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The bone strength also reduced postoperatively and appeared particularly around the implant peg. Strain-induced bone resorption is a likely source of the bone loss commonly observed in RTSA. The finite element glenoid bone remodeling simulation may be used as a tool to evaluate glenoid implant design. © 2020 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.The relationship between Renin-Angiotensin system (RAS) and COVID-19 pandemic and, in particular, RAS as part of the CoV-2 infection process via Angiotensin Converting Enzyme 2 (ACE2), the entry point of SARS-CoV-2, has resulted in conflicting suggestions regarding how RAS and its role(s) should inform treating COVID-19. ACE inhibitors or angiotensin II (Ang)-type 1 receptor blockers (ARBs), in fact, have been suggested to be avoided as they potentially upregulate ACE2 1 and, conversely, there are suggestions that ARBs might be beneficial 2 as SARS-CoV-2 causing ACE2 downregulation slows the Ang II conversion to the vasodilatory, anti-inflammatory, antioxidant and antiatherosclerotic Ang 1-7 3-5 , and the use of ARBs by blocking the excessive Ang II type-1 receptors activation, would be beneficial upregulating ACE2 activity and increasing Ang 1-7 levels. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.High mobility group box 1 (HMGB1), a nuclear protein, once released to the extracellular space, facilitates pain signals as well as inflammation. Intraplantar or intraspinal application of HMGB1 elicits hyperalgesia/allodynia in rodents by activating the advanced glycosylation end-product specific receptor (receptor for advanced glycation end-products; RAGE) or Toll-like receptor 4 (TLR4). Endogenous HMGB1 derived from neurons, perineuronal cells or immune cells accumulating in the dorsal root ganglion or sensory nerves participates in somatic and visceral pain consisting of neuropathic and/or inflammatory components. Endothelial thrombomodulin (TM) and recombinant human soluble TM, TMα, dramatically promote thrombin-dependent degradation of HMGB1, and systemic administration of TMα prevents and reverses various HMGB1-dependent pathological pain. Small molecules that directly inactivate HMGB1 or antagonize HMGB1-targeted receptors would be useful to reduce various intractable pain. Thus, HMGB1 and its receptors are considered to serve as promising targets in developing novel agents to prevent or treat pathological pain. This article is protected by copyright. All rights reserved.The global market of butanol is increasing due to its growing applications as solvent, flavoring agent and chemical precursor of several other compounds. Recently, the superior properties of n-butanol as a biofuel over ethanol have stimulated even more interest. (Bio)butanol is natively produced together with ethanol and acetone by Clostridium species through Acetone-Butanol-Ethanol fermentation, at non-competitive, low titers compared to petrochemical production. Different butanol production pathways have been expressed in Escherichia coli, a more accessible host compared to Clostridium species, to improve butanol titers and rates.. The bioproduction of butanol is here reviewed from a historical and theoretical perspective. All tested rational metabolic engineering strategies in E. Kenpaullone coli to increase butanol titers are reviewed manipulation of central carbon metabolism; elimination of competing pathways; cofactor balancing; development of new pathways; expression of homologous enzymes; consumption of different substrates and molecular biology strategies. The progress in the field of metabolic modeling and pathway generation algorithms and their potential application to butanol production are also summarized here. The main goals are to gather all the strategies, evaluate the respective progress obtained, identify and exploit the outstanding challenges. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.It may not be surprising that the brain as a lipid-rich organ shows perturbed lipid profiles in neurodegenerative conditions such as Alzheimer's disease. It is, however, more challenging to detect these changes as they may only occur in a spatially small area. This Editorial highlights the work by Kaya et al. using a raising technology called MALDI IMS to identify up- or downregulation of specific lipids in and around the amyloid plaque, one of the pathological hallmarks of Alzheimer's disease. Interestingly, such lipid changes were paralleled with disrupted myelin structure only at the border between white and gray matter. The sequestration of apolipoprotein E towards the amyloid plaque may provide a clue towards the underlying mechanisms leading to disrupted lipid profiles. This study highlights the necessity to increase research activities related to lipid metabolism in Alzheimer's disease and demonstrates that the technological progress now facilitates the advancement of this area. © 2020 International Society for Neurochemistry.The aim of this study was to determine the prevalence and type of cutaneous manifestations which occur in patients with granulomatosis with polyangiitis and to explore the potential association between cutaneous and systemic involvement in these patients. A retrospective case series study was designed, including all granulomatosis with polyangiitis cases diagnosed between 2010 and 2018 at the Hospital Universitario Virgen de las Nieves. Thirty-nine patients with granulomatosis with polyangiitis were identified, of which 53.85% presented cutaneous manifestations. In decreasing order of frequency, the types of cutaneous problems observed included palpable purpura, mucocutaneous ulcers, subcutaneous nodules, pyoderma gangrenosum-like ulcers, digital necrosis, papulonecrotic lesions and livedo reticularis. Patients with palpable purpura presented a higher frequency of renal involvement (p = 0.008). Cutaneous manifestations of granulomatosis with polyangiitis may facilitate early disease diagnosis. Likewise, a manifestation such as palpable purpura may be a predictor of kidney damage.To evaluate cellular response to oncostatin M (OSM) in comparison to interleukin (IL)-31, we analyzed monocyte chemoattractant protein 1 (MCP-1) as a readout for OSM responses with and without IL-4, IL-13, anti-OSM receptor β monoclonal antibody KPL-716, and anti-IL-31 receptor α antibody in human epidermal keratinocytes and human dermal fibroblasts in vitro. In human epidermal keratinocytes, OSM significantly induced STAT3 or STAT1 phosphorylation and synergized with IL-13 or IL-4 in elevating MCP-1. In human dermal fibroblasts, OSM results were similar, and leukemia inhibitory factor or IL-31 minimally activated STAT3 but not MCP-1. OSM significantly stimulated mRNA for type II IL-4 receptor and type II OSM receptor. KPL-716, not anti-IL-31Rα, significantly attenuated MCP-1 response to OSM and OSM + IL-4 in human epidermal keratinocytes and human dermal fibroblasts. OSM, not leukemia inhibitory factor or IL-31, synergized with IL-4 and IL-13 in human epidermal keratinocytes and human dermal fibroblasts, suggesting therapeutic potential of KPL-716 in inflammatory dermatologic diseases distinct from IL-31 inhibition.OBJECTIVE Accurate electronic phenotyping is essential to support collaborative observational research. Supervised machine learning methods can be used to train phenotype classifiers in a high-throughput manner using imperfectly labeled data. We developed 10 phenotype classifiers using this approach and evaluated performance across multiple sites within the Observational Health Data Sciences and Informatics (OHDSI) network. MATERIALS AND METHODS We constructed classifiers using the Automated PHenotype Routine for Observational Definition, Identification, Training and Evaluation (APHRODITE) R-package, an open-source framework for learning phenotype classifiers using datasets in the Observational Medical Outcomes Partnership Common Data Model. We labeled training data based on the presence of multiple mentions of disease-specific codes. Performance was evaluated on cohorts derived using rule-based definitions and real-world disease prevalence. Classifiers were developed and evaluated across 3 medical centers, ilf of the American Medical Informatics Association.BACKGROUND Seeking care from traditional healers for injury is a common practice in low- and middle-income countries, including Sudan. As little is known about specific patterns of the practice in the country, we aimed to investigate associated factors and the role of professional injury care availability. METHODS We used Sudan Household Health Survey 2010 data from a national stratified multistage cluster sample of 15 000 households. A multivariable Poisson regression (PR) model with robust variance was used to test potential associations of receiving care from a traditional healer in the first week after injury with age, gender, urban/rural residence, wealth index, educational attainment, cause of injury, time of injury occurrence and state-level injury-care bed density. RESULTS Of 1432 injured participants who sought some form of healthcare, 38% received care from a traditional healer. A significant negative association was found with educational attainment, age and wealth. The association between injury-care bed density and receiving care from a traditional healer was consistently evident only when the injury was caused by a road traffic accident (PR = 0.90, 95% CI 0.85 to 0.96). CONCLUSIONS Merely increasing the affordability or availability of injury care facilities may not impact reliance on traditional healers for all causes of injury. Therefore, injury care policies need to consider the role of traditional healers as part of the healthcare system. © The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.OBJECTIVES To characterize the types and magnitude of psychosocial burden present in caregivers who have a child with sickle cell disease (SCD) in Kenya and to identify predictors of caregiver psychosocial burden, including disease severity and financial hardship. METHODS Primary caregivers (N = 103) of children aged 1-10 years diagnosed with SCD completed surveys assessing multiple domains of caregiver quality of life (QOL), adjustment to child illness, mental health, and financial hardship. Descriptive statistics characterize psychosocial burden, and linear models assess associations. RESULTS On indicators of QOL, caregivers report multiple difficulties across most domains, including daily activities and physical, social, cognitive, and emotional well-being. Daily activities emerged as most burdensome. On indicators of parental adjustment to chronic illness, guilt and worry emerged as the greatest concern, followed by long-term uncertainty and unresolved sorrow and anger; relative to these, they reported higher levels of emotional resources. Financial hardship was high, as caregivers reported moderate to major financial losses due to the time spent caring for their child. General linear model analyses revealed that level of financial hardship was a significant predictor of all negative psychosocial outcomes. CONCLUSIONS Results document that Kenyan caregivers of children with SCD experience difficulties across multiple domains of functioning and that financial difficulties are likely associated with psychosocial burden. Results can guide intervention development for caregivers of children with SCD in low-resource, global contexts. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.