Multi-omics analysis identifies potential microbial and metabolite diagnostic biomarkers of bacterial vaginosis.

BACKGROUND: Bacterial vaginosis (BV) is a common clinical manifestation of a perturbed vaginal ecology associated with adverse sexual and reproductive health outcomes if left untreated. The existing diagnostic modalities are either cumbersome or require skilled expertise, warranting alternate tests. Application of machine-learning tools to heterogeneous and high-dimensional multi-omics datasets finds promising potential in data integration and may aid biomarker discovery. OBJECTIVES: The present study aimed to evaluate the potential of the microbiome and metabolome-derived biomarkers in BV diagnosis. Interpretable machine-learning algorithms were used to evaluate the utility of an integrated-omics-derived classification model. METHODS: Vaginal samples obtained from reproductive-age group women with (n = 40) and without BV (n = 40) were subjected to 16S rRNA amplicon sequencing and LC-MS-based metabolomics. The vaginal microbiome and metabolome were characterized, and machine-learning analysis was performed to build a classification model using biomarkers with the highest diagnostic accuracy. RESULTS: Microbiome-based diagnostic model exhibited a ROC-AUC (10-fold CV) of 0.84 ± 0.21 and accuracy of 0.79 ± 0.18, and important features were Aerococcus spp., Mycoplasma hominis, Sneathia spp., Lactobacillus spp., Prevotella spp., Gardnerella spp. and Fannyhessea vaginae. The metabolome-derived model displayed superior performance with a ROC-AUC of 0.97 ± 0.07 and an accuracy of 0.92 ± 0.08. Beta-leucine, methylimidazole acetaldehyde, dimethylethanolamine, L-arginine and beta cortol were among key predictive metabolites for BV. A predictive model combining both microbial and metabolite features exhibited a high ROC-AUC of 0.97 ± 0.07 and accuracy of 0.94 ± 0.08 with diagnostic performance only slightly superior to the metabolite-based model. CONCLUSION: Application of machine-learning tools to multi-omics datasets aid biomarker discovery with high predictive performance. Metabolome-derived classification models were observed to have superior diagnostic performance in predicting BV than microbiome-based biomarkers.

Dynamic release of gentamicin sulfate (GS) from alginate dialdehyde (AD)-crosslinked casein (CAS) films for antimicrobial applications.

In the present work, antibiotic drug gentamicin sulfate (GS) has been loaded into alginate dialdehyde-crosslinked casein (CAS) films for wound dressing applications. The films have been characterized by Fourier transform infrared spectroscopy, X-ray diffraction analysis and scanning electron microscopy. The dynamic release of model drug GS has been investigated in the physiological fluid at 37 °C. The drug release data has been interpreted in the terms of various kinetic models such as Power function model, first order model and Schott model. The release data was found to be well fitted by Schott model. The various diffusion coefficients are also evaluated. The adsorption of model therapeutic protein BSA on the film has been investigated. The maximum adsorption is found to be 5.7 mg/cm2.The films were tested for their antibacterial and anti-fungal action. Finally, the in vivo wound healing study was carried out on Albino wistar rats.

Study of prognostic significance of antenatal ultrasonography and renin angiotensin system activation in predicting disease severity in posterior urethral valves.

AIMS: Study on prognostic significance of antenatal ultrasonography and renin angiotensin system activation in predicting disease severity in posterior urethral valves. MATERIALS AND METHODS: Antenatally diagnosed hydronephrosis patients were included. Postnatally, they were divided into two groups, posterior urethral valve (PUV) and non-PUV. The studied parameters were: Gestational age at detection, surgical intervention, ultrasound findings, cord blood and follow up plasma renin activity (PRA) values, vesico-ureteric reflux (VUR), renal scars, and glomerular filtration rate (GFR). RESULTS: A total of 25 patients were included, 10 PUV and 15 non-PUV. All infants with PUV underwent primary valve incision. GFR was less than 60 ml/min/1.73 m(2) body surface area in 4 patients at last follow-up. Keyhole sign, oligoamnios, absent bladder cycling, and cortical cysts were not consistent findings on antenatal ultrasound in PUV. Cord blood PRA was significantly higher (P < 0.0001) in PUV compared to non-PUV patients. Gestational age at detection of hydronephrosis, cortical cysts, bladder wall thickness, and amniotic fluid index were not significantly correlated with GFR while PRA could differentiate between poor and better prognosis cases with PUV. CONCLUSIONS: Ultrasound was neither uniformly useful in diagnosing PUV antenatally, nor differentiating it from cases with non-PUV hydronephrosis. In congenital hydronephrosis, cord blood PRA was significantly higher in cases with PUV compared to non-PUV cases and fell significantly after valve ablation. Cord blood PRA could distinguish between poor and better prognosis cases with PUV.

Psychological assessment and lived experiences of recovered COVID-19 patients who presented for convalescent plasma donation.

BACKGROUND: Increasingly, it has been seen that patients recovering from COVID-19 may face a second battle of coping with its mental health ramifications. These psychological issues can even be experienced by patients who were asymptomatic or had mild to moderate symptoms, potentially impacting their quality of life. METHODOLOGY: This was a prospective observational study to analyse the psychological impact of COVID-19 in recovered patients who presented as prospective convalescent plasma (CP) donors. An interview for the psychological assessment of the prospective donors was carried out. Depression and anxiety in the participants were assessed by HAM-A, and HAM-D scores and Quality of Life were assessed using the WHOQOL-BREF scale. RESULTS: A total of 51 prospective donors were assessed, with a mean age of 34.37 (±9.08) years, with the majority being males (46). No clinically significant depression and anxiety were found on the basis of HAM-D and HAM-A scores. The worst affected quality of life parameter, based on the WHOQOL-BREF scale, was physical quality of life followed by environmental, psychological, and social relationships. Moreover, due to infection, social stigma was experienced by 49.02% of the donors, while 21.97% had anxiety related to convalescent plasma donation as a common livid experience. CONCLUSION: Poor quality of life and social stigma during the recovery phase is prevalent in COVID-19 recovered patients, for which formulation of holistic support strategies are the need of the hour.

Patients with inflammatory bowel disease may have a transforming growth factor-beta-, interleukin (IL)-2- or IL-10-deficient state induced by intrinsic neutralizing antibodies.

Ulcerative colitis (UC) and Crohn's disease (CD) are considered to be immunologically mediated disorders that share certain features with murine models of colitis. Whether any of these models are physiologically relevant to the human condition remains controversial. The hypothesis is that increased amounts of antibodies neutralizing transforming growth factor (TGF)-beta, interleukin (IL)-2 or IL-10 create a relative immunodeficient state in inflammatory bowel disease (IBD) that predisposes to disease. To evaluate this, serum samples from patients with UC or CD and from normal healthy individuals were studied by enzyme-linked immunosorbent assays. Antibodies recognizing TGF-beta were most prevalent in UC (P<0.01); anti-IL-10 antibodies were elevated in CD (P<0.05), while anti-IL-2 antibodies were the same for all three groups. Importantly, the percentage of IBD patients with at least one of the antibody levels greater than any control value was 30% for UC and 33% for CD. To verify the presence of these antibodies, immobilized TGF-beta was exposed to UC sera and the attached proteins identified by Western blot assay. The proteins proved to be exclusively immunoglobulin (Ig) G. To evaluate the neutralizing activity of these antibodies, cytokine-specific IgG from subjects in each group of patients was incubated with TGF-beta, IL-2 or IL-10 before addition to a bioassay with changes in viability determined by a colorimetric analysis. Antibodies from most individuals in all three groups neutralized the action of each cytokine. This study shows that about one-third of IBD patients may have a relative deficiency of TGF-beta, IL-2 or IL-10 due to an increase in neutralizing antibodies in their sera.

Magnetic nanoparticles for drug delivery applications.

In recent past magnetic nanoparticles have been explored for a number of biomedical applications due to their superparamagnetic moment with high magnetic saturation value. For these biomedical applications, magnetic nanoparticles require being monodispersed so that the individual nanoparticle has almost identical physico-chemical properties for biodistribution, bioelimination and contrast imaging potential. Further, the surface functionalization/modification of magnetic nanoparticles ultimately facilitate the protein or DNA separation, detection and magnetic resonance imaging contrast, drug delivery and hyperthermia applications. The essential goal of this review is to evaluate the recent advances of magnetic nanoparticles for tumor, brain targeting and hyperthermia applications.

Circadian rhythm of peak expiratory flow rate in healthy north Indian men.

Peak expiratory flow rate (PEFR) variability follows a specific pattern in asthmatics as well as in healthy individuals. There is scarcity of data for Indian healthy subjects. The PEFR (L/min.) was measured with Wright's portable peak flow meter at 05:00, 8:00, 11:00, 14:00, 17:00, 20:00 and 23:00 hours in 42 healthy, non-smoking adults of age group between 18-26 years. The variability of PEFR revealed a circadian pattern. PEFR levels tend to increase from morning at 5:00 hours till evening at 17:00 hours, with peak PEFR in evening at 17:00 hours, after which there was a progressive fall in PEFR levels, till morning 5:00 hours. This study provides the preliminary reference data of circadian pattern of PEFR in healthy individuals.

Synthesis of polymer stabilized silver and gold nanostructures.

This review article is focused on the various approaches that have been made to synthesize metal nanoparticles with predetermined shape, size, and fair stability. Due emphasis has been given on polymer stabilized nanoparticles. In addition use of other varieties of stabilizers like inorganic salts, organic compounds, organic solvent, biological molecules, etc. have also been discussed. Finally, formation of two and three-dimensional nanostructures like nanowires, nanodiscs, nanoprisms has also been revealed.

Nano cellulose dispersed chitosan film with Ag NPs/Curcumin: An in vivo study on Albino Rats for wound dressing.

With an aim to develop chitosan film with controllable swelling behavior and maximum antimicrobial efficacy, we hereby report cellulose nano crystals loaded chitosan films with Curcumin/Ag nano particles embedded as strong antimicrobial agents. The CNC had average size of 40-90nm with poly dispersity index of 3.641. The TEM analysis of Ag NPs, produced via DMF reduction, revealed a particle size range of 15-25nm. The Surface Plasmon resonance (SPR) of these Ag NPs shifted from 380 to 440nm, with the increase in concentration of Ag (I). The TGA of the film samples Ch/CNC, and Ch/CNC (Ag463/Cur450) exhibited% weight loss of around 95 and 80 respectively, thus indicating higher stability due to presence of Ag NPs. In XRD analysis 2θ reflections at 38.12, 44.28 and 66.46°, confirmed the presence planes (1 1), (2 0) and (2 0) respectively. In skin irritation test, the mean Erythema scores observed after 72h was zero for both the Curcumin and Ag NPs/Curcumin loaded films. The percent wound reduction, observed for the film samples Ch/CNC (Cur450) and Ch/CNC (Ag NP463/Cur450) was 57.8 and 97.2 respectively, indicating better suitability of Ag NPs/Curcumin loaded film.

Controlled release of Doxycycline from gum acacia/poly(sodium acrylate) microparticles for oral drug delivery.

In the present work, Doxycycline loaded gum acacia (GA)/poly(sodium acrylate) (SA) hydrogels were prepared for the oral drug delivery of model drug Doxycycline. The hydrogels were characterized by X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy (FTIR) scanning electron microscopy (SEM) and Zeta potential. The dynamic release of Doxycycline was investigated in the physiological fluids at 37°C. Various kinetic models such as Power function model, Schott model and Higuchi model were applied to interpret the release data. Schott model was found to be most fitted. The Doxycycline loaded hydrogels were tested for their antibacterial action against E. coli.

Synthesis of nanosilver loaded chitosan/poly(acrylamide-co-itaconic acid) based inter-polyelectrolyte complex films for antimicrobial applications.

In the present work, AgNPs loaded chitosan/poly(acrylamide-co-itaconic acid) inter-polyelectrolyte complex (IPC) films have been prepared for antimicrobial applications. The AgNPs-loaded IPC films have been characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), Scanning electron microscopy (SEM), Thermogravimetric analysis (TGA) and Surface plasmon resonance (SPR). Particle size of synthesized AgNPs was found to be in the range 10-30nm. These films exhibited a remarkable antibacterial property against strong pathogen E.Coli, thus offering their candidature for antimicrobial applications.

Water absorption and moisture permeation properties of chitosan/poly(acrylamide-co-itaconic acid) IPC films.

In this work, aqueous solutions of chitosan (Ch) and [poly(acrylamide(AAm)-co-itaconicacid(IA)] have been mixed to yield Ch/poly(AAm-co-IA) Inter-polyelectrolyte complex (IPC) films. The films were characterized by FTIR, X-ray diffraction (XRD) and thermo gravimetric analysis (TGA). There was remarkable increase in the crystalline nature of IPC films. The films were investigated for their water absorption capacity in the physiological fluid (PF) of pH 7.4 at 37 °C. The amount of IA present in the film forming solutions affected the water absorption behavior of the resulting films. The dynamic water uptake data were interpreted by various kinetic models. The effect of pH on the swelling ratio (SR) indicated that the films showed highest swelling in lower as well as higher pH media. The water vapor transmission rates (WVTR) were obtained in the range of 6000-6645 g/m(2)/day.

Double urethral obstruction in a neonate - a case report.

Posterior urethral valves are the most common cause of lower urinary tract obstruction in a male child, generally occurring as an isolated anomaly. Congenital anterior urethral diverticulum, although less common, can also cause urethral obstruction. We report a rare combination of the two anomalies in which the proximal, more severe anomaly prevented the initial expression of the other.

Technetium-99m-HMPAO SPECT cerebral blood flow study in children with craniosynostosis.

UNLABELLED: Premature closure of cranial sutures (primary craniosynostosis) in children leads to characteristic skull deformities and prevents the constricted brain from growing normally. Although the cause remains unknown, several etiological factors have been cited. Recently, hypovascularity has been reported as a possible cause of craniosynostosis. METHODS: In a prospective study regional cerebral blood flow studies were carried out with 99mTc-HMPAO SPECT in seven children with craniosynostoses. Five preoperative and six postoperative studies were conducted and the results correlated with radiological and surgical findings. RESULTS: Preoperative studies revealed regional hypovascularity in the underlying cerebral hemisphere, corresponding to the fused sutures. Postoperative studies revealed disappearance of these perfusion defects in most cases, indicating normalization of perfusion following surgical decompression. CONCLUSION: This study establishes the presence of cerebral hypovascularity in craniosynostoses and suggests that early surgery and release of craniostenosis is essential to achieve optimum perfusion and brain development.

Differential effects of hypothyroidism on Na-K-ATPase mRNA alpha isoforms in the developing rat brain.

In the developing rat cerebrum, the level of different isoforms of Na-K-ATPase mRNA increases significantly during the first three postnatal weeks, which represent the critical period of synaptogenesis and myelination-the two thyroid hormone-sensitive maturational events. To determine the possible functional relationship of these isoforms with maturational events in the developing brain and their mode of regulation by T3, we have examined the effect of hypothyroidism on the expression of the different alpha-isoforms (alpha 1, alpha 2, and alpha 3) of Na-K-ATPase mRNA covering the first 3 wk of postnatal development. Quantitation of these mRNAs from cerebra of 1-, 5-, 10-, 15-, and 20-d-old normal and hypothyroid rats by Northern blot analysis indicate that alpha 3 mRNA is not only predominantly expressed throughout this entire period of study but also represents the species which is most severely affected in the hypothyroid brain. The relative sensitivity for the expression of these mRNAs to T3 were alpha 3 > alpha 1 > alpha 2. These results, together with the report of predominant expression of the alpha 3 isoform in neuronal cells, suggest specific functional involvement of this isoform with the decisive maturational events in the rat brain. Kinetic studies on in vivo induction of Na-K-ATPase alpha-mRNAs by T3 in the 15-d-old hypothyroid rat shows clear stimulation of all the isoforms within 1 h of the administration of the optimal dose (200 micrograms T3/100 g body wt) suggesting a direct, possibly transcriptional effect of the hormone on the expression of these genes.

Changes in carbohydrate metabolism of testicular germ cells during meiosis in the rat.

A study was undertaken to estimate the activities of the key enzymes of glycolysis, the pentose phosphate pathway and the tricarboxylic acid (TCA) cycle in purified rat spermatocytes and spermatids, which have been shown to die in glucose-containing medium and require lactate/pyruvate for maintaining normal ATP concentrations. The aim was to elucidate the changes in the glycolytic and oxidative potential of germ cells undergoing meiosis. Pachytene spermatocytes and round spermatids from adult rat testis were purified to approximately 90% purity by trypsin digestion followed by a combination of centrifugal elutriation and Percoll density gradient centrifugation. After the purity and viability of these cells had been established, their contents of hexokinase, phosphofructokinase, lactate dehydrogenase (LDH) and LDH-X of glycolysis, glucose 6-phosphate dehydrogenase of the pentose phosphate pathway and citrate synthase, aconitase, malate dehydrogenase and 2-oxoglutarate dehydrogenase of the TCA cycle were estimated. These enzymes were also estimated in epididymal spermatozoa for comparison with the testicular germ cells. The results indicate greater activity of glycolytic and pentose phosphate pathway enzymes in spermatocytes than in spermatids, which exhibited greater activity of TCA cycle enzymes than the former. The difference in activity was statistically significant for most of the enzymes studied. In contrast, spermatozoa exhibited markedly greater activity of glycolytic enzymes and significantly lower activity of pentose phosphate pathway and TCA cycle enzymes than did the testicular germ cells. We conclude that the unusual dependence of spermatids exclusively on lactate may be due to their lower glycolytic potential, whereas spermatocytes with comparatively greater glycolytic activity have an intermediate dependence on lactate and are therefore able to utilise lactate, pyruvate, or both, while retaining a better ability to utilise glucose. Spermatozoa with the greatest glycolytic potential and the lowest TCA cycle activity appear to be 'programmed' to utilise exclusively glucose/fructose for energy.