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191.
Katerina A. Christopoulos Susan Olender Andrea M. Lopez Helen-Maria Lekas Jessica Jaiswal Will Mellman Elvin Geng Kimberly A. Koester 《PLoS medicine》2015,12(8)
Background
Patients retained in HIV care but not on antiretroviral therapy (ART) represent an important part of the HIV care cascade in the United States. Even in an era of more tolerable and efficacious ART, decision making in regards to ART offer and uptake remains complex and calls for exploration of both patient and provider perspectives. We sought to understand reasons for lack of ART usage in patients meeting the Health Resources Services Administration definition of retention as well as what motivated HIV primary care appointment attendance in the absence of ART.Methods and Findings
We conducted a qualitative study consisting of 70 in-depth interviews with ART-naïve and ART-experienced patients off ART and their primary care providers in two urban safety-net HIV clinics in San Francisco and New York. Twenty patients and their providers were interviewed separately at baseline, and 15 dyads were interviewed again after at least 3 mo and another clinic visit in order to understand any ART use in the interim. We applied dyadic analysis to our data. Nearly all patients were willing to consider ART, and 40% of the sample went on ART, citing education on newer antiretroviral drugs, acceptance of HIV diagnosis, social support, and increased confidence in their ability to adhere as facilitators. However, the strength of the provider recommendation of ART played an important role. Many patients had internalized messages from providers that their health was too good to warrant ART. In addition, providers, while demonstrating patient-centered care through sensitivity to patients experiencing psychosocial instability, frequently muted the offer of ART, at times unintentionally. In the absence of ART, lab monitoring, provider relationships, access to social services, opiate pain medications, and acute symptoms motivated care. The main limitations of this study were that treatment as prevention was not explored in depth and that participants were recruited from academic HIV clinics in the US, making the findings most generalizable to this setting.Conclusions
Provider communication with regard to ART is a key focus for further exploration and intervention in order to increase ART uptake for those retained in HIV care. 相似文献192.
Rebecca A. Drummond Amanda L. Collar Muthulekha Swamydas Carlos A. Rodriguez Jean K. Lim Laura M. Mendez Danielle L. Fink Amy P. Hsu Bing Zhai Hatice Karauzum Constantinos M. Mikelis Stacey R. Rose Elise M. N. Ferre Lynne Yockey Kimberly Lemberg Hye Sun Kuehn Sergio D. Rosenzweig Xin Lin Prashant Chittiboina Sandip K. Datta Thomas H. Belhorn Eric T. Weimer Michelle L. Hernandez Tobias M. Hohl Douglas B. Kuhns Michail S. Lionakis 《PLoS pathogens》2015,11(12)
Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense. Humans deficient in the C-type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system (CNS). However, how CARD9 promotes protective antifungal immunity in the CNS remains unclear. Here, we show that a patient with CARD9 deficiency had impaired neutrophil accumulation and induction of neutrophil-recruiting CXC chemokines in the cerebrospinal fluid despite uncontrolled CNS Candida infection. We phenocopied the human susceptibility in Card9
-/- mice, which develop uncontrolled brain candidiasis with diminished neutrophil accumulation. The induction of neutrophil-recruiting CXC chemokines is significantly impaired in infected Card9
-/- brains, from both myeloid and resident glial cellular sources, whereas cell-intrinsic neutrophil chemotaxis is Card9-independent. Taken together, our data highlight the critical role of CARD9-dependent neutrophil trafficking into the CNS and provide novel insight into the CNS fungal susceptibility of CARD9-deficient humans. 相似文献
193.
Kimberly L. H. Carpenter Adrian Angold Nan-Kuei Chen William E. Copeland Pooja Gaur Kevin Pelphrey Allen W. Song Helen L. Egger 《PloS one》2015,10(1)
Objective
In this prospective, longitudinal study of young children, we examined whether a history of preschool generalized anxiety, separation anxiety, and/or social phobia is associated with amygdala-prefrontal dysregulation at school-age. As an exploratory analysis, we investigated whether distinct anxiety disorders differ in the patterns of this amygdala-prefrontal dysregulation.Methods
Participants were children taking part in a 5-year study of early childhood brain development and anxiety disorders. Preschool symptoms of generalized anxiety, separation anxiety, and social phobia were assessed with the Preschool Age Psychiatric Assessment (PAPA) in the first wave of the study when the children were between 2 and 5 years old. The PAPA was repeated at age 6. We conducted functional MRIs when the children were 5.5 to 9.5 year old to assess neural responses to viewing of angry and fearful faces.Results
A history of preschool social phobia predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces. Preschool generalized anxiety predicted less functional connectivity between the amygdala and dorsal prefrontal cortices in response to fearful faces. Finally, a history of preschool separation anxiety predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces and greater school-age functional connectivity between the amygdala and dorsal prefrontal cortices to angry faces.Conclusions
Our results suggest that there are enduring neurobiological effects associated with a history of preschool anxiety, which occur over-and-above the effect of subsequent emotional symptoms. Our results also provide preliminary evidence for the neurobiological differentiation of specific preschool anxiety disorders. 相似文献194.
Hajer Ayari-Jeridi Kimberly Moran Amel Chebbi Hédi Bouguila Imen Abbes Khaoula Charradi Amel Benammar-Elgaa?ed Arupa Ganguly 《PloS one》2015,10(1)
Retinoblastoma, an embryonic neoplasm of retinal origin, is the most common primary intraocular malignancy in children. Somatic inactivation of both alleles of the RB1 tumor suppressor gene in a retinal progenitor cell through diverse mechanisms including genetic and epigenetic modifications, is the crucial event in initiation of tumorigenesis in most cases of isolated unilateral retinoblastoma. We analyzed DNA from tumor tissue and from peripheral blood to determine the RB1 mutation status and seek correlations with clinical features of 37 unrelated cases of Tunisian origin with sporadic retinoblastoma. All cases were unilateral except one who presented with bilateral disease, in whom no germline coding sequence alteration was identified. A multi-step mutation scanning protocol identified bi-allelic inactivation of RB1 gene in 30 (81%) of the samples tested. A total of 7 novel mutations were identified. There were three tumors without any detectable mutation while a subset contained multiple mutations in RB1 gene. The latter group included tumors collected after treatment with chemotherapy. There were seven individuals with germline mutations and all presented with advanced stage of tumor. There was no difference in age of onset of RB based on the germline mutation status. Thus 20% of the individuals with sporadic unilateral RB in this series carried germline mutations and indicate the importance of genetic testing all children with sporadic retinoblastoma. These findings help to characterize the spectrum of mutations present in the Tunisian population and can improve genetic diagnosis of retinoblastoma. 相似文献
195.
Janice L. Farlow Hai Lin Laura Sauerbeck Dongbing Lai Daniel L. Koller Elizabeth Pugh Kurt Hetrick Hua Ling Rachel Kleinloog Pieter van der Vlies Patrick Deelen Morris A. Swertz Bon H. Verweij Luca Regli Gabriel J. E. Rinkel Ynte M. Ruigrok Kimberly Doheny Yunlong Liu Joseph Broderick Tatiana Foroud FIA Study Investigators 《PloS one》2015,10(3)
196.
197.
Kimberly M. Koporc Eric Strunz Cassandra Holloway David G. Addiss William Lin 《PLoS neglected tropical diseases》2015,9(12)
Background
Between 2007 and 2012, Children Without Worms (CWW) oversaw the Johnson & Johnson (J&J) donation of Vermox (mebendazole) for treatment of school-age children to control soil-transmitted helminthiasis (STH). To identify factors associated with on-time, delayed, or missed mass drug administration (MDA) interventions, and explore possible indicators for supply chain performance for drug donation programs, we reviewed program data for the 14 STH-endemic countries CWW supported during 2007–2012.Methodology
Data from drug applications, shipping records, and annual treatment reports were tracked using Microsoft Excel. Qualitative data from interviews with key personnel were used to provide additional context on the causes of delayed or missed MDAs. Four possible contributory factors to delayed or missed MDAs were considered: production, shipping, customs clearance, and miscellaneous in-country issues. Coverage rates were calculated by dividing the number of treatments administered by the number of children targeted during the MDA.Principal Findings
Of the approved requests for 78 MDAs, 54 MDAs (69%) were successfully implemented during or before the scheduled month. Ten MDAs (13%) were classified as delayed; seven of these were delayed by one month or less. An additional 14 MDAs (18%) were classified as missed. For the 64 on-time or delayed MDAs, the mean coverage was approximately 88%.Conclusions and Significance
To continue to assess the supply chain processes and identify areas for improvement, we identified four indicators or metrics for supply chain performance that can be applied across all neglected tropical disease (NTD) drug donation programs: (1) donor having available inventory to satisfy the country request for donation; (2) donor shipping the approved number of doses; (3) shipment arriving at the Central Medical Stores one month in advance of the scheduled MDA date; and (4) country programs implementing the MDA as scheduled. 相似文献198.
199.
Mylarappa Ningappa Juhoon So Joseph Glessner Chethan Ashokkumar Sarangarajan Ranganathan Jun Min Brandon W. Higgs Qing Sun Kimberly Haberman Lori Schmitt Silvia Vilarinho Pramod K. Mistry Gerard Vockley Anil Dhawan George K. Gittes Hakon Hakonarson Ronald Jaffe Shankar Subramaniam Donghun Shin Rakesh Sindhi 《PloS one》2015,10(9)
Background & Aims
Altered extrahepatic bile ducts, gut, and cardiovascular anomalies constitute the variable phenotype of biliary atresia (BA).Methods
To identify potential susceptibility loci, Caucasian children, normal (controls) and with BA (cases) at two US centers were compared at >550000 SNP loci. Systems biology analysis was carried out on the data. In order to validate a key gene identified in the analysis, biliary morphogenesis was evaluated in 2-5-day post-fertilization zebrafish embryos after morpholino-antisense oligonucleotide knockdown of the candidate gene ADP ribosylation factor-6 (ARF6, Mo-arf6).Results
Among 39 and 24 cases at centers 1 and 2, respectively, and 1907 controls, which clustered together on principal component analysis, the SNPs rs3126184 and rs10140366 in a 3’ flanking enhancer region for ARF6 demonstrated higher minor allele frequencies (MAF) in each cohort, and 63 combined cases, compared with controls (0.286 vs. 0.131, P = 5.94x10-7, OR 2.66; 0.286 vs. 0.13, P = 5.57x10-7, OR 2.66). Significance was enhanced in 77 total cases, which included 14 additional BA genotyped at rs3126184 only (p = 1.58x10-2, OR = 2.66). Pathway analysis of the 1000 top-ranked SNPs in CHP cases revealed enrichment of genes for EGF regulators (p<1 x10-7), ERK/MAPK and CREB canonical pathways (p<1 x10-34), and functional networks for cellular development and proliferation (p<1 x10-45), further supporting the role of EGFR-ARF6 signaling in BA. In zebrafish embryos, Mo-arf6 injection resulted in a sparse intrahepatic biliary network, several biliary epithelial cell defects, and poor bile excretion to the gall bladder compared with uninjected embryos. Biliary defects were reproduced with the EGFR-blocker AG1478 alone or with Mo-arf6 at lower doses of each agent and rescued with arf6 mRNA.Conclusions
The BA-associated SNPs identify a chromosome 14q21.3 susceptibility locus encompassing the ARF6 gene. arf6 knockdown in zebrafish implicates early biliary dysgenesis as a basis for BA, and also suggests a role for EGFR signaling in BA pathogenesis. 相似文献200.
Gaetane Nocturne Stephan Pavy Saida Boudaoud Raphaèle Seror Philippe Goupille Philippe Chanson Désirée van der Heijde Floris van Gaalen Francis Berenbaum Xavier Mariette Karine Briot Antoine Feydy Pascal Claudepierre Philippe Dieudé Joanne Nithitham Kimberly E. Taylor Lindsey A. Criswell Maxime Dougados Christian Roux Corinne Miceli-Richard 《PloS one》2015,10(8)