Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel testis-stimulating factor in familial male precocious puberty.

BACKGROUND Familial male precocious puberty is a gonadotropin-independent form of precocious puberty that occurs only in males. The cause of the disorder is unknown. To examine the hypothesis that the plasma of boys with familial male precocious puberty contains a novel stimulator of testicular testosterone production, we developed a bioassay using adult male cynomolgus monkeys. METHODS We collected plasma from 12 boys with familial male precocious puberty, 7 normal prepubertal boys of similar ages and with similar plasma gonadotropin levels, and 1 boy with hypogonadotropic hypogonadism and infused it into the testicular artery of adult male cynomolgus monkeys that had been pretreated with gonadotropin-releasing-hormone antagonist to inhibit the endogenous secretion of gonadotropins. Testicular venous effluent was collected at 15-minute intervals for 3 or 5 hours for the measurement of testosterone. RESULTS The mean (+/- SE) peak testosterone response, as compared with base line, was significantly greater in the monkeys infused with plasma from the 12 boys with familial male precocious puberty than in the monkeys infused with plasma from the 7 normal prepubertal boys and the boy with hypogonadotropic hypogonadism (385 +/- 51 vs. 184 +/- 25 percent, P less than 0.005) in the three-hour studies. Plasma from 92 percent of the boys with familial male precocious puberty and 12.5 percent of the normal prepubertal boys stimulated a response greater than 195 percent of base-line values. In the animals studied for five hours after receiving a second dose of antagonist, the mean peak testosterone response, as compared with base line, was significantly greater in the monkeys infused with plasma from three boys with familial male precocious puberty than in the monkeys infused with plasma from three normal prepubertal boys (363 +/- 81 vs. 115 +/- 6 percent, P less than 0.01). The mean area under the testosterone-response curve was significantly larger in the monkeys infused with plasma from the boys with familial male precocious puberty in the five-hour studies (154 +/- 34 vs. -58 +/- 10 percent, P less than 0.005), but not in the three-hour studies. CONCLUSIONS These findings support the presence of a circulating testis-stimulating factor in the plasma of boys with familial male precocious puberty. The production of such a factor would explain the biologic nature of the disorder.
Chronic Traumatic Encephalopathy and Alienation Induced Suicide: A Christian Personalism Perspective

Suicide among athletes and military personnel diagnosed with chronic traumatic encephalopathy (CTE) was an international concern (Korngold, Farrell, & Fozdar, 2013; Wortzel, Shura, & Brenner, 2013; Kristof, 2012; Meterko, et al., 2012; Omalu, et al., 2011). Omalu (2013) and Tanner (2010) observed a correlation between brain injury and perceived social alienation resulting in injuries. It is suggested that, due to the unique social bonds created within each group, athletes and military personnel formed individual identities based on the dynamics of the group. Current psychotherapeutic approaches had limited effectiveness dealing with suicidal tendencies. Utilizing Seeman's (1959, 1967, 1971, 1975, and 1983) five alienation factors as redefined under a Christian Neo-Thomistic Personalist approach (Schmidt, 2011, 2012) could provide insight into why CTE-related suicide occurred and thereby initiate discussion regarding adjustments to social and cultural aspects of faith in treatment programs.
Magnetic resonance imaging of angiographically occult runoff vessels in peripheral arterial occlusive disease.

BACKGROUND Bypass grafting to arteries of the lower leg has become standard surgical management of advanced peripheral vascular disease. Its success depends on identifying suitable distal vessels. Preoperative preparation includes imaging of the arteries of the lower leg, usually by conventional contrast arteriography. An alternative procedure, magnetic resonance (MR) angiography, has been successfully employed in patients with various cardiovascular diseases, but its possible value in patients with peripheral vascular disease has received little attention. METHODS We used both conventional and MR angiography in preoperative studies of the lower-leg vessels of 23 patients (25 legs) with peripheral arteriosclerosis and arterial insufficiency, and developed independent therapeutic plans based on the information provided by each technique. When the plans differed, the interventional procedure judged more likely to save the limb was performed. The findings of conventional and MR angiography were verified by intraoperative arteriography, postinterventional arteriography, or direct operative exploration. RESULTS MR angiography detected all vessels identified by conventional angiography, whereas conventional arteriography failed to detect 22 percent of the runoff vessels identified by MR angiography. The detection by MR angiography of vessels not identified by conventional angiography altered the surgical management of the disorders of four patients (17 percent) and guided successful bypass procedures. CONCLUSIONS MR angiography is a noninvasive technique with greater sensitivity than conventional contrast arteriography for detecting distal runoff vessels in patients with peripheral arterial occlusive disease.
Traditional NSAIDs and coxibs: is one better than the other?

This editorial refers to ‘Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib. The Standard care versus Celecoxib Outcome Trial (SCOT)’, by T.M. MacDonald et al. , doi: 10.1093/eurheartj/ehw387. Pain from arthritis is a common symptom for which patients often seek medical attention. In fact, osteoarthritis (OA) is the most common joint disorder in the USA and affects 10% of men and 13% ofwomen aged 60 years or older,1 and the prevalence rates are comparable in Europe.2 Current strategies for managing arthritis pain include analgesics such as acetominophen and aspirin, narcotic analgesics (opioids), traditional non-steroidal anti-inflammatory drugs (NSAIDs), and selective cyclooxygenase 2 inhibitors (coxibs). The global pain market in 2009 was valued at >US$50 billion, including US$27 billion in the seven major economies with ∼35% of the sales …
A defective visual pathway in children with reading disability.

BACKGROUND The possibility that reading disability in children is associated with visual problems is in dispute. We sought to test the existence of this association by using electrophysiologic techniques to measure the processing of visual information in the magnicellular and parvicellular visual pathways of the brain. METHODS Visual evoked potentials were measured with scalp electrodes in children 8 to 11 years old who were normal readers and in those with reading disability. The potentials were measured for targets with low (0.5 cycle per degree of visual angle) and high (4.5 cycles per degree) spatial frequency, surrounded by either a steady background or a uniform-field flickering 12 times per second. A flickering field normally reduces the amplitude and increases the latency of a transient potential evoked by a low-spatial-frequency target, which preferentially excites the magnicellular visual pathway, but has little effect on the response to a high-spatial-frequency target. RESULTS With a steady background, the latencies of the early components (N1 and P1) of the visual evoked potentials were longer in the reading-disabled children than in the normal readers when the low-spatial-frequency target was used, but not when the high-spatial-frequency target was used. In normal readers, the flickering background increased the latency and reduced the amplitude of the early components, whereas in the reading-disabled children only the amplitude was affected. No differences were observed in either group with the high-spatial-frequency target. CONCLUSIONS The pattern of results suggests that the response of the magnicellular visual pathway is slowed in reading-disabled children, who do not, however, have a general slowing of the visual response. The possibility that there is a cause-and-effect relation between these findings and reading disability will require further study.
The distribution of FV Leiden gene mutation in patients with obstructive sleep apnea

Abstract Aim . We aimed to investigate whether this polymorphism has any effects on the development of the differences in the progression of the OSAS patients. Methods . The patient group was selected from patients admitted to the our Sleep Laboratory. Total 122 subjects, 44 OSAS patients (only), 32 OSAS patients with cardio vascular diseases (CVD) and 46 controls, were enrolled in the study. The control group consisted of healthy volunteers who had no symptoms of OSAS and scored 0 on the Epworth sleepiness scale. In order to determine gene mutations, DNA isolation was performed from peripheral blood samples. Results . While mean weight and BMI were significantly different, no significant differences were found between patient and control groups in terms of FV Leiden allele distributions. Conclusion . FV Leiden mutation does not affect progression in patients with OSAS Keywords : Obstructive sleep apnea, polymorphism, mutation Ozet Amac . Bu calismada OSAS hastalarinin progresyonunda farkliliklar olusmasinda FV Leiden polimorfizminin herhangi bir etkisi olup olmadigini arastirmayi amacladik. Yontem . Hasta grubu uyku laboratuvarimiza basvuran hastalardan secildi. Toplam 122 kisi ( 44 OSAS hastasi (yalnizca), 32 kardiyovaskuler hastaligi (KVH) olan OSAS hastasi ve 46 kontrol grubu) calismamiza katildi. Kontrol grubu OSAS semptomlari bulunmayan, Epworth uykusuzluk skalasi 0 olan saglikli gonululerden olusturuldu. Gen mutasyonlarini belirlemek icin DNA izolasyonu periferik kandan yapildi. Bulgular . BMI ve agirlik ortalamalari onemli oranda farkliyken, FV Leiden allel dagilimlari acisindan hasta ve kontrol gruplari arasinda onemli bir farklilik bulunamadi. Sonuc . FV Leiden mutasyonu OSAS hastalarinda progresyonu etkilememektedir Anahtar sozcukler : Obstruktif uyku apnesi, polimorfizm, mutasyon
Plasma 5α-Reduced Androgens in Men and Hirsute Women: Role of Adrenals and Gonads

Abstract The contributions of the adrenal glands and gonads to the plasma content of the 5α-reduced androgens [androsterone, 3α-androstanediol (3α-diol), and 5α-dihydrotestosterone (DHT)] and two of their precursors (androstenedione and testosterone) were evaluated in men and women. Androsterone values were markedly reduced and 3α-diol values were moderately reduced (P < 0.003 and P < 0.03, respectively) in men with Addison's disease compared to normal men. Metyrapone administration to women produced supranormal concentrations of androsterone (P < 0.02), 3α-diol (P < 0.003), and androstenedione (P < 0.003), whereas DHT and testosterone values were not elevated significantly. Oral contraceptives administered for several weeks to six normal women resulted in subnormal plasma levels of androsterone (P < 0.004) and androstenedione (P < 0.04). All five androgens were elevated significantly in thirty premenopausal women with idiopathic hirsutism and reduced significantly (P < 0.05–0.001) by 3 weeks of therapy w.
Effect of telephone-administered vs face-to-face cognitive behavioral therapy on adherence to therapy and depression outcomes among primary care patients: a randomized trial.

CONTEXT Primary care is the most common site for the treatment of depression. Most depressed patients prefer psychotherapy over antidepressant medications, but access barriers are believed to prevent engagement in and completion of treatment. The telephone has been investigated as a treatment delivery medium to overcome access barriers, but little is known about its efficacy compared with face-to-face treatment delivery. OBJECTIVE To examine whether telephone-administered cognitive behavioral therapy (T-CBT) reduces attrition and is not inferior to face-to-face CBT in treating depression among primary care patients. DESIGN, SETTING, AND PARTICIPANTS A randomized controlled trial of 325 Chicago-area primary care patients with major depressive disorder, recruited from November 2007 to December 2010. INTERVENTIONS Eighteen sessions of T-CBT or face-to-face CBT. MAIN OUTCOME MEASURES The primary outcome was attrition (completion vs noncompletion) at posttreatment (week 18). Secondary outcomes included masked interviewer-rated depression with the Hamilton Depression Rating Scale (Ham-D) and self-reported depression with the Patient Health Questionnaire-9 (PHQ-9). RESULTS Significantly fewer participants discontinued T-CBT (n = 34; 20.9%) compared with face-to-face CBT (n = 53; 32.7%; P = .02). Patients showed significant improvement in depression across both treatments (P < .001). There were no significant treatment differences at posttreatment between T-CBT and face-to-face CBT on the Ham-D (P = .22) or the PHQ-9 (P = .89). The intention-to-treat posttreatment effect size on the Ham-D was d = 0.14 (90% CI, -0.05 to 0.33), and for the PHQ-9 it was d = -0.02 (90% CI, -0.20 to 0.17). Both results were within the inferiority margin of d = 0.41, indicating that T-CBT was not inferior to face-to-face CBT. Although participants remained significantly less depressed at 6-month follow-up relative to baseline (P < .001), participants receiving face-to-face CBT were significantly less depressed than those receiving T-CBT on the Ham-D (difference, 2.91; 95% CI, 1.20-4.63; P < .001) and the PHQ-9 (difference, 2.12; 95% CI, 0.68-3.56; P = .004). CONCLUSIONS Among primary care patients with depression, providing CBT over the telephone compared with face-to-face resulted in lower attrition and close to equivalent improvement in depression at posttreatment. At 6-month follow-up, patients remained less depressed relative to baseline; however, those receiving face-to-face CBT were less depressed than those receiving T-CBT. These results indicate that T-CBT improves adherence compared with face-to-face delivery, but at the cost of some increased risk of poorer maintenance of gains after treatment cessation. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00498706.
Actualización sobre el síndrome de QT largo congénito

El sindrome de QT largo congenito se caracteriza por la prolongacion del intervalo QT y anomalias de la onda T del electrocardiograma, asociados con una predisposicion para la aparicion de arritmias ventriculares malignas (torsion de puntas), sincope, fibrilacion ventricular y muerte subita (MS) cardiaca. El entrenamiento para realizar las mediciones, la variabilidad de la penetracion y de las mutaciones, los solapamientos, las formas mixtas y los sindromes de superposicion, pueden dificultar el diagnostico y con ello, la conducta terapeutica. Esta revision pretende actualizar aspectos esenciales relacionados con el diagnostico, bases geneticas, mecanismos fisiopatologicos y moleculares, asi como conducta terapeutica, de esta compleja canalopatia. (AU) The congenital long QT syndrome is characterized by a prolongation of the QT interval and T wave abnormalities on the ECG, associated to a predisposition for the appearance of malignant ventricular arrhythmias (torsade de pointes), syncope, ventricular fibrillation and sudden cardiac death (SCD). Training in taking the measurements, penetrance and mutation variability, overlaps, mixed forms and overlap syndrome may all hamper diagnostic and therapeutic management. The present review intends to update essential aspects related to the diagnosis, genetic bases, physiopathological and molecular mechanisms, and therapeutic management of this complex channelopathy. (AU)
Corrección de la anemia en pacientes diabéticos con enfermedad renal crónica sin tratamiento sustitutivo: enseñanzas del estudio TREAT

Correspondencia: ÁLM de Francisco Servicio de Nefrología. Hospital Universitario Valdecilla. Santander. martinal@unican.es Uno de los avances terapéuticos más importantes para el control de la anemia del paciente con enfermedad renal crónica (ERC) fue la síntesis de la eritopoyetina humana recombinante (rHuEPO) en 1985. Para quienes en aquellos momentos tratábamos a pacientes en diálisis con hemoglobinas de 5 a 7 g/dl únicamente nos quedaba la posibilidad de realizar múltiples transfusiones que no sólo aumentaban la posibilidad de infecciones virales sino que también sensibilizaban a los pacientes ante un eventual trasplante renal o producían sobrecarga de hierro. Los resultados de los ensayos clínicos fueron tan claros que la rHuEPO fue aceptada por las agencias regulatorias sanitarias como agente terapéutico en 1988, sólo 3 años después de su descubrimiento.
A massive outbreak in Milwaukee of cryptosporidium infection transmitted through the public water supply.

BACKGROUND Early in the spring of 1993 there was a widespread outbreak of acute watery diarrhea among the residents of Milwaukee. METHODS We investigated the two Milwaukee water-treatment plants, gathered data from clinical laboratories on the results of tests for enteric pathogens, and examined ice made during the time of the outbreak for cryptosporidium oocysts. We surveyed residents with confirmed cryptosporidium infection and a sample of those with acute watery diarrhea consistent with cryptosporidium infection. To estimate the magnitude of the outbreak, we also conducted a survey using randomly selected telephone numbers in Milwaukee and four surrounding counties. RESULTS There were marked increases in the turbidity of treated water at the city's southern water-treatment plant from March 23 until April 9, when the plant was shut down. Cryptosporidium oocysts were identified in water from ice made in southern Milwaukee during these weeks. The rates of isolation of other enteric pathogens remained stable, but there was more than a 100-fold increase in the rate of isolation of cryptosporidium. The median duration of illness was 9 days (range, 1 to 55). The median maximal number of stools per day was 12 (range, 1 to 90). Among 285 people surveyed who had laboratory-confirmed cryptosporidiosis, the clinical manifestations included watery diarrhea (in 93 percent), abdominal cramps (in 84 percent), fever (in 57 percent), and vomiting (in 48 percent). We estimate that 403,000 people had watery diarrhea attributable to this outbreak. CONCLUSIONS This massive outbreak of watery diarrhea was caused by cryptosporidium oocysts that passed through the filtration system of one of the city's water-treatment plants. Water-quality standards and the testing of patients for cryptosporidium were not adequate to detect this outbreak.
A longitudinal study of human immunodeficiency virus transmission by heterosexual partners. European Study Group on Heterosexual Transmission of HIV.

BACKGROUND Worldwide, the predominant mode of human immunodeficiency virus (HIV) transmission is heterosexual intercourse, but the risk of heterosexual transmission and the effectiveness of measures to prevent it are not well defined. METHODS We conducted a prospective study of HIV-negative subjects whose only risk of HIV infection was a stable heterosexual relationship with an HIV-infected partner. Every six months the subjects were interviewed, tested for HIV, and counseled about safe sexual practices. RESULTS A total of 304 HIV-negative subjects (196 women and 108 men) were followed for an average of 20 months. During the study, 130 couples (42.8 percent) ended their sexual relationships, most often because of the HIV-infected partner's illness or death. Of the 256 couples who continued to have sexual relations for more than three months after enrollment in the study, only 124 (48.4 percent) used condoms consistently for vaginal and anal intercourse. Among these couples, none of the seronegative partners became infected with HIV, despite a total of about 15,000 episodes of intercourse. Among the 121 couples who used condoms inconsistently, the rate of seroconversion was 4.8 per 100 person-years (95 percent confidence interval, 2.5 to 8.4). Eleven couples refused to answer questions about condom use. The risk of transmission increased with advanced stages of HIV infection in the index partners (P < 0.02) and with genital infection in the HIV-negative partners (P < 0.04). Withdrawal to avoid ejaculation in the vagina had a protective effect in uninfected women (P < 0.02). CONCLUSIONS Consistent use of condoms for heterosexual intercourse is highly effective in preventing the transmission of HIV. Among couples not using condoms regularly, the risk of HIV transmission varies widely.
Prognostic assessment of stable coronary artery disease as determined by coronary computed tomography angiography: a Danish multicentre cohort study

Aims To examine the 3.5 year prognosis of stable coronary artery disease (CAD) as assessed by coronary computed tomography angiography (CCTA) in real-world clinical practice, overall and within subgroups of patients according to age, sex, and comorbidity. Methods and results This cohort study included 16,949 patients (median age 57 years; 57% women) with new-onset symptoms suggestive of CAD, who underwent CCTA between January 2008 and December 2012. The endpoint was a composite of late coronary revascularization procedure >90 days after CCTA, myocardial infarction, and all-cause death. The Kaplan–Meier estimator was used to compute 91 day to 3.5 year risk according to the CAD severity. Comparisons between patients with and without CAD were based on Cox-regression adjusted for age, sex, comorbidity, cardiovascular risk factors, concomitant cardiac medications, and post-CCTA treatment within 90 days. The composite endpoint occurred in 486 patients. Risk of the composite endpoint was 1.5% for patients without CAD, 6.8% for obstructive CAD, and 15% for three-vessel/left main disease. Compared with patients without CAD, higher relative risk of the composite endpoint was observed for non-obstructive CAD [hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.01–1.63], obstructive one-vessel CAD (HR: 1.83; 95% CI: 1.37–2.44), two-vessel CAD (HR: 2.97; 95% CI: 2.09–4.22), and three-vessel/left main CAD (HR: 4.41; 95% CI :2.90–6.69). The results were consistent in strata of age, sex, and comorbidity. Conclusion Coronary artery disease determined by CCTA in real-world practice predicts the 3.5 year composite risk of late revascularization, myocardial infarction, and all-cause death across different groups of age, sex, or comorbidity burden.