Miracle-dz/UniFAR-FTUs huggingface dataset:
Dysfunction of the beta- and alpha-adrenergic systems in a model of congestive heart failure. The pacing-overdrive dog.

The functional integrity of the beta- and alpha-adrenergic stimulatory pathways in a rapid ventricular pacing model of congestive heart failure in dogs was investigated; normal dogs served as controls. Total beta-adrenergic receptor density was 35% lower (p less than 0.01) in the pacing-overdrive dogs, and the beta-adrenergic receptor-mediated stimulation of adenylate cyclase (Vmax) was found to be 68% and 72% lower (p less than 0.01) in the left and right ventricles of the paced dogs. In addition, the basal adenylate cyclase activity was found to be 56% and 68% lower (p less than 0.01) in the left and right ventricles of the failing heart. Similarly, the Vmax of 5'-guanylylimidodiphosphate (GppNHp) and forskolin stimulation of adenylate cyclase activity was significantly lower, 70% and 55%, respectively (p less than 0.01), in both ventricles of the paced dogs. However, although the concentration yielding half-maximal velocity for beta-agonist and GppNHp stimulation of adenylate cyclase was similar in both groups, that for forskolin stimulation of the enzyme was significantly increased (p less than 0.01). Pertussis toxin-mediated ADP-ribosylation of membranes from control and failing hearts revealed a significant decrease in the inhibitory guanine nucleotide binding protein content (48 +/- 9%, p less than 0.01) in the hearts of the paced dogs. Moreover, although the pertussis toxin treatment increased the basal and the forskolin-stimulated adenylate cyclase activity in both normal and failing heart membranes, the adenylate cyclase activity remained significantly depressed in the failing heart after pertussis toxin treatment (p less than 0.01). Consistent with the depressed adenylate cyclase activity, mechanical studies on isolated papillary muscles and trabeculae revealed a decrease in baseline total tension (from 7.0 +/- 0.7 to 3.8 +/- 0.4 g/mm2, p less than 0.01) and dT/dt (from 26 +/- 8 to 13 +/- 1 g/mm2/sec, p less than 0.01) in the pacing-overdrive model. Tension generation and dT/dt observed in the paced dogs in response to increasing concentrations of forskolin demonstrated a rightward shift in the dose-response curve and a decrease in maximal forskolin stimulation (p less than 0.01). Similarly, maximal tension and dT/dt in the presence of isoproterenol was significantly lower than in the normal dogs (p less than 0.01). The decrease in beta-adrenergic responsiveness was accompanied by a decrease and rightward shift in alpha 1-adrenergic responsiveness (increase in tension was 1.1 +/- 0.1 g/mm2 in paced dogs versus 2.1 +/- 0.1 g/mm2 in controls, p less than 0.01). (ABSTRACT TRUNCATED AT 400 WORDS)
Through the Looking Glass at Early-Life Exposures and Breast Cancer Risk

The global increase in the proportion of women diagnosed with breast cancer, inadequate access to screening and high cost of treatment for breast cancer argue strongly for a greater focus on preventive strategies. But at what age is it appropriate to begin targeting preventive approaches? The recognized role of perinatal nutrition in neurologic development and the relation of maternal nutritional status to birthweight and subsequent risk of hypertension, diabetes, and cardiovascular disease identify pregnancy and early childhood as potential phases for prevention. This review examines indicators of hormonal and nutritional exposures in early life and breast cancer risk through the lens of the life course paradigm integrated with maternal and child health research and methodology. Compared to women who were normal birthweight (2500–3999 g), women who weighed ≥ 4,000 g at birth have a 20 percent to 5-fold increased risk of premenopausal breast cancer. Women born preterm and likely to be small- or large-for-date also have an increased risk. Birth length is directly associated with risk and has a larger magnitude of effect than birthweight. Prior preeclamptics and their daughters have a lower risk of breast cancer than comparable normotensives. An association between infant feeding practices and breast cancer is unclear without improved exposure assessment and analysis. Rapid childhood and pubertal linear growth increases breast cancer risk, while greater body fat over the same periods reduces risk. Growth data thus far have not been calculated in Z-scores from reference growth curves for comparison across studies. Events and secular trends influencing birth cohorts may not be adequately addressed, thereby limiting the interpretation and implications of the findings. Research in nonhuman primates may help uncover underlying mechanisms.
HIV controllers: a genetically determined or inducible phenotype?

Less than 0.5% of human immunodeficiency virus‐1 (HIV‐1)‐infected patients maintain viral load below the threshold of detection by conventional assays for many years without antiretroviral therapy. These patients are known as HIV controllers (HICs) and offer a unique opportunity to explore and unravel efficient mechanisms of defense against HIV. An intense research effort has led to identifying viral and host factors that contribute to the control of viral replication. Although the host factors appear to be the primary determinants for HIV control, different genomic, transcriptomic, and immunological profiles have been described in HICs. This supports the existence of different mechanisms of control. We review here the most significant data in the field, including our own work, in the light of a crucial question: whether the ability to achieve and maintain the control of HIV replication is linked to genetic or immunological features specific to HIC or can be induced by vaccine or therapeutic approaches in the general population.
Analgesic efficacy of ultrasound-guided transversus abdominis plane block in patients undergoing open appendicectomy.

BACKGROUND Transversus abdominis plane (TAP) block is a new regional anaesthetic technique that blocks abdominal neural afferents by introducing local anaesthetic into the neuro-fascial plane between the internal oblique and the transversus abdominis muscles. We evaluated its analgesic efficacy in patients undergoing open appendicectomy in a randomized controlled double-blinded clinical trial. METHODS Fifty-two adult patients undergoing open appendicectomy were randomized to undergo standard care (n=26) or to undergo a right-sided TAP block with bupivacaine (n=26). In addition, all patients received patient-controlled i.v. morphine analgesia, regular acetaminophen, and non-steroidal anti-inflammatory drug, as required, in the postoperative period. All patients received standard anaesthetic, and after induction of anaesthesia, the TAP group received an ultrasound-guided unilateral TAP block. Each patient was assessed after operation by a blinded investigator at 30 min and 24 h after surgery. RESULTS Ultrasound-guided TAP block significantly reduced postoperative morphine consumption in the first 24 h [mean (sd) 28 (18) vs 50 (19) mg, P<0.002]. Postoperative visual analogue scale pain scores were also reduced in the TAP block group soon after surgery [median (IQR) 4.5 (3-5.3) vs 8.5 (7.5-10), P<0.001] and at 24 h [5.2 (4-6.2) vs 8 (7-8.5), P<0.001]. There were no complications attributable to the TAP block. CONCLUSIONS Ultrasound-guided TAP block holds considerable promise as a part of a balanced postoperative analgesic regimen for patients undergoing open appendicectomy.
A preliminary experimental study on the cardiac toxicity of glutamate and the role of &agr;‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor in rats

Background Monosodium L‐glutamate (MSG) is a food flavour enhancer and its potential harmfulness to the heart remains controversial. We investigated whether MSG could induce cardiac arrhythmias and apoptosis via the &agr;‐amino‐3‐hydro×y‐5‐methyl‐4‐iso×azolepropionic acid (AMPA) receptor. Methods Myocardial infarction (MI) was created by ligating the coronary artery and ventricular arrhythmias were monitored by electrocardiogram in the rat in vivo. Neonatal rat cardiomyocytes were isolated and cultured. Cell viability was estimated by 3‐(4,5)‐dimethylthiahiazo(‐z‐yl)‐3,5‐di‐phenytetrazoliumromide (MTT) assay. Calcium mobilization was monitored by confocal microscopy. Cardiomyocyte apoptosis was evaluated by acridine orange staining, flow cytometry, DNA laddering, reverse transcription‐polymerase chain reaction (RT‐PCR) and Western blotting. Results MSG (i.v.) decreased the heart rate at 0.5 g/kg and serious bradycardia at 1.5 g/kg, but could not induce ventricular tachyarrhythmias in normal rats in vivo. In rats with acute MI in vivo, however, MSG (1.5 g/kg, i.v.) induced ventricular tachyarrhythmias and these arrhythmias could be prevented by blocking the AMPA and N‐methyl‐d‐aspartate (NMDA) receptors. Selectively activating the AMPA or NMDA receptor induced ventricular tachyarrhythmias in MI rats. At the cellular level, AMPA induced calcium mobilization, oxidative stress, mitochondrial dysfunction and apoptosis in cultured cardiomyocytes, especially when the AMPA receptor desensitization were blocked by cyclothiazide. The above toxic cellular effects of AMPA were abolished by AMPA receptor blockade or by H2O2 scavengers. Conclusions MSG induces bradycardia in normal rats, but triggers lethal tachyarrhythmias in myocardial infarcted rats probably by hindering AMPA receptors. AMPA receptor overstimulation also induces cardiomyocyte apoptosis, which may facilitate arrhythmia.
Intraarticular, epidural, and intravenous analgesia after total knee arthroplasty

Background: After total knee arthroplasty, patients regularly suffer from severe pain. It is unclear whether epidural or systemic pain therapy is superior in terms of postoperative pain relief, patients’ comfort and side effects. A new therapeutic approach, intraarticular opioids, has been suggested with the detection of opioid receptors in inflamed tissue. This method has proven suitable for clinical use in small operations (e.g. knee arthroscopy). In this study, we compared epidural analgesia and intraarticular application of morphine plus “on‐demand” intravenous analgesia to “on‐demand” intravenous analgesia alone.
Patterns of maternal distress among children with cancer and their association with child emotional and somatic distress.

OBJECTIVE To identify patterns of distress among mothers of children with cancer over the initial 6 months of treatment and to examine these patterns as predictors of child somatic and emotional distress. METHOD Data were gathered regarding maternal perceived stress and affective distress from mothers of children (N = 65, mean age = 8.3 years) with cancer at 2 to 5 weeks postdiagnosis, then at 12 to 14 weeks and 22 to 24 weeks. Mothers and nurses provided indexes of child somatic and emotional distress at these assessments. RESULTS Hierarchical and k-means cluster analyses revealed four distinct patterns of maternal distress: high, moderate, declining, and low. The high maternal distress group reported higher child emotional distress at all three points but higher child somatic distress only at the final assessment. Maternal distress group was unrelated to nurse-reported child distress. CONCLUSIONS The identification of four empirically derived patterns of maternal distress may explain some of the variance in the literature regarding parental distress vis-à-vis pediatric cancer treatment and may have relevance to intervention efforts. Differences in the relations between maternal distress groups and mother- and nurse-reported child distress underscore the importance of collecting child distress data from multiple sources.
Macrolide Resistance and emm Type Distribution of Invasive Pediatric Group A Streptococcal Isolates: Three-Year Prospective Surveillance From a Children’s Hospital

Objective: Macrolide-resistant group A streptococci (GAS) have been suggested to have more invasive potential. An M protein-based GAS vaccine is currently in development. We sought to define the GAS emm types and macrolide resistance rates among pediatric invasive GAS isolates collected prospectively during a recent 40-month period at our children’s hospital. Patients and Methods: We prospectively identified and collected GAS isolates from patients with invasive GAS disease (isolates from normally sterile sites). Susceptibility assays for erythromycin and clindamycin were performed by E-test. emm typing was performed by the Centers for Disease Control and Prevention. Clinical characteristics of patients were identified by chart review. Results: A total of 37 patient isolates were identified, of which 35 isolates were able to be characterized. Four patients had underlying illness. No macrolide resistance was detected among the isolates. The most common emm types causing invasive disease were emm 1.0 (43%) and emm 12.0 (11.1%). Conclusions: In this group of 35 invasive GAS isolates, no cases of macrolide resistance were found. emm type 1 accounted for the highest percentage of invasive disease, followed by emm type 12. The type-specific GAS M protein-based vaccine currently in development includes the emm types of 33 of 35 (94%) of the invasive emm types in this series.
Characterization of calcium currents in functionally mature mouse spinal motoneurons

Motoneurons integrate synaptic input and produce output in the form of trains of action potentials such that appropriate muscle contraction occurs. Motoneuronal calcium currents play an important role in the production of this repetitive firing. Because these currents change in the postnatal period, it is necessary to study them in animals in which the motor system is ‘functionally mature’, that is, animals that are able to weight‐bear and walk. In this study, calcium currents were recorded using whole‐cell patch‐clamp techniques from large (> 20 μm) ventral horn cells in lumbar spinal cord slices prepared from mature mice. Ninety percent (nine out of 10) of the recorded cells processed for choline acetyltransferase were found to be cholinergic, confirming their identity as motoneurons. A small number of motoneurons were found to have currents with low‐voltage‐activated (T‐type) characteristics. Pharmacological dissection of the high‐voltage‐activated current demonstrated ω‐agatoxin‐TK‐ (P/Q‐type), ω‐conotoxin GVIA‐ (N‐type), and dihydropyridine‐ and FPL‐64176‐sensitive (L‐type) components. A cadmium‐sensitive component of the current that was insensitive to these chemicals (R‐type) was also seen in these cells. These results indicate that the calcium current in lumbar spinal motoneurons from functionally mature mice is mediated by a number of different channel subtypes. The characterization of these calcium channels in mature mammalian motoneurons will allow for the future study of their modulation and their roles during behaviours such as locomotion.
Association between personality traits and future choice of specialisation among Swedish doctors: a cross-sectional study

Background Medical students’ choice of their future specialty is influenced by several factors, including working conditions and type of patient relations. The aim of this study was to investigate the association between the choice of specialty and personality traits. Methods This is a cross-sectional questionnaire-based study of 399 alumni from Karolinska Institutet Medical School who were assumed to undergo specialty training at the time of the survey in 2013. The Big Five Inventory was used to assess the personality traits extraversion, agreeableness, conscientiousness, neuroticism and openness to experience. Medical specialties were categorised as primary care, psychiatry, internal medicine and surgical and hospital service specialties. Adjustments were made for demographic factors and the method of selection for medical school admission. Results The response rate was 72% (n=289, of which 262 were in training to become specialists). Among these, surgeons scored lower in agreeableness than physicians in primary care, internal medicine and hospital services. Psychiatrists and hospital service physicians showed lower conscientiousness compared with surgeons. Conclusions We found distinctive differences in personality traits between medical specialties even after adjusting for other potential explanatory variables. Since there are differences between specialties, for example, surgeons and psychiatrists, this supports previous findings that personality may affect medical students’ specialty choice also in a Swedish setting.
Therapeutic Potential of Induced Neural Stem Cells for Spinal Cord Injury*

Background: The therapeutic potential of induced neural stem cells (iNSCs) that are directly converted from fibroblasts still remains elusive. Results: Engrafted iNSCs enhance functional recovery after spinal cord injury in the rat model. Conclusion: The directly converted iNSCs hold therapeutic potential. Significance: This is the first report describing the therapeutic potential of iNSCs. The spinal cord does not spontaneously regenerate, and treatment that ensures functional recovery after spinal cord injury (SCI) is still not available. Recently, fibroblasts have been directly converted into induced neural stem cells (iNSCs) by the forced expression defined transcription factors. Although directly converted iNSCs have been considered to be a cell source for clinical applications, their therapeutic potential has not yet been investigated. Here we show that iNSCs directly converted from mouse fibroblasts enhance the functional recovery of SCI animals. Engrafted iNSCs could differentiate into all neuronal lineages, including different subtypes of mature neurons. Furthermore, iNSC-derived neurons could form synapses with host neurons, thus enhancing the locomotor function recovery. A time course analysis of iNSC-treated SCI animals revealed that engrafted iNSCs effectively reduced the inflammatory response and apoptosis in the injured area. iNSC transplantation also promoted the active regeneration of the endogenous recipient environment in the absence of tumor formation. Therefore, our data suggest that directly converted iNSCs hold therapeutic potential for treatment of SCI and may thus represent a promising cell source for transplantation therapy in patients with SCI.
Triploidy: antenatal sonographic features with post‐mortem correlation

A retrospective study was performed comparing the antenatal ultrasound (US) scan features with post‐mortem findings in 20 triploid fetuses surviving beyond the first trimester. US scans showed a range of abnormalities including oligohydramnios (60 per cent of cases), intra‐uterine growth retardation (IUGR, 55 per cent), central nervous system (CNS) abnormalities (45 per cent), and placental abnormalities (55 per cent). There were obstetric complications in 30 per cent of cases. Post‐mortem examinations confirmed these findings but also demonstrated additional anomalies including facial dysmorphism, limb abnormalities (syndactyly, talips equinovarus and thigh muscle hypertrophy), and anomalies of cardio‐vascular, respiratory and genito‐urinary system. The placenta was normal in 16 per cent of cases, enlarged with cystic change in 47 per cent, small in 32 per cent and infarcted in 5 per cent of cases. Various factors including oligohydramnios, abnormal fetal position, less sophisticated equipment in mid‐1980s and relative inexperience of early observers contributed to the reduced sensitivity of US scans in diagnosis of various defects. However, triploidy should be considered in all cases showing early second‐trimester IUGR with or without oligohydramnios, a major CNS abnormality and/or an enlarged placenta with or without changes of partial hydatidiform mole. As triploidy is associated with increased obstetric complications, fetal karyotyping should be offered to confirm the diagnosis so that appropriate obstetric intervention can be instituted. Copyright © 1998 John Wiley & Sons, Ltd.
Association of obesity with periodontitis, tooth loss and oral hygiene in non-smoking adults.

BACKGROUND Periodontitis was found to be significantly related to obesity as well as the number of missing teeth and oral hygiene. However, the studies addressing these relationships often included smokers and diabetics, and none was performed in Eastern European patients. The aim of this cross-sectional study was to investigate associations between obesity and periodontitis, oral hygiene, and tooth loss in a sample of non-smoking Croatian subjects aged 31-75 years. METHODS A total of 320 patients were recruited by convenient sampling at the Dental Clinic, Clinical Hospital Centre in Rijeka, Croatia. Periodontal examination and data on tooth loss were completed in 292 subjects and each participant completed a structured written questionnaire with questions regarding oral hygiene, education, height, and weight. Periodontitis was categorized as early, moderate and advanced. In multiple regression analysis, periodontitis was used as predictor variable, and BMI, oral hygiene, tooth loss, and education level were used as dependent variables. RESULTS Use of interdental brushes/flossing and number of missing teeth correlated significantly with BMI, but the same could not be proven for periodontitis and frequency of tooth brushing. However, logistic regression proved that the subset of obese, poorly educated women aged 36-55 years were 5-6 times more likely to develop severe forms of periodontal disease. CONCLUSIONS Obesity was associated with tooth loss, oral hygiene, and education level in the investigated group. BMI could not be correlated with severity of periodontal disease, except in poorly educated women aged 36-55 years.
Human capital, gender, and labor force incorporation: The case of immigrants from the Former Soviet Union

Women immigrating to the United States from the Former Soviet Union (FSU) were expected to incorporate seamlessly into the US labor force because of their strong educational and professional backgrounds. Using 2000 Census data, we find that FSU women were less successful than both FSU men and other non-Hispanic white female immigrants. After controlling for other factors, FSU women were more likely to rely on public assistance and less likely to be employed. If employed, they worked in less prestigious occupations and earned much less.These findings draw attention to the particular difficulties of incorporation of this wave of relatively advantaged immigrants.
CD4/major histocompatibility complex class II interaction analyzed with CD4‐ and lymphocyte activation gene‐3 (LAG‐3)‐Ig fusion proteins

We analyzed CD4 major histocompatibility complex (MHC) class II interactions with CD4 and lymphocyte activation gene (LAG)‐3 recombinant fusion proteins termed CD4Ig and LAG‐3Ig. CD4Ig bound MHC class II molecules expressed on the cell surface only when used in the micromolar range. This weak CD4Ig binding was specific, since it was inhibited by anti‐CD4 and anti‐MHC class II mAb. LAG‐3Ig bound MHC class II molecules with intermediate avidity (Kd = 60 nM at 37°C). Using LAG‐3Ig as a competitor in a CD4/MHC class II‐dependent cellular adhesion assay, we showed that this recombinant molecule was able to block CD4/MHC class II interaction. In contrast, no inhibition was observed in a CD4/MHC class II‐dependent T cell cytotoxicity assay. Together, these results suggest that co‐engagement of the TcR with CD4 alters the CD4/MHC class II molecular interaction to become insensitive to LAG‐3Ig competition.