Psychiatric and medical admissions observed among elderly patients with new-onset epilepsy

<p>Abstract</p> <p>Background</p> <p>Inpatient utilization associated with incidence of geriatric new-onset epilepsy has not been characterized in any large study, despite recognized high levels of risk factors (comorbidity).</p> <p>Methods</p> <p>Retrospective study using administrative data (Oct '01-Sep '05) from the Veterans Health Administration from a nationwide sample of 824,483 patients over age 66 in the retrospective observational Treatment In Geriatric Epilepsy Research (TIGER) study. Psychiatric and medical hospital admissions were analyzed as a function of patient demographics, comorbid psychiatric, neurological, and other medical conditions, and new-onset epilepsy.</p> <p>Results</p> <p>Elderly patients experienced a 15% hospitalization rate in FY00 overall, but the subset of new-onset epilepsy patients (n = 1,610) had a 52% hospitalization rate. New-onset epilepsy was associated with three-fold increased relative odds of psychiatric admission and nearly five-fold increased relative odds of medical admission. Among new-onset epilepsy patients, alcohol dependence was most strongly associated with psychiatric admission during the first year after epilepsy onset (odds ratio = 5.2; 95% confidence interval 2.6-10.0), while for medical admissions the strongest factor was myocardial infarction (odds ratio = 4.7; 95% confidence interval 2.7-8.3).</p> <p>Conclusion</p> <p>From the patient point of view, new-onset epilepsy was associated with an increased risk of medical admission as well as of psychiatric admission. From an analytic perspective, omitting epilepsy and other neurological conditions may lead to overestimation of the risk of admission attributable solely to psychiatric conditions. Finally, from a health systems perspective, the emerging picture of the epilepsy patient with considerable comorbidity and demand for healthcare resources may merit development of practice guidelines to improve coordinated delivery of care.</p

The role of glacier mice in the invertebrate colonisation of glacial surfaces: the moss balls of the Falljökull, Iceland

Glacier surfaces have a surprisingly complex ecology. Cryoconite holes contain diverse invertebrate communities while other invertebrates, such as Collembola often graze on algae and windblown dead organic on the glacier surface. Glacier mice (ovoid unattached moss balls) occur on some glaciers worldwide. Studies of these glacier mice have concentrated on their occurrence and mode of formation. There are no reports of the invertebrate communities. But, such glacier mice may provide a suitable favourable habitat and refuge for a variety of invertebrate groups to colonise the glacier surface. Here we describe the invertebrate fauna of the glacier mice (moss balls) of the Falljökull, Iceland. The glacier mice were composed of Racomitrium sp. and varied in size from 8.0 to 10.0 cm in length. All glacier mice studied contained invertebrates. Two species of Collembola were present. Pseudisotoma sensibilis (Tullberg, 1876) was numerically dominant with between 12 and 73 individuals per glacier mouse while Desoria olivacea (Tullberg, 1871) occurred but in far lower numbers. Tardigrada and Nematoda had mean densities of approximately 200 and 1,000 respectively. No Acari, Arachnida or Enchytraeidae were observed which may be related to the difficulty these groups have in colonizing the glacier mice. We suggest that glacier mice provide an unusual environmentally ameliorated microhabitat for an invertebrate community dwelling on a glacial surface. The glacier mice thereby enable an invertebrate fauna to colonise an otherwise largely inhospitable location with implications for carbon flow in the system

Genetic variation in the HLA region is associated with susceptibility to herpes zoster.

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P&gt;1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine

Patterns of primary care and mortality among patients with schizophrenia or diabetes: a cluster analysis approach to the retrospective study of healthcare utilization

Abstract Background Patients with schizophrenia have difficulty managing their medical healthcare needs, possibly resulting in delayed treatment and poor outcomes. We analyzed whether patients reduced primary care use over time, differentially by diagnosis with schizophrenia, diabetes, or both schizophrenia and diabetes. We also assessed whether such patterns of primary care use were a significant predictor of mortality over a 4-year period. Methods The Veterans Healthcare Administration (VA) is the largest integrated healthcare system in the United States. Administrative extracts of the VA's all-electronic medical records were studied. Patients over age 50 and diagnosed with schizophrenia in 2002 were age-matched 1:4 to diabetes patients. All patients were followed through 2005. Cluster analysis explored trajectories of primary care use. Proportional hazards regression modelled the impact of these primary care utilization trajectories on survival, controlling for demographic and clinical covariates. Results Patients comprised three diagnostic groups: diabetes only (n = 188,332), schizophrenia only (n = 40,109), and schizophrenia with diabetes (Scz-DM, n = 13,025). Cluster analysis revealed four distinct trajectories of primary care use: consistent over time, increasing over time, high and decreasing, low and decreasing. Patients with schizophrenia only were likely to have low-decreasing use (73% schizophrenia-only vs 54% Scz-DM vs 52% diabetes). Increasing use was least common among schizophrenia patients (4% vs 8% Scz-DM vs 7% diabetes) and was associated with improved survival. Low-decreasing primary care, compared to consistent use, was associated with shorter survival controlling for demographics and case-mix. The observational study was limited by reliance on administrative data. Conclusion Regular primary care and high levels of primary care were associated with better survival for patients with chronic illness, whether psychiatric or medical. For schizophrenia patients, with or without comorbid diabetes, primary care offers a survival benefit, suggesting that innovations in treatment retention targeting at-risk groups can offer significant promise of improving outcomes.http://deepblue.lib.umich.edu/bitstream/2027.42/78274/1/1472-6963-9-127.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78274/2/1472-6963-9-127.pdfPeer Reviewe

You had to be there: Anachronism and the limits of laughing at the Middle Ages

Comic medievalism is one of the most widespread but least examined forms of postmedieval response. Its combination of comic modality, modern sensibility and historical vision captures what postmedieval audiences have deemed amusing about medieval society. But some instances have been less successful. ‘You had to be there,’ the phrase marking the failure of a comic attempt, and the relationship of that failure to the loss of immediacy, is realized in comic medievalism through the temporal fragility of laughter, historical mediation and temporal paradox. This essay explores some limitpoints to the comic reception of the Middle Ages, focusing especially on its use of anachronism

Validation of a 22-Gene Genomic Classifier in Patients With Recurrent Prostate Cancer An Ancillary Study of the NRG/RTOG 9601 Randomized Clinical Trial

IMPORTANCE: Decipher (Decipher Biosciences Inc) is a genomic classifier (GC) developed to estimate the risk of distant metastasis (DM) after radical prostatectomy (RP) in patients with prostate cancer. OBJECTIVE: To validate the GC in the context of a randomized phase 3 trial. DESIGN, SETTING, AND PARTICIPANTS: This ancillary study used RP specimens from the phase 3 placebo-controlled NRG/RTOG 9601 randomized clinical trial conducted from March 1998 to March 2003. The specimens were centrally reviewed, and RNA was extracted from the highest-grade tumor available in 2019 with a median follow-up of 13 years. Clinical-grade whole transcriptomes from samples passing quality control were assigned GC scores (scale, 0-1). A National Clinical Trials Network–approved prespecified statistical plan included the primary objective of validating the independent prognostic ability of GC for DM, with secondary end points of prostate cancer–specific mortality (PCSM) and overall survival (OS). Data were analyzed from September 2019 to December 2019. INTERVENTIONS: Salvage radiotherapy (sRT) with or without 2 years of bicalutamide. MAIN OUTCOMES AND MEASURES: The preplanned primary end point of this study was the independent association of the GC with the development of DM. RESULTS: In this ancillary study of specimens from a phase 3 randomized clinical trial, GC scores were generated from 486 of 760 randomized patients with a median follow-up of 13 years; samples from a total of 352 men (median [interquartile range] age, 64.5 (60-70) years; 314 White [89.2%] participants) passed microarray quality control and comprised the final cohort for analysis. On multivariable analysis, the GC (continuous variable, per 0.1 unit) was independently associated with DM (hazard ratio [HR], 1.17; 95% CI, 1.05-1.32; P = .006), PCSM (HR, 1.39; 95% CI, 1.20-1.63; P < .001), and OS (HR, 1.17; 95% CI, 1.06-1.29; P = .002) after adjusting for age, race/ethnicity, Gleason score, T stage, margin status, entry prostate-specific antigen, and treatment arm. Although the original planned analysis was not powered to detect a treatment effect interaction by GC score, the estimated absolute effect of bicalutamide on 12-year OS was less when comparing patients with lower vs higher GC scores (2.4% vs 8.9%), which was further demonstrated in men receiving early sRT at a prostate-specific antigen level lower than 0.7 ng/mL (−7.8% vs 4.6%). CONCLUSIONS AND RELEVANCE: This ancillary validation study of the Decipher GC in a randomized trial cohort demonstrated association of the GC with DM, PCSM, and OS independent of standard clinicopathologic variables. These results suggest that not all men with biochemically recurrent prostate cancer after surgery benefit equally from the addition of hormone therapy to sRT. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT0000287

Iron homeostasis and oxidative stress in idiopathic pulmonary alveolar proteinosis: a case-control study

<p>Abstract</p> <p>Background</p> <p>Lung injury caused by both inhaled dusts and infectious agents depends on increased availability of iron and metal-catalyzed oxidative stress. Because inhaled particles, such as silica, and certain infections can cause secondary pulmonary alveolar proteinosis (PAP), we tested the hypothesis that idiopathic PAP is associated with an altered iron homeostasis in the human lung.</p> <p>Methods</p> <p>Healthy volunteers (n = 20) and patients with idiopathic PAP (n = 20) underwent bronchoalveolar lavage and measurements were made of total protein, iron, tranferrin, transferrin receptor, lactoferrin, and ferritin. Histochemical staining for iron and ferritin was done in the cell pellets from control subjects and PAP patients, and in lung specimens of patients without cardiopulmonary disease and with PAP. Lavage concentrations of urate, glutathione, and ascorbate were also measured as indices of oxidative stress.</p> <p>Results</p> <p>Lavage concentrations of iron, transferrin, transferrin receptor, lactoferrin, and ferritin were significantly elevated in PAP patients relative to healthy volunteers. The cells of PAP patients had accumulated significant iron and ferritin, as well as considerable amounts of extracellular ferritin. Immunohistochemistry for ferritin in lung tissue revealed comparable amounts of this metal-storage protein in the lower respiratory tract of PAP patients both intracellularly and extracellularly. Lavage concentrations of ascorbate, glutathione, and urate were significantly lower in the lavage fluid of the PAP patients.</p> <p>Conclusion</p> <p>Iron homeostasis is altered in the lungs of patients with idiopathic PAP, as large amounts of catalytically-active iron and low molecular weight anti-oxidant depletion are present. These findings suggest a metal-catalyzed oxidative stress in the maintenance of this disease.</p

Brain Phenotype of Transgenic Mice Overexpressing Cystathionine β-Synthase

The cystathionine β-synthase (CBS) gene, located on human chromosome 21q22.3, is a good candidate for playing a role in the Down Syndrome (DS) cognitive profile: it is overexpressed in the brain of individuals with DS, and it encodes a key enzyme of sulfur-containing amino acid (SAA) metabolism, a pathway important for several brain physiological processes.Here, we have studied the neural consequences of CBS overexpression in a transgenic mouse line (60.4P102D1) expressing the human CBS gene under the control of its endogenous regulatory regions. These mice displayed a ∼2-fold increase in total CBS proteins in different brain areas and a ∼1.3-fold increase in CBS activity in the cerebellum and the hippocampus. No major disturbance of SAA metabolism was observed, and the transgenic mice showed normal behavior in the rotarod and passive avoidance tests. However, we found that hippocampal synaptic plasticity is facilitated in the 60.4P102D1 line.We demonstrate that CBS overexpression has functional consequences on hippocampal neuronal networks. These results shed new light on the function of the CBS gene, and raise the interesting possibility that CBS overexpression might have an advantageous effect on some cognitive functions in DS

Proteomic Basis of the Antibody Response to Monkeypox Virus Infection Examined in Cynomolgus Macaques and a Comparison to Human Smallpox Vaccination

Monkeypox is a zoonotic viral disease that occurs primarily in Central and West Africa. A recent outbreak in the United States heightened public health concerns for susceptible human populations. Vaccinating with vaccinia virus to prevent smallpox is also effective for monkeypox due to a high degree of sequence conservation. Yet, the identity of antigens within the monkeypox virus proteome contributing to immune responses has not been described in detail. We compared antibody responses to monkeypox virus infection and human smallpox vaccination by using a protein microarray covering 92–95% (166–192 proteins) of representative proteomes from monkeypox viral clades of Central and West Africa, including 92% coverage (250 proteins) of the vaccinia virus proteome as a reference orthopox vaccine. All viral gene clones were verified by sequencing and purified recombinant proteins were used to construct the microarray. Serum IgG of cynomolgus macaques that recovered from monkeypox recognized at least 23 separate proteins within the orthopox proteome, while only 14 of these proteins were recognized by IgG from vaccinated humans. There were 12 of 14 antigens detected by sera of human vaccinees that were also recognized by IgG from convalescent macaques. The greatest level of IgG binding for macaques occurred with the structural proteins F13L and A33R, and the membrane scaffold protein D13L. Significant IgM responses directed towards A44R, F13L and A33R of monkeypox virus were detected before onset of clinical symptoms in macaques. Thus, antibodies from vaccination recognized a small number of proteins shared with pathogenic virus strains, while recovery from infection also involved humoral responses to antigens uniquely recognized within the monkeypox virus proteome

Gene expression profiling reveals differential effects of sodium selenite, selenomethionine, and yeast-derived selenium in the mouse

The essential trace mineral selenium is an important determinant of oxidative stress susceptibility, with several studies showing an inverse relationship between selenium intake and cancer. Because different chemical forms of selenium have been reported to have varying bioactivity, there is a need for nutrigenomic studies that can comprehensively assess whether there are divergent effects at the molecular level. We examined the gene expression profiles associated with selenomethionine (SM), sodium selenite (SS), and yeast-derived selenium (YS) in the intestine, gastrocnemius, cerebral cortex, and liver of mice. Weanling mice were fed either a selenium-deficient (SD) diet (<0.01 mg/kg diet) or a diet supplemented with one of three selenium sources (1 mg/kg diet, as either SM, SS or YS) for 100 days. All forms of selenium were equally effective in activating standard measures of selenium status, including tissue selenium levels, expression of genes encoding selenoproteins (Gpx1 and Txnrd2), and increasing GPX1 enzyme activity. However, gene expression profiling revealed that SS and YS were similar (and distinct from SM) in both the expression pattern of individual genes and gene functional categories. Furthermore, only YS significantly reduced the expression of Gadd45b in all four tissues and also reduced GADD45B protein levels in liver. Taken together, these results show that gene expression profiling is a powerful technique capable of elucidating differences in the bioactivity of different forms of selenium