A social profile of deaths related to sickle cell disease in India : a case for an ethical policy response

India accounts for 14.5 percent of the global SCD newborns, roughly over 42,000 a year, second to sub-Saharan Africa. Despite the availability of cheap diagnostic and treatment options, SCD remains a largely neglected disease within healthcare policy and practice. Epidemiological modeling based on small, often dated, regional studies (largely from sub-Saharan Africa) estimate that between 50 and 90 percent of affected children will/die before the age of 5 years. This premise, coupled with targets of reducing under 5 mortality (SDG 4), privileges public health interventions for screening and prevention of new births, undermining investments in long-term health and social care. This paper presents a retrospective, descriptive analysis of the socio-demographic profile of 447 patients diagnosed with sickle cell or sickle-beta thalassemia, who died following admission at a tertiary care entre in India. We used anonymized hospital records of 3,778 sickle cell patients, admitted in pediatric and adult/medical wards between January 2016 and February 2021. A majority of hospital deaths occurred in the second and third decades of life, following a hospital admission for a week. The overall mortality during 2016–2019 was 14% with little gender difference over time. Contrary to our expectations, the number of hospital deaths did not increase during the first year of the COVID-19 pandemic, between 2020 and 2021. The conclusion highlights the importance of longitudinal, socio-demographic data on deaths as providing important insights for identifying ethical policy interventions focused on improving SCD outcomes over time, reducing inequities in access to care, and preventing what might be considered “excess” deaths

COMPUTATIONAL COMPLEXITY OF APPROXIMATE AND PRECISE DATA WITH CONSTRAINT AUTOMATON

The DNA molecules packaged in structures called chromosomes within the cells of living organisms encode hereditary information that is passed on to their offspring. Using transcription and translation, the genes within these DNA molecules help in protein synthesis. Thus chromosomal DNA serves as a blueprint for the chemical processes of life. In order to analyze a DNA sequence by currently available technology, we have to cut it into small fragments, e.g. by using restriction enzymes. The application of different restriction enzymes to the multiple copies of the same DNA sequence generates many overlapping fragments. In order to construct the original DNA, these fragments need to be sequenced and assembled. This problem of finding the original order of the fragments is called the genome map assembly problem. This research proposes a constraint automaton solution to solve the genome map assembly problem for both error prone and error free data. Plasmid vectors puc57, pKLAC1-malE, pTXB1 and phage vector Adenovirus2, having a size in base pairs of 2710, 6706, 10153 and 35937 respectively, were used to prove that computational time for solving genome map assembly problem using constraint automaton solution is linear with both precise and approximate data

Numerical Approximation for Nonlinear Noisy Leaky Integrate-and-Fire Neuronal Model

We consider a noisy leaky integrate-and-fire (NLIF) neuron model. The resulting nonlinear time-dependent partial differential equation (PDE) is a Fokker-Planck Equation (FPE) which describes the evolution of the probability density. The finite element method (FEM) has been proposed to solve the governing PDE. In the realistic neural network, the irregular space is always determined. Thus, FEM can be used to tackle those situations whereas other numerical schemes are restricted to the problems with only a finite regular space. The stability of the proposed scheme is also discussed. A comparison with the existing Weighted Essentially Non-Oscillatory (WENO) finite difference approximation is also provided. The numerical results reveal that FEM may be a better scheme for the solution of such types of model problems. The numerical scheme also reduces computational time in comparison with time required by other schemes

Embryonic Zebrafish Model - A Well-Established Method for Rapidly Assessing the Toxicity of Homeopathic Drugs - Toxicity Evaluation of Homeopathic Drugs Using Zebrafish Embryo Model -

Objectives: Advancements in nanotechnology have led to nanoparticle (NP) use in various fields of medicine. Although the potential of NPs is promising, the lack of documented evidence on the toxicological effects of NPs is concerning. A few studies have documented that homeopathy uses NPs. Unfortunately, very few sound scientific studies have explored the toxic effects of homeopathic drugs. Citing this lack of high-quality scientific evidence, regulatory agencies have been reluctant to endorse homeopathic treatment as an alternative or adjunct treatment. This study aimed to enhance our insight into the impact of commercially-available homeopathic drugs, to study the presence of NPs in those drugs and any deleterious effects they might have, and to determine the distribution pattern of NPs in zebrafish embryos (Danio rerio). Methods: Homeopathic dilutions were studied using high-resolution transmission electron microscopy with selected area electron diffraction (SAED). For the toxicity assessment on Zebrafish, embryos were exposed to a test solution from 4 - 6 hours post-fertilization, and embryos/larvae were assessed up to 5 days post-fertilization (dpf) for viability and morphology. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. Around 5 dpf was found to be the optimum developmental stage for evaluation. Results: The present study aimed to conclusively prove the presence of NPs in all high dilutions of homeopathic drugs. Embryonic zebrafish were exposed to three homeopathic drugs with two potencies (30CH, 200CH) during early embryogenesis. The resulting morphological and cellular responses were observed. Exposure to these potencies produced no visibly significant malformations, pericardial edema, and mortality and no necrotic and apoptotic cellular death. Conclusion: Our findings clearly demonstrate that no toxic effects were observed for these three homeopathic drugs at the potencies and exposure times used in this study. The embryonic zebrafish model is recommended as a well-established method for rapidly assessing the toxicity of homeopathic drugs

Evaluation of histopathological and ultrastructural changes in the testicular cells of Wistar rats post chronic exposure to gold nanoparticles

9-15Gold nanoparticles (GNP) have numerous therapeutic potentials due to their ability to cross blood barriers. However, limited data is available showing GNPs crossing the blood testicular barrier. Here we report results of chronic exposure (90 days) to GNPs ranging in size 5 to 20 nm in male Wistar rats. Histopathological and transmission electron microscopy (TEM) analysis show GNPs distributed and accumulated in majority of the testicular tissues. This shows the ability of GNPs of specific sizes to cross the blood testicular barrier effectively, indicating possible insignificant toxicity to spermatogenesis process due to chronic exposure. Thus, GNPs of smaller size can possibly be used for various therapeutic and diagnostic purposes

Bisphenol A-induced ultrastructural changes in the testes of common marmoset

Background & objectives: Bisphenol A (BPA) is an endocrine disruptor that is widely used in the manufacture of polycarbonate plastics, epoxy resins and dental sealants. It is known to have adverse effects on spermatogenesis in rodents. This study was aimed to evaluate the effects of BPA in adult common marmoset owing to its similarities with human spermatogenesis. Methods: Sixteen marmosets were divided into four groups (n=4 per group) and given oral doses of BPA (2.5, 12.5 and 25 μg/kg BW/day) for 70 days to cover two spermatogenic cycles, and the control group received only vehicle (honey). Testes were processed for histological and transmission electron microscopy studies. Results: Histology of the testis showed sloughing of germ cells into the lumen, increase in interstitial space and vacuolation of Sertoli cell cytoplasm. Ultrastructural analysis of the testis revealed several degenerative effects on the basement membrane, Sertoli cells, Leydig cells and other developing germ cells in the 12.5 and 25 μg/kg BW/day groups as compared to control. Interpretation & conclusions: The observed ultrastructural changes caused by BPA in testicular morphology might be indicative of a perturbed sperm production. Considering the genetic and spermatogenic similarities of common marmoset (Callithrix jacchus) and humans, the study findings are of significance. Further studies are, however, needed to elucidate the mechanism of action

DNA methylation biomarkers to identify epigenetically abnormal spermatozoa in male partners from couples experiencing recurrent pregnancy loss

Previously, we showed that DNA methylation defects in spermatozoa from male partners of couples undergoing recurrent pregnancy loss (RPL) could be a contributing paternal factor. In the present study, we aimed to determine whether the methylation levels of selected imprinted genes can be used as diagnostic markers to identify epigenetically abnormal spermatozoa sample in these cases. The methylation levels of selected imprinted genes in spermatozoa, which were previously found to be differentially methylated, were combined into a probability score (between 0–1) using multiple logistic regression. Different combinations of these genes were investigated using Receiver Operating Characteristic analysis, and the threshold values were experimentally validated in an independent cohort of 38 control and 45 RPL spermatozoa samples. Among the different combinations investigated, a combination of five imprinted genes comprising IGF2-H19 DMR, IG-DMR, ZAC, KvDMR, and PEG3 (AUC = 0.88) with a threshold value of 0.61 was selected with a specificity of 90.41% and sensitivity of 70%. The results from the validation study indicated that 97% of the control samples had probability scores below this threshold, whereas 40% of the RPL samples were above this threshold with a post-hoc power of 97.8%. Thus, this combination can correctly classify control samples and potentially identify epigenetically abnormal spermatozoa samples in the male partners of couples undergoing RPL. We propose that the combined DNA methylation levels of these imprinted genes can be used as a diagnostic tool to identify spermatozoa samples with epigenetic defects which could contribute to the pathophysiology of RPL and the couple could be counselled appropriately

SB-RA-2001 Inhibits Bacterial Proliferation by Targeting FtsZ Assembly

FtsZ has been recognized as a promising antimicrobial drug target because of its vital role in bacterial cell division. In this work, we found that a taxane SB-RA-2001 inhibited the proliferation of <i>Bacillus subtilis</i> 168 and <i>Mycobacterium smegmatis</i> cells with minimal inhibitory concentrations of 38 and 60 μM, respectively. Cell lengths of these microorganisms increased remarkably in the presence of SB-RA-2001, indicating that it inhibits bacterial cytokinesis. SB-RA-2001 perturbed the formation of the FtsZ ring in <i>B. subtilis</i> 168 cells and also affected the localization of the late cell division protein, DivIVA, at the midcell position. Flow cytometric analysis of the SB-RA-2001-treated cells indicated that the compound did not affect the duplication of DNA in <i>B. subtilis</i> 168 cells. Further, SB-RA-2001 treatment did not affect the localization of the chromosomal partitioning protein, Spo0J, along the two ends of the nucleoids and also had no discernible effect on the nucleoid segregation in <i>B. subtilis</i> 168 cells. The agent also did not appear to perturb the membrane potential of <i>B. subtilis</i> 168 cells. <i>In vitro</i>, SB-RA-2001 bound to FtsZ with modest affinity, promoted the assembly and bundling of FtsZ protofilaments, and reduced the GTPase activity of FtsZ. GTP did not inhibit the binding of SB-RA-2001 to FtsZ, suggesting that it does not bind to the GTP binding site on FtsZ. A computational analysis indicated that SB-RA-2001 binds to FtsZ in the cleft region between the C-terminal domain and helix H7, and the binding site of SB-RA-2001 on FtsZ resembled that of PC190723, a well-characterized inhibitor of FtsZ. The findings collectively suggested that SB-RA-2001 inhibits bacterial proliferation by targeting the assembly dynamics of FtsZ, and this can be exploited further to develop potent FtsZ-targeted antimicrobials

Additional file 1: of Evaluation of the mobile nurse training (MNT) intervention – a step towards improvement in intrapartum practices in Bihar, India

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