Miracle-dz/UniFAR-FTUs huggingface dataset:
Iatrogenic effects of alcohol and drug prevention programs.

OBJECTIVE Understanding prevention program risks and the contextual factors associated with negative program outcomes is critical to assisting the development of public policy that is aimed at avoiding future prevention-related harm while maximizing prevention success. The purpose of this review was to systematically analyze published studies evaluating substance use prevention programs, to determine whether iatrogenic effects have occurred, and if so, what types of harmful effects resulted and under what circumstances. METHOD A search of electronic bibliographic databases in allied health, education, medicine, psychology and general literature was conducted, spanning the years from 1980 to the present. RESULTS Evidence of negative program effects was found in 17 evaluation studies for which 43 negative outcomes were documented. The most common type of negative outcome resulting from prevention programs was behavioral effects consisting primarily of increases in consumption, especially alcohol use. Drug prevention programs resulted in greater increases in alcohol use, cigarette use, marijuana use and multiple drug use than did alcohol prevention programs. Negative program outcomes appear to exist as three possible scenarios, described in this article. CONCLUSIONS Researchers, publishers and practitioners should pay special attention to measuring, monitoring and reporting negative outcomes of prevention programs in the future, so that we might learn more about which program elements interact with which contextual factors to cause harm to which groups of youth.
Arthrogryposis multiplex congenita‐like syndrome associated with median cleft lip and palates: First prenatally detected case

An early second‐trimester prenatal ultrasound diagnosis of an arthrogryposis multiplex congenita‐like syndrome associated with median clefts is reported. A molecular biological work‐up was performed to search for a potentially overlapping syndrome and dysostosis. Autopsy and postmortem radiogram were performed to confirm the ultrasound diagnosis. Prenatal diagnosis enabled early detection of multiple fetal malformations, thus allowing early termination of pregnancy. Moreover, three‐dimensional ultrasound with volume rendering in the maximum surface mode demonstrated its value in diagnosing oro‐facial clefts, even at an early stage of fetal development.
Increased Sensitivity to Etomidate in the Elderly: Initial Distribution versus Altered Brain Response

To determine the effect of aging on the pharmacokinetics and pharmacodynamics of etomidate, we administered etomidate (5 to 10 mg/min) by intravenous infusion to 21 healthy surgical patients, age 22 to 82 yr. Etomidate produced progressive slowing of the EEG to an easily recognized pattern (stage 3) that determined the dosage endpoint. Subsequent power-spectrum analysis of the EEG gave the median frequency. Median frequency values and simultaneous measurements of blood etomidate concentration were incorporated into a sigmoid Emax pharmacodynamic model that permitted an estimate of IC50, the blood etomidate concentration which produced a 50% reduction in the median frequency. The dose of etomidate required to reach the uniform EEG endpoint decreased significantly with increasing age (r2 = .68) as did the dose needed to produce maximal median frequency depression (r2 = .69). None of the parameters of the pharmacodynamic effect model, including IC50, correlated with age, suggesting that increased brain sensitivity in the elderly does not cause the age-related change in dose requirement. The initial distribution volume for etomidate decreased significantly with increasing age (r = .56), implying that a higher initial blood concentration in the elderly following any given dose of etomidate is part of the cause of the lower dose requirement in the elderly patient. A contracted initial distribution volume in the elderly may result from well described physiologic changes of age. Etomidate clearance also decreased with age. Age-dependent changes in etomidate pharmacokinetics rather than altered brain responsiveness may be the basis for the decreased etomidate dose requirement in the elderly.
Antiarrhythmic effect of ranolazine in combination with class III drugs in an experimental whole-heart model of atrial fibrillation.

BACKGROUND Ranolazine is evaluated for antiarrhythmic therapy of atrial fibrillation (AF). The electrophysiologic mechanisms of ranolazine in combination with class III drugs were studied in an isolated whole-heart model of stretch-related AF. METHODS AND RESULTS Thirty rabbits were fed with amiodarone (50 mg/kg/day, n = 10), dronedarone (50 mg/kg/day, n = 10), or placebo (n = 10) for 6 weeks. Subsequently, in isolated hearts, AF was induced by high-rate atrial pacing and acute atrial dilatation. In placebo-treated hearts, d,l-sotalol (50 μM) was acutely administered. Ranolazine (10 μM) was additionally infused in all groups. Chronic amiodarone (+26 ± 7 ms, P < 0.05) or dronedarone (+22 ± 4 ms, P < 0.05) as well as acute application of d,l-sotalol (+20 ± 3 ms, P < 0.05) increased atrial action potential duration (aAPD90 ). Additional treatment with ranolazine did not significantly change aAPD90 (P = ns). Class III drugs did not affect interatrial conduction time, while ranolazine significantly increased it (amiodarone group: +15 ± 3 ms, dronedarone group: +11 ± 3 ms, sotalol group: +15 ± 6 ms; P < 0.05 each). Ranolazine led to an additional increase in atrial effective refractory period (aERP), thus leading to an enhanced atrial postrepolarization refractoriness (aPRR, +17 ± 6 ms, +21 ± 4 ms and +16 ± 8 ms, P < 0.05, respectively). Acute atrial dilatation increased AF incidence compared with baseline. Amiodarone-pretreated hearts showed a lower incidence of AF. Additional infusion of ranolazine further diminished AF. Dronedarone or acute infusion of sotalol did not significantly suppress AF, while additional treatment with ranolazine in these groups also reduced AF incidence. CONCLUSION In this study, ranolazine on top of class III antiarrhythmic therapy had a beneficial effect. The increase in interatrial conduction time and marked atrial aPRR suppressed AF. These results shed further light on a potential therapeutic benefit of ranolazine on top of conventional antiarrhythmic therapy for rhythm control in AF.
Comparative Effectiveness of Injection Therapies in Lateral Epicondylitis

Background: Injection therapy with glucocorticoids has been used since the 1950s as a treatment strategy for lateral epicondylitis (tennis elbow). Lately, several novel injection therapies have become available. Purpose: To assess the comparative effectiveness and safety of injection therapies in patients with lateral epicondylitis. Study Design: Systematic review and meta-analysis. Methods: Randomized controlled trials comparing different injection therapies for lateral epicondylitis were included provided they contained data for change in pain intensity (primary outcome). Trials were assessed using the Cochrane risk of bias tool. Network (random effects) meta-analysis was applied to combine direct and indirect evidence within and across trial data using the final end point reported in the trials, and results for the arm-based network analyses are reported as standardized mean differences (SMDs). Results: Seventeen trials (1381 participants; 3 [18%] at low risk of bias) assessing injection with 8 different treatments—glucocorticoid (10 trials), botulinum toxin (4 trials), autologous blood (3 trials), platelet-rich plasma (2 trials), and polidocanol, glycosaminoglycan, prolotherapy, and hyaluronic acid (1 trial each)—were included. Pooled results (SMD [95% confidence interval]) showed that beyond 8 weeks, glucocorticoid injection was no more effective than placebo (−0.04 [−0.45 to 0.35]), but only 1 trial (which did not include a placebo arm) was at low risk of bias. Although botulinum toxin showed marginal benefit (−0.50 [−0.91 to −0.08]), it caused temporary paresis of finger extension, and all trials were at high risk of bias. Both autologous blood (−1.43 [−2.15 to −0.71]) and platelet-rich plasma (−1.13 [−1.77 to −0.49]) were also statistically superior to placebo, but only 1 trial was at low risk of bias. Prolotherapy (−2.71 [−4.60 to −0.82]) and hyaluronic acid (−5.58 [−6.35 to −4.82]) were both more efficacious than placebo, whereas polidocanol (0.39 [−0.42 to 1.20]) and glycosaminoglycan (−0.32 [−1.02 to 0.38]) showed no effect compared with placebo. The criteria for low risk of bias were only met by the prolotherapy and polidocanol trials. Conclusion: This systematic review and network meta-analysis of randomized controlled trials found a paucity of evidence from unbiased trials on which to base treatment recommendations regarding injection therapies for lateral epicondylitis.
Probing the tertiary structure of proteins by limited proteolysis and mass spectrometry: The case of minibody

A strategy that combines limited proteolysis experiments and mass spectrometrie analysis of the fragments generated has been developed to probe protease‐accessible sites on the protein surface. This integrated approach has been employed to investigate the tertiary structure of the Minibody, a de novo designed 64‐residue protein consisting of a β‐sheet scaffold based on the heavy‐chain variable‐domain structure of a mouse immunoglobulin and containing two segments corresponding to the hypervariable H1 and H2 regions. The low solubility of the protein prevented a detailed characterization by NMR and/or X‐ray. Different proteases were used under strictly controlled conditions and the cleavage sites were mapped onto the anticipated Minibody model, leading to the identification of the most exposed regions. A single‐residue mutant was constructed and characterized, following the same procedure, showing a slightly higher correspondence with the predicted model. This strategy can be used to effectively supplement NMR and X‐ray investigations of protein tertiary structure, where these procedures cannot provide definitive data, or to verify and refine protein models.
Dissecting the Immune Response to Moloney Murine Sarcoma/Leukemia Virus-Induced Tumors by Means of a DNA Vaccination Approach

ABSTRACT The intramuscular inoculation of Moloney murine sarcoma/leukemia (M-MSV/M-MuLV) retroviral complex gives rise to sarcomas that undergo spontaneous regression due to the induction of a strong immune reaction mediated primarily by cytotoxic T lymphocytes (CTL). We used a DNA-based vaccination approach to dissect the CTL response against the Gag and Env proteins of M-MSV/M-MuLV in C57BL/6 (B6) mice and to evaluate whether plasmid DNA-immunized mice would be protected against a subsequent challenge with syngeneic tumor cells expressing the viral antigens. Intramuscular DNA vaccination induced CTL against both Gag and Env proteins. A detailed analysis of epitopes recognized by CTL generated in mice inoculated with the whole virus and with the Gag-expressing plasmid confirmed the presence of an immunodominant peptide in the leader sequence of Gag protein (Gag85–93, CCLCLTVFL) that is identical to that described in B6 mice immunized with Friend MuLV-induced leukemia cells. Moreover, CTL generated by immunization with the Env-encoding plasmid recognized a subdominant Env peptide (Env189–196, SSWDFITV), originally described in the B6.CH-2bm13 mutant strain. B6 mice immunized with the Gag-expressing plasmid were fully protected against a lethal tumor challenge with M-MuLV-transformed MBL-2 leukemia cells, while vaccination with the Env-expressing plasmid resulted in rejection of the tumor in 44% of the mice and in increased survival of an additional 17% of the animals. Taken together, these results indicate the existence of a hierarchy in the capacity of different structural viral proteins to induce a protective immune response against retrovirus-induced tumors.
Analysis of Intersubject Variations in Intracochlear and Middle Ear Surface Anatomy for Cochlear Implantation

Hypothesis We hypothesize that surface landmarks surrounding the round window typically used to guide electrode placement during cochlear implantation (CI) exhibit substantial variability with respect to intracochlear anatomy. Background Recent publications suggest that both atraumatic electrode insertion and electrode location within the scala tympani can affect auditory performance after CI. However, current techniques for electrode insertion rely on surface landmarks alone for navigation, without actual visualization of intracochlear structures other than what can be seen through a surgically created cochleostomy. In this study, we quantify how well the position of intracochlear anatomy is predicted by surface landmarks surrounding the round window. Methods Structures representing middle ear surface and intracochlear anatomy were reconstructed in &mgr;CT scans of 10 temporal bone specimens. These structures were then reoriented into a normalized coordinate system to facilitate measurement of inter-subject anatomical shape variations. Results Only minor intersubject variations were detected for intracochlear anatomy (maximum deviation, 0.71 mm; standard deviation, 0.21 mm), with greatest differences existing near the hook and apex. Larger intersubject variations in intracochlear structures were detected when considered relative to surface landmarks surrounding the round window (maximum deviation, 0.83 mm; standard deviation, 0.54 mm). Conclusion The cochlea and its scala exhibit considerable variability in relation to middle ear surface landmarks. While support for more precise, atraumatic CI electrode insertion techniques is growing in the otologic community, landmark guided insertion techniques have limited precision. Refining the CI insertion process may require the development of image-guidance systems for use in otologic surgery.
Growth of Cowdria ruminantium, the Causative Agent of Heartwater, in a Tick Cell Line

ABSTRACT The tick-borne rickettsia Cowdria ruminantium has been propagated continuously for over 500 days in the Ixodes scapularis tick cell line IDE8 by using the Gardel isolate from bovine endothelial cells as an inoculum. Infection of the tick cells was confirmed by PCR, karyotyping, electron microscopy, and reinfection of bovine cells.
Adaptive functioning and psychiatric symptoms in adolescents with borderline personality disorder.

OBJECTIVE To examine adaptive functioning and psychopathology in adolescents with DSM-IV borderline personality disorder. METHOD 177 psychiatric outpatients (derived from 2 samples collected between March 1998 and July 1999 and between November 2000 and September 2002) aged 15 to 18 years were assessed using a structured interview for personality disorder diagnoses. Three groups, namely (1) those with a borderline personality disorder, (2) those with a personality disorder other than borderline personality disorder ("other personality disorder"), and (3) those without any personality disorder ("no personality disorder"), were compared on measures of psychiatric symptoms and psychosocial functioning. Primary outcome measures were Axis I diagnoses, Youth Self-Report, Young Adult Self-Report, Health of the Nation Outcome Scales for Children and Adolescents, Social and Occupational Functioning Assessment Scale, and sociodemographic variables. RESULTS The borderline personality disorder group (N = 46) had the most severe psychiatric symptoms and functional impairment across a broad range of domains, followed by the other personality disorder (N = 88) and no personality disorder (N = 43) groups, respectively. Borderline personality disorder was a significant predictor over and above Axis I disorders and other personality disorder diagnoses for psychopathology, general functioning, peer relationships, self-care, and family and relationship functioning. CONCLUSIONS The borderline personality disorder diagnosis should not be ignored or substituted by Axis I diagnoses in adolescent clinical practice, and early intervention strategies need to be developed for this disorder.
Prospective study of restless legs syndrome and mortality among men

Objective: To prospectively examine whether men with restless legs syndrome (RLS) had an increased risk of mortality. Method: This was a prospective cohort study of 18,425 US men free of diabetes, arthritis, and renal failure in the Health Professionals Follow-up Study (HPFS). In 2002, RLS was assessed using a set of standardized questions. Deaths were identified from state vital statistics records, the National Death Index, family reports, and the postal system. Results: During 8 years of follow-up (2002–2010), we documented 2,765 deaths. In an age-adjusted model, RLS was associated with a 39% increased risk of mortality (hazard ratio [HR] = 1.39; 95% confidence interval [CI] 1.19–1.62; p < 0.0001). The association between RLS and mortality was slightly attenuated after further adjustment for body mass index, lifestyle factors, chronic conditions, sleep duration, and other sleep-related disorders (adjusted HR = 1.30; 95% CI 1.11–1.52; p = 0.003). When we further excluded those with major chronic conditions (e.g., cancer, high blood pressure, cardiovascular disease, and other comorbidities), the adjusted HR was 1.92 (95% CI 1.03–3.56; p = 0.04). The interactions between RLS and other risk factors (older age, overweight, short sleep duration, smoking, low physical activity, and unhealthy diet) in relation to total mortality risk were not significant (p for interaction >0.2 for all). Conclusion: We observed that men with RLS had a higher overall mortality and this association was independent of known risk factors. The increased mortality in RLS was more frequently associated with respiratory disease, endocrine disease, nutritional/metabolic disease, and immunologic disorders. Future research exploring the pathophysiologic relationship between these disorders and RLS is warranted.
Cancer with diabetes: prevalence, metabolic control, and survival in an academic oncology practice.

OBJECTIVE To determine the prevalence of diabetes mellitus, glycemic control, and impact of diabetes on overall survival in an academic oncology practice. METHODS Data on cancer patients (1999 to 2008) were retrieved from the institutional cancer registry and linked to electronic files to obtain diabetes status and hemoglobin A1c (A1C) values within the first 6 months of cancer diagnosis. Overall survival by cancer type with and without diabetes was compared using Cox regression. RESULTS Excluding skin and hematologic malignancies, 15,951 cancer cases were identified. Overall diabetes prevalence was 6.8% (n = 1,090), declining over time (P<0.001). Diabetes was common among patients with pancreatic (9.8% [61 of 624]), colorectal (7.7% [89 of 1,151]), or bladder cancers (7.6% [68 of 899]). Patients with diabetes were older (mean age, 70 versus 66 years; P<0.001) and more likely to be male (66.3% [723 of 1,090] versus 60.2% [8,949 of 14,858]; P<0.001). The mean A1C among diabetic cancer patients was 6.8% and did not differ across cancer types (P = 0.80). Only 58.6% (331 of 565) of diabetic cancer patients had all A1C <7.0% during the first 6 months following cancer diagnosis. Pancreatic cancer patients with coexisting diabetes had better overall survival than pancreatic cancer patients without diabetes (hazard ratio, 0.60; 95% confidence interval 0.44 to 0.80; P<0.001). Conversely, diabetic prostate cancer patients had worse overall survival than prostate cancer patients without diabetes (hazard ratio, 1.36; 95% confidence interval 1.05 to 1.76; P = 0.02). CONCLUSION In this academic oncology practice, diabetes was common, glycemic control often was suboptimal, and survival varied by cancer type. Additional study is needed to optimize glucose management and investigate mechanisms underlying age, sex, and survival differences.
Determining optimal follow‐up in the management of human papillomavirus‐positive oropharyngeal cancer

Determining the optimal follow‐up for patients can help maximize the use of health care resources. This is particularly true in a growing epidemic such as human papillomavirus‐positive oropharyngeal squamous cell carcinoma (HPV+OPSCC). The objective of the current study was to evaluate time to disease recurrence or late toxicity in this cohort of patients to optimize patient management.
Targeting mitochondrially mediated plasticity to develop improved therapeutics for bipolar disorder

Introduction: Bipolar disorder (BPD) is a severe illness with few treatments available. Understanding BPD pathophysiology and identifying potential relevant targets could prove useful for developing new treatments. Remarkably, subtle impairments of mitochondrial function may play an important role in BPD pathophysiology. Areas covered: This article focuses on human studies and reviews evidence of mitochondrial dysfunction in BPD as a promising target for the development of new, improved treatments. Mitochondria are crucial for energy production, generated mainly through the electron transport chain (ETC) and play an important role in regulating apoptosis and calcium (Ca2+) signaling as well as synaptic plasticity. Mitochondria move throughout the neurons to provide energy for intracellular signaling. Studies showed polymorphisms of mitochondria-related genes as risk factors for BPD. Postmortem studies in BPD also show decreased ETC activity/expression and increased nitrosative and oxidative stress (OxS) in patient brains. BPD has been also associated with increased OxS, Ca2+ dysregulation and increased proapoptotic signaling in peripheral blood. Neuroimaging studies consistently show decreased energy levels and pH in brains of BPD patients. Expert opinion: Targeting mitochondrial function, and their role in energy metabolism, synaptic plasticity and cell survival, may be an important avenue for development of new mood-stabilizing agents.
Person-centred cochlear implant care: Assessing the need for clinic intervention in adults with cochlear implants using a dual approach of an online speech recognition test and a questionnaire

Objectives: To evaluate the feasibility of adults with cochlear implants using an online speech recognition test and questionnaire at home to assess whether they need to come to the clinic or not. Methods: A prospective single-centre feasibility study evaluating • An online speech recognition test (digit triplet test (DTT)). • A long-term follow-up questionnaire to assess aspects that a clinician would ask in a face-to-face appointment. • A satisfaction questionnaire to assess patient perception of remote speech recognition testing. • Seventeen people using cochlear implants aged from 34 to 84 years took part. Results: • The majority of adults were able and willing to use tools at home to assess if they need to come to the centre. • The DTT speech reception threshold was repeatable on three occasions within 3 weeks. • The majority of adults felt positive about testing their own hearing using the DTT at home. However, only a minority (two out of 17) felt they preferred remote testing to clinic testing (the majority was undecided). Conclusion: The concept of a dual approach of online speech recognition test and questionnaire both done at home has potential to identify which adults with cochlear implants require clinic intervention, although sensitivity and specificity measures are unknown. A clinic visit remains the gold standard of care, but remote care may supplement traditional care pathways.