Tailored microbial consortium producing hydrolytic enzyme cocktail for maximum saccharification of wheat straw.

The potential of hydrolytic enzyme cocktail obtained from designed bacterial consortium WSh-1 comprising Bacillus subtilis CRN 16, Paenibacillus dendritiformis CRN 18, Niallia circulans CRN 24, Serratia marscens CRN 29, and Streptomyces sp. CRN 30, was investigated for maximum saccharification. Activity was further enhanced to 1.01 U/ml from 0.82 U/ml by supplementing growth medium with biotin and cellobiose as a cofactor and inducer. Through kinetic analysis, the enzyme cocktail showed a high wheat straw affinity with Michaelis-Menten constant (Km) of 0.68 µmol/L and a deconstruction rate (Vmax) of 4.5 U/ml/min. The statistical optimization of critical parameters increased saccharification to 89 %. The optimized process in a 5-L lab-scale bioreactor yielded 501 mg/g of reducing sugar from NaOH-pretreated wheat straw. Lastly, genomic insights revealed unique abundant oligosaccharide deconstruction enzymes with the most diverse CAZyme profile. The consortium-mediated enzyme cocktails offer broader versatility with efficiency for the economical and sustainable valorization of lignocellulosic waste.

Genomic dissection of Niallia sp. for potential application in lignocellulose hydrolysis and bioremediation.

Genus Niallia has recently been separated taxonomic group from the Bacillus based on conserved signature indels in the genome. Unlike bioremediation, its role in plant biomass hydrolysis has not garnered considerable attention. The present study investigates the genomic potential of a novel Niallia sp. CRN 25 for applications in lignocellulose hydrolysis, significant enzyme production, and bioremediation. The CRN 25 strain exhibits xylosidase, cellobiosidase, α-arabinosidase, and α-D-galactosidase activity as 0.03 U/ml whereas ß-D-glucosidase and glucuronidase as 0.06 U/ml and 0.01 U/ml, respectively. Further genome sequencing reveals nine copies of GH43 gene coding for hemicellulose-specific xylanase enzyme attached to the CBM 6 domain for increased processivity. The presence of ß-glucosidase and ß-galactosidase indicates the possible application of CRN 25 in facilitating the valorization of plant biomass into value-added products. Apart from this, genes of FMN-dependent NADH-azoreductase, cytochrome P450, and nitrate reductase, playing a crucial role in bioremediation processes, were annotated. Biosynthetic gene clusters (BGCs), responsible for synthesizing specialized metabolites of terpenes and lasso peptides, were also found in the genome. Conclusively genomic sketch of Niallia sp. CRN 25 reveals versatile metabolic potential for diverse environmental applications.

Nicotine Formulation Influences the Autonomic and Arrhythmogenic Effects of Electronic Cigarettes.

INTRODUCTION: Evidence is mounting that electronic cigarette (e-cig) use induces cardiac sympathetic dominance and electrical dysfunction conducive to arrhythmias and dependent upon nicotine. A variety of nicotine types and concentrations are available in e-cigs, but their relative cardiovascular effects remain unclear. Here we examine how different nicotine forms (racemic, free-base, and salt) and concentrations influence e-cig-evoked cardiac dysfunction and arrhythmogenesis and provide a mechanism for nicotine-salt-induced autonomic imbalance. METHODS: ECG-telemetered C57BL/6J mice were exposed to filtered air (FA) or e-cig aerosols from propylene glycol and vegetable glycerin solvents either without nicotine (vehicle) or with increasing nicotine concentrations (1%, 2.5%, and 5%) for three 9-min puff sessions per concentration. Spontaneous ventricular premature beat (VPB) incidence rates, heart rate, and heart rate variability (HRV) were compared between treatments. Subsequently, to test the role of ß1-adrenergic activation in e-cig-induced cardiac effects, mice were pretreated with atenolol and exposed to either FA or 2.5% nicotine salt. RESULTS: During puffing and washout phases, ≥ 2.5% racemic nicotine reduced heart rate and increased HRV relative to FA and vehicle controls, indicating parasympathetic dominance. Relative to both controls, 5% nicotine salt elevated heart rate and decreased HRV during washout, suggesting sympathetic dominance, and also increased VPB frequency. Atenolol abolished e-cig-induced elevations in heart rate and declines in HRV during washout, indicating e-cig-evoked sympathetic dominance is mediated by ß1-adrenergic stimulation. CONCLUSIONS: Our findings suggest that inhalation of e-cig aerosols from nicotine salt-containing e-liquids could increase the cardiovascular risks of vaping by inducing sympathetic dominance and cardiac arrhythmias. IMPLICATIONS: Exposure to e-cig aerosols containing commercially relevant concentrations of nicotine salts may increase nicotine delivery and impair cardiac function by eliciting ß1-adrenoceptor-mediated sympathoexcitation and provoking ventricular arrhythmias. If confirmed in humans, our work suggests that regulatory targeting of nicotine salts through minimum pH standards or limits on acid additives in e-liquids may mitigate the public health risks of vaping.

Potential of camel rumen derived Bacillus subtilis and Bacillus velezensis strains for application in plant biomass hydrolysis.

Rumen inhabiting Bacillus species possesses a high genetic potential for plant biomass hydrolysis and conversion to value-added products. In view of the same, five camel rumen-derived Bacillus strains, namely B. subtilis CRN 1, B. velezensis CRN 2, B. subtilis CRN 7, B. subtilis CRN 11, and B. velezensis CRN 23 were initially assayed for diverse hydrolytic activities, followed by genome mining to unravel the potential applications. CRN 1 and CRN 7 showed the highest endoglucanase activity with 0.4 U/ml, while CRN 23 showed high ß-xylosidase activity of 0.36 U/ml. The comprehensive genomic insights of strains resolve taxonomic identity, clusters of an orthologous gene, pan-genome dynamics, and metabolic features. Annotation of Carbohydrate active enzymes (CAZymes) reveals the presence of diverse glycoside hydrolases (GH) GH1, GH5, GH43, and GH30, which are solely responsible for the effective breakdown of complex bonds in plant polysaccharides. Further, protein modeling and ligand docking of annotated endoglucanases showed an affinity for cellotrioside, cellobioside, and ß-glucoside. The finding indicates the flexibility of Bacillus-derived endoglucanase activity on diverse cellulosic substrates. The presence of the butyrate synthesis gene in the CRN 1 strain depicts its key role in the production of important short-chain fatty acids essential for healthy rumen development. Similarly, antimicrobial peptides such as bacilysin and non-ribosomal peptides (NRPS) synthesized by the Bacillus strains were also annotated in the genome. The findings clearly define the role of Bacillus sp. inside the camel rumen and its potential application in various plant biomass utilizing industry and animal health research sectors.

Workplace Culture and Biomarkers of Health Risk.

Workplace culture has been studied for impact on health risk; however, connections with robust biologic markers of health remain to be established. We examined associations between the work environment and urinary levels of catecholamines and their metabolites as biomarkers of sympathetic nervous system activity, indicative of stress. We recruited participants (n = 219; 2018-2019) from a cardiovascular risk cohort to investigate workplace culture, well-being, and stress. Participants completed seven questionnaires. Urine samples were used to measure catecholamines and their metabolites by LC/MS/MS. Pearson correlation and linear regression models were used after adjusting for demographics and creatinine. Participants reporting higher well-being had lower urinary levels of dopamine, serotonin, and 3-methoxytyramine. Participants reporting a more engaged and more positive workplace had lower levels of dopamine and 3-methoxytyramine. Reported workplace isolation was correlated with higher levels of dopamine and 3-methoxytyramine. Given correlations between catecholamines, we used 3-methoxytyramine for linear regression. In fully adjusted models, in environments with a more positive culture, levels of 3-methoxytyramine remained lower (ß = -0.065 ± 0.025, p = 0.01) and indicated a positive association between workplace isolation and 3-methoxytyramine (ß = 0.064 ± 0.030, p = 0.04). These findings are consistent with an important relationship between workplace environment and sympathetic nervous system activity.

Effects of Environmental Polycyclic Aromatic Hydrocarbons Exposure and Pro-Inflammatory Activity on Type 2 Diabetes Mellitus in US Adults.

Polycyclic aromatic hydrocarbons (PAHs) are formed due to natural and anthropogenic activities and known for their potential impact and persistence in the environment. PAHs exposure has been linked to cause adverse health effect including lung cancer, heart conditions and genetic mutations. The understanding of metabolic effects of PAHs exposure is less clear especially in the presence of pro-inflammatory stress like alcoholism or diabetes. The aim of this article is to understand the metabolic effects of PAHs exposure on Type 2 Diabetes Mellitus (T2DM) by analyzing the clinical biomarkers data retrieved from the National Health and Nutrition Examination Survey, Center for Disease Control (CDC NHANES) (2015-16). This study has also accessed the interactive impact of PAHs and other proinflammatory factors, like alcohol intake on the metabolic syndrome on T2DM. We investigated urinary levels of hydroxylated PAHs metabolites (OH-PAHs) along with demographic, clinical and laboratory data. Generalize linear model Univariate factorial ANOVA was used to evaluate the group differences in the demographics, PAH exposure, drinking patterns, clinical data, and biomarker levels. Linear regression model was used to analyze the association of biomarkers, PAH exposure and drinking data. Multivariable regression model was used for multi-independent model to assess comorbidity association and their effect sizes on the clinical outcomes. The results indicated that BMI (p = 0.002), and age (≤0.001) are independent demographic risk factors for T2DM in high PAHs exposure. Acute proinflammatory activity characterized by CRP, is augmented by elevated monocyte levels (p ≤ 0.001) and stepwise addition of 1-Hydroxynapthelene (p = 0.005), and 2-Hydroxynapthelene (p = 0.001) independently. Prevalence of highest average drinks over time is observed in the high PAHs exposure; with males drinking almost twice compared to females in highly exposed population. Pathway response of T2DM shows sexual dimorphism; with males showing association with triglycerides (p ≤ 0.001), and females with CRP (p = 0.015) independently with HbA1C. The arrangement of CRP, absolute monocyte levels, serum triglycerides and average drinks over time predict the HbA1C levels (adjusted R2 = 0.226, p ≤ 0.001) in individuals with high PAHs exposure. Findings from this investigation support the pathological role of high exposure of PAHs in the exacerbation of metabolic disorder syndrome involving T2DM. Sexual dimorphism is reflected in alcohol drinking, with males drinking more in the high PAHs exposure group. Alcohol drinking as an independent factor was associated with the T2DM indicator, HbA1C in individuals with high PAHs exposure.

Genome plasticity as a paradigm of antibiotic resistance spread in ESKAPE pathogens.

The major reason behind the spread of antibiotic resistance genes (ARGs) is persistent selective pressure in the environment encountered by bacteria. Genome plasticity plays a crucial role in dissemination of antibiotic resistance among bacterial pathogens. Mobile genetic elements harboring ARGs are reported to dodge bacterial immune system and mediate horizontal gene transfer (HGT) under selective pressure. Residual antibiotic pollutants develop selective pressures that force the bacteria to lose their defense mechanisms (CRISPR-cas) and acquire resistance. The present study targets the ESKAPE organisms (namely, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) causing various nosocomial infections and emerging multidrug-resistant species. The role of CRISPR-cas systems in inhibition of HGT in prokaryotes and its loss due to presence of various stressors in the environment is also focused in the study. IncF and IncH plasmids were identified in all strains of E. faecalis and K. pneumoniae, carrying Beta-lactam and fluoroquinolone resistance genes, whereas sal3, phiCTX, and SEN34 prophages harbored aminoglycoside resistance genes (aadA, aac). Various MGEs present in selected environmental niches that aid the bacterial genome plasticity and transfer of ARGs contributing to its spread are also identified.

Environmental Distribution, Metabolic Fate, and Degradation Mechanism of Chlorpyrifos: Recent and Future Perspectives.

Pesticides play a significant role in crop production and have become an inevitable part of the modern environment due to their extensive distribution throughout the soil ecosystem. Prophylactic applications of chlorpyrifos (CP) affect soil fertility, modify soil microbial community structure, and pose potential health risks to the nontarget organisms. Bioremediation through microbial metabolism is found to be an ecofriendly and cheaper process for CP removal from the environment. So far, various bacterial and fungal communities have been reported for CP and its metabolites degradation. Organophosphorus hydrolase (OPH) and methyl parathion hydrolase (MPH) are crucial bacterial enzymes for CP degradation as they efficiently hydrolyze the unbreakable P-O and P = S bond. This review discusses the prospects of toxicity level, persistency, and harmful effects of CP on the environment. CP degradation mechanisms, metabolic pathways, and key enzymes, along with their structural details, are also featured. The highlights on molecular docking with OPH and MPH enzyme for CP show the best binding affinity with OPH; hence, it is an essential part of CP degradation. Simultaneously, metagenomic analysis of soil from contaminated agricultural lands and wastewater was analyzed with the goal to identify the dominant CP degraders and enzymes. The identification of potent degraders, key enzymes, and evaluation of microbial community dynamics upon pesticide exposure can be used as a warning for its dissemination and biomagnification into the food chain.

Isolation, purification and characterization of a novel esterase from camel rumen metagenome.

Bacterial esterases are gaining the importance in pharmaceuticals and agrochemical industries due to their excellent biocatalytic properties and a wide range of applications. In the present study, a novel gene encoding an esterase (designated as Est-CR) was identified from shotgun metagenomic sequencing data of camel rumen (Camelus dromedarius) liquor. The open reading frame consisted of 1,224bp, which showed 84.03% sequence identity to Bacteroidales bacterium, corresponding to a protein of 407 amino acids and has a catalytic domain belonging to an esterase. Est-CR belonged to family V with GLSMG domain. The purified enzyme with a molecular mass of 62.64 kDa was checked on SDS-PAGE, and its expression was confirmed by western blotting. The enzyme was active and stable over a broad range of temperature (35-65 °C), displayed the maximum activity at 50 °C and pH 7.0. Individually all metal ions inhibited the enzyme activity, while in combination, K2+, Ca2+, Mg2+ and Mn2+ metal ions enhanced the enzyme activity. The detergents strongly inhibited the activity, while EDTA (10 mM) increased the activity of the Est-CR enzyme. The enzyme showed specificity to short-chain substrates and displayed an optimum activity against butyrate ester. This novel enzyme might serve as a promising candidate to meet some harsh industrial processes enzymatic needs.

Electronic cigarette solvents, pulmonary irritation, and endothelial dysfunction: role of acetaldehyde and formaldehyde.

After more than a decade of electronic cigarette (E-cig) use in the United States, uncertainty persists regarding E-cig use and long-term cardiopulmonary disease risk. As all E-cigs use propylene glycol and vegetable glycerin (PG-VG) and generate abundant saturated aldehydes, mice were exposed by inhalation to PG-VG-derived aerosol, formaldehyde (FA), acetaldehyde (AA), or filtered air. Biomarkers of exposure and cardiopulmonary injury were monitored by mass spectrometry (urine metabolites), radiotelemetry (respiratory reflexes), isometric myography (aorta), and flow cytometry (blood markers). Acute PG-VG exposure significantly affected multiple biomarkers including pulmonary reflex (decreased respiratory rate, -50%), endothelium-dependent relaxation (-61.8 ± 4.2%), decreased WBC (-47 ± 7%), and, increased RBC (+6 ± 1%) and hemoglobin (+4 ± 1%) versus air control group. Notably, FA exposure recapitulated the prominent effects of PG-VG aerosol on pulmonary irritant reflex and endothelial dysfunction, whereas AA exposure did not. To attempt to link PG-VG exposure with FA or AA exposure, urinary formate and acetate levels were measured by GC-MS. Although neither FA nor AA exposure altered excretion of their primary metabolite, formate or acetate, respectively, compared with air-exposed controls, PG-VG aerosol exposure significantly increased post-exposure urinary acetate but not formate. These data suggest that E-cig use may increase cardiopulmonary disease risk independent of the presence of nicotine and/or flavorings. This study indicates that FA levels in tobacco product-derived aerosols should be regulated to levels that do not induce biomarkers of cardiopulmonary harm. There remains a need for reliable biomarkers of exposure to inhaled FA and AA.NEW & NOTEWORTHY Use of electronic cigarettes (E-cig) induces endothelial dysfunction (ED) in healthy humans, yet the specific constituents in E-cig aerosols that contribute to ED are unknown. Our study implicates formaldehyde that is formed in heating of E-cig solvents (propylene glycol, PG; vegetable glycerin, VG). Exposure to formaldehyde or PG-VG-derived aerosol alone stimulated ED in female mice. As ED was independent of nicotine and flavorants, these data reflect a "universal flaw" of E-cigs that use PG-VG.Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/e-cigarettes-aldehydes-and-endothelial-dysfunction/.

Unraveling the camel rumen microbiome through metaculturomics approach for agriculture waste hydrolytic potential.

Cellulose is the most abundant natural polymer present on Earth in the form of agriculture waste. Hydrolysis of agriculture waste for simple fermentable reducing sugars is the bottleneck in the area of biofuel generation and other value-added products. The present study aims to utilize the camel rumen as a bioreactor for potent cellulolytic and hemicellulolytic bacteria by altering the feed types with varying cellulosic concentrations. A total of 6716 bacterial cultures were subjected to three layers of screening, where plate zymography and chromophoric substrate screening served as primary screening method for cellulolytic and hemicellulolytic potential. The potential isolates were genetically grouped using RAPD, and 51 representative isolates from each group were subjected to molecular identification through 16S rDNA sequencing, followed by quantification of various cellulolytic and hemicellulolytic enzymes. Out of 51 potent isolates, 5 isolates had high endoglucanase activity ranging from 0.3 to 0.48 U/ml. The selected five key isolates identified as Pseudomonas, Paenibacillus, Citrobacter, Bacillus subtilis, and Enterobacter were employed for hydrolyzing the various agriculture residues and resulted in approximately 0.4 mg/ml of reducing sugar. Furthermore, the metaculturomics approach was implemented to deduce the total cultured diversity through 16S rRNA amplicon library sequencing. The metaculturomics data revealed the dominance of proteobacteria and unidentified bacterial population in all four feed types, which indicates the possibility of culturing novel cellulose-deconstructing bacteria. Moreover, the presence of diverse hydrolytic enzymes in cultured isolates supports the usage of these bacteria in bio-processing of agriculture waste residues and obtaining the biofuels and other value-added products.

Artificial Intelligence, Machine Learning, and Cardiovascular Disease.

Artificial intelligence (AI)-based applications have found widespread applications in many fields of science, technology, and medicine. The use of enhanced computing power of machines in clinical medicine and diagnostics has been under exploration since the 1960s. More recently, with the advent of advances in computing, algorithms enabling machine learning, especially deep learning networks that mimic the human brain in function, there has been renewed interest to use them in clinical medicine. In cardiovascular medicine, AI-based systems have found new applications in cardiovascular imaging, cardiovascular risk prediction, and newer drug targets. This article aims to describe different AI applications including machine learning and deep learning and their applications in cardiovascular medicine. AI-based applications have enhanced our understanding of different phenotypes of heart failure and congenital heart disease. These applications have led to newer treatment strategies for different types of cardiovascular diseases, newer approach to cardiovascular drug therapy and postmarketing survey of prescription drugs. However, there are several challenges in the clinical use of AI-based applications and interpretation of the results including data privacy, poorly selected/outdated data, selection bias, and unintentional continuance of historical biases/stereotypes in the data which can lead to erroneous conclusions. Still, AI is a transformative technology and has immense potential in health care.

Therapeutic Prospects for Th-17 Cell Immune Storm Syndrome and Neurological Symptoms in COVID-19: Thiamine Efficacy and Safety, In-vitro Evidence and Pharmacokinetic Profile.

Introduction Emerging infectious diseases, especially the coronavirus disease identified in 2019 (COVID-19), can be complicated by a severe exacerbation in the Th17 cell-mediated IL-17 proinflammatory immune storm. This enhanced immune response plays a major role in mortality and morbidity, including neurological symptoms. We hypothesized that countering the cytokine storm with thiamine may have therapeutic efficacy in lowering the Th17 cell proinflammatory response. We used an in vitro study and corroborated those results in disease controls (DC). We developed an effective dose range and model for key pharmacokinetic measures with the potential of targeting the cytokine storm and neurological symptoms of COVID-19. Study Participants and Methods We investigated the effect of a three-week 200 mg dose of thiamine in lowering the Th17 response in sixteen DC (proinflammatory origin due to heavy alcohol drinking) patients; and eight healthy control/volunteers (HV) as a pilot clinical-translational investigation. To further investigate, we performed an in vitro study evaluating the effectiveness of thiamine treatment in lowering the Th17 proinflammatory response in a mouse macrophage cell line (RAW264.7) treated with ethanol. In this in vitro study, 100 mg/day equivalent (0.01 ug/ml) thiamine was used. Based on recent publications, we compared the results of the IL-17 response from our clinical and in vitro study to those found in other proinflammatory disease conditions (metabolic conditions, septic shock, viral infections and COVID-19), including symptoms, and dose ranges of effective and safe administration of thiamine. We developed a dose range and pharmacokinetic profile for thiamine as a novel intervention strategy in COVID-19 to alleviate the effects of the cytokine storm and neurological symptoms. Results The DC group showed significantly elevated proinflammatory cytokines compared to HV. Three-week of 200 mg daily thiamine treatment significantly lowered the baseline IL-17 levels while increased IL-22 levels (anti-inflammatory response). This was validated by an in vitro macrophage response using a lower thiamine dose equivalent (100 mg), which resulted in attenuation of IL-17 and elevation of IL-22 at the mRNA level compared to the ethanol-only treated group. In humans, a range of 79-474 mg daily of thiamine was estimated to be effective and safe as an intervention for the COVID-19 cytokine storm. A literature review showed that several neurological symptoms of COVID-19 (which exist in 45.5% of the severe cases) occur in other viral infections and neuroinflammatory states that may also respond to thiamine treatment. Discussion The Th17 mediated IL-17 proinflammatory response can potentially be attenuated by thiamine. Thiamine, a very safe drug even at very high doses, could be repurposed for treating the cytokine/immune storm of COVID-19 and the subsequent neurological symptoms observed in COVID-19 patients. Further studies using thiamine as an interventional/prevention strategy in severe COVID-19 patients could identify its precise anti-inflammatory role.

Functional genomics assessment of lytic polysaccharide mono-oxygenase with glycoside hydrolases in Paenibacillus dendritiformis CRN18.

Recently discovered Lytic Polysaccharide Mono-Oxygenase (LPMO) enhances the enzymatic deconstruction of complex polysaccharide by oxidation. The present study demonstrates the agricultural waste hydrolyzing capabilities of Paenibacillus dendritiformis CRN18, which exhibits the enzyme activity of exo-glucanase, ß-glucosidase, ß-glucuronidase, endo-1, 4 ß-xylanases, arabinosidase, and α-galactosidase as 0.1U/ml, 0.3U/ml, 0.09U/ml, 0.1U/ml, 0.05U/ml, and 0.41U/ml, respectively. The genome analysis of strain reveals the presence of four LPMO genes, along with lignocellulolytic genes. The gene structure of LPMO and its phylogenetic analysis shows the evolutionary relatedness with the Bacillus LPMO gene. Gene position of LPMOs in the genome of strains shows the close association of two LPMOs with chitin active enzyme GH18, and the other two are associated with hemicellulases (GH39, GH23). Protein-protein interaction and gene networking of LPMO sheds light on the co-occurrence, neighborhood, and interaction of LPMOs with chitinase and xylanase enzymes. Structural prediction of LPMOs unravels the information of the LPMO's binding site. Although the LPMO has been explored for its oxidative mechanism, a little light has been shed on its gene structure. This study provides insights into the LPMO gene structure in P. dendritiformis CRN18 and its potential in lignocellulose hydrolysis.

Dysregulation in Plasma ω3 Fatty Acids Concentration and Serum Zinc in Heavy Alcohol-Drinking HCV Patients.

Alcohol use disorder (AUD) patients comorbid with hepatitis C virus (HCV) infection (HCV + AUD) could have progressively severe clinical sequels of liver injury and inflammation. Serum zinc and several polyunsaturated fatty acids (PUFAs) get dysregulated in AUD as well as HCV. However, the extent of dysregulation of PUFAs and zinc deficiency and their interaction in HCV + AUD as a comorbid pathology has not been studied. We examined the role of dysregulation of FAs and low zinc in HCV + AUD patients. 138 male and female participants aged 21-67 years were grouped as HCV-only (Gr. 1; n = 13), HCV + AUD (Gr. 2; n = 25), AUD without liver injury (Gr. 3; n = 37), AUD with liver injury (Gr. 4; n = 51), and healthy volunteers (Gr. 5 or HV; n = 12). Drinking history, individual demographic measures, fasting fatty acids, liver function, and zinc were measured and analyzed. HCV + AUD patients showed the highest ALT level compared to the rest of the groups. Serum zinc concentrations were the lowest, and the proinflammatory shift was the highest (characterized by ω6 : ω3 ratio) in the HCV + AUD patients. Total ω3, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA5,3) were the lowest in HCV + AUD patients. Total ω3, α-linoleic acid (α-LA) along with covariable number of drinking days past 90 days (NDD90), eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA5,3) independently showed significant association with low zinc in the HCV + AUD patients. Heavy drinking pattern showed that NDD90 has a significant mediating role in the representation of the relationship between candidate ω3 PUFAs and zinc uniquely in the HCV + AUD patients. Low serum zinc showed a distinctively stronger association with total and candidate ω3s in the HCV + AUD patients compared to the patients with HCV or AUD alone, supporting dual mechanism involved in the exacerbation of the proinflammatory response in this comorbid cohort. This trial is registered with NCT#00001673.

Comprehensive Review of Abdominopelvic Mesenchymal Tumors With Radiologic Pathologic Correlation and Update on Current Treatment Guidelines-Part 2.

Soft-tissue sarcomas are a diverse group of rare mesenchymal malignancies accounting for only 1% of all solid adult malignancies. These have been categorized in 12 broad groups by the World Health Organization (WHO) with their recent update in 2013. Majority of them lack specific imaging features serving as imaging conundrums for a radiologist. These are often large masses at presentation as they are asymptomatic or cause vague clinical symptoms. These tumors are challenging for surgeons as well as they find it difficult to achieve complete resection because of complex intra-abdominal anatomy and their close relationship with critical structures. Often, a multidisciplinary approach is required to decide on the most appropriate management for these complex cases so as to provide optimal patient care. Knowledge of the WHO classification, pathologic features, and treatment options available helps the radiologist make a meaningful contribution in multidisciplinary discussions of such cases and overall patient care. Liposarcoma (well-differentiated and dedifferentiated liposarcomas), leiomyosarcoma, and gastrointestinal stromal tumor are the 3 most common primary intra-abdominal sarcomas. In part 1 of this article, general features of soft-tissue sarcomas and some of the common tumors from WHO category 1-4 found in abdomen and pelvis are discussed. Part 2 will focus on common tumors from remainder of the WHO categories.

Zoonosis: An Emerging Link to Antibiotic Resistance Under "One Health Approach".

Current scenario in communicable diseases has generated new era that identifies the "One health" approach to understand the sharing and management of etiological agents with its impact on ecosystem. Under this context the relevance of zoonotic diseases generates major concern. The indiscriminate and higher use of antibiotics in animal husbandry creates substantial pressure on the gut microbiome for development of resistance due to shorter generation time and high density. Thus, gut works as a bioreactor for the breeding of ARBs in this scenario and are continuously released in different niches. These ARBs transfer resistance genes among native flora through horizontal gene transfer events, vectors and quorum sensing. About 60% of infectious diseases in human are caused by zoonotic pathogens have potential to carry ARGs which could be transmitted to humans. The well documented zoonotic diseases are anthrax cause by Bacillus anthracis, bovine tuberculosis by Mycobacterium tuberculosis, brucellosis by Brucella abortus, and hemorrhagic colitis by Escherichia coli. Similarly, most of the antibiotics are not completely metabolized and released in unmetabolized forms which enters the food chain and affect various ecological niches through bioaccumulation. The persistence period of antibiotics ranges from < 1 to 3466 days in environment. The consequences of misusing the antibiotic in livestock and their fate in various ecological niches have been discussed in this review. Further the light sheds on antibiotics persistence and it biodegradation through different abiotic and biotic approaches in environment. The knowledge on personnel hygiene and strong surveillance system for zoonotic disease including ARBs transmission, prevention and control measures should be established to regulate the spread of AMR in the environment and subsequently to the human being through a food web.

Repurposing Treatment of Wernicke-Korsakoff Syndrome for Th-17 Cell Immune Storm Syndrome and Neurological Symptoms in COVID-19: Thiamine Efficacy and Safety, In-Vitro Evidence and Pharmacokinetic Profile.

Coronavirus disease identified in 2019 (COVID-19) can be complicated by the Th17 cell-mediated IL-17 proinflammatory response. We tested if thiamine can effectively lower the Th17 response in a clinical study [Proinflammatory state in alcohol use disorder patients termed as disease controls (DC)] and corroborated the results using an in vitro study. We developed an effective dose range and model for key pharmacokinetic measures with the potential of targeting the cytokine storm and neurological symptoms of COVID-19. Three-week 200 mg dose of thiamine was administered to sixteen DC patients. Eight healthy volunteers (HV) were also included in this investigation. A subsequent in vitro study was performed to validate the effectiveness of thiamine [100 mg/day equivalent (0.01 µg/ml)] treatment in lowering the Th17 proinflammatory response in a mouse macrophage cell line (RAW264.7) treated with ethanol. Based on recent publications, we compared the results of the IL-17 response from our clinical and in vitro study to those found in other proinflammatory disease conditions (metabolic conditions, septic shock, viral infections and COVID-19) and effective and safe dose ranges of thiamine. We developed a pharmacokinetic profile for thiamine dose range as a novel intervention strategy in COVID-19. DC group showed significantly elevated proinflammatory cytokines compared to HV. Thiamine-treated DC patients showed significant lowering in IL-17 and increase in the IL-22 levels. In humans, a range of 79-474 mg daily of thiamine was estimated to be effective and safe as an intervention for the COVID-19 cytokine storm. A literature review showed that several neurological symptoms of COVID-19 (∼45.5% of the severe cases) occur in other viral infections and neuroinflammatory states that may also respond to thiamine treatment. Thiamine, a very safe drug even at very high doses, could be repurposed for treating the Th17 mediated IL-17 immune storm, and the subsequent neurological symptoms observed in COVID-19. Further studies using thiamine as an intervention/prevention strategy in COVID-19 patients could identify its precise anti-inflammatory role.

Association between residential greenness and exposure to volatile organic compounds.

Residential proximity to vegetation and plants is associated with many health benefits, including reduced risk of cardiovascular disease, diabetes and mental stress. Although the mechanisms by which proximity to greenness affects health remain unclear, plants have been shown to remove particulate air pollution. However, the association between residential-area vegetation and exposure to volatile organic chemicals (VOCs) has not been investigated. We recruited a cohort of 213 non-smoking individuals and estimated peak, cumulative, and contemporaneous greenery using satellite-derived normalized difference vegetation index (NDVI) near their residence. We found that the urinary metabolites of exposure to VOCs - acrolein, acrylamide, acrylonitrile, benzene, 1-bromopropane, propylene oxide were inversely associated (7-31% lower) with 0.1 higher peak NDVI values within 100 m radius of the participants' home. These associations were significant at radii ranging from 25 to 300 m. Strongest associations were observed within a 200 m radius, where VOC metabolites were 22% lower per 0.1 unit higher NDVI. Of the 18 measured urinary metabolites, 7 were positively associated with variation of greenness within a 200 m radius of homes. The percent of tree canopy and street trees around participants' residence were less strongly associated with metabolite levels. The associations between urinary VOC metabolites and residential NDVI values were stronger in winter than in summer, and in participants who were more educated, White, and those who lived close to areas of high traffic. These findings suggest high levels of residential greenness are associated with lower VOC exposure, particularly in winter.

Recruitment and retention of US South Asians for an epidemiologic cohort: Experience from the MASALA study.

INTRODUCTION: There are few longitudinal studies about South Asians (SAs) and little information about recruitment and retention approaches for this ethnic group. METHODS: We followed 906 SAs enrolled in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort for 5 years. Surviving participants were invited for a second clinical exam from 2015 to 2018. A new wave of participants was recruited during 2017-2018. We assessed the yields from different methods of recruitment and retention. RESULTS: A total of 759 (83%) completed the second clinical exam, and 258 new participants were enrolled. Providing a nearby community hospital location for the study exam, offering cab/shared ride reimbursement, and conducting home visits were the most effective methods for enhancing retention. New participant recruitment targeted women and individuals with lower socioeconomic status, and we found that participant referrals and active community engagement were most effective. Mailing invitational letters to those identified by electronic health records had very low yield. CONCLUSION: Recruitment and retention strategies that address transportation barriers and increase community engagement will help increase the representation of SAs in health research.