Regular clinic attendance in two large San Francisco HIV primary care settings.

Although poor clinic attendance is associated with increased morbidity and mortality among HIV-infected individuals, less is known about predictors of retention and the acceptability of targeted interventions to increase regular clinic attendance. To better understand which patients are at risk for irregular clinic attendance and to explore interventions to aid in retention to care, we surveyed patients attending two outpatient HIV clinics affiliated with the University of California, San Francisco. A total of 606 participants were surveyed, and the analysis was restricted to the 523 male respondents. Of this group, 45% (N = 299) reported missing at least one visit a year. Missing a clinic visit was associated with being African American (aOR = 1.99; 95%CI 1.12-3.52), being a man who has sex with both men and women (aOR=2.72; 95%CI 1.16-6.37), and reporting at least weekly methamphetamine use (aOR=5.79; 95%CI 2.47-13.57). Participants who reported a monthly income greater than $2000 were less likely to miss an appointment (aOR = 0.56; 95%CI 0.34-0.93). Regarding possible retention interventions, most patients preferred phone calls over other forms of support. These findings support the need for ongoing engagement support with particular attention to at-risk sub-groups.

The late presenting STEMI: How ECG scores can be used to estimate event time.

INTRODUCTION: Patients presenting with ST elevation myocardial infarction (STEMI) derive significant benefit from timely percutaneous coronary intervention (PCI). Electrocardiogram (ECG) scoring systems can complement history to estimate the infarction age and inform clinical decision-making. CASE: A 76year old man presented with eight days of dyspnea on exertion and chest pain. Triage ECG showed ST elevation and Q waves in the anterior leads. The patient was taken for coronary angiography and found to have a 100% occlusion of the left anterior descending artery. DISCUSSION: Determining timing of acute coronary syndromes is challenging. ECG indices aid clinical history by quantifying infarction acuity.

Interaction with amyloid beta peptide compromises the lipid binding function of apolipoprotein E.

Apolipoprotein (apo) E is an exchangeable apolipoprotein that plays an integral role in cholesterol transport in the plasma and the brain. It is also associated with protein misfolding or amyloid proteopathy of the beta amyloid peptide (Abeta) in Alzheimer's disease (AD) and cerebral amyloid angiopathy. The C-terminal domain (CT) of apoE encompasses two types of amphipathic alpha helices: a class A helix (residues 216-266) and a class G* helix (residues 273-299). This domain also harbors high-affinity lipoprotein binding and apoE self-association sites that possibly overlap. The objective of this study is to examine if the neurotoxic oligomeric Abeta interacts with apoE CT and if this association affects the lipoprotein binding function of recombinant human apoE CT. Site-specific fluorescence labeling of single cysteine-containing apoE CT variants with donor probes were employed to identify the binding of Abeta bearing an acceptor probe by intermolecular fluorescence resonance energy-transfer analysis. A higher efficiency of energy transfer was noted with probes located in the class A helix than with those located in the class G* helix of apoE CT. In addition, incubation of apoE CT with Abeta severely impaired the lipid binding ability and the overall amount of lipid-associated apoE CT. However, when apoE CT is present in a lipid-bound state, Abeta appears to be localized within the lipid milieu of the lipoprotein particle and not associated with any specific segments of the protein. When our data are taken together, they suggest that Abeta association compromises the fundamental lipoprotein binding function of apoE, which may have implications not only in terms of amyloid buildup but also in terms of the accumulation of cholesterol at extracellular sites.

Terminal Pleistocene epoch human footprints from the Pacific coast of Canada.

Little is known about the ice age human occupation of the Pacific Coast of Canada. Here we present the results of a targeted investigation of a late Pleistocene shoreline on Calvert Island, British Columbia. Drawing upon existing geomorphic information that sea level in the area was 2-3 m lower than present between 14,000 and 11,000 years ago, we began a systematic search for archaeological remains dating to this time period beneath intertidal beach sediments. During subsurface testing, we uncovered human footprints impressed into a 13,000-year-old paleosol beneath beach sands at archaeological site EjTa-4. To date, our investigations at this site have revealed a total of 29 footprints of at least three different sizes. The results presented here add to the growing body of information pertaining to the early deglaciation and associated human presence on the west coast of Canada at the end of the Last Glacial Maximum.

No Ifs, Ands, or Buts: Leveraging Population Health to Focus on the Care of Patients Who Smoke.

We developed a multidisciplinary curriculum to improve our residents' proficiency with smoking cessation counseling and prescribing of nicotine replacement therapy (NRT). The curriculum included a didactic portion, informational handouts, and a panel management component during which residents did telephone outreach and clinic in-reach to address high rates of smoking among patients. Residents rated their confidence with smoking cessation counseling and clinical knowledge before and after the intervention. We also tracked the number of patients flagged in the electronic medical record as smokers, the number of patients contacted, and the number of patients who received counseling. Although we did not make statistically significant improvements in perceived confidence with prescribing NRT, we found that there is an urgent need to address smoking cessation in the primary care setting and that working with a clinical pharmacist and psychologist offered a comprehensive approach. Furthermore, by anchoring the intervention with a population health component, almost 200 patients benefited from outreach efforts.

Nationwide increase in hospitalizations for heroin-related soft tissue infections: Associations with structural market conditions.

INTRODUCTION: Little is known about trends in national rates of injection-related skin and soft tissue infections (SSTI) and their relationship to the structural risk environment for heroin users. Use of Mexican-sourced "Black Tar" heroin, predominant in western US states, may have greater risk for SSTI compared with eastern US powder heroin (Colombian-sourced) due to its association with non-intravenous injection or from possible contamination. METHODS: Using nationally representative hospital admissions data from the Nationwide Inpatient Sample and heroin price and purity data from the Drug Enforcement Administration, we looked at rates of hospital admissions for opiate-related SSTI (O-SSTI) between 1993 and 2010. Regression analyses examined associations between O-SSTI and heroin source, form and price. RESULTS: Hospitalization rates of O-SSTI doubled from 4 to 9 per 100,000 nationally between 1993 and 2010; the increase concentrated among individuals aged 20-40. Heroin market features were strongly associated with changes in the rate of SSTI. Each $100 increase in yearly heroin price-per-gram-pure was associated with a 3% decrease in the rate of heroin-related SSTI admissions. Mexican-sourced-heroin-dominant cities had twice the rate of O-SSTI compared to Colombian-sourced-heroin-dominant cities. DISCUSSION: Heroin-related SSTI are increasing and structural factors, including heroin price and source-form, are associated with higher rates of SSTI hospital admissions. Clinical and harm reduction efforts should educate heroin users on local risk factors, e.g., heroin type, promote vein health strategies and provide culturally sensitive treatment services for persons suffering with SSTI.

Pheochromocytoma crisis is not a surgical emergency.

CONTEXT: Pheochromocytoma crisis is a feared and potentially lethal complication of pheochromocytoma. OBJECTIVE: We sought to determine the best treatment strategy for pheochromocytoma crisis patients and hypothesized that emergency resection is not indicated. DESIGN: Retrospective cohort study (1993-2011); literature review (1944-2011). SETTING: Tertiary referral center. PATIENTS: There were 137 pheochromocytoma patients from our center and 97 pheochromocytoma crisis patients who underwent adrenalectomy from the literature. INTERVENTION: Medical management of pheochromocytoma crisis; adrenalectomy. MAIN OUTCOME MEASURE(S): Perioperative complications, conversion, and mortality. RESULTS: In our database, 25 patients (18%) presented with crisis. After medical stabilization and α-blockade, 15 patients were discharged and readmitted for elective surgery and 10 patients were operated on urgently during the same hospitalization. None underwent emergency surgery. Postoperatively, patients who underwent elective surgery had shorter hospital stays (1.7 vs 5.7 d, P = 0.001) and fewer postoperative complications (1 of 15 [7%] vs 5 of 10 [50%], P = 0.045) and were less often admitted to the intensive care unit (1 of 15 [7%] vs 5 of 10 [50%], P = 0.045) in comparison with urgently operated patients. There was no mortality. Review of the literature (n = 97) showed that crisis patients who underwent elective or urgent surgery vs emergency surgery had less intraoperative (13 of 31 [42%] vs 20 of 25 [80%], P < 0.001) and postoperative complications (15 of 45 [33%] vs 15 of 21 [71%], P = 0.047) and a lower mortality (0 of 64 vs 6 of 33 [18%], P = 0.002). CONCLUSIONS: Management of patients presenting with pheochromocytoma crisis should include initial stabilization of the acute crisis followed by sufficient α-blockade before surgery. Emergency resection of pheochromocytoma is associated with high surgical morbidity and mortality.

Structure-guided protein engineering modulates helix bundle exchangeable apolipoprotein properties.

Apolipoprotein (apo) E plays a major role in lipid metabolism by mediating cellular uptake of lipoprotein particles through interaction with members of the low density lipoprotein (LDL) receptor family. The primary region of apoE responsible for receptor binding has been limited to a cluster of basic amino acids between residues 134 and 150, located in the fourth helix of the N-terminal domain globular helix bundle structure. To investigate structural and functional requirements of this "receptor binding region" we engineered an apolipoprotein chimera wherein residues 131-151 of human apoE were substituted for residues 146-166 (helix 5) of Manduca sexta apolipophorin III (apoLp-III). Recombinant hybrid apolipoprotein was expressed in Escherichia coli, isolated, and characterized. Hybrid apolipoprotein and apoE3-N-terminal, but not apoLp-III, bound to heparin-Sepharose. Far UV circular dichroism spectroscopy revealed the presence of predominantly alpha-helix secondary structure, and stability studies revealed a urea denaturation midpoint of 1.05 m, similar to wild-type apoLp-III. Hybrid apolipoprotein-induced dimyristoylphosphatidylcholine (DMPC) bilayer vesicle solubilization activity was significantly enhanced compared with either parent protein, consistent with detection of solvent-exposed hydrophobic regions on the protein in fluorescent dye binding experiments. Unlike wild-type apoLp-III.DMPC complexes, disc particles bearing the hybrid apolipoprotein competed with 125ILDL for binding to the LDL receptor on cultured human skin fibroblasts. We conclude that a hybrid apolipoprotein containing a key receptor recognition element of apoE preserves the structural integrity of the parent protein while conferring a new biological activity, illustrating the potential of helix swapping to introduce desirable biological properties into unrelated or engineered apolipoproteins.