Genetic resistance to experimental infection with Mycobacterium bovis in red deer (Cervus elaphus)

Tuberculosis (Tb) caused by Mycobacterium bovis is a worldwide threat to livestock and humans. One control strategy is to breed livestock that are more resistant to Mycobacterium bovis. In a 3-year heritability study 6 farmed red deer stags were selected from 39 on the basis of their differing responses to experimental challenge via the tonsillar sac with approximately 500 CFU of M. bovis. Two stags remained uninfected, two were moderately affected, and two developed serious spreading Tb. Seventy offspring, bred from these six stags by artificial insemination using stored semen, were similarly challenged with M. bovis. The offspring showed patterns of response to M. bovis challenge similar to those of their sires, providing evidence for a strong genetic basis to resistance to Tb, with an estimated heritability of 0.48 (standard error, 0.096; P < 0. 01). This is the first time the heritability of Tb resistance in domestic livestock has been measured. The breeding of selection lines of resistant and susceptible deer will provide an ideal model to study the mechanisms of Tb resistance in a ruminant and could provide an additional strategy for reducing the number and severity of outbreaks of Tb in farmed deer herds. Laboratory studies to identify genetic and immunological markers for resistance to Tb are under way. Preliminary studies showed no associations between NRAMP or DRB genes and resistance to Tb in deer. Patterns of immune responses seen in resistant animals suggest that both innate and acquired pathways of immunity are necessary to produce the resistant phenotype.     

Heparins as essential antioxidants

Chronically inflamed tissues contain significant concentrations of oxygen radicals, possibly generated by transition metal species such as Fe(II) and Cu(I). In addition, the pH of such tissues may well be lower than that of normal counterpart tissues. In this communication, the effect of variation of pH on the antioxidant activity of caeruloplasmin (a copper-containing acute-phase protein possessing important ferroxidase and other antioxidant activities) and of heparin are reported. Heparin, unlike caeruloplasmin, retains antioxidant activity at low pH. Heparins possess a variety of metal cation-binding chemical groups allowing them to bind damaging Cu(I) and Fe(II) ions and consequently prevent their redox involvement in oxygen radical-generating Fenton reactions. In conclusion, heparins may function as endogenous antioxidants and sequestration and/or oxidation by them, of ions such as Fe(II), may contribute to their effectiveness.

     

Morphologic and clinical determinants of response to therapy in small cell carcinoma of the lung

The authors reviewed a series of 29 cases of small cell carcinoma of the lung in order to determine the influence of histologic type and other prognostic factors on response to combination chemotherapy and survival. Comparing classical (lymphocyte-like and fusiform) versus nonclassical histologic types (polygonal and other), no significant difference could be found in response to therapy (CR + PR 11/16 versus 8/11), median survival (7 versus 6 months) or median survival of responders (9 versus 10 months). Furthermore, tumors with atypical histology ("other") behaved similar to the overall series. Of clinical factors investigated, only decreased performance status and presence of metastatic disease were significant prognostic indicators. The results suggest that tumor histologic type is not a useful prognostic indicator in small cell carcinoma, and that atypical tumors resembling small cell carcinoma appear to respond similarly to classical small cell carcinoma and should probably be treated as such.     

Treating Anger and Aggression in Military Populations: Research Updates and Clinical Implications

Anger is a common symptom among military populations with posttraumatic stress disorder (PTSD); yet, anger treatment has received relatively little attention in the literature. This discrepancy is surprising given that excessive anger is a key predictor of treatment outcome in PTSD. This study seeks to (a) build a case for the importance of a more explicit approach to understanding and treating anger in our military and veteran populations, (b) summarize the current literature base on treatment factors and treatment outcomes for treating anger and related symptoms among veterans, and (c) offer clinical and research implications and recommendations based on current findings and on the expertise of the authors in completing a large‐scale study of anger treatment with veterans.     

Modulation of potassium channels in the hearts of transgenic and mutant mice with altered polyamine biosynthesis

Inward rectification of cardiac I(K1)channels was modulated by genetic manipulation of the naturally occurring polyamines. Ornithine decarboxylase (ODC) was overexpressed in mouse heart under control of the cardiac alpha -myosin heavy chain promoter (alpha MHC). In ODC transgenic hearts, putrescine and cadaverine levels were highly elevated ( identical with 35-fold for putrescine), spermidine was increased 3.6-fold, but spermine was essentially unchanged. I(K1)density was reduced by identical with 38%, although the voltage-dependence of rectification was essentially unchanged. Interestingly, the fast component of transient outward (I(to,f)) current was increased, but the total outward current amplitude was unchanged. I(K1)and I(to)currents were also studied in myocytes from mutant Gyro (Gy) mice in which the spermine synthase gene is disrupted, leading to a complete loss of spermine. I(K1)current densities were not altered in Gy myocytes, but the steepness of rectification was reduced indicating a role for spermine in controlling rectification. Intracellular dialysis of myocytes with putrescine, spermidine and spermine caused reduction, no change and increase of the steepness of rectification, respectively. Taken together with kinetic analysis of I(K1)activation these results are consistent with spermine being a major rectifying factor at potentials positive to E(K), spermidine dominating at potentials around and negative to E(K), and putrescine playing no significant role in rectification in the mouse heart.     

Serving Veterans in their Communities: Evaluation of an Online Resource for Behavioral Health Care Providers

Many veterans receive behavioral health care services from providers in their communities. The Community Provider Toolkit (the Toolkit) is a website developed by the National Center for PTSD and the Department of Veterans Affairs intended to provide community mental health care providers with key veteran-focused educational resources. This mixed-methods study examined the potential impact of the Toolkit on provider knowledge and behaviors. Sixty-four clinicians in the community who currently or plan to provide services to veterans were surveyed. The majority of providers found the website useful and easy to navigate. After visiting the site, many providers found additional online and educational resources that they would add to a hypothetical treatment plan. Forty-five providers completed a 1-month follow-up survey focused on use of the Toolkit. Results indicate that the Toolkit may be a valuable tool for increasing provider knowledge about veteran-specific resources.

     

Physical activity,mental health and well-being of adults during initial COVID-19 containment strategies: A multi-country cross-sectional analysis

ObjectivesTo assess physical activity (PA), mental health and well-being of adults in the United Kingdom (UK), Ireland, New Zealand and Australia during the initial stages of National governments’ Coronavirus disease (COVID-19) containment responses.DesignObservational, cross-sectional.MethodsAn online survey was disseminated to adults (n = 8,425; 44.5 ± 14.8y) residing in the UK, Ireland, New Zealand and Australia within the first 2-6 weeks of government-mandated COVID-19 restrictions. Main outcome measures included: Stages of Change scale for exercise behaviour change; International Physical Activity Questionnaire (short-form); World Health Organisation-5 Well-being Index; and the Depression Anxiety and Stress Scale-9.ResultsParticipants who reported a negative change in exercise behaviour from before initial COVID-19 restrictions to during the initial COVID-19 restrictions demonstrated poorer mental health and well-being compared to those demonstrating either a positive-or no change in their exercise behaviour (p < 0.001). Whilst women reported more positive changes in exercise behaviour, young people (18-29y) reported more negative changes (both p < 0.001). Individuals who had more positive exercise behaviours reported better mental health and well-being (p < 0.001). Although there were no differences in PA between countries, individuals in New Zealand reported better mental health and well-being (p < 0.001).ConclusionThe initial COVID-19 restrictions have differentially impacted upon PA habits of individuals based upon their age and sex, and therefore have important implications for international policy and guideline recommendations. Public health interventions that encourage PA should target specific groups (e.g., men, young adults) who are most vulnerable to the negative effects of physical distancing and/or self-isolation.