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High dose radiation exposures are rare. However, medical management of such incidents is crucial due to mortality and tissue injury risks. Rapid radiation biodosimetry of high dose accidental exposures is highly challenging, considering that they usually involve non uniform fields leading to partial body exposures. The gold standard, dicentric assay and other conventional methods have limited application in such scenarios. As an alternative, we propose Premature Chromosome Condensation combined with Fluorescent In-situ Hybridization (G0-PCC-FISH) as a promising tool for partial body exposure biodosimetry. In the present study, partial body exposures were simulated ex-vivo by mixing of uniformly exposed blood with unexposed blood in varying proportions. After G0-PCC-FISH, Dolphin's approach with background correction was used to provide partial body exposure dose estimates and these were compared with those obtained from conventional dicentric assay and G0-PCC-Fragment assay (conventional G0-PCC). Dispersion analysis of aberrations from partial body exposures was carried out and compared with that of whole-body exposures. The latter was inferred from a multi-donor, wide dose range calibration curve, a-priori established for whole-body exposures. With the dispersion analysis, novel multi-parametric methodology for discerning the partial body exposure from whole body exposure and accurate dose estimation has been formulated and elucidated with the help of an example. Dose and proportion dependent reduction in sensitivity and dose estimation accuracy was observed for Dicentric assay, but not in the two PCC methods. G0-PCC-FISH was found to be most accurate for the dose estimation. G0-PCC-FISH has potential to overcome the shortcomings of current available methods and can provide rapid, accurate dose estimation of partial body and high dose accidental exposures. Biological dose estimation can be useful to predict progression of disease manifestation and can help in pre-planning of appropriate & timely medical intervention.

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Inferior vena cava (IVC) indices are commonly used to assess the need for fluid bolus during shock. It needs expertise and is difficult to do during surgical procedures. Plethysmograph variability index (PVI) is a simpler non-invasive tool used to measure fluid responsiveness in adults. However, the data on PVI in neonates is limited. This cross-sectional observational study was done at a tertiary level NICU to correlate PVI and IVC among spontaneously breathing neonates. The PVI was documented using the Masimo Radical 7 pulse oximeter. The IVC collapsibility index (IVC CI) was determined by bedside ultrasound. The Spearman correlation coefficient was analyzed. The PVI showed strong positive correlation with IVC CI (rho = 0.64, 95% CI: 0.474-0.762) (p <0.001). Thus, PVI can be a useful tool for hemodynamic monitoring of neonates. However, further studies are needed before applying it to clinical use.

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OBJECTIVES: To establish normative data of plethysmograph variability index (PVI), a simple non-invasive tool to measure fluid responsiveness, in neonates. METHODS: All healthy term and late preterm neonates were enrolled. PVI was recorded by pulse-oximeter on first three days of life along with other vital parameters. Data was analysed using SPSS software. RESULTS: The median PVI value was noted to be 21 with a wide range. The distribution of PVI did not differ according to day of life/ gestational age/ gender/ weight for gestational age. It did not significantly correlate with heart rate, gestational age or birth weight. A weak positive correlation was noted between PVI and PI (Rho = 0.157, p <0.001). CONCLUSIONS: PVI normative data in neonates has been presented. Serial trend of PVI values is more useful than a single value in making clinical decisions.

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Background: Retinopathy of prematurity (ROP) and abnormal brain development share similar risk factors and mechanisms. There has been contrasting evidence on the association of ROP with adverse neurodevelopmental outcomes. Objective: We analysed the association between ROP at levels of severity and treatment with all neurodevelopmental outcomes until adolescence. Data source: We followed PRISMA guidelines and searched Medline and Embase between 1 August 1990 and 31 March 2022. Study selection and participants: Randomised or quasi-randomised clinical trials and observational studies on preterm infants (<37 weeks) with ROP [type 1 or severe ROP, type 2 or milder ROP, laser or anti-vascular endothelial growth factor (VEGF) treated] were included. Data extraction and synthesis: We included studies on ROP and any neurocognitive or neuropsychiatric outcomes. Outcomes: The primary outcomes were as follows: cognitive composite scores evaluated between the ages of 18 and 48 months by the Bayley Scales of Infant and Toddler Development (BSID) or equivalent; neurodevelopmental impairment (NDI; moderate to severe NDI or severe NDI), cerebral palsy, cognitive impairment; and neuropsychiatric or behavioural problems. The secondary outcomes were as follows: motor and language composite scores evaluated between the ages of 18 and 48 months by BSID or equivalent; motor/language impairment; and moderate/severe NDI as defined by the authors. Results: In preterm infants, "any ROP" was associated with an increased risk of cognitive impairment or intellectual disability [n = 83,506; odds ratio (OR): 2.56; 95% CI: 1.40-4.69; p = 0.002], cerebral palsy (n = 3,706; OR: 2.26; 95% CI: 1.72-2.96; p < 0.001), behavioural problems (n = 81,439; OR: 2.45; 95% CI: 1.03-5.83; p = 0.04), or NDI as defined by authors (n = 1,930; OR: 3.83; 95% CI: 1.61-9.12; p = 0.002). Type 1 or severe ROP increased the risk of cerebral palsy (OR: 2.19; 95% CI: 1.23-3.88; p = 0.07), cognitive impairment or intellectual disability (n = 5,167; OR: 3.56; 95% CI: 2.6-4.86; p < 0.001), and behavioural problems (n = 5,500; OR: 2.76; 95% CI: 2.11-3.60; p < 0.001) more than type 2 ROP at 18-24 months. Infants treated with anti-VEGF had higher odds of moderate cognitive impairment than the laser surgery group if adjusted data (gestational age, sex severe intraventricular haemorrhage, bronchopulmonary dysplasia, sepsis, surgical necrotising enterocolitis, and maternal education) were analysed [adjusted OR (aOR): 1.93; 95% CI: 1.23-3.03; p = 0.04], but not for cerebral palsy (aOR: 1.29; 95% CI: 0.65-2.56; p = 0.45). All outcomes were adjudged with a "very low" certainty of evidence. Conclusion and relevance: Infants with "any ROP" had higher risks of cognitive impairment or intellectual disability, cerebral palsy, and behavioural problems. Anti-VEGF treatment increased the risk of moderate cognitive impairment. These results support the association of ROP and anti-VEGF treatment with adverse neurodevelopmental outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022326009.

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A rapid and reliable method for biodosimetry of populations exposed to ionizing radiation in the event of an incident or accident is crucial for initial triage and medical attention. DNA-double strand breaks (DSBs) are indicative of radiation exposure, and DSB-repair proteins (53BP1, γH2AX, ATM, etc.) are considered sensitive markers of DSB quantification. Phospho-53BP1 and γH2AX immunofluorescence technique serves as a sensitive, reliable, and reproducible tool for the detection and quantification of DSB-repair proteins, which can be used for biological dose estimations. In this study, dose-response curves were generated for 60Co-γ-rays induced phospho-53 Binding Protein 1 (phospho-53BP1) foci at 1, 2, 4, 8, 16, and 24 h, post-irradiation for a dose range of 0.05-4 Gy using fluorescence microscopy. Following ISO recommendations, minimum detection limits (MDLs) were estimated to be 16, 18, 25, 40, 50, and 75 mGy for dose-response curves generated at 1, 2, 4, 8, 16, and 24 h post-irradiation. Colocalization and correlation of phospho-53BP1 and γH2AX were also measured in irradiated peripheral blood lymphocytes (PBLs) to gain dual confirmation. Comparative evaluation of the established curve was made by γH2AX-immunofluorescence, dicentric chromosome assay (DCA), and reciprocal translocation (RT) assays by reconstructing the dose of 6 dose-blinded samples. Coefficients of respective in-house established dose-response curves were employed to reconstruct the blind doses. Estimated doses were within the variation of 4.124%. For lower doses (0.052 Gy), phospho-53BP1 and γH2AX assays gave closer estimates with the variation of -4.1 to + 9% in comparison to cytogenetic assays, where variations were -8.5 to 24%. For higher doses (3 and 4 Gy), both the cytogenetic and immunofluorescence (phospho-53BP1 and γH2AX), assays gave comparable close estimates, with -11.3 to + 14.3% and -10.3 to -13.7%, variations, respectively.

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Thorium (232Th), long lived (14.05 billion years) most stable thorium isotope, is thrice naturally abundant than uranium. 232Th occurs as rocky deposits and black monazite sands on the earth's crust geographically distributed in coastal South India and other places globally. Monazite sand comprises of cerium and large quantities of radioactive thorium. The environmental hazard lies in monazite rich area being termed as High Background Radiation Area (HBRA). In this study, we mimicked the HBRA under controlled chamber conditions using thorium oxalate as a thorium source for BALB/c mice exposure. Furthermore, sequential radio-disintegration of 232 Th leads to thoron (220Rn), the noble gas and other daughter products/progeny predominantly via alpha decay/emissions. Such progeny tend to attach to aerosol and dust particles having potential inhalation hazard followed by alpha emissions and damages that we evaluated in mouse lung tissues post thoron inhalation. Secondly, along with the radio disintegration and alpha emission, high energy gamma is also generated that can travel to various distant organs through the systemic circulation, as significant findings of our study as damages to the liver and kidney. The mechanistic findings include the damages to the hematological, immunological and cellular antioxidant systems along with activation of canonical NF-κß pathway via double stranded DNA damage.

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BACKGROUND: Large numbers of preterm infants are born in middle-income countries and neonatal care is improving in these countries. Few studies have compared clinical outcome in preterm infants in a tertiary neonatal unit in a middle-income country with one in a high-income country. OBJECTIVE: To compare the short-term outcome in preterm infants of ≤30 weeks gestation admitted to a tertiary neonatal unit in Bengaluru, India and in London, UK. METHODS: This was a retrospective observational study using anonymised data from electronic patient records. Preterm infants born at ≤30 weeks gestation admitted to neonatal units in Bengaluru (n = 294) and London (n = 740) over a 5-year period (January 2011 to December 2015) were compared. RESULTS: Fewer mothers in the Bengaluru centre received antenatal steroids (37% vs 73%, p < 0.001). The incidence of retinopathy of prematurity requiring treatment (12.9% vs 7.7%, NS), treated patent ductus arteriosus (32.3% vs 10.7%, NS) and blood culture-positive sepsis (32.4% vs 1.7%, p < 0.001) was higher in infants in the Indian centre. Overall survival was 83% vs 87.2% (NS) in the Bengaluru and the London cohorts, respectively. Survival of infants born at ≤28 weeks gestation was lower in Bengaluru than in London [24 weeks: 33.0% vs 79.3% (NS); 25 weeks: 50.0% vs 78.9%, p = 0.02; 26 weeks: 45.2% vs 86.5%, p < 0.01; 27 weeks: 79.3% vs 91.3% (NS); 28 weeks 82.5% vs 94.1%, p = 0.03]. CONCLUSION: The survival of infants ≤28 weeks gestation was significantly lower in the Bengaluru centre. Increasing the provision of antenatal corticosteroids may improve the outcome in these infants. ABBREVIATIONS: BPD: bronchopulmonary dysplasia; CPAP: continuous positive airway pressure; EPR: electronic patient records; HIC: high-income countries; HDU: high dependency unit; hsPDA: haemodynamically significant patent ductus arteriosus; IVH: intraventricular haemorrhage; ITU: Intensive Care Unit, IUGR: intrauterine growth restriction; LAMA: leaving against medical advice; LMIC: low- and middle-income countries; NICU: neonatal intensive care unit; NNFI: National Neonatal Forum of India; NS: not significant; NTS: neonatal transfer service; NNAP: National Neonatal Audit Programme; NHM: National Health Mission; NMR: neonatal mortality rate; NEC: necrotising enterocolitis; NS: not significant; PDA: patent ductus arteriosus; ROP: retinopathy of prematurity; SCBU: special care baby unit; VLBW: very low birthweight; WHO: World Health Organization.

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OBJECTIVE: To compare postductal heart rate and saturation (SpO2) measurements from the wireless PO device obtained by iVital+ against measurements by the standard Masimo (SET technology) monitor in the monitoring of neonates. METHODS: Pulse oximetry reading of newborns were assessed in terms of heart rate and saturations with two PO simultaneously attached to postductal site and data comparison was done. RESULTS: Out of the 1000 cumulative recordings, the mean difference between HR obtained from both PO was 0.415 and level of agreement was 2.3 beats per minute. For SpO2 mean difference between devices was 1.21 and level of agreement was 1.5%. There was very little difference between SpO2 measurements when the Masimo SpO2 was ≥ 70%. CONCLUSION: As this pulse oximeter is small, portable and accuracy is as comparable to Masimo, this provides a good solution for efficaciously monitoring neonates. It can also be used in the monitoring of children with suspected or affected with COVID-19 in hospital and ICU settings as also in the quarantine facilities. This reduces the need for constant presence of medical and nursing personnel.

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Aggressive overlapping of stochastic activities during phases of vaccine development has been critical to making effective vaccines for COVID-19 available to the public, at "pandemic" speed. In cyclical projects wherein activities can be overlapped, downstream tasks may need rework on account of having commenced prior to receiving requisite information that is only available upon completion of upstream task(s). We provide a framework to understand the interplay between stochastic overlap duration and rework due to overlap, and its impact on minimizing expected completion time for a cyclical project. We motivate the problem using the new paradigm for planning vaccine development projects. It best exemplifies features and scenarios in our model that were not considered and are also not apparent in the examples for cyclical development projects in the literature focused on engineered and manufactured products. We find that planning overlapping in scenarios that may be deemed ineffective with an assumption of deterministic tasks, can actually be beneficial when analyzed using stochastic task duration. We determine optimal planned start times for stochastic tasks as a function of a parameter that proxies for the extent of net gain/loss from overlap to minimize expected completion time for the project. We show that in situations with a net gain from overlap it is optimal to start the downstream task concurrently unless the downstream task does not stochastically dominate the upstream task and the net gain from overlap is not low enough. However, in situations with a net loss from overlap it is always optimal to have some degree of overlap in a stochastic task environment. We find that project rescheduling flexibility is always beneficial in a scenario with net loss from overlap and only beneficial in a scenario with net gain from overlap when the downstream task does not stochastically dominate the upstream task and the net gain from overlap is high enough. Our results on overlapping in 1-to-1, 1-to-n, and n-to-1 stochastic task configurations guide the development of an effective heuristic. Our heuristic offers good solution quality and is scalable to large networks as its computational complexity is linear in the number of tasks.

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Cystic hydatid disease or cystic echinococcosis (CE) is a globally endemic zoonosis caused by the larval cyst stage of the tapeworm Echinococcus granulosus Concomitant presence of CE and hepatocellular carcinoma (HCC) is a rare clinical scenario. A 70-year-old male patient presented with acute abdominal pain to the surgical outpatient department. On evaluation, a cystic lesion with solid components and free fluid in the abdomen was observed, which led to multiple differentials in the working diagnosis. A CT showed the mass to have a delayed enhancement. Surgical exploration revealed a partially ruptured hydatid cyst with daughter cysts in the abdominal cavity and a solid-component mass lesion. We proceeded with a right partial hepatectomy. Pathological evaluation revealed a pale mass lesion with a large collapsed cyst. HCC with unusual dense fibrillar fibrosis and cystic interface with normal parenchyma was observed. This case connects the multimodal assessment of radiology, surgery and pathology.

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PURPOSE: This phase 4, randomized, open-label, multicenter study in healthy Indian infants and toddlers evaluated the safety, tolerability, and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) formulated in a multidose vial (MDV) or single prefilled syringe (PFS). METHODS: Healthy Indian infants (6 weeks of age) were randomized 1:1 to receive either PCV13-MDV or PCV13-PFS concomitant with routine pediatric vaccines. Subjects received a single dose of either PCV13-MDV or PCV13-PFS as a 4-dose schedule (infant series: 1 dose at 6, 10, and 14 weeks of age; toddler dose: 12 months of age). Safety was assessed, including local reactions, systemic events, and adverse events (AEs). Immunogenicity 1 month after both the infant series and toddler dose was measured by concentrations of serotype-specific immunoglobulin G (IgG) antibodies and opsonophagocytic activity titers. RESULTS: Rates and severities of local reactions and systemic events up to 7 days after each dose of either PCV13-MDV or PCV13-PFS were generally similar, with the majority being of mild or moderate severity. PCV13-MDV had a safety profile comparable with PCV13-PFS; both groups experienced a similar frequency of AEs. PCV13-MDV elicited immune responses comparable with those induced by PCV13-PFS. Clear boosting of immune responses after the PCV13-MDV toddler dose was observed; ≥96% of subjects showed serotype-specific IgG concentrations at or above the defined thresholds 1 month after the PCV13-MDV toddler dose. CONCLUSIONS: PCV13-MDV was safe, well tolerated, and immunogenic in healthy Indian infants and toddlers when coadministered with routine pediatric vaccinations. Safety and immunogenicity of PCV13-MDV was comparable with PCV13-PFS. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT03548337.

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Mitotic cell fusion induced Premature Chromosome Condensation (G0-PCC) assay in human lymphocytes allows rapid detection of cytogenetic damage in interphase stage, within few hours after blood collection. Hence, it is the most suitable method for rapid and high dose biodosimetry. Mitotic cells, used for G0-PCC could be either freshly isolated or previously cryo-preserved. However, under emergency scenarios, only cryo-preserved cells can be relied upon, fresh isolation will only delay the process by 18-24 h. Impact of cryopreservation on mitotic cells and their efficacy to induce PCC are not reported. In the present study, we investigated effect of cryopreservation on mitotic cells and refined the parameters for G0-PCC. More than 95% of the cells were recoverable after 4 months of cryopreservation, within 20 min recovery at 37 °C, without significant change in the mitotic index or viability. Recovered mitotic cells have shown mitotic index of 89 ± 4% and viability of 90 ± 4%, similar to that of freshly isolated cells. Decrease in metaphases was observed within 40 min after recovery as the mitotic cells progressed through cell cycle and reduced to 21% at 1.5 h. Nevertheless, in presence of Colcemid, the cells progressed slowly and considerably high metaphase index (60%) persisted up to ~ 2 h. The recovered cells efficiently fused with lymphocytes and induced PCC. Average PCC index varied from 10 to 20%, which did not change with cryopreservation duration. Post fusion incubation duration of 2 h was found to be optimum for proper chromosome condensation. In conclusion, use of cryo-preserved mitotic cells is the most practical approach for rapid biodosimetry. The cells can be recovered quickly and efficiently without alteration in viability or mitotic index. Recovered cells are fully competent to induce G0-PCC.

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PURPOSE: Natural radiation is the major source of human exposure to ionizing radiation. About 52% of the total dose received from the high natural background radiations (HNBR) areas are due to inhalation dose from radon (222Rn)/thoron (220Rn) and their progenies. Hence, we reviewed the biological effects of 222Rn/220Rn and their progenies on lung tissue, and the possible role of lung stem cells in salvaging the damage caused by 222Rn/220Rn and their progenies. MATERIALS AND METHOD: We have extensively reviewed articles among several hits obtained in PubMed, Scopus, and Elsevier databases with keywords 'Radon/Thoron' OR Thoron progeny/Radon progeny OR 'Thoron/Radon inhalation and lungs', and proceed for further analysis. Also, databases related to oxidative damage to lung stem cells by radiation and the repair mechanisms involved by the lung stem cells were also included. RESULTS: Based on the existing epidemiological data on radon in residential buildings, we found that evidence exists on the association of radon induced lung carcinogenesis, but the data regarding the role of thoron induced lung damage is very limited and inconclusive. We also found that limited information has been provided based on ecological designs, leading to poor documentation of health statistics, in particular, organ-specific cancer rates. Finally, we tried to elucidate the possible mechanisms of lung injury induced by thoron inhalation and the probable role of lung stem cell toward the redemption of such oxidative damages. CONCLUSION: Existing epidemiological data on thoron inhalation and associated health outcomes are limited and inconclusive. Further, in vivo experiments, with respect to radon/thoron inhalation dose rate ranges corresponding to the HNBR areas will be helpful in understanding the cellular and molecular effects.

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We report on the implementation experience of carrying out data collection and other activities for a public health evaluation study on whether U.S. President's Emergency Plan for AIDS Relief (PEPFAR) investment improved utilization of health services and health system strengthening in Uganda. The retrospective study period focused on the PEPFAR scale-up, from mid-2005 through mid-2011, a period of expansion of PEPFAR programing and health services. We visited 315 health care facilities in Uganda in 2011 and 2012 to collect routine health management information system data forms, as well as to conduct interviews with health system leaders. An earlier phase of this research project collected data from all 112 health district headquarters, reported elsewhere. This article describes the lessons learned from collecting data from health care facilities, project management, useful technologies, and mistakes. We used several new technologies to facilitate data collection, including portable document scanners, smartphones, and web-based data collection, along with older but reliable technologies such as car batteries for power, folding tables to create space, and letters of introduction from appropriate authorities to create entrée. Research in limited-resource settings requires an approach that values the skills and talents of local people, institutions and government agencies, and a tolerance for the unexpected. The development of personal relationships was key to the success of the project. We observed that capacity building activities were repaid many fold, especially in data management and technology.

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To explore possible applications of iodoacetate (IA), a glycolytic inhibitor, in cancer treatment, we screened its cytotoxicity and radioprotective/sensitizing efficacy in three different mammalian cell lines; A549 (human lung carcinoma), MCF7 (human mammary cancer), a non-cancerous CHO (Chinese hamster ovary) cells and human lymphocytes. Experiments were carried out using IA concentrations ranging from 0.01 to 2.5 µg/ml, with or without 60Coγ-radiation. In the outcomes, IA was found to exhibit higher toxicity in the cancer cells, whereas it was non-toxic/marginally toxic to the non-cancerous cells. Considerably higher glucose uptake in both cancer cells lines was observed indicating higher rates of glycolysis. IA significantly inhibited glycolysis as reflected by GAPDH activity inhibition. Radiomodifying effects of IA were found to be concentration dependent in both cancerous and non-cancerous cells. The response in non-cancerous was found to be biphasic: at lower concentrations, it offered significant radioprotection; however, the protection decreased with increasing concentration. Moreover, at the highest tested concentration, marginal radiosensitization was also observed (as indicated by clonogenic assay). In both cancer cells, IA offered significant amount of radiosensitization which was considerably high at higher concentrations. Further experiments were carried out to estimate the Dose Modification Factor (DMF) to quantify and compare relative radiosensitization by IA in cancer and normal cell lines. The DMF was calculated for three different concentrations of IA, 0.5, 1, and 1.5 µg/ml, and corresponding values were found to be 1.26, 1.43, and 1.89 for A549 cancer cells, whereas for normal CHO cells, it was 1.13, 1.13, and 1.24. In conclusion, differential killing and radiosensitizing effects of IA suggest that it may have potential use as a anticancer agent and radiosensitizer in cancer therapy.

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