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Hedgehog signaling is a highly conserved pathway that plays pivotal roles in morphogenesis, tumorigenesis, osteogenesis, and wound healing. Previous investigations in patients with Gorlin syndrome found low harm avoidance traits, and increased volumes in the cerebrum, cerebellum, and cerebral ventricles, suggesting the association between brain morphology and the constitutive hyperactivation of hedgehog signaling, while the changes of regional brain volumes in upregulated hedgehog signaling pathway remains unclear so far. Herein, we investigated comprehensive brain regional volumes using quantitative structural brain MRI, and identified increased volumes of amygdala, striatum, and pallidum on the global segmentation, and increased volumes of the lateral and medial parts of the central nucleus of the amygdala on the detail segmentation in Ptch heterozygous deletion mice. Our data may enhance comprehension of the association between brain morphogenic changes and hyperactivity in hedgehog signaling.

Abstract Background Somali Red Crescent Society (SRCS), supported by Norwegian Red Cross, has implemented community-based surveillance (CBS) in Somaliland. This methodology aims to reduce the high risk of epidemics by strengthening early warning and response from and at community level, particularly where there is a weak public health surveillance system. CBS is implemented through SRCS community volunteers, who report signals from the community via SMS to the software platform Nyss. This paper presents key findings from the CBS programme evaluation. Methods A retrospective observational mixed-methods approach to evaluate the CBS programme was conducted, using routine CBS data from 2021 for Awdal and Togdheer regions and qualitative interviews with stakeholders’ representatives. Results The usefulness of the CBS programme in preventing, detecting, and responding to disease outbreaks was acknowledged by the stakeholders’ representatives. 83% of the signals in Awdal region matched a Community Case Definition (CCD) and were escalated to the Ministry of Health and Development (MoHD)). For Togdheer region, 97% were escalated. Verification of signals by supervisors and escalation to the authorities was done timely.Alert outcome and response action was not well recorded, therefore there is limited evidence on sensitivity. The programme was shown to be simple and can be flexibly adjusted for new diseases and changing CCDs.Stakeholders appreciated being engaged, the good collaboration, their participation throughout the implementation and expressed high acceptance of the programme. Conclusion CBS can support early warning and response for a variety of public health risks. Improved documentation for alert outcomes could help to better evaluate the sensitivity of CBS. A participatory approach is vital to achieve successful community volunteer engagement. Software tools, such as the Nyss platform, can be useful to support effective and efficient CBS implementation.

Characterizing Alzheimer’s disease (AD) progression remains a significant clinical challenge. The initial stages of AD are marked by the accumulation of amyloid-beta plaques and Tau tangles, with cognitive functions often appearing normal, and clinical symptoms may not manifest until up to 20 years after the prodromal period begins. Comprehensive longitudinal studies analyzing brain-wide structural connectomics in the early stages of AD, especially those with large sample sizes, are scarce. In this study, we investigated a longitudinal diffusion-weighted imaging dataset of 264 subjects to assess the predictive potential of diffusion data for AD. Our findings indicate the potential of a simple prognostic biomarker for disease progression based on the hemispheric lateralization of mean tract volume for tracts originating from the supramarginal and paracentral regions, achieving an accuracy of 86%, a sensitivity of 86%, and a specificity of 93% when combined with other clinical indicators. However, diffusion-weighted imaging measurements alone did not provide strong predictive accuracy for clinical variables, disease classification, or disease conversion. By conducting a comprehensive tract-by-tract analysis of diffusion-weighted characteristics contributing to the characterization of AD and its progression, our research elucidates the potential of diffusion MRI as a tool for the early detection and monitoring of neurodegenerative diseases and emphasizes the importance of integrating multi-modal data for enhanced predictive analytics.

Down syndrome (DS) is a genetic disorder characterized by intellectual disability whose etiology includes an additional partial or full copy of chromosome 21. Brain surface morphometry analyses can potentially assist in providing a better understanding of structural brain differences, and may help characterize DS-specific neurodevelopment. We performed a retrospective surface morphometry study of 73 magnetic resonance imaging (MRI) examinations of DS patients (aged 1 day to 22 years) and compared them to a large cohort of 993 brain MRI examinations of neurotypical participants, aged 1 day to 32 years. Surface curvature measurements, absolute surface area measurements, and surface areas as a percentage of total brain surface area (%TBSA) were extracted from each brain region in each examination. Results demonstrate broad reductions in surface area and abnormalities of surface curvature measurements across the brain in DS. After adjusting our regional surface area measurements as %TBSA, abnormally increased presentation in DS relative to neurotypical controls was observed in the left precentral, bilateral entorhinal, left parahippocampal, and bilateral perirhinal cortices, as well as Brodmann’s area 44 (left), and the right temporal pole. Findings suggest the presence of developmental abnormalities of regional %TBSA in DS that can be characterized from clinical MRI examinations.

In this interventional pilot study, we investigated the effects of a modified ketogenic diet (KD) on children with autism spectrum disorder (ASD). We previously observed improved behavioral symptoms in this cohort following the KD; this trial was registered with Clinicaltrials.gov (NCT02477904). This report details the alterations observed in the microbiota, inflammation markers, and microRNAs of seven children following a KD for a duration of 4 months. Our analysis included blood and stool samples, collected before and after the KD. After 4 months follow up, we found that the KD led to decreased plasma levels of proinflammatory cytokines (IL-12p70 and IL-1b) and brain-derived neurotrophic factor (BDNF). Additionally, we observed changes in the gut microbiome, increased expression of butyrate kinase in the gut, and altered levels of BDNF-associated miRNAs in the plasma. These cohort findings suggest that the KD may positively influence ASD sociability, as previously observed, by reducing inflammation, reversing gut microbial dysbiosis, and impacting the BDNF pathway related to brain activity.

Hypoglycemia has not been previously reported as a postoperative complication of mitral valve repair (MVR) in dogs; however, the authors have encountered cases of hypoglycemia after MVR. This study aimed to determine the incidence of hypoglycemia in dogs after MVR and investigate its causes. Blood glucose levels were measured at multiple timepoints in dogs undergoing MVR. Simultaneously, insulin and glucagon blood concentrations in dogs with hypoglycemia preoperatively and postoperatively were compared to verify the physiological responses to hypoglycemia. Furthermore, risk factors for hypoglycemia, using variables selected based on the characteristics of MVR and dogs undergoing MVR, were examined prospectively. The incidence of hypoglycemia after MVR was 14.2%, and plasma glucagon concentrations increased in these dogs (mean: 260 pg/mL and 644 pg/mL pre- and postoperatively, p < 0.001), whereas serum insulin concentrations decreased (median: 0.50 ng/mL and 0.29 ng/mL pre- and postoperatively, p = 0.002). Therefore, hyperinsulinemia or hypoglucagonemia is unlikely to be the cause of postoperative hypoglycemia. The identified risk factors for hypoglycemia included low body weight and asymptomatic myxomatous mitral valve disease. Monitoring blood glucose levels after MVR should be included in the standard hospitalization plan to prevent hypoglycemic emergencies in dogs.

Diffusion magnetic resonance imaging (MRI) tractography is a powerful tool for non-invasively studying brain architecture and structural integrity by inferring fiber tracts based on water diffusion profiles. This study provided a thorough set of baseline data of structural connectomics biomarkers for 809 healthy participants between the ages of 1 and 35 years. The data provided can help to identify potential biomarkers that may be helpful in characterizing physiological and anatomical neurodevelopmental changes linked with healthy brain maturation and can be used as a baseline for comparing abnormal and pathological development in future studies. Our results demonstrate statistically significant differences between the sexes, representing a potentially important baseline from which to establish healthy growth trajectories. Biomarkers that correlated with age, potentially representing useful methods for assessing brain development, are also presented. This baseline information may facilitate studies that identify abnormal brain development associated with a variety of pathological conditions as departures from healthy sex-specific age-dependent neural development. Our findings are the result of combining the use of mainstream analytic methods with in-house-developed open-source software to help facilitate reproducible analyses, inclusive of many potential biomarkers that cannot be derived from existing software packages. Assessing relationships between our identified regional tract measurements produced by our technology and participant characteristics/phenotypic data in future analyses has tremendous potential for the study of human neurodevelopment.