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Aims: Local failure remains the major concern in grade 4 glioma or glioblastoma (GBM). Pilot studies have shown a radiotherapy (RT) dose-response relationship in GBM. Here we present our preliminary data of RT dose escalation using 68 Ga-Pentixafor PET scan. High 68 Ga-pentixafor uptake in glioma cells helps in sharp demarcation between tumour and normal brain., Materials and Methods: This phase II prospective study was conducted from 2018 to 2020. Thirty, biopsy-proven cases of grade 4 glioma were included. All patients underwent post-operative MRI of the brain and 68 Ga-Pentixafor PET scan. RT was planned in 2-phases. Phase-1 GTV (GTV1) comprised of T2/flair abnormality, PET-avid disease and post-op cavity. A margin of 2cm was given to GTV-1 to create phase-1 CTV (CTV1), which was further expanded to 0.5cm to generate phase-1 PTV (PTV1). A radiation dose of 46Gy/23fr was prescribed to PTV-1. Phase-2 GTV (GTV2) consisted of CT/MRI contrast-enhancing lesion, PET avid disease and post-op cavity. A margin of 0.5 cm was given to GTV2 to create phase-2 CTV (CTV2) which was expanded to 0.5 cm to create phase-2 PTV (PTV2). RT dose of 14 Gy/7 fr was prescribed to PTV2. PET avid disease was delineated as GTV PET and a margin of 3mm was given to generate PTV-PET which received escalated RT dose of 21 Gy/7fr by simultaneous integrated boost (SIB) in phase 2 (Total dose to PTV PET = 67 Gy/30 fr). All patients received concurrent and adjuvant temozolomide. The data was prospectively maintained in Microsoft Excel sheet. SPSS v 23 was used for statistical analysis. The primary endpoints were estimation of the overall survival (OS) and progression-free survival (PFS), and secondary endpoint was to measure the incidence of radiation necrosis. Categorical variables were reported as frequency and percentage and quantitative variables were reported as median and range., Results: Data from thirty patients were analysed. A median OS of 23 months was observed with estimated 1, 2 and 3 years OS of 90%, 40% and 17.8% respectively. A significant association of OS was seen with the extent of surgery (p = 0.04) and kernofsky performance status (p = 0.007). No patient developed significant radiation necrosis., Conclusions: The index study did not show any survival benefit from dose escalation RT. However, all of the patients tolerated the treatment well and none of them developed radiation necrosis. Considering the small sample size as a limitation of the index study, the role of 68 Ga-pentixafor PET scan for radiation dose escalation should be further explored., Clinical Trial Number: CTRI/2019/05/019146., (Copyright © 2024. Published by Elsevier Ltd.)

Development of an efficient electrocatalyst for the nitrogen reduction reaction (NRR) to serve as an sustainable alternative to the Haber-Bosch process has proven highly challenging. Single atom catalysts (SACs), which have the maximum atom utilization efficiency, are among the most promising candidates. Single atoms can be incorporated to a catalytic system by doping or substitution or by attaching a molecular coordination complex to a substrate and the different insertion modes allow the chemical environment to be varied. We have used DFT to investigate vanadium SACS for NRR activity with a focus on varying the coordination environment of the V atom. Phthalocyanine, porphyrin and graphene like coordination environments with varying N-coordination have been studied. Vanadium phthalocyanine (VphN4) is the most promising of the investigated systems. It features a high selectivity relative the HER reaction and relatively strong binding of N2 relatively H, which prevents poisoning of the surface by hydrogen. VphN4 also has the lowest overpotential among the studied systems. The electrocatalytic properties of VphN4 deposited as a monolayer on the Ag (111) surface have been investigated. This system, which already has been prepared, shows promising properties for use as a catalytic electrode for the NRR reaction., (© 2024 Wiley‐VCH GmbH.)

Purpose: Duchenne muscular dystrophy (DMD), a genetically linked muscle disease, is one of the most devastating diseases with currently no cure. Developing essential social skills as a child moves into adolescence is particularly problematic in DMD. The present study is an exploration of the social challenges faced by children with DMD., Methods: A qualitative study was conducted among ten children diagnosed with DMD receiving treatment in a neuromuscular disorder clinic of a tertiary referral care center in Southern India. Participants were recruited purposively and were interviewed face-to-face and through telephone. The recorded interviews were transcribed and analyzed using reflexive thematic analysis., Results: Mean age of the children was 13.9 (range: 13-15) at the time of the interviews, and six children had stopped schooling. The overarching theme generated from the interviews was struggle to belong, a yearning for normalcy in social spaces. Major identified themes were challenges with schooling, disabling society, feeling of being alone , and feeling of being a burden to the family., Conclusion: The study highlighted the struggles of children that become a complex social problem for them. Efforts need to be made to be child-centric and encourage inclusion by improving accessibility and social support through sensitization programs.

This study aimed to estimate radon concentrations in groundwater and surface water to evaluate radon ( 222 Rn) contamination in drinking water within the Amreli region of Saurashtra, Gujarat, India. Water samples from 84 sites, covering about 3000 km 2 , were analyzed using the RAD7 device from Durridge Instruments. Samples were collected in 250 ml radon-tight bottles. Radon concentrations ranged from 0.1 to 13.6 Bq/L, averaging 4.52 Bq/L. At three sites (P9, P29, P35), radon levels exceeded the USEPA limit of 11.1 Bq/L. P9 and P29 are near the Tulsishyam geothermal area, while P35 is close to the Savarkundla fault. Geothermal fluids in Tulsishyam may facilitate radon migration, and swarm-type earthquakes near Savarkundla could also contribute to radon migration. Concurrently, physicochemical parameters like Potential of Hydrogen (pH) and Total Dissolved Solid (TDS) were measured, with no significant correlation found between radon levels and these parameters. Samples were taken from tube wells with depths ranging from 105 to 750 feet, averaging 359 feet. A strong and significant correlation (0.83) was observed between radon concentration and water depth. Health risks from radon exposure were assessed by estimating annual effective dose rates for different age groups through ingestion and inhalation. In some instances, the annual effective dose rate surpassed the WHO-recommended value of 100 µSv/year. However, in most instances, the presence of radon in the water does not indicate a significant radiological risk., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: We studied the temporal course of hypothalamic-pituitary-adrenal (HPA) dysfunction in patients with coronavirus disease 2019 (COVID-19)., Methods: Three hundred and two patients (median age 54 years (interquartile range (IQR) 42-64), 76% males) were recruited. The HPA axis was evaluated by morning cortisol and adrenocorticotrophic hormone (ACTH) at admission (n = 232). Adrenal insufficiency (AI) during acute illness was defined using a morning cortisol <83 nmol/L. AI at 12 months follow-up was defined using a peak cortisol <406 nmol/L in the ACTH stimulation test (APST) (n = 90). Those with AI at 12 months were further assessed by APST every 6 months for recovery of hypoadrenalism., Results: The median morning cortisol and ACTH levels during COVID-19 were 295 (IQR 133-460) nmol/L and 3.9 (0.8-6.9) pmol/L, respectively. AI was present in 33 (14%) patients; ACTH was elevated in three and low or inappropriately normal in the rest 30 patients. At 12 months, AI was seen in 13% (12/90) patients, with all cases being hypothalamic-pituitary in origin; five (42%) of them had not met the diagnostic criteria for AI during COVID-19. AI diagnosed at admission persisted at 12 months in seven patients and recovered in seven; the remaining 19 patients were lost to follow-up. The presence of AI at 12 months was independent of severity and steroid use during COVID-19. A morning cortisol <138 nmol/L during COVID-19 predicted the presence of AI at 12 months. All patients showed recovery of the HPA axis in the ensuing 12 months., Conclusion: Central AI was common during acute COVID-19 and at 12 months of follow-up. AI can be late onset, developing after recovery from COVID-19, and was transient in nature.

Introduction: The India Hypertension Control Initiative (IHCI) emphasizes decentralized patient-centric care to boost hypertension control in public healthcare facilities. We documented the decentralization process, enrolment pattern by facility type, and treatment outcomes in nine districts of Punjab and Maharashtra states, India, from 2018-2022., Methods: We detailed the shift in hypertension care from higher facilities to Health and Wellness Centres (HWCs) using the World Health Organization (WHO) health system pillar framework. We reviewed hypertension treatment records in 4,045 public facilities from nine districts in the two states, focusing on indicators including registration numbers, the proportion of controlled, uncontrolled blood pressure (BP), and missed visits among those under care., Results: The decentralization process involved training, treatment protocol provision, supervision, and monitoring. Among 394,038 individuals registered with hypertension from 2018-2021, 69% were under care in 2022. Nearly half of those under care (129,720/273,355) received treatment from HWCs in 2022. Care of hypertensive individuals from district hospitals (14%), community health centres (20%), and primary health centres (24%) were decentralized to HWCs. Overall BP control rose from 20% (4,004/20,347) in 2019 to 58% (157,595/273,355) in 2022, while missed visits decreased from 61% (12,394/20,347) in 2019 to 26% (70,894/273,355) in 2022. This trend was consistent in both states. HWCs exhibited the highest BP control and the lowest missed visits throughout the study period compared to other facility types., Conclusion: We documented an increase in decentralized access to hypertension treatment and improved treatment outcomes over four years. We recommend operationalizing hypertension care at HWCs to other districts in India to improve BP control., (© 2024. The Author(s).)

Water, although an important part of everyday life, is acts as one of the most significant contaminants in various applications such as biomedical monitoring, chemical production, petroleum-based fuel and food processing. In fact, the presence of water in other solvents is a huge concern. For the quantification of trace water content, different methods such as Karl-Fischer, electrochemical, nuclear magnetic resonance, chromatography, and thermogravimetric analysis have been used. Although every technique has its own benefit, each one suffers from several drawbacks that include high detection costs, lengthy procedures and specialized operations. Nowadays, the development of fluorescence-based chemical probes has become an exciting area of research for the quick and accurate estimation of water content in organic solvents. A variety of chemical processes such as hydrolysis reaction, metal ions promoted oxidation reaction, suppression of the -C═N isomerization, protonation and deprotonation reactions, and molecular aggregation have been well researched in the last few years for the fluorescent detection of trace water. These chemical processes eventually lead to different photophysical events such as aggregation-induced emission (AIE), aggregation-induced emission enhancement (AIEE), aggregation-caused quenching (ACQ), fluorescent resonance energy transfer (FRET), charge transfer, photo-induced electron transfer (PET), excited state intramolecular proton transfer (ESIPT) that are responsible for the detection. This review presents a summary of the fluorescence-based chemosensors reported in recent years. The design of water sensors, sensing mechanisms and their potential applications are reviewed and discussed., Competing Interests: Declaration of competing interest All the authors declare that they have no established conflicting financial interests or personal relationships that may have influenced the research presented in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, fluorescent gold nanoclusters (AuNCs) conjugated with pyridoxal-5-phosphate (PLP) were synthesized, characterized, and used for Zn 2+ fluorescence turn-on sensing. PLP was conjugated over the surface of papain-stabilized fluorescent gold nanoclusters (pap-AuNCs; λ ex  = 380 nm, λ em  = 670 nm) by forming imine linkage. Due to this modification, the red color emitting pap-AuNCs changed to orange color emitting nanoclusters PLP&#95;pap-AuNCs. The nano-assembly PLP&#95;pap-AuNCs detect Zn 2+ selectively by showing a notable fluorescence enhancement at 477 nm. Zn 2+ detection with PLP&#95;pap-AuNCs was quick and easy, with an estimated detection limit of 0.14 µM. Further, paper strips and cotton buds coated with PLP&#95;pap-AuNCs were developed for affordable on-site visual detection of Zn 2+ . Finally, the detection of Zn 2+ in actual environmental water samples served as validation of the usefulness of PLP&#95;pap-AuNCs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A series of novel Ru(II)/Ir(III)/Re(I)-based organometallic complexes [ Ru 2 L1 , Ru 2 L2 , Ir 2 L1 , Ir 2 L2 , Re 2 L1 , and Re 2 L2 ] have been synthesized to assess their potency and selectivity against multiple cancer cells A549, HCT-116, and HCT-116 colon CSCs. The cytotoxic screening of the synthesized complexes has revealed that complex Ru 2 L1 and Ir 2 L2 are two proficient complexes among all, but Ru 2 L1 is the most potent complex. A significant binding constant value was observed for DNA and BSA in all complexes. Significant lipophilic properties allow them to penetrate cancer cell membranes, and substantial quantum yield (ϕ f ) values support bioimaging potential. Again, these complexes are particular for mitochondrial localization and produce a profuse amount of ROS to damage the mitochondrial DNA and then G1 phase cell-cycle arrest. Protein expression analysis unveiled that pro-apoptotic Bax protein overexpressed in Ru 2 L1 -treated cells, whereas antiapoptotic Bcl-2 protein was expressed twofold in Ir 2 L2 -treated cells, which correlated with autophagy reticence.

Competing Interests: There are no conflicts of interest.

Lipoblastoma in the inguinal regional is a rare occurrence in children and can present as a surgical surprise during pediatric herniotomies. Irreducible inguinal hernia is one of the most common surgical problems dealt by pediatric surgery residents in emergency. We report a case of inguinal lipoblastoma presenting as irreducible groin swelling. Complete excision of the mass was done with no recurrence till date., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Indian Association of Pediatric Surgeons.)

Piperlongumine, or piplartine (PL), is a bioactive alkaloid isolated from Piper longum L. and a potent phytoconstituent in Indian Ayurveda and traditional Chinese medicine with a lot of therapeutic benefits. Apart from all of its biological activities, it demonstrates multimodal anticancer activity by targeting various cancer-associated pathways and being less toxic to normal cells. According to their structure-activity relationship (SAR), the trimethylphenyl ring (cinnamoyl core) and 5,6-dihydropyridin-2-(1H)-one (piperdine core) are responsible for the potent anticancer activity. However, it has poor intrinsic properties (low aqueous solubility, poor bioavailability, etc.). As a result, pharmaceutical researchers have been trying to optimise or modify the structure of PL to improve the drug-likeness profiles. The present review selected 26 eligible research articles on PL derivatives published between 2012 and 2023, followed by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) format. We have thoroughly summarised the anticancer potency, mode of action, SAR and drug chemistry of the proposed PL-derivatives against different cancer cells. Overall, SAR analyses with respect to anticancer potency and drug-ability revealed that substitution of methoxy to hydroxyl, attachment of ligustrazine and 4-hydroxycoumarin heterocyclic rings in place of phenyl rings, and attachment of heterocyclic rings like indole at the C7-C8 olefin position in native PL can help to improve anticancer activity, aqueous solubility, cell permeability, and bioavailability, making them potential leads. Hopefully, the large-scale collection and critical drug-chemistry analyses will be helpful to pharmaceutical and academic researchers in developing potential, less-toxic and cost-effective PL-derivatives that can be used against different cancers., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Intracranial aneurysm (IA) has the potential to rupture. Despite scientific advances, we are still not in a position to screen patients for IA and identify those at risk of rupture. It is critical to comprehend the molecular basis of disease to facilitate the development of novel diagnostic strategies. We used transcriptomics to identify the dysregulated genes and understand their role in the disease biology. In particular, RNA-Seq was performed in tissue samples of controls, unruptured IA, and ruptured IA. Dysregulated genes (DGs) were identified and analyzed to understand the functional aspects of molecules. Subsequently, candidate genes were validated at both transcript and protein level. There were 314 DGs in patients with unruptured IA when compared to control samples. Out of these, SPARC and OSM were validated as candidate molecules in unruptured IA. PI3K-AKT signaling pathway was found to be an important pathway for the formation of IA. Similarly, 301 DGs were identified in the samples of ruptured IA when compared with unruptured IAs. CTSL was found to be a key candidate molecule which along with Hippo signaling pathway may be involved in the rupture of IA. We conclude that activation of PI3K-AKT signaling pathway by OSM along with up-regulation of SPARC is important for the formation of IA. Further, regulation of Hippo pathway through PI3K-AKT signaling results in the down-regulation of YAP1 gene. This along with up-regulation of CTSL leads to further weakening of aneurysm wall and its subsequent rupture., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)