Miracle-dz/UniFAR-FTUs huggingface dataset:
Fecal Microbial Transplant Capsules Are Safe in Hepatic Encephalopathy: A Phase 1, Randomized, Placebo‐Controlled Trial

Hepatic encephalopathy (HE) can cause major morbidity despite standard of care (SOC; rifaximin/lactulose). Fecal microbial transplant (FMT) enemas postantibiotics are safe, but the effect of FMT without antibiotics using the capsular route requires investigation. The aim of this work was to determine the safety, tolerability, and impact on mucosal/stool microbiota and brain function in HE after capsular FMT in a randomized, single‐blind, placebo‐controlled clinical trial in Virginia. Patients with cirrhosis with recurrent HE with MELD (Model for End‐Stage Liver Disease) <17 on SOC were randomized 1:1 into receiving 15 FMT capsules versus placebo from a single donor enriched in Lachnospiraceae and Ruminococcaceae. Endoscopies with duodenal and sigmoid biopsies, stool analysis, cognition, serum lipopolysaccharide‐binding protein (LBP), and duodenal antimicrobial peptide (AMP) expression at baseline were used. Clinical follow‐up with SOC maintenance was performed until 5 months. FMT‐assigned patients underwent repeat endoscopies 4 weeks postenrollment. Twenty subjects on lactulose/rifaximin were randomized 1:1. MELD score was similar at baseline (9.6 vs. 10.2) and study end (10.2 vs. 10.5). Six patients in the placebo group required hospitalizations compared to 1 in FMT, which was deemed unrelated to FMT. Infection/HE episodes were similar between groups. Baseline microbial diversity was similar in all tissues between groups. Post‐FMT, duodenal mucosal diversity (P = 0.01) increased with higher Ruminococcaceae and Bifidobacteriaceae and lower Streptococcaceae and Veillonellaceae. Reduction in Veillonellaceae were noted post‐FMT in sigmoid (P = 0.04) and stool (P = 0.05). Duodenal E‐cadherin (P = 0.03) and defensin alpha 5 (P = 0.03) increased whereas interleukin‐6 (P = 0.02) and serum LBP (P = 0.009) reduced post‐FMT. EncephalApp performance improved post‐FMT only (P = 0.02). Conclusion: In this phase 1 study, oral FMT capsules are safe and well tolerated in patients with cirrhosis and recurrent HE. FMT was associated with improved duodenal mucosal diversity, dysbiosis, and AMP expression, reduced LBP, and improved EncephalApp performance. Further studies are needed to prove efficacy.
Hepatitis E Virus Infections Among Human Immunodeficiency Virus–Positive Individuals During an Outbreak of Acute Hepatitis A in Taiwan

Hepatitis A virus (HAV) and hepatitis E virus (HEV) share the similar fecal‐oral transmission route. During an outbreak of sexually transmitted acute hepatitis A among men who have sex with men (MSM) worldwide between 2015 and 2017, we investigated the possibility of sexual transmission and related morbidity of HEV infection among human immunodeficiency virus (HIV)‐positive patients. From March 1, 2015 to August 31, 2017, anti‐HEV immunoglobulin G was retrospectively determined among 3,293 HIV‐positive patients, who were mainly MSM (87.6%) with a median CD4 count of 575 cells/μL. Prevalence and incidence of HEV infection were 3.7% (123 of 3,293) and 4.35 per 1,000 person‐years of follow‐up (PYFU), respectively, which were significantly lower compared with those of HAV infection (31.1% [996 of 3,204] and 12.61 per 1,000 PYFU, respectively). The number of patients with HEV infection did not increase with the hepatitis A epidemic. The factor associated with prevalent HEV infection was older age (per 1‐year increase, adjusted odds ratio, 1.07; 95% confidence interval, 1.05‐1.09), but neither sexual orientation nor acquisition of sexually transmitted infections was related to prevalent or incident HEV infection. Among 23 patients with incident HEV infection, 22 patients had viremia caused by HEV genotype 4. No patients had prolonged HEV viremia or clinical symptoms, and only a mild elevation of serum aminotransferase, ranging from 34 to 77 IU/L, was noted. Although 4 patients had hepatitis for a prolonged duration of between 8 and 17 months, no abdominal imaging revealed liver fibrosis or cirrhosis. Conclusion: HEV endemicity remained low among HIV‐positive patients in Taiwan during the outbreak of acute hepatitis A. Our data suggest that sexual transmission of HEV with significant morbidity of HEV infection, if any, is rare in this population.
Self- and peer-rated character strengths: How do they relate to satisfaction with life and orientations to happiness?

This paper addresses the question as to whether previously reported findings on a positive relation between character strengths, satisfaction with life, and orientations to happiness (OTH) can be replicated for peer ratings of character strengths. A sample of 334 Swiss adults completed questionnaires and collected informant ratings by 634 peers. Self- and peer ratings converged well and suggest that, primarily: the strengths of hope, zest, and curiosity – but also gratitude and love – play key roles in the interplay of strengths and satisfaction with life. Peer ratings of strengths also related positively with the endorsement of a pleasurable, engaged, and meaningful life. Further analyses show that the OTH predict satisfaction with life beyond self- and peer-rated character strengths. There, the engaged life (i.e. endorsement of flow) was most relevant. This study supports earlier findings that argue for an important role of character strengths when describing the well-being of a person.
Toward solving the etiological mystery of primary biliary cholangitis

Primary biliary cholangitis (PBC) is considered a model autoimmune disease due to its signature anti‐mitochondrial antibody (AMA) autoantibody, female predominance, and relatively specific portal infiltration and cholestasis. The identification and cloning of the major mitochondrial autoantigens recognized by AMA have served as an immunologic platform to identify the earliest events involved in loss of tolerance. Despite the relatively high concordance rate in identical twins, genome‐wide association studies have not proven clinically useful and have led to suggestions of epigenetic events. To understand the natural history and etiology of PBC, several murine models have been developed, including spontaneous models, models induced by chemical xenobiotic immunization, and by “designer” mice with altered interferon metabolism. Herein, we describe five such models, including 1) NOD.c3c4 mice, 2) dominant negative form of transforming growth factor receptor type II mice, 3) interleukin‐2R α−/− mice, 4) adenylate‐uridylate‐rich element Del−/− mice, and 5) 2‐octynoic acid‐conjugated bovine serum albumin immunized mice. Individually there is no perfect murine model, but collectively the models point to loss of tolerance to PDC‐E2, the major mitochondrial autoantigen, as the earliest event that occurs before clinical disease is manifest. Although there is no direct association of AMA titer and PBC disease progression, it is noteworthy that the triad of PBC monocytes, biliary apotopes, and AMA leads to an intense proinflammatory cytokine burst. Further, the recurrence of PBC after liver transplantation indicates that, due to major histocompatibility complex restriction, disease activity must include not only adaptive immunity but also innate immune mechanisms. We postulate that successful treatment of PBC may require a personalized approach with therapies designed for different stages of disease. (Hepatology Communications 2017;1:275–287)
Engaging parliamentarians as advocates for women's health: Findings from Kenya and Namibia

Abstract Members of parliament (MPs) are well placed to promote national health policies that improve women's access to quality health care, including HIV services. To catalyse political will and leadership, the International Centre for Research on Women, Centre for the Study of AIDS at the University of Pretoria, International Community of Women Living with HIV/AIDS and Realising Rights: The Ethical Globalisation Initiative, conducted the Parliamentarians for Women's Health project in select African countries. This paper focusses on participatory community assessments – a methodology used by the project to improve MPs’ understanding of women's health issues, particularly HIV/AIDS, and to increase their engagement with civil society in order to better represent women's health needs and concerns. In-depth interviews with eight MPs from Kenya and Namibia highlight the value of the assessments in identifying women's health problems and service gaps. The MPs reported that they undertook various activities after the assessments, including gathering more information about women's health from local communities, pushing for new parliamentary committees to be a platform for health issues, using the information from the assessments to inform policy, more carefully reviewing budget allocations and establishing relationships with civil society. Participatory methods can be used to meet political leaders’ needs for information and communities’ needs to influence policymaking that affects their lives.
Inhibition of hepatitis B virus DNA polymerase by enantiomers of penciclovir triphosphate and metabolic basis for selective inhibition of HBV replication by penciclovir

The deoxyguanosine analog penciclovir (PCV; 9‐[4‐hydroxy‐3‐hydroxymethyl‐but‐1‐yl]guanine), has shown potent antiviral activity against herpes viruses and hepadnaviruses. Efficacy against chronic hepatitis B virus (HBV) infection has been demonstrated in an animal model and in recent clinical trials of famciclovir, the oral form of PCV. The antiviral activity of PCV is believed to be dependent on the intracellular formation of PCV‐triphosphate (PCV‐TP) which is presumed to inhibit HBV replication by interfering with viral DNA polymerase activity. The (S)‐enantiomer is preferentially formed in herpes virus‐infected cells, and is the more active against the herpes simplex virus; however, little is known about the biochemical mechanisms of PCV phosphorylation or of interference with viral replication in HBV‐infected cells. Here, we report that in contrast with herpes simplex virus, the (R)‐enantiomer of PCV‐TP is a more potent inhibitor of HBV DNA polymerase‐reverse transcriptase (pol‐RT) in vitro than the (S)‐enantiomer. In assays for HBV DNA pol‐RT activity, in which purified viral core particles were the enzyme source, the IC50s for (R)‐ and (S)‐enantiomers of PCV‐TP were 2.5 micromol/L and 11 micromol/L, respectively. The estimated Kis for (R)‐ and (S)‐ PCV‐TP were approximately 0.03 micromol/L and approximately . 04 micromol/L, respectively, about 3‐fold lower than the Km for deoxyguanosine triphosphate (dGTP) in the same system. In addition, we report that PCV metabolism is similar in both control (HepG2) and in HBV‐transfected (2.2.15) hepatoblastoma cells in vitro, indicating that cellular enzyme(s) catalyze PCV phosphorylation. Peak PCV‐TP concentrations of about . 4 micromol/L were reached in both cell types in less than 12 hours, and intracellular PCV‐TP was exceptionally stable with a half‐life of about 18 hours. These observations provide a mechanistic basis for the potent activity of PCV against HBV.
Prevalence of herpesviridae and hepatitis B virus DNA in the liver of patients with non‐A, non‐B fulminant hepatic failure

Members of the herpes virus family and hepatitis B virus (HBV) have been implicated as etiologic agents in non‐A, non‐B (NANB) fulminant hepatic failure (FHF), but the frequency of infection with these agents has not been established using appropriate controls. To examine this issue, we studied 50 NANB FHF patients and 104 liver transplant recipients from North America and Europe. Hepatic DNA was analyzed by polymerase chain reaction (PCR) for evidence of Epstein‐Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus I (HSV I) and II (HSV II), varicella‐zoster virus (VZV), and human herpes virus‐6 (HHV‐6) nucleic acid sequences. The prevalence of HBV was assessed in North American subjects only. HSV I, HSV II, VZV, and HHV‐6 viral sequences were not observed in any samples. Three of 50 FHF (6%) and 14 of 104 control patients (13%) were positive for CMV DNA. Two of 50 FHF (4%) and 10 of 104 control patients (10%) had EBV DNA, and HBV DNA was observed in 3 of 10 North American FHF patients (30%) and 3 of 59 controls (5%) without serum markers for HBV infection. The finding of HBV DNA in the liver of seronegative controls from North America but not Europe suggests that occult hepatitis B sequences in patients with NANB FHF may simply reflect geographic differences. The majority of cryptogenic FHF cases cannot be attributed to infection with herpes viruses or HBV.
Developing policy options for SARS and SARS-like diseases – a Delphi study

Abstract The objective of the SARSControl Delphi study was to develop options for national and international emerging infectious diseases policies. The aim of this paper is to present the results of the study, which gathered expert opinions on gaps and inconsistencies concerning preparedness and response planning for Severe Acute Respiratory Syndrome (SARS) and SARS-like diseases. The Delphi technique was employed, which comprised a pilot round, two written rounds and a face-to-face meeting. The Delphi panel consisted of 38 experts from 22 countries, who highlighted the necessity to test plans and stressed the importance of surveillance measures for the swift containment of communicable disease outbreaks and the inclusion of detailed triage plans in national pandemic plans. The experts also suggested a need to define criteria for testing pandemic preparedness plans at different regional levels. New policy alternatives were identified, such as the need for generic plans on pandemics and universal access to healthcare during an outbreak. The usefulness of some non-medical interventions, such as bans on travel, could not be established and need further research. Dissemination of the findings will help to bridge gaps and rectify inconsistencies in current pandemic planning and response strategies for SARS and SARS-like diseases, as well as add valuable knowledge towards the development of national and international emerging infectious disease policies.
Epidemiology of Intimate Partner Homicide-Suicide Events Among Women of Childbearing Age in Maryland, 1994–2003

Intimate partner homicide-suicide (IPH-IPS) among women during the childbearing years leaves irreversible outcomes that are devastating and have lasting repercussions for surviving children, families, and communities. An estimated one-third of all intimate partner homicides of women aged 15 to 50 end in suicide. The purpose of this study was to describe the temporal trends and characteristics of both victims of IPH-IPS. Data were collected using a retrospective, cross-sectional analysis of medical examiner records for women aged 10 to 50 in Maryland, during 1994–2003. Seventy-five IPH-IPS incidents were identified over the 10-year period. Of those, 94.7% were a female homicide followed by a male suicide. The average rate of IPH-IPS was 0.52 per 100,000 women aged 10 to 50. About half of the couples were within 5 years of the age of each other, married or separated and the same race. Eleven percent of the women were pregnant/1-year postpartum when they died. The findings presented represent a significant public health problem that has a unique pattern compared with other populations studied. Understanding this problem involves a more comprehensive assessment of both victims. There is a need for a national surveillance system that identifies IPH-IPS events and provides information on both victims that includes individual and relationship characteristics.
Ductal Carcinoma In Situ: Controversies in Diagnosis, Biology, and Treatment

Abstract: A clinically relevant classification and understanding of the biology of ductal carcinoma in situ (DCIS) is mandated by the increasing numbers of mammographically detected lesions of limited size being considered for breast‐conserving therapy. DCIS is a morphologically and biologically diverse assemblage of lesions that are conventionally classified in an arbitrary and largely descriptive manner based on architectural features. Several classifications of DCIS based on nuclear grade and necrosis have been shown to stratify DCIS into subtypes associated with vastly different risks of local recurrence and invasive transformation. Breast‐conserving therapy for DCIS is dependent on adequate surgical excision, even more so than for invasive breast carcinomas, but the surgical procedure itself is made difficult by the limited ability to define the pathologic extent of the lesion on the basis of mammographic microcalcification, the vagaries of the localization procedure, and the multifocal nature of some DCIS subtypes. Proper tissue processing and interpretation, particularly with regard to the presence of or misinterpretation of microinvasion, all affect the success of breast‐conserving therapy.
Superego: An attachment perspective

With the help of attachment theory and research, the paper attempts to broaden and build on classical and current views on the superego. Attachment theory’s epigenetic approach and the concept of the subliminal superego are described. The superego, it is argued, is as much concerned with safety as sex. The superego is ‘heir’, not just to the Oedipus complex or Klein’s pre‐oedipal constellation, but also to the attachment relationship. Under favourable developmental conditions a ‘mature superego’ emerges, facilitating, in the presence of an internal secure base, maturational boundary crossings towards adult sexuality. In the light of the above, the paper reviews Lear’s updating of Strachey’s model of psychic change and explores the concept of transgression in relation to the ‘professional superego’, its development and maturation. Theoretical arguments are illustrated with clinical examples.
Hepatitis B virus X protein transactivates the inducible nitric oxide synthase promoter

The capability of hepatitis B virus (HBV) to increase the transcription of the human hepatic inducible nitric oxide synthase (iNOS) by transactivating its promoter has been studied. We have observed by reverse‐transcription polymerase chain reaction (RT‐PCR) that although the mRNA for the iNOS was almost undetectable in the human hepatoblastoma cell line, HepG2, it was constitutively expressed in the 2.2. 15 cell line (a derivative of the HepG2 that produces complete HBV particles). Transfection of HepG2 and 2.2. 15 cells with the p1iNOS‐CAT plasmid (containing a 1.1‐kb fragment of the iNOS promoter) resulted in an increase in chloramphenicol acetyl transferase (CAT) activity in 2.2. 15 cells. Similar results were observed when HepG2 and Chang liver cell lines were cotransfected with the p1iNOS‐CAT plasmid and the complete HBV genome. It was shown that pX was responsible for the transactivation by cotransfection of HepG2 cells with the p1iNOS‐CAT and plasmids expressing the HBV‐encoded pX protein, core antigen, and e antigen. Cotransfection of HepG2 cells with the pX expression plasmids and a series of deletion mutants of the 1.1‐kb iNOS promoter fragments established that transactivation by pX depends on the presence of at least one nuclear factor‐κB (NF‐κB) binding site. This was further confirmed by cotransfecting cells with a plasmid expressing the NF‐κB inhibitor, IκB.
Human leukocyte antigen class II and III alleles and severity of hepatitis C virus–related chronic liver disease

Hepatitis C outcome is likely related both to viral factors and host's immune responses. We correlated the severity of liver disease with human leukocyte antigen (HLA) genes (C4A, C4B, TNFA, TNFB, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, TAP1, and TAP2) in three groups of subjects: 99 patients with chronic hepatitis, 41 asymptomatic carriers, and 179 uninfected controls. Patients with grade/stage 3 to 4 hepatitis significantly differentiated for their low frequency of alleles TNFB*1, DRB1*1104, and DRB3*03, which had a protective role, and high frequency of allele DRB1*1001, which was associated with disease severity. HLA‐DRB*11 subtypes were differentially distributed: DRB1*1104 was most frequent in carriers, whereas DRB1*1101 was more frequent in patients. The TAP1C,2A haplotype was also underrepresented in patients with respect to controls. Finally, a decrease of heterozygous subjects was observed in patients with respect to carriers at the DQB1 locus. Multivariate analysis by correspondence analysis and multiple logistic regression indicated that age, sex, and hepatitis C virus (HCV) type were the strongest risk factors; however, some immunogenetic variables (TNFB*1, DRB1*1104, and DRB3*03) showed an independent contribution, especially in comparing patients with extreme manifestations of disease. The involvement of different genes in various HLA subregions suggests that anti‐HCV responses are modulated by a complex gene interplay rather than by single alleles
A new malaria protocol in a Congolese refugee camp in West Tanzania

Abstract The objective of this study was to evaluate the impact of a new malaria protocol introduced in 2007 at Nyarugusu Refugee Camp. In accordance with this protocol, the delivery of a diagnostic test (rapid diagnostic test or microscopy) was made compulsory prior to the administration of antimalarial drugs (ACTs: artemisinin-based combination therapies). We collected camp clinic records on outpatient malaria diagnoses from 2004 through 2007 and compared the morbidity percentages attributed to malaria during these years, as well as the actual incidence of malaria in 2006 and 2007. Our analyses demonstrate that malaria accounted for 45.8% of all morbidity in 2004 (64,557 malaria cases out of 1,40,669 total morbidity), followed by corresponding figures of 47.8% for 2005 (94,389 malaria cases out of 1,97,400) and 47.9% for 2006 (60,760 malaria cases out of 1,26,754); however, the values dropped sharply to 22.8% in 2007 (20,136 malaria cases out of 88,254). We found a similar drastic drop in the incidence of malaria from an average of 182.415 cases/1000 inhabitants/month in 2006 to only 35.635 cases/1000 inhabitants/month in 2007. The results of our study suggest that because of the overlap of symptoms from malarial and non-malarial febrile illnesses, diagnosing malaria on clinical and epidemiological bases may lead to its overdiagnosis. This could result in both the overprescription of antimalarials and the underdiagnosis and inappropriate treatment of non-malarial febrile processes. The use of affordable and available tests can increase the accuracy of malaria diagnoses, so that only real malaria cases would be treated as such. This would help curb the uncontrolled administration of antimalarials to prevent the development of resistance to new malarial treatments and thus decrease treatment expenses. This way, financial, material and human resources can be allocated to other health issues that currently go unnoticed.