Miracle-dz/UniFAR-FTUs huggingface dataset:
Liver Angiopoietin‐2 Is a Key Predictor of D e N ovo or Recurrent Hepatocellular Cancer After Hepatitis C Virus Direct‐Acting Antivirals

Recent reports suggested that direct acting antivirals (DAAs) might favor hepatocellular carcinoma (HCC). In study 1, we studied the proangiogenic liver microenvironment in 242 DAA‐treated chronic hepatitis C patients with advanced fibrosis. Angiopoietin‐2 (ANGPT2) expression was studied in tissue (cirrhotic and/or neoplastic) from recurrent, de novo, nonrecurrent HCC, or patients never developing HCC. Circulating ANGPT2,vascular endothelial growth factor (VEGF), and C‐reactive protein (CRP) were also measured. In study 2, we searched for factors associated with de novo HCC in 257 patients with cirrhosis of different etiologies enrolled in a dedicated prospective study. Thorough biochemical, clinical, hemodynamic, endoscopic, elastographic, and echo‐Doppler work‐up was performed in both studies. In study 1, no patients without cirrhosis developed HCC. Of 183 patients with cirrhosis, 14 of 28 (50.0%) with previous HCC recurred whereas 21 of 155 (13.5%) developed de novo HCC. Patients with recurrent and de novo HCCs had significantly higher liver fibrosis (LF) scores, portal pressure, and systemic inflammation than nonrecurrent HCC or patients never developing HCC. In recurrent/de novo HCC patients, tumor and nontumor ANGPT2 showed an inverse relationship with portal vein velocity (PVv; r = –0.412, P = 0.037 and r = –0.409, P = 0.047 respectively) and a positive relationship with liver stiffness (r = 0.526, P = 0.007; r = 0.525, P = 0.003 respectively). Baseline circulating VEGF and cirrhotic liver ANGPT2 were significantly related (r = 0.414, P = 0.044). VEGF increased during DAAs, remaining stably elevated at 3‐month follow‐up, when it significantly related with serum ANGPT2 (r = 0.531, P = 0.005). ANGPT2 expression in the primary tumor or in cirrhotic tissue before DAAs was independently related with risk of HCC recurrence (odds ratio [OR], 1.137; 95% confidence interval [CI], 1.044‐1.137; P = 0.003) or occurrence (OR, 1.604; 95% CI, 1.080‐2.382; P = 0.019). In study 2, DAA treatment (OR, 4.770; 95% CI, 1.395‐16.316; P = 0.013) and large varices (OR, 3.857; 95% CI, 1.127‐13.203; P = 0.032) were independent predictors of de novo HCC. Conclusion: Our study indicates that DAA‐mediated increase of VEGF favors HCC recurrence/occurrence in susceptible patients, that is, those with more severe fibrosis and splanchnic collateralization, who already have abnormal activation in liver tissues of neo‐angiogenetic pathways, as shown by increased ANGPT2. (Hepatology 2018; 00:000‐000).
Physical fitness assessment of older adults in the primary care setting

Purpose: To explore the relationships between the physical fitness and the demographic characteristics, general health and well‐being, social support, and physical activity in a group of community‐dwelling older adults. This study also assessed the feasibility of obtaining physical fitness measures in the primary care setting. Data sources: Thirty‐four persons older than 60 years completed self‐report measures and the Senior Fitness Test (SFT), a battery of fitness measures normed for older adults. Self‐report measures included demographics, general health and well‐being (SF‐36), social support (Social Support for Physical Activity Scale), and physical activity levels (Physical Activity Scale for the Elderly). Conclusions: Physically active older adults had significantly better upper and lower body strength, aerobic endurance, and dynamic balance. Older adults who reported better general health and had fewer chronic conditions scored better on the physical fitness tests. The SFT took 10‐15 min to complete in the primary care setting. Implications for practice: Physical fitness measures give primary care providers objective information to develop a physical activity program for their patients. A physical activity program that includes recommendations for aerobic endurance, strength, flexibility, and/or balance that is based on objective findings may be a useful tool to promote better health and physical fitness in older adults.
Cytokine‐Producing B Cells Promote Immune‐Mediated Bile Duct Injury in Murine Biliary Atresia

Biliary atresia (BA) is a neonatal T cell–mediated, inflammatory, sclerosing cholangiopathy. In the rhesus rotavirus (RRV)–induced neonatal mouse model of BA (murine BA), mice lacking B cells do not develop BA, and the lack of B cells is associated with loss of T‐cell and macrophage activation. The aim of this study was to determine the mechanism of B cell–mediated immune activation (antigen presentation versus cytokine production) in murine BA. Normal neonatal B cells in the liver are predominantly at pro‐B and pre‐B cellular development. However, BA mice exhibit a significant increase in the number and activation status of mature liver B cells. Adoptively transferred B cells into RRV‐infected, B cell–deficient mice were able to reinstate T‐cell and macrophage infiltration and biliary injury. Nonetheless, neonatal liver B cells were incompetent at antigen presentation to T cells. Moreover, 3‐83 immunoglobulin transgenic mice, in which B cells only present an irrelevant antigen, developed BA, indicating a B‐cell antigen–independent mechanism. B cells from BA mice produced a variety of innate and adaptive immune cytokines associated with immune activation. In vitro trans‐well studies revealed that BA B cells secreted cytokines that activated T cells based on increased expression of T‐cell activation marker cluster of differentiation 69. Conclusion: Neonatal liver B cells are highly activated in murine BA and contribute to immune activation through production of numerous cytokines involved in innate and adaptive immunity; this work provides increased knowledge on the capacity of neonatal B cells to contribute to an inflammatory disease through cytokine‐mediated mechanisms, and future studies should focus on targeting B cells as a therapeutic intervention in human BA.
Assessing postprandial glucose using 1,5‐anhydroglucitol: An integrative literature review

Purpose: Recent studies have determined postprandial blood glucose is an independent risk factor for macrovascular complications. This risk exists, despite having HbA1C results within acceptable ranges for diabetes. 1,5‐Anhydroglucitol (1,5AG) has been proposed as an appropriate indicator to detect and screen for postprandial hyperglycemia (PPHG). This review discusses the efficacy of 1,5AG to predict PPHG in order to reveal those who may be at risk for macrovascular complications. Data Sources: An electronic search was conducted from 2003 to 2008 in the following databases: Medline, CINAHL, Health Source: Nursing/Academic Edition, and Pre‐CINAHL. Any articles relating to 1,5AG as a marker for PPHG were used. The search was limited to any human research articles published in English. All articles were reviewed for additional relevant studies. Conclusions: 1,5AG was found to be a reliable indicator of PPHG, even when HbA1C levels were within target ranges. 1,5AG may be a simple and effective tool for primary care providers to identify those at risk for macrovascular complications, who would otherwise go unnoticed if assessed by HbA1C alone.
Comparison of Visual Acuity Charts in Young Adults and Patients with Diabetic Retinopathy

Purpose To compare visual acuity (VA) assessed in healthy eyes and eyes with diabetic retinopathy (DR) using three different logMAR charts: the Sloan letter European-wide chart, the tumbling E chart, and the Landolt C chart. Methods Measurements on one eye of 40 volunteers (aged 29 ± 4 years) without visual impairment and 31 DR patients (aged 70 ± 9 years) with mild/moderate visual impairment were included. Visual acuity was assessed, with habitual refractive correction, using each of the three charts. Bland-Altman charts were constructed, and 95% limits of agreement were calculated to measure agreement. Results Mean VA in the group of young adults was −0.05 ± 0.10 (Sloan letter), −0.02 ± 0.13 (tumbling E), and 0.00 ± 0.12 (Landolt C) logMAR. Average VA estimates differed to a statistically significant extent between all charts. Mean VA in the DR group was 0.46 ± 0.25 (Sloan letter), 0.48 ± 0.26 (tumbling E), and 0.59 ± 0.28 (Landolt C). A statistically significant difference was observed for average Sloan letter versus Landolt C (p < 0.001) and tumbling E versus Landolt C (p < 0.001) acuities. Moreover, in healthy eyes, a moderate correlation (r = −0.38, p = 0.015) was found between the discrepancy in Sloan letter and Landolt C acuity and the mean VA estimate. The 95% limits of agreement were wide (more than approximately 0.2 logMAR for each comparison) and wider in the DR group chart comparisons than in healthy eyes. Conclusions Landolt C charts resulted in worse VA estimates compared with letter and tumbling E charts in both young adults and visually impaired subjects with DR. These differences seem more pronounced in DR patients who exhibit worse VAs. The specific study population must be considered in comparing outcomes from different clinical practices.
Costs of physical health care for self-injuring patients

Self-injury is a major clinical problem on the women9s wards at Ashworth Hospital. Ashworth Hospital is one of three special hospitals within England and Wales that provides assessment, treatment and rehabilitation for those legally detained patients under the Mental Health Act (1983) who suffer from a mental disorder and require conditions of special security because of their dangerousness. There is extensive literature on the psychological aspects of self-injury. However, since patients with self-injury present with damage to the body, it is surprising that there is little information on the physical health care and associated resource costs of this behaviour.
The past, present and future of meridian system research

Abstract Acupuncture points and meridians have been discovered to have high electric conductance which is related to high density of gap junctions. Neurohumoral approach in acupuncture research was instrumental in establishing the scientific validity of acupuncture. Recent advances in the morphogenetic singularity theory suggest that acupuncture points originate from the organizing centers in morphogenesis. This theory explains many puzzles in both developmental biology and acupuncture research, including the distribution and non-specific activation of organizing centers and acupuncture points, the high electric conductance of acupuncture points, the polarity effect of electroacupuncture and side-effect profile of acupuncture, as well as the ontogeny, phylogeny and physiological function of the meridian system and chakra system. Most of these have not been explained by any neurohumoral theory. In several ‘prospective blind trials’, research results have supported its corollary on the role of singularity and separatrix in morphogenesis, the predictions on the high electric conductance and the high density of gap junction at the organizing centers. These advances have implications in multiple disciplines of biomedicine beyond acupuncture.
Mild head injury

Although mild head injury is the most prevalent type of head injury in children and adolescents, only a relatively small number of studies on this kind of head injury have been reported. This article summarizes a review of studies examining cognitive, academic, and psychosocial outcomes in children who sustained mild head injuries. Despite earlier claims of mild head injury being a “silent epidemic,” the studies, which were published from 1970 to 1998, provide no compelling evidence to support this view.
Thrombolytic therapy administered to patients with complete heart block complicating acute myocardial infarction

BackgroundThrombolytic therapy has frequently been withheld from patients with complete heart block lollowing acute myocardial infarction because of significant hypotension and the risk of bleeding should temporary transvenous pacing be required. We assessed the course of patients with acute myocardial infarction complicated initially by complete heart block who received thrombolytic therapy. MethodsPatients had clinical and ECG evidence of acute myocardial infarction of less than 6 hours' duration, were in complete heart block when first assessed, and were suitable for thrombolytic therapy. Coronary angiography was performed during the hospital stay, and left ventricular function was assessed by radionuclide ventriculography during convalescence. ResultsTwenty-one patients were treated: 20 had an inferior myocardial infarction and 17 patients were first seen outside the hospital. Initial systolic blood pressure in 13 of 21 (62%) was 90 mm Hg or less. Thrombolytic therapy commenced at 154 minutes (mean) after the onset of infarction and 12 patients received prehospital thrombolysis. All patients had received intravenous atropine, and in seven 1:1 atrioventricular conduction had occurred. Of the 12 who remained in complete heart block at the time of receiving the thrombolytic agent, 10 reverted to 1:1 atrioventricular conduction and one to chronic atrial fibrillation within 2 hours. Of the two in second-degree atrioventricular block, both reverted to 1:1 atrioventricular conduction within 7 hours. Only four patients required temporary transvenous pacing (in three for complete heart block). Coronary artery patency was 79% (15 of 19), and mean global left ventricular ejection fraction was 57% ± 10%. No hemorrhagic complications occurred; only one patient with anterior myocardial infarction and cardiogenic shock died. ConclusionsThrombolytic therapy administered to patients with myocardial infarction complicated by complete heart block is safe and frequently results in resumption of normal atrioventricular conduction, thus reducing the need for pacing and improving prognosis.
Should patients be optimistic about surgery? Resolving a conflicted literature

ABSTRACT Following surgery, some patients suffer distress, disappointment, regret, poor adjustment, and poor quality-of-life. Surgeons may define ‘success’ based on objective clinical outcomes, but patients’ perceptions of surgical success rely primarily on a comparison to their initial expectations. We review the literature on the relationship between patients’ surgical expectations and psychosocial outcomes and attempt to resolve a conflict in the literature. Specifically, we propose that conflicting conclusions regarding the merits of optimism primarily stem from differing methodological approaches by researchers in the field. Studies that examine preoperative expectations in isolation typically conclude that optimism is positively associated with beneficial psychosocial outcomes. Studies that compare preoperative expectations to objective surgical outcomes typically conclude that optimism, particularly unrealistic optimism, is associated with detrimental psychosocial outcomes. As a whole, the evidence strongly supports an association between optimistic expectations and positive psychosocial outcomes following surgery if those expectations are based in reality. If preoperative optimism ultimately turns out to be unrealistic, however, it is likely to be a postoperative liability.
Fertility in Tanzania: Do contraception and sub-fertility matter?

The author investigated the effects of contraception upon waiting times to conception in Tanzania determined the prevalence of subfertility and infertility and assessed whether impaired fertility remains a problem in Tanzania. Analysis is limited to conceptions which resulted in a live birth and is based upon data from the 1991/92 Tanzania Demographic and Health Survey. Current fertility in Tanzania is affected by both contraceptive use and subfertility. The data indicate that 25% of parous women had ever used contraception while only 3% had used it before their first child was born. The median waiting time to conception for parous women using contraception was 22 months compared to 15 months for non-contracepting women. Subfertility is also prevalent in the country especially among women whose partner does not sleep at home. The risk of conception was generally lower for non-Christian women and those married more than once. These latter women may suffer from subfertility of pathological origin.
The peptide‐based thrombin inhibitor CRC 220 is a new substrate of the basolateral rat liver organic anion‐transporting polypeptide

The peptidomimetic thrombin inhibitor CRC 220, 4‐methoxy‐2,3,6‐trimethylphenylsulfonyl‐L‐aspartyl‐D‐4‐amidinop henylalanyl‐ piperidide, is taken up into isolated rat hepatocytes through active, carrier‐mediated transport. This uptake is inhibited by bile acids. Functional expression in Xenopus laevis oocytes was performed to identify the transport system responsible for the hepatocellular CRC 220 uptake. Injection of poly(A)+RNA in X. laevis oocytes resulted in a two‐ to three‐times higher uptake of CRC 220, compared with uninjected or water‐injected control oocytes. Taurocholate (200 mumol/L) inhibited this uptake completely. No uptake of the peptidomimetic thrombin inhibitor was observed, when X. laevis oocytes were injected with complementary RNA (cRNA) encoding either the cloned rat liver Na+‐ dependent taurocholate transporter Ntcp, the renal oligopeptide carrier rhaPT or the intestinal oligopeptide transporter PepT1. However, after injection of cRNA of the cloned rat liver Na+‐independent organic anion transporting polypeptide oatp, a specific and saturable CRC 220 uptake was observed (Michaelis‐Menten constant 29.5 mumol/L). Cis‐inhibition with known oatp‐substrates, e.g., 20 mumol/L Bromsulphalein (BSP), 2007 mumol/L taurocholate and 2007 mumol/L cholate, occurred in oatp‐expressing X. laevis oocytes, whereas substrates of the two peptide carriers as well as dipeptide‐ and single‐amino acid constituents of the thrombin inhibitor itself lacked any significant inhibitory effects. These data show that the modified dipeptide CRC 220 is a highly selective substrate of the organic anion transporting polypeptide oatp in the basolateral plasma membrane of rat hepatocytes.
A specific antibody response to HCV E2 elicited in mice by intramuscular inoculation of plasmid DNA containing coding sequences for E2

As the chimpanzee, the only reliable animal model for hepatitis C virus (HCV) infection, is impractical for early stage testing of HCV vaccine candidates, we have evaluated the immune response in mice to an experimental plasmid based HCV vaccine. We used this system because DNA vaccines can be rapidly constructed without the necessity of large scale protein production and purification. In this preliminary study we tested the immune response in mice to HCV envelope glycoprotein, E2, induced by a eukaryotic expression plasmid. Protein expression was monitored by immunofluorescence in transfected tissue culture cells. Each mouse was inoculated intramuscular with 100 microg plasmid DNA and some mice were boosted after 5 weeks. Among 12 BALB/C mice inoculated, 10 developed antibody to E2 by the second week. The antibody levels increased steadily before reaching a plateau in mice receiving the booster, but in the nonboosted mice the antibody declined over time. The serum from one mouse was tested against a series of overlapping peptides covering most of E2. This serum contained antibodies recognizing two distinct epitopes beginning at amino acid 57 and amino acid 113 but no antibody was directed against peptides representing the hypervariable region of E2, antibody to which is thought to be important in HCV neutralization. We have shown that the use of plasmid based vaccines can induce a specific immune response in mice against HCV antigens. This system should be useful as the first step in vaccine development.
Cholangiocarcinoma in patients with primary sclerosing cholangitis: A multicenter case‐control study

Patients with primary sclerosing cholangitis (PSC) have a significantly increased risk of developing cholangiocarcinoma (CCA). Risk factors for developing such a complication are not well defined. We conducted a multicenter, case‐control study to determine the risk factors and possible predictors for CCA in patients with PSC. The demographic, clinical, and laboratory features of 26 PSC patients with CCA diagnosed over a 7‐year period at eight academic centers were compared with 87 patients with PSC but no CCA (controls). There was no statistically significant difference in demographics, smoking, signs or symptoms or complications of PSC, indices of disease severity (Mayo Risk score or Child‐Pugh score), frequency or duration or complications of inflammatory bowel disease (IBD), frequency of biliary surgery, or therapeutic endoscopy between the two groups. Alcohol consumption was significantly associated with CCA in patients with PSC (odds ratio: 2.95; 95% CI: 1.04‐8.3). Serum carbohydrate antigen 19‐9 (CA 19‐9) was significantly higher in patients with CCA than those without (177 ± 89 and 61 ± 58 U/mL, respectively;P = .002). A serum CA 19‐9 level > 100 U/mL had 75% sensitivity and 80% specificity in identifying PSC patients with CCA. In conclusion, alcohol consumption was a risk factor for having CCA in PSC patients. The indices of severity of liver disease were not associated with CCA in patients with PSC. Serum CA 19‐9 appeared to have good ability to discriminate PSC patients with and without CCA.
Local arterial vasoconstriction induced by octreotide in patients with cirrhosis

Peripheral vasodilation initiates the hyperdynamic circulation in cirrhosis. Somatostatin and its analogues, such as octreotide, have a vasoconstrictive effect in cirrhotic patients and experimental animals with portal hypertension. The exact mechanism of octreotide‐induced vasoconstriction remains unknown. To investigate whether octreotide produces vasoconstriction through suppression of vasodilatory peptides, such as glucagon, or through a local effect, we evaluated the effect of an intra‐arterial dose on forearm blood flow (FBF), while measuring systemic glucagon levels. FBF was measured in 10 cirrhotic patients by venous occlusion plethysmography. The brachial artery of the nondominant arm was catheterized, and vasoactive drugs were administered: methacholine 4 μg/min; octreotide 20 μg/h, and octreotide 20 μg/h + methacholine 4 μg/min. Each infusion, lasting 5 minutes, was followed by saline for washout. FBF was measured in both arms during the last minute of each infusion and at the end of washout, with the uninfused arm acting as the control. Nitrates and nitrites, octreotide, and glucagon blood levels were determined at baseline and after each infusion. Percent change in flow (%▵) was obtained by comparing the flow during drug administration to that during the preceding saline infusion. Saline infusion did not alter FBF, but octreotide infusion resulted in a 34% ± 7.7 (P < .005) reduction in FBF in the infused arm. FBF in the control arm was unchanged despite a significant decrease in systemic glucagon levels. Methacholine infusion increased FBF around 300%, which was not altered by the concomitant infusion of octreotide. Octreotide has a local vasoconstrictive effect that seems nitric oxide (NO)‐independent. Octreotide probably has a facilitating effect over vasoconstrictors increased in chronic liver diseases.
Burn-Out: The High Cost of High Achievement

What is burn-out? You can get a lot of opinions, including the view (perhaps a semantic argument in some instances) that there is no such thing. In the terms of this book, it is often a condition in which likely-to-succeed persons begin "exhibiting signs of something amiss between themselves and their environment. " Clinical psychologist Freudenberger says he has experienced it himself; that what is happening is not just something inside the persons affected. No, suggest the authors, "much had to be attributed to the times we live in, the swift acceleration of change, the depersonalization of neighborhoods, schools, and work situations. " In any case, whatever burn-out is or is not, it is a much-discussed subject these days, and physicians may want to examine as many viewpoints as possible. This book, of course, offers one of them.