Quantitative 3D electron microscopy characterization of mitochondrial structure, mitophagy, and organelle interactions in murine atrial fibrillation.

Atrial fibrillation (AF) is the most common clinical arrhythmia, however there is limited understanding of its pathophysiology including the cellular and ultrastructural changes rendered by the irregular rhythm, which limits pharmacological therapy development. Prior work has demonstrated the importance of reactive oxygen species (ROS) and mitochondrial dysfunction in the development of AF. Mitochondrial structure, interactions with other organelles such as sarcoplasmic reticulum (SR) and T-tubules (TT), and degradation of dysfunctional mitochondria via mitophagy are important processes to understand ultrastructural changes due to AF. However, most analysis of mitochondrial structure and interactome in AF has been limited to two-dimensional (2D) modalities such as transmission electron microscopy (EM), which does not fully visualize the morphological evolution of the mitochondria during mitophagy. Herein, we utilize focused ion beam-scanning electron microscopy (FIB-SEM) and perform reconstruction of three-dimensional (3D) EM from murine left atrial samples and measure the interactions of mitochondria with SR and TT. We developed a novel 3D quantitative analysis of FIB-SEM in a murine model of AF to quantify mitophagy stage, mitophagosome size in cardiomyocytes, and mitochondrial structural remodeling when compared with control mice. We show that in our murine model of spontaneous and continuous AF due to persistent late sodium current, left atrial cardiomyocytes have heterogenous mitochondria, with a significant number which are enlarged with increased elongation and structural complexity. Mitophagosomes in AF cardiomyocytes are located at Z-lines where they neighbor large, elongated mitochondria. Mitochondria in AF cardiomyocytes show increased organelle interaction, with 5X greater contact area with SR and are 4X as likely to interact with TT when compared to control. We show that mitophagy in AF cardiomyocytes involves 2.5X larger mitophagosomes that carry increased organelle contents. In conclusion, when oxidative stress overcomes compensatory mechanisms, mitophagy in AF faces a challenge of degrading bulky complex mitochondria, which may result in increased SR and TT contacts, perhaps allowing for mitochondrial Ca2+ maintenance and antioxidant production.

Investigating the impacts of climate change on hydroclimatic extremes in the Tar-Pamlico River basin, North Carolina.

Evaluating the forthcoming impacts of climate change is important for formulating efficient and flexible approaches to water resource management. General Circulation Models (GCMs) are primary tools that enable scientists to study both past and potential future climate changes, as well as their impacts on policies and actions. In this work, we quantify the future projected impacts of hydroclimatic extremes on the coastal, risk-prone Tar-Pamlico River basin in North Carolina using GCMs from the Sixth International Coupled Model Intercomparison Project (CMIP6). These models incorporate projected future societal development scenarios (Shared Socioeconomic Pathways, SSPs) as defined in the Intergovernmental Panel on Climate Change (IPCC) Sixth Assessment Report (AR6). Specifically, we have utilized historical residential expansion data, the Soil and Water Assessment Tool Plus (SWAT+), the Standardized Precipitation Index (SPI), and the Interquartile Range (IQR) method for analyzing extremes from 2024 to 2100. Our findings include: (1) a trend toward wetter conditions is identified with an increase in flood events toward 2100; (2) projected increases in the severity of flood peaks are found, quantified by a rise of 21% compared to the 2000-2020 period; (3) downstream regions are forecast to experience severe droughts up to 2044; and (4) low-lying and coastal regions are found as particularly susceptible to higher flood peaks and more frequent drought events between 2045 and 2100. This work provides valuable insights into the anticipated shifts in natural disaster patterns and supports decision-makers and authorities in promoting adaptive strategies and sustainable policies to address challenges posed by future climate changes in the Tar-Pamlico region and throughout the state of North Carolina, United States.

In-Vitro Cytotoxic Evaluation of Titanium Dioxide Nanoparticle Using L929 Cell Lines.

Tooth movement in orthodontic therapy is connected to the frictional force that is created as the wire passes over the bracket. It is possible for teeth to move quickly when friction is at a minimum. Wires coated with nanoparticles have been found to reduce friction as a result of current developments in the orthodontics sector. Having an antimicrobial property is an added benefit. To reduce the friction generated by brackets, wires, and bands by lessening their cytotoxicity, this study examines the potential use of TiO2 nanoparticles in orthodontics. A monolayer of L929 was utilized in an indirect cytotoxicity test to evaluate the cytotoxicity of the coated orthodontic wire. The absence of reactive zones in our sample data demonstrates that TiO2 is not cytotoxic. Considering the results of our study, we conclude that TiO2 is secure for use as a coating for orthodontic devices.

Jaws of knowledge: an analysis of temporomandibular joint insights in dental training-a quasi-experiment study.

Objectives: To access the knowledge of undergraduate and postgraduate students of the dental college on basic anatomy, physiology, clinical examination, and pathology of the temporomandibular joint (TMJ). Materials and Methods: A total of 610 undergraduate and postgraduate students of dental college, were included in this study. The questionnaire was pretested for validation and distributed online through Google forms. Results: A pairwise comparison showed that the percentage of correct answers for interns significantly differed from that of IV Bachelor of Dental Surgery (P=0.050) and postgraduate students (P=0.048) (below average: up to 6 correct answers, good: 7-11 correct answers, excellent: 12 or more correct answers). Conclusion: TMJ diseases are common in daily life but frequently go undiagnosed and untreated due to a lack of clinical expertise. This demonstrates the necessity of providing instructions that give students in-depth knowledge and abilities for TMJ issues in clinical practice.

BCLA CLEAR Presbyopia: Epidemiology and impact.

The global all-ages prevalence of epidemiologically-measured 'functional' presbyopia was estimated at 24.9% in 2015, affecting 1.8 billion people. This prevalence was projected to stabilise at 24.1% in 2030 due to increasing myopia, but to affect more people (2.1 billion) due to population dynamics. Factors affecting the prevalence of presbyopia include age, geographic location, urban versus rural location, sex, and, to a lesser extent, socioeconomic status, literacy and education, health literacy and inequality. Risk factors for early onset of presbyopia included environmental factors, nutrition, near demands, refractive error, accommodative dysfunction, medications, certain health conditions and sleep. Presbyopia was found to impact on quality-of-life, in particular quality of vision, labour force participation, work productivity and financial burden, mental health, social wellbeing and physical health. Current understanding makes it clear that presbyopia is a very common age-related condition that has significant impacts on both patient-reported outcome measures and economics. However, there are complexities in defining presbyopia for epidemiological and impact studies. Standardisation of definitions will assist future synthesis, pattern analysis and sense-making between studies.

A convenient spectrophotometric test for screening skin-sensitizing chemicals using reactivity with glutathione in chemico.

To initiate skin sensitization, haptens react with endogenous proteins. During this process, skin sensitizers react with small endogenous molecules containing thiol or amino groups. In this study, a simple spectrophotometric method to identify skin sensitizers in chemico was developed using the reactivity of glutathione (GSH) with test chemicals in a 96-well plate. To quantitate the remaining GSH following the reaction with a skin sensitizer, 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) was employed. The optimized experimental conditions included the pH- and time-dependent stability of GSH, stability of derivatized products of GSH with optimal concentration and incubation time of DTNB, incubation time of GSH with the test chemicals, and molar ratios of GSH to the test chemicals. With the optimized conditions with both acetonitrile and DMSO as vehicles and incubation of GSH with test chemicals in 1:10 and 1:15 ratios for 24 h at 4 °C, 23 skin sensitizers and 23 non-sensitizers, based on the local lymph node assay, were tested to determine the predictive capacity of individual conditions. The best result showed a predictive capacity of 95.2% sensitivity, 91.3% specificity, and 93.2% accuracy, with 93.2% consistency in three trials, when 5.8% depletion was used as a cut-off value in 1:10 of GSH:test chemicals in DMSO. It would be an economic and useful screening tool for determining the skin sensitization potential of small molecules, because the present method employs simple endogenous GSH as an electron donor for sensitizers with a spectrophotometric detection system in 96-well plates, and because the method requires neither experimental animals nor cell cultures. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00218-9.

Glycolate oxidase-1 gene variants influence the risk of hyperoxaluria and renal stone development.

PURPOSE: Oxalate is an excellent calcium ion attractor with great abundance in the human body, and the liver is the major source of oxalate. The Glycolate oxidase-1 (GOX1) gene is solely responsible for the glycolate and glyoxylate metabolism and produces oxalate. This study has been designed to comprehend the association of genetic variants of the GOX1 gene with the risk of hyperoxaluria and renal stone disease in the Indian population. METHOD: The present study is a candidate gene approach prospective case-control study carried out on 300 participants (150 cases and 150 controls) at Muljibhai Patel Urological Hospital, Gujarat, India. Biochemical parameters, including serum levels of calcium, creatinine, parathyroid hormone, and 24-h urine metabolites, were performed. The genotyping of GOX1 gene variants rs6086287, rs2235250, rs2255183, and rs2294303 was performed using a customized TaqMan assay probe by RT-PCR. RESULT: Parathyroid hormone, serum creatinine, and urine metabolites were significantly elevated in nephrolithiasis compared to healthy individuals. All mutated homozygous genotypes GG (rs6086287), TT (rs2235250), GG (rs2255183), and CC (rs2294303) were significantly associated with a high risk of renal stone disease. Individuals diagnosed with hyperoxaluria and carrying TG (rs6086287), AG (rs2255183), and TT (rs2294303) genotypes have a significantly high risk of renal stone disease. Moreover, haplotype analysis and correlation analysis also confirmed the strong association between genetic variants and nephrolithiasis. CONCLUSION: Genetic variants of the GOX1 genes were associated with renal stone disease. In the presence of risk genotype and hyperoxaluria, the susceptibility to develop renal stone disease risk gets modulated.

Non-Linear Optics at Twist Interfaces in h-BN/SiC Heterostructures.

Understanding the emergent electronic structure in twisted atomically thin layers has led to the exciting field of twistronics. However, practical applications of such systems are challenging since the specific angular correlations between the layers must be precisely controlled and the layers have to be single crystalline with uniform atomic ordering. Here, an alternative, simple, and scalable approach is suggested, where nanocrystallinetwo-dimensional (2D) film on 3D substrates yields twisted-interface-dependent properties. Ultrawide-bandgap hexagonal boron nitride (h-BN) thin films are directly grown on high in-plane lattice mismatched wide-bandgap silicon carbide (4H-SiC) substrates to explore the twist-dependent structure-property correlations. Concurrently, nanocrystalline h-BN thin film shows strong non-linear second-harmonic generation and ultra-low cross-plane thermal conductivity at room temperature, which are attributed to the twisted domain edges between van der Waals stacked nanocrystals with random in-plane orientations. First-principles calculations based on time-dependent density functional theory manifest strong even-order optical nonlinearity in twisted h-BN layers. This work unveils that directly deposited 2D nanocrystalline thin film on 3D substrates could provide easily accessible twist-interfaces, therefore enabling a simple and scalable approach to utilize the 2D-twistronics integrated in 3D material devices for next-generation nanotechnology.

Evaluating hydrological alterations and recommending minimum flow release from the Ujjani dam to improve the Bhima River ecosystem health.

Numerous anthropogenic activities like the construction of large dams, storages, and barrages changed the watershed characteristics impacting ecosystem health. In this study, the hydrological alterations (HAs) that have occurred in the Bhima River due to the construction of the Ujjani dam were analyzed. The hydraulic analysis is also performed to determine the hydraulic parameter and recommend the lowest flow release from the dam for improving ecosystem health. Fifty-eight years of data starting from the year 1960 to 2018 were gathered at Yadgir station, which is located downstream of the Ujjani dam. The data were divided into pre- and post-construction river flow discharge. To check for the change in the river flow regime for the post-dam construction period, HA was calculated using Flow Health Software (FHS). The results demonstrate that the dam impoundment reduces high flows primarily by storing flood flow for water supply, irrigation, etc. The velocity and depth provided by the environmental design flow for a flow health (FH) score of 0.62 give a very good habitat to fishes. A minimum release of 24.8 m3/s from the dam is recommended. This study will help policymakers mitigate the impacts of degrading ecosystem health of the Bhima River.

Heteroatom Functionalization of H-Terminated Diamond Surfaces.

Diamond surface functionalization has received significant research interest recently. Specifically, H-termination has been widely adopted because it endows the diamond surface with negative electron affinity and the hole carrier is injected in the presence of surface transfer dopants. Exploring different functional groups' attachment on diamond surfaces and their impact on the electronic structure, using wet and dry chemical approaches, would hence be of interest in engineering diamond as a semiconductor. Here, we report the functionalization of the H-terminated diamond surface with nitrogen and sulfur heteroatoms. Surface characterization of functionalized diamond surfaces shows that these groups are well-distributed and covalently bonded to diamonds. Four chemical functional groups (-SH, -S-S-, -S-O, and -S=O) were found on the sulfurized diamond surface, and two groups (-NH2 and =NH) upon amination. We also report co-functionalization of surface with N and S (N-S), where sulfurization promotes sequential amination efficiency with reduced exposure time. Electrical measurement shows that heteroatom-modified diamond surfaces possess higher conductivity than H-terminated diamonds. Density functional theory (DFT) shows that upon functionalization with various N/S ratios, the conduction band minimum and valence band maximum downshift, which lowers the bandgap in comparison to an H-terminated diamond. These observations suggest the possibility of heteroatom functionalizations with enhanced surface electrical conductivity on the diamond that are useful for various electronic applications.

Initial experience of comparison between two slimmest single-use flexible ureteroscopes: Indoscope Sleek (Bioradmedisys™) Versus Uscope PU3033A (Pusen™): A single-center prospective study.

PURPOSE: A single-use digital flexible ureteroscope (fURS) has become a cost-effective alternative option to reusable fURS. The requirement of large-diameter access sheath for passage of 9.5 Fr single-use fURS has not always achieved in the first attempt in all cases leading to stage stone clearance. Recently, two slimmest single-use digital disposable fURSs have been introduced by Bioradmedisys™ and Pusen™ to mitigate the accessibility problem, without or with small size access sheath. Primary objective was to compare in vivo performance and surgical outcomes with two single-use fURS: 7.5Fr Indoscope (Bioradmedisys™, Pune, India) and 7.5Fr Uscope PU3033A (Pusen, Zhuhai, China). METHODS: 60 patients undergoing Retrograde Intrarenal Surgery (RIRS) with < 2 cm renal stones were prospectively randomized into: Group A (30 patients) for Indoscope and Group B (30 patients) for Uscope PU3033A. Pre-operative, intra-operative, and post-operative parameters were evaluated. In vivo visibility and maneuverability were rated on 5-point Likert scale by the operating surgeon. At one-month stone clearance was assessed with ultrasound and X-ray KUB. Data were analyzed using SPSS 23.0. RESULTS: Patient demographics and stone characteristics were comparable in both groups. Indoscope had significantly higher visibility (p < 0.05) than Uscope; however, the maneuverability scores were comparable between both the groups (p > 0.05). 28 patients in group A and 26 patients in group B achieved complete stone clearance (p = 0.38). Scope failure was observed in 1 case of group B (p = 0.31). CONCLUSION: We conclude that 7.5Fr Indoscope has better vision than 7.5Fr Uscope and the rest of in vivo performances were comparable with similar outcomes and complications among both scopes.

Study of the predictive factors affecting outcomes of patients undergoing transperitoneal laparoscopic donor nephrectomy.

PURPOSE: We aim to study the preoperative and intraoperative factors and compare against specific outcomes in patients undergoing transperitoneal laparoscopic donor nephrectomy and see if we could find what were the predictive factors for these outcomes. METHODS: This is a prospective cohort study done in a single high-volume transplant center. 153 kidney donors were evaluated over a period of 1 year. The preoperative factors such as age, gender, smoking status, obesity, visceral obesity, perinephric fat thickness, number of vessels, anatomic abnormalities, comorbidities, and side of kidney and intraoperative factors such as lay of colon on the kidney, height of splenic or hepatic flexure of colon, loaded or unloaded colon, and sticky mesenteric fat were compared against specific outcomes such as duration of surgery, duration of hospital stay, postoperative paralytic ileus, and postoperative wound complications. RESULTS: Multivariate logistic regression models were used to study the variables of interest against the various outcomes. There were three positive risk factors for increased hospital stay, which were perinephric fat thickness and height of splenic or hepatic flexure of colon and smoking history. There was one positive risk factor for postoperative paralytic ileus which is lay of colon with relation to kidney and there was one positive risk factor for postoperative wound complication which was visceral fat area. CONCLUSION: The predictive factors for adverse postoperative outcomes after transperitoneal laparoscopic donor nephrectomy were perinephric fat thickness, height of splenic or hepatic flexure, smoking status, lay or redundancy of colon with relation to kidney and visceral fat area.

Phase Stability of Hexagonal/Cubic Boron Nitride Nanocomposites.

Boron nitride (BN) is an exceptional material, and among its polymorphs, two-dimensional (2D) hexagonal and three-dimensional (3D) cubic BN (h-BN and c-BN) phases are most common. The phase stability regimes of these BN phases are still under debate, and phase transformations of h-BN/c-BN remain a topic of interest. Here, we investigate the phase stability of 2D/3D h-BN/c-BN nanocomposites and show that the coexistence of two phases can lead to strong nonlinear optical properties and low thermal conductivity at room temperature. Furthermore, spark-plasma sintering of the nanocomposite shows complete phase transformation to 2D h-BN with improved crystalline quality, where 3D c-BN possibly governs the nucleation and growth kinetics. Our demonstration might be insightful in phase engineering of BN polymorph-based nanocomposites with desirable properties for optoelectronics and thermal energy management applications.

Strain-tunable Berry curvature in quasi-two-dimensional chromium telluride.

Magnetic transition metal chalcogenides form an emerging platform for exploring spin-orbit driven Berry phase phenomena owing to the nontrivial interplay between topology and magnetism. Here we show that the anomalous Hall effect in pristine Cr2Te3 thin films manifests a unique temperature-dependent sign reversal at nonzero magnetization, resulting from the momentum-space Berry curvature as established by first-principles simulations. The sign change is strain tunable, enabled by the sharp and well-defined substrate/film interface in the quasi-two-dimensional Cr2Te3 epitaxial films, revealed by scanning transmission electron microscopy and depth-sensitive polarized neutron reflectometry. This Berry phase effect further introduces hump-shaped Hall peaks in pristine Cr2Te3 near the coercive field during the magnetization switching process, owing to the presence of strain-modulated magnetic layers/domains. The versatile interface tunability of Berry curvature in Cr2Te3 thin films offers new opportunities for topological electronics.

A Critical Review of Thermal Boundary Conductance across Wide and Ultrawide Bandgap Semiconductor Interfaces.

The emergence of wide and ultrawide bandgap semiconductors has revolutionized the advancement of next-generation power, radio frequency, and opto- electronics, paving the way for chargers, renewable energy inverters, 5G base stations, satellite communications, radars, and light-emitting diodes. However, the thermal boundary resistance at semiconductor interfaces accounts for a large portion of the near-junction thermal resistance, impeding heat dissipation and becoming a bottleneck in the devices' development. Over the past two decades, many new ultrahigh thermal conductivity materials have emerged as potential substrates, and numerous novel growth, integration, and characterization techniques have emerged to improve the TBC, holding great promise for efficient cooling. At the same time, numerous simulation methods have been developed to advance the understanding and prediction of TBC. Despite these advancements, the existing literature reports are widely dispersed, presenting varying TBC results even on the same heterostructure, and there is a large gap between experiments and simulations. Herein, we comprehensively review the various experimental and simulation works that reported TBCs of wide and ultrawide bandgap semiconductor heterostructures, aiming to build a structure-property relationship between TBCs and interfacial nanostructures and to further boost the TBCs. The advantages and disadvantages of various experimental and theoretical methods are summarized. Future directions for experimental and theoretical research are proposed.

Stage Migration in Renal Malignancies in COVID Era: A Single-Center Analysis.

The COVID-19 disease, caused by SARS-CoV-2 virus, attained the status of a pandemic by March 2020. There was apprehension among patients suffering from renal malignancies about balancing cancer treatment and preventing COVID-19 infection transmission. We analyzed 184 patients with renal malignancies retrospectively, who presented to our institute over 2 years: 91 patients of renal malignancies in pre-COVID era (March 2019-Feb 2020) and 93 patients in COVID era (March 2020-Feb 2021). The parameters analyzed were age, tumor size, clinical presentation, clinical stage, pathological stage, nuclear grade, and presence of metastasis. Level of significance was kept at 95%, and p value <0.05 was considered significant. The age of patients was comparable in both groups (p: 0.381). Clinical presentation was also similar in both groups whereas there were more cases diagnosed during routine evaluation in pre-COVID era (p: 0.022). Tumor size was 5.84 ± 3.03cm vs. 7.10±3.83cm (p: 0.017) in pre-COVID vs. COVID era, respectively. Patients in COVID era had significantly higher clinical stage (p = 0.041), pathological stage (p =0.027), nuclear grade (p = 0.007), and presence of metastasis (p = 0.005) as compared to pre-COVID era. Patients, who underwent Nephron-sparing surgery, also had higher pathological stage in COVID era. COVID overshadowed the management of renal malignancies. There was a clear shift and stage migration in patients of renal malignancies in COVID era as compared to pre-COVID era, probably because of less routine health check-ups and patients deferring hospital visits due to fear of contracting COVID infection.

Post Surgical Outcomes in Paediatric Adenotonsillar Hypertrophy with Obstructive Sleep Apnea: Subjective and Objective Evaluation.

The aim of the study was to determine the post surgical outcomes in pediatric adenotonsillar hypertrophy with OSA using portable polysomnography (PSG), OSA 18 Questionnaire and Quality of life (QoL) scores. Secondly to correlate the subjective outcomes with objective scores of polysomonography. A prospective, single-arm, nonrandomized, single center study was performed at a tertiary care centre on children aged 3-12 years (n = 30) with adenoid hypertrophy/ tonsillar hypertrophy/adenotonsillar hypertrophy and symptoms suggestive of OSA. All subjects underwent appropriate surgical intervention. A portable PSG and OSA 18 questionnaire evaluation was performed pre surgery and 06 weeks post surgery to assess objective and clinical assessment for OSA. The mean age of children enrolled in the study was 8.68 ± 3 years. The mean pre treatment AHI was 12.56 ± 13.16 which improved to 1.72 ± 1.53 post surgery and was statistically significant (p < 0.05, Wilcoxon signed rank test). There was a statistically significant improvement in other PSG indices such as RDI and ODI post surgery also. The mean total symptom score (TSS) and QoL score also showed a statistically significant improvement post treatment (p < 0.05). However there was no correlation between the PSG and OSA 18 questionnaire scores pre and post surgery. Children with OSA like symptoms can undergo a portable polysomnography pre and post surgery to demonstrate severity of OSA and objectively monitor improvement in OSA post treatment. In the absence of availability of PSG, OSA 18 questionnaire is a suitable alternative to monitor disease severity and outcomes. Further studies may plan to include impact of paediatric OSA on other function such as the cardiac, dentition & malocclusion and neurocognitive function.

Revealing the influence of bias in a letter acuity identification task: A noisy template model.

In clinical testing of visual acuity, it is often assumed that performance reflects sensory abilities and observers do not exhibit strong biases for or against specific letters, but this assumption has not been extensively tested. We re-analyzed single-letter identification data as a function of letter size, spanning the resolution threshold, for 10 Sloan letters at central and paracentral visual field locations. Individual observers showed consistent letter biases across letter sizes. Preferred letters were named much more often and others less often than expected (group averages ranged from 4% to 20% across letters, where the unbiased rate was 10%). In the framework of signal detection theory, we devised a noisy template model to distinguish biases from differences in sensitivity. When bias varied across letter templates the model fitted very well - much better than when sensitivity varied without bias. The best model combined both, having substantial biases and small variations in sensitivity across letters. The over- and under-calling decreased at larger letter sizes, but this was well-predicted by template responses that had the same additive bias for all letter sizes: with stronger inputs (larger letters) there was less opportunity for bias to influence which template gave the biggest response. The neural basis for such letter bias is not known, but a plausible candidate is the letter-recognition machinery of the left temporal lobe. Future work could assess whether such biases affect clinical measures of visual performance. Our analyses so far suggest very small effects in most settings.