A perspective on SIDS pathogenesis. The hypotheses: plausibility and evidence

Several theories of the underlying mechanisms of Sudden Infant Death Syndrome (SIDS) have been proposed. These theories have born relatively narrow beach-head research programs attracting generous research funding sustained for many years at expense to the public purse. This perspective endeavors to critically examine the evidence and bases of these theories and determine their plausibility; and questions whether or not a safe and reasoned hypothesis lies at their foundation. The Opinion sets specific criteria by asking the following questions: 1. Does the hypothesis take into account the key pathological findings in SIDS? 2. Is the hypothesis congruent with the key epidemiological risk factors? 3. Does it link 1 and 2? Falling short of any one of these answers, by inference, would imply insufficient grounds for a sustainable hypothesis. Some of the hypotheses overlap, for instance, notional respiratory failure may encompass apnea, prone sleep position, and asphyxia which may be seen to be linked to co-sleeping. For the purposes of this paper, each element will be assessed on the above criteria

HealthCall for the smartphone: technology enhancement of brief intervention in HIV alcohol dependent patients

Background: Heavy drinking jeopardizes the health of patients in HIV primary care. In alcohol dependent patients in HIV primary care, a technological enhancement of brief intervention, HealthCall administered via interactive voice response (HealthCall-IVR) was effective at reducing heavy drinking. The smartphone offered a technology platform to improve HealthCall. Methods: Working with input from patients, technology experts, and HIV clinic personnel, we further developed HealthCall, harnessing smartphone technological capacities (HealthCall-S). In a pilot study, we compared rates of HealthCall-S daily use and drinking outcomes in 41 alcohol dependent HIV-infected patients with the 43 alcohol dependent HIV-infected patients who used HealthCall-IVR in our previous efficacy study. Procedures, clinic, personnel, and measures were largely the same in the two studies, and the two groups of patients were demographically similar (~90% minority). Results: Pilot patients used HealthCall-S a median of 85.0% of the 60 days of treatment, significantly greater than the corresponding rate (63.8%) among comparison patients using HealthCall-IVR (p < .001). Mean end-of-treatment drinks per drinking day was similar in the two groups. Patients were highly satisfied with HealthCall-S (i.e., 92% reported that they liked using HealthCall-S). Conclusions: Among alcohol dependent patients in HIV primary care, HealthCall delivered via smartphone is feasible, obtains better patient engagement than HealthCall-IVR, and is associated with decreased drinking. In HIV primary care settings, HealthCall-S may offer a way to improve drinking outcomes after brief intervention by extending patient engagement with little additional demands on staff time

Cannabinoid Administration Attenuates the Progression of Simian Immunodeficiency Virus

Δ9-Tetrahydrocannabinol (Δ9-THC), the primary psychoactive component in marijuana, is FDA approved to ameliorate AIDS-associated wasting. Because cannabinoid receptors are expressed on cells of the immune system, chronic Δ9-THC use may impact HIV disease progression. We examined the impact of chronic Δ9-THC administration (0.32 mg/kg im, 2 × daily), starting 28 days prior to inoculation with simian immunodeficiency virus (SIVmac251; 100 TCID50/ml, iv), on immune and metabolic indicators of disease during the initial 6 month asymptomatic phase of infection in rhesus macaques. SIVmac251 inoculation resulted in measurable viral load, decreased lymphocyte CD4+/CD8+ ratio, and increased CD8+ proliferation. Δ9-THC treatment of SIV-infected animals produced minor to no effects in these parameters. However, chronic Δ9-THC administration decreased early mortality from SIV infection (p = 0.039), and this was associated with attenuation of plasma and CSF viral load and retention of body mass (p = NS). In vitro, Δ9-THC (10 μm) decreased SIV (10 TCID50) viral replication in MT4-R5 cells. These results indicate that chronic Δ9-THC does not increase viral load or aggravate morbidity and may actually ameliorate SIV disease progression. We speculate that reduced levels of SIV, retention of body mass, and attenuation of inflammation are likely mechanisms for Δ9-THC-mediated modulation of disease progression that warrant further study

Molecular Basis of Cannabis-Induced Schizophrenia-Relevant Behaviours: Insights from Animal Models

Introduction: Cannabis use is a well-established component risk factor for schizophrenia; however, the mechanisms by which cannabis use increases schizophrenia risk are unclear. Animal models can elucidate mechanisms by which chronic cannabinoid treatment can induce schizophrenia-relevant neural changes, in a standardised manner often not possible using patient-based data. Methods: We review recent literature (within the past 10 years) using animal models of chronic and subchronic treatment with cannabinoids which target the cannabinoid 1 receptor [i.e. ∆9-tetrahydrocannabinol, CP55,940 and WIN55,212-2]. Schizophrenia-relevant behavioural consequences of chronic cannabinoid treatment are first briefly summarised, followed by a detailed account of changes to several receptor systems [e.g. cannabinoid, dopaminergic, glutamatergic, γ-aminobutyric acid (GABAe)rgic, serotonergic, noradrenergic], dendritic spine morphology and inflammatory markers following chronic cannabinoids. We distinguish between adolescent and adult cannabinoid treatments, to determine if adolescence is a period of susceptibility to schizophrenia-relevant molecular changes. Results: Chronic cannabinoid treatment induces behaviours relevant to positive, negative and cognitive symptoms of schizophrenia. Chronic cannabinoids also cause region- and subtype-specific changes to receptor systems (e.g. cannabinoid, dopaminergic, glutamatergic, GABAergic), as well as changes in dendritic spine morphology and upregulation of inflammatory markers. These changes often align with molecular changes observed in post-mortem tissue from schizophrenia patients and correspond with schizophrenia-relevant behavioural change in rodents. There is some indication that adolescence is a period of susceptibility to cannabinoid-induced schizophrenia-relevant neural change, but more research in this field is required to confirm this hypothesis. Conclusions: Animal models indicate several molecular mechanisms by which chronic cannabinoids contribute to schizophrenia-relevant neural and behavioural change. It is likely that a number of these mechanisms are simultaneously impacted by chronic cannabinoids, thereby increasing schizophrenia risk in individuals who use cannabis. Understanding how cannabinoids can affect several molecular targets provides critical insight into the complex relationship between cannabis use and schizophrenia risk