Deleterious Changes Research Articles

The role of hepatic lipid composition in obesity‐related metabolic disease

Obesity is a primary antecedent to non-alcoholic fatty liver disease whose cardinal feature is excessive hepatic lipid accumulation. Although total hepatic lipid content closely associates with hepatic and systemic metabolic dysfunction, accumulating evidence suggests that the composition of hepatic lipids may be more discriminatory. This review summarises cross-sectional human studies using liver biopsy/lipidomics and proton magnetic resonance spectroscopy to characterise hepatic lipid composition in people with obesity and related metabolic disease. A comprehensive literature search identified 26 relevant studies published up to 31st March 2021 which were included in the review. The available evidence provides a consistent picture showing that people with hepatic steatosis possess elevated saturated and/or monounsaturated hepatic lipids and a reduced proportion of polyunsaturated hepatic lipids. This altered hepatic lipid profile associates more directly with metabolic derangements, such as insulin resistance, and may be exacerbated in non-alcoholic steatohepatitis. Further evidence from lipidomic studies suggests that these deleterious changes may be related to defects in lipid desaturation and elongation, and an augmentation of the de novo lipogenic pathway. These observations are consistent with mechanistic studies implicating saturated fatty acids and associated bioactive lipid intermediates (ceramides, lysophosphatidylcholines and diacylglycerol) in the development of hepatic lipotoxicity and wider metabolic dysfunction, whilst monounsaturated fatty acids and polyunsaturated fatty acids may exhibit a protective role. Future studies are needed to prospectively determine the relevance of hepatic lipid composition for hepatic and non-hepatic morbidity and mortality; and to further evaluate the impact of therapeutic interventions such as pharmacotherapy and lifestyle interventions.

Chronic Ethanol Exposure Induces Deleterious Changes in Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells.

Chronic alcohol consumption in adults can induce cardiomyopathy, arrhythmias, and heart failure. In newborns, prenatal alcohol exposure can increase therisk of congenital heart diseases. Understanding biological mechanisms involved in the long-term alcohol exposure-induced cardiotoxicity is pivotal to the discovery of therapeutic strategies. In this study, cardiomyocytes derived from human pluripotent stem cells (hiPSC-CMs) were treated with clinically relevant doses of ethanol for various durations up to 5weeks. The treated cells were characterized for their cellular properties and functions, and global proteomic profiling was conducted to understand the molecular changes associated with long-term ethanol exposure. Increased cell death, oxidative stress, deranged Ca2+ handling, abnormal action potential, altered contractility, and suppressed structure development were observed in ethanol-treated cells. Many dysregulated proteins identified by global proteomic profiling were involved in apoptosis, heart contraction, and extracellular collagen matrix. In addition, several signaling pathways including the Wnt and TGFβ signaling pathways were affected due to long-term ethanol treatment. Therefore, chronic ethanol treatment of hiPSC-CMs induces cardiotoxicity, impairs cardiac functions, and alters protein expression and signaling pathways. This study demonstrates the utility of hiPSC-CMs as a novel model for chronic alcohol exposure study and provides the molecular mechanisms associated with long-term alcohol exposure in human cardiomyocytes.

Inhaled Corticosteroids and the Lung Microbiome in COPD.

The Global Initiative for Chronic Obstructive Lung Disease 2021 Report recommends inhaled corticosteroid (ICS)-containing regimens as part of pharmacological treatment in patients with chronic obstructive lung disease (COPD) and frequent exacerbations, particularly with eosinophilic inflammation. However, real-world studies reveal overprescription of ICS in COPD, irrespective of disease presentation and inflammatory endotype, leading to increased risk of side effects, mainly respiratory infections. The optimal use of ICS in COPD therefore remains an area of intensive research, and additional biomarkers of benefit and risk are needed. Although the interplay between inflammation and infection in COPD is widely acknowledged, the role of the microbiome in shaping lower airway inflammation has only recently been explored. Next-generation sequencing has revealed that COPD disease progression and exacerbation frequency are associated with changes in the composition of the lung microbiome, and that the immunosuppressive effects of ICS can contribute to potentially deleterious airway microbiota changes by increasing bacterial load and the abundance of potentially pathogenic taxa such as Streptococcus and Haemophilus. Here, we explore the relationship between microbiome, inflammation, ICS use and disease phenotype. This relationship may inform the benefit:risk assessment of ICS use in patients with COPD and lead to more personalised pharmacological management.

Neuroimaging and biomarker evidence of neurodegeneration in asthma

Epidemiologic studies have shown that Alzheimer's disease (AD) and related dementias (ADRD) are seen more frequently with asthma, especially with greater asthma severity or exacerbation frequency. To examine the changes in brain structure that may underlie this phenomenon, we examined diffusion-weighted magnetic resonance imaging (dMRI) and blood-based biomarkers of AD (phosphorylated tau 181, p-Tau181), neurodegeneration (neurofilament light chain, NfL), and glial activation (glial fibrillary acidic protein, GFAP). dMRI data were obtained in 111 individuals with asthma, ranging in disease severity from mild to severe, and 135 healthy controls. Regression analyses were used to test the relationships between asthma severity and neuroimaging measures, as well as AD pathology, neurodegeneration, and glial activation, indexed by plasma p-Tau181, NfL, and GFAP, respectively. Additional relationships were tested with cognitive function. Asthma participants had widespread and large-magnitude differences in several dMRI metrics, which were indicative of neuroinflammation and neurodegeneration, and which were robustly associated with GFAP and, to a lesser extent, NfL. The AD biomarker p-Tau181 was only minimally associated with neuroimaging outcomes. Further, asthma severity was associated with deleterious changes in neuroimaging outcomes, which in turn were associated with slower processing speed, a test of cognitive performance. Asthma, particularly when severe, is associated with characteristics of neuroinflammation and neurodegeneration, and may be a potential risk factor for neural injury and cognitive dysfunction. There is a need to determine how asthma may affect brain health and whether treatment directed toward characteristics of asthma associated with these risks can mitigate these effects.

Macroautophagy and aging: The impact of cellular recycling on health and longevity

Aging is associated with many deleterious changes at the cellular level, including the accumulation of potentially toxic components that can have devastating effects on health. A key protective mechanism to this end is the cellular recycling process called autophagy. During autophagy, damaged or surplus cellular components are delivered to acidic vesicles called lysosomes, that secure degradation and recycling of the components. Numerous links between autophagy and aging exist. Autophagy declines with age, and increasing evidence suggests that this reduction plays important roles in both physiological aging and the development of age-associated disorders. Studies in pharmacologically and genetically manipulated model organisms indicate that defects in autophagy promote age-related diseases, and conversely, that enhancement of autophagy has beneficial effects on both healthspan and lifespan. Here, we review our current understanding of the role of autophagy in different physiological processes and their molecular links with aging and age-related diseases. We also highlight some recent advances in the field that could accelerate the development of autophagy-based therapeutic interventions.

Using Phage Display to Develop Ubiquitin Variant Modulators for E3 Ligases

Ubiquitin is a small 8.6 kDa protein that is a core component of the ubiquitin-proteasome system. Consequently, it can bind to a diverse array of proteins with high specificity but low affinity. Through phage display, ubiquitin variants (UbVs) can be engineered such that they exhibit improved affinity over wildtype ubiquitin and maintain binding specificity to target proteins. Phage display utilizes a phagemid library, whereby the pIII coat protein of a filamentous M13 bacteriophage (chosen because it is displayed externally on the phage surface) is fused with UbVs. Specific residues of human wildtype ubiquitin are soft and randomized (i.e., there is a bias towards to native wildtype sequence) to generate UbVs so that deleterious changes in protein conformation are avoided while introducing the diversity necessary for promoting novel interactions with the target protein. During the phage display process, these UbVs are expressed and displayed on phage coat proteins and panned against a protein of interest. UbVs that exhibit favorable binding interactions with the target protein are retained, whereas poor binders are washed away and removed from the library pool. The retained UbVs, which are attached to the phage particle containing the UbV's corresponding phagemid, are eluted, amplified, and concentrated so that they can be panned against the same target protein in another round of phage display. Typically, up to five rounds of phage display are performed, during which a strong selection pressure is imposed against UbVs that bind weakly and/or promiscuously so that those with higher affinities are concentrated and enriched. Ultimately, UbVs that demonstrate higher specificity and/or affinity for the target protein than their wildtype counterparts are isolated and can be characterized through further experiments.

Screening and prevention of hepatitis C virus reactivation during chemotherapy.

Hepatitis C virus (HCV) reactivation occurs in 23% of HCV-infected cancer patients receiving chemotherapy. Forty-three percent of the patients with reactivation of HCV during chemotherapy develop a hepatitis flare. Most of the cancer patients with HCV reactivation have an unremarkable clinical course following an HCV-related hepatitis flare during chemotherapy. However, 26%–57% of the cancer patients developing an acute flare of chronic hepatitis C during chemotherapy require unanticipated discontinuation or dose reduction of chemotherapy, which results in deleterious changes in the cancer treatment plan. Although an optimal strategy for HCV screening in cancer patients receiving chemotherapy has not been established, universal pre-chemotherapy HCV testing for patients with hematological malignancies is recommended by current guidelines. All the currently approved direct-acting antivirals (DAAs) can be used in cancer patients, but the use of DAAs during chemotherapy should avoid drug–drug interactions between chemotherapy and antiviral agents. If there are no contraindications or anticipated drug–drug interactions, DAAs treatment can be administered before, during, or after chemotherapy. In conclusion, HCV reactivation occurs in approximately one-fourth of HCV-infected cancer patients receiving chemotherapy. An HCV-related hepatitis flare during chemotherapy may lead to the discontinuation of potentially life-saving chemotherapy. Currently, universal HCV screening is recommended in hematological malignancy patients before chemotherapy, but there is no evidence-based guideline for other cancer patients. DAAs treatment can cure HCV infection and prevent HCV reactivation during chemotherapy.

Impact of cisplatin administration on cerebellar cortical structure and locomotor activity of infantile and juvenile albino rats: the role of oxidative stress.

The central neurotoxicity of cisplatin (CisPt) has always raised questions especially during development, but few studies are available. Hence, this work was designed to assess the CisPt's impacts on the postnatal rat cerebellum via evaluation of locomotor activity, histological and immunohistochemical studies, and to focus on cerebellar oxidative stress-related alterations. Eighty newborn pups were divided into 2 equal experimental groups: the control group was kept without any treatment and CisPt-treated group received a single subcutaneous injection of CisPt (5μg /g b.w.) in their nape at PD10. Ten rats at PD11, PD17, and PD30 ages were weighed, then deeply anesthetized and sacrificed. For locomotor assessment, 20 pups were divided equally into control and CisPt-treated groups and tested at PD11-13, PD15-17, and PD28-30 ages. CisPt-treated rats suffered from decreased motor activity and showed decreased body and cerebellar weights, reduced levels of enzymatic antioxidants (SOD and CAT), and non-enzymatic antioxidant defense (GSH), and increase of lipid peroxidation marker (MDA). Histopathologically, CisPt sowed deleterious changes within cerebellar cortical layers in the form of vacuolations, decreased thickness, and hemorrhage (in PD17), while Purkinje cells exhibited profound degenerative changes in the form of swelling, disrupted arrangement, distortion, and nuclear shrinkage. In CisPt-treated rats, GFAP demonstrated upregulated, hypertrophied, and branched Bergmann glial fibers and reactive astrogliosis. Immuno-localization of Ki-67-positive cells revealed defective migration associated with decreased proliferation in early ages in addition to glial proliferation in PD30. In conclusion, CisPt causes oxidative stress-related deleterious effects on structure of developing cerebellar cortex and affects locomotor activity.

Lithium as a Neuroprotective Agent for Bipolar Disorder: An Overview.

Lithium (Li+) is a first option treatment for adult acute episodes of Bipolar Disorder (BD) and for the prophylaxis of new depressed or manic episodes. It is also the preferred choice as maintenance treatment. Numerous studies have shown morphological abnormalities in the brains of BD patients, suggesting that this highly heritable disorder may exhibit progressive and deleterious changes in brain structure. Since treatment with Li+ ameliorates these abnormalities, it has been postulated that Li+ is a neuroprotective agent in the same way atypical antipsychotics are neuroprotective in patients diagnosed with schizophrenia spectrum disorders. Li+'s neuroprotective properties are related to its modulation of nerve growth factors, inflammation, mitochondrial function, oxidative stress, and programmed cell death mechanisms such as autophagy and apoptosis. Notwithstanding, it is not known whether Li+-induced neuroprotection is related to the inhibition of its putative molecular targets in a BD episode: the enzymes inositol-monophosphatase, (IMPase), glycogen-synthase-kinase 3β (GSK3), and Protein kinase C (PKC). Furthermore, it is uncertain whether these neuroprotective mechanisms are correlated with Li+'s clinical efficacy in maintaining mood stability. It is expected that in a nearby future, precision medicine approaches will improve diagnosis and expand treatment options. This will certainly contribute to ameliorating the medical and economic burden created by this devastating mood disorder.

Presence of microplastics alone and co-existence with hydrochar unexpectedly mitigate ammonia volatilization from rice paddy soil and affect structure of soil microbiome

Microplastics (MPs), as an emerging pollutant, may cause deleterious changes to the nitrogen cycle in terrestrial ecosystems. However, single impact of MPs and synergistic effects of MPs with hydrochar on ammonia (NH3) volatilization and soil microbiome in paddy fields has been largely unexplored. In this study, polyethylene (PE), polyacrylonitrile (PAN) and straw-derived hydrochar (HBC) were selected for observations in an entire rice cycle growth period. Results showed that under the condition of 0.5% (w/w) MPs concentration, presence of MPs alone and co-existence of MPs and HBC (MPs + HBC) unexpectedly mitigated cumulative NH3 volatilization from paddy soil compared with the control with no MPs or HBC addition. MPs + HBC increased NH3 volatilization by 37.8–46.2% compared with MPs alone, indicating that co-existence of MPs and HBC weaken the mitigation effect of MPs on NH3 volatilization. Additionally, results of nitrogen cycle related microorganisms closely related to NH3 volatilization demonstrated that MPs + HBC altered the bacterial community structure and species diversity. These findings provide an important opportunity to advance our understanding of the impacts of MPs in agricultural environment and soils, and provide a sound theoretical basis for rationalizing the application of HBC in soil with MPs.

The Effectiveness Of HRV As A Predictor Of Renal Health And Function In The Absence Of Cardiometabolic Diseases. A Pilot Study

Heart rate variability (HRV) is a non-invasive way to assess the autonomic nervous system (ANS) influence on the myocardium. The myocardium and cardiovascular system undergo changes throughout the aging process, specifically, renal vascular function. However, in the absence of cardiometabolic diseases, the ANS does not experience the same deleterious changes observed in at-risk populations. What is unknown is if HRV can predict renal health and function (RH/F) in the absence of cardiometabolic diseases. PURPOSE: To determine if HRV is correlated to RH/F in the absence of cardiometabolic diseases. METHODS: Thirteen healthy individuals (n = 7 male; n = 6 female, Age 37 ± 12.7 years, %BF 19.7 ± 6.6, VO2max 42.3 ± 6.7 ml/ /kg/min) completed a single health assessment to quantify HRV to RH/F. HRV was measured for 5 mins in the supine position using an elastic belt and Bluetooth monitor (Polar H7). CardioMood software was used to process HRV variables high frequency (HF), low frequency (LF), total power (TP) were assessed for frequency domain, and standard deviation of all NN intervals (SDNN) and the square root of the mean of the squares of successive R-R interval differences (RMSSD) for the time domain. Blood and urine samples were collected by the same technician under standardized conditions. Serum creatinine (sCR), urine creatinine (uCr), cystatin C (CyC), and urine epidermal growth factor (uEGF) were used to calculate estimates of renal health and function via uEGF/uCr ratio (uEGFR), estimated glomerular filtration rate (eGFR) - modification of diet in renal disease (MDRD), CKD-EPI, and SCr/CyC eGFR. Data were analyzed using a Pearson Correlation between HRV and RH/F markers. All analyses were performed using SAS (v.9.3). RESULTS: HRV frequency domain variables LF, HF, LF/HF, and TP, and time domain, SDNN, and RMSSD were all significantly (p < 0.05) correlated to renal function markers sCR, MDRD, SCr-EPI, and SCr/CyC eGFR. There were no significant correlations observed between HRV and renal health variables (p > 0.05). CONCLUSION: There is a direct correlation between ANS and renal function when using HRV in individuals with the absence of cardiometabolic diseases. However, markers of renal health are not correlated to ANS.

Association between smoking history and optical coherence tomography angiography findings in diabetic patients without diabetic retinopathy.

PurposeTo investigate any associations between cigarette smoking and retinal microvascular changes in diabetic patients without visible retinopathy.DesignRetrospective, cross-sectional study.Participants1099 eyes from 1099 diabetic patients with no clinical evidence of diabetic retinopathy (DR) were included in this study.MethodsDiabetic patients underwent optical coherence tomography angiography (OCTA) scanning at Zuckerberg San Francisco General Hospital and Trauma Center between April 2018 and September 2019. Patient demographic and clinical information was collected. Standard bivariate statistics and multivariate linear regression were performed.Main outcome measuresOCTA parameters included metrics related to the foveal avascular zone (FAZ; area, perimeter, circularity), perfusion density (PD; full, center, inner), and vessel length density (VLD; full, center, inner).ResultsThe study population included 750 non-smokers and 349 smokers. FAZ perimeter was the only OCTA parameter that was significantly different between the two groups on uncontrolled analysis (P = 0.033). Multivariate regression analyses revealed significant associations between lower VLD full (β = -0.31, P = 0.048), lower VLD inner (β = -0.35, P = 0.046) and a history of smoking. No significant associations between cigarette smoking and either FAZ or PD were detected.ConclusionsOur results suggest that smoking is likely associated with deleterious changes in the retinal microvasculature of patients with a history of diabetes and no visible DR. Based on these findings, diabetic patients with a history of smoking may benefit from higher prioritization in terms of ophthalmic screening.

Therapeutic Role of Annona muricata Fruit and Bee Venom Against MNU-Induced Breast Cancer in Pregnant Rats and its Complications on the Ovaries.

AimTo evaluate the potential therapeutic role of Annona muricata (graviola) fruit and bee venom (BV) against N-methylnitrosourea (MNU)-induced breast cancer in pregnant female rats and complications in the ovaries.MethodsA total of 24 female rats were induced with a single dose of MNU (50 mg/kg body weight). After confirmation of positive tumor marker, female rats were placed with the males for mating. The pregnant rats were randomly divided into four groups (n=6): MNU-induced only (group 1), MNU-induced rats and supplemented with A. muricata 200 mg/kg diet (group 2), MNU-induced and treated with two doses of BV 75 μg/kg (group 3), and MNU-induced and treated with both A. muricata and BV (group 4).ResultsIn group 1, the breast tissue of mothers revealed pronounced cellular hyperplasia and histopathological signs. Also, the ovarian tissue of mothers and their offspring displayed deleterious histological changes. In groups 2 and 4, histopathological signs and cellular hyperplasia markedly disappeared in breast tissue. However, the histopathological signs induced by MNU in the ovarian tissue reversed to normal in groups 2–4. Also in groups 2–4, levels of serum MMP1, NFκB, and TNFα significantly decreased, and serum caspase 3 significantly increased either in mother rats or their offspring compared to the MNU-alone group. Levels of serum MDA significantly decreased; however, levels of serum antioxidants (CAT and SOD) significantly increased in all groups 2–4 compared to MNU-alone group.ConclusionA. muricata has a more powerful therapeutic role than BV against MNU-induced breast cancer in rats; however, both have a powerful ameliorative role against ovarian histopathological alterations induced by MNU. Such ameliorative effects of A. muricata and BV are mainly attributed to their antioxidant, anti-inflammatory, and antiproliferative constituents.

Protective Effect of Curcumin on Lipid Profile in Rats Intoxicated by Cyclophosphamide

The present study was carried out to evaluate the protective effects of curcumin on Cyclophosphamide-induced deleterious lipid profile in rats. Experimental rats were randomly divided into four groups of five rats each. Group 1: served as the control rats, Group 2: was administered daily curcumin at a dose (150 mg/kg b.wt). Group 3: a single dose of cyclophosphamide (150 mg/kg, i.p.) intraperitoneal injection, Group 4: was injected with cyclophosphamide + curcumin along the experimental period (30 days). The results refer to a significant elevation of lipid parameters (cholesterol, triglyceride and LDL-C) while a significant decrease in some other parameters (HDL-C). On the 30 days in rats injected intraperitoneal with cyclophosphamide as compared to the control groups. The administration of the curcumin has beneficial and decrease side effects against the deleterious changes of CCl4. Concluded that supplementation of curcumin reverted these abnormalities in the lipid levels to near normalcy after cyclophosphamide administration.

Therapeutic Effects of Royal Jelly on Some Biochemical Parameters in Nephrotoxicity Induced by Carbon Tetrachloride (Ccl4) In Albino Rats.

The present study was designed to determine the possible therapeutic effects of royal jelly against carbon tetrachloride (CCl4) induced oxidative stress and biochemical changes in the kidney of albino rats. A patch of 20 male albino rats averaged weights (190±10 g) at the beginning of the experiment were divided into 4 main groups according to the treatment and requirements of the experiment. The rats injected i.p. with CCl4 at a dose (1 mL/kg, 1:1 in olive oil) twice per week and received, via gavage, royal jelly at a dose (400 mg/kg b. wt) along the experimental period. Each group contains 5 rats that were sacrificed on the45 days from the start of the experiment. The results refer to a significant elevation of renal parameters (creatinine, blood Urea and Uric acid) on the 6th week in rats injected intraperitoneal with CCl4 as compared to the control groups. The administration of the royal jelly has beneficial and decrease side effects against the deleterious changes of CCl4. In conclusion, according to the results obtained the administration of the royal jelly provides considerable nephroprotective effects against intoxicated with CCl4 in male Wister albino rats by preventing oxidative stress through ROS scavenger and improvement in the former biochemical parameters.

Cueing Changes in Peak Vertical Ground Reaction Force to Improve Coordination Dynamics in Walking

s Biofeedback has been effectively implemented to improve the mediation and distribution of joint loads during gait, however, the inability to effectively coordinate lower limb movement by altering loading patterns may increase pathological stress and risk of injury and deleterious joint changes. This study examined the influence cueing an increase or decrease in lower extremity loading has on inter- and intralimb joint coordination during gait, applied herein for 12 persons following anterior cruciate ligament reconstruction across three loading conditions (control, high, and low). Visual biofeedback was presented on a screen via a force-measuring treadmill with targeted changes prescribed based on stride-to-stride peak vertical ground reaction forces bilaterally. The pattern and stability of coordination dynamics among each of the ankle, hip and knee joint pairs were assessed via discrete relative phase and cross-recurrence quantification analyses for each condition. High and low loading altered the pattern and stability of intralimb coordination; low loading led to decreased coordination stability (20° greater than control condition) and high loading resulted in a more tightly coupled coordination pattern (higher %CDET). With thoughtful consideration for movement control, biofeedback can be used to target mechanisms leading to long-term deleterious joint adaptations.

Comparison of the fertility of tumor suppressor gene-deficient C57BL/6 mouse strains reveals stable reproductive aging and novel pleiotropic gene

Tumor suppressor genes are involved in maintaining genome integrity during reproduction (e.g., meiosis). Thus, deleterious alleles in tumor suppressor-deficient mice would exhibit higher mortality during the perinatal period. A recent aging model proposes that perinatal mortality and age-related deleterious changes might define lifespan. This study aimed to quantitatively understand the relationship between reproduction and lifespan using three established tumor suppressor gene (p53, APC, and RECQL4)-deficient mouse strains with the same C57BL/6 background. Transgenic mice delivered slightly reduced numbers of 1st pups than wild-type mice [ratio: 0.81–0.93 (p = 0.1–0.61)] during a similar delivery period, which suggest that the tumor suppressor gene-deficient mice undergo relatively stable reproduction. However, the transgenic 1st pups died within a few days after birth, resulting in a further reduction in litter size at 3 weeks after delivery compared with that of wild-type mice [ratio: 0.35–0.68 (p = 0.034–0.24)] without sex differences, although the lifespan was variable. Unexpectedly, the significance of reproductive reduction in transgenic mice was decreased at the 2nd or later delivery. Because mice are easily affected by environmental factors, our data underscore the importance of defining reproductive ability through experiments on aging-related reproduction that can reveal a trade-off between fecundity and aging and identify RECQL4 as a novel pleiotropic gene.

Effect of Cyclosporin - A on the Lung of Adult Male Albino Rats and The Possible Protective Role of Vitamin E

Abstract Background: Cyclosporine A (Cs A) is an immunosup-pressive agent which used in treatment of various autoimmune diseases. Aim of Study: Evaluation of the effect of cyclosporin-A administration on the histological structure on the lung in adult male rat and the protective role of vitamin E. Material and Methods: Forty adult male albino rats were divided equally into four groups. Group 1 received distilled water, Group 2 received oral daily dose of cyclosporine A (10mg/kg/body weight) for 4 weeks, Group 3 (a co-treated group) received oral daily dose of vitamin E (200mg/kg/body weight) simultaneously with cyclosporine A (10mg/kg/body weight) for 4 weeks, and Group 4 (a pre-treated group) received oral daily dose of vitamin E (200mg/kg) 2 hours prior to treatment with cyclosporine A (10mg/kg body weight) for 4 weeks. Lung specimens were taken out and processed for histopathological examination and for assessment of lung tissue levels of oxidative stress markers (MDA, SOD, GSH, and CAT). Results: Histopathological examination using light and electron microscope revealed that cyclosporine-A induced deleterious histopathological changes in the lungs of adult male albino rats. Focal destruction of alveolar walls, formation of emphysematous air spaces, distortion of the interalveolar septa, peri-bronchial inflammatory cell infiltration and con-gestion with fibrosis. Pneumocytes type I showed an irregular nucleus. Pneumocytes type II revealed irregular pyknotic nuclei, numerous vacuolated or empty lamellar bodies with loss of their lamellar arrangement, and distorted surface microvilli. There was significant increase in lung malondial-dehyde (MDA) level, with significant decrease in lung super-oxide dismutase (SOD), glutathione peroxidase (GSH), and catalase (CAT). Vitamin E either with or before receiving cyclosporin-A reduced lung affection with improved level of oxidative markers in the lung homogenates. Conclusion: Vitamin E reduced cyclosporin-A lung affec-tion with improved level of oxidative markers in the lung homogenates.

Perceived Stress and Molecular Bacterial Vaginosis in the National Institutes of Health Longitudinal Study of Vaginal Flora.

Vaginal microbiota provide the first line of defense against urogenital infections primarily through protective actions of Lactobacillus species Perceived stress increases susceptibility to infection through several mechanisms, including suppression of immune function. We investigated whether stress was associated with deleterious changes to vaginal bacterial composition in a subsample of 572 women in the Longitudinal Study of Vaginal Flora, sampled from 1999 through 2002. Using Cox proportional hazards models, both unadjusted and adjusted for sociodemographic factors and sexual behaviors, we found that participants who exhibited a 5-unit-increase in Cohen's Perceived Stress Scale had greater risk (adjusted hazard ratio (HR)=1.40, 95% confidence interval (CI): 1.13, 1.74) of developing molecular bacterial vaginosis (BV), a state with low Lactobacillus abundance and diverse anaerobic bacteria. A 5-unit increase in stress score was also associated with greater risks of transitioning from the L. iners-dominated community state type (26% higher) to molecular-BV (adjusted HR= 1.26, 95% CI: 1.01, 1.56) or maintaining molecular-BV from baseline (adjusted HR= 1.23, 95% CI: 1.01, 1.47). Inversely, women with baseline molecular-BV reporting a 5-unit stress increase were less likely to transition to microbiota dominated by L. crispatus, L. gasseri, or L. jensenii (adjusted HR= 0.81, 95% CI: 0.68, 0.99). These findings suggest that psychosocial stress is associated with vaginal microbiota composition, inviting a more mechanistic exploration of the relationship between psychosocial stress and molecular-BV.

Nutritional management of individuals with obesity and COVID-19: ESPEN expert statements and practical guidance

The COVID-19 pandemics has created unprecedented challenges and threats to patients and healthcare systems worldwide. Acute respiratory complications that require intensive care unit (ICU) management are a major cause of morbidity and mortality in COVID-19 patients. Among other important risk factors for severe COVID-19 outcomes, obesity has emerged along with undernutrition-malnutrition as a strong predictor of disease risk and severity. Obesity-related excessive body fat may lead to respiratory, metabolic and immune derangements potentially favoring the onset of COVID-19 complications. In addition, patients with obesity may be at risk for loss of skeletal muscle mass, reflecting a state of hidden malnutrition with a strong negative health impact in all clinical settings. Also importantly, obesity is commonly associated with micronutrient deficiencies that directly influence immune function and infection risk. Finally, the pandemic-related lockdown, deleterious lifestyle changes and other numerous psychosocial consequences may worsen eating behaviors, sedentarity, body weight regulation, ultimately leading to further increments of obesity-associated metabolic complications with loss of skeletal muscle mass and higher non-communicable disease risk. Therefore, prevention, diagnosis and treatment of malnutrition and micronutrient deficiencies should be routinely included in the management of COVID-19 patients in the presence of obesity; lockdown-induced health risks should also be specifically monitored and prevented in this population. In the current document, the European Society for Clinical Nutrition and Metabolism (ESPEN) aims at providing clinical practice guidance for nutritional management of COVID-19 patients with obesity in various clinical settings.