Voriconazole-Associated Periostitis: New Insights into Pathophysiology and Management

Voriconazole-associated periostitis (VAP) is an underrecognized and unpredictable side effect of long-term voriconazole therapy. We report two cases of VAP occurring in the post-transplant setting: a 68-year-old lung transplant recipient who required ongoing voriconazole therapy, in whom urinary alkalinization was used to promote fluoride excretion and minimize voriconazole-related skeletal toxicity, and a 68-year-old stem-cell transplant recipient with a high voriconazole dose requirement, identified on pharmacogenomic testing to be a CYP2C19 ultrarapid metabolizer, the dominant enzyme in voriconazole metabolism. This is the first reported case of pharmacogenomic profiling in VAP and may explain the variability in individual susceptibility to this uncommon adverse effect. Our findings provide new insights into both the management and underlying pathophysiology of VAP. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research

Seasonal palmar keratoderma in erythropoietic protoporphyria indicates autosomal recessive inheritance

Erythropoietic protoporphyria (EPP) is an inherited disorder that results from partial deficiency of ferrochelatase (FECH). It is characterized clinically by acute photosensitivity and, in 2% of patients, liver disease. Inheritance is usually autosomal dominant with low penetrance but is recessive in about 4% of families. A cross-sectional study of 223 patients with EPP in the United Kingdom identified six individuals with palmar keratoderma. We now show that these and three additional patients, from six families, have an inherited subtype of EPP which is characterized by seasonal palmar keratoderma, relatively low erythrocyte protoporphyrin concentrations, and recessive inheritance. No patient had evidence of liver dysfunction; four patients had neurological abnormalities. Patients were hetero- or homoallelic for nine different FECH mutations; four of which were previously unreported. Prokaryotic expression predicted that FECH activities were 2.7–25% (mean 10.6%) of normal. Neither mutation type nor FECH activity provided an explanation for the unusual phenotype. Our findings show that palmar keratoderma is a clinical indicator of recessive EPP, identify a phenotype that occurs in 38% of reported families with recessive EPP that to our knowledge is previously unreported, and suggest that patients with this phenotype may carry a lower risk of liver disease than other patients with recessive EPP

Passage efficiency of offset and straight orifices for upstream movements of Iberian barbel in a pool-type fishway

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Marrow-isolated adult multilineage inducible cells embedded within a biologically-inspired construct promote recovery in a mouse model of peripheral vascular disease

Peripheral vascular disease is one of the major vascular complications in individuals suffering from diabetes and in the elderly that is associated with significant burden in terms of morbidity and mortality. Stem cell therapy is being tested as an attractive alternative to traditional surgery to prevent and treat this disorder. The goal of this study was to enhance the protective and reparative potential of marrow-isolated adult multilineage inducible (MIAMI) cells by incorporating them within a bio-inspired construct (BIC) made of 2 layers of gelatin B electrospun nanofibers. We hypothesized that the BIC would enhance MIAMI cell survival and engraftment, ultimately leading to a better functional recovery of the injured limb in our mouse model of critical limb ischemia compared to MIAMI cells used alone. Our study demonstrated that MIAMI cell-seeded BIC resulted in a wide range of positive outcomes with an almost full recovery of blood flow in the injured limb, thereby limiting the extent of ischemia and necrosis. Functional recovery was also the greatest when MIAMI cells were combined with BICs, compared to MIAMI cells alone or BICs in the absence of cells. Histology was performed 28 days after grafting the animals to explore the mechanisms at the source of these positive outcomes. We observed that our critical limb ischemia model induces an extensive loss of muscular fibers that are replaced by intermuscular adipose tissue (IMAT), together with a highly disorganized vascular structure. The use of MIAMI cells-seeded BIC prevented IMAT infiltration with some clear evidence of muscular fibers regeneration

Biocides

The use of chemical biocides in medical, industrial and domestic environments is a first line defense in the prevention and control of microbial growth. Although biocide treatments eliminate most surface contamination, some microorganisms may survive and give rise to substantial problems, and numerous reports have highlighted the survival of microorganisms after cleaning and disinfection in different environments. Microorganisms may have intrinsic resistance to biocides which is commonly associated with cellular impermeability. However, the continuous exposure to biocides may increase microbial resistance by cellular mutations or acquisition genetic elements. The increasing use of biocides is also a concern related to their putative environmental toxicity. Therefore, new biocidal solutions are needed to combat effectively the evolution of microbes developing resistance while having a low or no environmental toxicity impact. Phytochemicals are an attractive source of eco-friendly, relatively inexpensive and widely available new broad-spectrum antimicrobials with low levels of cutaneous cytotoxicity and environmental toxicity. This article will highlight the cleaning and disinfection processes in microbial growth control as well as the properties of biocides commonly used, the processes involved in their antimicrobial action, the factors influencing their efficacy, and the mechanisms of cellular and biofilm resistance. In addition, it will cover the main classes of phytochemicals with antimicrobial properties and their mode of action.This work was the result of the projects: POCI-01-0145-FEDER-030219; POCI-01-0145-FEDER-028397; POCI-01–0145-FEDER006939 (Laboratory for Process Engineering, Environment, Biotechnology and Energy – UID/EQU/00511/2013) funded by the European Regional Development Fund (ERDF), through COMPETE2020 – Programa Operacional Competitividade e Internacionalização (POCI) and by national funds, through FCT – Fundação para a Ciência e a Tecnologia, and the project NORTE‐01-0145‐FEDER‐000005 – LEPABE-2-ECO-INNOVATION, supported by North Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF).info:eu-repo/semantics/publishedVersio