Frequency, Distribution of Congenital Anomaly and Associated Maternal Risk Factors.

This study was done to find out the maternal risk factors associated with congenital anomaly. This cross-sectional observational study was carried out in the Department of Obstetrics and Gynaecology, Bangabandhu Sheikh Mujib Medical University (BSMMU) Hospital, Dhaka, Bangladesh from January 2011 to December 2011. During this study period 78 patients had pregnancy with congenital anomaly and delivered in the Department of Obstetrics and Gynaecology. Women with ultrasound report of congenitally abnormal fetus irrespective of gestational age were included. Clinical evaluation of neonates was done by experienced neonatologist. The frequency of congenital anomaly was 3.46%. Most of the women belong to age <35 years (97.43%). Congenital anomalies more commonly were seen in the primiparas (64.10%). Most frequent associated risk factor was the history of abortions (35.89%). Maternal infections during antenatal period were also high (15.58%). There were 58 males (74.35%) and 20 females (25.64%). There was positive history of delivery of congenital abnormal babies in 6 cases (7.6%). Mothers of eight cases (10.25%) had history of drug ingestion during pregnancy. Four cases (5.12%) of mothers had hypothyroidism and 6 cases of mothers (7.69%) had diabetes mellitus respectively.

A Case Report on Percutaneous Coronary Intervention in Chronic Total Occlusion by Retrograde Visualization.

As bilateral approach is paramount in chronic total occlusions with retrograde flow, the use of two radial arteries, two femoral arteries or combination technique using one radial and one femoral artery will probably be increasingly reported in the near future. After puncture of opposite groin, a diagnostic 6 Fr catheter is used to intubate the ostium of the contralateral artery. By visualizing the distal vessel in multiple projections, contralateral injections help to direct the progression of the wire in the occluded segment towards the distal true lumen and confirm the intraluminal position of the wire after the occluded segment. We are reporting a case with chronic total occlusion where we used bilateral femoral access and simultaneous contrast injection to visualize retrograde flow in LAD while opening CTO through ante-grade pathway.

Epitope-based peptide vaccine design and target site depiction against Ebola viruses: an immunoinformatics study.

Ebola viruses (EBOVs) have been identified as an emerging threat in recent year as it causes severe haemorrhagic fever in human. Epitope-based vaccine design for EBOVs remains a top priority because a mere progress has been made in this regard. Another reason is the lack of antiviral drug and licensed vaccine although there is a severe outbreak in Central Africa. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites using various immunoinformatics and docking simulation tools. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell was checked for the selected protein. The peptide region spanning 9 amino acids from 42 to 50 and the sequence TLASIGTAF were found as the most potential B and T cell epitopes, respectively. This peptide could interact with 12 HLAs and showed high population coverage up to 80.99%. Using molecular docking, the epitope was further appraised for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post-therapeutic strategy, docking study of predicted 3D structure identified suitable therapeutic inhibitor against targeted protein. However, this computational epitope-based peptide vaccine designing and target site prediction against EBOVs open up a new horizon which may be the prospective way in Ebola viruses research; the results require validation by in vitro and in vivo experiments.

The effect of distance on observed mortality, childhood pneumonia and vaccine efficacy in rural Gambia.

We investigated whether straight-line distance from residential compounds to healthcare facilities influenced mortality, the incidence of pneumonia and vaccine efficacy against pneumonia in rural Gambia. Clinical surveillance for pneumonia was conducted on 6938 children living in the catchment areas of the two largest healthcare facilities. Deaths were monitored by three-monthly home visits. Children living >5 km from the two largest healthcare facilities had a 2·78 [95% confidence interval (CI) 1·74-4·43] times higher risk of all-cause mortality compared to children living within 2 km of these facilities. The observed rate of clinical and radiological pneumonia was lower in children living >5 km from these facilities compared to those living within 2 km [rate ratios 0·65 (95% CI 0·57-0·73) and 0·74 (95% CI 0·55-0·98), respectively]. There was no association between distance and estimated pneumococcal vaccine efficacy. Geographical access to healthcare services is an important determinant of survival and pneumonia in children in rural Gambia.

Advancements in Utilizing Natural Compounds for Modulating Autophagy in Liver Cancer: Molecular Mechanisms and Therapeutic Targets.

Autophagy, an intrinsic catabolic mechanism that eliminates misfolded proteins, dysfunctional organelles, and lipid droplets, plays a vital function in energy balance and cytoplasmic quality control, in addition to maintaining cellular homeostasis. Liver cancer such as hepatocellular carcinoma (HCC) is one of the most common causes of cancer deaths globally and shows resistance to several anticancer drugs. Despite the rising incidence and poor prognosis of malignant HCC, the underlying molecular mechanisms driving this aggressive cancer remain unclear. Several natural compounds, such as phytochemicals of dietary and non-dietary origin, affect hepatocarcinogenesis signaling pathways in vitro and in vivo, which may help prevent and treat HCC cells. Current HCC cells treatments include chemotherapy, radiation, and surgery. However, these standard therapies have substantial side effects, and combination therapy enhances side effects for an acceptable therapeutic benefit. Therefore, there is a need to develop treatment strategies for HCC cells that are more efficacious and have fewer adverse effects. Multiple genetic and epigenetic factors are responsible for the HCC cells to become resistant to standard treatment. Autophagy contributes to maintain cellular homeostasis, which activates autophagy for biosynthesis and mitochondrial regulation and recycling. Therefore, modifying autophagic signaling would present a promising opportunity to identify novel therapies to treat HCC cells resistant to current standard treatments. This comprehensive review illustrates how natural compounds demonstrate their anti-hepatocellular carcinoma function through autophagy.

Exploring Importance and Regulation of Autophagy in Cancer Stem Cells and Stem Cell-Based Therapies.

Autophagy is a globally conserved cellular activity that plays a critical role in maintaining cellular homeostasis through the breakdown and recycling of cellular constituents. In recent years, there has been much emphasis given to its complex role in cancer stem cells (CSCs) and stem cell treatment. This study examines the molecular processes that support autophagy and how it is regulated in the context of CSCs and stem cell treatment. Although autophagy plays a dual role in the management of CSCs, affecting their removal as well as their maintenance, the intricate interaction between the several signaling channels that control cellular survival and death as part of the molecular mechanism of autophagy has not been well elucidated. Given that CSCs have a role in the development, progression, and resistance to treatment of tumors, it is imperative to comprehend their biological activities. CSCs are important for cancer biology because they also show a tissue regeneration model that helps with organoid regeneration. In other words, the manipulation of autophagy is a viable therapeutic approach in the treatment of cancer and stem cell therapy. Both synthetic and natural substances that target autophagy pathways have demonstrated promise in improving stem cell-based therapies and eliminating CSCs. Nevertheless, there are difficulties associated with the limitations of autophagy in CSC regulation, including resistance mechanisms and off-target effects. Thus, the regulation of autophagy offers a versatile strategy for focusing on CSCs and enhancing the results of stem cell therapy. Therefore, understanding the complex interactions between autophagy and CSC biology would be essential for creating therapeutic treatments that work in both regenerative medicine and cancer treatment.

Pattern of congenital heart diseases.

This prospective observational study was done to find out the frequency of various forms of congenital heart disease (CHD) diagnosed by echocardiography. During the study period (January 2002 to December 2005) 2050 patients were screened by echocardiography. All patients were evaluated by cardiologists and had chest radiograph, electrocardiogram and echocardiography. Total 2050 patients were studied and among them 1071 had congenital heart disease. Male was 561(52.38%) and female was 510(47.62%). Atrial septal defect (ASD) was 374(34.92%), ventricular septal defect (VSD) was 318(29.69%), patent ductus arteriosus (PDA) 83(7.75%), pulmonary stenosis (PS) 58(5.42%), tetralogy of Fallot 162(15.13%), transposition of great vessels (TGA) 16(1.49%), Ebstein anomaly 5(0.4%), coarctation of aorta 1(0.09%) and single ventricle 2(0.19%). This distribution is more or less similar to that reported in studies at home and abroad. In this study atrial septal defect (ASD) was the commonest in acyanotic CHD and tetralogy of Fallot was the commonest cyanotic CHD.

The risk of variant Creutzfeldt-Jakob disease among UK patients with bleeding disorders, known to have received potentially contaminated plasma products.

The risk of variant Creutzfeldt-Jakob disease (vCJD) from potentially infected plasma products remains unquantified. This risk has been assessed for 787 UK patients with an inherited bleeding disorder prospectively followed-up for 10-20 years through the UK Haemophilia Centre Doctors' Organisation (UKHCDO) Surveillance Study. These patients had been treated with any of 25 'implicated' clotting factor batches from 1987 to 1999, which included in their manufacture, plasma from eight donors who subsequently developed clinical vCJD. Variant CJD infectivity of these batches was estimated using plasma fraction infectivity estimates and batch-manufacturing data. Total potential vCJD infectivity received by each patient has been estimated by cumulating estimated infectivity from all doses received during their lifetime. Of 787 patients, 604 (77%) were followed-up for over 13 years following exposure to an implicated batch. For these 604 patients, the estimated vCJD risk is ≥ 1% for 595, ≥ 50% for 164 and 100% for 51. This is additional to background UK population risk due to dietary exposure. Of 604 patients, 94 (16%) received implicated batches linked to donors who developed clinical vCJD within 6 months of their donations. One hundred and fifty-one (25%) had received their first dose when under 10 years of age. By 1st January 2009, none of these patients had developed clinical vCJD. The absence of clinical vCJD cases in this cohort to date suggests that either plasma fraction infectivity estimates are overly precautionary, or the incubation period is longer for this cohort than for implicated cellular blood product recipients. Further follow-up of this cohort is needed.

Effect of hydration with or without n-acetylcysteine on contrast induced nephropathy in patients undergoing coronary angiography and percutaneous coronary intervention.

Contrast induced nephropathy (CIN), an acute decline in renal function after the administration of intravenous contrast in the absence of other causes, is the third leading cause of acute renal failure in hospitalized patients. Antioxidant N-acetylcysteine prevents acute contrast nephrotoxicity in patients with impaired renal function who underwent coronary angiography (CAG) and percutaneous coronary intervention (PCI). Hydration is the cornerstone in preventing CIN. N-acetylcysteine has additive preventive affect. We compared N-acetylcysteine plus hydration with hydration alone in preventing CIN. Patients were assigned to receive either premedication with hydration with normal saline (1ml/kg/hour-12 hour before and 12 hour after CAG and intravenous PCI) alone or to receive both hydration and oral N acetylcysteine (600mg bid for 2 days, starting day before CAG and PCI). Main out come was occurrence of ≥25% or ≥0.5mg/dl increase in serum creatinine level within 24 to 48 hours after contrast administration; change in creatinine clearance and serum creatinine level. Six patients (12%) of hydration group i.e. Group A and none of the patients of N-acetylcysteine All group i.e. Group B develop CIN (p=0.012). Baseline serum creatinine level was slightly higher in N-acetylcysteine group than hydration group (1.52±0.32 and 1.44±0.22). After 24 hours of CAG and PCI serum creatinine level lower than base line in N-acetylcysteine group but slightly higher than base line in hydration group (1.42±0.39 and 1.51±0.38). Difference in serum creatinine in both the groups were statistically significant (p=0.006 in N-acetylcysteine group and p=0.029 in hydration group). Creatinine clearance rate significantly improved in N-acetylcysteine group after coronary intervention. In conclusion, N-acetylcysteine and hydration prevent CIN better than hydration alone in high risk patients.

Contrast induced nephropathy in patients with pre-existing renal impairment undergoing coronary angiogram and percutaneous transluminal coronary angioplasty.

Contrast induced nephropathy is the third leading cause of acute renal failure in hospitalized patients. However, its incidence and risk factors in Bangladeshi population undergoing coronary angiogram and percutaneous coronary intervention is not clear. This study was to assess the incidence of contrast induced nephropathy in patients, with or without pre existing renal impairment, undergoing coronary angiogram and percutaneous transluminal coronary angioplasty in Bangladeshi population. Two hundred patients undergoing coronary angiogram and percutaneous were included in the study .Patients having history of contrast allergy and patients on renal dialysis were excluded from the study. Serum creatinine level was estimated before the undergoing procedure. Creatinine clearance rate was calculated by applying Cockcroft Gault formula to the preprocedure serum creatinine level. Patients were assigned to one of the two groups, that is with or without chronic renal insufficiency. Serum creatinine levels were again estimated at the end of 24 hours of contrast exposure. The rise of serum creatinine by ≥0.5mg/dl or ≥25% occurring within 24 hours of contrast administration was defined as contrast induced nephropathy. The incidences of Contrast induced nephropathy (CIN) in these groups were compared. We tried to analyze whether there is relation between the incidence of CIN with contrast volume, chronic renal insufficiency, diabetes mellitus, and coronary procedures undergone. We enrolled 120 pre existing chronic renal insufficiency patients and 80 patients without pre existing chronic renal insufficiency. In this study 21.7% of pre existing chronic renal insufficiency group and 6.3% of no pre existing chronic renal insufficiency group developed contrast induced nephropathy (p=0.003). Contrast induced nephropathy is an iatrogenic disorder and pre existing renal impairment is one of the risk factors for developing contrast induced nephropathy.

Association of cardiac ischemic score and coronary collateral circulation.

Coronary collateral circulation maintains myocardial perfusion in coronary atherosclerotic disease. The indicators of cardiac ischemia, (Angina pectoris on exertion, during emotion, previous myocardial infarction and prior coronary intervention) are associated with presence of coronary collateral circulation. In this prospective observational cross sectional study, 128 patients with history of angina pectoris on exertion and or during emotion and or myocardial infarction and or previous coronary intervention were enrolled. The cardiac ischemic score (range 1-4) was calculated by adding 1 point for each of the above four clinical factors, which can be easily assessed. Presence of coronary collaterals in coronary angiogram was defined as Rentrop grade ≥1. Patients were divided into two groups. Group A patients having Rentrop grade 0 and Group B patients are with collateral circulation, having Rentrop grade 1-3. Patients having cardiac ischemic score (range 1-4) are compared in these groups. Maximum (83.3%) patients of Group B with coronary collateral circulation had cardiac ischemic score 2-4, but majority (86.4%) of Group A patients without collaterals showed the score only 1. Thus the cardiac ischemic score is strongly associated with the presence of coronary collaterals.

Haemodynamic and end tidal CO2 changes state after inflation and deflation of pneumatic tourniquet on extremities.

The use of a tourniquet for obtaining a bloodless field is an essential and accepted tool for extremity surgery. A prospective study was done on 30 adult patients undergoing elective limb surgery requiring tourniquet application for haemodynamic and End tidal CO2 (EtCO2) changes. After the induction of general anaesthesia a tourniquet was applied on the limb. There was gradual increase in heart rate & EtCO2 through out the whole period of tourniquet inflation. There was also significant increase of mean arterial pressure during the inflation period. At the end of surgery tourniquet was deflated. Tourniquet time was 76.83+/-16.94 minutes. After deflation of the tourniquet, heart rate & EtCO2 value increased & the values were maximum at 5 minutes. These values came down to the base line at 15 minutes. There was significant decrease of mean arterial pressure (MAP) at 5 minute; it also came to the base at 15 minute. These changes are usually benign but can be significant in patients with co-existing cardiovascular & intracranial diseases. In conclusion, we recommend the haemodynamic and End tidal CO2 monitoring as well as rapid fluid infusion along with hyperventilation for 15-30 minutes after deflation of tourniquet.

Microbes responsible for acute exacerbation of COPD.

This study was designed to find out the microbes responsible for acute exacerbation of chronic obstructive pulmonary disease (COPD). This study was carried out in the National Institute of Diseases of the Chest & Hospital (NIDCH), Dhaka during the period of January 2003 to December 2003. The study was a prospective case control study. There were 88 male and 2 female patients. The majority of the study subjects fell within the range of 50-70 years. All were smokers. 30 stable COPD patients were taken as control for comparison of sputum culture results of acute exacerbated COPD patients. A standard proforma with questionnaire was designed and filled to select patient with COPD. The patients were selected according to the predetermined criteria viz FEV1<70% predicted and FEV1/FVC % <70% of predicted. Morning specimen of sputum was collected after appropriate preparation and physical character of the sputum were noted. Sputum was immediately sent to microbiology lab for culture. Out of 30 stable COPD patients 6(20%) showed positive sputum culture for bacteria, Pseudomonas 3, Klebsiella 1, Streptococcus pneumoniae 1 and Haemophilus influenza 1. Majority of them were Gram-negative organism. Out of 60 patients with acute exacerbation of COPD 39 patients (65%) showed positive culture for bacteria. Pseudomonas 15, Klebsiella 8, Acinetobacter 4, Enterobacter 2, Moraxella catarrhalis 2 and mixed organisms like, Pseudomonas + Klebsiella 2 and Pseudononas + Acinobacter 1. Majority were Gram-negative bacilli viz. Pseudomonas and Klebsiella spp. species. From this study it was concluded that the prevalence of lower airway bacterial colonization in outpatients with stable COPD is high and is mainly due to Gram-negative bacilli like Pseudomonas spp. The greater rate of isolation of pathogenic bacteria in exacerbated COPD than in stable COPD in this study, supports the pathogenic role of bacteria in a proportion of acute exacerbations of chronic obstructive pulmonary disease. The organism commonly play pathogenic role in acute exacerbations of COPD are Pseudomonas and Klebsiella. Acinobacter Moraxella catarrhalis and Enterobacter also contributed in exacerbation of COPD.

Improvement of Left Ventricular Systolic Function after Percutaneous Coronary Intervention in Diabetic Patients with Non-ST elevated Myocardial Infarction.

Long term mortality is higher in Non-ST-segment elevated myocardial infarction (NSTEMI) patients than STEMI paitents. NSTEMI are a high risk factor for ensuing cardiovascular events in diabetic patients. But, use of drug eluting stents (DES) will further improve outcomes in patients with diabetes suffering early percutaneous coronary intervention (PCI). The aim of the study was to determine the changes in left ventricular (LV) systolic activity after successful PCI in NSTEMI diabetic patients was compared with non-diabetic patients. This comparative clinical study was performed in the Department of Cardiology, University Cardiac Center, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2017 to June 2018. Thirty (30) diabetic and 34 non-diabetic patients with NSTEMI undergoing percutaneous coronary intervention were included in the study. In all patients PCI with drug eluting stent was performed successfully. Earlier echocardiography (2-Dimensional) was done, at release subsequent PCI and 3 months afterward to evaluate the LV systolic activity and compare to diabetics and non-diabetics at all levels of evaluation to assess the outcome of intervention. At baseline LVEF was rather lower in diabetic group than non-diabetic group patients. In diabetics patients segments with abnormal wall motion (WMA) was higher than non-diabetics patients. While the LVEDD, LVIDd and LVIDs were significantly larger in the earlier group than those in the latter group, the LVESV was no different in both groups. At release from hospital, no significant enhancement was observed in either group following PCI in terms of LVEF, number of segments with WMA, LVIDd and LVIDs. However, both LVEDV and LVESV reduced successfully in both groups with decrease of LVESV being more marked in non-diabetics compared with diabetics (p=0.018). However, 3 months after PCI, LVEF improved (8.4±1.2%) in diabetics and 7.9±1.2% in non diabetics patients but this improvement between two groups was not statically significant (p=0.631). Similarly baseline to 3 months after PCI LVIDs reduces in diabetics patients (5.7±1.9%) and 4.8±1.1% in non diabetics patients but the difference between both groups was not significant (p=0.201). Diabetic patients more frequently required 2 stents (p=0.30), while stent's diameter and length did not differ between the study groups. This study demonstrated that improvement of the parameters of left ventricular systolic function after using of drug eluting stent in NSTEMI diabetic patients was not lower to the non diabetic group under same condition. So, suggestion of PCI with drug eluting stent may be extended in NSTEMI diabetic patient.

Ethnobotanical study and phytochemical profiling of Heptapleurum hypoleucum leaf extract and evaluation of its antimicrobial activities against diarrhea-causing bacteria.

BACKGROUND: Due to the development of superbugs as a result of unprescribed and frequent use of antibiotics in recent years, an alternate form of medicine had to be introduced. In light of this global threat, researchers all over the world have been gravitating towards herbal medicines. In order to find out new ways of saving the planet using medicinal plants, ethnobotanical studies must be carried out. Concerning this, an ethnobotanical study has been done in this paper to identify potential medicinal plants in Rangamati, Bangladesh. RESULTS: For the ethnobotanical survey, randomized 104 people were interviewed and 62 different plant species were found to treat 19 different kinds of diseases and 84% of people reported to be completely recovered. Furthermore, among the 19 diseases found, the majority of them were common cold, abdominal pain or gastric, diarrhea, and dysentery. From the 62 different plant species, Heptapleurum hypoleucum, used for the treatment of diarrhea, was selected for conducting further studies due to its heavy use as reported by the tribal people. In this study, the aqueous, ethanol, and methanol extracts of Heptapleurum hypoleucum were subjected to microbial susceptibility assays using the agar well diffusion method. The test microorganisms were Salmonella typhi, Streptococcus pneumoniae, Staphylococcus aureus, Shigella flexneri, and Escherichia coli. Among these, the most susceptible organisms were Staphylococcus aureus (21 mm) and Salmonella typhi (19 mm) in the ethanolic extract. Also, the methanolic extract showed an inhibition zone of 13 mm against E. coli, which was more than that of the antibiotic's (11 mm). Phytochemical screening of the plant revealed that it contains alkaloids, phenols, steroids, and flavonoids, but lacks saponins and tannins. CONCLUSION: To combat the rising threat of antibiotic resistance, ethnoscience needs to be consolidated with modern biotechnological techniques to make the most use of the vast amount of natural resources. The findings of this study indicate that Heptapleurum hypoleucum, an ethnobotanical medicinal plant, has shown comparable antimicrobial activity with commercial antibiotics against several diarrhea-causing pathogens and also contains several medically important phytochemicals.

Comparison between Glyceryl Trinitrate and Trimetazidine in Ischaemic Cardiomyopathy Patients.

Ischaemic cardiomyopathy (ICM) remains a major health problem, both in developed and developing countries like Bangladesh where it causes a significant number of morbidity and mortality. The treatment and outcome of ICM chiefly depends on the presence and extent of hibernating myocardium. In this regard addressing anginal symptoms is the key to patients' comfort as well to achieving the goal of treatment. Glyceryl trinitrate (GTN) and trimetazidine (TMZ) are two widely used drugs for relieving angina. This pilot study was designed to answer some of the confusions and controversies regarding their use and to bring precision in decision making in the treatment of ICM. Here, comparison of GTN and trimetazidine were done by assessing the symptoms by NYHA and CCS class following their use in ICM patients, admitted in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from 15th October, 2015 to 15th April, 2016, who were randomly placed in two groups in a prospective manner. Most of the patients were in age group 51-60 years and were male in both the groups. It was observed that there was no significant difference in NYHA and CCS class at base line and at discharge between two groups (p>0.05). But statistically significant (p<0.05), improvement noted at 6 weeks and 12 weeks in GTN group in comparison to trimetazidine group. GTN stood out to be a better option than TMZ in the treatment of ICM. Moreover GTN is a cheaper option than TMZ.

Bacteremia in Childhood Life-Threatening Infections in Urban Gambia: EUCLIDS in West Africa.

BACKGROUND: The limited availability of microbiology services in sub-Saharan Africa impedes accurate diagnosis of bacterial pathogens and understanding of trends in prevalence and antibiotic sensitivities. We aimed to characterize bacteremia among hospitalized children in The Gambia and to identify factors associated with bacteremia and mortality. METHODS: We prospectively studied children presenting with suspected severe infection to 2 urban hospitals in The Gambia, between January 2013 and September 2015. Demographic and anthropometric data, clinical features, management, and blood culture results were documented. Urine screens for antibiotic activity were performed in a subset of participants. RESULTS: Of 411 children enrolled (median age, 29 months; interquartile range, 11-82), 79.5% (325 of 409) reported prehospital antibiotic use. Antimicrobial activity by urinary screen for antibiotic activity was detected in 70.8% (n = 80 of 113). Sixty-six bacterial pathogens were identified in 65 (15.8%) participants and Staphylococcus aureus predominated. Gram-positive organisms were more commonly identified than Gram-negative (P < .01). Antibiotic resistance against first-line antimicrobials (ampicillin and gentamicin) was common among Gram-negative bacteria (39%; range, 25%-100%). Factors significantly associated with bacteremia included the following: gender, hydration status, musculoskeletal examination findings, admission to the Medical Research Council The Gambia at London School of Hygiene & Tropical Medicine hospital, and meeting sepsis criteria. Those associated with increased mortality were presence of a comorbidity, clinical pallor, tachypnea, and altered consciousness. Tachycardia was associated with reduced mortality. CONCLUSIONS: The bacteremia rate in children with suspected childhood life-threatening infectious diseases in The Gambia is high. The pattern of pathogen prevalence and antimicrobial resistance has changed over time compared with previous studies illustrating the importance of robust bacterial surveillance programs in resource-limited settings.

An Immunopharmacoinformatics Approach in Development of Vaccine and Drug Candidates for West Nile Virus.

An outbreak of West Nile Virus (WNV) like the recent Ebola can be more epidemic and fatal to public health throughout the world. WNV possesses utmost threat as no vaccine or drug is currently available for its treatment except mosquito control. The current study applied the combined approach of immunoinformatics and pharmacoinformatics to design potential epitope-based vaccines and drug candidates against WNV. By analyzing the whole proteome of 2994 proteins, the WNV envelope glycoprotein was selected as a therapeutic target based on its highest antigenicity. After proper assessment "KSFLVHREW" and "ITPSAPSYT" were found to be the most potential T and B-cell epitopes, respectively. Besides, we have designed and validated four novel drugs from a known WNV inhibitor, AP30451 by adopting computational approaches. Toxicity assessment and drug score confirmed the effectiveness of these drug candidates. This in silico research might greatly facilitate the wet lab experiments to develop vaccine and drug against WNV.

Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial.

BACKGROUND: Pneumonia is estimated to cause 2 million deaths every year in children. Streptococcus pneumoniae is the most important cause of severe pneumonia. We aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children. METHODS: We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause admissions. Analyses were per protocol and intention to treat. FINDINGS: 529 children assigned vaccine and 568 allocated placebo were not included in the per-protocol analysis. Results of per-protocol and intention-to-treat analyses were similar. By per-protocol analysis, 333 of 8189 children given vaccine had an episode of radiological pneumonia compared with 513 of 8151 who received placebo. Pneumococcal vaccine efficacy was 37% (95% CI 27-45) against first episode of radiological pneumonia. First episodes of clinical pneumonia were reduced overall by 7% (95% CI 1-12). Efficacy of the conjugate vaccine was 77% (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50% (21-69) against disease caused by all serotypes, and 15% (7-21) against all-cause admissions. We also found an efficacy of 16% (3-28) against mortality. 110 serious adverse events arose in children given the pneumococcal vaccine compared with 131 in those who received placebo. INTERPRETATION: In this rural African setting, pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and invasive pneumococcal disease, and can substantially reduce admissions and improve child survival. Pneumococcal conjugate vaccines should be made available to African infants.

Treating Diabetes Mellitus: Pharmacophore Based Designing of Potential Drugs from Gymnema sylvestre against Insulin Receptor Protein.

Diabetes mellitus (DM) is one of the most prevalent metabolic disorders which can affect the quality of life severely. Injectable insulin is currently being used to treat DM which is mainly associated with patient inconvenience. Small molecules that can act as insulin receptor (IR) agonist would be better alternatives to insulin injection. Herein, ten bioactive small compounds derived from Gymnema sylvestre (G. sylvestre) were chosen to determine their IR binding affinity and ADMET properties using a combined approach of molecular docking study and computational pharmacokinetic elucidation. Designing structural analogues were also performed for the compounds associated with toxicity and less IR affinity. Among the ten parent compounds, six were found to have significant pharmacokinetic properties with considerable binding affinity towards IR while four compounds were associated with toxicity and less IR affinity. Among the forty structural analogues, four compounds demonstrated considerably increased binding affinity towards IR and less toxicity compared with parent compounds. Finally, molecular interaction analysis revealed that six parent compounds and four analogues interact with the active site amino acids of IR. So this study would be a way to identify new therapeutics and alternatives to insulin for diabetic patients.