Pattern of Prescribing Analgesics and Their Response in Cancer Patients Attending Outpatient Department of Palliative Care Service in Two Teaching Hospitals of Bangladesh.

Palliative care is a valued aspect of clinical care which is an urgent humanitarian need for people worldwide with cancer and other chronic fatal diseases. Patients experience many different symptoms including severe pain in advanced cancer. Palliative care focuses on relief from symptoms, pain and stress by using different analgesics and adjuvant. The goal of palliative care is to improve the quality of life. So, this prospective observational study was carried out to assess pattern of drugs used and their response to pain in cancer patients attending out-patient department of palliative care service in two teaching hospitals of Bangladesh. One hundred forty (140) cancer patients were purposively selected who attended in out-patient department of palliative care unit in Bangabandhu Sheikh Mujib Medical University (BSMMU) and Dhaka Medical College Hospital (DMCH) from July 2018 to June 2019. Outcome variables were commonly presenting complaints, pain intensity, commonly prescribed drugs and analgesic prescription according to WHO three-step analgesic ladder, etc. The mean age ±SD of the respondents was 51.30±15.38 years, male-female ratio 1:1. Common sites of cancer were alimentary origin (20.0%), genitourinary system (17.86%), hepatobiliary system (11.43%), respiratory system (10.71%). The prescribed drugs were analgesics (96.4%), PPIs (74.3%), laxatives (62.1%), anti-emetics (38.6%), multivitamins (32.9%), H2 antagonists (17.1%), sedatives (17.1%), and corticosteroids (8.6%). Level 1 analgesics (Paracetamol or other NSAIDs) were prescribed to 42.65%, level 2 analgesics (Tramadol) were prescribed to 50.00% patients and level 3 analgesics (Morphine) were prescribed to 51.42% patients. The relation between and receiving three levels of analgesic prescriptions was statistically significant. The association between level of analgesic prescription was significant with site of cancer (p<0.001) and intensity of pain (p<0.001). This study showed that morphine was prescribed to more than half of the patients. Other level of analgesics were also used either single or in combination. Younger and male patients were treated more with level III analgesics. Prescribing analgesics were dependent on sites of cancer and intensity of pain.

Male reproductive traits are differentially affected by dietary macronutrient balance but unrelated to adiposity.

Dietary factors influence male reproductive function in both experimental and epidemiological studies. However, there are currently no specific dietary guidelines for male preconception health. Here, we use the Nutritional Geometry framework to examine the effects of dietary macronutrient balance on reproductive traits in C57BL/6 J male mice. Dietary effects are observed in a range of morphological, testicular and spermatozoa traits, although the relative influence of protein, fat, carbohydrate, and their interactions differ depending on the trait being examined. Interestingly, dietary fat has a positive influence on sperm motility and antioxidant capacity, differing to typical high fat diet studies where calorie content is not controlled for. Moreover, body adiposity is not significantly correlated with any of the reproductive traits measured in this study. These results demonstrate the importance of macronutrient balance and calorie intake on reproductive function and support the need to develop specific, targeted, preconception dietary guidelines for males.

Extensive genetic diversity with novel mutations in spike glycoprotein of severe acute respiratory syndrome coronavirus 2, Bangladesh in late 2020.

In Bangladesh, coronavirus disease 2019 (COVID-19) has been highly prevalent during late 2020, with nearly 500 000 confirmed cases. In the present study, the spike (S) protein of severe acute respiratory coronavirus 2 (SARS-CoV-2) circulating in Bangladesh was genetically investigated to elucidate the diversity of mutations and their prevalence. The nucleotide sequence of the S protein gene was determined for 15 SARS-CoV-2 samples collected from eight divisions in Bangladesh, and analysed for mutations compared with the reference strain (hCoV-19/Wuhan/WIV04/2019). All the SARS-CoV-2 S genes were assigned to B.1 lineage in G clade, and individual S proteins had 1-25 mutations causing amino acid substitution/deletion. A total of 133 mutations were detected in 15 samples, with D614G being present in all the samples; 53 were novel mutations as of January 2021. On the receptor-binding domain, 21 substitutions including ten novel mutations were identified. Other novel mutations were located on the N-terminal domain (S1 subunit) and dispersed sites in the S2 subunit, including two substitutions that remove potential N-glycosylation sites. A P681R substitution adjacent to the furin cleavage site was detected in one sample. All the mutations detected were located on positions that are functionally linked to host transition, antigenic drift, host surface receptor binding or antibody recognition sites, and viral oligomerization interfaces, which presumably related to viral transmission and pathogenic capacity.

Contribution of Noncanonical Antigens to Virulence and Adaptive Immunity in Human Infection with Enterotoxigenic E. coli.

Enterotoxigenic Escherichia coli (ETEC) contributes significantly to the substantial burden of infectious diarrhea among children living in low- and middle-income countries. In the absence of a vaccine for ETEC, children succumb to acute dehydration as well as nondiarrheal sequelae related to these infections, including malnutrition. The considerable diversity of ETEC genomes has complicated canonical vaccine development approaches defined by a subset of ETEC pathovar-specific antigens known as colonization factors (CFs). To identify additional conserved immunogens unique to this pathovar, we employed an "open-aperture" approach to capture all potential conserved ETEC surface antigens, in which we mined the genomic sequences of 89 ETEC isolates, bioinformatically selected potential surface-exposed pathovar-specific antigens conserved in more than 40% of the genomes (n = 118), and assembled the representative proteins onto microarrays, complemented with known or putative colonization factor subunit molecules (n = 52) and toxin subunits. These arrays were then used to interrogate samples from individuals with acute symptomatic ETEC infections. Surprisingly, in this approach, we found that immune responses were largely constrained to a small number of antigens, including individual colonization factor antigens and EtpA, an extracellular adhesin. In a Bangladeshi cohort of naturally infected children <2 years of age, both EtpA and a second antigen, EatA, elicited significant serologic responses that were associated with protection from symptomatic illness. In addition, children infected with ETEC isolates bearing either etpA or eatA genes were significantly more likely to develop symptomatic disease. These studies support a role for antigens not presently targeted by vaccines (noncanonical) in virulence and the development of adaptive immune responses during ETEC infections. These findings may inform vaccine design efforts to complement existing approaches.

Leprosy patients with deformities at post-elimination stage: The Bangladesh experience.

Background: Disability assessment in leprosy patients is a very important factor in the evaluation of the effectiveness of a leprosy elimination program. Little information exists on deformities in leprosy patients in Bangladesh. Objectives: To describe the pattern and prevalence of deformities in leprosy patients after leprosy has been declared eliminated from Bangladesh in 1998. Methods: A descriptive retrospective cross-sectional study was carried out in Chittagong Medical College Hospital using the registered records of patients for the period 2004-2013. Results: Out of 670 leprosy patients, 213 (31.79%) had deformities. The prevalence of deformity was for grade 1: 92 (43.20%), for grade 2: 121 (56.80%). Among the patients with deformity, males 144 (67.60%) outnumbered females 69 (32.40%). Four age groups were considered. The calculated age-specific cumulative detection rates showed the highest case detection in >40 years group at 81 (38.02%). The rate of children (<14 years) was less at 7 (3.29%). Of the 213 patients with deformity, the borderline tuberculoid patients were totalled 79 (37.08%), which was higher than other forms of leprosy. Among the 121 patients with limb deformity, 57 (8.50%) had claw hand followed by wrist drop 31 (4.63%), foot drop 30 (4.48%). Three (0.45%) had a nerve abscess, 27 (4.02%) had a trophic ulcer and 7 (1.05%) patients had ocular complications. Conclusion: The grade 2 deformities among newly detected leprosy patients were still high. Claw hand was the most common deformity in the upper limbs, whereas foot drop and trophic ulcer were the most common deformities in the lower limbs. Although leprosy according to the World Health Organization has been eliminated globally, the disease continues to be a significant cause of peripheral neuropathy, deformity, disability and disfigurement in some developing countries like Bangladesh.

Comparative effects of ascobin and glutathione on copper homeostasis and oxidative stress metabolism in mitigation of copper toxicity in rice.

Copper (Cu) pollution of agricultural land is a major threat to crop production. Exogenous chemical treatment is an easily accessible and rapid approach to remediate metal toxicity, including Cu toxicity in plants. We compared the effects of ascobin (ASC; ascorbic acid:citric acid at 2:1) and glutathione (GSH) in mitigation of Cu toxicity in rice. Plants subjected to Cu stress displayed growth inhibition and biomass reduction, which were connected to reduced levels of chlorophylls, RWC, total phenolic compounds, carotenoids and Mg2+ . Increased accumulation of ROS and malondialdehyde indicated oxidative stress in Cu-stressed plants. However, application of ASC or GSH minimized the inhibitory effects of Cu stress on rice plants by restricting Cu2+ uptake and improving mineral balance, chlorophyll content and RWC. Both ASC and GSH pretreatments reduced levels of ROS and malondialdehyde and improved activities of antioxidant enzymes, suggesting their roles in alleviating oxidative damage. A comparison on the effects of ASC and GSH under Cu stress revealed that ASC was more effective in restricting Cu2+ accumulation (69.5% by ASC and 57.1% by GSH), Ca2+ and Mg2+ homeostasis, protection of photosynthetic pigments and activation of antioxidant defence mechanisms [catalase (110.4%), ascorbate peroxidase (76.5%) and guaiacol peroxidase (39.0%) by ASC, and catalase (58.9%) and ascorbate peroxidase (59.9%) by GSH] in rice than GSH, eventually resulting in better protection of ASC-pretreated plants against Cu stress. In conclusion, although ASC and GSH differed in induction of stress protective mechanisms, both were effective in improving rice performance in response to Cu phytotoxicity.

Challenges in conducting trials for pediatric tuberculous meningitis: lessons from the field.

SETTING: TBM-KIDS is a phase I/II trial enrolling children with tuberculous meningitis (TBM) in three tertiary referral centers in India and Malawi.OBJECTIVE: To describe the challenges encountered in conducting the first randomized clinical trial of antimicrobial agents in pediatric TBM.DESIGN: The sources of the data were primarily monthly trial reports, non-enrollment case report forms, study diaries and registers maintained for recruitment, experiences shared by key team members during regular study calls and comments from site review visits. We reviewed, broadly categorized, and describe in detail the challenges encountered by study teams in trial implementation.RESULTS: Over 17 months, 3371 children with clinical presentations consistent with meningoencephalitis or undergoing lumbar puncture were assessed for eligibility; 21 (<1%) met enrollment criteria. We encountered challenges related to diagnosis, management of sick children, large catchment areas, adverse event attribution, concomitant medications, infrastructure requirements, expensive pediatric formulations with short expiry, and detection of treatment response in a highly variable disease across the age continuum. Training and adaptation of tools for neurocognitive and neurologic function assessment were necessary. Special care was undertaken to explain study participation to distraught caregivers and manage children longitudinally.CONCLUSION: Interventional trials in pediatric TBM are challenging but are critically important for improving the treatment of a disease that disables children physically, cognitively and emotionally. Sharing these challenges may help to address them more effectively as a TB research community and to advance treatments for this at-risk population.

Establishing next-generation pest control services in rice fields: eco-agriculture.

Pesticides are commonly used in food crop production systems to control crop pests and diseases and ensure maximum yield with high market value. However, the accumulation of these chemical inputs in crop fields increases risks to biodiversity and human health. In addition, people are increasingly seeking foods in which pesticide residues are low or absent and that have been produced in a sustainable fashion. More than half of the world's human population is dependent on rice as a staple food and chemical pesticides to control pests is the dominant paradigm in rice production. In contrast, the use of natural enemies to suppress crop pests has the potential to reduce chemical pesticide inputs in rice production systems. Currently, predators and parasitoids often do not persist in rice production landscapes due to the absence of shelter or nutritional sources. In this study, we modified the existing rice landscape through an eco-engineering technique that aims to increase natural biocontrol agents for crop protection. In this system, planting nectar-rich flowering plants on rice bunds provides food and shelter to enhance biocontrol agent activity and reduce pest numbers, while maintaining grain yield. The abundance of predators and parasitoids and parasitism rates increased significantly in the eco-engineering plots compared to the insecticide-treated and control plots. Moreover, a significantly lower number of principal insect pests and damage symptoms were found in treatments where flowering plants were grown on bunds than in plots where such plants were not grown. This study indicates that manipulating habitat for natural enemies in rice landscapes enhances pest suppression and maintains equal yields while reducing the need for insecticide use in crop fields.

To evaluate the extent of awareness about hazards of blood transfusion among the blood recipients.

This cross-sectional, observational study was carried out among the blood receiving patients conducted in the Department of Transfusion Medicine, Bangabandhu Sheikh Mujib Medical University from April 2008 to August 2009, over 126 purposively selected, to evaluate the extent of awareness about hazards of blood transfusion among the blood recipient. In this study 74.1% of male and 73.3% of female respondents had correct knowledge of blood transfusion (p>0.05). In literate group 85(91.4%) had knowledge about blood donation and transfusion compared to 8(8.6%) in illiterate group with significant statistical difference (p=0.001). Different misconception and lack of awareness about safe blood transfusion is present among people receiving blood and blood products. Illiterate persons have significant less level of knowledge about safe blood transfusion. So the number of educational programs on blood-donation should be expanded and transmitted to encourage possible receivers to take blood from nonprofessional volunteer donor and to carry out relevant screening tests before receiving blood products. Furthermore, they should know that all measures besides screening tests are implemented by blood banks to ensure that blood donation is safe for donors and that transfusion of the donated blood is safe for recipients.

Compatibility of a combination of tiamulin and chlortetracycline with salinomycin in feed during a pulsed medication program coadministration in broilers.

In an earlier study, the continuous medication of broiler feed with a combination of tiamulin (TIA; 20 mg/kg), chlortetracycline (CTC; 60 mg/kg), and the ionophore anticoccidial salinomycin (SAL; 60 mg/kg) caused an initial increase in BW and feed efficiency (FE; g of weight gain/kg of feed intake). However, as doses increased to combinations of 30 mg/kg of TIA and 90 mg/kg of CTC or 50 mg/kg of TIA and 150 mg/kg of CTC, there was a dose-related reduction in growth rate and FE. This was thought to be due to the interaction between TIA and SAL. In this study, using a protocol similar to the previous trial, broiler chicks were administered SAL at 60 mg/kg via the feed and the same inclusion rates of TIA + CTC. However, instead of feeding the birds continuously, considering the cost of TIA and possibly to compensate for the depressed growth attributable to the interaction with SAL, they were pulse-dosed for 1 to 10 d and again at 21 to 27 d, and the whole trial lasted 35 d to see if the intermittent pulses might reduce production losses. A total of 200 straight-run 1-d-old broiler chicks (Hubbard classic) were randomly distributed into 4 groups, with each group consisting of 5 cages containing 10 birds. The 20 cages were allocated to the 4 treatment groups on a random basis. The control diet, containing only SAL at 60 mg/kg, was fed to all birds throughout the 35-d trial, including the period during the gaps between dosing (i.e., d 11 to 20 and d 28 to 35). Feed and water were available for the whole trial period. Several serum enzymes (creatine kinase, lactate dehydrogenase, and aspartate aminotransferase) were determined from blood samples taken on d 35. Blood samples were also collected at 1, 19, and 35 d of age and were examined for antibody titers to Mycoplasma gallisepticum and Mycoplasma synoviae. Necropsy and histopathology of the birds (n = >or=4) were conducted during weekly intervals. There was no significant difference in weight gain, feed intake, and FE when the groups treated with TIA + CTC were compared with the control group (P > 0.05). There was no relationship between mortality and inclusion rates of the medication. No clinical signs of an interaction were exhibited during the trial, which was supported by necropsy and serum enzyme results. Maternally derived antibodies against M. gallisepticum were identified at the start of the trial but disappeared within 19 d, and infection with M. gallisepticum or M. synoviae was found neither serologically nor clinically during the trial. The results demonstrated that intermittent pulse administration of TIA at 50 mg/kg + CTC at 150 mg/kg from d 1 to 10 and d 21 to 27, along with continuous feeding of SAL (60 mg/kg), would be possible without altering performance and while maintaining the health status of the broilers. However, further research is required on the presence of artificial infections with Mycoplasma pathogens to determine the efficacy of the combination of TIA +CTC.

Compatibility of a combination of tiamulin plus chlortetracycline with salinomycin in feed during a long-term co-administration in broilers.

The pleuromutilin antibiotic tiamulin (TIA) is known to produce a negative interaction in broilers when administered in combination with several ionophore anticoccidials such as salinomycin (SAL). Chlortetracycline (CTC), when administered simultaneously with TIA, has demonstrated a synergistic antimicrobial effect. A 35-d feeding study was conducted in cages to evaluate the interaction effect of a combination of TIA plus CTC at increasing inclusion levels when administered concurrently with SAL. A total of 200 one-day-old broiler chicks were distributed into 4 groups, and each group consisted of 5 cages containing 10 birds in each. Replicate cages were distributed randomly. Feed for all groups contained 60 ppm SAL, but additionally, 0, 20, 30, and 50 ppm TIA and 0, 60, 90, and 150 ppm CTC were included, respectively. Several enzymes (creatine phosphokinase, lactate dehydrogenase, and aspartate aminotransferase) were determined from blood samples taken at the end of the trial. Blood samples were also collected during d 0, 19, and 35 and were analyzed for antibody titers against Mycoplasma gallisepticum and Mycoplasma synoviae. Necropsy of a few birds (20, 8, 20, 12, and 12 on d 7, 14, 21, 28, and 35, respectively) was conducted at weekly intervals. Results indicated that there was a significant depression of weight gain (P < 0.05) in group 4 (TIA 50 + CTC 150) only. The final weights were 1,809 +/- 130, 1,859 +/- 52, 1,703 +/- 47, and 1,617 +/- 98 g for groups 1 (TIA 0 + CTC 0), 2 (TIA 20 + CTC 60), 3 (TIA 30 + CTC 90), and 4 (TIA 50 + CTC 150), respectively. However, feed intake and feed conversion efficiency (g of weight gain/kg of feed intake) were not significantly affected in any of the groups. There was no dose-related adverse effect on mortality or clinical signs exhibited during the trial, and this was supported by necropsy. Maternally derived antibodies against M. gallisepticum were present at the beginning of the trial but disappeared within 19 d. Otherwise, there was no apparent infection by M. gallisepticum or M. synoviae throughout the trial. The results demonstrate that 50 ppm TIA plus 150 ppm CTC along with 60 ppm SAL caused only a depression of growth, but no adverse signs of interaction were detected. Taking into consideration all the aspects of the cost of production, the 20 ppm TIA plus 60 ppm CTC was the most cost-effective level to administer continuously with 60 ppm SAL via the feed, but it would be important to do an additional study using an artificial infection with M. gallisepticum or M. synoviae to know whether this inclusion rate would be sufficient to protect against an infectious challenge.