Role of color doppler in the diagnosis of intra uterine growth restriction (IUGR)

Background: The purpose of our study was to evaluate the diagnostic efficacy of the pulsatility index (PI) and resistive index (RI) in uterine artery, umbilical artery and middle cerebral artery in the diagnosis of IUGR and prediction of adverse perinatal outcome.Methods: A total of 100 clinically suspected IUGR cases were enrolled in the study. A detailed history and examination was done, color doppler carried out serially every three weeks starting from 30 weeks till delivery, subsequently confirmation of fetal growth restriction (FGR) was done by assessing the newborn parameters for growth restriction.Results: Doppler measurement for uterine artery showed higher efficacy as compared to umbilical artery and middle cerebral artery findings. The uterine artery RI was found to be 84.6% sensitive and 82.9% specific even at 30 weeks. Uterine artery PI too showed a good diagnostic efficacy with an accuracy of 79%, a sensitivity of 76.9%, a specificity of 82.9%.Both PI and RI for uterine artery showed a relatively higher specificity.Conclusion: Here we concluded that once IUGR is suspected, Doppler velocimetry may be useful as a part of evaluation and uterine artery analysis identifies a subgroup with an increased risk for developing IUGR.

The Relationship between Economic Growth and Financial Sector Development in Indonesia

What is the relationship between the finance sector development and economic growth? This paper is intended to analyze a fewer number of important financial factors using econometric analysis on some selected indicators of Indonesian financial sector during the period 1988 - 2013. This paper then tries to check whether the identified financial factors development cause economic growth or economic growth causes financial factors development. The Granger – Causality test shows that no financial factor significantly causes economic growth; rather economic growth causes the financial sector development during the period. In general, the financial sector of Indonesia is being unstably deepened with response to the demand of economic growth since 1988

PKCε Overexpression, Irrespective of Genetic Background, Sensitizes Skin to UVR-Induced Development of Squamous-Cell Carcinomas

Chronic exposure to UVR is the major etiologic factor in the development of human skin cancers including squamous-cell carcinoma (SCC). We have previously shown that protein Kinase C epsilon (PKCε) transgenic mice on FVB/N background, which overexpress PKCε protein approximately eightfold over endogenous levels in epidermis, exhibit about threefold more sensitivity than wild-type littermates to UVR-induced development of SCC. To determine whether it is PKCε and not the mouse genetic background that determines susceptibility to UVR carcinogenesis, we cross-bred PKCε FVB/N transgenic mice with SKH-1 hairless mice to generate PKCε-overexpressing SKH-1 hairless mice. To evaluate the susceptibility of PKCε SKH-1 hairless transgenic mice to UVR carcinogenesis, the mice were exposed to UVR (1–2KJm−2) three times weekly from a bank of six kodacel-filtered FS40 sunlamps. As compared with the wild-type hairless mice, PKCε overexpression in SKH-1 hairless mice decreased the latency (12 weeks), whereas it increased the incidence (twofold) and multiplicity (fourfold) of SCC. The SKH hairless transgenic mice were observed to be as sensitive as FVB/N transgenic mice to UVR-induced development of SCC and expression of proliferative markers (proliferating cell nuclear antigen, signal transducers and activators of transcription 3, and extracellular signal-regulated kinase 1/2). The results indicate that PKCε level dictates susceptibility, irrespective of genetic background, to UVR carcinogenesis

Impact of Th1 CD4 Follicular Helper T Cell Skewing on Antibody Responses to an HIV-1 Vaccine in Rhesus Macaques.

Generating durable humoral immunity through vaccination depends upon effective interactions of follicular helper T (Tfh) cells with germinal center (GC) B cells. Th1 polarization of Tfh cells is an important process shaping the success of Tfh-GC B cell interactions by influencing costimulatory and cytokine-dependent Tfh help to B cells. However, the question remains as to whether adjuvant-dependent modulation of Tfh cells enhances HIV-1 vaccine-induced antienvelope (anti-Env) antibody responses. We investigated whether an HIV-1 vaccine platform designed to increase the number of Th1-polarized Tfh cells enhances the magnitude and quality of anti-Env antibodies. Utilizing a novel interferon-induced protein 10 (IP-10)-adjuvanted HIV-1 DNA prime followed by a monophosphoryl lipid A and QS-21 (MPLA+QS-21)-adjuvanted Env protein boost (DIP-10 PALFQ) in macaques, we observed higher anti-Env serum IgG titers with greater cross-clade reactivity, specificity for V1V2, and effector functions than in macaques primed with DNA lacking IP-10 and boosted with MPLA-plus-alum-adjuvanted Env protein (DPALFA) The DIP-10 PALFQ vaccine regimen elicited higher anti-Env IgG1 and lower IgG4 antibody levels in serum, showing for the first time that adjuvants can dramatically impact the IgG subclass profile in macaques. The DIP-10 PALFQ regimen also increased vaginal and rectal IgA antibodies to a greater extent. Within lymph nodes, we observed augmented GC B cell responses and the promotion of Th1 gene expression profiles in GC Tfh cells. The frequency of GC Tfh cells correlated with both the magnitude and avidity of anti-Env serum IgG. Together, these data suggest that adjuvant-induced stimulation of Th1-Tfh cells is an effective strategy for enhancing the magnitude and quality of anti-Env antibody responses.IMPORTANCE The results of the RV144 trial demonstrated that vaccination could prevent HIV transmission in humans and that longevity of anti-Env antibodies may be key to this protection. Efforts to improve upon the prime-boost vaccine regimen used in RV144 have indicated that booster immunizations can increase serum anti-Env antibody titers but only transiently. Poor antibody durability hampers efforts to develop an effective HIV-1 vaccine. This study was designed to identify the specific elements involved in the immunological mechanism necessary to produce robust HIV-1-specific antibodies in rhesus macaques. By clearly defining immune-mediated pathways that improve the magnitude and functionality of the anti-HIV-1 antibody response, we will have the foundation necessary for the rational development of an HIV-1 vaccine

The novel cyst nematode effector protein 30D08 targets host nuclear functions to alter gene expression in feeding sites

• Cyst nematodes deliver effector proteins into host cells to manipulate cellular processes and establish a metabolically hyperactive feeding site. The novel 30D08 effector protein is produced in the dorsal gland of parasitic juveniles, but its function has remained unknown. • We demonstrate that expression of 30D08 contributes to nematode parasitism, the protein is packaged into secretory granules, and is targeted to the plant nucleus where it interacts with SMU2 (homologue of suppressor of mec-8 and unc-52 2), an auxiliary spliceosomal protein. • We show that SMU2 is expressed in feeding sites and a smu2 mutant is less susceptible to nematode infection. In Arabidopsis expressing 30D08 under the SMU2 promoter, several genes were found to be alternatively spliced and the most abundant functional classes represented among differentially expressed genes were involved in RNA processing, transcription and binding, as well as in development, hormone and secondary metabolism representing key cellular processes known to be important for feeding site formation. • In conclusion, we demonstrated that the 30D08 effector is secreted from the nematode and targeted to the plant nucleus where its interaction with a host auxiliary spliceosomal protein may alter the pre-mRNA splicing and expression of a subset of genes important for feeding site formation

An artificial intelligence-based decision support system for early and accurate diagnosis of Parkinson’s Disease

People with Parkinson’s Disease (PD) might struggle with sadness, restlessness, or difficulty speaking, chewing, or swallowing. A diagnosis can be challenging because there is no specific PD test. It is diagnosed by doctors using a neurological exam and a medical history. This study proposes several Machine Learning (ML) algorithms to predict PD. These ML algorithms include K-Nearest Neighbor (KNN), Random Forest (RF), Support Vector Machine (SVM), and eXtreme Gradient Boosting algorithms (XGBoost), and their ensemble methods using publicly available PD dataset with 195 instances. The ML algorithms are used to predict and classify PD using homogeneous XGBoost ensemble techniques with reduced amount of entropy. Synthetic Minority Oversampling Technique (SMOTE) is utilized to handle imbalanced data, and 10-fold cross-validation is employed for evaluation. The results show that the homogeneous XGBoost-Random Forest outperforms other ML methods with 98% accuracy and Matthew’s correlation coefficient value 0.93

Novel Ancestry-Specific Primary Open-Angle Glaucoma Loci and Shared Biology With Vascular Mechanisms and Cell Proliferation

Primary open-angle glaucoma (POAG), a leading cause of irreversible blindness globally, shows disparity in prevalence and manifestations across ancestries. We perform meta-analysis across 15 biobanks (of the Global Biobank Meta-analysis Initiative) (n = 1,487,441: cases = 26,848) and merge with previous multi-ancestry studies, with the combined dataset representing the largest and most diverse POAG study to date (n = 1,478,037: cases = 46,325) and identify 17 novel significant loci, 5 of which were ancestry specific. Gene-enrichment and transcriptome-wide association analyses implicate vascular and cancer genes, a fifth of which are primary ciliary related. We perform an extensive statistical analysis of SIX6 and CDKN2B-AS1 loci in human GTEx data and across large electronic health records showing interaction between SIX6 gene and causal variants in the chr9p21.3 locus, with expression effect on CDKN2A/B. Our results suggest that some POAG risk variants may be ancestry specific, sex specific, or both, and support the contribution of genes involved in programmed cell death in POAG pathogenesis

Pharmacist provision of primary health care: a modified Delphi validation of pharmacists' competencies

<p>Abstract</p> <p>Background</p> <p>Pharmacists have expanded their roles and responsibilities as a result of primary health care reform. There is currently no consensus on the core competencies for pharmacists working in these evolving practices. The aim of this study was to develop and validate competencies for pharmacists' effective performance in these roles, and in so doing, document the perceived contribution of pharmacists providing collaborative primary health care services.</p> <p>Methods</p> <p>Using a modified Delphi process including assessing perception of the frequency and criticality of performing tasks, we validated competencies important to primary health care pharmacists practising across Canada.</p> <p>Results</p> <p>Ten key informants contributed to competency drafting; thirty-three expert pharmacists replied to a second round survey. The final primary health care pharmacist competencies consisted of 34 elements and 153 sub-elements organized in seven CanMeds-based domains. Highest importance rankings were allocated to the domains of care provider and professional, followed by communicator and collaborator, with the lower importance rankings relatively equally distributed across the manager, advocate and scholar domains.</p> <p>Conclusions</p> <p>Expert pharmacists working in primary health care estimated their most important responsibilities to be related to direct patient care. Competencies that underlie and are required for successful fulfillment of these patient care responsibilities, such as those related to communication, collaboration and professionalism were also highly ranked. These ranked competencies can be used to help pharmacists understand their potential roles in these evolving practices, to help other health care professionals learn about pharmacists' contributions to primary health care, to establish standards and performance indicators, and to prioritize supports and education to maximize effectiveness in this role.</p

Antigen-specific clonal expansion and cytolytic effector function of CD8+ T lymphocytes depend on the transcription factor Bcl11b

CD8+ T lymphocytes mediate the immune response to viruses, intracellular bacteria, protozoan parasites, and tumors. We provide evidence that the transcription factor Bcl11b/Ctip2 controls hallmark features of CD8+ T cell immunity, specifically antigen (Ag)-dependent clonal expansion and cytolytic activity. The reduced clonal expansion in the absence of Bcl11b was caused by altered proliferation during the expansion phase, with survival remaining unaffected. Two genes with critical roles in TCR signaling were deregulated in Bcl11b-deficient CD8+ T cells, CD8 coreceptor and Plcγ1, both of which may contribute to the impaired responsiveness. Bcl11b was found to bind the E8I, E8IV, and E8V, but not E8II or E8III, enhancers. Thus, Bcl11b is one of the transcription factors implicated in the maintenance of optimal CD8 coreceptor expression in peripheral CD8+ T cells through association with specific enhancers. Short-lived Klrg1hiCD127lo effector CD8+ T cells were formed during the course of infection in the absence of Bcl11b, albeit in smaller numbers, and their Ag-specific cytolytic activity on a per-cell basis was altered, which was associated with reduced granzyme B and perforin

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk