Genomic confirmation of hybridisation and recent inbreeding in a vector-isolated Leishmania population.

Although asexual reproduction via clonal propagation has been proposed as the principal reproductive mechanism across parasitic protozoa of the Leishmania genus, sexual recombination has long been suspected, based on hybrid marker profiles detected in field isolates from different geographical locations. The recent experimental demonstration of a sexual cycle in Leishmania within sand flies has confirmed the occurrence of hybridisation, but knowledge of the parasite life cycle in the wild still remains limited. Here, we use whole genome sequencing to investigate the frequency of sexual reproduction in Leishmania, by sequencing the genomes of 11 Leishmania infantum isolates from sand flies and 1 patient isolate in a focus of cutaneous leishmaniasis in the Çukurova province of southeast Turkey. This is the first genome-wide examination of a vector-isolated population of Leishmania parasites. A genome-wide pattern of patchy heterozygosity and SNP density was observed both within individual strains and across the whole group. Comparisons with other Leishmania donovani complex genome sequences suggest that these isolates are derived from a single cross of two diverse strains with subsequent recombination within the population. This interpretation is supported by a statistical model of the genomic variability for each strain compared to the L. infantum reference genome strain as well as genome-wide scans for recombination within the population. Further analysis of these heterozygous blocks indicates that the two parents were phylogenetically distinct. Patterns of linkage disequilibrium indicate that this population reproduced primarily clonally following the original hybridisation event, but that some recombination also occurred. This observation allowed us to estimate the relative rates of sexual and asexual reproduction within this population, to our knowledge the first quantitative estimate of these events during the Leishmania life cycle.

Proto Tai Chi: In search of a promising group exercise for the frail elderly.

The purpose of this study was to conduct a pilot evaluation of a Proto Tai Chi exercise program for older adults and gain insight into the design of future trials involving those who are physically and cognitively frail. Proto Tai Chi (aka Wu Qin Xi) is a simple and intuitive Chinese exercise from which Tai Chi evolved. Twenty-four older adults (74.2 ± 7.5 years, range 65-92) participated in a 5-day, 90-minute/day structured evaluation of a Proto Tai Chi exercise program. Mean completed exercise time by participants per protocol was 98.6%. Participants reported the program to be enjoyable and beneficial. Preliminary efficacy of the program was supported by improvement in measures of walking speed and range of motion at post-test. Results indicate that Proto Tai Chi is a well-accepted exercise option for older adults that may improve physical function and mobility. These preliminary findings merit further investigation in the frail elderly.

A role for the vesicle-associated tubulin binding protein ARL6 (BBS3) in flagellum extension in Trypanosoma brucei.

The small GTPase Arl6 is implicated in the ciliopathic human genetic disorder Bardet-Biedl syndrome, acting at primary cilia in recruitment of the octomeric BBSome complex, which is required for specific trafficking events to and from the cilium in eukaryotes. Here we describe functional characterisation of Arl6 in the flagellated model eukaryote Trypanosoma brucei, which requires motility for viability. Unlike human Arl6 which has a ciliary localisation, TbARL6 is associated with electron-dense vesicles throughout the cell body following co-translational modification by N-myristoylation. Similar to the related protein ARL-3A in T. brucei, modulation of expression of ARL6 by RNA interference does not prevent motility but causes a significant reduction in flagellum length. Tubulin is identified as an ARL6 interacting partner, suggesting that ARL6 may act as an anchor between vesicles and cytoplasmic microtubules. We provide evidence that the interaction between ARL6 and the BBSome is conserved in unicellular eukaryotes. Overexpression of BBS1 leads to translocation of endogenous ARL6 to the site of exogenous BBS1 at the flagellar pocket. Furthermore, a combination of BBS1 overexpression and ARL6 RNAi has a synergistic inhibitory effect on cell growth. Our findings indicate that ARL6 in trypanosomes contributes to flagellum biogenesis, most likely through an interaction with the BBSome.

Effect of exercise on cardiac and metabolic outcomes in people living with HIV.

Poorly controlled HIV infection and antiretroviral therapy, especially the use of protease inhibitors, are among the causes that contribute to the development of cardiovascular disease in people living with HIV (PLWH). Poor lifestyle choices (smoking, lack of physical activity, poor diet) and individual factors such as high stress, physical or emotional trauma, depression, and so forth contribute to the overall risk of developing cardiovascular disease. The purpose of this review was to critically evaluate the more recent aerobic and resistance exercise studies and their impact on cardiovascular and metabolic risk factors in PLWH.

Brain-derived neurotrophic factor modulates antiretroviral-induced mechanical allodynia in the mouse.

Nucleoside reverse transcriptase inhibitors (NRTIs) are key components of HIV/AIDS treatment to reduce viral load. However, these drugs can induce chronic neuropathic pain, leading to increased morbidity in HIV patients. This study examines the role of brain-derived neurotrophic factor (BDNF) in the spinal dorsal horn (SDH) in development of mechanical allodynia in male C57BL/6J mice treated with the NRTI stavudine (d4T). After d4T administration, mice developed increased neuronal activity and BDNF expression in the SDH and hind paw mechanical allodynia that was exacerbated by intrathecal BDNF administration. Intrathecal BDNF alone also increased neuronal activity and caused mechanical allodynia. Because excess BDNF amplified d4T-induced mechanical allodynia and neuronal activity, the impact of decreasing BDNF in the SDH was investigated. After d4T, BDNF heterozygous mice were less allodynic than wild-type littermates, which was negated by intrathecal BDNF administration. Finally, pretreatment with intrathecal trkB-Fc chimera prior to d4T or administration of the tyrosine kinase inhibitor K252a 3 days after d4T blocked BDNF-mediated signaling, significantly attenuated the development of mechanical allodynia (trkB-Fc), and decreased neuronal activity (trkB-Fc and K252a). Taken together, these findings provide evidence that BDNF in the SDH contributes to the development of NRTI-induced painful peripheral neuropathy and may represent a new therapeutic opportunity.

The stage-regulated HASPB and SHERP proteins are essential for differentiation of the protozoan parasite Leishmania major in its sand fly vector, Phlebotomus papatasi.

The stage-regulated HASPB and SHERP proteins of Leishmania major are predominantly expressed in cultured metacyclic parasites that are competent for macrophage uptake and survival. The role of these proteins in parasite development in the sand fly vector has not been explored, however. Here, we confirm that expression of HASPB is detected only in vector metacyclic stages, correlating with the expression of metacyclic-specific lipophosphoglycan and providing the first definitive protein marker for this infective sand fly stage. Similarly, SHERP is expressed in vector metacyclics but is also detected at low levels in the preceding short promastigote stage. Using genetically modified parasites lacking or complemented for the LmcDNA16 locus on chromosome 23 that contains the HASP and SHERP genes, we further show that the presence of this locus is essential for parasite differentiation to the metacyclic stage in Phlebotomus papatasi. While wild-type and complemented parasites transform normally in late-stage infections, generating metacyclic promastigotes and colonizing the sand fly stomodeal valve, null parasites accumulate at the earlier elongated nectomonad stage of development within the abdominal and thoracic midgut of the sand fly. Complementation with HASPB or SHERP alone suggests that HASPB is the dominant effector molecule in this process.

Genome-wide screen identifies drug-induced regulation of the gene giant axonal neuropathy (Gan) in a mouse model of antiretroviral-induced painful peripheral neuropathy.

Painful peripheral neuropathy is a debilitating complication of the treatment of HIV with nucleoside reverse transcriptase inhibitors (NRTIs). Patients are living longer with these drugs; however many develop excruciating, unremitting, and often treatment-limiting neuropathy that is resistant to conventional pain management therapies. Improving patient comfort and quality of life is paramount and depends on a clearer understanding of this devastating side effect. The mechanisms underlying the development of NRTI-induced neuropathy, however, remain unclear. Using a mouse model of NRTI-induced neuropathy, the authors conducted an unbiased whole-genome microarray screen to identify molecular targets in the spinal dorsal horn, which is the location where integration of ascending sensory transmission and descending modulatory effects occur. Analysis of the microarray data identified a change in the gene giant axonal neuropathy 1 (Gan1). Mutation of this gene has been linked to the development of giant axonal neuropathy (GAN), a rare autosomal recessive condition characterized by a progressive sensorimotor neuropathy. Gan1 has not been previously linked to nerve pathologies in other populations. In this study, downregulation of the Gan1 gene and the gene protein product, gigaxonin, was validated via quantitative polymerase chain reaction ([qPCR] gene expression) and Western blot analyses (protein level). Our report is the first to suggest that Gan1 might be a novel molecular target in the development of NRTI-induced peripheral neuropathy with implications for new therapeutic approaches to preventing or reducing a significant side effect of HIV treatment.

Feasibility and acceptability of stepping exercise for cardiovascular fitness in women.

Nurses conducting clinical research often test the feasibility and acceptability of interventions before using them in large-scale experimental studies. This article specifically reviews stepping exercise as an intervention with women. In a literature review, three stepping modes (steptreadmill, bench/step, and stepper) were compared, with the steptreadmill being identified as the most advantageous for use in experimental research. An exemplar was constructed to illustrate feasibility and acceptability of steptreadmill exercise (motorized stair climbing) in 11 women with hypertension. Steptreadmill exercise is feasible and acceptable and shows promise for use in experimental studies where strict control over the exercise performed is required.

Integrative Review of Factors That Affect the Use of Postpartum Care Services in Developing Countries.

OBJECTIVE: To identify factors that affect the use of postpartum care services in developing countries. DATA SOURCES: PubMed, CINAHL, Global Health, EMBASE, and grey literature were searched for relevant articles in 2015 and 2016 with no publication date limit imposed. STUDY SELECTION: Thirteen studies met inclusion criteria and were assessed for quality with the use of a checklist developed by Fowkes and Fulton (1991) and a checklist developed by the Critical Appraisal Skills Programme (2017). DATA EXTRACTION: The integrative review framework of Whittemore and Knafl (2005) guided the conduct of the review. DATA SYNTHESIS: Results were synthesized based on the three delays model of Thaddeus and Maine (1994). Factors that negatively affected women's decisions to seek postpartum care (Phase I delays) included lack of women's autonomy, lack of exposure to mass media, no pregnancy/birth/postpartum complications, lack of awareness of postpartum care, negative provider attitude, lower levels of women's and husbands' education, women's and husbands' farming occupations, increasing number of children, and lower level of household income. Perceived easy access to a health care facility was associated with lesser odds of using postpartum care (Phase II delay). Hospitals, public health care facilities, and long queuing at a health care facility were associated with decreased postpartum care use (Phase III delays). CONCLUSION: The most common determinants of how women used postpartum care were complications and the education levels and occupations of the women and their husbands. Further research is needed to identify health facility and accessibility factors that affect postpartum care use to develop effective interventions to improve the use of postpartum care.

Outcomes of a Culturally Tailored Partially Randomized Patient Preference Controlled Trial to Increase Physical Activity Among Low-Income Immigrant Latinas.

INTRODUCTION: Almost half (47.8%) of adult Latinas report they never engage in any leisure time physical activity (PA) which is an independent risk factor for the development of cardiovascular disease and other chronic illnesses. There is a pressing need to develop and test PA interventions among Latinas. Therefore, the purpose of this study was to evaluate the effects of a PA Intervention for Latinas, a culturally tailored, promotora-facilitated 12-week PA intervention. It was hypothesized that at the completion of the intervention, participants would have (a) higher daily PA levels; (b) improved aerobic fitness, muscle strength, and flexibility; and (c) lower body mass index and percentage of body fat. METHODOLOGY: A partially randomized patient preference trial design with lag group was used to test the intervention. Participants ( N = 76) attended twice weekly, low-impact aerobic/Latin dance PA classes taught by laywomen trained as promotoras. RESULTS: Significant improvements were measured in aerobic fitness, muscle strength and flexibility, and daily PA levels ( p < .001). Sixty percent of the participants attended at least 60% of the PA sessions. DISCUSSION: Findings suggest laywomen trained as promotoras can successfully facilitate the delivery of an intervention to increase PA among immigrant Latinas.

Cardiopulmonary responses and adherence to exercise in women newly diagnosed with breast cancer undergoing adjuvant therapy.

Cardiopulmonary responses to an 8-week moderate-intensity aerobic exercise intervention and adherence to exercise during and after intervention were assessed in 41 women newly diagnosed with breast cancer undergoing adjuvant therapy. The intervention was primarily aimed at minimizing deconditioning. Women were randomly assigned to the intervention or control group, completed graded exercise tests before and after intervention, and encouraged to continue their exercise postintervention. Over time, only the intervention group showed significant decreases in resting heart rate, resting systolic blood pressure (SBP), P <.05 each, and maximum SBP, P <.02, and an increase in VO2 peak, P <.001, although resting SBP was higher in the intervention group at both timepoints, P <.05. The adherence rate to 8-week exercise intervention was 78.3% with average weekly attendance of 2.4 sessions and 42.7 minutes (27.8 minutes within target heart rate) exercise per session. Overall physical activity levels over 16 weeks postintervention did not differ between 2 groups. However, the within-group analysis indicated that only the intervention group showed a significant increase in voluntary activity, P < .02, and energy expenditure, P < .02, and a decrease in sedentary activity, P < .02. These findings indicate that moderate-intensity aerobic exercise is beneficial in reducing deconditioning of cardiopulmonary responses in newly diagnosed breast cancer women undergoing adjuvant therapy.

Physician-initiated daily verbal reminders decrease the duration of indwelling urinary catheter use compared with nurse-initiated reminders.

We compared the effectiveness of physician-initiated daily verbal reminders to primary care providers with nurse-initiated daily verbal reminders in decreasing the duration of inappropriate indwelling urinary catheter use in hospitalized patients. Catheter use duration was significantly decreased in the physician-initiated intervention group compared with the nurse-initiated intervention group (0.5 ± 0.8 vs 1.7 ± 2.7 days, respectively; P = .03).

Failure to implement respiratory isolation: why does it happen?

BACKGROUND: Respiratory isolation for 90% of individuals with acid-fast bacillus (AFB)-smear-positive tuberculosis (TB) is a recommended performance indicator in recent Infectious Diseases Society of America and Centers for Disease Control and Prevention guidelines. However, compliance with respiratory isolation reported from multiple centers in the United States and Europe falls short of that goal. OBJECTIVE: To identify missed clues in TB patients who are not appropriately isolated. DESIGN: Retrospective survey. SETTING: A 900-bed voluntary hospital. PATIENTS: All patients with AFB-smear-positive TB admitted between January 1995 and December 1999 who were not appropriately isolated. RESULTS: There were 173 TB cases admitted, including 106 with pulmonary TB. AFB smears were positive in 82 cases; 24 (29%) of these were not appropriately isolated. During the study period, the number of TB cases declined, but the proportion of appropriately isolated patients did not change. Most isolation failure cases were men (median age, 45.5 years); 21 of these patients were black, 2 were Hispanic white, and 1 was Asian, but none was non-Hispanic white. All isolation failure cases had at least one characteristic predictive of TB that could have been elicited at admission (eg, abnormal chest radiograph findings consistent with TB, fever, weight loss, a history of TB, a positive result on tuberculin skin test, hemoptysis, and human immunodeficiency virus infection). CONCLUSION: Consistent with experiences at other hospitals, we found that the rate of isolation failure remained unchanged despite an overall decline in TB cases. In our experience, almost all isolation failures could be avoided by careful review of the history, physical examination, and chest radiograph for characteristics classically considered predictive of TB.

Aerobic exercise training for depressive symptom management in adults living with HIV infection.

Aerobic exercise training may help prevent or reduce depressive symptoms experienced by persons living with HIV infection. However, the psychological effects of aerobic exercise have not been studied extensively. This study evaluated the effects of an aerobic exercise training program on self-reported symptoms of depression in HIV-infected adults and examined the convergent validity of two widely used depressive symptom scales. Sixty HIV-infected adults participated in a randomized, controlled trial of a supervised 12-week aerobic exercise training program. As compared to study controls, exercise participants showed reductions in depressive symptoms on all indices, and total depressive symptoms scores were highly correlated. Additional study of the psychological effects of aerobic exercise programs in the target population is recommended.