Nevin Manimala

Toxins (Basel). 2021 Nov 12;13(11):797. doi: 10.3390/toxins13110797.

ABSTRACT

Snakebite-induced acute kidney injury (AKI) is frequently observed in patients following bites from vipers such as Russell’s viper (Daboia russelii) in India. Currently, the levels of serum creatinine are mainly used as a marker to determine the necessity for renal replacement therapy (RRT) (haemodialysis) in severe cases of AKI. However, it takes up to 48 h to ascertain a distinct change in creatinine levels compared to its baseline level upon admission. The time lost between admission and the 48 h timepoint significantly affects the clinical management of snakebite victims. Moreover, early diagnosis of AKI and decision on the necessity for RRT in snakebite victims is critical in saving lives, reducing long-term complications, and minimising treatment costs arising from expensive haemodialysis. Neutrophil gelatinase-associated lipocalin (NGAL) has been recently studied as a robust early marker for AKI in non-snakebite patients. However, its suitability for clinical use in snakebite victims has not been rigorously established. Here, we demonstrate the clinical significance of plasma NGAL as a robust marker for RRT following AKI using a large cohort (309) of Russell’s viper victims without any pre-existing health conditions. NGAL levels upon admission are positively correlated with creatinine levels at 48 h in different stages of AKI. Overall, NGAL acts as a robust early marker to ascertain the need for RRT following Russell’s viper bites. The quantification of NGAL can be recommended as a routine test in hospitals that treat snakebites to decide on RRT at early time points instead of waiting for 48 h to confirm the increase in creatinine levels. The diagnostic use of NGAL in Russell’s viper victims with pre-existing comorbidities and for other vipers should be evaluated in future studies.

PMID:34822581 | DOI:10.3390/toxins13110797

Mar Drugs. 2021 Nov 22;19(11):649. doi: 10.3390/md19110649.

ABSTRACT

Aeromonas spp. are generally found in aquatic environments, although they have also been isolated from both fresh and processed food. These Gram-negative, rod-shaped bacteria are mostly infective to poikilothermic animals, although they are also considered opportunistic pathogens of both aquatic and terrestrial homeotherms, and some species have been associated with gastrointestinal and extraintestinal septicemic infections in humans. Among the different pathogenic factors associated with virulence, several cell-surface glucans have been shown to contribute to colonization and survival of Aeromonas pathogenic strains, in different hosts. Lipopolysaccharide (LPS), capsule and α-glucan structures, for instance, have been shown to play important roles in bacterial-host interactions related to pathogenesis, such as adherence, biofilm formation, or immune evasion. In addition, glycosylation of both polar and lateral flagella has been shown to be mandatory for flagella production and motility in different Aeromonas strains, and has also been associated with increased bacterial adhesion, biofilm formation, and induction of the host proinflammatory response. The main aspects of these structures are covered in this review.

PMID:34822520 | DOI:10.3390/md19110649

Mar Drugs. 2021 Nov 16;19(11):640. doi: 10.3390/md19110640.

ABSTRACT

The marine environment is potentially a prolific source of small molecules with significant biological activities. In recent years, the development of new chromatographic phases and the progress in cell and molecular techniques have facilitated the search for marine natural products (MNPs) as novel pharmacophores and enhanced the success rate in the selection of new potential drug candidates. However, most of this exploration has so far been driven by anticancer research and has been limited to a reduced number of taxonomic groups. In this article, we report a test study on the screening potential of an in-house library of natural small molecules composed of 285 samples derived from 57 marine organisms that were chosen from among the major eukaryotic phyla so far represented in studies on bioactive MNPs. Both the extracts and SPE fractions of these organisms were simultaneously submitted to three different bioassays-two phenotypic and one enzymatic-for cytotoxic, antidiabetic, and antibacterial activity. On the whole, the screening of the MNP library selected 11 potential hits, but the distribution of the biological results showed that SPE fractionation increased the positive score regardless of the taxonomic group. In many cases, activity could be detected only in the enriched fractions after the elimination of the bulky effect due to salts. On a statistical basis, sponges and molluscs were confirmed to be the most significant source of cytotoxic and antimicrobial products, but other phyla were found to be effective with the other therapeutic targets.

PMID:34822511 | DOI:10.3390/md19110640

Metabolites. 2021 Oct 28;11(11):743. doi: 10.3390/metabo11110743.

ABSTRACT

Small-compound databases contain a large amount of information for metabolites and metabolic pathways. However, the plethora of such databases and the redundancy of their information lead to major issues with analysis and standardization. A lack of preventive establishment of means of data access at the infant stages of a project might lead to mislabelled compounds, reduced statistical power, and large delays in delivery of results. We developed MetaFetcheR, an open-source R package that links metabolite data from several small-compound databases, resolves inconsistencies, and covers a variety of use-cases of data fetching. We showed that the performance of MetaFetcheR was superior to existing approaches and databases by benchmarking the performance of the algorithm in three independent case studies based on two published datasets.

PMID:34822401 | DOI:10.3390/metabo11110743

Metabolites. 2021 Oct 28;11(11):742. doi: 10.3390/metabo11110742.

ABSTRACT

Beneficial effects of n-3 fatty acids on metabolic biomarkers in patients with type 2 diabetes (T2DM) has been reported. The objectives of this current research were to investigate the effects of n-3 supplementation on metabolic factors, weight, and body mass index (BMI) in patients with type 2 diabetes mellitus (T2DM), using a meta-analysis of randomized, controlled trials (RCTs). Online databases PubMed, Embase, Web of Science, and Science Direct were searched until 2021 to identify eligible articles. Thirty trials were included. The results showed that n-3 consumption can significantly reduce glycemic factors including fasting blood sugar (FBS) (-0.36 (-0.71 to -0.01)), glycated hemoglobulin (HbA1c) (-0.74 (-1.13 to -0.35)), and homeostatic model assessment of insulin resistance (HOMA.IR) (-0.58 (-1.13 to -0.03)). Furthermore, significant improvement in lipid profile including triglycerides (TG) (-0.27 (-0.37 to -0.18)), total cholesterol (-0.60 (-0.88 to -0.32)), low density lipoprotein (LDL) (-0.54 (-0.85 to -0.23)), and high-density lipoprotein (HDL) (0.60 (0.23 to 0.96)) levels were found in the present meta-analysis. The reduction in the inflammatory marker’s tumor necrosis factor-alpha (TNF-α) (-0.13 (-0.75 to 0.48)) and c-reactive protein (CRP) (-0.72 (-1.70 to 0.27)), as well as weight (-0.09 (-0.24 to 0.07)) and BMI (-0.13 (-0.29 to 0.02)) were not statistically significant. Furthermore, the findings revealed that the optimal dose and duration of n-3 consumption for patients with T2DM is 1000-2000 mg/d for more than 8 weeks. The present meta-analysis and review reveals that n-3 supplementation can improve glycemic factors and lipid profile in patients with T2DM. Furthermore, n-3 supplementation may provide beneficial effects on inflammatory markers and body weight if used at the appropriate dose and duration.

PMID:34822400 | DOI:10.3390/metabo11110742

Metabolites. 2021 Oct 28;11(11):738. doi: 10.3390/metabo11110738.

ABSTRACT

Steroid hormones act as important regulators of physiological processes including gene expression. They provide possible mechanistic explanations of observed sex-dimorphisms in obesity and coronary artery disease (CAD). Here, we aim to unravel causal relationships between steroid hormones, obesity, and CAD in a sex-specific manner. In genome-wide meta-analyses of four steroid hormone levels and one hormone ratio, we identified 17 genome-wide significant loci of which 11 were novel. Among loci, seven were female-specific, four male-specific, and one was sex-related (stronger effects in females). As one of the loci was the human leukocyte antigen (HLA) region, we analyzed HLA allele counts and found four HLA subtypes linked to 17-OH-progesterone (17-OHP), including HLA-B*14*02. Using Mendelian randomization approaches with four additional hormones as exposure, we detected causal effects of dehydroepiandrosterone sulfate (DHEA-S) and 17-OHP on body mass index (BMI) and waist-to-hip ratio (WHR). The DHEA-S effect was stronger in males. Additionally, we observed the causal effects of testosterone, estradiol, and their ratio on WHR. By mediation analysis, we found a direct sex-unspecific effect of 17-OHP on CAD while the other four hormone effects on CAD were mediated by BMI or WHR. In conclusion, we identified the sex-specific causal networks of steroid hormones, obesity-related traits, and CAD.

PMID:34822396 | DOI:10.3390/metabo11110738

Metabolites. 2021 Oct 27;11(11):737. doi: 10.3390/metabo11110737.

ABSTRACT

Determining biomarkers and better characterizing the biochemical progression of nonalcoholic fatty liver disease (NAFLD) remains a clinical challenge. A targeted ¹H-NMR study of serum, combined with clinical variables, detected and localized biomarkers to stages of NAFLD in morbidly obese females. Pre-surgery serum samples from 100 middle-aged, morbidly obese female subjects, grouped on gold-standard liver wedge biopsies (non-NAFLD; steatosis; and fibrosis) were collected, extracted, and analyzed in aqueous (D₂O) buffer (¹H, 600 MHz). Profiled concentrations were subjected to exploratory statistical analysis. Metabolites varying significantly between the non-NAFLD and steatosis groups included the ketone bodies 3-hydroxybutyrate (↓; p = 0.035) and acetone (↓; p = 0.012), and also alanine (↑; p = 0.004) and a putative pyruvate signal (↑; p = 0.003). In contrast, the steatosis and fibrosis groups were characterized by 2-hydroxyisovalerate (↑; p = 0.023), betaine (↓; p = 0.008), hypoxanthine (↓; p = 0.003), taurine (↓; p = 0.001), 2-hydroxybutyrate (↑; p = 0.045), 3-hydroxyisobutyrate (↑; p = 0.046), and increasing medium chain fatty acids. Exploratory classification models with and without clinical variables exhibited overall success rates ca. 75-85%. In the study conditions, inhibition of fatty acid oxidation and disruption of the hepatic urea cycle are supported as early features of NAFLD that continue in fibrosis. In fibrosis, markers support inflammation, hepatocyte damage, and decreased liver function. Complementarity of NMR concentrations and clinical information in classification models is shown. A broader hypothesis that standard-of-care sera can yield metabolomic information is supported.

PMID:34822395 | DOI:10.3390/metabo11110737

Metabolites. 2021 Oct 22;11(11):723. doi: 10.3390/metabo11110723.

ABSTRACT

Gestational diabetes mellitus (GDM) is one of the most frequent pregnancy complications with potential adverse outcomes for mothers and newborns. Its effects on the newborn appear during the neonatal period or early childhood. Therefore, an early diagnosis is crucial to prevent the development of chronic diseases later in adult life. In this study, the urinary metabolome of babies born to GDM mothers was characterized. In total, 144 neonatal and maternal (second and third trimesters of pregnancy) urinary samples were analyzed using targeted metabolomics, combining liquid chromatographic mass spectrometry (LC-MS/MS) and flow injection analysis mass spectrometry (FIA-MS/MS) techniques. We provide here the neonatal urinary concentration values of 101 metabolites for 26 newborns born to GDM mothers and 22 newborns born to healthy mothers. The univariate analysis of these metabolites revealed statistical differences in 11 metabolites. Multivariate analyses revealed a differential metabolic profile in newborns of GDM mothers characterized by dysregulation of acylcarnitines, amino acids, and polyamine metabolism. Levels of hexadecenoylcarnitine (C16:1) and spermine were also higher in newborns of GDM mothers. The maternal urinary metabolome revealed significant differences in butyric, isobutyric, and uric acid in the second and third trimesters of pregnancy. These metabolic alterations point to the impact of GDM in the neonatal period.

PMID:34822382 | DOI:10.3390/metabo11110723

Medicines (Basel). 2021 Nov 12;8(11):70. doi: 10.3390/medicines8110070.

ABSTRACT

COVID-19 has had a significant impact on global health systems. The aim of this study was to evaluate how imaging volumes and imaging types in radiology departments have been affected by the COVID-19 pandemic across different locations.

METHODS: Imaging volumes in the Aseer region (in the south of Saudi Arabia) across main hospitals were reviewed retrospectively including all cases referred from different locations (outpatient, inpatient and emergency departments). Data for years 2019 and 2020 were compared. The mean monthly cases were compared using a t-test.

RESULTS: The total imaging volumes in 2019 were 205,805 compared to 159,107 in 2020 with a 22.7% overall reduction. A substantial decline was observed in both the April to June and the July to September periods of approximately 42.9% and 44.4%, respectively. With respect to location, between April and June, the greatest decline was observed in outpatient departments (76% decline), followed by emergency departments (25% decline), and the least impact was observed in inpatient departments, with only 6.8% decline over the same period. According to modality type, the greatest decreases were reported in nuclear medicine, ultrasound, MRI, and mammography, by 100%, 76%, 74%, and 66%, respectively. Our results show a statistically significant (p-value ≤ 0.05) decrease of cases in 2020 compared to 2019, except for mammography procedures.

CONCLUSION: There has been a significant decline in radiology volumes due to COVID-19. The overall reduction in radiology volumes was dependent on the stage/period of lockdown, location, and imaging modality.

PMID:34822367 | DOI:10.3390/medicines8110070

JMIR Aging. 2021 Nov 24;4(4):e16006. doi: 10.2196/16006.

ABSTRACT

BACKGROUND: The rapid diffusion of the internet has decreased consumer reliance on health care providers for health information and facilitated the patients’ ability to be an agent in control of their own health. However, empirical evidence is limited regarding the effects of health-related internet use among older adults, which is complicated by the proliferation of online health and medical sources of questionable scientific accuracy.

OBJECTIVE: We explore the effects of health-related internet use, education, and eHealth literacy on medical encounters and patient-reported outcomes. Patient-reported outcomes are categorized into two dimensions: (1) self-reported health problem and (2) affective distress (feeling worried and anxious) due to information obtained. We were particularly interested in whether education and eHealth literacy moderate the association between perceived strain in medical encounters and patient-reported outcomes.

METHODS: Our study sample consisted of online panel members who have used the internet as a resource for health information, randomly drawn from one of the largest probability-based online research panels. This paper specifically reports results obtained from older panel members (age≥60 years: n=194). First, we examined descriptive statistics and bivariate associations (Pearson correlations and independent samples t tests). We used hierarchical ordinary least squares regression analyses by running separate regressions for each patient-reported outcome. In model 1, we entered the main effects. In model 2, technology and medical encounter variables were included. Model 3 added the statistical interaction terms.

RESULTS: Age (β=-.17; P=.02), gender (β=-.22; P=.01), and medical satisfaction (β=-.28; P=.01) were significant predictors of self-reported health problems. Affective distress was positively predicted by gender (β=.13; P=.05) and satisfaction with medical encounters (β=.34; P<.001) but negatively predicted by education (β=-.18; P=.03) and eHealth literacy (β=-.32; P=.01). The association between experiencing a health problem in relation to health-related internet use and perception of strained medical encounters was greater among respondents with lower levels of education (β=-.55; P=.04). There was also a significant interaction between education and eHealth literacy in predicting the level of affective distress (β=-.60; P=.05), which indicated that higher levels of education predicted lower averages of feeling anxiety and worry despite lower eHealth literacy. Older women reported higher averages of affective distress (β=.13; P=.05), while older men reported higher averages of experiencing a self-reported health problem (β=-.22; P=.01).

CONCLUSIONS: This study provides evidence for the effect of health-related internet use on patient-reported outcomes with implications for medical encounters. The results could be used to guide educational and eHealth literacy interventions for older individuals.

PMID:34822340 | DOI:10.2196/16006