Miracle-dz/UniFAR-FTUs huggingface dataset:
Striatal dopaminergic reward response relates to age of first drunkenness and feedback response in at‐risk youth

Dopamine receptor concentrations, primarily in the striatum, are hypothesized to contribute to a developmental imbalance between subcortical and prefrontal control systems in emerging adulthood potentially biasing motivation and increasing risky behaviors. Positron emission tomography studies have found significant reductions in striatal dopamine D2 receptors, and blunted amphetamine‐induced dopamine release, in substance users compared with healthy controls. Extant literature is limited and inconsistent concerning vulnerability associated with having a family history of substance abuse (FH+). Some studies have reported familial liability associated with higher dopamine receptor levels, reduced dopamine response to stimulant challenges and decreased response to oral alcohol. However, other reports have failed to find group differences based on family history. We explored the interaction of familial liability and behavioral risk with multi‐modal molecular and neural imaging of the dopaminergic system. Forty‐four young adult male subjects performed monetary incentive delay tasks during both [11C]raclopride positron emission tomography and functional magnetic resonance imaging scans. FH+ subjects were identified as low (n = 24) or high risk (n = 9) based on early initiation of drunkenness. FH+ high‐risk subjects exhibited heightened striatal dopamine response to monetary reward but did not differ in neural activations compared with FH+ low risk subjects and controls with no familial loading (n = 11). Across all subjects, a negative relationship was found between dopamine release and age of first drunkenness and a positive relationship with neural response to reward receipt. These results suggest that in at‐risk individuals, higher dopamine transmission associated with monetary reward may represent a particularly useful neurobiological phenotype.
Attenuated frontal and sensory inputs to the basal ganglia in cannabis users

Heavy cannabis use is associated with reduced motivation. The basal ganglia, central in the motivation system, have the brain's highest cannabinoid receptor density. The frontal lobe is functionally coupled to the basal ganglia via segregated frontal–subcortical circuits conveying information from internal, self‐generated activity. The basal ganglia, however, receive additional influence from the sensory system to further modulate purposeful behaviors according to the context. We postulated that cannabis use would impact functional connectivity between the basal ganglia and both internal (frontal cortex) and external (sensory cortices) sources of influence. Resting‐state functional connectivity was measured in 28 chronic cannabis users and 29 controls. Selected behavioral tests included reaction time, verbal fluency and exposition to affective pictures. Assessments were repeated after one month of abstinence. Cannabis exposure was associated with (1) attenuation of the positive correlation between the striatum and areas pertaining to the ‘limbic’ frontal–basal ganglia circuit, and (2) attenuation of the negative correlation between the striatum and the fusiform gyrus, which is critical in recognizing significant visual features. Connectivity alterations were associated with lower arousal in response to affective pictures. Functional connectivity changes had a tendency to normalize after abstinence. The results overall indicate that frontal and sensory inputs to the basal ganglia are attenuated after chronic exposure to cannabis. This effect is consistent with the common behavioral consequences of chronic cannabis use concerning diminished responsiveness to both internal and external motivation signals. Such an impairment of the fine‐tuning in the motivation system notably reverts after abstinence.
Bi‐directional cannabinoid signalling in the basolateral amygdala controls rewarding and aversive emotional processing via functional regulation of the nucleus accumbens

Functional connections between the basolateral amygdala (BLA) and nucleus accumbens (NAc) are involved critically in opiate‐reward processing. In the BLA, inhibitory GABAergic substrates are inhibited by cannabinoid CB1 receptor (CB1R) activation and can modulate BLA projections to various limbic regions, including the NAc. However, the potential role of CB1R transmission in the regulation of opiate‐related memory formation via the BLA → NAc circuit is not understood. Using an unbiased conditioned place preference paradigm in rats, we examined the effects of intra‐BLA CB1R modulation by either direct pharmacological activation or blockade of CB1R transmission. We report that intra‐BLA CB1R activation switches normally rewarding effects of morphine into strongly aversive effects. In contrast, CB1R blockade strongly potentiates normally subreward threshold effects of morphine. Next, using targeted microinfusions of an NMDA receptor antagonist to either the core or shell (NASh) subdivisions of the NAc, we found that selective blockade of NMDA transmission in the NA shell, but not core, prevented both intra‐BLA CB1 blockade‐mediated opiate reward potentiation and CB1 activation‐mediated aversion effects. Finally, using multi‐unit, in vivo electrophysiological recordings in the NASh, we report that the ability of intra‐BLA CB1R modulation to control opiate reward salience and motivational valence is associated with distinct reward or aversion neuronal activity patterns and bi‐directional regulation of intra‐NASh fast‐spiking interneurons versus medium spiny neurons. These findings identify a unique mechanism whereby bi‐directional BLA CB1R transmission can regulate opiate‐related motivational processing and control affective states through functional modulation of mesolimbic neuronal activity.
Gender equality in India for children with congenital heart disease: looking for answers

The prevalence of congenital heart disease in India has been reported as 2.25–5.2/1000 live births compared with 8–10/1000 live births in other parts of the world.1–4 This is likely to be an underestimate, however, because an unknown number of cases go unreported, particularly those delivered by unqualified personnel in rural areas where monitoring is inadequate. Specialist care of congenital heart disease in rural India is generally suboptimal due to the lack of paediatric cardiac surgical and interventional facilities. Consequently, patients have to travel long distances to metropolitan cities to avail themselves of treatment. Unlike adult cardiac care in metropolitan India, paediatric interventional and surgical care is still in a phase of development and facilities have not been prioritised in many hospitals because costs are high and return on the investment relatively low.5 Parental preference for male children exists in many sections of Indian society, where girls with congenital heart disease are not provided with the same treatment opportunities as boys. The prevalence of the male to female ratio of congenital heart disease in India has been variously reported as 1:1, 1.1:1 and 1.25:1.6–9 Given the almost equal gender prevalence, …
Correlation of Serum and Synovial Osteocalcin, Osteoprotegerin and Tumor Necrosis Factor-Alpha with the Disease Severity Score in Knee Osteoarthritis

Abstract Objectives: Study of circulating and synovial levels of osteocalcin, osteoprotegerin and tumor necrosis factor-alpha (TNF-α) in patients with different stages of knee osteoarthritis and correlation analysis of these parameters with disease severity. Methods: We enrolled 20 patients with different stages of knee osteoarthritis. The IKDC score (International Knee Documentation Comittee, 2000) was determined for each patient. Based on these data patients were divided into two groups: group I (advanced osteoarthritis) and group II (early osteoarthritis). Serum and synovial fluid levels of osteocalcin, osteoprotegerin, TNF-α were determined. Results: For the entire group the level of osteocalcin in the serum showed higher values than in the synovial fluid. We found statistically significant differences in the serum levels of osteocalcin between the two groups (group I: 2.18 ± 0.54 ng/ml, group II: 6.07 ± 1.98 ng/ml, p = 0.019). Serum and synovial osteocalcin in the whole study lot could not be correlated with the disease score, however we observed a tendency towards significant negative correlation between the serum osteocalcin and IKDC score for group I and between synovial osteocalcin and IKDC score in group II. In the entire group, synovial osteoprotegerin concentration was six times higher than the serum osteoprotegerin level (p <0.0001) and TNF-α showed higher circulating levels than local concentrations. Conclusions: In the advanced osteoarthritis group the serum and synovial osteocalcin show lower values than in the early osteoarthritis group, which means that as the disease progresses, bone anabolism decreases. In the case of osteoprotegerin, no significant difference between the two groups was detected.
Almanac 2011: stable coronary artery disease. An editorial overview of selected research that has driven recent advances in clinical cardiology

### Diagnostic strategies The widespread application of specialist clinics for early evaluation of patients with chest pain has focused attention on the effectiveness of diagnostic testing. In a study of nearly 400 000 patients with suspected coronary artery disease, the diagnostic yield of cardiac catheterisation was only 37.6%, leading to calls for better strategies for risk stratification.1 As pointed out in correspondence, the low yield was probably due to verification bias, itself a consequence of basing referral decisions in low- risk populations on non-invasive tests such as exercise ECG.2 Similar considerations prompted the NICE guideline group to recommend a more selective approach to non-invasive testing based on a careful clinical assessment of disease probability in patients presenting with stable chest pain.3 For those, with unequivocal histories at the extremes of diagnostic probability ( 90%) no diagnostic tests were considered necessary, while for patients with a high probability of disease (60–90%) invasive angiography without prior ischaemia testing was recommended. The NICE call for CT calcium scoring in patients with a low (10–30%) probability of disease generated greatest concern, particularly after a report that 19% of patients without coronary calcification—who would have been ruled out for angina in the NICE algorithm—had obstructive (>50% stenosis) disease.4 However, the population referred for angiography in this study had a high pre-test probability of disease and in lower-risk populations CT calcium scoring retains a high diagnostic sensitivity.5 NICE recommendations were driven largely by cost-effectiveness analysis but whether they will improve the diagnostic yield of cardiac catheterisation remains to be seen. ### Circulating biomarkers in stable angina The clinical role of circulating biomarkers for diagnosis of obstructive coronary artery disease in patients with suspected angina has yet to be defined. In one study, blood samples for the N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) and various inflammatory markers were …
Neural response to alcohol taste cues in youth: effects of the OPRM1 gene

Genetic variations in the mu‐opioid receptor (OPRM1) gene have been related to high sensitivity to rewarding effects of alcohol. The current study focuses on the neural circuitry underlying this phenomenon using an alcohol versus water taste‐cue reactivity paradigm in a young sample at relatively early stages of alcohol use, thus limiting the confound of variations in duration of alcohol use. Drinkers (17–21 years old) were selected on genotype carrying the AA—(n = 20) or the AG—(n = 16) variant of the A118G single nucleotide polymorphism (SNP) of the OPRM1 gene (rs1799971), and underwent functional magnetic resonance imaging (fMRI). Magnitude of the neural activity and frontostriatal functional connectivity in response to alcohol versus water were investigated. The AG‐group demonstrated reduced activation in prefrontal and parietal regions, including the inferior and middle frontal gyrus, superior and inferior parietal lobule, compared with the AA‐group. No activation differences were observed in the mesolimbic pathway. Connectivity from the ventral‐striatum to frontal regions for alcohol > water trials was higher in the AG than the AA group. For the dorsal‐striatum seed region, the AG group showed increased connectivity to non‐PFC regions. These results indicate that adolescents carrying the G‐allele may be more vulnerable for the alcohol to hijack the reward system in the absence of frontal control to regulate craving. This implies that findings of hyperactivation in the mesolimbic structures of G‐allele carriers in earlier studies might result from both genetic susceptibility and heavy drinking.
Essential values of cocaine and non‐drug alternatives predict the choice between them

This study investigated the relationship between reinforcer value and choice between cocaine and two non‐drug alternative reinforcers in rats. The essential value (EV, a behavioral economic measure based on elasticity of demand) of intravenous cocaine and food (Experiment 1) or saccharin (Experiment 2) was determined in the first phase of each experiment. Food had higher EV than cocaine, whereas the EVs of cocaine and saccharin did not differ. In the second phase of each experiment, rats were allowed to make mutually exclusive choices between cocaine and the non‐drug alternative reinforcer. The main findings were that the EV of cocaine was a positive predictor of cocaine preference and the EV of food or saccharin was a negative predictor of cocaine preference. An analysis of within‐session patterns of choice behavior revealed sequential dependencies, whereby rats were more likely to choose cocaine on a particular trial after having chosen the non‐drug alternative on previous trials. When the time between choices was increased, these sequential dependencies disappeared. The results of these experiments are consistent with the suggestion that addiction‐like behavior involves both overvaluation of drug reinforcers and undervaluation of non‐drug reinforcers.
Altered interhemispheric resting‐state functional connectivity in young male smokers

With the help of advanced neuroimaging approaches, previous studies revealed structural and functional brain changes in smokers compared with healthy non‐smokers. Homotopic resting‐state functional connectivity between the corresponding regions in cerebral hemispheres may help us to deduce the changes of functional coordination in the whole brain of young male smokers. Functional homotopy reflects an essential aspect of brain function and communication between the left and right cerebral hemispheres, which is important for the integrity of brain function. However, few studies used voxel mirrored homotopic connectivity (VMHC) method to investigate the changes of homotopic connectivity in young male smokers. Twenty‐seven young male smokers and 27 matched healthy male non‐smokers were recruited in our study. Compared with healthy male non‐smokers, young male smokers showed decreased VMHC values in the insula and putamen, and increased VMHC values in the prefrontal cortex. Correlation analysis demonstrated that there were significant positive correlations between the average VMHC values of the prefrontal cortex and pack‐years in young male smokers. In addition, significant negative correlation was found between the average VMHC values in the insula and pack‐years. Our results revealed the disrupted homotopic resting‐state functional connectivity in young male smokers. The novel findings may extend our understanding of smoking.
Prognostic value of cardiac troponin in chronic stable heart failure: a systematic review

Context Cardiac troponins have become the ‘gold standard’ for diagnosing myocardial infarction. Elevation of cardiac troponins is noted in patients with chronic stable heart failure, but comparative prognostic value of different assay types is not established. Objective To perform a systematic review for investigating the prognostic value of the different types of cardiac troponins (including low and high sensitivity) in chronic stable heart failure. Data sources Search of three databases, PubMed, The Cochrane Library and Web of Science, was made in April 2012. Study selection All studies which provided information on prognosis based upon the baseline cardiac troponin elevation in chronic stable heart failure were included. Limits applied were adults, humans and English language. Data extraction Two authors individually reviewed all studies and extracted data on patient and study characteristics along with primary and secondary outcomes. Results 16 of the 365 papers from three databases were finally included for data analysis. Elevated baseline cardiac troponin in patients with chronic stable heart failure was associated with a high risk of mortality (HR 2.85; 95% CI 2.02 to 4.03) and combined adverse cardiovascular outcome (HR 2.38; 95% CI 1.63 to 3.49). Although high-sensitivity assay detected cardiac troponin in higher proportion of patients compared with low-sensitivity assay, there was no statistically significant difference among both groups (p=0.54). Conclusions Elevated baseline cardiac troponin level identified chronic stable heart failure patients who are at a higher risk of mortality and combined adverse cardiovascular outcomes. There was no statistically significant difference between high- and low-sensitivity cardiac troponins.
Time‐dependent neuronal changes associated with craving in opioid dependence: an fMRI study

Relapse after initially successful treatment is a significant problem facing the treatment of opioid dependence. Evidence suggests craving elicited by re‐exposure to drug cues may precipitate relapse. Attempts to identify neural biomarkers of cue‐elicited craving have yielded inconsistent findings. We aimed to apply a novel continuous functional magnetic resonance imaging technique to follow the minute‐to‐minute evolution of brain responses, which correlate with the waxing and waning of craving. Newly detoxified male opioid‐dependent patients and healthy control participants attended two separate, counterbalanced, functional magnetic resonance imaging scanning sessions during which they viewed a 10‐minute video (drug cue or neutral cue) followed by 5 minutes of fixation. Participants rated the intensity of their craving throughout each session. We hypothesized that subcortical/ventral prefrontal cortex (PFC) regions and dorsal PFC regions would show different associations with craving reflecting their putative roles in appetitive processing versus cognitive control. Compared with controls, drug cue (minus neutral cue) video recruited the left amygdala and was temporally correlated with craving. In contrast, dorsal anterior cingulate blood‐oxygen‐level‐dependent signal time course was higher than controls only during a period after cue exposure when craving levels were declining. Against expectations, neither the ventral striatum nor ventral PFC was significantly recruited by drug cue exposure. Findings suggest that the amygdala has a central role in craving, whereas the dorsal anterior cingulate may control craving in treatment‐seeking patients. Time course analysis yielded new insights into the neural substrates of craving that could objectively validate development of psychological and pharmacological approaches to sustained abstinence.
Prevalence, predictors and clinical impact of unique and multiple chronic total occlusion in non-infarct-related artery in patients presenting with ST-elevation myocardial infarction

Objectives To investigate the predictors and impact on long-term survival of one chronic total occlusion (CTO) or multiple CTOs in patients presenting with ST-elevation myocardial infarction (STEMI). Design Single-centre retrospective observational study. Setting University-based tertiary referral centre. Patients Between 2006 and 2011, a total of 2020 consecutive patients referred with STEMI were categorised into single vessel disease, multivessel disease (MVD) without CTO, with one CTO or with multiple CTOs. Intervention Primary percutaneous coronary intervention. Main outcome measure The primary end-point was the 1-year mortality. Results The prevalence of single vessel disease, MVD without CTO, with one CTO or with multiple CTOs was 70%, 22%, 7.2% and 0.8%, respectively. Independent clinical predictors for the presence of CTO were cardiogenic shock (OR 5.05; 95% CI 3.29 to 7.64), prior myocardial infarction (OR 2.06; 95% CI 1.35 to 3.09), age >65 years (OR 1.94; 95% CI 1.40 to 2.71) and history of angina (OR 1.94; 95% CI 1.29 to 2.87). Mortality was worse in patients with multiple CTOs (76.5%) compared with those with one CTO (28.1%) or without CTO (7.3%) (p<0.0001). After adjustment for left ventricular ejection fraction and renal function, MVD was an independent predictor for 1-year mortality (HR: 1.81; 95% CI 1.18 to 2.77, p=0.007), but CTO was not (HR: 1.07; 95% CI 0.66 to 1.73, p=0.78). Conclusions Simple clinical factors are associated with the presence of CTO in non-infarct-related artery in patients presenting with STEMI. In these patients, long-term survival was independently associated with MVD, left ventricular ejection fraction and renal function, but not with CTO per se.
Protecting Victims of Domestic Violence in Caribbean Communities

SUMMARY A decade after the courts in many English-speaking Caribbean jurisdictions were granted the power to issue restraining orders to victims of domestic violence, battered women have not experienced the full benefits of such policy. Using the experiences of battered women in the English-speaking Caribbean state of Barbados, this study argues that there are significant challenges for victims, caused by cultural, social and economic factors that have not been appropriately addressed by domestic violence legislation. Marginalized by the court and legal system in the English-speaking Caribbean, many battered women seek out alternatives to the legal system for coping with domestic violence. Therefore when they migrate to countries like the United States where more accommodations are made for victims of domestic violence, they are unlikely to engage with the legal system and make their suffering known. Women might also be silenced by fears of violating immigration laws in the United States as well as risking personal loss due to the severe punishment of their partners when indicted by the legal system.