Miracle-dz/UniFAR-FTUs huggingface dataset:
Elder Abuse: Some Caucasian-American Views

ABSTRACT To gain a greater understanding of what “elder abuse” means to the American public, a random sample of adults from seven culturally diverse counties in North Carolina was interviewed. Caucasian-Americans from five different counties and regions of the state were represented in the sample. The Caucasian-American groups' responses were compared with each other and with those of a panel of elder mistreatment experts. There were areas of agreement and disagreement. The relevance of the findings is discussed in relation to research, practice, education, and policy.
Noninvasive fatty liver markers predict liver disease mortality in the U.S. population

Nonalcoholic fatty liver disease (NAFLD) contributes to premature death along with obesity, diabetes, and cardiovascular disease (CVD). We examined whether hepatic steatosis (HS) on ultrasound and liver enzyme activities were associated with increased liver disease mortality in the U.S. National Health and Nutrition Examination Survey (NHANES), 1988‐1994, with up to 23 years of linked‐mortality data. Survey‐linked National Death Index records were analyzed among 14,527 adult participants who were negative for viral hepatitis B and C and iron overload. HS on ultrasound was categorized as normal, mild, moderate, or severe. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma‐glutamyltransferase (GGT) elevation was defined as the highest sex‐specific decile. Cumulative mortality was 36.2% from all causes, including 16.3% from CVD, 10.8% from cancer, 5.4% from diabetes, and 1.1% from liver disease. Severe HS was associated with increased liver disease mortality in both age‐adjusted (hazard ratio [HR]: 3.92; 95% confidence interval [CI]: 1.49‐10.27; P for trend: 0.011) and multivariate‐adjusted analyses (HR, 2.68; 95% CI: 1.02‐7.03; P for trend: 0.072). HS was not independently associated with mortality from all causes, CVD, cancer, or diabetes. Higher liver disease mortality was found with elevated ALT (HR, 4.08; 95% CI: 1.99‐8.33), AST (HR, 4.33; 95% CI: 2.18‐8.59), and GGT (HR, 7.91; 95% CI: 3.06‐20.46). GGT elevation was associated with increased overall mortality (HR, 1.45; 95% CI: 1.21‐1.74). Liver enzymes were otherwise unrelated to overall or cause‐specific mortality. Conclusions: In the U.S. population, severe hepatic steatosis on ultrasound and liver enzyme elevation were associated with increased liver disease mortality, but were not independently associated with mortality from all causes (except for GGT), CVD, cancer, or diabetes. (Hepatology 2016;63:1170–1183)
The 3‐month readmission rate remains unacceptably high in a large North American cohort of patients with cirrhosis

In smaller single‐center studies, patients with cirrhosis are at a high readmission risk, but a multicenter perspective study is lacking. We evaluated the determinants of 3‐month readmissions among inpatients with cirrhosis using the prospective 14‐center North American Consortium for the Study of End‐Stage Liver Disease cohort. Patients with cirrhosis hospitalized for nonelective indications provided consent and were followed for 3 months postdischarge. The number of 3‐month readmissions and their determinants on index admission and discharge were calculated. We used multivariable logistic regression for all readmissions and for hepatic encephalopathy (HE), renal/metabolic, and infection‐related readmissions. A score was developed using admission/discharge variables for the total sample, which was validated on a random half of the total population. Of the 1353 patients enrolled, 1177 were eligible on discharge and 1013 had 3‐month outcomes. Readmissions occurred in 53% (n = 535; 316 with one, 219 with two or more), with consistent rates across sites. The leading causes were liver‐related (n = 333; HE, renal/metabolic, and infections). Patients with cirrhosis and with worse Model for End‐Stage Liver Disease score or diabetes, those taking prophylactic antibiotics, and those with prior HE were more likely to be readmitted. The admission model included Model for End‐Stage Liver Disease and diabetes (c‐statistic = 0.64, after split‐validation 0.65). The discharge model included Model for End‐Stage Liver Disease, proton pump inhibitor use, and lower length of stay (c‐statistic = 0.65, after split‐validation 0.70). Thirty percent of readmissions could not be predicted. Patients with liver‐related readmissions consistently had index‐stay nosocomial infections as a predictor for HE, renal/metabolic, and infection‐associated readmissions (odds ratio = 1.9‐3.0). Conclusions: Three‐month readmissions occurred in about half of discharged patients with cirrhosis, which were associated with cirrhosis severity, diabetes, and nosocomial infections; close monitoring of patients with advanced cirrhosis and prevention of nosocomial infections could reduce this burden. (Hepatology 2016;64:200–208)
Acetyl‐coenzyme A carboxylase alpha promotion of glucose‐mediated fatty acid synthesis enhances survival of hepatocellular carcinoma in mice and patients

Solid tumors often suffer from suboptimal oxygen and nutrient supplies. This stress underlies the requirement for metabolic adaptation. Aberrantly activated de novo lipogenesis is critical for development and progression of human hepatocellular carcinoma (HCC). However, whether de novo lipogenesis influences biological behaviors of HCCs under conditions of metabolic stress are still poorly understood. Here, we show that HCCs display distinct levels of glucose‐derived de novo lipogenesis, which are positively correlated with their survival responses to glucose limitation. The enhanced lipogenesis in HCCs is characterized by an increased expression of rate‐limiting enzyme acetyl‐coenzyme A carboxylase alpha (ACCα). ACCα‐mediated fatty acid (FA) synthesis determines the intracellular lipid content that is required to maintain energy hemostasis and inhibit cell death by means of FA oxidation (FAO) during metabolic stress. In accord, overexpression of ACCα facilitates tumor growth. ACCα forms a complex with carnitine palmitoyltransferase 1A (CPT1A) and prevents its mitochondria distribution under nutrient‐sufficient conditions. During metabolic stress, phosphorylation of ACCα leads to dissociation of the complex and mitochondria localization of CPT1A, thus promoting FAO‐mediated cell survival. Therefore, ACCα could provide both the substrate and enzyme storage for FAO during glucose deficiency. Up‐regulation of ACCα is also significantly correlated with poorer overall survival and disease recurrence postsurgery. Multivariate Cox's regression analysis identified ACCα as an effective predictor of poor prognosis. Conclusion: These results present novel mechanistic insight into a pivotal role of ACCα in maintaining HCC survival under metabolic stress. It could be exploited as a novel diagnostic marker and therapeutic target. (Hepatology 2016;63:1272–1286)
Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha

Matrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect on primary hepatocyte function is unknown. We hypothesized that increased matrix rigidity in fibrotic livers would activate mechanotransduction in hepatocytes and lead to inhibition of liver‐specific functions. To determine the physiologically relevant ranges of matrix stiffness at the cellular level, we performed detailed atomic force microscopy analysis across liver lobules from normal and fibrotic livers. We determined that normal liver matrix stiffness was around 150 Pa and increased to 1‐6 kPa in areas near fibrillar collagen deposition in fibrotic livers. In vitro culture of primary hepatocytes on collagen matrix of tunable rigidity demonstrated that fibrotic levels of matrix stiffness had profound effects on cytoskeletal tension and significantly inhibited hepatocyte‐specific functions. Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α), whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network. Fibrotic levels of matrix stiffness activated mechanotransduction in primary hepatocytes through focal adhesion kinase. In addition, blockade of the Rho/Rho‐associated protein kinase pathway rescued HNF4α expression from hepatocytes cultured on stiff matrix. Conclusion: Fibrotic levels of matrix stiffness significantly inhibit hepatocyte‐specific functions in part by inhibiting the HNF4α transcriptional network mediated through the Rho/Rho‐associated protein kinase pathway. Increased appreciation of the role of matrix rigidity in modulating hepatocyte function will advance our understanding of the mechanisms of hepatocyte dysfunction in liver cirrhosis and spur development of novel treatments for chronic liver disease. (Hepatology 2016;64:261–275)
Current Concepts and New Trends in the Diagnosis and Management of Recurrent Miscarriage

Abstract Pregnancy is a proinflammatory and hypercoagulable state. Miscarriage concerns approximately 15% of pregnancies. Recurrent miscarriage is a rather rare condition with an estimated incidence of 1% to 3%. However, despite years of investigation, the etiology is not established in up to 50% of cases. A multidisciplinary approach in the evaluation of miscarriage is essential to understand the cause and risk of recurrence. Although genetic factors are the major cause of spontaneous miscarriages, their relationship with recurrent miscarriage is less frequent. Recently, many kinds of genetic polymorphisms have also been found to be associated. Endocrine disorders such as poorly controlled diabetes, polycystic ovary syndrome, and hypothyroidism are linked with recurrent miscarriage. The relationship between recurrent miscarriage and subclinical thyroid disorders and thyroid autoimmunity is disputed, especially in early miscarriages. Uterine malformations should be considered as a cause of recurrent miscarriage. Although autoimmune-based recurrent miscarriage has been described, mainly antiphospholipid antibodies, the role of alloimmune mechanisms remains poorly understood. The influence of congenital thrombophilia is controversial. Antiphospholipid syndrome or antiphospholipid antibody–related recurrent miscarriage, and some endocrinologic disorders, have a specific and effective treatment. Still, the effectiveness of some common treatments needs to be demonstrated. Target Audience: Obstetricians and gynecologists, family physicians Learning Objectives: After completing this CME activity, physicians should be better able to determine the various causes of recurrent miscarriage, evaluate the physiopathologic basis of some disorders, diagnose and treat women with recurrent miscarriage, and identify new trends in clinical research in this field.
Perioperative Care of an Adolescent With 11-Beta-Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) is the result of an autosomal recessive disorder affecting one of the several steps required for the synthesis of cortisol from cholesterol by the adrenal cortex. 11? -hydroxylase deficiency accounts for 5-8% of all cases of CAH with an incidence estimated at 1 in 100,000 - 200,000 newborns. We present a 14-year-old girl with CAH due to 11? -hydroxylase deficiency who presented for surgical treatment of virilization. The perioperative care of patients with CAH should address issues related to the deficient and excessive production of specific mineralocorticoids and corticosteroids by the adrenal cortex. The authors discuss the perioperative implications of the disorder and review previous reports of anesthetic care for such patients. J Med Cases. 2015;6(5):221-225 doi: http://dx.doi. org/10.14740/jmc2125w
Mechanisms and Prevention of Alloimmunization in Pregnancy

Transfusion only occasionally gives rise to antibody production, because blood cells per se are not markedly immunogenic. However, the immunological changes that occur during pregnancy increase the risk of alloimmunization against red blood cells, platelets, and/or leukocytes. Fetal-maternal bleeding during pregnancy or in relation to delivery is the antigenic stimuli for immunization against red blood cells, whereas other mechanisms, such as trophoblast-derived microparticles, may also play a role in the production of antibodies against platelets. Antibody-mediated immune suppression has for 4 decades successfully been used for prevention of RhD immunization. Result from a mouse model of fetal and neonatal alloimmune thrombocytopenia (FNAIT) suggests that the same principle may be applied for the prevention of FNAIT. A European Union–funded consortium is presently in the process of developing a hyperimmune anti–human platelet antigen 1a (HPA-1a) immunoglobulin G. The idea is to prevent HPA-1a immunization by administering the drug to nonimmunized HPA-1a–negative women after delivery of an HPA-1a–positive child. The anti–HPA-1a will be purified from plasma collected from women who previously have given birth to a child with FNAIT caused by anti–HPA-1a. If the results of the planned phase III trial are favorable, it is possible that a product for prevention of FNAIT will be available within this decade. Target Audience: Obstetricians and gynecologists, family physicians Learning Objectives: After completing this CME activity, physicians should be better able to evaluate the immunological principles behind alloimmunization in pregnancy, compare the attributes of the 3 major hypotheses regarding how Rh prophylaxis works, and explain the most recent endeavors to develop a prophylaxis against fetal and neonatal alloimmune thrombocytopenia.
Autophagy protein ATG5 regulates CD36 expression and anti-tumor MHC class II antigen presentation in dendritic cells

ABSTRACT Macroautophagy/autophagy has been implicated in cytoplasmic and viral antigen presentation on major histocompatibility complex (MHC) class II molecules. However, the role of autophagy in the presentation of phagocytized tumor-associated antigens in vivo remains unclear. Following the administration of apoptotic tumor cells and in vivo chemotherapy, mice with a dendritic cell–specific deletion of Atg5, a key autophagy gene, exhibit reduced CD4+ T-cell priming but not CD8+ cytotoxic T-cell priming. Interestingly, Atg5-deficient dendritic cells have an elevated expression of scavenger receptor CD36 and show excessive lipid accumulation. Atg5-deficient dendritic cells increased CD36-dependent phagocytosis of apoptotic tumor cells. CD36 blockade ameliorates elevated phagocytosis and increases CD4+ T-cell priming in dendritic cells; intratumoral CD36 blockade inhibits tumor growth. Our results demonstrate that Atg5 is required for proper antigen phagocytosis and presentation to MHC class II via modulation of CD36 in dendritic cells and may be a future therapeutic target for anti-tumor therapy. Abbreviations: APC: antigen-presenting cell; ATG: autophagy-related; BMDC: bone marrow–derived dendritic cell; BODIPY: 4,4-difluoro-1,3,5,7,8-pentamethyl-4-bora-3a,4a-diaza-s-indacene; CSFE: carboxyfluorescein diacetate succinimidyl ester; DAPI: 4ʹ,6-diamidino-2-phenylindole; IFNG/IFN-γ: interferon gamma; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MHC: major histocompatibility complex; NLDC: neonatal liver–derived dendritic cell; PDCD1/PD-1: programmed cell death 1; PI: propidium iodide; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol 3-phosphate; SERPINB/OVA: serine (or cysteine) peptidase inhibitor, clade B; TIMD4/TIM-4: T cell immunoglobulin and mucin domain containing 4
Risk of hepatocellular carcinoma after sustained virological response in Veterans with hepatitis C virus infection

The long‐term prognosis in terms of risk or predictors of developing hepatocellular carcinoma (HCC) among patients with sustained virological response (SVR) remains unclear. We conducted a retrospective cohort study using data from the Veterans Affairs VA hepatitis C virus (HCV) Clinical Case Registry in patients with positive HCV RNA between October 1999 and August 2009 and follow‐up through December 2010. HCV treatment (interferon with or without ribavirin) and SVR (RNA test negative at least 12 weeks after the end of treatment) were determined. We used Cox's proportional hazards models to calculate hazard ratios (HRs) for potential predictors (demographic, virological, and clinical) associated with HCC development post‐SVR. We identified 33,005 HCV‐infected individuals who received treatment, of whom 10,817 achieved SVR. Among these patients, 100 developed new HCC during a total follow‐up of 30,562 person‐years for an overall incidence rate of 0.33% per year. Annual risk of HCC remained considerably high among patients with cirrhosis (1.39%) and those cured after age 64 (0.95%). Patients with diabetes (adjusted HR = 1.88; 1.21‐2.91) or genotype 3 infection (adjusted HR = 1.62; 0.96‐2.734) were significantly more likely to develop HCC. Conclusions: Risk of HCC after HCV cure, though considerably reduced, remains relatively high at 0.33% per year. Older age and/or presence of cirrhosis at the time of SVR are associated with a high enough risk to warrant surveillance. Diabetes is also a risk factor for post‐SVR HCC. (Hepatology 2016;64:130–137)
Bayesian Joint Modelling of Disease Progression Marker and Time to Death Event of HIV/AIDS Patients under ART Follow-up

Objectives: To develop separate and joint statistical models in the Bayesian framework for longitudinal measurements and time to death event data of HIV/AIDS patients. Study design: Longitudinal study. Place and Duration of Study: The population of study includes all HIV/AIDS patients who had been under follow up of Antiretroviral Therapy (ART) from January 2006 to December 2012 at Shashemene Referral Hospital in Ethiopia. Methodology: The posterior model was analyzed using Gibbs sampler by sampling from the distributions of the parameters given the data. Convergence of each sample was maintained.
Sleep deprivation is an additional stress for parents staying in hospital.

PURPOSE This study aims to describe the sleep experience of parents staying overnight with their children in hospital. DESIGN AND METHODS Parents (n = 102) completed the Verran and Snyder-Halpern Sleep Scale following a night spent with their children in an Australian tertiary pediatric hospital. RESULTS Parents experienced sleep deprivation and poor quality of sleep, reporting a mean sleep period of 4.6 hr (SD = 2.1). Having only one child in the room was the only variable that significantly influenced the quality or amount of parental sleep. PRACTICE IMPLICATIONS Parental sleep deprivation needs to be acknowledged and accommodated when nurses and parents negotiate the care of children in hospital.
The Humpty Dumpty Falls Scale: a case-control study.

PURPOSE The purpose of this descriptive study was to assess whether the Humpty Dumpty Falls Scale (HDFS) identifies hospitalized pediatric patients at high risk for falls. DESIGN AND METHODS The study was a matched case-control design. A chart review of 153 pediatric cases who fell and 153 controls who did not fall were pair-matched by age, gender, and diagnosis. RESULTS High-risk patients fell almost twice as often as low-risk patients (odds ratio 1.87, confidence interval = 1.01, 3.53, p = .03). PRACTICE IMPLICATIONS A Falls Prevention Pediatric Program with the HDFS tool addresses the Joint Commission Patient Safety Goals, but further research is needed to examine HDFS sensitivity-specificity.
The secretin/secretin receptor axis modulates liver fibrosis through changes in transforming growth factor‐β1 biliary secretion in mice

The secretin/secretin receptor (SR) axis is up‐regulated by proliferating cholangiocytes during cholestasis. Secretin stimulates biliary proliferation by down‐regulation of let‐7a and subsequent up‐regulation of the growth‐promoting factor, nerve growth factor (NGF). It is not known whether the secretin/SR axis plays a role in subepithelial fibrosis observed during cholestasis. Our aim was to determine the role of the secretin/SR axis in activation of biliary fibrosis in animal models and human primary sclerosing cholangitis (PSC). Studies were performed in wild‐type (WT) mice with bile duct ligation (BDL), BDL SR−/− mice, or Mdr2−/− mouse models of cholestatic liver injury. In selected studies, the SR antagonist (Sec 5‐27) was used to block the secretin/SR axis. Biliary proliferation and fibrosis were evaluated as well as secretion of secretin (by cholangiocytes and S cells), expression of markers of fibrosis, transforming growth factor‐β1 (TGF‐β1), transforming growth factor‐β1 receptor (TGF‐β1R), let‐7a, and downstream expression of NGF. Correlative studies were performed in human control and PSC liver tissue biopsies, serum, and bile. SR antagonist reduced biliary proliferation and hepatic fibrosis in BDL WT and Mdr2−/− mice. There was decreased expression of let‐7a in BDL and Mdr2−/− cholangiocytes that was associated with increased NGF expression. Inhibition of let‐7a accelerated liver fibrosis was attributed to cholestasis. There was increased expression of TGF‐β1 and TGF‐β1R. Significantly higher expression of secretin, SR, and TGF‐β1 was observed in PSC patient liver samples compared to healthy controls. In addition, there was higher expression of fibrosis genes and remarkably decreased expression of let‐7a and increased expression of NGF compared to the control. Conclusion: The secretin/SR axis plays a key role in regulating the biliary contribution to cholestasis‐induced hepatic fibrosis. (Hepatology 2016;64:865‐879)
St Jude Medical-Biocor bovine pericardial bioprosthesis: long-term survival

OBJECTIVE: The objective of this work is to present long-term results of valve replacement using SJM-BiocorTM bovine pericardial bioprostheses. METHODS: From 1992 to 2000, 304 patients were discharged from hospital after bioprosthesis implantation. Ages ranged from 15 to 83 years (mean: 60.6 ± 14.3 years) and 50.3% were male. Patient deaths and events related to bioprosthesis (infection, thromboembolism and structural failure) were considered for estimation of cumulative probability of survival and event-free survival. RESULTS: Total follow-up was 931.0 patients-year. During follow-up there were 28 (9.2%) deaths. Causes were bioprosthesis failure in five (1.6%), cardiac in seven (2.3%), non-cardiac in four (1.3%), and unknown in 12 (3.9%) patients. Events related to bioprosthesis were: endocarditis: 18 (5.9%), fibrocalcic degeneration: 15 (4.9%), thromboembolism: three (1.0%), hemolysis: one (0.3%). Bioprosthesis dysfunctions resulted in 16 (5.2%) reoperations due to fibrocalcic degeneration (nine), endocarditis (six) and thromboembolism (one). Probability of survival was higher in the young population ( 60 year, n=187): 82.0 ± 13.3% vs. 58.8 ± 13.6% in the 9th year. Event-free survival was 77.5 ± 3.7% for 5th year and 40.2 ± 9.0% for 10th year. Overall estimative of structural failure for a SJM-BiocorTM was 5% in 5th year increasing to 20% in the 10th year. In the aortic position the values were zero and 8%, respectively. Considering current clinical conditions, 88.5% are in NYHA class I, 9.1% in class II and 2.3% in class III. CONCLUSIONS: SJM-BiocorTM bovine pericardial bioprostheses resulted in satisfactory survival of patients, related to low prevalence of bioprosthesis dysfunction.