A computational model to uncover the biophysical underpinnings of neural firing heterogeneity in dissociated hippocampal cultures.

Calcium (Ca2+ ) imaging reveals a variety of correlated firing in cultures of dissociated hippocampal neurons, pinpointing the non-synaptic paracrine release of glutamate as a possible mediator for such firing patterns, although the biophysical underpinnings remain unknown. An intriguing possibility is that extracellular glutamate could bind metabotropic receptors linked with inositol trisphosphate (IP3 ) mediated release of Ca2+ from the endoplasmic reticulum of individual neurons, thereby modulating neural activity in combination with sarco/endoplasmic reticulum Ca2+ transport ATPase (SERCA) and voltage-gated Ca2+ channels (VGCC). However, the possibility that such release may occur in different neuronal compartments and can be inherently stochastic poses challenges in the characterization of such interplay between various Ca2+ channels. Here we deploy biophysical modeling in association with Monte Carlo parameter sampling to characterize such interplay and successfully predict experimentally observed Ca2+ patterns. The results show that the neurotransmitter level at the plasma membrane is the extrinsic source of heterogeneity in somatic Ca2+ transients. Our analysis, in particular, identifies the origin of such heterogeneity to an intrinsic differentiation of hippocampal neurons in terms of multiple cellular properties pertaining to intracellular Ca2+ signaling, such as VGCC, IP3 receptor, and SERCA expression. In the future, the biophysical model and parameter estimation approach used in this study can be upgraded to predict the response of a system of interconnected neurons.

Impact of the COVID-19 Pandemic on the Provision of Dialysis Service and Mortality in Veterans Receiving Maintenance Hemodialysis in the VA: An Interrupted Time-Series Analysis.

INTRODUCTION: According to the US Renal Data System (USRDS), patients with end-stage kidney disease (ESKD) on maintenance dialysis had higher mortality during early COVID-19 pandemic. Less is known about the effect of the pandemic on the delivery of outpatient maintenance hemodialysis and its impact on death. We examined the effect of pandemic-related disruption on the delivery of dialysis treatment and mortality in patients with ESKD receiving maintenance hemodialysis in the Veterans Health Administration (VHA) facilities, the largest integrated national healthcare system in the USA. METHODS: Using national VHA electronic health records data, we identified 7,302 Veterans with ESKD who received outpatient maintenance hemodialysis in VHA healthcare facilities during the COVID-19 pandemic (February 1, 2020, to December 31, 2021). We estimated the average change in the number of hemodialysis treatments received and deaths per 1,000 patients per month during the pandemic by conducting interrupted time-series analyses. We used seasonal autoregressive moving average (SARMA) models, in which February 2020 was used as the conditional intercept and months thereafter as conditional slope. The models were adjusted for seasonal variations and trends in rates during the pre-pandemic period (January 1, 2007, to January 31, 2020). RESULTS: The number (95% CI) of hemodialysis treatments received per 1,000 patients per month during the pre-pandemic and pandemic periods were 12,670 (12,525-12,796) and 12,865 (12,729-13,002), respectively. Respective all-cause mortality rates (95% CI) were 17.1 (16.7-17.5) and 19.6 (18.5-20.7) per 1,000 patients per month. Findings from SARMA models demonstrate that there was no reduction in the dialysis treatments delivered during the pandemic (rate ratio: 0.999; 95% CI: 0.998-1.001), but there was a 2.3% (95% CI: 1.5-3.1%) increase in mortality. During the pandemic, the non-COVID hospitalization rate was 146 (95% CI: 143-149) per 1,000 patients per month, which was lower than the pre-pandemic rate of 175 (95% CI: 173-176). In contrast, there was evidence of higher use of telephone encounters during the pandemic (3,023; 95% CI: 2,957-3,089), compared with the pre-pandemic rate (1,282; 95% CI: 1,241-1,324). CONCLUSIONS: We found no evidence that there was a disruption in the delivery of outpatient maintenance hemodialysis treatment in VHA facilities during the COVID-19 pandemic and that the modest rise in deaths during the pandemic is unlikely to be due to missed dialysis.

Molecular characterization and prevalence of bovine hemoprotozoan and rickettsial organism from Bhubaneswar, Eastern India.

The blood parasites adversely affect the bovine population and are one of the major hindrances to productivity and health of livestock, globally. This study aimed to study the prevalence of some bovine hemoparasites, their molecular characterization, and associated risk factors in and around Bhubaneswar, a place in Eastern India. Microscopy (Giemsa stained thin blood smear) and polymerase chain reaction (PCR)-based prevalence studies were undertaken for a total of 106bovine blood samples belonging to different breed, age, and sex presented to Veterinary Clinical Complex. DNA was extracted by conventional method and primer targeting msp5 gene (382 bp) for Anaplasma marginale, Tams1 gene (572 bp) for Theileria annulata and VSG RoTat 1.2 gene (110 bp) for Trypanosoma evansi, were used. Sequencing and phylogenetic analysis were also carried out for representative PCR products. The risk factors were correlated with prevalence by logistic regression analysis. Blood smear examination revealed a prevalence an overall of 48.11% (51/106) out of which the prevalence of T. annulata, A. marginale and T. evansi, and concurrent infection were reported to be 26.42%, 10.38%, 3.77%, and 7.55% respectively. All the samples found positive in microscopy were also found positive in PCR. PCR assay revealed an overall prevalence of 73.58% (T. annulata: 37.74%, A. marginale:17.92%, T. evansi: 5.66% and concurrent infection:12.26%). A higher prevalence was observed in the age group of 2-4 years (37.74%), females (61.32%) and cross-bred Jersey (50%). Representative PCR products were sequenced and assigned by GenBank (OL550058: A. marginale; OL604429: T. annulata and OL550059: T. evansi). There is a paucity of disease mapping of these parasites in most parts of the country. The study is probably the first report of molecular characterization of T. evansi and A. marginale from the region which gives some information of possible genetic diversity of the isolates circulating in the region. Future research should include large-scale epidemiological surveys as well as concurrent diagnosis of these hemoparasites for better treatment and control strategies.

Mechanical microscopy of cancer cells: TGF-ß induced epithelial to mesenchymal transition corresponds to low intracellular viscosity in cancer cells.

Viscosity is an essential parameter that regulates bio-molecular reaction rates of diffusion-driven cellular processes. Hence, abnormal viscosity levels are often associated with various diseases and malfunctions like cancer. For this reason, monitoring intracellular viscosity becomes vital. While several approaches have been developed for in vitro and in vivo measurement of viscosity, analysis of intracellular viscosity in live cells has not yet been well realized. Our research introduces a novel, natural frequency-based, non-invasive method to determine the intracellular viscosity in cells. This method can not only efficiently analyze the differences in intracellular viscosity post modulation with molecules like PEG or glucose but is sensitive enough to distinguish the difference in intra-cellular viscosity among various cancer cell lines such as Huh-7, MCF-7, and MDAMB-231. Interestingly, TGF-ß a cytokine reported to induce epithelial to mesenchymal transition (EMT), a feature associated with cancer invasiveness resulted in reduced viscosity of cancer cells, as captured through our method. To corroborate our findings with existing methods of analysis, we analyzed intra-cellular viscosity with a previously described viscosity-sensitive molecular rotor-based fluorophore-TPSII. In parity with our position sensing device (PSD)-based approach, an increase in fluorescence intensity was observed with viscosity enhancers, while, TGF-ß exposure resulted in its reduction in the cells studied. This is the first study of its kind that attempts to characterize differences in intracellular viscosity using a novel, non-invasive PSD-based method.

Utilization of hepatitis C virus-positive donors in kidney transplantation.

PURPOSE OF REVIEW: Direct-acting antivirals (DAA) have transformed kidney transplantation by increasing the donor pool from hepatitis C virus (HCV)-infected donors and allowing HCV nucleic acid amplification testing (NAT) donor-positive/recipient-negative (D+/R-) transplantation over the last 7 years. Willingness to accept kidneys from HCV-infected donors and timing/duration of DAA therapy have been evolving. RECENT FINDINGS: By 2021, most of the HCV NAT+ kidneys (92.6%) were transplanted to HCV-naive recipients. Despite the availability of effective DAA therapy, the discard rate of HCV NAT kidneys has been stagnant around 25%. The proportion of wait-listed patients willing to accept a deceased donor kidney from HCV Ab+ and HCV NAT+ donors increased 20-fold between 2015 and 2022. Wait-listed time to receive HCV NAT+ kidneys has been rising and most of the kidneys are transplanted to HCV-naive recipients. The proportion of deceased donor kidney transplants performed in recipients with HCV seropositivity decreased from 5.1 to 2.8% during the same period. Relatively short courses of DAA therapy (7-8 days) appear to be effective to decrease HCV transmission (<5%) and achieve sustained virological response at 12 weeks if administered prior to revascularization. SUMMARY: Further studies are needed to evaluate long-term outcomes of HCV NAT D+/R- transplantation and the best course of DAA treatment.

A novel heterozygote allele in caprine melanocortin 1 receptor (MC1R) gene: an association with heat stress traits.

Climate change negatively influences the productive and reproductive abilities of goats. There is a need to understand the relationship between heat stress and genes that may aid in the development of climate-resilient goats. Melanism variation in goats plays a role in thermoregulation, in which the melanogenic genes have a pleiotropic effect on the regulation of physiological responses and behavior that are altered due to heat stress in the animals. Thus, the present study was conducted to establish a possible association between the coat color gene (MC1R) and heat stress characteristics. The physiological responses and cortisol levels were recorded in forty different coat-colored goats. The genotyping of the animals revealed four SNPs at the 183rd (C/T), 332nd (C/G), 748th (G/T), and 801st (C/G) positions, among which the black and brown goat populations had novel SNPs at the 332nd position. Eight haplotypes were constructed, and an association study revealed that haplotypes (CCGG, TCGG, and CCTC) that were linked to white animals had lower cortisol values, rectal temperature, skin temperature, and respiration rate. The multivariate and cluster analyses revealed that the white goats were distinct from the rest of the goats. In addition, the docking results revealed the residues that were forming the interaction complex, which could play a role in melanogenesis in the animals and, in turn, the heat stress ability of the goats. Altogether, the results of the present study could pave the way for more research into coat color genes and their relationship with heat stress traits.

Outcomes of Simultaneous Liver-Kidney Transplantation Using Kidneys of Deceased Donors With Acute Kidney Injury.

Outcomes from simultaneous liver-kidney transplantation (SLKT) when using kidneys from donors with acute kidney injury (AKI) have not been studied. We studied 5344 SLKTs between May 1, 2007, and December 31, 2019, by using Organ Procurement and Transplantation Network registry data supplemented with United Network for Organ Sharing-DonorNet data. Designating a donor as having AKI required by definition that the following criteria were met: (1) the donor's condition aligned with the Kidney Disease: Improving Global Outcomes (KDIGO) international consensus guidelines and the terminal serum creatinine (Scr) level was ≥1.5 times the minimum Scr level for deceased donors before organ recovery and (2) the terminal Scr level was ≥1.5 mg/dL (a clinically meaningful and intuitive Scr threshold for defining AKI for transplant providers). The primary outcomes were liver transplant all-cause graft failure (ACGF; defined as graft failures and deaths) and kidney transplant death-censored graft failure (DCGF) at 1 year after transplant. The donors with AKI were young, had good organ quality, and had a short cold ischemia time. In the study cohort, 4482 donors had no AKI, whereas 862 had AKI (KDIGO AKI stages: 1, n = 521; 2, n = 202; and 3, n = 138). In the group with AKI and the group with no AKI, respectively, liver ACGF at 1 year (11.1% versus 12.9% [P = 0.13]; hazard ratio [HR], 1.20; 95% confidence interval [CI], 0.97-1.49) and kidney DCGF at 1 year (4.6% versus 5.7% [P = 0.18]; HR, 1.27; 95% CI, 0.95-1.70) did not differ in the full multivariable Cox proportional hazard models. Selected kidneys from deceased donors with AKI can be considered for SLKT.

Changing patterns in medication prescription for gestational diabetes during a time of guideline change in the USA: a cross-sectional study.

OBJECTIVE: To define patterns of prescription and factors associated with choice of pharmacotherapy for gestational diabetes mellitus (GDM), namely metformin, glyburide and insulin, during a period of evolving professional guidelines. DESING: Cross-sectional study. SETTING: US commercial insurance beneficiaries from Market-Scan (late 2015 to 2018). STUDY DESIGN: We included women with GDM, singleton gestations, 15-51 years of age on pharmacotherapy. The exposure was pharmacy claims for metformin, glyburide and insulin. MAIN OUTCOMES: Pharmacotherapy for GDM with either oral agent, metformin or glyburide, compared with insulin as the reference, and secondarily, consequent treatment modification (addition and/or change) to metformin, glyburide or insulin. RESULTS: Among 37 762 women with GDM, we analysed data from 10 407 (28%) with pharmacotherapy, 21% with metformin (n = 2147), 48% with glyburide (n = 4984) and 31% with insulin (n = 3276). From late 2015 to 2018, metformin use increased from 17 to 29%, as did insulin use from 26 to 44%, whereas glyburide use decreased from 58 to 27%. By 2018, insulin was the most common pharmacotherapy for GDM; metformin was more likely to be prescribed by 9% compared with late 2015/16, but glyburide was less likely by 45%. Treatment modification occurred in 20% of women prescribed metformin compared with 2% with insulin and 8% with glyburide. CONCLUSIONS: Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for GDM among a privately insured US population during a time of evolving professional guidelines. Further evaluation of the relative effectiveness and safety of metformin compared with insulin is needed. TWEETABLE ABSTRACT: Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for gestational diabetes mellitus in the USA.

Frequency and prediction of persistent urinary tract dilation in third trimester and postnatal urinary tract dilation in infants following diagnosis in second trimester.

OBJECTIVE: To determine the frequency, associated characteristics and prognostic value of the current risk stratification system for prenatal urinary tract dilation (UTD) for predicting persistent UTD in the third trimester and subsequent postnatal UTD in the infant, following diagnosis in the second trimester. METHODS: This was a single-institution retrospective cohort study of singleton pregnancies diagnosed with unilateral or bilateral UTD in the second trimester (before 28 weeks' gestation) with follow-up in the third trimester (at or after 28 weeks) between January 2017 and May 2019. In all cases, the prenatal diagnosis and stratification to low-risk (Grade A1) or increased-risk (Grade A2-3) UTD was made using the 2014 UTD consensus classification system. The primary outcomes included persistent prenatal UTD in the third trimester and postnatal UTD up to 6 months of age. We performed multivariable analysis to assess whether patient and second- and third-trimester sonographic characteristics (such as UTD laterality, other renal abnormality (calyceal dilation, abnormal parenchymal appearance, abnormal ureter or bladder) and anteroposterior renal pelvic diameter (AP-RPD)) were associated with the study outcomes. We assessed the predictive value of the current risk stratification system (Grade A1 vs Grade A2-3) in the second and third trimesters for persistent prenatal UTD and postnatal UTD using the area under the receiver-operating-characteristics curve (AUC). RESULTS: Of 26 620 second-trimester ultrasound assessments in the study period, 347 patients were diagnosed with UTD in the second trimester and had third-trimester follow-up, of whom 150/347 (43% (95% CI, 38-49%)) had persistent UTD in the third trimester. Among the 282/347 (81%) patients with postnatal follow-up available, the frequency of postnatal UTD was 49/282 (17% (95% CI, 13-22%)), and among the subset with persistent UTD in the third trimester, the frequency of postnatal UTD was 46/102 (45% (95% CI, 35-55%)). The most frequent postnatal diagnosis was transient UTD (76%), followed by duplicated collecting system (10%). Of infants originally diagnosed with UTD in the second trimester, 2% (7/347) required surgery; stated differently, of the 49 infants with postnatal UTD, 14% (7/49) required surgery. At second-trimester diagnosis, sonographic predictors of both persistent prenatal UTD and postnatal UTD included the presence of other renal abnormality and UTD Grade A2-3. At third-trimester follow-up, predictors of postnatal UTD were larger mean AP-RPD and UTD Grade A2-3, while all cases had other renal abnormality. Second-trimester diagnosis of UTD Grade A2-3 had satisfactory discrimination for predicting persistent prenatal UTD (AUC, 0.64 (95% CI, 0.58-0.70)) and postnatal UTD (AUC, 0.72 (95% CI, 0.63-0.81)), as did third-trimester UTD Grade A2-3 for predicting postnatal UTD (AUC, 0.66 (95% CI, 0.56-0.76)). CONCLUSIONS: The majority of cases of prenatal UTD did not result in postnatal UTD, and of those that did, very few required surgery. Follow-up third-trimester assessment after a second-trimester diagnosis of UTD is warranted. The current risk stratification system by UTD grade, based on the 2014 UTD consensus classification, can be used to predict postnatal UTD with fair accuracy. Further research is needed to determine whether the predictive performance of this system can be improved by incorporating additional risk factors. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of large-for-gestational-age infant by fetal growth charts and hemoglobin A1c level in pregnancy complicated by pregestational diabetes.

OBJECTIVES: To compare the ability of three fetal growth charts (Fetal Medicine Foundation (FMF), Hadlock and National Institutes of Child Health and Human Development (NICHD) race/ethnicity-specific) to predict large-for-gestational age (LGA) at birth in pregnant individuals with pregestational diabetes, and to determine whether inclusion of hemoglobin A1c (HbA1c) level improves the predictive performance of the growth charts. METHODS: This was a retrospective analysis of individuals with Type-1 or Type-2 diabetes with a singleton pregnancy that resulted in a non-anomalous live birth. Fetal biometry was performed between 28 + 0 and 36 + 6 weeks of gestation. The primary exposure was suspected LGA, defined as estimated fetal weight ≥ 90th percentile using the Hadlock (Formula C), FMF and NICHD growth charts. The primary outcome was LGA at birth, defined as birth weight ≥ 90th percentile, using 2017 USA natality reference data. The performance of the three growth charts to predict LGA at birth, alone and in combination with HbA1c as a continuous measure, was assessed using the area under the receiver-operating-characteristics curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value. RESULTS: Of 358 assessed pregnant individuals with pregestational diabetes (34% with Type 1 and 66% with Type 2), 147 (41%) had a LGA infant at birth. Suspected LGA was identified in 123 (34.4%) by the Hadlock, 152 (42.5%) by the FMF and 152 (42.5%) by the NICHD growth chart. The FMF growth chart had the highest sensitivity (77% vs 69% (NICHD) vs 63% (Hadlock)) and the Hadlock growth chart had the highest specificity (86% vs 76% (NICHD) and 82% (FMF)) for predicting LGA at birth. The FMF growth chart had a significantly higher AUC (0.79 (95% CI, 0.74-0.84)) for LGA at birth compared with the NICHD (AUC, 0.72 (95% CI, 0.68-0.77); P < 0.001) and Hadlock (AUC, 0.75 (95% CI, 0.70-0.79); P < 0.01) growth charts. Prediction of LGA improved for all three growth charts with the inclusion of HbA1c measurement in comparison to each growth chart alone (P < 0.001 for all); the FMF growth chart remained more predictive of LGA at birth (AUC, 0.85 (95% CI, 0.81-0.90)) compared with the NICHD (AUC, 0.79 (95% CI, 0.73-0.84)) and Hadlock (AUC, 0.81 (95% CI, 0.76-0.86)) growth charts. CONCLUSIONS: The FMF fetal growth chart had the best predictive performance for LGA at birth in comparison with the Hadlock and NICHD race/ethnicity-specific growth charts in pregnant individuals with pregestational diabetes. Inclusion of HbA1c improved further the prediction of LGA for all three charts. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Mutants lacking global regulators, fis and arcA, in Escherichia coli enhanced growth fitness under acetate metabolism by pathway reprogramming.

Global regulatory transcription factors play a significant role in controlling microbial metabolism under genetic and environmental perturbations. A system-level effect of carbon sources such as acetate on microbial metabolism under disrupted global regulators has not been well established. Acetate is one of the major substrates available in various nutrient niches such as the mammalian gut and a keto diet. A substantial amount of acetate gets secreted in aerobic metabolism. Therefore, investigating the study on acetate metabolism is highly significant. It is known that the global regulators fis and arcA regulate acetate uptake genes in E. coli under glucose conditions. This study deciphered the growth and flux distribution of E. coli transcription regulatory knockouts Δfis, ΔarcA and double deletion mutant, ΔarcAΔfis under acetate using 13C-metabolic flux analysis (MFA), which has not been investigated before. We observed that the mutants exhibited an expeditious growth rate (~ 1.2-1.6-fold) with a proportionate increase in acetate uptake rates compared to the wild type. 13C-MFA displayed the distinct metabolic reprogramming of intracellular fluxes via the TCA cycle, anaplerotic pathway and gluconeogenesis, which conferred an advantage of a faster growth rate with better carbon usage in all the mutants. This resulted in higher metabolic fluxes through the TCA cycle (~ 18-90%), lower gluconeogenesis (~ 15-35%) and higher CO2 and ATP production with the proportional increase in growth rate. The study reveals a novel insight by stating the sub-optimality of the wild-type strain grown under acetate substrate aerobically. These mutant strains efficiently oxidize acetate, thus acting as potential candidates for the biosynthesis of isoprenoids, biofuels, vitamins and various pharmaceutical products.Key Points• Mutants exhibited a better balance between energy and precursor synthesis than WT.• Leveraged in the unravelling of regulatory control under various nutrient shifts.• Metabolic readjustment resulted in optimal biomass requirement and faster growth.

Exploring the druggable proteome of Candida species through comprehensive computational analysis.

Candida albicans and non-albicans Candida spp. are major cause of systemic mycoses. Antifungal drugs such as azoles and polyenes are not efficient to successfully eradicate Candida infection owing to their fungistatic nature or low bioavailability. Here, we have adopted a comprehensive computational workflow for identification, prioritization and validation of targets from proteomes of Candida albicans and Candida tropicalis. The protocol involves identification of essential drug-target candidates using subtractive genomics, protein-protein interaction network properties and systems biology based methods. The essentiality of the novel metabolic and non-metabolic targets was established by performing in silico gene knockouts, under aerobic as well as anaerobic conditions, and in vitro drug inhibition assays respectively. Deletion of twelve genes that are involved in amino acid, secondary metabolite, and carbon metabolism showed zero growth in metabolic model under simulated conditions. The algorithm, used in this study, can be downloaded from http://pbit.bicnirrh.res.in/offline.php and executed locally.

Structural, optical, photocatalytic, and optoelectronic properties of Zn2SnO4 nanocrystals prepared by hydrothermal method.

Zn2SnO4 (ZTO) nanocrystals are extensively studied in various fields. However, size-dependent ZTO nanocrystals are still challenging to understand their structural, optical, photocatalytic, and optoelectronic properties. ZTO nanocrystals are synthesized by a facile hydrothermal reaction method. The structural properties of the synthesized ZTO nanocrystals are studied by x-ray diffraction and transmission electron microscope. The sizes of the ZTO nanocrystals are controlled by the pH values of the precursor and the molar ratios of the Zn:Sn in the starting materials. ZTO nanocrystals with the small size of 6 nm and large size of 270 nm are obtained by our method. The Eu3+ ions are doped into ZTO nanocrystals to probe size-dependent Eu doping sites, which shows significant potential applications in light emitting diode phosphors. Moreover, the photocatalytic activity of ZTO nanocrystals on rhodamine (RhB) decoloration are investigated, and the results show that 6 nm ZTO nanocrystals show better performance in the photocatalytic decoloration of RhB compared to 270 nm nanocrystals. Most importantly, we design and fabricate optoelectronic devices to detect IR light based on our nanocrystals and a self-prepared NIR cyanine dye. The device based on small sized ZTO nanocrystals exhibits better device performance under 808 nm IR light compared to that of the large sized ZTO nanocrystals. We believe this work represents ZTO size-dependent properties in term of structural, optical, photocatalytic, and optoelectronic properties as a multifunctional material.

Prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm: a prospective cohort.

OBJECTIVE: To determine the association between prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm (<28 weeks of gestation). DESIGN: The Extremely Low Gestational Age Newborn (ELGAN) Study, a prospective cohort. SETTING: Ten-year follow-up of extremely preterm infants born at 14 US hospitals between 2002 and 2004. METHODS: Prenatal tobacco smoke exposure was defined as a mother's report at enrolment of active (i.e. maternal) and passive smoking during pregnancy. Poisson regression with generalized estimating equations was used. Models adjusted for mother's age, race/ethnicity, education, insurance, pre-pregnancy body mass index, US region, multiple gestation and infant's sex; and in sensitivity analysis, gestational age at delivery and clinical subtype of preterm birth, given their classification as intermediate and non-confounding variables. MAIN OUTCOMES: Neurological impairment at 10 years, epilepsy, cerebral palsy and cognitive impairment. RESULTS: Of 1200 ELGAN study survivors, 856 were assessed at 10 years of age with neurological outcomes, of whom 14% (118/856) had active tobacco exposure during pregnancy and 24% (207/852) had passive tobacco exposure. Compared with children who were not exposed prenatally to tobacco, children exposed to active tobacco use during pregnancy had a higher risk of epilepsy (14% versus 5%; adjusted relative risk: 1.68, 95% CI 1.45-1.92). This risk remained after adjustment for gestational age at delivery and clinical subtype of preterm birth. Prenatal tobacco smoke exposure was not associated with other assessed neurological outcomes, including cerebral palsy and multiple measures of cognitive impairment. CONCLUSIONS: Among children born extremely preterm, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life. TWEETABLE ABSTRACT: Among infants born before 28 weeks of gestation, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life.

Characterization of graphene/pine wood biochar hybrids: Potential to remove aqueous Cu2.

Biochar-based hybrid composites containing added nano-sized phases are emerging adsorbents. Biochar, when functionalized with nanomaterials, can enhance pollutant removal when both the nanophase and the biochar surface act as adsorbents. Three different pine wood wastes (particle size < 0.5 mm, 10 g) were preblended with 1 wt% of three different graphenes in aqueous suspensions, designated as G1, G2, and G3. G1 (SBET, 8.1 m2/g) was prepared by sonicating graphite made from commercial synthetic graphite powder (particle size 7-11 µm). G2 (312.0 m2/g) and G3 (712.0 m2/g) were purchased commercial graphene nanoplatelets (100 mg in 100 mL deionized water). These three pine wood-graphene mixtures were pyrolyzed at 600 °C for 1 h to generate three graphene-biochar adsorbents, GPBC-1, GPBC-2, and GPBC-3 containing 4.4, 4.9, and 5.0 wt% of G1, G2, and G3 respectively. Aqueous Cu2+ adsorption capacities were 10.6 mg/g (GPBC-1), 4.7 mg/g (GPBC-2), and 5.5 mg/g (GPBC-3) versus 7.2 mg/g for raw pine wood biochar (PBC) (0.05 g adsorbent dose, Cu2+ 75 mg/L, 25 mL, pH 6, 24 h, 25 ± 0.5 °C). Increased graphene surface areas did not result in adsorption increases. GPBC-1, containing the lowest nanophase surface area with the highest Cu2+ capacity, was chosen to evaluate its Cu2+ adsorption characteristics further. Results from XPS showed that the surface concentration of oxygenated functional groups on the GPBC-1 is greater than that on the PBC, possibly contributing to its greater Cu2+ removal versus PBC. GPBC-1 and PBC uptake of Cu2+ followed the pseudo-second-order kinetic model. Langmuir maximum adsorption capacities and BET surface areas were 18.4 mg/g, 484.0 m2/g (GPBC-1) and 9.2 mg/g, 378.0 m2/g (PBC). This corresponds to 3.8 × 10-2 versus 2.4 × 10-2 mg/m2 of Cu2+ removed on GPBC-1 (58% more Cu2+ per m2) versus PBC. Cu2+ adsorption on both these adsorbents was spontaneous and endothermic.

Long-term outcomes in children with Hirschsprung's disease and transition zone bowel pull-through: impact of surgical techniques and role for conservative approach.

PURPOSE: Presence of transition zone (TZ) in the pulled colon can impact the outcome of surgery in children with Hirschsprung's disease. There is a wide variation in terminology used to define TZ and its management. We present our series of managing 11 such children with considerations for conservative management. METHODS: Eleven of 114 children operated for Hirschsprung's disease had features of TZ on the 4-quadrant doughnut assessment of proximal anastomosing margin. They were followed up for development of obstructive symptoms, failure of pull-through procedure or bowel-related complications. Intervention done were observation with laxatives, dilatation, Botox injection and redo pull-through. RESULTS: Of the 11 children, 6 underwent Duhamel's procedure and 5, transanal endorectal pull-through (TERP). Features identified on HPE were presence of hypertrophic nerve bundles involving 2 or 3 quadrants in the circumferential doughnut biopsy of proximal anastomosing margin. Observed symptoms included constipation, enterocolitis, increased bowel frequency and soiling. Intervention done were use of laxatives with bowel management program in six and Botox injections in four. Only one child with TZ in 3 quadrants required redo surgery. Mean follow-up was 5.2 years with resolution of symptoms in most. CONCLUSION: This study highlights the role of conservative management with good outcomes in children with TZ bowel pull-through having hypertrophic nerve fibers and normal ganglion pattern. Children who underwent Duhamel's procedure had little impact with the presence of TZ at anastomotic margin and majority of those undergoing TERP benefitted from Botox injection. Conservative management can be attempted successfully to prevent redo surgical interventions as they can lead to poorer outcomes. Only those children not responding to conservative measures need to be planned for revision surgery.

Effects of land use and climate change on water scarcity in rivers of the Western Ghats of India.

This paper assesses the long-term combined effects of land use (LU) and climate change on river hydrology and water scarcity of two rivers of the Western Ghats of India. The historical LU changes were studied for four decades (1988-2016) using the maximum likelihood algorithm and the long-term LU (2016-2075) was estimated using the Dyna-CLUE prediction model. Five General Circulation Models (GCMs) were utilized to assess the effects of climate change (CC) and the Soil and Water Assessment Tool (SWAT) model was used for hydrological modeling of the two river catchments. To characterize granular effects of LU and CC on regional hydrology, a scenario approach was adopted and three scenarios depicting near-future (2006-2040), mid-future (2041-2070), and far-future (2071-2100) based on climate were established. The present rate of LU change indicated a reduction in forest cover by 20% and an increase in urbanized areas by 9.5% between 1988 and 2016. It was estimated that forest cover in the catchments may be expected to halve compared to the present-day LU (55% in 2016 to 23% in 2075), along with large-scale conversion to agricultural lands (13.5% in 2016 to 49.5% in 2075). As a result of changes to LU and forecasted climate, it was found that rivers in the Western Ghats of India might face scarcity of fresh water in the next two decades until the year 2040. However, because of large-scale LU conversion toward the year 2050, streamflow in rivers might increase as high as 70.94% at certain times of the year. Although an increase in streamflow is perceived favorable, the streamflow changes during summer and winter may be expected to affect the cropping calendar and crop yield. The changes to streamflow were also linked to a 4.2% increase in ecologically sensitive wetlands of the Aghanashini river catchment.

Trends in utilization of deceased donor kidneys based on hepatitis C virus status and impact of public health service labeling on discard.

BACKGROUND: Kidneys from deceased donors infected with hepatitis C virus (HCV) are underutilized. Most HCV virus-infected donors are designated as Public Health Service increased donors (PHS-IR). Impact of PHS and HCV designations on discard is not well studied. METHODS: We queried the UNOS data set for all deceased donor kidneys between January 2015 and December 2018. The final study cohort donors (n = 38 702) were stratified into three groups based on HCV antibody (Ab) and NAT status: (a) Ab-/NAT- (n = 35 861); (b) Ab+/NAT- (n = 973); and (c) Ab±/NAT+ (n = 1868). We analyzed utilization/discard rates of these organs, the impact of PHS-IR and HCV designations on discard using multivariable two-level hierarchical logistic regression models, forecasted number of HCV viremic donors/kidneys by 2023. RESULTS: During the study period, (a) the number of viremic donor kidneys increased 2 folds; (b) the multilevel mixed-effects logistic regression models showed that, overall, the PHS labeling (OR 1.20, CI 95% CI 1.15-1.29) and HCV designation (OR 2.29; 95% CI 2.15-2.43) were independently associated with increased risk of discard; (c) contrary to the general perception, PHS-IR kidneys across all HCV groups, compared to PHS-IR kidneys were more likely to be discarded; (d) we forecasted that the number of kidneys from HCV viremic donor kidneys might increase from 1376 in 2019 to 2092 in 2023. CONCLUSION: Hepatitis C virus viremic kidneys might represent 10%-15% of deceased donor organ pool soon with the current rate of the opioid epidemic. PHS labeling effect on discard requires further discussion of the utility of this classification.

Validity of diffusion-weighted magnetic resonance imaging in the evaluation of acute pyelonephritis in comparison with contrast-enhanced computed tomography.

PURPOSE: Applications of diffusion-weighted magnetic resonance imaging outside the brain have gained increasing importance in recent years, and recent studies have shown the usage of diffusion-weighted (DW) imaging in diagnosing pyelonephritis based on renal cortical and medullary apparent diffusion coefficient (ADC) values. The aim of this study was to assess the validity of DW magnetic resonance (MR) imaging in comparison with contrast-enhanced computed tomography (CECT) in diagnosing pyelonephritis. MATERIAL AND METHODS: A cross-sectional observational study was conducted for a period of six months in a tertiary hospital in Coimbatore. All patients with clinical and laboratory diagnosis of acute pyelonephritis, who were referred for radiological imaging (CECT), were taken into the study. Out of 112 patients with a clinical and laboratorial diagnosis of acute pyelonephritis (APN), who underwent both DW MR and CECT, diagnosis of APN was made in 100 patients based on CECT, while in 12 cases the investigation (CECT) was negative. Finally, these 100 patients were included in the study. The validity of DW MR imaging in diagnosing APN was assessed by deriving sensitivity, specificity, and positive and negative predictive value in comparison with CECT findings. RESULTS: The validity report of DW MR imaging in the detection of APN showed a very high sensitivity (96-100%) and specificity (86-90%) and very low false positives (6-10%) and negatives (< 5%), and it also showed that in the areas of affected renal parenchyma ADC values were consistently lower compared to unaffected renal parenchyma. CONCLUSION: Based on the generated hypothesis, DW MR imaging of the kidneys seems to be highly sensitive and specific for the detection of focal or diffuse infections within the kidney in comparison with CECT.

Investigating host-bacterial interactions among enteric pathogens.

BACKGROUND: In 2017, World Health Organization (WHO) published a catalogue of 12 families of antibiotic-resistant "priority pathogens" that are posing the greatest threats to human health. Six of these dreaded pathogens are known to infect the human gastrointestinal system. In addition to causing gastrointestinal and systemic infections, these pathogens can also affect the composition of other microbes constituting the healthy gut microbiome. Such aberrations in gut microbiome can significantly affect human physiology and immunity. Identifying the virulence mechanisms of these enteric pathogens are likely to help in developing newer therapeutic strategies to counter them. RESULTS: Using our previously published in silico approach, we have evaluated (and compared) Host-Pathogen Protein-Protein Interaction (HPI) profiles of four groups of enteric pathogens, namely, different species of Escherichia, Shigella, Salmonella and Vibrio. Results indicate that in spite of genus/ species specific variations, most enteric pathogens possess a common repertoire of HPIs. This core set of HPIs are probably responsible for the survival of these pathogen in the harsh nutrient-limiting environment within the gut. Certain genus/ species specific HPIs were also observed. CONSLUSIONS: The identified bacterial proteins involved in the core set of HPIs are expected to be helpful in understanding the pathogenesis of these dreaded gut pathogens in greater detail. Possible role of genus/ species specific variations in the HPI profiles in the virulence of these pathogens are also discussed. The obtained results are likely to provide an opportunity for development of novel therapeutic strategies against the most dreaded gut pathogens.