Rifabutin loaded inhalable ß-glucan microparticle based drug delivery system for pulmonary TB.

Inhalable microparticle-based anti TB drug delivery systems are being investigated extensively for Tuberculosis [TB] treatment as they offer efficient and deep lung deposition with several advantages over conventional routes. It can reduce the drug dose, treatment duration and toxic effects and optimize the drug bioavailability. Yeast derived ß-glucan is a ß-[1-3/1-6] linked biocompatible polymer and used as carrier for various biomolecules. Due to presence of glucan chains, particulate glucans act as PAMP and thereby gets internalized via receptor mediated phagocytosis by the macrophages. In this study, ß-glucan microparticles were prepared by adding l-leucine as excipient, and exhibited 70% drug [Rifabutin] loading efficiency. Further, the sizing and SEM data of particles revealed a size of 2-4 µm with spherical dimensions. The FTIR and HPLC data confirmed the ß-glucan composition and drug encapsulations efficiency of the particles. The mass median aerodynamic diameter [MMAD] and geometric standard deviation [GSD] data indicated that these particles are inhalable in nature and have better thermal stability as per DSC thermogram. These particles were found to be non-toxic upto a concentration of 80 µg/ml and were found to be readily phagocytosed by human macrophage cells in-vitro as well as in-vivo by lung alveolar macrophage. This study provides a framework for future design of inhalable ß-glucan particle based host-directed drug delivery system against pulmonary TB.

A feasibility randomized controlled trial of culturally adapted Getting Better Bite-by-Bite (Ca-GBBB) intervention for individuals with eating disorders in Pakistan.

BACKGROUND: Eating disorders (EDs) are serious mental health conditions that affect a person physically and psychologically. In the past, EDs were only recognized as a cultural phenomenon/societal by-product of the West. However, research evidence marks its presence in non-western countries also, including South Asia. This study aims to evaluate the feasibility and acceptability of a manualized psychological intervention called Getting Better Bite by Bite (GBBB) in individuals who screened positive on measures of EDs in Pakistan. METHODS: The proposed study is a feasibility randomized controlled trial (fRCT). The study will be conducted at five sites across Pakistan: Karachi, Hyderabad, Lahore, Rawalpindi, and Multan to recruit a total of 80 participants. Eligible participants will be randomized to either (1) the intervention group; in which they will receive one-to-one sessions of GBBB along with routine care or (2) the routine care group; in which they will only have access to the routine care. We have received ethics approval by the National Bioethics Committee. The study is registered at clinicaltrials.gov (NCT05724394). The study team has received permission from recruitment centers: hospitals (i.e. the psychiatry department of public and private hospitals based in these cities), fitness centers (i.e., gyms), educational institutes (i.e., colleges and universities), and community settings (i.e. community health clinics). Self-referrals from General Practitioners and community settings will be accepted. The intervention manual has been translated into Urdu and a multidisciplinary team including service users has culturally adapted the content of intervention for local context. DISCUSSION: This study will provide evidence on feasibility and acceptability of a culturally adapted intervention for individuals who screen positive on measures of EDs. The findings of this study will inform a fully powered Randomized Controlled Trial of the proposed intervention. TRIAL REGISTRATION: The study is registered on clinicaltrials.gov (NCT05724394). Protocol version (1.0. 1st June 2022).

Oxidative Stress in Prediabetic Young Adults.

Background Malondialdehyde (MDA) and nitric oxide (NO) are considered specific biomarkers for oxidative stress. Oxidative stress in prediabetics with an augmented potential for the onset of diabetes is at least partly responsible for the various complications of diabetes. Evidence shows that the early features of cell injury are due to transient acute elevations in blood glucose. This study aims to determine whether oxidative stress in prediabetic young adults increases the risk of developing diabetes. Aim and objectives We envisaged a study to determine whether the parameters representing oxidative stress are deranged in prediabetics. Materials and methods The study was conducted on prediabetic young individuals from 18 to 35 years, screened from the tertiary-level hospital, and a similar group of non-prediabetic young individuals identified from the same in a tertiary-level hospital in India. Results We observed significant elevations in prediabetics in the following oxidative stress parameters: MDA (P= <0.001), and NO (P= <0.001); indicating that these parameters were significantly higher among the prediabetics than the controls. We also observed significantly greater body weight, waist circumference, and BMI among the prediabetics than the controls. Conclusion Early identification and appropriate treatment of hyperglycemia in prediabetics is essential, as impairments in pancreatic beta-cell functioning and resistance to insulin are already present before the onset of type 2 diabetes mellitus (T2DM). Owing to the high potential for mortality and morbidity due to cardiovascular diseases (CVDs) as a complication of diabetes, treatment plans must be put in place early enough so that complications can be prevented. Inflammation and oxidative stress may be viewed as valuable targets to hinder the evolution of T2DM from prediabetes.

Industrial prospects on regulatory gaps and barriers in pharmaceutical exports and their counteraction: Local experiential with global implication.

BACKGROUND: The pharmaceutical sector in Pakistan has grown over a period with export potential, however, there are certain barriers in the framework that regulate the growth and export of domestically manufactured pharmaceuticals. The purpose of this study was to highlight the current challenges that hinder the export of pharmaceuticals, especially to the countries with stringent regulatory authorities (SRA), as perceived by the domestic pharmaceutical industry experts, and to highlight the facilitators that may help to resolve the identified challenges. METHODS: In a qualitative study, the data were collected from the consented experts from the pharmaceutical industries in Lahore, Karachi, Peshawar, and Quetta. Industrial experts with a minimum of 10 years of experience and who were serving at managerial levels or above were recruited through purposive sampling. The semi-structured interviews were conducted for the collection of data from industrial experts. Thematic content analysis was applied to conclude the data. RESULTS: Data analysis generated 4 themes and 16 codes. The export of pharmaceuticals, despite having greater potential was regarded as poor, which was attributed to the following: (a) inadequate industrial research and development, particularly on new molecules (b) non-compliance with the cGMP standards, (c) absence of high-tech equipment, (d) unwillingness of the pharmaceutical companies for bioequivalence studies on their generics, (e) unavailability of locally manufactured active pharmaceutical ingredients, (f) disruption in the supply of imported raw material, (g) poor international market perception about local pharmaceutical products and (h) lack of support from regulatory in process expedition. The respondents also suggested the measures for overcoming the above challenges to boost the export of domestic pharmaceuticals and expand their international market share in countries with SRA. CONCLUSION: Export from Pakistan to the SRA countries can be enhanced with mandatory bioequivalence studies during generic registration. The pharmaceuticals export could effectively contribute to the national economy.

Is it safe to implant a penile prosthesis in a solid organ transplant recipient? A systematic review.

Solid organ transplant recipients exhibit an elevated incidence of erectile dysfunction, attributed to comorbidities and specific factors associated with organ failure. While treatment mirrors the general population's, response rates are lower, and there is a heightened concern about implanting a penile prosthesis in immunocompromised patients due to the potential occurrence of severe complications. The aim of this study was to assess the safety of penile prostheses in this population. Among fourteen included studies, ten were case reports or series of cases, and four were non randomized case-control studies with non-transplanted patients as controls. Complications affected 34 patients (11.15%), with mechanical device failures in 18 cases (5.9%) and infections in 13 cases (4.26%). Most infections required hospitalization, antibiotic treatment, and prosthesis removal, with two cases of life-threatening Fournier's gangrene. Case-control studies revealed no differences in overall reoperation rates between transplant recipients and controls. However, pelvic organ transplant recipients undergoing three-piece prosthesis implantation showed higher complications rates related to reservoir issues. Despite limited evidence, case-control studies demonstrated a generally low/moderate risk of bias within each specific domain, although overall bias was moderate/severe. As a result, clinicians may mitigate concerns regarding penile prosthesis implantation in solid organ transplant recipients.

Management of Massive Flank Hernia After Lateral Lumbar Fusion: Preoperative Botulinum Toxin Injections and Open Repair - A Case Report.

BACKGROUND Incisional flank hernias represent a complication after lateral lumbar spine surgery. Given the increasing rate of lateral lumbar interbody fusions, the rate of incisional flank hernias will increase. Since there are no reports of open massive flank hernia repair utilizing preoperative botulinum injections, we sought to publish this technique to provide surgeons with an innovative method for preoperatively treating patients with massive flank hernias. CASE REPORT A 75-year-old man with a history of coronary artery disease, chronic kidney disease, and abdominal hernia repair presented for evaluation of left lateral abdominal and left lower back bulging for 5 months. The symptoms began after an L2-L4 lateral lumbar spinal fusion. Physical examination revealed a left posterior lateral flank bulge. Computed tomography (CT) showed a fat-containing left posterolateral abdominal hernia. The patient was scheduled for CT-guided lateral abdominal wall botulinum injections, followed by open flank hernia repair. He tolerated the surgery well, was admitted for pain control, and discharged on day 2. Repeat imaging with CT at 3 months showed no evidence of patient's prior hernia defect. CONCLUSIONS Open flank hernia repair, in conjunction with preoperative botulinum toxin injections, allows for optimal visualization and re-approximation of the myofascial components of flank hernia defects. Failure to achieve adequate myofascial and skin closure, along with mesh reinforcement, in open flank hernia repair can result in various surgical site complications, including incisional flank hernia recurrence. We recommend further investigation on the benefits of botulinum injections as an adjunct in management of massive flank hernias.

Toward High Contrast and Noninvasive Fluorescence Switches via an O-Fused Ring 5,7-Dihydroxy-4-methyl-2,2,3-triphenylbenzofuran-6(2H)-one Strategy.

An unprecedented O-fused ring 5,7-dihydroxy-4-methyl-2,2,3-triphenylbenzofuran-6(2H)-one (3) was first time synthesized. Further, a series of novel dialkyl/fluoroalkyl derivatives of compound 3, 5,7-dialkoxy/fluoroalkoxy-4-methyl-2,2,3-triphenylbenzofuran-6(2H)-one, were obtained with noninvasive fluorescence switching characteristics and aggregation-induced emission properties. Compared with fluoroalkyl derivatives, the alkyl analogs exhibited a significant bathochromic shift in solid-state fluorescence emission. Notably, these noninvasive fluorescent molecular switches could be facilely tuned through light and heat stimulation, which successfully achieved high contrast and reversible fluorescent emission between orange and yellow endowing them with potential applications in data encryption materials. In addition, the single crystal data of compounds 3 and 7-CF3 displayed weak intermolecular interactions in different directions, resulting in twisted conformation and antiparallel slip stacking. Interestingly, the polymer dimethyl silicone film doped with 7-C3F7 also showed an evident light-responsive behavior, meeting the criterion for fluorescent materials in the optical field.

Metacarpal Stress Fractures in Athletes: A Systematic Review.

BACKGROUND: Stress fractures in general are common injuries; however, there is limited literature on metacarpal stress fractures in athletes. Our objective is to contribute the first systematic review of metacarpal stress fractures in athletes, with a particular focus on epidemiology, presentation, and outcomes. METHODS: A systematic review regarding metacarpal stress fractures in athletes was performed via PubMed, EMBASE, MedLine, Cochrane, and Web of Science. Inclusion criteria consisted of case reports and case series of metacarpal stress fractures in athletes. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: A total of 11 studies (29 cases) were included. The mean patient age was 17 years, with 12 men and 15 women. The most common sports were tennis and badminton. The most common presentation was pain in the dorsal aspect of the hand related to activity. All patients underwent successful nonoperative management, with mean return to play of 9 weeks. CONCLUSIONS: Metacarpal stress fractures can present with significant pain and impact performance in athletes who perform sports involving repetitive movements of the hand and wrist. Nonoperative treatment, consisting of abstinence from sport until the patient was pain free combined with gradual return to play, was successful for all patients. The addition of proper technique and training load can result in satisfactory return to play. For patients who present with hand pain related to exercise, particularly a young racquet sport player, metacarpal stress fractures are a "can't miss" diagnosis associated with significant functional impairment.

Light-absorbing impurities in glacial environments over western Himalaya from reanalysis data and in situ observations.

In context with the scientific evidence of aerosol deposition induced snow and glacier melt, this paper provides baseline information about the spatiotemporal variability of aerosols and snow-ice chemistry filling the data and knowledge gap over the western Himalaya, India based on recently published paper [1]. A systematic approach was employed that entailed analysis of aerosol variability over four decades using MERRA-2 (Modern-Era Retrospective analysis for Research and Applications) data over five major mountain ranges in the western Himalaya. Further, data about nine physicochemical parameters was generated over three selected glaciers in the study area. HYSPLIT (HYbrid Single Particle Lagrangian Integrated Trajectory) model simulated air mass sources at weekly intervals. This dataset is valuable for future investigations aimed at understanding and characterizing the impacts of light-absorbing impurities on radiative forcing, albedo changes, snow-melt, glacier recession and water quality in the western Himalaya.

An enhanced pattern detection and segmentation of brain tumors in MRI images using deep learning technique.

Neuroscience is a swiftly progressing discipline that aims to unravel the intricate workings of the human brain and mind. Brain tumors, ranging from non-cancerous to malignant forms, pose a significant diagnostic challenge due to the presence of more than 100 distinct types. Effective treatment hinges on the precise detection and segmentation of these tumors early. We introduce a cutting-edge deep-learning approach employing a binary convolutional neural network (BCNN) to address this. This method is employed to segment the 10 most prevalent brain tumor types and is a significant improvement over current models restricted to only segmenting four types. Our methodology begins with acquiring MRI images, followed by a detailed preprocessing stage where images undergo binary conversion using an adaptive thresholding method and morphological operations. This prepares the data for the next step, which is segmentation. The segmentation identifies the tumor type and classifies it according to its grade (Grade I to Grade IV) and differentiates it from healthy brain tissue. We also curated a unique dataset comprising 6,600 brain MRI images specifically for this study. The overall performance achieved by our proposed model is 99.36%. The effectiveness of our model is underscored by its remarkable performance metrics, achieving 99.40% accuracy, 99.32% precision, 99.45% recall, and a 99.28% F-Measure in segmentation tasks.

Anti-inflammatory effects of thymol: an emphasis on the molecular interactions through in vivo approach and molecular dynamic simulations.

Thymol (THY), as the natural monoterpene phenol, acts against oxidative stress and inflammatory processes. This study aimed to evaluate the anti-inflammatory effects and possible molecular mechanisms of THY via formalin-induced mouse and egg albumin-induced chick models alongside molecular docking and molecular dynamic (MD) simulations. THY (7.5, 15, and 30 mg/kg) was investigated, compared to celecoxib and ketoprofen (42 mg/kg), as anti-inflammatory standards. THY dose-dependently and significantly (p < 0.05) decreased paw-licking and edema diameter parameters in formalin (phases I and II) and egg albumin-induced models. Moreover, THY (15 mg/kg) exerted better anti-inflammatory effects in combination with the standard drug ketoprofen than alone and with celecoxib. In silico studies demonstrated elevated binding affinities of THY with cyclooxygenase-2 (COX-2) than the COX-1 enzyme, and the ligand binds at a similar location where ketoprofen and celecoxib interact. The results of MD simulations confirmed the stability of the test ligand. THY exerted anti-inflammatory effects on Swiss mice and young chicks, possibly by interacting with COX-2. As a conclusion, THY might be a hopeful drug candidate for the management of inflammatory disorders.

Single parenthood and depression: A thorough review of current understanding.

Background: Single parenthood is becoming increasingly common in today's society for various reasons such as divorce, the death of a spouse, or the choice of parenthood. Regrettably, there seems to be no significant concern among world leaders regarding depression arising from single parenting. Aim: This article aimed to explore the prevalence of depression in single parents, the factors contributing to it, and its effects on their physical and emotional well-being. Additionally, it aims to investigate the long-lasting effects of depression in single parents, effective therapeutic approaches to tackle these issues and offer proactive suggestions for relevant global stakeholders. Methodology: A selection of studies was identified through electronic databases such as PubMed, Embase, and PsycINFO databases. The search strategy encompassed terms related to single parenthood, depression, mental health, prevalence, risk factors, and treatment modalities. Included studies comprised of peer-reviewed research articles, systematic reviews, meta-analyses, and observational studies published in English. Result: Today, there is a growing prevalence of single parenthood due to a range of factors, including divorce, the loss of a partner, and intentional decisions regarding single parenthood. However, this transition comes with challenges, including the risk of developing depression. Depression is a serious mental health condition affecting many individuals worldwide. Raising a child alone increases the likelihood of developing depression for the parent due to the increased burden and responsibilities. Such parents tend to have low self-esteem, suicide/suicide attempts, and so forth and children born by those parents are vulnerable to depression, physical abuse, infections, etc. Conclusion: Future research should focus on identifying effective interventions for treating depression among single parents and improving the availability of mental health facilities for this vulnerable population, especially in places with a high prevalence of depression. Mental health physicians in collaboration with obstetricians and gynecologists across the globe should offer counseling and mediation services during pre-conception care visits for both single and partnered parents.

MXene, protein, and KCl-assisted ionic conductive hydrogels with excellent anti-freezing capabilities, self-adhesive, ultra-stretchability, and remarkable mechanical properties for a high-performance wearable flexible sensor.

Developing a hydrogel with switchable features and freeze tolerance is remarkably significant for designing flexible electronics to adjust various application needs. Herein, MXenes, AFPs (antifreeze proteins), and potassium chloride (KCl) were introduced to a polyacrylamide (PAM) polymer network to design an anti-freezing hydrogel. The ionic hydrogels are characterized by excellent ionic conductivity, presenting adjustable properties of remarkable mechanical strength and self-adhesion to meet individualized application demands. The capability of KCl and AFPs to inhibit ice crystals gives hydrogels with anti-icing properties under a low-temperature atmosphere. The PAM/MXene15/AFP30/KCl15 hydrogel demonstrated negligible hysteresis behavior, quick electromechanical response (0.10 s), and excellent sensitivity (gauge factor (GF) = 13.1 within the strain range of 1200-2000%). The resulting hydrogel could be immobilized on the animal or human skin to detect different body movements and physiological motions, offering reproducibility and precise accuracy as primary advantages. The approach of developing materials with tunable features, along with inorganic salt and the fish-inspired freeze-tolerance method, offers a new prospect for wearable gadgets.

Unlocking Optimal Glycemic Interpretation: Redefining HbA1c Analysis in Female Patients With Diabetes and Iron-Deficiency Anemia Using Machine Learning Algorithms.

OBJECTIVE: In response to the nuanced glycemic challenges faced by women with iron deficiency anemia (IDA) associated with diabetes, this study uses advanced machine learning algorithms to redefine hemoglobin (Hb)A1c measurement values. We aimed to improve the accuracy of glycemic interpretation by recognizing the critical interaction between erythrocytes, iron, and glycemic levels in this specific demographic group. METHODS: This retrospective observational study included 17,526 adult women with HbA1c levels recorded from 2017 to 2022. Samples were classified as diabetic, prediabetic, or non-diabetic based on HbA1c and fasting blood glucose (FBG) levels for distribution analysis without impacting model training. Support Vector Machines, Linear Regression, Random Forest, and K-Nearest Neighbor algorithms as machine learning (ML) methods were used to predict HbA1c levels. Following the training of the model, HbA1c values were predicted for the IDA samples using the trained model. RESULTS: According to our results, there has been a 0.1 unit change in HbA1c values, which has resulted in a clinical decision change in some patients. DISCUSSION: Using ML to analyze HbA1c results in women with IDA may unveil distinctions among patients whose HbA1c values hover near critical medical decision thresholds. This intersection of technology and laboratory science holds promise for enhancing precision in medical decision-making processes.

Bifunctional Zirconium Phosphate with Greigite for Electrochemical Detection and Simultaneous Removal of Heavy Metal Ions and Nitro Compounds.

Electrochemical sensing is emerging as a method of choice for the sensing and monitoring of contaminants in water. Various sensing platforms have been designed for sensing heavy metal ions and organic pollutants in water bodies. Herein, we report a new electrochemical platform that can be used for the detection of both heavy metal ions and nitro-based organic contaminants in water bodies. The electrochemical sensor uses a modified electrode based on Fe3S4-impregnated zirconium phosphate (ZrP) nanoparticles synthesized by a simple ultrasonication method. The ZrP@Fe3S4 nanoparticles were thoroughly characterized by power X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), and ζ-potential studies. The material exhibits an excellent electrochemical performance for the detection of Pb2+, Hg2+, nitrophenol, nitroaniline, and picric acid with low limits of detection of ca. 0.93, 0.70, 0.98, 1.10, and 1.53 ppm, respectively. Since ZrP@Fe3S4 nanoparticles are magnetically recyclable, their adsorption capacity and recyclability have been thoroughly investigated for the uptake of Pb2+ and Hg2+ ions from contaminated water. We observed that the adsorption of Pb2+ and Hg2+ ions on ZrP@Fe3S4 is best described by the Langmuir isotherm and pseudo-second-order kinetic models, with adsorption capacities of 219.44 and 118.4 mg/g, respectively. Similarly, the removal efficiency of ZrP@Fe3S4 was found to be 91, 57.6, and 31.3% for nitrophenol, nitroaniline, and picric acid, respectively. Furthermore, the theoretical calculations using density functional theory (DFT) were carried out to find the adsorption energy, affinity, and point of adsorption, which are in line with the experimental results. DFT calculations further suggest that the incorporation of Fe3S4 on ZrP improves the surface charge density and promotes efficient electron transfer between the electrode and the analyte. We have shown the real-time analysis of Dal lake water as a proof of concept, and the synthesized composite exhibits good recovery and promising results for metal ion sensing. ZrP@Fe3S4 demonstrated an excellent cycling stability and long-term stability without noticeable degradation for 1 week.

Emerging roles of long noncoding RNA H19 in human lung cancer.

Lung cancer holds the position of being the primary cause of cancer-related fatalities on a global scale. Furthermore, it exhibits the highest mortality rate among all types of cancer. The survival rate within a span of 5 years is less than 20%, primarily due to the fact that the disease is often diagnosed at an advanced stage, resulting in less effective treatment options compared to earlier stages. There are two main types of primary lung cancer: nonsmall-cell lung cancer, which accounts for approximately 80%-85% of all cases, and small-cell lung cancer, which is categorized based on the specific type of cells in which the cancer originates. The understanding of the biology of this disease and the identification of oncogenic driver alterations have significantly transformed the landscape of therapeutic approaches. Long noncoding RNAs (lncRNAs) play a crucial role in regulating various physiological and pathological processes through diverse molecular mechanisms. Among these lncRNAs, lncRNA H19, initially identified as an oncofetal transcript, has garnered significant attention due to its elevated expression in numerous tumors. Extensive research has confirmed its involvement in tumorigenesis and malignant progression by promoting cell growth, invasion, migration, epithelial-mesenchymal transition, metastasis, and therapy resistance. This comprehensive review aims to provide an overview of the aberrant overexpression of lncRNA H19 and the molecular pathways through which it contributes to the advancement of lung cancer. The findings of this review highlight the potential for further investigation into the diagnosis and treatment of this disease, offering promising avenues for future research.

Significant influence of land use types and anthropogenic activities on the distribution of microplastics in soil: A case from a typical mining-agricultural city.

Microplastics pollution in soil has become a prominent issue in the field of ecological environment. However, relevant data on the microplastics pollution characteristics in mining industry-agricultural soil ecosystems is still limited. In this study, an extensive investigation on the characteristics of microplastics pollution in typical mining-agricultural city soil was conducted, revealing abundances, features, and influencing factors of microplastics in five land use types including facility farmland (FF), traditional farmland (TF), residential land (RL), industrial land (IL), and grassland (GL). The results showed that the distribution of microplastics abundances exhibits a nonuniform pattern, and the highest microplastics abundance was found in FF (3738 ± 2097 items·kg-1) compared with the other four land use types of this study area. Moreover, the key polymers identified were polypropylene (PP) and polyethylene (PE) with a smaller size (<0.01 mm) accounting for the majority at ,45 %, primary colors of microplastics were transparent with the dominant shapes being fibers and fragments. Additionally, principal component analysis and cluster analysis characterized microplastics features across various land use patterns, revealing that agricultural plastic waste, irrigation, and fertilization may be the main the primary sources of agricultural microplastics, while domestic sewage, household waste (include construction waste), and mining transportation activities are the potential urban sources. Correlation analysis indicates a positive relationship between TN, TP, SOC, and the abundances of microplastics (P < 0.05), and a negative relationship between pH and microplastic abundances. Furthermore, Cd, Cu, and As exhibit a significant positive correlation with microplastic characteristics (P < 0.05). Notably, the distribution trends of Cd content and microplastic abundance are similar. Overall, comprehensive analysis of environmental dynamics on microplastics in agricultural soil in coal industrial cities is crucial for developing effective measures to prevent and control microplastic pollution.

Dynamics of small molecule-enzyme interactions: Novel benzenesulfonamides as multi-target agents endowed with inhibitory effects against some metabolic enzymes.

In contemporary medicinal chemistry, employing a singular small molecule to concurrently multi-target disparate molecular entities is emerging as a potent strategy in the ongoing battle against metabolic disease. In this study, we present the meticulous design, synthesis, and comprehensive biological evaluation of a novel series of 1,2,3-triazolylmethylthio-1,3,4-oxadiazolylbenzenesulfonamide derivatives (8a-m) as potential multi-target inhibitors against human carbonic anhydrase (EC.4.2.1.1, hCA I/II), α-glycosidase (EC.3.2.1.20, α-GLY), and α-amylase (EC.3.2.1.1, α-AMY). Each synthesized sulfonamide underwent rigorous assessment for inhibitory effects against four distinct enzymes, revealing varying degrees of hCA I/II, a-GLY, and a-AMY inhibition across the tested compounds. hCA I was notably susceptible to inhibition by all compounds, demonstrating remarkably low inhibition constants (KI) ranging from 42.20 ± 3.90 nM to 217.90 ± 11.81 nM compared to the reference standard AAZ (KI of 439.17 ± 9.30 nM). The evaluation against hCA II showed that most of the synthesized compounds exhibited potent inhibition effects with KI values spanning the nanomolar range 16.44 ± 1.53-70.82 ± 4.51 nM, while three specific compounds, namely 8a-b and 8d, showcased lower inhibitory potency than other derivatives that did not exceed that of the reference drug AAZ (with a KI of 98.28 ± 1.69 nM). Moreover, across the spectrum of synthesized compounds, potent inhibition profiles were observed against diabetes mellitus-associated α-GLY (KI values spanning from 0.54 ± 0.06 µM to 5.48 ± 0.50 µM), while significant inhibition effects were noted against α-AMY, with IC50 values ranging between 0.16 ± 0.04 µM and 7.81 ± 0.51 µM) compared to reference standard ACR (KI of 23.53 ± 2.72 µM and IC50 of 48.17 ± 2.34 µM, respectively). Subsequently, these inhibitors were evaluated for their DPPH· and ABTS+· radical scavenging activity. Moreover, molecular docking investigations were meticulously conducted within the active sites of hCA I/II, α-GLY, and α-AMY to provide comprehensive elucidation and rationale for the observed inhibitory outcomes.

Comparison of long-term clinical outcomes of bioabsorbable polymer versus durable polymer drug-eluting stents: a systematic review and meta-analysis.

BACKGROUND: One million individuals in the USA die from acute myocardial infarction (MI), which currently affects 3 million people globally. The available data about the early and late outcomes of both biodegradable polymer drug-eluting stents (BP-DES) and durable polymer drug-eluting stents exhibit inconsistency. We performed a meta-analysis comparing the safety and efficacy of BP-DES with DP-DES. METHODS: PubMed, Google Scholar, EMBASE, Cochrane, Ovid Medline, and Clinical Trials.gov databases were used to find out studies comparing BP-DES to DP-DES. All the analyses used the random-effects model. RESULTS: A total of 18 studies were incorporated in this meta-analysis that involved 28,874 patients, out of which 11,997 received the BP Stent, and the rest of 16,578 received the DP stent. Thorough analyses revealed that the risk of all-cause death was significantly higher in the BP-DES group (5.4% vs 2.7%) (RR 1.22, p 0.02) for two years or less than two-year follow-up. For studies with more than two years of follow-up, all-cause death was 9.07% (599/6603) in BP-DES and 9.47% (531/5602) in the DP-DES group but failed to achieve statistically significant levels (RR 0.97, p 0.58). CONCLUSIONS: The study revealed no clinically significant (P value was > 0.05) differences in all-cause death, cardiac death, target lesion revascularization (TLR), late stent thrombosis, device-oriented composite endpoint/target lesion failure (DOCE/TLF), myocardial infarction (MI), target vessel MI, target vessel revascularization (TVR), target vessel infarction (TVI) between BP-DES and DP-DES for more than two years of follow-up. Additionally, all-cause death was only outcomes which found to have a statistically significant difference for less than two years of follow-up, while remaining were statistically non-significant.

Quantitative analysis of solid dosage forms of Atenolol by Raman spectroscopy.

OBJECTIVE: To develop a Raman spectroscopy-based analytical model for quantification of solid dosage forms of active pharmaceutical ingredient (API) of Atenolol.Significance: For the quantitative analysis of pharmaceutical drugs, Raman Spectroscopy is a reliable and fast detection method. As part of this study, Raman Spectroscopy is explored for the quantitative analysis of different concentrations of Atenolol. METHODS: Various solid-dosage forms of Atenolol were prepared by mixing API with excipients to form different solid-dosage formulations of Atenolol. Multivariate data analysis techniques, such as Principal Component Analysis (PCA) and Partial least square regression (PLSR) were used for the qualitative and quantitative analysis, respectively. RESULTS: As the concentration of the drug increased in formulation, the peak intensities of the distinctive Raman spectral characteristics associated with the API (Atenolol) gradually increased. Raman spectral data sets were classified using PCA due to their distinctive spectral characteristics. Additionally, a prediction model was built using PLSR analysis to assess the quantitative relationship between various API (Atenolol) concentrations and spectral features. With a goodness of fit value of 0.99, the root mean square errors of calibration (RMSEC) and prediction (RMSEP) were determined to be 1.0036 and 2.83 mg, respectively. The API content in the blind/unknown Atenolol formulation was determined as well using the PLSR model. CONCLUSIONS: Based on these results, Raman spectroscopy may be used to quickly and accurately analyze pharmaceutical samples and for their quantitative determination.