Advanced computational analysis of CD40LG variants in atypical X-linked hyper-IgM syndrome.

X-Linked Hyper-IgM Syndrome is caused by pathogenic variants in CD40LG. Three patients with atypical clinical and immunological features were identified with variants in CD40LG requiring further characterization. Flow cytometry was used to evaluate CD40L protein expression and binding capacity to a surrogate receptor, CD40-muIg. Though functional anomalies were observed, there was still a lack of clarity regarding the underlying mechanism. We developed structural models for wild-type and the three variants of CD40L protein observed in these patients (p. Lys143Asn, Leu225Ser and Met36Arg) to evaluate structural alterations by molecular mechanic calculations, and assess protein movement by molecular dynamic simulations. These studies demonstrate that functional analysis of variants of unknown significance in CD40LG can be supplemented by advanced computational analysis in atypical clinical contexts. These studies in combination identify the deleterious effects of these variants and potential mechanisms for protein dysfunction.

"Making the Mentally Ill Count", lessons from a Health and Demographic Surveillance System for people with mental and neurological disorders in the Kintampo districts of Ghana.

BACKGROUND: Persons with mental and neurological disorders (PMNDs) are among the most marginalised groups in developing countries, as they are socially excluded and overlooked in most developmental efforts. Due to high levels of stigma and other operational difficulties, PMNDs are often marginalised in routine enumeration exercises. Health and Demographic Surveillance System is an important public health research platform especially in countries that lacks reliable data systems, as it registers and monitor basic demographic and health events such as births, deaths and migration in a geographically defined population. This information is essential for policy development and resource distribution and service delivery. We aim to document the reasons for not counting PMNDs in our communities and demonstrate the usefulness of the Kintampo Health and Demographic Surveillance Systems (KHDSS) platform in counting PMNDs over time. We also documented strategies in providing vital information that helps in establishing the rights of PMNDs. METHODS: As a longitudinal study, psychiatric case register was established. Both quantitative and qualitative data collection techniques were used to solicit responses from stakeholders regarding the non-consideration of PMNDs as part of household membership in the study area. PMNDs were identified using the KHDSS and followed every 6 months. The "targeted" (actively searching for PMNDs) and "service provision" (providing medical treatment for PMNDs) approaches were adopted to enhance the identification of PMNDs. RESULTS: Stigma was the main reason cited for the non-counting of PMNDs in the area. Following a "targeted" and "service provision" approach, the number of PMNDs enrolled into the psychiatric case register went up to 68% in 2010; as against the previous levels of 49 and 54% in 2005 and 2008 respectively. The study highlights the intrinsic value of such an approach for social inclusion of PMNDs. CONCLUSIONS: Stigma against PMNDs was report in this study. We provided evidence that the KHDSS platform is useful for identification of PMNDs for service provision. The paper highlights evidence for policy formulation and implementation.

The experience of caregivers of people living with serious mental disorders: a study from rural Ghana.

BACKGROUND: Families and friends who give care to people with mental disorders (MDs) are affected in a variety of ways and degrees. The interplay of caregiving consequences: poverty, discrimination and stigma, lack of support from others, diminished social relationships, depression, emotional trauma, and poor or interrupted sleep are associated caregiver burden. OBJECTIVE: The burden of care on caregivers of people living with MDs was assessed in two districts located in the middle part of Ghana. Coping strategies and available support for caregivers of MDs were also assessed. DESIGN: A qualitative study was carried out involving 75 caregivers of participants with MDs registered within the Kintampo Health and Demographic Surveillance Systems. Data were gathered from caregivers about their experiences in providing care for their relations with MDs. RESULTS: Caregivers reported various degrees of burden, which included financial, social exclusion, emotional, depression, and inadequate time for other social responsibilities. Responsibilities around caregiving were mostly shared among close relatives but to a varying and limited extent. Religious prayers and the anticipation of cure were the main coping strategies adopted by caregivers, with expectation of new treatments being discovered. CONCLUSIONS: Emotional distress, stigma, financial burden, lack of support networks, social exclusion, health impact, and absence of decentralised mental health services were experienced by family caregivers. These findings highlight the need for interventions to support people with MDs and their caregivers. This might include policy development and implementation that will decentralise mental health care provision including psychosocial support for caregivers. This will ameliorate families' financial and emotional burden, facilitate early diagnosis and management, reduce travel time to seek care, and improve the quality of life of family caregivers of persons with MDs.

Neoplasia escamosa de la superficie ocular en pacientes con pterigión en Perú / Squamous neoplasia of the ocular surface in patients with pterygium in Peru

Objetivos. Estimar la frecuencia de neoplasia escamosa de la superficie ocular (NESO) no sospechada en pterigión, la precisión del diagnóstico clínico y las características demográficas y clínicas asociadas. Materiales y métodos. Se examinaron los informes histopatológicos de los pacientes con diagnóstico clínico de pterigión y/o NESO que fueron quirúrgicamente tratados entre marzo de 2009 y diciembre de 2012 en el Instituto Nacional de Oftalmología en Lima, Perú. La precisión del diagnóstico clínico para identificar la NESO se evaluó mediante la sensibilidad, especificidad y los cocientes de probabilidad. Se realizaron modelos de regresión log-log negativos para identificar las características demográficas y clínicas asociadas con un aumento de las probabilidades de diagnosticar NESO. Resultados. Se examinaron 3021 informes de histopatología. La frecuencia de NESO no sospechada en pterigión fue de 0,65%. El diagnóstico clínico presentó una sensibilidad del 85%, una especificidad del 99%, un cociente de probabilidad positiva de 111,89 y un cociente probabilidad negativa de 0,15. Las características asociadas fueron el sexo masculino (OR 1,15; IC 95%:1,01-1,30), pacientes de 61 a 80 años (OR 1,54; IC 95%: 1,28-1,85), ≥ de 81 años (OR 3,10; IC 95%: 2,09-4,58), pacientes con lesiones recurrentes (OR 1,59; IC 95%: 1,03-2,46) y lesiones en el lado temporal (OR 3,57; IC 95%: 2,63-4,85) presentaron mayor probabilidad de NESO. Conclusiones. Se encontró una baja frecuencia de NESO no sospechada, sin embargo, es recomendable realizar el estudio histopatológico de forma rutinaria para evitar diagnósticos erróneos de NESO como pterigión. (AU)

Objectives. To estimate the frequency of unsuspected ocular surface squamous neoplasia (OSSN) in pterygium, the accuracy of clinical diagnosis, and associated demographic and clinical characteristics. Materials and methods. We reviewed histopathological reports of patients with a clinical diagnosis of pterygium and/or OSSN who were surgically treated between March 2009 and December 2012 at the National Eye Institute in Lima, Peru. The accuracy of the clinical diagnosis of OSSN was assessed by sensitivity, specificity, and likelihood ratios. Models of negative log-log regression were performed to identify demographic and clinical characteristics associated with increased odds of diagnosing OSSN. Results. 3,021 histopathological reports were reviewed. The frequency of unsuspected OSSN in pterygium was 0.65%. Clinical diagnosis had a sensitivity of 85%, a specificity of 99%, a positive likelihood ratio of 111.89, and a negative likelihood ratio of 0.15. Associated characteristics were male gender (OR =1.15; 95% CI: 1.01 to 1.30), age group of 61- 80 years (OR = 1.54, 95% CI: 1.28 to 1.85) ≥ 81 years (OR = 3.10; 95% CI: 2.09 to 4.58), presence of recurrent lesions (OR = 1.59; 95% CI: 1.03 to 2.46) and temporal location lesions (OR = 3.57; 95% CI: 2.63 to 4.85). These characteristics were associated with a greater likelihood of OSSN. Conclusions. A low frequency of unsuspected OSSN was found; however, it is recommended to routinely perform histopathology studies to avoid misdiagnosis of OSSN as pterygium. (AU)