Search

Carolina Valencia,1 Rogelio A Coronado,2 Corey B Simon,3,4 Thomas W Wright,5 Michael W Moser,5 Kevin W Farmer,5 Steven Z George3,6,7 1Department of Applied Medicine and Rehabilitation, Indiana State University, Terre Haute, IN, 2Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, TN, 3Department of Physical Therapy, College of Public Health and Health Professions, University of Florida, Gainesville, FL, 4Department of Community Dentistry and Behavioral Science, College of Dentistry, University of Florida, Gainesville,FL, 5Department of Orthopaedics and Rehabilitation, University of Florida, Gainesville, FL, 6Center for Pain Research and Behavioral Health, University of Florida, Gainesville, FL, 7Brooks–PHHP Research Collaboration, Jacksonville, FL, USA Background: There is limited literature investigating preoperative physical therapy (pre-op PT) treatment on pain intensity and disability after musculoskeletal surgery. The purposes of the present cohort study were to describe patient characteristics for those who had and did not have pre-op PT treatment and determine whether pre-op PT influenced the length of postoperative physical therapy (post-op PT) treatment (number of sessions) and 3-month and 6-month postsurgical outcomes, such as pain intensity and disability. Patients and methods: A total of 124 patients (mean age =43 years, 81 males) with shoulder pain were observed before and after shoulder arthroscopic surgery. Demographic data, medical history, and validated self-report questionnaires were collected preoperatively and at 3 months and 6 months after surgery. Analysis of variance models were performed to identify differences across measures for patients who had pre-op PT treatment and those who did not and to examine outcome differences at 3 months and 6 months. Alpha was set at the 0.05 level for statistical significance. Results: Males had less participation in pre-op PT than females (P=0.01). In contrast, age, pain intensity, disability, and pain-associated psychological factors did not differ between pre-op PT treatment groups (P>0.05). Subacromial bursectomies were more commonly performed in patients having pre-op PT treatment (P

Control of food or bolus flow properties is part of several strategies to address aspiration pneumonia in dysphagic patients. An important alternative is the use of prescribed ready-to-use (RTU) oral nutritional supplements (ONS) specially designed for the nutritional support at different stages of dysphagia. However, it is clear that there are significant differences among products designed for the same level or stage of dysphagia. On the other hand, videofluoroscopy has become a key technique for the evaluation of swallowing and, thus, dysphagia. In this study, a new approach for designing RTU ONS products, specifically spoon-thick consistency products, has been carried out. The scientific approach has been based, first, on the characterization of the rheological properties of a standard barium-based commercial product used in videofluoroscopy studies and, then, matching the viscous flow properties of the RTU ONS product accordingly, by taking into consideration both formulation and process conditions. The results obtained clearly suggest that it is possible to obtain an excellent viscous flow behaviour similarity of both swallow barium test feed and RTU ONS produced at industrial scale. In this sense, both linear viscoelasticity properties and non-linear relaxation modulus have to be optimised to obtain the rheological similarity previously mentioned.

BACKGROUND:Granulocyte-macrophage colony-stimulating factor auto-antibodies (GMAbs) suppress neutrophil-extrinsic GM-CSF signaling and increase risk for stricturing behavior in Crohn's disease (CD). We aimed to define clinical, genomic, and functional associations with neutrophil-intrinsic GM-CSF signaling. METHODS:Missense mutations in CSF2RA, CSF2RB, JAK2, STAT5A, and STAT5B were identified using whole-exome sequencing in 543 pediatric inflammatory bowel disease (IBD) patients. Neutrophil-intrinsic GM-CSF signaling was defined using the GM-CSF-induced STAT5 stimulation index (GMSI) in 180 pediatric IBD patients and 26 non-IBD controls. Reduced GM-CSF signaling (GMSI-Lo) was defined as the 20th percentile within the control group. Variation in neutrophil phospho-protein abundance, bacterial killing, and the global pattern of gene expression with the GMSI was determined. RESULTS:We validated 18 potentially damaging missense mutations in CSF2RA and CSF2RB. CSF2RA A17G carriage increased from 10% in those with intact neutrophil GMSI to 32% in those with low GMSI (P = 0.02). The frequency of reduced Staphylococcus aureus killing increased from 17% in those with intact neutrophil GMSI to 35% in GMSI-Lo neutrophils (P = 0.043). Crohn's disease neutrophils with low GMSI exhibited specific alterations in phospho-protein networks and genes regulating cytokine production, wound healing, and cell survival and proliferation. Stricturing behavior increased from 7% in patients with both low GMAb and intact GMSI to 64% in patients with both elevated GMAb and low GMSI (P < 0.0001). CONCLUSIONS:Low/normal neutrophil-intrinsic GM-CSF signaling is associated with CSF2RA missense mutations, alterations in gene expression networks, and higher rates of disease complications in pediatric CD.

Although there has been considerable debate about whether paternal mitochondrial DNA (mtDNA) transmission may coexist with maternal transmission of mtDNA, it is generally believed that mitochondria and mtDNA are exclusively maternally inherited in humans. Here, we identified three unrelated multigeneration families with a high level of mtDNA heteroplasmy (ranging from 24 to 76%) in a total of 17 individuals. Heteroplasmy of mtDNA was independently examined by high-depth whole mtDNA sequencing analysis in our research laboratory and in two Clinical Laboratory Improvement Amendments and College of American Pathologists-accredited laboratories using multiple approaches. A comprehensive exploration of mtDNA segregation in these families shows biparental mtDNA transmission with an autosomal dominantlike inheritance mode. Our results suggest that, although the central dogma of maternal inheritance of mtDNA remains valid, there are some exceptional cases where paternal mtDNA could be passed to the offspring. Elucidating the molecular mechanism for this unusual mode of inheritance will provide new insights into how mtDNA is passed on from parent to offspring and may even lead to the development of new avenues for the therapeutic treatment for pathogenic mtDNA transmission.

Iron-sulfur (Fe-S) clusters are ubiquitous cofactors essential to various cellular processes, including mitochondrial respiration, DNA repair, and iron homeostasis. A steadily increasing number of disorders are being associated with disrupted biogenesis of Fe-S clusters. Here, we conducted whole-exome sequencing of patients with optic atrophy and other neurological signs of mitochondriopathy and identified 17 individuals from 13 unrelated families with recessive mutations in FDXR, encoding the mitochondrial membrane-associated flavoprotein ferrodoxin reductase required for electron transport from NADPH to cytochrome P450. In vitro enzymatic assays in patient fibroblast cells showed deficient ferredoxin NADP reductase activity and mitochondrial dysfunction evidenced by low oxygen consumption rates (OCRs), complex activities, ATP production and increased reactive oxygen species (ROS). Such defects were rescued by overexpression of wild-type FDXR. Moreover, we found that mice carrying a spontaneous mutation allelic to the most common mutation found in patients displayed progressive gait abnormalities and vision loss, in addition to biochemical defects consistent with the major clinical features of the disease. Taken together, these data provide the first demonstration that germline, hypomorphic mutations in FDXR cause a novel mitochondriopathy and optic atrophy in humans.

Background & aimsThe etiology of acute liver failure (ALF) remains elusive in almost half of affected children. We hypothesized that inherited mitochondrial and fatty acid oxidation disorders were occult etiological factors in patients with idiopathic ALF and impaired energy metabolism.MethodsTwelve patients with elevated blood molar lactate/pyruvate ratio and indeterminate etiology were selected from a retrospective cohort of 74 subjects with ALF because their fixed and frozen liver samples were available for histological, ultrastructural, molecular and biochemical analysis.ResultsA customized next-generation sequencing panel for 26 genes associated with mitochondrial and fatty acid oxidation defects revealed mutations and sequence variants in five subjects. Variants involved the genes ACAD9, POLG, POLG2, DGUOK, and RRM2B; the latter not previously reported in subjects with ALF. The explanted livers of the patients with heterozygous, truncating insertion mutations in RRM2B showed patchy micro- and macrovesicular steatosis, decreased mitochondrial DNA (mtDNA) content