Miracle-dz/UniFAR-FTUs huggingface dataset:
Gray matter heterotopias and brachytelephalangic chondrodysplasia punctata: A complication of hyperemesis gravidarum induced vitamin K deficiency?

We report a patient with brachytelephalangic chondrodysplasia punctata and gray matter heterotopias. This brain abnormality has not been reported previously in association with chondrodysplasia punctata (CDP). The propositus was the son of nonconsanguineous healthy parents of normal stature and of Northern European descent. He had a healthy elder brother. A previous pregnancy had been terminated following detection of Dandy–Walker malformation in a female fetus; that pregnancy was complicated by hyperemesis gravidarum that resolved when the mother received intravenous hydration and watersoluble vitamins at 14 weeks of gestation. There was no post mortem examination of the tissue after the termination. There was no other family history of birth defects. The prenatal period of our patient was also complicated by maternal hyperemesis gravidarum and fetal malformation. The emesis began early in the pregnancy and persisted despite treatment with oral ondansetron. By 8 weeks of gestation, his mother became dehydrated and required intravenous hydration. She subsequently required outpatient intravenous hydration once a week until 18 weeks of gestation, and she lost a total of 18 kg between 8 and 18 weeks of gestation. The mother reported that she had stopped eating most food by 9 weeks of gestation. At 18 weeks of gestation, she presented with signs of intravascular volume depletion, and her blood chemistries were consistent with chronic vomiting and malnutrition (K 1.9 mEq/L; magnesium 1.6 mEq/L; calcium 8 mg/dl; phosphorus 0.9 mg/dl; albumin 2.1 g/dl; prothrombin time and partial prothombin time, not tested). At that time, she was started on total parenteral nutrition. A fetal ultrasound at 20 weeks of gestation showed a biparietal diameter of 4.6 cm (92th centile), an abdominal circumference of 14.9 cm (90th centile), a femur length of 2.6 cm (43th centile), and abnormal nasal formation. Fetal ultrasounds at 24 and 33weeks revealed an echogenic intracardiac focus and polyhydramnios with a mature-appearing grade 3 placenta respectively. Amniocentesis at 33 weeks showed dark straw-colored amniotic fluid with an immature fetal lung profile. There was no prenatal history of maternal use of alcohol, recreational drugs, warfarin, or prescribed medications other than ondansetron. Also, there was no prenatal history of maternal infection, systemic lupus erythematosus (SLE), or bleeding. The propositus was delivered at 34 weeks of gestational age by spontaneous vaginal delivery. He developed respiratory distress secondary to narrow airways and required mechanical ventilation. At birth his weight, length, and head circumference were 2,540 g (75th–90th centile), 45.1 cm (25th–50th centile), and 33 cm (25th–50th centile), respectively. Physical examination was remarkable for severe nasal hypoplasia and short digits. His limbs were
Test-retest reliability of computerized concussion assessment programs.

CONTEXT Computer-based neurocognitive assessment programs commonly are used to assist in concussion diagnosis and management. These tests have been adopted readily by many clinicians based on existing test-retest reliability data provided by test developers. OBJECTIVE To examine the test-retest reliability of 3 commercially available computer-based neurocognitive assessments using clinically relevant time frames. DESIGN Repeated-measures design. SETTING Research laboratory. PATIENTS OR OTHER PARTICIPANTS 118 healthy student volunteers. MAIN OUTCOME MEASURE(S) The participants completed the ImPACT, Concussion Sentinel, and Headminder Concussion Resolution Index tests on 3 days: baseline, day 45, and day 50. Each participant also completed the Green Memory and Concentration Test to evaluate effort. Intraclass correlation coefficients were calculated for all output scores generated by each computer program as an estimate of test-retest reliability. RESULTS The intraclass correlation coefficient estimates from baseline to day 45 assessments ranged from . 15 to . 39 on the ImPACT, . 23 to . 65 on the Concussion Sentinel, and . 15 to . 66 on the Concussion Resolution Index. The intraclass correlation coefficient estimates from the day 45 to day 50 assessments ranged from . 39 to . 61 on the ImPACT, . 39 to . 66 on the Concussion Sentinel, and . 03 to . 66 on the Concussion Resolution Index. All participants demonstrated high levels of effort on all days of testing, according to Memory and Concentration Test interpretive guidelines. CONCLUSIONS Three contemporary computer-based concussion assessment programs evidenced low to moderate test-retest reliability coefficients. Our findings do not appear to be due to suboptimal effort or other factors related to poor test performance, because persons identified by individual programs as having poor baseline data were excluded from the analyses. The neurocognitive evaluation should continue to be part of a multifaceted concussion assessment program, with priority given to those scores showing the highest reliability.
131I ablation treatment in young females after the Chernobyl accident.

UNLABELLED The Chernobyl accident resulted in a number of cases of thyroid cancer in females under the age of 20 y. Many of these individuals were treated with surgical removal of the thyroid gland followed by 131I ablation of residual thyroid tissue. Epidemiologic evidence demonstrates that 131I treatment for thyroid cancer or hyperthyroidism in adult women confers negligible risk of breast cancer. However, comparable data for younger women do not exist. Studies of external radiation exposure indicate that, for radiation exposures of as low as 0.2-0.7 Gy, the risk of breast cancer is greater for infant and adolescent female breast tissues than for adult female breast tissues. METHODS The effective half-time of 131I measured in athyrotic patients was used together with the OLINDA/EXM computer code to estimate doses to breast tissue in 10-y-old, 15-y-old, and young adult females from ablation treatment. RESULTS The dose to pediatric and young adult female breast tissue associated with a 5.6-GBq (150 mCi) ablation treatment may range from 0.35 to 0.55 Gy, resulting in a lifetime risk of breast cancer ranging from 2-4 cases per 100 such individuals exposed and a lifetime risk of solid tumors ranging from 8 to 17 solid tumors per 100 such individuals exposed. Administration of multiple ablation treatments, as often occurs with metastases, could result in doses ranging from 0.7 to 1 Gy, with corresponding increases in the lifetime cancer risk. CONCLUSION These estimates suggest the need for additional research and a possible need for surveillance of young Chernobyl thyroid cancer patients who received 131I ablation treatment.
Pneumonia Pathogen Characterization Is an Independent Determinant of Hospital Readmission

BACKGROUND Hospital readmissions for pneumonia occur often and are difficult to predict. For fiscal year 2013, the Centers for Medicare & Medicaid Services readmission penalties have been applied to acute myocardial infarction, heart failure, and pneumonia. However, the overall impact of pneumonia pathogen characterization on hospital readmission is undefined. METHODS This was a retrospective 6-year cohort study (August 2007 to September 2013). RESULTS We evaluated 9,624 patients with a discharge diagnosis of pneumonia. Among these patients, 4,432 (46.1%) were classified as having culture-negative pneumonia, 1,940 (20.2%) as having pneumonia caused by antibiotic-susceptible bacteria, 2,991 (31.1%) as having pneumonia caused by potentially antibiotic-resistant bacteria, and 261 (2.7%) as having viral pneumonia. The 90-day hospital readmission rate for survivors (n = 7,637, 79.4%) was greatest for patients with pneumonia attributed to potentially antibiotic-resistant bacteria (11.4%) followed by viral pneumonia (8.3%), pneumonia attributed to antibiotic-susceptible bacteria (6.6%), and culture-negative pneumonia (5.8%) (P < .001). Multiple logistic regression analysis identified pneumonia attributed to potentially antibiotic-resistant bacteria to be independently associated with 90-day readmission (OR, 1.75; 95% CI, 1.56-1.97; P < .001). Other independent predictors of 90-day readmission were Charlson comorbidity score > 4, cirrhosis, and chronic kidney disease. Culture-negative pneumonia was independently associated with lower risk for 90-day readmission. CONCLUSIONS Readmission after hospitalization for pneumonia is relatively common and is related to pneumonia pathogen characterization. Pneumonia attributed to potentially antibiotic-resistant bacteria is associated with an increased risk for 90-day readmission, whereas culture-negative pneumonia is associated with lower risk for 90-day readmission.
The M4 Gene of Murine Gammaherpesvirus Modulates Productive and Latent Infection In Vivo

ABSTRACT Murine gammaherpesvirus 68 (MHV-68) infection of mice represents a viable small-animal model for the study of gammaherpesvirus pathogenesis. MHV-76 is a deletion mutant of MHV-68, which lacks four MHV-68-specific genes (M1 to M4) and eight viral tRNA-like sequences at the 5′ end of the genome. These genes are implicated in latency and/or immune evasion. Consequently, MHV-76 is attenuated in the acute phase of in vivo infection with respect to MHV-68. Little is known about the role of M4 in viral infection, except that it is expressed as an immediate-early/early transcript during lytic replication of MHV-68 in vitro. To elucidate the contribution M4 makes to in vivo pathogenesis, we created a novel MHV-76 mutant (MHV-76inM4), in which the region of MHV-68 coding for M4 and accompanying putative promoter elements were inserted into the 5′ region of the MHV-76 genome. The growth of MHV-76inM4 in vitro was indistinguishable from that of MHV-76 and MHV-68. However, virus titers from MHV-76inM4-infected BALB/c mice were significantly increased with respect to MHV-76 at early times in the lung. In addition, at days 17 and 21 postinfection, there was a significant elevation in latent viral load in splenocytes of MHV-76inM4-infected mice compared to MHV-76. Like MHV-76-infected mice, MHV-76inM4-infected mice display no evidence of overt splenomegaly, a finding characteristic of MHV-68 infection. M4 expression in vivo was detectable during productive infection in the lung and during the establishment of latency in the spleen, but in general M4 was not detectable during long-term latency (day 100 postinfection).
Quantifying distraction and interruption in urological surgery

Background: To enhance safety in surgery, it is necessary to develop a variety of tools for measuring and evaluating the system of work. One important consideration for safety in any high-risk work is the frequency and effect of distraction and interruption. Aim: To quantify distraction and interruption to the sterile surgical team in urology. Methods: Observation of the behaviour of the surgical team and their task activity determined distraction and interruption recorded. Using an ordinal scale, an observer rated each salient distraction or interruption observed in relation to the team’s involvement. Results: The frequency of events and their attached ratings were high, deriving from varying degrees of equipment, procedure and environment problems, telephones, bleepers and conversations. Discussion: With further refinement and testing, this method may be useful for distinguishing ordinal levels of work interference in surgery and helpful in raising awareness of its origin for postoperative surgical team debriefing.
Enhanced fibroblast contraction of 3D collagen lattices and integrin expression by TGF-beta1 and -beta3: mechanoregulatory growth factors?

Generation of contractile forces as fibroblasts attach and migrate through collagenous substrates is a fundamental behavior, yet its regulation and consequences are obscure. Although the transforming growth factor-betas (TGF-beta) are similarly important in fibrosis and tissue repair, their role in contraction is controversial. Using a quantitative, 3D collagen culture model we have measured the effects of TGF-beta1 and -beta3 on contractile forces generated by human dermal fibroblasts. Maximal stimulation was between 7.5 and 15 ng/ml of TGF-beta1. Higher doses were inhibitory (30 ng/ml), giving a bell-shaped dose response. The initial rate of force generation was increased sevenfold (15 ng/ml). A similar response pattern was seen with TGF-beta3 alone. However, the addition of both isoforms together stimulated a biphasic increase in force generation, suggesting that there was a distinct temporal cooperativity between the two isforms. This very early onset (10-20 min) of stimulation suggested that TGF-beta might act through cell attachment and integrin function and the effect of TFG-beta on expression of fibronectin (FnR) and vitronectin (VnR) integrin receptors was monitored over the same time scale. TGF-beta1 dramatically up-regulated VnR expression, relative to FnR, over time but the optimal time for this was 2-4 h later than that of force stimulation. It is concluded that TGF-beta1 and -beta3 behave here primarily as mechanoregulatory growth factors and that stimulation of integrin expression may be a consequence of the altered cell stress.
Rationale, Design, and Methodological Aspects of the BUDAPEST‐GLOBAL Study (Burden of Atherosclerotic Plaques Study in Twins—Genetic Loci and the Burden of Atherosclerotic Lesions)

The heritability of coronary atherosclerotic plaque burden, coronary geometry, and phenotypes associated with increased cardiometabolic risk are largely unknown. The primary aim of the Burden of Atherosclerotic Plaques Study in Twins—Genetic Loci and the Burden of Atherosclerotic Lesions (BUDAPEST‐GLOBAL) study is to evaluate the influence of genetic and environmental factors on the burden of coronary artery disease. By design this is a prospective, single‐center, classical twin study. In total, 202 twins (61 monozygotic pairs, 40 dizygotic same‐sex pairs) were enrolled from the Hungarian Twin Registry database. All twins underwent non–contrast‐enhanced computed tomography (CT) for the detection and quantification of coronary artery calcium and for the measurement of epicardial fat volumes. In addition, a single non–contrast‐enhanced image slice was acquired at the level of L3‐L4 to assess abdominal fat distribution. Coronary CT angiography was used for the detection and quantification of plaque, stenosis, and overall coronary artery disease burden. For the primary analysis, we will assess the presence and volume of atherosclerotic plaques. Furthermore, the 3‐dimensional coronary geometry will be assessed based on the coronary CT angiography datasets. Additional phenotypic analyses will include per‐patient epicardial and abdominal fat quantity measurements. Measurements obtained from monozygotic and dizygotic twin pairs will be compared to evaluate the genetic or environmental effects of the given phenotype. The BUDAPEST‐GLOBAL study provides a unique framework to shed some light on the genetic and environmental influences of cardiometabolic disorders.
E-cigarette aerosols induce lower oxidative stress in vitro when compared to tobacco smoke

Abstract Tobacco smoking is a risk factor for various diseases. The underlying cellular mechanisms are not fully characterized, but include oxidative stress, apoptosis, and necrosis. Electronic-cigarettes (e-cigarettes) have emerged as an alternative to and a possible means to reduce harm from tobacco smoking. E-cigarette vapor contains significantly lower levels of toxicants than cigarette smoke, but standardized methods to assess cellular responses to exposure are not well established. We investigated whether an in vitro model of the airway epithelium (human bronchial epithelial cells) and commercially available assays could differentiate cellular stress responses to aqueous aerosol extracts (AqE) generated from cigarette smoke and e-cigarette aerosols. After exposure to AqE concentrations of 0.063–0.500 puffs/mL, we measured the intracellular glutathione ratio (GSH:GSSG), intracellular generation of oxidant species, and activation of the nuclear factor erythroid-related factor 2 (Nrf2)-controlled antioxidant response elements (ARE) to characterize oxidative stress. Apoptotic and necrotic responses were characterized by increases in caspase 3/7 activity and reductions in viable cell protease activities. Concentration-dependent responses indicative of oxidative stress were obtained for all endpoints following exposure to cigarette smoke AqE: intracellular generation of oxidant species increased by up to 83%, GSH:GSSG reduced by 98.6% and transcriptional activation of ARE increased by up to 335%. Caspase 3/7 activity was increased by up to 37% and the viable cell population declined by up to 76%. No cellular stress responses were detected following exposure to e-cigarette AqE. The methods used were suitably sensitive to be employed for comparative studies of tobacco and nicotine products.
Clinical inquiries. What laboratory monitoring is appropriate to detect adverse drug reactions in patients on cholesterol-lowering agents?

Recommendations for measuring serum aminotransferase levels before initiating pharmacologic treatment for hypercholesterolemia, after 12 weeks of therapy, and periodically afterward are based on expert opinion. It is not recommended that serum creatine kinase (CK) levels be monitored for elevation indicative of myopathy during cholesterol-lowering therapy. (Grade of recommendation: D, based on expert opinion without explicit critical appraisal)
Pulmonary antioxidant defences and protein damage during the ageing process of both sexes

The free radical theory holds that the senescence is caused by oxidative damage that results from an imbalance between reactive oxygen and nitrogen species (RONS) and antioxidant defences. Hence, it plays an important role in the field of gerontology. We evaluated, in male and female rats, the activities of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and total superoxide dismutase (tSOD), as well as oxidative protein damage in pulmonary tissue at 3, 6, 12, and 20 months of age. The results show an increase in the activities of all antioxidant enzymes at 12 months of age in female rats, suggesting an association with the reproductive life cycle. Protein damage in female pulmonary tissues did not change significantly throughout the ageing process. In male rats, the activity of GPx in 20 months of age showed an inter‐gender increase, while the tSOD and GPx showed higher activities in 20 months of age in the intra‐gender analysis. The male lung showed higher protein damage at 6 months of age. These findings suggest that antioxidant enzymatic activity is connected to the reproductive life cycle. Copyright © 2009 John Wiley & Sons, Ltd.
Membrane Fas Ligand Activates Innate Immunity and Terminates Ocular Immune Privilege1

It has been proposed that the constitutive expression of Fas ligand (FasL) in the eye maintains immune privilege, in part through inducing apoptosis of infiltrating Fas+ T cells. However, the role of FasL in immune privilege remains controversial due to studies that indicate FasL is both pro- and anti-inflammatory. To elucidate the mechanism(s) by which FasL regulates immune privilege, we used an ocular tumor model and examined the individual roles of the membrane-bound and soluble form of FasL in regulating ocular inflammation. Following injection into the privileged eye, tumors expressing only soluble FasL failed to trigger inflammation and grew progressively. By contrast, tumors expressing only membrane FasL 1) initiated vigorous neutrophil-mediated inflammation, 2) terminated immune privilege, and 3) were completely rejected. Moreover, the rejection coincided with activation of both innate and adaptive immunity. Interestingly, a higher threshold level of membrane FasL on tumors is required to initiate inflammation within the immune privileged eye, as compared with nonprivileged sites. The higher threshold is due to the suppressive microenvironment found within aqueous humor that blocks membrane FasL activation of neutrophils. However, aqueous humor is unable to completely block the proinflammatory effects of tumor cells that express high levels of membrane FasL. In conclusion, our data indicate that the function of FasL on intraocular tumors is determined by the microenvironment in conjunction with the form and level of FasL expressed.
Molecular Forms of Acetylcholinesterase and Butyrylcholinesterase in the Aged Human Central Nervous System

The distributions of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) molecular forms and their solubility characteristics were examined, using density gradient centrifugation, in various regions of the postmortem human CNS. Total AChE activity varied extensively (50‐fold) among the regions investigated, being highest in the telencephalic subcortical structures (caudate nucleus and nucleus of Meynert); intermediate in the substantia nigra, cerebellum, and spinal cord; and least in the fornix and cortical regions (hippocampus and temporal and parietal cortex). Total BChE activity was, in contrast, much more evenly distributed, with only a threefold variation between the regions studied. Although the patterns of molecular forms of each enzyme were broadly similar among the different areas, regional variations in the distribution and abundance of the various forms of AChE were much greater than those of BChE. Thus, although the tetrameric G4 form of AChE constituted the majority of the total AChE activity in all regions examined, the ratio of the G4 form to the monomeric Gl form, the latter of which constituted the majority of the remaining activity, varied markedly, ranging from 21 in the caudate nucleus to 1.7 in the tem poral cortex. In addition to the G4 and Gl forms of AChE, the dimeric G2 form was observed in the nucleus of Meynert and a fast‐sedimenting (16S) species was found in samples of both the parietal cortex and spinal cord. In contrast, the G4 and Gl forms of BChE were the only molecular species observed in the different areas and the G4.G1 ratio varied from 3.3 in the substantia nigra to 0.9 in the temporal cortex. Regarding the solubility characteristics of the individual AChE and BChE molecular forms, the majority of the G4 form of AChE was extractable only in the presence of detergent, indicating a predominantly membrane‐bound localization of this species. The smaller AChE forms (Gl and G2) and both the Gl and G4 forms of BChE were all relatively evenly distributed between soluble and membrane‐bound species. These findings are discussed in relation to neurochemical and neuroanatomical, particularly cholinergic, features of the regions examined.
Standard Setting: the application of the Receiver Operating Characteristic method

Nedelesky, Ebel and Angoff methods, which are commonly used in medical education, are considered testcentred approaches. These traditional methods are grounded in the subjective judgments of standard setters. Sometimes standard setters use the results of classical test theory (e.g. item difficulty and item discrimination parameters) to judge the behaviour of a minimally competent (borderline) student. However, the test centred approaches are based on a mathematical consensus of standard setter’s judgements rather than an analysis of the test questions. 4 A shortcoming of these methods is that if the standard setters are changed the passing mark could be changed. 5 In the student-centred approach, student abilities (ability scores) are calculated to identify a minimally competent student. A common standard setting method of the student - centred approach is the “borderline method” which is usually used in OSCEs, where standard setters identify students who performed between competent and unsatisfactory levels using a global rating scale. The pass mark of the station is then the average of the checklist scores for borderline students. Most objective tests currently use the test-centred approaches with more attention increasingly being given to