Miracle-dz/UniFAR-FTUs huggingface dataset:
Absence of receptor interacting protein kinase 3 prevents ethanol‐induced liver injury

Hepatocyte cell death via apoptosis and necrosis are major hallmarks of ethanol‐induced liver injury. However, inhibition of apoptosis is not sufficient to prevent ethanol‐induced hepatocyte injury or inflammation. Because receptor‐interacting protein kinase (RIP) 3–mediated necroptosis, a nonapoptotic cell death pathway, is implicated in a variety of pathological conditions, we tested the hypothesis that ethanol‐induced liver injury is RIP3‐dependent and RIP1‐independent. Increased expression of RIP3 was detected in livers of mice after chronic ethanol feeding, as well as in liver biopsies from patients with alcoholic liver disease. Chronic ethanol feeding failed to induce RIP3 in the livers of cytochrome P450 2E1 (CYP2E1)‐deficient mice, indicating CYP2E1‐mediated ethanol metabolism is critical for RIP3 expression in response to ethanol feeding. Mice lacking RIP3 were protected from ethanol‐induced steatosis, hepatocyte injury, and expression of proinflammatory cytokines. In contrast, RIP1 expression in mouse liver remained unchanged following ethanol feeding, and inhibition of RIP1 kinase by necrostatin‐1 did not attenuate ethanol‐induced hepatocyte injury. Ethanol‐induced apoptosis, assessed by terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick‐end labeling–positive nuclei and accumulation of cytokeratin‐18 fragments in the liver, was independent of RIP3. Conclusion: CYP2E1‐dependent RIP3 expression induces hepatocyte necroptosis during ethanol feeding. Ethanol‐induced hepatocyte injury is RIP3‐dependent, but independent of RIP1 kinase activity; intervention of this pathway could be targeted as a potential therapeutic strategy. (HEPATOLOGY 2013)
Postpartum Maternal Sleep, Maternal Depressive Symptoms and Self-Perceived Mother–Infant Emotional Relationship

This study examined the links between maternal sleep, maternal depressive symptoms, and mothers’ perceptions of their emotional relationship with their infant in a self-recruited sample of mothers. Eighty mothers of infants 3–18 months old completed sleep diaries for 5 consecutive nights, and questionnaires assessing sleep (Insomnia Severity Index [ISI]), depressive symptom severity (Edinburgh Postnatal Depression Scale [EPDS]), and perceived mother–infant relationship (Postpartum Bonding Questionnaire [PBQ] and Maternal Postnatal Attachment Questionnaire [MPAQ]). Significant correlations, controlling for depression severity, were found between more disturbed maternal sleep and more negative maternal perceptions of the mother-infant relationship. Regression analyses revealed that EPDS showed the strongest association with PBQ, whereas ISI demonstrated the strongest association with MPAQ. The present study highlights the importance of deepening and expanding our understanding of the negative implications of maternal sleep problems.
The Use of Media as a Sleep Aid in Adults

A sample of 844 adults, aged 18–94 years old, was queried about media habits and sleep behavior in face-to-face interviews with standardized questionnaires. A substantial proportion of this sample reported using books (39.8%), television (31.2%), music (26.0%), Internet (23.2%), and videogames (10.3%) as a sleep aid. The use of media as sleep aids was associated with increased fatigue and higher scores on the Pittsburgh Sleep Quality Index (PSQI), indicating poorer sleep quality. There was no relationship with sleep duration. Finally, results suggest that media use coincides with later bedtimes, but also later rise times, a process called time shifting.
Retinol binding protein 4 stimulates hepatic sterol regulatory element‐binding protein 1 and increases lipogenesis through the peroxisome proliferator‐activated receptor‐γ coactivator 1β‐dependent pathway

Recent studies have revealed the essential role of retinol binding protein 4 (RBP4) in insulin resistance. However, the impact of RBP4 on aberrant lipogenesis, the common hepatic manifestation in insulin resistance states, and the underlying mechanism remain elusive. The present study was designed to examine the effect of RBP4 on sterol regulatory element‐binding protein (SREBP‐1) and hepatic lipogenesis. Treatment with human retinol‐bound RBP4 (holo‐RBP4) significantly induced intracellular triglyceride (TAG) synthesis in HepG2 cells and this effect is retinol‐independent. Furthermore, RBP4 treatment enhanced the levels of mature SREBP‐1 and its nuclear translocation, thereby increasing the expression of lipogenic genes, including fatty acid synthase (FAS), acetyl coenzyme A carboxylase‐1 (ACC‐1), and diacylglycerol O‐acyltransferase 2 (DGAT‐2). Stimulation of HepG2 cells with RBP4 strongly up‐regulated the expression of transcriptional coactivator peroxisome proliferator‐activated receptor‐γ coactivator 1β (PGC‐1β) at both the messenger RNA (mRNA) and protein levels. The transcriptional activation of PGC‐1β is necessary and sufficient for the transcriptional activation of SREBP‐1 in response to RBP4. The cyclic adenosine monophosphate (cAMP)‐response element binding protein (CREB) was identified as the target transcription factor involved in the RBP4‐mediated up‐regulation of PGC‐1β transcription as a result of phosphorylation on Ser133. Furthermore, in vivo RBP4 infusion induced SREBP‐1c activation and consequently accelerated hepatic lipogenesis and plasma TAG in C57BL/6J mice, a phenomenon not observed in Ppargc1b knockout mice. Conclusion: These findings reveal a novel mechanism by which RBP4 achieves its effects on hepatic lipid metabolism. (HEPATOLOGY 2013;8:564‐575)
The combined effect of recombinant human epidermal growth factor and erythropoietin on full‐thickness wound healing in diabetic rat model

Diabetic wound is a chronic wound in which normal process of wound healing is interrupted. Lack of blood supply, infection and lack of functional growth factors are assumed as some of the conditions that lead to non‐healing environment. Epidermal growth factor (EGF) acts primarily to stimulate epithelial cell growth across wound. Erythropoietin (EPO) is a haematopoietic factor, which stimulates the production, differentiation and maturation of erythroid precursor cells. This study hypothesised combining these two factors, non‐healing process of diabetic wound will be compensated and eventually lead to acceleration of wound healing compared with single growth factor treatment. A total of 30 diabetic Sprague–Dawley rats were divided into three treatment groups (single treatment of rh‐EPO or rh‐EGF or combined treatment on a full‐thickness skin wound). To assess the wound healing effects of the components, the wound size and the healing time were measured in each treatment groups. The skin histology was examined by light microscopy and immunohistochemical analysis of proliferating markers was performed. The combined treatment with rh‐EPO and rh‐EGF improved full‐thickness wound significantly (P < 0·05) accelerating 50% healing time with higher expression of Ki‐67 compared with single growth factor‐treated groups. The combined treatment failed to accelerate the total healing time when compared with single growth factor treatments. However, the significant improvement were found in wound size reduction in the combined treatment group on day 4 against single growth factor‐treated groups (P < 0·05). This study demonstrated that the combined treatment of rh‐EPO and rh‐EGF improved the wound healing possibly through a synergistic action of each growth factor. This application provides further insight into combined growth factor therapy on non‐healing diabetic wounds.
Association Between Sleep Problems and Symptoms of Attention Deficit Hyperactivity Disorder in Adolescence: Results From a Large Population-Based Study

Sleep problems and symptoms of ADHD are common in adolescence, but detailed epidemiological assessment of their association is lacking. Using data from a recent population-based study, 9,846 adolescents aged 16 to 19 provided detailed information on sleep and symptoms of ADHD. Results confirmed a large overlap between self-reported symptoms of ADHD and all sleep variables studied. Symptoms of ADHD were linked to shorter sleep duration, longer sleep latency, and nocturnal wake time, as well as larger sleep deficiency. ADHD symptoms also increased the odds of insomnia and delayed sleep phase syndrome. The associations were only partially explained by confounders (mainly depression). The findings suggest that sleep problems should be included as a treatment target in efforts to reduce symptoms of ADHD in adolescence.
To Drug or Not to Drug: A Qualitative Study of Patients’ Decision-Making Processes for Managing Insomnia

Treatment preferences play a key role in dictating sleep health outcomes. However, patients’ treatment beliefs, attitudes, and experiences that inform preference conceptualization remain an unknown phenomenon. Therefore, this study aims to explore patient perceptions toward pharmacotherapy and the nonpharmacological management of insomnia. Fifty-one patients with insomnia were recruited from specialist clinics and general community settings. Participants completed a brief questionnaire followed by an in-depth semistructured interview that was digitally recorded, transcribed verbatim, and subjected to Framework Analysis to identify emergent themes. Three key themes were identified: Resolving Insomnia, Self-Imposed Treatment Boundaries, and Treatment Uptake. Patients’ illness, treatment, and psychosocial beliefs and experiences are closely linked to treatment choice. Being attuned to these influences during the clinical encounter can facilitate treatment selection that is meaningful for the patient.
Assessing Stress-Induced Sleep Reactivity in College Students: The European Portuguese Version of the Ford Insomnia Response to Stress Test (FIRST)

ABSTRACT Objective and Background: Over the past few years, the comprehensive models of insomnia have exhibited impressive developments. However, there is scarce knowledge on predisposing or vulnerability factors for insomnia. One of the most promising constructs to aid in filling this gap is stress-induced sleep reactivity assessed through self-report. Our aim was to study the psychometric properties of the European Portuguese version of the Ford Insomnia Response to Stress Test (FIRST). Participants: We recruited a large sample of students attending medical school (N = 699). Methods: Several analyses were carried out such as internal consistency, construct validity, and discriminant groups’ analysis. Results: It was observed that FIRST-PT shows good internal consistency (Cronbach´s alpha = .81) and validity indicators. Interestingly, and contrary to what was observed in the previously published studies on psychometric properties of the FIRST, it was observed that a two-factor solution (Factor I = rumination, Factor II = worry) was the most adequate one to explain the correlation matrix, accounting for approximately 44% of the total variance. Conclusions: The FIRST-PT proved to be a useful and reliable tool to measure stress-induced sleep reactivity. However, these results should be replicated in other groups, particularly clinical samples, in order to verify the stability of its factorial dimension.
Associations of Insomnia Symptoms With Blood Pressure and Resting Heart Rate: The HUNT Study in Norway

ABSTRACT Objective: Although elevated heart rate and blood pressure might represent biologically plausible links for the association of insomnia symptoms with increased risk of cardiovascular disease (CVD), few large studies have investigated the associations of insomnia symptoms with these factors. Our aim was to investigate the associations of self-reported insomnia symptoms with systolic and diastolic blood pressure and resting heart rate in a large population-based study. Participants: Self-reported information on insomnia symptoms, including sleep initiation problems, frequent awakening and early awakenings during night, and measurements of resting heart rate and blood pressure were collected from a total of 50,806 men and women who participated in the third wave of the Nord-Trøndelag Health Study (HUNT-3) in 2006–2008. Methods: In multivariable analyses, we adjusted for sociodemographic factors, lifestyle factors, established CVD risk factors, and snoring or breathing pauses. Results: Compared to participants reporting none of the insomnia symptoms, those having all three insomnia symptoms several times a week had lower diastolic blood pressure (–0.80 [95% CI: –1.47 to –0.14] mmHg, p = 0.02), lower systolic blood (–1.69 [95% CI: –2.76 to –0.63) mmHg, p < 0.001), and higher resting heart rate (0.83 [95% CI: 0.11 to 1.55] beats/minute, p = 0.02). Conclusions: We found a modest positive association of insomnia symptoms with resting heart rate, and a modest inverse association of insomnia with blood pressure. However, the actual differences were small, and likely of less clinical importance. Prospective studies are needed to establish whether the potential link between insomnia and CVD is mediated through changes in heart rate and/or blood pressure.
Dendritic cells limit fibroinflammatory injury in nonalcoholic steatohepatitis in mice

Nonalcoholic steatohepatitis (NASH) is the most common etiology of chronic liver dysfunction in the United States and can progress to cirrhosis and liver failure. Inflammatory insult resulting from fatty infiltration of the liver is central to disease pathogenesis. Dendritic cells (DCs) are antigen‐presenting cells with an emerging role in hepatic inflammation. We postulated that DCs are important in the progression of NASH. We found that intrahepatic DCs expand and mature in NASH liver and assume an activated immune phenotype. However, rather than mitigating the severity of NASH, DC depletion markedly exacerbated intrahepatic fibroinflammation. Our mechanistic studies support a regulatory role for DCs in NASH by limiting sterile inflammation through their role in the clearance of apoptotic cells and necrotic debris. We found that DCs limit CD8+ T‐cell expansion and restrict Toll‐like receptor expression and cytokine production in innate immune effector cells in NASH, including Kupffer cells, neutrophils, and inflammatory monocytes. Consistent with their regulatory role in NASH, during the recovery phase of disease, ablation of DC populations results in delayed resolution of intrahepatic inflammation and fibroplasia. Conclusion: Our findings support a role for DCs in modulating NASH. Targeting DC functional properties may hold promise for therapeutic intervention in NASH. (HEPATOLOGY 2013;58:589–602)
The antimalarial ferroquine is an inhibitor of hepatitis C virus†, ‡

Hepatitis C virus (HCV) is a major cause of chronic liver disease. Despite recent success in improving anti‐HCV therapy, additional progress is still needed to develop cheaper and interferon (IFN)‐free treatments. Here, we report that ferroquine (FQ), an antimalarial ferrocenic analog of chloroquine, is a novel inhibitor of HCV. FQ potently inhibited HCV infection of hepatoma cell lines by affecting an early step of the viral life cycle. The antiviral activity of FQ on HCV entry was confirmed with pseudoparticles expressing HCV envelope glycoproteins E1 and E2 from six different genotypes. In addition to its effect on HCV entry, FQ also inhibited HCV RNA replication, albeit at a higher concentration. We also showed that FQ has no effect on viral assembly and virion secretion. Using a binding assay at 4°C, we showed that FQ does not prevent attachment of the virus to the cell surface. Furthermore, virus internalization was not affected by FQ, whereas the fusion process was impaired in the presence of FQ as shown in a cell‐cell fusion assay. Finally, virus with resistance to FQ was selected by sequential passage in the presence of the drug, and resistance was shown to be conferred by a single mutation in E1 glycoprotein (S327A). By inhibiting cell‐free virus transmission using a neutralizing antibody, we also showed that FQ inhibits HCV cell‐to‐cell spread between neighboring cells. Combinations of FQ with IFN, or an inhibitor of HCV NS3/4A protease, also resulted in additive to synergistic activity. Conclusion: FQ is a novel, interesting anti‐HCV molecule that could be used in combination with other direct‐acting antivirals. (HEPATOLOGY 2013)
The Short-Term Efficacy of an Unguided Internet-Based Cognitive-Behavioral Therapy for Insomnia: A Randomized Controlled Trial With a Six-Month Nonrandomized Follow-Up

ABSTRACT Objective: Insomnia is a major health problem, and the need for effective and accessible treatment is urgent. The aim of the current study was to evaluate the short-term efficacy of an unguided Internet-based cognitive-behavioral treatment program for insomnia (CBTi), called SHUTi (Sleep Healthy Using the Internet). Methods: This study used a parallel arm randomized controlled trial in Norway. Participants were randomly allocated to the SHUTi condition or a Web-based patient education condition. Both groups were assessed before and after the nine-week intervention period (online sleep diaries and questionnaires). The SHUTi participants were reassessed in a six-month nonrandomized follow-up. Primary outcome measures were the Insomnia Severity Index (ISI) and the Bergen Insomnia Scale (BIS). Results: A total of 181 participants were included in the study; SHUTi condition (n = 95), patient education condition (n = 86). Intention-to-treat mixed-model repeated-measures analysis revealed that the SHUTi group had better short-term outcomes compared with the patient education group on most sleep measures. The SHUTi group showed a significant decrease on the primary outcomes, the ISI (dbetween = –1.77, 95% CI = –2.23, –1.31) and the BIS (dbetween = –1.00, 95% CI = –1.32, –.68). Improvements were maintained among the completing SHUTi participants at the six-month nonrandomized follow-up. However, dropout attrition was high. Conclusion: Unguided Internet-based CBTi produced significant short-term improvements in sleep in patients with chronic insomnia. This highlights the benefits of making Internet-delivered CBTi programs available as a standard first-line treatment option in public health services. Nevertheless, the rate of dropout attrition (participants not completing post-assessment) in this trial limits the generalizability of the findings.
Comparison of Sleep Characteristics, Patterns, and Problems in Young Children Within the Southeast Asian Region

ABSTRACT Background and objectives: Optimal sleeping habits are important for health development of infants. The role of culture in sleep habits cannot be underestimated. We aimed to characterize sleep patterns, sleep practices, and sleep problems; and assess the sleep settings and parental perceptions of sleep problems in children from birth to 36 months in countries in the Southeast Asian (SEA) region. Participants: Parents and caregivers of infants and toddlers (birth to 36 months old) from countries in Southeast Asia participated in this study. Methods: Data was collected using the Brief Infant Sleep Questionnaire for a total of 5,987 children from 6 countries in the SEA region (967 Indonesia/ID, 997 Malaysia/MY, 1,034 Philippines/PH, 1,001 Singapore/SG, 988 Thailand/TH, and 1,000 Vietnam/VN). Results: The sleep variables varied among SEA children studied. Bedtimes and nighttime sleep varied across the region by as much as 1 hr 34 min and 1 hr 15 min respectively. Conclusions: Despite being geographically very close together and having some common sociocultural characteristics, sleep variables in the young child within the SEA region do differ in significant ways.
Nursing Student Clinical Shift Completion as a Predictor of NCLEX Failure

As competition for clinical sites increases, hospitals and nursing schools report the use of nontraditional student placements such as one 12-hour clinical shift; that was an option offered by the author’s school. The author discusses implementation of 12-hour shifts and compared NCLEX fail rates of students on one 12-hour shift with students who had 2 weekly 6-hour shifts.
An investigation of the mental health needs of children looked after by craigavon and banbridge health and social services trust

Rates of mental health difficulties were investigated among children in substitute care across five childcare teams in Craigavon and Banbridge H+SS Trust. A total of 64 children were assessed using a behavioural screening instrument. Results indicate that more than 60% of 4–10 year olds assessed may have a diagnosable psychiatric disorder. The presence of such a disorder is probable in almost 50%. Among the 11–16 year olds assessed, the proportion likely to have a diagnosable disorder is slightly higher at almost two-thirds of the sample group. A significant number of children appeared in more than one diagnostic category, indicating the complexity of their presentation and probable co-morbid diagnoses. The implications of these results for further research and for the provision of mental health services to young people in substitute care are discussed.
Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients With liver cirrhosis

Entecavir is a potent antiviral agent with high genetic barrier to resistance, hence it is currently recommended as first‐line antiviral therapy for chronic hepatitis B (CHB). The aim of this study was to investigate the efficacy of entecavir on clinical outcomes and deaths. It was a retrospective‐prospective cohort study based on two cohorts of patients. The entecavir cohort included consecutive CHB patients who had received entecavir 0.5 mg/day for at least 12 months. The historical control cohort included untreated patients recruited since 1997 who underwent routine clinical care. The primary outcome was the 5‐year cumulative probability of hepatic events, defined as any cirrhotic complications, hepatocellular carcinoma (HCC), and/or liver‐related mortality. A total of 1,446 entecavir‐treated patients (72% men; age, 51 ± 12 years; follow‐up, 36 ± 13 months) and 424 treatment‐naïve patients (65% men; age, 41 ± 13 years; follow‐up, 114 ± 31 months) were studied. Overall, there was no difference in hepatic events between the entecavir and control cohorts. Among patients with liver cirrhosis (482 entecavir‐treated, 69 treatment‐naïve), entecavir‐treated patients had reduced risks of all clinical outcomes when compared with treatment‐naïve patients with cirrhosis after adjusted for model for end‐stage liver disease score: hepatic events (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.34‐0.78; P = 0.002), HCC (HR, 0.55; 95% CI, 0.31‐0.99; P = 0.049), liver‐related mortality (HR, 0.26; 95% CI, 0.13‐0.55; P < 0.001), and all‐cause mortality (HR, 0.34; 95% CI, 0.18‐0.62; P < 0.001). Entecavir‐treated patients with cirrhosis who failed to achieve undetectable hepatitis B virus DNA (105/482 [22%]) had comparable risk of hepatic events as the untreated patients. Conclusion: Entecavir therapy reduces the risks of hepatic events, HCC, liver‐related and all‐cause mortality of CHB patients with liver cirrhosis in 5 years, particularly among those who had maintained viral suppression. (Hepatology 2013;58:1537–1547)