Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognosis of immune-tolerant phase chronic hepatitis B

We read with great surprise the article by Kim et al 1 reporting high risks of hepatocellular carcinoma (HCC) and death in patients with untreated chronic hepatitis B who were classified by them as patients in ‘immune-tolerant’ (IT) phase. This conclusion contradicts to the general belief that there is little or no disease progression during the IT phase of chronic HBV infection, as best demonstrated in a 5-year histological follow-up study.2 Some issues of serious concern on this study, especially their IT phase patients, require clarification and further discussion to minimise misleading messages. IT phase of perinatally acquired chronic HBV infection is typically seen in Asian children or young adults with high HBV DNA, normal alanine aminotransferase (ALT), hepatitis B e-antigen (HBeAg) seropositivity and normal or minimal …
Dysbiosis of maternal and neonatal microbiota associated with gestational diabetes mellitus

Objective The initial colonisation of the human microbiota and the impact of maternal health on neonatal microbiota at birth remain largely unknown. The aim of our study is to investigate the possible dysbiosis of maternal and neonatal microbiota associated with gestational diabetes mellitus (GDM) and to estimate the potential risks of the microbial shift to neonates. Design Pregnant women and neonates suffering from GDM were enrolled and 581 maternal (oral, intestinal and vaginal) and 248 neonatal (oral, pharyngeal, meconium and amniotic fluid) samples were collected. To avoid vaginal bacteria contaminations, the included neonates were predominantly delivered by C-section, with their samples collected within seconds of delivery. Results Numerous and diverse bacterial taxa were identified from the neonatal samples, and the samples from different neonatal body sites were grouped into distinct clusters. The microbiota of pregnant women and neonates was remarkably altered in GDM, with a strong correlation between certain discriminatory bacteria and the oral glucose tolerance test. Microbes varying by the same trend across the maternal and neonatal microbiota were observed, revealing the intergenerational concordance of microbial variation associated with GDM. Furthermore, lower evenness but more depletion of KEGG orthologues and higher abundance of some viruses (eg, herpesvirus and mastadenovirus) were observed in the meconium microbiota of neonates associated with GDM. Conclusion GDM can alter the microbiota of both pregnant women and neonates at birth, which sheds light on another form of inheritance and highlights the importance of understanding the formation of early-life microbiome.
Proton pump inhibitors increase the risk of cholecystitis: a population-based case–control study

We read with great interest the article by Cheung et al 1 reporting long-term exposure to proton pump inhibitors (PPIs) following Helicobacter pylori (HP) eradication associated with increased risk of gastric cancer. PPIs are widely used worldwide to treat gastro-oesophageal reflux disorder, peptic ulcer and HP, but multiple reports have found they got some negative effects, such as increasing risk of the intra-abdominal infection, like spontaneous bacterial peritonitis,2 pseudomembranous colitis,3 liver abscess4 and affecting the gut microbiome.5 6 PPIs may theoretically increase risk of gaining acute cholecystitis due to the increasing the number of enteric organisms and risk of secondary infection; however, few reports have supported this hypothesis. Thus, we conducted a nationwide population-based case–control study to analyse the relationship between PPI exposure and …
MOSFET-only Mixer/IIR filter with gain using parametric amplification

This paper describes the design of a discrete-time passive Mixer/IIR filter. The use of an improved MOS Parametric Amplification leads to a moderate gain in the signal path and improved noise performance, instead of the conversion loss inherent to passive mixers. Simulation results demonstrate that, employing the proposed MPA structure based on a modified double-complementary topology with floating terminals, an improvement of over 4 dB in the overall circuit gain and up to 2 dB in the noise figure can be achieved.
Low-power ripple-free chopper amplifier with correlated double sampling de-chopping

This paper presents a new solution to obtain a spurs-free high precision amplifier. The method involves input chopping and correlated double sampling signal de-chopping. The offset is removed by using DC coupling. The proposed method, verified with transistor level simulations, is applied to a rail-to-rail input amplifier with 187 dB DC gain and 13.7 µA current consumption.
Glutamate transporter GLT‐1 mediates N‐acetylcysteine inhibition of cocaine reinstatement

Both pre‐clinical and clinical studies indicate that N‐acetylcysteine (NAC) may be useful in treating relapse to addictive drug use. Cocaine self‐administration in rats reduces both cystine‐glutamate exchange and glutamate transport via GLT‐1 in the nucleus accumbens, and NAC treatment normalizes these two glial processes critical for maintaining glutamate homeostasis. However, it is not known if one or both of these actions by NAC is needed to inhibit relapse to cocaine seeking. To determine whether the restoration of GLT‐1 and/or cystine‐glutamate exchange is required for NAC to inhibit cue‐induced reinstatement of cocaine seeking, we utilized the rat self‐administration/extinction/reinstatement model of cocaine relapse. Rats were pre‐treated in the nucleus accumbens with vivo‐morpholino antisense oligomers targeting either GLT‐1 or xCT (catalytic subunit of the cystine‐glutamate exchanger) overlapping with daily NAC administration during extinction (100 mg/kg, i.p. for the last 5 days). Rats then underwent cue‐induced reinstatement of active lever pressing in the absence of NAC, to determine if preventing NAC‐induced restoration of one or the other protein was sufficient to block the capacity of chronic NAC to inhibit reinstatement. The vivo‐morpholino suppression of xCT reduced cystine‐glutamate exchange but did not affect NAC‐induced reduction of reinstated cocaine seeking. In contrast, suppressing NAC‐induced restoration of GLT‐1 not only prevented NAC from inhibiting reinstatement, but augmented the capacity of cues to reinstate cocaine seeking. We hypothesized that the increased reinstatement after inhibiting NAC induction of GLT‐1 resulted from increased extracellular glutamate, and show that augmented reinstatement is prevented by blocking mGluR5. Restoring GLT‐1, not cystine‐glutamate exchange, is a key mechanism whereby daily NAC reduces cue‐induced cocaine reinstatement.
Carcinogênese de cabeça e pescoço: impacto do polimorfismo MTHFD1 G1958A

OBJECTIVE: To investigate the MTHFD1 G1958A polymorphism involved in the folate metabolism as a risk for head and neck cancer, and to find the association of the polymorphism with the risk factors and clinical and histopathological characteristics. METHODS: Retrospective study investigating MTHFD1 G1958A polymorphism in 694 subjects (240 patients in the Case Group and 454 in the Control Group) by Restriction Fragment Length Polymorphism (RFLP) Analysis. Multiple logistic regression and chi-square tests were used in the statistical analysis. RESULTS: Multivariable analysis showed that smoking and age over 42 years were disease predictors (p < 0.05). MTHFD1 1958GA or AA genotypes were associated with smoking (p = 0.04) and alcoholism (p = 0.03) and were more often found in more advanced stage tumors (p = 0.04) and in patients with a shorter survival (p = 0.03). CONCLUSION: The presence of MTHFD1 G1948A polymorphism associated with smoking and alcoholism raises the head and neck cancer risk.
Intention to start cigarette smoking among Iranian male adolescents: usefulness of an extended version of the theory of planned behaviour

Background Smoking is one of the risk behaviours that begin in adolescence, and therefore identifying predictors of smoking is necessary for planning prevention programmes. Objectives To examine the ability of the extended theory of planned behaviour (TPB) to predict the intention to smoke. Methods This was a cross-sectional study carried out in Iran, 2011. The data were collected by a self-administered questionnaire which included items on demographics, smoking behaviour, components of the TPB model (attitude, subjective norms, perceived behaviour control and intention) and an added construct on smoking self-identity. Data were analysed using descriptive, correlation and linear regression statistics. Results 365 male high school students with a mean age of 16.5 (SD=1.2) years were studied. Fifty-five (15.1%) of the students surveyed were current smokers. All components of the TPB model and smoking self identity were statistically significantly related to intention to smoke (p<0.001). The TPB constructs with and without smoking self-identity accounted for 58.5% (adjusted R2) and 54.8% of the variance observed for intention to smoke, respectively. Result also revealed the highest weights for perceived behaviour control (β=−0.35). Conclusions The extended model of the TPB predicted ‘intention to smoke’ better than the original TPB. The findings of this study might be used as a framework in designing heart disease prevention programmes. Thus the findings have implications for both health promotion specialists and cardiologists. They could place an emphasis on perceived behaviour control, specifying that individuals who do not smoke should not start and if they are smokers it is possible to stop smoking.
Acceptability of the Female Condom Among Women at Risk for HIV Infection

Few HIV/AIDS educational programs have been tailored specifically for women, and most have promoted methods requiring the full participation and cooperation of male partners. This study introduced drug-involved women to the female condom—a female-controlled method of protection from HIV and other sexually transmitted diseases. The primary aim was to assess the acceptability of this new device among high-risk women in St. Louis, San Antonio, and Rio de Janeiro. All respondents participated in a female condom education program, were asked to try the condom, and to report their experiences at two points of contact. Outcome data indicated that a sizable proportion of the women followed up used the female condom during vaginal sex on one or more occasions. In addition, many women also preferred the female condom to the male condom in terms of overall satisfaction, suggesting that there is a viable role for this device in the HIV prevention field.
Regulation of dopaminergic markers expression in response to acute and chronic morphine and to morphine withdrawal

Dopamine (DA) is thought to represent a teaching signal and has been implicated in the induction of addictive behaviours. Dysfunction of DA homeostasis leading to high or low DA levels is causally linked to addiction. Previously, it has been proposed that the transcription factors Nurr1 and Pitx3, which are critical for transcription of a set of genes involved in DA metabolism in the mesolimbic pathway, are associated with addiction pathology. Using quantitative real‐time polymerase chain reaction, immunofluorescence and Western blotting, we studied the effects of single morphine administration, morphine dependence and withdrawal on the DA markers DA transporters (DAT), vesicular monoamine transporters (VMAT2) and DA 2 receptor subtype (DRD2), DA 1 receptor subtype as well as tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and/or nucleus accumbens (NAc). In addition, Nurr1 and Pitx3 expression was also measured. Present data showed a high degree of colocalization of Nurr1 and Pitx3 with TH+ neurons in the VTA. We found that the increased Nurr1 and/or Pitx3 levels during morphine dependence and in morphine‐withdrawn rats were associated to an increase of DAT, VMAT2 and DRD2. Altogether, present data indicate that morphine dependence and withdrawal induced consistent alterations of most of the DA markers, which was correlated with transcription factors involved in the maintenance of DA neurons in drug‐reward pathways, suggesting that Nurr1 and Pitx3 regulation might be associated with controlling adaptation to chronic morphine and to morphine withdrawal‐induced alterations of DA neurons activity in the mesolimbic pathway.
Meta‐analysis of biventricular vs. right ventricular pacing mode in patients with atrial fibrillation undergoing atrioventricular nodal ablation: what was the quality of the included trials? ‐ reply

We read with interest the meta-analysis by Chatterjee et al. which reported that, compared with right ventricular (RV) pacing, biventricular (BiV) pacing had no effects on mortality, adverse events, or exercise capacity, but significantly improved quality of life and left ventricular ejection fraction (LVEF) in patients with atrial fibrillation (AF) undergoing atrioventricular nodal ablation (AVNA). We would like to raise a number of questions regarding this meta-analysis. The authors stated that the Jadad score was used to perform quality assessment of the included randomized controlled trials (RCTs). However, the actual results of their assessment were not provided. Although the Jadad score remains a commonly used scale, its use is discouraged by the Cochrane Collaboration, an organization that publishes the highest number of meta-analyses. The main issue with the Jadad score is that it ignores the impact of allocation concealment, which has been known as an important source of biases. On our preliminary assessment of the published trial reports, none of them explicitly described the method of randomization sequence concealment, and two studies [Doshi et al. (2005) and Orlov et al. (2010)] did not provide any information on the method of randomization. We feel that it is of great importance and relevance for a meta-analysis to include adequate quality assessment in order to show the readers that the conclusions drawn are indeed valid. There are also a few questions on the results presented. A flow diagram illustrating the study selection process shows that the four included trials were selected out of 36 potentially relevant citations. However, for the 32 excluded records, reasons for exclusion were only provided for 29. In addition, we are uncertain how Chatterjee et al. extracted data on all-cause and cardiac mortality from Brignole et al. (2011) since the trial publication did not describe mortality rates per group. The current evidence on the benefits of BiV pacing over RV pacing in patients with AF and left ventricular systolic dysfunction remains inconclusive. Despite the above issues, we welcome the findings of this interesting and well-written meta-analysis, and congratulate Chatterjee and colleagues for their effort in rightly highlighting the need for further randomized evidence to establish an effective selection strategy of AF patients at risk of the adverse effects of RV pacing who would thereby benefit from BiV pacing.
Pulling habits out of rats: adenosine 2A receptor antagonism in dorsomedial striatum rescues meth‐amphetamine‐induced deficits in goal‐directed action

Addiction is characterized by a persistent loss of behavioral control resulting in insensitivity to negative feedback and abnormal decision‐making. Here, we investigated the influence of methamphetamine (METH)‐paired contextual cues on decision‐making in rats. Choice between goal‐directed actions was sensitive to outcome devaluation in a saline‐paired context but was impaired in the METH‐paired context, a deficit that was also found when negative feedback was provided. Reductions in c‐Fos‐related immunoreactivity were found in dorsomedial striatum (DMS) but not dorsolateral striatum after exposure to the METH context suggesting this effect reflected a loss specifically in goal‐directed control in the METH context. This reduction in c‐Fos was localized to non‐enkephalin‐expressing neurons in the DMS, likely dopamine D1‐expressing direct pathway neurons, suggesting a relative change in control by the D1‐direct versus D2‐indirect pathways originating in the DMS may have been induced by METH‐context exposure. To test this suggestion, we infused the adenosine 2A receptor antagonist ZM241385 into the DMS prior to test to reduce activity in D2 neurons relative to D1 neurons in the hope of reducing the inhibitory output from this region of the striatum. We found that this treatment fully restored sensitivity to negative feedback in a test conducted in the METH‐paired context. These results suggest that drug exposure alters decision‐making by downregulation of the circuitry mediating goal‐directed action, an effect that can be ameliorated by acute A2A receptor inhibition in this circuit.
Incubation of extinction responding and cue‐induced reinstatement, but not context‐ or drug priming‐induced reinstatement, after withdrawal from methamphetamine

In rats trained to self‐administer methamphetamine, extinction responding in the presence of drug‐associated contextual and discrete cues progressively increases after withdrawal (incubation of methamphetamine craving). The conditioning factors underlying this incubation are unknown. Here, we studied incubation of methamphetamine craving under different experimental conditions to identify factors contributing to this incubation. We also determined whether the rats' response to methamphetamine priming incubates after withdrawal. We trained rats to self‐administer methamphetamine in a distinct context (context A) for 14 days (6 hours/day). Lever presses were paired with a discrete light cue. We then tested groups of rats in context A or a different non‐drug context (context B) after 1 day, 1 week or 1 month for extinction responding with or without the discrete cue. Subsequently, we tested the rats for reinstatement of drug seeking induced by exposure to contextual, discrete cue, or drug priming (0, 0.25 and 0.5 mg/kg). Operant responding in the extinction sessions in contexts A or B was higher after 1 week and 1 month of withdrawal than after 1 day; this effect was context‐independent. Independent of the withdrawal period, operant responding in the extinction sessions was higher when responding led to contingent delivery of the discrete cue. After extinction, discrete cue‐induced reinstatement, but not context‐ or drug priming‐induced reinstatement, progressively increased after withdrawal. Together, incubation of methamphetamine craving, as assessed in extinction tests, is primarily mediated by time‐dependent increases in non‐reinforced operant responding, and this effect is potentiated by exposure to discrete, but not contextual, cues.
The gut in the brain: the effects of bariatric surgery on alcohol consumption

Obesity represents a major medical and public health problem worldwide. Efforts have been made to develop novel treatments, and among them bariatric surgery is used as an effective treatment to achieve significant, long‐term weight loss and alleviate medical problems related to obesity. Alcohol use disorder (AUD) is also a leading cause of morbidity and mortality worldwide. Recent clinical studies have revealed a concern for bariatric surgery patients developing an increased risk for alcohol consumption, and for AUD. A better understanding of the relationship between bariatric surgery and potential later development of AUD is important, given the critical need of identifying patients at high risk for AUD. This paper reviews current clinical and basic science research and discusses potential underlying mechanisms. Special emphasis in this review is given to recent work suggesting that, alterations in alcohol metabolism/pharmacokinetics resulting from bariatric surgery are unlikely to be the primary or at least the only explanation for increased alcohol use and development of AUD, as changes in brain reward processing are also likely to play an important role. Additional studies are needed to clarify the potential role and mechanisms of how bariatric surgery may increase alcohol use and lead to AUD development.
Hypertension in pregnancy: the NICE guidelines

Hypertension in pregnancy may indicate a chronic medical problem, gestational hypertension (new hypertension without proteinuria) or pre-eclampsia (new hypertension with new proteinuria). Chronic hypertension can mimic gestational hypertension and strongly predisposes to superimposed pre-eclampsia. Gestational hypertension is often benign but may also be an early stage in the development of pre-eclampsia. Pre-eclampsia is not benign. Previously the first cause of maternal death in the UK, it is now the second.1 Maternal deaths from pre-eclampsia have not fallen recently and, most disturbingly, are associated with the highest rates of substandard care, of all causes of maternal deaths.1 It is also the most important reason for iatrogenic prematurity, a major contributor to perinatal mortality and a substantial cause of fetal growth restriction, especially with preterm disease.2 Pre-eclampsia cannot be reliably prevented or reversed once it is established except by delivery, which removes the cause—namely, the placenta. Nevertheless, the past 30 years have seen considerable advances in its management. For both mother and baby the outlook is better than it was, at least in the developed world. The new NICE guidelines for the management of hypertension in pregnancy (available on line at http://www.nice.org.uk/guidance/CG1), comprising more than 1000 pages including appendices, ambitiously review every aspect of management and the evidence upon which recommendations are based. The breadth of the guidelines reflects the complexities of their subject. They deal with many specific obstetric issues but of course the management of hypertension itself is a primary focus. Cardiovascular, obstetric or intensive care doctors will, or may be, involved at some stage, and these guidelines are also addressed to them. Hypertension is defined as in table 1. Methods of measuring blood pressure are specified separately in the NICE guidelines on antenatal care3, where the need to use devices validated specifically for use …
Further Observations on Ventricular Tachycardia As Studied by Electrical Stimulation of the Heart

Initiation and termination of tachycardia was studied by electrical stimulation of the heart in 14 patients with ventricular tachycardia (VT) not related to acute myocardial infarction (group A) and in six patients in whom the tachycardia occurred within 24 hours after the onset of acute myocardial infarction (group B). Results favor re-entry as the mechanism of tachycardia in group A patients. In group B abnormal automaticity seems more likely. In one patient with chronic recurrent VT the arrhythmia could be terminated by a single atrial premature beat. In a patient with Wolff-Parkinson-White syndrome and old myocardial infarction, VT could be initiated by a single atrial premature beat. One patient was studied while having VT during acute myocardial infarction and again five weeks later. In the acute phase of myocardial infarction no evidence for re-entry could be obtained; during the second study, however, ventricular tachycardias could be initiated and terminated by a single ventricular premature beat fulfilling the criteria of re-entry.