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AbstractThe co‐occurrence of chronic pain and alcohol use disorders (AUDs) involves complex interactions between genetic and neurophysiological aspects, and the research has reported mixed findings when they both co‐occur. There is also an indication of a gender‐dependent effect; males are more likely to use alcohol to cope with chronic pain problems than females. Recently, a new conceptualization has emerged, proposing that the negative affective component of pain drives and maintains alcohol‐related behaviors. We studied in a longitudinal fashion alterations in alcohol drinking patterns and pain thresholds in a mouse model of chronic neuropathic pain in a sex‐dependent manner. Following partial denervation (spared nerve injury [SNI]), stimulus‐evoked pain responses were measured before chronic alcohol consumption, during drinking, during a deprivation phase, and following an episode of excessive drinking. During the course of alcohol drinking, we observed pronounced sex differences in pain thresholds. Male mice showed a strong increase in pain thresholds, suggesting an analgesic effect induced by alcohol over time, an effect that was not observed in female mice. SNI mice did not differ from sham‐operated controls in baseline alcohol consumption. However, following a deprivation phase and the reintroduction of ethanol, male SNI mice but not female mice showed more pronounced excessive drinking than controls. Finally, we observed decreased central ethanol sensitivity in male SNI mice but not in females. Together with our finding, that ethanol is able to decrease a pain‐induced negative affective memory we come to following conclusion. We propose that a lower sensitivity to the intoxicating effects of alcohol together with the ability of alcohol to reduce the negative affective component of pain may explain the higher co‐occurrence of AUD in male chronic pain patients.

It has been estimated that more than 80% of alcoholics are also nicotine dependent and that, vice versa, the rate of alcoholism is substantially increased by a factor of 4-10 in the nicotine-dependent population. However, the cause for this very high degree of comorbidity is still largely unknown. At the molecular and cellular level, both drugs have very different mechanisms of action. Nicotine specifically activates ligand-gated ion channels in the brain, which are normally gated by acetylcholine, while alcohol interacts with various neurotransmitter receptors. Despite this diversity, both drugs seem to engage the endogenous opioid system as a modulator of some of its pharmacological effect. An acute exposure to nicotine or alcohol leads to a release of opioid peptides in specific brain regions, thus resulting in an activation of their corresponding receptors. If the brain is exposed repeatedly or chronically to these drugs, adaptive changes in the level and expression of opioid peptides and receptors occur. These adaptive changes are thought to contribute to the homeostatic or allostatic adaptations of the brain, which have been associated with drug dependence. This review summarizes pharmacological and genetic studies in animal models and in humans that have addressed the role of specific opioid peptides and receptors in various stages of the addiction process.

Ethanol exerts its behavioural effects largely by interacting with receptors for brain neurotransmitters. However, the molecular mechanisms involving these interactions and the pathogenesis of alcohol-withdrawal symptomatology are still not well understood. Until recently, no data were available about homocysteine (Hcy) levels in acute alcohol intoxication of chronic alcoholics and in patients undergoing withdrawal from alcohol. Hcy, blood-alcohol concentrations, vitamins B6, B12, and folate concentrations were assessed in 29 chronic alcoholics, who underwent withdrawal from alcohol. We observed increased Hcy levels in most patients. Hcy levels steadily decreased during the observation period. We postulate that hyperhomocysteinaemia and excitatory amino acid neurotransmitters, by their agonism at the N-methyl-D-aspartate receptor, may partly mediate alcohol-associated withdrawal symptomatology. The importance of assessing serum Hcy levels in order to detect methylation deficiency in patients with chronic alcoholism and for possible therapeutic strategies is discussed.

AbstractThirty‐four alcoholics were treated with acupuncture to the ear and the body in a randomized single‐blind placebo‐controlled design over 14 days. Orthodox points and placebo needles to orthodox points were used daily for a total of 10 treatments starting on the first day of admission as add‐on therapy to standard medication with carbamazepine. The primary outcome was the Clinical Institute Withdrawal Assessment (CIWA‐Ar‐scale) assessed on days 1‐6, 9 and 14. No initial differences were found regarding sociodemographic data, drinking history and alcohol‐related data, indicating successful randomization. Longitudinal analysis of the Clinical Institute Withdrawal Assessment (CIWA‐Ar‐scale) data showed that patients assigned to acupuncture had a general tendency towards better outcome results and significantly fewer withdrawal symptoms on day 14 (Wilcoxon‐W=177.500, Z=‐2.009, p = 0.045). No significant differences were found in the Beck Depression Inventory (BDI), State‐Trait Anxiety Inventory (STAI X1 and X2) and Eigenschaftswoerterliste (EWL S60). We conclude that acupuncture as an adjunctive treatment to carbamazepine medication shows promise for the treatment of alcohol withdrawal symptoms. Further investigation of this treatment modality appears to be warranted.

Climate change is a global problem, which affects the various geographical regions at different levels. It is also associated with a wide range of human health problems, which pose a burden to health systems, especially in regions such as Africa. Indeed, across the African continent public health systems are under severe pressure, partly due to their fragile socioeconomic conditions. This paper reports on a cross-sectional study in six African countries (Ghana, Nigeria, South Africa, Namibia, Ethiopia, and Kenya) aimed at assessing their vulnerabilities to climate change, focusing on its impacts on human health. The study evaluated the levels of information, knowledge, and perceptions of public health professionals. It also examined the health systems’ preparedness to cope with these health hazards, the available resources, and those needed to build resilience to the country’s vulnerable population, as perceived by health professionals. The results revealed that 63.1% of the total respondents reported that climate change had been extensively experienced in the past years, while 32% claimed that the sampled countries had experienced them to some extent. Nigerian respondents recorded the highest levels (67.7%), followed by Kenya with 66.6%. South Africa had the lowest level of impact as perceived by the respondents (50.0%) when compared with the other sampled countries. All respondents from Ghana and Namibia reported that health problems caused by climate change are common in the two countries. As perceived by the health professionals, the inadequate resources reiterate the need for infrastructural resources, medical equipment, emergency response resources, and technical support. The study’s recommendations include the need to improve current policies at all levels (i.e., national, regional, and local) on climate change and public health and to strengthen health professionals’ skills. Improving the basic knowledge of health institutions to better respond to a changing climate is also recommended. The study provides valuable insights which may be helpful to other nations in Sub-Saharan Africa.

Introduction: During the COVID-19 lockdown significant improvements in urban air quality were detected due to the absence of motorized vehicles. It is crucial to perpetuate such improvements to maintain and improve public health simultaneously. Therefore, this exploratory study approached bicycle infrastructure in the case of Munich (Germany) to find out which specific bicycle lanes meet the demands of its users, how such infrastructure looks like, and which characteristics are potentially important. Methods: To identify patterns of bicycle infrastructure in Munich exploratory data is collected over the timespan of three consecutive weeks in August by a bicycle rider at different times of the day. We measure position, time, velocity, pulse, level of sound, temperature and humidity. In the next step, we qualitatively identified different segments and applied a cluster analysis to quantitatively describe those segments regarding the measured factors. The data allows us to identify which bicycle lanes have a particular set of measurements, indicating a favorable construction for bike riders. Results: In the exploratory dataset, five relevant segment clusters are identified: viscous, slow, inconsistent, accelerating, and best-performance. The segments that are identified as best-performance enable bicycle riders to travel efficiently and safely at amenable distances in urban areas. They are characterized by their width, little to no interaction with motorized traffic as well as pedestrians, and effective traffic light control. Discussion: We propose two levels of discussion: (1) revolves around what kind of bicycles lanes from the case study can help to increase bicycle usage in urban areas, while simultaneously improving public health and mitigating climate change challenges and (2) discussing the possibilities, limitations and necessary improvements of this kind of exploratory methodology.

SummaryFunctions of porcine polymorphonuclear neutrophils are evaluated with in vitro test systems. Results are compared with those from human PMN and the relevance for in vivo conditions is discussed. Ethanol was inhibitory to all porcine PMN functions investigated here. Influex, a combination product, containing extracts of Echinacea, Aconitum, Apis and Lachesis stimulated adherence, chemotaxis, and phagocytosis, but inhibited chemiluminescence. These results suggest an effect of the product in the generation of reactive oxygen species.ZusammenfassungGranulozytenfunktionen beim Schwein: Messung und BeeinflussungVerschiedene Funktionen neutrophiler Granulozyten des Schweines werden mit Hilfe von in vitro‐Systemen gemessen und die Ergebnisse mit entsprechenden Werten verglichen, die für menschliche Neutrophile beschrieben sind. Die Aussagekraft der erhaltenen Ergebnisse für in vivo‐Verhältnisse wird diskutiert. Alle hier beschriebenen Granulozytenfunktionen wurden durch Alkohol gehemmt. Influex, ein Kombinationspräparat, das Extrakte aus Echinacea, Aconitum, Apis und Lachesis enthält, stimulierte Adhärenz, Chemotaxis und Phagozytose, hemmte jedoch die Chemolumineszenz. Die Ergebnisse lassen einen Einfluß des Präparates auf die Bildung von reaktiven Sauerstoffspezies vermuten.

The Pan-African Consortium for the Evaluation of Anti-Tuberculosis Antibiotics (PanACEA) was designed to build tuberculosis (TB) trial capacity whilst conducting clinical trials on novel and existing agents to shorten and simplify TB treatment. PanACEA has now established a dynamic network of 11 sub-Saharan clinical trial sites and four European research institutions.In 2011, a capacity development program, funded by the European & Developing Countries Clinical Trials Partnership (EDCTP), was launched with four objectives, aiming at strengthening collaborating TB research sites to reach the ultimate goal of becoming self-sustainable institutions: networking; training; conducting clinical trials; and infrastructure scaling-up of sites.Assessment in six sub-Saharan TB-endemic countries (Gabon, Kenya, South Africa, Tanzania, Uganda and Zambia) were performed through a structured questionnaire, site visits, discussion with the PanACEA consortium, setting of milestones and identification of priorities and followed-up with evaluations of each site. The results of this needs-based assessment was then translated into capacity development measures.In the initial phase, over a four-year period (March 2011 - June 2014), the programme scaled-up six sites; conducted a monitoring training program for 11 participants; funded five MSc and four PhD students, fostering gender balance; conducted four epidemiological studies; supported sites to conduct five Phase II studies and formed a sustainable platform for TB research (panacea-tb.net).Our experience of conducting TB clinical trials within the PanACEA programme environment of mentoring, networking and training has provided a sound platform for establishing future sustainable research centres. Our goal of facilitating emergent clinical TB trial sites to better initiate and lead research activities has been mostly successful.

Based on a targeted literature review, this vision paper emphasizes the importance of dementia-sensitive built space. The article specifically focuses on supporting spatial orientation and wayfinding for people living with dementia. First, we discuss types of wayfinding challenges, underlying processes, and consequences of spatial disorientation in the context of dementia of the Alzheimer’s type. Second, we focus on current efforts aimed at planning and evaluating dementia-sensitive built space, i.e., environmental design principles, interventions, evaluation tools, strategies, and planning processes. Third, we use our findings as a starting point for developing an interdisciplinary research vision aimed at encouraging further debates and research about: (1) the perspective of a person with dementia, specifically in the context of wayfinding and spatial orientation, and (2) how this perspective supplements planning and design processes of dementia-sensitive built space. We conclude that more closely considering the perspective of people with dementia supports the development of demographically sustainable future cities and care institutions.

The relative biological effectiveness (RBE) varies along the treatment field. However, in clinical practice, a constant RBE of 1.1 is assumed, which can result in undesirable side effects. This study provides an accurate overview of current clinical practice for considering proton RBE in Europe.A survey was devised and sent to all proton therapy centres in Europe that treat patients. The online questionnaire consisted of 39 questions addressing various aspects of RBE consideration in clinical practice, including treatment planning, patient follow-up and future demands.All 25 proton therapy centres responded. All centres prescribed a constant RBE of 1.1, but also applied measures (except for one eye treatment centre) to counteract variable RBE effects such as avoiding beams stopping inside or in front of an organ at risk and putting restrictions on the minimum number and opening angle of incident beams for certain treatment sites. For the future, most centres (16) asked for more retrospective or prospective outcome studies investigating the potential effect of the effect of a variable RBE. To perform such studies, 18 centres asked for LET and RBE calculation and visualisation tools developed by treatment planning system vendors.All European proton centres are aware of RBE variability but comply with current guidelines of prescribing a constant RBE. However, they actively mitigate uncertainty and risk of side effects resulting from increased RBE by applying measures and restrictions during treatment planning. To change RBE-related clinical guidelines in the future more clinical data on RBE are explicitly demanded.