The formation and function of the neutrophil phagosome.

Neutrophils are the most abundant circulating leukocyte and are crucial to the initial innate immune response to infection. One of their key pathogen-eliminating mechanisms is phagocytosis, the process of particle engulfment into a vacuole-like structure called the phagosome. The antimicrobial activity of the phagocytic process results from a collaboration of multiple systems and mechanisms within this organelle, where a complex interplay of ion fluxes, pH, reactive oxygen species, and antimicrobial proteins creates a dynamic antimicrobial environment. This complexity, combined with the difficulties of studying neutrophils ex vivo, has led to gaps in our knowledge of how the neutrophil phagosome optimizes pathogen killing. In particular, controversy has arisen regarding the relative contribution and integration of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-derived antimicrobial agents and granule-delivered antimicrobial proteins. Clinical syndromes arising from dysfunction in these systems in humans allow useful insight into these mechanisms, but their redundancy and synergy add to the complexity. In this article, we review the current knowledge regarding the formation and function of the neutrophil phagosome, examine new insights into the phagosomal environment that have been permitted by technological advances in recent years, and discuss aspects of the phagocytic process that are still under debate

DNA Footprints: Using Parasites to Detect Elusive Animals, Proof of Principle in Hedgehogs

The Western European Hedgehog (Erinaceous europaeus) is a nocturnal animal that is in decline in much of Europe, but the monitoring of this species is subjective, prone to error, and an inadequate basis for estimating population trends. Here, we report the use of Crenosoma striatum, a parasitic nematode specific to hedgehogs as definitive hosts, to detect hedgehog presence in the natural environment. This is achieved through collecting and sampling the parasites within their intermediate hosts, gastropoda, a group much simpler to locate and sample in both urban and rural habitats. C. striatum and Crenosoma vulpis were collected post-mortem from the lungs of hedgehogs and foxes, respectively. Slugs were collected in two sessions, during spring and autumn, from Skomer Island (n = 21), which is known to be free of hedgehogs (and foxes); and Pennard, Swansea (n = 42), known to have a healthy hedgehog population. The second internal transcribed spacer of parasite ribosomal DNA was used to develop a highly specific, novel, PCR based multiplex assay. Crenosoma striatum was found only at the site known to be inhabited by hedgehogs, at an average prevalence in gastropods of 10% in spring and autumn. The molecular test was highly specific: One mollusc was positive for both C. striatum and C. vulpis, and differentiation between the two nematode species was clear. This study demonstrates proof of principle for using detection of specific parasite DNA in easily sampled intermediate hosts to confirm the presence of an elusive nocturnal definitive host species. The approach has great potential as an adaptable, objective tool to supplement and support existing ecological survey methods

Logarithmic rate dependence in deforming granular materials

Rate-independence for stresses within a granular material is a basic tenet of many models for slow dense granular flows. By contrast, logarithmic rate dependence of stresses is found in solid-on-solid friction, in geological settings, and elsewhere. In this work, we show that logarithmic rate-dependence occurs in granular materials for plastic (irreversible) deformations that occur during shearing but not for elastic (reversible) deformations, such as those that occur under moderate repetitive compression. Increasing the shearing rate, \Omega, leads to an increase in the stress and the stress fluctuations that at least qualitatively resemble what occurs due to an increase in the density. Increases in \Omega also lead to qualitative changes in the distributions of stress build-up and relaxation events. If shearing is stopped at t=0, stress relaxations occur with \sigma(t)/ \sigma(t=0) \simeq A \log(t/t_0). This collective relaxation of the stress network over logarithmically long times provides a mechanism for rate-dependent strengthening.Comment: 4 pages, 5 figures. RevTeX

Quantum physics in inertial and gravitational fields

Covariant generalizations of well-known wave equations predict the existence of inertial-gravitational effects for a variety of quantum systems that range from Bose-Einstein condensates to particles in accelerators. Additional effects arise in models that incorporate Born reciprocity principle and the notion of a maximal acceleration. Some specific examples are discussed in detail.Comment: 25 pages,1 figure,to appear in "Relativity in Rotating Frame

Building blocks of community positive health: the contribution of Kenyan communities

BACKGROUND: Beyond the health system, people draw on a complex system of everyday community resources to strengthen human and environmental health. These resources, and the community members who use them, are often overlooked by traditional approaches to planetary health. We aimed to apply a resourcefulness approach to define community positive health and the systems of resources that support this, and to define ways in which communities can pursue and sustain health agendas driven by local priorities. METHODS: Through a multi-site, mixed-methods research project, we worked with different groups of community members across three diverse field sites in Kenya, in the Baringo, Siaya, and Nakuru counties. We used a mixture of qualitative (78 focus discussion groups), participatory (67 activities, such as cognitive mapping, community timelines and mapping, tree diagrams, patient journeys, and walking interviews), and data-driven approaches to understand community concepts of positive health and collaboratively define the building blocks that shape community positive health. FINDINGS: Preliminary research findings indicated that community positive health was defined by building blocks that included nutrition, clean water, education, and adequate local infrastructure. Crucially, these building blocks were underpinned by intangible community resources, such as culture, knowledge, and social cohesion. With cognitive mapping, we understood how communities leveraged these building blocks into a functioning community-level system. However, one of the greatest challenges felt by each community was the detrimental effects of climate change, contributing alongside human action and inaction to droughts, floods, and natural resource degradation. INTERPRETATION: This initial stage of research defined community positive health and uncovered systems of local resources. Findings will be refined in a further stage of research to co-produce a pilot-tested, validated toolkit to enable resourcefulness-based approaches to community positive health. This output will be supported by an inclusive knowledge-building process that will set the stage to support communities to make more effective decisions about the use of local resources. FUNDING: Belmont Forum by the UK Natural Environment Research Council

Think global, act local: using a translocal approach to understand community-based organisations’ responses to planetary health crises during COVID-19

Little is known on how community-based responses to planetary health crises, such as the COVID-19 pandemic, can integrate concerns about livelihoods, equity, health, wellbeing, and the environment. We used a translocal learning approach to co-develop insights on community-based responses to complex health and environmental and economic crises with leaders from five organisations working with communities at the front line of intersecting planetary health challenges in Finland, India, Kenya, Peru, and the USA. Translocal learning supports collective knowledge production across different localities in ways that value local perspectives but transcend national boundaries. There were three main findings from the translocal learning process. First, thanks to their proximity to the communities they served, community-based organisations (CBOs) can quickly identify the ways in which COVID-19 might worsen existing social and health inequities. Second, localised CBO actions are key to supporting communities with unique challenges in the face of systemic planetary health crises. Third, CBOs can develop rights-based, ecologically-minded actions responding to local priorities and mobilising available resources. Our findings show how solutions to planetary health might come from small-scale community initiatives that are well connected within and across contexts. Locally-focused globally-aware actions should be harnessed through greater recognition, funding, and networking opportunities. Globally, planetary health initiatives should be supported by applying the principles of subsidiarity and translocalism

Potential Role for Peptidylarginine Deiminase 2 (PAD2) in Citrullination of Canine Mammary Epithelial Cell Histones

Peptidylarginine Deiminases (PADs) convert arginine residues on substrate proteins to citrulline. Previous reports have documented that PAD2 expression and activity varies across the estrous cycle in the rodent uterus and pituitary gland, however, the expression and function of PAD2 in mammary tissue has not been previously reported. To gain more insight into potential reproductive roles for PAD2, in this study we evaluated PAD2 expression and localization throughout the estrous cycle in canine mammary tissue and then identified possible PAD2 enzymatic targets. Immunohistochemical and immunofluorescence analysis found PAD2 expression is low in anestrus, limited to a distinct, yet sparse, subset of epithelial cells within ductal alveoli during estrus/early diestrus, and encompasses the entire epithelium of the mammary duct in late diestrus. At the subcellular level, PAD2 is expressed in the cytoplasm, and to a lesser extent, the nucleus of these epithelial cells. Surprisingly, stimulation of canine mammary tumor cells (CMT25) shows that EGF, but not estrogen or progesterone, upregulates PAD2 transcription and translation suggesting EGF regulation of PAD2 and possibly citrullination in vivo. To identify potential PAD2 targets, anti-pan citrulline western blots were performed and results showed that citrullination activity is limited to diestrus with histones appearing to represent major enzymatic targets. Use of site-specific anti-citrullinated histone antibodies found that the N-terminus of histone H3, but not H4, appears to be the primary target of PAD activity in mammary epithelium. This observation supports the hypothesis that PAD2 may play a regulatory role in the expression of lactation related genes via histone citrullination during diestrus

Difficulty Accessing Syringes Mediates the Relationship Between Methamphetamine Use and Syringe Sharing Among Young Injection Drug Users

Injection drug users (IDU) who use methamphetamine (MA) are at an increased risk of HIV infection due to engagement in injection-related risk behavior including syringe sharing. In this cohort study of young IDU aged 18-30, we investigated the relationship between injection MA use and syringe sharing, and whether difficulty accessing sterile syringes mediated this association. Behavioral questionnaires were completed by 384 IDU in Vancouver, Canada between October 2005 and May 2008. Generalized estimating equations were used to estimate direct and indirect effects. The median age of participants was 24 (IQR: 22–27) and 214 (55.7%) were male. Injecting MA was independently associated with syringe sharing. Mediation analyses revealed that difficulty accessing sterile syringes partially mediated the association between injecting MA and syringe sharing. Interventions to reduce syringe sharing among young methamphetamine injectors must address social and structural barriers to accessing HIV prevention programs

How does gender influence the recognition of cardiovascular risk and adherence to self-care recommendations? : a study in polish primary care

Background: Studies have shown a correlation between gender and an ability to change lifestyle to reduce the risk of disease. However, the results of these studies are ambiguous, especially where a healthy lifestyle is concerned. Additionally, health behaviors are strongly modified by culture and the environment. Psychological factors also substantially affect engagement with disease-related lifestyle interventions. This study aimed to examine whether there are differences between men and women in the frequency of health care behavior for the purpose of reducing cardiovascular risk (CVR), as well as cognitive appraisal of this type of risk. We also aimed to identify the psychological predictors of engaging in recommended behavior for reducing the risk of cardiovascular disease after providing information about this risk in men and women. Methods: A total of 134 consecutive eligible patients in a family practice entered a longitudinal study. At initial consultation, the individual’s CVR and associated health burden was examined, and preventive measures were recommended by the physician. Self-care behavior, cognitive appraisal of risk, and coping styles were then assessed using psychological questionnaires. Six months after the initial data collection, the frequency of subjects’ self-care behavior was examined. Results: We found an increase in health care behavior after providing information regarding the rate of CVR in both sexes; this increase was greater for women than for men. Women followed self-care guidelines more often than men, particularly for preventive measures and dietary advice. Women were more inclined to recognize their CVR as a challenge. Coping style, cognitive appraisal, age, level of health behaviors at baseline and CVR values accounted for 48% of the variance in adherence to self-care guidelines in women and it was 52% in men. In women, total risk of CVD values were most important, while in men, cognitive appraisal of harm/loss was most important. Conclusions: Different predictors of acquisition of health behavior are encountered in men and women. Our results suggest that gender-adjusted motivation models influencing the recognition process need to be considered to optimize compliance in patients with CVR

Negotiating the transition from adolescence to motherhood: Coping with prenatal and parenting stress in teenage mothers in Mulago hospital, Uganda

<p>Abstract</p> <p>Background</p> <p>Adolescence is a transitional stage from childhood to adulthood that is characterized by physical, physiological, psychosocial and behavioral changes that are influenced to a large extent by the age, culture and socialization of the individual. To explore what adolescent mothers perceive as their struggles during the period of transition from childhood to parenthood (through motherhood) and to describe strategies employed in coping with stress of pregnancy, motherhood and parenthood.</p> <p>Methods</p> <p>Longitudinal qualitative study involving twenty two in-depth interviews and six focus group discussions among pregnant adolescents who were followed from pregnant to delivery, from January 2004 to August 2005. Participant were selected by theoretical sampling and data was analyzed using grounded theory.</p> <p>Results</p> <p>Overall, young adolescents reported more anxiety, loss of self esteem (when they conceived), difficulty in accessing financial, moral and material support from parents or partners and stigmatization by health workers when they sought care from health facilities. Three strategies by which adolescent mothers cope with parenting and pregnancy stress that were described as utilizing opportunities (thriving), accommodating the challenges (bargaining and surviving), or failure (despairing), and varied in the extent to which they enabled adolescents to cope with the stress.</p> <p>Conclusion</p> <p>Adolescents on the transition to motherhood have variable needs and aspirations and utilize different strategies to cope with the stress of pregnancy and parenthood.</p