Frequency of worsening liver function in severe dengue hepatitis patients receiving paracetamol: A retrospective analysis of hospital data.

Objective: To determine the frequency of worsening liver function among hospital in-patients with severe dengue hepatitis receiving paracetamol. Methods: This retrospective study was conducted at the Department of Medicine, Aga Khan University Hospital, Karachi, and comprised records of dengue patients with severe hepatitis who received paracetamol for control of fever between June 2007 and December 2014. Alanine aminotransferase at baseline and following paracetamol administration was noted, as well as dosage and duration of paracetamol, along with participants\u27 demographic details. Frequency of patients who developed worsening or improvement of alanine aminotransferase was also noted. SPSS 19 was used for data analysis. Results: Of the 113 subjects, 73(64.6%) were male and 40(35.4%) were female. Overall improvement was observed in subsequent alanine aminotransferase levels (491 units per litre, IQR 356.5 TO 775 vs 151 units per litre, IQR 49.5 to 299.5). Most commonly prescribed dose of paracetamol was 2g (IQR 1 to 5 grams), which was taken for a median duration of 1 day (IQR 1 to 3 days). Moreover, 100(88.5 %) patients showed improvement in alanine aminotransferase. Only 13(11.5 %) patients developed worsening of alanine aminotransferase. Of those with worsening liver function, 8(61.5 %) were discharged home with no clinical deterioration and 5(38.5 %) deaths were observed. However, causes of deaths were unrelated to liver dysfunction. Conclusion: The frequency of worsening liver function following paracetamol administration in patients with severe dengue hepatitis was relatively low

Sociodemographic factors associated with IgG and IgM seroprevalence for human cytomegalovirus infection in adult populations of Pakistan: A seroprevalence survey

Background: The seroprevalence of human cytomegalovirus (HCMV) infection ranges from 30 to 90 % in developed countries. Reliable estimates of HCMV seroprevalence are not available for Pakistan. This study determined the seroprevalence and sociodemographic factors associated with HCMV infection in adult populations of Karachi, Pakistan. Methods: A seroprevalence survey was conducted on 1000 adults, including residents of two semi-urban communities, and visitors to a government and a private hospital. Questionnaire-based interviews were conducted. Sera were analysed for HCMV-specific IgG and IgM. Chi-square or Fisher’s exact test was used for comparing sociodemographic variables against seropositivity of HCMV-IgG or IgM. Multiple logistic regression modeling was performed for IgG seroprevalence and adjusted odds ratios were computed. Results: The seroprevalence of HCMV-IgG and IgM was 93.2 and 4.3 % respectively. 95.3 % of individuals who were IgM seropositive were also seropositive for IgG. Around 6 % (15/250) of women of childbearing age remained uninfected and were therefore susceptible to primary infection. HCMV-IgG seroprevalence was associated with being female (p = 0.001), increasing age (p = 0.002) and crowding index (p = 0.003) and also with lower levels of both education (p \u3c 0.001) and income (p = 0.008). Seroprevalence also differed significantly by marital status (p = 0.008) and sampling location (p \u3c 0.001). A logistic regression model for HCMV-IgG seroprevalence showed associations with being female (OR = 1.89; 95 % CI: 1.10–3.25), increasing age (OR = 3.95; 95 % CI: 1.79–8.71) and decreasing income (OR = 0.72; 95 % CI: 0.54–0.96). A strong association was observed between increased seroprevalence of HCMV-IgM and decreasing household size (p = 0.008).Conclusions: Seroprevalence of HCMV is very high in Pakistan, although 6 % of women of childbearing age remain at risk of primary infection. The IgM seropositivity observed in some individuals living in small household size (1–3 individuals) with persistent HCMV infection could have resulted from a recurrent HCMV infection. Future longitudinal research in pregnant women and neonates is required to study the trends in HCMV seroprevalence over time in Pakistan for the development of a potential HCMV prevention and vaccination programme

Effect of Diabetes Mellitus on Tuberculosis Treatment Outcome and Adverse Reactions in Patients Receiving Directly Observed Treatment Strategy in India: A Prospective Study

Despite successful implementation of directly observed treatment, short course (DOTS) in India, the growing number of diabetes mellitus (DM) patients appears to be a cause in the increasing tuberculosis (TB) incidence, affecting their management. In this regard, a prospective study was conducted on DOTS patients in three primary health care centers in urban slum region of South Delhi, India, to evaluate the effect of DM on sputum conversion, treatment outcome, and adverse drug reactions (ADR) due to anti-TB treatment. Eligible TB patients underwent blood glucose screening at treatment initiation. Disease presentation, clinical outcome, and ADRs were compared between patients of TB with and without DM. Out of 316 patients, the prevalence of DM was found to be 15.8%, in which 19.4% and 9.6% were PTB and EPTB patients, respectively. DM patients have observed higher sputum positivity (OR 1.247 95% CI; 0.539-2.886) at the end of 2-month treatment and poor outcome (OR 1.176 95% CI; at the completion of treatment compared with non DM patients. Presence of DM was significantly associated (OR 3.578 95% CI; 1.114-11.494, = 0.032) with the development of ADRs. DM influences the treatment outcome of PTB patients in our setting and also on the ADR incidence

Expression of the androgen receptor, pAkt, and pPTEN in breast cancer and their potential in prognostication

BACKGROUND: Importance of androgen receptor (AR) as an independent prognostic marker in Pakistani women with breast cancer (BCa) remains unexplored. Our aim was to identify the expression and potential prognostic value of AR, its upstream regulator (pAkt) and target gene (pPTEN) in invasive BCa. METHODS: This study used a cohort of 200 Pakistani women with invasive BCa diagnosed during 2002-2011. Expression of AR, pAkt and pPTEN was determined on formalin fixed paraffin embedded tissue sections by immunohistochemistry. The association of AR, pAkt and pPTEN with clinicopathological parameters was determined. Survival analyses were undertaken on patients with ≥ 5 years of follow-up (n = 82). RESULTS: Expression of AR, pAkt and pPTEN was observed in 47.5%, 81.3% and 50.6% of patients, respectively. AR-expressing tumors were low or intermediate in grade (P \u3c .001) and expressed ER (P = .002) and PR (P = .001). Patients with AR+ tumors had significantly higher OS (Mean OS = 10.2 ± 0.465 years) compared to patients with AR− tumors (Mean OS = 5.8 ± 0.348 years) (P = .047). Furthermore, AR-positivity was associated with improved OS in patients receiving endocrine therapy (P = .020). Patients with AR+ /pAkt+ /pPTEN− tumors, had increased OS (Mean OS = 7.1 ± 0.535 years) compared to patients with AR−/pAkt+/pPTEN− tumors (Mean OS = 5.1 ± 0.738 years). CONCLUSION: AR-expressing tumors are frequently characterized by low or intermediate grade tumors, expressing ER and PR. In addition, expression of AR, pAkt and pPTEN, could be considered in prognostication of patients with invasive BCa

A NOVEL ACYCLIC DITERPENIC ALCOHOL ISOLATED FROM ANTIOXIDANT ACTIVE ETHANOL EXTRACT OF LEAVES OF CENTAUROTHAMNUS MAXIMUS GROWN IN SAUDI ARABIA

Background: Isolation and characterization of a new compound from the antioxidant active ethanol extract of leaves of an endemic plant Centaurothamnus maximus. Methods: The air dried powdered leaves of the plant was extracted successively with n-hexane, dichloromethane, ethyl acetate and ethanol. The obtained extracts were concentrated under reduced pressure using rotary evaporator. The antioxidant activity was carried out on various concentrations (1000, 500, 100, 50 and 10 µg/ml) of all the extracts by DPPH free radical scavenging method. After screening for antioxidant potential the ethanol fraction was selected for the isolation of phytoconstituents by column chromatography using LiChroprep RP-18 as stationary phase and water, MeOH and CHCl3 in different combinations as eluent. The chemical structures of the isolated compounds were elucidated by 1D and 2D NMR spectroscopic techniques (DEPT, COSY, H M B C and HSQC) aided by EIMS mass and IR spectra. Results: The antioxidant activity of ethanol extract was highly comparable with standard ascorbic acid as compared to other extracts. A new compound along with two known compounds has been isolated from antioxidant active ethanol extract. The chemical structure of unknown compound was established as 2, 6, 10, 14-tetramethyl hexadec-12-cis-en-5α, 7α, 9α, 14α-tetraol (CM1) while the known compound isolated Luteolin-7-O-β-glucopyranosyl-6''-O-(6''→1''')-β-D-rhamno-pyranoside (CM-2) and stigmast-5,22–dien-3β –ol (CM3). Conclusion: On the basis of interpretation of different spectroscopy data we concluded that the compound CM1 is an acyclic diterpenic alcohol. The authors are reporting the isolation of CM1 from plant source for the first time but CM2 and CM3 are known compounds. Ethanol extract of leaves can be recommended as potent antioxidant for ethno-medical purposes. The antioxidant properties might be due to some well-known antioxidants like (CM-2) and other falvonoidal compounds

Pharmacological Evaluation of Secondary Metabolites and Their Simultaneous Determination in the Arabian Medicinal Plant Plicosepalus curviflorus Using HPTLC Validated Method

© The Author(s) 2019. The present study aimed to identify biologically active secondary metabolites from the rare plant species, Pulsatilla patens subsp. patens and the cultivated P. vulgaris subsp. vulgaris. Chromatographic fractionation of the ethanolic extract of the roots of P. patens subsp. patens resulted in the isolation of two oleanane-type glycosides identified as hederagenin 3-O-β-d-glucopyranoside (2.7 mg) and hederagenin 3-O-β-d-galactopyranosyl-(1→2)-β-d-glucopyranoside (3.3 mg, patensin). HPLC analysis of the methanolic extract of the crude root of P. patens subsp. patens and P. vulgaris subsp. vulgaris revealed the presence of Pulsatilla saponin D (hederagenin 3-O-α-l-rhamnopyranosyl(1→2)-[β-d-glucopyranosyl(1→4)]-α-l-arabinopyranoside). Chromatographic analysis using GC-MS of the silylated methanolic extracts from the leaves and roots of these species identified the presence of carboxylic acids, such as benzoic, caffeic, malic, and succinic acids. The extracts from Pulsatilla species were tested for their antifungal, antimicrobial, and antimalarial activities, and cytotoxicity to mammalian cell lines. Both P. patens subsp. patens and P. vulgaris subsp. vulgaris were active against the fungus Candida glabrata with the half-maximal inhibitory concentration (IC 50 ) values of 9.37 µg/mL and 11 µg/mL, respectively. The IC 50 values for cytotoxicity evaluation were in the range of 32–38 μg/mL for P. patens subsp. patens and 35–57 μg/mL for P. vulgaris subsp. vulgaris for each cell line, indicating general cytotoxic activity throughout the panel of evaluated cancer and noncancer cells

The state of indoor air quality in Pakistan—a review

Background and purpose: In Pakistan, almost 70% of the population lives in rural areas. Ninety-four percent of households in rural areas and 58% in urban areas depend on biomass fuels (wood, dung, and agricultural waste). These solid fuels have poor combustion efficiency. Due to incomplete combustion of the biomass fuels, the resulting smoke contains a range of health-deteriorating substances that, at varying concentrations, can pose a serious threat to human health. Indoor air pollution accounts for 28,000 deaths a year and 40 million cases of acute respiratory illness. It places a significant economic burden on Pakistan with an annual cost of 1% of GDP. Despite the mounting evidence of an association between indoor air pollution and ill health, policy makers have paid little attention to it. This review analyzes the existing information on levels of indoor air pollution in Pakistan and suggests suitable intervention methods. Methods: This review is focused on studies of indoor air pollution, due to biomass fuels, in Pakistan published in both scientific journals and by the Government and international organizations. In addition, the importance of environmental tobacco smoke as an indoor pollutant is highlighted. Results: Unlike many other developing countries, there are no long-term studies on the levels of indoor air pollution. The limited studies that have been undertaken indicate that indoor air pollution should be a public health concern. High levels of particulate matter and carbon monoxide have been reported, and generally, women and children are subject to the maximum exposure. There have been a few interventions, with improved stoves, in some areas since 1990. However, the effectiveness of these interventions has not been fully evaluated. Conclusion: Indoor air pollution has a significant impact on the health of the population in Pakistan. The use of biomass fuel as an energy source is the biggest contributor to poor indoor air quality followed by smoking. In order to arrest the increasing levels of indoor pollution, there is a dire need to recognize it as a major health hazard and formulate a national policy to combat it. An integrated effort, with involvement of all stakeholders, could yield promising results. A countrywide public awareness campaign, on the association of indoor air pollution with ill health, followed by practical intervention would be an appropriate approach. Due to the current socioeconomic conditions in the country, development and adoption of improved cooking stoves for the population at large would be the most suitable choice. However, the potential of biogas as a fuel should be explored further, and modern fuels (natural gas and LPG) need to be accessible and economical. Smoking in closed public spaces should be banned, and knowledge of the effect of smoking on indoor air quality needs to be quantified. © 2010 Springer-Verlag

Patterns of active and passive smoking, and associated factors, in the South-east Anatolian Project (SEAP) region in Turkey

BACKGROUND: Smoking is an important health threat in Turkey. This study aimed to determine the frequency of and main factors associated with smoking in persons of 15 years and over, and the frequency of passive smoking in homes in the South-east Anatolian Project (SEAP) Region in Turkey. METHODS: A cross sectional design was employed. The sample waschosen by the State Institute of Statistics using a stratified cluster probability sampling method. 1126 houses representing the SEAP Region were visited. Questionnaires about tobacco smoking and related factors were applied to 2166 women and 1906 men (of 15 years old and above) in their homes. Face-to-face interview methods were employed. Participants were classified as current, ex, and non-smokers. The presence of a regular daily smoker in a house was used as an indication of passive smoking. The chi-square andlogistic regressionanalysis methods were used for the statistical analysis. RESULTS: The prevalence of smoking, in those of 15 years and over, was 11.8% in women and 49.7% in men. The prevalence of current smokers was higher in urban (34.5 %) than in rural (22.8 %) regions. The mean of total cigarette consumption was 6.5 packs/year in women and 17.9 packs/year in men. There was at least one current smoker in 70.1% of the houses. CONCLUSION: Smoking is a serious problem in the South-eastern Anatolian Region. Male gender, middle age, a high level of education and urban residency were most strongly associated with smoking

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)