Microbial Keratitis After Penetrating and Endothelial Keratoplasty

Introduction: The purpose of this study is to review the incidence, risk factors, and outcomes of bacterial and fungal keratitis after penetrating keratoplasty (PK) and endothelial keratoplasty (EK). Methods: The medical records at Wills Eye Hospital were reviewed for all cases of confirmed microbial keratitis following PK or EK performed between May 1, 2007 and September 1, 2018. Charts were examined to obtain demographic information, past ocular history, details of the microbial keratitis, and graft outcomes. Results:A total of 2100 transplants (1269 PK and 831 EK) were performed in 1864 eyes of 1601 patients. The incidence of microbial keratitis after PK (7.5%) was significantly higher than after EK (1.3%) (p Discussion: : Microbial keratitis is a relatively common occurrence in patients with prior keratoplasty, and particularly in eyes with prior PK or multiple prior transplants. Infection is an important cause of graft failure and further surgical intervention. To the best of our knowledge, this is the largest review of microbial keratitis in cases of prior PK, and the only review in eyes with prior EK

Inpatient COVID-19 mortality has reduced over time: Results from an observational cohort

BACKGROUND: The Covid-19 pandemic in the United Kingdom has seen two waves; the first starting in March 2020 and the second in late October 2020. It is not known whether outcomes for those admitted with severe Covid were different in the first and second waves. METHODS: The study population comprised all patients admitted to a 1,500-bed London Hospital Trust between March 2020 and March 2021, who tested positive for Covid-19 by PCR within 3-days of admissions. Primary outcome was death within 28-days of admission. Socio-demographics (age, sex, ethnicity), hypertension, diabetes, obesity, baseline physiological observations, CRP, neutrophil, chest x-ray abnormality, remdesivir and dexamethasone were incorporated as co-variates. Proportional subhazards models compared mortality risk between wave 1 and wave 2. Cox-proportional hazard model with propensity score adjustment were used to compare mortality in patients prescribed remdesivir and dexamethasone. RESULTS: There were 3,949 COVID-19 admissions, 3,195 hospital discharges and 733 deaths. There were notable differences in age, ethnicity, comorbidities, and admission disease severity between wave 1 and wave 2. Twenty-eight-day mortality was higher during wave 1 (26.1% versus 13.1%). Mortality risk adjusted for co-variates was significantly lower in wave 2 compared to wave 1 [adjSHR 0.49 (0.37, 0.65) p<0.001]. Analysis of treatment impact did not show statistically different effects of remdesivir [HR 0.84 (95%CI 0.65, 1.08), p = 0.17] or dexamethasone [HR 0.97 (95%CI 0.70, 1.35) p = 0.87]. CONCLUSION: There has been substantial improvements in COVID-19 mortality in the second wave, even accounting for demographics, comorbidity, and disease severity. Neither dexamethasone nor remdesivir appeared to be key explanatory factors, although there may be unmeasured confounding present

B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by autoimmune-mediated demyelination and neurodegeneration. The CNS of patients with MS harbors expanded clones of antigen-experienced B cells that reside in distinct compartments including the meninges, cerebrospinal fluid (CSF), and parenchyma. It is not understood whether this immune infiltrate initiates its development in the CNS or in peripheral tissues. B cells in the CSF can exchange with those in peripheral blood, implying that CNS B cells may have access to lymphoid tissue that may be the specific compartment(s) in which CNS-resident B cells encounter antigen and experience affinity maturation. Paired tissues were used to determine whether the B cells that populate the CNS mature in the draining cervical lymph nodes (CLNs). High-throughput sequencing of the antibody repertoire demonstrated that clonally expanded B cells were present in both compartments. Founding members of clones were more often found in the draining CLNs. More mature clonal members derived from these founders were observed in the draining CLNs and also in the CNS, including lesions. These data provide new evidence that B cells traffic freely across the tissue barrier, with the majority of B cell maturation occurring outside of the CNS in the secondary lymphoid tissue. Our study may aid in further defining the mechanisms of immunomodulatory therapies that either deplete circulating B cells or affect the intrathecal B cell compartment by inhibiting lymphocyte transmigration into the CNS

Genetic variation in the myeloperoxidase gene and cognitive impairment in Multiple Sclerosis

There is evidence that multiple sclerosis (MS) may associated with cognitive impairment in 25 to 40% of cases. The gene encoding myeloperoxidase (MPO) is involved in molecular pathways leading to β-amyloid deposition. We investigated a functional biallelic (G/A) polymorphism in the promoter region (-463) of the MPO gene in 465 patients affected by MS, divided into 204 cognitively normal and 261 impaired. We did not find significant differences in allele or genotype distributions between impaired and preserved MS patients. Our findings suggest that MPO polymorphism is not a risk factor for cognitive impairment in MS

Implementing treat-to-target urate-lowering therapy during hospitalisations for gout flares.

OBJECTIVES: To evaluate a strategy designed to optimise care and increase uptake of urate-lowering therapy (ULT) during hospitalisations for gout flares. METHODS: We conducted a prospective cohort study to evaluate a strategy that combined optimal in-hospital gout management with a nurse-led, follow-up appointment, followed by handover to primary care. Outcomes, including ULT initiation, urate target attainment, and re-hospitalisation rates, were compared between patients hospitalised for flares in the 12 months post-implementation and a retrospective cohort of hospitalised patients from 12 months pre-implementation. RESULTS: 119 and 108 patients, respectively, were hospitalised for gout flares in the 12 months pre- and post-implementation. For patients with 6-month follow-up data available (n = 94 and n = 97, respectively), the proportion newly initiated on ULT increased from 49.2% pre-implementation to 92.3% post-implementation (age/sex-adjusted odds ratio (aOR) 11.5; 95% confidence interval (CI) 4.36-30.5; p < 0.001). After implementation, more patients achieved a serum urate ≤360 micromol/L within 6 months of discharge (10.6% pre-implementation vs. 26.8% post-implementation; aOR 3.04; 95% CI 1.36-6.78; p = 0.007). The proportion of patients re-hospitalised for flares was 14.9% pre-implementation vs. 9.3% post-implementation (aOR 0.53, 95% CI 0.22 to 1.32; p = 0.18). CONCLUSION: Over 90% of patients were initiated on ULT after implementing a strategy to optimise hospital gout care. Despite increased initiation of ULT during flares, recurrent hospitalisations were not more frequent following implementation. Significant relative improvements in urate target attainment were observed post-implementation; however, for the majority of hospitalised gout patients to achieve urate targets, closer primary-secondary care integration is still needed

Simulating radiation damage in a bcc Fe system with embedded yttria nanoparticles

This paper was accepted for publication in the journal Journal of Nuclear Materials and the definitive published version is available at http://dx.doi.org/10.1016/j.jnucmat.2013.02.016We present a molecular dynamics study of radiation damage arising from nuclear collisions close to embedded yttria nanoparticles in a bcc Fe matrix. The model assumes a perfect body-centred cubic (bcc) iron matrix in which yttria nano-particles are embedded as a simplified model of an Oxide Dispersion Strengthened steel. It is shown how the nano-particles interact with nearby initiated collision cascades, through cascade blocking and absorbing energy. Fe defects accumulate at the interface both directly from the ballistic collisions and also by attraction of defects generated close by. The nano-particles generally remain intact during a radiation event and release absorbed energy over times longer than the ballistic phase of the collision cascade

Menopausal Status Modifies Breast Cancer Risk Associated with the Myeloperoxidase (MPO) G463A Polymorphism in Caucasian Women: A Meta-Analysis

BACKGROUND: Breast cancer susceptibility may be modulated partly through polymorphisms in oxidative enzymes, one of which is myeloperoxidase (MPO). Association of the low transcription activity variant allele A in the G463A polymorphism has been investigated for its association with breast cancer risk, considering the modifying effects of menopausal status and antioxidant intake levels of cases and controls. METHODOLOGY/PRINCIPAL FINDINGS: To obtain a more precise estimate of association using the odds ratio (OR), we performed a meta-analysis of 2,975 cases and 3,427 controls from three published articles of Caucasian populations living in the United States. Heterogeneity among studies was tested and sensitivity analysis was applied. The lower transcriptional activity AA genotype of MPO in the pre-menopausal population showed significantly reduced risk (OR 0.56-0.57, p = 0.03) in contrast to their post-menopausal counterparts which showed non-significant increased risk (OR 1.14; p = 0.34-0.36). High intake of antioxidants (OR 0.67-0.86, p = 0.04-0.05) and carotenoids (OR 0.68-0.86, p = 0.03-0.05) conferred significant protection in the women. Stratified by menopausal status, this effect was observed in pre-menopausal women especially those whose antioxidant intake was high (OR 0.42-0.69, p = 0.04). In post-menopausal women, effect of low intake elicited susceptibility (OR 1.19-1.67, p = 0.07-0.17) to breast cancer. CONCLUSIONS/SIGNIFICANCE: Based on a homogeneous Caucasian population, the MPO G463A polymorphism places post-menopausal women at risk for breast cancer, where this effect is modified by diet

Diferencias intra e inter individuales en inteligencia social de estudiantes portugueses

Social intelligence is a favorable condition for career decision-making and development. The social intelligence indices of Portuguese students in school years prior to a career transition are characterized and intra and interindividual differences are analyzed. Participants were 1095 students (552, 50.4% women) with a mean age of 14.78 years (SD = 1.86), in the 8th (542, 49.5%), 10th (295, 26.9%) and 11th (258, 23.6%) grades. The Cognitive Test of Social Intelligence (PCIS) was administered at two moments, six months apart. Results indicate that the 8th grade obtained higher average scores in Problem Solving, Motivation and Self-confidence (time 1), while the 10th grade obtained better results in Problem Solving, Motivation and Familiarity (time 2). Between the assessment moments, all school years register an increase in Problem Solving and Self-confidence in social situations. These results constitute favorable psychological conditions for the promotion of ethical questioning in career guidance interventions.A inteligência social constitui uma condição favorável à tomada de decisão e ao desenvolvimento vocacional. Este trabalho visa caracterizar os níveis de inteligência social, e analisar as diferenças intra e interindividuais, em alunos portugueses em anos de pré-transição vocacional. Participaram 1095 alunos (552, 50% mulheres), com uma média de idades de 14,78 anos (DP = 1,86), do 8º, 10º, e 11º níveis escolares. Administrou-se a Prova Cognitiva de Inteligência Social (PCIS), em dois momentos (T1 e T2), com seis meses de intervalo. Os resultados indicam que o 8º ano obteve resultados médios superiores, nos índices de Resolução de Problemas, Motivação e Autoconfiança (T1), enquanto o 10º ano obteve resultados superiores, em Resolução de Problemas, Motivação e Familiaridade (T2). Entre momentos de avaliação, registra-se, para todos os níveis escolares, um aumento em Resolução de Problemas e Autoconfiança em situações sociais. Estes resultados constituem condições psicológicas favoráveis à promoção do questionamento ético nas intervenções de orientação vocacional.La inteligencia social es una condición favorable para la toma de decisiones y el desarrollo de la carrera. Se caracterizan los niveles de inteligencia social y sus diferencias intra e interindividuales en estudiantes portugueses en transición pre-profesional. Participaron 1095 estudiantes (552, 50.4% mujeres) con una edad media de 14.78 (DE = 1.86), del 8º (542, 49,5%), 10º (295, 26.9%) y 11º (258, 23.6%) años escolares. Se administró la Prueba Cognitiva de Inteligencia Social (PCIS) en dos ocasiones, con seis meses de diferencia. Los resultados indican que los estudiantes del 8º grado obtuvieron puntajes medios más altos en la Resolución de Problemas, Motivación y Confianza (T1), mientras que los del 10º grado obtuvieron mejores resultados en la Resolución de Problemas, Motivación y Familiaridad (T2). Entre momentos de evaluación se registra, para todos los años, un aumento en la Resolución de Problemas y Confianza en situaciones sociales. Estos resultados constituyen condiciones psicológicas favorables a la promoción del cuestionamiento ético en las intervenciones de orientación profesional.Project coordinated by the fourth author and co-funded by the Foundation for Science and Technology and the Compete Program - PTDC/CPE-CED/098896/200