Serine protease from Indian Cobra venom: its anticoagulant property and effect on human fibrinogen

An unusual low molecular weight serine protease (NnP28) has been purified from Indian Cobra (Naja naja) venom from the western region of the Indian sub-continent. We reported the purification and characterization of low molecular NnP28, emphasizing its role on human fibrinogen and anticoagulant property. NnP28 was purified using gel filtration column chromatography followed by ion exchange chromatography. Protein gel electrophoresis revealed its molecular weight approximate to 28 kDa. The exact molecular mass of NnP28 was found to be 27.12 kDa by mass spectrometry, hydrolyzing casein specifically, inhibited by PMSF suggesting it has a serine protease. NnP28 prolonged the clotting time of re-calcified human citrated plasma and activated partial thromboplastin time (APTT) exhibiting anticoagulant property. NnP28 exhibited fibrinogenolytic activity. Thus, the present study demonstrates the presence of unusual low molecular weight serine protease, emphasizing its importance of region-specific Indian cobra species

Purification and biochemical characterization of a novel secretory dipeptidyl peptidase IV from porcine serum

Purification of DPP-IV enzyme from porcine serum, is presented in this study for the first time. The high molecular weight DPP-IV from porcine serum was fractioned using Sephadex G-75 gel filtration followed by DEAE Sephadex anion exchange and Sephadex G-100 gel filtration chromatography columns with a final yield of 11.25%. The SDS-PAGE of the purified sample showed a single band of molecular mass nearing 160 kDa. Distinct single band was observed after PAS staining confirmed it to be a glycoprotein. The purified enzyme showed an optimum pH and temperature of 8 and 37 degrees C, respectively. The enzyme effectively cleaved fluorogenic substrate Gly-Pro-AMC with Km and Vmax of 4.578 mu M and 90.84 nmoles/min, respectively. Purified DPP-IV activity was inhibited by Diprotin A with an IC(50)value of 8.473 mu M. Among the three plant extracts used to study DPP-IV inhibition, the aqueous hot extract ofTerminalia chebulashowed the highest inhibition of 87.19%, followed by the aqueous cold extract ofMomordica carantia, ( 31.6%) andAzadirachta indica(34.16%) at the concentration of 25 mu g

Trauma admissions among victims of domestic violence at a tertiary care hospital in north-western Tanzania: an urgent call to action

Background: Despite the growing recognition of domestic violence as a public health and human rights concern, it remains rampant in developing countries and has a negative impact on the victim’s health. This study describes the injury characteristics and treatment outcome of trauma associated with domestic violence in north-western Tanzania.Methods: This was a descriptive prospective study of patients who were managed for domestic violence related trauma at Bugando Medical Centre in Mwanza, Tanzania from April 2009 to March 2014.Results: A total of 324 patients (M: F = 1: 10.6) were studied. Majority of the patients were in the second and third decades of life. The perpetrators were mainly husbands and ex-partners (55.5%). Suspecting sexual partner being unfaithful was the most common reason given by victims for domestic violence in 63.4% of cases. Blunt and sharp objects (56.8%) were the most common weapons used. Gunshot injuries were recorded in 0.6% of cases. The head/neck was commonly affected in 68.5%. Soft tissue injuries (77.8%) were the most frequent type of injuries. The majority of patients (65.4%) sustained mild injuries. Twenty-three (7.1%) patients were HIV positive. Surgical treatment was performed in only 34.6% of cases.  Complication rate was 26.8%. The median hospital stay was 12 days. Mortality rate was 6.5%. The main predictors of mortality were advanced age (> 60 years),  late presentation,  severity of injury, severe head injury, HIV seropositivity, low CD 4 count (<200 cells), surgical site infection (p<0.001). More than two-thirds of patients were lost to follow up.Conclusion: Domestic violence related trauma remains rampant in northwestern Tanzania and contributes significantly to high morbidity and mortality. Urgent preventive measures targeting at reducing the occurrence of domestic physical violence is necessary to reduce the morbidity and mortality resulting from these injuries.

The Dynamics of the Southwest Monsoon Current in 2016 from High-Resolution In Situ Observations and Models

The strong stratification of the Bay of Bengal (BoB) causes rapid variations in sea surface temperature (SST) that influence the development of monsoon rainfall systems. This stratification is driven by the salinity difference between the fresh surface waters of the northern bay and the supply of warm, salty water by the Southwest Monsoon Current (SMC). Despite the influence of the SMC on monsoon dynamics, observations of this current during the monsoon are sparse. Using data from high-resolution in situ measurements along an east–west section at 8°N in the southern BoB, we calculate that the northward transport during July 2016 was between 16.7 and 24.5 Sv (1 Sv ≡ 106 m3 s−1), although up to ⅔ of this transport is associated with persistent recirculating eddies, including the Sri Lanka Dome. Comparison with climatology suggests the SMC in early July was close to the average annual maximum strength. The NEMO 1/12° ocean model with data assimilation is found to faithfully represent the variability of the SMC and associated water masses. We show how the variability in SMC strength and position is driven by the complex interplay between local forcing (wind stress curl over the Sri Lanka Dome) and remote forcing (Kelvin and Rossby wave propagation). Thus, various modes of climatic variability will influence SMC strength and location on time scales from weeks to years. Idealized one-dimensional ocean model experiments show that subsurface water masses advected by the SMC significantly alter the evolution of SST and salinity, potentially impacting Indian monsoon rainfall

The railroad switch effect of seasonally reversing currents on the Bay of Bengal high salinity core

The Southwest Monsoon Current (SMC) flows eastward from the Arabian Sea into the Bay of Bengal (BoB) during summer, advecting a core of high salinity water. This high salinity core has been linked with Arabian Sea High Salinity Water that is presumed to enter the BoB directly from the Arabian Sea via the SMC. Here we show that the high salinity core originates primarily from the western equatorial Indian Ocean, reaching the BoB via the Somali Current, the Equatorial Undercurrent and the SMC. Years with anomalously saline high salinity cores are linked with the East Africa Coastal Current and the Somali Current winter convergence, and an anomalously strong Equatorial Undercurrent. Seasonal reversals that occur at the Somali Current and SMC junctions act as 'railroad switches' diverting water masses to different basins in the northern Indian Ocean. Interannual fluctuations of the Equatorial Undercurrent are linked to wind stress and El Nino

Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study

Background: Human genetic factors are important determinants of malaria risk. We investigated associations between multiple candidate polymorphisms—many related to the structure or function of red blood cells—and risk for severe Plasmodium falciparum malaria and its specific phenotypes, including cerebral malaria, severe malaria anaemia, and respiratory distress. Methods: We did a case-control study in Kilifi County, Kenya. We recruited as cases children presenting with severe malaria to the high-dependency ward of Kilifi County Hospital. We included as controls infants born in the local community between Aug 1, 2006, and Sept 30, 2010, who were part of a genetics study. We tested for associations between a range of candidate malaria-protective genes and risk for severe malaria and its specific phenotypes. We used a permutation approach to account for multiple comparisons between polymorphisms and severe malaria. We judged p values less than 0·005 significant for the primary analysis of the association between candidate genes and severe malaria. Findings: Between June 11, 1995, and June 12, 2008, 2244 children with severe malaria were recruited to the study, and 3949 infants were included as controls. Overall, 263 (12%) of 2244 children with severe malaria died in hospital, including 196 (16%) of 1233 with cerebral malaria. We investigated 121 polymorphisms in 70 candidate severe malaria-associated genes. We found significant associations between risk for severe malaria overall and polymorphisms in 15 genes or locations, of which most were related to red blood cells: ABO, ATP2B4, ARL14, CD40LG, FREM3, INPP4B, G6PD, HBA (both HBA1 and HBA2), HBB, IL10, LPHN2 (also known as ADGRL2), LOC727982, RPS6KL1, CAND1, and GNAS. Combined, these genetic associations accounted for 5·2% of the variance in risk for developing severe malaria among individuals in the general population. We confirmed established associations between severe malaria and sickle-cell trait (odds ratio [OR] 0·15, 95% CI 0·11–0·20; p=2·61 × 10−58), blood group O (0·74, 0·66–0·82; p=6·26 × 10−8), and –α3·7-thalassaemia (0·83, 0·76–0·90; p=2·06 × 10−6). We also found strong associations between overall risk of severe malaria and polymorphisms in both ATP2B4 (OR 0·76, 95% CI 0·63–0·92; p=0·001) and FREM3 (0·64, 0·53–0·79; p=3·18 × 10−14). The association with FREM3 could be accounted for by linkage disequilibrium with a complex structural mutation within the glycophorin gene region (comprising GYPA, GYPB, and GYPE) that encodes for the rare Dantu blood group antigen. Heterozygosity for Dantu was associated with risk for severe malaria (OR 0·57, 95% CI 0·49–0·68; p=3·22 × 10−11), as was homozygosity (0·26, 0·11–0·62; p=0·002). Interpretation: Both ATP2B4 and the Dantu blood group antigen are associated with the structure and function of red blood cells. ATP2B4 codes for plasma membrane calcium-transporting ATPase 4 (the major calcium pump on red blood cells) and the glycophorins are ligands for parasites to invade red blood cells. Future work should aim at uncovering the mechanisms by which these polymorphisms can result in severe malaria protection and investigate the implications of these associations for wider health. Funding: Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative

Postnatal depression across countries and cultures : a qualitative study

Background: Postnatal depression seems to be a universal condition with similar rates in different countries. However, anthropologists question the cross-cultural equivalence of depression, particularly at a life stage so influenced by cultural factors. Aims: To develop a qualitative method to explore whether postnatal depression is universally recognised, attributed and described and to enquire into people’s perceptions of remedies and services for morbid states of unhappiness within the context of local services. Method: The study took place in 15 centres in 11 countries and drew on three groups of informants: focus groups with new mothers, interviews with fathers and grandmothers, and interviews with health professionals.Textual analysis of these three groups was conducted separately in each centre and emergent themes compared across centres. Results: All centres described morbid unhappiness after childbirth comparable to postnatal depression but not all saw this as an illness remediable by health interventions. Conclusions: Although the findings of this study support the universality of a morbid state of unhappiness following childbirth, they also support concerns about the cross-cultural equivalence of postnatal depression as an illness requiring the intervention of health professionals; this has implications for future research

On the limits of sexual health literacy: Insights from Ugandan schoolgirls

This article makes the case that current conceptions of sexual health literacy have limited relevance to the Ugandan context because they assume that knowledge of unsafe sexual practices will lead to changes in behavior and lifestyle. Drawing on a longitudinal case study with 15 Ugandan schoolgirls in rural Uganda from August 2004 to September 2006, this study argues that despite being well-informed about the risks and responsibilities of sexual activity, poverty and sexual abuse severely constrained options for these young women. Although many believed in the value of abstaining from sexual activity until marriage, they engaged in transactional sex to pay for school fees, supplies, clothing, and food. Further, fear of sexual abuse, early pregnancy, and HIV–AIDS compromised attempts to embrace sexuality. The article concludes with implications of the study for research and policy on sexual health literacy in Uganda and other poorly resourced regions of the world

Risk of nontyphoidal Salmonella bacteraemia in African children is modified by STAT4

Nontyphoidal Salmonella (NTS) is a major cause of bacteraemia in Africa. The disease typically affects HIV-infected individuals and young children, causing substantial morbidity and mortality. Here we present a genome-wide association study (180 cases, 2677 controls) and replication analysis of NTS bacteraemia in Kenyan and Malawian children. We identify a locus in STAT4, rs13390936, associated with NTS bacteraemia. rs13390936 is a context-specific expression quantitative trait locus for STAT4 RNA expression, and individuals carrying the NTS-risk genotype demonstrate decreased interferon-gamma (IFN gamma) production in stimulated natural killer cells, and decreased circulating IFN gamma concentrations during acute NTS bacteraemia. The NTS-risk allele at rs13390936 is associated with protection against a range of autoimmune diseases. These data implicate interleukin-12-dependent IFN gamma-mediated immunity as a determinant of invasive NTS disease in African children, and highlight the shared genetic architecture of infectious and autoimmune disease.Peer reviewe

The World Starts With Me: A multilevel evaluation of a comprehensive sex education programme targeting adolescents in Uganda

<p>Abstract</p> <p>Background</p> <p>This paper evaluates the effect of the World Starts With Me (WSWM), a comprehensive sex education programme in secondary schools in Uganda. The aim of the present study was to assess the effects of WSWM on socio-cognitive determinants of safe sex behaviour (delay; condom use and non-coercive sex).</p> <p>Methods</p> <p>A survey was conducted both before and immediately after the intervention among students in intervention (<it>N </it>= 853) and comparison (<it>N </it>= 1011) groups. A mixed model repeated measures analysis was performed to assess the effectiveness of the WSWM programme on the main socio-cognitive determinants of safe sex behaviour at post-test. A similar post-hoc comparison was made between schools based on completeness and fidelity of implementation of WSWM.</p> <p>Results</p> <p>Significant positive effects of WSMW were found on beliefs regarding what could or could not prevent pregnancy, the perceived social norm towards delaying sexual intercourse, and the intention to delay sexual intercourse. Furthermore, significant positive effects of WSWM were found on attitudes, self-efficacy and intention towards condom use and on self-efficacy in dealing with sexual violence (pressure and force for unwanted sex). A reversed effect of intervention was found on knowledge scores relating to non-causes of HIV (petting, fondling and deep kissing). A follow-up comparison between intervention schools based on completeness of the programme implementation revealed that almost all significant positive effects disappeared for those schools that only implemented up to 7 out of 14 lessons. Another follow-up analysis on the basis of implementation fidelity showed that schools with a "partial" fidelity score yielded more significant positive effects than schools with a "full" fidelity of implementation score.</p> <p>Conclusions</p> <p>The study showed an intervention effect on a number of socio-cognitive determinants. However, the effectiveness of WSWM could be improved by giving more systematic attention to the context in which such a programme is to be implemented. Implications for the systematic development and implementation of school-based safe sex interventions in Uganda will be discussed.</p