Structure-property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives.

Presented here is the design, synthesis, and study of a variety of novel hydrogen-bonding-capable π-conjugated N-heteroacenes, 1,4-dihydropyrazino[2,3-b]quinoxaline-2,3-diones (DPQDs). The DPQDs were accessed from the corresponding weakly hydrogen-bonding dicyanopyrazinoquinoxaline (DCPQ) suspensions with excess potassium hydroxide, resulting in moderate to good yields. Both families of compounds were analyzed by UV-vis and NMR spectroscopy, where the consequences of hydrogen bonding capability could be assessed through the structure-property studies. Conversion of the DCPQs into hydrogen-bonding capable DPQDs results in modulation of frontier MO energies, higher molar extinction coefficients, enhanced crystallinity, and on-average higher thermal stability (where in some cases the 5% weight loss temperature is increased by up to 100 °C). Single crystal X-ray diffraction data could be obtained for three DPQDs. One reveals pairwise hydrogen bonding in the solid state as well as a herringbone packing arrangement rendering it a promising candidate for additional studies in the context of organic optoelectronic devices.

CuInS2 quantum dots-based unipolar resistive switching for non-volatile memory applications.

Recent advancements have established quantum dots (QDs) as a promising alternative to conventional bulk materials in the fabrication of nanoscale integrated electronic devices. The appeal of QDs lies in their amenability to low-temperature processes and solution-based methodologies, facilitating the construction of devices with enhanced versatility and efficiency. The ternary metal chalcogenide CuInS2 QDs are one of the foremost, eco-friendly, and highly stable materials. In this study, CuInS2 QDs are employed as a functional layer in a memristive device featuring an Al/CuInS2/ITO configuration. The CuInS2 QDs have been synthesized by a hot injection method and characterized using X-ray diffraction (XRD) and transmission electron microscopy (TEM) to reveal their structural features. The Al/CuInS2/ITO device shows a unipolar resistive switching (RS) behaviour with a high on/off ratio of 105. The switching parameters have been studied for 100 cycles of SET/RESET. The SET and RESET voltages are found to be 1.66 ± 0.25 V and 0.69 ± 0.17 V. The spatial variability of switching parameters in the Al/CuInS2/ITO structure has also been studied for 9 different devices. The device also exhibits unipolar RS behaviour in the optimum temperature range of 0 °C to 50 °C. These outcomes demonstrate the impressive performance of CuInS2 QDs, indicating their potential for future energy-efficient and large-scale non-volatile memory applications.

Effect of different doses of dexmedetomidine as an adjuvant to lignocaine nebulization: A comparative study during awake flexible fiberoptic bronchoscopy.

Background and Aims: Mild to moderate sedation during bronchoscopy is essential for patient safety, comfort during and after the procedure, and to facilitate the performance of the bronchoscopist. Dexmedetomidine is a highly selective, centrally acting α-2 agonist used to provide conscious sedation during various procedures. The aim of this study was to compare the efficacy of three different doses of dexmedetomidine nebulization as an adjuvant to lignocaine during bronchoscopy. Material and Methods: Ninety American Society of Anesthesiologists physical status I/II patients, aged from 18 to 60 years, scheduled for an elective bronchoscopy, were recruited. They were divided into three groups: 30 patients in each group. Group I: The patient was nebulized with a mixture of 4 ml of 4% lignocaine and dexmedetomidine 0.5 µg/kg. Group II: The patient was nebulized with a mixture of 4% lignocaine, 4 ml, and dexmedetomidine, 1 µg/kg. Group III: The patient was nebulized with 4% lignocaine 4 ml and dexmedetomidine 1.5 µg/kg. Results: The mean cough score was (1.17 ± 0.37), (1.40 ± 0.49), and (1.70 ± 0.75) in group III, group II, and group I, respectively. A significant difference was found between the groups. Patients were more comfortable with a statistically significant difference in the comfort score in group III as compared to group II and group I. Conclusion: Dexmedetomidine nebulization in a dose of 1.5 µg/kg (compared to 1 µg/kg or 0.5 µg/kg) as an adjuvant to lignocaine, provides better bronchoscopy conditions and patient satisfaction.

Effect of exogenous melatonin implant on post-thaw semen quality of buffalo bulls.

Melatonin is an intracellular antioxidant of sperm membrane that protects the cells from lipid peroxidation. Yet, its role as an antioxidant on semen quality of buffalo bulls is still obscure. The present study was undertaken to assess the effect of exogenous melatonin implant (18 mg/50 kg bodyweight) on post-thaw sperm characteristics, oxidative stress, endocrinological profiles and fertility of buffalo bulls. Six apparently healthy breeding Murrah buffalo bulls were randomly selected at bull farm, Guru Angad Dev Veterinary and Animal Sciences University for the present study and divided into two groups viz. control (n = 3) and melatonin implanted group (n = 3). A total of 120 ejaculates were collected from bulls of both groups (n = 60 each) throughout the study period. Most beneficial effects of melatonin implants were observed during post-implantation period. The percentages of post-thaw sperm total and progressive motility, viability and mitochondrial membrane potential were higher (p < .05) in melatonin implanted buffalo bulls compared to controls during post-implantation period. Following melatonin implantation, MDA production in post-thaw semen was lower (p < .05) in melatonin implanted group than in control group. Plasma melatonin and testosterone concentrations were higher (p < .05) in buffalo bulls implanted with melatonin as compared to their control counterparts. No differences (p > .05) in plasma LH concentrations were observed in both groups. First service pregnancy rate was 43.3% using semen of melatonin implanted bulls and 30.0% with semen of controls (p > .05). Thus, melatonin was able to protect sperm membrane against oxidative damage and improve post-thaw semen quality, thereby resulting in higher fertilizing potential of spermatozoa.

Comparative evaluation of tocilizumab and itolizumab for treatment of severe COVID-19 in India: a retrospective cohort study.

Background: Itolizumab downregulates the synthesis of proinflammatory cytokines and adhesion molecules by inhibiting CD6 leading to lower levels of interferon-γ, interleukin-6, and tumor necrotic factor-α and reduced T-cell infiltration at inflammatory sites. This study aims to compare the effects of tocilizumab and itolizumab in the management of severe coronavirus disease 2019 (COVID-19). Methods: The study population was adults (>18 years) with severe COVID-19 pneumonia admitted to the intensive care unit receiving either tocilizumab or itolizumab during their stay. The primary outcome was clinical improvement (CI), defined as a two-point reduction on a seven-point ordinal scale in the status of the patient from initiating the drug or live discharge. The secondary outcomes were time until CI, improvement in PO2/FiO2 ratio, best PO2/FiO2 ratio, need for mechanical ventilation after administration of study drugs, time to discharge, and survival days. Results: Of the 126 patients included in the study, 92 received tocilizumab and 34 received itolizumab. CI was seen in 46.7% and 61.7% of the patients in the tocilizumab and itolizumab groups, respectively and was not statistically significant (P=0.134). The PO2/FiO2 ratio was significantly better with itolizumab compared to tocilizumab (median [interquartile range]: 315 [200-380] vs. 250 [150-350], P=0.043). The incidence of serious adverse events due to the study drugs was significantly higher with itolizumab compared to tocilizumab (14.7% vs. 3.3%, P=0.032). Conclusions: The CI with itolizumab is similar to tocilizumab. Better oxygenation can be achieved with itolizumab and it can be a substitute for tocilizumab in managing severe COVID-19.

Comparative evaluation of nebulised dexmedetomidine vs fentanyl for the treatment of post-dural puncture headache (PDPH) in parturients after caesarean section under spinal anaesthesia: A randomised controlled study.

Background and Aims: The incidence of post-dural puncture headache (PDPH) following spinal anaesthesia in the obstetric population is around 0.5%-2%. Hydration, bed rest, caffeine, paracetamol, non-steroid anti-inflammatory drugs, epidural blood patches, etc., are the various modalities used for its management. This study aims to compare nebulised dexmedetomidine versus fentanyl for the treatment of PDPH in parturients after caesarean section under spinal anaesthesia. Methods: Ninety obstetric patients aged 18-35 years with American Society of Anesthesiologists (ASA) physical status II/III and suffering from PDPH as per the criteria of the International Headache Society after caesarean section under spinal anaesthesia were recruited in this double-blinded randomised study. Patients were randomised to Group D (dexmedetomidine 1 µg/kg nebulisation), Group F (fentanyl 1 µg/kg nebulisation), and Group S (saline nebulisation 4mL). The nebulisation was done 12 hourly for 72 hours. Assessment parameters included pain score and the requirement of additional treatment such as paracetamol, caffeine, and epidural blood patch. Analysis of variance test was used for continuous quantitative variables, and the Kruskal-Wallis test was used for quantitative discrete data. Results: The pain scores at 1, 6, 12, 24, 48, and 72 hours following nebulisation were significantly lower in Group D in comparison to groups F and S (P < 0.001). The number of patients requiring additional analgesic therapy was lower in Group D in comparison to patients in other groups (P < 0.001). Conclusion: Dexmedetomidine nebulisation resulted in effective reduction in PDPH symptoms and pain scores. Nebulisation with fentanyl did not alleviate PDPH symptoms when compared to the control group.

Recent Advances in Molecular Pathways and Therapeutic Implications for Peptic Ulcer Management: A Comprehensive Review.

Peptic ulcers, recognized for their erosive impact on the gastrointestinal mucosa, present a considerable challenge in gastroenterology. Epidemiological insights underscore the global prevalence of peptic ulcers, affecting 5-10+% of individuals, with a yearly incidence of 0.3 to 1.9 cases per thousand. Recent decades have witnessed a decline in complications, attributed to improved diagnostics and therapeutic advancements. The review deepens into H. pylori-associated and NSAID-induced ulcers, emphasizing their distinct prevalence in developing and industrialized nations, respectively. Despite advancements, managing peptic ulcers remains challenging, notably in H. pylori-infected individuals facing recurrence and the rise of antibiotic resistance. The pathophysiology unravels the delicate balance between protective and destructive factors, including the intricate molecular mechanisms involving inflammatory mediators such as TNF-α, ILs, and prostaglandins. Genetic and ethnic factors, rare contributors, and recent molecular insights further enhance our understanding of peptic ulcer development. Diagnostic approaches are pivotal, with upper gastrointestinal endoscopy standing as the gold standard. Current treatment strategies focus on H. pylori eradication, NSAID discontinuation, and proton pump inhibitors. Surgical options become imperative for refractory cases, emphasizing a comprehensive approach. Advances include tailored H. pylori regimens, the emergence of vonoprazan, and ongoing vaccine development. Challenges persist, primarily in antibiotic resistance, side effects of acid suppressants, and translating natural compounds into standardized therapies. Promising avenues include the potential H. pylori vaccine and the exploration of natural compounds, with monoterpenes showing therapeutic promise. This review serves as a compass, guiding healthcare professionals, researchers, and policymakers through the intricate landscape of peptic ulcer management.

Circuit-based intervention corrects excessive dentate gyrus output in the fragile X mouse model.

Abnormal cellular and circuit excitability is believed to drive many core phenotypes in fragile X syndrome (FXS). The dentate gyrus is a brain area performing critical computations essential for learning and memory. However, little is known about dentate circuit defects and their mechanisms in FXS. Understanding dentate circuit dysfunction in FXS has been complicated by the presence of two types of excitatory neurons, the granule cells and mossy cells. Here we report that loss of FMRP markedly decreased excitability of dentate mossy cells, a change opposite to all other known excitability defects in excitatory neurons in FXS. This mossy cell hypo-excitability is caused by increased Kv7 function in Fmr1 knockout (KO) mice. By reducing the excitatory drive onto local hilar interneurons, hypo-excitability of mossy cells results in increased excitation/inhibition ratio in granule cells and thus paradoxically leads to excessive dentate output. Circuit-wide inhibition of Kv7 channels in Fmr1 KO mice increases inhibitory drive onto granule cells and normalizes the dentate output in response to physiologically relevant theta-gamma coupling stimulation. Our study suggests that circuit-based interventions may provide a promising strategy in this disorder to bypass irreconcilable excitability defects in different cell types and restore their pathophysiological consequences at the circuit level.

Gas chromatography tandem mass spectrometric analysis of alkylphosphonofluoridic acids as verification targets of nerve agents.

Alkylphosphonofluoridic Acids (APFA) are the major thermal degradation products of G- and A-series nerve agents and thus play a vital role in the verification analysis of Chemical Weapons Convention. Present study focuses on the development of sample clean-up, derivatization procedures and gas chromatography tandem mass spectrometric analysis of APFA in aqueous samples. APFA were found to be much more delicate than the corresponding alkylphosphonic acids and thus required subtle optimizations. Retention of analytes on silica and polymer-based anion exchangers followed by elution under alkaline conditions yielded best recoveries. Elution under acidic conditions led to partial or complete degradation of the analytes to alkylphosphonic acids. Silylation reactions, particularly with MTBSTFA were found the best in terms of chromatographic responses and resolution of the derivative peaks. Methylations with diazomethane, which requires acidic reaction media, failed to produce desired yields of the derivatives. Under optimized conditions, the analytes produced the recoveries ranging from 76.9 to 94.5% with RSD ≤9.2%. The best LOD's in the tandem mass spectrometric analysis ranged from 13 to 56 ng/ml. The applicability of the method was tested by spiking the analytes in the retained aqueous samples received for the 52nd proficiency test conducted by the Organization for the Prohibition of Chemical Weapons (OPCW).

Modified Thoracolumbar Interfascial Plane Block Versus Erector Spinae Plane Block in Patients Undergoing Spine Surgeries: A Randomized Controlled Trial.

BACKGROUND: Lumbar spine surgery is associated with significant postoperative pain. Interfascial plane blocks, such as erector spinae plane (ESP) and thoracolumbar interfascial plane (TLIP) blocks, can play a significant role in multimodal analgesic regimens. METHODS: Sixty patients aged 18 to 60 years undergoing elective single or double-level lumbar discectomy or primary lumbar laminoplasty were recruited into this randomized double­blind study. All patients received general anesthesia and were randomly allocated to either modified TLIP (mTLIP) block (group M) or ESP block (group E). Postoperative and intraoperative fentanyl consumption, and postoperative pain scores, were recorded. RESULTS: Total 48 h postoperative fentanyl consumption was higher in Group M (189.66±141.11 µg) than in Group E (124.16±80.83 µg; P =0.031). In the first 24 postoperative hours, fentanyl consumption was higher in Group M (150.3±120.9 µg) than in group E (89.9±65.3 µg; P =0.01) but was similar between groups in postoperative hours 24to 48 (39.0±20.2 µg versus 34.7±17.1 µg in group M and group E, respectively; P =0.37). Additional intraoperative fentanyl requirement was 57.66±21.76 µg in group M compared with 40.33±21.89 µg in group E ( P <0.01). Postoperative pain scores were higher in group M than in group E at 1, 2, 4, 6, 12, and 24 hours postoperatively ( P <0.001), but similar at 48 hours ( P =0.164). CONCLUSION: Compared with the mTLIP block, the ESP block was associated with lower pain scores and a small decrease in perioperative fentanyl consumption in patients undergoing lumbar spine surgeries. Both blocks could form a part of a multimodal analgesic regimen in spine surgery patients.

Unilateral Syndactyly, Hemihypertrophy, and Hyperpigmentation with Mosaic 2q35 Deletion.

Pigmentary mosaicism (PM) is a clinical condition of dyspigmentation with chromosomal abnormality. PM presents with both cutaneous and extracutaneous manifestation. Hypomelanosis of Ito and linear and whorled nevoid hypermelanosis are syndromic disorders in which PM is one of the manifestations. We present a case of a 1-year-old child with a unique constellation of symptoms of unilateral syndactyly, hemihypertrophy, and skin hyperpigmentation. Karyotype from peripheral blood was normal. We found genetic aberration (mosaic 2q35 deletion) in the present case from fibroblast cultured from the affected area. This unique constellation of symptoms was previously reported once but genetic study was not done from the affected tissue. This case highlights the need of considering fibroblast culture-based genetic study rather than doing simple karyotype from peripheral blood. Genetic study also established the molecular basis of symptoms in the above case.

Additional intracervical prostaglandin reduces induction to calving time in buffaloes affected with incomplete cervical dilatation post-uterine detorsion.

Conventional induction protocol (CIP) of calving in buffaloes employs the intramuscular (IM) administration of dexamethasone (40 mg) and cloprostenol sodium (500 µg). If there is no progression in terms of cervical dilatation, then a second dose of cloprostenol sodium (500 µg) is administered intramuscularly. This protocol possesses certain demerits: (1) a wide range of response time intervals, and (2) increased risk of fetal membrane retention. Considering the cervix as a caudal continuation of the myometrium with its own contractile potential, and the limitations of CIP, we developed intracervical (IC) drug administration route in buffaloes. The proposed technique was evaluated for its use in a total of 22 cases of incomplete cervical dilatation in uterine torsion-affected buffaloes (IC-14 and IM-8). In addition to CIP, the IC group received an intracervical injection of cloprostenol sodium (500 µg) at the start of the experiment whereas the IM group received an extra intramuscular dose of cloprostenol sodium (500 µg) either after 24 h or when no progression in cervical dilatation is noticed. Surprisingly, the average response time during the experiment in the IC group was 5.8 h shorter (p < 0.000) than in the IM group (IC-5.7 ± 0.17 h vs. IM-11.9 ± 0.74 h). The duration from calving to fetal membrane expulsion (IC-12.8 ± 0.60 h vs. IM-17.5 ± 1.40 h; p < 0.002) and incidence of retention of fetal membrane were also less in the IC group (57.1% vs. 87.5%). The proposed intracervical drug administration potentiates cervical dilatation and can be regarded as a safe, effective, and feasible technique for attaining reliable results.

Exploring the brain epitranscriptome: perspectives from the NSAS summit.

Increasing evidence reinforces the essential function of RNA modifications in development and diseases, especially in the nervous system. RNA modifications impact various processes in the brain, including neurodevelopment, neurogenesis, neuroplasticity, learning and memory, neural regeneration, neurodegeneration, and brain tumorigenesis, leading to the emergence of a new field termed neuroepitranscriptomics. Deficiency in machineries modulating RNA modifications has been implicated in a range of brain disorders from microcephaly, intellectual disability, seizures, and psychiatric disorders to brain cancers such as glioblastoma. The inaugural NSAS Challenge Workshop on Brain Epitranscriptomics hosted in Crans-Montana, Switzerland in 2023 assembled a group of experts from the field, to discuss the current state of the field and provide novel translational perspectives. A summary of the discussions at the workshop is presented here to simulate broader engagement from the general neuroscience field.

Theileria annulata Induced Bilateral Ocular Signs in Cattle and Its Successful Therapeutic Management: A Case Report.

Bovine tropical theileriosis is one of the potentially fatal disease of dairy cattle, which is caused by hemoparasite Theleria annulata. About seven years old cross-bred cow was presented with complaint of pyrexia, inappetance, lacrimation and ocular swelling since last 5 days. The clinical examination showed elevated rectal temperature (39.4 °C), mild enlarged pre-scapular lymph nodes, bilateral bulging of temporal fossa, protruded pale and icteric conjunctivae of the eyes with lacrimation and presence of ticks on body. The case was suspected for haemoprotozoan disease. Blood and serum sample were collected for hematological, blood smear examination and molecular examination (PCR), and biochemical analysis respectively. Microscopic examination of blood smear revealed intra-erythrocytic signet ring shaped periplasm of Theileria annulata. Hemato-biochemical examination revealed anemia, hypoproteinemia, hypoalbuminemia and jaundice. Further, PCR assay was done using T. annulata-specific primer pair, Cyto b1 gene targeting the amplicon of 312 bp showed specific band on Gel-electrophoresis. Therapeutic regimen was started with Buparvaquone @ 2.5 mg/kg body weight IM single dose followed by Oxytetracycline @ 10 mg/kg body weight IV in 500 ml of NS for 5 days and Prednisolone @ 0.25 mg/kg body weight IM for 3 days along with supportive therapy. The cattle well responded to the therapy and complete regression of ocular signs was observed within one week of treatment.

Circuit-based intervention corrects excessive dentate gyrus output in the Fragile X mouse model.

Abnormal cellular and circuit excitability is believed to drive many core phenotypes in fragile X syndrome (FXS). The dentate gyrus is a brain area performing critical computations essential for learning and memory. However, little is known about dentate circuit defects and their mechanisms in FXS. Understanding dentate circuit dysfunction in FXS has been complicated by the presence of two types of excitatory neurons, the granule cells and mossy cells. Here we report that loss of FMRP markedly decreased excitability of dentate mossy cells, a change opposite to all other known excitability defects in excitatory neurons in FXS. This mossy cell hypo-excitability is caused by increased Kv7 function in Fmr1 KO mice. By reducing the excitatory drive onto local hilar interneurons, hypo-excitability of mossy cells results in increased excitation/inhibition ratio in granule cells and thus paradoxically leads to excessive dentate output. Circuit-wide inhibition of Kv7 channels in Fmr1 KO mice increases inhibitory drive onto granule cells and normalizes the dentate output in response to physiologically relevant theta-gamma coupling stimulation. Our study suggests that circuit-based interventions may provide a promising strategy in this disorder to bypass irreconcilable excitability defects in different cell types and restore their pathophysiological consequences at the circuit level.