Reproductive Health and Coronavirus Disease 2019-Induced Economic Contracture: Lessons From the Great Recession.

The coronavirus disease 2019 (COVID-19) pandemic has magnified disparities in care, including within reproductive health. There has been limited research on the implications of the financial calamity COVID-19 has precipitated on reproductive health, including restricted access to contraception and prenatal care, as well as adverse perinatal outcomes resulting from economic contracture. We therefore examined the Great Recession (the period of economic downturn from 2007-2009 also referred to as the 2008 recession) to discuss how the current financial difficulties may influence reproductive health now and in the years to come. The existing literature examining the impacts of economic downturn on reproductive health provides a resounding body of evidence supporting the need for state and federal investment in comprehensive reproductive health care. Policies directed at expanding access to programs such as Special Supplemental Nutrition Program for Women, Infants, and Children and Medicaid (WIC), extending Medicaid coverage to 12 months' postpartum, continuing coverage for telehealth services, and lowering barriers to access through mobile care units would help mitigate anticipated effects of a recession on reproductive health.

Variation in the interpretation and application of the Medicaid sterilization consent form among Medicaid officials.

OBJECTIVE: The Medicaid consent policy has been identified as a major barrier to desired permanent contraception, particularly for low-income communities and communities of color. As each state may modify their state Medicaid sterilization consent form, variation in the form has been reported. This study aims to characterize state-level variation in Medicaid Title XIX consent form interpretation and application. STUDY DESIGN: We aimed to collect primary data from Medicaid officials in all 50 United States from January to May 2020 via a 25-question electronic survey regarding state-level consent form implementation. Questions targeted consent form details and definitions, insurance and billing, clinician correspondence, and administrative processes. We used Qualtrics XM to collect survey responses. We performed descriptive statistics on the survey responses. There were no exclusion criteria. RESULTS: We had 41 responses from 36/50 states (72% participation rate). Heterogeneity existed in the key definitions of "Premature Delivery" and "Emergency Abdominal Surgery." One in five respondents reported the consent form was only available in English. Variation among Current Procedural Terminology codes covered in each state's sterilization policy were noted. Nearly a quarter of respondents did not know how Medicaid informed healthcare providers of consent form denials. Most participants (90%) were unaware of differences between state sterilization policies. CONCLUSION: This study demonstrates variation in terms of consent form definitions, procedures covered, correspondence with clinicians, and administrative review processes among state Medicaid offices regarding the sterilization consent form. Greater transparency is necessary in order to reduce administrative barriers to desired permanent contraception. IMPLICATIONS: Inconsistent interpretation poses an administrative barrier to care, raises concern regarding appropriate clinician reimbursement, and can potentially lead to unnecessarily denying patients the contraceptive option of their choice. Permanent contraception policies should be equitable no matter insurance status, preserve reproductive autonomy and effectively protect vulnerable populations.

An optical nanoreporter of endolysosomal lipid accumulation reveals enduring effects of diet on hepatic macrophages in vivo.

The abnormal accumulation of lipids within the endolysosomal lumen occurs in many conditions, including lysosomal storage disorders, atherosclerosis, nonalcoholic fatty liver disease (NAFLD), and drug-induced phospholipidosis. Current methods cannot monitor endolysosomal lipid content in vivo, hindering preclinical drug development and research into the mechanisms linking endolysosomal lipid accumulation to disease progression. We developed a single-walled carbon nanotube-based optical reporter that noninvasively measures endolysosomal lipid accumulation via bandgap modulation of its intrinsic near-infrared emission. The reporter detected lipid accumulation in Niemann-Pick disease, atherosclerosis, and NAFLD models in vivo. By applying the reporter to the study of NAFLD, we found that elevated lipid quantities in hepatic macrophages caused by a high-fat diet persist long after reverting to a normal diet. The reporter dynamically monitored endolysosomal lipid accumulation in vivo over time scales ranging from minutes to weeks, indicating its potential to accelerate preclinical research and drug development processes.

Preclinical assessment of antiviral combination therapy in a genetically humanized mouse model for hepatitis delta virus infection.

Chronic delta hepatitis, caused by hepatitis delta virus (HDV), is the most severe form of viral hepatitis, affecting at least 20 million hepatitis B virus (HBV)-infected patients worldwide. HDV/HBV co- or superinfections are major drivers for hepatocarcinogenesis. Antiviral treatments exist only for HBV and can only suppress but not cure infection. Development of more effective therapies has been impeded by the scarcity of suitable small-animal models. We created a transgenic (tg) mouse model for HDV expressing the functional receptor for HBV and HDV, the human sodium taurocholate cotransporting peptide NTCP. Both HBV and HDV entered hepatocytes in these mice in a glycoprotein-dependent manner, but one or more postentry blocks prevented HBV replication. In contrast, HDV persistently infected hNTCP tg mice coexpressing the HBV envelope, consistent with HDV dependency on the HBV surface antigen (HBsAg) for packaging and spread. In immunocompromised mice lacking functional B, T, and natural killer cells, viremia lasted at least 80 days but resolved within 14 days in immunocompetent animals, demonstrating that lymphocytes are critical for controlling HDV infection. Although acute HDV infection did not cause overt liver damage in this model, cell-intrinsic and cellular innate immune responses were induced. We further demonstrated that single and dual treatment with myrcludex B and lonafarnib efficiently suppressed viremia but failed to cure HDV infection at the doses tested. This small-animal model with inheritable susceptibility to HDV opens opportunities for studying viral pathogenesis and immune responses and for testing novel HDV therapeutics.

Pluripotent Stem Cell-Derived Hepatocyte-like Cells: A Tool to Study Infectious Disease.

PURPOSE OF REVIEW: Liver disease is an important clinical and global problem and is the 16th leading cause of death worldwide and responsible for 1 million deaths worldwide each year. Infectious disease is a major cause of liver disease specifically and overall is even a greater cause of patient morbidity and mortality. Tools to study human liver disease and infectious disease have been lacking which has significantly hampered the study of liver disease generally and hepatotropic pathogens more specifically. Historically, hepatoma cell lines have been used for in vitro cell culture models to study infectious disease. Significant differences between human hepatoma cell lines and the human hepatocyte has hampered our understanding of hepatocyte pathogen infection and hepatocyte--pathogen interactions. RECENT FINDINGS: Despite these limitations, great progress was made in the understanding of specific aspects of the life cycle of the canonical hepatocyte viral pathogen, Hepatitis C Virus. Over time various specific drugs targeting various proteins of the HCV virion or aspects of the HCV viral life cycle have been created that enable almost complete elimination of the virus in vitro and clinically. These drugs, direct-acting antivirals have enabled achieving sustained virologic response in over 90-95 percent of patients. SUMMARY: Despite the development of direct-acting antivirals and the extreme success in achieving sustained virologic response, there has only been limited success elucidating host-pathogen interactions largely due to the poor nature of the hepatoma platform. Alternative approaches are needed. Pluripotent stem cells are renewable, can be derived from a single donor and can be efficiently and reproducibly differentiated towards many cell types including ectodermal-, endodermal-, and mesodermal-derived lineages. The development of pluripotent stem cell-derived hepatocyte-like cells (iHLCS) changes the paradigm as robust cells with the phenotype and function of hepatocytes can be readily created on demand with a variety of genetic background or alterations. iHLCs are readily used as models to study human drug metabolism, human liver disease, and human hepatotropic infectious disease. In this review, we discuss the biology of the HCV virus, the use of iHLCs as models to study human liver disease, and review the current work on using iHLCs to study HCV infection.

Engraftment of human induced pluripotent stem cell-derived hepatocytes in immunocompetent mice via 3D co-aggregation and encapsulation.

Cellular therapies for liver diseases and in vitro models for drug testing both require functional human hepatocytes (Hum-H), which have unfortunately been limited due to the paucity of donor liver tissues. Human pluripotent stem cells (hPSCs) represent a promising and potentially unlimited cell source to derive Hum-H. However, the hepatic functions of these hPSC-derived cells to date are not fully comparable to adult Hum-H and are more similar to fetal ones. In addition, it has been challenging to obtain functional hepatic engraftment of these cells with prior studies having been done in immunocompromised animals. In this report, we demonstrated successful engraftment of human induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (iPS-H) in immunocompetent mice by pre-engineering 3D cell co-aggregates with stromal cells (SCs) followed by encapsulation in recently developed biocompatible hydrogel capsules. Notably, upon transplantation, human albumin and α1-antitrypsin (A1AT) in mouse sera secreted by encapsulated iPS-H/SCs aggregates reached a level comparable to the primary Hum-H/SCs control. Further immunohistochemistry of human albumin in retrieved cell aggregates confirmed the survival and function of iPS-H. This proof-of-concept study provides a simple yet robust approach to improve the engraftment of iPS-H, and may be applicable to many stem cell-based therapies.