The Global Forest Transition as a Human Affair

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Epidemiology of injuries presenting to the national hospital in Kampala, Uganda: implications for research and policy

BackgroundDespite the growing burden of injuries in LMICs, there are still limited primary epidemiologic data to guide health policy and health system development. Understanding the epidemiology of injury in developing countries can help identify risk factors for injury and target interventions for prevention and treatment to decrease disability and mortality.AimTo estimate the epidemiology of the injury seen in patients presenting to the government hospital in Kampala, the capital city of Uganda.MethodsA secondary analysis of a prospectively collected database collected by the Injury Control Centre-Uganda at the Mulago National Referral Hospital, Kampala, Uganda, 2004-2005.ResultsFrom 1 August 2004 to 12 August 2005, a total of 3,750 injury-related visits were recorded; a final sample of 3,481 records were analyzed. The majority of patients (62%) were treated in the casualty department and then discharged; 38% were admitted. Road traffic injuries (RTIs) were the most common causes of injury for all age groups in this sample, except for those under 5 years old, and accounted for 49% of total injuries. RTIs were also the most common cause of mortality in trauma patients. Within traffic injuries, more passengers (44%) and pedestrians (30%) were injured than drivers (27%). Other causes of trauma included blunt/penetrating injuries (25% of injuries) and falls (10%). Less than 5% of all patients arriving to the emergency department for injuries arrived by ambulance.ConclusionsRoad traffic injuries are by far the largest cause of both morbidity and mortality in Kampala. They are the most common cause of injury for all ages, except those younger than 5, and school-aged children comprise a large proportion of victims from these incidents. The integration of injury control programs with ongoing health initiatives is an urgent priority for health and development

Identification guide to the heterobranch sea slugs (Mollusca: Gastropoda) from Bocas del Toro, Panama

The Bocas del Toro Archipelago is located off the Caribbean coast of Panama. Until now, only 19 species of heterobranch sea slugs have been formally reported from this area; this number constitutes a fraction of total diversity in the Caribbean region. The Bocas del Toro Archipelago is located off the Caribbean coast of Panama. Until now, only 19 species of heterobranch sea slugs have been formally reported from this area; this number constitutes a fraction of total diversity in the Caribbean region. This increase in known diversity strongly suggests that the distribution of species within the Caribbean is still poorly known and species ranges may need to be modified as more surveys are conducted.https://doi.org/10.1186/s41200-016-0048-

Quantifying the Adaptive Potential of an Antibiotic Resistance Enzyme

For a quantitative understanding of the process of adaptation, we need to understand its “raw material,” that is, the frequency and fitness effects of beneficial mutations. At present, most empirical evidence suggests an exponential distribution of fitness effects of beneficial mutations, as predicted for Gumbel-domain distributions by extreme value theory. Here, we study the distribution of mutation effects on cefotaxime (Ctx) resistance and fitness of 48 unique beneficial mutations in the bacterial enzyme TEM-1 β-lactamase, which were obtained by screening the products of random mutagenesis for increased Ctx resistance. Our contributions are threefold. First, based on the frequency of unique mutations among more than 300 sequenced isolates and correcting for mutation bias, we conservatively estimate that the total number of first-step mutations that increase Ctx resistance in this enzyme is 87 [95% CI 75–189], or 3.4% of all 2,583 possible base-pair substitutions. Of the 48 mutations, 10 are synonymous and the majority of the 38 non-synonymous mutations occur in the pocket surrounding the catalytic site. Second, we estimate the effects of the mutations on Ctx resistance by determining survival at various Ctx concentrations, and we derive their fitness effects by modeling reproduction and survival as a branching process. Third, we find that the distribution of both measures follows a Fréchet-type distribution characterized by a broad tail of a few exceptionally fit mutants. Such distributions have fundamental evolutionary implications, including an increased predictability of evolution, and may provide a partial explanation for recent observations of striking parallel evolution of antibiotic resistance

Diverse Applications of Nanomedicine

The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic. \ua9 2017 American Chemical Society

11β-hydroxysteroid dehydrogenase type 2 deficiency accelerates atherogenesis and causes proinflammatory changes in the endothelium in apoe^-/- mice

Mineralocorticoid receptor (MR) activation is pro inflammatory and pro atherogenic. Antagonism of MR improves survival in humans with congestive heart failure caused by atherosclerotic disease. In animal models, activation of MR exacerbates atherosclerosis. The enzyme 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) prevents inappropriate activation of the mineralocorticoid receptor (MR) from inappropriate activation by glucocorticoids by inactivating glucocorticoids in mineralocorticoid-target tissues. To determine whether glucocorticoid-mediated activation of MR increases atheromatous plaque formation we generated Apoe(−/−)/11β-HSD2(−/−) double-knockout (E/b2) mice. On chow diet, E/b2 mice developed atherosclerotic lesions by 3 months of age, while Apoe(−/−) mice remained lesion-free. Brachiocephalic plaques in 3 month-old E/b2 mice showed increased macrophage and lipid content and reduced collagen content compared to similar sized brachiocephalic plaques in 6 month old Apoe(−/−) mice. Crucially, treatment of E/b2 mice with eplerenone, an MR antagonist, reduced plaque development and macrophage infiltration while increasing collagen and smooth muscle cell content without any effect on systolic blood pressure (SBP). In contrast, reduction of SBP in E/b2 mice using the epithelial sodium channel (ENaC) blocker amiloride produced a less profound atheroprotective effect. Vascular cell adhesion molecule 1 (VCAM-1) expression was increased in the endothelium of E/b2 mice compared to Apoe(−/−) mice. Similarly, aldosterone increased VCAM-1 expression in mouse aortic endothelial cells, an effect mimicked by corticosterone only in the presence of an 11β-HSD2 inhibitor. Thus, loss of 11β-HSD2 leads to striking atherogenesis associated with activation of MR stimulating pro-inflammatory processes in the endothelium of E/b2 mice

Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease A Randomized Clinical Trial

Importance Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. Objective To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. Design, Setting, and Participants Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. Interventions Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. Main Outcomes and Measures Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form– physical functioning subscale score (SF-36), and the change in the Berg Balance Test. Results Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was –2.5 units (95% CI, –3.7 to –1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, –0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. Conclusions and Relevance Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety

Mammal responses to global changes in human activity vary by trophic group and landscape

Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human–wildlife interactions along gradients of human influence.Peer reviewe