Elucidating sources and roles of Granzymes A and B during bacterial infection and sepsis

During bacterial sepsis, proinflammatory cytokines contribute to multiorgan failure and death in a pro- cess regulated in part by cytolytic cell granzymes. When challenged with a sublethal dose of the identi- fied mouse pathogen Brucella microti, wild-type (WT) and granzyme A (gzmA)/ mice eliminate the organism from liver and spleen in 2 or 3 weeks, whereas the bacteria persist in mice lacking perforin or granzyme B as well as in mice depleted of Tc cells. In comparison, after a fatal challenge, only gzmA/ mice exhibit increased survival, which correlated with reduced proinflammatory cytokines. Depletion of natural killer (NK) cells protects WT mice from sepsis without influencing bacterial clearance and the transfer of WT, but not gzmA/ NK, cells into gzmA/ recipients restores the susceptibility to sepsis. Therefore, infection-related pathology, but not bacterial clearance, appears to require gzmA, suggesting the protease may be a therapeutic target for the prevention of bacterial sepsis without affecting immune control of the pathogen

Lifetime self-reported arthritis is associated with elevated levels of mental health burden: A multi-national cross sectional study across 46 low- and middle-income countries

Population-based studies investigating the relationship of arthritis with mental health outcomes are lacking, particularly among low- and middle-income countries (LMICs). We investigated the relationship between arthritis and mental health (depression spectrum, psychosis spectrum, anxiety, sleep disturbances and stress) across community-dwelling adults aged ≥18 years across 46 countries from the World Health Survey. Symptoms of psychosis and depression were established using questions from the Mental Health Composite International Diagnostic Interview. Severity of anxiety, sleep problems, and stress sensitivity over the preceding 30 days were self-reported. Self-report lifetime history of arthritis was collected, including presence or absence of symptoms suggestive of arthritis: pain, stiffness or swelling of joints over the preceding 12-months. Multivariable logistic regression analyses were undertaken. Overall, 245,706 individuals were included. Having arthritis increased the odds of subclinical psychosis (OR = 1.85; 95%CI = 1.72–1.99) and psychosis (OR = 2.48; 95%CI = 2.05–3.01). People with arthritis were at increased odds of subsyndromal depression (OR = 1.92; 95%CI = 1.64–2.26), a brief depressive episode (OR = 2.14; 95%CI = 1.88–2.43) or depressive episode (OR = 2.43; 95%CI = 2.21–2.67). Arthritis was also associated with increased odds for anxiety (OR = 1.75; 95%CI = 1.63–1.88), sleep problems (OR = 2.23; 95%CI = 2.05–2.43) and perceived stress (OR = 1.43; 95%CI = 1.33–1.53). Results were similar for middle-income and low-income countries. Integrated interventions addressing arthritis and mental health comorbidities are warranted to tackle this considerable burden

Expression of a barley cystatin gene in maize enhances resistance against phytophagous mites by altering their cysteine-proteases

Phytocystatins are inhibitors of cysteine-proteases from plants putatively involved in plant defence based on their capability of inhibit heterologous enzymes. We have previously characterised the whole cystatin gene family members from barley (HvCPI-1 to HvCPI-13). The aim of this study was to assess the effects of barley cystatins on two phytophagous spider mites, Tetranychus urticae and Brevipalpus chilensis. The determination of proteolytic activity profile in both mite species showed the presence of the cysteine-proteases, putative targets of cystatins, among other enzymatic activities. All barley cystatins, except HvCPI-1 and HvCPI-7, inhibited in vitro mite cathepsin L- and/or cathepsin B-like activities, HvCPI-6 being the strongest inhibitor for both mite species. Transgenic maize plants expressing HvCPI-6 protein were generated and the functional integrity of the cystatin transgene was confirmed by in vitro inhibitory effect observed against T. urticae and B. chilensis protein extracts. Feeding experiments impaired on transgenic lines performed with T. urticae impaired mite development and reproductive performance. Besides, a significant reduction of cathepsin L-like and/or cathepsin B-like activities was observed when the spider mite fed on maize plants expressing HvCPI-6 cystatin. These findings reveal the potential of barley cystatins as acaricide proteins to protect plants against two important mite pests

Climate change adaptation in European river basins

This paper contains an assessment and standardized comparative analysis of the current water management regimes in four case-studies in three European river basins: the Hungarian part of the Upper Tisza, the Ukrainian part of the Upper Tisza (also called Zacarpathian Tisza), Alentejo Region (including the Alqueva Reservoir) in the Lower Guadiana in Portugal, and Rivierenland in the Netherlands. The analysis comprises several regime elements considered to be important in adaptive and integrated water management: agency, awareness raising and education, type of governance and cooperation structures, information management and—exchange, policy development and—implementation, risk management, and finances and cost recovery. This comparative analysis has an explorative character intended to identify general patterns in adaptive and integrated water management and to determine its role in coping with the impacts of climate change on floods and droughts. The results show that there is a strong interdependence of the elements within a water management regime, and as such this interdependence is a stabilizing factor in current management regimes. For example, this research provides evidence that a lack of joint/participative knowledge is an important obstacle for cooperation, or vice versa. We argue that there is a two-way relationship between information management and collaboration. Moreover, this research suggests that bottom-up governance is not a straightforward solution to water management problems in large-scale, complex, multiple-use systems, such as river basins. Instead, all the regimes being analyzed are in a process of finding a balance between bottom-up and top–down governance. Finally, this research shows that in a basin where one type of extreme is dominant—like droughts in the Alentejo (Portugal) and floods in Rivierenland (Netherlands)—the potential impacts of other extremes are somehow ignored or not perceived with the urgency they might deserv

Overfeeding, Autonomic Regulation and Metabolic Consequences

The autonomic nervous system plays an important role in the regulation of body processes in health and disease. Overfeeding and obesity (a disproportional increase of the fat mass of the body) are often accompanied by alterations in both sympathetic and parasympathetic autonomic functions. The overfeeding-induced changes in autonomic outflow occur with typical symptoms such as adiposity and hyperinsulinemia. There might be a causal relationship between autonomic disturbances and the consequences of overfeeding and obesity. Therefore studies were designed to investigate autonomic functioning in experimentally and genetically hyperphagic rats. Special emphasis was given to the processes that are involved in the regulation of peripheral energy substrate homeostasis. The data revealed that overfeeding is accompanied by increased parasympathetic outflow. Typical indices of vagal activity (such as the cephalic insulin release during food ingestion) were increased in all our rat models for hyperphagia. Overfeeding was also accompanied by increased sympathetic tone, reflected by enhanced baseline plasma norepinephrine (NE) levels in both VMH-lesioned animals and rats rendered obese by hyperalimentation. Plasma levels of NE during exercise were, however, reduced in these two groups of animals. This diminished increase in the exercise-induced NE outflow could be normalized by prior food deprivation. It was concluded from these experiments that overfeeding is associated with increased parasympathetic and sympathetic tone. In models for hyperphagia that display a continuously elevated nutrient intake such as the VMH-lesioned and the overfed rat, this increased sympathetic tone was accompanied by a diminished NE response to exercise. This attenuated outflow of NE was directly related to the size of the fat reserves, indicating that the feedback mechanism from the periphery to the central nervous system is altered in the overfed state.

Understanding the experience of initiating community-based physical activity and social support by people with serious mental illness: a systematic review using a meta-ethnographic approach

Background People with long-term serious mental illness live with severe and debilitating symptoms that can negatively influence their health and quality of life, leading to outcomes such as premature mortality, morbidity and obesity. An interplay of social, behavioural, biological and psychological factors is likely to contribute to their poor physical health. Participating in regular physical activity could bring symptomatic improvements, weight loss benefits, enhanced wellbeing and when undertaken in a community-based group setting can yield additional, important social support benefits. Yet poor uptake of physical activity by people with serious mental illness is a problem. This review will systematically search, appraise and synthesise the existing evidence that has explored the experience of community-based physical activity initiation and key features of social support within these contexts by adults with schizophrenia, bipolar affective disorder, major depressive disorder or psychosis using the meta-ethnography approach. This new understanding may be key in designing more acceptable and effective community-based group PA programmes that meet patients’ need and expectations. Methods This will be a systematic review of qualitative studies using the meta-ethnography approach. The following databases will be searched: ASSIA, CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, Health Technology Assessment Database, MEDLINE, PsycINFO, Sociological Abstracts, SPORTDiscus and Web of Science. Grey literature will also be sought. Eligible studies will use qualitative methodology; involve adults (≥18 years) with schizophrenia, bipolar affective disorder, major depressive disorder or psychosis; will report community-based group physical activity; and capture the experience of physical activity initiation and key features of social support from the perspective of the participant. Study selection and assessment of quality will be performed by two reviewers. Data will be extracted by one reviewer, tabled, and checked for accuracy by the second reviewer. The meta-ethnography approach by Noblit and Hare [1] will be used to synthesise the data. Discussion This systematic review is expected to provide new insights into the experience of community-based group physical activity initiation for adults who have a serious mental illness to inform person-centred improvements to the management of serious mental illness through physical activity. Registration The protocol has been registered on the International Prospective Register of Systematic Reviews (PROSPERO) on 22/03/2017; http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42017059948 (registration number CRD42017059948). Keywords Serious mental illness - Physical activity - Community - Social support - Exercise - Sport - Adults - Patient experience - Qualitative research - Meta-ethnography - Systematic revie

Violence against primary school children with disabilities in Uganda: a cross-sectional study.

BACKGROUND: 150 million children live with disabilities globally, and a recent systematic review found 3 to 4 times the levels of violence versus non-disabled children in high income countries. However, almost nothing is known about violence against disabled children in lower income countries. We aim to explore the prevalence, patterns and risk factors for physical, sexual and emotional violence among disabled children attending primary school in Luwero District, Uganda. METHODS: We performed a secondary analysis of data from the baseline survey of the Good Schools Study. 3706 children and young adolescents aged 11-14 were randomly sampled from 42 primary schools. Descriptive statistics were computed and logistic regression models fitted. RESULTS: 8.8% of boys and 7.6% of girls reported a disability. Levels of violence against both disabled and non-disabled children were extremely high. Disabled girls report slightly more physical (99.1% vs 94.6%, p = 0.010) and considerably more sexual violence (23.6% vs 12.3%, p = 0.002) than non-disabled girls; for disabled and non-disabled boys, levels are not statistically different. The school environment is one of the main venues at which violence is occurring, but patterns differ by sex. Risk factors for violence are similar between disabled and non-disabled students. CONCLUSIONS: In Uganda, disabled girls are at particular risk of violence, notably sexual violence. Schools may be a promising venue for intervention delivery. Further research on the epidemiology and prevention of violence against disabled and non-disabled children in low income countries is urgently needed

Changes in Parasite Virulence Induced by the Disruption of a Single Member of the 235 kDa Rhoptry Protein Multigene Family of Plasmodium yoelii

Invasion of the erythrocyte by the merozoites of the malaria parasite is a complex process involving a range of receptor-ligand interactions. Two protein families termed Erythrocyte Binding Like (EBL) proteins and Reticulocyte Binding Protein Homologues (RH) play an important role in host cell recognition by the merozoite. In the rodent malaria parasite, Plasmodium yoelii, the 235 kDa rhoptry proteins (Py235) are coded for by a multigene family and are members of the RH. In P. yoelii Py235 as well as a single member of EBL have been shown to be key mediators of virulence enabling the parasite to invade a wider range of host erythrocytes. One member of Py235, PY01365 is most abundantly transcribed in parasite populations and the protein specifically binds to erythrocytes and is recognized by the protective monoclonal antibody 25.77, suggesting a key role of this particular member in virulence. Recent studies have indicated that overall levels of Py235 expression are essential for parasite virulence. Here we show that disruption of PY01365 in the virulent YM line directly impacts parasite virulence. Furthermore the disruption of PY01365 leads to a reduction in the number of schizonts that express members of Py235 that react specifically with the mcAb 25.77. Erythrocyte binding assays show reduced binding of Py235 to red blood cells in the PY01365 knockout parasite as compared to YM. While our results identify PY01365 as a mediator of parasite virulence, they also confirm that other members of Py235 are able to substitute for PY01365

Factors associated with regular physical activity participation among people with severe mental ill health

Purpose People with severe mental ill health (SMI) are less physically active and more sedentary than the general population. There is limited research investigating the correlates of physical activity (PA) in people with SMI impeding development of successful interventions. This study aimed to assess the factors associated with regular participation of PA among a large sample of people with SMI. Methods The data for this study were collected from the ‘Lifestyle Health and Wellbeing’ (HWB) cohort that collected data through self-administered questionnaire from participants with SMI. Self-reported participation in regular PA was the main outcome variable. Potential predictors of PA were grouped as demographic, biological, psychological and behavioural variables. Multivariable logistic regressions were conducted considering PA participation as the dependent variable adjusted for possible correlated predictors. Results In total, 3,287 people with SMI (mean (SD) age 47.7 (14.58) years, 59% male) were included; 38% reported undertaking regular PA and 61% wanted to undertake more physical activity. Multivariable logistic regressions showed that the following factors were associated with undertaking more regular PA: being male, aged 18-65 years, having a body mass index between 18.5 and 30 kg/m2, having better self-perceived general health condition, not having a health problem that limits activity, giving higher importance to maintain a healthy lifestyle, and eating more fruit and vegetables. Conclusions Having a better self-perceived general health and placing importance on maintaining a healthy lifestyle were important predictors of regular PA. Lifestyle interventions targeting increased PA among people with SMI should be shaped by their health perception and informed by their needs