Inflammatory-stimuli-responsive turn-on NIR fluorogenic theranostic prodrug: adjuvant delivery of diclofenac and hydrogen sulfide attenuates acute inflammatory disorders.

Prolonged use of very commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs) is often associated with undesired side effects, including gastrointestinal ulcers due to the non-selective inhibition of cyclooxygenases. We describe the development of an inflammatory-stimuli-responsive turn-on fluorogenic theranostic prodrug DCF-HS for adjuvant drug delivery. Upon activation by reactive oxygen species (ROS), the prodrug releases diclofenac DCF (active drug) and the NIR fluorophore DCI-NH2 along with carbonyl sulfide (COS). The second activation of COS by the enzyme carbonic anhydrase (CA) generates hydrogen sulfide (H2S). The prodrug was conveniently synthesized using multi-step organic synthesis. The UV-Vis and fluorescence studies revealed the selective reactivity of DCF-HS towards ROS such as H2O2 in the aqueous phase and the desired uncaging of the drug DCF with turn-on NIR fluorescent reporter under physiological conditions. Furthermore, the release of fluorophore DCI-NH2 and drug DCF was confirmed using the reverse phase HPLC method. Compatibility of prodrug activation was studied next in the cellular medium. The prodrug DCF-HS was non-toxic in a representative cancer cell line (HeLa) and a macrophage cell line (RAW 264.7) up to 100 µM concentration, indicating its biocompatibility. The intracellular ROS-mediated activation of the prodrug with the release of NIR dye DCI-NH2 and H2S was investigated in HeLa cells using the H2S-selective probe WSP2. The anti-inflammatory activity of the active drug DCF from the prodrug DCF-HS was studied in the lipopolysaccharide (LPS)-induced macrophage cell line and compared to that of the parent drug DCF using western blot analysis and it was found that the active drug resulted in pronounced inhibition of COX-2 in a dose-dependent manner. Finally, the anti-inflammatory potential of the prodrug and the turn-on fluorescence were validated in the inflammation-induced Wister rat models.

Dual-Stimuli-Activatable Hybrid Prodrug for the Self-Immolative Delivery of an Anticancer Agent and Hydrogen Sulfide with Turn-On Fluorescence.

Stimuli-responsive fluorogenic prodrugs are advantageous for the targeted drug delivery enabling real-time non-invasive monitoring with turn-on fluorescence. We report herein the dual-stimuli (ROS and CA)-responsive thiocarbamate-based prodrug (AM-TCB) for the turn-on fluorogenic delivery of the naphthalimide-based anticancer agent amonafide along with the gasotransmitter hydrogen sulfide (H2 S). A carbamate-based prodrug AM-CB was also designed, capable of releasing the anticancer agent amonafide without any H2 S. The prodrugs were synthesized using multi-step organic synthesis. UV-Vis and fluorescence spectroscopic studies revealed selective reactivity of the boronate ester group of prodrugs towards ROS (primarily H2 O2 ) with the release of amonafide and COS/CO2 via self-immolative processes. Hydrolysis of the generated COS by carbonic anhydrase (CA) produces H2 S. While the prodrug AM-TCB retained the anticancer activity of free amonafide in cancer cells (MDA-MB-231 and HeLa), unlike amonafide, it enhanced the cellular viability of the non-malignant cells (HEK-293). Fluorescence imaging in HeLa cells revealed the simultaneous delivery of the anticancer agent and H2 S from AM-TCB with turn-on fluorescence. Western blot studies further revealed the cytoprotective effects of the released H2 S from AM-TCB. The present adjuvant strategy therefore would be helpful in future for ameliorating the anticancer drug-induced side-effects.

Suspected Isolated Cardiac Sarcoidosis Initially Presenting as Sustained Ventricular Tachycardia.

A 65-year-old man was found to have suspected isolated cardiac sarcoidosis on a positron emission tomography (PET) scan to investigate the cause of sustained monomorphic tachycardia. The patient had episodes of palpitations 12 months prior to this admission, but no cause was ever discovered. Cardiac magnetic resonance (CMR) imaging revealed severe hypokinesis of the inferior segments of the left ventricle, which prompted a subsequent 18F-fluorodeoxyglucose (18F-FDG) PET/CT. The findings were consistent with potential isolated cardiac sarcoidosis as a cause of the fibrosis seen in the left ventricle. As such, the patient was commenced on immunosuppressive therapy and remains well to this day after being fitted with an implantable cardioverter defibrillator (ICD). Isolated cardiac sarcoidosis is a rare phenomenon but remains a diagnostic and therapeutic challenge for clinicians. We report a case of how isolated cardiac sarcoidosis can present as a cause of ventricular tachycardia.

Impact of COVID-19 pandemic on tourism geographies of Bangladesh: study on Sylhet region.

This qualitative study examines the impact of the COVID-19 pandemic on tourism geographies of Sylhet region in Bangladesh developing analytical linkages between pandemic and tourism geography. On the basis of in-depth interviews, the study explores micro effects on diverse actors involved in the tourism process of Sylhet division. As one of the emerging tourism hubs, why Sylhet region demands special treatment from local, national and international authorities and policymakers to mitigate the adverse effects of the ongoing coronavirus pandemic, has been investigated in this paper. However, the central argument of the study is that the COVID-19 pandemic has severely affected the demand and supply chains, local businesses, transportations, hotels and restaurants, tea industry, corporations, and local professional lives due to the imposed restrictions on human mobility, causing a sharp decline in socio-economic activities of Sylhet's tourism geographies.

In-Home Older Adults' Activity Pattern Monitoring Using Depth Sensors: A Review.

The global population is aging due to many factors, including longer life expectancy through better healthcare, changing diet, physical activity, etc. We are also witnessing various frequent epidemics as well as pandemics. The existing healthcare system has failed to deliver the care and support needed to our older adults (seniors) during these frequent outbreaks. Sophisticated sensor-based in-home care systems may offer an effective solution to this global crisis. The monitoring system is the key component of any in-home care system. The evidence indicates that they are more useful when implemented in a non-intrusive manner through different visual and audio sensors. Artificial Intelligence (AI) and Computer Vision (CV) techniques may be ideal for this purpose. Since the RGB imagery-based CV technique may compromise privacy, people often hesitate to utilize in-home care systems which use this technology. Depth, thermal, and audio-based CV techniques could be meaningful substitutes here. Due to the need to monitor larger areas, this review article presents a systematic discussion on the state-of-the-art using depth sensors as primary data-capturing techniques. We mainly focused on fall detection and other health-related physical patterns. As gait parameters may help to detect these activities, we also considered depth sensor-based gait parameters separately. The article provides discussions on the topic in relation to the terminology, reviews, a survey of popular datasets, and future scopes.

Genomic and evolutionary study from SARS-CoV-2 virus isolates from Bangladesh during the early stage of pandemic strongly correlate with European origin and not with China.

The goal of this study was to identify the genomic variants and determine molecular epidemiology of SARS-CoV-2 virus during the early pandemic stage in Bangladesh. Viral RNA was extracted, converted to cDNA, and amplified using Ion AmpliSeq™ SARS-CoV-2 Research Panel. 413 unique mutants from 151 viral isolates were identified. 80% of cases belongs to 8 mutants: 241C toT, 1163A toT, 3037C toT, 14408C toT, 23403A toG, 28881G toA, 28,882 G toA, and 28883G toC. Observed dominance of GR clade variants that have strong presence in Europe, suggesting European channel a possible entry route. Among 37 genomic mutants significantly associated with clinical symptoms, 3916CtoT (associated with sore-throat), 14408C to T (associated with cough-protection), 28881G to A, 28882G to A, and 28883G to C (associated with chest pain) were notable. These findings may inform future research platforms for disease management and epidemiological study.

The Characteristics and Patterns of Drug-Resistant Pulmonary Tuberculosis in Eastern India.

BACKGROUND: Drug-resistant tuberculosis is a major public health problem throughout the world and accounts for substantial morbidity and mortality rates in India, too. Early diagnosis is the corner stone of tuberculosis treatment. State-level and cluster-wise variations in drug resistance is a possibility and should be regularly checked in from time to time. MATERIALS AND METHODS: The present prospective cohort study (January 2019 to May 2022) was conducted in Darbhanga Medical College and Hospital on drug-resistant pulmonary tuberculosis patients. Sputum specimens were collected from designated centers. Rapid molecular drug-resistance testing (genotypic tests) and growth-based drug-susceptibility testing (DST) (phenotypic tests) were performed in the National Tuberculosis Elimination Program certified Laboratory. RESULTS: A total of 268 patients with drug-resistant pulmonary tuberculosis were included in the study group. The treatment outcomes revealed as cured in 100 (37.31%); treatment completed in 43 (16.04%); died in 56 (20.89%); treatment failed in 22 (8.21%); loss of follow up in 34 (12.69%); and transferred out in 13 (4.85%) drug-resistant pulmonary tuberculosis patients. Adverse events were recorded in 199 (74.25%) of the drug-resistant pulmonary tuberculosis patients. CONCLUSIONS: Drug-resistant pulmonary tuberculosis patients are a matter of concern and need to be addressed.

Stimuli-responsive prodrug of non-steroidal anti-inflammatory drug diclofenac: self-immolative drug release with turn-on near-infrared fluorescence.

Reactive oxygen species (ROS)-responsive near infrared (NIR) fluorogenic prodrug DCI-ROS is developed for the self-immolative release of diclofenac (DCF) with turn-on fluorescence. The non-toxic prodrug exhibited turn-on red fluorescence with endogenous ROS in cancer cells and inhibited COX-2 expression in the inflammation-induced macrophage cells. The prodrug strategy thus would be helpful for the controlled fluorogenic delivery of DCF for inflammatory diseases.

Vision-based human fall detection systems using deep learning: A review.

Human fall is one of the very critical health issues, especially for elders and disabled people living alone. The number of elder populations is increasing steadily worldwide. Therefore, human fall detection is becoming an effective technique for assistive living for those people. For assistive living, deep learning and computer vision have been used largely. In this review article, we discuss deep learning (DL)-based state-of-the-arts non-intrusive (vision-based) fall detection techniques. We also present a survey on fall detection benchmark datasets. For a clear understanding, we briefly discuss different metrics which are used to evaluate the performance of the fall detection systems. This article also gives a future direction on vision-based human fall detection techniques.

COVID-19 vaccine demand, hesitancy, and nationalism: a case of protection motivation behavior in Bangladesh.

INTRODUCTION: Immunization, as a process of fighting against the COVID-19, has gained important research appeal, but very limited endeavor has been paid for vaccine behavioral studies in underdeveloped and developing countries. This study explores the vaccine demand, hesitancy, and nationalism as well as vaccine acceptance and domestic vaccine preference among young adults in Bangladesh. METHODOLOGY: This quantitative study followed the snowball sampling technique and collected responses from 1,018 individuals from various social media platforms. The analysis covered both descriptive and inferential statistics including chi-square, F-statistic, and logistic regression. RESULTS: The findings of the fully-adjusted regression model suggest that the individuals who had more vaccine demand were 3.29 times (95% confidence interval = 2.39-4.54; p < 0.001) higher to accept vaccine compared to those who had no vaccine demand. Conversely, vaccine hesitancy was negatively associated with vaccine acceptance. Here, the odds ratio was found 0.70 (95% confidence interval = 0.62-0.80; p < 0.001), which means that those who had higher vaccine hesitancy were about 30% less likely to accept vaccines than those who had no hesitancy. In addition, the persons who had vaccine nationalism were 1.75 times (95% confidence interval = 1.62-1.88; p < 0.001) more prone to prefer domestic vaccine. CONCLUSIONS: This study suggests that policymakers may take initiatives for making people aware and knowledgeable about the severity and vulnerability to specific health threats. In this concern, perception and efficacy-increasing programs may take part in increasing protection motivation behaviors like vaccine acceptance and (domestic) vaccine preference.

Benzimidazole- and Imidazole-Fused Selenazolium and Selenazinium Selenocyanates: Ionic Organoselenium Compounds with Efficient Peroxide Scavenging Activities.

Three new classes of ionic organoselenium compounds containing cationic benzimidazolium and imidazolium ring systems with selenocyanates as counterions are described. The cyclization of N,N'-disubstituted benzimidazolium and imidazolium bromides having N-(CH2)2-Br and N-(CH2)3-Br groups in the presence of potassium selenocyanate (KSeCN) led to formation of the corresponding selenazolium selenocyanates (21a, 21b, 22a, and 22b) and selenazinium selenocyanates (21c, 21d, 22c, and 22d). However, the open-chain selenocyanates with additional selenocyanate counterions (21e, 21f, 22e, and 22f) were formed from the N,N'-disubstituted benzimidazolium and imidazolium bromides having N-(CH2)6-Br groups. Mechanistic studies were carried out to understand the feasibility of such cyclization processes in the presence of KSeCN. The compounds were studied further for their potencies to catalytically reduce H2O2 in the presence of thiols. Interestingly, the cyclic selenazolium (21a, 21b, 22a, and 22b) and selenazinium compounds (21c, 21d, 22c, and 22d) exhibited significantly higher antioxidant activities than the corresponding acyclic selenocyanates (21f, 22e, and 22f). Selected compounds (22d and 22e) were further evaluated for their potencies in modulating the intracellular level of reactive oxygen species (ROS) in a representative macrophage cell line (RAW 264.7). Owing to the cationic nature of compounds, they may target and scavenge mitochondrial ROS in the cellular medium.

Reports of Coding-Complete Genome Sequences of Five 2019 Novel Coronavirus (SARS-CoV-2) Strains Isolated in Bangladesh.

This study determined five coding-complete genome sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains isolated from oropharyngeal swab specimens of Bangladeshi patients who were diagnosed with coronavirus disease 2019 (COVID-19) and had no travel history.

Trisulfides over disulfides: highly selective synthetic strategies, anti-proliferative activities and sustained H2S release profiles.

Temperature- and solvent-induced selective synthesis of trisulfides and disulfides is demonstrated. A remarkable selectivity was achieved using Na2S as a sulfur-transfer agent under mild, greener, catalyst-free and additive-free conditions. This study reveals trisulfides as a better model than disulfides in general for a sustained release of H2S and potent anti-cancer activities.

A Novel Pathogenic ß-Thalassemia Mutation Identified at Codon 8 (HBB: c.27delG) in a Bangladeshi Family Acquired De Novo.

In Bangladesh, the practice of ß-thalassemia (ß-thal) carrier screening and prenatal diagnosis (PND) by ß-globin gene sequencing has been initiated to prevent the birth of affected children. The study aimed to describe a novel de novo mutation of the ß-globin gene and its clinical implication. Out of 100 Bangladeshi ß-thal carrier families, one patient with hematological and clinical features associated with ß-thal and her parents were included. Molecular characterizations of ß-globin gene mutations were performed by direct sequencing. A novel nucleotide deletion mutation at codon 8 in the first exon of the ß-globin gene (HBB: c.27delG) was found in a 1-year-old child of the studied family in a heterozygous state along with common Hb E (HBB: c.79G>A). The mutation caused a frameshift to a new stop codon at codon 18 resulting in a ß0-thal phenotype. The proband exhibited a ß-thal intermedia (ß-TI)-like genotype, however, showed ß-thal major (ß-TM)-like complications and was transfusion-dependent. Her mother had a profile consistent with the Hb E trait, while the father had normal hematological indices. Mutation analyses revealed the mother to be heterozygous for Hb E, while the father had a normal genotype. The novel mutation was assumed to be inherited de novo by the paternity test. The study documented a novel pathogenic mutation in the ß-globin gene in a Bangladeshi family by ß-globin gene sequencing.

Phylogenetic analysis and forensic evaluation among Rakhine, Marma, Hajong, and Manipuri tribes from four culturally defined regions of Bangladesh using 17 Y-chromosomal STRs.

We have analyzed haplotypes for 17 Y chromosomal STR loci in Bangladeshi mainstream Bengali population and four largest ethnic groups inhabiting the North-Eastern and Southern region of Bangladesh using AmpFlSTR® Yfiler® PCR amplification systems. A total of 667 haplotypes from Bangladeshi Bangali, 157 from Rakhine, 144 from Marma, 112 from Hajong, and 136 from Manipuri individuals were observed with corresponding discrimination capacity (DC) of 0.973 for Bengali, 0.723 for Rakhine, 0.743 for Marma, 0.794 for Hajong, and 0.720 for Manipuri groups, respectively. In order to investigate genetic relationship and the pattern of paternal contributions of the studied population, a comparison of the studied data with the published data from Y-STR haplotype reference database (YHRD) was conducted based on analysis of molecular variance (AMOVA). Construction of neighbour-joining tree revealed that the Rakhine population lies closer to a clade consisting, Korean and Japanese population. The Hajong population showed close affinity with Riang (Tripura, India) tribe followed by Marma population. On the other hand, Manipuri group is closely related to Thai population followed by Tamil and mainstream Bengali population.

Genetic diversity study on 12 X-STR loci of investigator® Argus X STR kit in Bangladeshi population.

The X-chromosome short tandem repeat (STR) loci are of particular interest for solving complex kinship and paternity cases. Here, we report the genetic data from 209 unrelated Bangladeshi individuals (102 males and 107 females) that were genotyped using the 12 X-chromosomal STR markers included in the Investigator® Argus X-12 kit (Qiagen). The 12 X-STR markers are located in four linkage groups (linkage group I: DXS10135, DXS10148, and DXS8378; linkage group II: DXS7132, DXS10079, and DXS10074; linkage group III: DXS10103, HPRTB, and DXS10101; and linkage group IV: DXS10146, DXS10134, and DXS7423). Allelic frequencies of the 12 X-STR loci and haplotype frequencies of the four linkage groups were investigated. No significant difference was observed in the allele frequencies of males and females. Distributions of heterozygosity were observed from 64.5 to 92.5% among the studied 12 X STR loci. DXS10135 and DXS10101 loci were found to be most polymorphic. For all the four linkage groups, the haplotype diversity was found to be greater than 0.986. A total of 95, 73, 66, and 74 haplotypes were observed in linkage groups I, II, III, and IV, respectively. Hardy-Weinberg equilibrium tests showed no significant deviation from expected values for all 12 loci (p > 0.05). The exact test for pairwise linkage disequilibrium for the 12 loci in the male samples did not show any significant linkage disequilibrium except the DXS10103 and DXS10101 loci after the p values were corrected by Bonferroni's correction for multiple testing (p > 0.05/66). A combined power of discrimination in male and female individuals were 0.999999998159791 and 0.999999999999993, respectively. The combined mean exclusion chance were 0.999997635 in deficiency cases, 0.999999996 in normal trio cases, and 0.999999178 in duo cases. The currently investigated Bangladeshi population showed significant differences when compared with previously reported X-STR data from other 12 populations. The results of the data analysis indicated that all the loci in the Investigator® Argus X 12 kit were fairly informative and might be useful in forensic application and kinship analysis in Bangladeshi population.

Genetic polymorphism studies on 22 autosomal STR loci of the PowerPlex Fusion System in Bangladeshi population.

Genetic polymorphism of 22 autosomal STR loci included in PowerPlex® Fusion System (D3S1358, D1S1656, D2S441, D10S1248, D13S317, Penta E, D16S539, D18S51, D2S1338, CSF1PO, Penta D, TH01, vWA, D21S11, D7S820, D5S818, TPOX, D8S1179, D12S391, D19S433, FGA and D22S1045) was studied in 188 unrelated Bangladeshi Bengali individuals. Allele frequencies and forensic efficiency parameters such as, the power of discrimination (PD), observed and expected heterozygosity (Ho & He), polymorphism information content (PIC), probability of match (PM), power of exclusion (PE) and typical paternity index was calculated for the loci. The combined PM and PE for all 22 STR loci were calculated to be 5.29×10-27 and 0.99999999945 respectively. The dataset indicated the usefulness of these loci in personal identification, parentage testing and complex kinship analysis in Bangladeshi population. A neighbor-joining tree was constructed based on pair-wise Nei's genetic distance by comparing allele frequency data for the 22 loci with six other populations. The analysis showed that Bangladeshi population lies closer to a clade consisting Japan, the Philippines and East Timot populations.

Phylogenetic and forensic studies of the Bangladeshi population using next-generation PowerPlex® Y23 STR marker system.

Haplotype diversity and allele frequencies of 23 Y chromosomal short tandem repeat (STR) loci included in the next-generation PowerPlex® Y23 System were studied in 137 Bangladeshi Bengali males. A total of 134 different haplotypes were observed with a discrimination capacity (DC) of 0.978, indicating a high potential for differentiating between male individuals in this population. The highest allele frequency (0.818) was observed in locus DYS391. Locus DYS385a/b showed the highest gene diversity (0.945) while locus DYS391 showed the lowest gene diversity (0.302). Double alleles were detected in three loci. On the other hand, four null alleles were detected in a single haplotype at DYS448, DYS549, DYS392, and DYS385a/b locus, respectively. The haplotype data is available in the Y chromosome haplotype reference database under accession number YA003445. To understand the genetic diversity of Bangladeshi Bengali population, a pairwise genetic distances (Rst) was calculated by comparing with 23 population studies consisting 4249 haplotypes. The analysis placed the Bangladeshi population along with Indian Tamil and Indo-Pakistani population in a clade separated from the rest.