Miracle-dz/UniFAR-FTUs huggingface dataset:
Examination of high‐antibiotic users in a multi‐institutional cohort of chronic rhinosinusitis patients

In addition to known concerns regarding antibiotic overuse, recent research indicates that excessive antibiotic use is associated with poorer long‐term health. Given that rhinosinusitis is the leading condition accounting for antibiotic prescriptions in the ambulatory setting, we aimed to evaluate characteristics associated with greater antibiotic use in chronic rhinosinusitis (CRS).
Prevalence of hyperinflation and its reversibility in asthma patients with poorly controlled disease or significant dyspnea

Introduction : Inflammation in asthma involves proximal and distal airways. The latter may induce a significant hyperinflation (HI). Aim: To evaluate the prevalence of HI by body plethysmography in asthmatic patients with poorly controlled disease and/or significant dyspnea. Methods : In 324 patients (age 49 ± 17; FEV1 75 ± 18 % pred) insufficient asthma control was defined by an ACT score < 20 (n = 302) or a significant dyspnea by a MRC score ≥ 1 (n=22). HI was defined by either a RV > pred + 1.64 RSD (=RV-HI) or a FRC > 120 % pred (= FRC-HI). HI reversibility after bronchodilator was defined by a decrease of RV > 20 % or a reduction of FRC > 10 % from baseline. Change in dyspnea and chest tightness were evaluated by a VAS. Results : HI was found in 49 % (RV-HI) and 47 % (FRC-HI) of cases. Prevalence of HI was higher in patients with a FEV1 80 % pred: 78 % for RV-HI and 70 % for FRC-HI, vs 34 % and 40 %, respectively. ACT score was lower in patients with FRC-HI (13.4 ± 4 vs 14.6 ± 4; p = 0.004). Post-bronchodilator change was -10 ± 13 % for FRC, and - 12 ± 21 % for RV. HI reversibility was obtained in 59 % of cases with RV-HI and 47 % of cases with FRC-HI. Chest tightness decrease after bronchodilator was greater in patients with baseline FRC-HI (- 44 ± 25 vs - 37 ± 24 mm, p = 0.02). Dyspnea improvement was higher in those with baseline RV-HI (- 45 ± 26 mm vs - 38 ± 23, p = 0.02). Conclusion : Hyperinflation is frequent in poorly controlled asthma, including patients with normal FEV1, suggesting an involvement of distal airways. It appears reversible in more than half of cases.
The role of qualitative metasynthesis in evidence-based physical therapy

Abstract Background: Qualitative metasynthesis is a method for systematically identifying, examining, comparing, and interpreting findings from multiple published qualitative studies on specific topics. It has been argued that qualitative metasynthesis may be useful for increasing the transferability of findings from single qualitative studies to broader contexts, in part addressing the limitations of qualitative research regarding its generalizability and thus its application to evidence-based practice. Objectives: The aim of this paper is to provide an introduction to qualitative metasynthesis, to examine its potential application to physical therapy, and to discuss and debate its strengths and limitations. Major findings: Only one qualitative metasynthesis appears to have been published in physical therapy journals to date, although many other qualitative metasyntheses potentially relevant to physical therapy (on topics such as neurological, musculoskeletal, and cardiac conditions) have been published in journals intended for interprofessional audiences. Qualitative metasynthesis may be beneficial in terms of its capacity to progress theory related to physical therapy, and as a way of introducing qualitative research into public policy and development of clinical practice. Some challenges exist regarding aspects of qualitative metasynthesis, such as the place of critical appraisal of qualitative studies and the representativeness of findings from qualitative metasyntheses. These challenges continue to be enthusiastically debated. Conclusion: Uptake of qualitative metasynthesis in journals dedicated to physical therapy has been limited, but physical therapists may find qualitative metasyntheses relevant to their work outside these profession-specific forums. Qualitative metasynthesis may in the future play an important role in the development of physical therapy practice.
Depressive symptoms in opiate addicts on methadone maintenance

Abstract Sixty seven opiate dependent addicts receiving methadone maintenance completed the Beck Depression Inventory. A high level of depressive symptoms was found. Eighteen (27%) scored in the moderately depressed range while thirty eight (56%) scored in the severely depressed range. There was no statistically significant association between either sex or HIV status and level of symptom reporting. The clinical implications of depressive symptoms in opiate addicts are discussed.
Increasing evidence‐based treatments to reduce coronary heart disease mortality in Sweden: quantifying the potential gains

Abstract. Björck L, Capewell S, Bennett K, Lappas G, Rosengren A (Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; University of Liverpool, Liverpool, United Kingdom; Trinity College and St. James’s Hospital, Dublin, Ireland). Increasing evidence‐based treatments to reduce coronary heart disease mortality in Sweden: quantifying the potential gains. J Intern Med 2011; 269: 452–467.
Homogeneity of active demyelinating lesions in established multiple sclerosis

Four different patterns of demyelination have been described in active demyelinating lesions of multiple sclerosis (MS) patients that were biopsied shortly after disease onset. These patterns were suggested to represent heterogeneity of the underlying pathogenesis. The aim of this study was to determine whether lesion heterogeneity also exists in an unselected collection of autopsy material from patients with established MS.
Multimerization of Glycosylphosphatidylinositol-anchored High Density Lipoprotein-binding Protein 1 (GPIHBP1) and Familial Chylomicronemia from a Serine-to-Cysteine Substitution in GPIHBP1 Ly6 Domain*

Background: GPIHBP1 binds lipoprotein lipase (LPL) and transports it to the capillary lumen. Results: A GPIHBP1 missense mutation (S107C) leads to the formation of GPIHBP1 multimers that cannot bind LPL. Conclusion: An extra cysteine leads to GPIHBP1 multimerization, defective LPL binding, and hypertriglyceridemia. Significance: This study identifies a novel mechanism by which GPIHBP1 mutations interfere with LPL binding and cause hypertriglyceridemia. GPIHBP1, a glycosylphosphatidylinositol-anchored glycoprotein of microvascular endothelial cells, binds lipoprotein lipase (LPL) within the interstitial spaces and transports it across endothelial cells to the capillary lumen. The ability of GPIHBP1 to bind LPL depends on the Ly6 domain, a three-fingered structure containing 10 cysteines and a conserved pattern of disulfide bond formation. Here, we report a patient with severe hypertriglyceridemia who was homozygous for a GPIHBP1 point mutation that converted a serine in the GPIHBP1 Ly6 domain (Ser-107) to a cysteine. Two hypertriglyceridemic siblings were homozygous for the same mutation. All three homozygotes had very low levels of LPL in the preheparin plasma. We suspected that the extra cysteine in GPIHBP1-S107C might prevent the trafficking of the protein to the cell surface, but this was not the case. However, nearly all of the GPIHBP1-S107C on the cell surface was in the form of disulfide-linked dimers and multimers, whereas wild-type GPIHBP1 was predominantly monomeric. An insect cell GPIHBP1 expression system confirmed the propensity of GPIHBP1-S107C to form disulfide-linked dimers and to form multimers. Functional studies showed that only GPIHBP1 monomers bind LPL. In keeping with that finding, there was no binding of LPL to GPIHBP1-S107C in either cell-based or cell-free binding assays. We conclude that an extra cysteine in the GPIHBP1 Ly6 motif results in multimerization of GPIHBP1, defective LPL binding, and severe hypertriglyceridemia.
Cystatin C as a marker of cognitive function in elders: Findings from the health ABC study

We determined whether serum cystatin C, a novel measure of kidney function that colocalizes with brain β‐amyloid, is associated with cognition among 3,030 elders. Those with high cystatin C (n = 445; 15%) had worse baseline scores on Modified Mini‐Mental State Examination or Digit Symbol Substitution Test (p ≤ 0.02) compared with those with intermediate/low level and 7 years greater decline (p ≤ 0.04). Incident cognitive impairment (decline ≥1.0 standard deviation) was greatest among those with high cystatin C (Modified Mini‐Mental State Examination: 38 vs 25%; adjusted odds ratio, 1.92; 95% confidence interval, 1.37–2.69; Digit Symbol Substitution: 38 vs 26%; odds ratio, 1.54; 95% confidence interval, 1.10–2.15). Ann Neurol 2008
Randomized Controlled Trial of CI Therapy for Progressive MS: Increased Real-World Function and Neuroplasticity on MRI (I7-1.008)

OBJECTIVE: Evaluate Constraint-Induced Movement therapy (CI therapy) for real-world function and neuroplasticity in progressive MS. BACKGROUND: Progressive MS lacks an established effective treatment. CI therapy has shown efficacy for arm use in stroke and cerebral palsy in clinical trials, but its efficacy for MS is undetermined. However, pilot findings were positive (Mark et al, Mult Scler 2008). Therefore, we conducted a randomized trial for MS. Because CI therapy has increased neuroplasticity in stroke and cerebral palsy, we also evaluated changes on cortical structure in MS. DESIGN/METHODS: 20 adults with chronic progressive MS were randomized to 35 hours of either CI therapy or Complementary & Alternative Medicine (CAM) treatments (aquatherapy, massage, yoga). Both groups had identical expectations to improve. Outcomes were post-treatment changes in real-world arm use on the Motor Activity Log (MAL) and cortical grey matter structure from brain MRI at 3T on voxel-based morphometry. RESULTS: The MAL significantly improved after CI therapy (mean 2.7 points) compared to CAM (0.5 points), p = 0.0005. The Effect Size for CI therapy was 3.9 (very large), while for CAM it was 0.5 (moderate). There were no adverse events or patient dropouts. The CI therapy patients also had significantly increased cortical grey matter over bilateral sensorimotor areas after treatment ( p <0.02), unlike the CAM patients. CONCLUSIONS: CI therapy appears to be efficacious for improving real-world arm use in progressive hemiparetic MS and significantly increases cortical grey matter structural plasticity. Together, these findings suggest that CI therapy, but not CAM, can counteract the progressive functional loss and CNS degeneration of progressive MS. Supported by: National MS Society grant RG 4221 and NIH grant HD061767. Disclosure: Dr. Mark has nothing to disclose. Dr. Taub has nothing to disclose. Dr. Uswatte has nothing to disclose. Dr. Cutter has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals Inc., Cleveland Clinic, Daiichi Pharmaceutical Corp., GlaxoSmithKline Inc., Genmab, Biopharmaceuticals, Eli Lilly & Co., Medivation, and Modigenetech. Dr. Cutter has received research support from the Consortium of Multiple Sclerosis Centers. Dr. Morris has nothing to disclose. Dr. McKay has nothing to disclose. Dr. Bowman has nothing to disclose. Dr. Haddad has nothing to disclose. Dr. Rickards has nothing to disclose. Dr. Sterling has nothing to disclose.
Proteomic Analysis Reveals Age-related Changes in Tendon Matrix Composition, with Age- and Injury-specific Matrix Fragmentation*

Background: Alterations in tendon matrix composition with aging and injury are poorly understood. Results: Aging and injury resulted in distinct protein profiles, with age-specific peptide fragmentation in injury. Conclusion: Identification of protein cleavages associated with aging and injury suggest impaired maintenance and repair in aged tendon. Significance: Novel peptide fragments identified are potential biomarkers of tendon injury and age-related degeneration. Energy storing tendons, such as the human Achilles and equine superficial digital flexor tendon (SDFT), are highly prone to injury, the incidence of which increases with aging. The cellular and molecular mechanisms that result in increased injury in aged tendons are not well established but are thought to result in altered matrix turnover. However, little attempt has been made to fully characterize the tendon proteome nor determine how the abundance of specific tendon proteins changes with aging and/or injury. The aim of this study was, therefore, to assess the protein profile of normal SDFTs from young and old horses using label-free relative quantification to identify differentially abundant proteins and peptide fragments between age groups. The protein profile of injured SDFTs from young and old horses was also assessed. The results demonstrate distinct proteomic profiles in young and old tendon, with alterations in the levels of proteins involved in matrix organization and regulation of cell tension. Furthermore, we identified several new peptide fragments (neopeptides) present in aged tendons, suggesting that there are age-specific cleavage patterns within the SDFT. Proteomic profile also differed between young and old injured tendon, with a greater number of neopeptides identified in young injured tendon. This study has increased the knowledge of molecular events associated with tendon aging and injury, suggesting that maintenance and repair of tendon tissue may be reduced in aged individuals and may help to explain why the risk of injury increases with aging.
Developmental plasticity connects visual cortex to motoneurons after stroke

We report motor cortical function in the left occipital cortex of a subject who suffered a left middle cerebral artery stroke early in development. Transcranial magnetic stimulation of the left occipital cortex evoked contraction of right hand muscles. Electroencephalogram recorded over the left occipital cortex showed: 1) coherence with electromyogram from a right hand muscle; 2) a typical sensorimotor Mu rhythm at rest that was suppressed during contraction of right hand muscles. This is the first evidence that cortical plasticity extends beyond reshaping of primary sensory cortical fields to respecification of the cortical origin of subcortically projecting pathways. ANN NEUROL 2010;67:132–136
A short history of blebbing

Blebs are protrusions of the cell membrane. They are the result of actomyosin contractions of the cortex, which cause either transient detachment of the cell membrane from the actin cortex or a rupture in the actin cortex. Then, cytosol streams out of the cell body and inflates the newly formed bleb. During expansion, which lasts ∼30 s, the bleb is devoid of actin and the surface area increases through further tearing of membrane from the cortex and convective flows of lipids in the plane of the membrane through the bleb neck. Once expansion slows, an actin cortex is reconstituted. First actin‐membrane linker proteins, such as ezrin, are recruited to the bleb, then actin, actin‐bundling proteins and finally myosin motor proteins. Retraction lasts ∼2 min and is powered by myosin motor proteins. Though it has been less studied than other actin‐based membrane protrusions such as lamellipodia or filopodia, blebbing is a common feature of cell physiology during cell movement, cytokinesis, cell spreading and apoptosis. This review will succinctly attempt to summarize what we know about the mechanisms involved in blebbing, when it appears in cell physiology and what open questions remain.
Definitions, regulations and health claims associated with dietary fibre and wholegrain foods.

Abstract: Consumers worldwide are becoming increasingly interested in healthy eating, and have consequently (re)discovered the value of wholegrain-based and fibre-rich products. Governments and industry associations are developing regulations and guidelines for labelling, while authorities and scientific bodies are issuing and renewing dietary guidelines for recommended intake and assessing the numerous health claim proposals submitted by the industry. After a short outline on definitions and related analytical methods, this chapter presents an overview of the current state of affairs.
Receptor Tyrosine Kinases, TYRO3, AXL, and MER, Demonstrate Distinct Patterns and Complex Regulation of Ligand-induced Activation*

Background: The mechanisms by which ligands activate TAM receptors (TYRO3, AXL, and MER) are not well understood. Results: We created a series of TAM reporter cell lines and interrogated ligand-inducible TAM activation. Conclusion: TAMs are differentially activated by GAS6 and protein S and have distinct requirements for phosphatidylserine. Significance: Results reveal molecular mechanisms and rationale for non-overlapping functions of TAMs. TYRO3, AXL, and MER receptors (TAMs) are three homologous type I receptor-tyrosine kinases that are activated by endogenous ligands, protein S (PROS1) and growth arrest-specific gene 6 (GAS6). These ligands can either activate TAMs as soluble factors, or, in turn, opsonize phosphatidylserine (PS) on apoptotic cells (ACs) and serve as bridging molecules between ACs and TAMs. Abnormal expression and activation of TAMs have been implicated in promoting proliferation and survival of cancer cells, as well as in suppressing anti-tumor immunity. Despite the fact that TAM receptors share significant similarity, little is known about the specificity of interaction between TAM receptors and their ligands, particularly in the context of ACs, and about the functional diversity of TAM receptors. To study ligand-mediated activation of TAMs, we generated a series of reporter cell lines expressing chimeric TAM receptors. Using this system, we found that each TAM receptor has a unique pattern of interaction with and activation by GAS6 and PROS1, which is also differentially affected by the presence of ACs, PS-containing lipid vesicles and enveloped virus. We also demonstrated that γ-carboxylation of ligands is essential for the full activation of TAMs and that soluble immunoglobulin-like TAM domains act as specific ligand antagonists. These studies demonstrate that, despite their similarity, TYRO3, AXL, and MER are likely to perform distinct functions in both immunoregulation and the recognition and removal of ACs.
Quantitative off‐axis electron holography of GaAs p‐n junctions prepared by focused ion beam milling

Focused Ion beam (FIB) prepared GaAs p‐n junctions have been examined using off‐axis electron holography. Initial analysis of the holograms reveals an experimentally determined built‐in potential in the junctions that is significantly smaller than predicted from theory. In this paper we show that through combinations of in situ annealing and in situ biasing of the specimens, by varying the intensity of the incident electron beam, and by modifying the FIB operating parameters, we can develop an improved understanding of phenomena such as the electrically ‘inactive’ thickness and subsequently recover the predicted value of the built‐in potential of the junctions.
Veterinary toxicology: basic and clinical principles.

"Veterinary Toxicology" is a unique single reference that teaches the basic principles of veterinary toxicology to any student at the DVM, MS or PhD level and will continue to serve as a clinical reference for practicing veterinary toxicologists, poison control centers, marine biologists, environmentalists, and animal scientists. While most comparable texts are primarily directed toward the field of human toxicology, this is the one text needed to thoroughly prepare future veterinarians on the newest approaches for diagnosing poisoning cases in all animals from chemicals and plants of a diverse nature as a result of inadvertent, accidental, or malicious intents. Many chapters are provided on topics not covered in any previous books such as target organ toxicity, radiation and radioactive materials, FDA regulatory issues, and ethics in veterinary toxicology. This title includes: new chapters covering important and timely topics such as melamine and cyanuric acid, toxicogenomics, toxic gases and veterinary medical geology; and, provides expanded look at international topics, such as epidemiology of animal poisonings, regulatory guidelines and poisonous plants in Europe. This is a heavily contributed book with chapters written by qualified and well-experienced authorities across all areas of veterinary toxicology. Problem solving strategies are offered for treatment as well as in-depth knowledge of the basic mechanisms of veterinary toxicology.
Primary infection with the Epstein‐Barr virus and risk of multiple sclerosis

To determine whether multiple sclerosis (MS) risk increases following primary infection with the Epstein‐Barr virus (EBV), we conducted a nested case‐control study including 305 individuals who developed MS and 610 matched controls selected among the >8 million active‐duty military personnel whose serum has been stored in the Department of Defense Serum Repository. Time of EBV infection was determined by measuring antibody titers in serial serum samples collected before MS onset among cases, and on matched dates among controls. Ten (3.3%) cases and 32 (5.2%) controls were initially EBV negative. All of the 10 EBV‐negative cases became EBV positive before MS onset; in contrast, only 35.7% (n = 10) of the 28 controls with follow‐up samples seroconverted (exact p value = 0.0008). We conclude that MS risk is extremely low among individuals not infected with EBV, but it increases sharply in the same individuals following EBV infection. ANN NEUROL 2010;67:824–830
Chemical Structure and Morphology of Dorsal Root Ganglion Neurons from Naive and Inflamed Mice*

Background: Roles of lipids and carbohydrates in sensory transduction are understudied. Results: Localization of lipids and carbohydrates in neuronal subsets is identified and associated with enrichment of endoplasmic reticulum; lipids increased in nociceptors during inflammation but not in TRPA1-deficient neurons. Conclusion: Chemical morphology varies in sensory subpopulations; TRPA1-mediated lipid increases may underlie mechanical sensitization with inflammation. Significance: Lipids and carbohydrates may mediate inflammatory pain. Fourier transform infrared spectromicroscopy provides label-free imaging to detect the spatial distribution of the characteristic functional groups in proteins, lipids, phosphates, and carbohydrates simultaneously in individual DRG neurons. We have identified ring-shaped distributions of lipid and/or carbohydrate enrichment in subpopulations of neurons which has never before been reported. These distributions are ring-shaped within the cytoplasm and are likely representative of the endoplasmic reticulum. The prevalence of chemical ring subtypes differs between large- and small-diameter neurons. Peripheral inflammation increased the relative lipid content specifically in small-diameter neurons, many of which are nociceptive. Because many small-diameter neurons express an ion channel involved in inflammatory pain, transient receptor potential ankyrin 1 (TRPA1), we asked whether this increase in lipid content occurs in TRPA1-deficient (knock-out) neurons. No statistically significant change in lipid content occurred in TRPA1-deficient neurons, indicating that the inflammation-mediated increase in lipid content is largely dependent on TRPA1. Because TRPA1 is known to mediate mechanical and cold sensitization that accompanies peripheral inflammation, our findings may have important implications for a potential role of lipids in inflammatory pain.