Human Aquaporin 4281-300 Is the Immunodominant Linear Determinant in the Context of HLA-DRB1*03:01: Relevance for Diagnosing and Monitoring Patients With Neuromyelitis Optica

OBJECTIVE To identify linear determinants of human aquaporin 4 (hAQP4) in the context of HLA-DRB1*03:01. DESIGN In this controlled study with humanized experimental animals, HLA-DRB1*03:01 transgenic mice were immunized with whole-protein hAQP4 emulsified in complete Freund adjuvant. To test T-cell responses, lymph node cells and splenocytes were cultured in vitro with synthetic peptides 20 amino acids long that overlap by 10 amino acids across the entirety of hAQP4. The frequency of interferon γ, interleukin (IL) 17, granulocyte-macrophage colony-stimulating factor, and IL-5-secreting CD4+ T cells was determined by the enzyme-linked immunosorbent sport assay. Quantitative immunofluorescence microscopy was performed to determine whether hAQP4281-300 inhibits the binding of anti-hAQP4 recombinant antibody to surface full-length hAQP4. SETTING Academic neuroimmunology laboratories. SUBJECTS Humanized HLA-DRB1*03:01+/+ H-2b-/- transgenic mice on a B10 background. RESULTS Peptide hAQP4281-300 generated a significantly (P <.01) greater TH1 and TH17 immune response than any of the other linear peptides screened. This 20mer peptide contains 2 dominant immunogenic 15mer peptides. hAQP4284-298 induced predominantly an IL-17 and granulocyte-macrophage colony-stimulating factor TH cell phenotype, whereas hAQP4285-299 resulted in a higher frequency of TH1 cells. hAQP4281-300 did not interfere with recombinant AQP4 autoantibody binding. CONCLUSIONS hAQP4281-330 is the dominant linear immunogenic determinant of hAQP4 in the context of HLA-DRB1*03:01. Within hAQP4281-330 are 2 dominant immunogenic determinants that induce differential TH phenotypes. hAQP4 determinants identified in this study can serve as diagnostic biomarkers in patients with neuromyelitis optica and may facilitate the monitoring of treatment responses to pharmacotherapies.     

Bioactive triterpenoids from Atriplex lasiantha

Chromatographic purification of the ethyl acetate soluble fraction from the methanolic extract of Atriplex lasiantha yielded a new triterpenoid, 7β,15α,16β-trihydroxyolean-12-ene-28,30-dioic acid-3-O-β-d-xylopyranoside (1), along with two known triterpenoids, rotundifolioside I (2) and corchorusin B (3). Structures of the compounds 1–3 were elucidated through sophisticated NMR studies and high resolution mass spectrometry. The three isolates (1–3) were evaluated for antibacterial, antioxidant, and antiurease activities. Compound 2 exhibited the best antibacterial activity against Escherichiacoli with IC₅₀ value of 66.25 μg/ml, whereas, all the tested compounds exhibited antioxidant (IC₅₀ values of 68.7–75.4 μg/ml) and antiurease (IC₅₀ values of 25.5–49.3 μg/ml) activities, respectively.     

Knowledge, Attitude and Practice of Contraception in Rural Kashmir

Background

Human fertility is determined by many factors such as customs, morals and habits of social groups with regard to marital obligation of life. Acceptance of family planning methods varies within and between societies and there are many factors which are responsible for such variation at community, family and individual level. Socioeconomic environment, culture and education are few of them that play a vital role. Jammu and Kashmir state in general and Kashmir valley in particular is a Muslim-dominated population with traditionally a conservative society. Apart from family customs and influence of the elders, religious background has always been behind the passive resistance, or at the best indifference towards contraception. This study makes an attempt to assess the knowledge, attitude and practice of contraception in rural Kashmir.

Objective

To assess the knowledge, attitude and practice of contraception in rural Kashmir.

Study Design

Community-based Cross-Sectional study.

Study period

December 2006 to May 2008.

Participants

1900 currently married women in the age group of 15–49 years of age.

Setting

Rural households.

Methods

1900 currently married women, aged 15–49 years, selected by multi-stage random sampling technique from three districts of Kashmir valley who were interviewed at home using a pretested oral questionnaire. The assessment of various socioeconomic and other variables made as per the available standard procedures and scales.

Analysis

Percentage, Chi square test and Bivariate analysis.

Results

Knowledge of the contraceptive methods was fairly good especially for terminal methods i.e. female sterilization (97.7 %). Main source of information on contraception was obtained from mass media (60.4 %). Contraceptive practice was significantly related to number of living children, literacy, socioeconomic status and type of family.

Conclusion

What is needed is to promote and stress contraceptive methods and their advantages using mass media approach and to explore more and more participation of private sector.     

Evidence from district level inputs to improve quality of care for maternal and newborn health: interventions and findings

District level healthcare serves as a nexus between community and district level facilities. Inputs at the district level can be broadly divided into governance and accountability mechanisms; leadership and supervision; financial platforms; and information systems. This paper aims to evaluate the effectivness of district level inputs for imporving maternal and newborn health. We considered all available systematic reviews published before May 2013 on the pre-defined district level interventions and included 47 systematic reviews.Evidence suggests that supervision positively influenced provider’s practice, knowledge and client/provider satisfaction. Involving local opinion leaders to promote evidence-based practice improved compliance to the desired practice. Audit and feedback mechanisms and tele-medicine were found to be associated with improved immunization rates and mammogram uptake. User-directed financial schemes including maternal vouchers, user fee exemption and community based health insurance showed significant impact on maternal health service utilization with voucher schemes showing the most significant positive impact across all range of outcomes including antenatal care, skilled birth attendant, institutional delivery, complicated delivery and postnatal care. We found insufficient evidence to support or refute the use of electronic health record systems and telemedicine technology to improve maternal and newborn health specific outcomes.There is dearth of evidence on the effectiveness of district level inputs to improve maternal newborn health outcomes. Future studies should evaluate the impact of supervision and monitoring; electronic health record and tele-communication interventions in low-middle-income countries.     

Survivin Promoter Polymorphism (-31 C/G): A Genetic Risk Factor for Oral Cancer

Background: The polymorphism of survivin gene at its promoter region is one of the risk factors for OSCC . Thispolymorphism involves substitution of G for C (9904341), and it is present at the cell cycle dependent elements andcell cycle homology region repressor binding motif of promoter. This study aimed to find the association betweensurvivin -31C/G polymorphism and prevalence of OSCC in a subset of Pakistani population. Methodology: Thiscase-control study was conducted on 47 cases with and 101 healthy individuals with no family history of cancer. We usedpolymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) protocols. Results: The mostcommon site of oral cancer in our research was the buccal mucosa followed by tongue and the least one was the labialmucosa. The histological tumor type of all 47 cases was squamous cell type. In our research, stage II had the highestprevalence, accounting for 34% of patients, while the prevalence of stage I was 31% in the case group. The prevalenceof stage III and IV was 25% and 8%, respectively. The numbers of moderately and poorly differentiated tumors wereequal. We found a significant association between the CC genotype of survivin and OSCC prevalence (OR was 9.395at 95% CI: 1.0202-86.5251, p-value= 0.04). The GG genotype also showed significant P value (OR: 0.4709 with 95%CI: 0.2323- 0.9546 at a P VALUE of 0.0367). while no significant P value was noted for CG genotype (OR: 1.4317 with95% CI: 0.7513 -2.8658, p- value= 0.31). Conclusion: Survivin -31G/C polymorphism was strongly associated withOSCC prevalence. The C allele was more common in case group as compared to healthy individuals living in Pakistan.     

Association between leptin,obesity, hormonal interplay and male infertility

Male infertility is a major health problem worldwide. We investigated a possible association between leptin, obesity, hormonal interplay and male infertility. This cross‐sectional study of 313 males (178 infertile and 135 fertile) was carried out in 2017. The subjects were categorised by body mass index (BMI) and body fat percentage (BF%) into normal weight, overweight and obese. Significantly higher levels of BMI and BF% (p‐value < 0.001) and lower levels of FSH, LH, testosterone, and SHBG (p‐value < 0.001) were found in infertile males. However, no significant difference was observed in leptin levels (p‐value = 0.35). Leptin levels were significantly higher, and all the sex hormones were significantly lower (p‐value < 0.001) in obese subjects, whereas according to BF% only leptin, FSH and SHBG were significantly different. Leptin showed a significant positive correlation with BMI and BF% (p < 0.001). A strong positive link to serum testosterone was found with age, FSH, and LH (p < 0.001) and a negative one with BMI and BF% (p < 0.001). In mutivariable anlaysis, after adjusting for the other covariates, a significant association between FSH and testosterone (p‐value <0.001) was found. Serum leptin levels did not differ significantly in fertile and infertile groups, and no association was found with infertility. Furthermore, male obesity was found to be associated with infertility with the decrease in levels of sex hormones.     

Hypertension and tachycardia during adrenal manipulation

The purpose of this report is to draw attention to haemodynamic changes during intraoperative adrenal gland manipulation. Severe hypertension, ventricular tachycardia and subendocardial ischaemia occurred during the manipulation of adrenal gland in a patient who underwent live related donor nephrectomy. The patient responded well to intravenous lidocaine. Plasma norepinephrine concentration was elevated at the time of event. Further investigations after surgery excluded the possibility of phaeochromocytoma. In two years follow-up patient remains well. Suspicion for the cause of the event remains the excessive release of catecholamines with manipulation of a normal adrenal gland. The presence of halothane might have contributed to the arrythmia.     

Exploring the Challenges Facing Women with Disabilities in Exclusive Breastfeeding in a Metropolitan Area in Ghana: A Qualitative Study

Maternal and Child Health Journal - Whereas extant literature abounds with works on breastfeeding and its implications for child health and survival, there is very limited research on the...     

ATP induces mild hypothermia in rats but has a strikingly detrimental impact on focal cerebral ischemia

Ischemic stroke is a devastating condition lacking effective therapies. A promising approach to attenuate ischemic injury is mild hypothermia. Recent studies show that adenosine nucleotides can induce hypothermia in mice. The purpose of the present study was to test the hypothesis that adenosine 5′-triphosphate (ATP) induces mild hypothermia in rats and reduces ischemic brain injury. We found that intraperitoneal injections of ATP decreased core body temperature in a dose-dependent manner; the dose appropriate for mild hypothermia was 2 g/kg. When ATP-induced hypothermia was applied to stroke induced by middle cerebral artery occlusion, however, a neuroprotective effect was not observed. Instead, the infarct volume grew even larger in ATP-treated rats. This was accompanied by an increased rate of seizure events, hemorrhagic transformation, and higher mortality. Continuous monitoring of physiologic parameters revealed that ATP reduced heartbeat rate and blood pressure. ATP also increased blood glucose, accompanied by severe acidosis and hypocalcemia. Western blotting showed that ATP decreased levels of both phospho-Akt and total-Akt in the cortex. Our results reveal that, despite inducing hypothermia, ATP is not appropriate for protecting the brain against stroke. Instead, we show for the first time that ATP treatment is associated with exaggerated ischemic outcomes and dangerous systemic side effects.