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Multiple Quantitative Structure-Activity Relationship (QSAR) analysis is widely used in drug discovery for lead identification. Human Immunodeficiency Virus (HIV) protease is one of the key targets for the treatment of Acquired Immunodeficiency Syndrome (AIDS). One of the major challenges for the design of HIV-1 protease inhibitors (HIV PRIs) is to increase the inhibitory activities against the enzyme to a level where the problem associated to drug resistance may be considerably delayed. Herein, chemometric analyses were performed with 346 structurally diverse HIV PRIs with experimental bioactivities against a sub-type B mutant to develop highly predictable QSAR models and also to identify the effective structural determinants for higher affinity against HIV PR. The QSAR models were developed using OCHEM-based machine learning tools (ASNN, FSMLR, KNN, RF, MANN and XGBoost), with descriptors calculated by eight different software packages. Simultaneously, a Monte Carlo optimization-based QSAR modelling was performed using SMILES and graph-based descriptors to understand fragment and topochemical contributions. To validate the actual predictability of all these models, an additional set of 104 compounds (also with known experimental activities) with slightly different chemical space were employed. This ligand-based study serves as a crucial benchmark for further development of the HIV protease inhibitors with improved activities.

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Schizophrenia is a complex disorder of thinking and behaviour (0.3-0.7% of the population is affected). The over-expression of phosphodiesterase 10A (PDE10A) enzyme may be a potential target for schizophrenia and Huntington's disease. Because 3D QSAR analysis is one of the most frequently used modelling techniques, in the present study, five different 3D QSAR tools, namely CoMFA, CoMSIA, kNN-MFA, Open3DQSAR and topomer CoMFA methods, were used on a dataset of pyrimidine-based PDE10A inhibitors. All developed models were validated internally and externally. The non-commercial Open3DQSAR produced the best statistical results amongst 3D QSAR tools. The structural interpretations obtained from different methods were thoroughly analysed and were justified on the basis of information obtained from the crystal structure. Information from one method was mostly validated by the results of other methods and vice versa. In the current work, the use of multiple tools in the same analysis revealed more complete information about the structural requirements of these compounds. On the basis of the observations of the 3D QSAR studies, 12 new compounds were designed for better PDE10A inhibitory activity. The current investigation may help in further designing new PDE10A inhibitors with promising activity.

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BACKGROUND: Healthcare facility hand hygiene impacts patient care, healthcare worker safety, and infection control, but low-income countries have few data to guide interventions. AIM: To conduct a nationally representative survey of hand hygiene infrastructure and behaviour in Bangladeshi healthcare facilities to establish baseline data to aid policy. METHODS: The 2013 Bangladesh National Hygiene Baseline Survey examined water, sanitation, and hand hygiene across households, schools, restaurants and food vendors, traditional birth attendants, and healthcare facilities. We used probability proportional to size sampling to select 100 rural and urban population clusters, and then surveyed hand hygiene infrastructure in 875 inpatient healthcare facilities, observing behaviour in 100 facilities. FINDINGS: More than 96% of facilities had 'improved' water sources, but environmental contamination occurred frequently around water sources. Soap was available at 78-92% of handwashing locations for doctors and nurses, but just 4-30% for patients and family. Only 2% of 4676 hand hygiene opportunities resulted in recommended actions: using alcohol sanitizer or washing both hands with soap, then drying by air or clean cloth. Healthcare workers performed recommended hand hygiene in 9% of 919 opportunities: more after patient contact (26%) than before (11%). Family caregivers frequently washed hands with only water (48% of 2751 opportunities), but with little soap (3%). CONCLUSION: Healthcare workers had more access to hand hygiene materials and performed better hand hygiene than family, but still had low adherence. Increasing hand hygiene materials and behaviour could improve infection control in Bangladeshi healthcare facilities.

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The incidence of tuberculosis (TB) is increasing globally. The diagnbsis of TB in elderly is often delayed due to the atypical presentation. There is also therapeutic problems because of presence of comorbidity, nutritional and socio-economic factors and increased incidence of adverse drug reactions and mortality. A prospective study was conducted among patients presenting with pulmonary tuberculosis at the department of TB and respiratory medicine in a tertiary care hospital between January, 2006 to July, 2006. Thirty patients aged more than 65 years were studied for their clinical characteristics, comorbid illnesses, sputum status, radiological features and adverse drug reactions. They were contrasted against the same parameters in 40 patients aged 65 years or less. The study showed that pulmonary TB in the elderly is characterised by (a) atypical symptoms, (b) more extensive radiological lesion with lower zone preponderance, (c) higher sputum positivity, (d) more frequent comorbidity, (e) more frequent side-effects and (f) higher mortality.

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Sera from 205 cattle, 17 sheep and 306 goats were tested for Toxoplasma gondii antibodies by using a commercial latex agglutination test. Titres considered diagnostically significant (> or = 1:64) were detected in 16.10% of cattle, 17.65% of sheep and 12.09% of goats. Results indicate that T. gondii infection in domestic ruminants in Bangladesh is widespread.

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