Miracle-dz/UniFAR-FTUs huggingface dataset:
How common is the most common adult movement disorder? Estimates of the prevalence of essential tremor throughout the world

Essential tremor (ET) is the most common adult movement disorder, as much as 20 times more prevalent than Parkinson's disease. Estimates of the crude prevalence of ET range widely from 0.08 to 220 cases per 1000 persons, a 2750‐fold difference. There has been no formal attempt to synthesize these disparate results. Our purpose is to provide an overview of existing studies, to examine methodologic issues that may account for this tremendous variability in results, and to provide a more precise estimate of the prevalence of ET. Nineteen studies of the prevalence of ET were reviewed. Factors that contribute to broad range of prevalence estimates include (a) differences in study design that influence validity and (b) differences in characteristics of study populations that influence comparability of studies. If we limit our examination to studies that (a) provided diagnostic criteria for ET, (b) defined ET as an action tremor, and (c) used community‐based rather than service‐based designs, then five studies remain, and the prevalence of ET is 4.1 to 39.2 cases per 1000, a 9.6‐fold difference. Four of these five provided age‐stratified data. Among these four, the prevalence of ET in those over the age of 60 years was 13.0 to 50.5 cases per 1000, a 3.9‐fold difference.
Sarcomeric genotyping in hypertrophic cardiomyopathy.

OBJECTIVE To pool results from studies of patients with hypertrophic cardiomyopathy (HCM) to elucidate important phenotypic differences among genotypes. MATERIAL AND METHODS Data published from November 1998 through November 2004 were gathered and compared from unrelated study population genotyping studies from the Mayo Clinic (Rochester, Minn), Harvard Medical School (Boston, Mass), France, Germany, Sweden, Finland, and Spain. Standard statistical analysis techniques were used to pool and compare data across genotypes with respect to frequency of mutations, age at diagnosis, and degree of hypertrophy (left ventricular wall thickness). RESULTS The French study population harbored the highest frequency of mutations (61%), followed by the Mayo Clinic (38%), Harvard Medical School (36%), and Swedish (30%) study populations. For every study population, mutations in myosin binding protein C (MYBPC3) were the most common cause of HCM. Patients with a family history of HCM had mutations more frequently than those without. This pooled analysis revealed no statistically significant differences in left ventricular wall thickness or in mean age at diagnosis across all genotypes. CONCLUSIONS Differentiation of sarcomeric genotypes, such as MYBPC3-HCM and MYH7-HCM, is not possible on the basis of currently reported phenotypic data. A myriad of genetic and/or environmental modifiers in addition to the primary disease-causing genetic substrate must play an important role in determining a patient's particular phenotype.
Modulation of Prion Protein Oligomerization, Aggregation, and β-sheet Conversion by 4,4′-Dianilino-1,1′-binaphthyl-5,5′-sulfonate (bis-ANS)*

The prion protein (PrP) is the major agent implicated in the diseases known as transmissible spongiform encephalopathies. The onset of transmissible spongiform encephalopathy is related to a change in conformation of the PrPC, which loses most of its α-helical content, becoming a β-sheet-rich protein, known as PrPSc. Here we have used two Syrian hamster prion domains (PrP 109–141 and PrP 109–149) and the murine recombinant PrP (rPrP 23–231) to investigate the effects of anilino-naphtalene compounds on prion oligomerization and aggregation. Aggregation in the presence of bis-ANS (4,4′-dianilino-1,1′-binaphthyl-5,5′-sulfonate), ANS (1-anilinonaphthalene-8-sulfonate), and AmNS (1-amino-5-naphtalenesulfonate) was monitored. Bis-ANS was the most effective inhibitor of prion peptide aggregation. Bis-ANS binds strongly to rPrP 23–231 leading to a substantial increase in β-sheet content and to limited oligomerization. More strikingly, the binding of bis-ANS to full-length rPrP is diminished by the addition of nanomolar concentrations of oligonucleotides, demonstrating that they compete for the same binding site. Thus, bis-ANS displays properties similar to those of nucleic acids, causing oligomerization and conversion to β-sheet (Cordeiro, Y., Machado, F., Juliano, L., Juliano, M. A., Brentani, R. R., Foguel, D., and Silva, J. L. (2001) J. Biol. Chem. 276, 49400–49409). This dual effect of bis-ANS on prion protein makes this compound highly important to sequester crucial conformations of the protein, which may be useful to the understanding of the disease and to serve as a lead for the development of new therapeutic strategies.
Experimentally Induced Motion Sickness in Fish: Possible Role of the Otolith Organs

Objective--Although the occurrence of motion sickness is largely attributed to sensory conflict, the reasons for the highly variable inter-individual susceptibility to motion sickness remain unclear. One cause may be asymmetry between otoconial masses in the right and left inner ear. This hypothesis has been supported by experiments in fish under conditions of prolonged weightlessness and parabolic flight. In swordtail fish (Xiphophorus helleri) we examined the extent to which a Coriolis force environment, which has a strong motion sickness-triggering effect, disturbs swimming behaviour or produces motion sickness. Material and Methods--In a sealed aquarium, fish (n=22) were subjected to Coriolis stimulation by constant vertical axis rotation, combined with pendular oscillation around a horizontal axis. Results--Initially, at low stimulus intensity, all fish showed active compensatory swimming behaviour. However, while the majority (n=19) maintained active compensation movements at higher stimulus levels, the others (n=3) entered a passive uncoordinated state, from which they recovered again after reduction of stimulus intensity. On examination of the otoconial mass, we found asymmetries between the right and left utricles in all three cases and between the saccules in one case. Conclusion--We conclude that a lateral preponderance of the otoconial masses in the utricle or saccule promotes motion sickness under experimental conditions. The utricle appears to play a more important role in this than the saccule.
Fatigue induced by a cross-country skiing KO sprint.

PURPOSE The aims of the present study were 1) to analyze whether the KO sprint simulation induced a phenomenon of fatigue of upper and lower limbs and 2) if there was any fatigue, to determine its origin. METHODS Seven elite male skiers were tested before and after a simulation of KO sprints consisting of three 1200-m laps separated by 12 min of recovery. Surface electromyographic activity and force obtained under voluntary and electrically evoked contractions (single twitch) on knee-extensor muscles were analyzed to distinguish neural adaptations from contractile changes. A maximal power output test of the upper limbs was also performed. RESULTS During the last lap, the final sprint velocity was significantly lower than during the first lap. After the KO sprint, knee-extensor voluntary (-9.8 +/- 9.5%) and evoked (-16.2 +/- 11.9%) isometric force and upper-limb power output (-11.0 +/- 9.3%) and force (-11.3 +/- 8.7%) significantly decreased, whereas the blood lactate concentration increased to 11.6 mM. On the other hand, no changes were seen in RMS measurement during maximal voluntary contractions, RMS normalized by M-wave amplitude, or M-wave characteristics. CONCLUSION Changes in performance, lactate concentration, knee-extensor strength, and upper-limb power indicated that the KO sprint test led the skiers to a state of fatigue. On lower-limb muscles, the decrease of knee-extensor strength was exclusively caused by peripheral fatigue, which was at least in part attributable to a failure of the excitation-contraction coupling.
The variability of liver graft function and urinary 6β‐hydroxycortisol to cortisol ratio during liver regeneration in liver transplant recipients

Abstract: The urinary ratio of 6β‐hydroxycortisol to cortisol (6β‐OHF/F) is considered to be the simplest and most practical method for estimation of hepatic cytochrome P450 3A4 (CYP3A4) activity as a non‐invasive marker of human in vivo CYP3A4 activity. However, the inter‐ and intra‐individual variability of the urinary 6β‐OHF/F ratio during liver regeneration and the effect of variability on optimal dose of tacrolimus have not yet been clarified. The objective of this study was to clarify the change in the urinary 6β‐OHF/F ratio during liver regeneration and to determine the effect of the liver graft function on the optimal tacrolimus dose in liver transplant recipients. Two liver transplant recipients (one male and one female) and eight healthy volunteers (five males and three females) were enrolled in this study. Urine samples were collected from the recipients from 08.00 hours for 24 h on post‐transplant period, 1–10 and 21–30 days postoperatively. In the healthy volunteers, morning spot urine samples were collected at 08.00 hours. The mean urinary 6β‐OHF/F ratio in the immediate postoperative period was significantly low (p < 0.05). However, a marked difference in the regulation of CYP3A4 activity during liver regeneration was found in the two recipients. A significant correlation was found between the urinary 6β‐OHF/F ratio and the C/D ratio of tacrolimus (R = 0.658, p < 0.05). The urinary 6β‐OHF/F ratio is a useful probe for estimating the variability of CYP3A4 activity in liver transplant recipients in early postoperative phase. Future studies should evaluate the clinical usefulness of the urinary 6β‐OHF/F ratio as a predictor of tacrolimus pharmacokinetics in liver transplantation.
High-Affinity Aptamers to Subtype 3a Hepatitis C Virus Polymerase Display Genotypic Specificity

ABSTRACT Research into antiviral agents directed at hepatitis C virus (HCV) proteins is commonly based and tested on a single genotype, namely, genotype 1. This is despite the high level of variability of the RNA virus and the frequency of infection with genotypes other than genotype 1. The systematic evolution of ligands by exponential enrichment (SELEX) is a novel in vitro approach used in this study that allows rapid screening of vast nucleic acid libraries to isolate sequences (termed aptamers) that bind to target proteins with high affinity. The SELEX approach was used in the present study to isolate DNA aptamers to the RNA-dependent RNA polymerase (RdRp) (nonstructural protein 5B [NS5B]) of HCV subtype 3a, with the aim of inhibiting polymerase activity. Ten rounds of selection were performed using a Biacore 2000 as the partitioning system. Two aptamers, r10/43 and r10/47, were chosen for further studies on the basis of their abilities to bind the HCV RdRp and inhibit polymerase activity. The affinities (equilibrium dissociation constants) of these aptamers for the HCV subtype 3a polymerase were estimated to be 1.3 ± 0.3 nM (r10/43) and 23.5 ± 6.7 nM (r10/47). The inhibition constants of r10/43 and r10/47 were estimated to be 1.4 ± 2.4 nM and 6.0 ± 2.3 nM, respectively. Inhibition of HCV 3a polymerase was specific for r10/47, while r10/43 also demonstrated some inhibitory effect on norovirus and φ6 polymerase activity. Neither r10/43 nor r10/47 was able to inhibit the RdRp activity of HCV genotype 1a and 1b polymerases. This study is the first description of an inhibitor specific to the HCV subtype 3a polymerase.
Influence of topical administration of n‐3 and n‐6 essential and n‐9 nonessential fatty acids on the healing of cutaneous wounds

Injury triggers a series of physiological events at the wound site. These include an inflammatory response that is established shortly after the injury, which is then followed by an intense formation of tissue over a period of days. Poly‐ and monounsaturated fatty acids exert major functions on the inflammatory responses, either in the form of phospholipids anchored in the cell membrane or as soluble lipoic mediators. We present evidence that linolenic (n‐3), linoleic (n‐6), and oleic (n‐9) fatty acids can modulate the closure of surgically induced skin wounds. We found that n‐9 fatty acids induced faster wound closure when compared to n‐3, n‐6, and control. In addition, n‐9 fatty acids strongly inhibited the production of nitric oxide at the wound site. A mild improvement on wound closure was observed in the n‐6 fatty acid‐treated animals concurrent with a peak in nitric oxide production at 48 hours postsurgery. N‐3 fatty acid treatment significantly delayed wound closure. Furthermore, we showed that n‐3 fatty acid induced a peak in nitric oxide at 3 hours postsurgery and an intense deposition of extracellular matrix after 5 days of treatment. Thus, our results suggest a relevant role and potential therapeutic implication for fatty acids on skin wound healing.
Multicenter italian experience in liver transplantation for hepatocellular carcinoma in HIV-infected patients.

BACKGROUND The aim of our work is to assess the clinical outcomes of liver transplantation (LT) for hepatocellular carcinoma (HCC) in HIV-coinfected patients. This is a multicenter study involving three Italian transplant centers in northern Italy: University of Modena, University of Bologna, and University of Udine. PATIENTS AND METHODS We compared 30 HIV-positive patients affected by HCC who underwent LT with 125 HIV-uninfected patients who received the same treatment from September 2004 to June 2009. At listing, there were no differences between HIV-infected and -uninfected patients regarding HCC features. Patients outside the University of California, San Francisco criteria (UCSF) were considered eligible for LT if a down-staging program permitted a reduction of tumor burden. RESULTS HIV-infected patients were younger, they were more frequently anti-HCV positive, and a higher number of HIV-infected patients presented a coinfection HBV-HCV. Pre-LT treatments (liver resection and or locoregional treatments) were similar between the two groups. Histological characteristics of the tumor were similar in patients with and without HIV infection. No differences were observed in terms of overall survival and HCC recurrence rates. CONCLUSION LT for HCC is a feasible procedure and the presence of HIV does not particularly affect the post-LT outcome.
The relationship between mid-infrared and sub-millimetre variability of deeply embedded protostars

Funding: The contribution of CCP was funded by a Leverhulme Trust Research Project Grant. AS is supported by the STFC grant no. ST/R000824/1. GJH is supported by general grant 11773002 awarded by the National Science Foundation of China. DJ is supported by NRC Canada and by an NSERC Discovery Grant. J-EL and GB are supported by the Basic Science Research Program through the National Research Foundation of Korea (grant no. NRF-2018R1A2B6003423) and the Korea Astronomy and Space Science Institute under the R&D program supervised by the Ministry of Science, ICT and Future Planning. G.B. was also supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (NRF-2017H1A2A1043046-Global Ph.D.Fellowship Program).
Comparison of fluorine-18-fluorodeoxyglucose PET, MRI and endoscopy for staging head and neck squamous-cell carcinomas.

UNLABELLED Accurate, preoperative assessment of tumor extent and lymph node involvement is mandatory for individualized therapy in patients with squamous-cell carcinomas (SCCs) of the head and neck region. Metabolic imaging, [18F]fluorodeoxyglucose (FDG) PET and MRI were compared with postoperative, histologic tissue characterization. METHODS Dynamic and static PET with 370 MBq [18F]FDG up to 60 min postinjection and MRI were compared prospectively in 22 patients with head and neck SCCs. PET results with and without attenuation correction were compared with postoperative T and N stages based on pathologic findings. RESULTS Kinetic characteristics and tracer uptake intensity were similar in primary tumors and lymph node metastases. In both, FDG uptake did not reach a plateau phase 60 min postinjection. There was no statistically significant correlation of FDG uptake with plasma glucose level or histologic grading. All primary tumors were clearly demonstrated by PET, which tended to overestimate tumor size. The sensitivity and specificity for detecting individual lymph node involvement were 90% and 96%, respectively, for PET and, thus, significantly higher for MRI (78% and 71%, respectively; p < 0.05). N stages were correctly identified by MRI in only 4 patients; PET correctly staged lymph nodes in 15 of 17 patients. Based on "neck sides", the sensitivity and specificity were higher for PET, 89% and 100%, respectively, compared with MRI values of 72% and 56%, respectively. CONCLUSION FDG-PET may be helpful in detecting occult primary tumors with positive lymph nodes.
Seasonal Variation in Diverticulitis: Evidence From Both Hemispheres

BACKGROUND: Diverticulitis is a common and morbid disease with incompletely understood risk factors and pathophysiology. Geographic and, recently, seasonal trends in diverticulitis have been described in the United States. OBJECTIVE: The purpose of this study was to investigate and compare seasonal trends in urgent hospital admission for diverticulitis in geographically distinct populations in the northern and southern hemispheres. DESIGN: Inpatient, urgent admissions for diverticulitis were identified within the Dr Foster Intelligence Global Comparators Dataset, a global benchmarking collaborative. SETTINGS: Admissions to participating hospitals in the United Kingdom, Australia, and the United States were identified between 2008 and 2013. PATIENTS: A total of 18,672 urgent admissions for diverticulitis were identified among 5.5-million admissions. MAIN OUTCOME MEASURES: Four separate hypothesis testing methods were used to identify seasonal trends in diverticulitis admissions among international patient populations. RESULTS: Seasonal trends were present in all 3 countries. A summer peak was observed in both hemispheres using multiple statistical testing methods. Logistic regression analyses identified summer months as significantly associated with diverticulitis admission in all 3 countries. LIMITATIONS: This study is limited by restriction to inpatient admissions, reliance on administrative data, and participation of select hospitals within the database. CONCLUSIONS: These data suggest a shared seasonal risk factor among geographically distinct populations for diverticulitis.
Harmonization in laboratory medicine: more than clinical chemistry?

Abstract The goal of harmonizing laboratory information is to contribute to quality in patient care, ultimately improving upon patient outcomes and safety. The main focus of harmonization and standardization initiatives has been on analytical processes within the laboratory walls, clinical chemistry tests in particular. However, two major evidences obtained in recent years show that harmonization should be promoted not only in the analytical phase but also in all steps of the testing process, encompassing the entire field of laboratory medicine, including innovative areas (e.g. “omics”) rather than just conventional clinical chemistry tests. A large body of evidence demonstrates the vulnerability of the extra-analytical phases of the testing cycle. Because only “good biological samples” can assure good analytical quality, a closer interconnection between the different phases of the cycle is needed. In order to provide reliable and accurate laboratory information, harmonization activities should cover all steps of the cycle from the “pre-pre-analytical” phase (right choice of test at right time for right patient) through the analytical steps (right results with right report) to the “post-post-analytical” steps (right and timely acknowledgment of laboratory information, right interpretation and utilization with any necessary advice as to what to do next with the information provided). In addition, modern clinical laboratories are performing a broad menu of hundreds of tests, covering both traditional and innovative subspecialties of the discipline. In addition, according to a centered viewpoint, harmonization initiatives should not be addressed exclusively to clinical chemistry tests but should also include all areas of laboratory medicine.
Oxygen Toxicity and Reactive Oxygen Species: The Devil Is in the Details

Reactive oxygen species (ROS) serve as cell signaling molecules for normal biologic processes. However, the generation of ROS can also provoke damage to multiple cellular organelles and processes, which can ultimately disrupt normal physiology. An imbalance between the production of ROS and the antioxidant defenses that protect cells has been implicated in the pathogenesis of a variety of diseases, such as cancer, asthma, pulmonary hypertension, and retinopathy. The nature of the injury will ultimately depend on specific molecular interactions, cellular locations, and timing of the insult. This review will outline the origins of endogenous and exogenously generated ROS. The molecular, cellular, pathologic, and physiologic targets will then be discussed with a particular emphasis on aspects relevant to child development. Finally, antioxidant defenses that scavenge ROS and mitigate associated toxicities will be presented, with a discussion of potential therapeutic approaches for the prevention and/or treatment of human diseases using enzymatic and nonenzymatic antioxidants.
Muscle fiber type distribution in the normal human levator veli palatini muscle.

OBJECTIVE This study examined the muscle fiber type distribution within the normal adult levator veli palatini muscle. METHODS Levator veli palatini muscle tissue was harvested from the palates of 12 (seven female, five male) adult noncleft cadavers. Adjacent sections were stained for adenosine triphosphatase at pH 10.4 or 4.2. After mounting, magnifying, and photographing, Type I versus Type II fiber types were differentiated by the intensity of, or by the inhibition of, staining of matched fibers at each pH level. Type I fibers stained light at pH 10.4 and dark at pH 4.2, while Type II fibers stained light at pH 4.2 and dark at pH 10.4. MAIN OUTCOME MEASURES The number of fibers counted for each specimen ranged from 60 to 616. The numbers of Type I and Type II stained fibers appearing in each muscle tissue sample were determined and expressed as a percentage of the total number of fibers identified. A few identified fibers could not be labelled as either Type I or Type II. RESULTS The overall proportion of Type I fibers, averaged across all specimens, was 59.8%. Male specimens had 67.4% Type I fibers and 31.8% Type II fibers, while female specimens had 54.4% Type I fibers and 44.4% Type II fibers. CONCLUSIONS Observed fiber type distributions were similar to those reported for other articulatory muscles, but differed slightly from previously reported distributions for normal levator veli palatini. The distributions observed in this study provide a baseline against which to relate fiber type data from the levator veli palatini of cleft palates to the functional status of the velopharyngeal mechanism.