnose F1, F2, F3, and F4, 91 (53.5%), 117 (68.8%), and 110 (64.7%) patients, respectively, were correctly classified according to histological results.ELF demonstrated considerable diagnostic value in fibrosis staging in Asian CHB patients, especially in predicting F≥2. However, LSM consistently provided better performance for predicting F≥3 and F4

The HIF-1/glial TIM-3 axis controls inflammation-associated brain damage under hypoxia.

Inflammation is closely related to the extent of damage following cerebral ischaemia, and the targeting of this inflammation has emerged as a promising therapeutic strategy. Here, we present that hypoxia-induced glial T-cell immunoglobulin and mucin domain protein (TIM)-3 can function as a modulator that links inflammation and subsequent brain damage after ischaemia. We find that TIM-3 is highly expressed in hypoxic brain regions of a mouse cerebral hypoxia-ischaemia (H/I) model. TIM-3 is distinctively upregulated in activated microglia and astrocytes, brain resident immune cells, in a hypoxia-inducible factor (HIF)-1-dependent manner. Notably, blockade of TIM-3 markedly reduces infarct size, neuronal cell death, oedema formation and neutrophil infiltration in H/I mice. Hypoxia-triggered neutrophil migration and infarction are also decreased in HIF-1α-deficient mice. Moreover, functional neurological deficits after H/I are significantly improved in both anti-TIM-3-treated mice and myeloid-specific HIF-1α-deficient mice. Further understanding of these insights could serve as the basis for broadening the therapeutic scope against hypoxia-associated brain diseases

NHERF2 specifically interacts with LPA(2) receptor and defines the specificity and efficiency of receptor-mediated phospholipase C-beta 3 activation

Lysophosphatidic acid (LPA) activates a family of cognate G protein-coupled receptors and is involved in various pathophysiological processes. However, it is not clearly understood how these LPA receptors are specifically coupled to their downstream signaling molecules. This study found that LPA, but not the other LPA receptor isoforms, specifically interacts with Na+/H+ exchanger regulatory factor2 (NHERF2). In addition, the interaction between them requires the C-terminal PDZ domain-binding motif of LPA(2) and the second PDZ domain of NHERF2. Moreover, the stable expression of NHERF2 potentiated LPA-induced phospholipase C-beta (PLC-beta) activation, which was markedly attenuated by either a mutation in the PDZ-binding motif of LPA(2) or by the gene silencing of NHERF2. Using its second PDZ domain, NHERF2 was found to indirectly link LPA(2) to PLC-beta3 to form a complex, and the other PLC-beta isozymes were not included in the protein complex. Consistently, LPA(2)-mediated PLC-beta activation was specifically inhibited by the gene silencing of PLC-beta3. In addition, NHERF2 increases LPA-induced ERK activation, which is followed by cyclooxygenase-2 induction via a PLC-dependent pathway. Overall, the results suggest that a ternary complex composed of LPA(2), NHERF2, and PLC-beta3 may play a key role in the LPA2-mediated PLC-beta signaling pathwayclose606

Dynamic relocalization of NHERF1 mediates chemotactic migration of ovarian cancer cells toward lysophosphatidic acid stimulation

NHERF1/EBP50 (Na+/H+ exchanger regulating factor 1; Ezrin-binding phosphoprotein of 50 kDa) organizes stable protein complexes beneath the apical membrane of polar epithelial cells. By contrast, in cancer cells without any fixed polarity, NHERF1 often localizes in the cytoplasm. The regulation of cytoplasmic NHERF1 and its role in cancer progression remain unclear. In this study, we found that, upon lysophosphatidic acid (LPA) stimulation, cytoplasmic NHERF1 rapidly translocated to the plasma membrane, and subsequently to cortical protrusion structures, of ovarian cancer cells. This movement depended on direct binding of NHERF1 to C-terminally phosphorylated ERM proteins (cpERMs). Moreover, NHERF1 depletion downregulated cpERMs and further impaired cpERM-dependent remodeling of the cell cortex, suggesting reciprocal regulation between these proteins. The LPA-induced protein complex was highly enriched in migratory pseudopodia, whose formation was impaired by overexpression of NHERF1 truncation mutants. Consistent with this, NHERF1 depletion in various types of cancer cells abolished chemotactic cell migration toward a LPA gradient. Taken together, our findings suggest that the high dynamics of cytosolic NHERF1 provide cancer cells with a means of controlling chemotactic migration. This capacity is likely to be essential for ovarian cancer progression in tumor microenvironments containing LPA