Brown adipose tissue (BAT) is able to rapidly generate heat and metabolise macronutrients, such as glucose and lipids, through activation of mitochondrial uncoupling protein 1 (UCP1). Diet can modulate UCP1 function but the capacity of individual nutrients to promote the abundance and activity of UCP1 is not well established. Caffeine consumption has been associated with loss of body weight and increased energy expenditure, but whether it can activate UCP1 is unknown. This study examined the effect of caffeine on BAT thermogenesis in vitro and in vivo . Stem cell-derived adipocytes exposed to caffeine (1 mM) showed increased UCP1 protein abundance and cell metabolism with enhanced oxygen consumption and proton leak. These functional responses were associated with browning-like structural changes in mitochondrial and lipid droplet content. Caffeine also increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression and mitochondrial biogenesis, together with a number of BAT selective and beige gene markers. In vivo , drinking coffee (but not water) stimulated the temperature of the supraclavicular region, which co-locates to the main region of BAT in adult humans, and is indicative of thermogenesis. Taken together, these results demonstrate that caffeine can promote BAT function at thermoneutrality and may have the potential to be used therapeutically in adult humans.

Objective Universal HIV screening is recommended but challenging to implement. Selectively targeting those at risk is thought to miss cases, but prior studies are limited by narrow risk criteria, incomplete implementation, and absence of direct comparisons. We hypothesized that targeted HIV screening, when fully implemented and using maximally broad risk criteria, could detect nearly as many cases as universal screening with many fewer tests. Methods This single-center, cluster-randomized trial compared universal and targeted patient selection for HIV screening in a lower prevalence urban emergency department. Patients were excluded for age (<18, >64), known HIV infection, or prior approach for HIV testing that day. Targeted screening was offered for any risk indicator identified from charts, staff referral, or self-disclosure. Universal screening was offered regardless of risk. Baseline seroprevalence was estimated from consecutive de-identified blood samples. Results There were 9,572 eligible visits during which the patient was approached. For universal screening, 40.8% (1,915/4,692) consented with six newly diagnosed (0.31%, CI95 0.13%–0.65%). For targeted screening, 37% (1,813/4,880) had no testing indication. Of the 3,067 remaining, 1,454 (47.4%) consented with 3 newly diagnosed (0.22%, CI95 0.06%–0.55%). Estimated seroprevalence was 0.36% (CI95 0.16%–0.70%). Targeted screening had a higher proportion consenting (47.4% v. 40.8%, p<0.002), but a lower proportion of ED encounters with testing (29.7% v. 40.7%, p<0.002). Conclusions Targeted screening, even when fully implemented with maximally permissive selection, offered no important increase in positivity rate or decrease in tests performed. Universal screening diagnosed more cases, because more were tested, despite a modestly lower consent rate.

Chronic excessive alcohol intoxications evoke cumulative damage to tissues and organs. We examined prefrontal cortex (Brodmann’s area (BA) 9) from 20 human alcoholics and 20 age, gender, and postmortem delay matched control subjects. H & E staining and light microscopy of prefrontal cortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a disruption of subcortical neuron patterning in alcoholic subjects. BA 9 tissue homogenisation and one dimensional polyacrylamide gel electrophoresis (PAGE) proteomics of cytosolic proteins identified dramatic reductions in the protein levels of spectrin β II, and α- and β-tubulins in alcoholics, and these were validated and quantitated by Western blotting. We detected a significant increase in α-tubulin acetylation in alcoholics, a non-significant increase in isoaspartate protein damage, but a significant increase in protein isoaspartyl methyltransferase protein levels, the enzyme that triggers isoaspartate damage repair in vivo. There was also a significant reduction in proteasome activity in alcoholics. One dimensional PAGE of membrane-enriched fractions detected a reduction in β-spectrin protein levels, and a significant increase in transmembranous α3 (catalytic) subunit of the Na+,K+-ATPase in alcoholic subjects. However, control subjects retained stable oligomeric forms of α-subunit that were diminished in alcoholics. In alcoholics, significant loss of cytosolic α- and β-tubulins were also seen in caudate nucleus, hippocampus and cerebellum, but to different levels, indicative of brain regional susceptibility to alcohol-related damage. Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioural abnormalities attributed to alcoholics.

Objective Differences in the prevalence of undiagnosed HIV between different types of emergency departments (EDs) are not well understood. We seek to define missed opportunities for HIV diagnosis within 3 geographically proximate EDs serving different patient populations in a single metropolitan area. Methods For an urban academic, an urban community, and a suburban community ED located within 10 miles of one another, we reviewed visit records for a cohort of patients who received a new diagnosis of HIV between July 1999 and June 2003. Missed opportunities for earlier HIV diagnosis were defined as ED visits in the year before diagnosis, during which there was no documented ED HIV testing offer or test. Outcomes were the number of missed opportunity visits and the number of patients with a missed opportunity for each ED. We secondarily reviewed medical records for missed opportunity encounters, using an extensive list of indications that might conceivably trigger testing. Results Among 276 patients with a new HIV diagnosis, 123 (44.5%) visited an ED in the year before diagnosis or received a diagnosis in the ED. The urban academic ED HIV testing program diagnosed 23 (8.3%) cases and offered testing to 24 (8.7%) patients who declined. Missed opportunities occurred during 187 visits made by 76 (27.5%) patients. These included 70 patients with 157 visits at the urban academic ED, 9 patients with 24 visits at the urban community ED, and 4 patients with 6 visits at the suburban community ED. Medical records were available for 172 of the 187 missed opportunity visits. Visits were characterized by the following potential testing indicators: HIV risk factors (58; 34%), related diagnosis indicating risk (7; 4%), AIDS-defining illness (8; 5%), physician suspicion of HIV (29; 17%), and nonspecific signs or symptoms of illness potentially consistent with HIV (126; 73%). Conclusion Geographically proximate EDs differ in their opportunities for earlier HIV diagnosis, but all 3 sites had missed opportunities. Many ED patients with undiagnosed HIV have potential indications for testing documented even in the absence of a dedicated risk assessment, although most of these are nonspecific signs or symptoms of illness that may not be clinically useful selection criteria.