Chapter III: Management of cardiovascular risk factors and medical therapy

Critical limb ischaemia (CLI) is a particularly severe manifestation of lower limb atherosclerosis posing a major threat to both limb and life of affected patients. Besides arterial revascularisation, risk-factor modification and administration of antiplatelet therapy is a major goal in the treatment of CLI patients. Key elements of cardiovascular risk management are smoking cessation and treatment of hyperlipidaemia with dietary modification or statins. Moreover, arterial hypertension and diabetes mellitus should be adequately treated. In CLI patients not suitable for arterial revascularisation or subsequent to unsuccessful revascularisation, parenteral prostanoids may be considered. CLI patients undergoing surgical revascularisation should be treated with beta blockers. At present, neither gene nor stem-cell therapy can be recommended outside clinical trials. Of note, walking exercise is contraindicated in CLI patients due to the risk of worsening pre-existing or causing new ischaemic wounds. CLI patients are oftentimes medically frail and exhibit significant comorbidities. Co-existing coronary heart and carotid as well as renal artery disease should be managed according to current guidelines. Considering the above-mentioned treatment goals, interdisciplinary treatment approaches for CLI patients are warranted. Aim of the present manuscript is to discuss currently existing evidence for both the management of cardiovascular risk factors and treatment of co-existing disease and to deduct specific treatment recommendations.

Glomerulonephropathy in Aged Captive Key Largo Woodrats (Neotoma floridana smalli)

A retrospective review of mortality records of Key Largo woodrats (Neotoma floridana smalli) in a captive breeding program revealed chronic renal disease in 5 of 6 woodrats older than 4 years of age. Two of the 5 woodrats with chronic renal disease also had clinical evidence of diabetes mellitus. Kidneys from all 5 woodrats were examined via light microscopy, histochemical staining, immunohistochemical staining, and transmission electron microscopy. The dietary histories of the affected animals were examined as well. The most striking histopathologic abnormality in the affected kidneys was the presence of large protein casts within cortical and medullary tubules in combination with lesions of membranous glomerulopathy and glomerulosclerosis. Transmission electron microscopy revealed thickening and undulation of the tubular and glomerular mesangial basement membranes with the variable presence of electron-dense deposits within the capillary endothelial basement membrane. Patchy glomerular immunoreactivity for IgG was noted in 2 cases, but IgA and IgM immunoreactivity were not present. The pathologic changes in the kidneys of the Key Largo woodrats mirrored many of the features of chronic progressive nephropathy commonly diagnosed in laboratory rats. Woodrats in the captive population were fed an ad libitum high-protein diet similar to diets that have been shown in laboratory rats to exacerbate the development and progression of chronic progressive nephropathy. It is concluded that Key Largo woodrats develop glomerulonephropathy with features similar to chronic progressive nephropathy described in laboratory rats. Age, concomitant disease, and dietary factors may contribute to the development and severity of this potentially age-limiting disease in Key Largo woodrats.

Primary care physician supply and other key determinants of health care utilisation: The case of Switzerland

Background The Swiss government decided to freeze new accreditations for physicians in private practice in Switzerland based on the assumption that demand-induced health care spending may be cut by limiting care offers. This legislation initiated an ongoing controversial public debate in Switzerland. The aim of this study is therefore the determination of socio-demographic and health system-related factors of per capita consultation rates with primary care physicians in the multicultural population of Switzerland. Methods The data were derived from the complete claims data of Swiss health insurers for 2004 and included 21.4 million consultations provided by 6564 Swiss primary care physicians on a fee-for-service basis. Socio-demographic data were obtained from the Swiss Federal Statistical Office. Utilisation-based health service areas were created and were used as observational units for statistical procedures. Multivariate and hierarchical models were applied to analyze the data. Results Models within the study allowed the definition of 1018 primary care service areas with a median population of 3754 and an average per capita consultation rate of 2.95 per year. Statistical models yielded significant effects for various geographical, socio-demographic and cultural factors. The regional density of physicians in independent practice was also significantly associated with annual consultation rates and indicated an associated increase 0.10 for each additional primary care physician in a population of 10,000 inhabitants. Considerable differences across Swiss language regions were observed with reference to the supply of ambulatory health resources provided either by primary care physicians, specialists, or hospital-based ambulatory care. Conclusion The study documents a large small-area variation in utilisation and provision of health care resources in Switzerland. Effects of physician density appeared to be strongly related to Swiss language regions and may be rooted in the different cultural backgrounds of the served populations.

Droughts and famines: The underlying factors and the causal links among agro-pastoral households in semi-arid Makueni district, Kenya

Famines are often linked to drought in semi-arid areas of Sub-Saharan Africa where not only pastoralists, but also increasingly agro-pastoralists are affected. This study addresses the interplay between drought and famine in the rural semi-arid areas of Makueni district, Kenya, by examining whether, and how crop production conditions and agro-pastoral strategies predispose smallholder households to drought-triggered food insecurity. If this hypothesis holds, then approaches to deal with drought and famine have to target factors causing household food insecurity during non-drought periods. Data from a longitudinal survey of 127 households, interviews, workshops, and daily rainfall records (1961–2003) were analysed using quantitative and qualitative methods. This integrated approach confirms the above hypothesis and reveals that factors other than rainfall, like asset and labour constraints, inadequate policy enforcement, as well as the poverty-driven inability to adopt risk-averse production systems play a key role. When linking these factors to the high rainfall variability, farmer-relevant definitions and forecasts of drought have to be applied.

Cell population, viability, and some key immunomodulatory molecules in different milk somatic cell samples in dairy cows

Immune cells in the milk are most important in combating pathogens that invade the mammary gland. This study investigated the immune competence and viability of somatic milk cells that are already resident in milk and udders free of infection. Cells were studied in freshly removed milk to simulate conditions in the udder. Effects of incubation, cell preparation, and immunological stimulation with 0.5 mug/ml lipopolysaccharide (LPS) from Escherichia coli were analysed. Viability and differential counts of milk cells between high and low somatic cell count (SCC) quarters, and cisternal and alveolar milk with and without LPS stimulation were compared. Incubation and preparation of cells caused a cell loss which further increased with time independently of SCC and milk fraction. The viability of these cells was stable until 3 h post incubation and decreased until 6 h. Cell populations differed between both investigations, but did not change during the course of the experiment. mRNA expression of immune and apoptosis factors of the cells, measured by qPCR, did not change substantially: mRNA expression of caspase 3, Toll like receptor 4, and GM-CSF did not change, whereas the expression of the death receptor Fas/APO-1 (CD95), lactoferrin and lysozyme was decreased at 6 h. Cyclooxygenase-2 and TNF-alpha mRNA expression were decreased after 6 h of LPS treatment. In comparison with other studies in vivo or in vitro (in cell culture), in this study where cells are studied ex vivo (removed from the udder but kept in their natural environment, the milk) resident milk cells seem to be more vulnerable, less viable, less able to respond to stimulation, and thus less immune competent compared with cells that have freshly migrated from blood into milk after pathogen stimulation. The cell viability and differential cell count differed between high- and low-SCC milk and between cisternal and alveolar milk depending on the individual cow. In conclusion, the results support the view that for a most effective defence against invading pathogens the mammary gland is reliant on the recruitment of fresh immune cells from the blood.

Mitochondrial Outer Membrane Proteome of Trypanosoma brucei Reveals Novel Factors Required to Maintain Mitochondrial Morphology

Trypanosoma brucei is a unicellular parasite that causes devastating diseases in humans and animals. It diverged from most other eukaryotes very early in evolution and, as a consequence, has an unusual mitochondrial biology. Moreover, mitochondrial functions and morphology are highly regulated throughout the life cycle of the parasite. The outer mitochondrial membrane defines the boundary of the organelle. Its properties are therefore key for understanding how the cytosol and mitochondria communicate and how the organelle is integrated into the metabolism of the whole cell. We have purified the mitochondrial outer membrane of T. brucei and characterized its proteome using label-free quantitative mass spectrometry for protein abundance profiling in combination with statistical analysis. Our results show that the trypanosomal outer membrane proteome consists of 82 proteins, two-thirds of which have never been associated with mitochondria before. 40 proteins share homology with proteins of known functions. The function of 42 proteins, 33 of which are specific to trypanosomatids, remains unknown. 11 proteins are essential for the disease-causing bloodstream form of T. brucei and therefore may be exploited as novel drug targets. A comparison with the outer membrane proteome of yeast defines a set of 17 common proteins that are likely present in the mitochondrial outer membrane of all eukaryotes. Known factors involved in the regulation of mitochondrial morphology are virtually absent in T. brucei. Interestingly, RNAi-mediated ablation of three outer membrane proteins of unknown function resulted in a collapse of the network-like mitochondrion of procyclic cells and for the first time identified factors that control mitochondrial shape in T. brucei.

Towards a taxonomy of common factors in psychotherapy-results of an expert survey

BACKGROUND: How change comes about is hotly debated in psychotherapy research. One camp considers 'non-specific' or 'common factors', shared by different therapy approaches, as essential, whereas researchers of the other camp consider specific techniques as the essential ingredients of change. This controversy, however, suffers from unclear terminology and logical inconsistencies. The Taxonomy Project therefore aims at contributing to the definition and conceptualization of common factors of psychotherapy by analyzing their differential associations to standard techniques. METHODS: A review identified 22 common factors discussed in psychotherapy research literature. We conducted a survey, in which 68 psychotherapy experts assessed how common factors are implemented by specific techniques. Using hierarchical linear models, we predicted each common factor by techniques and by experts' age, gender and allegiance to a therapy orientation. RESULTS: Common factors differed largely in their relevance for technique implementation. Patient engagement, Affective experiencing and Therapeutic alliance were judged most relevant. Common factors also differed with respect to how well they could be explained by the set of techniques. We present detailed profiles of all common factors by the (positively or negatively) associated techniques. There were indications of a biased taxonomy not covering the embodiment of psychotherapy (expressed by body-centred techniques such as progressive muscle relaxation, biofeedback training and hypnosis). Likewise, common factors did not adequately represent effective psychodynamic and systemic techniques. CONCLUSION: This taxonomic endeavour is a step towards a clarification of important core constructs of psychotherapy. KEY PRACTITIONER MESSAGE: This article relates standard techniques of psychotherapy (well known to practising therapists) to the change factors/change mechanisms discussed in psychotherapy theory. It gives a short review of the current debate on the mechanisms by which psychotherapy works. We provide detailed profiles of change mechanisms and how they may be generated by practice techniques.

Behavioral and psychosocial factors associated with sexual risk in a population of crack cocaine users

The purpose of this dissertation was to examine the relationship between key psychosocial and behavioral components of the Transtheoretical Model and the Theory of Reasoned Action for sexual risk reduction in a population of crack cocaine smokers and sex workers, not in drug treatment. ^ The first study examined the results of an analysis of the association between two principal constructs in the Transtheoretical Model, the processes of change and the stages of change for condom use, in a high risk population. In the analysis of variance for all respondents, the overall F-test revealed that people in different stages have different levels of experiential process use, F(3,317) = 17.79, p = 0.0001 and different levels of behavioral process use, F(3,317) = 28.59, p = .0001. For the experiential processes, there was a significant difference between the precontemplation/contemplation stage, and both the action, and maintenance, stages.^ The second study explored the relationship between the Theory of Reasoned Action “beliefs” and the stages-of-change in the same population. In the analysis of variance for all participants, the results indicate that people in different stages did value the positive beliefs differently, F(3,502) = 15.38, p = .0001 but did not value the negative beliefs differently, F(3,502) = 2.08, p = .10. ^ The third study explored differences in stage-of-change by gender, partner type drug use, and HIV status. Three discriminant functions emerged, with a combined χ2(12) = 139.57, p = <.0001. The loading matrix of correlations between predictors and discriminant functions demonstrate that the strongest predictor for distinguishing between the precontemplation/contemplation stage and the preparation, action, and maintenance stages (first function) is partner type (.962). The loadings on the second discriminant function suggest that once partner type has been accounted for, ever having HIV/AIDS (.935) was the best predictor for distinguishing between the first three stages and the maintenance stage. ^ These studies demonstrate that behavioral change theories can contribute important insight to researchers and program planners attempting to alter HIV risk behavior in high-risk populations. ^

CCL5/RANTES is a key chemoattractant released by degenerative intervertebral discs in organ culture.

Release of chemotactic factors in response to tissue damage has been described for different musculoskeletal tissues, including the intervertebral disc (IVD). This study investigated the chemoattractants that are released by induced degenerative IVDs and may be involved in recruiting mesenchymal stem cells (MSCs). Bovine caudal discs were cultured within a bioreactor and loaded under conditions that mimicked physiological or degenerative settings. Between days 4-6, medium was replaced by PBS, which was subsequently used for proteomic, ELISA and immunoprecipitation analyses of secreted chemokines and cytokines. A Boyden chamber assay was used to observe human MSC migration towards native and chemokine depleted media. Gene expression levels of chemokine receptors in human MSCs were analysed, and CCL5 was localised in bovine and human IVD by immunohistochemistry. Proteomic analysis revealed the presence of CCL5 and CXCL6 within conditioned media. Higher concentrations of CCL5 were found in the degenerative media, and a relationship was found between interleukin-1β and CCL5 concentration. Chemokine immunoprecipitation showed that MSCs had a significantly reduced chemotactic migration towards CCL5-immunoprecipitated and CCL5/CXCL6 co-immunoprecipitated media, whilst CXCL6 depletion did not change MSC chemotaxis. MSCs showed a significant increase in mRNA expression of the CCL5 receptors, CCR1 and CCR4, upon culture in degenerative media. Furthermore, CCL5 was identified in bovine and human disc tissue by immunohistochemistry. Hence, CCL5 may be a key chemoattractant that is produced and released by the intervertebral disc cells. Therefore, these factors could be used to enhance stem/progenitor cell mobilisation in regenerative therapies for early stages of disc degeneration.

Institutions as key drivers of collective action in WUAs [Water User Associations] of Uzbekistan

This paper presents a multifactor approach for performance assessment of Water Users Associations (WUAs) in Uzbekistan in order to identify the drivers for improved and effi cient performance of WUAs. The study was carried out in the Fergana Valley where the WUAs were created along the South Fergana Main Canal during the last 10 years. The farmers and the employees of 20 WUAs were questioned about the WUAs’ activities and the quantitative and qualitative data were obtained. This became a base for the calculation of 36 indicators divided into 6 groups: Water supply, technical conditions, economic conditions, social and cultural conditions, organizational conditions and information conditions. All the indicators assessed with a differentiated point system adjusted for subjectivity of several of them give the total maximal result for the associations of 250 point. The WUAs of the Fergana Valley showed the score between 145 and 219 points, what refl ects a highly diverse level of the WUAs performance in the region. The analysis of the indicators revealed that the key points of the WUA’s success are the organizational and institutional conditions including the participatory factors and awareness of both the farmers and employees about the work of WUA. The research showed that the low performance of the WUAs is always explained by the low technical and economic conditions along with weak organization and information dissemination conditions. It is clear that it is complicated to improve technical and economic conditions immediately because they are cost-based and cost-induced. However, it is possible to improve the organizational conditions and to strengthen the institutional basis via formal and information institutions which will gradually lead to improvement of economic and technical conditions of WUAs. Farmers should be involved into the WUA Governance and into the process of making common decisions and solving common problems together via proper institutions. Their awareness can also be improved by leading additional trainings for increasing farmers’ agronomic and irrigation knowledge, teaching them water saving technologies and acquainting them with the use of water measuring equipment so it can bring reliable water supply, transparent budgeting and adequate as well as equitable water allocation to the water users.

Prophylaxis of infectious complications with colony-stimulating factors in adult cancer patients undergoing chemotherapy-evidence-based guidelines from the Infectious Diseases Working Party AGIHO of the German Society for Haematology and Medical Oncology (DGHO).

BACKGROUND Current evidence on myelopoietic growth factors is difficult to overview for the practicing haematologist/oncologist. International guidelines are sometimes conflicting, exclude certain patient groups, or cannot directly be applied to the German health system. This guideline by the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Medical Oncology (DGHO) gives evidence-based recommendations for the use of G-CSF, pegylated G-CSF, and biosimilars to prevent infectious complications in cancer patients undergoing chemotherapy, including those with haematological malignancies. METHODS We systematically searched and evaluated current evidence. An expert panel discussed the results and recommendations. We then compared our recommendations to current international guidelines. RESULTS We summarised the data from eligible studies in evidence tables, developed recommendations for different entities and risk groups. CONCLUSION Comprehensive literature search and expert panel consensus confirmed many key recommendations given by international guidelines. Evidence for growth factors during acute myeloid leukaemia induction chemotherapy and pegfilgrastim use in haematological malignancies was rated lower compared with other guidelines.

Plant diversity drives soil microbial biomass carbon in grasslands irrespective of global environmental change factors

Soil microbial biomass is a key determinant of carbon dynamics in the soil. Several studies have shown that soil microbial biomass significantly increases with plant species diversity, but it remains unclear whether plant species diversity can also stabilize soil microbial biomass in a changing environment. This question is particularly relevant as many global environmental change (GEC) factors, such as drought and nutrient enrichment, have been shown to reduce soil microbial biomass. Experiments with orthogonal manipulations of plant diversity and GEC factors can provide insights whether plant diversity can attenuate such detrimental effects on soil microbial biomass. Here, we present the analysis of 12 different studies with 14 unique orthogonal plant diversity × GEC manipulations in grasslands, where plant diversity and at least one GEC factor (elevated CO2, nutrient enrichment, drought, earthworm presence, or warming) were manipulated. Our results show that higher plant diversity significantly enhances soil microbial biomass with the strongest effects in long-term field experiments. In contrast, GEC factors had inconsistent effects with only drought having a significant negative effect. Importantly, we report consistent non-significant effects for all 14 interactions between plant diversity and GEC factors, which indicates a limited potential of plant diversity to attenuate the effects of GEC factors on soil microbial biomass. We highlight that plant diversity is a major determinant of soil microbial biomass in experimental grasslands that can influence soil carbon dynamics irrespective of GEC.

Analysing factors determining the adoption of environmental management measures on the highlands of Ethiopia

A study was conducted on the highlands of Ethiopia to identify and analyse the factors determining the adoption of environmental management measures. In 1985, Ethiopia was classified into low –and high-potential areas based on the suitability of the natural environment for rain-fed agriculture. To address these objectives, case study areas were selected from low-potential and high-potential areas randomly. Data were collected through face-to-face interview and key informants, focus group discussion and field observation. In the low-potential areas, the physical environment ‒ particularly soil and forest environments have shown substantial recovery. Similarly, the water environment has improved. However, in the high-potential areas sampled, these resources are still being degraded. Clear understanding of the benefits of soil conservation structures by farmers, active involvement and technical support from the government and full and genuine participation of farmers in communal environmental resources management activities were found to be main factors in the adoption of environmental management measures.

Improving residency training with the help of multisource feedback: Generation of a model of influencing factors

Background: Feedback is considered to be one of the most important drivers of learning. One form of structured feedback used in medical settings is multisource feedback (MSF). This feedback technique provides the opportunity to gain a differentiated view on a doctor’s performance from several perspectives using a questionnaire and a facilitating conversation, in which learning goals are formulated. While many studies have been conducted on the validity, reliability and feasibility of the instrument, little is known about the impact of factors that might influence the effects of MSF on clinical performance. Summary of Work: To study under which circumstances MSF is most effective, we performed a literature review on Google Scholar with focus on MSF and feedback in general. Main key-words were: MSF, multi-source-feedback, multi source feedback, and feedback each combined with influencing/ hindering/ facilitating factors, effective, effectiveness, doctors-intraining, and surgery. Summary of Results: Based on the literature, we developed a preliminary model of facilitating factors. This model includes five main factors influencing MSF: questionnaire, doctor-in-training, group of raters, facilitating supervisor, and facilitating conversation. Discussion and Conclusions: Especially the following points that might influence MSF have not yet been sufficiently studied: facilitating conversation with the supervisor, individual aspects of doctors-in-training, and the causal relations between influencing factors. Overall there are only very few studies focusing on the impact of MSF on actual and long-term performance. We developed a preliminary model of hindering and facilitating factors on MSF. Further studies are needed to better understand under which circumstances MSF is most effective. Take-home messages: The preliminary model might help to guide further studies on how to implement MSF to use it at its full potential.

Environmental and behavioral risk factors for moderate or severe rotavirus diarrhea in children less than 24 months

On a global basis rotaviruses are the most important agents involved in childhood diarrhea. In developing countries they account for 6% of all diarrheas and 20% of all diarrhea related deaths of children under 5 years of age, with over 1 billion episodes and over 4 million deaths annually. Given the disease burden, there is a need for better understanding the risk factors involved in rotavirus disease, to identify areas of intervention. In order to provide this information, two areas were developed: a review of the literature, examining the causal evidence for rotavirus diarrhea and a case comparison study. The case comparison study analyzed two areas: identifying climate factors and, identifying environmental and behavioral risk factors. The literature review showed that few analytical studies have identified specific risk factors such as home environment, and a winter seasonal trend for temperate areas, but in key areas evidence is contradictory. The case comparison study for climate factors demonstrated that seasonality occurs in a tropical country like Venezuela and that a complex interplay between weather conditions contribute to the seasonal pattern. A positive association between rain fall (OR 4.1); dew point (OR 2.3) and temperature differential during the day (OR 1.4) and, an inverse association with temperature (OR 0.5) and relative humidity (OR 0.8) was found. This information is useful in understanding the seasonal pattern of rotavirus and for planning health care needs. The second analysis demonstrated that environmental variables such as crowding (OR 14.3), contact with someone with an infectious disease (OR 4.9) and animal ownership (OR 2.3) were important. Restricting the analysis to animal owners demonstrated that living In a rural settling (OR 13.8), defecating in inappropriate places (OR 7.2), crowding(4.2) and indoor animals (4.0) are of importance. Behavioral variables identified were: lack of breast feeding (OR 4.0) and visiting when someone was sick (OR 3.4). Biological and demographic variables of importance were: age, with a dose response relationship; undernurishment (OR 11.3) and household per capita monthly income less than US $ 16.30 (OR 8.5). Using a diarrhea compeer group we found that, although some of the previous variables were of importance, no major differences were found. These findings are important in identifying paths for prevention and further research. ^