Modified Kramer's versus Kramer's Method for Clinical Assessment of Jaundice in Term and Near-Term Neonates.

OBJECTIVES: To compare the performance of Modified Kramer's and Kramer's methods in terms of agreement with total serum bilirubin (TSB). METHODS: This cross-sectional study was done in Level-III neonatal unit in New Delhi. Visibly jaundiced neonates born at ≥35 wk of gestation were enrolled and examined by (i) conventional Kramer's, (ii) Modified Kramer's in artificial (MK-A) and (iii) natural daylight (MK-N), and finally sampled for estimation of TSB by point-of-care spectrophotometry. The primary outcomes were agreement of Kramer's and Modified Kramer's with TSB and accuracy in terms of proportion of bilirubin estimates lying within ±2 mg/dL of TSB; secondary outcome was agreement of MK-A and MK-N with TSB. RESULTS: A total of 144 neonates with median gestation of 37 wk and mean birth weight of 2788 g were enrolled. Bland Altman analysis between Kramer's and TSB yielded mean difference of 1.7 mg/dL, 95% limits of agreement (LOA) -3.1 to 6.6 mg/dL. For Modified Kramer's and TSB, mean difference was -0.02 mg/dL, 95% LOA -4.7 to 4.7 mg/dL under artificial light; 0.02 mg/dL, 95% LOA -4.2 to 4.2 mg/dL under natural daylight. MK-N had highest proportion of bilirubin estimates lying within ±2 mg/dL of TSB (68.7%) as compared to MK-A (59.7%) [OR, 1.77; 95% CI, 1.09 to 2.86] and Kramer's (45.8%) [OR, 1.65; 95% CI, 1.27 to 2.15]. CONCLUSIONS: Though all the three methods had poor agreement with TSB, Modified Kramer's method when performed in natural light had reasonable accuracy, however limited clinical utility, in evaluation of clinical jaundice.

Need for Repeat-Hospitalization in Very Low Birth Weight or Very Preterm Infants: A Prospective Cohort Study.

OBJECTIVE: To determine the incidence of repeat-hospitalization amongst neonates with gestation <32 wk or birth weight <1500 g within 6 mo of birth. METHODS: All live births with gestation <32 wk or birth weight <1500 g born at a level-III NICU were prospectively enrolled and followed up through routine visits, multimedia and telephonically, fortnightly for re-hospitalization details till 6 mo of postnatal age. Main outcome measures were incidence, causes and risk factors for repeat-hospitalization. RESULTS: Of the 131 neonates enrolled, incidence and incidence density of repeat-hospitalization were 16% (95% CI 10.2-23.4) and 3.6 per 100 person-months, respectively. The most common causes for repeat-hospitalizations were pneumonia (n = 8; 29.6%), sepsis (n = 5, 18.5%), gastroenteritis (n = 3, 11.1%) and severe anemia (n = 2, 7.4%). Majority of repeat-hospitalizations (92.6%; 95% CI 74.1-98.5) occurred within 2 mo of discharge. The median hospital stay during repeat-hospitalizations was 4 d (IQR 1-21). On multivariate analysis, lower socioeconomic status was significantly associated with repeat-hospitalization (aOR 5.9, 1.3-23). Death after discharge occurred in 3 (2.3%) infants and were due to sudden infant death syndrome, complex cyanotic heart disease and pneumonia with multiple co-morbidities (one each). All deaths occurred at home. CONCLUSIONS: Nearly one-sixth of very low birth weight (VLBW) or very preterm infants required repeat-hospitalization after discharge, primarily within 2 mo of discharge. Infections, especially pneumonia, being the most common reason. A comprehensive follow-up package of post-discharge care for prevention of morbidities and timely hospital care for ongoing morbidities is required for optimal long-term survival of these infants.

Whole genome sequencing followed by functional analysis of genomic deletion encompassing ERCC8 and NDUFAF2 genes in a non-consanguineous Indian family reveals dysfunctional mitochondrial bioenergetics leading to infant mortality.

Genomic investigations on an infant who presented with a putative mitochondrial disorder led to identification of compound heterozygous deletion with an overlapping region of ∼142 kb encompassing two nuclear encoded genes namely ERCC8 and NDUFAF2. Investigations on fetal-derived fibroblast culture demonstrated impaired bioenergetics and mitochondrial dysfunction, which explains the phenotype and observed infant mortality in the present study. The genetic findings from this study extended the utility of whole-genome sequencing as it led to development of a MLPA-based assay for carrier screening in the extended family and the prenatal testing aiding in the birth of two healthy children.

Photo/electro catalytic green hydrogen production promoted by Ga modified Co0.6Cu0.4Fe2O4 nano catalysts.

The current work concentrates on the fabrication of Ga doped Co0.6Cu0.4Fe2O4 nanocatalysts via sol-gel auto-combustion (SGA) for the production of green and sustainable source of energy i.e., hydrogen through photocatalytic and electrocatalytic routes. Single-phased cubic crystal structure with Fd3m geometry was observed through XRD patterns. FESEM images show the aggregated and spherical shaped grains with distinct grain boundaries and average grain size of 1.04 and 1.39 µm for the Co0.6Cu0.4Fe2O4, and Co0.6Cu0.4Ga0.02Fe1.98O4 nanomaterials. Soft magnetic behaviour with a coercivity (Hc) and saturation magnetization (Ms) of 235.32-357.26 Oe and 54.65-61.11 emu/g was obtained for the produced nanomaterials. The estimation of photocatalytic nature for generating H2 was conducted using the sacrificial agents i.e., 0.128 M Na2S and 0.079 M Na2SO3. The analysis focused on measuring the maximum H2 generation was achieved by photocatalysts throughout three consecutive 4-h cycles. Out of all compositions, Co0.6Cu0.4Ga0.02Fe1.98O4 nanomaterial have the highest photocatalytic activity of 16.71 mmol gcat-1. However, the electrocatalytic behaviour of prepared Co0.6Cu0.4GaxFe2-xO4 (x = 0.00-0.03) electrocatalysts were determined for HER (Hydrogen evolution reaction) reaction. The overpotential values of Co0.6Cu0.4Fe2O4, Co0.6Cu0.4Ga0.01Fe1.99O4, Co0.6Cu0.4Ga0.02Fe1.98O4, and Co0.6Cu0.4Ga0.03Fe1.97O4 catalysts at 10 mA cm-2 were -0.81, -0.85, -1.03, and 1.21 V, correspondingly. Thus, at cathode current density of 10 mA/cm-2, an elevation in overpotential was noted, which indicates that the undoped Co0.6Cu0.4Fe2O4 (x = 0.00) electrocatalyst have remarkable electrocatalytic HER activity. Consequently, owing to photo/electro catalytic water splitting traits, the prepared catalysts are highly efficient for the green hydrogen generation.

ICF1-Syndrome-Associated DNMT3B Mutations Prevent De Novo Methylation at a Subset of Imprinted Loci during iPSC Reprogramming.

Parent-of-origin-dependent gene expression of a few hundred human genes is achieved by differential DNA methylation of both parental alleles. This imprinting is required for normal development, and defects in this process lead to human disease. Induced pluripotent stem cells (iPSCs) serve as a valuable tool for in vitro disease modeling. However, a wave of de novo DNA methylation during reprogramming of iPSCs affects DNA methylation, thus limiting their use. The DNA methyltransferase 3B (DNMT3B) gene is highly expressed in human iPSCs; however, whether the hypermethylation of imprinted loci depends on DNMT3B activity has been poorly investigated. To explore the role of DNMT3B in mediating de novo DNA methylation at imprinted DMRs, we utilized iPSCs generated from patients with immunodeficiency, centromeric instability, facial anomalies type I (ICF1) syndrome that harbor biallelic hypomorphic DNMT3B mutations. Using a whole-genome array-based approach, we observed a gain of methylation at several imprinted loci in control iPSCs but not in ICF1 iPSCs compared to their parental fibroblasts. Moreover, in corrected ICF1 iPSCs, which restore DNMT3B enzymatic activity, imprinted DMRs did not acquire control DNA methylation levels, in contrast to the majority of the hypomethylated CpGs in the genome that were rescued in the corrected iPSC clones. Overall, our study indicates that DNMT3B is responsible for de novo methylation of a subset of imprinted DMRs during iPSC reprogramming and suggests that imprinting is unstable during a specific time window of this process, after which the epigenetic state at these regions becomes resistant to perturbation.

Revolutionizing Tuberculosis Treatment: Uncovering New Drugs and Breakthrough Inhibitors to Combat Drug-Resistant Mycobacterium tuberculosis.

Tuberculosis (TB) is a global health threat that causes significant mortality. This review explores chemotherapeutics that target essential processes in Mycobacterium tuberculosis, such as DNA replication, protein synthesis, cell wall formation, energy metabolism, and proteolysis. We emphasize the need for new drugs to treat drug-resistant strains and shorten the treatment duration. Emerging targets and promising inhibitors were identified by examining the intricate biology of TB. This review provides an overview of recent developments in the search for anti-TB drugs with a focus on newly validated targets and inhibitors. We aimed to contribute to efforts to combat TB and improve therapeutic outcomes.

Feeding Outcomes in Preterm Neonates with Antenatal Abnormal Umbilical Artery Doppler Profile: A Retrospective Cohort Study.

Neonates with absent-or-reversed umbilical artery end-diastolic flow (AREDF) are at an increased risk of feeding problems. In this retrospective study, authors evaluated the incidence of feed intolerance in 213 preterm neonates (January 2017-May 2022) with AREDF. The median (IQR) gestation and birth weight were 32 (30, 33) wk and 1120 (840, 1425) g, respectively. Of 213 neonates, 103 (48.4%; 95% CI 41.5%, 55.3%) neonates developed feed intolerance. Twelve of 213 neonates developed any stage necrotizing enterocolitis (NEC) (5.6%; 95% CI 2.9%, 9.6%) at a median age of 10 d. On multivariate regression, gestation was the only independent predictor of feed intolerance (OR 1.48; 95% CI 1.28, 1.70; for every 1 wk decrease below 36 wk). Almost 50% of preterm neonates with AREDF develop feed intolerance. Alternative feeding strategies warrant exploration to optimise nutrition in these neonates.

Screening and molecular dynamics simulation of compounds inhibiting MurB enzyme of drug-resistant Mycobacterium tuberculosis: An in-silico approach.

Mycobacterium tuberculosis (MTB) is becoming more and more resistant to drugs and it is a common problem, making current antimicrobials ineffective and highlighting the need for new TB drugs. One of the promising targets for treating MTB is MurB enzymes. This study aimed to identify potential inhibitors of MurB enzymes in M. tuberculosis, as drug resistance among MTB is a significant problem. Attempts are being made to conduct a virtual screening of 30,417 compounds, and thirty-two compounds were chosen for further analysis based on their binding conformations. The selected compounds were assessed for their drug-likeness, pharmacokinetics, and physiochemical characteristics, and seven compounds with binding energy lower than flavin (FAD) were identified. Further, molecular dynamics simulation analysis of these seven compounds found that four of them, namely DB12983, DB15688, ZINC084726167, and ZINC254071113 formed stable complexes with the MurB binding site, exhibiting promising inhibitory activity. These compounds have not been mentioned in any other study, indicating their novelty. The study suggests that these four compounds could be promising candidates for treating MTB, but their effectiveness needs to be validated through in vitro and in vivo experiments. Overall, the findings of this study provide new insight into potential drug targets and candidates for combating drug-resistant MTB.

Catalytic Acceptorless Dehydrogenation (CAD) of Secondary Benzylic Alcohols into Value-Added Ketones Using Pd(II)-NHC Complexes.

For the creation of adaptable carbonyl compounds in organic synthesis, the oxidation of alcohols is a crucial step. As a sustainable alternative to the harmful traditional oxidation processes, transition-metal catalysts have recently attracted a lot of interest in acceptorless dehydrogenation reactions of alcohols. Here, using well-defined, air-stable palladium(II)-NHC catalysts (A-F), we demonstrate an effective method for the catalytic acceptorless dehydrogenation (CAD) reaction of secondary benzylic alcohols to produce the corresponding ketones and molecular hydrogen (H2). Catalytic acceptorless dehydrogenation (CAD) has been successfully used to convert a variety of alcohols, including electron-rich/electron-poor aromatic secondary alcohols, heteroaromatic secondary alcohols, and aliphatic cyclic alcohols, into their corresponding value-added ketones while only releasing molecular hydrogen as a byproduct.

Feasibility, Sustainability, and Effectiveness of the Implementation of "Facility-Team-Driven" Approach for Improving the Quality of Newborn Care in South India.

OBJECTIVES: The primary objective of the study was to assess the feasibility and sustainability of the implementation of the point of care quality improvement (POCQI) methodology for improving the quality of neonatal care at the level 2 special newborn care unit (SNCU). Additional objective was to evaluate the effectiveness of the quality improvement (QI) and preterm baby package training model. METHODS: This study was conducted in a level-II SNCU. The study period was divided into baseline; intervention and sustenance phases. The primary outcome i.e., feasibility was defined as completion of training for 80% or more health care professionals (HCPs) through workshops, their attendance in subsequent review meetings and, successful accomplishment of at least two plan-do-study-act (PDSA) cycles in each project. RESULTS: Of the total, 1217 neonates were enrolled during the 14 mo study period; 80 neonates in the baseline, 1019 in intervention and 118 in sustenance phases. Feasibility of training was achieved within a month of initiation of intervention phase; 22/24 (92%) nurses and 14/15 (93%) doctors attended the meetings. The outcomes of individual projects suggested an improvement in proportion of neonates being given exclusive breast milk on day 5 (22.8% to 78%); mean difference (95% CI) [55.2 (46.5 to 63.9)]. Neonates on any antibiotics declined, proportion of any enteral feeds on day one and duration of kangaroo mother care (KMC) increased. Proportion of neonates receiving intravenous fluids during phototherapy decreased. CONCLUSIONS: The present study demonstrates the feasibility, sustainability, and effectiveness of a facility-team-driven QI approach augmented with capacity building and post-training supportive supervision.

Draft Genome Sequence of Novel Streptomyces sp. Strain AJ-1, Isolated from a Leafcutter Ant in Uttarakhand, India.

We present the draft genome sequence of Streptomyces sp. strain AJ-1, which was isolated from a leafcutter ant found in Uttarakhand, India. The genome assembly resulted in 43 contigs, with a combined length of 6,948,422 bp and a GC content of 73.5%. Through genome annotation, we identified 5,951 protein-coding genes and 67 tRNA genes.

Procalcitonin for Detecting Culture-Positive Sepsis in Neonates: A Prospective, Multicenter Study.

INTRODUCTION: It is unclear if serum procalcitonin (PCT) estimated at sepsis suspicion can help detect culture-positive sepsis in neonates. We evaluated the diagnostic performance of PCT in culture-positive sepsis in neonates. METHODS: This was a prospective study (February 2016 to September 2020) conducted in four level-3 units in India. We enrolled neonates suspected of sepsis in the first 28 days of life. Neonates with birth weight <750 g, asphyxia, shock, and major malformations were excluded. Blood for PCT assay was drawn along with the blood culture at the time of suspicion of sepsis and before antibiotic initiation. The investigators labeled the neonates as having culture-positive sepsis or "no sepsis" based on the culture reports and clinical course. PCT assay was performed by electrochemiluminescence immunoassay, and the clinicians were masked to the PCT levels while assigning the label of sepsis. Primary outcomes were the sensitivity, specificity, and likelihood ratios to identify culture-positive sepsis. RESULTS: The mean birth weight (SD) and median gestation (IQR) were 2,113 (727) g and 36 (32-38) weeks, respectively. Of the 1,204 neonates with eligible cultures, 155 (12.9%) had culture-positive sepsis. Most (79.4%) were culture-positive within 72 h of birth. The sensitivity, specificity, and positive and negative likelihood ratios at 2 ng/mL PCT threshold were 52.3% (95% confidence interval: 44.1-60.3), 64.5% (60.7-68.1), 1.47 (1.23-1.76), and 0.74 (0.62-0.88), respectively. Adding PCT to assessing neonates with 12.9% pretest probability of sepsis generated posttest probabilities of 18% and 10% for positive and negative test results, respectively. CONCLUSION: Serum PCT did not reliably identify culture-positive sepsis in neonates.

Magnetically recoverable sol-gel auto-combustion developed Ni1-xCuxDyyFe2-yO4 magnetic nanoparticles for photocatalytic, electrocatalytic, and antibacterial applications.

Copper and dysprosium doped NiFe2O4 magnetic nanomaterials, Ni1-xCuxDyyFe2-yO4 (x = y = 0.00, 0.01, 0.02, 0.03), was prepared by utilizing sol-gel auto-combustion approach to inspect the photodegradation of methylene blue (MB) pollutant and also, to perform the electrocatalytic water splitting and antibacterial studies. The XRD analysis reveal the growth of a single-phase spinel cubic structure for produced nanomaterials. The magnetic traits show an increasing trend in saturation magnetization (Ms) from 40.71 to 47.90 emu/g along with a decreasing behaviour of coercivity from 158.09 to 156.34 Oe at lower and higher Cu and Dy doping content (x = 0.0-0.01). The study of optical band gap values of copper and dysprosium-doped nickel nanomaterials decreased from 1.71 to 1.52 eV. This will increase the photocatalytic degradation of methylene blue pollutant from 88.57% to 93.67% under natural sunlight, respectively. These findings clearly show that under natural sunlight irradiation for 60 min, the produced N4 photocatalyst displays the greatest photocatalytic activity with a maximum removal percentage of 93.67%. The electrocatalytic characteristics of produced magnetic nanomaterials for both HER and OER were examined with a Calomel electrode taking as a reference in a 0.5 N H2SO4 and 0.1 N KOH electrolyte. The N4 electrode demonstrated considerable 10 and 0.024 mA/cm2 of current density, with onset potentials of 0.99 and 1.5 V for HER and OER and also, have tafel slopes of 58.04 and 295 mV/dec, respectively. The antibacterial activity for produced magnetic nanomaterials was examined against various bacteria (Bacillus subtilis, Staphylococcus aureus, S. typhi, and P. aeruginosa) in which N3 sample produced significant inhibition zone against gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) but no zone of inhibition against gram-negative bacteria (S. typhi and P. aeruginosa). With all these superior traits, the produced magnetic nanomaterials are highly valuable for the wastewater remediation, hydrogen evolution, and biological applications.

Insight into phytase-producing microorganisms for phytate solubilization and soil sustainability.

The increasing demand for food has increased dependence on chemical fertilizers that promote rapid growth and yield as well as produce toxicity and negatively affect nutritional value. Therefore, researchers are focusing on alternatives that are safe for consumption, non-toxic, cost-effective production process, and high yielding, and that require readily available substrates for mass production. The potential industrial applications of microbial enzymes have grown significantly and are still rising in the 21st century to fulfill the needs of a population that is expanding quickly and to deal with the depletion of natural resources. Due to the high demand for such enzymes, phytases have undergone extensive research to lower the amount of phytate in human food and animal feed. They constitute efficient enzymatic groups that can solubilize phytate and thus provide plants with an enriched environment. Phytases can be extracted from a variety of sources such as plants, animals, and microorganisms. Compared to plant and animal-based phytases, microbial phytases have been identified as competent, stable, and promising bioinoculants. Many reports suggest that microbial phytase can undergo mass production procedures with the use of readily available substrates. Phytases neither involve the use of any toxic chemicals during the extraction nor release any such chemicals; thus, they qualify as bioinoculants and support soil sustainability. In addition, phytase genes are now inserted into new plants/crops to enhance transgenic plants reducing the need for supplemental inorganic phosphates and phosphate accumulation in the environment. The current review covers the significance of phytase in the agriculture system, emphasizing its source, action mechanism, and vast applications.

SCOPE: Surveillance of COVID-19 in pregnancy- results of a multicentric ambispective case-control study on clinical presentation and maternal outcomes in India between April to November 2020.

OBJECTIVE: To determine the clinical manifestations, risk factors, treatment modalities and maternal outcomes in pregnant women with lab-confirmed COVID-19 and compare it with COVID-19 negative pregnant women in same age group. DESIGN: Multicentric case-control study. DATA SOURCES: Ambispective primary data collection through paper-based forms from 20 tertiary care centres across India between April and November 2020. STUDY POPULATION: All pregnant women reporting to the centres with a lab-confirmed COVID-19 positive result matched with controls. DATA QUALITY: Dedicated research officers extracted hospital records, using modified WHO Case Record Forms (CRF) and verified for completeness and accuracy. STATISTICAL ANALYSIS: Data converted to excel files and statistical analyses done using STATA 16 (StataCorp, TX, USA). Odds ratios (ORs) with 95% confidence intervals (CI) estimated using unconditional logistic regression. RESULTS: A total of 76,264 women delivered across 20 centres during the study period. Data of 3723 COVID positive pregnant women and 3744 age-matched controls was analyzed. Of the positive cases 56·9% were asymptomatic. Antenatal complications like preeclampsia and abruptio placentae were seen more among the cases. Induction and caesarean delivery rates were also higher among Covid positive women. Pre-existing maternal co-morbidities increased need for supportive care. There were 34 maternal deaths out of the 3723(0.9%) positive mothers, while covid negative deaths reported from all the centres were 449 of 72,541 (0·6%). CONCLUSION: Covid-19 infection predisposed to adverse maternal outcomes in a large cohort of Covid positive pregnant women as compared to the negative controls.

Carboxymethyl cellulose based sustainable hydrogel for colon-specific delivery of gentamicin.

The current research includes the synthesis, improvement of NaCMC-cl-DMAA/AAc hydrogel and in-situ controlled release of gentamicin within various pH environments. The prepared hydrogel was then modified using boron nitride nanosheets aiming to enhancement in the adsorption rate. The prepared hydrogels were investigated by FTIR, XRD, FESEM, TGA/DSC, swelling and cell viability analysis. Cytotoxicity study indicated that prepared sample has a cytocompatibility nature towards healthy normal human cell line (FR2 cells). By changing the pH environment, the drug release properties of the hydrogels can be controlled. The cumulative rate of release for NaCMC-cl-DMAA/AAc hydrogel was 76.5 % at pH = 2.2 and 87.5 % at pH = 7.4. Whereas drug release rate for NaCMC-cl-DMAA/AAc-BNNSs hydrogel composite was 78.6 % at pH = 2.2 and 97.3 % at pH = 7.4 within 4320 min. Gentamicin release kinetics have been determined using the Korsemeyar-Peppas model, which confirms the drug release mechanism.

Improving photocatalytic efficiency of MnFe2O4 ferrites via doping with Zn2+/La3+ ions: photocatalytic dye degradation for water remediation.

The interference of industrial effluents such as dyes, surfactants, metals, polycyclic aromatic hydrocarbons, and pharmaceutical waste has become a severe global problem for human health due to their carcinogenic, mutagenic, and toxic properties. Ferrites were considered promising photocatalysts for the degradation of organic and inorganic dyes. This study mainly focused on improving the photocatalytic performance of MnFe2O4 nanoferrites via doping of Zn2+ and La3+ ions. The zinc and lanthanum substituted Mn1-xZnxLayFe2-yO4 nanoferrites were prepared by the sol-gel auto-combustion technique for the degradation of organic textile malachite green dye (MGD) under the natural solar irradiation. The synthesized nanoferrites were investigated for their structural properties, surface morphology and elemental analysis, optical studies, magnetic properties, and photocatalytic performance by XRD, FESEM/EDX, FTIR/Raman spectrum, vibrating sample magnetometer, and UV-visible spectrophotometer, respectively. The substitution of zinc and lanthanum improved the photocatalytic efficiency of nanoferrites, and about 96% of MGD was degraded by Mn0.97Zn0.03La0.04Fe1.96O4 after 60 min of irradiation. The results showed the pseudo-first-order kinetics for dye degradation using undoped and Zn/La-doped MnFe2O4 photocatalysts.