Round Window Visibility in Cochlear Implantation : Pre-operative Prediction Using Various Radiological Parameters.

Purpose: The round window approach has become the most preferred route for electrode insertion in cochlear implant surgery; however, it is not possible at times due to difficult round window membrane (RWM) visibility. Our study aims to investigate the relationship between preoperative radiological parameters and the surgical visibility of the RWM in Cochlear implant patients. Methodology: A prospective cross-sectional study of 31 patients, age < 6 years, with bilateral severe to profound sensorineural hearing loss was conducted at a tertiary care hospital. The preoperative HRCT temporal bone scan was studied, and the parameters evaluated were facial nerve location, facial recess width, and RWM visibility prediction. All patients were operated on via the posterior tympanotomy. The surgical RWM visibility was done after optimal drilling of the posterior tympanotomy recess. The relationship between the radiological parameters and surgical visibility of RWM was evaluated. Results: The difference in the facial nerve location as per the type of RWM was found to be significant (p value < 0.05). However, the facial recess width was not significantly associated with RWM visibility. The radiological prediction of RWM visibility by tracing the prediction line over RWM was significantly associated with intraoperative RWM visibility. Conclusion: The goal to look for preoperative scans is to predict the ease or difficulty of RWM visibility during surgery. The difficult visualization of the RWM, can result in dire intraoperative consequences. A comprehensive understanding of preoperative radiological parameters, coupled with meticulous surgical planning, is crucial to address these challenges effectively by focusing on enhancing RWM visualization.

The 'Insertion/Deletion' Polymorphism, rs4340 and Diabetes Risk: A Pilot Study from a Hospital Cohort.

The insertion/deletion, I/D polymorphism, in the gene encoding Angiotensin Converting Enzyme, ACE is a popular genetic marker for cardiovascular disease, CVD. With alarming rise in diabetes, the risk of CVD among Indian subjects is further enhanced. The present study explored the role of ACE I/D polymorphism, rs4340 as a genetic marker and its association with diabetes. Genomic DNA, isolated from a cohort of 410 urban subjects attending our hospital, was genotyped using polymerase chain reaction followed by electrophoresis. Among the subjects, 84 had type-2 diabetes and 68 had hypertension while 258 were free from these risk factors. Majority (57/84) of diabetic subjects were also suffering from hypertension. Genotype frequencies of ACE I/D polymorphism, of diabetic (84) patients were not different from that of non-diabetic subjects (258). In sharp contrast, we found significant differences, in genotype frequencies of women with diabetes (n = 38) compared to non-diabetic women (70). Diabetic women had significantly higher prevalence of the high risk 'D' allele. Analysis of odds ratio, OR revealed that women with 'D/D' genotype, exhibited threefold risk (OR 3.12, 95% CI 1.21-8.05; p = 0.018) of diabetes, in the recessive model (D/D vs I/I + I/D). Further when we analysed Odds ratio of diabetic women (8) who were free from hypertension, the results revealed even a greater, 6- fold (OR 6.0, 95% CI 1.29-27.96, p = 0.027) risk of diabetes for D/D homozygous women (D/D vs I/I + I/D). These results suggest 'sex-specific' association of ACE 'I/D' polymorphism, with type-2 diabetes, affecting women while there was no influence observed among men. In view of the increased cardiovascular mortality among Indians, data from our pilot study if confirmed in a larger cohort, could add value to our future intervention efforts.

Trends in Cancer Mortality Disparities Between Black and White Individuals in the US, 2000-2020.

This cross-sectional study compares trends in estimated age-adjusted cancer mortality rates between non-Hispanic Black and non-Hispanic White individuals in the US from 2000 to 2020.

A snapshot of injecting drug consumption from the analysis of used syringes within the Medically Supervised Injecting Centre in Sydney, Australia.

INTRODUCTION: The administration of illicit drugs by injection is associated with considerable harm, including an increased risk of overdose. The chemical analysis of used syringes can enhance knowledge on injecting drug consumption beyond traditional data sources (self-report surveys). This additional information may be useful during significant global events like the COVID-19 pandemic. This study aimed to examine a snapshot of the drugs injected at the Medically Supervised Injecting Centre (MSIC) in Sydney, Australia, in 2019-2020. METHODS: Used syringes were collected from MSIC across three periods throughout 2019 and 2020 (February 2019, March-April 2020 and June-September 2020). Drug residues were extracted from used syringes using methanol before detection by gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. The chemical analysis results were compared to self-report data obtained from MSIC clients. RESULTS: Heroin (46-53%), methamphetamine (24-34%) and pharmaceutical opioids (15-27%) were the most common drug residues detected. The chemically detected drugs had declining coherence with the drugs self-reported by MSIC clients across the time periods examined. DISCUSSION AND CONCLUSIONS: There was no significant change in the drugs injected (heroin, methamphetamine and pharmaceutical opioids) across the three periods collected throughout varying COVID-19 lockdown restrictions. Changes in the frequency of other drugs injected and discrepancies between chemical analysis and self-report were potentially related to regulatory changes, degradation or misinformed sales. Routine chemical analysis of used syringes has provided an alternative information source to promote awareness of current drug trends and aid harm reduction.

Primary Uterine Alveolar Soft Part Sarcoma in a Postmenopausal Woman: Histopathologic and Immunohistochemical Characteristics of a Rare Case.

BACKGROUND: Primary uterine alveolar soft part sarcoma (ASPS) is a rare, indolent mesenchymal malignancy with less than 40 patients documented in the literature. CASE: We report an example of ASPS in a 61-year-old postmenopausal woman. Macroscopically, the uterus showed multiple nodular masses. Microscopic examination revealed tumor arranged in nests and alveolar pattern. The tumor cells were moderately to markedly pleomorphic, epithelioid to polygonal, with eccentrically placed nuclei, vesicular chromatin, prominent macro-nucleoli, and moderate to abundant eosinophilic cytoplasm. PAS-positive and diastase-resistant intracytoplasmic crystals were also seen in some tumor cells. On immunohistochemistry, the tumor cells showed diffuse positivity for vimentin and nuclear positivity for TFE3, a surrogate marker for ASPS. These were negative for SMA, desmin, CD10, h-caldesmon, cyclin D1, EMA, Melan A, and CD34. SMARCB1 expression was retained. Based on the histopathology and IHC, a final diagnosis of uterine ASPS was rendered. CONCLUSIONS: Knowledge of the characteristic histopathologic and immunohistochemical features can help accurately diagnose such rare tumors. Knowledge of the characteristic histopathologic and immunohistochemical features can help accurately diagnose such rare sarcoma in an uncommon site with an unusual age.

Association of educational attainment with cancer mortality in a national cohort study of black and white adults: A mediation analysis.

Background: Low educational attainment is associated with excess cancer mortality. However, the mechanisms driving this association remain unknown. Methods: Using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we evaluated the associations of participant and parental/caregiver education with cancer mortality using Cox proportional hazards models, adjusting for socio-demographic characteristics and health conditions. We used principal components analysis to generate indices of measures representing the social determinants of health (SDOH) and health behaviors. We used structural equation modeling to determine if the association between educational attainment and cancer mortality was mediated by these domains. Results: Among 30,177 REGARDS participants included in this analysis, 3798 (12.6%) had less than a high school degree. In fully adjusted models, those without a high school education experienced about 50% greater risk of death than high school graduates and higher (White participants HR: 1.47; 95% CI: 1.23, 1.76 and Black HR: 1.54; 95% CI: 1.33, 1.79). There was evidence of a modest mediation effect for the association between education and cancer mortality by the SDOH domain score (White total effect HR: 1.25; 95% CI: 1.18, 1.33, indirect effect HR: 1.04; 95% CI: 1.03, 1.05, direct effect HR: 1.21; 95% CI: 1.14, 1.28 and Black total effect HR: 1.24; 95% CI: 1.18, 1.29, indirect effect HR: 1.04; 95% CI: 1.03, 1.05, direct effect HR: 1.19; 95% CI: 1.14, 1.24). There was no evidence of mediation by the health behaviors score. No significant associations were found for female caregiver/mother's or male caregiver/father's education (N = 13,209). Conclusions: In conclusion, participant education was strongly associated with cancer mortality, and this association was partially mediated by the SDOH domain score.

Alcoholic foamy degeneration: an unusual presentation of the alcoholic liver disease diagnosed on autopsy.

Alcoholic foamy degeneration (AFD) is an uncommon presentation of alcoholic liver disease (ALD) with characteristic histologic findings of foamy-looking hepatocytes due to the presence of abundant microvesicles of fat within the cytoplasm predominantly in perivenular and midzonal regions without inflammation and fibrosis. It is underdiagnosed as the patients quickly recover after alcoholic abstinence and are rarely caught on biopsies. AFD has better prognosis than alcoholic hepatitis, and the injury mechanism is different, warranting a different diagnosis. We present an uncommon case of AFD incidentally diagnosed during autopsy in a chronic alcoholic and diabetic man.

The nutrient sensor CRTC & Sarcalumenin / Thinman represent a new pathway in cardiac hypertrophy.

Obesity and type 2 diabetes are at epidemic levels and a significant proportion of these patients are diagnosed with left ventricular hypertrophy. CREB R egulated T ranscription C o-activator ( CRTC ) is a key regulator of metabolism in mammalian hepatocytes, where it is activated by calcineurin (CaN) to increase expression of gluconeogenic genes. CaN is known its role in pathological cardiac hypertrophy, however, a role for CRTC in the heart has not been identified. In Drosophila , CRTC null mutants have little body fat and exhibit severe cardiac restriction, myofibrillar disorganization, cardiac fibrosis and tachycardia, all hallmarks of heart disease. Cardiac-specific knockdown of CRTC , or its coactivator CREBb , mimicked the reduced body fat and heart defects of CRTC null mutants. Comparative gene expression in CRTC loss- or gain-of-function fly hearts revealed contra-regulation of genes involved in glucose, fatty acid, and amino acid metabolism, suggesting that CRTC also acts as a metabolic switch in the heart. Among the contra-regulated genes with conserved CREB binding sites, we identified the fly ortholog of Sarcalumenin, which is a Ca 2+ -binding protein in the sarcoplasmic reticulum. Cardiac knockdown recapitulated the loss of CRTC cardiac restriction and fibrotic phenotypes, suggesting it is a downstream effector of CRTC we named thinman ( tmn ). Importantly, cardiac overexpression of either CaN or CRTC in flies caused hypertrophy that was reversed in a CRTC mutant background, suggesting CRTC mediates hypertrophy downstream of CaN, perhaps as an alternative to NFAT. CRTC novel role in the heart is likely conserved in vertebrates as knockdown in zebrafish also caused cardiac restriction, as in fl ies. These data suggest that CRTC is involved in myocardial cell maintenance and that CaN-CRTC- Sarcalumenin/ tmn signaling represents a novel and conserved pathway underlying cardiac hypertrophy.

Healthcare access dimensions and uterine cancer survival: a national cancer database study.

Objective: Disparities exist throughout diagnosis, treatment, and survival for Black patients with uterine cancer. There is limited data on how several healthcare access (HCA) dimensions contribute to these disparities in patients with advanced stage uterine cancer. Methods: Using the National Cancer Database (NCDB), we identified patients aged 40-89 years with Stage III-IV uterine cancer between 2004-2015 who received chemotherapy and/or radiotherapy. Race/ethnicity were classified as non-Hispanic (NH)-Black, Hispanic, and NH-White. Variables defined in the NCDB were used to assess HCA affordability, availability, and accessibility. Kaplan-Meier estimates, log-rank test, and multivariable Cox proportional hazards models were used to analyze overall survival. Results: Of 43,134 patients, 78.8% of the cohort identified as NH-White, 15.3% NH-Black, and 5.9% Hispanic. NH-Black patients were the most likely to have type II (75.6% vs. 53.9% and 55.4%) and stage IV (40.8% vs. 30.7% and 32.3%) disease compared to NH-White and Hispanic patients. NH-Black patients were more likely than NH-White and Hispanic patients to have government funded insurance (58.6% vs. 50.3% and 50.4%), live in low-income areas (46.4% vs. 14.2% and 29.9%), and receive only chemotherapy (53.5% vs. 43.1% and 46.2%). Having private insurance and receiving treatment at an academic facility were positive predictors of survival. NH-Black patients had worse survival than NH-White patients after adjusting for clinical characteristics and healthcare access dimensions (HR 1.29; 95% CI 1.24, 1.34). Conclusion: While HCA affordability and availability predicted survival in patients with advanced stage uterine cancer, additional factors contribute to racial disparities. Compared to NH-White patients, NH-Black patients had more aggressive disease, received only chemotherapy rather than combined therapy, and had worse survival regardless of cancer subtype. Additional dimensions of healthcare access must be explored to remedy uterine cancer disparities.

A suite of selective pressures supports the maintenance of alleles of a Drosophila immune peptide.

The innate immune system provides hosts with a crucial first line of defense against pathogens. While immune genes are often among the fastest evolving genes in the genome, in Drosophila, antimicrobial peptides (AMPs) are notable exceptions. Instead, AMPs may be under balancing selection, such that over evolutionary timescales multiple alleles are maintained in populations. In this study, we focus on the Drosophila antimicrobial peptide Diptericin A, which has a segregating amino acid polymorphism associated with differential survival after infection with the Gram-negative bacteria Providencia rettgeri. Diptericin A also helps control opportunistic gut infections by common Drosophila gut microbes, especially those of Lactobacillus plantarum. In addition to genotypic effects on gut immunity, we also see strong sex-specific effects that are most prominent in flies without functional diptericin A. To further characterize differences in microbiomes between different diptericin genotypes, we used 16S metagenomics to look at the microbiome composition. We used both lab reared and wild caught flies for our sequencing and looked at overall composition as well as the differential abundance of individual bacterial families. Overall, we find flies that are homozygous serine for diptericin A are better equipped to survive a systemic infection from P. rettgeri, but in general homozygous arginine flies have a longer lifespan after being fed common gut commensals. Our results suggest a possible mechanism for the maintenance of genetic variation of diptericin A through the complex interactions of sex, systemic immunity, and the maintenance of the gut microbiome.

Nanomembranes-Affiliated Water Remediation: Chronology, Properties, Classification, Challenges and Future Prospects.

Water contamination has become a global crisis, affecting millions of people worldwide and causing diseases and illnesses, including cholera, typhoid, and hepatitis A. Conventional water remediation methods have several challenges, including their inability to remove emerging contaminants and their high cost and environmental impact. Nanomembranes offer a promising solution to these challenges. Nanomembranes are thin, selectively permeable membranes that can remove contaminants from water based on size, charge, and other properties. They offer several advantages over conventional methods, including their ability to remove evolving pollutants, low functioning price, and reduced ecological influence. However, there are numerous limitations linked with the applications of nanomembranes in water remediation, including fouling and scaling, cost-effectiveness, and potential environmental impact. Researchers are working to reduce the cost of nanomembranes through the development of more cost-effective manufacturing methods and the use of alternative materials such as graphene. Additionally, there are concerns about the release of nanomaterials into the environment during the manufacturing and disposal of the membranes, and further research is needed to understand their potential impact. Despite these challenges, nanomembranes offer a promising solution for the global water crisis and could have a significant impact on public health and the environment. The current article delivers an overview on the exploitation of various engineered nanoscale substances, encompassing the carbonaceous nanomaterials, metallic, metal oxide and metal-organic frameworks, polymeric nano-adsorbents and nanomembranes, for water remediation. The article emphasizes the mechanisms involved in adsorption and nanomembrane filtration. Additionally, the authors aim to deliver an all-inclusive review on the chronology, technical execution, challenges, restrictions, reusability, and future prospects of these nanomaterials.

Comparison of Two Different Intervals of Misoprostol Administration in Second Trimester Abortions.

Objective: Comparison of two different intervals of misoprostol administration after mifepristone in second trimester abortions. Materials and methods: This 12-month prospective study was conducted at a tertiary care facility. Only pregnancies with congenital deformity or sterilisation failure were included in the study's recruitment of 100 women who visited the hospital for a second trimester abortion between 12 and 20 weeks; cases with scarred uteri were omitted. In a systematic random selection of 50 women in each group, the administration of 200 mg of mifepristone orally was followed by two distinct intervals of intravaginal misoprostol administration at 24- and 48-hour intervals. After 24 hours, group A women received intravaginal 400 mcg misoprostol three hourly, up to a maximum of five doses, while group B received the same doses after 48 hours. Induction abortion interval noted on various parameters and paired t test and chi square test applied. Results: The mean IAI following misoprostol administration was 8.14 2±.03 hours in group A and 7.71 ±2.56 hours in group B. This difference was statistically insignificant. Average misoprostol doses for group A were 1.68±0.71 and for the group, B were 1.68±0.84; both doses were found to be statistically insignificant when used to induce abortion. All women aborted successfully in each group. There was no significant difference in side effects in both groups. Conclusion: Based on the results it was observed that shorter interval between mifepristone and misoprostol i.e., 24 hours can be chosen to decrease the hospital stay as there was no significant difference was seen after intravaginal misoprostol in terms of induction abortion interval, number of doses and side effects.

The genetic basis of variation in immune defense against Lysinibacillus fusiformis infection in Drosophila melanogaster.

The genetic causes of phenotypic variation often differ depending on the population examined, particularly if the populations were founded by relatively small numbers of genotypes. Similarly, the genetic causes of phenotypic variation among similar traits (resistance to different xenobiotic compounds or pathogens) may also be completely different or only partially overlapping. Differences in genetic causes for variation in the same trait among populations suggests context dependence for how selection acts on those traits. Similarities in the genetic causes of variation for different traits, on the other hand, suggests pleiotropy which would also influence how natural selection shapes variation in a trait. We characterized immune defense against a natural Drosophila pathogen, the Gram-positive bacterium Lysinibacillus fusiformis, in three different populations and found almost no overlap in the genetic architecture of variation in survival post infection. However, when comparing our results to a similar experiment with the fungal pathogen, B. bassiana, we found a convincing shared QTL peak for both pathogens. This peak contains the Bomanin cluster of Drosophila immune effectors. Loss of function mutants and RNAi knockdown experiments confirms a role of some of these genes in immune defense against both pathogens. This suggests that natural selection may act on the entire cluster of Bomanin genes (and the linked region under the QTL) or specific peptides for specific pathogens.

Growing Utilization of Radical Chemistry in the Synthesis of Pharmaceuticals.

Our current unhealthy lifestyle and the exponential surge in the population getting affected by a variety of diseases have made pharmaceuticals or drugs an imperative part of life, making the development of innovative strategies for drug discovery or the introduction of refined, cost-effective and modern technologies for the synthesis of clinically used drugs, a need of the hour. Ever since their discovery, free radicals and radical cations or anions as reactive intermediates have captivated the chemists, resulting in an exceptional utilization of these moieties throughout the field of chemical synthesis, owing to their unprecedented and widespread reactivity. Sticking with the idea of not judging the book by its cover, despite the conventional thought process of radicals being unstable and difficult to control entities, scientists and academicians around the globe have done an appreciable amount of work utilizing both persistent as well as transient radicals for a variety of organic transformations, exemplifying them with the synthesis of significant biologically active pharmaceutical ingredients. This review truly accounts for the organic radical transformations including radical addition, radical cascade cyclization, radical/radical cross-coupling, coupling with metal-complexes and radical cations coupling with nucleophiles, that offers fascinating and unconventional approaches towards the construction of intricate structural frameworks of marketed APIs with high atom- and step-economy; complementing the otherwise employed traditional methods. This tutorial review presents a comprehensive package of diverse methods utilized for radical generation, featuring their reactivity to form critical bonds in pharmaceutical total synthesis or in building key starting materials or intermediates of their synthetic journey, acknowledging their excellence, downsides and underlying mechanisms, which are otherwise poorly highlighted in the literature. Despite great achievements over the past few decades in this area, many challenges and obstacles are yet to be unraveled to shorten the distance between the academics and the industry, which are all discussed in summary and outlook.

The impact of substrate dampness on the transfer of glass fragments to upper garments when breaking windows.

Glass fragments are often recovered from garments worn by the authors of certain types of crimes and are useful as they present strong connections to the scene at both the source and activity level. It is known that the transfer of glass fragments is impacted when recipient garments are dampened, such as by rain, however, the details of the effect are not clear. This research aimed to determine the impact of substrate dampness on glass retention. Across the three test garments, a cotton t-shirt was found to increase in retentiveness with increasing dampness, while a wool/polyester blend jumper and a cotton hoodie were both found to increase only to a point, before decreasing again when the garment was saturated. This is attributed to the construction of the fabrics, as it does not appear to be related to the identity of the textile itself. It was also found that the size distribution of fragments changed with dampness. All the garments retained a smaller proportion of fragments less than 0.5 mm in size when saturated or dampened than when dry, along with an increase in the proportion of fragments in the 1-1.5 mm and greater than 1.5 mm size categories. These results indicate that is important to consider the impact of substrate dampening when relevant, and that this consideration must be done holistically as different substrates respond to dampening in different ways. It also indicates that consideration of the size distribution in fragment populations may reveal additional information in complex scenarios.