Sero-epidemiology and risk factor analysis of human brucellosis in Punjab, Pakistan: a cross sectional study.

Human brucellosis is a neglected zoonotic problem worldwide with a high degree of morbidity in humans and is mostly overlooked due to other febrile conditions. The aim of this study was to evaluate the sero-prevalence and risk factors of human brucellosis among subjects living in Punjab, Pakistan. In this cross-sectional study, human blood samples were collected from seven districts of Punjab, Pakistan. Information regarding personal data, demographic data and potential risk factors was collected through a structured questionnaire. Detection of anti-Brucella antibodies was done through Rose Bengal Plate Test (RBPT) and Enzyme Linked Immunosorbent Assay (ELISA). Descriptive analysis, Chi square test and Odds ratio was applied using STATA software version 12. The sero-prevalence of human brucellosis was 13.13% with significantly higher percentage in males 17.23% and age group 25-40 years 16.50% (P=< 0.001). The demographic factors positively associated with human brucellosis were lack of education (P = 0.003; OR = 1.85) and farming as an occupation (P =<0.001; OR = 2.50) Similarly, among the risk factors studied, keeping animals at home (P =<0.001; OR = 2.03), slaughtering of animals (P =<0.001; OR = 15.87) and consuming raw milk (P =<0.001; OR = 5.42) were the factors strongly connected with human brucellosis. A massive awareness should be given to livestock farmers and individuals directly linked to animals regarding risk factors and transmission of brucellosis. Consumption of unpasteurized milk and its products should be condemned to curtail this neglected disease.

In silico analysis of Naegleria fowleri cathepsin B paralogs: important drug targets.

Naegleria fowleri is a deadly human pathogen that causes primary amoebic meningoencephalitis (PAM). In this study, in silico investigations of two important N. fowleri cathepsin B paralogs, i.e., copies of genes resulting from a gene duplication event, were carried out using comparative modeling and molecular dynamics (MD) simulations. Comparative models of both paralogs showed significant architectural similarity with their template, i.e., rat cathepsin B. However, in N. fowleri cathepsin B (UniProt ID: X5D761) and putative cathepsin B (UniProt ID: M1HE19) enzymes, eleven and fifteen residues in the occluding loop regions were deleted, respectively, suggesting that these enzymes have a short occluding loop. Thus, it is concluded that N. fowleri cathepsin B and putative cathepsin B enzymes lack exopeptidase activity but possess enhanced endopeptidase activity and an affinity for macromolecular inhibitors. MD simulations further confirmed that prosegments (macromolecular inhibitors) bond more tightly with both enzymes than with wild-type cathepsin B. Additionally, a mutation was identified at an important N-glycosylation site; this mutation is believed to affect cathepsin B targeting inside the cell and make cathepsin B available in the extracellular environment. Due to this important N-glycosylation site mutation, these enzymes are secreted in the extracellular environment via an alternative, still unknown, posttranslational processing strategy. The present study is the first to predict the three-dimensional folds of N. fowleri cathepsin B paralogous enzymes, including a detailed description of the active site architecture and information about propeptide binding mode. This information can contribute to the discovery of novel and selective treatments that are effective against N. fowleri.

Sero-epidemiology and risk factor analysis of human brucellosis in Punjab, Pakistan: a cross sectional study

@#Human brucellosis is a neglected zoonotic problem worldwide with a high degree of morbidity in humans and is mostly overlooked due to other febrile conditions. The aim of this study was to evaluate the sero-prevalence and risk factors of human brucellosis among subjects living in Punjab, Pakistan. In this cross-sectional study, human blood samples were collected from seven districts of Punjab, Pakistan. Information regarding personal data, demographic data and potential risk factors was collected through a structured questionnaire. Detection of anti-Brucella antibodies was done through Rose Bengal Plate Test (RBPT) and Enzyme Linked Immunosorbent Assay (ELISA). Descriptive analysis, Chi square test and Odds ratio was applied using STATA software version 12. The sero-prevalence of human brucellosis was 13.13% with significantly higher percentage in males 17.23% and age group 25-40 years 16.50% (P=< 0.001). The demographic factors positively associated with human brucellosis were lack of education (P = 0.003; OR = 1.85) and farming as an occupation (P =<0.001; OR = 2.50) Similarly, among the risk factors studied, keeping animals at home (P =<0.001; OR = 2.03), slaughtering of animals (P =<0.001; OR = 15.87) and consuming raw milk (P =<0.001; OR = 5.42) were the factors strongly connected with human brucellosis. A massive awareness should be given to livestock farmers and individuals directly linked to animals regarding risk factors and transmission of brucellosis. Consumption of unpasteurized milk and its products should be condemned to curtail this neglected disease.

General fractional integral inequalities for convex and m-convex functions via an extended generalized Mittag-Leffler function.

In this paper some new general fractional integral inequalities for convex and m-convex functions by involving an extended Mittag-Leffler function are presented. These results produce inequalities for several kinds of fractional integral operators. Some interesting special cases of our main results are also pointed out.

Unresolved questions regarding human hereditary deafness.

Human hearing loss is a common neurosensory disorder about which many basic research and clinically relevant questions are unresolved. This review on hereditary deafness focuses on three examples considered at first glance to be uncomplicated, however, upon inspection, are enigmatic and ripe for future research efforts. The three examples of clinical and genetic complexities are drawn from studies of (i) Pendred syndrome/DFNB4 (PDS, OMIM 274600), (ii) Perrault syndrome (deafness and infertility) due to mutations of CLPP (PRTLS3, OMIM 614129), and (iii) the unexplained extensive clinical variability associated with TBC1D24 mutations. At present, it is unknown how different mutations of TBC1D24 cause non-syndromic deafness (DFNB86, OMIM 614617), epilepsy (OMIM 605021), epilepsy with deafness, or DOORS syndrome (OMIM 220500) that is characterized by deafness, onychodystrophy (alteration of toenail or fingernail morphology), osteodystrophy (defective development of bone), mental retardation, and seizures. A comprehensive understanding of the multifaceted roles of each gene associated with human deafness is expected to provide future opportunities for restoration as well as preservation of normal hearing.

Mutations of SGO2 and CLDN14 collectively cause coincidental Perrault syndrome.

Perrault syndrome (PS) is a genetically heterogeneous disorder characterized by primary ovarian insufficiency (POI) in females and sensorineural hearing loss in males and females. In many PS subjects, causative variants have not been found in the five reported PS genes. The objective of this study was to identify the genetic cause of PS in an extended consanguineous family with six deaf individuals. Whole exome sequencing (WES) was completed on four affected members of a large family, and variants and co-segregation was confirmed by Sanger sequencing. All hearing impaired individuals, including the proband, are homozygous for a pathogenic variant of CLDN14, but this only explains the deafness. The PS proband is also homozygous for a frameshift variant (c.1453_1454delGA, p.(Glu485Lysfs*5)) in exon 7 of SGO2 encoding shugoshin 2, which is the likely cause of her concurrent ovarian insufficiency. In mouse, Sgol2a encoding shugoshin-like 2a is necessary during meiosis in both sexes to maintain the integrity of the cohesin complex that tethers sister chromatids. Human SGO2 has not previously been implicated in any disorder, but in this case of POI and perhaps others, it is a candidate for unexplained infertility.

Bottom-up fabrication of graphene on Ru(0001) via molecular self-assembly.

A bottom-up fabrication of graphene via molecular self-assembly of p-Terphenyl on Ru(0001) has been investigated by scanning tunneling microcopy and density functional theory. Upon annealing of the sample at 450 °C, the intermediate stage is observed, in which the adsorbed p-Terphenyl molecules and graphitized flakes converted from the molecules coexist, implying the onset of dehydrogenation of p-Terphenyl. At the annealing temperature of 480 °C, the graphitized flakes start to convert into graphene. An adsoption energy of 5.99 eV is calculated for an individual p-Terphenyl molecule on Ru(0001), denoting a strong interaction between the adsorbate and substrate. The intermolecular interaction brings an extra adsorption energy of 0.28 eV for each molecule in the di-molecule adsorption system. During the conversion process from adsorbed molecule into graphene, the intermolecular interaction leads to the increase of the dehydrogenation barrier from 1.52 to 1.64 eV.

Prevalence of rheumatic heart disease in school children of urban Lahore.

OBJECTIVE: To determine the prevalence of rheumatic heart disease (RHD) among school children in urban and semiurban areas of Lahore, Pakistan. METHODS: A cross-sectional survey of school children aged 5-15 years from 70 schools of urban and semiurban Lahore was carried out by a team of cardiologists. Children were screened by clinical examination and diagnosis confirmed by echocardiography. Sociodemographic data were also collected. RESULTS: Of 24 980 children screened, 986 (3.9%) had a confirmed cardiac lesion; 546 had RHD, 440 had congenital heart disease. The prevalence of RHD was 21.9/1000 children screened (95% CI 20.1 to 23.7). Their mean (SD) age was 10.7 (2.6) years and the female:male ratio was 1.6:1. Most (92.5%) were unaware of the diagnosis and less than 2% were taking rheumatic prophylaxis. All children belonged to a low socioeconomic group and 67% were undernourished. CONCLUSION: The prevalence of RHD in the urban school population of Lahore is among the highest in the world. The younger age of onset is a special feature and most are unaware of the diagnosis, and hence not receiving life-saving secondary prophylaxis.

Lipoxygenase inhibitory tetraketones: potential remedial source for inflammation and asthma.

OBJECTIVE: A series of tetraketones has been synthesized by way of a one pot synthesis and screened for inhibitory activity against the enzyme lipoxygenase. METHOD: An efficient and high yielding one pot synthesis to tetraketones [2-22] has been developed by way of tetraethyl ammonium bromide (Et4N+Br-) mediated condensation of cyclohexane-1, 3-dione [1] with a variety of aldehydes. Lipoxygenase enzyme solution was prepared so that enzyme concentration in reaction mixture was adjusted to give rates of 0.05 absorbance/minute. The test compounds were prepared in methanol of concentrations 50, 25, 12.5, 6.25 and 3.125 microM. The reaction mixture contained 160 microL (100 mM) sodium phosphate buffer (pH 8.0), 10 microL of test-compound solution and 20 microL of lipoxygenase solution. The contents were mixed and incubated for 10 minutes at 25 degrees C. The reaction was then initiated by the addition of 10 microL substrate solution (linoleic acid, 0.5 mM, 0.12% w/v tween 20 in the ratio of 1:2), with the formation of (9Z, 11E)-(13S)-13-hydroperoxyoctadeca-9,11-dienoate, the change of absorbance at 234 nm was followed for 6 minutes. The concentrations of the test compounds that inhibited the lipoxygenase activity by 50% (IC50) were determined by monitoring the effect of increasing concentrations of these compounds in the assays on the degree of inhibition. The IC50 values were calculated by means of the EZ-Fit Enzyme-Kinetics Program (Perrella Scientific Inc., Amherst, U.S.A.). RESULT: The tetraketones [2-22] were synthesized in high yields (91-98%) using mild reaction conditions. Most of these compounds showed significant inhibitory activity against the enzyme lipoxygenase. It was found that the presence of substituents which increase delocalization of electrons enhances the inhibitory activity. CONCLUSION: It is concluded that the study is likely to lead to the discovery of therapeutically efficient agents against important disorders such as inflammation and asthma.

Tobacco use among school personnel in Rajasthan, India.

BACKGROUND: A very little information about tobacco use among school personnel is available. This is a step to have cross country and within country data using standardized methodology. AIMS: To obtain baseline information about tobacco use prevalence, knowledge and attitude among school personnel. STUDY DESIGN: Two stage cluster sample. SETTING: A state of Rajasthan. MATERIALS AND MATERIALS AND METHODS: A cross-sectional study, using anonymous self-administered questionnaire. A sample of schools with probability proportional to the enrollment in grades 8-10. All school personnel in sampled schools were eligible to participate. STATISTICAL ANALYSIS: Percentage, 95% confidence interval. RESULTS: School response rate was 97.4% (75/77) and school personnel response rate was 67.2% (909/1352). Majority of school personnel (men 69%, women 31%) were school teachers (78.3%). The prevalence of ever any tobacco use was reported by 35.9%, more among men than women (46.2% vs. 13.0%). The prevalence of current daily smoking was reported by 14.4% (men 20.6%, women 0.8%) and occasional by 7.3%, where as current daily smokeless tobacco use was 11.7% (men 16.4%, women 1.1%) and occasional 13.6%. Current daily tobacco use was significantly more among men than women. Four out of nine reported their schools have a tobacco prohibiting policy for both students (48.4%) as well as for school personnel (44.4%) and about same (47.2%) reported their schools enforce its tobacco policy or rule. Over 85% of all school personnel strongly support the tobacco control policies and wanted training in tobacco cessation and prevention. CONCLUSION: First study from Rajasthan to report tobacco use among school personnel. School personnel not only strongly support the tobacco control policies but also ready to work for its successful implementation with proper training.

Puerperal insanity in the 19th and 20th centuries.

All patients with puerperal psychosis admitted to the Royal Edinburgh Hospital within 90 days of childbirth during the periods 1880-90 and 1971-80 were compared. The majority of cases in both groups had an affective illness with an acute presentation and a fixed interval of onset. The 19th-century cases had a more florid presentation and a greater length of admission (mean, 151 days) to the hospital than the 20th-century ones (mean, 39 days). The incidence of the disorder rose from 0.34 per 1000 childbirths per year in the 19th-century group to 1.04 in the 20th-century one, but this could be explained by nosocomial factors. Most 19th-century cases occurred in multigravid women, which questions the association of puerperal psychosis with primiparae.