Peripheral artery disease and physical function in women with and without HIV.

OBJECTIVES: Peripheral artery disease (PAD) is associated with decreased physical function and increased mortality in the general population. We previously found that PAD is common in middle-aged women with and without HIV infection, but its association with functional decline is unclear. We examine the contribution of PAD to functional decline in the Women's Interagency HIV Study, controlling for traditional cardiovascular risk factors and HIV-related factors. METHODS: Analysis included 1839 participants (72% with HIV) with measured ankle-brachial index (ABI) and 4 m gait speed. ABI values categorized PAD severity. Linear models with repeated measures estimated the association of PAD severity with log-transformed gait speed after controlling for demographic, behavioral, and metabolic risk factors, and HIV/hepatitis C virus status. RESULTS: Median age was 50 years and more than 70% were Black. Compared with normal ABI, there was a dose-response relationship between increasing PAD severity and slower gait speed in univariable analyses: 6% slower gait speed for low-normal ABI [95% confidence interval (CI): 4-9%], 10% for borderline PAD (95% CI: 6-13%), 14% for mild PAD (95% CI: 9-18%), and 16% for moderate-severe PAD (95% CI: 5-25%). PAD severity remained associated with slower gait speed in multivariable analyses. HIV/hepatitis C virus co-infection was independently associated with 9% (95% CI: 4-14%) slower gait speed compared with those with neither infection. Among women with HIV, neither CD4+ cell count nor HIV-RNA level was associated with gait speed. CONCLUSION: In middle-aged women with and without HIV infection, greater PAD severity is associated with progressively slower gait speed. Early detection of subclinical PAD may decrease the risk of lower extremity functional impairment and its long-term health consequences.

Carcinoid Crisis-Induced Acute Systolic Heart Failure.

Carcinoid crisis is a life-threatening manifestation of carcinoid syndrome characterized by profound autonomic instability in the setting of catecholamine release from stress, tumor manipulation, or anesthesia. Here, we present an unusual case of carcinoid crisis leading to acute systolic heart failure requiring mechanical circulatory support. (Level of Difficulty: Intermediate.).

Health behaviors of young adult heroin injectors in the Seattle area.

BACKGROUND: Recent indicators point to substantial increases in the number of young heroin users across much of the United States as well as across Washington State. This study characterizes this younger generation of heroin injectors in order to inform public health responses. METHODS: A cross-sectional analysis was conducted using street-intercept surveys at King County, WA syringe exchange programs in 2013. Survey responses were restricted to heroin injectors (n=389) and then categorized by the participant's age (<30 and ≥30) for a descriptive epidemiological analysis. A manual stepwise logistic regression tested the independent relationship of user characteristics with being under the age of 30. RESULTS: In regression analyses, adjusting for other characteristics, young adults were significantly (p<0.05) more likely to: re-use syringes 2-4 times (OR=2.28 compared to those who used a syringe once), share syringes (OR=2.92), report they were "hooked on" prescription-type opioids prior to using heroin (OR=2.54), have had a sexual partner in the prior year (opposite sex OR=7.37, same sex OR=23.29, both genders OR=22.04), and report powder cocaine use in the prior 3 months (OR=2.49) compared to those ages 30 and older. Young adults were significantly less likely to report using pain medicines (OR=0.33), having an abscess in the prior year (OR=0.33) or having tested positive for hepatitis C (OR=0.22) than older adults adjusting for other variables. CONCLUSIONS: Younger heroin injectors engage in risky injection practices more than older heroin injectors. Along with other significant differences, these findings have implications for outreach programs and medical care for younger heroin injectors.

Developmental changes in propagation patterns and transmitter dependence of waves of spontaneous activity in the mouse cerebral cortex.

Waves of spontaneous electrical activity propagate across many regions of the central nervous system during specific stages of early development. The patterns of wave propagation are critical in the activation of many activity-dependent developmental programs. It is not known how the mechanisms that initiate and propagate spontaneous waves operate during periods in which major changes in neuronal structure and function are taking place. We have recently reported that spontaneous waves of activity propagate across the neonatal mouse cerebral cortex and that these waves are initiated at pacemaker sites in the septal nucleus and ventral cortex. Here we show that spontaneous waves occur between embryonic day 18 (E18) and postnatal day 12 (P12), and that during that period they undergo major changes in transmitter dependence and propagation patterns. At early stages, spontaneous waves are largely GABA dependent and are mostly confined to the septum and ventral cortex. As development proceeds, wave initiation depends increasingly on AMPA-type glutamate receptors, and an ever increasing fraction of waves propagate into the dorsal cortex. The initiation sites and restricted propagation of waves at early stages are highly correlated with the position of GABAergic neurons in the cortex. The later switch to a glutamate-based mechanism allows propagation of waves into the dorsal cortex, and appears to be a compensatory mechanism that ensures continued wave generation even as GABA transmission becomes inhibitory.

Bimodal septal and cortical triggering and complex propagation patterns of spontaneous waves of activity in the developing mouse cerebral cortex.

Spontaneous waves of activity that propagate across large structures during specific developmental stages play central roles in CNS development. To understand the genesis and functions of these waves, it is critical to understand the spatial and temporal patterns of their propagation. We recently reported that spontaneous waves in the neonatal cerebral cortex originate from a ventrolateral pacemaker region. We have now analyzed a large number of spontaneous waves using calcium imaging over the entire area of coronal slices from E18-P1 mouse brains. In all waves, the first cortical region active is this ventrolateral pacemaker. In half of the waves, however, the cortical pacemaker activity is itself triggered by preceding activity in the septal nuclei. Most waves are restricted to the septum and/or ventral cortex, with only some invading the dorsal cortex or the contralateral hemisphere. Waves fail to propagate at very stereotyped locations at the boundary between ventral and dorsal cortex and at the dorsal midline. Waves that cross these boundaries pause at these same locations. Waves at these stages are blocked by both picrotoxin and CNQX, indicating that both GABA(A) and AMPA receptors are involved in spontaneous activity.