Complete Genome Sequence of the N2-Fixing Broad Host Range Endophyte Klebsiella pneumoniae 342 and Virulence Predictions Verified in Mice

We report here the sequencing and analysis of the genome of the nitrogen-fixing endophyte, Klebsiella pneumoniae 342. Although K. pneumoniae 342 is a member of the enteric bacteria, it serves as a model for studies of endophytic, plant-bacterial associations due to its efficient colonization of plant tissues (including maize and wheat, two of the most important crops in the world), while maintaining a mutualistic relationship that encompasses supplying organic nitrogen to the host plant. Genomic analysis examined K. pneumoniae 342 for the presence of previously identified genes from other bacteria involved in colonization of, or growth in, plants. From this set, approximately one-third were identified in K. pneumoniae 342, suggesting additional factors most likely contribute to its endophytic lifestyle. Comparative genome analyses were used to provide new insights into this question. Results included the identification of metabolic pathways and other features devoted to processing plant-derived cellulosic and aromatic compounds, and a robust complement of transport genes (15.4%), one of the highest percentages in bacterial genomes sequenced. Although virulence and antibiotic resistance genes were predicted, experiments conducted using mouse models showed pathogenicity to be attenuated in this strain. Comparative genomic analyses with the presumed human pathogen K. pneumoniae MGH78578 revealed that MGH78578 apparently cannot fix nitrogen, and the distribution of genes essential to surface attachment, secretion, transport, and regulation and signaling varied between each genome, which may indicate critical divergences between the strains that influence their preferred host ranges and lifestyles (endophytic plant associations for K. pneumoniae 342 and presumably human pathogenesis for MGH78578). Little genome information is available concerning endophytic bacteria. The K. pneumoniae 342 genome will drive new research into this less-understood, but important category of bacterial-plant host relationships, which could ultimately enhance growth and nutrition of important agricultural crops and development of plant-derived products and biofuels

The role of peptides in bone healing and regeneration: A systematic review

Background: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. Methods: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. Results: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. Conclusion: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge

Robustness of common hemodynamic indicators with respect to numerical resolution in 38 middle cerebral artery aneurysms

Background: Using computational fluid dynamics (CFD) to compute the hemodynamics in cerebral aneurysms has received much attention in the last decade. The usability of these methods depends on the quality of the computations, highlighted in recent discussions. The purpose of this study is to investigate the convergence of common hemodynamic indicators with respect to numerical resolution. Methods: 38 middle cerebral artery bifurcation aneurysms were studied at two different resolutions (one comparable to most studies, and one finer). Relevant hemodynamic indicators were collected from two of the most cited studies, and were compared at the two refinements. In addition, correlation to rupture was investigated. Results: Most of the hemodynamic indicators were very well resolved at the coarser resolutions, correlating with the finest resolution with a correlation coefficient >0.95. The oscillatory shear index (OSI) had the lowest correlation coefficient of 0.83. A logarithmic Bland-Altman plot revealed noticeable variations in the proportion of the aneurysm under low shear, as well as in spatial and temporal gradients not captured by the correlation alone. Conclusion: Statistically, hemodynamic indicators agree well across the different resolutions studied here. However, there are clear outliers visible in several of the hemodynamic indicators, which suggests that special care should be taken when considering individual assessment

Grandparents caring for grandchildren in skip-generation households in Cambodia: lived experiences and ethical issues

Contrary to common conceptions, low- and middle-income countries are rapidly ageing. Despite prevalent depictions of older people as dependent and burdensome, many older people make important contributions to their families and societies that have been largely overlooked in policy and research. Older people’s roles as caregivers for their grandchildren represents a prime example of this. This study aims to understand the lived experiences of grandparents who become primary caregivers to their grandchildren in skip-generation households in rural Cambodia. Based on thematic analysis of in-depth, semi-structured interviews and focus group discussions with 40 grandparent caregivers, this study offers insights into grandparents’ lived experiences, namely what drives skip-generation caregiving, grandparents’ roles and responsibilities, and issues pertaining to health and healthcare of grandparents and grandchildren in skip-generation households. Additionally, analysis of 18 in-depth interviews with professional stakeholders working in relevant fields of policy and practice reveal their perspectives on the current situation of skip-generation families and the various institutions and policies that impact their lives. The analysis shows that grandparents play a major and essential role as caregivers to their grandchildren in skip-generation households. However, due to widespread poverty and a dearth of formal and informal support for skip-generation households, grandparents face considerable struggles, including scarcity of money, food and healthcare, physical and mental health problems and moral dilemmas in trying to navigate their everyday caregiving responsibilities. Grandmothers appear to shoulder a disproportionately high caregiving burden. Professional stakeholders underscored that skip-generation households face multiple sources of vulnerability and viewed skip-generation households as makers of family vulnerability. Structural factors, including poverty, gendered roles and a weak healthcare system, largely determine the precarity of grandparent caregivers’ lives. By examining the findings presented in this thesis through the lens of intersectionality theory, the analysis foregrounds important overlapping and interconnected structural drivers that underpin and shape the lives of these skip-generation caregivers. In a context of increasing and long-term labour migration, grandparents’ and their family’s agency is constrained by the intersection of wider structural factors, including poverty, gender inequalities, poor healthcare infrastructure, and lack of access to social security and support. Applying a social relational approach to understanding migration and caregiving in Cambodia, the analysis further exposes the broader social processes and relations that shape child rearing and reproduction within these rural migrant families. This helps to expose the otherwise mostly hidden social reproductive labour of ‘left-behind’ grandparents, in the face of their adult children’s migration—a labour which to date has remained largely unseen. Existing policy initiatives on ageing and care in Cambodia currently fall short of addressing the issues faced by skip-generation grandparents and their families. Future policies and programmes need to recognise and address the broader intersecting structural drivers that underpin the complex vulnerabilities facing skip-generation households. Within this, it is essential that future policies account for the evidently shifting dynamics with regards to caregiving roles and social reproductive work within the family, in order to develop more equitable policies and social security mechanisms that adequately support skip-generation grandparents and their families.</p

Determining barriers to creating an enabling environment in Cambodia: results from a baseline study with key populations and police

Introduction: Cambodian law enforcement's limited acceptance of harm reduction has hindered HIV program effectiveness. With funding from the Australian Department of Foreign Affairs and Trade, FHI 360 supported the Ministry of Interior to implement the Police Community Partnership Initiative (PCPI) in Cambodia's capital Phnom Penh. To guide this, FHI 360 conducted a baseline study examining police and key populations’ attitudes and practices towards one another, including fear and occurrence of arrest. Methods: Between December 2012 and January 2013, a cross‐sectional survey of 199 police post officers, 199 people who use drugs (PWUD) including people who inject drugs (PWID), 199 men who have sex with men (MSM), 200 transgender women (TGW) and 200 female entertainment workers (FEW) was conducted in five Phnom Penh districts. Eligible participants were ≥18 years, members of a key population from selected hotspots or police officers, deputy chiefs or chiefs. Results: Key populations’ median age was 25 years (IQR: 22–30); 40% had completed only primary school. Police were male (99.5%), with median age 43 years (IQR: 30 to 47), and 45 and 25% high school and university completion rates, respectively. Key populations feared arrest for carrying needles and syringes (67%), condoms (23%) and 19% felt afraid to access health services. Close to 75% of police reported body searching and 58% arresting key populations in the past six months for using drugs (64%), selling or distributing drugs (36%) or being violent (13%). Self‐reported arrests (23% PWUD, 6% MSM, 6% TGW, 12% FEW; p Conclusions: Key populations’ fear of accessing harm reduction and health services and police's negative attitudes and practices towards key populations present major barriers to HIV prevention efforts in Cambodia. To create an enabling environment and ensure police are allies in the Cambodian HIV response, interventions should tackle underlying negative attitudes among police towards key populations and vice versa.</br

Navigating 'ethics in practice': An ethnographic case study with young women living with HIV in Zambia

While ‘procedural ethics’ provides essential frameworks for governing global health research, reflecting on ‘ethics in practice’ offers important insights into addressing ethically important moments that arise in everyday research. Particularly for ethnographic research, renowned for it’s fluid and spontaneous nature, engaging with ‘ethics in practice’ has the potential to enhance research practice within global health. We provide a case study for such reflexivity, exploring ‘ethics in practice’ of ethnographic research with middle-income young women living with HIV in Lusaka, Zambia. We explore the ethical issues arising from the layered interaction of the population (young women), the disease under investigation (HIV), the method of study (ethnographic), and the setting (Zambia, a lower middle income country). We describe how we navigated five key practical ethical tensions that arose, namely the psycho-emotional benefits of the research, the negotiated researcher-participant relationship, protecting participants’ HIV status, confidentiality and data ownership, and researcher obligations after the end of the research. We exemplify reflexive engagement with ‘ethics in practice’ and suggest that engaging with ethics in this way can make important contributions towards developing more adequate ethical guidelines and research practice in global public health

Ageism, Healthy Life Expectancy and Population Ageing: How Are They Related?

Evidence shows that ageism negatively impacts the health of older adults. However, estimates of its prevalence are lacking. This study aimed to estimate the global prevalence of ageism towards older adults and to explore possible explanatory factors. Data were included from 57 countries that took part in Wave 6 of the World Values Survey. Multilevel Latent Class Analysis was performed to identify distinct classes of individuals and countries. Individuals were classified as having high, moderate or low ageist attitudes; and countries as being highly, moderately or minimally ageist, by aggregating individual responses. Individual-level (age, sex, education and wealth) and contextual-level factors (healthy life expectancy, population health status and proportion of the population aged over 60 years) were examined as potential explanatory factors in multinomial logistic regression. From the 83,034 participants included, 44%, 32% and 24% were classified as having low, moderate and high ageist attitudes, respectively. From the 57 countries, 34 were classified as moderately or highly ageist. The likelihood of an individual or a country being ageist was significantly reduced by increases in healthy life expectancy and the proportion of older people within a country. Certain personal characteristics—younger age, being male and having lower education—were significantly associated with an increased probability of an individual having high ageist attitudes. At least one in every two people included in this study had moderate or high ageist attitudes. Despite the issue’s magnitude and negative health impacts, ageism remains a neglected global health issue