Mirtazapine versus megestrol acetate in treatment of anorexia-cachexia in advanced cancer patients: a randomized, double-blind trial.

OBJECTIVE: Cancer-related anorexia-cachexia comprises one of the most common syndromes of advanced cancer patients. The management of cancer-related anorexia-cachexia is a great challenge in clinical practice. There are no definite practice guidelines yet for the prevention and treatment of cancer-related anorexia-cachexia. This study is considered to find out whether there is any role of mirtazapine in the improvement of anorexia in cancer patients. METHODS: A total of 80 cancer-anorexia patients were enrolled. Patients in the trial arm received the standard chemotherapy medication plus one tablet of mirtazapine 15 mg daily at night orally for 8 weeks starting from the day of an initial assessment. The control arm received the standard chemotherapy medication plus one tablet of megestrol acetate 160 mg daily orally for 8 weeks starting from the day of an initial assessment. Each patient was assessed by validated versions of Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale v 4 questionnaires. RESULTS: After 4 and 8 weeks each patient was evaluated again using the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale tool. The quality of life of each patient was assessed by European Organization for Research and Treatment QLQ-C30 v 3.0. After 4 to 8 weeks of treatment, the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale score in cancer anorexia patients in the mirtazapine improved anorexia significantly. However, the improvement after 4 to 8 weeks was not statistically significant when it was compared with the megestrol acetate (P > 0.05). CONCLUSIONS: Therefore, the findings of this study reveal that mirtazapine might be a potential alternative to megestrol acetate, as it has shown potential efficacy as like as megestrol acetate.

Autism spectrum disorder among 16- to 30-month-old children in Bangladesh: Observational cross-sectional study.

LAY ABSTRACT: A nationwide survey was done in Bangladesh to assess autism spectrum disorder prevalence in 16- to 30-month-old children at urban-rural distribution and to determine the association with socioeconomic and demographic conditions. A three-stage cluster sampling method was used where districts from all divisions were selected in the first stage, census enumeration areas as blocks of households were selected in the second stage and households (within the blocks) were selected in the third stage. Thereby, it included 38,440 children from 37,982 households (71% rural, 29% urban) aged 16-30 months from 30 districts of eight divisions of Bangladesh. Screening was done with a 'Red Flag' tool and Modified Checklist for Toddlers and a final diagnosis using Diagnostic and Statistical Manual of Mental Disorders, 5th Edition for autism spectrum disorder. Autism spectrum disorder prevalence was 17 per 10,000 young children - in other words, one in 589 young children. Boys were found at higher risk of autism (one in 423 boys; one in 1026 girls). Prevalence of autism spectrum disorder was higher in urban environments than in rural ones - 25/10,000 and 14/10,000, respectively. More autism spectrum disorder children were found in advanced age groups of parents, especially mothers, and in households with a higher wealth quintile. This survey is significant as it covers both urban and rural areas and specifically targets very young children. The involvement of the Bangladesh Bureau of Statistics, as well as support from the entire healthcare system infrastructure, makes this survey more representative on a national level. Its results will form a database to support the development of an effective early intervention programme in Bangladesh. We hope it will prove useful for researchers, clinicians and frontline healthcare workers, and inform the decisions of policymakers and funders in Bangladesh.

Genetic variations of CYP2R1 (rs10741657) in Bangladeshi adults with low serum 25(OH)D level-A pilot study.

BACKGROUND: Some studies revealed that despite having sufficient sun exposure and dietary supply, the level of serum 25(OH)D in Bangladeshi adults is lower than its normal range. Genetic pattern of an individual is also an essential factor that regulates the level of serum 25(OH)D. However, the genetic variations of CYP2R1 (rs10741657) and their association with low serum 25(OH)D level in Bangladeshi adults are yet to be explored. OBJECTIVE: This study was conducted to determine the frequency of variants of rs10741657 of CYP2R1 gene and its association with low serum 25(OH)D level among Bangladeshi adults. METHOD: This pilot study was conducted among thirty individuals with low serum 25(OH)D level as the study population and ten subjects with sufficient serum 25(OH)D level as controls based on the inclusion and exclusion criteria. Genetic analysis of rs10741657 of CYP2R1 including primer designing, DNA extraction, PCR of target region with purification and Sanger sequencing of the PCR products were done accordingly. For statistical analysis, One-way ANOVA followed by LSD test, Freeman-Halton extension of Fisher's exact test, Chi-square test (χ2) test and unpaired student t-test were performed. RESULTS: In this study, genetic variants of CYP2R1 (rs10741657) among the study population were genotype GG (63.30%), GA (30%) and AA (6.7%). Minor allele frequency of the study population was 0.217. The association between GG and GA genotypes of CYP2R1 (rs10741657) with low serum 25(OH)D level among the study population was found and it was statistically significant. Statistically significant differences were also observed between the genotypes and alleles of the study population and controls. CONCLUSIONS: The presence of 'GG' and 'GA' genotypes of rs1041657 in CYP2R1 gene is associated with low serum 25(OH)D level among Bangladeshi adults in this pilot study.

Endophytic Bacteria Enterobacter hormaechei Fabricated Silver Nanoparticles and Their Antimicrobial Activity.

Antimicrobial resistance (AMR), one of the greatest issues for humankind, draws special attention to the scientists formulating new drugs to prevent it. Great emphasis on the biological synthesis of silver nanoparticles (AgNPs) for utilization in single or combinatorial therapy will open up new avenues to the discovery of new antimicrobial drugs. The purpose of this study was to synthesize AgNPs following a green approach by using an endophytic bacterial strain, Enterobacter hormaechei, and to assess their antimicrobial potential against five pathogenic and four multidrug-resistant (MDR) microbes. UV-Vis spectroscopy, fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), and zeta potential (ζ) were used to characterize the synthesized AgNPs. Endophytic E. hormaechei-mediated AgNPs (Eh-AgNPs) were represented by a strong UV-Vis absorbance peak at 418 nm within 5 min, forming spherical and polydispersed nanoparticles in the size range of 9.91 nm to 92.54 nm. The Eh-AgNPs were moderately stable with a mean ζ value of -19.73 ± 3.94 mV. The presence of amine, amide, and hydroxyl functional groups was observed from FTIR analysis. In comparison to conventional antibiotics, the Eh-AgNPs were more effective against Bacillus cereus (ATCC 10876) and Candida albicans (ATCC 10231), exhibiting 9.14 ± 0.05 mm and 8.24 ± 0.05 mm zones of inhibition (ZOIs), respectively, while displaying effective inhibitory activity with ZOIs ranging from 10.98 ± 0.08 to 13.20 ± 0.07 mm against the MDR bacteria. Eh-AgNP synthesis was rapid and eco-friendly. The results showed that Eh-AgNPs are promising antimicrobial agents that can be used in the development and formulation of new drugs to curb the menace of antimicrobial resistance in pathogenic and MDR microbes.

Convalescent plasma transfusion therapy in severe COVID-19 patients- a safety, efficacy and dose response study: A structured summary of a study protocol of a phase II randomized controlled trial.

OBJECTIVES: General: To assess the safety, efficacy and dose response of convalescent plasma (CP) transfusion in severe COVID-19 patients Specific: a. To identify the appropriate effective dose of CP therapy in severe patients b. To identify the efficacy of the therapy with their end point based on clinical improvement within seven days of treatment or until discharge whichever is later and in-hospital mortality c. To assess the clinical improvement after CP transfusion in severe COVID-19 patients d. To assess the laboratory improvement after CP transfusion in severe COVID-19 patients TRIAL DESIGN: This is a multicentre, multi-arm phase II Randomised Controlled Trial. PARTICIPANTS: Age and sex matched COVID-19 positive (by RT-PCR) severe cases will be enrolled in this trial. Severe case is defined by the World Health Organization (W.H.O) clinical case definition. The inclusion criteria are 1. Respiratory rate > 30 breaths/min; PLUS 2. Severe respiratory distress; or SpO2 ≤ 88% on room air or PaO2/FiO2≤ 300 mm of Hg, PLUS 3. Radiological (X-ray or CT scan) evidence of bilateral lung infiltrate, AND OR 4. Systolic BP < 90 mm of Hg or diastolic BP <60 mm of Hg. AND/OR 5. Criteria 1 to 4 AND or patient in ventilator support Patients' below18 years, pregnant and lactating women, previous history of allergic reaction to plasma, patients who have already received plasma from a different source will be excluded. Patients will be enrolled at Bangabandhu Sheikh Mujib Medical University (BSMMU) hospital, Dhaka medical college hospital (DMCH) and Mugda medical college hospital (MuMCH). Apheretic plasma will be collected at the transfusion medicine department of SHNIBPS hospital, ELISA antibody titre will be done at BSMMU and CMBT and neutralizing antibody titre will be checked in collaboration with the University of Oxford. Patients who have recovered from COVID-19 will be recruited as donors of CP. The recovery criteria are normality of body temperature for more than 3 days, resolution of respiratory symptoms, two consecutively negative results of sputum SARS-CoV-2 by RT-PCR assay (at least 24 hours apart) 22 to 35 days of post onset period, and neutralizing antibody titre ≥ 1:160. INTERVENTION AND COMPARATOR: This RCT consists of three arms, a. standard care, b. standard care and 200 ml CP and c. standard care and 400 ml CP. Patients will receive plasma as a single transfusion. Intervention arms will be compared to the standard care arm. MAIN OUTCOMES: The primary outcome will be time to clinical improvement within seven days of treatment or until discharge whichever is later and in-hospital mortality. The secondary outcome would be improvement of laboratory parameters after therapy (neutrophil, lymphocyte ratio, CRP, serum ferritin, SGPT, SGOT, serum creatinine and radiology), length of hospital stay, length of ICU stay, reduction in proportion of deaths, requirement of ventilator and duration of oxygen and ventilator support. RANDOMISATION: Randomization will be done by someone not associated with the care or assessment of the patients by means of a computer generated random number table using an allocation ratio of 1:1:1. BLINDING (MASKING): This is an open level study; neither the physician nor the patients will be blinded. However, the primary and secondary outcome (oxygen saturations, PaO2/FiO2, BP, day specific laboratory tests) will be recorded using an objective automated method; the study staff will not be able to influence the recording of these data. NUMBER TO BE RANDOMISED (SAMPLE SIZE): No similar study has been performed previously. Therefore no data are available that could be used to generate a sample size calculation. This phase II study is required to provide some initial data on efficacy and safety that will allow design of a larger study. The trial will recruit 60 participants (20 in each arm). TRIAL STATUS: Protocol version 1.4 dated May 5, 2020 and amended version 1.5, dated June 16, 2020. First case was recruited on May 27, 2020. By August 10, 2020, the trial had recruited one-third (21 out of 60) of the participants. The recruitment is expected to finish by October 31, 2020. TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT04403477 . Registered 26 May, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trial's website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

Secondary Metabolites Profiling of Acinetobacter baumannii Associated with Chili (Capsicum annuum L.) Leaves and Concentration Dependent Antioxidant and Prooxidant Properties.

Secondary bioactive compounds of endophytes are inevitable biomolecules of therapeutical importance. In the present study, secondary metabolites profiling of an endophytic bacterial strain, Acinetobacter baumannii, were explored using GC-MS study. Presence of antioxidant substances and antioxidant properties in chloroform (CHL), diethyl ether (DEE), and ethyl acetate (EA) crude extracts of the endophytic bacteria were studied. Total phenolic content (TPC), total flavonoid content (TFC), total antioxidant capacity (TAC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and ferrous ion chelating assay were evaluated. A total of 74 compounds were identified from the GC-MS analysis of the EA extract representing mostly alkane compounds followed by phenols, carboxylic acids, aromatic heterocyclic compounds, ketones, aromatic esters, aromatic benzenes, and alkenes. Among the two phenolic compounds, namely, phenol, 2,4-bis(1,1-dimethylethyl)- and phenol, 3,5-bis(1,1-dimethylethyl)-, the former was found in abundance (11.56%) while the latter was found in smaller quantity (0.14%). Moreover, the endophytic bacteria was found to possess a number of metal ions including Fe(II) and Cu(II) as 1307.13 ± 2.35 ppb and 42.38 ± 0.352 ppb, respectively. The extracts exhibited concentration dependent antioxidant and prooxidant properties at high and low concentrations, respectively. The presence of phenolic compounds and metal ions was believed to play an important role in the antioxidant and prooxidant potentials of the extracts. Further studies are suggested for exploring the untapped resource of endophytic bacteria for the development of novel therapeutic agents.

Silver Nanoparticles Synthesized by Using the Endophytic Bacterium Pantoea ananatis are Promising Antimicrobial Agents against Multidrug Resistant Bacteria.

Antibiotic resistance is one of the most important global problems currently confronting the world. Different biomedical applications of silver nanoparticles (AgNPs) have indicated them to be promising antimicrobial agents. In the present study, extracellular extract of an endophytic bacterium, Pantoea ananatis, was used for synthesis of AgNPs. The synthesized AgNPs were characterized by UV⁻Vis spectroscopy, FTIR, transmission electron microscopy (TEM), scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), and Zeta potential. The antimicrobial potential of the AgNPs against pathogenic Staphylococcus aureus subsp. aureus (ATCC 11632), Bacillus cereus (ATCC 10876), Escherichia coli (ATCC 10536), Pseudomonas aeruginosa (ATCC 10145) and Candida albicans (ATCC 10231), and multidrug resistant (MDR) Streptococcus pneumoniae (ATCC 700677), Enterococcus faecium (ATCC 700221) Staphylococcus aureus (ATCC 33592) Escherichia coli (NCTC 13351) was investigated. The synthesized spherical-shaped AgNPs with a size range of 8.06 nm to 91.32 nm exhibited significant antimicrobial activity at 6 µg/disc concentration against Bacillus cereus (ATCC 10876) and Candida albicans (ATCC 10231) which were found to be resistant to conventional antibiotics. The synthesized AgNPs showed promising antibacterial efficiency at 10 µg/disc concentration against the MDR strains. The present study suggests that AgNPs synthesized by using the endophytic bacterium P. ananatis are promising antimicrobial agent.

Heavy Metal Adsorption onto Kappaphycus sp. from Aqueous Solutions: The Use of Error Functions for Validation of Isotherm and Kinetics Models.

Biosorption process is a promising technology for the removal of heavy metals from industrial wastes and effluents using low-cost and effective biosorbents. In the present study, adsorption of Pb(2+), Cu(2+), Fe(2+), and Zn(2+) onto dried biomass of red seaweed Kappaphycus sp. was investigated as a function of pH, contact time, initial metal ion concentration, and temperature. The experimental data were evaluated by four isotherm models (Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich) and four kinetic models (pseudo-first-order, pseudo-second-order, Elovich, and intraparticle diffusion models). The adsorption process was feasible, spontaneous, and endothermic in nature. Functional groups in the biomass involved in metal adsorption process were revealed as carboxylic and sulfonic acids and sulfonate by Fourier transform infrared analysis. A total of nine error functions were applied to validate the models. We strongly suggest the analysis of error functions for validating adsorption isotherm and kinetic models using linear methods. The present work shows that the red seaweed Kappaphycus sp. can be used as a potentially low-cost biosorbent for the removal of heavy metal ions from aqueous solutions. Further study is warranted to evaluate its feasibility for the removal of heavy metals from the real environment.

Secretion of arsenic, cholesterol, vitamin E, and zinc from the site of arsenical melanosis and leucomelanosis in skin.

BACKGROUND: Melanosis and leucomelanosis with or without keratosis are the earliest symptoms of arsenicosis. Uneven distribution of arsenical melanosis and leucomelanosis in skin led us to investigate the possibility of preferential secretion of arsenic and three constituents of sweat; cholesterol, vitamin E, and zinc. METHODS: Twenty-four-hour skin secretion was collected from skin lesions and unaffected sites of 20 patients. Skin secretions were collected from 20 people exposed to arsenic-contaminated drinking water and 20 healthy, unexposed individuals. RESULTS: The secretion of arsenic from the skin of healthy controls (mean ± SE; unit: µg/in.(2) of skin/24 h; chest: 0.6 ± 0.2; back: 0.3 ± 0.1; abdomen: 0.5 ± 0.2) was increased several folds in arsenic-exposed controls (chest: 8.4 ± 1.8; back: 8.3 ± 1.9; abdomen: 6.7 ± 1.8) and patients (chest: 9.2 ± 1.3; back: 7.8 ± 1.3; abdomen: 5.2 ± 1.0). There was no difference in the skin lesions and unaffected sites in patients. However, the secretion of cholesterol was significantly lower in the chest of patients (190 ± 36) and healthy controls (686 ± 100) (p < 0.001). Secretions of vitamin E were low in healthy controls (chest: 8.5 ± 3.1; back: 5.2 ± 1.7; and abdomen: 8.7 ± 2.4), higher in arsenic-exposed controls (chest: 30.2 ± 8.1; back: 16.3 ± 8.9; and abdomen: 24.8 ± 9.3), and highest in patients [chest: 91.4 ± 14.9 (p < 0.0001 vs. control); back: 72.4 ± 13.2 (p < 0.001 vs. control); and abdomen: 46.8 ± 12.9]. Chronic intake of arsenic led to several folds higher secretion of zinc both in patients and in arsenic-exposed controls. One molecule of arsenic appears to be co-secreted with two molecules of zinc. CONCLUSION: Arsenic skin lesions showed no alteration in secretion of arsenic, although the secretion of cholesterol, vitamin E, and zinc was changed. Potential implications are discussed.

Corn extracts lower tissue arsenic level in rat.

This study was carried out to see whether corn extracts could reduce the accumulation of arsenic in different tissues of rat. Exposure to arsenic (700 microg/rat/day) orally for 15 days led to significant accumulation of arsenic and significant reduction in the concentration of reduced glutathione (GSH) in different tissues. While water, salt, ethanol and alkali extracts of corn were co-administered at a dose of 0.5 mL/rat/day orally by stomach tube during last 8 days, arsenic concentration decreased significantly in all tissues and reduced glutathione (GSH) concentration increased significantly in tissues except heart and skin. Among the extracts, water extract produced maximum reduction of arsenic (69.07% in liver, 64.98% in kidney, 63.47% in lung, 57.55% in heart and 69.30% in skin) and elevation of reduced glutathione level in all tissues (17.03% in liver, 46.73% in lung, 32.67% in heart and 55.38% in skin) except kidney, in which maximum elevation of reduced glutathione was attained by ethanol extract (23.14%). This study suggests that corn extracts might protect rats from accumulation of arsenic in different tissues and oxidative stress, which is reflected by the increasing reduced glutathione concentration in those tissues.

Effect of enalapril and losartan on proteinuria in type 2 diabetic nephropathy patients.

A prospective, open label, parallel group and randomized study was conducted to see the effect of enalapril and losartan on proteinuria in type 2 diabetic nephropathy patients. 18 patients (proteinuria 2 0.5 gm/day and serum creatinine <3 mg/dL) were selected and then randomly grouped to receive enalapril (5-40 mg/day, n=10) and losartan (25-200 mg/day, n=8) in increasing dose for 16 weeks. No statistically significant alteration in the urinary total protein, protein creatinine ratio, serum creatinine, estimated glomerular filtration rate, serum potassium and blood pressure was observed in any group. After attaining maximum dose (40 mg and 200 mg respectively), enalapril group showed significant (p < 0.04) reduction of protein creatinine ratio in comparison to losartan group. It may be concluded that 40 mg enalapril or 200 mg losartan are not sufficient to reduce proteinuria and blood pressure significantly in type 2 proteinuric diabetics with renal dysfunction although both drugs were well tolerated at high doses.