Source-based morphometry reveals structural brain pattern abnormalities in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11DS) is the most frequently occurring microdeletion in humans. It is associated with a significant impact on brain structure, including prominent reductions in gray matter volume (GMV), and neuropsychiatric manifestations, including cognitive impairment and psychosis. It is unclear whether GMV alterations in 22q11DS occur according to distinct structural patterns. Then, 783 participants (470 with 22q11DS: 51% females, mean age [SD] 18.2 [9.2]; and 313 typically developing [TD] controls: 46% females, mean age 18.0 [8.6]) from 13 datasets were included in the present study. We segmented structural T1-weighted brain MRI scans and extracted GMV images, which were then utilized in a novel source-based morphometry (SBM) pipeline (SS-Detect) to generate structural brain patterns (SBPs) that capture co-varying GMV. We investigated the impact of the 22q11.2 deletion, deletion size, intelligence quotient, and psychosis on the SBPs. Seventeen GMV-SBPs were derived, which provided spatial patterns of GMV covariance associated with a quantitative metric (i.e., loading score) for analysis. Patterns of topographically widespread differences in GMV covariance, including the cerebellum, discriminated individuals with 22q11DS from healthy controls. The spatial extents of the SBPs that revealed disparities between individuals with 22q11DS and controls were consistent with the findings of the univariate voxel-based morphometry analysis. Larger deletion size was associated with significantly lower GMV in frontal and occipital SBPs; however, history of psychosis did not show a strong relationship with these covariance patterns. 22q11DS is associated with distinct structural abnormalities captured by topographical GMV covariance patterns that include the cerebellum. Findings indicate that structural anomalies in 22q11DS manifest in a nonrandom manner and in distinct covarying anatomical patterns, rather than a diffuse global process. These SBP abnormalities converge with previously reported cortical surface area abnormalities, suggesting disturbances of early neurodevelopment as the most likely underlying mechanism.

Including the Household: Individual, Community and Household Factors Affecting Antiretroviral Therapy Adherence After ART Initiation in Cape Town, South Africa.

Antiretroviral therapy (ART) adherence is crucial for health outcomes of people living with HIV (PLHIV), influenced by a complex interplay of individual, community, and household factors. This article focuses on the influence of household factors, as well as individual and community factors, on ART adherence among PLHIV in Cape Town who have recently initiated ART. Baseline data for a cluster-randomized controlled trial were collected from 316 PLHIV in 12 districts in Cape Town between 6th May 2021 and 22nd May 2022. Zero-inflated Poisson models, with cluster-adjusted standard errors, were used to analyse the association between individual, household, and community factors and ART adherence measures. At the household-level, household support was associated with both better self-rated adherence (exp(ß) = 0.81, z = - 4.68, p < 0.001) and fewer days when pills were missed (exp(ß) = 0.65, z = - 2.92, p = 0.003). Psychological violence (exp(ß) = 1.37, z = 1.97, p = 0.05) and higher household asset scores (exp(ß) = 1.29, z = - 2.83, p = 0.05) were weakly associated with poorer ART adherence. At the individual-level, male gender (exp(ß) = 1.37, z = 3.95, p < 0.001) and reinitiating ART (exp(ß) = 1.35, z = 3.64, p < 0.001) were associated with worse self-rated ART adherence; higher education levels (exp(ß) = 0.30 times, z = - 3.75, p < 0.001) and better HIV knowledge (exp(ß) = 0.28, z = - 2.83, p = 0.005) were associated with fewer days where pills were missed. At the community-level, community stigma was associated with worse self-rated ART adherence (exp(ß) = 1.24, z = 3.01, p = 0.003). When designing interventions to improve ART adherence, household, individual and community factors should all be considered, particularly in addressing gender-based disparities, reducing stigma, tackling violence, and enhancing household support.Clinical Trial Number: Pan African Clinical Trial Registry, PACTR201906476052236. Registered on 24 June 2019.

RESUMEN: La adherencia a la terapia antirretroviral (TAR) es crucial para los resultados de salud de las personas que viven con el VIH (PLHIV), influenciada por una compleja interacción de factores individuales, comunitarios y del hogar. Este artículo se centra en la influencia de los factores del hogar, individuales y comunitarios en la adherencia al TAR entre personas que iniciaron recientemente el TAR en Ciudad del Cabo. Se recopilaron datos de referencia para un ensayo de control aleatorio por grupos de 316 PLHIV en 12 distritos de Ciudad del Cabo entre el 6 de mayo de 2021 y el 22 de mayo de 2022. Se utilizaron modelos de Poisson inflados a cero, con errores estándar ajustados por conglomerado para estudiar la asociación entre factores individuales, del hogar o comunitarios con dos medidas de adhesión al TAR: por un lado la auto declaración de adhesión, y por otro la cantidad de días en que se olvidó de tomar la medicina en los últimos 4 días. A nivel del hogar, el apoyo del hogar se asoció con una mejor adherencia auto declarada (exp(ß) = 0.81, z = − 4.68, p < 0.001) y menos días en los que se omitió la medicina (exp(ß) = 0.65, z = − 2.92, p = 0.003). La violencia psicológica (exp(ß) = 1.37, z = 1.97, p = 0.05) y las puntuaciones más altas de activos del hogar (exp(ß) = 1.29, z = − 2.83, p = 0.05) se asociaron con una peor adherencia al TAR. A nivel individual, el sexo masculino (exp(ß) = 1.37, z = 3.95, p < 0.001) y el reinicio del TAR (exp(ß) = 1.35, z = 3.64, p < 0.001) se asociaron con una peor adherencia al TAR autodeclarada; niveles de educación más altos (exp(ß) = 0.30 times, z = − 3.75, p < 0.001) y un mejor conocimiento sobre el VIH (exp(ß) = 0.28, z = − 2.83, p = 0.005) se asociaron con menos días en los que se omitió la medicina. A nivel comunitario, el estigma comunitario se asoció con una peor autodelaración de adhesión del TAR (exp(ß) = 1.24, z = 3.01, p = 0.003). Para mejorar la adherencia al TAR, se deben tener en cuenta los factores del hogar, así como los individuales y comunitarios, particularmente al abordar las disparidades de género, reducir el estigma, abordar la violencia y mejorar el apoyo del hogar.

Effect of fractional exhaled nitric oxide (FENO)-based asthma management during pregnancy versus usual care on infant development, temperament, sensory function and autism signs.

Asthma during pregnancy is associated with a range of adverse perinatal outcomes. It is also linked to increased rates of neurodevelopmental conditions in the offspring. We aimed to assess whether fractional exhaled nitric oxide (FENO)-based asthma management during pregnancy improves child developmental and behavioural outcomes compared to usual care. The Breathing for Life Trial was a randomised controlled trial that compared FENO-based asthma management during pregnancy to usual care. Participants were invited to the developmental follow-up, the Breathing for Life Trial - Infant Development study, which followed up infants at 6 weeks, 6 months and 12 months. The primary outcomes were measured in infants at 12 months using the Bayley-III: Cognitive, Language and Motor composite scores. Secondary outcomes included Bayley-III social-emotional and adaptive behaviour scores, autism likelihood and sensory and temperament outcomes. The exposure of interest was the randomised intervention group. Two hundred and twenty-two infants and their 217 participating mothers were recruited to the follow-up; 107 mothers were in the intervention group and 113 were in the control group. There was no evidence of an intervention effect for the primary outcomes: Bayley-III cognitive (mean = 108.9 control, 108.5 intervention, p = 0.93), language (mean = 95.9 control, 95.6 intervention, p = 0.87) and motor composite scores (mean = 97.2 control, 97.9 intervention, p = 0.25). Mean scores for secondary outcomes were also similar among infants born to control and FENO group mothers, with few results reaching p < 0.05. CONCLUSION:  In this sample, FENO-guided asthma treatment during pregnancy did not improve infant developmental outcomes in the first year of life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ACTRN12613000202763. WHAT IS KNOWN: • Maternal asthma during pregnancy has been associated with increased rates of neurodevelopmental conditions in offspring, including intellectual disability and autism. WHAT IS NEW: • This is the first study to examine how managing asthma during pregnancy via a FENO-guided algorithm or usual care affects infant developmental and behavioural outcomes. While the results of the study showed no impact of the intervention, and therefore do not support the integration of FENO-based management of asthma in antenatal settings for optimal infant development, they do send a positive message about the implications of active asthma management during pregnancy on infant developmental outcomes.

Increasing mercury bioaccumulation and biomagnification rates of Nile perch (Lates niloticus L.) in Winam Gulf, Lake Victoria, Kenya.

The Nile perch (Lates niloticus L.) commercial fishery for Lake Victoria in East Africa is an important source of revenue and employment. We focused on shifts in food web structure and total mercury (THg) bioaccumulation and biomagnification in Nile perch, and lower food web items collected from Winam Gulf (Kenya) sampled 24 years apart (1998 and 2022). Stable isotope carbon (δ13C) values were higher in all species from 2022 compared to 1998. Stable nitrogen isotope (δ15N) values in baseline organisms were lower in 2022 compared to 1998. In Nile perch, δ15N values were correlated with total length, but the δ15N-length regressions were steeper in 1998 compared to 2022 except for one large (158 cm) Nile perch from 1998 with an uncharacteristically low δ15N value. Total Hg concentrations were lower in lower trophic species from 2022 compared to 1998. However, the THg bioaccumulation rate (as a function of fish length) in Nile perch was greater in 2022 compared to 1998 resulting in 24.2 % to 42.4 % higher wet weight dorsal THg concentrations in 2022 Nile perch for market slot size (50 to 85 cm) fish. The contrasting observations of increased THg bioaccumulation with size in 2022 against decreases in the rate of trophic increase with size and lower THg concentrations of lower food web items imply reduced fish growth and potential bioenergetic stressors on Winam Gulf Nile perch. All samples except 1 large Nile perch (139 cm total length collected in 2022) had THg concentrations below the European Union trade limit (500 ng/g wet weight). However, for more vulnerable individuals (women, children and frequent fish eaters), we recommend a decrease in maximum monthly meal consumption for 55-75 cm Nile perch from 16 meals per month calculated for 1998 to a limit of 8 meals per month calculated for 2022.