Safety, feasibility, and impact on the gut microbiome of kefir administration in critically ill adults.

BACKGROUND: Dysbiosis of the gut microbiome is frequent in the intensive care unit (ICU), potentially leading to a heightened risk of nosocomial infections. Enhancing the gut microbiome has been proposed as a strategic approach to mitigate potential adverse outcomes. While prior research on select probiotic supplements has not successfully shown to improve gut microbial diversity, fermented foods offer a promising alternative. In this open-label phase I safety and feasibility study, we examined the safety and feasibility of kefir as an initial step towards utilizing fermented foods to mitigate gut dysbiosis in critically ill patients. METHODS: We administered kefir in escalating doses (60 mL, followed by 120 mL after 12 h, then 240 mL daily) to 54 critically ill patients with an intact gastrointestinal tract. To evaluate kefir's safety, we monitored for gastrointestinal symptoms. Feasibility was determined by whether patients received a minimum of 75% of their assigned kefir doses. To assess changes in the gut microbiome composition following kefir administration, we collected two stool samples from 13 patients: one within 72 h of admission to the ICU and another at least 72 h after the first stool sample. RESULTS: After administering kefir, none of the 54 critically ill patients exhibited signs of kefir-related bacteremia. No side effects like bloating, vomiting, or aspiration were noted, except for diarrhea in two patients concurrently on laxatives. Out of the 393 kefir doses prescribed for all participants, 359 (91%) were successfully administered. We were able to collect an initial stool sample from 29 (54%) patients and a follow-up sample from 13 (24%) patients. Analysis of the 26 paired samples revealed no increase in gut microbial α-diversity between the two timepoints. However, there was a significant improvement in the Gut Microbiome Wellness Index (GMWI) by the second timepoint (P = 0.034, one-sided Wilcoxon signed-rank test); this finding supports our hypothesis that kefir administration can improve gut health in critically ill patients. Additionally, the known microbial species in kefir were found to exhibit varying levels of engraftment in patients' guts. CONCLUSIONS: Providing kefir to critically ill individuals is safe and feasible. Our findings warrant a larger evaluation of kefir's safety, tolerability, and impact on gut microbiome dysbiosis in patients admitted to the ICU. TRIAL REGISTRATION: NCT05416814; trial registered on June 13, 2022.

GMWI-webtool: a user-friendly browser application for assessing health through metagenomic gut microbiome profiling.

SUMMARY: We recently introduced the Gut Microbiome Wellness Index (GMWI), a stool metagenome-based indicator for assessing health by determining the likelihood of disease given the state of one's gut microbiome. The calculation of our wellness index depends on the relative abundances of health-prevalent and health-scarce species. Encouragingly, GMWI has already been utilized in various studies focusing on differences in the gut microbiome between cases and controls. Herein, we introduce the GMWI-webtool, a user-friendly browser application that computes GMWI, health-prevalent/-scarce species' relative abundances, and α-diversities from stool shotgun metagenome taxonomic profiles. Users of our interactive online tool can visualize their results and compare them side-by-side with those from our pooled reference dataset of metagenomes, as well as export data in.csv format and high-resolution figures. AVAILABILITY AND IMPLEMENTATION: GMWI-webtool is freely available here: https://gmwi-webtool.github.io/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Effect of endogenous hormones, antisperm antibody and oxidative stress on semen quality of crossbred bulls.

The present study was designed to evaluate the effect of factors like hormones, antisperm antibody (ASA), and oxidative stress and its relation with semen quality in crossbred bulls. Ejaculates from two bulls were categorized into good (n = 12) and poor (n = 12) based on initial progressive motility, that is, ≥70% and ≤50%, respectively. The level of hormones like Testosterone (p < 0.05) and PGE2 (p < 0.01) was significantly higher in good-quality ejaculates compared to poor-quality ejaculates; however, estradiol (p < 0.05), progesterone, oxidative stress, and ASAs were significantly higher (p < 0.01) in poor-quality ejaculates compared to good-quality ejaculates. Therefore, it could be concluded that oxidative stress and hormonal imbalance might have resulted in high number of dead and defective spermatozoa which was ultimately responsible for poor quality semen ejaculates.

Heavy metals controlling cardiovascular diseases risk factors in myocardial infarction patients in critically environmentally heavy metal-polluted steel industrial town Mandi-Gobindgarh (India).

Heavy metals (HMs) have a very significant clinical role in the pathogenesis, progression and management of cardiovascular diseases (CVDs). The prevalence of CVDs was reported to be higher in critically environmentally HM-polluted (EHMP) steel industrial town Mandi-Gobindgarh (India) for the last more than a decade. To ascertain the role of HMs in the onset of CVDs, the present study was chosen to investigate HMs content in myocardial infarction (MI) patients from EHMP steel industrial town Mandi-Gobindgarh. Total of 110 MI patients along with number- and age-matched healthy volunteers were recruited in the present investigation. The CVDs risk factors estimated in MI patients were overweight (higher body mass index), hypertension (higher systolic and diastolic blood pressures), dyslipidaemia (higher serum cholesterol, triglycerides and lower HDL cholesterol), inflammation (higher-serum C reactive protein and aldosterone) and elevated oxidative stress (higher urinary 8-hydroxydeoxyguanosine). An imbalance of serum electrolyte concentrations including Na (hypernatremia), Ca (hypercalcaemia) and K (hypokalaemia) was also observed in MI patients in which CVDs risk factors were found to correlate positively with serum Na and Ca and negatively with serum K, respectively. Hair HM analysis was used as a bio-indicator for monitoring body HM status from past environmental HM exposure in which CVDs risk factors were observed to correlate positively with higher hair concentrations of Zn, Fe, Mo, Pb, As, Ca and Na and negatively with lower hair concentrations of Cu, Mg, Mn and K in MI patients, respectively. Thus, higher hair concentrations of Zn and Pb indicate their higher environmental exposure and possible cause of higher CVDs risk factors in MI patients from Mandi-Gobindgarh.

Porcine scabies induces marked apoptosis, increased pro-inflammatory cytokines IL-1, TNF-α and shedding of ICAM-1.

BACKGROUND: Scabies is one of the leading causes of morbidity in pigs worldwide. Limited data are available regarding the role of immune reactions in the development of porcine scabies. MATERIALS AND METHODS: The aim of this study was to investigate key pro-inflammatory cytokines (IL-1, TNF-α), soluble variant of adhesion molecule ICAM-1 and mite-mediated apoptosis of peripheral leukocytes in 20 pigs with scabies, in addition to 10 healthy controls. The pigs with at least three typical clinical signs and found positive for Sarcoptes scabiei var. suis in microscopy were recruited for the present study. RESULTS: IL-1 acted as the major pro-inflammatory cytokine as serum IL-1 concentrations showed significantly (p < .05) higher levels (7-fold increase) in cases than in controls. The minor cytokine TNF-α was 4-fold higher during scabies, and its mean serum concentration was significantly increased (p < .05) in cases when compared to healthy controls. Soluble ICAM-1 levels were significantly higher (p < .05) in all the pigs of infested group compared with the controls. The percentage of apoptotic and necrotic leukocytes was found to be significantly higher (p < .05) in scabies positive pigs as compared to the healthy controls. CONCLUSION: It is concluded that systemic elevation in pro-inflammatory cytokines IL-1 and TNF-α, shedding of soluble ICAM-1 variant in peripheral blood and increased rate of host-cell apoptosis in peripheral leukocytes might be implicated in the immunopathology of naturally acquired porcine scabies.

Interpreting HbA1c in Presence of Deficiency Anemias.

HbA1c is used extensively for the diagnosis and management of diabetes mellitus. It constitutes 80% of glycated HbA1(Glycated haemoglobin(GHb)A), and depends upon blood glucose and RBC life span. RBC life span varies with anemia, leading to a consequent alteration in the HbA1c value irrespective of the circulating blood glucose concentration. But to the best of our knowledge no Hb cut offs have been derived for appropriate interpretation of HbA1c. The prevalence of anemia in Indian population is nearly 40% as per its definition by WHO-Hb < 12 g/dL in females and < 13 g/dL in males-with most cases attributable to nutritional deficiencies. Hence, we aimed to identify Hb cut-off for accurate interpretation of HbA1c in presence of deficiency anemias. Partial correlation between random blood glucose (RBG) and HbA1c was studied in 1312 subjects, 470 of whom had deficiency-related anemia]. The data was adjusted for age, sex and Hb. Partial correlation between RBG and HbA1c was highly significant (p < 0.0001) till Hb of 8.1 gm/dL. Significance reduced to p = 0.003 and p = 0.006 as the cut off of Hb reduced to 7.1 gm/dL and 5.0 gm/dL, respectively, but was not lost. Hence, caution in interpretation of HbA1c is not required till an Hb of 5 g/dL.

Mutation update: Variants of the CYB5R3 gene in recessive congenital methemoglobinemia.

NADH-cytochrome b5 reductase 3 deficiency is an important genetic cause of recessive congenital methemoglobinemia (RCM) and occurs worldwide in autosomal recessive inheritance. In this Mutation Update, we provide a comprehensive review of all the pathogenic mutations and their molecular pathology in RCM along with the molecular basis of RCM in 21 new patients from the Indian population, including four novel variants: c.103A>C (p.Thr35Pro), c.190C>G (p.Leu64Val), c.310G>T (p.Gly104Cys), and c.352C>T (p.His118Tyr). In this update, over 78 different variants have been described for RCM globally. Molecular modeling of all the variants reported in CYB5R3 justifies association with the varying severity of the disease. The majority of the mutations associated with the severe form with a neurological disorder (RCM Type 2) were associated with the FAD-binding domain of the protein while the rest were located in another domain of the protein (RCM Type 1).

G6PD A- is the major cause of G6PD deficiency among the Siddis of Karnataka, India.

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human erythroenzymopathy affecting more than 400 million people worldwide. G6PD deficiency was reported in India more than 50 years ago and the prevalence rate varies from 5.7% to 27.9% in different caste and tribal groups.Aim: To study the prevalence of, and the mutations causing, G6PD deficiency among the Siddis of Karnataka.Subjects and methods: A total of 755 individuals were screened using the DPIP dye decolorisation method and the deficiency was further confirmed by quantitative assay. Molecular characterisation was performed by PCR-RFLP method and DNA sequencing. Biochemical characterisation was performed as per WHO criteria.Results: Of the 755 individuals, 71 individuals (9.4%) were found to be G6PD deficient with an enzyme activity ranging from 0.02 to 3.83 IU/gm Hb. Mutational analysis could be performed on 49 G6PD deficient individuals and 45 (91.8%) of them showed the presence of the G6PD A- variant while the remaining 4 (8.2%) had the G6PD Kerala-Kalyan mutation. Microsatellite analysis in G6PD A- individuals showed the presence of 166/195 bp, AC/CTT alleles.Conclusions: G6PD deficiencies among the Siddis are predominantly due to G6PD A- mutation. Furthermore, biochemical parameters and the microsatellite repeat markers in the Siddi A- chromosome confirmed they are African descendants with Indian admixture.

Adsorption of heavy metals on conventional and nanostructured materials for wastewater treatment purposes: A review.

The problem of water pollution is of a great concern. Adsorption is one of the most efficient techniques for removing noxious heavy metals from the solvent phase. This paper presents a detailed information and review on the adsorption of noxious heavy metal ions from wastewater effluents using various adsorbents - i.e., conventional (activated carbons, zeolites, clays, biosorbents, and industrial by-products) and nanostructured (fullerenes, carbon nanotubes, graphenes). In addition to this, the efficiency of developed materials for adsorption of the heavy metals is discussed in detail along with the comparison of their maximum adsorption capacity in tabular form. A special focus is made on the perspectives of further wider applications of nanostructured adsorbents (especially, carbon nanotubes and graphenes) in wastewater treatment.

Fabrication of a Food Nano-Platform Sensor for Determination of Vanillin in Food Samples.

Herein, we describe the fabrication of NiO decorated single wall carbon nanotubes (NiO-SWCNTs) nanocomposites using the precipitation method. The synthesized NiO-SWCNTs nanocomposites were characterized by X-ray diffraction (XRD) and Transmission electron microscopy (TEM). Remarkably, NiO-SWCNTs and 1-butylpyridinium hexafluorophosphate modified carbon paste electrode (CPE/NiO-SWCNTs/BPrPF6) were employed for the electrochemical detection of vanillin. The vanillin sensor showed an ultra-high sensitivity of 0.3594 µA/µM and a low detection limit of 0.007 µM. In the final step, the NiO-SWCNTs/BPrPF6 was used as the suitable tool for food analysis.

Bone-specific alkaline phosphatase - a potential biomarker for skeletal growth assessment.

OBJECTIVE: The present study was aimed to assess levels of serum Bone-specific alkaline phosphatase (BALP) and serum Insulin-like growth factor-1 (IGF-1) and comparing with cervical vertebral maturation index (CVMI) stages. DESIGN: Cross-sectional study. SETTING: Maulana Azad Institute of Dental Sciences, New Delhi, India. PARTICIPANTS: 150 subjects (75 males and 75 females) in the age group of 8-20 years. METHODS: Subjects were divided into six CVMI stages. Enzyme-linked immunosorbant assay was performed for the estimation of serum BALP and serum IGF-1 levels. Mann-Whitney U test was performed to compare mean ranks of serum BALP and serum IGF-1 with different CVMI stages. Spearman correlation between serum BALP and serum IGF-1 was done across 6 CVMI stages. RESULTS: Peak serum IGF-1 levels were found at CVMI stages 4 and 3 for males and females respectively. Peak levels for serum BALP were found at stage 3 for both genders with significant differences from other stages. A statistically significant correlation was seen between serum IGF-1 and serum BALP from CVMI stages 1 to 3 and 4 to 6 (p < .01). CONCLUSIONS: BALP showed promising results and can be employed as a potential biomarker for the estimation of growth status.

Aggregation-induced enhanced green light emission from a simple donor-π-acceptor (D-π-A) material: a structure-property relationship study.

Organic D-π-A materials, possessing intramolecular charge transfer, have attracted much scientific attention in recent years because of their potential applications in the development of organic light emitting devices (OLEDs). Two new compounds, A1 and A2, having a D-π-A skeleton have been synthesized and single crystals were grown by the solution growth technique. Both compounds were characterized for crystallographic, thermal and photophysical properties. Upon photo-excitation in the solid state, A1 showed very strong green light emission while A2 gave sky-blue emission with much lower intensity. A single crystal X-ray diffraction study revealed that in the crystal lattice of A1, both the donor and acceptor groups are involved in the intermolecular interactions. This results in the restricted intramolecular rotation (RIR) of the D and A moieties, and enables A1 to emit more intensely in the solid state due to aggregation-induced emission (AIE). Intense green light emission, along with a good crystalline nature indicates that A1 might be a potential candidate for opto-electronic devices.

Evaluation of 75 g glucose load in non-fasting state [Diabetes in Pregnancy Study group of India (DIPSI) criteria] as a diagnostic test for gestational diabetes mellitus.

BACKGROUND & OBJECTIVES: There is no consensus regarding optimal standard for diagnosis of gestational diabetes mellitus (GDM). In this study, use of 75 g glucose load in non-fasting state [Diabetes in Pregnancy Study Group of India (DIPSI) criteria] as a diagnostic test for GDM in pregnant women was compared with different oral glucose tolerance tests (OGTTs). METHODS: This prospective study included 936 pregnant women, who underwent plasma glucose evaluation two hours after the challenge of 75 g glucose load irrespective of the timing of last meal (DIPSI criteria for GDM). After three days, standard 75 g OGTT was done in all women irrespective of previous plasma glucose value. Accuracy of the first result was compared to OGTT using cut-offs as per the World Health Organization (WHO) and International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria for the diagnosis of GDM. RESULTS: Of the total 936 pregnant women, 73 (7.8%) patients had plasma glucose value ≥140 mg/dl when measured two hours after glucose load. When comparing with the WHO and IADPSG criteria, the sensitivity values were 65.1 and 74.1 per cent, respectively, and the corresponding specificity values were 96.3 and 96.9 per cent, respectively. On comparing with the WHO OGTT, only 41 of the 73 (56.2%) were true positives, whereas when IADPSG criteria were used, true positives were 46 (63%). False negative cases were also present when classified by the WHO and IADPSG criteria though in lesser numbers than false positives. The positive predictive values (PPVs) for the WHO and IADPSG criteria were 56.1 and 63 per cent, respectively, and their corresponding negative predictive values were 97.7 and 97.9 per cent, respectively. INTERPRETATION & CONCLUSIONS: Our findings showed that when 75 g glucose load in non-fasting state was used as a diagnostic test for GDM, almost one quarter of patients with GDM escaped diagnosis as sensitivity values were low. On the other hand, some GDM cases were falsely labelled as normal as this test did not account for cases of fasting hyperglycaemia. In addition, comparison with other OGTTs showed low PPVs. Hence, use of DIPSI criteria for diagnosing GDM must be reconsidered till further validation.

Pre-concentration of trace amount of bisphenol A in water samples by palm leaf ash and determination with high-performance liquid chromatography.

Palm leaf ash was characterized and used as low-cost adsorbent for solid-phase extraction and preconcentration of bisphenol A (BPA) in real water samples. Analysis of BPA was carried out using HPLC involving Eurospher 100-5-C18 (25 cm × 4.5 mm, particle size 5 µm) column and water-acetonitrile (40:60, v/v) as mobile phase. The adsorption was achieved quantitatively at a pH of 6 with elution by 3 mL acetonitrile. The limits of detection and enrichment factor were 0.02 µg L(-1) and 333, respectively. Under optimum conditions the relative standard deviation (RSD) was 2% (n = 10). Comparison of qualification criteria of presented preconcentration procedure with other research indicated that palm leaf ash adsorbent was better than many of the adsorbents in terms of cost and reusability. Also, the limit of detection, precision and enrichment factor were comparable and even better than the previously reported methods. Finally, the efficiency of method was computed by determination of trace amounts of BPA in sea, river, mineral and tap waters with recoveries of 93.3-105.5% and RSDs of 0.61-3.12%.. Briefly, the developed solid-phase extraction and Preparative layer chromatography (PLC) methods may be used for bisphenol A monitoring in any environmental water sample. Copyright © 2016 John Wiley & Sons, Ltd.

A Fast Strategy for Determination of Vitamin B9 in Food and Pharmaceutical Samples Using an Ionic Liquid-Modified Nanostructure Voltammetric Sensor.

Vitamin B9 or folic acid is an important food supplement with wide clinical applications. Due to its importance and its side effects in pregnant women, fast determination of this vitamin is very important. In this study we present a new fast and sensitive voltammetric sensor for the analysis of trace levels of vitamin B9 using a carbon paste electrode (CPE) modified with 1,3-dipropylimidazolium bromide (1,3-DIBr) as a binder and ZnO/CNTs nanocomposite as a mediator. The electro-oxidation signal of vitamin B9 at the surface of the 1,3-DIBr/ZnO/CNTs/CPE electrode appeared at 800 mV, which was about 95 mV less positive compared to the corresponding unmodified CPE. The oxidation current of vitamin B9 by square wave voltammetry (SWV) increased linearly with its concentration in the range of 0.08-650 µM. The detection limit for vitamin B9 was 0.05 µM. Finally, the utility of the new 1,3-DIBr/ZnO/CNTs/CPE electrode was tested in the determination of vitamin B9 in food and pharmaceutical samples.

Divergences in gene repertoire among the reference Prevotella genomes derived from distinct body sites of human.

BACKGROUND: The community composition of the human microbiome is known to vary at distinct anatomical niches. But little is known about the nature of variations, if any, at the genome/sub-genome levels of a specific microbial community across different niches. The present report aims to explore, as a case study, the variations in gene repertoire of 28 Prevotella reference genomes derived from different body-sites of human, as reported earlier by the Human Microbiome Consortium. RESULTS: The pan-genome for Prevotella remains "open". On an average, 17% of predicted protein-coding genes of any particular Prevotella genome represent the conserved core genes, while the remaining 83% contribute to the flexible and singletons. The study reveals exclusive presence of 11798, 3673, 3348 and 934 gene families and exclusive absence of 17, 221, 115 and 645 gene families in Prevotella genomes derived from human oral cavity, gastro-intestinal tracts (GIT), urogenital tract (UGT) and skin, respectively. Distribution of various functional COG categories differs significantly among the habitat-specific genes. No niche-specific variations could be observed in distribution of KEGG pathways. CONCLUSIONS: Prevotella genomes derived from different body sites differ appreciably in gene repertoire, suggesting that these microbiome components might have developed distinct genetic strategies for niche adaptation within the host. Each individual microbe might also have a component of its own genetic machinery for host adaptation, as appeared from the huge number of singletons.

Highly sensitive and selective colorimetric and off-on fluorescent reversible chemosensors for Al³âº based on the rhodamine fluorophore.

A series of rhodamine derivatives L1-L3 have been prepared and characterized by IR, 1H-NMR, 13C-NMR and ESI-MS. These compounds exhibited selective and sensitive "turn-on" fluorescent and colorimetric responses to Al3+ in methanol. Upon the addition of Al(III), the spiro ring was opened and a metal-probe complex was formed in a 1:1 stoichiometry, as was further confirmed by ESI-MS spectroscopy. The chemo-dosimeters L1-L3 exhibited good binding constants and low detection limits towards Al(III). We also successfully demonstrate the reversibility of the metal to ligand complexation (opened ring to spirolactam ring).

Emergence of photoautotrophic minimal protocell-like supramolecular assemblies, "Jeewanu" synthesied photo chemically in an irradiated sterilised aqueous mixture of some inorganic and organic substances.

Sunlight exposed sterilised aqueous mixture of ammonium molybdate, diammonium hydrogen phosphate, biological minerals and formaldehyde showed photochemical formation of self-sustaining biomimetic protocell-like supramolecular assemblies "Jeewanu" (Bahadur and Ranganayaki J Brit Interplanet Soc 23:813-829 1970). The structural and functional characteristics of Jeewanu suggests that in possible prebiotic atmosphere photosy nergistic collaboration of non-linear processes at mesoscopic level established autocatalytic pathways on mineral surfaces by selforganisation and self recognition and led to emergence of similar earliest energy transducing supramolecular assemblies which might have given rise to common universal ancestor on the earth or elsewhere.

Cerebrospinal fluid proteomic signatures are associated with symptom severity of first-episode psychosis.

Apart from their diagnostic, monitoring, or prognostic utility in clinical settings, molecular biomarkers may be instrumental in understanding the pathophysiology of psychiatric disorders, including schizophrenia. Using untargeted metabolomics, we recently identified eight cerebrospinal fluid (CSF) metabolites unique to first-episode psychosis (FEP) subjects compared to healthy controls (HC). In this study, we sought to investigate the CSF proteomic signatures associated with FEP. We employed 16-plex tandem mass tag (TMT) mass spectrometry (MS) to examine the relative protein abundance in CSF samples of 15 individuals diagnosed with FEP and 15 age-and-sex-matched healthy controls (HC). Multiple linear regression model (MLRM) identified 16 differentially abundant CSF proteins between FEP and HC at p < 0.01. Among them, the two most significant CSF proteins were collagen alpha-2 (IV) chain (COL4A2: standard mean difference [SMD] = -1.12, p = 1.64 × 10-4) and neuron-derived neurotrophic factor (NDNF: SMD = -1.03, p = 4.52 × 10-4) both of which were down-regulated in FEP subjects compared to HC. We also identified several potential CSF proteins associated with the pathophysiology and the symptom profile and severity in FEP subjects, including COL4A2, NDNF, hornerin (HRNR), contactin-6 (CNTN6), voltage-dependent calcium channel subunit alpha-2/delta-3 (CACNA2D3), tropomyosin alpha-3 chain (TPM3 and TPM4). Moreover, several protein signatures were associated with cognitive performance. Although the results need replication, our exploratory study suggests that CSF protein signatures can be used to increase the understanding of the pathophysiology of psychosis.