Low-latency gravitational wave alert products and their performance at the time of the fourth LIGO-Virgo-KAGRA observing run.

Multimessenger searches for binary neutron star (BNS) and neutron star-black hole (NSBH) mergers are currently one of the most exciting areas of astronomy. The search for joint electromagnetic and neutrino counterparts to gravitational wave (GW)s has resumed with ALIGO's, AdVirgo's and KAGRA's fourth observing run (O4). To support this effort, public semiautomated data products are sent in near real-time and include localization and source properties to guide complementary observations. In preparation for O4, we have conducted a study using a simulated population of compact binaries and a mock data challenge (MDC) in the form of a real-time replay to optimize and profile the software infrastructure and scientific deliverables. End-toend performance was tested, including data ingestion, running online search pipelines, performing annotations, and issuing alerts to the astrophysics community. We present an overview of the low-latency infrastructure and the performance of the data products that are now being released during O4 based on the MDC. We report the expected median latency for the preliminary alert of full bandwidth searches (29.5 s) and show consistency and accuracy of released data products using the MDC. We report the expected median latency for triggers from early warning searches (-3.1 s), which are new in O4 and target neutron star mergers during inspiral phase. This paper provides a performance overview for LIGO-Virgo-KAGRA (LVK) low-latency alert infrastructure and data products using theMDCand serves as a useful reference for the interpretation of O4 detections.

iNOS regulates hematopoietic stem and progenitor cells via mitochondrial signaling and is critical for bone marrow regeneration.

Hematopoietic stem cells (HSCs) replenish blood cells under steady state and on demand, that exhibit therapeutic potential for Bone marrow failures and leukemia. Redox signaling plays key role in immune cells and hematopoiesis. However, the role of reactive nitrogen species in hematopoiesis remains unclear and requires further investigation. We investigated the significance of inducible nitric oxide synthase/ nitric oxide (iNOS/NO) signaling in hematopoietic stem and progenitor cells (HSPCs) and hematopoiesis under steady-state and stress conditions. HSCs contain low levels of NO and iNOS under normal conditions, but these increase upon bone marrow stress. iNOS-deficient mice showed subtle changes in peripheral blood cells but significant alterations in HSPCs, including increased HSCs and multipotent progenitors. Surprisingly, iNOS-deficient mice displayed heightened susceptibility and delayed recovery of blood progeny following 5-Fluorouracil (5-FU) induced hematopoietic stress. Loss of quiescence and increased mitochondrial stress, indicated by elevated MitoSOX and MMPhi HSCs, were observed in iNOS-deficient mice. Furthermore, pharmacological approaches to mitigate mitochondrial stress rescued 5-FU-induced HSC death. Conversely, iNOS-NO signaling was required for demand-driven mitochondrial activity and proliferation during hematopoietic recovery, as iNOS-deficient mice and NO signaling inhibitors exhibit reduced mitochondrial activity. In conclusion, our study challenges the conventional view of iNOS-derived NO as a cytotoxic molecule and highlights its intriguing role in HSPCs. Together, our findings provide insights into the crucial role of the iNOS-NO-mitochondrial axis in regulating HSPCs and hematopoiesis.

Litsea glutinosa extract promotes fracture healing and prevents bone loss via BMP2/SMAD1 signaling.

Estrogen deficiency is one of the main causes for postmenopausal osteoporosis. Current osteoporotic therapies are of high cost and associated with serious side effects. So there is an urgent need for cost-effective anti-osteoporotic agents. Anti-osteoporotic activity of Litsea glutinosa extract (LGE) is less explored. Moreover, its role in fracture healing and mechanism of action is still unknown. In the present study we explore the osteoprotective potential of LGE in osteoblast cells and fractured and ovariectomized (Ovx) mice models. Alkaline phosphatase (ALP), MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and mineralization assays revealed that LGE treatment increased osteoblast cell differentiation, viability and mineralization. LGE treatment at 0.01 µg increased the expression of BMP2, PSMAD, RUNX2 and type 1 col. LGE also mitigated RANKL-induced osteoclastogenesis. Next, drill hole injury Balb/C mice model was treated with LGE for 12 days. Micro-CT analysis and Calcein labeling at the fracture site showed that LGE (20 mg/kg) enhanced new bone formation and bone regeneration, also increased expression of BMP2/SMAD1 signaling genes at fracture site. Ovx mice were treated with LGE for 1 month. µCT analysis indicated that the treatment of LGE at 20 mg/kg dose prevented the alteration in bone microarchitecture and maintained bone mineral density and bone mineral content. Treatment also increased bone strength and restored the bone turnover markers. Furthermore, in bone samples, LGE increased osteogenesis by enhancing the expression of BMP2/SMAD1 signaling components and decreased osteoclast number and surface. We conclude that LGE promotes osteogenesis via modulating the BMP2/SMAD1 signaling pathway. The study advocates the therapeutic potential of LGE in osteoporosis treatment.

Design, synthesis and biological evaluation of novel pyrimidine derivatives as bone anabolic agents promoting osteogenesis via the BMP2/SMAD1 signaling pathway.

Anti-resorptive inhibitors such as bisphosphonates are widely used but they have limited efficacy and serious side effects. Though subcutaneous injection of teriparatide [PTH (1-34)] is an effective anabolic therapy, long-term repeated subcutaneous administration is not recommended. Henceforth, orally bio-available small-molecule-based novel therapeutics are unmet medical needs to improve the treatment. In this study, we designed, synthesized, and carried out a biological evaluation of 31 pyrimidine derivatives as potent bone anabolic agents. A series of in vitro experiments confirmed N-(5-bromo-4-(4-bromophenyl)-6-(2,4,5-trimethoxyphenyl)pyrimidin-2-yl)hexanamide (18a) as the most efficacious anabolic agent at 1 pM. It promoted osteogenesis by upregulating the expression of osteogenic genes (RUNX2 and type 1 col) via activation of the BMP2/SMAD1 signaling pathway. In vitro osteogenic potential was further validated using an in vivo fracture defect model where compound 18a promoted the bone formation rate at 5 mg kg-1. We also established the structure-activity relationship and pharmacokinetic studies of 18a.

Non-surgical correction of knee flexion deformity in persons with haemophilia: A staged multidisciplinary approach.

INTRODUCTION: Flexion deformity of the knee is a common complication following recurrent haemarthrosis in persons with haemophilia (PWH) on episodic factor replacement therapy, restricting independent mobility. There is limited literature on the comprehensive management of this condition. This report provides the outcome of a staged multidisciplinary approach for the correction of knee flexion deformity (KFD) even in limited resource settings. PATIENTS AND METHODS: The data of 49 consecutive PWH who were treated for KFD were analysed. The approach included graded physical therapy (PT), followed by serial casting and/or mobilisation under anaesthesia (MUA). MUA was done in carefully selected knees. Surgical correction was opted when non-surgical methods failed. RESULTS: Of the 49 patients (55 knees), with a median KFD of 40 degrees (range: 10-90), 26/55 (47%) were corrected by graded PT. With serial casting, 9/19 (47%) knees had their KFD corrected. MUA was done for 11 knees of which five achieved correction (45%). Surgical correction was required for only seven knees (12.7%). Following this approach, KFD improved from 40 degrees (range: 10-90) to 15 degrees (range: 0-40), with only minor loss of flexion from 105 (range: 60-155) to 90 degrees (range: 30-150). Out of 55 KFD, 46 (83.6%) KFD were corrected; non-surgical, 39 (70.9%) and surgery, seven (12.7%). The remaining patients (nine KFD; 16.4%) were able to achieve their functional goal despite not meeting the correction criteria. CONCLUSION: This study shows that in PWH, functionally significant KFD correction can be achieved in about 71%, through non-surgical methods, even without prophylactic factor replacement.

Bone Fracture-healing Properties and UPLC-MS Analysis of an Enriched Flavonoid Fraction from Oxystelma esculentum.

Oxystelma esculentum has been used as a folk medicine to treat jaundice, throat infections, and skin problems. In the current study, the bone fracture-healing properties of a flavonoid-enriched fraction (Oxy50-60F) of O. esculentum were investigated in Swiss mice using a drill-hole injury model. Oxy50-60F (1 mg/kg/day, 5 mg/kg/day, and 10 mg/kg/day) was administered orally (from the next day) after a 0.6 mm drill-hole injury in mice femur mid-diaphysis for 7 days and 14 days. Parathyroid hormone (40 µg/kg; 5 times/week) was given subcutaneously as the positive control. Confocal imaging for bone regeneration, micro-architecture of femur bones, ex vivo mineralization, hematoxyline and eosin staining, measurement of reactive oxygen species, and gene expression of osteogenic and anti-inflammatory genes were studied. Quercetin, kaempferol, and isorhamnetin glycosides were identified in the active fraction using mass spectrometry techniques. Our results confirm that Oxy50-60F treatment promotes fracture healing and callus formation at drill-hole sites and stimulates osteogenic and anti-inflammatory genes. Oxy50-60F administration to fractured mice exhibited significantly better micro-CT parameters in a dose-dependent manner and promoted nodule mineralization at days 7 and 14 post-injury. Oxy50-60F also prevents ROS generation by increasing expression of the SOD2 enzyme. Overall, this study reveals that Oxy50-60F has bone regeneration potential in a cortical bone defect model, which supports its use in delayed-union and non-union fracture cases.

Biomechanical properties of cornea and ocular aberrations in myopic eyes.

PURPOSE: To study the correlation of corneal topography, corneal biomechanical properties, and ocular aberrations with the magnitude of refractive error in myopic eyes. METHODS: All myopic patients attending the clinic for refractive surgery were recruited. Data recorded included visual acuity, axial length (AL), central corneal thickness (CCT), manifest refraction spherical equivalent (MRSE), topography (Pentacam - Oculus), corneal biomechanical factors [ocular response analyzer (ORA)], and optical aberrations (iTrace). They were further categorized into group 1 (suitable for femto-LASIK) and group 2 (unsuitable for femto-LASIK). RESULTS: Sixty eyes (30 myopes) of mean age 22.78 ± 2.71 years were enrolled. A negative correlation of refractive error was noted with AL (ρ = -0.9; P < 0.001), total aberrations (ρ = 0.53; P < 0.001), and lower-order aberrations (LOA) (ρ = 0.54; P < 0.001). A strongly positive correlation was noted between CCT and corneal hysteresis (CH) (ρ = 0.63; P < 0.001), CCT and CRF (ρ = 0.56; P < 0.001), CH and corneal resistance factor (CRF) (ρ = 0.83; P < 0.001), and Goldmann equivalent intraocular pressure (IOPg) and corneal compensated intraocular pressure (IOPcc) (ρ = 0.78; P < 0.001). An increase in higher-order aberrations (HOAs) as well as lower-order aberrations (LOAs) was noted with increasing sim-K [HOA (r = 0.73, P = 0.001); LOA (r = 0.601, P = 0.014)] and increasing CRF [HOA (r = 0.5, P = 0.006); LOA (r = 0.732, P = 0.001)] in group 2. The amount of refractive error, axial length, central corneal thickness, and sim-K were significantly different in the two groups. CONCLUSION: Increasing degree of myopia is associated with an increase in axial length, total aberrations, and lower-order aberrations. Corneal biomechanical parameters have a strong correlation with each other. Lower corneal biomechanics are noted in high myopes as they have weaker and thinner corneas. Corneal biomechanics and ocular aberrations do not differ significantly between cases suitable for femto-LASIK and cases unsuitable for femto-LASIK.

Surgical Resection of Retrosternal Goitre: The Four-Finger Technique.

Retrosternal goitre (RSG) is a thyroid gland with more than 50% of its mass located below the thoracic inlet. Pre-operative Computed Tomography can visualise the anatomical relations between the RSG and each mediastinal component, and the level of extension. Most cases of RSG can be resected via the cervical approach, as the thoracic approach carries a greater risk of complications. We describe a four finger technique for total thyroidectomy in five cases of RSG through a neck incision, without the need for a sternotomy. The recurrent laryngeal nerve (RLN) was identified early in the Baehr's triangle. The thyroid was mobilised in the neck by ligation of the feeding vessels and separated from the tracheal attachments. The retrosternal portion was then delivered into the neck by blunt dissection, keeping two fingers of each hand close to the thyroid gland. The RLN and parathyroids were identified early in the surgery to avoid the complications of hoarseness and hypoalcemia, respectively.

Comparative Evaluation of Intracanal Smear Layer Removal by Different Root Canal Irrigants: A Scanning Electron Microscope Study.

Aim: The purpose of the study is to compare and evaluate the efficacy of different root canal irrigants-100, 75, 50, and 25% neem extract, 100, 75, 50, and 25% apple cider vinegar (ACV), a combination of 5.25% sodium hypochlorite (NaOCl) and 17% ethylenediaminetetraacetic acid (EDTA), and saline on smear layer removal using a scanning electron microscope (SEM). Materials and methods: A total of 80 freshly extracted single-rooted teeth were collected and divided into 10 groups-group I: normal saline (negative control), group II: NaOCl with EDTA (positive control), group III: 100% neem extract, group IV: 75% neem extract, group V: 50% neem extract, group VI: 25% neem extract, group VII: 100% ACV, group VIII: 75% ACV, group IX: 50% ACV, and group X: 25% ACV. The samples were irrigated with a specific group of irrigants, then split in a longitudinal axis and processed for analysis in an SEM. Microphotographs were obtained and scored according to Torabinejad et al. Results: Microphotographs were assessed and showed that 100% neem extract was similar to NaOCl with EDTA, followed by 75% neem extract and 100% ACV. Conclusion: This study showed that 100% neem extract removed the smear layer, similar to the NaOCl with EDTA. How to cite this article: Sudhakar S, Gupta N, Ghambir N, et al. Comparative Evaluation of Intracanal Smear Layer Removal by Different Root Canal Irrigants: A Scanning Electron Microscope Study. Int J Clin Pediatr Dent 2023;16(4):633-638.

The Applications of 2D Materials for Electrochemical Biosensing, Drug Delivery, and Environmental Monitoring.

Two-dimensional (2D) nanomaterials (NMs) have diverse mechanical, chemical and optical properties due to which they have received a lot of attention in various fields such as biosensors, imaging, tissue engineering, drug delivery, etc. A thorough understanding of the synthetic procedure, physical properties and electrochemical properties of 2D materials will be quite useful in the development of novel and high-efficient electrocatalysts for the electroanalytical application of our interest. This review article summarises the synthesis and application of graphene, graphitic carbon nitride, transition metal dichalcogenides and phosphorene for electrochemical biosensing, drug delivery application and environmental monitoring. Numerous synthetic approaches which have been adopted to synthesize the 2D materials have been covered and discussed. Also, the reasons behind the catalytic activity of various types of 2D materials and their application as electrode modifier for the development of an efficient biosensor for the point-of-care analysis of biomolecule and drug delivery and environmental monitoring have been discussed in detail. This review article will give valuable information and future insights to the researchers working in the field of biosensor, drug delivery and environmental monitoring. We anticipate that this review may be of significance for the field to understand the properties as well as the electroanalytical applications of 2D materials, especially in biosensing, drug and environmental monitoring.

Oestrogen treatment restores dentate gyrus development in premature newborns by IGF1 regulation.

Prematurely-born infants cared for in the neonatal units suffer from memory and learning deficits. Prematurity diminishes neurogenesis and synaptogenesis in the hippocampal dentate gyrus (DG). This dysmaturation of neurons is attributed to elevated PSD95, NMDR2A, and IGF1 levels. Since oestrogen treatment plays key roles in the development and plasticity of DG, we hypothesized that 17ß-estradiol (E2) treatment would ameliorate neurogenesis and synaptogenesis in the DG, reversing cognitive deficits in premature newborns. Additionally, E2-induced recovery would be mediated by IGF1 signalling. These hypotheses were tested in a rabbit model of prematurity and nonmaternal care, in which premature kits were gavage-fed and reared by laboratory personnel. We compared E2- and vehicle-treated preterm kits for morphological, molecular, and behavioural parameters. We also treated kits with oestrogen degrader, RAD1901, and assessed IGF1 signalling. We found that E2 treatment increased the number of Tbr2+ and DCX+ neuronal progenitors and increased the density of glutamatergic synapses in the DG. E2 treatment restored PSD95 and NMDAR2A levels and cognitive function in preterm kits. Transcriptomic analyses showed that E2 treatment contributed to recovery by influencing interactions between IGF1R and neurodegenerative, as well as glutamatergic genes. ERα expression was reduced on completion of E2 treatment at D7, followed by D30 elevation. E2-induced fluctuation in ERα levels was associated with a reciprocal elevation in IGF1/2 expression at D7 and reduction at D30. ERα degradation by RAD1901 treatment enhanced IGF1 levels, suggesting ERα inhibits IGF1 expression. E2 treatment alleviates the prematurity-induced maldevelopment of DG and cognitive dysfunctions by regulating ERα and IGF1 levels.

Role of RhoG as a regulator of cellular functions: integrating insights on immune cell activation, migration, and functions.

BACKGROUND: RhoG is a multifaceted member of the Rho family of small GTPases, sharing the highest sequence identity with the Rac subfamily members. It acts as a molecular switch, when activated, plays a central role in regulating the fundamental processes in immune cells, such as actin-cytoskeleton dynamics, transendothelial migration, survival, and proliferation, including immunological functions (e.g., phagocytosis and trogocytosis) during inflammatory responses. METHOD: We have performed a literature review based on published original and review articles encompassing the significant effect of RhoG on immune cell functions from central databases, including PubMed and Google Scholar. RESULTS AND CONCLUSIONS: Recently published data shows that the dynamic expression of different transcription factors, non-coding RNAs, and the spatiotemporal coordination of different GEFs with their downstream effector molecules regulates the cascade of Rho signaling in immune cells. Additionally, alterations in RhoG-specific signaling can lead to physiological, pathological, and developmental adversities. Several mutations and RhoG-modulating factors are also known to pre-dispose the downstream signaling with abnormal gene expression linked to multiple diseases. This review focuses on the cellular functions of RhoG, interconnecting different signaling pathways, and speculates the importance of this small GTPase as a prospective target against several pathological conditions.

Maternal Zika Virus Infection in the First Trimester and Fetal Stigmata in the Third Trimester.

Zika is a flavivirus that is transmitted primarily by the bite of an infected Aedes mosquito. It can also be transmitted by blood transfusion, sexual contact, and from an infected mother to the unborn baby. Zika virus infection is of particular concern in pregnancy as transplacental transmission of the virus has the potential to cause significant fetal morbidity. Ultrasonography plays a pivotal role in the fetal surveillance of a pregnant woman infected with Zika. There have been outbreaks of Zika virus infection in various parts of India, the most recent occurring in Kanpur in November 2021. We report a case of a primigravida who had Zika virus infection during the first trimester of pregnancy but the fetus presented with the sequelae of infection in the third trimester. This report highlights the sonographic red flags for fetal Zika infection and the importance of serial monitoring in pregnant women exposed to Zika virus.

An adding up of an exceptionally rare case report: Primary Squamous cell carcinoma of Jejunum from North India.

Squamous cell carcinoma (SCC) of lower gastrointestinal tract is a rare tumor and duodenum is the most common site of involvement. In addition, involvement of jejunum by SCC is further exceptionally rare, and only nominal cases are present world literature. Being a very infrequent finding, a clinician and a pathologist must be aware of this rare entity. Diagnosis requires histopathology along with clinico-radiological correlation since merely histopathology is unable to differentiate between primary and metastatic tumor. Treatment modality is totally different in primary and secondary tumor of lower gastrointestinal tract. Being an extremely rare case of primary SCC of jejunum in an elderly female makes it eligible to be acknowledged at the global platform of medical literature.

Monitoring genotoxic, biochemical and morphotoxic potential of penoxsulam and the protective role of European blueberry (Vaccinium myrtillus L.) extract.

The present study aimed at exploring to explore the penoxsulam toxicity and protective effects of blueberry extract in roots of Allium cepa L. The effective concentration (EC50) of penoxsulam was determined at 20 µg/L by the root growth inhibition test as the concentration reducing the root length by 50%. The bulbs of A. cepa L. were treated with tap water, blueberry extracts (25 and 50 mg/L), penoxsulam (20 µg/L) and combination of blueberry extracts (25 and 50 mg/L) with penoxsulam (20 µg/L) for 96 h. The results revealed that penoxsulam exposure inhibited cell division, rooting percentage, growth rate, root length and weight gain in the roots of A. cepa L. In addition, it induced chromosomal anomalies such as sticky chromosome, fragment, unequal distribution of chromatin, bridge, vagrant chromosome and c-mitosis and DNA strand breaks. Further, penoxsulam treatment enhanced malondialdehyde content and SOD, CAT and GR antioxidant enzyme activities. Molecular docking results supported the up-regulation of antioxidant enzyme SOD, CAT and GR. Against all these toxicity, blueberry extracts reduced penoxsulam toxicity in a concentration-dependent manner. The highest amount of recovery for cytological, morphological and oxidative stress parameters was observed when using blueberry extract at a concentration of 50 mg/L. In addition, blueberry extracts application showed a positive correlation with weight gain, root length, mitotic index and rooting percentage whereas a negative correlation with micronucleus formation, DNA damage, chromosomal aberrations, antioxidant enzymes activities and lipid peroxidation indicating its protecting effects. As a result, it has been seen that the blueberry extract can tolerate all these toxic effects of penoxsulam depending on the concentration, and it has been understood that it is a good protective natural product against such chemical exposures.

Rainfed assessment of foxtail millet (Setaria italica L. beauv) germplasms through genotyping and principal component analysis.

Introduction: Foxtail millet (Setaria italica L. beauv) is an important crop in underdeveloped countries; however, yield levels are low. The use of varied germplasm in a breeding approach is critical for increasing productivity. Foxtail millet can be cultivated effectively in a wide range of environmental circumstances but it is best suited to hot and dry climates. Methods: In the current study, multivariant traits were used to define 50 genotypes in the first year and 10 genotypes in the second year. The phenotypic correlations among all traits in the entire germplasm were assessed, and the data acquired for all quantitative characters were subjected to analysis of variance for augmented block design. Furthermore, WINDOWS STAT statistical software was used to carry out a principal component analysis (PCA). The presence of substantial variations in most symptoms was shown by analysis of variance. Results: Genotypic coefficient of variation (GCV) projections for grain yields were the highest, followed by panicle lengths and biological yields. Plant height and leaf length had the highest PCV estimates, followed by leaf width. Low GCV and phenotypic coefficient of variation (PCV) were measured as leaf length and 50% flowering in days. According to the PCV study, direct selection based on characters, panicle weight, test weight, and straw weight had a high and positive effect on grain yield per plant in both the rainy and summer seasons, indicating the true relationship between these characters and grain yield per plant, which aids indirect selection for these traits and thus improves grain yield per plant. Variability in foxtail millet germplasm enables plant breeders to effectively select appropriate donor lines for foxtail millet genetic improvement. Discussion: Based on the average performance of genotypes considered superior in terms of grain yield components under Prayagraj agroclimatic conditions, the best five genotypes were: Kangni-7 (GS62), Kangni-1 (G5-14), Kangni-6 (GS-55), Kangni-5 (GS-389), and Kangni-4 (GS-368).

Synthesis of amide derivatives of 3-aryl-3H-benzopyrans as osteogenic agent concomitant with anticancer activity.

The present study reports a series of 3-aryl-3H-benzopyran-based amide derivatives as osteogenic agents concomitant with anticancer activity. Six target compounds viz 22e, 22f, 23i, and 24b-d showed good osteogenic activity at 1 pM and 100 pM concentrations. One of the potential molecules, 24b, effectively induced ALP activity and mRNA expression of osteogenic marker genes at 1 pM and bone mineralization at 100 pM concentrations. These molecules also presented significant growth inhibition of osteosarcoma (MG63) and estrogen-dependent and -independent (MCF-7 and MDA-MB-231) breast cancer cells. The most active compound, 24b, inhibited the growth of all the cancer cells within the IC50 10.45-12.66 µM. The mechanistic studies about 24b showed that 24b induced apoptosis via activation of the Caspase-3 enzyme and inhibited cancer cell migration. In silico molecular docking performed for 24b revealed its interaction with estrogen receptor-ß (ER-ß) preferentially.