Miracle-dz/UniFAR-FTUs huggingface dataset:
Fetal exposure to moderate ethanol doses: heightened operant responsiveness elicited by ethanol-related reinforcers.

BACKGROUND Prenatal exposure to moderate ethanol doses during late gestation modifies postnatal ethanol palatability and ingestion. The use of Pavlovian associative procedures has indicated that these prenatal experiences broaden the range of ethanol doses capable of supporting appetitive conditioning. Recently, a novel operant technique aimed at analyzing neonatal predisposition to gain access to ethanol has been developed. Experiment 1 tested the operant conditioning technique for developing rats described by Arias and colleagues (2007) and Bordner and colleagues (2008). In Experiment 2, we analyzed changes in the disposition to gain access to ethanol as a result of moderate prenatal exposure to the drug. METHODS In Experiment 1, newborn pups were intraorally cannulated and placed in a supine position that allowed access to a touch-sensitive sensor. Paired pups received an intraoral administration of a given reinforcer (milk or quinine) contingent upon physical contact with the sensor. Yoked controls received similar reinforcers only when Paired pups activated the circuit. In Experiment 2, natural reinforcers (water or milk) as well as ethanol (3% or 6% v/v) or an ethanol-related reinforcer (sucrose compounded with quinine) were tested. In this experiment, pups had been exposed to water or ethanol (1 or 2 g/kg) during gestational days 17 to 20. RESULTS Experiment 1 confirmed previous results showing that 1-day-old pups rapidly learn an operant task to gain access to milk, but not to gain access to a bitter tastant. Experiment 2 showed that water and milk were highly reinforcing across prenatal treatments. Furthermore, general activity during training was not affected by prenatal exposure to ethanol. Most importantly, prenatal ethanol exposure facilitated conditioning when the reinforcer was 3% v/v ethanol or a psychophysical equivalent of ethanol's gustatory properties (sucrose-quinine). CONCLUSIONS The present results suggest that late prenatal experience with ethanol changes the predisposition of the newborn to gain access to ethanol-related stimuli. In conjunction with prior literature, this study emphasizes the fact that intrauterine experience with ethanol not only augments ethanol's palatability and ingestion, but also facilitates the acquisition of response-stimulus associations where the drug acts as an intraoral reinforcer.
Extending the Theory of Normative Social Behavior to Predict Hand-Washing among Koreans

ABSTRACT The current study tests the predictions of the theory of normative social behavior (TNSB) in a hand-washing context in a Korean sample and extends the theory to examine the role of perceived publicness, a variable believed to activate face concerns, as a moderator of the norm–behavior relationship. The findings show substantial main effects for all of the study variables on behavior. In addition, the descriptive norm–behavior relationship is moderated by perceived publicness and outcome expectations, but the nature of the interactions is not consistent with that evidenced in previous literature on US samples. Implications for normative theory and communication campaigns are discussed.
Revisiting intragastric ethanol intubation as a dependence induction method for studies of ethanol reward and motivation in rats.

BACKGROUND The purpose of this study was to re-examine intragastric ethanol intubation as a dependence induction method that effectively induces physical dependence upon ethanol over a short time period, is devoid of intrinsic stress artifacts, inexpensive, and easy to implement. METHODS Male Wistar rats were subjected to ethanol dependence induction via intragastric ethanol intubation. Ethanol solution (final concentration 20%, made up in a dietary liquid vehicle consisting of powdered milk, sucrose, and water) was intubated 4 times per day, at 4-hour intervals, for 6 consecutive days (for a total of 10 g/kg/day). The utility of this procedure was evaluated for inducing physical dependence, determined by daily and final withdrawal ratings. Anxiety-like behavior associated with ethanol dependence history was examined using the elevated plus-maze (EPM) test, conducted 5 days after ethanol withdrawal. To evaluate whether potential stress-like effects of intragastric intubation per se produce lasting effects on behavior, experimentally naive rats were compared with vehicle-intubated rats for anxiety-like behavior on the EPM. RESULTS Blood alcohol levels reached stable levels between 200 and 250 mg%, measured 1 hour after the second and third ethanol intubation on days 2, 4, and 6. Ethanol-treated rats developed significant somatic withdrawal signs, recorded daily between 10 and 12 hours after the last ethanol administration. At 5 days postwithdrawal, ethanol-treated rats showed significant anxiety-like behavior, measured by decreased open arm time and open arm entries on the EPM, compared with vehicle controls. Additionally, ethanol postdependent rats showed decreased open arm time compared with experimentally naive rats. EPM performance did not differ between vehicle-intubated and naive rats. No withdrawal seizures were observed and mortality rate was near zero. CONCLUSIONS These findings suggest that intragastric ethanol administration produces a behavioral profile consistent with ethanol dependence (i.e., significant withdrawal signs after termination of ethanol exposure and elevated anxiety-like behavior persisting beyond completion of physical withdrawal), and that the intubation procedure itself does not produce lasting nonspecific anxiety-like effects. Thus, under the conditions employed here, this procedure provides an effective tool for inducing and evaluating the consequences of ethanol dependence in animal models of ethanol reward and motivation.
Phase I clinical study of diphtheria toxin-interleukin 3 fusion protein in patients with acute myeloid leukemia and myelodysplasia

DT388IL3 fusion protein containing the catalytic and translocation domains of diphtheria toxin fused to human interleukin 3 was administered in an inter-patient dose escalation trial by 15 min i.v. infusions every other day for up to 6 doses to patients with chemo-refractory acute myeloid leukemia (AML) and myelodysplasia (MDS). The maximal tolerated dose was >12.5 µg/kg/dose. Transient grade 3 transaminasemia and grade 2 fevers, chills, hypoalbuminemia, and hypotension occurred. Peak DT388IL3 levels correlated with dose and day of administration but not antibody titer. Anti-DT388IL3 antibodies developed in most patients between day 15 and 30. Of 40 evaluable AML patients, 1 had a CR (8 months) and 1 had PR (3 months). Of 5 MDS patients, 1 had a PR (4 months). Because of the prolonged infusion schedule, many patients failed to receive six doses. DT388IL3 produces remissions in patients with relapsed/refractory AML and MDS with minimal toxicities, and alternate schedules of administration are needed to enhance the response rate.
Aurora A kinase RNAi and small molecule inhibition of Aurora kinases with VE-465 induce apoptotic death in multiple myeloma cells

The expression of RHAMM and other centrosome-associated genes are known to correlate with the extent of centrosome amplification in multiple myeloma, and with poor prognosis. RHAMM has a significant interaction with TPX2, a protein which regulates the localization and action of Aurora A kinase (AURKA) at the spindle poles. AURKA is known to be a central determinant of centrosome and spindle function and is a target for cancer therapy. Given these observations, we investigated the role of Aurora kinases as therapeutic targets in myeloma. Here we report that AURKA is expressed ubiquitously in myeloma, to varying degrees, in both cell lines and patients' bone marrow plasma cells. siRNA targeting AURKA induces apoptotic cell death in myeloma cell lines. The Aurora kinase inhibitor VE-465 also induces apoptosis and death in myeloma cell lines and primary myeloma plasma cells. The combination of VE-465 and dexamethasone improves cell killing compared with the use of either agent alone, even in cells resistant to the single agents. The phenotype of myeloma cells treated with VE-465 is consistent with published reports on the effects of Aurora kinase inhibition. Aurora kinase inhibitors should be pursued as potential treatments for myeloma.
Clinical and bacteriological profile of Uti patients attending a north Indian tertiary care center

Objective: Urinary tract infection (UTI) is a common cause of morbidity in patients attending our hospital. Recently UTI has become more complicated and difficult to treat because of appearance of pathogens resistant to the commonly used antimicrobial agents. The main aim of the study was to determine the causative agents and antibiotic susceptibility pattern of UTI patients attending our hospital. Materials and methods: A prospective cross sectional study was conducted in asymptomatic and symptomatic UTI patients attending medicine and nephrology clinics of Jawaharlal Nehru Medical College Hospital, Aligarh from June 2012 to July 2014. A total of 1843 patients were investigated for urinary tract infection. Clean catch mid-stream urine specimens collected were subjected to urine culture and sensitivity tests. Results: Significant bacteriuria was detected in 19.3% and 55.4% of asymptomatic and symptomatic patients, respectively. The overall prevalence of significant bacteriuria in both groups was 33.4% with female sex, diabetes, obstructive uropathy, previous instrumentation and chronic kidney disease being the major risk factors. The most common pathogens isolated were Escherichia coli (52.4%) followed by Klebsiella pneumoniae (12.3%), Citrobacter spp (9.1%), Enterococcus (6.9%), Proteus spp (5.3%), Coagulase negative staphylococcus (5.3%) and Staph Aureus(4.0%). Most susceptible antibiotic was Amikacin, Cefoperazone-sulbactum, Piperacillin-tazobactum and Nitrofurantoin for most of the isolates. E. coli which was the main isolate was found to be most susceptible to Amikacin (78.3%), Cefoperazone-sulbactum 72.8%, Piperacillin-tazobactum (70.5%), Gentamicin (69.3%) and Nitrofurantoin (67.3%). Conclusion: This study highlights the common pathogens causing UTI in our area and their antibiotic sensitivity patterns which could help clinicians in starting rational empirical antibiotic therapy for such patients while awaiting urine culture reports.
The Fleas found on Rats and their Relation to Plague

unusual circumstance with other orders of insects, but the fact that the fleas undergo a complete metamorphosis suggests a high degree of specialization prior to the acquirement of their semi-parasitic habits. Possibly the most remarkable characteristic of the order is the close general similarity in regard to size, form and structure of the species comprising it, amounting in some cases almost to identity, in relation to the extreme modification and
Chronic myelomonocytic leukemia with antecedent refractory anemia with excess blasts: Further evidence for the arbitrary nature of current classification systems

From a retrospective analysis of our series of myelodysplastic patients, we found 16 patients who were initially diagnosed as having a refractory anemia with excess of blasts (RAEB) according to FAB criteria, but later on (median time 4 months, range 2–8) developed a peripheral monocytosis >1 × 109/L, leading to a disease re-classification into a dysplastic type of chronic myelomonocytic leukemia (MD-CMML). Analysis of clinical and prognostic aspects in this subgroup of patients as compared with those of primarily diagnosed MD-CMML patients, showed some significant differences in Hb level, platelet count, percentage of immature circulating precursor (IPC), bone marrow blastosis and trilineage dysplasia. Median survival for present group of patients was 33 months compared with 20 months for MD-CMML. Different prognostic scores were applied for evaluation of risk distribution and relative impact on survival prediction. We suggest on a possible atypical presentation of CMML and indicate a careful attention to be addressed to myelodysplastic patients who develop peripheral monocytosis, who might have a CMML variant, with more favourable prognosis and prolonged survival. Furthermore, we believe this is a further evidence for the arbitrary nature of current classification systems, which definitely exclude CMML from myelodysplastic syndromes.
Role of GABRA2 in moderating subjective responses to alcohol.

BACKGROUND Human twin studies have shown that certain responses to alcohol, including subjective perceptions, are genetically influenced. Previous studies have provided evidence that a low level of response to alcohol predicts future alcohol use disorders in humans. Recent genetic studies suggest an association between alcohol dependence and genetic variation in the γ-aminobutyric acid A (GABA(A)) receptor α2 subunit gene (GABRA2). Based on a haplotypic association of alcohol dependence with GABRA2, we investigated whether GABRA2 alleles are associated with the subjective responses to clamped alcohol concentration. METHODS One hundred and ten healthy social drinkers (53 men) underwent the alcohol clamp. Fifteen minutes after the start of an intravenous infusion of alcohol, the breath alcohol concentration was clamped at a target of 50 ± 5 mg/dl for 165 minutes. Subjective physiologic responses to alcohol and stimulant and sedative effects of alcohol were measured repeatedly during the alcohol clamp. Because aldehyde dehydrogenase 2 (ALDH2) has been shown to have a great impact on the subjective responses to alcohol, we divided subjects by ALDH2 genotype for further analyses. To examine the role of genetic variation in GABRA2, 7 single nucleotide polymorphisms (SNPs) that were informative in association studies were included as factors in the analysis. RESULTS Among these 7 SNPs, 3 SNPs (rs279869, rs279858, and rs279837) located in the middle of the GABRA2 gene showed significant associations with subjective effects of alcohol. Subjects with 1 or 2 copies of the more common allele showed greater subjective responses to alcohol than did individuals homozygous for the alcohol dependence-associated allele regardless of ALDH2 genotype. CONCLUSIONS These findings confirm and extend the observation that the GABRA2 alleles affect the subjective responses to alcohol, and suggest that the genetic variations in GABRA2 might play a role in the risk of alcohol use disorders by moderating the subjective effects of alcohol.
A systematic evaluation and validation of subtypes of adolescent alcohol use motives: genetic and environmental contributions.

BACKGROUND Alcohol use motives are closely associated with specific profiles of alcohol use and reflect a subjectively derived decisional framework based on a motivational style of responding. Adult twin studies typically estimate the heritability of alcohol use motives to be between 7 and 42%, although relatively little is known about genetic and environmental influences upon alcohol use motives in adolescence. METHODS Latent class analysis (LCA) models containing 1 through 5 classes were fitted to the data derived from 1,422 adolescent twin and siblings self-reported alcohol use motives. Using twin models, we estimated the genetic, shared, and nonshared environmental influences to the class membership data derived from the LCA. RESULTS Four drinking motives classes were identified (family-oriented, social, enhancement/social, and coping/social). The coping/social and enhancement/social classes were differentiated from the social class on measures of depression, delinquency, and aggressive behavior. Analyses indicated that nonadditive genetic factors accounted for 76% of the variance in the coping/social motives class and additive genetic influences accounted for 66% of the variance in the social motives class. There was a moderate contribution of genetic factors and shared environmental factors influencing class membership of enhancement/social motivated drinkers (28 and 20% explained variance, respectively). Substantial shared environmental influences were revealed for membership of the family-oriented class (75%). CONCLUSIONS Heritable influences may predispose individuals to drink to cope with negative affect, for social reasons, and to a lesser extent for enhancement. Familial environmental influences shape family-oriented motives for drinking in adolescents.
Personality moderates the longitudinal relationship between psychological symptoms and alcohol use in adolescents.

BACKGROUND A great deal of research has emerged on the comorbidity between alcohol misuse and psychological symptoms (e.g., depression, anxiety, and antisocial behavior or conduct disorder) in adolescence. Research has also shown that personality traits underlie vulnerability to alcohol use and psychological symptoms, but how personality moderates this association has not been comprehensively examined. The goals of this study are to clarify (i) whether early alcohol use effects the rate of change of psychological symptoms and vice versa, (ii) whether initial levels and rate of change in both domains vary according to individual differences in personality traits, and (iii) whether personality moderates the relationship between alcohol use and psychological symptoms. METHODS Self-reported alcohol use, depression, anxiety, and antisocial behavior were collected from 393 adolescents at four separate time points across an 18-month period. Parallel growth models were used to assess the main objectives of the study. Personality traits [anxiety sensitivity (AS), hopelessness (H), impulsivity (IMP), and sensation seeking (SS)] were included as time-invariant predictors of initial levels and rates of change of each construct. RESULTS The results indicated that elevated levels of depression predicted faster rates of increase in alcohol use. Personality-specific relationships were demonstrated across all models. IMP was shown to moderate the relationship between alcohol use and depression, suggesting that adolescents who showed a susceptibility to elevated levels of IMP, and heavier drinking were less likely to demonstrate a normative decline in depression. Adolescents with higher levels of AS and anxiety were more likely to show a faster rate of increase in alcohol use. CONCLUSIONS These results highlight the importance of examining personality traits in studying the associations between alcohol use and psychological symptoms.
Refining the treatment of follicular lymphoma

Many effective treatments are currently available for patients with follicular lymphoma (FL). However, given the heterogeneity of this disease, identifying the most beneficial treatment for an individual patient remains a challenge, although clinical, genetic and biological features can all potentially be used to refine therapies in individual cases. The Follicular Lymphoma international prognostic index (FLIPI) algorithm is a valuable prognostic tool for risk categorisation. Despite its current limitations, further investigation will help to develop the role of FLIPI in treatment decision–making, and will increase its value in identifying the optimal therapy for individuals. Biological factors such as bulky disease, over-expression of Bcl-2, or histological grade can help to identify patients at high risk of relapse, and distinguish between the benefits of early intervention vs. a watch-and-wait policy in early-stage FL. The tumor microenvironment plays an important role in the development of FL, and identification of biological and genetic markers could help clinicians determine the prognosis of individual patients. Although much work remains to be done, a greater understanding of the biology of FL will lead to the development of novel therapeutic targets and therapies, bringing individualised treatment a step closer.
Relationship between admission grades and performances of students in the first professional examination in a new medical school

In order to determine the relationship between the quality of Senior Secondary School Certificate Examination (SSCE) results, Joint Admissions and Matriculation Board organised Universities Matriculation Examination (JAMB-UME) scores, and student's academic performance at Lagos state University College of Medicine (LASUCOM), Nigeria, records of students admitted into the Medical School in 1998/99 were studied. Data transformations were completed and subsequently standardized. Standard descriptive statistics and correlation coefficient were used to determine the correlation between the variables. The results showed that there was no significant correlation between the SSCE and the JAMB scores. In addition, correlation between JAMB and the student performance at 100 level and pre -clinical sciences also proved to be non significant. These results indicate that SSCE is a better predicator of students' performance at pre -clinical sciences examination than JAMB Scores. African Journal of Biomedical Research Vol. 8(1) 2005: 51-57
Peripheral blood lymphocyte counts during standard conformal radiotherapy and TomoTherapy/IMRT for prostate cancer

Abstract Lymphopaenia is the earliest and the most sensitive routinely assessed biological parameter of corporeal radiation exposure in clinical practice; bone marrow, lymph nodes and peripheral blood lymphocyte populations are also at risk. During radical prostate radiotherapy, in 28 patients, the mean peripheral lymphocyte count fell from 1.76 × 109/l (standard deviation (SD) 0.63, 95% confidence interval (conf.) 0.23) to 1.10 × 109/l (SD 0.38, conf. 0.14), (p < 0.05). The question was asked as to whether intensity-modulated radiation therapy (IMRT) by TomoTherapy would cause more lymphopaenia than three-field conformal radiotherapy, bearing in mind the ‘low dose bath’ effect of IMRT and the long ‘beam-on’ times. Thirteen patients receiving three-field conformal radiotherapy experienced a fall in peripheral lymphocyte counts from 2.02 (SD: 0.62. conf. 0.43) to 1.17 × 109/l (SD: 0.47, conf. 0.26) after 34–38 Gy, as compared to a fall from 1.6 × 109/l (SD: 0.6, conf. 0.35) to 1.04 × 109/l (SD: 0.3, conf. 0.15) for 15 TomoTherapy patients—non-significant differences. We conclude that for this (approximately) standard, small-volume pelvic radiotherapy and to the dose under scrutiny, we cannot detect differences between the two radiotherapy techniques in terms of the lymphopaenia accruing. Neutrophil counts were similarly non-significantly different.
Excimer formation by stacking G-quadruplex blocks.

Such ultrafast decay rates certainly help to minimizethe extent of deleterious photoreactions. However, this optimi-zation principle for photochemical stability is to some extentviolated in the case of oligonucleotides, for which, in additionto the ultra-short excited-state lifetime of the majority popula-tion, long fluorescence decay components spanning hundredsof picoseconds have been identified.