Functional Relaxation and Guided Imagery as Complementary Therapy in Asthma: A Randomized Controlled Clinical Trial

Background: Asthma is a frequently disabling and almost invariably distressing disease that has a high overall prevalence. Although relaxation techniques and hypnotherapeutic interventions have proven their effectiveness in numerous trials, relaxation therapies are still not recommended in treatment guidelines due to a lack of methodological quality in many of the trials. Therefore, this study aims to investigate the efficacy of the brief relaxation technique of functional relaxation (FR) and guided imagery (GI) in adult asthmatics in a randomized controlled trial. Methods: 64 patients with extrinsic bronchial asthma were treated over a 4-week period and assessed at baseline, after treatment and after 4 months, for follow-up. 16 patients completed FR, 14 GI, 15 both FR and GI (FR/GI) and 13 received a placebo relaxation technique as the control intervention (CI). The forced expiratory volume in the first second (FEV 1) as well as the specific airway resistance (sR(aw)) were employed as primary outcome measures. Results: Participation in FR, GI and FR/GI led to increases in FEV 1 (% predicted) of 7.6 +/- 13.2, 3.3 +/- 9.8, and 8.3 +/- 21.0, respectively, as compared to -1.8 +/- 11.1 in the CI group at the end of the therapy. After follow-up, the increases in FEV 1 were 6.9 +/- 10.3 in the FR group, 4.4 +/- 7.3 in the GI and 4.5 +/- 8.1 in the FR/GI, compared to -2.8 +/- 9.2 in the CI. Improvements in sR(aw) (% predicted) were in keeping with the changes in FEV 1 in all groups. Conclusions: Our study confirms a positive effect of FR on respiratory parameters and suggests a clinically relevant long-term benefit from FR as a nonpharmacological and complementary therapy treatment option. Copyright (C) 2009 S. Karger AG, Base

Predictors of nurses’ and midwives’ intentions to provide maternal and child healthcare services to adolescents in South Africa

BACKGROUND: Adolescent mothers are at a much higher risk for maternal mortality compared to mothers aged 20 years and above. Newborns born to adolescent mothers are also more likely to have low birth weight, with the risk of long-term effects such as early onset of adult diabetes than newborns of older mothers. Few studies have investigated the determinants of adequate quality maternal and child healthcare services to pregnant adolescents. This study was conducted to gain an understanding of nurses’ and midwives’ intentions to provide maternal and child healthcare and family planning services to adolescents in South Africa. METHODS: A total of 190 nurses and midwives completed a cross-sectional survey. The survey included components on demographics, knowledge of maternal and child healthcare (MCH) and family planning (FP) services, attitude towards family planning services, subjective norms regarding maternal and child healthcare and family planning services, self-efficacy with maternal and child healthcare and family planning services, and intentions to provide maternal and child healthcare and family planning services to adolescents. Pearson’s correlation analysis was conducted to determine the association between knowledge, attitude, subjective norms, self-efficacy, and intention variables for FP and MCH services. A 2-step linear regression analysis was then conducted for both FP and MCH services to predict the intentions to provide FP and MCH services to adolescents. RESULTS: Self-efficacy to conduct MCH services (β = 0.55, p < 0.01) and years of experience as a nurse- midwife (β = 0.14, p < 0.05) were associated with stronger intentions to provide the services. Self-efficacy to provide FP services (β = 0.30, p < 0.01) was associated with stronger intentions to provide FP services. CONCLUSIONS: Self-efficacy has a strong and positive association with the intentions to provide both MCH and FP services, while there is a moderate association with attitude and norms. There is a need to improve and strengthen nurses’ and midwives’ self-efficacy in conducting both MCH and FP services in order to improve the quality and utilization of the services by adolescents in South Africa.IS

The T cell differentiation landscape is shaped by tumour mutations in lung cancer

Tumour mutational burden (TMB) predicts immunotherapy outcome in non-small cell lung cancer (NSCLC), consistent with immune recognition of tumour neoantigens. However, persistent antigen exposure is detrimental for T cell function. How TMB affects CD4 and CD8 T cell differentiation in untreated tumours and whether this affects patient outcomes is unknown. Here, we paired high-dimensional flow cytometry, exome, single-cell and bulk RNA sequencing from patients with resected, untreated NSCLC to examine these relationships. TMB was associated with compartment-wide T cell differentiation skewing, characterized by loss of TCF7-expressing progenitor-like CD4 T cells, and an increased abundance of dysfunctional CD8 and CD4 T cell subsets with strong phenotypic and transcriptional similarity to neoantigen-reactive CD8 T cells. A gene signature of redistribution from progenitor-like to dysfunctional states was associated with poor survival in lung and other cancer cohorts. Single-cell characterization of these populations informs potential strategies for therapeutic manipulation in NSCLC

Regional Management Units for Marine Turtles: A Novel Framework for Prioritizing Conservation and Research across Multiple Scales

Background: Resolving threats to widely distributed marine megafauna requires definition of the geographic distributions of both the threats as well as the population unit(s) of interest. In turn, because individual threats can operate on varying spatial scales, their impacts can affect different segments of a population of the same species. Therefore, integration of multiple tools and techniques - including site-based monitoring, genetic analyses, mark-recapture studies and telemetry - can facilitate robust definitions of population segments at multiple biological and spatial scales to address different management and research challenges. Methodology/Principal Findings: To address these issues for marine turtles, we collated all available studies on marine turtle biogeography, including nesting sites, population abundances and trends, population genetics, and satellite telemetry. We georeferenced this information to generate separate layers for nesting sites, genetic stocks, and core distributions of population segments of all marine turtle species. We then spatially integrated this information from fine-to coarse-spatial scales to develop nested envelope models, or Regional Management Units (RMUs), for marine turtles globally. Conclusions/Significance: The RMU framework is a solution to the challenge of how to organize marine turtles into units of protection above the level of nesting populations, but below the level of species, within regional entities that might be on independent evolutionary trajectories. Among many potential applications, RMUs provide a framework for identifying data gaps, assessing high diversity areas for multiple species and genetic stocks, and evaluating conservation status of marine turtles. Furthermore, RMUs allow for identification of geographic barriers to gene flow, and can provide valuable guidance to marine spatial planning initiatives that integrate spatial distributions of protected species and human activities. In addition, the RMU framework - including maps and supporting metadata - will be an iterative, user-driven tool made publicly available in an online application for comments, improvements, download and analysis

Neuromuscular disease genetics in under-represented populations: increasing data diversity

Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses ‘solved’ or ‘possibly solved’ ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% ‘solved’ and ∼13% ‘possibly solved’ outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally

Teenage pregnancy rates and associations with other health risk behaviours: a threewave cross-sectional study among South African school-going adolescents

BACKGROUND: Teenage pregnancy still remains high in low and middle-income countries (LMIC), as well as in highincome countries (HIC). It is a major contributor to maternal and child morbidity and mortality rates. Furthermore, it has social consequences, such as perpetuating the cycle of poverty including early school dropout by the pregnant adolescent, especially in sub-Saharan Africa (SSA). Few studies in SSA have investigated the trends in teenage pregnancy and the associated factors, while this is critical in fully understanding teenage pregnancy and for promotion of reproductive health among adolescents at large in SSA. METHODS: To examine the trends in teenage pregnancy and to identify associations with other health risk behaviours in South Africa (SA), a total of 31 816 South African school-going adolescents between 11 to 19 years of age were interviewed in three cross-sectional surveys. Data from the first (2002, n = 10 549), second (2008, n = 10 270) and the third (2011, n = 10 997) nationally representative South African youth risk behaviour surveys (YRBS) were used for this study. RESULTS: The overall prevalence of having ever been pregnant among the combined 3-survey sample was selfreported to be 11.0 % and stable across the three surveys. Sexual intercourse among adolescents in SA has decreased from 41.9 % in 2002 to 36.9 % in 2011. However, pregnancy among girls who ever had sex increased from 17.3 % (95 % CI: 0.16–0.19) in 2002, to 23.6 % (95 % CI: 0.21–0.26) in 2008 and decreased to 21.3 % (95 % CI: 0.19–0.23) in 2011. The odds for ever been pregnant were higher for girls who had 2 or more sexual partners (OR: 1.250, 95 % CI: 1.039–1.503), girls who ever used alcohol before sex (OR: 1.373, 95 % CI: 1.004–1.878), practised binge-drinking during the last month (OR: 0.624, 95 % CI: 0.503–0.774), and girls who used mandrax (OR: 1.968, 95 % CI: 1,243–3.117). The odds for never been pregnant were lower for those who used condoms (OR: 0.462, 95 % CI: 0.309–0.691). CONCLUSIONS: Girls continue to become pregnant at unacceptably high rates in SA. Sexual intercourse among adolescents in SA has decreased slightly. However, among those who are sexually active pregnancy prevalence rates have increased. More over, this is in the context of high prevalence of HIV and other STI. There is a need to address adolescents’ sexual and reproductive health, and several health risk behaviours, including substance use, that are associated with teenage pregnancy in SA.IS

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

The Intracranial Tuberculoma That Was Thought to Be Neurosarcoidosis

Intracranial tuberculomas and neurosarcoidosis, although both granulomatous disorders, are distinct clinical entities which are managed quite differently. As much as they are different from each other, it may be difficult to differentiate their neurologic manifestations from one another or even from other intrinsic masses of the brain. Intracranial tuberculomas are rare in developed countries thus making their underdiagnosis likely