2021 Adult Foster Home Resident and Community Characteristics Report on Adult Foster Homes

This report describes results from an annual study of Oregon adult foster homes (AFH). Data contained in this report include home and owner characteristics; monthly charges and payment sources; and resident characteristics, personal and health-related needs. The study’s purpose was to collect and report data that can inform and advise policymakers, state and county agency staff, aging advocates and AFH owners about the status of AFHs in Oregon. These data were collected between December 2020 and February 2021. This report constitutes the first year during the COVID-19 pandemic that these annual data were collected

2021 Community-Based Care: Resident and Community Characteristics Report on Assisted Living, Residential Care, and Memory Care Communities

This report summarizes findings from the 7th annual study of Oregon assisted living (AL) and residential care (RC) facilities, including memory care (MC) communities. The purpose of this report is to inform Oregon Department of Human Services (ODHS), providers, consumers, and other interested parties about this sector of long-term services and supports (LTSS) and ensure data-informed policy decisions. The report contains information about various resident and community characteristics, including capacity and supply, resident demographics and health services use, and community services, policies, fees, and staffing. These data were collected between winter 2020 and spring 2021. This report constitutes the first year during the COVID-19 pandemic that these annual data were collected

Proteomic and Biological Analysis of the Effects of Metformin Senomorphics on the Mesenchymal Stromal Cells

Senotherapeutics are new drugs that can modulate senescence phenomena within tissues and reduce the onset of age-related pathologies. Senotherapeutics are divided into senolytics and senomorphics. The senolytics selectively kill senescent cells, while the senomorphics delay or block the onset of senescence. Metformin has been used to treat diabetes for several decades. Recently, it has been proposed that metformin may have anti-aging properties as it prevents DNA damage and inflammation. We evaluated the senomorphic effect of 6 weeks of therapeutic metformin treatment on the biology of human adipose mesenchymal stromal cells (MSCs). The study was combined with a proteome analysis of changes occurring in MSCs’ intracellular and secretome protein composition in order to identify molecular pathways associated with the observed biological phenomena. The metformin reduced the replicative senescence and cell death phenomena associated with prolonged in vitro cultivation. The continuous metformin supplementation delayed and/or reduced the impairment of MSC functions as evidenced by the presence of three specific pathways in metformin-treated samples: 1) the alpha-adrenergic signaling, which contributes to regulation of MSCs physiological secretory activity, 2) the signaling pathway associated with MSCs detoxification activity, and 3) the aspartate degradation pathway for optimal energy production. The senomorphic function of metformin seemed related to its reactive oxygen species (ROS) scavenging activity. In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS

The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver

LKB1 is a master kinase that regulates metabolism and growth through adenosine monophosphate-activated protein kinase (AMPK) and 12 other closely related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. Here we report that the salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressors downstream of LKB1 in the liver. The selective SIK inhibitor HG-9-91-01 promotes dephosphorylation of transcriptional co-activators CRTC2/3 resulting in enhanced gluconeogenic gene expression and glucose production in hepatocytes, an effect that is abolished when an HG-9-91-01-insensitive mutant SIK is introduced or LKB1 is ablated. Although SIK2 was proposed as a key regulator of insulin-mediated suppression of gluconeogenesis, we provide genetic evidence that liver-specific ablation of SIK2 alone has no effect on gluconeogenesis and insulin does not modulate SIK2 phosphorylation or activity. Collectively, we demonstrate that the LKB1-SIK pathway functions as a key gluconeogenic gatekeeper in the liver

Accelerated diabetic wound healing by topical application of combination oral antidiabetic agents-loaded nanofibrous scaffolds: An in vitro and in vivo evaluation study

The combination of oral antidiabetic drugs, pioglitazone, metformin, and glibenclamide, which also exhibit the strongest anti-inflammatory action among oral antidiabetic drugs, were loaded into chitosan/gelatin/polycaprolactone (PCL) by electrospinning and polyvinyl pyrrolidone (PVP)/PCL composite nanofibrous scaffolds by pressurized gyration to compare the diabetic wound healing effect. The combination therapies significantly accelerated diabetic wound healing in type-1 diabetic rats and organized densely packed collagen fibers in the dermis, it also showed better regeneration of the dermis and epidermis than single drug-loaded scaffolds with less inflammatory cell infiltration and edema. The formation of the hair follicles started in 14 days only in the combination therapy and lower proinflammatory cytokine levels were observed compared to single drug-loaded treatment groups. The combination therapy increased the wettability and hydrophilicity of scaffolds, demonstrated sustained drug release over 14 days, has high tensile strength and suitable cytocompatibility on L929 (mouse fibroblast) cell and created a suitable area for the proliferation of fibroblast cells. Consequently, the application of metformin and pioglitazone-loaded chitosan/gelatin/PCL nanofibrous scaffolds to a diabetic wound area offer high bioavailability, fewer systemic side effects, and reduced frequency of dosage and amount of drug

Model-Independent Searches for New Quarks at the LHC

New vector-like quarks can have sizable couplings to first generation quarks without conflicting with current experimental constraints. The coupling with valence quarks and unique kinematics make single production the optimal discovery process. We perform a model-independent analysis of the discovery reach at the Large Hadron Collider for new vector-like quarks considering single production and subsequent decays via electroweak interactions. An early LHC run with 7 TeV center of mass energy and 1 fb-1 of integrated luminosity can probe heavy quark masses up to 1 TeV and can be competitive with the Tevatron reach of 10 fb-1. The LHC with 14 TeV center of mass energy and 100 fb-1 of integrated luminosity can probe heavy quark masses up to 3.7 TeV for order one couplings.Comment: 37 pages, 11 figures, 7 table

Psychometric evaluation of the nine-item problematic Internet use questionnaire (PIUQ-9) in nine European samples of internet users

Objectives: The nine-item Problematic Internet Use Questionnaire (PIUQ-9) is a brief self-report screening instrument for problematic internet use. The main objective of the present study was to explore the psychometric properties of the PIUQ-9 among nine different language-based samples of European internet users (Italian, German, French, Polish, Turkish, Hungarian, English, and Greek). Methods: The total sample comprised 5,593 internet users (38.1% men), aged between 18 and 87 years (M = 25.81; SD = 8.61). Via online recruitment, participants completed the PIUQ-9, the Brief Symptom Inventory (BSI) and items about time spent online. Results: Confirmatory factor analysis demonstrated that the bifactor model with one general factor (i.e., general problem) and two-specific factors (i.e., obsession and neglect + control disorder) yielded acceptable or good fit indices in all subsamples except for one. The common variance index in the bifactor model indicated that the general problem factor explained from 57.0 to 76.5% of common variance, which supports the presence of a strong global factor. According to the multiple indicators multiple causes (MIMIC) model, psychiatric symptoms had a moderate-to-strong direct effect on the general problem factor in all subsamples, ranging from β = 0.28 to β = 0.52 supporting the construct validity of the scale. Furthermore, in a majority of the subsamples, time spent online during the weekend had considerably higher effect sizes on the general problem factor than time spent online during weekdays. Conclusion: The present study highlights the appropriate psychometric properties of the PIUQ-9 across a number of European languages and cultures

Influences of Excluded Volume of Molecules on Signaling Processes on Biomembrane

We investigate the influences of the excluded volume of molecules on biochemical reaction processes on 2-dimensional surfaces using a model of signal transduction processes on biomembranes. We perform simulations of the 2-dimensional cell-based model, which describes the reactions and diffusion of the receptors, signaling proteins, target proteins, and crowders on the cell membrane. The signaling proteins are activated by receptors, and these activated signaling proteins activate target proteins that bind autonomously from the cytoplasm to the membrane, and unbind from the membrane if activated. If the target proteins bind frequently, the volume fraction of molecules on the membrane becomes so large that the excluded volume of the molecules for the reaction and diffusion dynamics cannot be negligible. We find that such excluded volume effects of the molecules induce non-trivial variations of the signal flow, defined as the activation frequency of target proteins, as follows. With an increase in the binding rate of target proteins, the signal flow varies by i) monotonically increasing; ii) increasing then decreasing in a bell-shaped curve; or iii) increasing, decreasing, then increasing in an S-shaped curve. We further demonstrate that the excluded volume of molecules influences the hierarchical molecular distributions throughout the reaction processes. In particular, when the system exhibits a large signal flow, the signaling proteins tend to surround the receptors to form receptor-signaling protein clusters, and the target proteins tend to become distributed around such clusters. To explain these phenomena, we analyze the stochastic model of the local motions of molecules around the receptor.Comment: 31 pages, 10 figure

Synaptic vesicle dynamic changes in a model of fragile X

__Background:__ Fragile X syndrome (FXS) is a single-gene disorder that is the most common heritable cause of intellectual disability and the most frequent monogenic cause of autism spectrum disorders (ASD). FXS is caused by an expansion of trinucleotide repeats in the promoter region of the fragile X mental retardation gene (Fmr1). This leads to a lack of fragile X mental retardation protein (FMRP), which regulates translation of a wide range of messenger RNAs (mRNAs). The extent of expression level alterations of synaptic proteins affected by FMRP loss and their consequences on synaptic dynamics in FXS has not been fully investigated. __Methods:__ Here, we used an Fmr1 knockout (KO) mouse model to investigate the molecular mechanisms underlying FXS by monitoring protein expression changes using shotgun label-free liquid-chromatography mass spectrometry (LC-MSE) in brain tissue and synaptosome fractions. FXS-associated candidate proteins were validated using selected reaction monitoring (SRM) in synaptosome fractions for targeted protein quantification. Furthermore, functional alterations in synaptic release and dynamics were evaluated using live-cell imaging, and interpretation of synaptic dynamics differences was investigated using electron microscopy. __Results:__ Key findings relate to altered levels of proteins involved in GABA-signalling, especially in the cerebellum. Further exploration using microscopy studies found reduced synaptic vesicle unloading of hippocampal neurons and increased vesicle unloading in cerebellar neurons, which suggests a general decrease of synaptic transmission. __Conclusions:__ Our findings suggest that FMRP is a regulator of synaptic vesicle dynamics, which supports the role of FMRP in presynaptic functions. Taken together, these studies provide novel insights into the molecular changes associated with FXS

The co-presence of deletion 7q, 20q and inversion 16 in therapy-related acute myeloid leukemia developed secondary to treatment of breast cancer with cyclophosphamide, doxorubicin, and radiotherapy: a case report

Introduction. Therapy-related acute myeloid leukemia occurs as a complication of treatment with chemotherapy, radiotherapy, immunosuppressive agents or exposure to environmental carcinogens. Case presentation. We report a case of therapy-related acute myeloid leukemia in a 37-year-old Turkish woman in complete remission from breast cancer. Our patient presented to our facility with fatigue, fever, sore throat, peripheral lymphadenopathy, and moderate hepatosplenomegaly. On peripheral blood and bone marrow aspirate smears, monoblasts were present. Immunophenotypic analysis of the bone marrow showed expression of CD11b, CD13, CD14, CD15, CD33, CD34, CD45 and human leukocyte antigen-DR, findings compatible with the diagnosis of acute monoblastic leukemia (French-American-British classification M5a). Therapy-related acute myeloid leukemia developed three years after adjuvant chemotherapy consisting of an alkylating agent, cyclophosphamide and DNA topoisomerase II inhibitor, doxorubicin and adjuvant radiotherapy. Cytogenetic analysis revealed a 46, XX, deletion 7 (q22q34), deletion 20 (q11.2q13.1) karyotype in five out of 20 metaphases and inversion 16 was detected by fluorescence in situ hybridization. There was no response to chemotherapy (cytarabine and idarubicin, FLAG-IDA protocol, azacitidine) and our patient died in the 11th month after diagnosis. Conclusions: The median survival in therapy-related acute myeloid leukemia is shorter compared to de novo acute myeloid leukemia. Also, the response to therapy is poor. In therapy-related acute myeloid leukemia, complex karyotypes have been associated with abnormalities of chromosome 5, rather than 7. To the best of our knowledge, this is the first case of therapy-related acute myeloid leukemia showing the co-presence of deletion 7q, 20q and the inversion 16 signal. © 2012 Yonal et al; licensee BioMed Central Ltd