Genetic association in CYP3A4 and CYP3A5 genes elevate the risk of prostate cancer.

BACKGROUND: CYP3A4 and CYP3A5 are biologically potential genes responsible for prostate cancer. AIM: We aimed to analyse the expression and association of CYP3A4 and CYP3A5 genes in prostate cancer. SUBJECTS AND METHODS: Web-based bioinformatics tools were used to assess the association of CYP3A4 and CYP3A5 genes with prostate cancer risks. A case-control study of 210 prostate cancer cases and 207 controls was also approved to determine the allelic variants of the CYP3A4 gene- rs2740574 (CYP3A4*1B) and the variant of CYP3A5 gene-rs776746 (CYP3A5*3) using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The risk of prostate cancer was estimated as odds ratio (OR) and 95% confidence interval (CI) using unrestricted logistic regression models. RESULTS: Our in silico data confirmed that both CYP3A4 and CYP3A5 genes are significantly associated with higher prostate cancer risks. In the case of CYP3A4*1B polymorphism, the heterozygote (*1 A/*1B), mutant (*1B/*1B), and combined heterozygote plus mutant (*1A/*1B+*1B/*1B) genotypes showed 3.52-fold, 3.90-fold, and 3.67-fold increased risk of prostate cancer, respectively. In the case of CYP3A5*3 polymorphism, the heterozygote (*1/*3), mutant (*3/*3), and combined (*1/*3+*3/*3) genotypes were found to be significantly associated with 5.11-, 5.49-, and 5.28-fold greater risk of prostate cancer, respectively. CONCLUSION: Our results indicate that CYP3A4*1B and CYP3A5*3 are significantly associated with increased prostate cancer risk.KEY MESSAGESBioinformatics tools were used and concluded that the CYP3A4 and CYP3A5 genes were significantly associated with the development and progression of prostate cancer.CYP3A4 and CYP3A5 polymorphisms were significantly associated with an increased risk of prostate cancer.Polymerase Chain Reaction (PCR)-Restriction Fragment Length Polymorphism (RFLP) was used to estimate polymorphisms of prostate cancer progression in the Bangladeshi population.

Lipoid Proteinosis: Identification of a Novel Nonsense Mutation c.1246C>T:p.R416X in ECM1 gene from Bangladesh.

Lipoid proteinosis is a rare multisystem genodermatosis inherited as autosomal recessive trait. We report a case of lipoid proteinosis in a 10-year-old boy born to first-degree consanguineous parents presented with marked hoarseness of voice, accelerated photoaging appearance, enlarged and erythematous tongue with restricted movement and widespread dermatoses. Biopsy of oral mucosa revealed Periodic acid-Schiff (PAS)-positive amorphous eosinophilic hyaline deposits. Mutational analysis revealed a homozygous nonsense mutation with C to T substitution at nucleotide position 1246(c.1246C>T) in exon-8 of the extracellular matrix protein 1 gene leading to a stop codon. Both the parents were unaffected heterozygous carriers. To our knowledge, this is the first case report of lipoid proteinosis with evidence of a novel nonsense genetic mutation from Bangladesh.

Epidemiological, clinical, and public health response characteristics of a large outbreak of diphtheria among the Rohingya population in Cox's Bazar, Bangladesh, 2017 to 2019: A retrospective study.

BACKGROUND: Unrest in Myanmar in August 2017 resulted in the movement of over 700,000 Rohingya refugees to overcrowded camps in Cox's Bazar, Bangladesh. A large outbreak of diphtheria subsequently began in this population. METHODS AND FINDINGS: Data were collected during mass vaccination campaigns (MVCs), contact tracing activities, and from 9 Diphtheria Treatment Centers (DTCs) operated by national and international organizations. These data were used to describe the epidemiological and clinical features and the control measures to prevent transmission, during the first 2 years of the outbreak. Between November 10, 2017 and November 9, 2019, 7,064 cases were reported: 285 (4.0%) laboratory-confirmed, 3,610 (51.1%) probable, and 3,169 (44.9%) suspected cases. The crude attack rate was 51.5 cases per 10,000 person-years, and epidemic doubling time was 4.4 days (95% confidence interval [CI] 4.2-4.7) during the exponential growth phase. The median age was 10 years (range 0-85), and 3,126 (44.3%) were male. The typical symptoms were sore throat (93.5%), fever (86.0%), pseudomembrane (34.7%), and gross cervical lymphadenopathy (GCL; 30.6%). Diphtheria antitoxin (DAT) was administered to 1,062 (89.0%) out of 1,193 eligible patients, with adverse reactions following among 229 (21.6%). There were 45 deaths (case fatality ratio [CFR] 0.6%). Household contacts for 5,702 (80.7%) of 7,064 cases were successfully traced. A total of 41,452 contacts were identified, of whom 40,364 (97.4%) consented to begin chemoprophylaxis; adherence was 55.0% (N = 22,218) at 3-day follow-up. Unvaccinated household contacts were vaccinated with 3 doses (with 4-week interval), while a booster dose was administered if the primary vaccination schedule had been completed. The proportion of contacts vaccinated was 64.7% overall. Three MVC rounds were conducted, with administrative coverage varying between 88.5% and 110.4%. Pentavalent vaccine was administered to those aged 6 weeks to 6 years, while tetanus and diphtheria (Td) vaccine was administered to those aged 7 years and older. Lack of adequate diagnostic capacity to confirm cases was the main limitation, with a majority of cases unconfirmed and the proportion of true diphtheria cases unknown. CONCLUSIONS: To our knowledge, this is the largest reported diphtheria outbreak in refugee settings. We observed that high population density, poor living conditions, and fast growth rate were associated with explosive expansion of the outbreak during the initial exponential growth phase. Three rounds of mass vaccinations targeting those aged 6 weeks to 14 years were associated with only modestly reduced transmission, and additional public health measures were necessary to end the outbreak. This outbreak has a long-lasting tail, with Rt oscillating at around 1 for an extended period. An adequate global DAT stockpile needs to be maintained. All populations must have access to health services and routine vaccination, and this access must be maintained during humanitarian crises.

Microbiology of Chronic Suppurative Otitis Media: An update from a Tertiary Care Hospital in Bangladesh.

OBJECTIVES: Chronic suppurative otitis media is a major cause of acquired hearing impairment, especially in children of developing countries. The study sought to explore the bacteriological profile and their antimicrobial susceptibility among patients of chronic suppurative otitis media from a tertiary care hospital in Bangladesh. METHODS: A cross sectional microbiological study was conducted at the Department of Microbiology, Rajshahi Medical College, Bangladesh from January to December 2019. Aural swabs were collected aseptically from clinically suspected patients irrespective of age and gender attending the ear, nose and throat outpatient department of Rajshahi Medical College Hospital. Aerobic bacterial culture was done and isolates were identified through standard bacteriological identification scheme. Antimicrobial susceptibility testing of isolates was done by modified Kirby-Bauer disk diffusion method following Clinical and Laboratory Standards Institute guidelines. RESULTS: Of 96 swabs, culture yielded a total of 73 bacterial isolates from 68(70.8%) culture-positive plates including 63 (65.6%) unimicrobial and 5 (5.2%) polymicrobial (mixed growth of a pair of bacteria) growths. Frequency distribution revealed, 40(55%) gram-negative and 33(45%) gram-positive bacteria with Staphylococcus aureus was the leading isolate (37%) followed by Pseudomonas aeruginosa (31.5%), Escherichia coli (13.7%), coagulase-negative Staphylococcus (8.2%), Klebsiella pneumoniae (5.5%) and Proteus spp. (4.1%). Gram-positive bacteria were found to be highly susceptible (100%) to Linezolid and Vancomycin followed by Imipenem (83 to 96.3%), while moderate to high resistance (44 to 67%) was observed against Ciprofloxacin, Ceftriaxone, Ceftazidime, Amoxicillin/Clavulanate and Clindamycin. For gram-negative bacteria, susceptibility ranged from 67 to 100% to Imipenem, 67 to 96% to Piperacillin/Tazobactam and 67 to 83% to Gentamicin, while moderate to high resistance (50 to 75%) was observed against Ciprofloxacin, Ceftriaxone, Ceftazidime and Amoxicillin/Clavulanate. CONCLUSION: Moderate to high level of multidrug-resistance especially to 3rd generation cephalosporins, Ciprofloxacin and Amoxicillin/Clavulanate is an alarming situation. It warns reinforcement of judicious antibiotic prescription and introduction of antibiotic stewardship program in the tertiary care hospitals.

High prevalence of multidrug resistant uropathogens: A recent audit of antimicrobial susceptibility testing from a tertiary care hospital in Bangladesh.

OBJECTIVES: Urinary tract infections due to multi drug resistant bacteria have been on the rise globally with serious implications for public health. The objective of this study was to explore the prevalence of multi drug resistant uropathogens and to correlate the urinary tract infections with some demographic and clinical characteristics of patients admitted in a tertiary care hospital in Bangladesh. METHODS: A cross sectional prospective study was conducted at Shaheed Ziaur Rahman Medical College Hospital, Bogura, Bangladesh among clinically suspected urinary tract infection patients from January to December, 2018. Clean-catch midstream or catheter-catch urine samples were subjected to bacteriological culture using chromogenic agar media. Antimicrobial susceptibility testing of the isolates was done by Kirby-Bauer disk diffusion method following Clinical and Laboratory Standards Institute guidelines. Descriptive statistical methods were used for data analysis. RESULTS: Culture yielded a total of 537 (42.8%) significant bacterial growths including 420 (78.2%) multi drug resistant uropathogens from 1255 urine samples. Escherichia coli was the most common isolate (61.6%) followed by Klebsiella spp. (22.5%), Pseudomonas spp. (7.8%), Staphylococcus aureus (5.4%) and Enterobacter spp. (2.6%) with multi drug resistance frequency of 77.6%, 71.9%, 90.5%, 86.2% and 92.9% respectively. There was female preponderance (M:F; 1:1.97; P=0.007) but insignificant differences between paediatric and adult population (43.65% vs. 42.57%) and also among different age groups. Diabetes, chronic renal failure, fever and supra-pubic pain had significant association as co-morbidities and presentations of urinary tract infections (P<0.05). Multi drug resistance ranged from 3.7 to 88.1% including moderate to high resistance found against commonly used antibiotics like ciprofloxacin, cephalosporin, azithromycin, aztreonam, cotrimoxazole and nalidixic acid (28.6 to 92.9%). Isolates showed 2.4 to 32.2% resistance to nitrofurantoin, amikacin, netilmicin and carbapenems except Pseudomonas spp. (66.7% resistance to nitrofurantoin) and Enterobacter spp. (28.6 to 42.9% resistance to carbapenems). CONCLUSION: There is very high prevalence of multi drug resistant uropathogens among hospitalized patients and emergence of carbapenem resistance is an alarming situation. Antibiotic stewardship program is highly recommended for hospitals to combat antimicrobial resistance.

Current status of gonococcal antimicrobial susceptibility with special reference to Azithromycin and Ceftriaxone: Report from a tertiary care hospital in Bangladesh.

OBJECTIVES: Successful treatment of gonorrhea has always been jeopardized by the emergence of resistance to antibiotics recommended as first-line therapies. The present investigation was carried out to demonstrate the current status of antimicrobial susceptibility of N. gonorrhoeae with a special reference to azithromycin and ceftriaxone. METHODS: Microscopical detection in Gram-stained smear and isolation by culture in Thayer-Martin medium were done for 60 clinically suspected gonorrhea patients using urethral discharge or prostatic secretion for male and endocervical secretion for female. Isolates of N. gonorrhoeae were subjected to antimicrobial susceptibility testing by modified Kirby Bauer disk diffusion method against eight antimicrobial drugs including azithromycin and ceftriaxone. RESULTS: Culture yielded a total of 25(42%) isolates of N. gonorrhoeae from 60 clinically suspected patients of both sexes; 21 from male (17 from urethral discharge and 04 from prostatic secretion) and 04 from female (endocervical secretion). Isolates of N. gonorrhoeae showed moderate to high resistance (60 to 88%) to penicillin, tetracycline, cotrimoxazole, erythromycin, ciprofloxacin and cefixime. While resistance to azithromycin and ceftriaxone was 60% and 48% respectively, which was also moderate. CONCLUSION: Our findings indicate moderate to the high resistance of N. gonorrhoeae to conventional antibiotics. It also showed moderate resistance to azithromycin and ceftriaxone, current dual therapy recommended by the WHO for the treatment of genital gonorrhea, which is alarming.

Association of TP53 gene polymorphisms with susceptibility of bladder cancer in Bangladeshi population.

TP53 is considered to be the most frequently mutated gene in every forms of human cancer. The objective of this study was to evaluate the association of TP53 codon 72 and 248 polymorphisms with the susceptibility and severity of bladder cancer in Bangladeshi population. A case-control study on 102 bladder cancer patients and 140 control subjects was conducted. The genotype analysis was done by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. The patients with Pro/Pro genotypes at 72 position were at high risk (odds ratio (OR) = 3.02; 95 % confidence interval (95 % CI) = 1.42 to 6.40) of developing bladder cancer. The cigarette smokers with Pro/Pro genotypes at 72 position were found to have a 3.91-fold increased risk to develop bladder cancer (OR = 3.91; 95 % CI = 1.33 to 11.5). There was no significant association of codon 248 polymorphisms with bladder cancer in the study population. Taken together, these findings indicate an association between p53 codon72 polymorphism and bladder cancer risk in Bangladeshi population.

Development and comparative evaluation of two antigen detection tests for Visceral Leishmaniasis.

BACKGROUND: Visceral leishmaniasis (VL) can be fatal without timely diagnosis and treatment. Treatment efficacies vary due to drug resistance, drug toxicity and co-morbidities. It is important to monitor treatment responsiveness to confirm cure and curtail relapse. Currently, microscopy of spleen, bone marrow or lymph node biopsies is the only definitive method to evaluate cure. A less invasive test for treatment success is a high priority for VL management. METHODS: In this study, we describe the development of a capture ELISA based on detecting Leishmania donovani antigens in urine samples and comparison with the Leishmania Antigen ELISA, also developed for the same purpose. Both were developed as prototype kits and tested on patient urine samples from Sudan, Ethiopia, Bangladesh and Brazil, along with appropriate control samples from endemic and non-endemic regions. Sensitivity and specificity were assessed based on accurate detection of patients compared to control samples. One-Way ANOVA was used to assess the discrimination capacity of the tests and Cohen's kappa was used to assess their correlation. RESULTS: The Leishmania Antigen Detect ELISA demonstrated >90% sensitivity on VL patient samples from Sudan, Bangladesh and Ethiopia and 88% on samples from Brazil. The Leishmania Antigen ELISA was comparable in performance except for lower sensitivity on Sudanese samples. Both were highly specific. To confirm utility in monitoring treatment, urine samples were collected from VL patients at days 0, 30 and 180 post-treatment. For the Leishmania Antigen Detect ELISA, positivity was high at day 0 at 95%, falling to 21% at day 30. At day 180, all samples were negative, corresponding well with clinical cure. A similar trend was also seen for the Leishmania Antigen ELISA albeit; with lower positivity of 91% at Day 0 and more patients, remaining positive at Days 30 and 180. DISCUSSION: The Leishmania Antigen Detect and the Leishmania Antigen ELISAs are standardized, user- friendly, quantitative and direct tests to detect Leishmania during acute VL as well as to monitor parasite clearance during treatment. They are a clear improvement over existing options. CONCLUSION: The ELISAs provide a non-invasive method to detect parasite antigens during acute infection and monitor its clearance upon cure, filling an unmet need in VL management. Further refinement of the tests with more samples from endemic regions will define their utility in monitoring treatment.

Spontaneous echo contrast masking thrombus in giant left atrium of mitral stenosis-a dilemma in clinical diagnosis.

Spontaneous echo contrast (SEC) and thrombus in enlarged left atrium (LA) are common in mitral valvular disease (MVD) and SEC is considered to be a prethrombotic condition. Reliable exclusion of LA thrombus is important before any definitive curative attempts like percutaneous transluminal mitral commissurotomy (PTMC), closed mitral commissurotomy (CMC) or innovative therapies like pulmonary vein isolation and percutaneous closure of the LA appendage. Echocardiography, particularly the transesophageal echocardiography (TEE) is considered to be the gold standard for the diagnosis and to exclude LA thrombus. However, LA thrombus may remain rarely undetected even by TEE potentially making the interventions a risky job. We present a case of mitral stenosis (MS) with giant LA where profuse, dense SEC masked the underlying thrombus in the LA cavity.

Nimbolide B and nimbic acid B, phytotoxic substances in neem leaves with allelopathic activity.

Neem (Azadirachta indica) has been widely used as a traditional medicine and several bioactive compounds have been isolated from this species, but to date no potent allelopathic active substance has been reported. Therefore, we investigated possible allelopathic property and phytotoxic substances with allelopathic activity in neem. An aqueous methanol extract of neem leaves inhibited the growth of roots and shoots of cress, lettuce, alfalfa, timothy, crabgrass, ryegrass, barnyard grass and jungle rice. The extracts were then purified by several chromatographic runs while monitoring the inhibitory activity and two phytotoxic substances were isolated. The chemical structures of the two substances were determined by spectral data to correspond to novel compounds, nimbolide B (1) and nimbic acid B (2). Nimbolide B inhibited the growth of cress and barnyard grass at concentrations greater than 0.1‒3.0 µM. Nimbic acid B inhibited the growth of cress and barnyard grass at concentrations greater than 0.3-1.0 µM. These results suggest that nimbolide B and nimbic acid B may contribute to the allelopathic effects caused by neem leaves.

Comparative evaluation of chromogenic agar medium and conventional culture system for isolation and presumptive identification of uropathogens.

OBJECTIVE: Urine is the most frequent specimen received for culture/sensitivity by clinical laboratories. The microbiological performance of HiCrome UTI agar medium was compared with Blood agar and MacConkey agar for isolation and presumptive identification of bacteria from urine culture. METHODS: A total of 443 consecutively collected midstream and/or catheter-catch urine samples from patients attending the Islami Bank Medical College Hospital, Rajshahi, Bangladesh during January to December, 2012 were cultured. Urine samples showing pus cells ≥ 5/HPF were inoculated on to Blood agar (BA), MacConkey agar (MAC) and HiCrome UTI agar (CA) media simultaneously and incubated overnight aerobically at 37(0)C. Rate of isolation and presumptive identification of bacterial species were compared for different media. RESULTS: Culture yielded a total of 199 bacterial isolates from 189 (42.67%) positive plates including 179 (40.40%) unimicrobial and 10 (2.26%) polymicrobial (mixed growth of pair of bacteria) growths. Both HiCrome UTI agar and Blood agar media supported 100% growths while 151 (75.88%) growths were observed on MacConkey agar. The rate of presumptive identification was found significantly higher on HiCrome UTI agar (97.49%) than MAC agar (67.34%) (P<0.001) as primary urine culture medium. Of 199 isolates, E. coli was found to be the leading uropathogen isolated from 118 (59.30%) samples with its presumptive identification rate of 95.76%, 93.22% and 5.93% on CA, MAC and BA respectively. All 10 (100%) polymicrobial growths were demonstrated distinctly on CA against only 01(10%) on each BA and MAC. CONCLUSION: HiCrome UTI agar was found to be more useful as primary urine culture medium in both higher rate of isolation and presumptive identification of uropathogens in comparison to conventional media. Its inherent characteristics in demonstrating polymicrobial growth and ease of rapid identification by distinct colony colour are unique.

Advances of polyolefins from fiber to nanofiber: fabrication and recent applications.

Polyolefins are a widely accepted commodity polymer made from olefinic monomer consisting of carbon and hydrogen. This thermoplastic polymeric material is formed through reactive double bonds of olefins by the addition polymerization technique and it possesses a diverse range of unique features for a large variety of applications. Among the various types, polyethylene and polypropylene are the prominent classes of polyolefins that can be crafted and manipulated into diversified products for numerous applications. Research on polyolefins has boomed tremendously in recent times owing to the abundance of raw materials, low cost, lightweight, high chemical resistance, diverse functionalities, and outstanding physical characteristics. Polyolefins have also evidenced their potentiality as a fiber in micro to nanoscale and emerged as a fascinating material for widespread high-performance use. This review aims to provide an elucidation of the breakthroughs in polyolefins, namely as fibers, filaments, and yarns, and their applications in many domains such as medicine, body armor, and load-bearing industries. Moreover, the development of electrospun polyolefin nanofibers employing cutting-edge techniques and their prospective utilization in filtration, biomedical engineering, protective textiles, and lithium-ion batteries has been illustrated meticulously. Besides, this review delineates the challenges associated with the formation of polyolefin nanofiber using different techniques and critically analyzes overcoming the difficulties in forming functional nanofibers for the innovative field of applications.

2-[(1,3-Benzo-thia-zol-2-yl)imino-meth-yl]-6-meth-oxy-phenol: a new monoclinic polymorph.

The title compound, C15H12N2O2S, is a P21/c polymorph of a previously reported P21/n polymorph [Büyükgüngör et al. (2004 ▶). Acta Cryst. E60, o1414-o1416]. The dihedral angle between the benzo-thia-zole (r.m.s. deviation = 0.010 Å) and the benzene ring of 7.86 (6)° compares with 10.76 (10)° in the literature structure. The meth-oxy substituent is almost coplanar with the benzene ring to which it is attached [C-O-C-C torsion angle = 178.31 (14)°] and the conformation about the imine bond [1.287 (2) Å] is E. There is an intra-molecular O-H⋯N hydrogen bond and the hy-droxy O and thio-ether S atoms are syn. In the crystal, columns are formed along the b axis as centrosymmetric dimeric aggregates, mediated by C-H⋯O inter-actions and linked by π-π inter-actions between the thia-zole and benzene rings [centroid-to-centroid distance = 3.8256 (10) Å].

Addressing the effect of meteorological factors and agricultural subsidy on agricultural productivity in India: a roadmap toward environmental sustainability.

In the last two decades, the extensive literature that has measured agricultural productivity and growth rate remains controversial and provides few strategies about its main determinants. The present study aims to find out the key determinants of food grain yield (FGY) and examine the role of climate change and agricultural subsidy (SUB) in the context of India using annually data spanning from 1991 to 2018. The current study applied the ARDL modelling to investigate the impacts of climatic factors (average rainfall (RF), mean temperature (AT), and carbon emission (CO2) and agricultural subsidy (SUB) on food grain yield (FGY) in the short-and long-term in India. The estimated outcomes indicate that climatic factors such as RF have a positive impact while AT and CO2 have a negative effect on FGY. Similarly, non-climate variables such as gross capital formation (GCF) and fertilizer usage (FERT) positively contributed to FGY, while the area under crop (LUC), SUB, and employment (AL) negatively affected FGY in India. The results from Granger causality divulge that climatic and non-climatic elements are the main determinants of food grain yield, which have been playing play a significant role in enhancing food grain production and ensuring food security in India. Based on empirical outcomes and findings, some key policy implications emerged. Precisely, government and policy developers should focus on technological innovation and precision agriculture to increase agriculture production and productivity. Government should create funds to curb the climate change problem and promote eco-friendly renewable energy.

Conventional methods and future trends in antimicrobial susceptibility testing.

Antimicrobial susceptibility testing is an essential task for selecting appropriate antimicrobial agents to treat infectious diseases. Constant evolution has been observed in methods used in the diagnostic microbiology laboratories. Disc diffusion or broth microdilution are classical and conventional phenotypic methods with long turnaround time and labour-intensive but still widely practiced as gold-standard. Scientists are striving to develop innovative, novel and faster methods of antimicrobial susceptibility testing to be applicable for routine microbiological laboratory practice and research. To meet the requirements, there is an increasing trend towards automation, genotypic and micro/nano technology-based innovations. Automation in detection systems and integration of computers for online data analysis and data sharing are giant leaps towards versatile nature of automated methods currently in use. Genotypic methods detect a specific genetic marker associated with resistant phenotypes using molecular amplification techniques and genome sequencing. Microfluidics and microdroplets are recent addition in the continuous advancement of methods that show great promises with regards to safety and speed and have the prospect to identify and monitor resistance mechanisms. Although genotypic and microfluidics methods have many exciting features, however, their applications into routine clinical laboratory practice warrant extensive validation. The main impetus behind the evolution of methods in antimicrobial susceptibility testing is to shorten the overall turnaround time in obtaining the results and to enhance the ease of sample processing. This comprehensive narrative review summarises major conventional phenotypic methods and automated systems currently in use, and highlights principles of some of the emerging genotypic and micro/nanotechnology-based methods in antimicrobial susceptibility testing.

Antibody-drug conjugates: the paradigm shifts in the targeted cancer therapy.

Cancer is one of the deadliest diseases, causing million of deaths each year globally. Conventional anti-cancer therapies are non-targeted and have systemic toxicities limiting their versatile applications in many cancers. So, there is an unmet need for more specific therapeutic options that will be effective as well as free from toxicities. Antibody-drug conjugates (ADCs) are suitable alternatives with the right potential and improved therapeutic index for cancer therapy. The ADCs are highly precise new class of biopharmaceutical products that covalently linked a monoclonal antibody (mAb) (binds explicitly to a tumor-associated surface antigen) with a customized cytotoxic drug (kills cancer cells) and tied via a chemical linker (releases the drug). Due to its precise design, it brings about the target cell killing sparing the normal counterpart and free from the toxicities of conventional chemotherapy. It has never been so easy to develop potential ADCs for successful therapeutic usage. With relentless efforts, it took almost a century for scientists to advance the formula and design ADCs for its current clinical applications. Until now, several ADCs have passed successfully through preclinical and clinical trials and because of proven efficacy, a few are approved by the FDA to treat various cancer types. Even though ADCs posed some shortcomings like adverse effects and resistance at various stages of development, with continuous efforts most of these limitations are addressed and overcome to improve their efficacy. In this review, the basics of ADCs, physical and chemical properties, the evolution of design, limitations, and future potentials are discussed.

Antimicrobial Resistance: A Growing Serious Threat for Global Public Health.

Antibiotics are among the most important discoveries of the 20th century, having saved millions of lives from infectious diseases. Microbes have developed acquired antimicrobial resistance (AMR) to many drugs due to high selection pressure from increasing use and misuse of antibiotics over the years. The transmission and acquisition of AMR occur primarily via a human-human interface both within and outside of healthcare facilities. A huge number of interdependent factors related to healthcare and agriculture govern the development of AMR through various drug-resistance mechanisms. The emergence and spread of AMR from the unrestricted use of antimicrobials in livestock feed has been a major contributing factor. The prevalence of antimicrobial-resistant bacteria has attained an incongruous level worldwide and threatens global public health as a silent pandemic, necessitating urgent intervention. Therapeutic options of infections caused by antimicrobial-resistant bacteria are limited, resulting in significant morbidity and mortality with high financial impact. The paucity in discovery and supply of new novel antimicrobials to treat life-threatening infections by resistant pathogens stands in sharp contrast to demand. Immediate interventions to contain AMR include surveillance and monitoring, minimizing over-the-counter antibiotics and antibiotics in food animals, access to quality and affordable medicines, vaccines and diagnostics, and enforcement of legislation. An orchestrated collaborative action within and between multiple national and international organizations is required urgently, otherwise, a postantibiotic era can be a more real possibility than an apocalyptic fantasy for the 21st century. This narrative review highlights on this basis, mechanisms and factors in microbial resistance, and key strategies to combat antimicrobial resistance.

How technological innovation and electricity consumption affect environmental quality? A road map towards achieving environmental sustainability.

Still the world witnessed an upturn in environmental degradation in spite of commitment to climate change across the nations. However, this study attempts to examine linkages among environmental degradation, technological innovation, and electricity consumption in India from 1981 to 2018 using time series data. To examine the long-run equilibrium relationship among the studied variables, we used robust econometric methods such as the autoregressive distributed lag (ARDL), fully modified ordinary least square (FMOLS), and dynamic ordinary least square (DOLS) methods. Furthermore, Granger causality also investigates through the vector error correction model (VECM) model, to assess inter-connotation among the underlying variables. From our empirical findings, urbanization, financial development, and technological innovation have a negative impact on carbon emissions, indicating long-term improvements in environmental quality. While economic development and electricity consumption are deteriorating environmental quality in India. The study's findings suggest that policymakers should prioritize renewable energy, which decreases environmental damage without impeding economic growth.

Chlorido{4-cyclo-hexyl-1-[1-(pyridin-2-yl-κN)ethyl-idene]thio-semicarbazidato-κ(2)N(1),S}diphenyl-tin(IV).

The distorted octa-hedral geometry about the Sn(IV) atom in the title compound, [Sn(C(6)H(5))(2)(C(14)H(19)N(4)S)Cl], is defined by the N,N,S-tridentate Schiff base ligand, two mutually trans ipso-C atoms of the Sn-bound phenyl groups, and the Cl atom which is trans to the azo N atom. The two five-membered chelate rings and pyridyl ring are almost coplanar with the dihedral angle between the outer five-membered chelate and pyridine rings being 5.39 (8)°. Centrosymmetric dimers feature in the crystal packing mediated by N-H⋯S hydrogen bonds, leading to eight-membered {⋯HNCS}(2) synthons. The dimeric aggregates are connected into a three-dimensional architecture by C-H⋯Cl and C-H⋯π inter-actions, as well as π-π inter-actions occurring between centrosymmetrically related pyridine rings [centroid-centroid distance = 3.6322 (13) Å].

n-Butyldichlorido{4-cyclo-hexyl-1-[1-(pyridin-2-yl-κN)ethyl-idene]thio-semi-carb-azi-dato-κ²N¹,S}tin(IV).

Two independent mol-ecules comprise the asymmetric unit in the title compound, [Sn(C4H9)(C14H19N4S)Cl2]. In each mol-ecule, the Sn(IV) atom exists within a distorted octa-hedral geometry defined by the N,N',S-tridentate mono-deprotonated Schiff base ligand, two mutually trans Cl atoms, and the α-C atom of the n-butyl group; the latter is trans to the azo-N atom. The greatest distortion from the ideal geometry is found in the nominally trans angle formed by the S and pyridyl-N atoms at Sn [151.72 (7) and 152.04 (7)°, respectively]. In the crystal, mol-ecules are consolidated into a three-dimensional architecture by a combination of N-H⋯Cl, C-H⋯π and π-π inter-actions [inter-centroid distances = 3.6718 (19) and 3.675 (2) Å].