Hemodynamically significant patent ductus arteriosus profile in preterm neonates (26-34 weeks' gestation) undergoing surfactant replacement therapy in India: a prospective observational study.

Surfactant administration significantly improves respiratory outcomes in preterm infants with respiratory distress syndrome (RDS). However, surfactant administration may lead to hemodynamic alterations, particularly in the heart, affecting the patent ductus arteriosus (PDA), the consequences of which are not fully understood. This prospective observational study took place in an Indian neonatal care unit from July 2019 to November 2020, enrolling preterm neonates (26-34 weeks' gestation) with RDS needing non-invasive positive pressure ventilation. They were divided into two groups: those who received surfactant while on respiratory support and those who did not. All newborns in the study had an initial echocardiogram within 24 h to detect PDA flow. Subsequent echocardiograms were conducted between 48 and 72 h or earlier based on symptoms. Of 220 infants requiring respiratory support, 84 were enrolled, with 42 in each group. While demographic variables were similar, the surfactant group had a lower median gestational age (29.0 vs. 31.0 weeks). In the surfactant group, a significantly higher percentage of neonates had hemodynamically significant PDA (hsPDA) compared to the non-surfactant group (54.76% vs. 26.19%, P-value = .008). Multiple logistic regression found no significant association between gestation, birth weight, or shock and hsPDA occurrence. Pulmonary hemorrhage occurred more often in the surfactant group. Bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) > grade 2, and necrotizing enterocolitis (NEC) ≥ grade 2 did not differ significantly between the groups. Surfactant therapy via the less invasive surfactant administration technique was associated with a higher incidence of hsPDA. While surfactant is crucial for neonatal respiratory care, its potential hemodynamic effects, including hsPDA, should be considered.

Understanding Kenyan policymakers' perspectives about the introduction of new maternal vaccines.

New vaccine policy adoption is a complex process, especially in low-and-middle-income countries (LMICs), requiring country policymakers to navigate challenges such as competing priorities, human and financial resource constraints, and limited logistical capacity. Since the Expanded Programme on Immunization's (EPI) beginning, most new vaccine introductions under this structure have not been aimed at adult populations. The majority of adult vaccines offered under the EPI are not typically tested among and tailored for pregnant persons, except those that are specifically recommended for pregnancy. Given that new maternal vaccines, including RSV and GBS vaccines, are on the horizon, it is important to understand what barriers may arise during the policy development and vaccine introduction process. In this study, we sought to understand information needs among maternal immunization policymakers and decision-makers in Kenya for new vaccine maternal policy adoption through in-depth interviews with 20 participants in Nakuru and Mombasa counties in Kenya. Results were mapped to an adapted version of an established framework by Levine et al., (2010) focused on new vaccine introduction in LMICs. Participants reported that the policy process for new maternal vaccine introduction requires substantial evidence as well as coordination among diverse stakeholders. Importantly, our findings suggest that the process for new maternal vaccines does not end with the adoption of a new policy, as intended recipients and various actors can determine the success of a vaccine program. Previous shortcomings, in Kenya, and globally during HPV vaccine introduction show the need to allocate adequate resources in education of communities given the sensitive target group. With maternal vaccines targeting a sensitive group - pregnant persons- in the pipeline, we are at an opportune time to understand how to ensure successful vaccine introduction with optimal acceptance and uptake, while also addressing vaccine hesitancy to increase population benefit.

Effects of metformin on glucose metabolism and mitochondrial function in patients with obstructive sleep apnea: A pilot randomized trial.

Obstructive sleep apnea (OSA) is associated with increased risk for diabetes, and standard treatment with positive airway pressure (PAP) device shows inconsistent effects on glucose metabolism. Metformin is known to treat and prevent diabetes, but its effects on skeletal muscle mitochondrial function are not completely understood. Here, we evaluate the effects of metformin on glucose metabolism and skeletal muscle mitochondrial function in patients with OSA. Sixteen adults with obesity (50.9 ± 6.7 years, BMI: 36.5 ± 2.9 kg/m2 ) and moderate-to-severe OSA were provided with PAP treatment and randomized to 3 months of placebo (n = 8) or metformin (n = 8) treatment in a double-blind parallel-group design. Whole body glucose metabolism was determined by oral glucose tolerance test. A skeletal muscle biopsy was obtained to evaluate mitochondrial respiratory capacity and expression of proteins related to mitochondrial dynamics and energy metabolism. Whole body insulin-sensitivity (Matsuda index) did not change in metformin or placebo treated groups. However, metformin treatment prevented increases in insulin release relative to placebo during follow-up. Insulin area under the curve (AUC) and insulin to glucose AUC ratio increased in placebo but remained unchanged with metformin. Furthermore, metformin treatment improved skeletal muscle mitochondrial respiratory capacity and dynamics relative to placebo. Metformin treatment prevented the decline in whole body glucose homeostasis and skeletal muscle mitochondrial function in patients with moderate to severe OSA. Patients with OSA may benefit from the addition of metformin to prevent diabetes.

Crop type discrimination using Geo-Stat Endmember Extraction and machine learning algorithms.

The identification of crop diversity in today's world is very crucial to ensure adaptation of the crop with changing climate for better productivity as well as food security. Towards this, Hyperspectral Remote Sensing (HRS) is an efficient technique based on imaging spectroscopy that offers the opportunity to discriminate crop types based on morphological as well as physiological features due to availability of contiguous spectral bands. The current work utilized the benefits of Airborne Visible Infrared Imaging spectrometer- New Generation (AVIRIS-NG) data and explored the techniques for classification and identification of crop types. The endmembers were identified using the Geo-Stat Endmember Extraction (GSEE) algorithm for pure pixels identification and to generate the spectral library of the different crop types. Spectral feature comparison was done among AVIRIS-NG, Analytical Spectral Device (ASD)-Spectroradiometer and Continuum Removed (CR) spectra. The best-fit spectra obtained with the Reference ASD-Spectroradiometer and Pure Pixel spectral library were then used for crop discrimination using the ten supervised classifiers namely Spectral Angle Mapper (SAM), Spectral Information Divergence (SID), Support Vector Machine (SVM), Minimum Distance Classifier (MDC), Binary Encoding, deep learning-based Convolution Neural Network (CNN) and different algorithms of Ensemble learning such as Tree Bag, AdaBoost (Adaptive Boosting), Discriminant and RUSBoost (Random Under Sampling). In total, nine crop types were identified, namely, wheat, maize, tobacco, sorghum, linseed, castor, pigeon pea, fennel and chickpea. The performance evaluation of the classifiers was made using various metrics like Overall Accuracy, Kappa Coefficient, Precision, Recall and F1 score. The classifier 2D-CNN was found to be the best with Overall Accuracy, Kappa Coefficient, Precision, Recall and F1 score values of 89.065 %, 0.871,87.565%, 89.541% and 88.678% respectively. The output of this work can be utilized for large scale mapping of crop types at the species level in a short interval of time of a large area with high accuracy.

Case Report: Lepromatous Leprosy Masquerading as Acute Suppurative Lymphadenitis.

Leprosy is a chronic cutaneous infection. It is usually characterized by thickened nerves and maculo-anesthetic patches. Leprosy often has an unusual presentation, which is a diagnostic challenge. In this case report, we present a case of an elderly male who presented with fever and chronic pus-draining axillary, cervical, and inguinal lymph nodes. He also had a weak left foot for the previous 5 months. During his hospital stay, he developed additional papular lesions over his extremities. We performed fine needle aspiration from the lymph nodes and skin biopsy, which were suggestive of lepromatous leprosy. We initiated him on antileprosy medication. On follow-up, he was responsive to therapy. Although skin and nerve involvement in leprosy is common, this case had an atypical presentation of discharging lymph nodes.

Barriers to breast cancer screening in Singapore: A literature review.

INTRODUCTION: Breast cancer is a leading cause of cancer death among women, and its age-standardised incidence rate is one of the highest in Asia. We aimed to review studies on barriers to breast cancer screening to inform future policies in Singapore. METHOD: This was a literature review of both quantitative and qualitative studies published between 2012 and 2020 using PubMed, Google Scholar and Cochrane databases, which analysed the perceptions and behaviours of women towards breast cancer screening in Singapore. RESULTS: Through a thematic analysis based on the Health Belief Model, significant themes associated with low breast cancer screening uptake in Singapore were identified. The themes are: (1) high perceived barriers versus benefits, including fear of the breast cancer screening procedure and its possible outcomes, (2) personal challenges that impede screening attendance and paying for screening and treatment, and (3) low perceived susceptibility to breast cancer. CONCLUSION: Perceived costs/barriers vs benefits of screening appear to be the most common barriers to breast cancer screening in Singapore. Based on the barriers identified, increasing convenience to get screened, reducing mammogram and treatment costs, and improving engagement with support groups are recommended to improve the screening uptake rate in Singapore.

Overfeeding-induced weight gain elicits decreases in sex hormone-binding globulin in healthy males-Implications for body fat distribution.

OBJECTIVE: Obesity and upper-body fat elevates cardiometabolic risk. However, mechanisms predisposing to upper-body fat accumulation are not completely understood. In males, low testosterone (T) frequently associates with obesity, and estrogen deficiency may contribute to upper-body adiposity. This study examines the effects of overfeeding-induced weight gain on changes in gonadal hormones in healthy males and its association with regional fat depots. METHODS: Twenty-five males (age: 29.7 ± 6.9 years; BMI: 24.7 ± 3.1 kg/m2 ) were overfed for 8 weeks to gain approximately 5% body weight. Changes in total and regional fat depots were assessed using dual-energy x-ray absorptiometry and abdominal computed tomography scans. Circulating T, estrone (E1), 17-ß estradiol (E2), and sex hormone-binding globulin (SHBG) concentrations were measured at baseline and after weight gain. RESULTS: Overfeeding resulted in 3.8 (3.3, 4.9) kg weight gain with increased total body fat. Weight gain did not alter circulating T (p = 0.82), E1 (p = 0.52), or E2 (p = 0.28). However, SHBG decreased (p = 0.04) along with consequent increases in T/SHBG (p = 0.02) and E2/SHBG (p = 0.03) ratios. Importantly, baseline E2/SHBG ratio was inversely associated with increases in upper-body fat mass (ρ = -0.43, p = 0.03). CONCLUSIONS: Modest weight gain does not alter circulating gonadal hormones in males but may increase bioavailability of T and E2 via decreases in SHBG. The association between baseline E2/SHBG and regional fat mass suggests that higher levels of bioavailable E2 may protect from upper-body fat accumulation during overfeeding-induced modest weight gain in healthy males. Our study suggests a complex relationship between adipose tissue, gonadal hormones, and fat accumulation in males.

Identificação da velocidade anormal da dilatação de pupila como biomarcador de lesão cerebral em pacientes neurocríticos / Identification of abnormal pupil dilation velocity as a biomarker of cerebral injury in neurocritically ill patients

RESUMO Objetivo: Calcular as velocidades médias da dilatação de pupila para classificar a gravidade da lesão derivada da escala de coma de Glasgow, estratificada por variáveis de confusão. Métodos: Neste estudo, analisaram-se 68.813 exames das pupilas para determinar a velocidade normal de dilatação em 3.595 pacientes com lesão cerebral leve (13 - 15), moderada (9 - 12) ou grave (3 - 8), segundo a escala de coma de Glasgow. As variáveis idade, sexo, raça, tamanho da pupila, tempo de permanência na unidade de terapia intensiva, pressão intracraniana, uso de narcóticos, classificação pela escala de coma de Glasgow e diagnóstico foram consideradas confundidoras e controladas para análise estatística. Empregou-se regressão logística com base em algoritmo de classificação com aprendizado de máquina para identificar os pontos de corte da velocidade de dilatação para as categorias segundo a escala de coma de Glasgow. Resultados: As razões de chance e os intervalos de confiança desses fatores se mostraram estatisticamente significantes em sua influência sobre a velocidade de dilatação. A classificação com base na área sob a curva mostrou que, para o grau leve, na escala de coma de Glasgow, o limite da velocidade de dilatação foi de 1,2mm/s, com taxas de falsa probabilidade de 0,1602 e 0,1902 e áreas sob a curva de 0,8380 e 0,8080, respectivamente, para os olhos esquerdo e direito. Para grau moderado na escala de coma de Glasgow, a velocidade de dilatação foi de 1,1mm/s com taxas de falsa probabilidade de 0,1880 e 0,1940 e áreas sob a curva de 0,8120 e 0,8060, respectivamente, nos olhos esquerdo e direito. Mais ainda, para o grau grave na escala de coma de Glasgow, a velocidade de dilatação foi de 0,9mm/s, com taxas de falsa probabilidade de 0,1980 e 0,2060 e áreas sob a curva de 0,8020 e 0,7940, respectivamente, nos olhos esquerdo e direito. Esses valores foram diferentes dos métodos prévios de descrição subjetiva e das velocidades de dilatação previamente estimadas. Conclusão: Observaram-se velocidades mais lentas de dilatação pupilar em pacientes com escores mais baixos na escala de coma de Glasgow, indicando que diminuição da velocidade pode indicar grau mais grave de lesão neuronal.

ABSTRACT Objective: To calculate mean dilation velocities for Glasgow coma scale-derived injury severity classifications stratified by multiple confounding variables. Methods: In this study, we examined 68,813 pupil readings from 3,595 patients to determine normal dilation velocity with brain injury categorized based upon a Glasgow coma scale as mild (13 - 15), moderate (9 - 12), or severe (3 - 8). The variables age, sex, race, pupil size, intensive care unit length of stay, intracranial pressure, use of narcotics, Glasgow coma scale, and diagnosis were considered as confounding and controlled for in statistical analysis. Machine learning classification algorithm-based logistic regression was employed to identify dilation velocity cutoffs for Glasgow coma scale categories. Results: The odds ratios and confidence intervals of these factors were shown to be statistically significant in their influence on dilation velocity. Classification based on the area under the curve showed that for the mild Glasgow coma scale, the dilation velocity threshold value was 1.2mm/s, with false probability rates of 0.1602 and 0.1902 and areas under the curve of 0.8380 and 0.8080 in the left and right eyes, respectively. For the moderate Glasgow coma scale, the dilation velocity was 1.1mm/s, with false probability rates of 0.1880 and 0.1940 and areas under the curve of 0.8120 and 0.8060 in the left and right eyes, respectively. Furthermore, for the severe Glasgow coma scale, the dilation velocity was 0.9mm/s, with false probability rates of 0.1980 and 0.2060 and areas under the curve of 0.8020 and 0.7940 in the left and right eyes, respectively. These values were different from the previous method of subjective description and from previously estimated normal dilation velocities. Conclusion: Slower dilation velocities were observed in patients with lower Glasgow coma scores, indicating that decreasing velocities may indicate a higher degree of neuronal injury.

Belowground fungal volatiles perception in okra (Abelmoschus esculentus) facilitates plant growth under biotic stress.

Microbial volatile organic compounds (mVOCs) have great potential in plant ecophysiology, yet the role of belowground VOCs in plant stress management remains largely obscure. Analysis of biocontrol producing VOCs into the soil allow detailed insight into their interaction with soil borne pathogens for plant disease management. A root interaction trial was set up to evaluate the effects of VOCs released from Trichoderma viride BHU-V2 on soil-inhabiting fungal pathogen and okra plant growth. VOCs released into soil by T. viride BHU-V2 inhibited the growth of collar rot pathogen, Sclerotium rolfsii. Okra plants responded to VOCs by increasing the root growth (lateral roots) and total biomass content. VOCs exposure increased defense mechanism in okra plants by inducing different enzyme activities i.e. chitinase (0.89 fold), ß-1,3-glucanase (0.42 fold), peroxidase (0.29 fold), polyphenol oxidase (0.33 fold) and phenylalanine lyase (0.7 fold) when inoculated with S. rolfsii. In addition, T. viride BHU-V2 secreted VOCs reduced lipid peroxidation and cell death in okra plants under pathogen inoculated condition. GC/MS analysis of VOCs blend revealed that T. viride BHU-V2 produced more number of antifungal compounds in soil medium as compared to standard medium. Based on the above observations it is concluded that okra plant roots perceive VOCs secreted by T. viride BHU-V2 into soil that involved in induction of plant defense system against S. rolfsii. In an ecological context, the findings reveal that belowground microbial VOCs may play an important role in stress signaling mechanism to interact with plants.

Comparative Study of Postoperative Pain Relief Using Preincisional Versus Postincisional Infiltration With 0.25% Bupivacaine in Abdominal Hysterectomy Under General Anesthesia.

Background and Aims: Hysterectomy, probably the most common non-pregnancy related surgery performed in gynaecology, is associated with moderate to severe post-operative pain. Wound infiltration with local anaesthetic agent reduces the transmission of pain from the wound, in addition, local inflammatory response to the injury is also suppressed. The infiltration of local anaesthesia can be done either pre- or post-operatively. The present study was designed to determine the efficacy of pre-incisional infiltration versus post-incisional infiltration with 0.25% Bupivacaine in providing post-operative pain relief in patients undergoing abdominal hysterectomy. Methods: In Prospective Interventional Randomised study, 90 female patients posted for elective abdominal hysterectomy under general anaesthesia were randomly allocated into three equal groups of 30 patients each. Group I: Patients receiving subcutaneous infiltration with 40 mL of 0.25% Bupivacaine 5 mins before skin incision. Group II: Patients receiving subcutaneous infiltration of surgical area with 40 mL of 0.25% Bupivacaine at end of surgery (after peritoneal closure). Group III Control Group: Patients receiving no local anaesthetic infiltration. Observations were made for the duration of effective analgesia from end of the surgery until the first use of rescue analgesic along with the frequency and cumulative amount of rescue analgesics in 24 hours. Results: We found that at baseline, pain score of patients in Group III (3.87±1.17) was maximum followed by that in Group I (2.57±0.90) and minimum in Group II (2.20±0.61). Requirement of first analgesia was earliest in Group III (79.50±23.90 minutes) followed by Group I (136.83±13.16 minutes) and last in Group II (146.17±12.78 minutes), in addition, cumulative dose of analgesia was required by patients in Group III (152.50±36.76 mg) followed by that in Group I (132.50±37.80 mg) and minimum by that in Group II (115.00±38.06 mg). Conclusion: Subcutaneous infiltration of Bupivacaine either pre-incisional or post-incisional, helped to reduce the immediate post-operative pain intensity, delayed the first rescue analgesic requirement, reduced the post-operative dose and frequency of rescue analgesia. However, post-incisional intervention had an edge over pre-incisional intervention.

Seed biopriming with antagonistic microbes and ascorbic acid induce resistance in tomato against Fusarium wilt.

Seed biopriming is an emerging technique to enhance seed germination under stress conditions. An integrated approach of tomato seed biopriming with ascorbic acid, Trichoderma asperellum BHU P-1 and Ochrobactrum sp. BHU PB-1 was applied to observe the response against wilt pathogen of tomato Fusarium oxysporum f. sp. lycopersici (FOL). Tomato seeds bioprimed with the aforementioned application expressed augmented seed germination and activated of defense response. Seed germination was recorded higher (80 %) at low concentration (1 pM) of ascorbic acid as compared to high concentration of 1 mM (41 %). Combination of both ascorbic acid and antagonistic microbe treatments (T5 & T6) significantly reduced disease incidence (up to 28 %) in tomato plants at 10 days. T5 and T6 treated plants exhibited higher accumulation of total phenol content and increased activity of Phenylammonia lyase (PAL), Peroxidase (PO), Chitinase (Chi) and Polyphenol oxidase (PPO) as compared to control (T1) plants. ROS formation in the form of H2O2 was also found to be reduced in combined treatment. Histochemical analysis revealed that phenylpropanoid pathway (lignin deposition) was more activated in combined priming treatment plants as compared to individual treatment upon challenge inoculation with FOL. Transcript expression analysis of defense genes confirmed the up-regulation of PAL (2.1 fold), Chi (0.92 fold), Pathogenesis related proteins (PR) (1.58 fold) and Lipoxygenase (Lox) (0.72 fold) in T6 treatment as compared to T1 treatment plants at 96 h. This study reveals that ascorbic acid treatment with antagonistic microbes through seed priming effectively induced seed germination and elicited defense mechanism to control wilt disease in tomato plants.

Chronic Intermittent Hypoxia Triggers a Senescence-like Phenotype in Human White Preadipocytes.

Obstructive sleep apnea (OSA) is a common sleep disorder associated with obesity. Emerging evidence suggest that OSA increases the risk of cardiovascular morbidity and mortality partly via accelerating the process of cellular aging. Thus, we sought to examine the effects of intermittent hypoxia (IH), a hallmark of OSA, on senescence in human white preadipocytes. We demonstrate that chronic IH is associated with an increased generation of mitochondrial reactive oxygen species along with increased prevalence of cells with nuclear localization of γH2AX & p16. A higher prevalence of cells positive for senescence-associated ß-galactosidase activity was also evident with chronic IH exposure. Intervention with aspirin, atorvastatin or renin-angiotensin system (RAS) inhibitors effectively attenuated IH-mediated senescence-like phenotype. Importantly, the validity of in vitro findings was confirmed by examination of the subcutaneous abdominal adipose tissue which showed that OSA patients had a significantly higher percentage of cells with nuclear localization of γH2AX & p16 than non-OSA individuals (20.1 ± 10.8% vs. 10.3 ± 2.7%, Padjusted < 0.001). Furthermore, the frequency of dual positive γH2AX & p16 nuclei in adipose tissue of OSA patients receiving statin, aspirin, and/or RAS inhibitors was comparable to non-OSA individuals. This study identifies chronic IH as a trigger of senescence-like phenotype in preadipocytes. Together, our data suggest that OSA may be considered as a senescence-related disorder.

Sphingobacterium sp. BHU-AV3 Induces Salt Tolerance in Tomato by Enhancing Antioxidant Activities and Energy Metabolism.

Salt tolerant bacteria can be helpful in improving a plant's tolerance to salinity. Although plant-bacteria interactions in response to salt stress have been characterized, the precise molecular mechanisms by which bacterial inoculation alleviates salt stress in plants are still poorly explored. In the present study, we aimed to determine the role of a salt-tolerant plant growth-promoting rhizobacteria (PGPR) Sphingobacterium BHU-AV3 for improving salt tolerance in tomato through investigating the physiological responses of tomato roots and leaves under salinity stress. Tomato plants inoculated with BHU-AV3 and challenged with 200 mM NaCl exhibited less senescence, positively correlated with the maintenance of ion balance, lowered reactive oxygen species (ROS), and increased proline content compared to the non-inoculated plants. BHU-AV3-inoculated plant leaves were less affected by oxidative stress, as evident from a reduction in superoxide contents, cell death, and lipid peroxidation. The reduction in ROS level was associated with the increased antioxidant enzyme activities along with multiple-isoform expression [peroxidase (POD), polyphenol oxidase (PPO), and superoxide dismutase (SOD)] in plant roots. Additionally, BHU-AV3 inoculation induced the expression of proteins involved in (i) energy production [ATP synthase], (ii) carbohydrate metabolism (enolase), (iii) thiamine biosynthesis protein, (iv) translation protein (elongation factor 1 alpha), and the antioxidant defense system (catalase) in tomato roots. These findings have provided insight into the molecular mechanisms of bacteria-mediated alleviation of salt stress in plants. From the study, we can conclude that BHU-AV3 inoculation effectively induces antioxidant systems and energy metabolism in tomato roots, which leads to whole plant protection during salt stress through induced systemic tolerance.

Sustainable Low-Concentration Arsenite [As(III)] Removal in Single and Multicomponent Systems Using Hybrid Iron Oxide-Biochar Nanocomposite Adsorbents-A Mechanistic Study.

Rice and wheat husks were converted to biochars by slow pyrolysis (1 h) at 600 °C. Iron oxide rice husk hybrid biochar (RHIOB) and wheat husk hybrid biochar (WHIOB) were synthesized by copyrolysis of FeCl3-impregnated rice or wheat husks at 600 °C. These hybrid sorbents were characterized using X-ray photoelectron spectroscopy, X-ray diffraction, scanning electron microscopy (SEM), SEM-energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, physical parameter measurement system, and Brunauer-Emmett-Teller (BET) surface area techniques. Fe3O4 was the predominant iron oxide present with some Fe2O3. RHIOB and WHIOB rapidly chemisorbed As(III) from water (∼24% removal in first half an hour reaching up to ∼100% removal in 24 h) at surface Fe-OH functions forming monodentate ≡Fe-OAs(OH)2 and bidentate (≡Fe-O)2AsOH complexes. Optimum removal occurred in the pH 7.5-8.5 range for both RHIOB and WHIOB, but excellent removal occurred from pH 3 to 10. Batch kinetic studies at various initial adsorbate-adsorbent concentrations, temperatures, and contact times gave excellent pseudo-second-order model fits. Equilibrium data were fitted to different sorption isotherm models. Fits to isotherm models (based on R 2 and χ2) on RHIOB and WHIOB followed the order: Redlich-Peterson > Toth > Sips = Koble-Corrigan > Langmuir > Freundlich = Radke-Prausnitz > Temkin and Sips = Koble-Corrigan > Toth > Redlich-Peterson > Langmuir > Temkin > Freundlich = Radke-Prausnitz, respectively. Maximum adsorption capacities, Q RHIOB 0 = 96 µg/g and Q WHIOB 0 = 111 µg/g, were obtained. No As(III) oxidation to As(V) was detected. Arsenic adsorption was endothermic. Particle diffusion was a rate-determining step at low (≤50 µg/L) concentrations, but film diffusion controls the rate at ≥100-200 µg/L. Binding interactions with RHIOB and WHIOB were established, and the mechanism was carefully discussed. RHIOB and WHIOB can successfully be used for As(III) removal in single and multicomponent systems with no significant decrease in adsorption capacity in the presence of interfering ions mainly Cl-, HCO3 -, NO3 -, SO4 2-, PO4 3-, K+, Na+, Ca2+. Simultaneous As(III) desorption and regeneration of RHIOB and WHIOB was successfully achieved. A very nominal decrease in As(III) removal capacity in four consecutive cycles demonstrates the reusability of RHIOB and WHIOB. Furthermore, these sustainable composites had good sorption efficiencies and may be removed magnetically to avoid slow filtration.

Hospital-level Antibiotic Use and Complexity of Care Among Neonates.

BACKGROUND: Despite increasing neonatal antibiotic stewardship efforts, understanding of interhospital variation in neonatal antibiotic use is limited. METHODS: A retrospective cohort study was conducted among primarily academically affiliated hospitals participating in the Vizient Clinical Database/Resource Manager. Neonatal discharges were identified by admission age <1 month, excluding nonviable neonates and normal newborns. Hospitals with ≥100 neonatal discharges and complete data for January-December 2016 were included. Antibiotic use was measured in days of therapy per 1000 patient-days (DOT/1000 pd). A composite measure of neonatal care complexity (NCC; low, medium, high) was based on the volume of very low-birth-weight neonates and neonates undergoing surgical procedures, cardiac surgery, or extracorporeal membranous oxygenation. RESULTS: The 118 included hospitals represented 184 716 neonatal discharges; 22 hospitals with low NCC, 56 with medium NCC, and 40 with high NCC. Mean antibiotic DOT/1000 pd was 363 (standard deviation [SD], 94) in high NCC hospitals, 243 (SD, 88) in medium NCC hospitals, and 184 (SD, 122) in low NCC hospitals. Increasing NCC was associated with higher antibiotic use, with an incidence rate ratio (IRR) of 1.95 (95% confidence interval [CI], 1.55 to 2.47) for high vs low NCC and IRR 1.31 (95% CI, 1.05 to 1.64) for medium vs low NCC. Increasing case mix index was associated with higher antibiotic use (IRR 1.86 per unit increase; 95% CI, 1.50 to 2.31). CONCLUSIONS: Aggregate antibiotic use among hospitalized neonates varies based on care complexity. Substantial variation despite stratification by complexity suggests incomplete risk adjustment and/or avoidable variation in care.

Telomere Length and Risk of Major Adverse Cardiac Events and Cancer in Obstructive Sleep Apnea Patients.

Telomere length (TL) is associated with cardiovascular disease (CVD) and cancer. Obstructive sleep apnea (OSA) is also linked to higher risk of CVD and cancer, and to TL. We investigated the association between TL and risk of major adverse cardiac events (MACE) and cancer in OSA patients. We studied 210 individuals undergoing sleep-related studies between 2000 and 2007. Baseline characteristics and follow-up data (available in 164 subjects) were obtained from clinic records. Incidence rates were calculated for the entire group and by OSA status. Hazard ratios were calculated to estimate effects of OSA and TL on risk of MACE and cancer. In total, 32 individuals (20%) developed MACE and/or cancer during 12.7-year follow-up. The OSA group had a higher likelihood of cancer (16.0 vs. 4.9 events per 1000 person-years, P = 0.044) but no clear evidence of an elevated incidence of MACE (10.8 vs. 4.8 events per 1000 person-years, P = 0.293) compared to the non-OSA group. There was no association between TL and MACE- (HR = 1.01, 95% CI 0.78-1.28), or cancer-risk (HR = 1.18, 95% CI 0.96-1.43). Our study warrants further investigation of any modulating effect of OSA on TL and the risk of MACE and cancer.

The failed bladder closure in cloacal exstrophy: Management and outcomes.

PURPOSE: Cloacal exstrophy (CE) is the most severe presentation of the Exstrophy-Epispadias Complex (EEC) and is associated with an omphalocele, making the bladder and abdominal wall closure difficult. If the bladder closure fails, a secondary closure is necessary. The objective of this study is to identify patient or surgical factors associated with a successful secondary closure. METHODS: The institution's EEC database was reviewed for CE patients between 1975 and 2015. Inclusion criteria included a failed primary bladder closure with a secondary closure. Patient demographics, surgical factors and outcomes of the secondary bladder closure were reviewed. RESULTS: Twenty-four patients met inclusion criteria. 8/8 patients had a successful two-staged closure at the author's institution (100%); 2/16 patients had a successful closure at an outside institution (12.5%). Older median age at secondary closure was associated with outcome, p = 0.045. Pelvic osteotomy was associated with successful secondary closure, p = 0.013. Using Buck's immobilization with external fixation was associated with a higher proportion of successful secondary closures compared to Spica cast, p = 0.012. CONCLUSION: Successful reclosure in CE patients is associated with the use of osteotomy as well as Buck's immobilization with external fixation. While successful reclosure can be achieved, it is often at the cost of multiple procedures and, therefore, all efforts should be expended to achieve a successful primary closure. TYPE OF STUDY: Prognostic. LEVEL OF EVIDENCE: III.

Comparative Expression of Renin-Angiotensin Pathway Proteins in Visceral Versus Subcutaneous Fat.

Body fat distribution contributes to obesity-related metabolic and cardiovascular disorders. Visceral fat is more detrimental than subcutaneous fat. However, the mechanisms underlying visceral fat-mediated cardiometabolic dysregulation are not completely understood. Localized increases in expression of the renin angiotensin system (RAS) in adipose tissue (AT) may be implicated. We therefore investigated mRNA and protein expression of RAS components in visceral versus subcutaneous AT using paired samples from individuals undergoing surgery (N = 20, body mass index: 45.6 ± 6.2 kg/m2, and age: 44.6 ± 9.1 years). We also examined RAS-related proteins in AT obtained from individuals on renin angiotensin aldosterone system (RAAS) targeted drugs (N = 10, body mass index: 47.2 ± 9.3 kg/m2, and age: 53.3 ± 10.1 years). Comparison of protein expression between subcutaneous and visceral AT samples showed an increase in renin (p = 0.004) and no change in angiotensinogen (p = 0.987) expression in visceral AT. Among proteins involved in angiotensin peptide generation, angiotensin converting enzyme (p = 0.02) was increased in subcutaneous AT while chymase (p = 0.001) and angiotensin converting enzyme-2 (p = 0.001) were elevated in visceral fat. Furthermore, visceral fat expression of angiotensin II type-2 receptor (p = 0.007) and angiotensin II type-1 receptor (p = 0.031) was higher, and MAS receptor (p < 0.001) was lower. Phosphorylated-p53 (p = 0.147), AT fibrosis (p = 0.138) and average adipocyte size (p = 0.846) were similar in the two depots. Nonetheless, visceral AT showed increased mRNA expression of inflammatory (TNFα, p < 0.001; IL-6, p = 0.001) and oxidative stress markers (NOX2, p = 0.038; NOX4, p < 0.001). Of note, mRNA and protein expression of RAS components did not differ between subjects taking or not taking RAAS related drugs. In summary, several RAS related proteins are differentially expressed in subcutaneous versus visceral AT. This differential expression may not alter AngII but likely increases Ang1-7 generation in visceral fat. These potential differences in active angiotensin peptides and receptor expression in the two depots suggest that localized RAS may not be involved in differences in visceral vs subcutaneous AT function in obese individuals. Our findings do not support a role for localized RAS differences in visceral fat-mediated development of cardiovascular and metabolic pathology.

Intermittent hypoxia regulates vasoactive molecules and alters insulin-signaling in vascular endothelial cells.

Vascular dysfunction and insulin resistance (IR) are associated with obstructive sleep apnea (OSA), which is characterized by frequent episodes of nocturnal intermittent hypoxia (IH). While it is recognized that the balance between vasoconstrictive (endothelin-1) and vasodilatory molecules (nitric oxide, NO) determine vascular profile, molecular mechanisms contributing to vascular dysfunction and IR in OSA are not completely understood. Caveolin-1 is a membrane protein which regulates endothelial nitric oxide synthase (eNOS) activity which is responsible for NO generation and cellular insulin-signaling. Hence, we examined the effects of IH on caveolin-1, eNOS, and endothelin-1 in human coronary artery endothelial cells in the context of IR. Chronic 3-day IH exposure up-regulated caveolin-1 and endothelin-1 expression while reducing NO. Also, IH altered insulin-mediated activation of AKT but not ERK resulting in increased endothelin-1 transcription. Similarly, caveolin-1 overexpression attenuated basal and insulin-stimulated NO synthesis along with impaired insulin-dependent activation of AKT and eNOS, with no effect on insulin-stimulated ERK1/2 phosphorylation and endothelin-1 transcription. Our data suggest that IH contributes to a vasoconstrictive profile and to pathway-selective vascular IR, whereby insulin potentiates ET-1 expression. Moreover, IH may partly mediate its effects on NO and insulin-signaling via upregulating caveolin-1 expression.

Design and Synthesis of Ligand Efficient Dual Inhibitors of Janus Kinase (JAK) and Histone Deacetylase (HDAC) Based on Ruxolitinib and Vorinostat.

Concomitant inhibition of multiple oncogenic pathways is a desirable goal in cancer therapy. To achieve such an outcome with a single molecule would simplify treatment regimes. Herein the core features of ruxolitinib (1), a marketed JAK1/2 inhibitor, have been merged with the HDAC inhibitor vorinostat (2), leading to new molecules that are bispecific targeted JAK/HDAC inhibitors. A preferred pyrazole substituted pyrrolopyrimidine, 24, inhibits JAK1 and HDACs 1, 2, 3, 6, and 10 with IC50 values of less than 20 nM, is <100 nM potent against JAK2 and HDAC11, and is selective for the JAK family against a panel of 97 kinases. Broad cellular antiproliferative potency of 24 is supported by demonstration of JAK-STAT and HDAC pathway blockade in hematological cell lines. Methyl analogue 45 has an even more selective profile. This study provides new leads for assessment of JAK and HDAC pathway dual inhibiton achieved with a single molecule.