Clinical characteristics of antimitochondrial antibody-positive patients at a safety net health care system in Arizona.

Background and aimsTo assess whether aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (AP) levels can predict the diagnosis of primary biliary cholangitis (PBC) or any other diagnoses and whether PBC occurs either simultaneously or independently of other liver diseases among antimitochondrial antibody (AMA)-positive patients.MethodsDemographic and clinical variables were assessed in 90 AMA-positive patients with and without liver biopsies. These patients were further categorised as having a diagnosis of PBC, overlap syndrome or 'not established with a diagnosis of PBC'. Receiver operating characteristic curves were constructed to determine the thresholds of liver enzymes that predict these three diagnoses.ResultsThe 48 patients with liver biopsies were more frequently female and had significantly higher AP levels compared with the non-liver biopsy group. Based on liver biopsy findings, 12, 12 and 22 patients were assigned a diagnosis of PBC, overlap syndrome with autoimmune hepatitis and PBC and 'not established diagnosis of PBC', respectively. Seven of 12 patients classified as PBC had AP level of ˂200 IU. AST, ALT and AP levels were significant predictors of a diagnosis of overlap syndrome compared with the rest of the patients; however, these tests were not discriminatory between diagnoses of PBC and 'not established with PBC'. Findings of fatty liver and bile duct injury on liver biopsies were not significantly associated with any liver test pattern.ConclusionsAs the liver test pattern did not correlate with the liver biopsy findings of PBC or other non-PBC diagnoses in AMA-positive patients at risk for other disease, a liver biopsy and/or non-invasive liver assessment along with serum liver tests should be interpreted to complete liver evaluation

A Bayesian Evidence Synthesis Approach to Estimate Disease Prevalence in Hard-To-Reach Populations: Hepatitis C in New York City

Existing methods to estimate the prevalence of chronic hepatitis C (HCV) in New York City (NYC) are limited in scope and fail to assess hard-to-reach subpopulations with highest risk such as injecting drug users (IDUs). To address these limitations, we employ a Bayesian multi-parameter evidence synthesis model to systematically combine multiple sources of data, account for bias in certain data sources, and provide unbiased HCV prevalence estimates with associated uncertainty. Our approach improves on previous estimates by explicitly accounting for injecting drug use and including data from high-risk subpopulations such as the incarcerated, and is more inclusive, utilizing ten NYC data sources. In addition, we derive two new equations to allow age at first injecting drug use data for former and current IDUs to be incorporated into the Bayesian evidence synthesis, a first for this type of model. Our estimated overall HCV prevalence as of 2012 among NYC adults aged 20-59 years is 2.78% (95% CI 2.61-2.94%), which represents between 124,900 and 140,000 chronic HCV cases. These estimates suggest that HCV prevalence in NYC is higher than previously indicated from household surveys (2.2%) and the surveillance system (2.37%), and that HCV transmission is increasing among young injecting adults in NYC. An ancillary benefit from our results is an estimate of current IDUs aged 20-59 in NYC: 0.58% or 27,600 individuals

Cell Type of Origin Influences the Molecular and Functional Properties of Mouse Induced Pluripotent Stem Cells

Induced pluripotent stem cells (iPSCs) have been derived from various somatic cell populations through ectopic expression of defined factors. It remains unclear whether iPSCs generated from different cell types are molecularly and functionally similar. Here we show that iPSCs obtained from mouse fibroblasts, hematopoietic and myogenic cells exhibit distinct transcriptional and epigenetic patterns. Moreover, we demonstrate that cellular origin influences the in vitro differentiation potentials of iPSCs into embryoid bodies and different hematopoietic cell types. Notably, continuous passaging of iPSCs largely attenuates these differences. Our results suggest that early-passage iPSCs retain a transient epigenetic memory of their somatic cells of origin, which manifests as differential gene expression and altered differentiation capacity. These observations may influence ongoing attempts to use iPSCs for disease modeling and could also be exploited in potential therapeutic applications to enhance differentiation into desired cell lineages.Stem Cell and Regenerative Biolog

Small business in Ukraine as the engine of national economic development

У статті розглянуто стан малого підприємництва в Україні, охарактеризовано слабкі сторони його діяльності та чинники, що впливають на даний сектор економіки. Для переконливішого пояснення зроблених висновків, наведено статистичну інформацію щодо частки малих підприємств України в загальній кількості підприємств і їх розподіл за регіонами.This article examines the state of small business in Ukraine, gives a description of the weaknesses of its activities; describes factors that affect this sector of the economy. For a more convincing explanation of the findings, statistics on the share of small business in Ukraine, the total number of companies and their distribution by region are presented

Anti-SARS-CoV-2 antibody dynamics after primary vaccination with two-dose inactivated whole-virus vaccine, heterologous mRNA-1273 vaccine booster, and Omicron breakthrough infection in Indonesian health care workers

Background: Data on the dynamics and persistence of humoral immunity against SARS-CoV-2 after primary vaccination with two-dose inactivated vaccine (CoronaVac) are limited. This study evaluated the sequential effects of prior infection, heterologous boosting with mRNA-1273 (Moderna), and the occurrence of Omicron vaccine-breakthrough infection (VBI) thereafter. Methods: We evaluated anti-spike IgG (Abbott) and neutralising (cPASS/GenScript) antibody (nAb) titers up to one year after mRNA-1273 boost in two-dose-CoronaVac-primed Indonesian healthcare workers (August 2021-August 2022). We used linear mixed modeling to estimate the rate of change in antibody levels, and logistic regression to examine associations between antibody levels and VBI. Results: Of 138 participants, 52 (37.7%) had a prior infection and 78 (56.5%) received an mRNA-1273 booster. After two-dose CoronaVac, antibody titers had significantly declined within 180 days, irrespective of prior infection. After mRNA-1273 booster, anti-spike IgG (1.47% decline/day) and Omicron B.1.1.529/BA.2 nAbs declined between day 28–90, and IgG titers plateaued between day 90–360. During the BA.1/BA.2 wave (February–March 2022), 34.6% (27/78) of individuals experienced a VBI (median 181 days after mRNA-1273), although none developed severe illness. VBI was associated with low pre-VBI anti-spike IgG and B.1.1.529/BA.2 nAbs, which were restored post-VBI. Conclusions: mRNA-1273 booster after two-dose CoronaVac did not prevent BA.1/BA.2 VBI. Periodic vaccine boosters may be warranted against emerging SARS-CoV-2 variants

National and regional asthma programmes in Europe.

peer reviewedThis review presents seven national asthma programmes to support the European Asthma Research and Innovation Partnership in developing strategies to reduce asthma mortality and morbidity across Europe. From published data it appears that in order to influence asthma care, national/regional asthma programmes are more effective than conventional treatment guidelines. An asthma programme should start with the universal commitments of stakeholders at all levels and the programme has to be endorsed by political and governmental bodies. When the national problems have been identified, the goals of the programme have to be clearly defined with measures to evaluate progress. An action plan has to be developed, including defined re-allocation of patients and existing resources, if necessary, between primary care and specialised healthcare units or hospital centres. Patients should be involved in guided self-management education and structured follow-up in relation to disease severity. The three evaluated programmes show that, thanks to rigorous efforts, it is possible to improve patients' quality of life and reduce hospitalisation, asthma mortality, sick leave and disability pensions. The direct and indirect costs, both for the individual patient and for society, can be significantly reduced. The results can form the basis for development of further programme activities in Europe

Global Perspectives on Immunization During Pregnancy and Priorities for Future Research and Development: An International Consensus Statement.

Immunization during pregnancy has been recommended in an increasing number of countries. The aim of this strategy is to protect pregnant women and infants from severe infectious disease, morbidity and mortality and is currently limited to tetanus, inactivated influenza, and pertussis-containing vaccines. There have been recent advancements in the development of vaccines designed primarily for use in pregnant women (respiratory syncytial virus and group B Streptococcus vaccines). Although there is increasing evidence to support vaccination in pregnancy, important gaps in knowledge still exist and need to be addressed by future studies. This collaborative consensus paper provides a review of the current literature on immunization during pregnancy and highlights the gaps in knowledge and a consensus of priorities for future research initiatives, in order to optimize protection for both the mother and the infant

Modification of BRCA1-associated breast cancer risk by HMMR overexpression

Breast cancer risk for carriers of BRCA1 pathological variants is modified by genetic factors. Genetic variation in HMMR may contribute to this effect. However, the impact of risk modifiers on cancer biology remains undetermined and the biological basis of increased risk is poorly understood. Here, we depict an interplay of molecular, cellular, and tissue microenvironment alterations that increase BRCA1-associated breast cancer risk. Analysis of genome-wide association results suggests that diverse biological processes, including links to BRCA1-HMMR profiles, influence risk. HMMR overexpression in mouse mammary epithelium increases Brca1-mutant tumorigenesis by modulating the cancer cell phenotype and tumor microenvironment. Elevated HMMR activates AURKA and reduces ARPC2 localization in the mitotic cell cortex, which is correlated with micronucleation and activation of cGAS-STING and non-canonical NF-kappa B signaling. The initial tumorigenic events are genomic instability, epithelial-to-mesenchymal transition, and tissue infiltration of tumor-associated macrophages. The findings reveal a biological foundation for increased risk of BRCA1-associated breast cancer. The effect of hyaluronan-mediated motility receptor (HMMR) expression in BRCA1-associated breast cancer risk remains unknown. Here, HMMR overexpression induces the activation of cGAS-STING and non-canonical NF-kappa B signalling, instigating an immune permissive environment for breast cancer development

Towards BioDBcore: a community-defined information specification for biological databases

The present article proposes the adoption of a community-defined, uniform, generic description of the core attributes of biological databases, BioDBCore. The goals of these attributes are to provide a general overview of the database landscape, to encourage consistency and interoperability between resources and to promote the use of semantic and syntactic standards. BioDBCore will make it easier for users to evaluate the scope and relevance of available resources. This new resource will increase the collective impact of the information present in biological database