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Introduction: This paper examines the correlates of needle and syringe sharing among People Who Inject Drugs in Dhaka city, Bangladesh, which is currently experiencing a steep increase in HIV prevalence despite the ongoing presence of Needle Exchange Programs., Methodology: This was a retrospective chart review with cross-sectional design that extracted data from 783 male People Who Inject Drugs enrolled into five Opioid Substitution Treatment clinics in Dhaka city between April 2010 and January 2016. Data were retrieved from the program's electronic database. Needle and syringe sharing constituted the borrowing or lending of needles and syringes from others within the past month preceding data collection., Results: Buprenorphine was the preferred injection drug and 44.6% shared needles and syringes within the past month. Multivariate analysis indicated that People Who Inject Drugs who were homeless (OR = 8.1, 95% CI = 1.4-44.9, p < 0.05), living with friends (OR = 6.8, 95% CI = 2.5-18.2, p < 0.001), injecting 2-3 times/day (OR = 4.8, 95% CI = 1.2-19.7, p < 0.05), injecting more than three times/day (OR = 4.8, 95% CI = 1.1-20.0, p < 0.05), not using condom with non-commercial female sex partners (OR = 3.3, 95% CI = 1.8-6.0, p < 0.05), bought sex from female sex workers (OR = 2.9, 95% CI = 1.0-8.3, p < 0.05), and did non-suicidal self-injury (OR = 1.8, 95% CI = 1.0-3.0, p < 0.05) were more likely to share needles and syringes., Conclusions: This study demonstrates that operating a standalone harm reduction approach that just provides sterile needles and syringes may not adequately curb needle and syringe sharing among People Who Inject Drugs., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2021 Muhammad MM Hemel, Md. Masud Reza, Tanveer KI Shafiq, Md. Iqbal Kabir, AKM Masud Rana, Sharful Islam Khan.)

Hydrocephalus (HCP) is occurred when there is inequality in the formation and absorption of CSF to such a level which causes accumulation of fluid and causing raised intracranial pressure. Hydrocephalus is the most frequent neurosurgical problem encountered in the paediatric age group. CSF diversion surgically is needed as treatment for certain condition. Endoscopic third ventriculostomy (ETV) and Ventriculo-peritoneal shunt (VPS) are most widely used CSF diversion procedure. Therefore, this study was conducted for comparing the surgical outcome of ETV and VP shunt in obstructive hydrocephalus. This is a prospective experimental study conducted in the Department of Neurosurgery, Dhaka Medical College and Hospital (DMCH) and Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from January 2017 to December 2019. Paediatric patients of both sex and 6 months to 18 years of age with obstructive hydrocephalus undergone endoscopic third ventriculostomy (ETV) or ventriculo-peritoneal shunt (VP shunt) were included after fulfilling inclusion and exclusion criteria. The patients divided into two groups (Group A and Group B). The Group A included 30 patients who treated by Endoscopic third ventriculostomy and the Group B include 30 patients, who was treated by Ventriculo-peritoneal shunt. Surgical outcome was analyzed in two procedures separately. In Group A (ETV group) symptomatic improvement, GCS score improves earlier and post-operative complications relatively less than Group B (VP shunt group). But in VP shunt group 3 months follow up reveals- improvement of papilledema, Occipital frontal circumference (OFC) regression and fontanelle size improvement was more than that of ETV group. This study concluded with suggesting that Endoscopic third ventriculostomy (ETV) is technologically superior surgical technique than VP shunt. Though ETV showed relatively more immediate procedural failure and intraventricular hemorrhage but long-term outcome is better and also associated with lower incidence of infection and re-operation in comparison to VP shunt.

Background: Besides HIV, people who inject drugs (PWID) experience other biomedical adversities, including injection-related injuries and infections. Yet, they are often inadequately addressed due to the prioritisation of HIV-related issues. This article explored the risk environment and socio-structural adversities of PWID living with injection-related injuries and infections, as well as existing management and treatment challenges of these conditions in harm reduction interventions., Methods: We undertook an ethnographic study from April 2018 to December 2019 in selected areas of Dhaka, Bangladesh. This component of the study involved 2500 hours of observations and informal conversations, 35 in-depth interviews and five focus group discussions with PWID experiencing injection-related injuries and infections. We also performed seven key-informant interviews with service providers and clinical experts. We applied thematic analysis and used various theoretical social scientific conceptualisations to analyse the relationship between the biomedical realities and socio-structural vulnerabilities of PWID., Results: Our findings indicated that PWID's physical, legal and socio-economic environments predisposed PWID to risky practices which ultimately precipitated injection-related injuries and infections. These injection-related injuries and infections consequently displaced them in spheres of social exclusion, stigmatisation, physical pain and disability and, hence, fueled their feelings of distress and despondence. Our findings also presented limitations in the management strategy of these injection-related injuries and infections. Specifically, service providers misconstrued all these complexities as "abscesses", thus applying a simplistic "one-size-fits-all" approach without accounting for the diversity of these complexities. This led to a paucity of tailored care and management approaches which could precipitate unfavourable treatment outcomes, such as chronic and complicated cases with antibiotic resistance., Conclusion: Injection-related injuries and infections nestled PWID within various prongs of biomedical and socio-structural adversity, without viable and targeted treatment modalities. Thus, it is integral to nurture a multifaceted harm reduction intervention tailored to their biomedical and socio-structural needs., Competing Interests: Declarations of Interest None., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Patients with cirrhosis suffer from fluid and electrolyte imbalance. The usually reported electrolyte disorders include hyperkalemia, hyponatremia, and hypokalemia. The regional data about the prevalence and risk factors associated with hyperkalemia in cirrhotic patients are not sufficient enough. The purpose of this study is to determine various risk factors associated with hyperkalemia, which will assist in the early detection of cirrhotic patients at risk of hyperkalemia., Methods: This cross-sectional study was conducted in the internal medicine and gastroenterology departments of a tertiary care hospital in Pakistan from March 2021 to June 2021. Sonographically documented liver cirrhosis patients (n=500), of either gender and between the ages of 18 and 70 years, were enrolled in the study. After enrollment, patients' demographics were noted in a self-structured questionnaire. Participant's Child-Pugh score was also noted in the questionnaire. After a detailed history, 5 mL of venous blood was drawn in two vials via phlebotomy and send to the laboratory to measure serum potassium, creatinine, albumin, and bilirubin levels., Result: Out of the total 500 participants, 101 (20.2%) participants had hyperkalemia. It was significantly more prevalent in participants with Child-Pugh C class and in those with a serum creatinine of more than 1.3 mg/dL. Similarly, it was more prevalent in participants with albumin levels less than 2.5 mg/dL., Conclusion: Hyperkalemia is associated with Child-Pugh class C. It has a direct relationship with serum creatinine levels which is an indicator of renal function, and an inverse relationship with serum albumin levels, an indicator of hepatic synthetic function., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Gurnani et al.)

Simple isoquinoline alkaloids (heliamine, dehydroheliamine), a phthalide isoquinoline alkaloid noscapine, and an aporphine alkaloid boldine are biosynthetically derived from an amino acid tyrosine. These substrates and a simple synthetic isoquinoline alkaloid (2-acetyl-7-amino-1,2,3,4-tetrahydroisoquinoline) contain an isoquinoline nucleus. The biotransformation of these substrates via reduction, oxidation, hydroxylation, and N-oxidation reactions with different microorganism produced nine metabolites, namely: N-(2-acetyl-1,2,3,4-tetrahydroisoquinolin-7-yl) acetamide (Metabolite 1), heliamine N-oxide (Metabolite 2), 6,7-dimethoxyisoquinoline (Metabolite 3), 3,4-dihydro-6,7-dimethoxy isoquinolin-1-one (Metabolite 4), heliamine (Metabolite 5), dehydroheliamine N-oxide (Metabolite 6), cotarnine (Metabolite 7), 5-hydroxy cotarnine (Metabolite 8), and boldine N-oxide (Metabolite 9). Primarily, the metabolites are structurally elucidated by one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) analyses, and high-resolution electrospray ionization mass spectrometry (HR-ESIMS). Furthermore, the substrates and their isolated metabolites are evaluated in vitro for their anti-inflammatory, antimicrobial, cytotoxicity, and anticancer activities. The in vitro studies reveal that some of the isolated compounds are potential as anti-inflammatory, antitumor, and antimicrobial leads., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Multiple myeloma (MM) remains an incurable disease with the majority of patients experiencing disease relapse despite response to initial therapy. Antibody-drug conjugates (ADCs) and bispecific T-cell engagers are innovative immunotherapeutic approaches currently in development for the treatment of MM. This systematic review summarizes the efficacy and safety of ADCs and bispecific T-cell engagers in relapsed refractory (RR) MM patients from 2010 to date. Comprehensive literature search was conducted on PubMed, EMBASE, Wiley Cochrane Library, Web of Science, and Clinicaltrials.gov . A total of 13 studies (n = 529) met inclusion eligibility. All studies were prospective in nature investigating ADCs or bispecific T-cell engagers in RR MM; 10 trials were phase 1 and 3 were phase 2. The median age of patients ranged from 24 to 82 years. Among trials with ADC regimens, the overall response (OR) ranged from 34 to 60% and complete response (CR) ranged from 3 to 6%. The most common non-hematologic adverse event (AE) of ADCs was keratopathy, while anemia and thrombocytopenia were the most common hematological AEs. With bispecific T-cell engagers , ORR ranged from 31 to 83%, CR ranged from 7 to 22%, and partial response (PR) ranged from 5 to 16%. The most common non-hematologic AE of bispecific T-cell engagers was cytokine release syndrome (CRS) while the most common hematological AE was neutropenia. Initial data appears to show good clinical activity and tolerable safety profiles, making ADCs and bispecific T-cell engagers promising agents for RRMM. Future studies with newer combinations and a longer follow-up are needed to determine the precise role of these novel therapies in the evolving paradigm of MM treatment., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Seven phenolic compounds (ferulic acid, caffeic acid, 4-methoxycinnamic acid, 3,4-dimethoxycinnamic acid, 3-hydroxy-4-methoxybenzaldehyde, 3-methoxy-4-hydroxypropiophenone and 1-O,2-O-digalloyl-6-O-trans-p-coumaroyl-β-D-glucopyranoside), a flavanonol (7-O-methylaromadendrin), two lignans (pinoresinol and matairesinol) and six diterpenic acids/alcohol (19-acetoxy-13-hydroxyabda-8(17),14-diene, totarol, 7-oxodehydroabietic acid, dehydroabietic acid, communic acid and isopimaric acid) were isolated from the hydroalcoholic extract of a Brazilian Brown Propolis and characterized by NMR spectral data analysis. The volatile fraction of brown propolis was characterized by CG-MS, composed mainly of monoterpenes and sesquiterpenes, being the major α-pinene (18.4 %) and β-pinene (10.3 %). This propolis chemical profile indicates that Pinus spp., Eucalyptus spp. and Araucaria angustifolia might be its primary plants source. The brown propolis displayed significant activity against Plasmodium falciparum D6 and W2 strains with IC 50 of 5.3 and 9.7 μg/mL, respectively. The volatile fraction was also active with IC 50 of 22.5 and 41.8 μg/mL, respectively. Among the compounds, 1-O,2-O-digalloyl-6-O-trans-p-coumaroyl-β-D-glucopyranoside showed IC 50 of 3.1 and 1.0 μg/mL against D6 and W2 strains, respectively, while communic acid showed an IC 50 of 4.0 μg/mL against W2 strain. Cytotoxicity was determined on four tumor cell lines (SK-MEL, KB, BT-549, and SK-OV-3) and two normal renal cell lines (LLC-PK1 and VERO). Matairesinol, 7-O-methylaromadendrin, and isopimaric acid showed an IC 50 range of 1.8-0.78 μg/mL, 7.3-100 μg/mL, and 17-18 μg/mL, respectively, against the tumor cell lines but they were not cytotoxic against normal cell lines. The crude extract of brown propolis displayed antimicrobial activity against C. neoformans, methicillin-resistant Staphylococcus aureus, and P. aeruginosa at 29.9 μg/mL, 178.9 μg/mL, and 160.7 μg/mL, respectively. The volatile fraction inhibited the growth of C. neoformans at 53.0 μg/mL. The compounds 3-hydroxy-4-methoxybenzaldehyde, 3-methoxy-4-hydroxypropiophenone and 7-oxodehydroabietic acid were active against C. neoformans, and caffeic and communic acids were active against methicillin-resistant Staphylococcus aureus., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

The phloeodictine-based 6-hydroxy-2,3,4,6-tetrahydropyrrolo[1,2- a ]pyrimidinium structural moiety with an n -tetradecyl side chain at C-6 has been demonstrated to be a new antifungal template. Thirty-four new synthetic analogues with modifications of the bicyclic tetrahydropyrrolopyrimidinium skeleton and the N-1 side chain have been prepared and evaluated for in vitro antifungal activities against the clinically important fungal pathogens including Cryptococcus neoformans ATCC 90113, Candida albicans ATCC 90028, Candida glabrata ATCC 90030, Candida krusei ATCC 6258, and Aspergillus fumigatus ATCC 90906. Nineteen compounds ( 5 , 21 - 31 , 34 - 38 , 44 , and 48 ) showed antifungal activities against the aforementioned five fungal pathogens with minimum inhibitory concentrations (MICs) in the range 0.88-10 μM, and all were fungicidal with minimum fungicidal concentrations (MFCs) similar to the respective MIC values. Compounds 24 , 36 , and 48 were especially active against C. neoformans ATCC 90113 with MIC/MFC values of 1.0/1.0, 1.6/1.6, and 1.3/2.0 μM but exhibited low cytotoxicity with an IC 50 > 40 μM against the mammalian Vero cells. The structure and antifungal activity relationship indicates that synthetic modifications of the phloeodictines can afford analogues with potent antifungal activity and reduced cytotoxicity, necessitating further preclinical studies of this new class of antifungal compounds.

The world is still in need of an effective therapy to treat coronavirus disease-19 (COVID-19). This cross-sectional study was conducted on COVID-19 survivors in Saudi Arabia to investigate the influence of a healthy diet on the recovery time from COVID-19. A questionnaire was developed to assess participants' dietary habits, based on the 2015 Dutch food-based dietary guidelines. A total of 738 COVID-19 survivors participated in the study, of whom 237 (32.1%) were hospitalized for COVID-19 treatment while 501 (76.9%) were not hospitalized, and 320 (43.4%) were females and 418 (56.6%) were males. Overall, no significant difference was noted in healthy diet score between males and females; however, this score was significantly lower for Saudis compared to non-Saudis. Among the non-hospitalized patients, eating a more healthy diet was associated with a shorter duration of recovery ( p < 0.05) and was significantly affected by gender (15.8 ± 9.3 male vs. 12.1 ± 8.9 female; p < 0.001) and marital status (12.1 ± 8.4 singles vs. 13.7 ± 9.3 married vs. 16.1 ± 11.8 divorced; p < 0.05). In contrast, no significant correlation was found with age or BMI. In this study, a more healthy diet was associated with a shorter duration of recovery from COVID-19. However, further studies are needed to thoroughly investigate the relationship between diet and recovery time from COVID-19.

An efficient synthesis of rac -6-desmethyl-5β-hydroxy-d-secoartemisinin 2 , a tricyclic analog of R -(+)-artemisinin 1 , was accomplished and the racemate was resolved into the (+)- 2b and (-)- 2a enantiomers via their Mosher Ester diastereomers. Antimalarial activity resided with only the artemisinin-like enantiomer R -(-)- 2a . Several new compounds 9 - 16 , 19a , 19b , 22 and 29 were synthesized from rac - 2 but the C-5 secondary hydroxyl group was surprisingly unreactive. For example, the formation of carbamates and Mitsunobu reactions were unsuccessful. In order to assess the unusual reactivity of 2 , a single crystal X-ray crystallographic analysis revealed a close intramolecular hydrogen bond from the C-5 alcohol to the oxepane ether oxygen (O-11). All products were tested in vitro against the W-2 and D-6 strains of Plasmodium falciparum . Several of the analogs had moderate activity in comparison to the natural product 1 . Iron (II) bromide-promoted rearrangement of 2 gave, in 50% yield, the ring-contracted tetrahydrofuran 22 , while the 5-ketone 15 provided a monocyclic methyl ketone 29 (50%). Neither 22 nor 29 possessed in vitro antimalarial activity. These results have implications in regard to the antimalarial mechanism of action of artemisinin.

Azilsartan is found to be more potent than other angiotensin receptor blockers in reducing blood pressure. However, its effect on the heart following myocardial infarction remains to be established. For the first time, we investigated the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonistic and cardioprotective properties of azilsartan. Computational modeling studies of interactions between azilsartan and PPAR-γ revealed azilsartan as an agonist of PPAR-γ and showed the mechanism of azilsartan in cardioprotection. Our study compared the cardioprotective potential of telmisartan to that of azilsartan in a murine model of myocardial ischemia-reperfusion injury by comparing their antioxidant, ant apoptotic, anti-inflammatory, mitogen-activated protein kinase (MAPK)-modulating ability, and PPAR-γ agonistic activity. Male Wistar rats were grouped into four to receive vehicle (dimethyl sulfoxide [0.05%] 2 ml/kg) telmisartan (10 mg/kg p.o.), azilsartan (10 mg/kg p.o.) or azilsartan with specific PPAR-γ blocker, GW 9662 for 28 days. Ischemia was induced for 45 min on the 29th day followed by 60 min of reperfusion. Telmisartan and azilsartan pretreatment significantly nearly normalized cardiac parameters and preserved structural changes. Both drugs inhibited oxidative burst, inflammation, as well as cell death by modulating apoptotic protein expression along with reduction in 4',6-diamidino-2-phenylindole/terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. An increment in pro-survival kinase ERK paralleled with a reduction in p38 and JNK was also revealed by MAPK pathway studies, after administration of these drugs. Interestingly, the aforementioned changes induced by both drugs were reversed by administration of the specific PPAR-γ antagonist, GW9662. However, we found that azilsartan upregulated PPAR-γ to a lesser extent as compared to telmisartan and the latter may be preferred in hypertensive patients at risk of myocardial infarction., (© 2021 Wiley Periodicals LLC.)

Ethnopharmacological Relevance: Aloysia polystachya (Griseb) Moldenke (Verbenaceae), popularly known as "burrito", is a South American species widely prescribed by local Brazilian healers for the treatment of cardiovascular diseases. However, its antihypertensive and cardioprotective effects are still unknown., Aim: To evaluate the role of the ethanol-soluble fraction of A. polystachya leaves (ESAP) against hypertension in spontaneously hypertensive rats (SHRs), as well as its safety, morphoanatomical and phytochemical aspects., Materials and Methods: First, the leaves and stems of A. polystachya were analyzed by optical and scanning electron microscopy in order to provide anatomical data for quality control. Then, ESAP was obtained and its chemical profile was analyzed by LC-DAD-MS. In addition, the cytotoxic and acute toxicity potential of ESAP were evaluated in six cell lines and in female Wistar rats, respectively. Next, female spontaneously hypertensive rats (SHRs) received ESAP (30, 100, 300 mg/kg), hydrochlorothiazide (25 mg/kg), or vehicle once daily for 28 days. Weekly kidney function was monitored by analyzing urinary parameters. At the end of the 28-day treatment, the electrocardiographic profile, blood pressure, and renal and mesenteric vascular reactivity were evaluated. Relative organ (heart, kidney, and liver) weights and biochemical parameters were also evaluated. Finally, the heart, kidneys, and aorta were collected for determination of the tissue redox state, cardiac morphometry, and histopathological analysis., Results: The chemical profile of ESAP was composed by organic acids, a nucleoside, methoxylated flavones and glycosylated compounds including phenolic acids, phenylpropanoids, iridoids and monoterpenes. No signs of toxicity were observed in all cell's lines nor in female Wistar rats submitted to this trial. All SHRs from the negative control group presented a reduction in renal function, alterations in the renal and mesenteric vascular reactivity, and electrocardiographic and morphometric changes typical of ventricular hypertrophy. Oral prolonged ESAP-administration in SHRs was able to reverse renal, electrocardiographic and hemodynamic changes induced by hypertension. Moreover, ESAP-treatment was able to modulate the vascular and renal arterial reactivity and tissue redox state. The aforementioned data were accompanied by reduction of cardiac hypertrophy., Conclusion: In this study, we present important anatomical and phytochemical data that contributed to the correct identification and quality control of A. polystachya. In addition, we have shown that ESAP is safe after acute administration and present significant cardioprotective effects (at 30, 100, and 300 mg/kg doses) in SHRs after prolonged treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Phytochemical investigation of Callistemon citrinus (Curtis) Skeels (syn. Callistemon lanceolatus (Sm.) Sweet and Melaleuca citrina (Curtis) Dum.Cours.) leaves resulted in the isolation of five undescribed compounds, including one acylphloroglucinol derivative and four monoterpene galloylglucosides, in addition to 29 known diverse secondary metabolites. Interestingly, this study reports chemosystematically significant isolation of the monoterpene galloylglucosides from the genus for the first time. Furthermore, exploration of the isolated compounds as inhibitors of inflammation-related molecular targets, molecular docking studies targeting human adipocyte lipid-binding protein FABP4 (3P6H) and human nitric oxide synthase (3E7G) were carried out in order with the in vitro evaluation of the isolated compounds for their anti-microbial and inhibitory of inducible nitric oxide synthase (iNOS) activities. Molecular docking studies revealed that eighteen compounds showed lower docking scores than ibuprofen, the native ligand in the crystal structure 3P6H, and nine compounds showed lower docking scores than AR-C95791, the native ligand in the binding site of 3E7G. Additionally, in vitro studies revealed that seven compounds showed moderate iNOS inhibitory activity. They also were moderately cytotoxic to HepG2, LLC-PK 1 and Vero cells. Pulverulentone A showed moderate antibacterial activity against MRSA (IC 50 22.2 μM) and antifungal activity against C. neoformans, while corosolic acid showed strong antibacterial activity against VRE (IC 50 15.9 μM).Thus, the in silico and in vitro studies indicated that some isolated compounds hold potentials as inhibitors of iNOS activity and anti-microbial agents., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Women who inject drugs (WWID) experience various complexities, risks and vulnerabilities attributed to unequal gendered power differentials. This article has aimed to explore the unequal gendered power dynamics that influence HIV risks and vulnerabilities among WWID in Dhaka, Bangladesh., Methods: This paper is based on an ethnographic study conducted from April 2018 to December 2019 in Dhaka, Bangladesh. This component of the study constituted 2500 h of extensive field observations, 15 in-depth interviews and five focus groups exclusively with WWID. We also interviewed 15 key-informants including programme managers, an academician and harm reduction service providers. Data were thematically analysed in relation to the four bases of gendered power theorised by gender scholars Pratto and Walker which include force, resource control, asymmetrical obligations and consensual ideologies., Results: The first base, "force", highlighted situations where WWID were compelled into risky injecting and sexual behaviours to avoid violent ramifications or losing their safety nets with intimate partners. The second base, "resource control", depicted unequal access to commodities where men exercised their dominance over money and drugs. The third base, "social obligations", depicted the propensity of WWID to obey their partners and clients, thus precipitating their risky behaviours. The fourth base, consensual ideologies, were linked to weakened negotiation powers of WWID, thus increasing their propensity to risky injecting and sexual behaviours alongside poly-drug use. Despite several instances of gender-based violence and oppression, WWID have fallen victim to gender-blind interventions, as demonstrated by study observations and anecdotes., Conclusion: Gender-based violence and oppression were depicted as prominent driving forces exacerbating WWID's HIV risks and vulnerabilities. If these issues are overlooked, the HIV burden will continue permeating among WWID. Thus, stakeholders need to look beyond the lens of conventional harm reduction modalities and synergize evidence-based gendered dynamics to formulate a gender-responsive comprehensive service package for WWID., Competing Interests: Declarations of Interest None declared., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Improving the bioavailability of a drug at the ocular surface presents a profound challenge. Due to ocular physiological barriers, conventional eye drops exhibit poor bioavailability of drugs. Sustained-release nanoparticles may improve the residence time and hence increase absorption of the drug from the corneal surface. The current study focuses on the development of a nanoparticle-based system for the ophthalmic sustained delivery of moxifloxacin, to enhance ocular retention and bioavailability of the drug. PLGA was used as the matrix-forming polymer in the nanoparticle formulation. Nanoparticles were manufactured using a double emulsion (w/o/w) solvent evaporation technique. The formulation was optimized based on physicochemical properties, including size, polydispersity index, and stability. Nanoparticles were also evaluated for in-vitro drug release and pharmacokinetic evaluation in a rabbit model. The optimized formulation exhibited a relatively high initial release rate for six hours followed by sustained release of a drug via diffusion. The in-vivo ocular tolerance studies confirmed that moxifloxacin-loaded PLGA nanoparticles were non-irritating to the eye. The pharmacokinetic studies revealed that the nanoparticles provided a high C max , AUC, MRT, and low clearance rate when compared to commercial eye drops. It can be concluded that such PLGA nanoparticles offer the potential for improved bioavailability of moxifloxacin HCl.

Background: A number of countries across Asia have instituted "drug wars", aimed at eradicating drug supply and consumption. These wars often employ strategies like arbitrary arrest and detention, increased surveillance, harassment and sometimes extrajudicial killings. However, these measures have not been shown to effectively eliminate drug supply and consumption; rather they often predispose people who use drugs to increased risk and harm. Such a drug war was declared in the form of an anti-drug drive (ADD) in Bangladesh in 2018. This article examined the impact of the ADD on drug injecting activities and harm reduction service uptake among people who inject drugs (PWID)., Methods: An ethnographic study was conducted in Dhaka, Bangladesh. Study participants included PWID, harm reduction service providers and other drug and alcohol experts. Data collection consisted of 2500 hours of observations, 25 in-depth interviews, five focus group discussions and 15 key informant interviews. Data were analysed using thematic analysis., Results: ADD operations and activities subjected PWID to multifaceted forms of violence and harassment including extrajudicial killings, which significantly affected drug procurement and drug using practices and led to increased needle and syringe sharing and a likely increase in HIV transmission. The gradual disappearance of established drug markets, alongside the emergence of new ones at alternate locations, resulted in the dislocation of PWID from outreach services and further increased risky injecting practices such as needle and syringe sharing between new and unfamiliar injecting partners. These harms were compounded by unpredictable drug supply and price increases stemming from the ADD, which in turn also increased needle and syringe sharing. Harm reduction outreach services were not able to adequately adapt to the volatile, dynamic and risky nature of the ADD., Conclusion: The ADD not only precipitated risky injecting practices but also hindered the effective implementation of harm reduction outreach services and thus undermined public health. This warrants concerted efforts to nurture local evidence-based harm reduction approaches as opposed to punitive measures., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Acanthus ilicifolius Linn. (Acanthaceae) is a popular mangrove ethnomedicinal plant that cures several ailments, including asthma, diabetes, cancer, and many others. Our experiment was aimed at evaluating the anti-atherogenic effect of A. ilicifolius (leaf and stem) on a high-fat diet-induced atherogenic rat model. Atherosclerosis was developed in 12 weeks. Treatment with the standard drug (3 mg/kg b.w./day, p.o. of Simvastatin), separate doses of methanolic and ethanolic extracts of A. ilicifolius leaf (250 and 500 mg/kg b.w./day, p.o.), and stem (200 and 400 mg/kg b.w./day, p.o.) was subsequently conducted for additional 15 days. The anti-atherogenic effect was evaluated by estimating the change in body weight, systolic blood pressure, and lipid profile. Histopathology of aorta, liver, and kidney of atherogenic models was done for further evaluation. The antioxidant effect of different extracts was performed via DPPH (2,2-diphenyl-1-picrylhydrazyl) assay using ascorbic acid as standard. The anticoagulant effect was determined after 15 days of treatment with the same doses of the plant extracts and the standard Warfarin (2 mg/kg b.w./day, p.o.). When compared with atherogenic control, treatment with A. ilicifolius significantly reduced ( p  < 0.01) body weight, systolic blood pressure, and serum lipid levels while it elevated HDL (high-density lipoprotein) level in a dose-dependent manner. Moreover, bleeding and clotting time was significantly decreased ( p  < 0.01) under the treatment of plant extracts. The histopathological data showed considerable improvement in tissue morphology after treatment. Our study evidenced that the alcoholic extracts of A. ilicifolius leaf and stem have anti-atherogenic properties and may be recommended as a potential herbal remedy for preventing cardiovascular diseases., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Rubaba Karim et al.)

Introduction Male and female sexual dysfunction is frequently found in patients with hypertension. Many studies indicate that this is found more frequently in patients treated with beta-blockers rather than due to hypertension itself; however, almost all studies have been done on male population. This study aims to study the effect of two commonly used beta-blockers on sexual function of a hypertensive female patient. Methods This two-arm open-label randomized prospective study was conducted from April 1, 2019 to March 30, 2020 in a tertiary care hospital at Pakistan. One hundred and fifty participants randomized to group A were given nebivolol 5 mg once daily in addition to their current hypertensive treatment. Another 150 participants randomized to group B were given bisoprolol 5 mg once daily in addition to their hypertensive therapy. Sexual function was assessed on day 0 and day 90 using female sexual function index (FSFI). Results The mean sexual score in the nebivolol group significantly improved after day 90 in comparison to day 0 (24.16 ± 2.1 vs. 26.91 ± 2.6; p-value < 0.0001), while no difference in sexual score in bisoprolol group after day 90 was observed (24.14 ± 2.1 vs. 24.12 ± 2.0; p-value = 0.91). Conclusion In this study, nebivolol group was associated with a significant improvement in sexual function. This can be due to additional vasodilation properties and a low risk of sexual side effects associated with nebivolol., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Kumar et al.)

The use of traditional medicinal plants in Saudi Arabia stems mainly from consumers' belief in prophetic medicine. This study was conducted to explore changes in patients' use of dietary or herbal supplements among individuals infected with COVID-19 before and during infection and the association between herbal or dietary supplements and hospitalization. A cross-sectional, questionnaire-based study was conducted enrolling symptomatic patients who had recently recovered from COVID-19. Data were collected through phone interviews, and McNemar's test was used to investigate changes to consumption of dietary or herbal supplements before and during infection. Multivariable logistic regression was used to investigate the association between supplements use during patients' infection and hospitalization. A total of 738 patients were included in this study, of whom 32.1% required hospitalization. About 57% of participants were male with a mean age of 36.5 (±11.9) years. The use of lemon/orange, honey, ginger, vitamin C, and black seed among participants significantly increased during their infection. In contrast, patients using anise, peppermint, and coffee peel before their infection were more likely to stop using them during their infection. In addition, using lemon/orange ( p < 0.0001), honey ( p = 0.0002), ginger ( p = 0.0053), vitamin C ( p = 0.0006), black seed ( p < 0.0001), peppermint ( p = 0.0027), costus ( p = 0.0095), and turmeric ( p = 0.0012) was significantly higher among nonhospitalized patients than hospitalized ones. However, in the multivariable logistic regression, only use of vitamin C (OR = 0.51; 95% CI 0.33-0.79), peppermint (OR = 0.53; 95% CI 0.31-0.90), and lemon/orange (OR = 0.54; 95% CI 0.33-0.88) was associated with significantly lower odds of hospitalization. The study reveals that patients' consumption of dietary or herbal supplements changed in response to their COVID-19 infection, with hospitalized patients having a lower likelihood of using these supplements. Because some supplements were associated with lower odds of hospitalization, these supplements or their bioactive components should be further investigated as feasible options for COVID-19 treatment.

Now a day's variety of nanomaterials is available, among these Aluminum Alloys AA7072 and AA705 are significant due to their thermal, physical and mechanical characteristics. These extensively used in manufacturing of spacecraft, aircraft parts and building testing. Keeping in view the significance of nanoliquids, the analysis of methanol suspended by AA7072 and AA7075 alloys under the multiple physical flow conditions is reported. The model is successfully treated by coupling of RK and shooting algorithm and examined the results for the flow regimes by altering the ingrained physical parameters. Then physical interpretation of the results discussed comprehensively. To validate the analysis, a comparison between the presented and existing is reported under certain assumptions on the flow parameters. It is found that the results are reliable inline with existing once.

Introduction: The symptoms of coronavirus disease-19 (COVID-19) may range from mild to severe. Patients usually present with fever, cough, and other respiratory tract symptoms, but may also be asymptomatic. Some studies have also indicated the ocular involvement by the virus. This study aims to look deeply into all ophthalmic findings seen in COVID-19 patients and their clinical characteristics., Methods: This longitudinal study was conducted in the COVID-19 unit of a tertiary care hospital, Pakistan. Data of patients hospitalized with COVID-19 infection between July 2020 and March 2021 were included in the study. Ophthalmological examination was done at the time of admission and was repeated every alternate day to look for any ophthalmological manifestation., Results: Out of 441 (n= 441), 61 (13.8%) participants had ophthalmological findings on examination. Patients with ophthalmological findings were significantly younger compared to patients without ophthalmological findings (42 ± 6 years vs. 44 ± 7; p-value, 0.03). C-reactive protein (CRP) was also significantly higher in patients with ophthalmological findings (122.2 ± 16.2 vs. 112.8 ± 19.8; p-value, 0.005). The most common ophthalmological finding was conjunctival irritation (50.8%), followed by diplopia (27.8%) and cotton wool spots (27.8%)., Conclusion: Ophthalmological findings are prevalent in patients with COVID-19. In this study, patients with higher CRP levels were associated with ophthalmological findings. It is important to conduct ophthalmological examinations in patients with COVID-19, as they may give a clue about other complications associated with COVID-19., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Khan et al.)

Acute lymphoblastic leukemia (ALL) typically responds better when treated with multiagent chemotherapy in the pediatric and young adolescent populations. Treatment of relapsed/refractory (RR) ALL remains a challenge. Even after stem-cell transplantation and intensive chemotherapy, the prognosis of RR-ALL remains grave. The advent of chimeric antigen receptors has demonstrated promising results in RR-ALL. Chimeric antigen receptor-modified T cells (CAR-T) and engineered T cells are used to target cancer cells. In 2017, the US Food and Drug Administration approved CD19-specific CAR-T (tisagenlecleucel) therapy for RR-B-cell ALL in patients under 25 years old. In this systematic review, we discuss the efficacy and safety of CD19-specific CAR-T therapy in RR-B-cell ALL in the pediatric and young adult population. We searched the PubMed, Embase, Web of Science, Cochrane Library, and clinical trials databases. A total of 448 patients received a CD19-specific CAR-T product, and 446 patients had evaluable data. The age range was 0 to 30 years. The incidence rate of complete remission was 82%. The cumulative incidence of relapse after CD19-specific CAR-T therapy is 36%. Similarly, the incidence rate of grade 3 or higher adverse events of neutropenia, thrombocytopenia, neurotoxicity, infections, and cytokine release syndrome were 38%, 23%, 18%, 29%, and 19%, respectively. Our subgroup analysis shows the incidence rate of minimal residual negative complete remission was 69% with the CD28z costimulatory domain, 81% with the 4-1BB domain, and 77% with fourth-generation CD19-specific CAR-T therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Solid-state photodecarbonylation is an attractive but underutilized methodology to forge hindered C-C bonds in complex molecules. This study discloses the use of this reaction to assemble the vicinal quaternary stereocenter motif present in bis(cyclotryptamine) alkaloids. Our strategy was enabled by experimental and computational investigations of the role of substrate conformation on the success or failure of the solid-state photodecarbonylation reaction. This informed a crystal engineering strategy to optimize the key step of the total synthesis. Ultimately, this endeavor culminated in the successful synthesis of the bis(cyclotryptamine) alkaloid "psychotriadine," which features the elusive piperidinoindoline framework. Psychotriadine, a previously unknown compound, was identified in the extracts of the flower Psychotria colorata , suggesting it is a naturally occurring metabolite.

Coverage of HIV testing services (HTS) is generally low among men who have sex with men (MSM) and transgender women ( hijra ) in Bangladesh, thus impeding the national goal of attaining the 90-90-90 target. In this context, this article delineates HTS uptake barriers among these populations. This qualitative study entailed 30 in-depth interviews, six focus groups and seven key-informant interviews with purposively selected MSM and hijra , alongside service providers. Participants cited individual and interpersonal barriers such as low risk perception and misconceptions about HIV testing, programmatic barriers such as knowledge gaps among peer service providers, as well as community and structural barriers such as the criminalization and stigmatization of male-to-male sex. Considering these contexts, it is essential for stakeholders to improve the HTS modality using multipronged approaches to address the multifaceted barriers of HTS uptake.

Objective: HIV-1 subtyping data of Bangladeshi strains are available in global HIV Sequence Database up to 2007, and there is no sequence of drug resistance profile based on the pol gene segment. This study aimed to update HIV genotyping data and describe the drug resistance mutations for the first time from Bangladesh using specimens from the latest HIV sero-surveillance conducted in 2016., Study Design and Methods: During HIV sero-surveillance, a total of 1268 people who inject drugs (PWID) and 3765 female sex workers (FSW) were screened and among them, 230 (18.1%) PWID and 7 (0.2%) FSW were HIV positive. Among HIV positives, randomly selected 74 specimens (60 male-PWID, 7 female-PWID, and 7 FSW) were subjected to gag, pol, and env gene sequencing using gene-specific primers. Genotyping was decided based on the partial gag and env genes while transmission dynamics was based on the gag sequence (n = 237). Drug resistance profiles were obtained by using the algorithm of the established available drug resistance database., Results: HIV subtype C and C-related recombinants have remained the major circulating genotypes in Bangladesh. Although the recurring transmission of subtype C occurred among PWID, we identified possible transmission to other key populations (KPs), which suggests spillover from PWID through the sexual route. The prevalence of drug-resistant mutation was low, and all strains were susceptible to NRTIs and NNRTIs drugs. Unique recombination forms (URF) with genotype C for gag-pol and A1 for env was also identified., Conclusions: The study findings warrant continuous monitoring of HIV-positive individuals and future investigation to identify social networks within and between KPs to halt the transmission and prevent new infections., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Prosaposin (PSAP) has two forms: a precursor and a secreted form. The secreted form has neurotrophic, myelinotrophic, and myotrophic properties. The precursor form is a precursor protein of saposins A-D. Although the distribution of PSAP in male reproductive organs is well known, its distribution in female reproductive organs, especially in the oviduct, is unclear. Immunoblots and immunohistochemistry of oviducts showed that oviductal tissues contain PSAP proteins, and a significant increase in PSAP was observed in the estrus-metestrus phase compared to the diestrus-proestrus phase in the ampulla. To identify PSAP trafficking in cells, double-immunostaining was performed with antibodies against PSAP in combination with sortilin, mannose 6 phosphate receptor (M6PR), or low-density lipoprotein receptor-related protein 1 (LRP1). PSAP and sortilin double-positive reactions were observed near the nuclei, as well as in the apical portion of microvillous epithelial cells, whereas these reactions were only observed near the nuclei of ciliated epithelial cells. PSAP and M6PR double-positive reactions were observed near the nuclei of microvillous and ciliated epithelial cells. PSAP and M6PR double-positive reactions were also observed in the apical portion of microvillous epithelial cells. PSAP and LRP1 double-positive reactions were observed in the plasma membrane and apical portion of both microvillous and ciliated epithelial cells. Immunoelectron staining revealed PSAP immunoreactive small vesicles with exocytotic features at the apical portion of microvillous epithelial cells. These findings suggest that PSAP is present in the oviductal epithelium and has a pivotal role during pregnancy in providing an optimal environment for gametes and/or sperm in the ampulla.

Oakmoss and treemoss absolutes are the major natural extracts of concern as potential sources of skin sensitizers in cosmetics and personal care products (PCP). Two single constituents, atranol and chloroatranol, have been identified as primary culprits in both lichens, and industrial self-regulation has been proposed to limit their contents to less than 100 ppm. Nonetheless, evidence points to the presence of additional candidate skin sensitizers in these multicomponent extracts. These observations, along with a lack of data from non-animal alternative methods and the chemical variability of commercial absolutes, prompted further investigation of oakmoss absolute along with altranol-like compounds in these extracts. The major chemical constituents of a commercial sample were identified by two independent analytical techniques, GC-MS and HPLC-DAD-MS. The crude oakmoss extract and pure compounds were assayed with two in chemico methods (HTS-DCYA and DPRA) to gauge their chemical reactivity. Activation of inflammatory responses in vitro was also investigated by KeratinoSens™ and human cell line activation tests (h-CLAT). Based on weight of evidence, orcinol, ethyl orsellinate, and usnic acid were classified as candidate sensitizers, along with both atranols and oakmoss extract., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Methamphetamine use has increased among gender and sexually diverse people in several countries, including Bangladesh. This study aimed to explore the effects of methamphetamine on the sexual lives of these people in Dhaka, Bangladesh. An exploratory qualitative study was conducted, comprising 30 in-depth interviews with gender and sexually diverse people including males having sex with males, male sex workers, and transgender women (hijra) under HIV intervention coverage. Ten key informant interviews were also conducted with individuals who have expertise in relevant disciplines such as drug use, harm reduction, and HIV and AIDS. Digitally recorded data were manually analyzed under the thematic analysis framework. Findings indicated that many participants reported that methamphetamine brought changes in their sexual lives such as increased sexual drive, engagement in group sex, the increased ability to perform serial sex, transactional sex, impulsive and coercive sex, initiation and switching of male-to-male sexual practices, and limited condom use. Key informants noted that there is a dearth of methamphetamine-related services in Bangladesh. Methamphetamine use was found to lead to diverse effects on the sexual lives of gender and sexually diverse people, thus making it a driving force for shaping sexual practices and, hence, sexual risks. Therefore, it is essential for policy-level stakeholders and program managers to consider the risks of methamphetamine use due to their negative ramifications on sexual health, including HIV risks.

Background: Bulbine natalensis is an African-folk medicinal plant used as a dietary supplement for enhancing sexual function and muscle strength in males by presumably boosting testosterone levels, but no scientific information is available about the possible herb-drug interaction (HDI) risk when bulbine-containing supplements are concomitantly taken with prescription drugs., Purpose: This study was aimed to investigate the HDI potential of B. natalensis in terms of the pregnane X receptor (PXR)-mediated induction of major drug-metabolizing cytochrome P450 enzyme isoforms (i.e., CYP3A4 and CYP2C9) as well as inhibition of their catalytic activity., Results: We found that a methanolic extract of B. natalensis activated PXR (EC 50 6.2 ± 0.6 µg/ml) in HepG2 cells resulting in increased mRNA expression of CYP3A4 (2.40 ± 0.01 fold) and CYP2C9 (3.37 ± 0.3 fold) at 30 µg/ml which was reflected in increased activites of the two enzymes. Among the constituents of B. natalensis, knipholone was the most potent PXR activator (EC 50 0.3 ± 0.1 µM) followed by bulbine-knipholone (EC 50 2.0 ± 0.5 µM), and 6'-methylknipholone (EC 50 4.0 ± 0.5 µM). Knipholone was also the most effective in increasing the expression of CYP3A4 (8.47 ± 2.5 fold) and CYP2C9 (2.64 ± 0.3 fold) at 10 µM. Docking studies further confirmed the unique structural features associated with knipholones for their superior inductive potentials in the activation of PXR compared to other anthraquinones. In a CYP inhibition assay, the methanolic extract as well as the anthraquinones strongly inhibited the catalytic activity of CYP2C9 while, inhibition of CYP3A4 was weak., Conclusions: These results suggest that consumption of B. natalensis may pose a potential risk for HDI if taken with conventional medications that are substrates of CYP3A4 and CYP2C9 and may contribute to unanticipated adverse reactions or therapeutic failures. Further studies are warranted to validate these findings and establish their clinical relevancy., (Copyright © 2020. Published by Elsevier GmbH.)

Background: Recurrent lumbar disc herniation (RLDH) is one of the major causes for failure of primary surgery. The optimal surgical treatment of RLDH remains controversial., Aim: Retrospectively, we evaluate 135 patients and compare the clinical outcomes between fusion and nonfusion treatment of RLDH., Methods: Records of 75 men and 35 women aged 28-60 years for conventional revision discectomy alone (nonfusion) and 15 men and 10 women aged 30-65 years for revision discectomy with transforaminal lumbar interbody fusion (TLIF) and transpedicular screw fixation (fusion) were reviewed. Demographics, surgical data, and complications were collected and pre- and postoperative assessment were done by the Visual Analogue Scale (VAS) scale and Japanese Orthopaedic Association (JOA) score. The results after surgery were assessed according to the recovery rate as excellent, good, fair, and poor., Results: The mean follow-up period was 28.8 and 24.6 months in Group A (nonfusion) and Group B (fusion group), respectively. The preoperative data between both the groups showed no statistically significant difference. The postoperative mean VAS and JAO scores, recovery rate, and satisfaction rate showed no statistically significant difference except postoperative low back pain and occasional radicular pain and neurological deficit in nonfusion group which was significantly higher than that of fusion group. In comparison to fusion group, nonfusion group required significantly less operative time, less intraoperative blood loss, less postoperative hospital stay, no blood transfusion, and less total cost of the procedure. Satisfaction rate was 80% and 88% in nonfusion and fusion groups, respectively., Conclusions: Both convention revision discectomy (nonfusion) and discectomy with instrumented fusion (TLIF) surgery are effective in patients with RLDH., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Craniovertebral Junction and Spine.)

Background: Osteogenesis imperfecta (OI) is a heterogeneous group of collagen-related disorders characterized by osteopenia, bone fractures, spine deformities, and nonskeletal complications. Cardiopulmonary complications are the major cause of morbidity and mortality in adults with OI. The cause of such problems was often attributed solely to the presence of large scoliosis curves affecting pulmonary function and, indirectly, cardiovascular health. However, recent studies suggest this may not be the case. Therefore, determining the relationships and causative agents of cardiopulmonary problems in patients with OI, specifically pulmonary impairment, is important to improving the overall wellbeing, quality of life, and survival of these patients., Questions/purposes: (1) Is cardiopulmonary fitness in OI solely related to the presence of scoliosis? (2) What is the prevalence of heart and lung complications in this adult population? (3) Does the presence of pulmonary impairment impact quality of life in adults with OI?, Methods: This is a prospective observational cross-sectional study. Within 1 year, each participant (n = 30) completed pulmonary function testing, echocardiogram, ECG, chest CT, AP spine radiography, and quality-of-life assessments (SF-36, St. George's Respiratory Questionnaire, Functional Outcomes of Sleep Questionnaire, and Pittsburgh Sleep Quality Index). In terms of pulmonary function, we differentiated restrictive and obstructive physiology using the ratio of forced expiratory volume over one second to forced vital capacity (FEV1/FVC), with restrictive lung physiology defined as FEV1/FVC > 0.8 and obstructive lung physiology as FEV1/FVC < 0.7. Spine radiographs were evaluated for scoliosis. Chest CT images were reviewed to qualitatively assess the lungs. The statistical analysis involved a Kruskall-Wallis test with Bonferroni's correction and a bivariate correlation analysis using Spearman's rho correlation coefficient (p < 0.05)., Results: Sixteen of 23 participants with restrictive lung physiology had scoliosis; their ages ranged from 19 years to 67 years. There was no correlation between the magnitude of the scoliosis curve and deficient pulmonary function (R = 0.08; p = 0.68). Seven participants had normal pulmonary function. The average scoliosis curve was 44 ± 29°. Thirteen participants had abnormal ECG findings while 10 had abnormal echocardiogram results. All but two individuals with abnormal chest CT results were found to have bronchial wall thickening. There were no differences in pulmonary or cardiac findings between OI types, except for FVC and total lung capacity, which were lower in individuals with Type III OI than in those with other types of OI. FEV1/FVC correlated with St. George's Respiratory Questionnaire (R = 0.429; p = 0.02) but not with Functional Outcomes of Sleep Questionnaire (R = -0.26; p = 0.19) or SF-36 scores (physical component summary: R = -0.037, p = 0.85; mental component summary: R = -0.204, p = 0.29)., Conclusions: The lack of a relationship between decreased pulmonary function and the severity of scoliosis suggests that restrictive lung physiology in this population is likely because of factors intrinsic to OI and not entirely because of thoracic cage deformities. The fact that pulmonary impairment influences self-perceived quality of life exemplifies how detrimental such complications may be to everyday functioning. This also reinforces the importance of determining the underlying cause of cardiopulmonary impairment in this population to set clear clinical guidelines of care., Level of Evidence: Level II, prognostic study.

At high doses, green tea extracts and green tea's major active constituent, (-)-epigallocatechin gallate (EGCG), despite their generally perceived health benefits, have been suspected to cause hepatotoxicity in certain human populations. It has been reported that o -quinone metabolites of gallic acid or EGCG are causative agents for this hepatotoxicity. However, no experimental information is available at the molecular level on the possible role of NQO1 in the detoxification of EGCG and its metabolites, including reactive intermediates. In the present study, we investigated the possibility of NQO1 inhibition by EGCG and its metabolites by studying their interaction profiles and binding mechanism at the active site of NQO1 using molecular docking, binding free energy calculations, and molecular dynamics (MD) simulations. The binding free energy calculations showed that some metabolites exhibited strong predicted binding affinity and found that the binding orientation of the EGCG metabolites overlapped with that of dicoumarol found in an NQO1 X-ray crystal structure. The results suggest that these metabolites may act as strong NQO1 inhibitors, highlighting the need for experimental validation of this with appropriate biological methods. The Prime MM-GBSA computed average binding free energies after MD simulations of compounds 1 , 2 , 24 , 31 , and 33 revealed that these compounds highly favored van der Waals (VdW) and Coulombic interactions with NQO1. In addition, the MD results revealed that selected EGCG metabolites formed a stable and strong complex with NQO1, with amino acids W105, Y126, Y128, H161, F178, H194, F232, and F236 being critical for potential NQO1 binding. The current results together with experimental data as well as studies of the polymorphisms of NQO1 (especially C609T) may explain the observed idiosyncratic hepatotoxicity caused by the consumption of green tea and its constituents.

The methodology exploring the cardioprotective potential of the flavonoid Fisetin through its ability to modulate PPAR-γ was unraveled in the present study. Computational modelling through molecular docking based binding study of interactions between Fiestin and PPAR-γ revealed the potential role of Fisetin as an agonist of PPAR-γ. A murine model of cardiac ischemia-reperfusion injury was used to explore this further. Male Wistar Rats were randomly assigned to five groups. Fisetin (20 mg/kg; p. o) was administered for 28 days. Ischemia was induced for 45 min on the 29th day followed by 60 min of reperfusion. Fisetin pretreatment upregulated the expression of PPAR-γ in heart tissue significantly Cardioprotection was assessed by measurement of hemodynamic parameters, infarct size, ELISA for oxidative stress, immunohistochemistry and TUNEL assay for apoptosis, and western blot analysis for MAPK proteins and inflammation. PPAR-γ activation by fisetin led to significantly reduced infarct size, suppression of oxidative stress, reduction of cardiac injury markers, alleviation of inflammation, and inhibition of apoptosis The MAPK-based molecular mechanism showed a rise in a key prosurvival kinase, ERK1/ERK2 and suppression of JNK and p38 proteins. The aforementioned beneficial findings of fisetin were reversed on the administration of a specific antagonist of PPAR-γ. In conclusion, through our experiments, we have proved that fisetin protects the heart against ischemia-reperfusion injury and the evident cardioprotection is PPAR-γ dependant. In conclusion, our study has revealed a prime mechanism involved in the cardioprotective effects of fisetin. Hence, Fisetin may be evaluated in further clinical studies as a cardioprotective agent in patients undergoing reperfusion interventions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Methylene blue with a 10-N carbamoyl linkage was reported to be a hydroxyl radical triggered cleavable ligand. Probed by this platform, hemoproteins were demonstrated to be a much more efficient Fenton's catalyst than commonly used inorganic Fe(ii) salts. The applicability of this ligand was demonstrated through the capability of being triggered by elevated reactive oxygen species levels at diseased tissue, with malaria-parasitized erythrocytes as an in vitro model.

In Jordan, Salvia ceratophylla L. is traditionally used in the treatment of cancer, microbial infections, and urinary disorders. This study aimed: (1) to chemically characterize S. ceratophylla essential oil (EO) from South Jordan, by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS); and (2) to evaluate in vitro the cytotoxic, anti-inflammatory, and antiprotozoal activities of the EO, it's predominant components, and the hexane (A), ethyl acetate (B), methanol (C) and crude-methanol extracts (D). The analysis revealed that the EO has 71 compounds, with linalool (54.8%) as main constituent. Only the hexane extract (A) showed some cytotoxic activity against SK-MEL, KB, BT-549, SK-OV-3, LLC-PK1 and VERO cells lines with IC 50 between 60 and > 100 µg/mL. The EO inhibited NO production (IC 50 90 µg/mL) and NF-κB activity (IC 50 38 µg/mL). The extracts A, B, and D inhibited NO production and NF- κB activity with IC 50 between 32 and 150 µg/mL. Linalool considerably inhibited NO production (IC 50 18 µg/mL). The extracts tested did not exhibit antileishmanial activity. Regarding antitrypanosomal activity, the EO exhibited significant results with IC 50 2.65 µg/mL. In conclusion, Jordan S. ceratophylla EO represents a rich source of linalool and bears a promising therapeutic potential for further antitrypanosomal drug development.

Among general population sub-clinical primary hypothyroidism is common. The cross sectional descriptive type of observational study was conducted in medicine and allied wards in Mymensingh Medical College Hospital, Mymensingh, Bangladesh from January 2010 to December 2010; among 230 purposively selected hospitalized pre-dialysis patients with chronic kidney disease. The purpose of the study was to find out the prevalence of sub-clinical hypothyroidism in hospitalized pre-dialysis patients with chronic kidney disease. Data were collected from the patients using a case record form by face to face interview, clinical examination and laboratory investigations. The collected data were entered into SPSS version 20.0 and analyzed accordingly. Mean age of the patients was 47.2 years with a SD of ±2.05 years. Maximum patients were male with a male female ratio of 5:1. A significant number of patients were smoker- 11.8% of sub-clinical hypothyroidism group and 13.6% of euthyroid group. Among the patients 40 (17.40%) had sub-clinical hypothyroidism while the majority 190 (82.60%) did not have it. Estimated prevalence of sub-clinical hypothyroidism in hospitalized pre-dialysis patients with chronic kidney disease was 17.40%. Co-morbidities found in the patients were hypertension, diabetes mellitus, chronic glomerulonephritis and obstructive uropathy. All the patients (40, 100.0%) with sub-clinical hypothyroidism were hypertensive. On the other hand, 184 (97.1%) patients without sub-clinical hypothyroidism were hypertensive. Presence of co-morbidities in patients with sub-clinical hypothyroidism did not differ significantly (p>0.05) from patients without sub-clinical hypothyroidism. Patients in group with sub-clinical hypothyroidism were more over weight in comparison to patients without sub-clinical hypothyroidism (p<0.05). Biochemical parameters of patients with sub-clinical hypothyroidism differed significantly (p<0.05) from those of patients without sub-clinical hypothyroidism. There was no significant difference between urinary albumin of two groups of patients (p>0.05). Stage 4 CKD patients were more in sub-clinical hypothyroidism group in comparison to euthyroid group. As this study may not reflect the actual picture, further large scale multi-centric study is recommended to explore the real situation of sub-clinical hypothyroidism in patients with chronic kidney disease.

Introduction: Although Bangladesh is a country of generalised tuberculosis (TB) epidemic, the HIV prevalence is low among general populations, and 3.9% among key populations. Despite the high possibility of HIV-TB coinfection, scientifically tested approaches for increasing TB case detection among sexual minority people are yet to be developed and implemented in Bangladesh. Such approaches could foster service delivery linkages between communities and the government health system. Findings of this experimental research are likely to provide new insights for programme managers and policy planners for adopting a similar approach in order to enhance TB referral, thus ultimately increasing TB case detections and reducing the likelihood of TB-related mortalities and morbidities, irrespective of HIV status., Methods and Analysis: This operational research will follow a quasi-experimental design, applying both qualitative and quantitative methods, in two drop-in centres in three phases. Phase 1 will encompass baseline data collection and development of a community-based TB screening approach. In phase 2, the newly developed intervention will be implemented, followed by end-line data collection in phase 3. Qualitative data collection will be continued throughout the first and second phases. The baseline and end-line data will be compared both in the intervention and comparison areas to measure the impact of the intervention., Ethics and Dissemination: Ethical approval was obtained from the Institutional Review Board of International Centre for Diarrhoeal Disease Research, Bangladesh. The findings will be disseminated through diverse scientific forums including peer-reviewed journals, presentation at conferences and among the policy-makers for policy implication. The study started in January 2019 and will continue until June 2020., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Using flavonoids and dichlone as substrates, benzonaphthofuroquinones (1, 2, 3, 5, 6, novel; 4 new) and benzoylnaphthindolizinediones (7, 8, known; 9, new) were synthesized through common base-catalyzed method and a new method of combining base-catalyzed with O 2 /H 2 O exposing. The possible reaction mechanisms may involve the process like isomerization, hydration, oxidation, decomposition and intermolecular condensation. Benzonaphthofuroquinones (2, 3, 4, 5) were found to exhibit potent cytotoxicity against carcinoma cell lines and low toxicity to normal cell lines. The compounds 4 and 5 not only expressed a significant late-stage-apoptosis against human leukemia and melanoma, but also promoted the cleavage of caspase-3 and PARP in human leukemia, which suggested that the late-stage-apoptosis and caspase-3 pathway may be responsible for the cytotoxicities of these benzonaphthofuroquinones. The replacement of the furan ring with pyrrole system in benzoylnaphthindolizinediones (7, 8, 9) resulted in the loss of anticancer activity., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Skeletal dysplasias are a heterogeneous group of >400 genetic disorders characterized by abnormal bone growth. Many individuals experience joint pain and limitation, coming to require joint replacement much earlier than the average-statured population. In addition, prosthesis survival rate is less in the dysplastic population. The purpose of this study is to identify risk factors for surgery and provide recommendations to improve surgical outcomes., Methods: This a retrospective review of 29 individuals with a skeletal dysplasia who had 64 joint replacements between April 1985 and January 2019 at a single institution. We collected demographics, physical examination, medical history, imaging studies, surgical indication, and complications., Results: Spondyloepiphyseal dysplasia was the most common skeletal dysplasia (7), followed by pseudoachondroplasia (4) and multiple epiphyseal dysplasia (4). Average age of the cohort was 40.6 years (range 14-64). Hip arthroplasty (34) was the most commonly performed surgery. The majority of arthroplasties (75%) required custom components. Complication rate was 37.3%, most commonly pulmonary embolism (3) and pneumonia (3). Most complications (81.8%) occurred in individuals with either a pre-existing cardiopulmonary comorbidity or lumbar/sacral deformity. Body mass index did not correlate with complication severity (R = -0.042, P = .752) or rate (R = 0.006, P = .963)., Conclusion: Surgical complications are highest in patients with pre-existing cardiopulmonary conditions. Body mass index does not predict complications in this cohort. Preoperative evaluations for individuals with skeletal dysplasias should include comprehensive work-up of spine issues and extraskeletal systems that present an operative risk. Intraoperative protocol should include special consideration for placement on the table, airway maintenance, and spinal cord monitoring in select cases., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: A systematic assessment was done to examine the effect of HIV interventions among MSM in Dhaka, Bangladesh. MSM were defined as males having sex with males but did not sell sex in the last year. MSM are hidden, marginalized and stigmatized population groups not only in Bangladesh but also globally. In 2010, HIV interventions for MSM were expanded in 40 districts of Bangladesh through 65 drop-in-centres (DICs) and peer outreach workers., Methods: Data from two surveys on MSM in Dhaka in 2010 (baseline) and 2013 (midline) were used to analyse the effect of ongoing HIV prevention services. Both surveys used time location sampling to randomly select MSM for risk behaviour interviews. Two outcome variables were considered; condom use in the last anal sex act and consistent condom use during anal sex in the last month. Univariate and multivariate logistic regression methods were used to determine factors associated with condom use., Results: Condom use significantly increased at the midline than baseline (p<0.001 for both). Multivariate analysis showed that having comprehensive knowledge of HIV and participation in HIV prevention programme were positively associated with both last time and consistent condom use. MSM who had comprehensive knowledge of HIV were 1.9 times (95% CI: 1.3-2.8, p = 0.002) and 2.1 times (95% CI: 1.4-3.2, p<0.001) more likely to use condoms than those who did not have comprehensive knowledge of HIV. The likelihood of using condoms among MSM was more than double at the midline than the baseline (p<0.01 for both). However, odds of condom use was significantly lower among those who perceived themselves to be at risk or were not able to assess their own risk of HIV., Conclusion: To sustain positive changes in HIV risk behaviours, HIV prevention programmes for MSM need to be continued and strengthened., Competing Interests: The authors declare that they have no competing interests.

Background: Treatment option of postoperative discitis (POD) is either conservative or operative, but till date, there are no established validated protocols of the treatment of postoperative lumbar discitis., Aim: The aim of this study was to assess the outcome of conservative versus operative management of POD following single-level lumbar discectomy., Methods: We prospectively studied a total of 38 cases of POD. The patients were diagnosed clinically, radiologically, and by laboratory investigations and followed up with serial erythrocyte sedimentation rate (ESR), C-reactive protein, X-ray, computed tomography (CT), and magnetic resonance imaging. Demographic data, clinical variables, length of hospital stay, duration of antibiotic treatment, and posttreatment complications were collected, and pre- and postoperative assessment was done using the Visual Analog Scale (VAS) and Japanese Orthopaedic Association (JOA) score. Functional outcome of the study was measured by the modified criteria of Kirkaldy-Willis., Results: VAS score for pain was significantly decreased in both groups after treatment. However, posttreatment differences were not statistically significant. In posttreatment mean JOA score, differences were not statistically significant in both groups except the mean difference (-0.47) of restriction of daily activities, which was statistically significant (95% confidence interval: -0.88--0.07, P = 0.025, unpaired t -test). About 73.7% and 84.2% of the patients had a satisfactory functional outcome in conservative and operative management groups, respectively, at the end of 12-month follow-up., Conclusions: Operative management yielded better outcomes than traditional conservative treatment in terms of functional outcomes, length of hospital stays, and duration of antibiotic treatment as determined by both the pain and daily activity levels., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Craniovertebral Junction and Spine.)

Eleven diarylpentanoid/norlignan glucosides, along with five other specialized metabolites, were isolated and characterized from the hydro-alcoholic extract of Hypoxis hemerocallidea corms. Hypoxhemerolosides A-F were found to be undescribed compounds. Curcapicycloside was isolated and identified for the first time in its original form, previously it was reported as a methylated derivative. In addition, (1S,2R)-1-(3,4-dihydroxyphenyl)-5-(4-β-D-glucopyranoxy-3-hydroxyphenyl)-1-methoxypent-4-yn-2-ol and (1S,2R)-1-(3,4-dihydroxyphenyl)-1-ethoxy-5-(4-β-D-glucopyranoxy-3-hydroxyphenyl)pent-4-yn-2-ol were isolated and characterized as artifacts, generated during extraction/isolation procedures from possible 1-(3,4-dihydroxyphenyl)-5-(4-β-D-glucopyranoxy-3-hydroxyphenyl)pent-4-yne-1,2-diol. Structure elucidation was mainly achieved by the interpretation of 1D and 2D NMR and HRESIMS data. The isolated compounds were screened for anti-inflammatory activity in terms of iNOS and NF-κB inhibition as well as for cytotoxicity. Hypoxhemerolosides C-E and obtuside A moderately inhibited nitric oxide production in LPS-stimulated mouse macrophages (RAW 264.7)., Competing Interests: Declaration of competing interest The authors declare no conflict of interest regarding this article., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Using fragment-based design strategy, new pyridyl-indole hybrids 4a-y and indole intermediates 3a-e were synthesized using multicomponent one pot reaction. The synthesized compounds were subjected to screening for antimalarial activity against chloroquine sensitive (D6) and chloroquine resistant (W2) strains of Plasmodium falciparum. Several compounds exhibited antimalarial activity with IC 50 values in the range of 1.47-9.23 μM, and 1.16-7.66 μM, for D6 and W2 strains, respectively. Compounds 4a, 4k and 4u showed the highest selectivity index among all the tested compounds (S.I. ranged 3.8-10). Binding interactions between the active antimalarial compounds and the active site of quadruple mutant Plasmodium falciparum dihydrofolate reductase enzyme have been investigated using molecular docking analysis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The green alga Klebsormidium flaccidum var. zivo is a rich source of proteins, polyphenols, and bioactive small-molecule compounds. An approach involving chromatographic fractionation, anti-inflammatory activity testing, ultrahigh performance liquid chromatography-mass spectrometry profiling, chemometric analysis, and subsequent MS-oriented isolation was employed to rapidly identify its small-molecule anti-inflammatory compounds including hydroxylated fatty acids, chlorophyll-derived pheophorbides, carotenoids, and glycoglycerolipids. Pheophorbide a, which decreased intracellular nitric oxide production by inhibiting inducible nitric oxide synthase, was the most potent compound identified with an IC 50 value of 0.24 µM in lipopolysaccharides-induced macrophages. It also inhibited nuclear factor kappaB activation with an IC 50 value of 32.1 µM in phorbol 12-myristate 13-acetate-induced chondrocytes. Compared to conventional bioassay-guided fractionation, this approach is more efficient for rapid identification of multiple chemical classes of bioactive compounds from a complex natural product mixture.

Methylene blue (MB) with a 10-N-carbamoyl linkage was discovered and developed as a multifunctional far-red (660 nm) photocleavable ligand capable of rendering a series of MB-conjugated compounds with off-to-on fluorescence switch properties through the controlled release of MB.

Cisplatin-induced nephrotoxicity persists as a clinical problem despite several supportive measures to alleviate renal damage. Daidzein (DZ), a dietary isoflavone having antioxidant and anti-inflammatory activity, is investigated in this study for protective effects against cisplatin-induced renal injury in rats. DZ (25, 50, or 100 mg/kg; intraperitoneally; 10 days) was administered along with Cisplatin, single dose, on the 7th day of the experiment. On the 11th day, the rats were euthanized, and different samples were collected for analysis. Biochemical, histopathological, and molecular parameters were assessed to evaluate the effect of daidzein. Cisplatin injection resulted in renal dysfunction, lipid peroxidation that led to consumption of antioxidants, exaggerated apoptosis, and inflammation. These changes were associated with increase in the signaling proteins. DZ attenuated the toxic effects of cisplatin on the kidney at 100 mg/kg dose. The study concludes with the finding that daidzein imparts protection against the nephrotoxic effect of Cisplatin and can be considered as a novel, potential therapy., (© 2019 Wiley Periodicals, Inc.)