Hormonal contraceptives and the acquisition of sexually transmitted infections: an updated systematic review.

BACKGROUND:Evidence suggests that some forms of hormonal contraception (HC) increase women's risk of non-HIV sexually transmitted infections (STIs), yet evidence has not been reviewed since 2008. We conducted an updated systematic review to incorporate studies published between January 2009 and June 2017 to examine the relationship between HCs and incident and/or recurrent STIs. METHODS:We searched PubMed and EMBASE to identify prospective studies comparing risk of Chlamydia trachomatis, Neisseria gonorrhoeae, human papillomavirus (HPV), herpes simplex virus type 2 (HSV-2), Treponema pallidum, or Trichomonas vaginalis, between women using HC vs. non-hormonal methods or no methods. We summarize results by type of STI and HC and study quality using an adapted Newcastle-Ottawa Quality Assessment Scale. RESULTS:Thirty articles met the inclusion criteria. Depo-medroxyprogesterone acetate (DMPA) reduces the risk of trichomoniasis (consistent evidence) and may increase the risk of HSV-2 (strong effect, few studies); inconclusive evidence exists for HPV, chlamydia, gonorrhea and syphilis. Data on oral contraceptive pills (OCPs; generally not differentiated whether combined or progestin-only pills) suggest use is associated with a reduced risk of trichomoniasis with inconclusive findings for HSV-2, HPV, chlamydia, gonorrhea, and syphilis. Very few studies included norethisterone enanthate (Net-En) injectable, implants or the levonorgestrel IUD. CONCLUSIONS:DMPA and OCPs reduce the risk of trichomoniasis and DMPA may increase the risk of HSV-2. However, the potential for confounding cannot be ruled out. Future studies should specify the type of injectable or OCP used to increase understanding of biological pathways; more research is needed on implants and hormonal IUDs

Assessing Plasmodium falciparum transmission in mosquito-feeding assays using quantitative PCR.

BACKGROUND: Evaluating the efficacy of transmission-blocking interventions relies on mosquito-feeding assays, with transmission typically assessed by microscopic identification of oocysts in mosquito midguts; however, microscopy has limited throughput, sensitivity and specificity. Where low prevalence and intensity mosquito infections occur, as observed during controlled human malaria infection studies or natural transmission, a reliable method for detection and quantification of low-level midgut infection is required. Here, a semi-automated, Taqman quantitative PCR (qPCR) assay sufficiently sensitive to detect a single-oocyst midgut infection is described. RESULTS: Extraction of genomic DNA from Anopheles stephensi midguts using a semi-automated extraction process was shown to have equivalent extraction efficiency to manual DNA extraction. An 18S Plasmodium falciparum qPCR assay was adapted for quantitative detection of P. falciparum midgut oocyst infection using synthetic DNA standards. The assay was validated for sensitivity and specificity, and the limit of detection was 0.7 genomes/µL (95% CI 0.4-1.6 genomes/µL). All microscopy-confirmed oocyst infected midgut samples were detected by qPCR, including all single-oocyst positive midguts. The genome number per oocyst was assessed 8-9 days after feeding assay using both qPCR and droplet digital PCR and was 3722 (IQR: 2951-5453) and 3490 (IQR: 2720-4182), respectively. CONCLUSIONS: This semi-automated qPCR method enables accurate detection of low-level P. falciparum oocyst infections in mosquito midguts, and may improve the sensitivity, specificity and throughput of assays used to evaluate candidate transmission-blocking interventions

Assessment of High-Sensitivity C-Reactive Protein Levels as Diagnostic Discriminator of Maturity-Onset Diabetes of the Young Due to HNF1A Mutations

OBJECTIVE: Despite the clinical importance of an accurate diagnosis in individuals with monogenic forms of diabetes, restricted access to genetic testing leaves many patients with undiagnosed diabetes. Recently, common variation near the HNF1 homeobox A (HNF1A) gene was shown to influence C-reactive protein levels in healthy adults. We hypothesized that serum levels of high-sensitivity C-reactive protein (hs-CRP) could represent a clinically useful biomarker for the identification of HNF1A mutations causing maturity-onset diabetes of the young (MODY). RESEARCH DESIGN AND METHODS: Serum hs-CRP was measured in subjects with HNF1A-MODY (n = 31), autoimmune diabetes (n = 316), type 2 diabetes (n = 240), and glucokinase (GCK) MODY (n = 24) and in nondiabetic individuals (n = 198). The discriminative accuracy of hs-CRP was evaluated through receiver operating characteristic (ROC) curve analysis, and performance was compared with standard diagnostic criteria. Our primary analyses excluded approximately 11% of subjects in whom the single available hs-CRP measurement was >10 mg/l. RESULTS: Geometric mean (SD range) hs-CRP levels were significantly lower (

Pengaruh Gaya Kepemimpinan Terhadap Kinerja Karyawan (Studi Pada Karyawan Tetap Service Center Panasonic Surabaya)

Research entitled “The Influence Leadership Style on Employee Performance” conducted on permanent employees at Service Center Panasonic Surabaya aims to explain at influence of leadership style partially on employee performance. The research method used is explanatory research, collecting data using questionnaires distributed to all permanent employees of Panasonic Service Center Surabaya which amounted to 48 respondents. Data analysis used in this research is descriptive analysis and multiple linear regression using SPSS 18 for windows. The results showed Democratic Leadership Style had the most significant effect on employee performance compared Authoritarian Leadership Style and Laissez-Faire Leadership Style

Low Frequency Variants in the Exons Only Encoding Isoform A of HNF1A Do Not Contribute to Susceptibility to Type 2 Diabetes

Background: There is considerable interest in the hypothesis that low frequency, intermediate penetrance variants contribute to the proportion of Type 2 Diabetes (T2D) susceptibility not attributable to the common variants uncovered through genome-wide association approaches. Genes previously implicated in monogenic and multifactorial forms of diabetes are obvious candidates in this respect. In this study, we focussed on exons 8-10 of the HNF1A gene since rare, penetrant mutations in these exons (which are only transcribed in selected HNF1A isoforms) are associated with a later age of diagnosis of Maturity onset diabetes of the young (MODY) than mutations in exons 1-7. The age of diagnosis in the subgroup of HNF1A-MODY individuals with exon 8-10 mutations overlaps with that of early multifactorial T2D, and we set out to test the hypothesis that these exons might also harbour low-frequency coding variants of intermediate penetrance that contribute to risk of multifactorial T2D. Methodology and principal findings: We performed targeted capillary resequencing of HNF1A exons 8-10 in 591 European T2D subjects enriched for genetic aetiology on the basis of an early age of diagnosis (≤ 45 years) and/or family history of T2D (≥ 1 affected sibling). PCR products were sequenced and compared to the published HNF1A sequence. We identified several variants (rs735396 [IVS9-24T>C], rs1169304 [IVS8+29T>C], c.1768+44C>T [IVS9+44C>T] and rd61953349 [c.1545G>A, p.T515T] but no novel non-synonymous coding variants were detected. Conclusions and significance: We conclude that low frequency, nonsynonymous coding variants in the terminal exons of HNF1A are unlikely to contribute to T2D-susceptibility in European samples. Nevertheless, the rationale for seeking low-frequency causal variants in genes known to contain rare, penetrant mutations remains strong and should motivate efforts to screen other genes in a similar fashion

Identifying inequities in maternal and child health through risk stratification to inform health systems strengthening in Northern Togo

ObjectiveIn Togo, substantial progress in maternal and child health is needed to reach global development goals. To better inform clinic and community-based health services, this study identifies factors associated with maternal and child health care utilization in the Kara region of Northern Togo. Methods We conducted a population-representative household survey of four health clinic catchment areas of 1,075 women of reproductive age in 2015. Multivariable logistic regression was used to model individual and structural factors associated with utilization of four maternal and child health services. Key outcomes were: facility-based delivery, maternal postnatal health check by a health professional within the first six weeks of birth, childhood vaccination, and receipt of malaria medication for febrile children under age five within 72 hours of symptom onset. Results 83 percent of women who gave birth in the last 2 years delivered at a health facility. In adjusted models, the strongest predictor of facility delivery in the rural catchment areas was proximity to a health center, with women living under three kilometers having 3.7 (95% CI 1.7, 7.9) times the odds of a facility birth. Only 11 percent of women received a health check by a health provider at any time in the postnatal period. Postnatal health checks were less likely for women in the poorest households and for women who resided in rural areas. Children of polygamous mothers had half the odds of receiving malaria medication for fever within 72 hours of symptom onset, while children with increased household wealth status had increased odds of childhood vaccination and receiving treatment for malaria. Conclusion Our analysis highlights the importance of risk stratification analysis to inform the delivery and scope of maternal and child health programs needed to reach those with the least access to care

An experimental human blood stage model for studying Plasmodium malariae infection

Background: Plasmodium malariae is considered a ‘minor’ malaria parasite, although its global disease burden is underappreciated. The aim of this study was to develop an induced blood stage malaria (IBSM) model of P. malariae to study parasite biology, diagnostics, and treatment. Methods: This clinical trial involved two healthy subjects who were intravenously inoculated with cryopreserved P. malariae-infected erythrocytes. Subjects were treated with artemether-lumefantrine following development of clinical symptoms. Prior to antimalarial therapy, mosquito feeding assays were performed to investigate transmission, and blood samples were collected for rapid diagnostic testing and parasite transcription profiling. Serial blood samples were collected for biomarker analysis. Results: Both subjects experienced symptoms and signs typical of early malaria. Parasitaemia was detected 7 days post-inoculation and increased until antimalarial treatment was initiated 25 and 21 days post-inoculation for Subject 1 and 2 respectively (peak parasitaemia levels were 174,182 and 50,291 parasites/mL respectively). The parasite clearance half-life following artemether-lumefantrine treatment was 6.7 hours. Mosquito transmission was observed for one subject, while in vivo parasite transcription and biomarkers were successfully profiled. Conclusions: An IBSM model of P. malariae has been successfully developed and may be used to study the biology, diagnostics, and treatment of this neglected malaria species

Combining Information from Common Type 2 Diabetes Risk Polymorphisms Improves Disease Prediction

BACKGROUND: A limited number of studies have assessed the risk of common diseases when combining information from several predisposing polymorphisms. In most cases, individual polymorphisms only moderately increase risk (~20%), and they are thought to be unhelpful in assessing individuals' risk clinically. The value of analyzing multiple alleles simultaneously is not well studied. This is often because, for any given disease, very few common risk alleles have been confirmed. METHODS AND FINDINGS: Three common variants (Lys23 of KCNJ11, Pro12 of PPARG, and the T allele at rs7903146 of TCF7L2) have been shown to predispose to type 2 diabetes mellitus across many large studies. Risk allele frequencies ranged from 0.30 to 0.88 in controls. To assess the combined effect of multiple susceptibility alleles, we genotyped these variants in a large case-control study (3,668 controls versus 2,409 cases). Individual allele odds ratios (ORs) ranged from 1.14 (95% confidence interval [CI], 1.05 to 1.23) to 1.48 (95% CI, 1.36 to 1.60). We found no evidence of gene-gene interaction, and the risks of multiple alleles were consistent with a multiplicative model. Each additional risk allele increased the odds of type 2 diabetes by 1.28 (95% CI, 1.21 to 1.35) times. Participants with all six risk alleles had an OR of 5.71 (95% CI, 1.15 to 28.3) compared to those with no risk alleles. The 8.1% of participants that were double-homozygous for the risk alleles at TCF7L2 and Pro12Ala had an OR of 3.16 (95% CI, 2.22 to 4.50), compared to 4.3% with no TCF7L2 risk alleles and either no or one Glu23Lys or Pro12Ala risk alleles. CONCLUSIONS: Combining information from several known common risk polymorphisms allows the identification of population subgroups with markedly differing risks of developing type 2 diabetes compared to those obtained using single polymorphisms. This approach may have a role in future preventative measures for common, polygenic diseases

SMN Protein Can Be Reliably Measured in Whole Blood with an Electrochemiluminescence (ECL) Immunoassay: Implications for Clinical Trials

Spinal muscular atrophy (SMA) is caused by defects in the survival motor neuron 1 (SMN1) gene that encodes survival motor neuron (SMN) protein. The majority of therapeutic approaches currently in clinical development for SMA aim to increase SMN protein expression and there is a need for sensitive methods able to quantify increases in SMN protein levels in accessible tissues. We have developed a sensitive electrochemiluminescence (ECL)-based immunoassay for measuring SMN protein in whole blood with a minimum volume requirement of 5μL. The SMN-ECL immunoassay enables accurate measurement of SMN in whole blood and other tissues. Using the assay, we measured SMN protein in whole blood from SMA patients and healthy controls and found that SMN protein levels were associated with SMN2 copy number and were greater in SMA patients with 4 copies, relative to those with 2 and 3 copies. SMN protein levels did not vary significantly in healthy individuals over a four-week period and were not affected by circadian rhythms. Almost half of the SMN protein was found in platelets. We show that SMN protein levels in C/C-allele mice, which model a mild form of SMA, were high in neonatal stage, decreased in the first few weeks after birth, and then remained stable throughout the adult stage. Importantly, SMN protein levels in the CNS correlated with SMN levels measured in whole blood of the C/C-allele mice. These findings have implications for the measurement of SMN protein induction in whole blood in response to SMN-upregulating therapy

Binary Contamination in the SEGUE sample: Effects on SSPP Determinations of Stellar Atmospheric Parameters

Using numerical modeling and a grid of synthetic spectra, we examine the effects that unresolved binaries have on the determination of various stellar atmospheric parameters for SEGUE targets measured using the SEGUE Stellar Parameter Pipeline (SSPP). To model undetected binaries that may be in the SEGUE sample, we use a variety of mass distributions for the primary and secondary stars in conjunction with empirically determined relationships for orbital parameters to determine the fraction of G-K dwarf stars, as defined by SDSS color cuts, that will be blended with a secondary companion. We focus on the G-K dwarf sample in SEGUE as it records the history of chemical enrichment in our galaxy. To determine the effect of the secondary on the spectroscopic parameters, we synthesize a grid of model spectra from 3275 to 7850 K (~0.1 to 1.0 \msun) and [Fe/H]=-0.5 to -2.5 from MARCS model atmospheres using TurboSpectrum. We analyze both "infinite" signal-to-noise ratio (S/N) models and degraded versions, at median S/N of 50, 25 and 10. By running individual and combined spectra (representing the binaries) through the SSPP, we determine that ~10% of the blended G-K dwarf pairs with S/N>=25 will have their atmospheric parameter determinations, in particular temperature and metallicity, noticeably affected by the presence of an undetected secondary. To account for the additional uncertainty from binary contamination at a S/N~10, uncertainties of ~140 K and ~0.17 dex in [Fe/H] must be added in quadrature to the published uncertainties of the SSPP. (Abridged)Comment: 68 pages, 20 figures, 9 table