Asymptomatic neonatal herpes simplex virus infection in mice leads to long-term cognitive impairment.

Neonatal herpes simplex virus (nHSV) is a devastating infection impacting approximately 14,000 newborns globally each year. Infection is associated with high neurologic morbidity and mortality, making early intervention and treatment critical. Clinical outcomes of symptomatic nHSV infections are well-studied, but little is known about the frequency of, or outcomes following, sub-clinical or asymptomatic nHSV. Given the ubiquitous nature of HSV infection and frequency of asymptomatic shedding in adults, subclinical infections are underreported, yet could contribute to long-term neurological damage. To assess potential neurological morbidity associated with subclinical nHSV infection, we developed a low-dose (100 PFU) HSV infection protocol in neonatal C57BL/6 mice. At this dose, HSV DNA was detected in the brain by PCR but was not associated with acute clinical symptoms. However, months after initial inoculation with 100 PFU of HSV, we observed impaired mouse performance on a range of cognitive and memory performance tasks. Memory impairment was induced by infection with either HSV-1 or HSV-2 wild-type viruses, but not by a viral mutant lacking the autophagy-modulating Beclin-binding domain of the neurovirulence gene γ34.5. Retroviral expression of wild type γ34.5 gene led to behavioral pathology in mice, suggesting that γ34.5 expression may be sufficient to cause cognitive impairment. Maternal immunization and HSV-specific antibody treatment prevented offspring from developing neurological sequelae following nHSV-1 infection. Altogether, these results support the idea that subclinical neonatal infections may lead to cognitive decline in adulthood, with possible profound implications for research on human neurodegenerative disorders such as Alzheimer's Disease.

Diagnostic accuracy of prenatal ultrasound in coarctation of aorta: systematic review and individual participant data meta-analysis.

OBJECTIVE: To determine the diagnostic accuracy of prenatal ultrasound in detecting coarctation of the aorta (CoA). METHODS: An individual participant data meta-analysis was performed to report on the strength of association and diagnostic accuracy of different ultrasound signs in detecting CoA prenatally. MEDLINE, EMBASE and CINAHL were searched for studies published between January 2000 and November 2021. Inclusion criteria were fetuses with suspected isolated CoA, defined as ventricular and/or great vessel disproportion with right dominance on ultrasound assessment. Individual participant-level data were obtained by two leading teams. PRISMA-IPD and PRISMA-DTA guidelines were used for extracting data, and the QUADAS-2 tool was used for assessing quality and applicability. The reference standard was CoA, defined as narrowing of the aortic arch, diagnosed after birth. The most commonly evaluated parameters on ultrasound, both in B-mode and on Doppler, constituted the index test. Summary estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and likelihood ratios were computed using the hierarchical summary receiver-operating-characteristics model. RESULTS: The initial search yielded 72 studies, of which 25 met the inclusion criteria. Seventeen studies (640 fetuses) were included. On random-effects logistic regression analysis, tricuspid valve/mitral valve diameter ratio > 1.4 and > 1.6, aortic isthmus/arterial duct diameter ratio < 0.7, hypoplastic aortic arch (all P < 0.001), aortic isthmus diameter Z-score of < -2 in the sagittal (P = 0.003) and three-vessel-and-trachea (P < 0.001) views, pulmonary artery/ascending aorta diameter ratio > 1.4 (P = 0.048) and bidirectional flow at the foramen ovale (P = 0.012) were independently associated with CoA. Redundant foramen ovale was inversely associated with CoA (P = 0.037). Regarding diagnostic accuracy, tricuspid valve/mitral valve diameter ratio > 1.4 had a sensitivity of 72.6% (95% CI, 48.2-88.3%), specificity of 65.4% (95% CI, 46.9-80.2%) and DOR of 5.02 (95% CI, 1.82-13.9). The sensitivity and specificity values were, respectively, 75.0% (95% CI, 61.1-86.0%) and 39.7% (95% CI, 27.0-53.4%) for pulmonary artery/ascending aorta diameter ratio > 1.4, 47.8% (95% CI, 14.6-83.0%) and 87.6% (95% CI, 27.3-99.3%) for aortic isthmus diameter Z-score of < -2 in the sagittal view and 74.1% (95% CI, 58.0-85.6%) and 62.0% (95% CI, 41.6-78.9%) for aortic isthmus diameter Z-score of < -2 in the three-vessel-and-trachea view. Hypoplastic aortic arch had a sensitivity of 70.0% (95% CI, 42.0-88.6%), specificity of 91.3% (95% CI, 78.6-96.8%) and DOR of 24.9 (95% CI, 6.18-100). The diagnostic yield of prenatal ultrasound in detecting CoA did not change significantly when considering multiple categorical parameters. Five of the 11 evaluated continuous parameters were independently associated with CoA (all P < 0.001) but all had low-to-moderate diagnostic yield. CONCLUSIONS: Several prenatal ultrasound parameters are associated with an increased risk for postnatal CoA. However, diagnostic accuracy is only moderate, even when combinations of parameters are considered. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The centrality of community dynamics in the socio-economic recovery of devastated communities / El carácter central de la dinámica de la comunidad en la recuperación socio-económica de las comunidades devastadas

OBJECTIVE: To assess and explore the health and socio-economic outcomes of Jubilee, a community on the Caribbean island of Grenada hit by Hurricane Ivan in 2004 and to identify remaining barriers to recovery. METHODS: The assessment consisted of a mixed methods approach employing observations, household surveys, in-depth interviews and focus groups. RESULTS: Eighty-five per cent of the residents live in a single-family home type dwelling which is occupied by multiple families. Twenty-seven per cent of the respondents depended on a river or stream for water and 83% utilized an outdoor pit latrine. Construction accounted for 28% of the employment while 16% reported having no occupation. Public and private transportation was limited and 48% of the residents lived on less than one United States of America (US) dollar per day. Access to healthcare was reported by 89% and the prevalence of diabetes and hypertension was identified by 13% and 30% of the residents respectively. Social fragmentation within the community represents a barrier that keeps the community from developing common goals leading to full economic recovery. CONCLUSION: Jubilee has not fully recovered from the effects of Hurricane Ivan, but progress has been made in the reconstruction effort. These efforts have addressed the most immediate and basic needs of the community, mainly utility service infrastructure and home repairs. However, issues related to the community's economic recovery are still unresolved.

OBJETIVO: Evaluar y explorar la salud y los resultados socio-económicos de Jubilee, una comunidad de la isla caribeña de Granada, afectada por el huracán Iván en el 2004, e identificar los obstáculos que aún quedan para la recuperación. MÉTODOS: La evaluación consistió en un abordaje de métodos mezclados que empleaban la observación, encuestas domésticas, entrevistas detalladas, y grupos focales (grupos de discusión). RESULTADOS: El ochenta y cinco por ciento de los residentes viven en viviendas que son para una sola familia, pero están ocupadas por familias múltiples. El veinte por ciento de los encuestados dependían de un río o una corriente para obtener agua, y un 83% utilizaba letrinas de pozo exteriores. La construcción daba cuenta del 28% de los empleos, en tanto que el 16% reportó no tener ocupación. Tanto el transporte público como el privado se hallaban limitados, y el 48% de los residentes vivían con menos de un dólar americano (1 USD) por día. Acceso a la atención a la salud fue reportado por 89% y la prevalencia de la diabetes y la hipertensión fue identificada por el 13% y el 30% de los residentes, respectivamente. La fragmentación social dentro de la comunidad representa un obstáculo que impide que la comunidad desarrolle metas comunes, que conduzcan a una plena recuperación económica. CONCLUSIÓN: Jubilee no se ha recuperado totalmente de los efectos del huracán Iván, pero ha habido progreso en los esfuerzos por la reconstrucción. Estos esfuerzos han estado dirigidos a las necesidades básicas y más inmediatas de la comunidad, fundamentalmente a la reparación de las casas y las infraestructuras de servicios. Sin embargo, los problemas relacionados con la recuperación económica de la comunidad siguen aún sin solución.