Deciphering the Puzzle of Hypobaric Hypoxia Proteomics Prophylaxis and Modelling Approach

Hypoxia, particularly hypobaric hypoxia, is a multifaceted entity which includes certain molecular, patho-physiological and biochemical aspects. Any single aspect in itself cannot help us elucidate hypobaric hypoxia in its entirety. We observed three crucial lacunae within the existing literature. These include a lack of high-throughput investigations into redox PTMs, particularly NO-based PTMs; a prophylactic supplement with proven efficacy and safety which doesn’t involve medical supervision and is not contraindicated in hepatic, renal and cardiac insufficiencies; and a clinically validated rodent model of HAPE without any genetic/pharmacological manipulations. In the present study, we present an antagonistic interplay between nitrosylation and carbonylation which shows an additional NO-based network that is active in acclimatised individuals. Then we present a micronised aqueous suspension of silymarin which is efficacious at low doses in providing antioxidant, anti-inflammatory and hypoxia-adaptive vascular responses in addition to being a free radical quencher itself. Silymarin has an excellent safety and efficacy profile in humans. Finally, we create a SD rat model of HAPE which was used to reverse-translate a previously known HAPE marker in humans (SULT1A1) and elucidate the synergistic occurrence of HAPE and inflammation cascades. This is the first radiologically validated rodent HAPE model. In conclusion, we were able to elucidate the molecular, biochemical and patho-physiological aspects of hypobaric hypoxia which were left out by previous studies

Bacterial pathogens in wound infection and their antimicrobial susceptibility pattern in a medical college hospital, in Dhaka, Bangladesh

Background: Wound infection is a major health problem that results in prolong hospital stay, increased treatment cost and are responsible for significant mortality and morbidity worldwide. The aim of the present study was to isolate and identify the bacterial pathogens causing wound infection and to determine their antimicrobial susceptibility profile.Methods: This cross sectional study was conducted at the Department of Microbiology, Sir Salimullah Medical College, Dhaka from January 2016 to December 2016. Wound swab samples were collected and inoculated into appropriate media. The bacterial pathogens were identified by using standard microbiological methods. Antimicrobial susceptibility test were performed using disc diffusion technique following Kirby-Bauer method.Results: Out of 239 wound swab samples analyzed 173 (72.4%) were culture positive. Majority (35.3%) of culture positive cases were in age group 16-30 years and 60.1% were male. Staphylococcus aureus (36.9%) was the predominant isolate, followed by Escherichia coli (35.8%), Pseudomonas spp. (17.3%) and Proteus spp. (5.8%). Bacterial isolates were highly resistant Amoxicillin (89-100%), Cephalosporin (60-100%), Ciprofloxacin (53-71%), while they were least resistant to Imipenem (0-14%) and Amikacin (17-30%).  Conclusions: In the present study most of the isolates showed high rate of resistance to commonly used antibiotics. Therefore regular monitoring and rational use of antibiotic should be practiced

Acute Consumption of Flavan-3-ol-Enriched Dark Chocolate Affects Human Endogenous Metabolism

Flavan-3-ols and methylxanthines have potential beneficial effects on human health including reducing cardiovascular risk. We performed a randomized controlled crossover intervention trial to assess the acute effects of consumption of flavan-3-ol-enriched dark chocolate, compared with standard dark chocolate and white chocolate, on the human metabolome. We assessed the metabolome in urine and blood plasma samples collected before and at 2 and 6 h after consumption of chocolates in 42 healthy volunteers using a nontargeted metabolomics approach. Plasma samples were assessed and showed differentiation between time points with no further separation among the three chocolate treatments. Multivariate statistics applied to urine samples could readily separate the postprandial time points and distinguish between the treatments. Most of the markers responsible for the multivariate discrimination between the chocolates were of dietary origin. Interestingly, small but significant level changes were also observed for a subset of endogenous metabolites. H-1 NMR revealed that flavan-3-ol-enriched dark chocolate and standard dark chocolate reduced urinary levels of creatinine, lactate, some amino acids, and related degradation products and increased the levels of pyruvate and 4-hydroxyphenylacetate, a phenolic compound of bacterial origin. This study demonstrates that an acute chocolate intervention can significantly affect human metabolism

Comparative bio-accessibility, bioavailability and bioequivalence of quercetin, apigenin, glucoraphanin and carotenoids from freeze-dried vegetables incorporated into a baked snack versus minimally processed vegetables:Evidence from in vitro models and a human bioavailability study

The aim was to incorporate vegetables containing the phytochemicals quercetin, apigenin, glucoraphanin and carotenoids into a processed potato-based snack and assess their bioaccessibility and bioavailability. Three different processing routes were tested for incorporation and retention of phytochemicals in snacks using individually quick frozen or freeze-dried vegetables. No significant differences in the uptake or transport of quercetin or apigenin between a vegetable mix or snacks were observed using the CaCo-2 transwell model. Simulated in vitro digestions predicted a substantial release of quercetin and apigenin, some release of glucoraphanin but none for carotenes from either the snack or equivalent steamed vegetables. In humans, there were no significant differences in the bioavailability of quercetin, apigenin or glucoraphanin from the snack or equivalent steamed vegetables. We have shown that significant quantities of freeze-dried vegetables can be incorporated into snacks with good retention of phytochemicals and with similar bioavailability to equivalent steamed vegetables

Accumulation of Dietary S-Methyl Cysteine Sulfoxide in Human Prostate Tissue

Scope: Observational studies have associated consumption of cruciferous vegetables with reduced risk of prostate cancer. This effect has been associated with the degradation products of glucosinolates—thioglycosides that accumulate within crucifers. The possible role of S-methyl cysteine sulfoxide, a metabolite that also accumulates in cruciferous vegetables, and its derivatives, in cancer prevention is relatively unexplored compared to glucosinolate derivatives. The hypothesis that consuming a broccoli soup results in the accumulation of sulfate (a SMCSO derivative) and other broccoli-derived metabolites in prostate tissue is tested. Methods and results: Eighteen men scheduled for transperineal prostate biopsy were recruited into a 4-week parallel single blinded diet supplementation study (NCT02821728). Nine men supplemented their diet with three 300 mL portions of a broccoli soup each week for four weeks prior to surgery. Analyses of prostate biopsy tissues reveal no detectable levels of glucosinolates and derivatives. In contrast, SMCSO is detected in prostate tissues of the participants, with significantly higher levels in tissue of men in the supplementation arm. SMCSO was also found in blood and urine samples from a previous intervention study with the identical broccoli soup. Conclusion: The consequences of SMCSO accumulation in prostate tissues and its potential role in prevention of prostate cancer remains to be investigated

Transcriptional changes in prostate of men on active surveillance after a 12-mo glucoraphanin-rich broccoli intervention—results from the Effect of Sulforaphane on prostate CAncer PrEvention (ESCAPE) randomized controlled trial

Background Epidemiological evidence suggests that consumption of cruciferous vegetables is associated with reduced risk of prostate cancer progression, largely attributed to the biological activity of glucosinolate degradation products, such as sulforaphane derived from glucoraphanin. Because there are few therapeutic interventions for men on active surveillance for prostate cancer to reduce the risk of cancer progression, dietary approaches are an appealing option for patients. Objective We evaluated whether consumption of a glucoraphanin-rich broccoli soup for 1 y leads to changes in gene expression in prostate tissue of men with localized prostate cancer. Methods Forty-nine men on active surveillance completed a 3-arm parallel randomized double-blinded intervention study for 12 mo and underwent transperineal template biopsy procedures and dietary assessment at the start and end of the study. Patients received a weekly 300 mL portion of soup made from a standard broccoli (control) or from 1 of 2 experimental broccoli genotypes with enhanced concentrations of glucoraphanin, delivering 3 and 7 times that of the control, respectively. Gene expression in tissues from each patient obtained before and after the dietary intervention was quantified by RNA sequencing followed by gene set enrichment analyses. Results In the control arm, there were several hundred changes in gene expression in nonneoplastic tissue during the 12 mo. These were associated with an increase in expression of potentially oncogenic pathways including inflammation processes and epithelial–mesenchymal transition. Changes in gene expression and associated oncogenic pathways were attenuated in men on the glucoraphanin-rich broccoli soup in a dose-dependent manner. Although the study was not powered to assess clinical progression, an inverse association between consumption of cruciferous vegetables and cancer progression was observed. Conclusion Consuming glucoraphanin-rich broccoli soup affected gene expression in the prostate of men on active surveillance, consistent with a reduction in the risk of cancer progression. This trial was registered at clinicaltrials.gov as NCT01950143

Pregnancy as a risk factor for severe influenza infection: an individual participant data meta-analysis

Background: WHO identifies pregnant women to be at increased risk for severe outcomes from influenza virus infections and recommends that they be prioritized for influenza vaccination. The evidence supporting this, however, is inconsistent. Ecologic studies in particular suggest more severe outcomes from influenza infection during pregnancy than studies based on individual patient data. Individual studies however may be underpowered and, as reported in a previous systematic review, confounding factors could not be adjusted for. We therefore conducted an individual participant data meta-analysis to assess the risk for severe outcomes of influenza infection in pregnant women while adjusting for other prognostic factors. Methods: We contacted authors of studies included in a recently published systematic review. We pooled the individual participant data of women of reproductive age and laboratory confirmation of influenza virus infection. We used a generalized linear mixed model and reported odds ratios (OR) and 95% confidence intervals (CI). Results: A total of 33 datasets with data on 186,656 individuals were available, including 36,498 eligible women of reproductive age and known pregnancy status. In the multivariable model, pregnancy was associated with a 7 times higher risk of hospital admission (OR 6.80, 95%CI 6.02–7.68), among patients receiving medical care as in- or outpatients, pregnancy was associated with a lower risk of admission to intensive care units (ICU; OR 0.57, 95%CI 0.48–0.69), and was not significantly associated with death (OR 1.00, 95%CI 0.75–1.34). Conclusions: Our study found a higher risk of influenza associated hospitalization among pregnant women as compared to non-pregnant women. We did not find a higher mortality rate or higher likelihood of ICU admission among pregnant women who sought medical care. However, this study did not address whether a true community based cohort of pregnant women is at higher risk of influenza associated complications.Fil: Mertz, Dominik. Mc Master University; CanadáFil: Lo, Calvin Ka Fung. Mc Master University; CanadáFil: Lytvyn, Lyubov. Mc Master University; CanadáFil: Ortiz, Justin R.. Organizacion Mundial de la Salud; ArgentinaFil: Loeb, Mark. Mc Master University; CanadáFil: Ang, Li Wei. Ministry of Health; SingapurFil: Anlikumar, Mehta Asmita. Amrita Vishwa Vidyapeetham; IndiaFil: Bonmarin, Isabelle. Santé publique; FranciaFil: Borja Aburto, Victor Hugo. Instituto Mexicano del Seguro Social; MéxicoFil: Burgmann, Heinz. Medical University Vienna; AustriaFil: Carratalà, Jordi. Universidad de Barcelona; España. Instituto de Investigación Biomédica de Bellvitge; España. Spanish Network for Research in Infectious Diseases; EspañaFil: Chowell, Gerardo. Georgia State University; Estados Unidos. National Institutes of Health; Estados UnidosFil: Cilloniz, Catia. Universidad de Barcelona; España. Instituto de Investigaciones Biomédicas August Pi i Sunyer; EspañaFil: Cohen, Jessica. Centers for Disease Control and Prevention; Estados UnidosFil: Cutter, Jeffery. Ministry of Health; SingapurFil: Filleul, Laurent. Santé publique; Francia. French National Public Health Agency; FranciaFil: Garg, Shikha. Centers for Disease Control and Prevention; Estados UnidosFil: Geis, Steffen. London School of Hygiene and Tropical Medicine; Reino UnidoFil: Helferty, Melissa. Public Health Agency; CanadáFil: Huang, Wan Ting. Taiwan Centers for Disease Control; ChinaFil: Jain, Seema. Centers for Disease Control and Prevention; Estados UnidosFil: Sevic, Biljana Joves. Institute for Pulmonary Diseases of Vojvodina; SerbiaFil: Kelly, Paul. Australian Capital Territory Health Directorate; Australia. Australian National University Medical School; AustraliaFil: Kusznierz, Gabriela. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Instituto de Salud "Dr. C. G. Malbran". Instituto Nacional de Enfermedades Respiratorias; ArgentinaFil: Lehners, Nicola. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Lenzi, Luana. Universidade Federal do Paraná; BrasilFil: Ling, Ivan T.. Sir Charles Gairdner Hospital; AustraliaFil: Mitchell, Robyn. Public Health Agency; CanadáFil: Mulrennan, Siobhain A.. Sir Charles Gairdner Hospital; Canadá. University of Western Australia; AustraliaFil: Nishioka, Sergio A.. Ministerio de Salud de Brasil; BrasilFil: Norton, Robert. Townsville Hospital; AustraliaFil: Oh, Won Sup. Kangwon National University School of Medicine; Corea del SurFil: Orellano, Pablo Wenceslao. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The impact of different fertiliser management options and cultivars on nitrogen use efficiency and yield for rice cropping in the Indo-Gangetic Plain: two seasons of methane, nitrous oxide and ammonia emissions

This study presents detailed crop and gas flux data from two years of rice production at the experimental farm of the ICAR-Indian Agricultural Research Institute, New Delhi, India. In comparing 4 nitrogen (N) fertiliser regimes across 4 rice cultivars (CRD 310, IR-64, MTU 1010, P-44), we have added to growing evidence of the environmental costs of rice production in the region. The study shows that rice cultivar can impact yields of both grain, and total biomass produced in given circumstances, with the CRD 310 cultivar showing consistently high nitrogen use efficiency (NUE) for total biomass compared with other tested varieties, but not necessarily with the highest grain yield, which was P-44 in this experiment. While NUE of the rice did vary depending on experimental treatments (ranging from 41% to 73%), 73%), this did not translate directly into the reduction of emissions of ammonia (NH3) and nitrous oxide (N2O). Emissions were relatively similar across the different rice cultivars regardless of NUE. Conversely, agronomic practices that reduced total N losses were associated with higher yield. In terms of fertiliser application, the outstanding impact was of the very high methane (CH4) emissions as a result of incorporating farmyard manure (FYM) into rice paddies, which dominated the overall effect on global warming potential. While the use of nitrification and urease inhibiting substances decreased N2O emissions overall, NH3 emissions were relatively unaffected (or slightly higher). Overall, the greatest reduction in greenhouse gas (GHG) emissions came from reducing irrigation water added to the fields, resulting in higher N2O, but significantly less CH4 emissions, reducing net GHG emission compared with continuous flooding. Overall, genetic differences generated more variation in yield and NUE than agronomic management (excluding controls), whereas agronomy generated larger differences than genetics concerning gaseous losses. This study suggests that a mixed approach needs to be applied when attempting to reduce pollution and global warming potential from rice production and potential pollution swapping and synergies need to be considered. Finding the right balance of rice cultivar, irrigation technique and fertiliser type could significantly reduce emissions, while getting it wrong can result in considerably poorer yields and higher pollution

The prevalence of Giardia infection in dogs and cats, a systematic review and meta-analysis of prevalence studies from stool samples

Giardia has a wide range of host species and is a common cause of diarrhoeal disease in humans and animals. Companion animals are able to transmit a range of zoonotic diseases to their owners including giardiasis, but the size of this risk is not well known. The aim of this study was to analyse giardiasis prevalence rates in dogs and cats worldwide using a systematic search approach. Meta-analysis enabled to describe associations between Giardia prevalence and various confounding factors. Pooled prevalence rates were 15.2% (95% CI 13.8-16.7%) for dogs and 12% (95% CI 9.2-15.3%) for cats. However, there was very high heterogeneity between studies. Meta-regression showed that the diagnostic method used had a major impact on reported prevalence with studies using ELISA, IFA and PCR reporting prevalence rates between 2.6 and 3.7 times greater than studies using microscopy. Conditional negative binomial regression found that symptomatic animals had higher prevalence rates ratios (PRR) than asymptomatic animals 1.61 (95% CI 1.33-1.94) in dogs and 1.94 (95% CI 1.47-2.56) in cats. Giardia was much more prevalent in young animals. For cats >6 months, PRR=0.47 (0.42-0.53) and in dogs of the same age group PRR=0.36 (0.32-0.41). Additionally, dogs kept as pets were less likely to be positive (PRR=0.56 (0.41-0.77)) but any difference in cats was not significant. Faecal excretion of Giardia is common in dogs and slightly less so in cats. However, the exact rates depend on the diagnostic method used, the age and origin of the animal. What risk such endemic colonisation poses to human health is still unclear as it will depend not only on prevalence rates but also on what assemblages are excreted and how people interact with their pets