Role of White Blood Cell Count, Immature to Total Ratio and C-Reactive Protein in Early Detection of Clinically Suspected Neonatal Sepsis.

Despite recent advances in neonatal care, early detection of neonatal sepsis still remains challenging. Positive blood culture is the gold standard for definitive diagnosis of neonatal sepsis but is time consuming and demands a well equipped laboratory setting. Therefore, it becomes imperative to evaluate usefulness of white blood cell count, Immature to total (IT) ratio and C-reactive protein as potential markers in the early diagnosis of neonatal sepsis. The objective of the study was to evaluate role of white blood cell count, IT ratio and C-reactive protein in early detection of clinically suspected neonatal sepsis. This cross-sectional descriptive study was conducted from January 2017 to December 2018 at Special Care Newborn Unit (SCANU) of Rangpur Medical College Hospital, Rangpur, Bangladesh. After parental permission and ethical clearance, a total of 70 eligible neonates were included into the study. Estimation of total white blood cell count, IT ratio and C-reactive protein as well as blood culture were done for each case. Significance for Chi-Square test and Pearson's correlation coefficient test was predetermined as p<0.05. Of the total 70 neonates studied, 19(27.14%) were blood culture positive and most common organism was Escherichia coli (7/14, 37.0%). Among individual and combination tests, CRP was highly sensitive (100%) followed by WBC count (74.94%). Highly specific tests in diagnosing sepsis were combination test of IT ratio and CRP (88.23%) followed by combination test of WBC count and CRP (82.35%). Positive predictive value (PPV) was high for combination test of WBC count and CRP (90.90%) followed by combination test of IT ratio and CRP (90.47%). Negative predictive value (NPV) was high in CRP (100.0%) followed by WBC count (89.19%). IT ratio positively correlated with CRP (p=0.002) and there was significant association between raised CRP and WBC count (p=0.005) in neonatal sepsis. Diagnostic role of both individual and combination tests were significant in early detection of clinically suspected neonatal sepsis while awaiting results of blood culture. However, none of the combination tests were able to achieve 100.0% sensitivity.

The impact of state paid sick leave policies on weekday workplace mobility during the COVID-19 pandemic.

OBJECTIVES: This study aimed to evaluate whether the Families First Coronavirus Response Act (FFCRA) modified the association between pre-existing state paid sick leave (PSL) and weekday workplace mobility between February 15 and July 7, 2020. STUDY DESIGN: This was a longitudinal, observational study. METHODS: The 50 US states and Washington, D.C., were divided into exposure groups based on the presence or absence of pre-existing state PSL policies. Derived from Google COVID-19 Community Mobility Reports, the outcome was measured as the daily percent change in weekday workplace mobility. Mixed-effects, interrupted time series regression was performed to evaluate weekday workplace mobility after the implementation of the FFCRA on April 1, 2020. RESULTS: States with pre-existing PSL policies exhibited a greater drop in mobility following the passage of the FFCRA (ß = -8.86, 95% confidence interval: -11.6, -6.10, P < 001). This remained significant after adjusting for state-level health, economic, and sociodemographic indicators (ß = -3.13, 95% confidence interval: -5.92, -0.34; P = .039). CONCLUSIONS: Pre-existing PSL policies were associated with a significant decline in weekday workplace mobility after the FFCRA, which may have influenced local health outcomes. The presence of pre-existing state policies may differentially influence the impact of federal legislation enacted during emergencies.

Prevalence and Risk Factors of Secondary Hyperparathyroidism among CKD Patients and Correlation with Different Laboratory Parameters.

Hyperthyroidism is one of the major complications in CKD patients who results in a number of metabolic disorders and contributes to morbidity and mortality. The objective of the study was to investigate the prevalence and risk factors for secondary hyperparathyroidism among CKD patients as well as its correlation with different laboratory parameters. This was a cross-sectional study conducted among the admitted CKD patients of Sylhet MAG Osmani Medical College Hospital, Sylhet, Bangladesh from January 2019 to December 2019. Following recruitment, clinical parameters were extracted from the patients' medical records. Afterward, blood sample blood was collected to measure the biochemical parameters and serum parathyroid hormone levels. A binary logistic regression model was used to assess the factors associated with hyperparathyroidism. The mean±SD serum PTH in all CKD patients was 215.04±168.15 pg/ml. The overall prevalence of secondary hyperparathyroidism among CKD patients was 75.0% (32.0% in stage 3, 88.0% in stage 4 and 93.0% in stage 5 CKD). Serum PTH levels had a significant positive correlation with serum creatinine and serum phosphate levels and a significant negative correlation with serum albumin and serum calcium levels. However, only female sex was revealed as a significant risk factor in the adjusted regression model (aOR 0.26, 95% CI 0.07-0.98 for male sex compared to female sex). As the prevalence of secondary hyperparathyroidism increases in advanced stages of CKD, early detection and management of CKD are crucial to prevent metabolic disorders that could trigger the development of this complication.

A simultaneous liquid chromatographic analysis of niclosamide and bicalutamide in rat plasma by protein precipitation extraction.

OBJECTIVE: The aim of the study was to develop a simple, sensitive and cost-efficient bioanalytical method for the simultaneous determination of niclosamide and bicalutamide in rat plasma with appropriate validation. MATERIAL AND METHODS: Real-time estimation was carried out using Ultra Flow Liquid Chromatography. The solvent system consisting of 20mM sodium acetate buffer at pH 4.0 and acetonitrile (65: 35% v/v) is used as the mobile phase. The analytes were extracted by protein precipitation with acetonitrile and separated on an Eclipse plus C18 Column (25cm×5cm×4.6µm) with L1 packing in isocratic mode with a flow rate of 1ml/min at 254nm. The developed method was validated on the basis of the bioanalytical guidelines of the US American FDA. RESULT: The retention times of niclosamide and bicalutamide were 4.19min and 8.61min, respectively, with a running time of 15minutes. The calibration ranges are 50-600ng/ml for niclosamide and 100-1200ng/ml for bicalutamide. Regression equations for niclosamide and bicalutamide were y=55746x - 1E+06 and y=22051x-576888 with regression coefficient (R2) 0.9952 & 0.9982 using the unweighted and weighted linear regression with a weighting factor of 1/xo, 1/x, 1/√x, and 1/x2. The accuracy of niclosamide and bicalutamide were 46.01ng/ml to 584.10ng/ml and 82.30ng/ml to 1149.13ng/ml, respectively. The percentage recoveries for niclosamide and bicalutamide were 86.51-90.29% & 88.64-93.99%, respectively. CONCLUSIONS: The result of the present study show that the method developed is a simple, fast and precise method and is used in bioavailability and bioequivalence studies as well as during routine therapeutic drug monitoring of niclosamide and bicalutamide.

Biomedical publications in the selected CARICOM countries

Objective: To compare biomedical research productivity among selected CARICOM countries. Design and Methodology: Biomedical publications of the selected CARICOM countries (Bahamas, Barbados, Dominica, Guyana, Grenada, Haiti, Jamaica, Suriname, and Trinidad & Tobago) were retrieved using 'PubMed' and 'ScImago Journal & country Rank' (SJR) databases. The publications for each country were then normalized by factors such as total population, gross domestic product (GDP) and Internet usage rate. Results: Total number of papers published by all 9 countries was 7,281 and 8,378 in PubMed (1990- 2015) and SJR databases (1996-2017) respectively. Jamaica produced highest number of biomedical publications [PubMed: 3,928 (54%) and SJR: 2,850 (34%)]. However, when adjusted, Grenada had the highest research publications per million populations, per billion GDP and per 1,000 Internet users in both databases. For trend analysis, PubMed showed that Jamaica produced highest number of additional publications each year ­ on an average 4.8 followed by Trinidad & Tobago (4.4). According to SJR, Jamaica had also highest number of citations (42,311) and H-index (76) followed by Trinidad & Tobago (29,152 and 71). Barbados had the highest number of citations per document (24.9) followed by Haiti (18.4). Conclusion: There was a marked imbalance noted among the CARICOM countries in terms of biomedical research and publications. A CARICOM-wide research may be embarked to explore disparities in biomedical research productivity and thus formulate informed health policies to alleviate diseases and eradicate poverty.

Breakdown of Magnetic Order in the Pressurized Kitaev Iridate ß-Li_{2}IrO_{3}.

Temperature-pressure phase diagram of the Kitaev hyperhoneycomb iridate ß-Li_{2}IrO_{3} is explored using magnetization, thermal expansion, magnetostriction, and muon spin rotation measurements, as well as single-crystal x-ray diffraction under pressure and ab initio calculations. The Néel temperature of ß-Li_{2}IrO_{3} increases with the slope of 0.9 K/GPa upon initial compression, but the reduction in the polarization field H_{c} reflects a growing instability of the incommensurate order. At 1.4 GPa, the ordered state breaks down upon a first-order transition, giving way to a new ground state marked by the coexistence of dynamically correlated and frozen spins. This partial freezing in the absence of any conspicuous structural defects may indicate the classical nature of the resulting pressure-induced spin liquid, an observation paralleled to the increase in the nearest-neighbor off-diagonal exchange Γ under pressure.

Serum Homocysteine and its Association with Glycemic Control in Type 2 Diabetic Patients.

In developing countries like Bangladesh the prevalence of type 2 diabetes mellitus is increasing day by day. Among the long-term complications of diabetes mellitus, vascular complications represent a major cause of morbidity and mortality. Hyperglycemia is still considered the principal cause of diabetes complications. Total plasma homocysteine (tHcy) is an emerging cardiovascular risk factor. Hyperhomocysteinemia independently appears to be a stronger risk factor for mortality than other risk factors in type 2 diabetes than in non diabetes. It may partly explain the link between microalbuminurea and increased risk of cardiovascular disease. Objective of the study was to evaluate serum total homocysteine level and to correlate it with glycemic status in type 2 diabetic patients. This cross sectional study was conducted during the period of July 2011 to June 2013 on 95 patients of type 2 diabetes mellitus, attending the Endocrine OPD of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. The study was carried out in the Department of Biochemistry, Bangabandhu Sheikh Mujib Medical University, Shahbagh, Dhaka, Bangladesh. Study subjects were selected by purposive and convenient sampling technique. Study subjects were categorized according to the presence or absence of hyperhomocysteinemia. Among the total study population hyperhomocysteinemia was found in 21.05%. Among them number of male was greater. Overall glycemic control was poor in the patients. Mean HbA1c (%) was 8.31±2.04. Among those having hyperhomocysteinemia mean HbA1c (%) was significantly lower than those who had no hyperhomocysteinemia (7.2±1.5 vs. 8.6±2.06). Around one fifth of the type 2 diabetic patients had hyperhomocysteinemia. Those having hyperhomocysteinemia had significantly better glycemic control than those having no hyperhomocysteinemia.

Case characteristics among Middle East respiratory syndrome coronavirus outbreak and non-outbreak cases in Saudi Arabia from 2012 to 2015.

OBJECTIVES: As of 1 November 2015, the Saudi Ministry of Health had reported 1273 cases of Middle East respiratory syndrome (MERS); among these cases, which included 9 outbreaks at several hospitals, 717 (56%) patients recovered, 14 (1%) remain hospitalised and 543 (43%) died. This study aimed to determine the epidemiological, demographic and clinical characteristics that distinguished cases of MERS contracted during outbreaks from those contracted sporadically (ie, non-outbreak) between 2012 and 2015 in Saudi Arabia. DESIGN: Data from the Saudi Ministry of Health of confirmed outbreak and non-outbreak cases of MERS coronavirus (CoV) infections from September 2012 through October 2015 were abstracted and analysed. Univariate and descriptive statistical analyses were conducted, and the time between disease onset and confirmation, onset and notification and onset and death were examined. RESULTS: A total of 1250 patients (aged 0-109 years; mean, 50.825 years) were reported infected with MERS-CoV. Approximately two-thirds of all MERS cases were diagnosed in men for outbreak and non-outbreak cases. Healthcare workers comprised 22% of all MERS cases for outbreak and non-outbreak cases. Nosocomial infections comprised one-third of all Saudi MERS cases; however, nosocomial infections occurred more frequently in outbreak than non-outbreak cases (p<0.001). Patients contracting MERS during an outbreak were significantly more likely to die of MERS (p<0.001). CONCLUSIONS: To date, nosocomial infections have fuelled MERS outbreaks. Given that the Kingdom of Saudi Arabia is a worldwide religious travel destination, localised outbreaks may have massive global implications and effective outbreak preventive measures are needed.

Enhanced sensitivity to glucocorticoids in cytarabine-resistant AML.

We sought to identify drugs that could counteract cytarabine resistance in acute myeloid leukemia (AML) by generating eight resistant variants from MOLM-13 and SHI-1 AML cell lines by long-term drug treatment. These cells were compared with 66 ex vivo chemorefractory samples from cytarabine-treated AML patients. The models and patient cells were subjected to genomic and transcriptomic profiling and high-throughput testing with 250 emerging and clinical oncology compounds. Genomic profiling uncovered deletion of the deoxycytidine kinase (DCK) gene in both MOLM-13- and SHI-1-derived cytarabine-resistant variants and in an AML patient sample. Cytarabine-resistant SHI-1 variants and a subset of chemorefractory AML patient samples showed increased sensitivity to glucocorticoids that are often used in treatment of lymphoid leukemia but not AML. Paired samples taken from AML patients before treatment and at relapse also showed acquisition of glucocorticoid sensitivity. Enhanced glucocorticoid sensitivity was only seen in AML patient samples that were negative for the FLT3 mutation (P=0.0006). Our study shows that development of cytarabine resistance is associated with increased sensitivity to glucocorticoids in a subset of AML, suggesting a new therapeutic strategy that should be explored in a clinical trial of chemorefractory AML patients carrying wild-type FLT3.

HOX gene expression predicts response to BCL-2 inhibition in acute myeloid leukemia.

Inhibitors of B-cell lymphoma-2 (BCL-2) such as venetoclax (ABT-199) and navitoclax (ABT-263) are clinically explored in several cancer types, including acute myeloid leukemia (AML), to selectively induce apoptosis in cancer cells. To identify robust biomarkers for BCL-2 inhibitor sensitivity, we evaluated the ex vivo sensitivity of fresh leukemic cells from 73 diagnosed and relapsed/refractory AML patients, and then comprehensively assessed whether the responses correlated to specific mutations or gene expression signatures. Compared with samples from healthy donor controls (nonsensitive) and chronic lymphocytic leukemia (CLL) patients (highly sensitive), AML samples exhibited variable responses to BCL-2 inhibition. Strongest CLL-like responses were observed in 15% of the AML patient samples, whereas 32% were resistant, and the remaining exhibited intermediate responses to venetoclax. BCL-2 inhibitor sensitivity was associated with genetic aberrations in chromatin modifiers, WT1 and IDH1/IDH2. A striking selective overexpression of specific HOXA and HOXB gene transcripts were detected in highly BCL-2 inhibitor sensitive samples. Ex vivo responses to venetoclax showed significant inverse correlation to ß2-microglobulin expression and to a lesser degree to BCL-XL and BAX expression. As new therapy options for AML are urgently needed, the specific HOX gene expression pattern can potentially be used as a biomarker to identify venetoclax-sensitive AML patients for clinical trials.

Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia.

TCF3-PBX1 (E2A-PBX1) is a recurrent gene fusion in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), which is caused by the translocation t(1;19)(q23;p13). TCF3-PBX1 BCP-ALL patients typically benefit from chemotherapy; however, many relapse and subsequently develop resistant disease with few effective treatment options. Mechanisms driving disease progression and therapy resistance have not been studied in TCF3-PBX1 BCP-ALL. Here, we aimed to identify novel treatment options for TCF3-PBX1 BCP-ALL by profiling leukemia cells from a relapsed patient, and determine molecular mechanisms underlying disease pathogenesis and progression. By drug-sensitivity testing of leukemic blasts from the index patient, control samples and TCF3-PBX1 positive and negative BCP-ALL cell lines, we identified the phosphatidylinositide 3-kinase delta (p110δ) inhibitor idelalisib as an effective treatment for TCF3-PBX1 BCP-ALL. This was further supported by evidence showing TCF3-PBX1 directly regulates expression of PIK3CD, the gene encoding p110δ. Other somatic mutations to TP53 and MTOR, as well as aberrant expression of CXCR4, may influence additional drug sensitivities specific to the index patient and accompanied progression of the disease. Our results suggest that idelalisib is a promising treatment option for patients with TCF3-PBX1 BCP-ALL, whereas other drugs could be useful depending on the genetic context of individual patients.

Absence of low energy magnetic spin-fluctuations in isovalently and aliovalently doped LaCo2B2 superconducting compounds.

Magnetization, resistivity and (11)B, (59)Co NMR measurements have been performed on the Pauli paramagnet [Formula: see text], and the superconductors [Formula: see text] ([Formula: see text] K) and [Formula: see text] ([Formula: see text] K). The site selective NMR experiment reveals the multiband nature of the Fermi surface in these systems. The temperature independent Knight shift and 1/T 1 T clearly indicate the absence of correlated low energy magnetic spin-fluctuations in the normal state, which is in contrast to other Fe-based pnictides. The density of states (DOS) of Co 3d electrons has been enhanced in superconducting [Formula: see text] and [Formula: see text] with respect to the non superconducting reference compound [Formula: see text]. The occurrence of superconductivity is related to the DOS enhancement.

Novel drug candidates for blast phase chronic myeloid leukemia from high-throughput drug sensitivity and resistance testing.

Chronic myeloid leukemia in blast crisis (CML BC) remains a challenging disease to treat despite the introduction and advances in tyrosine kinase inhibitor (TKI) therapy. In this study we set out to identify novel candidate drugs for CML BC by using an unbiased high-throughput drug testing platform. We used three CML cell lines representing different types of CML blast phases (K562, EM-2 and MOLM-1) and primary leukemic cells from three CML BC patients. Profiling of drug responses was performed with a drug sensitivity and resistance testing platform comprising 295 anticancer agents. Overall, drug sensitivity scores and the drug response profiles of cell line and primary cell samples correlated well and were distinct from other types of leukemia samples. The cell lines were highly sensitive to TKIs and the clinically TKI-resistant patient samples were also resistant ex vivo. Comparison of cell line and patient sample data identified new candidate drugs for CML BC, such as vascular endothelial growth factor receptor and nicotinamide phosphoribosyltransferase inhibitors. Our results indicate that these drugs in particular warrant further evaluation by analyzing a larger set of primary patient samples. The results also pave way for designing rational combination therapies.

Isotopic dependence of the predissociations of the E(1)Π state of CO.

The predissociations of the E(1)Π state of CO are again studied. They include both the background predissociation attributed to the continuum of the A(1)Π state and the accidental predissociation due to the k(3)Π state. They are calculated using a coupled equations method. The three components of the k state are introduced. These predissociations are studied for different isotopologues and are shown to decrease with increasing reduced mass, in agreement with the experimental results of Ubachs et al. [J. Chem. Phys. 113, 547 (2000)].

New digital technologies for the surveillance of infectious diseases at mass gathering events.

Outbreaks of infectious diseases at mass gatherings can strain the health system of the host region and pose a threat to local and global health. In addition to strengthening existing surveillance systems, most host nations also use novel technologies to assess disease risk and augment traditional surveillance approaches. We review novel approaches to disease surveillance using the Internet, mobile phone applications, and wireless sensor networks. These novel approaches to disease surveillance can result in prompt detection.

Serosurveillance of Orientia tsutsugamushi and Rickettsia typhi in Bangladesh.

Scrub and murine typhus infections are under-diagnosed causes of febrile illness across the tropics, and it is not known how common they are in Bangladesh. We conducted a prospective seroepidemiologic survey across six major teaching hospitals in Bangladesh by using an IgM enzyme-linked immunosorbent assay. Results indicated recent exposure (287 of 1,209, 23.7% seropositive for Orientia tsutsugamushi and 805 of 1,209, 66.6% seropositive for Rickettsia typhi). Seropositive rates were different in each region. However, there was no geographic clustering of seropositive results for both organisms. There was no difference between those from rural or urban areas. Rickettsia typhi seroreactivity was positively correlated with age. Scrub typhus and murine typhus should be considered as possible causes of infection in Bangladesh.

Interpretation of the accidental predissociation of the E(1) Π state of CO.

A special case of predissociation, known as indirect or accidental predissociation observed in the Rydberg E(1)Π bound state of CO is discussed. We resort to ab initio potentials in order to determine the plausible mechanism for this predissociation. Values of the predissociation width for the valence k(3)Π state of CO, as obtained from Fermi's golden rule, are also reported. The predissociation width obtained for the mixed E(1)Π (v = 1, J = 7) state is 0.033 cm(-1) compared to the experimental value of 0.034 cm(-1). The mixed E - E(') state with J = 28, v = 0 is found to be in near resonance condition with the k(3)Π (v = 4, J = 28) state, thus providing the means to indirect predissociation.

Bacteriology and antibiotic sensitivity patterns of urinary tract infections in a tertiary hospital in Bangladesh.

Urinary tract infection (UTI) is common bacterial infection in mankind. The changing antimicrobial sensitivity in UTI demands use of appropriate antibiotics. This prospective study was performed in Comilla Medical Collage during the period of January 2011 to December 2011. Five hundred and fifty one urine specimens from clinically suspected UTI patients were examined by Semi quantitative culture method and their antimicrobial sensitivity patterns were determined by disc diffusion technique. The study was designed to isolate and identify the nature of bacteria in UTI with their sensitivity pattern to common antibiotics. Of the 551 tested sample 131 samples showed growth of pathogens among which the most prevalent were E. coli 98(75%) followed by Klebsiella pneumonia 14(10.7%) and Enterococcus 8(6%). The majority 96(73.3%) of the isolates were from female while the remaining were from male and this sex difference was statistically significant (p<0.001). Imipenem, meropenem, amikacin, nitrofurantoin, gentamycin, mecillinum and amoxyclav are found to be effective against 76-100% of the uropathogens. Most powerful antibiotics in our study were imipenem, meropenem, amikacin and nitrofurantoin which show their efficacy against 91-100% isolates. In more than 60% case shows their resistance against amoxycillin, nalidexic acid, cefixime, ciprofloxacin, cotrimoxazole and cephalosporins which raises the question regarding rationality to empirically use of these antibiotics in UTI with out culture and sensitivity reports.

Melioidosis in an adult male.

Infection with Burkholderia pseudomallei has been described, albeit rarely, patients in Bangladesh. Infection usually follows percutaneous inoculation or inhalation of the causative bacterium, which is present in soil and surface water in the endemic region. A 35-year-young male farmer presented with prolonged fever and significant weight loss. Patient gradually deteriorated despite getting different antibiotics including intravenous ceftriaxone and metronidazole. Panels of investigations were done which revealed no diagnostic confirmation except uncontrolled diabetes and multiple abscesses in different organs. Melioidosis was suspected and serum samples were positive for Burkholderia pseudomallei antibody. The case illustrates the importance of non-specific nature of the clinical presentation and high index of suspicion of uncommon diseases like melioidosis where the disease has not been considered as an endemic.