B-virus from pet macaque monkeys: an emerging threat in the United States?

Of primary concern when evaluating macaque bites are bacterial and B-virus infections. B-virus infection is highly prevalent (80% to 90%) in adult macaques and may cause a potentially fatal meningoencephalitis in humans. We examined seven nonoccupational exposure incidents involving 24 persons and eight macaques. Six macaques were tested for herpes B; four (67%) were seropositive. A common observation was that children were more than three times as likely to be bitten than adults. The virus must be assumed to be a potential health hazard in macaque bite wounds; this risk makes macaques unsuitable as pets

A duchenne muscular dystrophy gene hot spot mutation in dystrophin-deficient Cavalier King Charles Spaniels is amenable to exon 51 skipping

BACKGROUND Duchenne muscular dystrophy (DMD), which afflicts 1 in 3500 boys, is one of the most common genetic disorders of children. This fatal degenerative condition is caused by an absence or deficiency of dystrophin in striated muscle. Most affected patients have inherited or spontaneous deletions in the dystrophin gene that disrupt the reading frame resulting in unstable truncated products. For these patients, restoration of the reading frame via antisense oligonucleotide-mediated exon skipping is a promising therapeutic approach. The major DMD deletion "hot spot" is found between exons 45 and 53, and skipping exon 51 in particular is predicted to ameliorate the dystrophic phenotype in the greatest number of patients. Currently the mdx mouse is the most widely used animal model of DMD, although its mild phenotype limits its suitability in clinical trials. The Golden Retriever muscular dystrophy (GRMD) model has a severe phenotype, but due to its large size, is expensive to use. Both these models have mutations in regions of the dystrophin gene distant from the commonly mutated DMD "hot spot". METHODOLOGY/PRINCIPAL FINDINGS Here we describe the severe phenotype, histopathological findings, and molecular analysis of Cavalier King Charles Spaniels with dystrophin-deficient muscular dystrophy (CKCS-MD). The dogs harbour a missense mutation in the 5' donor splice site of exon 50 that results in deletion of exon 50 in mRNA transcripts and a predicted premature truncation of the translated protein. Antisense oligonucleotide-mediated skipping of exon 51 in cultured myoblasts from an affected dog restored the reading frame and protein expression. CONCLUSIONS/SIGNIFICANCE Given the small size of the breed, the amiable temperament and the nature of the mutation, we propose that CKCS-MD is a valuable new model for clinical trials of antisense oligonucleotide-induced exon skipping and other therapeutic approaches for DMD

Putting the Dietary Guidelines for Americans into Action through the National Strategy on Hunger, Nutrition, and Health

The United States is facing a crisis of widespread food insecurity and exceedingly high rates of diet-related diseases like diabetes, obesity, and hypertension. To address this challenge and set a course for improved nutrition and food access nationwide, the Biden-Harris Administration hosted the first White House Conference on Hunger, Nutrition, and Health in over 50 years on September 28, 2022. In the National Strategy, released in conjunction with the Conference, the Administration identified a set of actions that the federal government will take to help achieve its goal of ending hunger and increasing healthy eating and physical activity by 2030, so that fewer Americans experience diet-related diseases. Underpinning many of these actions is the Dietary Guidelines for Americans ( Dietary Guidelines ), which provides scientific advice on nutrition intake to meet nutrient needs, promote health, and prevent disease and serves as the cornerstone of federal food and nutrition programs. This manuscript details how expanded implementation of the Dietary Guidelines can help advance actions in the National Strategy and achieve the goals of the Administration

Putting the Dietary Guidelines for Americans into Action through the National Strategy on Hunger, Nutrition, and Health

The United States is facing a crisis of widespread food insecurity and exceedingly high rates of diet-related diseases like diabetes, obesity, and hypertension. To address this challenge and set a course for improved nutrition and food access nationwide, the Biden-Harris Administration hosted the first White House Conference on Hunger, Nutrition, and Health in over 50 years on September 28, 2022. In the National Strategy, released in conjunction with the Conference, the Administration identified a set of actions that the federal government will take to help achieve its goal of ending hunger and increasing healthy eating and physical activity by 2030, so that fewer Americans experience diet-related diseases. Underpinning many of these actions is the Dietary Guidelines for Americans ( Dietary Guidelines ), which provides scientific advice on nutrition intake to meet nutrient needs, promote health, and prevent disease and serves as the cornerstone of federal food and nutrition programs. This manuscript details how expanded implementation of the Dietary Guidelines can help advance actions in the National Strategy and achieve the goals of the Administration

Equine atypical myopathy associated with sycamore seed ingestion in a Przewalski foal

One of the 172 UK cases of equine atypical myopathy (EAM) reported to the Atypical Myopathy Alert Group (AMAG) in 2014 was that of a five-month old male Przewalski horse (Equus ferus przewalskii), resident at ZSL Whipsnade Zoo, UK. The foal presented initially with sudden-onset and repeated stretching of the neck as if dysphagic, with progressive weakness (including lying down), sweating and an unresponsive demeanour. General anaesthesia, induced with a combination of etorphine, midazolam and hyaluronidase, was required for each examination and subsequent treatment of the foal. Initial biochemical analysis showed a markedly increased plasma creatine kinase (CK) activity of 105,001 U/L, an increased aspartate amino transferase (AST) activity of 4194 U/L and a mildly increased inorganic phosphorus concentration of 2.35 mmol/L. The foal was unresponsive to treatment and had to be euthanased. Skeletal musculature and the myocardium showed the most significant pathological changes, with histological evidence of rhabdomyolysis, whilst urine organic acid analysis and an abnormal organic acid serum profile were supportive of multiple acyl Co-A dehydrogenase deficiency typical of EAM. This is the first description of EAM in a non-domestic equid

Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy

Mutations in the gene encoding dystrophin, a protein that maintains muscle integrity and function, cause Duchenne muscular dystrophy (DMD). The deltaE50-MD dog model of DMD harbors a mutation corresponding to a mutational “hotspot” in the human DMD gene. We used adeno-associated viruses to deliver CRISPR gene editing components to four dogs and examined dystrophin protein expression 6 weeks after intramuscular delivery (n = 2) or 8 weeks after systemic delivery (n = 2). After systemic delivery in skeletal muscle, dystrophin was restored to levels ranging from 3 to 90% of normal, depending on muscle type. In cardiac muscle, dystrophin levels in the dog receiving the highest dose reached 92% of normal. The treated dogs also showed improved muscle histology. These large-animal data support the concept that, with further development, gene editing approaches may prove clinically useful for the treatment of DMD

Towards a first-principles theory of surface thermodynamics and kinetics

Understanding of the complex behavior of particles at surfaces requires detailed knowledge of both macroscopic and microscopic processes that take place; also certain processes depend critically on temperature and gas pressure. To link these processes we combine state-of-the-art microscopic, and macroscopic phenomenological, theories. We apply our theory to the O/Ru(0001) system and calculate thermal desorption spectra, heat of adsorption, and the surface phase diagram. The agreement with experiment provides validity for our approach which thus identifies the way for a predictive simulation of surface thermodynamics and kinetics.Comment: 4 pages including 3 figures. Related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm