SUMMARYModulation of the sonic hedgehog (SHH) pathway is a crucial factor in cerebellar morphogenesis. Stimulation of granule neuron progenitor (GNP) proliferation is a central function of SHH signalling, but how this is controlled locally is not understood. We show that two sequentially expressed members of the contactin (CNTN) family of adhesion molecules, TAG1 and F3, act antagonistically to control SHH-induced proliferation: F3 suppresses SHH-induced GNP proliferation and induces differentiation, whereas TAG1 antagonises F3. Production of GNPs in TAG1-null mice is delayed and reduced. F3 and TAG1 colocalise on GNPs with the related L1-like adhesion molecule NrCAM, and F3 fails to suppress the SHH-induced proliferation of NrCAM-deficient GNPs. We show that F3 and SHH both primarily affect a group of intermediate GNPs (IPs), which, though actively dividing, also express molecules associated with differentiation, including -tubulin III (TuJ1) and TAG1. In vivo, intermediate progenitors form a discrete layer in the middle of the external germinal layer (mEGL), while F3 becomes expressed on the axons of postmitotic granule neurons as they leave the inner EGL (iEGL). We propose, therefore, that F3 acts as a localised signal in the iEGL that induces SHH-stimulated cells in the overlying mEGL to exit cell cycle and differentiate. By contrast, expression of TAG1 on GNPs antagonises this signal in the mEGL, preventing premature differentiation and sustaining GNP expansion in a paracrine fashion. Together, these findings indicate that CNTN and L1-like proteins play a significant role in modulating SHH-induced neuronal precursor proliferation.

BackgroundThis systematic review summarises evidence on the HIV testing barriers and intervention strategies among Caribbean populations and provides pertinent implications for future research endeavours designed to increase rates of HIV testing in the region.MethodsWe used a systematic approach to survey all literature published between January 2008 and November 2018 using four electronic databases (MEDLINE/PubMed, Embase, Web of Science and Global Health). Only peer-reviewed articles published in English that examined HIV testing uptake and interventions in the Caribbean with men, men who have sex with men, female sex workers, transgender women and incarcerated individuals were included.ResultsTwenty-one studies met the inclusion criteria. Lack of confidentiality, access to testing sites, stigma, discrimination, poverty and low HIV risk perception were identified as key barriers to HIV testing. These barriers often contributed to late HIV testing and were associated with delayed treatment initiation and decreased survival rate. Intervention strategies to address these barriers included offering rapid HIV testing at clinics and HIV testing outreach by trained providers and peers.ConclusionHIV testing rates remain unacceptably low across the Caribbean for several reasons, including stigma and discrimination. Future HIV testing interventions should target places where at-risk populations congregate, train laypersons to conduct rapid tests and consider using oral fluid HIV self-testing, which allows individuals to test at home.

Initiatives to increase access to quality rapid HIV diagnostics have had relative success in the Caribbean in recent years, including use of oral rapid HIV testing. However, to date, there has not been any investigation into the performance or acceptability of oral fluids HIV testing in the region. In this cross-sectional study in The Bahamas, 252 persons of unknown serostatus were tested side-by-side with two oral rapid test brands, and the results were compared with the national fingerprick algorithm. In addition, an exit survey was administered to 234 study participants to assess user test preference. The most frequent survey response was to have no test preference (47.8%), but of those who expressed a test preference, most preferred oral (34.4%) versus fingerprick (17.8%) method. Both OraQuick and AWARE were 100% concordant with the gold standard. Therefore, our results show that oral fluids rapid testing is preferred over fingerprick testing by a subset of the potential target population and performs well in a population of undiagnosed persons attending screening clinic in The Bahamas.

Identification and isolation of persons infected with SARS-COV-2 are key mitigation strategies in the current pandemic, and rapid antigen detection tests (RADTs) offer the promise of decreased turnaround time to diagnosis when compared with gold standard RT-PCR testing. We evaluated the analytical performance of the Abbott Panbio RADT on nasopharyngeal samples stored at the Ministry of Health National Reference Lab in Nassau, Bahamas. The Panbio demonstrated a test sensitivity of 94% and a specificity of 100% on 50 PCR negative samples and 50 samples presumed to be infectious based on having PCR cycle threshold values below 30. Additionally, in our examination of operator results there was low interpersonal variation (1%) among three blind operators and significant correlation between sample Ct value and perceived signal strength on the RADT device. However, three PCR positive samples below Ct 30 were misdiagnosed by RADT, including one sample with Ct value less than 20. These results support the use of the Panbio in symptomatic persons to detect active SARS-COV-2 infections, with the caveat that RADT-negative samples should be confirmed by RT-PCR.