Resolution of paraphyly in caesalpinioid legumes

The exceptionally large, diverse, and economically important plant family Leguminosae has traditionally comprised three subfamilies, the Caesalpinioideae, Mimosoideae and Papilionoideae. Following a large-scale molecular based phylogenetic analysis in which subfamily Caesalpinioideae was demonstrated to be highly paraphyletic, the number of subfamilies recognised was increased to six, with four new subfamilies being segregated from within the Caesalpinioideae, and the Mimosoideae being subsumed into the redefined Caesalpinioideae (as the mimosoid clade). The Caesalpinioideae, and delimitation of genera therein, has therefore been a key focus of the international legume taxonomic community in recent years. Two of the largest genera in the Caesalpinioideae sensu traditional are Bauhinia and Caesalpinia; the former comprises part of the newly created subfamily Cercidoideae, whilst the latter is retained within the Caesalpinioideae sensu novo. Both Bauhinia and Caesalpinia have historically been most commonly treated as large, pantropical and polymorphic genera, but have in the light of molecular phylogenetic evidence been revealed to paraphyletic. A number of generic segregates have been consequently delineated from within each of them, but polymorphism has persisted, suggesting the existence of further paraphyly. The aim of this study is to address this remaining paraphyly, using a combined morphological, molecular and biogeographical approach to investigate generic limits and define segregate genera. The work herein creates a new segregate genus from within Bauhinia s.l., based upon morphological, molecular, palynological, and biogeographical evidence. Details of the composition of two further generic segregates of Bauhinia s.l. are presented, their geographical distributions described, and the relevance of this to the generic limits explored. The status of the putative segregate genus Lasiobema is examined, with novel data on a poorly known species of the genus presented. The monophyly of Mezoneuron, a segregate genus of Caesalpinia s.l., is demonstrated with morphological and molecular data, and infrageneric relationships are explained. Preliminary findings reconstructing the evolutionary and biogeographical history of the genus are discussed. This study represents substantial progress towards resolving generic limits within two of the major groups of the Caesalpinioideae (sensu traditional), and provides data upon which further such studies can be built, setting the framework for identification and resolution of the remaining paraphyly

Using the Community Readiness Model to Select Communities for a Community-Wide Obesity Prevention Intervention

To build on a growing interest in community-based obesity prevention programs, methods are needed for matching intervention strategies to local needs and assets. We used the Community Readiness Model (CRM), a structured interview guide and scoring system, to assess community readiness to act on childhood obesity prevention, furthering a replication study of a successful intervention

Caring in the Margins: A Scholarship of Accompaniment for Advanced Transcultural Nursing Practice

Nurses must learn essential skills based in transcultural nursing to address issues of equity and social justice. The development of a model for nursing practice for an urban nurse-led drop-in center for individuals experiencing marginalization provides an opportunity for student nurses to learn transcultural nursing skills that shifts care from acknowledging the need of others to accompanying others on their health journey. The practice model provides the opportunity for undergraduate and graduate nursing students at Augsburg University to de-emphasize tasks and build relationships. Students learn to listen to others\u27 stories and acknowledge their struggles in the margins. Four stages of nursing practice skills, acknowledging others\u27 needs, attending to their struggles, affirming strengths, and ultimately accompanying others, are taught and experienced. At the core of the nursing practice model is the concept of “hospitality.” The nursing practice model serves as guide for student nurses to learn to suspend disbeliefs, withhold judgment, and ultimately reduce stereotypes and stigma to offer a safe space for individuals living in the margins seeking care. The future of nursing requires essential knowledge, skills, and attitudes that shift care from need-based care to accompaniment to address health inequities and provide culturally appropriate care

Occupational therapy in HomEcare Re-ablement Services (OTHERS): study protocol for a randomized controlled trial

Background: Homecare re-ablement services have been developed by local authorities in England in response to the government agenda for health and social care. These services aim to optimize users’ independence and ability to cope at home, and reduce the need for ongoing health and social care services. However, there is currently limited evidence and guidance regarding the optimum configuration and delivery of re-ablement services. In particular, the impact of occupational therapy input on service user outcomes has been highlighted as a specific research priority. Methods/Design: This feasibility randomized controlled trial (RCT) will recruit 50 people from one local authority led homecare re-ablement service in England. Those who provide informed consent will be randomized to receive either usual homecare re-ablement (without routine occupational therapy input) or usual homecare re-ablement plus an enhanced program targeted at activities of daily living (ADL), delivered by an occupational therapist. The primary aim of this study is to assess the feasibility of conducting a further, powered study. The participant outcomes assessed will be independence in personal and extended ADL, health and social care-related quality of life, number of care support hours, falls, acute and residential admissions and use of health and social care services. These will be assessed at two weeks, three months and six months post-discharge from the re-ablement service. Discussion: To our knowledge, this is the first RCT of occupational therapy in homecare re-ablement services. The results of this study will lay the foundations for a further powered study. The findings will be relevant to researchers, clinicians, commissioners and users of adult social care services

Outcomes, infectiousness, and transmission dynamics of patients with extensively drug-resistant tuberculosis and home-discharged patients with programmatically incurable tuberculosis: a prospective cohort study.

BACKGROUND: The emergence of programmatically incurable tuberculosis threatens to destabilise control efforts. The aim of this study was to collect prospective patient-level data to inform treatment and containment strategies. METHODS: In a prospective cohort study, 273 South African patients with extensively drug-resistant tuberculosis, or resistance beyond extensively drug-resistant tuberculosis, were followed up over a period of 6 years. Transmission dynamics, infectiousness, and drug susceptibility were analysed in a subset of patients from the Western Cape using whole-genome sequencing (WGS; n=149), a cough aerosol sampling system (CASS; n=26), and phenotypic testing for 18 drugs (n=179). FINDINGS: Between Oct 1, 2008, and Oct 31, 2012, we enrolled and followed up 273 patients for a median of 20·3 months (IQR 9·6-27·8). 203 (74%) had programmatically incurable tuberculosis and unfavourable outcomes (treatment failure, relapse, default, or death despite treatment with a regimen based on capreomycin, aminosalicylic acid, or both). 172 (63%) patients were discharged home, of whom 104 (60%) had an unfavourable outcome. 54 (31%) home-discharged patients had failed treatment, with a median time to death after discharge of 9·9 months (IQR 4·2-17·4). 35 (20%) home-discharged cases were smear-positive at discharge. Using CASS, six (23%) of 26 home-discharged cases with data available expectorated infectious culture-positive cough aerosols in the respirable range (<5 μm), and most reported inter-person contact with suboptimal protective mask usage. WGS identified 17 (19%) of the 90 patients (with available sequence data) that were discharged home before the diagnosis of 20 downstream cases of extensively drug-resistant tuberculosis with almost identical sequencing profiles suggestive of community-based transmission (five or fewer single nucleotide polymorphisms different and with identical resistance-encoding mutations for 14 drugs). 11 (55%) of these downstream cases had HIV co-infection and ten (50%) had died by the end of the study. 22 (56%) of 39 isolates in patients discharged home after treatment failure were resistant to eight or more drugs. However, five (16%) of 31 isolates were susceptible to rifabutin and more than 90% were likely to be sensitive to linezolid, bedaquiline, and delamanid. INTERPRETATION: More than half of the patients with programmatically incurable tuberculosis were discharged into the community where they remained for an average of 16 months, were at risk of expectorating infectious cough aerosols, and posed a threat of transmission of extensively drug-resistant tuberculosis. Urgent action, including appropriate containment strategies, is needed to address this situation. Access to delamanid, bedaquiline, linezolid, and rifabutin, when appropriate, must be accelerated along with comprehensive drug susceptibility testing. FUNDING: UK Medical Research Council, South African Medical Research Council, South African National Research Foundation, European & Developing Countries Clinical Trials Partnership, Oppenheimer Foundation, Newton Fund, Biotechnology and Biological Sciences Research Council, King Abdullah University of Science & Technology

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

The Combination of BH3-Mimetic ABT-737 with the Alkylating Agent Temozolomide Induces Strong Synergistic Killing of Melanoma Cells Independent of p53

Metastatic melanoma has poor prognosis and is refractory to most conventional chemotherapies. The alkylating agent temozolomide (TMZ) is commonly used in treating melanoma but has a disappointing response rate. Agents that can act cooperatively with TMZ and improve its efficacy are thus highly sought after. The BH3 mimetic ABT-737, which can induce apoptosis by targeting pro-survival Bcl-2 family members, has been found to enhance the efficacy of many conventional chemotherapeutic agents in multiple cancers. We found that combining TMZ and ABT-737 induced strong synergistic apoptosis in multiple human melanoma cell lines. When the drugs were used in combination in a mouse xenograft model, they drastically reduced tumor growth at concentrations where each individual drug had no significant effect. We found that TMZ treatment elevated p53 levels, and that the pro-apoptotic protein Noxa was elevated in TMZ/ABT-737 treated cells. Experiments with shRNA demonstrated that the synergistic effect of TMZ and ABT-737 was largely dependent on Noxa. Experiments with nutlin-3, a p53 inducer, demonstrated that p53 induction was sufficient for synergistic cell death with ABT-737 in a Noxa-dependent fashion. However, p53 was not necessary for TMZ/ABT-737 synergy as demonstrated by a p53-null line, indicating that TMZ and ABT-737 together induce Noxa in a p53-independent fashion. These results demonstrate that targeting anti-apoptotic Bcl-2 members is a promising method for treating metastatic melanoma, and that clinical trials with TMZ and Bcl-2 inhibitors are warranted

Host Genetics and Environmental Factors Regulate Ecological Succession of the Mouse Colon Tissue-Associated Microbiota

Background: The integration of host genetics, environmental triggers and the microbiota is a recognised factor in the pathogenesis of barrier function diseases such as IBD. In order to determine how these factors interact to regulate the host immune response and ecological succession of the colon tissue-associated microbiota, we investigated the temporal interaction between the microbiota and the host following disruption of the colonic epithelial barrier. Methodology/Principal Findings: Oral administration of DSS was applied as a mechanistic model of environmental damage of the colon and the resulting inflammation characterized for various parameters over time in WT and Nod2 KO mice. Results: In WT mice, DSS damage exposed the host to the commensal flora and led to a migration of the tissue-associated bacteria from the epithelium to mucosal and submucosal layers correlating with changes in proinflammatory cytokine profiles and a progressive transition from acute to chronic inflammation of the colon. Tissue-associated bacteria levels peaked at day 21 post-DSS and declined thereafter, correlating with recruitment of innate immune cells and development of the adaptive immune response. Histological parameters, immune cell infiltration and cytokine biomarkers of inflammation were indistinguishable between Nod2 and WT littermates following DSS, however, Nod2 KO mice demonstrated significantly higher tissue-associated bacterial levels in the colon. DSS damage and Nod2 genotype independently regulated the community structure of the colon microbiota