Swiss recommendations for the management of varicella zoster virus infections

Infections with varicella zoster virus (VZV) are common viral infections associated with significant morbidity. Diagnosis and management are complex, particularly in immunocompromised patients and during pregnancy. The present recommendations have been established by a multidisciplinary panel of specialists and endorsed by numerous Swiss medical societies involved in the medical care of such patients (Appendix). The aim was to improve the care of affected patients and to reduce complications.

Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.

OBJECTIVE Short-chain enoyl-CoA hydratase (ECHS1) is a multifunctional mitochondrial matrix enzyme that is involved in the oxidation of fatty acids and essential amino acids such as valine. Here, we describe the broad phenotypic spectrum and pathobiochemistry of individuals with autosomal-recessive ECHS1 deficiency. METHODS Using exome sequencing, we identified ten unrelated individuals carrying compound heterozygous or homozygous mutations in ECHS1. Functional investigations in patient-derived fibroblast cell lines included immunoblotting, enzyme activity measurement, and a palmitate loading assay. RESULTS Patients showed a heterogeneous phenotype with disease onset in the first year of life and course ranging from neonatal death to survival into adulthood. The most prominent clinical features were encephalopathy (10/10), deafness (9/9), epilepsy (6/9), optic atrophy (6/10), and cardiomyopathy (4/10). Serum lactate was elevated and brain magnetic resonance imaging showed white matter changes or a Leigh-like pattern resembling disorders of mitochondrial energy metabolism. Analysis of patients' fibroblast cell lines (6/10) provided further evidence for the pathogenicity of the respective mutations by showing reduced ECHS1 protein levels and reduced 2-enoyl-CoA hydratase activity. While serum acylcarnitine profiles were largely normal, in vitro palmitate loading of patient fibroblasts revealed increased butyrylcarnitine, unmasking the functional defect in mitochondrial β-oxidation of short-chain fatty acids. Urinary excretion of 2-methyl-2,3-dihydroxybutyrate - a potential derivative of acryloyl-CoA in the valine catabolic pathway - was significantly increased, indicating impaired valine oxidation. INTERPRETATION In conclusion, we define the phenotypic spectrum of a new syndrome caused by ECHS1 deficiency. We speculate that both the β-oxidation defect and the block in l-valine metabolism, with accumulation of toxic methacrylyl-CoA and acryloyl-CoA, contribute to the disorder that may be amenable to metabolic treatment approaches.

Meta-studies in land use science: Current coverage and prospects

Land use science has traditionally used case-study approaches for in-depth investigation of land use change processes and impacts. Meta-studies synthesize findings across case-study evidence to identify general patterns. In this paper, we provide a review of meta-studies in land use science. Various meta-studies have been conducted, which synthesize deforestation and agricultural land use change processes, while other important changes, such as urbanization, wetland conversion, and grassland dynamics have hardly been addressed. Meta-studies of land use change impacts focus mostly on biodiversity and biogeochemical cycles, while meta-studies of socioeconomic consequences are rare. Land use change processes and land use change impacts are generally addressed in isolation, while only few studies considered trajectories of drivers through changes to their impacts and their potential feedbacks. We provide a conceptual framework for linking meta-studies of land use change processes and impacts for the analysis of coupled human–environmental systems. Moreover, we provide suggestions for combining meta-studies of different land use change processes to develop a more integrated theory of land use change, and for combining meta-studies of land use change impacts to identify tradeoffs between different impacts. Land use science can benefit from an improved conceptualization of land use change processes and their impacts, and from new methods that combine meta-study findings to advance our understanding of human–environmental systems.