Osteoporosis Epidemiology Among Adults With Cerebral Palsy: Findings From Private and Public Administrative Claims Data

Individuals with cerebral palsy (CP) have an increased risk for the early development of osteoporosis; however, little is known about the epidemiology of osteoporosis for adults with CP, which is vital to inform clinical practice for osteoporosis prevention, treatment, and management. The purpose of this cross‐sectional study was to determine sex‐stratified prevalence of osteoporosis among adults with CP, as compared with adults without CP. Data from 2016 were extracted from Optum Clinformatics Data Mart (private insurance administrative claims data) and a random 20% sample from the fee‐for‐service Medicare (public insurance administrative claims data). Diagnostic codes were used to identify CP and osteoporosis diagnoses. Sex‐stratified prevalence of osteoporosis was compared between adults with and without CP for the following age groups: 18 to 30, 31 to 40, 41 to 50, 51 to 60, 61 to 70, and >70 years of age. The overall prevalence of osteoporosis was 4.8% for adults without CP (n = 8.7 million), 8.4% for privately insured adults with CP (n = 7,348), and 14.3% for publicly insured adults with CP (n = 21,907). Women and men with CP had a higher prevalence of osteoporosis compared with women and men without CP for all age groups. Finally, publicly insured women and men with CP had a higher prevalence of osteoporosis compared with privately insured women and men with CP for all age groups, except for the similar prevalence among the 18‐ to 30‐year age group. These findings suggest that osteoporosis is more prevalent among adults with CP compared with adults without CP. Study findings highlight the need for earlier screening and preventive medical services for osteoporosis management among adults with CP. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral ResearchPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152612/1/jbm410231_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152612/2/jbm410231.pd

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Regenerative peripheral nerve interface free muscle graft mass and function

BackgroundRegenerative peripheral nerve interfaces (RPNIs) transduce neural signals to provide high‐fidelity control of neuroprosthetic devices. Traditionally, rat RPNIs are constructed with ~150 mg of free skeletal muscle grafts. It is unknown whether larger free muscle grafts allow RPNIs to transduce greater signal.MethodsRPNIs were constructed by securing skeletal muscle grafts of various masses (150, 300, 600, or 1200 mg) to the divided peroneal nerve. In the control group, the peroneal nerve was transected without repair. Endpoint assessments were conducted 3 mo postoperatively.ResultsCompound muscle action potentials (CMAPs), maximum tetanic isometric force, and specific muscle force were significantly higher for both the 150 and 300 mg RPNI groups compared to the 600 and 1200 mg RPNIs. Larger RPNI muscle groups contained central areas lacking regenerated muscle fibers.ConclusionsElectrical signaling and tissue viability are optimal in smaller as opposed to larger RPNI constructs in a rat model.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/166376/1/mus27138.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/166376/2/mus27138_am.pd

Mapping Complex Traits in a Diversity Outbred F1 Mouse Population Identifies Germline Modifiers of Metastasis in Human Prostate Cancer.

It is unclear how standing genetic variation affects the prognosis of prostate cancer patients. To provide one controlled answer to this problem, we crossed a dominant, penetrant mouse model of prostate cancer to Diversity Outbred mice, a collection of animals that carries over 40 million SNPs. Integration of disease phenotype and SNP variation data in 493 F1 males identified a metastasis modifier locus on Chromosome 8 (LOD = 8.42); further analysis identified the genes Rwdd4, Cenpu, and Casp3 as functional effectors of this locus. Accordingly, analysis of over 5,300 prostate cancer patient samples revealed correlations between the presence of genetic variants at these loci, their expression levels, cancer aggressiveness, and patient survival. We also observed that ectopic overexpression of RWDD4 and CENPU increased the aggressiveness of two human prostate cancer cell lines. In aggregate, our approach demonstrates how well-characterized genetic variation in mice can be harnessed in conjunction with systems genetics approaches to identify and characterize germline modifiers of human disease processes. Cell Syst 2017 Jan 25; 4(1):31-45.e

Mapping complex traits in a diversity outbred f1 mouse population identifies germline modifiers of metastasis in human prostate cancer

It is unclear how standing genetic variation affects the prognosis of prostate cancer patients. To provide one controlled answer to this problem, we crossed a dominant, penetrant mouse model of prostate cancer to Diversity Outbred mice, a collection of animals that carries over 40 million SNPs. Integration of disease phenotype and SNP variation data in 493 F1 males identified a metastasis modifier locus on Chromosome 8 (LOD = 8.42); further analysis identified the genes Rwdd4, Cenpu, and Casp3 as functional effectors of this locus. Accordingly, analysis of over 5,300 prostate cancer patient samples revealed correlations between the presence of genetic variants at these loci, their expression levels, cancer aggressiveness, and patient survival. We also observed that ectopic overexpression of RWDD4 and CENPU increased the aggressiveness of two human prostate cancer cell lines. In aggregate, our approach demonstrates how well-characterized genetic variation in mice can be harnessed in conjunction with systems genetics approaches to identify and characterize germline modifiers of human disease processes.Jean M. Winter, Derek E. Gildea, Jonathan P. Andreas, Daniel M. Gatti, Kendra A. Williams, Minnkyong Lee ... et al

Contemplating the future: Mutating capitalism

After the fall of international communism in the former Soviet Union, capitalism has remained the only viable option for managing the economy. Economic and financial problems of capitalism of recent times, however, have brought forth debate about the role and shape of capitalism, and mainly its future. These problems have made it very clear that unbridled capitalism may not produce the proclaimed prosperity. Some have questioned its future viability in the present form and predicated its metamorphosing into a different kind that could make it more beneficial to the people and more resilient to survive. Questions regarding its future shape and form and the reasons for such predication are the subject of this article

Tumor-Associated Lymphocytes and Increased FoxP3+ Regulatory T Cell Frequency Correlate with More Aggressive Papillary Thyroid Cancer

Context: Ten to 30% of patients with papillary thyroid cancer (PTC) develop recurrent disease and may benefit from innovative adjuvant therapies. Immune-based therapies are under investigation to treat many types of cancer. The role of the immune system in PTC is poorly understood

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection