Pediatric Resident Knowledge, Confidence, and Experience in Transitioning Youth with Special Healthcare Needs

Background. The transition from pediatric to adult healthcare is vital to the 17% of adolescents with special healthcare needs (SHCN). Barriers to successful transition exist. The purpose of this study was to assess the baseline knowledge, confidence, and experience of pediatric residents in our state on transitioning adolescents with SHCN from pediatric to adult-oriented health care. Methods. An anonymous, voluntary, self-report survey was distributed electronically via Survey Monkey® to 2011-2012 pediatric residents in the state of Kansas (n = 39). Results. Of 39 pediatric residents, 21 (54%) completed the survey. Most (71%) had two or fewer adolescents with SHCN on their patient panel. Overall, the majority categorized their knowledge (71%) and experience (81%) transitioning adolescents with SHCN as minimal or very minimal. Conclusions. Pediatric residents report a general lack of knowledge, confidence, and experience in transitioning youth with SHCN. Additional training opportunities are needed to overcome the barriers in successful transition planning

Hubungan Antara Perhatian Orangtua Dan Hasil Belajar Pada Pembelajaran Tematik Integratif Siswa Kelas IV SD Negeri Kembangarum 2 Mranggen Demak

More less the studying result of students in 4th SD Negeri Kembangarum 2 Mranggen that influences some aspects, one of aspects is her parents?óÔé¼Ôäó not careless with them. Parents?óÔé¼Ôäó is constitute the?é?á first educator for children so that her parents?óÔé¼Ôäó has have responsibility to the studying result her children. The problem in this research contents is about Is there any correlation between of parents?óÔé¼Ôäó attention and the study result for thematic integrative learning in 4th SD Negeri Kembangarum 2 Mranggen Demak?. The hypothesis is that there is positive and significant correlation between of parents?óÔé¼Ôäó attention and the study result for thematic integrative learning in 4th SD Negeri Kembangarum 2 Mranggen Demak. The kind of this research is quantitative research. This research use correlation methode and submited the data use questionnaire and test. The colected data are analysed using product moment formula. The finding is that > on significancy level of 0,05. So the?é?á conclusion is there is positive and significant correlation between of parents?óÔé¼Ôäó attention and the study result for thematic integrative learning in 4th SD Negeri Kembangarum 2 Mranggen Demak

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in Pregnancy and Congenital Anomalies: Analysis of Linked Databases in Wales, Norway and Funen, Denmark

Background: Hypothesised associations between in utero exposure to selective serotonin reuptake inhibitors (SSRIs) and congenital anomalies, particularly congenital heart defects (CHD), remain controversial. We investigated the putative teratogenicity of SSRI prescription in the 91 days either side of first day of last menstrual period (LMP). Methods and Findings: Three population-based EUROCAT congenital anomaly registries- Norway (2004–2010), Wales (2000–2010) and Funen, Denmark (2000–2010)—were linked to the electronic healthcare databases holding prospectively collected prescription information for all pregnancies in the timeframes available. We included 519,117 deliveries, including foetuses terminated for congenital anomalies, with data covering pregnancy and the preceding quarter, including 462,641 with data covering pregnancy and one year either side. For SSRI exposures 91 days either side of LMP, separately and together, odds ratios with 95% confidence intervals (ORs, 95%CI) for all major anomalies were estimated. We also explored: pausing or discontinuing SSRIs preconception, confounding, high dose regimens, and, in Wales, diagnosis of depression. Results were combined in meta-analyses. SSRI prescription 91 days either side of LMP was associated with increased prevalence of severe congenital heart defects (CHD) (as defined by EUROCAT guide 1.3, 2005) (34/12,962 [0.26%] vs. 865/506,155 [0.17%] OR 1.50, 1.06–2.11), and the composite adverse outcome of 'anomaly or stillbirth' (473/12962, 3.65% vs. 15829/506,155, 3.13%, OR 1.13, 1.03–1.24). The increased prevalence of all major anomalies combined did not reach statistical significance (3.09% [400/12,962] vs. 2.67% [13,536/506,155] OR 1.09, 0.99–1.21). Adjusting for socio-economic status left ORs largely unchanged. The prevalence of anomalies and severe CHD was reduced when SSRI prescriptions were stopped or paused preconception, and increased when >1 prescription was recorded, but differences were not statistically significant. The dose-response relationship between severe CHD and SSRI dose (meta-regression OR 1.49, 1.12–1.97) was consistent with SSRI-exposure related risk. Analyses in Wales suggested no associations between anomalies and diagnosed depression. Conclusion: The additional absolute risk of teratogenesis associated with SSRIs, if causal, is small. However, the high prevalence of SSRI use augments its public health importance, justifying modifications to preconception care

External validation of a prediction model for estimating fat mass in Arab children and adolescents.

BACKGROUND/AIMS: Current childhood fat mass (FM) assessment techniques are not suitable for clinical and population-level adiposity assessment. A prediction model, which accurately estimates childhood FM using predictor variables of weight, height, age, sex and ethnicity, requires validation in Arab populations. We evaluate the model's performance in Kuwaiti, Lebanese and Moroccan children/adolescents. METHODS: Data from three cross-sectional studies on 471 individuals, aged 6-15 years, were obtained with complete information on predictors and the outcome of log transformed fat-free mass assessed by reference standard deuterium dilution (lnFFM). Country-specific predictive performance statistics of R2, calibration slope and calibration-in-the-large (measures the calibration/agreement between observed and predicted lnFFM with ideal values of 1 and 0, respectively) and root mean square error (RMSE) were quantified and pooled across countries via random-effects meta-analysis. FM estimates from bioimpedance were also available for Lebanese children and were compared to the reference standard. RESULTS: The model showed strong predictive ability in all populations. Pooled R2 calibration slope and calibration-in-the-large values on the original lnFFM scale were 87.73% (95% CI: 77.20, 98.26%), 0.95 (95% CI: 0.83, 1.08) and -0.03 (95% CI: -0.16, 0.11), respectively. Model intercepts were recalibrated in each country to improve accuracy; updated country-specific equations are provided. After recalibration, RMSEs on the FM scale were 1.3, 1.6 and 2.8 kg in Kuwait, Lebanon and Morocco, respectively. The RMSE from the model was lower than bioimpedance (2.4 kg) amongst Lebanese children. INTERPRETATION: The model explained a large proportion of the variance in FM, produced well-calibrated predictions and relatively low RMSEs in Arab settings. It predicted FM more accurately than bioimpedance, indicating its potential for implementation in clinical- and population-level settings, particularly in low- and middle-income countries

Analysis of pmpD Expression and PmpD Post-Translational Processing during the Life Cycle of Chlamydia trachomatis Serovars A, D, and L2

BACKGROUND: The polymorphic membrane protein D (PmpD) in Chlamydia is structurally similar to autotransporter proteins described in other bacteria and may be involved in cellular and humoral protective immunity against Chlamydia. The mechanism of PmpD post-translational processing and the role of its protein products in the pathogenesis of chlamydial infection have not been very well elucidated to date. METHODOLOGY/PRINCIPAL FINDINGS: Here we examined the expression and post-translational processing of the protein product of the pmpD gene during the life cycle of C. trachomatis serovars A, D, and L2. Each of these three serovars targets different human organs and tissues and encodes a different pmpD gene nucleotide sequence. Our quantitative real-time reverse transcription polymerase chain reaction results demonstrate that the pmpD gene is up-regulated at 12-24 hours after infection regardless of the Chlamydia serovar. This up-regulation is coincidental with the period of exponential growth and replication of reticulate bodies (RB) of Chlamydia and indicates a probable similarity in function of pmpD in serovars A, D, and L2 of Chlamydia. Using mass spectrometry analysis, we identified the protein products of post-translational processing of PmpD of C. trachomatis serovar L2 and propose a double pathway model for PmpD processing, with one cleavage site between the passenger and autotransporter domains and the other site in the middle of the passenger domain. Notably, when Chlamydia infected culture cells were subjected to low (28 degrees C) temperature, PmpD post-translational processing and secretion was found to be uninhibited in the resulting persistent infection. In addition, confocal microscopy of cells infected with Chlamydia confirms our earlier hypothesis that PmpD is secreted outside Chlamydia and its secretion increases with growth of the chlamydial inclusion. CONCLUSION/SIGNIFICANCE: The results of this current study involving multiple Chlamydia serovars support the general consensus that the pmpD gene is maximally expressed at mid infection and provide new information about PmpD as an autotransporter protein which is post-translationally processed and secreted outside Chlamydia during normal and low temperature induced persistent chlamydial infection

Identification of Estrogen Receptor Dimer Selective Ligands Reveals Growth-Inhibitory Effects on Cells That Co-Express ERα and ERβ

Estrogens play essential roles in the progression of mammary and prostatic diseases. The transcriptional effects of estrogens are transduced by two estrogen receptors, ERα and ERβ, which elicit opposing roles in regulating proliferation: ERα is proliferative while ERβ is anti-proliferative. Exogenous expression of ERβ in ERα-positive cancer cell lines inhibits cell proliferation in response to estrogen and reduces xenografted tumor growth in vivo, suggesting that ERβ might oppose ERα's proliferative effects via formation of ERα/β heterodimers. Despite biochemical and cellular evidence of ERα/β heterodimer formation in cells co-expressing both receptors, the biological roles of the ERα/β heterodimer remain to be elucidated. Here we report the identification of two phytoestrogens that selectively activate ERα/β heterodimers at specific concentrations using a cell-based, two-step high throughput small molecule screen for ER transcriptional activity and ER dimer selectivity. Using ERα/β heterodimer-selective ligands at defined concentrations, we demonstrate that ERα/β heterodimers are growth inhibitory in breast and prostate cells which co-express the two ER isoforms. Furthermore, using Automated Quantitative Analysis (AQUA) to examine nuclear expression of ERα and ERβ in human breast tissue microarrays, we demonstrate that ERα and ERβ are co-expressed in the same cells in breast tumors. The co-expression of ERα and ERβ in the same cells supports the possibility of ERα/β heterodimer formation at physio- and pathological conditions, further suggesting that targeting ERα/β heterodimers might be a novel therapeutic approach to the treatment of cancers which co-express ERα and ERβ

Attenuation of the Sensing Capabilities of PhoQ in Transition to Obligate Insect–Bacterial Association

Sodalis glossinidius, a maternally inherited endosymbiont of the tsetse fly, maintains genes encoding homologues of the PhoP-PhoQ two-component regulatory system. This two-component system has been extensively studied in facultative bacterial pathogens and is known to serve as an environmental magnesium sensor and a regulator of key virulence determinants. In the current study, we show that the inactivation of the response regulator, phoP, renders S. glossinidius sensitive to insect derived cationic antimicrobial peptides (AMPs). The resulting mutant strain displays reduced expression of genes involved in the structural modification of lipid A that facilitates resistance to AMPs. In addition, the inactivation of phoP alters the expression of type-III secretion system (TTSS) genes encoded within three distinct chromosomal regions, indicating that PhoP-PhoQ also serves as a master regulator of TTSS gene expression. In the absence of phoP, S. glossinidius is unable to superinfect either its natural tsetse fly host or a closely related hippoboscid louse fly. Furthermore, we show that the S. glossinidius PhoQ sensor kinase has undergone functional adaptations that result in a substantially diminished ability to sense ancestral signals. The loss of PhoQ's sensory capability is predicted to represent a novel adaptation to the static symbiotic lifestyle, allowing S. glossinidius to constitutively express genes that facilitate resistance to host derived AMPs