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The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Spleen injuries are among the most frequent trauma-related injuries. At present, they are classified according to the anatomy of the injury. The optimal treatment strategy, however, should keep into consideration the hemodynamic status, the anatomic derangement, and the associated injuries. The management of splenic trauma patients aims to restore the homeostasis and the normal physiopathology especially considering the modern tools for bleeding management. Thus, the management of splenic trauma should be ultimately multidisciplinary and based on the physiology of the patient, the anatomy of the injury, and the associated lesions. Lastly, as the management of adults and children must be different, children should always be treated in dedicated pediatric trauma centers. In fact, the vast majority of pediatric patients with blunt splenic trauma can be managed non-operatively. This paper presents the World Society of Emergency Surgery (WSES) classification of splenic trauma and the management guidelines.
The membrane proximal external region (MPER) of the HIV-1 glycoprotein gp41 is targeted by the broadly neutralizing antibodies 2F5 and 4E10. To date, no immunization regimen in animals or humans has produced HIV-1 neutralizing MPER-specific antibodies. We immunized llamas with gp41-MPER proteoliposomes and selected a MPER-specific single chain antibody (VHH), 2H10, whose epitope overlaps with that of mAb 2F5. Bi-2H10, a bivalent form of 2H10, which displayed an approximately 20-fold increased affinity compared to the monovalent 2H10, neutralized various sensitive and resistant HIV-1 strains, as well as SHIV strains in TZM-bl cells. X-ray and NMR analyses combined with mutagenesis and modeling revealed that 2H10 recognizes its gp41 epitope in a helical conformation. Notably, tryptophan 100 at the tip of the long CDR3 is not required for gp41 interaction but essential for neutralization. Thus bi-2H10 is an anti-MPER antibody generated by immunization that requires hydrophobic CDR3 determinants in addition to epitope recognition for neutralization similar to the mode of neutralization employed by mAbs 2F5 and 4E10.
The trade in bear parts for medicine and for status is a conservation challenge throughout Asia. The Asiatic black bear (Ursus thibetanus) and the sun bear (Helarctos malayanus) are endemic to this region, and populations are estimated to have declined throughout their ranges due to widespread illegal killing of bears and trade in parts, combined with loss of habitat. Previous studies have indicated that legislation alone is insufficient to prevent illegal hunting and trade, indicating instead a need to address demand for bear parts and products. We conducted mixed-method surveys in Cambodia to understand the key motivators for individuals to consume bear parts, and to understand whether specialised questioning techniques are applicable in this context. Bear part use is illegal in Cambodia and may therefore be considered a sensitive behaviour, in that individuals may be reluctant to admit to it. To counteract possible biases, four specialised questioning techniques were used in this study: randomised response technique (RRT), unmatched count technique (UCT), nominative technique (NT), and false consensus bias (FCB). All four methods serve to shield a respondent’s admittance of a sensitive behaviour from the interviewer. The results presented here show that great variability exists in anonymous methods’ efficacy in certain contexts. However, the results overall indicate that individuals in Cambodia are under-reporting their consumption of bear parts when directly asked, and that the prevalence of bear part use in Cambodia may be as high as 15% of the population, representing a significant conservation challenge.
Tigers are indisputably in danger of extinction due to habitat loss and demand for their parts. Tigers are extirpated in the wild from every country bar one in mainland East and Southeast Asia. Although consumption of tiger products is known to be established in China, less is known about demand for tiger products in Southeast Asia. In this study, we investigate tiger product demand in Vietnam, a major illegal wildlife consumer country. There has been little research into consumption, in particular the level of use, the products being consumed, variation in use of products between areas, and the motivations of consuming tiger products. Through a quantitative survey of 1120 individuals, we show that use of tiger products could be as high as ~11% of the sample in both urban centers of Vietnam, Hanoi and Ho Chi Minh City. Tiger bone glue is the predominant product used, for medicinal purposes. In Hanoi, it is generally purchased by the individual for self-use, while in Ho Chi Minh City it is generally purchased as a gift. In both cities, individuals were generally highly satisfied with the product, indicating entrenched belief in efficacy among consumers. Ultimately, our results show that tiger product use is relatively pervasive. We suggest that conservation organizations should focus on behavior change campaigns that are informed by the results here, and that are specific to each area and to the specific use of tiger product glue for medicine. By reducing demand, beleaguered tiger populations will have a greater chance of stabilization and eventual growth.
Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ~2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the Xchromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87×10-9; odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53×10-9; odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.