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PEO/PVDF–HFP [poly(ethylene oxide)/poly(vinylidene fluoride-co-hexafluoropropylene)] solid polymer electrolyte blend incorporating varying weights of LiTFSI [lithium bis (trifluoromethane) sulfonimide] salt was prepared. The blend with 20 wt.% of salt that exhibits maximum ionic conductivity was subjected to microstructural modification by exposing to low-energy ions of oxygen at different fluences. The ionic conductivity of the system increases by one order in magnitude when subjected to oxygen ion irradiation. The dielectric loss tangent curves are used to extract ions relaxation time. The relaxation time τ of the system is reduced from 1.42 to 0.71 μs upon irradiation which indicates enhanced segmental motion due to a rise in amorphous region in polymer matrix. The ion activation energy in the system decreases to 0.041 eV from 0.063 eV. Dielectric studies suggest an increase in dipoles in the irradiated systems possibly due to polymer chain scission in the matrix. The increase in disordered phase by ion irradiation is supported by change in crystallinity from 24% for the unirradiated systems to about 14% for the irradiated systems by X-ray diffraction and differential scanning calorimetry analysis. The shift in prominent peaks observed in Fourier transform infrared spectroscopy suggests possible scission of the polymer chains. [ABSTRACT FROM AUTHOR]

Dielectric and conductivity behaviors of nano ZnO doped polyvinyl alcohol (PVA) composites for various concentrations of dopant were investigated using impedance spectroscopy for a wide range of temperatures (303 K-423 K) and frequencies (5 Hz-30MHZ). The dielectric properties of host polymer matrix have been improved by the addition of nano ZnO and are found to be highly temperature dependent. Anomalous dielectric behavior was observed in the frequency range of 2.5 MHz-5 MHz. Increase in dielectric permittivity and dielectric loss was observed with respect to temperature. The Cole-Cole plot could be modeled by low resistance regions in a high resistance matrix and the lowest resistance was observed for the 10 mol. % films. The imaginary part of the electric modulus showed asymmetric peaks with the relaxation following Debye nature below and non-Debye nature above the peaks. The ac conductivity is found to obey Jonscher's power law, whereas the variation of dc conductivity with temperature was found to follow Arrhenius behavior. Two different activation energy values were obtained from Arrhenius plot indicating that two conduction mechanisms are involved in the composite films. Fitting the ac conductivity data to Jonscher's law indicates that large polaron assisted tunneling is the most likely conduction mechanism in the composites. Maximum conductivity is observed at 423K for all the samples and it is optimum for 10mol. % ZnO doped PVA composite film. Significant increase in dc and ac conductivities in these composite films makes them a potential candidate for application in electronic devices. [ABSTRACT FROM AUTHOR]

Different shapes of Co-aggregates were synthesized via reduction of a Co salt (CoCl2·6H2O) by chemical precipitation using glycerol, ethylene glycol and ethanol as solvents. The effect of solvent on the morphology, fcc or hcp phase-content and the magnetic properties of the synthesized samples were investigated. The Co-aggregates synthesized using glycerol have a dense spherical shape and high saturation magnetization (MS), whereas ethylene glycol leads to formation of flower-shaped spherical aggregates through loose packing of smaller plate-like particles which have a moderate MS value. When ethanol was used as a solvent, a dendritic (leaf like)-shape of the aggregates with the lowest MS value was obtained. The formation of the obtained morphology of the aggregates was explained based on the size of the solvent molecule, the viscosity of the solvent and the number of polar groups (–OH) present in the solvent molecules. The magnetic domain state and domain wall dynamics of all the Co-samples were investigated using 59Co Internal Field Nuclear Magnetic Resonance (IFNMR) spectroscopy at RT and at 77 K. Through the IFNMR spectroscopy, the presence of gain boundaries, single domain particles and multi-domain particles/aggregates with domain walls associated with fcc and hcp phases were identified and quantified. We observed that the use of ethanol facilitates formation of a higher amount of hcp phase in the sample than the use of glycerol or ethylene glycol. [ABSTRACT FROM AUTHOR]

Background: Pharmacologic termination of paroxysmal supraventricular tachycardia (PSVT) often requires medically supervised intervention. Intranasal etripamil, is an investigational fast-acting, nondihydropyridine, L-type calcium channel blocker, designed for unsupervised self-administration to terminate atrioventricular nodal-dependent PSVT. Phase 2 results showed potential safety and efficacy of etripamil in 104 patients with PSVT., Methods: NODE-301, a phase 3, multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of etripamil nasal spray administered, unsupervised in patients with symptomatic sustained PSVT. After a medically supervised etripamil test dose while in sinus rhythm, patients were randomized 2:1 to receive etripamil 70 mg or placebo. When PSVT symptoms developed, patients applied a cardiac monitor and attempted a vagal maneuver; if symptoms persisted, they self-administered blinded treatment. An independent Adjudication Committee reviewed continuous electrocardiogram recordings. The primary efficacy endpoint was termination of adjudicated PSVT within 5 hours after study drug administration., Results: NODE-301 accrued 156 positively adjudicated PSVT events treated with etripamil (n=107) or placebo (n=49). The hazard ratio for the primary endpoint, time-to-conversion to sinus rhythm during the 5-hour observation period, was 1.086 (95% CI, 0.726-1.623; P =0.12). In predefined sensitivity analyses, etripamil effects (compared with placebo) occurred at 3, 5, 10, 20, and 30 minutes ( P <0.05). For example, at 30 minutes, there was a 53.7% of SVT conversion in the treatment arm compared to 34.7% in the placebo arm (hazard ratio, 1.87 [95% CI, 1.09-3.22]; P =0.02). Etripamil was well tolerated; adverse events were mainly related to transient nasal discomfort and congestion (19.6% and 8.0%, respectively, of randomized treatment-emergent adverse events., Conclusions: Although the primary 5-hour efficacy endpoint was not met, analyses at earlier time points indicated an etripamil treatment effect in terminating PSVT. Etripamil self-administration during PSVT was safe and well tolerated. These results support continued clinical development of etripamil nasal spray for self-administration during PSVT in a medically unsupervised setting., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03464019.

The capsid-protein (CP) of chikungunya virus (CHIKV) is reported to generate a primary immune response in infected individuals during disease progression. CP-specific monoclonal antibodies (mAbs) developed in our laboratory, exhibited promising potential in diagnosing recent CHIKV infection in IgM capture ELISA. In this study we focused on the molecular and structural characterization of one such representative mAb ClVE4/D9 to delineate the epitope recognized by it using an immuno-informatics approach. The antigen-antibody interacting residues were found to lie within the dimer interface region of the CP, also predicted as a conformational epitope. This implies that the mAb could interfere during the process of nucleocapsid assembly, ultimately preventing budding and egress of the virus particle. The binding specificity of the mAb highlights the possibility of using this anti-CP antibody for therapeutic or prophylactic treatment against CHIKV.Communicated by Ramaswamy H. Sarma.

Patients with prostate cancer whose tumors bear deleterious mutations in DNA-repair pathways often respond to PARP inhibitors. Studies were conducted to compare the activity of several PARP inhibitors in vitro and their tissue exposure and in vivo efficacy in mice bearing PC-3M-luc-C6 prostate tumors grown subcutaneously or in bone. Niraparib, olaparib, rucaparib, and talazoparib were compared in proliferation assays, using several prostate tumor cell lines and in a cell-free PARP-trapping assay. PC-3M-luc-C6 cells were approximately 12- to 20-fold more sensitive to PARP inhibition than other prostate tumor lines, suggesting that these cells bear a DNA damage repair defect. The tissue exposure and efficacy of these PARP inhibitors were evaluated in vivo in PC-3M-luc-C6 subcutaneous and bone metastasis tumor models. A steady-state pharmacokinetic study in PC-3M-luc-C6 tumor-bearing mice showed that all of the PARP inhibitors had favorable subcutaneous tumor exposure, but niraparib was differentiated by superior bone marrow exposure compared with the other drugs. In a PC-3M-luc-C6 subcutaneous tumor efficacy study, niraparib, olaparib, and talazoparib inhibited tumor growth and increased survival to a similar degree. In contrast, in the PC-3M-luc-C6 bone metastasis model, niraparib showed the most potent inhibition of bone tumor growth compared with the other therapies (67% vs. 40%-45% on day 17), and the best survival improvement over vehicle control [hazard ratio (HR), 0.28 vs. HR, 0.46-0.59] and over other therapies (HR, 1.68-2.16). These results show that niraparib has superior bone marrow exposure and greater inhibition of tumor growth in bone, compared with olaparib, rucaparib, and talazoparib., (©2022 American Association for Cancer Research.)

Purpose: We aimed to evaluate a complicated appendicitis clinical practice guideline at our institution., Methods: Records were compared before and after protocol implementation. We standardized an ED consult pathway, antibiotic use and need for early appendectomy (EA) versus interval appendectomy (IA). We evaluated demographics, clinical characteristics, and outcomes. Subgroup analysis was performed to compare patients with small abscess treated with IA pre-protocol versus similar patients treated by EA post-protocol., Results: In total 246 patients were reviewed (Pre-protocol = 152, Post-protocol = 94). Pre-protocol early appendectomy rate was 51% versus 82% on post-protocol patients. There were no differences in demographics. Post-protocol the use of preoperative imaging significantly decreased (Pre 92% vs. 56%, p = 0.0001), as well as the use of discharge antibiotics (Pre 93% vs. Post 27%, p = 0.0001) with no change in abscess rate. Overall, post-protocol patients had fewer total CT scans performed (Pre 40% vs. Post 28%, p = 0.03) and decreased total length of stay (Pre 7.7 vs. Post 6.5 days, p = 0.049). On subgroup analysis, post-protocol EA with no or small abscess had lower median number of admissions, decreased total LOS (Pre IA 9 days vs. Post EA 5 days, p = 0.00001) and fewer complications (Pre IA 42% vs. EA 22%, p = 0.022)., Conclusion: The establishment of a standardized pediatric complicated appendicitis protocol may lead to improved outcomes and resource utilization. Patients presenting with no or small abscess may be the least likely to benefit from interval appendectomy., Level of Evidence: Level III., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The purpose of our study was to compare outcomes of infants with spontaneous intestinal perforation (SIP) treated with primary peritoneal drain versus primary laparotomy., Methods: We performed a multi-institution retrospective review of infants with diagnosis of SIP from 2012 to 2016. Clinical characteristics and outcomes were compared between infants treated with primary peritoneal drain vs infants treated with laparotomy., Results: We identified 171 patients treated for SIP (drain n = 110 vs. laparotomy n = 61). There were no differences in maternal or prenatal characteristics. There were no clinically significant differences in vital signs, white blood cell or platelet measures, up to 48 h after intervention. Patients who were treated primarily with a drain were more premature (24.9 vs. 27.2 weeks, p < 0.001) and had lower median birth weight (710 g vs. 896 g, p < 0.001). No significant differences were found in complications, time to full feeds, length of stay (LOS) or mortality between the groups. Primary laparotomy group had more procedures (median number 1 vs. 2, p = 0.002). There were 32 (29%) primary drain failures whereby a laparotomy was ultimately needed., Conclusions: SIP treated with primary drain is successful in the majority of patients with no significant differences in outcomes when compared to laparotomy with stoma., The Level of Evidence: III., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We report 3 atypical rubella cases in a family cluster in India. The index case-patient showed only mild febrile illness, whereas the other 2 patients showed acute encephalitis and died of the disease. We confirmed rubella in the index and third cases using next-generation sequencing and IgM.

Different shapes of Co-aggregates were synthesized via reduction of a Co salt (CoCl2·6H2O) by chemical precipitation using glycerol, ethylene glycol and ethanol as solvents. The effect of solvent on the morphology, fcc or hcp phase-content and the magnetic properties of the synthesized samples were investigated. The Co-aggregates synthesized using glycerol have a dense spherical shape and high saturation magnetization (MS), whereas ethylene glycol leads to formation of flower-shaped spherical aggregates through loose packing of smaller plate-like particles which have a moderate MS value. When ethanol was used as a solvent, a dendritic (leaf like)-shape of the aggregates with the lowest MS value was obtained. The formation of the obtained morphology of the aggregates was explained based on the size of the solvent molecule, the viscosity of the solvent and the number of polar groups (-OH) present in the solvent molecules. The magnetic domain state and domain wall dynamics of all the Co-samples were investigated using 59Co Internal Field Nuclear Magnetic Resonance (IFNMR) spectroscopy at RT and at 77 K. Through the IFNMR spectroscopy, the presence of gain boundaries, single domain particles and multi-domain particles/aggregates with domain walls associated with fcc and hcp phases were identified and quantified. We observed that the use of ethanol facilitates formation of a higher amount of hcp phase in the sample than the use of glycerol or ethylene glycol.

Chandipura virus (CHPV) is found to be associated with sporadic encephalitis outbreaks in humans in India since 1965. We report here, the investigation of CHPV activity during the period of June-August 2015 in the state of Gujarat, which revealed 24.44% positivity among 45 referred encephalitis cases. Phylogenetic study of the G gene sequences of strains from Gujarat 2015 along with available sequences of additional strains from different geographical locations and isolation years (1965-2015), indicated the relatedness of the 2015 strain to a group of the CHPV prototype strain of 1965 and the earliest outbreak strains of 2003. Analyses of selection pressure in the G gene revealed positively selected sites within the signal peptide region and a putative CHPV epitope. These results indicate a probable role of G protein-based immune selection and underline the need for continued surveillance to monitor genetic and antigenic variations in the CHPV., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In normal B-cells, B-cell antigen receptor (BCR) signaling can be negatively regulated by the low-affinity receptor FcγRIIb (CD32b). To better understand the role of FcγRIIb in chronic lymphocytic leukemia (CLL), we correlated its expression on 155 samples from newly-diagnosed Binet A patients with clinical characteristics and outcome. FcγRIIb expression was similar in normal B-cells and leukemic cells, this being heterogenous among patients and within CLL clones. FcγRIIb expression did not correlate with well known prognostic markers [disease stage, serum beta-2 microglobulin (B2M), IGHV mutational status, expression of ZAP-70 and CD38, and cytogenetics] except for a weak concordance with CD49d. Moreover, patients with low FcγRIIb expression (69/155, 44.5%) required therapy earlier than those with high FcγRIIb expression (86/155, 55.5%) (median 151.4 months vs. not reached; p=.071). These results encourage further investigation on the role of FcγRIIb in CLL biology and prognostic significance in larger series of patients.

Management of testicular rupture with a large tunical defect may not be feasible without excision of viable tissue. This study describes the use of a vascularized tunica vaginalis flap, without debridement of viable tissue, in four adolescents. Postoperative ultrasound showed good blood flow and 80% volume of the contralateral testis in two cases. Postoperative exam revealed normal exam and ultrasonographic appearance in three patients, the fourth was demonstrated to be small and undescended during evaluation of contralateral testicular torsion. This approach is recommended in cases of large tunical defects, as it avoids the debridement of viable testicular tissue., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Chandipura virus (CHPV) is a leading cause of acute encephalitis with high mortality in paediatric population in India. A micro-neutralization ELISA (MN-ELISA) assay was developed for the detection of neutralizing antibodies (Nab) against CHPV. This novel method gives read-out in the form of ELISA optical density (OD) values and has a shorter turn-around time (TAT) as compared to the conventional cytopathic effect (CPE)-based neutralization assay (MN-CPE). The assay was developed using an Indian strain of CHPV. During the development of the assay different parameters such as cell count, dilution of primary and secondary antibodies and time point for the test termination were optimized. The new and conventional assays were run in parallel where known positive and negative human serum samples were used as test controls. The conventional MN-CPE was terminated at 48h post-infection (p.i.) and stained with Amido black, while in the new assay, MN-ELISA was terminated at pre-determined 18h p.i. and the infected cells were fixed with acetone, followed by in-situ ELISA. Results of both the assays were compared. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the new test was 100% when compared with the conventional MN-CPE method as a 'gold standard'. The MN-ELISA showed two-fold higher antibody titer in one sample and one sample was additionally positive than MN-CPE ELISA., Conclusion: The MN-ELISA is rapid, more sensitive and read-out of results is by measurement of OD, which could be more accurate than manual observation of reduction in CPE. This novel test could be used as an alternative to the conventional MN-CPE based assay in sero-surveillance and in future vaccine studies., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Congenital lobar emphysema is a one of the rare variety of congenital abnormality of the lung causing respiratory distress in newborns and infants. Herein, we report a case of congenital lobar emphysema in a 3-week-old female admitted to the pediatric intensive care unit with severe respiratory distress. CT scan revealed a hyperinflated, hyperlucent left upper lobe, collapse of the ipsilateral lung and marked mediastinal shift to the right. The patient underwent emergency left upper lobectomy with improvement of her condition in the postoperative period. Histopathological findings confirmed the clinical diagnosis of congenital lobar emphysema with an unusual finding of pulmonary extramedullary hematopoiesis. Congenital lobar emphysema often presents a diagnostic and therapeutic dilemma and therefore requires a high index of suspicion in neonates presenting with respiratory distress to avoid morbidity and mortality.