No abstract

Background: Large-scale brain networks such as the default mode network (DMN) are often disrupted in Alzheimer’s disease (AD). Numerous studies have examined DMN functional connectivity in those with mild cognitive impairments (MCI), a presumed AD precursor, to discover a biomarker of AD risk. Prior reviews were qualitative or limited in scope or approach. Objective: We aimed to systematically and quantitatively review DMN resting state fMRI studies comparing MCI and healthy comparison (HC) groups. Methods: PubMed was searched for relevant articles. Study characteristics were abstracted and the number of studies showing no difference vs hyper- vs hypo-connectivity in MCI was tallied. A voxel-wise (ES-SDM) meta-analysis was conducted to identify regional group differences. Results: Qualitatively, our review of 57 MCI vs HC comparisons suggests substantial inconsistency; 9 showed no group difference, 8 showed MCI>HC and 22 showed HC>MCI across the brain, and 18 showed regionally-mixed directions of effect. The meta-analysis of 31 studies revealed areas of significant hypo- and hyper-connectivity in MCI, including hypoconnectivity in the posterior cingulate cortex/precuneus (z = −3.1, p< 0.0001). Very few individual studies, however, showed patterns resembling the meta-analytic results. Methodological differences did not appear to explain inconsistencies. Conclusions: The pattern of altered resting DMN function or connectivity in MCI is complex and variable across studies. To date, no index of DMN connectivity qualifies as a useful biomarker of MCI or risk for AD. Refinements to MCI diagnosis, including other biological markers, or longitudinal studies of progression to AD, might identify DMN alterations predictive of AD risk.

Background: Three-dimensional computed tomographic (CT) evaluation of the cervical vertebral column enables more accurate identification of osseous and soft tissue lesions than traditional latero-lateral radiography. However, examination of the complete cervical vertebral column has been limited by horse size, preventing evaluation of the caudal cervical vertebrae. Objectives: To describe a technique to enable CT myelography of the complete cervical spine and describe the findings in 51 horses. Animals: Records of 51 horses presented for evaluation of cervical vertebral lesions. Methods: A retrospective review of clinical records from all horses presented for CT myelography to further investigate possible cervical vertebral lesions was performed. A description of a novel approach to CT myelography in horses and retrospective review of the findings in clinical cases has been included. Results: Degenerative joint disease was identified at 1 or more dorsal articular process joint in 50/51 horses, of which 44/51 had a site of grade 2 or greater. Spinal cord compression was observed on CT myelography in 31/51 horses, whereas attenuation of the dorsal contrast column was identified radiographically in 11/50 horses. Thirty-three horses showed narrowing or obliteration of the intervertebral foramina at 1 or more site and osteochondral fragments were seen in 11/51 horses. Conclusions and Clinical Importance: Computed tomography myelography is relatively safe and an easily performed technique with the correct equipment, enabling evaluation of the cervical vertebral structures of horses in all planes and volumetrically. It is possible that lesion extent might be underestimated with this diagnostic modality, hence interpretation should be complimented with flexed and extended views radiographically.

Neuroinflammation is a common pathological correlate of HIV-associated neurocognitive disorders (HAND) in individuals on antiretroviral therapy (ART). Triggering receptor expressed on myeloid cells 2 (TREM2) regulates neuroinflammation, clears extracellular Amyloid (A)-β, surveys for damaged neurons, and orchestrates microglial differentiation. TREM2 has not been studied in HIV+ brain tissues. In this retrospective study, we investigated TREM2 expression levels and localization to microglia, Aβ protein levels, and tumor necrosis factor (TNF)-α transcript levels in the frontal cortices of 52 HIV+ decedents. All donors had been on ART; 14 were cognitively normal (CN), 17 had an asymptomatic neurocognitive impairment (ANI), and 21 had a minor neurocognitive disorder (MND). Total TREM2 protein levels were increased in the soluble and decreased in the membrane-enriched fractions of MND brain tissues compared to CN; however, brains from MND Hispanics showed the most robust alterations in TREM2 as well as significantly increased TNF-α mRNA and Aβ levels when compared to CN Hispanics. Significant alterations in the expression of total TREM2 protein and transcripts for TNF-α were not observed in non-Hispanics, despite higher levels of Aβ in the non-Hispanic CN group compared to the non-Hispanic MND groups. These findings show that decreased and increased TREM2 in membrane-bound fractions and in soluble-enriched fractions, respectively, is associated with increased Aβ and neuroinflammation in this cohort of HIV+ brains, particularly those identifying as Hispanics. These findings suggest a role for TREM2 in the brain of HIV+ individuals may deserve more investigation as a biomarker for HAND and as a possible therapeutic target. Open Data: Materials are available on https://cos.io/our-services/open-science-badges/ https://osf.io/93n6m/.

Background: Equine glandular gastric disease (EGGD) is common in domesticated horses and can be challenging to treat. Oral omeprazole (ORLO) is used widely but the clinical response is frequently poor.Objectives: To compare rates of EGGD healing and improvement between ORLO and a long-acting injectable omeprazole preparation (LAIO).Study design: Retrospective clinical study. Methods:The case records and gastroscopy images of horses presenting to masked for peer review over a 12-month period were reviewed, with images blindly assessed by one of the authors. Treatment responses to 4 mg/kg LAIO administered every 7 days for 2 and 4 weeks were compared with ORLO 4 mg/kg PO q24hrs for 4 weeks. Data were compared using a Mann-Whitney U test with post-hoc Dunn's test, Chi-squared test and a Fisher's exact test.Results: Thirty-three horses that received LAIO and 12 that received ORLO were identified. Nine horses in the LAIO had received other treatments previously. The groups were comparable in signalment and EGGD lesion severity. Long-acting injectable omeprazole was found to be non-inferior to ORLO. LAIO was associated with better healing rates than ORLO at 4 weeks (LAIO-80%; ORLO-42%; p = 0.02), and reduction in lesion severity at 2 and 4 weeks in the LAIO group but not in the ORLO group at 4 weeks. Eighteen percent of horses in the LAIO group and 50% in the ORLO group did not heal at 4 weeks. There was no association between rate of healing or improvement and resolution or improvement of clinical signs. Six localised and self-limiting injection site reactions were identified in 4 horses treated with LAIO (6.7%). Main limitations:Retrospective design, small numbers and the use of other treatments prior to use of LAIO.Conclusions: LAIO was found to be non-inferior to oral omeprazole for EGGD. Larger blinded randomised clinical trials are justified.