Vaporized nicotine use among patients in HIV care who smoke tobacco: perceived health effects and effectiveness as a smoking cessation tool.

Evidence suggests adverse health effects from vaporized nicotine (VN) use, such as electronic "e" cigarettes, and limited efficacy to aid tobacco cessation. People with HIV (PWH) smoke tobacco at higher rates than the general population, with greater morbidity, highlighting the necessity of effective tobacco cessation tools. PWH may be more vulnerable to adverse effects of VN. Using semi-structured 1:1 interviews, we examined health beliefs regarding VN, patterns of use, and perceived effectiveness for tobacco cessation among PWH in HIV care at three geographically diverse U.S. sites. PWH (n = 24) had limited understanding of VN product content or health effects, presuming VN less harmful than tobacco cigarettes (TC). VN failed to adequately replicate the psychoactive effects or desired ritual of smoking TC. Concurrent TC use, and continuous VN use throughout the day, was common. Satiety using VN was elusive, and consumption quantity was difficult to track. VN had limited desirability and durability as a TC cessation tool among the interviewed PWH.

Impact and correlates of sub-optimal social support among patients in HIV care.

Social support (SS) predicts health outcomes among patients living with HIV. We administered a brief, validated measure of SS, the Multifactoral Assessment of Perceived Social Support, within a patient-reported outcomes assessment of health domains in HIV care at 4 U.S. clinics in English and Spanish (n = 708). In univariate analysis, low SS was associated with poorer engagement in care, antiretroviral adherence, and health-related quality of life; current methamphetamine/crystal use, depression, anxiety, and HIV stigma (all p < 0.001); any use of either methamphetamines/crystal, illicit opioids, or cocaine/crack (p = 0.001), current marijuana use (p = 0.012), nicotine use (p = 0.005), and concern for sexually transmitted infection exposure (p = 0.001). High SS was associated with undetectable viral load (p = 0.031). Multivariate analyses found low SS independently associated with depression (risk ratio (RR) 3.72, 95% CI 2.93-4.72), lower adherence (RR 0.76, 95% CI 0.64-0.89), poor engagement in care (RR 2.05, 95% CI 1.44-2.96), and having more symptoms (RR 2.29, 95% CI 1.92-2.75). Medium SS was independently associated with depression (RR 2.59, 95% CI 2.00-3.36), poor engagement in care (RR 1.62, 95% CI 1.15-2.29) and having more symptoms (RR 1.75, 95% CI 1.44-2.13). SS assessment may help identify patients at risk for these outcomes.

Hyperactivity and cortical disinhibition in mice with restricted expression of mutant huntingtin to parvalbumin-positive cells.

Recent evidence suggests that interneurons are involved in the pathophysiology of Huntington Disease (HD). Abnormalities in the function of interneurons expressing the calcium buffer parvalbumin (PV) have been observed in multiple mouse models of HD, although it is not clear how PV-positive interneuron dysfunction contributes to behavioral and synaptic deficits. Here, we use the cre-lox system to drive expression of mutant huntingtin (mthtt) in parvalbumin (PV)-positive neurons and find that mutant mice exhibit diffuse mthtt immunoreactivity in PV-rich areas at 10months of age and mthtt aggregates in PV-positive processes at 24months of age. At midlife, mutant mice are hyperactive and display impaired GABA release in the motor cortex, characterized by reduced miniature inhibitory events and severely blunted responses to gamma frequency stimulation, without a loss of PV-positive interneurons. In contrast, 24month-old mutant mice show normalized behavior and responses to gamma frequency stimulation, possibly due to compensatory changes in pyramidal neurons or the formation of inclusions with age. These data indicate that mthtt expression in PV-positive neurons is sufficient to drive a hyperactive phenotype and suggest that mthtt-mediated dysfunction in PV-positive neuronal populations could be a key factor in the hyperkinetic behavior observed in HD. Further clarification of the roles for specific PV-positive populations in this phenotype is warranted to definitively identify cellular targets for intervention.

Protocol for a feasibility and early efficacy study of the Comprehensive Lifestyle Improvement Program for Prostate Cancer-2 (CLIPP2).

BACKGROUND: Although androgen deprivation therapy (ADT) for prostate cancer demonstrates improved overall and disease-free survival, it is associated with adverse effects such as obesity and metabolic syndrome that increase risk of cardiometabolic disease and diabetes type 2. ADT also leads to fatigue, depression and erectile dysfunction, which reduce quality of life (QoL). Lifestyle modification has shown promise in reducing obesity, metabolic syndrome and diabetes type 2 in other disease types. However, there is a paucity of data regarding the utility of lifestyle modification in men receiving ADT for prostate cancer. METHODS: The primary aim of the Comprehensive Lifestyle Improvement Program for Prostate Cancer-2 (CLIPP2) is to test the feasibility of conducting a 24-week lifestyle modification intervention in men on ADT for prostate cancer. Additionally, it will also determine the effect of this intervention on weight loss, cardiometabolic markers (secondary aim and markers of interest: serum glucose, insulin resistance, hemoglobin A1C and lipid panel), and QoL (tertiary aim). The intervention will be delivered weekly via telephone for the first 10 weeks and bi-weekly for the remaining 14 weeks. Questionnaires and serum samples will be collected at baseline, week 12, and week 24. Anthropometric measurements will be collected at baseline, week 6, week 12, week 18 and week 24. RESULTS: We hypothesize that the CLIPP2 intervention will produce a 7% weight loss that will result in improved markers associated with cardiometabolic disease and type 2 diabetes in the study population. CONCLUSION: Results will provide insight into the role of lifestyle modification in addressing ADT adverse effects as well as provide preliminary data to inform the development of future lifestyle interventions in this area. TRIAL REGISTRATION: NCT04228055 Clinicaltrials. gov.

Comprehensive Lifestyle Improvement Program for Prostate Cancer (CLIPP) is associated with improvement in weight and components of metabolic syndrome in men exposed to androgen deprivation therapy for prostate cancer.

BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer is associated with adverse effects, such as obesity and metabolic syndrome, which increase cardiovascular risk, the most common cause of non-cancer mortality in men diagnosed with prostate cancer. The Comprehensive Lifestyle Improvement Program for Prostate Cancer (CLIPP) was created to determine the feasibility of conducing a comprehensive lifestyle modification intervention in men on ADT for prostate cancer and determine its early efficacy in reducing obesity and metabolic syndrome. METHODS: A single-arm, open-label clinical trial was conducted by recruiting 31 men diagnosed with prostate cancer and exposed to ADT within the last 5 years. A multicomponent lifestyle modification program was delivered weekly for 16 weeks by a trained health coach. This was followed by 8 weeks of passive follow-up resulting in a total trial duration of 24 weeks. Feasibility was determined by calculating study recruitment, retention, and adherence rates. Weight and components of metabolic syndrome (waist circumference, triglycerides (TG), high-density lipoprotein (HDL), serum glucose, and blood pressure (BP)) were measured at baseline, 12, and 24 weeks. RESULTS: Recruitment, retention, and adherence rates were 47.1%, 90.3%, and 100%, respectively. Statistically significant improvements were noted between baseline and end of study measurements for weight (206.3 vs. 191.3 lbs, p < 0.001), waist (41.3 vs. 38.8 inches, p < 0.001), systolic BP (144.1 vs. 133.4 mm of Hg, p = 0.014), diastolic BP (83.3 vs. 76.2 mm of Hg, p = 0.0056), TG (146.0 vs. 113.8 mg/dl, p = 0.022), HDL (51.1 vs. 55.0 mg/dl, p = 0.012), and serum glucose (114.0 vs. 103.2 mg/dl, p = 0.013). CONCLUSION: CLIPP demonstrates feasibility and early efficacy of a multicomponent lifestyle modification intervention toward addressing obesity as well as components of metabolic syndrome in men on ADT for prostate cancer. This study provides strong preliminary data to develop future clinical trials in this population.

Ground and In-Flight Calibration of the OSIRIS-REx Camera Suite.

The OSIRIS-REx Camera Suite (OCAMS) onboard the OSIRIS-REx spacecraft is used to study the shape and surface of the mission's target, asteroid (101955) Bennu, in support of the selection of a sampling site. We present calibration methods and results for the three OCAMS cameras-MapCam, PolyCam, and SamCam-using data from pre-flight and in-flight calibration campaigns. Pre-flight calibrations established a baseline for a variety of camera properties, including bias and dark behavior, flat fields, stray light, and radiometric calibration. In-flight activities updated these calibrations where possible, allowing us to confidently measure Bennu's surface. Accurate calibration is critical not only for establishing a global understanding of Bennu, but also for enabling analyses of potential sampling locations and for providing scientific context for the returned sample.

Core-shell polymer nanorods by a two-step template wetting process.

One-dimensional core-shell polymer nanowires offer many advantages and great potential for many different applications. In this paper we introduce a highly versatile two-step template wetting process to fabricate two-component core-shell polymer nanowires with controllable shell thickness. PLLA and PMMA were chosen as model polymers to demonstrate the feasibility of this process. Solution wetting with different concentrations of polymer solutions was used to fabricate the shell layer and melt wetting was used to fill the shell with the core polymer. The shell thickness was analyzed as a function of the polymer solution concentration and viscosity, and the core-shell morphology was observed with TEM. This paper demonstrates the feasibility of fabricating polymer core-shell nanostructures using our two-step template wetting process and opens the arena for optimization and future experiments with polymers that are desirable for specific applications.

Effect of age and coronary artery disease on response to snow shoveling.

OBJECTIVES: The objective of this study was to evaluate the effect of age and coronary artery disease on responses to snow shoveling. BACKGROUND: Little information is available on the hemodynamic and metabolic responses to snow shoveling. METHODS: Sixteen men with asymptomatic coronary artery disease and relatively good functional work capacity, 13 older normal men and 12 younger normal men shoveled snow at a self-paced rate. Oxygen consumption, heart rate and blood pressure were determined. In nine men with coronary artery disease left ventricular ejection fraction was evaluated with an ambulatory radionuclide recorder. RESULTS: Oxygen consumption during snow shoveling differed (p < 0.05) among groups; it was lowest (18.5 +/- 0.8 ml/kg per min) in those with coronary artery disease, intermediate (22.2 +/- 0.9 ml/kg/min) in older normal men and highest (25.6 +/- 1.3 ml/kg/min) in younger normal men. Percent peak treadmill oxygen consumption and heart rate with shoveling in the three groups ranged from 60% to 68% and 75% to 78%, respectively. Left ventricular ejection fraction and frequency of arrhythmias during shoveling were similar to those during treadmill testing. CONCLUSIONS: During snow shoveling 1) the rate of energy expenditure selected varied in relation to each man's peak oxygen consumption; 2) older and younger normal men and asymptomatic men with coronary artery disease paced themselves at similar relative work intensities; 3) the work intensity selected represented hard work but was within commonly recommended criteria for aerobic exercise training; and 4) arrhythmias and left ventricular ejection fraction were similar to those associated with dynamic exercise.

Identification and characterization of 114/A10, an antigen highly expressed on the surface of murine myeloid and erythroid progenitor cells and IL-3-dependent cell lines.

Monoclonal antibody (mAb) 114/A10, raised against the murine bone marrow-derived multipotential hemopoietic progenitor cell line B6SUtA, identifies an antigen highly expressed by various interleukin-3 (IL-3)-dependent cell lines, the myelomonocytic cell line WEHI-3, and a large proportion of primary myeloid and erythroid colony-forming cells. Spleen- and bone marrow-derived 114/A10-positive cells were shown to selectively proliferate in vitro in response to pokeweed mitogen-stimulated spleen cell-conditioned medium or recombinant IL-3. Western blot analysis indicated that the antigen recognized by mAb 114/A10 has a mean relative molecular mass of approximately 150,000, although it is extremely heterogeneous in nature, and differs greatly in size range among different cell lines.

Expression of human glucocerebrosidase in murine macrophages: identification of efficient retroviral vectors.

Gaucher's disease is an autosomal recessive disorder characterized by a functional deficiency in beta-glucocerebrosidase enzymatic activity and the resultant accumulation of the glycolipid glucocerebroside in macrophages. Due to the nature of the affected cells, Gaucher's disease is an excellent candidate for gene therapy of hematopoietic stem cells and autologous bone marrow transplantation of transduced cells using retroviral vectors containing the glucocerebrosidase (GC) gene. In order to identify a retroviral vector capable of high levels of expression of the GC gene in macrophages, we have used the murine myeloid leukemia cell line, M1, a cell line that can be differentiated with interleukin-6 (IL-6) from blasts to macrophages. Two vectors use the Moloney murine leukemia virus (MoMLV) enhancer/promoter (LG vector) or the myeloproliferative sarcoma virus (MPSV) enhancer/MoMLV promoter (MG vector), both located in the viral long-terminal repeat (LTR); the third vector uses the phosphoglycerate kinase (PGK) promoter located internally in the vector (PG vector). The amphotropic PA317 and GP+am12 packaging cell lines were used as virus producer cells, and the GP+am12 cell line demonstrated higher titers, higher levels of GC protein expression, and specific GC enzymatic activity as well as higher transduction efficiencies for all three vectors. The LG retroviral vector was the most efficient in transducing the M1 cells. On average, higher levels of RNA and protein expression were seen in the M1 clones transduced with the LG vector, and these levels increased after differentiation. Thus, the LG retroviral vector in which the expression of the GC gene is driven by the MoMLV LTR enhancer/promoter is the best vector of the three studied for future studies for gene therapy of Gaucher's disease and other hematopoietic disorders that involve macrophages.

Evaluation of expression of transferred genes in differentiating myeloid cells: expression of human glucocerebrosidase in murine macrophages.

The retroviral vector LGSN, in which the human glucocerebrosidase (GC) cDNA is driven by the Moloney murine leukemia virus (MoMLV) long terminal repeat (LTR), was tested for expression in the murine myelomonocytic leukemia cell line M1 before and after induction of differentiation with interleukin-6 (IL-6). Southern analysis of the seven transduced clones selected for neomycin resistance in Geneticin (G-418 sulfate) demonstrated one to eight copies of intact provirus with rearrangements in only two clones. Absolute levels of human GC RNA and protein increased with increased copy numbers of provirus in the clones. Upon induction with IL-6 of the seven transduced clones to the macrophage phenotype, there was no significant change, overall, in RNA levels but some increase in human GC protein levels could be detected. Although this was the average trend, considerable clonal variation in RNA and protein levels was observed upon induction. Transduction of the M1 cells did not interfere with the ability of the cells to differentiate from blasts to macrophages as seen by the appearance of membrane receptors for the constant region of immunoglobulins (Fc gamma RI) and lysozyme production in the differentiated M1 cells. Thus, the M1 cell line can be used for testing retroviral vector expression in myeloid lineages at early and late stages of differentiation. This rapid in vitro testing of potential retroviral vectors will be beneficial for gene therapy of disorders that affect differentiated macrophages such as Gaucher's disease.

Identification and characterization of CD44RC, a novel alternatively spliced soluble CD44 isoform that can potentiate the hyaluronan binding activity of cell surface CD44.

Soluble CD44 proteins generated by proteolytic cleavage or aberrant intron retention have been shown to antagonize the ligand binding activity of the corresponding cell surface receptor, inducing apoptosis and inhibiting tumor growth. Interestingly, such findings appear to contradict recent studies demonstrating a correlation between the presence of high levels of soluble CD44 in the serum of cancer patients and poor prognosis. In the present study, we report the cloning of a novel, naturally occurring, differentially expressed, soluble CD44 isoform, designated CD44RC, which, in contrast to previously described soluble CD44 proteins, can dramatically enhance the hyaluronan binding activity of cell surface CD44. Sequence analysis suggests that CD44RC is generated by an alternative splicing event in which the 3' end of CD44 exon 2 is spliced into an internal splice acceptor site present within exon 18, altering reading frame and giving rise to a soluble protein with a unique COOH terminus. Functional studies suggest that CD44RC enhances hyaluronan binding by adhering to chondroitin sulfate side-chains attached to cell surface CD44, generating a multivalent complex with increased avidity for hyaluronan.

Role of amikacin in the management of intra-abdominal sepsis.

Controversy has developed regarding the antibiotic management of intra-abdominal sepsis because of the recent availability of the third-generation cephalosporins and ureidopenicillins as alternatives to traditional combination therapy (aminoglycosides plus clindamycin). Most observers now acknowledge the need to provide anti-anaerobic as well as anti-aerobic gram-negative drug coverage. Although most of the newer agents do provide such broad-spectrum coverage, doubt remains regarding their efficacy because of flaws in comparative study design and the observation that resistance to the newer agents, which may even extend to the aminoglycosides, can emerge in individual patients during single courses of antibiotic therapy. Indeed, such resistance is most likely to occur during the treatment of seriously ill, immunodepressed patients who have undergone multiple reoperation for persistent or recurrent intra-abdominal sepsis--the precise group for which the new drugs were most desired as less toxic alternatives to the aminoglycosides. On the basis of such observations, combination therapy with the aminoglycosides, appears to remain the most logical choice. In the setting of nosocomial sepsis and pathogen resistance to other aminoglycosides, amikacin may be especially effective. Recent surveillance data indicate that the use of amikacin under such circumstances not only may provide effective antibiotic therapy, but also may actually reduce the level of microbial resistance to the other aminoglycosides. Past concern regarding the development of resistance to amikacin has probably been excessive and should not deter the use of this agent under appropriate clinical circumstances.

Cardiac response to combined moderate heat and exercise in men with coronary artery disease.

The effect of moderate heat stress on cardiac performance during sustained moderate physical work was evaluated in men greater than or equal to 6 weeks after a cardiac event. Subjects (n = 10) performed upright leg cycle ergometer exercise at approximately 50% of peak oxygen uptake for up to 60 minutes in warm (30.0 +/- 0.9 degrees C) and thermoneutral (21.5 +/- 0.3 degrees C) environments. Cardiac output (carbon dioxide rebreathing method), left ventricular ejection fraction and relative left ventricular end-diastolic volume (portable nuclear VEST monitor) were periodically determined. In both environments, heart rate increased (p less than 0.05), stroke volume decreased (p less than 0.05), and cardiac output remained unchanged with exercise time. In the warmer environment, heart rate was increased (p less than 0.05) and stroke volume tended to be decreased (p less than 0.08), with no difference in cardiac output. In both environments, left ventricular ejection fraction did not change from minute 6 to 60 of exercise, whereas relative left ventricular end-diastolic volume decreased (p less than 0.05) with exercise time. Arterial blood pressure was unchanged from minute 6 to 60 in the warm environment. Arrhythmias were not altered by exercise time or environment, and no subjects had evidence of myocardial ischemia. The data indicate that although heart rate increased and stroke volume and relative left ventricular end-diastolic volume decreased with exercise time, cardiac output and left ventricular ejection fraction remained unchanged in both thermoneutral and warm environments.(ABSTRACT TRUNCATED AT 250 WORDS)

Energy expenditure during household tasks in women with coronary artery disease.

The energy expenditure for and heart rate responses to common household tasks were determined in 26 older (mean age 62 +/- 2 years) women with coronary artery disease (CAD). Each activity was performed at a self-determined pace for 6 or 8 minutes. The average oxygen uptake (ml/kg/min) for each task evaluated was 6.5 for washing dishes, 6.8 for ironing, 7.2 for scrubbing pans, 8.6 for unpacking groceries, 9.5 for vacuuming, 9.8 for sweeping, 10.1 for mopping, 12.0 for changing bed linens, and 12.4 for washing the floor (hands and knees). None of the subjects reported angina. Mean relative oxygen uptake (i.e., percentage of peak response with treadmill testing) ranged from 31 +/- 2% for washing dishes to 62 +/- 3% for changing the bed linens and washing the floor. Percentage of peak treadmill heart rate ranged from 62 +/- 2% for washing dishes to 73 +/- 2% for washing the floor. In 4 of the more physically demanding household activities (i.e., vacuuming, mopping, washing the floor, and changing bed linens), the responses of 10 age-matched normal women were evaluated. The absolute and relative demands of the tasks were similar between the CAD and normal groups. Results indicate that the mean energy expenditure rate of common household tasks evaluated in this study range from 2 to 4 METs, suggesting that most women with CAD who are able to achieve > or = 5 METs during a treadmill exercise test without adverse signs or symptoms should be able to resume these activities.

Molecular mechanisms regulating TNF-alpha production by tumor-associated macrophages.

The molecular mechanisms that regulate the production and/or functional activity of intratumoral tumor necrosis factor-alpha (TNF-alpha) remain poorly defined. To begin to address this issue we have examined the level of TNF-alpha mRNA and protein produced by macrophages present within immunogenic Fsa-R and non-immunogenic Fsa-N tumors grown in syngeneic Lps(d) C3H/HeJ and Lps(n) C3H/HeN mice. The results obtained indicate that macrophages isolated from tumors grown in Lps(d) C3H/HeJ mice express 5-10-fold less TNF-alpha than equivalent cells present in tumors grown in Lps(n) C3H/HeN mice. These data suggest that the mechanisms that operate within the tumor microenvironment to induce the production of TNF-alpha act, at least in part, via the same signal transduction pathway that is defective in Lps(d) C3H/HeJ mice. Interestingly, despite such differences in TNF-alpha production, tumors inoculated into C3H/HeJ and C3H/HeN mice grew at a similar rate and contained an almost identical proportion of macrophages. Moreover, tumor cells purified from tumors grown in C3H/HeJ and C3H/HeN mice produced similar quantities of the TNF-alpha-inducible cytokine GM-CSF. Thus, although differences in the level of TNF-alpha produced within tumors grown in C3H/HeN and C3H/HeJ mice are readily demonstrable, such differences appear to have little direct impact on the outcome of tumor growth.

Infantile refsum disease in four Amish sibs.

Infantile Refsum disease (IRD) appears with varying degrees of impaired vision, hearing loss, developmental delays, and neuromotor deficiencies. We report on four Amish sibs with IRD from a consanguineous marriage; biochemical testing supported the diagnosis of IRD. Of particular interest in this sibship are characteristic poorly formed yellow-orange teeth in at least three of the four affected sibs and behavior problems in the affected females.

Endogenous factors contributing to prosthetic device infections.

Although there is a direct association between the tissue reactivity of implants and their ability to potentiate infection, bacterial slime production and adherence to implant surfaces (generation of the biofilm) appear to play a primary role in the pathogenesis of most prosthesis infections.

'Breakthrough' enterococcal septicemia in surgical patients. 19 cases and a review of the literature.

We studied 19 surgical patients with 24 postoperative episodes of enterococcal septicemia not arising from the biliary or urinary tracts or from infected heart valves. Fifteen episodes occurred despite the administration of broad-spectrum antibiotics; in only one patient were these drugs effective against enterococcus. There were 14 episodes of enterococcemia in 11 patients following which the patient survived for at least one week. Thirteen (93%) of those episodes were treated with either ampicillin or drainage, or both. Five of the six long-term survivors received ampicillin therapy. Overall mortality was 68%. The data suggest that the enterococcus may emerge as a blood-borne pathogen in immunodepressed, postoperative patients receiving antibiotics for other infections of enteric origin. Antibiotic therapy specifically directed against this organism (and surgical drainage, if necessary) may be indicated during polymicrobial sepsis of enteric or mixed origin. If the spectrum of antibiotics does not include enterococcus, this organism can cause "breakthrough" sepsis, as can many other opportunistic organisms.

Stomach cancer following gastric surgery for benign disease.

The records of 1,079 patients with gastric carcinoma were reviewed. Of these, only 21 (about 2%) had had previous gastric surgery for benign disease, usually peptic ulcer. The average interval between the original gastric surgery and the discovery of stomach cancer was 26.9 years. The symptoms of cancer presentation were not distinguishable from other forms of the postgastrectomy syndrome. Gastric cancer tended to develop in these patients during the sixth decade of life, irrespective of when they had had their original gastric surgery, strongly suggesting an age-related factor. Although it would appear that previous gastric surgery for benign disease is not a major risk factor for the subsequent development of gastric cancer, such a relationship may exist. Patients who have undergone gastrectomy should be followed up carefully for the recurrence of symptoms.