Visual dysfunction in Parkinson's disease

Patients with Parkinson's disease have a number of specific visual disturbances. These include changes in colour vision and contrast sensitivity and difficulties with complex visual tasks such as mental rotation and emotion recognition. We review changes in visual function at each stage of visual processing from retinal deficits, including contrast sensitivity and colour vision deficits to higher cortical processing impairments such as object and motion processing and neglect. We consider changes in visual function in patients with common Parkinson's disease-associated genetic mutations including GBA and LRRK2 We discuss the association between visual deficits and clinical features of Parkinson's disease such as rapid eye movement sleep behavioural disorder and the postural instability and gait disorder phenotype. We review the link between abnormal visual function and visual hallucinations, considering current models for mechanisms of visual hallucinations. Finally, we discuss the role of visuo-perceptual testing as a biomarker of disease and predictor of dementia in Parkinson's disease

The role of immune correlates of protection on the pathway to licensure, policy decision and use of group B Streptococcus vaccines for maternal immunization: considerations from World Health Organization consultations.

The development of a group B Streptococcus (GBS) vaccine for maternal immunization constitutes a global public health priority, to prevent GBS-associated early life invasive disease, stillbirth, premature birth, maternal sepsis, adverse neurodevelopmental consequences, and to reduce perinatal antibiotic use. Sample size requirements for the conduct of a randomized placebo-controlled trial to assess vaccine efficacy against the most relevant clinical endpoints, under conditions of appropriate ethical standards of care, constitute a significant obstacle on the pathway to vaccine availability. Alternatively, indirect evidence of protection based on immunologic data from vaccine and sero-epidemiological studies, complemented by data from opsonophagocytic in vitro assays and animal models, could be considered as pivotal data for licensure, with subsequent confirmation of effectiveness against disease outcomes in post-licensure evaluations. Based on discussions initiated by the World Health Organization we present key considerations about the potential role of correlates of protection towards an accelerated pathway for GBS vaccine licensure and wide scale use. Priority activities to support progress to regulatory and policy decision are outlined

Assessing cognitive dysfunction in Parkinson’s: An online tool to detect visuo-perceptual deficits

BACKGROUND: People with Parkinson’s disease (PD) who develop visuo-perceptual deficits are at higher risk of dementia, but we lack tests that detect subtle visuoperceptual deficits and can be performed by untrained personnel. Hallucinations are associated with cognitive impairment and typically involve perception of complex objects. Changes in object perception may therefore be a sensitive marker of visuo-perceptual deficits in PD. Objective: We developed an online platform to test visuo-perceptual function. We hypothesised that (1) visuo-perceptual deficits in PD could be detected using online tests, (2) object perception would be preferentially affected, and (3) these deficits would be caused by changes in perception rather than response bias. METHODS: We assessed 91 people with PD and 275 controls. Performance was compared using classical frequentist statistics. We then fitted a hierarchical Bayesian signal detection theory model to a subset of tasks. RESULTS: People with PD were worse than controls at object recognition, showing no deficits in other visuoperceptual tests. Specifically, they were worse at identifying skewed images (P <.0001); at detecting hidden objects (P 5.0039); at identifying objects in peripheral vision (P <.0001); and at detecting biological motion (P 5.0065). In contrast, people with PD were not worse at mental rotation or subjective size perception. Using signal detection modelling, we found this effect was driven by change in perceptual sensitivity rather than response bias. CONCLUSIONS: Online tests can detect visuo-perceptual defi- cits in people with PD, with object recognition particularly affected. Ultimately, visuo-perceptual tests may be developed to identify at-risk patients for clinical trials to slow PD dementia

Oportunidades perdidas na prevenção da sífilis congênita e da transmissão vertical do HIV

OBJECTIVE: To estimate the prevalence of missed opportunities for congenital syphilis and HIV prevention in pregnant women who had access to prenatal care and to assess factors associated to non-testing of these infections. METHODS: Cross-sectional study comprising a randomly selected sample of 2,145 puerperal women who were admitted in maternity hospitals for delivery or curettage and had attended at least one prenatal care visit, in Brazil between 1999 and 2000. No syphilis and/or anti-HIV testing during pregnancy was a marker for missed prevention opportunity. Women who were not tested for either or both were compared to those who had at least one syphilis and one anti-HIV testing performed during pregnancy (reference category). The prevalence of missed prevention opportunity was estimated for each category with 95% confidence intervals. Factors independently associated with missed prevention opportunity were assessed through multinomial logistic regression. RESULTS: The prevalence of missed prevention opportunity for syphilis or anti-HIV was 41.2% and 56.0%, respectively. The multivariate analysis showed that race/skin color (non-white), schooling (OBJETIVO: Estimar la prevalencia de oportunidad de pérdida de prevención de la sífilis y el HIV entre gestantes que tuvieron acceso al pre-natal y factores asociados con la no evaluación de estos agravios. MÉTODOS: Se realizó estudio transversal con muestra aleatoria de 2.145 puérperas de Brasil, 1999 y 2000 admitidas en maternidades para parto o curetaje y que habían realizado al menos una consulta de pre-natal. La no realización del examen de prueba para sífilis y/o anti-HIV durante el embarazo fue usada como marcador para oportunidad de pérdida de prevención. Las mujeres que realizaron sólo examen de sífilis o sólo examen de anti-HIV, o que no realizaron ninguno, fueron comparadas con las que realizaron los dos (categoría de referencia). La prevalencia de oportunidad de pérdida de prevención fue estimada para cada categoría, con intervalo de confianza de 95%. Los factores asociados con la oportunidad de pérdida de prevención fueron analizados por medio de regresión logística multinomial. RESULTADOS: La prevalencia de oportunidad de pérdida de prevención para la realización de la prueba de sífilis o anti-HIV fue de 41,2% e 56,0%, respectivamente. El análisis multivariado indicó que raza/color (no blanca), escolaridad (< 8 años de estudio), estado civil (soltera), renta < 3 salarios mínimos, relación sexual durante el embarazo, no haber tenido sífilis anterior al embarazo actual, realización de seis o mas consultas de pre-natal y la realización de la última visita antes del tercer trimestre de embarazo, estaban asociados con mayor riesgo de tener oportunidad de pérdida de prevención. Se observó una asociación negativa entre estado civil (soltera), lugar de realización de pre-natal (hospital) y la realización de la primera consulta pre-natal en el tercer trimestre con oportunidad de pérdida de prevención. CONCLUSIONES: Altos porcentajes de gestantes no evaluadas señalan fallas en la prevención y control de la infección por HIV y de la sífilis congénita en los servicios de salud. Las gestantes continúan interrumpiendo el cuidado pre-natal precozmente y no logran realizar los procedimientos de selección para HIV y sífilis.OBJETIVO: Estimar a prevalência de oportunidade perdida de prevenção a sífilis e HIV entre gestantes que tiveram acesso ao pré-natal e fatores associados a não-testagem para esses agravos. MÉTODOS: Estudo transversal com amostra aleatória de 2.145 puérperas do Brasil, 1999 e 2000 admitidas em maternidades para parto ou curetagem e que haviam realizado pelo menos uma consulta de pré-natal. A não-realização de exame de teste para sífilis e/ou anti-HIV durante a gravidez foi usada como marcador para oportunidade perdida de prevenção. Mulheres que realizaram apenas exame de sífilis ou apenas o anti-HIV, ou não realizaram nenhum, foram comparadas àquelas que realizaram os dois (categoria de referência). A prevalência de oportunidade perdida de prevenção foi estimada para cada categoria, com intervalo de confiança de 95%. Os fatores associados com oportunidade perdida de prevenção foram analisados por meio de regressão logística multinomial. RESULTADOS: A prevalência de oportunidade perdida de prevenção para a realização do teste de sífilis ou anti-HIV foi de 41,2% e 56,0%, respectivamente. A análise multivariada indicou que raça/cor (não branca), escolaridade (< 8 anos de estudo), estado civil (solteira), rend

Hospitalized Children with 2009 Pandemic Influenza A (H1N1): Comparison to Seasonal Influenza and Risk Factors for Admission to the ICU

BACKGROUND: Limited data are available describing the clinical presentation and risk factors for admission to the intensive care unit for children with 2009 H1N1 infection. METHODS: We conducted a retrospective chart review of all hospitalized children with 2009 influenza A (H1N1) and 2008-09 seasonal influenza at The Children's Hospital, Denver, Colorado. RESULTS: Of the 307 children identified with 2009 H1N1 infections, the median age was 6 years, 61% were male, and 66% had underlying medical conditions. Eighty children (26%) were admitted to the ICU. Thirty-two (40%) of the ICU patients required intubation and 17 (53%) of the intubated patients developed acute respiratory distress syndrome (ARDS). Four patients required extracorporeal membrane oxygenation. Eight (3%) of the hospitalized children died. Admission to the ICU was significantly associated with older age and underlying neurological condition. Compared to the 90 children admitted during the 2008-09 season, children admitted with 2009 H1N1 influenza were significantly older, had a shorter length of hospitalization, more use of antivirals, and a higher incidence of ARDS. CONCLUSIONS: Compared to the 2008-09 season, hospitalized children with 2009 H1N1 influenza were much older and had more severe respiratory disease. Among children hospitalized with 2009 H1N1 influenza, risk factors for admission to the ICU included older age and having an underlying neurological condition. Children under the age of 2 hospitalized with 2009 H1N1 influenza were significantly less likely to require ICU care compared to older hospitalized children

Success of a suicidal defense strategy against infection in a structured habitat

Pathogen infection often leads to the expression of virulence and host death when the host-pathogen symbiosis seems more beneficial for the pathogen. Previously proposed explanations have focused on the pathogen's side. In this work, we tested a hypothesis focused on the host strategy. If a member of a host population dies immediately upon infection aborting pathogen reproduction, it can protect the host population from secondary infections. We tested this "Suicidal Defense Against Infection" (SDAI) hypothesis by developing an experimental infection system that involves a huge number of bacteria as hosts and their virus as pathogen, which is linked to modeling and simulation. Our experiments and simulations demonstrate that a population with SDAI strategy is successful in the presence of spatial structure but fails in its absence. The infection results in emergence of pathogen mutants not inducing the host suicide in addition to host mutants resistant to the pathogen

Evaluation of a novel real-time PCR test based on the ssrA gene for the identification of group B streptococci in vaginal swabs

<p>Abstract</p> <p>Background</p> <p>Despite the implementation of prevention guidelines, early-onset group B streptococci (GBS) disease remains a cause of neonatal morbidity and mortality worldwide. Strategies to identify women who are at risk of transmitting GBS to their infant and the administration of intrapartum antibiotics have greatly reduced the incidence of neonatal GBS disease. However, there is a requirement for a rapid diagnostic test for GBS that can be carried out in a labour ward setting especially for women whose GBS colonisation status is unknown at the time of delivery. We report the design and evaluation of a real-time PCR test (<it>RiboSEQ </it>GBS test) for the identification of GBS in vaginal swabs from pregnant women.</p> <p>Methods</p> <p>The qualitative real-time PCR <it>RiboSEQ </it>GBS test was designed based on the bacterial <it>ssrA </it>gene and incorporates a competitive internal standard control. The analytical sensitivity of the test was established using crude lysate extracted from serial dilutions of overnight GBS culture using the IDI Lysis kit. Specificity studies were performed using DNA prepared from a panel of GBS strains, related streptococci and other species found in the genital tract environment. The <it>RiboSEQ </it>GBS test was evaluated on 159 vaginal swabs from pregnant women and compared with the GeneOhm™ StrepB Assay and culture for the identification of GBS.</p> <p>Results</p> <p>The <it>RiboSEQ </it>GBS test is specific and has an analytical sensitivity of 1-10 cell equivalents. The <it>RiboSEQ </it>GBS test was 96.4% sensitive and 95.8% specific compared to "gold standard" culture for the identification of GBS in vaginal swabs from pregnant women. In this study, the <it>RiboSEQ </it>GBS test performed slightly better than the commercial BD GeneOhm™ StrepB Assay which gave a sensitivity of 94.6% and a specificity of 89.6% compared to culture.</p> <p>Conclusion</p> <p>The <it>RiboSEQ </it>GBS test is a valuable method for the rapid, sensitive and specific detection of GBS in pregnant women. This study also validates the <it>ssrA </it>gene as a suitable and versatile target for nucleic acid-based diagnostic tests for bacterial pathogens.</p

Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE-NI): an extension of the STROBE statement for neonatal infection research.

Neonatal infections are estimated to account for a quarter of the 2·8 million annual neonatal deaths, as well as approximately 3% of all disability-adjusted life-years. Despite this burden, few data are available on incidence, aetiology, and outcomes, particularly regarding impairment. We aimed to develop guidelines for improved scientific reporting of observational neonatal infection studies, to increase comparability and to strengthen research in this area. This checklist, Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE- NI), is an extension of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement. STROBE-NI was developed following systematic reviews of published literature (1996-2015), compilation of more than 130 potential reporting recommendations, and circulation of a survey to relevant professionals worldwide, eliciting responses from 147 professionals from 37 countries. An international consensus meeting of 18 participants (with expertise in infectious diseases, neonatology, microbiology, epidemiology, and statistics) identified priority recommendations for reporting, additional to the STROBE statement. Implementation of these STROBE-NI recommendations, and linked checklist, aims to improve scientific reporting of neonatal infection studies, increasing data utility and allowing meta-analyses and pathogen-specific burden estimates to inform global policy and new interventions, including maternal vaccines