STIGMA AND LOW SENSE OF COHERENCE AS LONG-TERM PREDICTORS OF DEPRESSIVE AND ANXIETY SYMPTOMS IN THE POPULATION AMID THE COVID-19 PANDEMIC

Background: The COVID-19 has had a profound negative impact on the population’s mental health. This study aimed to determine the prevalence of depressive and anxiety symptoms in the general population during the third wave of the COVID-19 pandemic and to identify risk factors associated with these symptoms after implementing initial prevention strategies. Subjects and methods: A cross-sectional study was conducted among 200 visitors to five general practices in February 2021 in Slovenia. The response rate was 82.0% (164/200). A structured survey was used to assess sociodemographic factors, depressive and anxiety symptoms, exposure to COVID-19 stressors, stress coping strategies used, and sense of coherence (SOC). A score of ≥10 points on the Patient Health Questionnaire-9 and ≥10 points on the General Anxiety Disorder-7 questionnaire were considered as cut-offs for screened depression and anxiety, respectively. The Mann-Whitney U test, chi-square test, and binary logistic regression were used for statistical analysis. Results: The prevalence of screened depression and anxiety was 24.4% and 12.9%, respectively. Independent predictors of depression were stigma related to COVID-19 (OR 2.42, 95% CI 1.57-3.73, p<0.001), low SOC (OR 5.89, 95% CI 2.21-15.72, p<0.001), and smoking (OR 3.53, 95% CI 1.23-10.10. p=0.019). Independent predictors of anxiety were religious rituals cancellation (OR 1.64, 95% CI 1.02-2.65, p=0.040), childcare responsibilities (OR 1.70, 95% CI 1.07-2.69, p=0.025), increased contact with close ones (OR 1.92, 95% CI 1.11-3.29, p=0.019), and low SOC (OR 5.21, 95% CI 1.22-22.31, p=0.026). Conclusions: Despite efforts to address the pandemic through prevention strategies and the burden of the pandemic decreasing, we still found a high prevalence of depressive and anxiety symptoms. While some risk factors can be addressed quickly, such as by providing stable childcare and schooling and enabling assess to mental health services for vulnerable families, others require a longer- term approach, such as strengthening SOC and reducing stigma

GSTM1 (Glutathione S-transferase M1)

Review on GSTM1, with data on DNA, on the protein encoded, and where the gene is implicated

Flame retardant effectiveness of nanodispersed organophosphorus-derivative in polyamide 6 textile filament yarns

The halogen-free flame retardant (FR) polyamide 6 (PA6) composite textile filament yarns fabricated via melt-compounding have never achieved effective flame retardancy. The main reason for that is related to the agglomeration of FR additives due to their poor compatibility with PA6 polymer chains. The formed FR agglomerates substantially reduce the flame retardant effectiveness, disable continuous melt-spinning process due to clogging of the filters and spinnerets, and significantly impair fibre tensile properties. Therefore, the goal of this study was to investigate how lowering of the FR additive size to the nanoscopic level affects melt-spinning process and flame retardancy of the nanocomposite PA6 filament yarns. To this aim, we established a new scalable approach for the production of new-generation PA6/FR nanocomposite filament yarns with uniformly distributed nano-dispersed halogen-free FR. So, instead of mixing FR additive with PA6 melt, we rather chose a step back, i.e. mixing of FR additive with ε-caprolactam melt and performing the in situ polymerization

Polymorphic expression of glutathione transferases A1, M1, P1 and T1 in epithelial ovarian cancer: a Serbian case-control study

PURPOSE: Since several studies have proposed that epithelial ovarian cancer should not be considered as a single disease entity and that it results from an accumulation of genetic changes, we aimed to assess the polymorphic expression of major cytosolic glutathione S-transferases (GSTM1, T1, A1 and P1) with respect to ovarian cancer susceptibility and aggressiveness. METHODS: This case-control study was conducted on 93 newly diagnosed epithelial ovarian cancer patients and 178 healthy matched controls. The multiplex polymerase chain reaction (PCR) was used to detect homozygous deletions of GSTM1 and GSTT1 genes. Analysis of the single nucleotide polymorphism (SNP) GSTA1 C69T was performed using PCR-restriction fragment length polymorphism (RFLP), while for SNP GSTP1 Ile105Val real-time PCR was used. RESULTS: No significant association to ovarian cancer risk was found for individual GSTM1, GSTA1 and GSTP1 genotypes (p>0.05). However, the carriers of GSTT1-active genotype were at 2-fold higher risk of ovarian cancer development (95%CI: 1.00-4.01, p=0.049), which was even more elevated in the subgroup of patients with positive family history of cancer. Moreover, the frequency of all three GST genotypes that might be associated to ovarian cancer risk (GSTT1-active, GSTA1-active and GSTP1-referent) was significantly higher in patients than in the control group (p=0.042). Even more, patients who were carriers of combination of these three genotypes represented over 64% of the total number of patients within any of the International Federation of Gynecology and Obstetrics (FIGO) stages of ovarian cancer. CONCLUSIONS: This study provides supportive evidence that GSTs might affect both susceptibility and progression of ovarian cance

Is Increased Susceptibility to Balkan Endemic Nephropathy in Carriers of Common GSTA1 (*A/*B) Polymorphism Linked with the Catalytic Role of GSTA1 in Ochratoxin A Biotransformation? Serbian Case Control Study and In Silico Analysis

Although recent data suggest aristolochic acid as a putative cause of Balkan endemic nephropathy (BEN), evidence also exists in favor of ochratoxin A (OTA) exposure as risk factor for the disease. The potential role of xenobiotic metabolizing enzymes, such as the glutathione transferases (GSTs), in OTA biotransformation is based on OTA glutathione adducts (OTHQ-SG and OTB-SG) in blood and urine of BEN patients. We aimed to analyze the association between common GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms and BEN susceptibility, and thereafter performed an in silico simulation of particular GST enzymes potentially involved in OTA transformations. GSTA1, GSTM1, GSTT1 and GSTP1 genotypes were determined in 207 BEN patients and 138 non-BEN healthy individuals from endemic regions by polymerase chain reaction (PCR). Molecular modeling in silico was performed for GSTA1 protein. Among the GST polymorphisms tested, only GSTA1 was significantly associated with a higher risk of BEN. Namely, carriers of the GSTA1*B gene variant, associated with lower transcriptional activation, were at a 1.6-fold higher BEN risk than those carrying the homozygous GSTA1*A/*A genotype (OR = 1.6; p = 0.037). In in silico modeling, we found four structures, two OTB-SG and two OTHQ-SG, bound in a GSTA1 monomer. We found that GSTA1 polymorphism was associated with increased risk of BEN, and suggested, according to the in silico simulation, that GSTA1-1 might be involved in catalyzing the formation of OTHQ-SG and OTB-SG conjugates

In situ prepared polyamide 6/DOPO-derivative nanocomposite for melt-spinning of flame retardant textile filaments

Abstract A novel flame retardant polyamide 6 (PA6)/bridged 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO)-derivative (PHED) nanocomposite textile filament yarns were developed. The scalable production approach includes in situ water-catalyzed ring-opening polymerization of e-caprolactam in the presence of the flame retardant PHED followed by melt-spinning of nanocomposite filament yarns and production of knitted fabrics. The specific chemical structure of the PHED additive enabled its excellent miscibility with molten e-caprolactam and the uninterrupted polymerization of e-caprolactam. The produced PA6/PHED nanocomposite was characterized by the preserved molecular structure of the polyamide 6 and uniformly distributed nano-dispersed FR at concentrations of 10 and 15 wt %. The PA6/PHED nanocomposite structure was successfully preserved after the melt-spinning processing. The PA6 nanocomposite filament yarns at the applied 15 wt %. loading of PHED showed (a) increased thermo-oxidative stability compared to neat PA6 up to 500 °C, with a 43% higher residue at 500 °C and (b) self-extinguishment of fiber strand and knitted samples within 1 s in standard vertical flame spread tests (ASTM D6413), followed by the significant reduction of the melt-dripping and the melt-drop flammability. Additionally, 1.2 mm-tick PA6/PHED bar samples achieved a V0 rating in UL94 vertical burning test at the applied 10 wt % concentration of PHED. This innovative and scalable approach could pave the way for the production of new-generation nanocomposite PA6 filament yarns with self-extinguishing properties at the macro-scale, which would be highly beneficial for increasing fire safety, whilst maintaining the use of a DOPO derivative at the minimum level

Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration

Intestinal organoids capture essential features of the intestinal epithelium such as crypt folding, cellular compartmentalization and collective movements. Each of these processes and their coordination require patterned forces that are at present unknown. Here we map three-dimensional cellular forces in mouse intestinal organoids grown on soft hydrogels. We show that these organoids exhibit a non-monotonic stress distribution that defines mechanical and functional compartments. The stem cell compartment pushes the extracellular matrix and folds through apical constriction, whereas the transit amplifying zone pulls the extracellular matrix and elongates through basal constriction. The size of the stem cell compartment depends on the extracellular-matrix stiffness and endogenous cellular forces. Computational modelling reveals that crypt shape and force distribution rely on cell surface tensions following cortical actomyosin density. Finally, cells are pulled out of the crypt along a gradient of increasing tension. Our study unveils how patterned forces enable compartmentalization, folding and collective migration in the intestinal epithelium

BMP axis in cancer cachexia

BACKGROUND Cancer cachexia is a devastating metabolic syndrome characterized by systemic inflammation and massive muscle and adipose tissue wasting. Although cancer cachexia is responsible for about 25% of cancer deaths, no effective therapies are available, and the underlying mechanisms have not been fully elucidated. Its occurrence complicates patients’ management, reduces tolerance to treatments and negatively affects patient quality of life. Muscle wasting, mainly due to increased protein breakdown rates, is one of the most prominent features of cachexia. Blocking muscle loss in cachexia mouse models dramatically prolongs survival even of animals in which tumor growth is not inhibited. Recent observations showed that bone morphogenetic protein (BMP) signaling, acting through Smad1, Smad5 and Smad8 (Smad1/5/8), is a master regulator of muscle homeostasis. BMP-Smad1/5/8 axis negatively regulates a novel ubiquitin ligase (MUSA1) required for muscle loss induced by denervation. MATERIALS AND METHODS First aim of the present work was to test if alterations of the BMP signaling pathway occur in cancer-induced muscle wasting in patients. For this purpose we checked the state of activation of the BMP pathway in muscle of cachectic vs non–cachectic patients affected by colon, pancreatic and esophagus cancer and in control subjects. We checked by Western Blot the phosphorylation levels of Smad1/5/8 and of Smad3 and by quantitative Real-Time PCR (qRT-PCR) the expression levels of different atrophy-related genes The second aim was to evaluate the degree of muscle atrophy and distribution of muscle fibers in patients and control subjects using morphometric and immunohistochemical analyses. We also performed analysis on distribution of NCAM positive muscle fibers to assess the effect of denervation on muscle tropism. RESULTS From December 2014 we collected 95 rectus abdominis muscle biopsies of cancer patients and 11 from control subjects. In line with the results we obtained in C26 mice model (a well-established cancer cachexia experimental model) Smad1/5/8 phosphorylation, readout of the state of activation of the BMP pathway, was nearly completely abrogated in the muscles of cancer cachectic patients compared to cancer non-cachectic ones. Interestingly, the level of phosphorylation of Smad3 was not significantly affected suggesting specific effects of cancer growth on BMP pathway. The expression levels of different atrophy-related genes including MUSA1 were induced in the cachectic muscles. Interestingly, several BMP related genes are also changing the expression during cancer growth. We also found a correlation between suppression of BMP pathway, expression of atrophy related genes and Noggin, known to block BMP pathway. Morphometric analysis shown that patients with cancer cachexia have smaller myofiber diameter (in particular fast type fibers) in comparison to age-matched controls. In skeletal muscle from cancer patients (either cachectic or non-cachectic) we detected a prevalence of flat shaped, angulated and severely atrophic myofibers (i.e. morphological features of denervated myofibers), big fiber-type grouping (i.e. typical hallmark of denervation/reinnervation events) and numerous NCAM positive myofibers (i.e. specific marker of denervation). CONCLUSIONS These findings are consistent with the hypothesis that BMP inhibition is permissive to cachexia onset. Since the reactivation of the BMP-dependent signaling and MUSA1 suppression was sufficient to prevent tumor-induced muscle atrophy in our C26 mouse model (data not shown), the present data suggest that the BMP axis can be an effective target for therapeutic approaches to counteract cachexia also in cancer patients. The results of morphometric and immunohistochemical studies collected till now may suggest that denervation contributes to myofiber atrophy in cancer cachexia

THE SENSE OF COHERENCE AND SUBJECTIVE WELL-BEING AS RESOURCES OF RESILIENCE IN THE TIME OF STRESSFUL SITUATIONS: COVID-19 OUTBREAK AND EARTHQUAKES

Background: The coronavirus outbreak was labeled a global pandemic by the WHO in March 2020. Simultaneously, an earthquake of 5.5 hit Croati . The present study investigated the association between the sense of coherence, subjective well-being, and emotional distress (depression, anxiety, and stress) that people went through while facing an acute stress situation of COVID-19 outbreak and the earthquakes. Subjects and methods: This cross-sectional study included 1152 subjects. Orientation to Life Questionnaires (OLQ-13), Personal Wellbeing Index (PWI) and DASS-21 scale were used in an anonymous online survey which was conducted on 22 March 2020 (the twelfth day of the COVID-19 outbreak in Croatia and the day of the earthquakes in the Capital). The results of the questionnaires were determined by the correlation analysis. Hierarchical multiple regression was used to evaluate the association between the subjective well-being and the sense of coherence on the emotional distress. Results: The sense of coherence correlated positively with subjective well-being (p<0.01) and negatively with all distress domains (p<0.01) as well as subjective well-being (p<0.01). Mild emotional distress was detected. Subjects who experienced the earthquakes showed a significantly higher degree of anxiety (p=0.005) and stress (p=0.003), with significantly decreased the two personal well-being domains: standard of living (p=0.023) and personal safety (p=0.026). Sense of coherence made a major contribution in explaining emotional distress (p<0.001). Conclusion: The results support the importance of improving coping efficiency of the sense of coherence with respect to obtaining an appropriate level of well-being and reducing emotional distress in acute stressful situations