Evaluating spectral performance for quantitative contrast-enhanced breast CT with a GaAs based photon counting detector: a simulation approach.

Quantitative contrast-enhanced breast computed tomography (CT) has the potential to improve the diagnosis and management of breast cancer. Traditional CT methods using energy-integrated detectors and dual-exposure images with different incident spectra for material discrimination can increase patient radiation dose and be susceptible to motion artifacts and spectral resolution loss. Photon Counting Detectors (PCDs) offer a promising alternative approach, enabling acquisition of multiple energy levels in a single exposure and potentially better energy resolution. Gallium arsenide (GaAs) is particularly promising for breast PCD-CT due to its high quantum efficiency and reduction of fluorescence x-rays escaping the pixel within the breast imaging energy range. In this study, the spectral performance of a GaAs PCD for quantitative iodine contrast-enhanced breast CT was evaluated. A GaAs detector with a pixel size of 100µm, a thickness of 500µm was simulated. Simulations were performed using cylindrical phantoms of varying diameters (10 cm, 12 cm, and 16 cm) with different concentrations and locations of iodine inserts, using incident spectra of 50, 55, and 60 kVp with 2 mm of added aluminum filtration and and a mean glandular dose of 10 mGy. We accounted for the effects of beam hardening and energy detector response using TIGRE CT open-source software and the publicly available Photon Counting Toolkit (PcTK). Material-specific images of the breast phantom were produced using both projection and image-based material decomposition methods, and iodine component images were used to estimate iodine intake. Accuracy and precision of the proposed methods for estimating iodine concentration in breast CT images were assessed for different material decomposition methods, incident spectra, and breast phantom thicknesses. The results showed that both the beam hardening effect and imperfection in the detector response had a significant impact on performance in terms of Root Mean Squared Error (RMSE), precision, and accuracy of estimating iodine intake in the breast. Furthermore, the study demonstrated the effectiveness of both material decomposition methods in making accurate and precise iodine concentration predictions using a GaAs-based photon counting breast CT system, with better performance when applying the projection-based material decomposition approach. The study highlights the potential of GaAs-based photon counting breast CT systems as viable alternatives to traditional imaging methods in terms of material decomposition and iodine concentration estimation, and proposes phantoms and figures of merit to assess their performance.

Emotion brain network topology in healthy subjects following passive listening to different auditory stimuli.

A large body of research establishes the efficacy of musical intervention in many aspects of physical, cognitive, communication, social, and emotional rehabilitation. However, the underlying neural mechanisms for musical therapy remain elusive. This study aimed to investigate the potential neural correlates of musical therapy, focusing on the changes in the topology of emotion brain network. To this end, a Bayesian statistical approach and a cross-over experimental design were employed together with two resting-state magnetoencephalography (MEG) as controls. MEG recordings of 30 healthy subjects were acquired while listening to five auditory stimuli in random order. Two resting-state MEG recordings of each subject were obtained, one prior to the first stimulus (pre) and one after the final stimulus (post). Time series at the level of brain regions were estimated using depth-weighted minimum norm estimation (wMNE) source reconstruction method and the functional connectivity between these regions were computed. The resultant connectivity matrices were used to derive two topological network measures: transitivity and global efficiency which are important in gauging the functional segregation and integration of brain network respectively. The differences in these measures between pre- and post-stimuli resting MEG were set as the equivalence regions. We found that the network measures under all auditory stimuli were equivalent to the resting state network measures in all frequency bands, indicating that the topology of the functional brain network associated with emotional regulation in healthy subjects remains unchanged following these auditory stimuli. This suggests that changes in the emotion network topology may not be the underlying neural mechanism of musical therapy. Nonetheless, further studies are required to explore the neural mechanisms of musical interventions especially in the populations with neuropsychiatric disorders.

Comprehensive review on glucose 6 phosphate dehydrogenase: A critical immunometabolic and redox switch in insects.

Mounting an active immune response is energy intensive and demands the reallocation of nutrients to maintain the body's resistance and tolerance against infections. Central to this metabolic adaptation is Glucose-6-phosphate dehydrogenase (G6PDH), a housekeeping enzyme involve in pentose phosphate pathway (PPP). PPP play an essential role in generating ribose, which is critical for nicotinamide adenine dinucleotide phosphate (NADPH). It is vital for physiological and cellular processes such as generating nucleotides, fatty acids and reducing oxidative stress. The G6PDH is extremely conserved enzyme across species in PP shunt. The deficiency of enzymes leads to serious consequences on organism, particularly on adaptation and development. Acute deficiency can lead to impaired cell development, halted embryonic growth, reduce sensitivity to insulin, hypertension and increase inflammation. Historically, research focusing on G6PDH and PPP have primarily targeted diseases on mammalian. However, our review has investigated the unique functions of the G6PDH enzyme in insects and greatly improved mechanistic understanding of its operations. This review explore how G6PDH in insects plays a crucial role in managing the redox balance and immune related metabolism. This study aims to investigate the enzyme's role in different metabolic adaptations.

Evaluating the correlation of sclerostin levels with obesity and type 2 diabetes in a multiethnic population living in Kuwait.

Obesity and Type 2 Diabetes Mellitus (T2DM) are intricate metabolic disorders with a multifactorial etiology, often leading to a spectrum of complications. Recent research has highlighted the impact of these conditions on bone health, with a particular focus on the role of sclerostin (SOST), a protein molecule integral to bone metabolism. Elevated circulating levels of SOST have been observed in patients with T2DM compared to healthy individuals. This study aims to examine the circulating levels of SOST in a multiethnic population living in Kuwait and to elucidate the relationship between SOST levels, obesity, T2DM, and ethnic background. The study is a cross-sectional analysis of a large cohort of 2083 individuals living in Kuwait. The plasma level of SOST was measured using a bone panel multiplex assay. The study found a significant increase in SOST levels in individuals with T2DM (1008.3 pg/mL, IQR-648) compared to non-diabetic individuals (710.6 pg/mL, IQR-479). There was a significant gender difference in median SOST levels, with males exhibiting higher levels than females across various covariates (diabetes, IR, age, weight, and ethnicity). Notably, SOST levels varied significantly with ethnicity: Arabs (677.4 pg/mL, IQR-481.7), South Asians (914.6 pg/mL, IQR-515), and Southeast Asians (695.2 pg/mL, IQR-436.8). Furthermore, SOST levels showed a significant positive correlation with gender, age, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, HbA1c, insulin, total cholesterol, triglycerides, HDL, LDL, ALT, and AST (p-Value ≥0.05). South Asian participants, who exhibited the highest SOST levels, demonstrated the most pronounced associations, even after adjusting for age, gender, BMI, and diabetes status (p-Value ≥0.05). The observed correlations of SOST with various clinical parameters suggest its significant role in the diabetic milieu, particularly pronounced in the South Asian population compared to other ethnic groups.

Review and Assessment of Material, Method, and Predictive Modeling for Fiber-Reinforced Polymer (FRP) Partially Confined Concrete Columns.

The repairing and strengthening of concrete structures using external and internal partial confinements are inevitable in the construction industry due to the new standards and rapid developments. The conventional materials and methods of confinement are unable to meet modern safety and functional standards. The fiber-reinforced polymer (FRP) enhances the strength and ductility of deteriorating and new concrete columns by reducing lateral confinement pressure and resistance against seismic shocks. The precise methods of partial confinement are inevitable for effective FRP-concrete bonding, durability, and cost-effectiveness under different loading conditions and to cope with external environmental factors. Predictive modeling and simulation techniques are pivotal for the optimization of confinement materials and methods by investigating the FRP-concrete novel confinement configurations, stress-strain responses, and failure modes. The novel materials and methods for concrete columns' partial confinement lack high compressive strength, ductility, chemical attack resistivity, and different fiber orientation impacts. This review provides an overview of recent confinement materials, novel methods, and advanced modeling and simulation techniques with a critical analysis of the research gaps for partial FRP confinement of concrete columns. The current challenges and future prospects are also presented.

Ethnic Variations in the Levels of Bone Biomarkers (Osteoprostegerin, Receptor Activator of Nuclear Factor Kappa-Β Ligand and Glycoprotein Non-Metastatic Melanoma Protein B) in People with Type 2 Diabetes.

The global incidence of Type 2 diabetes (T2D) is on the rise, fueled by factors such as obesity, sedentary lifestyles, socio-economic factors, and ethnic backgrounds. T2D is a multifaceted condition often associated with various health complications, including adverse effects on bone health. This study aims to assess key biomarkers linked to bone health and remodeling-Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor Kappa-Β Ligand (RANKL), and Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB)-among individuals with diabetes while exploring the impact of ethnicity on these biomarkers. A cross-sectional analysis was conducted on a cohort of 2083 individuals from diverse ethnic backgrounds residing in Kuwait. The results indicate significantly elevated levels of these markers in individuals with T2D compared to non-diabetic counterparts, with OPG at 826.47 (405.8) pg/mL, RANKL at 9.25 (17.3) pg/mL, and GPNMB at 21.44 (7) ng/mL versus 653.75 (231.7) pg/mL, 0.21 (9.94) pg/mL, and 18.65 (5) ng/mL in non-diabetic individuals, respectively. Notably, this elevation was consistent across Arab and Asian populations, except for lower levels of RANKL observed in Arabs with T2D. Furthermore, a positive and significant correlation between OPG and GPNMB was observed regardless of ethnicity or diabetes status, with the strongest correlation (r = 0.473, p < 0.001) found among Arab individuals with T2D. Similarly, a positive and significant correlation between GPNMB and RANKL was noted among Asian individuals with T2D (r = 0.401, p = 0.001). Interestingly, a significant inverse correlation was detected between OPG and RANKL in non-diabetic Arab individuals. These findings highlight dysregulation in bone remodeling markers among individuals with T2D and emphasize the importance of considering ethnic variations in T2D-related complications. The performance of further studies is warranted to understand the underlying mechanisms and develop interventions based on ethnicity for personalized treatment approaches.

Real-world effectiveness of sodium-glucose cotransporter-2 inhibitors on the progression of chronic kidney disease in patients without diabetes, with and without albuminuria.

AIM: To examine the renal effects of sodium-glucose cotransporter-2 (SGLT2) inhibition among non-diabetic individuals with chronic kidney disease (CKD) in a real-world setting. METHODS: We collected de-identified data on adults without diabetes and with an estimated glomerular filtration rate (eGFR) of 25-60 mL/min/1.73 m2, who initiated the SGLT2 inhibitors dapagliflozin or empagliflozin between September 2020 and November 2022 at Maccabi Healthcare Services, an Israeli health maintenance organization. We assessed the effects of SGLT2 inhibitors on renal function (changes in eGFR slope/time). Index date was defined as the date of the first dispensing of SGLT2 inhibitors. Annual baseline slope was calculated using all eGFR measurements during the 2 years prior to index date (median = 7 measurements), while annual follow-up slope was calculated from all evaluations during 90-900 days post index date, along with baseline measurement at index date (median = 6 measurements). Paired t tests were used to compare differences between baseline and follow-up annual slopes. RESULTS: Of a total of 354 participants with CKD, without diabetes, who received SGLT2 inhibitors and were followed for a median of 527 days, the mean age was 72.8 ± 11.8 years, 26% were female, and 91% used renin-angiotensin system blockade. The mean eGFR was 45.4 ± 9.5 mL/min/1.73 m2. The mean body mass index was 29.1 ± 5.4 kg/m2. During the year before index date, 146 participants (41%) had a urinary albumin to creatinine ratio (UACR) <30 mg/g, 81 (23%) had a UACR of 30-300 mg/g, 74 (21%) had a UACR >300 mg/g, and 53 (15%) had no UACR evaluation. The mean eGFR slope over time was -5.6 ± 7.7 mL/min/1.73 m2 per year at baseline, which improved to -1.7 ± 6.8 mL/min/1.73 m2 per year after SGLT2 inhibitor administration (p <0.001). This effect was independent of UACR. CONCLUSION: In a real-world study of primarily older non-diabetic adults with CKD, SGLT2 inhibition was associated with a slower rate of kidney function decline, regardless of baseline UACR level.

Bacteria associated with Comamonadaceae are key arsenite oxidizer associated with Pteris vittata root.

Pteris vittata (P. vittata), an arsenic (As) hyperaccumulator commonly used in the phytoremediation of As-contaminated soils, contains root-associated bacteria (RAB) including those that colonize the root rhizosphere and endosphere, which can adapt to As contamination and improve plant health. As(III)-oxidizing RAB can convert the more toxic arsenite (As(III)) to less toxic arsenate (As(V)) under As-rich conditions, which may promote plant survial. Previous studies have shown that microbial As(III) oxidation occurs in the rhizospheres and endospheres of P. vittata. However, knowledge of RAB of P. vittata responsible for As(III) oxidation remained limited. In this study, members of the Comamonadaceae family were identified as putative As(III) oxidizers, and the core microbiome associated with P. vittata roots using DNA-stable isotope probing (SIP), amplicon sequencing and metagenomic analysis. Metagenomic binning revealed that metagenome assembled genomes (MAGs) associated with Comamonadaceae contained several functional genes related to carbon fixation, arsenic resistance, plant growth promotion and bacterial colonization. As(III) oxidation and plant growth promotion may be key features of RAB in promoting P. vittata growth. These results extend the current knowledge of the diversity of As(III)-oxidizing RAB and provide new insights into improving the efficiency of arsenic phytoremediation.

Almond shell-derived biochar decreased toxic metals bioavailability and uptake by tomato and enhanced the antioxidant system and microbial community.

The effectiveness of almond shell-derived biochar (ASB) in immobilizing soil heavy metals (HMs) and its impact on soil microbial activity and diversity have not been sufficiently studied. Hence, a pot study was carried out to investigate the effectiveness of ASB addition at 2, 4, and 6 % (w/w) on soil biochemical characteristics and the bioavailability of Cd, Cu, Pb, and Zn to tomato (Solanum lycopersicum L.) plants, as compared to the control (contaminated soil without ASB addition). The addition of ASB promoted plant growth (up to two-fold) and restored the damage to the ultrastructure of chloroplast organelles. In addition, ASB mitigated the adverse effects of HMs toxicity by decreasing oxidative damage, regulating the antioxidant system, improving soil physicochemical properties, and enhancing enzymatic activities. At the phylum level, ASB addition enhanced the relative abundance of Actinobacteriota, Acidobacteriota, and Firmicutes while decreasing the relative abundance of Proteobacteria and Bacteroidota. Furthermore, ASB application increased the relative abundance of several fungal taxa (Ascomycota and Mortierellomycota) while reducing the relative abundance of Basidiomycota in the soil. The ASB-induced improvement in soil properties, microbial community, and diversity led to a significant decrease in the DTPA-extractable HMs down to 41.0 %, 51.0 %, 52.0 %, and 35.0 % for Cd, Cu, Pb, and Zn, respectively, as compared to the control. The highest doses of ASB (ASB6) significantly reduced the metals content by 26.0 % for Cd, 78.0 % for Cu, 38.0 % for Pb, and 20.0 % for Zn in the roots, and 72.0 % for Cd, 67.0 % for Cu, 46.0 % for Pb, and 35.0 % for Zn in the shoots, as compared to the control. The structural equation model predicts that soil pH and organic matter are driving factors in reducing the availability and uptake of HMs. ASB could be used as a sustainable trial for remediation of HMs polluted soils and reducing metal content in edible plants.

Potential of melatonin and Trichoderma harzianum inoculation in ameliorating salt toxicity in watermelon: Insights into antioxidant system, leaf ultrastructure, and gene regulation.

Melatonin (MT) is an extensively studied biomolecule with dual functions, serving as an antioxidant and a signaling molecule. Trichoderma Harzianum (TH) is widely recognized for its effectiveness as a biocontrol agent against many plant pathogens. However, the interplay between seed priming and MT (150 µm) in response to NaCl (100 mM) and its interaction with TH have rarely been investigated. This study aimed to evaluate the potential of MT and TH, alone and in combination, to mitigate salt stress (SS) in watermelon plants. The findings of this study revealed a significant decline in the morphological, physiological, and biochemical indices of watermelon seedlings exposed to SS. However, MT and TH treatments reduced the negative impact of salt stress. The combined application of MT and TH exerted a remarkable positive effect by increasing the growth, photosynthetic and gas exchange parameters, chlorophyll fluorescence indices, and ion balance (decreasing Na+ and enhancing K+). MT and TH effectively alleviated oxidative injury by inhibiting hydrogen peroxide formation in saline and non-saline environments, as established by reduced lipid peroxidation and electrolyte leakage. Moreover, oxidative injury induced by SS on the cells was significantly mitigated by regulation of the antioxidant system, AsA-GSH-related enzymes, the glyoxalase system, augmentation of osmolytes, and activation of several genes involved in the defense system. Additionally, the reduction in oxidative damage was examined by chloroplast integrity via transmission electron microscopy (TEM). Overall, the results of this study provide a promising contribution of MT and TH in safeguarding the watermelon crop from oxidative damage induced by salt stress.

Prophylactic Cholecystectomy is Safe in Patients Undergoing Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: While cholecystectomy is one of the most common operations performed in the United States, there is a continued debate regarding its prophylactic role in elective surgery. Particularly among patients with peritoneal carcinomatosis who undergo cytoreduction surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), further abdominal operations may pose increasing morbidity due to intraabdominal adhesions and potential recurrence. This bi-institutional retrospective study aims to assess postoperative morbidity associated with prophylactic cholecystectomy at the time of CRS-HIPEC. METHODS: We performed a bi-institutional retrospective analysis of 578 patients who underwent CRS-HIPEC from 2011 to 2021. Postoperative outcomes among patients who underwent prophylactic cholecystectomy at the time of CRS-HIPEC were compared to patients who did not, particularly rate of bile leak, hospital length of stay, rate of Clavien-Dindo classification morbidity grade III or greater, and number of hospital re-admissions within 30 days. RESULTS: Of the 535 patients available for analysis, 206 patients (38.3%) underwent a prophylactic cholecystectomy. Of the 3 bile leaks (1.5%) that occurred among patients who underwent prophylactic cholecystectomy, all 3 occurred in patients who underwent a concomitant liver resection. There were no significant differences in hospital length of stay, postoperative morbidity, and number of hospital re-admissions among patients who underwent prophylactic cholecystectomy compared to those who did not. CONCLUSION: Prophylactic cholecystectomy in patients undergoing CRS-HIPEC is not associated with increased morbidity or increased bile leak risk compared to historical data. While the benefits of prophylactic cholecystectomy are not yet elucidated, it may be considered to avoid potential future morbid operations for biliary disease.

International Diabetes Federation Position Statement on the 1-hour post-load plasma glucose for the diagnosis of intermediate hyperglycaemia and type 2 diabetes.

Many individuals with intermediate hyperglycaemia (IH), including impaired fasting glycaemia (IFG) and impaired glucose tolerance (IGT), as presently defined, will progress to type 2 diabetes (T2D). There is confirmatory evidence that T2D can be prevented by lifestyle modification and/or medications, in people with IGT diagnosed by 2-h plasma glucose (PG) during a 75-gram oral glucose tolerance test (OGTT). Over the last 40 years, a wealth of epidemiological data has confirmed the superior value of 1-h plasma glucose (PG) over fasting PG (FPG), glycated haemoglobin (HbA1c) and 2-h PG in populations of different ethnicity, sex and age in predicting diabetes and associated complications including death. Given the relentlessly rising prevalence of diabetes, a more sensitive, practical method is needed to detect people with IH and T2D for early prevention or treatment in the often lengthy trajectory to T2D and its complications. The International Diabetes Federation (IDF) Position Statement reviews findings that the 1-h post-load PG ≥ 155 mg/dL (8.6 mmol/L) in people with normal glucose tolerance (NGT) during an OGTT is highly predictive for detecting progression to T2D, micro- and macrovascular complications, obstructive sleep apnoea, cystic fibrosis-related diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, and mortality in individuals with risk factors. The 1-h PG of 209 mg/dL (11.6 mmol/L) is also diagnostic of T2D. Importantly, the 1-h PG cut points for diagnosing IH and T2D can be detected earlier than the recommended 2-h PG thresholds. Taken together, the 1-h PG provides an opportunity to avoid misclassification of glycaemic status if FPG or HbA1c alone are used. The 1-h PG also allows early detection of high-risk people for intervention to prevent progression to T2D which will benefit the sizeable and growing population of individuals at increased risk of T2D. Using a 1-h OGTT, subsequent to screening with a non-laboratory diabetes risk tool, and intervening early will favourably impact the global diabetes epidemic. Health services should consider developing a policy for screening for IH based on local human and technical resources. People with a 1-h PG ≥ 155 mg/dL (8.6 mmol/L) are considered to have IH and should be prescribed lifestyle intervention and referred to a diabetes prevention program. People with a 1-h PG ≥ 209 mg/dL (11.6 mmol/L) are considered to have T2D and should have a repeat test to confirm the diagnosis of T2D and then referred for further evaluation and treatment. The substantive data presented in the Position Statement provides strong evidence for redefining current diagnostic criteria for IH and T2D by adding the 1-h PG.

Toward robust and privacy-enhanced facial recognition: A decentralized blockchain-based approach with GANs and deep learning.

In recent years, the extensive use of facial recognition technology has raised concerns about data privacy and security for various applications, such as improving security and streamlining attendance systems and smartphone access. In this study, a blockchain-based decentralized facial recognition system (DFRS) that has been designed to overcome the complexities of technology. The DFRS takes a trailblazing approach, focusing on finding a critical balance between the benefits of facial recognition and the protection of individuals' private rights in an era of increasing monitoring. First, the facial traits are segmented into separate clusters which are maintained by the specialized node that maintains the data privacy and security. After that, the data obfuscation is done by using generative adversarial networks. To ensure the security and authenticity of the data, the facial data is encoded and stored in the blockchain. The proposed system achieves significant results on the CelebA dataset, which shows the effectiveness of the proposed approach. The proposed model has demonstrated enhanced efficacy over existing methods, attaining 99.80% accuracy on the dataset. The study's results emphasize the system's efficacy, especially in biometrics and privacy-focused applications, demonstrating outstanding precision and efficiency during its implementation. This research provides a complete and novel solution for secure facial recognition and data security for privacy protection.

Biological role and regulation of circular RNA as an emerging biomarker and potential therapeutic target for cancer.

Circular RNAs (circRNAs) are a unique family of endogenous RNAs devoid of 3' poly-A tails and 5' end caps. These single-stranded circRNAs, found in the cytoplasm, are synthesized via back-splicing mechanisms, merging introns, exons, or both, resulting in covalently closed circular loops. They are profusely expressed across the eukaryotic transcriptome and offer heightened stability against exonuclease RNase R compared to linear RNA counterparts. This review endeavors to provide a comprehensive overview of circRNAs' characteristics, biogenesis, and mechanisms of action. Furthermore, aimed to shed light on the potential of circRNAs as significant biomarkers in various cancer types. It has been performed an exhaustive literature review, drawing on recent studies and findings related to circRNA characteristics, synthesis, function, evaluation techniques, and their associations with oncogenesis. CircRNAs are intricately associated with tumor progression and development. Their multifaceted roles encompass gene regulation through the sponging of proteins and microRNAs, controlling transcription and splicing, interacting with RNA binding proteins (RBPs), and facilitating gene translation. Due to these varied roles, circRNAs have become a focal point in tumor pathology investigations, given their promising potential as both biomarkers and therapeutic agents. CircRNAs, due to their unique biogenesis and multifunctionality, hold immense promise in the realm of oncology. Their stability, widespread expression, and intricate involvement in gene regulation underscore their prospective utility as reliable biomarkers and therapeutic targets in cancer. As our understanding of circRNAs deepens, advanced techniques for their detection, evaluation, and manipulation will likely emerge. These advancements might catalyze the translation of circRNA-based diagnostics and therapeutics into clinical practice, potentially revolutionizing cancer care and prognosis.

QSPR analysis of distance-based structural indices for drug compounds in tuberculosis treatment.

Tuberculosis (TB) is one of the most contagious diseases that has a greater mortality rate than HIV/AIDS and the cases of TB are feared to rise as a repercussion of the COVID-19 pandemic. The pharmaceutical industry is constantly looking for ways to improve drug design processes in order to combat the growth of infections and cure newly identified syndromes or genetically based dysfunctions with the help of QSPR models. QSPR models are mathematical tools that establish relationships between a molecular structure and its physicochemical attributes using structural properties. Topological indices are such properties that are generated from the molecular graph without any empirically derived measurements. This work focuses on developing a QSPR model using distance-based topological indices for anti-tuberculosis medications and their diverse physicochemical features.

Empagliflozin Reduces Liver Fat in Individuals With and Without Diabetes.

OBJECTIVE: To examine the effect of empagliflozin on liver fat content in individuals with and without type 2 diabetes (T2D) and the relationship between the decrease in liver fat and other metabolic actions of empagliflozin. RESEARCH DESIGN AND METHODS: Thirty individuals with T2D and 27 without were randomly assigned to receive in double-blind fashion empagliflozin or matching placebo (2:1 ratio) for 12 weeks. Participants underwent 75-g oral glucose tolerance testing and measurement of liver fat content with MRS before therapy and at study end. Hepatic glucose production before the start of therapy was measured with 3-3H-glucose. RESULTS: Empagliflozin caused an absolute reduction of 2.39% ± 0.79% in liver fat content compared with an increase of 0.91% ± 0.64% in participants receiving placebo (P < 0.007 with ANOVA). The decrease in liver fat was comparable in both individuals with diabetes and those without (2.75% ± 0.81% and 1.93% ± 0.78%, respectively; P = NS). The decrease in hepatic fat content caused by empagliflozin was strongly correlated with baseline liver fat content (r = -0.62; P < 0.001), decrease in body weight (r = 0.53; P < 0.001), and improvement in insulin sensitivity (r = -0.51; P < 0.001) but was not related to the decrease in fasting plasma glucose or HbA1c or the increase in hepatic glucose production. CONCLUSIONS: Empagliflozin is effective in reducing liver fat content in individuals with and without T2D. The decrease in liver fat content is independent of the decrease in plasma glucose concentration and is strongly related to the decrease in body weight and improvement in insulin sensitivity.

The impact of increased hepatic glucose production caused by empagliflozin on plasma glucose concentration in individuals with type 2 diabetes and nondiabetic individuals.

AIM: To examine the impact of increased hepatic glucose production (HGP) on the decrease in plasma glucose concentration caused by empagliflozin in individuals living with diabetes and in nondiabetic individuals. METHODS: A total of 36 individuals living with diabetes and 34 nondiabetic individuals were randomized to receive, in double-blind fashion, empagliflozin or matching placebo in a 2:1 treatment ratio. Following an overnight fast, HGP was measured with 3-3 H-glucose infusion before, at the start of, and 3 months after therapy with empagliflozin. RESULTS: On Day 1 of empagliflozin administration, the increase in urinary glucose excretion (UGE) in individuals with normal glucose tolerance was smaller than in those with impaired glucose tolerance and those living with diabetes, and was accompanied by an increase in HGP in all three groups. The amount of glucose returned to the systemic circulation as a result of the increase in HGP was smaller than that excreted by the kidney during the first 3 h after empagliflozin administration, resulting in a decrease in fasting plasma glucose (FPG) concentration. After 3 h, the increase in HGP was in excess of UGE, leading to a small increase in plasma glucose concentration, which reached a new steady state. After 12 weeks, the amount of glucose returned to the circulation due to the empagliflozin-induced increase in HGP was comparable with that excreted by the kidney in all three groups. CONCLUSION: The balance between UGE and increase in HGP immediately after sodium-glucose cotransporter-2 (SGLT2) inhibition determined the magnitude of decrease in FPG and the new steady state which was achieved. After 12 weeks, the increase in HGP caused by empagliflozin closely matched the amount of glucose excreted by the kidneys; thus, FPG level remained stable despite the continuous urinary excretion of glucose caused by SGLT2 inhibition.

Exploring the diversity of CFTR gene mutations in cystic fibrosis individuals of South Asia.

OBJECTIVE: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene. This study aimed to identify the spectrum of CFTR variants reported in individuals with CF from South Asia (ISA). DATA SOURCES AND STUDY SELECTION: We conducted a PubMed search for CFTR variants reported in ISA. Full text of original articles and case reports was read to compile data on reported variants. To gather additional data, we independently cross-referenced each variant with the CFTR Mutation Database and ClinVar. RESULTS: Our investigation identified a total of 92 CFTR variants reported across 30 articles. The most frequently tested, and reported variant was ΔF508 with a global frequency of 69.74%. Notably, we found 14 pathogenic CFTR mutations shared among ISA, originating from more than one South Asian country: ΔF508, 1525-1 G > A, G542X, S549N, R117H, S549R, R709X, V456A, Y569D, L1077P, 1161delC, 1898 + 1 G > T, G551D, and 2184insA. CONCLUSION: In summary, the higher prevalence of consanguinity and the limited availability of CF diagnostic resources in South Asia considerably contribute to the prevalence of genetic disorders like CF. The spectrum of CFTR mutations exhibits noticeable variations within South Asian and other populations. The inclusion of current study-enlisted CFTR gene variants is highly recommended for CF disease genetic testing in South Asia which may aid in achieving a precise diagnosis, enhancing disease management, and discovering drugs for currently untreatable genetic variants. It is also imperative to conduct a comprehensive study in this region, especially in previously unexplored countries such as Nepal, Bhutan, Maldives, and Bangladesh.

Underdiagnosis of Hyperparathyroidism in Patients With Nephrolithiasis in a Community Setting.

Objective Untreated primary hyperparathyroidism (PHPT) has wide-ranging multisystemic effects. Recent studies based in the US have shown a less than 25% screening rate for PHPT. Our study aims to detect whether similar deficiencies exist in our community healthcare system while quantifying the prevalence of PHPT underdiagnosis and inadequate surgical referrals. Study design This retrospective quantitative study enrolled patients aged ≥18 years with imaged-confirmed nephrolithiasis at our healthcare facilities from 2017 to the present (n=2021). Patients with documented calcium levels and kidney/ureter stones were included. Descriptive and univariate analyses were performed. Results A total of 2021 subjects met the criteria to be enrolled in the study. 26.6% (n=537) of patients with nephrolithiasis had elevated calcium levels on record. 13.6% (n=73) of hypercalcemic patients were screened for PHPT with an intact parathyroid hormone (PTH). A majority (63%, n=46) of patients with intact PTH had PHPT defined as PTH levels >55 pg/mL. Ultimately, only 19.6% (n=9) of patients with PHPT were referred for surgical intervention, and there was no significant difference in referral rate between patients with PHPT and those without (p=0.913). Conclusions PHPT is underdiagnosed in our community, leading to a significantly low rate of surgical referral and delay in management. Implementation of hospital protocols to aid in improving diagnosis and interventions could improve outcomes for PHPT patients.

A paradigmatic approach to the molecular descriptor computation for some antiviral drugs.

In theoretical chemistry, topological indices are commonly employed to model the physico-chemical properties of chemical compounds. Mathematicians frequently use Zagreb indices to calculate a chemical compound's strain energy, melting point, boiling temperature, distortion, and stability. The current global pandemic caused by the new SARS-CoV-2, also known as COVID-19, is a significant public health concern. Various therapy modalities are advised. The issue has become worse since there hasn't been enough counseling. Researchers are looking at compounds that might be used as SARS and MERS therapies based on earlier studies. In several quantitative structure-property-activity relationships (QSPR and QSAR) studies, a variety of physiochemical properties are successfully represented by topological indices, a sort of molecular descriptor that just specifies numerical values connected to a substance's molecular structure. This study investigates several irregularity-based topological indices for various antiviral medicines, depending on the degree of irregularity. In order to evaluate the effectiveness of the generated topological indices, a QSPR was also carried out using the indicated pharmaceuticals, the various topological indices, and the various physiochemical features of these antiviral medicines. The acquired results show a substantial association between the topological indices being studied by the curve-fitting approach and the physiochemical properties of possible antiviral medicines.