The adult heart responds to increased workload with physiologic hypertrophy, cardiac stem cell activation, and new myocyte formation

Aims It is a dogma of cardiovascular pathophysiology that the increased cardiac mass in response to increased workload is produced by the hypertrophy of the pre-existing myocytes. The role, if any, of adult-resident endogenous cardiac stem/progenitor cells (eCSCs) and new cardiomyocyte formation in physiological cardiac remodelling remains unexplored. Methods and results In response to regular, intensity-controlled exercise training, adult rats respond with hypertrophy of the pre-existing myocytes. In addition, a significant number (∼7%) of smaller newly formed BrdU-positive cardiomyocytes are produced by the exercised animals. Capillary density significantly increased in exercised animals, balancing cardiomyogenesis with neo-angiogenesis. c-kitpos eCSCs increased their number and activated state in exercising vs. sedentary animals. c-kitpos eCSCs in exercised hearts showed an increased expression of transcription factors, indicative of their commitment to either the cardiomyocyte (Nkx2.5pos) or capillary (Ets-1pos) lineages. These adaptations were dependent on exercise duration and intensity. Insulin-like growth factor-1, transforming growth factor-β1, neuregulin-1, bone morphogenetic protein-10, and periostin were significantly up-regulated in cardiomyocytes of exercised vs. sedentary animals. These factors differentially stimulated c-kitpos eCSC proliferation and commitment in vitro, pointing to a similar role in vivo. Conclusion Intensity-controlled exercise training initiates myocardial remodelling through increased cardiomyocyte growth factor expression leading to cardiomyocyte hypertrophy and to activation and ensuing differentiation of c-kitpos eCSCs. This leads to the generation of new myocardial cells. These findings highlight the endogenous regenerative capacity of the adult heart, represented by the eCSCs, and the fact that the physiological cardiac adaptation to exercise stress is a combination of cardiomyocyte hypertrophy and hyperplasia (cardiomyocytes and capillaries)

Nutrient addition effects on tropical dry forests: a mini-review from microbial to ecosystem scales.

Humans have more than doubled inputs of reactive nitrogen globally and greatly accelerated the biogeochemical cycles of phosphorus and metals. However, the impacts of increased element mobility on tropical ecosystems remain poorly quantified, particularly for the vast tropical dry forest biome. Tropical dry forests are characterized by marked seasonality, relatively little precipitation, and high heterogeneity in plant functional diversity and soil chemistry. For these reasons, increased nutrient deposition may affect tropical dry forests differently than wet tropical or temperate forests. Here, we review studies that investigated how nutrient availability affects ecosystem and community processes from the microsite to ecosystem scales in tropical dry forests. The effects of N and P addition on ecosystem carbon cycling and plant and microbial dynamics depend on forest successional stage, soil parent material, and rainfall regime. Responses may depend on whether overall productivity is N- vs. P-limited, although data to test this hypothesis are limited. These results highlight the many important gaps in our understanding of tropical dry forest responses to global change. Large-scale experiments are required to resolve these uncertainties

A joint individual-based model coupling growth and mortality reveals that tree vigor is a key component of tropical forest dynamics

Tree vigor is often used as a covariate when tree mortality is predicted from tree growth in tropical forest dynamic models, but it is rarely explicitly accounted for in a coherent modeling framework. We quantify tree vigor at the individual tree level, based on the difference between expected and observed growth. The available methods to join nonlinear tree growth and mortality processes are not commonly used by forest ecologists so that we develop an inference methodology based on an MCMC approach, allowing us to sample the parameters of the growth and mortality model according to their posterior distribution using the joint model likelihood. We apply our framework to a set of data on the 20-year dynamics of a forest in Paracou, French Guiana, taking advantage of functional trait-based growth and mortality models already developed independently. Our results showed that growth and mortality are intimately linked and that the vigor estimator is an essential predictor of mortality, highlighting that trees growing more than expected have a far lower probability of dying. Our joint model methodology is sufficiently generic to be used to join two longitudinal and punctual linked processes and thus may be applied to a wide range of growth and mortality models. In the context of global changes, such joint models are urgently needed in tropical forests to analyze, and then predict, the effects of the ongoing changes on the tree dynamics in hyperdiverse tropical forests. (Résumé d'auteur

Supporting the provision of pharmacy medication reviews to marginalised (medically underserved) groups: a before/ after questionnaire study investigating the impact of a patient-professional co-produced digital educational intervention.

Objectives People who are marginalised (medically underserved) experience significant health disparities and their voices are often ‘seldom heard’. Interventions to improve professional awareness and engagement with these groups are urgently needed. This study uses a co-production approach to develop an online digital educational intervention in order to improve pharmacy staffs’ intention to offer a community pharmacy medication review service to medically underserved groups. Design Before/after (3 months) self-completion online questionnaire. Setting Community pharmacies in the Nottinghamshire (England) geographical area. Participants Community pharmacy staff. Intervention Online digital educational intervention. Primary and secondary outcome measures The primary outcome measure was ‘behaviour change intention’ using a validated 12-item survey measure. The secondary outcome measure was pharmacist self-reported recruitment of underserved groups to the medication review service. Results All pharmacies in the Nottinghamshire area (n=237) were approached in June 2017 and responses were received from 149 staff (from 122 pharmacies). At 3 months (after completing the baseline questionnaire), 96 participants (from 80 pharmacies) completed a follow-up questionnaire, of which two-thirds (n=62) reported completing the e-learning. A before/after comparison analysis found an improving trend in all the five constructs of behaviour change intention (intention, social influence, beliefs about capabilities, moral norms and beliefs about consequences), with a significant increase in mean score of participants’ ‘beliefs about capabilities’ (0.44; 95% CI 0.11 to 0.76, p=0.009). In the short-term, no significant change was detected in the number of patients being offered and the patient completing a medication review. Conclusions Although increases in the numbers of patients being offered a medication review was not detected, the intervention has the potential to significantly improve pharmacy professionals’ 'beliefs about capabilities' in the short-term. Wider organisational and policy barriers to engagement with marginasied groups may need to be addressed. Future research should focus on the interplay between digital learning and practice to better identify and understand effective practice change pathways

Availability of Food Preparation Supplies among Pregnant Women: Preliminary Results from the Decision Making, Eating, and Weight Gain during Pregnancy (DEW) Study

Background: Lack of cooking supplies may be a potential barrier to preparing healthy meals at home. We examined the availability of food preparation supplies among pregnant women in relation to sociodemographic characteristics. Methods: We used preliminary data (N=59) from an ongoing study which enrolled English-speaking women aged 18+ years, pregnant with singleton gestation \u3c36\u3eweeks, pre-pregnancy BMI 18.5-40 kg/m2, and planning to deliver at UMMHC. Women completed the Food Preparation Checklist (FPC) at home. The FPC asks women if 41 specific food preparation items; scores reflect number of items present in the home. Other variables were self-reported. Pearson’s correlation, t-tests, and ANOVAs provided comparisons. We constructed an adjusted linear regression model to explore FPC by sociodemographic characteristics. Results: Women were aged 30.3 (SD=4.1) years, 64.4% were non-Hispanic White, 84.8% were married or living with a partner, and 30.5% reported difficulty paying for basic expenses. Women were enrolled at 22.7 (SD=5.6) weeks gestation; 30.5% were primigravid. Mean pre-pregnancy BMI was 25.0 (SD=4.6) kg/m2; 25.4% were overweight and 17.0% obese. Average FPC score was 32.3 (SD=6.1; range:14-39). FPC scores were higher among Non-Hispanic White women (34.6±3.5 vs. 28.1±7.5, p\u3c0.0001), those with higher education (28.3±7.0 high school/GED or less, 31.0±6.2 some/college degree, vs. 34.7±4.6 some/degree graduate, p\u3c0.01), those married or living with a partner (33.3±5.7 vs. 26.9±5.7, p\u3c0.01), with lower pre-pregnancy BMI (r=-0.38, p\u3c0.01), and who had no difficulty paying for basic expenses (34.0±5.0 vs. 28.4±6.6, p\u3c0.001). In a model that additionally adjusted for pre-pregnancy BMI, non-Hispanic White women had on average 5.7 more food preparation items (95% CI: 3.2, 8.3) and those reporting difficulty paying for basic expenses 3.8 fewer items (95% CI: -6.8, -0.9). Conclusions: Understanding the food preparation supplies available to pregnant women may be useful when designing interventions to improve diet quality and promote healthy weight gain during pregnancy

Effects of interorganisational information technology networks on patient safety: a realist synthesis

Objective: Health services in many countries are investing in interorganisational networks, linking patients’ records held in different organisations across a city or region. The aim of the systematic review was to establish how, why and in what circumstances these networks improve patient safety, fail to do so, or increase safety risks, for people living at home. Design: Realist synthesis, drawing on both quantitative and qualitative evidence, and including consultation with stakeholders in nominal groups and semistructured interviews. Eligibility criteria: The coordination of services for older people living at home, and medicine reconciliation for older patients returning home from hospital. Information sources: 17 sources including Medline, Embase, CINAHL, Cochrane Library, Web of Science, ACM Digital Library, and Applied Social Sciences Index and Abstracts. Outcomes: Changes in patients’ clinical risks. Results: We did not find any detailed accounts of the sequences of events that policymakers and others believe will lead from the deployment of interoperable networks to improved patient safety. We were, though, able to identify a substantial number of theory fragments, and these were used to develop programme theories. There is good evidence that there are problems with the coordination of services in general, and the reconciliation of medication lists in particular, and it indicates that most problems are social and organisational in nature. There is also good evidence that doctors and other professionals find interoperable networks difficult to use. There was limited high-quality evidence about safety-related outcomes associated with the deployment of interoperable networks. Conclusions: Empirical evidence does not currently justify claims about the beneficial effects of interoperable networks on patient safety. There appears to be a mismatch between technology-driven assumptions about the effects of networks and the sociotechnical nature of coordination problems. PROSPERO registration number: CRD42017073004

Wildfire alters the structure and seasonal dynamics of nocturnal pollen‐transport networks

Wildfires drive global biodiversity patterns and affect plant–pollinator interactions, and are expected to become more frequent and severe under climate change. Post-fire plant communities often have increased floral abundance and diversity, but the effects of wildfires on the ecological process of pollination are poorly understood. Nocturnal moths are globally important pollinators, but no previous study has examined the effects of wildfire on nocturnal pollination interactions. We investigated the effects of wildfire on nocturnal pollen-transport networks. We analysed the abundance and species richness of moths and flowers, and the structure of these networks, at three burned and three unburned sites in Portugal for two years, starting eight months after a large fire. Nocturnal pollen-transport networks had lower complexity and robustness following the fire than at nearby unburned sites. Overall, 70% of individual moths carried pollen, and moths were found to be transporting pollen from 83% of the flower species present. Burned sites had significantly more abundant flowers, but less abundant and species-rich moths. Individual moths transported more pollen in summer at burned sites, but less in winter; however, total pollen transport by the moth assemblage at burned sites was just 20% of that at unburned sites. Interaction turnover between burned and unburned networks was high. Negative effects of fire upon moths will likely permeate to other taxa through loss of mutualisms. Therefore, if wildfires become more frequent under climate change, community resilience may be eroded. Understanding the responses of ecological networks to wildfire can inform management that promotes resilience and facilitates whole-ecosystem conservation

Conditional inactivation of the Men1 gene leads to pancreatic and pituitary tumorigenesis but does not affect normal development of these tissues

Mutations of the MEN1 gene, encoding the tumor suppressor menin, predispose individuals to the cancer syndrome multiple endocrine neoplasia type 1, characterized by the development of tumors of the endocrine pancreas and anterior pituitary and parathyroid glands. We have targeted the murine Men1 gene by using Cre recombinase-loxP technology to develop both total and tissue-specific knockouts of the gene. Conditional homozygous inactivation of the Men1 gene in the pituitary gland and endocrine pancreas bypasses the embryonic lethality associated with a constitutional Men1(-/-) genotype and leads to beta-cell hyperplasia in less than 4 months and insulinomas and prolactinomas starting at 9 months. The pituitary gland and pancreas develop normally in the conditional absence of menin, but loss of this transcriptional cofactor is sufficient to cause beta-cell hyperplasia in some islets; however, such loss is not sufficient to initiate pituitary gland tumorigenesis, suggesting that additional genetic events are necessary for the latter

A Compensatory Mutation Provides Resistance to Disparate HIV Fusion Inhibitor Peptides and Enhances Membrane Fusion

Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations. © 2013 Wood et al