bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of HIV‐positive patients lost to follow‐up in African treatment programmes
Authors: Zürcher Kathrin , Mooser Anne , Anderegg Nanina , Tymejczyk Olga , Couvillon Margaret J. , Nash Denis , Egger Matthias ,   the IeDEA and MESH consortia
Published: January 2017

AbstractObjectiveThe retention of patients on antiretroviral therapy (ART) is key to achieving global targets in response to the HIV epidemic. Loss to follow‐up (LTFU) can be substantial, with unknown outcomes for patients lost to ART programmes. We examined changes in outcomes of patients LTFU over calendar time, assessed associations with other study and programme characteristics and investigated the relative success of different tracing methods.MethodsWe performed a systematic review and logistic random‐effects meta‐regression analysis of studies that traced adults or children who started ART and were LTFU in sub‐Saharan African treatment programmes. The primary outcome was mortality, and secondary outcomes were undocumented transfer to another programme, treatment interruption and the success of tracing attempts.ResultsWe included 32 eligible studies from 12 countries in sub‐Saharan Africa: 20 365 patients LTFU were traced, and 15 708 patients (77.1%) were found. Compared to telephone calls, tracing that included home visits increased the probability of success: the adjusted odds ratio (aOR) was 9.35 (95% confidence interval [CI] 1.85–47.31). The risk of death declined over calendar time (aOR per 1‐year increase 0.86, 95% CI 0.78–0.95), whereas undocumented transfers (aOR 1.13, 95% CI 0.96–1.34) and treatment interruptions (aOR 1.31, 95% CI 1.18–1.45) tended to increase. Mortality was lower in urban than in rural areas (aOR 0.59, 95% CI 0.36–0.98), but there was no difference in mortality between adults and children. The CD4 cell count at the start of ART increased over time.ConclusionsMortality among HIV‐positive patients who started ART in sub‐Saharan Africa, were lost to programmes and were successfully traced has declined substantially during the scale‐up of ART, probably driven by less severe immunodeficiency at the start of therapy.
TRATAMIENTO SUSTANTIVO DE LAS COSTAS EN LA JURISPRUDENCIA DE LA CORTE INTERAMERICANA DE DERECHOS HUMANOS
Authors: Leiva-Poveda Jorge 
Published: January 2017

<p>El presente trabajo es la primera parte de un minucioso y exhaustivo análisis de los diversos criterios en materia de costas desarrollados por la Corte Interamericana de Derechos Humanos, concretamente respecto de las consideraciones sustantivas sobre este tema, verbigracia: fundamento normativo, procedencia según tipos de representación, criterios para la cuantificación y exoneración de este extremo en las sentencias condenatorias de ese Tribunal.<br />El objetivo de este estudio es ofrecer a investigadores universitarios y a potenciales litigantes en el Sistema Interamericano, una sistematización de los criterios utilizados por el Tribunal Continental, que permita conocer el tratamiento práctico de este instituto, más allá de las consideraciones genéricas y puramente teóricas frecuentemente expuestas en distintos foros. Como se verá a continuación, este documento muestra que la falta de regulación normativa de las costas ha impactado negativamente la seguridad jurídica del sistema, dados los diversos abordajes que la Corte Interamericana ha establecido en sus resoluciones en lo que hace a este tema.</p>
Use of Selective Fungal Culture Media Increases Rates of Detection of Fungi in the Respiratory Tract of Cystic Fibrosis Patients
Authors: Hong Gina , Miller Heather B. , Allgood Sarah , Lee Richard , Lechtzin Noah , Zhang Sean X. 
Published: January 2017

ABSTRACT

The prevalence of fungi in the respiratory tracts of cystic fibrosis (CF) patients has risen. However, fungal surveillance is not routinely performed in most clinical centers in the United States, which may lead to an underestimation of the true prevalence of the problem. We conducted a prospective study comparing the rates of detection for clinically important fungi (CIF), defined as
Aspergillus
,
Scedosporium
, and
Trichosporon
species and
Exophiala dermatitidis
, in CF sputa using standard bacterial and selective fungal culture media, including Sabouraud dextrose agar with gentamicin (SDA), inhibitory mold agar (IMA), and brain heart infusion (BHI) agar with chloramphenicol and gentamicin. We described the prevalence of these fungi in an adult CF population. A total of 487 CF respiratory samples were collected from 211 unique participants. CIF were detected in 184 (37.8%) samples. Only 26.1% of CIF-positive samples were detected in bacterial culture medium, whereas greater rates of detection for fungi were found in IMA (65.8%;
P
< 0.001), in SDA (at 30°C, 64.7%;
P
= 0.005), and in BHI agar (63.0%;
P
= 0.001). The prevalences of
Aspergillus
and
Scedosporium
species were 40.8% and 5.2%, respectively, which are greater than the nationally reported prevalence numbers of 20.4% and 1.9%. Selective fungal culture media and longer incubation periods yielded higher rates of detection for CIF in CF sputum samples compared with that detected in bacterial culture medium, resulting in an underdetection of fungi by bacterial culture alone. The prevalence of fungi in CF may be better estimated by using selective fungal culture media, and this may translate to important clinical decisions.
Investigation of a Candida guilliermondii Pseudo-outbreak Reveals a Novel Source of Laboratory Contamination
Authors: Kirby James E. , Branch-Elliman Westyn , LaSalvia Mary T. , Longhi Lorinda , MacKechnie Matthew , Urman Grigoriy , Baldini Linda M. , Muriel Fatima R. , Sullivan Bernadette , Yassa David S. , Gold Howard S. , Wagner Trevor K. , Diekema Daniel J. , Wright Sharon B. 
Published: January 2017

ABSTRACT

Candida guilliermondii
was isolated from sterile specimens with increasing frequency over a several-month period despite a paucity of clinical evidence suggesting true
Candida
infections. However, a health care-associated outbreak was strongly considered due to growth patterns in the microbiology laboratory that were more consistent with true infection than environmental contamination. Therefore, an extensive investigation was performed to identify its cause. With the exception of one case, patient clinical courses were not consistent with true invasive fungal infections. Furthermore, no epidemiologic link between patients was identified. Rather, extensive environmental sampling revealed
C. guilliermondii
in an anaerobic holding jar in the clinical microbiology laboratory, where anaerobic plates were prereduced and held before inoculating specimens.
C. guilliermondii
grows poorly under anaerobic conditions. Thus, we postulate that anaerobic plates became intermittently contaminated. Passaging from intermittently contaminated anaerobic plates to primary quadrants of aerobic media during specimen planting yielded a colonial growth pattern typical for true specimen infection, thus obscuring laboratory contamination. A molecular evaluation of the
C. guilliermondii
isolates confirmed a common source for pseudo-outbreak cases but not for the one true infection. In line with Reason's model of organizational accidents, active and latent errors coincided to contribute to the pseudo-outbreak. These included organism factors (lack of growth in anaerobic conditions obscuring plate contamination), human factors (lack of strict adherence to plating order, leading to only intermittent observation of aerobic plate positivity), and laboratory factors (novel equipment). All of these variables should be considered when evaluating possible laboratory-based pseudo-outbreaks.
Dynamic Modulation of Expression of Lentiviral Restriction Factors in Primary CD4+T Cells following Simian Immunodeficiency Virus Infection
Authors: Rahmberg Andrew R. , Rajakumar Premeela A. , Billingsley James M. , Johnson R. Paul 
Published: January 2017

ABSTRACTAlthough multiple restriction factors have been shown to inhibit HIV/SIV replication, little is known about their expressionin vivo. Expression of 45 confirmed and putative HIV/SIV restriction factors was analyzed in CD4+T cells from peripheral blood and the jejunum in rhesus macaques, revealing distinct expression patterns in naive and memory subsets. In both peripheral blood and the jejunum, memory CD4+T cells expressed higher levels of multiple restriction factors compared to naive cells. However, relative to their expression in peripheral blood CD4+T cells, jejunal CCR5+CD4+T cells exhibited significantly lower expression of multiple restriction factors, includingAPOBEC3G,MX2, andTRIM25, which may contribute to the exquisite susceptibility of these cells to SIV infection.In vitrostimulation with anti-CD3/CD28 antibodies or type I interferon resulted in upregulation of distinct subsets of multiple restriction factors. After infection of rhesus macaques with SIVmac239, the expression of most confirmed and putative restriction factors substantially increased in all CD4+T cell memory subsets at the peak of acute infection. Jejunal CCR5+CD4+T cells exhibited the highest levels of SIV RNA, corresponding to the lower restriction factor expression in this subset relative to peripheral blood prior to infection. These results illustrate the dynamic modulation of confirmed and putative restriction factor expression by memory differentiation, stimulation, tissue microenvironment and SIV infection and suggest that differential expression of restriction factors may play a key role in modulating the susceptibility of different populations of CD4+T cells to lentiviral infection.IMPORTANCERestriction factors are genes that have evolved to provide intrinsic defense against viruses. HIV and simian immunodeficiency virus (SIV) target CD4+T cells. The baseline level of expressionin vivoand degree to which expression of restriction factors is modulated by conditions such as CD4+T cell differentiation, stimulation, tissue location, or SIV infection are currently poorly understood. We measured the expression of 45 confirmed and putative restriction factors in primary CD4+T cells from rhesus macaques under various conditions, finding dynamic changes in each state. Most dramatically, in acute SIV infection, the expression of almost all target genes analyzed increased. These are the first measurements of many of these confirmed and putative restriction factors in primary cells or during the early events after SIV infection and suggest that the level of expression of restriction factors may contribute to the differential susceptibility of CD4+T cells to SIV infection.
Azacytidine Treatment Inhibits the Progression of Herpes Stromal Keratitis by Enhancing Regulatory T Cell Function
Authors: Varanasi Siva Karthik , Reddy Pradeep B. J. , Bhela Siddheshvar , Jaggi Ujjaldeep , Gimenez Fernanda , Rouse Barry T. 
Published: January 2017

ABSTRACTOcular infection with herpes simplex virus 1 (HSV-1) sets off an inflammatory reaction in the cornea which leads to both virus clearance and chronic lesions that are orchestrated by CD4 T cells. Approaches that enhance the function of regulatory T cells (Treg) and dampen effector T cells can be effective to limit stromal keratitis (SK) lesion severity. In this report, we explore the novel approach of inhibiting DNA methyltransferase activity using 5-azacytidine (Aza; a cytosine analog) to limit HSV-1-induced ocular lesions. We show that therapy begun after infection when virus was no longer actively replicating resulted in a pronounced reduction in lesion severity, with markedly diminished numbers of T cells and nonlymphoid inflammatory cells, along with reduced cytokine mediators. The remaining inflammatory reactions had a change in the ratio of CD4 Foxp3+Treg to effector Th1 CD4 T cells in ocular lesions and lymphoid tissues, with Treg becoming predominant over the effectors. In addition, compared to those from control mice, Treg from Aza-treated mice showed more suppressor activityin vitroand expressed higher levels of activation molecules. Additionally, cells inducedin vitroin the presence of Aza showed epigenetic differences in the Treg-specific demethylated region (TSDR) of Foxp3 and were more stable when exposed to inflammatory cytokines. Our results show that therapy with Aza is an effective means of controlling a virus-induced inflammatory reaction and may act mainly by the effects on Treg.IMPORTANCEHSV-1 infection has been shown to initiate an inflammatory reaction in the cornea that leads to tissue damage and loss of vision. The inflammatory reaction is orchestrated by gamma interferon (IFN-γ)-secreting Th1 cells, and regulatory T cells play a protective role. Hence, novel therapeutics that can rebalance the ratio of regulatory T cells to effectors are a relevant issue. This study opens up a new avenue in treating HSV-induced SK lesions by increasing the stability and function of regulatory T cells using the DNA methyltransferase inhibitor 5-azacytidine (Aza). Aza increased the function of regulatory T cells, leading to enhanced suppressive activity and diminished lesions. Hence, therapy with Aza, which acts mainly by its effects on Treg, can be an effective means to control virus-induced inflammatory lesions.
Advances in Myeloid-Like Cell Origins and Functions in the Model OrganismDrosophila melanogaster
Authors: El Chamy Laure , Matt Nicolas , Reichhart Jean-Marc 
Published: January 2017

ABSTRACTDrosophilahas long served as a valuable model for deciphering many biological processes, including immune responses. Indeed, the genetic tractability of this organism is particularly suited for large-scale analyses. Studies performed during the last 3 decades have proven that the signaling pathways that regulate the innate immune response are conserved betweenDrosophilaand mammals. This review summarizes the recent advances onDrosophilahematopoiesis and immune cellular responses, with a particular emphasis on phagocytosis.
Incidence of delivery wire recapture failure with the Pipeline Flex device
Authors: Mooney Michael A , Moon Karam , Gross Bradley A , Ducruet Andrew F , Albuquerque Felipe C 
Published: January 2017

BackgroundThe Pipeline Flex embolization device has several advantages over the first-generation Pipeline embolization device (Covidien, Dublin, Republic of Ireland). Despite these advantages, we have observed frequent difficulty in recapturing the device's delivery wire.ObjectiveTo prospectively document the incidence of failure to recapture the delivery wire.MethodsWe tracked our experience in patients undergoing endovascular treatment with a flow-diverting stent for cerebral aneurysms between 1 May and 30 September 2016. Patient and lesion characteristics, device dimensions, and technical outcomes of delivery wire recapture were prospectively recorded for each device.ResultsEighteen devices were deployed in 15 patients by the senior author (FCA) during this period. Failure to recapture the delivery wire occurred in 10 of 18 (56%) cases. No adverse outcomes of delivery wire recapture failure were encountered in this series.ConclusionsThe incidence of delivery wire recapture failure with the Pipeline Flex device is high. Failure to recapture the delivery wire carries a theoretical risk of stent displacement when re-navigating across the device, and endovascular surgeons should be aware of this limitation. Authors are encouraged to report delivery wire recapture failure rates in future clinical series in which the Pipeline Flex device is used.
Preliminary validation of the Knee Inflammation MRI Scoring System (KIMRISS) for grading bone marrow lesions in osteoarthritis of the knee: data from the Osteoarthritis Initiative
Authors: Jaremko Jacob L , Jeffery Dean , Buller M , Wichuk Stephanie , McDougall Dave , Lambert Robert GW , Maksymowych Walter P 
Published: January 2017

ObjectiveBone marrow lesions (BML) are an MRI feature of osteoarthritis (OA) offering a potential target for therapy. We developed the Knee Inflammation MRI Scoring System (KIMRISS) to semiquantitatively score BML with high sensitivity to small changes, and compared feasibility, reliability and responsiveness versus the established MRI Osteoarthritis Knee Score (MOAKS).MethodsKIMRISS incorporates a web-based graphic overlay to facilitate detailed regional BML scoring. Observers scored BML by MOAKS and KIMRISS on sagittal fluid-sensitive sequences. Exercise 1 focused on interobserver reliability in Osteoarthritis Initiative observational data, with 4 readers (two experienced/two new to KIMRISS) scoring BML in 80 patients (baseline/1 year). Exercise 2 focused on responsiveness in an open-label trial of adalimumab, with 2 experienced readers scoring BML in 16 patients (baseline/12 weeks).ResultsScoring time was similar for KIMRISS and MOAKS. Interobserver reliability of KIMRISS was equivalent to MOAKS for BML status (ICC=0.84 vs 0.79), but consistently better than MOAKS for change in BML: Exercise 1 (ICC 0.82 vs 0.53), Exercise 2 (ICC 0.90 vs 0.32), and in new readers (0.87–0.92 vs 0.32–0.51). KIMRISS BML was more responsive than MOAKS BML: post-treatment BML improvement in Exercise 2 reached statistical significance for KIMRISS (SRM −0.69, p=0.015), but not MOAKS (SRM −0.12, p=0.625). KIMRISS BML also more strongly correlated to WOMAC scores than MOAKS BML (r=0.80 vs 0.58, p<0.05).ConclusionsKIMRISS BML scoring was highly feasible, and was more reliable for assessment of change and more responsive to change than MOAKS BML for expert and new readers.
Comparison of a CHOP‐LAsp‐based protocol with and without maintenance for canine multicentric lymphoma
Authors: Lautscham E. M. , Kessler M. , Ernst T. , Willimzig L. , Neiger R. 
Published: January 2017

The recommendation to treat canine lymphoma with a discontinuous protocol is based on small case numbers and mostly historic controls. This study compares duration of first remission (DFR) and overall survival time (ST) with a discontinuous protocol to the same protocol with maintenance phase. 408 dogs were treated with a CHOP‐LAsp (C=cyclophosphamide; H=hydroxydaunorubicin; O=Oncovin; P=prednisolone; LAsp=l‐asparaginase)‐based 28‐week induction protocol. In 75 dogs (cohort 1), this was followed by a maintenance phase consisting of vincristine, chlorambucil and actinomycin‐D with a total treatment duration of two years. In the subsequent 333 dogs, therapy was discontinued after induction (cohort 2). Median DFR and ST in cohort 1 were 216 and 375 days and 184 and 304 days in cohort 2. 6‐Month, 1‐year and 2‐year survival rates in cohort 1 were 73 per cent, 50 per cent, 24 per cent and 67 per cent, 39 per cent, 21 per cent in cohort 2. There was no significant difference between the two protocols (P=0.291 for ST, P=0.071 for DFR). On multivariate analysis, corticosteroid pretreatment (P=0.005), thrombocytopenia at diagnosis (P=0.019), stage (P=0.009), substage b at relapse (P<0.001), age (P=0.002) and incomplete or unstable remission necessitating intensification of therapy (P=0.004) were negatively correlated with ST in both groups. This study supports the use of a discontinuous protocol for canine multicentric lymphoma.
Analytical Homogenization for Dynamic Analysis of Composite Membranes with Circular Inclusions in Hexagonal Lattice Structures
Authors: Andrianov I. V. , Awrejcewicz J. , Markert B. , Starushenko G. A. 
Published: January 2017

Free vibrations of a composite membrane with a hexagonal lattice circular inclusion are investigated. We aim at a study of the lower frequency spectrum, i.e. it is assumed that the minimum space period of the eigenform is essentially larger than the characteristic dimension of the cell periodicity of the analyzed structure. This implies a possibility of approximating the composite structure by the homogenized one with effective characteristics. The latter is yielded by the multi-scale homogenization approach. Introduction of slow and fast variables yields both counterpart quasistatic local problem regarding the periodically repeated cell and global (homogenized) dynamic problem for homogeneous material with effective properties. The most complicated part of this approach concerns in finding a solution to the local problem. It has been analytically found in the presented paper for relatively large inclusion sizes using lubrication approach. The performed numerical validation of the obtained results shows high accuracy of the implemented approach.
Exercise training decreases NADPH oxidase activity and restores skeletal muscle mass in heart failure rats
Authors: Cunha Telma F. , Bechara Luiz R. G. , Bacurau Aline V. N. , Jannig Paulo R. , Voltarelli Vanessa A. , Dourado Paulo M. , Vasconcelos Andrea R. , Scavone Cristóforo , Ferreira Júlio C. B. , Brum Patricia C. 
Published: January 2017

We have recently demonstrated that NADPH oxidase hyperactivity, NF-κB activation, and increased p38 phosphorylation lead to atrophy of glycolytic muscle in heart failure (HF). Aerobic exercise training (AET) is an efficient strategy to counteract skeletal muscle atrophy in this syndrome. Therefore, we tested whether AET would regulate muscle redox balance and protein degradation by decreasing NADPH oxidase hyperactivity and reestablishing NF-κB signaling, p38 phosphorylation, and proteasome activity in plantaris muscle of myocardial infarcted-induced HF (MI) rats. Thirty-two male Wistar rats underwent MI or fictitious surgery (SHAM) and were randomly assigned into untrained (UNT) and trained (T; 8 wk of AET on treadmill) groups. AET prevented HF signals and skeletal muscle atrophy in MI-T, which showed an improved exercise tolerance, attenuated cardiac dysfunction and increased plantaris fiber cross-sectional area. To verify the role of inflammation and redox imbalance in triggering protein degradation, circulating TNF-α levels, NADPH oxidase profile, NF-κB signaling, p38 protein levels, and proteasome activity were assessed. MI-T showed a reduced TNF-α levels, NADPH oxidase activity, and Nox2 mRNA expression toward SHAM-UNT levels. The rescue of NADPH oxidase activity induced by AET in MI rats was paralleled by reducing nuclear binding activity of the NF-κB, p38 phosphorylation, atrogin-1, mRNA levels, and 26S chymotrypsin-like proteasome activity. Taken together our data provide evidence for AET improving plantaris redox homeostasis in HF associated with a decreased NADPH oxidase, redox-sensitive proteins activation, and proteasome hyperactivity further preventing atrophy. These data reinforce the role of AET as an efficient therapy for muscle wasting in HF. NEW & NOTEWORTHY This study demonstrates, for the first time, the contribution of aerobic exercise training (AET) in decreasing muscle NADPH oxidase activity associated with reduced reactive oxygen species production and systemic inflammation, which diminish NF-κB overactivation, p38 phosphorylation, and ubiquitin proteasome system hyperactivity. These molecular changes counteract plantaris atrophy in trained myocardial infarction-induced heart failure rats. Our data provide new evidence into how AET may regulate protein degradation and thus prevent skeletal muscle atrophy.