Unraveling the potential of vitamins C and D as adjuvants in depression treatment with escitalopram in an LPS animal model.

Depression is linked with oxidative stress and inflammation, where key players include nitric oxide (NO), nuclear factor erythroid 2-related factor 2 (Nrf2), Brain-Derived Neurotrophic Factor (BDNF), and Heme Oxidase-1 (HO-1). Augmenting the efficacy of antidepressants represents a compelling avenue of exploration. We explored the potential of vitamins C and D as adjuncts to escitalopram (Esc) in a lipopolysaccharide (LPS)-induced depression model focusing on the aforementioned biomarkers. Male Swiss albino mice were stratified into distinct groups: control, LPS, LPS + Esc, LPS + Esc + Vit C, LPS + Esc + Vit D, and LPS + Esc + Vit C + Vit D. After a 7-day treatment period, a single LPS dose (2 mg/kg), was administered, followed by comprehensive assessments of behavior and biochemical parameters. Notably, a statistically significant (p < 0.05) alleviation of depressive symptoms was discerned in the Esc + Vit C + Vit D group versus the LPS group, albeit with concomitant pronounced sedation evident in all LPS-treated groups (p < 0.05). Within the cortex, LPS reduced (p < 0.05) the expression levels of NOx, Nrf2, BDNF, and HO-1, with only HO-1 being reinstated to baseline in the LPS + Esc + Vit D and the LPS + Esc + Vit C + Vit D groups. Conversely, the hippocampal NOx, Nrf2, and HO-1 levels remained unaltered following LPS administration. Notably, the combination of Esc, Vit C, and Vit D effectively restored hippocampal BDNF levels, which had been diminished by Esc alone. In conclusion, vitamins C and D enhance the therapeutic effects of escitalopram through a mechanism independent of Nrf2. These findings underscore the imperative need for in-depth investigations.

Understanding the Association of Self-Efficacy, Mood, and Demographics with Physical Activity in Syrian and Iraqi Refugees: A Cross-Sectional Study in Jordan.

Objective: This cross-sectional study aimed at investigating the influence of sociodemographic factors on physical activity among Syrian and Iraqi refugees in Jordan. In addition, it sought to determine the predictive ability of self-efficacy and mood in relation to the level of physical activity in this population. Methods: A convenient sample of refugees residing in Jordanian cities was collected. Participants completed a self-administered questionnaire pack consisting of a demographic data sheet, a physical activity level questionnaire, the Brunel Mood Scale, and the General Self-Efficacy Scale. Descriptive analysis was used to analyze demographic details, while the chi-square test examined the association between physical activity and demographic factors. The independent t-test assessed differences in self-efficacy and mood subscales in relation to physical activity. Logistic regression analysis was employed to identify potential predictors of the two categories of physical activity. Results: Most participants reported low levels of physical activity. The frequency of moderate-to-high physical activity was higher in male participants, those with higher education, better health, and higher income. Compared to participants of low physical activity, those in the moderate-to-high physical activity category expressed significantly higher mean score of self-efficacy but lower mean scores of tension, depression, anger, vigor, fatigue, and confusion, indicating better mood. The logistic regression analysis for physical activity indicated that the model was significant for education, income, good health perception, self-efficacy, and one mood subscale (vigor), with these variables collectively accounting for 11-18% of the variance (P value <0.001). Conclusion: The higher physical activity level is significantly associated with being male, higher education, higher income, better health, higher self-efficacy, and increased vigor. These findings highlight the importance of considering sociodemographic factors and psychological aspects, such as self-efficacy and mood, when addressing physical activity among refugees in Jordan.

Modulation of wheatgrass (Triticum aestivum Linn) toxicity against breast cancer cell lines by simulated microgravity.

This study scrutinizes the effects of simulated microgravity on the antioxidant and cytotoxic potential, along with the phytochemical content of wheatgrass (Triticum aestivum Linn). To imitate microgravity, wheatgrass seeds were germinated in a 3D-clinostat at different rotations per minute (5, 10, 15, and 20 rpm), together with terrestrial gravity control, over 10 days. After germination, the methanolic extracts were analyzed using UPLC-Triple Quad LCMS for their phytochemical composition and tested for their hydrogen peroxide, nitric oxide, and DPPH scavenging activities. The cytotoxic effects of these extracts were evaluated against normal skin fibroblasts, normal breast cells (MCF-10), and breast cancer cells (MCF-7 and MDA-231). The findings showed an extended root growth in wheatgrass germinated under microgravity (WGM) compared to under gravity (WGG). Additionally, WGM extracts demonstrated increased H2O2-, NO-, and DPPH-scavenging activities and a higher content of polyphenols and flavonoids than WGG extracts. These effects were amplified with an increase in clinostat rotations. Moreover, WGM extracts were found to contain a unique set of bioactive compounds (compounds that were detected in the microgravity-germinated wheatgrass but were either absent or present in lower concentrations in wheatgrass germinated under standard gravity conditions.), including pyridoxine, apigenin, and tocopherol, among others, which were absent in WGG. The UPLC-Triple Quad LCMS analysis revealed these unique bioactive compounds in WGM. Notably, WGM extracts showed enhanced cytotoxic effects against normal skin fibroblasts, normal MCF-10, MCF-7, and breast cancer MDA-231 cell lines, with increased cytotoxicity correlating with the number of clinostat rotations. Particularly, WGM extract (at 20 rpm) demonstrated significantly stronger cytotoxicity against MCF-7 breast cancer cells. Further in-depth gene expression analysis of MCF-7 cells exposed to WGM revealed a significant downregulation of genes integral to breast cancer pathways, tyrosine kinase signaling, and DNA repair, complemented by upregulation of certain cell survival and cytotoxic genes. These alterations in genetic pathways associated with cell survival, hormone responses, and cancer progression may elucidate the enhanced cytotoxicity observed in WGM extracts. Our findings underscore the potential of microgravity as a tool to enhance the cytotoxic capabilities of wheatgrass against cancer cell lines, presenting a promising direction for future research in the field of space biology and its implications for terrestrial health.

Effect of time-restricted eating on sex hormone levels in premenopausal and postmenopausal females.

OBJECTIVE: Concerns have been raised regarding the impact of time-restricted eating (TRE) on sex hormones in females. This study examined how TRE affects sex steroids in premenopausal and postmenopausal females. METHODS: This is a secondary analysis of an 8-week TRE study (4- to 6-hour eating window) conducted in adults with obesity. Men and perimenopausal females were excluded. Females were classified into two groups based on menstrual status: premenopausal (n = 12) or postmenopausal (n = 11). RESULTS: After 8 weeks, body weight decreased in premenopausal females (-3% ± 2%) and postmenopausal females (-4% ± 2%) (main effect of time, p < 0.001), with no difference between groups (no group × time interaction). Circulating levels of testosterone, androstenedione, and sex hormone binding globulin (SHBG) did not change in either group (no group × time interaction). Dehydroepiandrosterone (DHEA) concentrations decreased (p < 0.05) in premenopausal (-14% ± 32%) and postmenopausal females (-13% ± 34%; main effect of time, p = 0.03), with no difference between groups. Estradiol, estrone, and progesterone were measured only in postmenopausal females, and they remained unchanged. CONCLUSIONS: In premenopausal females, androgens and SHBG remained unchanged during TRE, whereas DHEA decreased. In postmenopausal females, estrogens, progesterone, androgens, and SHBG did not change, but DHEA was reduced.

The development and validation of a novel COVID19 stigma scale among healthcare workers (COVISS-HCWs).

BACKGROUND AND AIM: Fear of coronavirus disease 2019 (COVID-19) and its complications may result in stigmatization of individuals who may carry the virus. This is of special concern to healthcare workers who tolerate additional physical and emotional stress at times of pandemic. The aims of this study are to (1) develop and validate the COVID-19 Stigma Scale (COVISS-HCWs) survey; and (2) investigate the experience of stigma among healthcare workers possibly dealing with COVID-19 patients in five major public hospitals in Damascus, Syria. METHODS: We divided the sample into two parts and then underwent EFA on the first 350 participants, dividing the 14 questions into two dimensions. Furthermore, CFA was conducted on the other 350 participants to confirm how correctly a hypothesized model matched the factor structure by EFA, as described above. Moreover, the coefficient of determination (R2) and item-scale correlations (standardized factor loading) were estimated to establish the acceptability of the final structure of the COVISS-HCWs. Through a cross-sectional study, a convenience sample of 700 healthcare workers participated in a self-administered questionnaire containing a section for demographic variables and another for newly designed COVISS-HCWs. The scale comprises 14 adapted and novel items that measure two subscales: feelings of perceived harm and inferiority, and avoidance. Descriptive statistics, reliability, and validity were evaluated. RESULTS: The 14 COVISS-HCWs items were reduced to 11 items with a high Cronbach's α of 0.909. A significant correlation was observed between the responses to each COVISS-HCWs item and the corresponding subscale, and between each subscale and the overall scale. Feeling stigmatized was reported by 9.86% of the participants. Younger age, low socioeconomic status, and higher intensity of contact with COVID-19 patients significantly correlated with higher stigmatization. CONCLUSIONS: The novel COVISS-HCWs is a reliable and valid tool to evaluate stigma among healthcare workers during the COVID-19 pandemic. The Stigma prevalence among healthcare workers was 9.86%. Therefore, this must be addressed to prevent possible psychosocial and public health repercussions.

Validity and Reproducibility of a Food Frequency Questionnaire to Assess Macro and Micro-Nutrient Intake among a Convenience Cohort of Healthy Adult Qataris.

This study aimed at developing a valid culture-sensitive quantitative food frequency questionnaire (FFQ) for Qatari adults. A convenient sample of healthy Qataris (n = 107) were recruited from family members of Qatar University students. The Diet History Questionnaire II of the US National Cancer Institute was translated to Arabic language, back-translated to English, pilot tested, and then modified accordingly to be used in Qatari setting. Participants were asked to complete the translated version of the FFQ. This FFQ was then validated against three 24 h diet recall (24 hDR) including a weekend day. Participants were asked to complete the FFQ again after one-month period to measure its repeatability. Dietary data were analyzed using the dietary analysis software ESHA. The validity and reliability of FFQ were assessed by comparing the median intake of nutrients and foods and by calculating the Pearson correlation coefficients. The median nutrient intakes assessed by the second FFQ were higher than that reported in the baseline FFQ1 except for fat. The percentage of increase varies between 1.5% and 96%. Results of the second FFQ indicated an overestimation of intake for most nutrients (macro and micro). Macronutrient intakes assessed by the two FFQ and 24 hDR were strongly correlated. The correlation coefficients for micronutrient intakes between FFQ2 and 24hDR were lower than that of the two FFQs except for calcium (r = 0.55) and sodium (r = 0.643). They ranged from (-0.17) for fluorine to (0.643) for sodium. The agreement rates for classifying macronutrient intakes into same or adjacent quartile were between 79.4% and 100% for the two FFQs and between 71% and 100% for the second FFQ and 24hDR. The reported consumption of food groups estimated by FFQ2 was significantly higher than that reported by FFQ1. In conclusion, the developed FFQ was sufficiently valid to assess energy and macronutrients but not micronutrients. The reliability was adequate for most nutrients.

Novel in vitro and in vivo anti-Helicobacter pylori effects of pomegranate peel ethanol extract.

BACKGROUND AND AIM: Interest in plants with antimicrobial properties has been revived due to emerging problems associated with using antibiotics to eradicate Helicobacter pylori. Accordingly, this study aims to assess the antibacterial effects of Punica granatum and the possible synergistic effect of its extract along with metronidazole against H. pylori. MATERIALS AND METHODS: Pomegranate peel ethanol extracts (PPEE) was tested against a control strain of H. pylori (NCTC 11916) in vitro and in vivo in female Wistar rats. Moreover, the synergistic effect of PPEE in combination with metronidazole was tested in vitro. RESULTS: The PPEE exhibited a remarkable activity against H. pylori with a minimum inhibitory concentration (MIC) of 0.156 mg/mL. Furthermore, the extract exhibited a pronounced urease inhibitory activity (IC50 ~6 mg/mL) against the tested strain. A synergistic effect between PPEE and metronidazole was also observed (fractional inhibitory concentrations <0.5). Oral treatment of rats with PPEE for 8 days produced a significant reduction in H. pylori gastritis and a significant decrease in both lymphocytic and positive chronicity. CONCLUSION: Pomegranate extract is probably safe and represents a potential alternative and complementary therapy for reducing H. pylori associated with gastric ulcers.

Mood and demographical factors as predictors of body mass index among Syrian and Iraqi refugees in Jordan.

We studied whether mood and demographics are related to body mass index in a population of Syrian and Iraqi refugees residing in Jordan. Questionnaires and Brunel Mood Scale were used to collect demographical data. Data were analyzed using t-test and analysis of variance. A high prevalence of overweight and obesity was observed in this population (60.5%). Mood subscales were not associated with body mass index categories. However, body mass index as a continuous variable was associated with anger, depression, and fatigue scores. Linear regression revealed that age, ethnicity, unemployment, chronic illnesses, and physical activity level, but not mood, are associated with body mass index.

Weight loss efficacy of alternate day fasting versus daily calorie restriction in subjects with subclinical hypothyroidism: a secondary analysis.

This study compared the weight loss efficacy of alternate-day fasting (ADF) versus daily calorie restriction (CR) in adults with subclinical hypothyroidism. After 6 months, body weight decreased (P < 0.001) similarly by ADF (-7% ± 1%) and CR (-8% ± 2%). Insulin resistance decreased (P < 0.05) more by ADF versus CR. Free thyroxin and thyroid-stimulating hormone remained unchanged. Thus, ADF and CR produce similar weight loss in this population, without affecting thyroid hormone levels. Novelty Intermittent fasting and daily restriction produce similar reductions in body weight in subjects with subclinical hypothyroidism.

Increased adiposity in annexin A1-deficient mice.

Production of Annexin A1 (ANXA1), a protein that mediates the anti-inflammatory action of glucocorticoids, is altered in obesity, but its role in modulation of adiposity has not yet been investigated. The objective of this study was to investigate modulation of ANXA1 in adipose tissue in murine models of obesity and to study the involvement of ANXA1 in diet-induced obesity in mice. Significant induction of ANXA1 mRNA was observed in adipose tissue of both C57BL6 and Balb/c mice with high fat diet (HFD)-induced obesity versus mice on chow diet. Upregulation of ANXA1 mRNA was independent of leptin or IL-6, as demonstrated by use of leptin-deficient ob/ob mice and IL-6 KO mice. Compared to WT mice, female Balb/c ANXA1 KO mice on HFD had increased adiposity, as indicated by significantly elevated body weight, fat mass, leptin levels, and adipocyte size. Whereas Balb/c WT mice upregulated expression of enzymes involved in the lipolytic pathway in response to HFD, this response was absent in ANXA1 KO mice. A significant increase in fasting glucose and insulin levels as well as development of insulin resistance was observed in ANXA1 KO mice on HFD compared to WT mice. Elevated plasma corticosterone levels and blunted downregulation of 11-beta hydroxysteroid dehydrogenase type 1 in adipose tissue was observed in ANXA1 KO mice compared to diet-matched WT mice. However, no differences between WT and KO mice on either chow or HFD were observed in expression of markers of adipose tissue inflammation. These data indicate that ANXA1 is an important modulator of adiposity in mice, with female ANXA1 KO mice on Balb/c background being more susceptible to weight gain and diet-induced insulin resistance compared to WT mice, without significant changes in inflammation.

New pathways to control inflammatory responses in adipose tissue.

Obesity is characterized by the presence of chronic inflammation in adipose tissue, particularly in the visceral compartment, that has been causally linked to development of obesity-associated comorbidities. This link can be either direct or indirect, through induction of insulin resistance. This review summarizes recent evidence on potential pharmacological targets of adipose tissue inflammation, with emphasis on mediators that are being studied for intervention in chronic inflammatory diseases and are therefore viable therapeutical candidates. Specifically, we discuss evidence on the role of the inflammasome and its downstream products as a potential target for anti-inflammatory strategies as well as T regulatory (Treg) cells and mediators involved in the resolution phase of inflammation such as resolvins, protectins, annexin A1 (ANXA1) and galectins as potential targets for novel agonist therapies.

Increased adiposity, dysregulated glucose metabolism and systemic inflammation in Galectin-3 KO mice.

Obesity and type 2 diabetes are associated with increased production of Galectin-3 (Gal-3), a protein that modulates inflammation and clearance of glucose adducts. We used Lean and Diet-induced Obese (DIO) WT and Gal-3 KO mice to investigate the role of Gal-3 in modulation of adiposity, glucose metabolism and inflammation. Deficiency of Gal-3 lead to age-dependent development of excess adiposity and systemic inflammation, as indicated by elevated production of acute-phase proteins, number of circulating pro-inflammatory Ly6C(high) monocytes and development of neutrophilia, microcytic anemia and thrombocytosis in 20-week-old Lean and DIO male Gal-3 KO mice. This was associated with impaired fasting glucose, heightened response to a glucose tolerance test and reduced adipose tissue expression of adiponectin, Gal-12, ATGL and PPARγ, in the presence of maintained insulin sensitivity and hepatic expression of gluconeogenic enzymes in 20-week-old Gal-3 KO mice compared to their diet-matched WT controls. Expression of PGC-1α and FGF-21 in the liver of Lean Gal-3 KO mice was comparable to that observed in DIO animals. Impaired fasting glucose and altered responsiveness to a glucose load preceded development of excess adiposity and systemic inflammation, as demonstrated in 12-week-old Gal-3 KO mice. Finally, a role for the microflora in mediating the fasting hyperglycemia, but not the excessive response to a glucose load, of 12-week-old Gal-3 KO mice was demonstrated by administration of antibiotics. In conclusion, Gal-3 is an important modulator of glucose metabolism, adiposity and inflammation.

Current status of interventional radiology treatment of infrapopliteal arterial disease.

Treatment of infrapopliteal arteries has developed to a standard technique during the past two decades. With the introduction of innovative devices, a variety of techniques has been created and is still under investigation. Treatment options range from plain balloon angioplasty (POBA), all sorts of stent applications, such as bare metal, balloon expanding, self-expanding, coated and drug-eluting stents, and bio-absorbable stents, to latest developments, such as drug-eluting balloons. Regarding the scientific background, several prospective, randomized studies with relevant numbers of patients have been (or will be) published that are Level I evidence. In contrast to older studies, which primarily were based mostly on numeric parameters, such as diameters or residual stenoses, more recent study concepts focus increasingly on clinical features, such as amputation rate improvement or changes of clinical stages and quality of life standards. Although it is still not decided, which of the individual techniques might be the best one, we can definitely conclude that whatever treatment of infrapopliteal arteries will be used it is of substantial benefit for the patient. Therefore, the goal of this review is to give an overview about the current developments and techniques for the treatment of infrapopliteal arteries, to present clinical and technical results, to weigh individual techniques, and to discuss the recent developments.

Quality improvement guidelines for imaging detection and treatment of endoleaks following endovascular aneurysm repair (EVAR).

Major concerns after aortic aneurysm repair are caused by the presence of endoleaks, which are defined as persistent perigraft flow within the aortic aneurysm sac. Diagnosis of endoleaks can be performed with various imaging modalities, and indications for treatment are based on further subclassifications. Early detection and correct classification of endoleaks are crucial for planning patient management. The vast majority of endoleaks can be treated successfully by interventional means. Guidelines for Imaging Detection and Treatment of endoleaks are described in this article.

Inflammation-associated gene transcription and expression in mouse lungs induced by low molecular weight compounds from fungi from the built environment.

Few metabolites from fungi found indoors have been tested for inflammatory mediators endpoints in primary cultures of alveolar macrophages or in vivo. In this study, mice were intratracheally instilled with a single dose comprising 4x10(-5)moletoxin/kg lung wt dose of either atranone C, brevianamide, cladosporin, mycophenolic acid, neoechinulin A & B, sterigmatocystin or TMC-120A. These toxins are from fungi common on damp building materials. The dose used was comparable to the estimated doses of possible human exposure. Hematoxylin and eosin (H&E) histology and Alcian Blue/Periodic Acid Schiff (AB/PAS) histochemistry were used to evaluate lungs for time course (4h and 12h post-exposure (PE)) inflammatory and toxic changes. Reverse-transcription (RT)-PCR based arrays were also employed to evaluate time course inflammation-associated gene transcription in lung tissues of the different toxins. Immunohistochemistry (IHC) was used to probe MIP-2 and Tnf-alpha protein expression in treatment lungs to determine whether responses correspond with gene transcription data. Both histology and histochemistry revealed that toxin exposed lungs at 12h PE showed evidence of inflammation. H&E revealed that bronchioli were lined with irregularly thickened and sometimes sloughing epithelium and bronchiolar spaces supported infiltration of leukocytes, cellular and mucus-like debris while alveolar spaces supported swollen macrophages and modest amorphous debris accumulations. All toxin-instilled lungs exhibited copious mucus production and alveolar macrophages with red stained cytoplasm on bronchiolar surfaces, especially at 12h PE. Array analysis of 83 inflammation-associated genes extracted from lung tissue demonstrated a number of patterns, compared to controls. 82 genes assayed at 4h PE and 75 genes at 12h PE were significantly altered (p< or =0.05; >or =1.5-fold or < or =-1.5-fold change) in the different treatment animal groups. Expression of transcriptionally regulated genes was confirmed using immunohistochemistry that demonstrated MIP-2 and Tnf-alpha staining in respiratory bronchiolar epithelia, alveolar macrophages and alveolar type II cells. The transcriptional regulation in these genes in the treatment groups suggests that they may serve central roles in the immunomodulation of toxin-induced pro-inflammatory lung responses. Hierarchical cluster analysis revealed significant patterns of gene transcription linking the response of the toxins at equimolar doses in three groups: (1) brevianamide, mycophenolic acid and neoechinulin B, (2) neoechinulin A and sterigmatocystin, and (3) cladosporin, atranone C and TMC-120. The results further confirm the inflammatory nature of metabolites/toxins from such fungi can contribute to the development of non-allergenic respiratory health effects.

The effect of elevated dietary cholesterol on pulmonary surfactant function in adolescent mice.

It has been established that phospholipids and cholesterol interact in films of pulmonary surfactant (PS). Generally it is thought that phospholipids increase film stability whereas cholesterol increases film fluidity. To study this further, we modified dietary cholesterol in mice which received either standard rodent lacking cholesterol (sd), or high cholesterol (2%) diet (hc) for 1 month. Phospholipid stability was investigated by a capillary surfactometer (CS), which measures airflow resistance and patency. PS was collected by bronchiolar lavage and centrifuged to obtain the surface-active film (SAF). Results showed that the hc-SAF had significantly more cholesterol than sd-SAF. CS analyses at 37 degrees C showed no significance differences in airflow resistance between hc-SAF and sd-SAF. However, at 37 degrees C, sd-SAF showed greater ability to maintain patency compared to hc-SAF, whereas at 42 degrees C hc-SAF showed patency ability similar to sd-SAF. The results suggested that increased cholesterol in hc-SAF induced less stability in the SAF possibly due to cholesterol's fluidizing effect on phospholipids at physiological temperatures.

DNA fragmentation in developing lung fibroblasts exposed to Stachybotrys chartarum (atra) toxins.

Stachybotrys chartarum (atra) is a toxic mold that grows on water-damaged cellulose-based materials. Research has revealed also that inhalation of S. chartarum spores caused marked changes in respiratory epithelium, especially to developing lungs. We analyzed the epigenetic potential of S. chartarum spore toxins on developing rat lung fibroblasts using single cell gel electrophoresis (comet assay). Isolated fetal lung fibroblasts were exposed to S. chartarum spore toxins for 15 min, 3, 14, or 24 hr and control cells were exposed to saline under the same conditions. Cells were embedded in agarose, electrophoresed under alkaline conditions and silver stained. DNA damage was assessed in terms of fragmentation as measured by comet tail length (DNA migration) and intensity (% DNA contained within head and tail). Upon visual inspection, control fibroblasts showed no DNA fragmentation whereas S. chartarum-treated cells had definable comets of various degrees depending upon the time-course. Analyses of the comets revealed that exposure to S. chartarum spore toxins for at least 15 min to 14 hr, induced increased DNA fragmentation in a time-dependent manner. The fact that exposure to toxins for 24 hr showed less damage suggested that developing lung fibroblasts may have the capability of repairing DNA fragmentation.