Can the internet reduce the loneliness of 50+ living alone?

Published online: 12 May 2020Living alone has been indicated as a key variable to explain loneliness in older adults. In contemporary society, where technology has become one of the main means of communication and personal interaction, has the internet influenced the relationship between living alone and loneliness? This paper aims to answer this research question by using a sample of 64,297 individuals who were surveyed in SHARE project wave 6 – in European countries with different welfare regimes (Portugal, Greece, Italy and Spain, Denmark, Sweden, Austria, Belgium, France, Germany, Switzerland, Luxemburg, Poland, Czech Republic; Slovenia, Estonia, and Croatia). The results of the regression analysis evidence the moderating role of the internet on the relationship between living alone and feelings of loneliness in individuals aged 50 and over, so that the impact of living alone on loneliness is diminished for internet users as compared to their peers who do not use the internet. The results therefore reinforce the importance of policies aimed at fostering e-inclusion as a way of reducing the loneliness of older adultsThis work was supported by European Commission; Fundação para a Ciência e a Tecnologia; U.S National Institute on Aging; Fundação Calouste Gulbenkian; German Ministry of Education and Researc

A contractile injection system stimulates tubeworm metamorphosis by translocating a proteinaceous effector

The swimming larvae of many marine animals identify a location on the sea floor to undergo metamorphosis based on the presence of specific bacteria. Although this microbe–animal interaction is critical for the life cycles of diverse marine animals, what types of biochemical cues from bacteria that induce metamorphosis has been a mystery. Metamorphosis of larvae of the tubeworm Hydroides elegans is induced by arrays of phage tail-like contractile injection systems, which are released by the bacterium Pseudoalteromonas luteoviolacea. Here we identify the novel effector protein Mif1. By cryo-electron tomography imaging and functional assays, we observe Mif1 as cargo inside the tube lumen of the contractile injection system and show that the mif1 gene is required for inducing metamorphosis. Purified Mif1 is sufficient for triggering metamorphosis when electroporated into tubeworm larvae. Our results indicate that the delivery of protein effectors by contractile injection systems may orchestrate microbe–animal interactions in diverse contexts

Peptidyl-Prolyl Isomerase 1 Regulates Ca(2+) Handling by Modulating Sarco(endo)plasmic Reticulum Calcium ATPase and Na(2+)/Ca(2+) Exchanger 1 Protein Levels and Function

BACKGROUND: Aberrant Ca(2+) handling is a prominent feature of heart failure. Elucidation of the molecular mechanisms responsible for aberrant Ca(2+) handling is essential for the development of strategies to blunt pathological changes in calcium dynamics. The peptidyl-prolyl cis-trans isomerase peptidyl-prolyl isomerase 1 (Pin1) is a critical mediator of myocardial hypertrophy development and cardiac progenitor cell cycle. However, the influence of Pin1 on calcium cycling regulation has not been explored. On the basis of these findings, the aim of this study is to define Pin1 as a novel modulator of Ca(2+) handling, with implications for improving myocardial contractility and potential for ameliorating development of heart failure. METHODS AND RESULTS: Pin1 gene deletion or pharmacological inhibition delays cytosolic Ca(2+) decay in isolated cardiomyocytes. Paradoxically, reduced Pin1 activity correlates with increased sarco(endo)plasmic reticulum calcium ATPase (SERCA2a) and Na(2+)/Ca(2+) exchanger 1 protein levels. However, SERCA2a ATPase activity and calcium reuptake were reduced in sarcoplasmic reticulum membranes isolated from Pin1-deficient hearts, suggesting that Pin1 influences SERCA2a function. SERCA2a and Na(2+)/Ca(2+) exchanger 1 associated with Pin1, as revealed by proximity ligation assay in myocardial tissue sections, indicating that regulation of Ca(2+) handling within cardiomyocytes is likely influenced through Pin1 interaction with SERCA2a and Na(2+)/Ca(2+) exchanger 1 proteins. CONCLUSIONS: Pin1 serves as a modulator of SERCA2a and Na(2+)/Ca(2+) exchanger 1 Ca(2+) handling proteins, with loss of function resulting in impaired cardiomyocyte relaxation, setting the stage for subsequent investigations to assess Pin1 dysregulation and modulation in the progression of heart failure

Reversal of Fragile X Phenotypes by Manipulation of AβPP/Aβ Levels in Fmr1KO Mice

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the leading known genetic cause of autism. Fragile X mental retardation protein (FMRP), which is absent or expressed at substantially reduced levels in FXS, binds to and controls the postsynaptic translation of amyloid β-protein precursor (AβPP) mRNA. Cleavage of AβPP can produce β-amyloid (Aβ), a 39–43 amino acid peptide mis-expressed in Alzheimer's disease (AD) and Down syndrome (DS). Aβ is over-expressed in the brain of Fmr1KO mice, suggesting a pathogenic role in FXS. To determine if genetic reduction of AβPP/Aβ rescues characteristic FXS phenotypes, we assessed audiogenic seizures (AGS), anxiety, the ratio of mature versus immature dendritic spines and metabotropic glutamate receptor (mGluR)-mediated long-term depression (LTD) in Fmr1KO mice after removal of one App allele. All of these phenotypes were partially or completely reverted to normal. Plasma Aβ1–42 was significantly reduced in full-mutation FXS males compared to age-matched controls while cortical and hippocampal levels were somewhat increased, suggesting that Aβ is sequestered in the brain. Evolving therapies directed at reducing Aβ in AD may be applicable to FXS and Aβ may serve as a plasma-based biomarker to facilitate disease diagnosis or assess therapeutic efficacy

A contractile injection system stimulates tubeworm metamorphosis by translocating a proteinaceous effector

The swimming larvae of many marine animals identify a location on the sea floor to undergo metamorphosis based on the presence of specific bacteria. Although this microbe–animal interaction is critical for the life cycles of diverse marine animals, what types of biochemical cues from bacteria that induce metamorphosis has been a mystery. Metamorphosis of larvae of the tubeworm Hydroides elegans is induced by arrays of phage tail-like contractile injection systems, which are released by the bacterium Pseudoalteromonas luteoviolacea. Here we identify the novel effector protein Mif1. By cryo-electron tomography imaging and functional assays, we observe Mif1 as cargo inside the tube lumen of the contractile injection system and show that the mif1 gene is required for inducing metamorphosis. Purified Mif1 is sufficient for triggering metamorphosis when electroporated into tubeworm larvae. Our results indicate that the delivery of protein effectors by contractile injection systems may orchestrate microbe–animal interactions in diverse contexts

U.S. Physicians’ Views on Financing Options to Expand Health Insurance Coverage: A National Survey

Background: Physician opinion can influence the prospects for health care reform, yet there are few recent data on physician views on reform proposals or access to medical care in the United States. Objective: To assess physician views on financing options for expanding health care coverage and on access to health care. Design and Participants: Nationally representative mail survey conducted between March 2007 and October 2007 of U.S. physicians engaged in direct patient care. Measurements: Rated support for reform options including financial incentives to induce individuals to purchase health insurance and single-payer national health insurance; rated views of several dimensions of access to care. Main results: 1,675 of 3,300 physicians responded (50.8%). Only 9% of physicians preferred the current employer-based financing system. Forty-nine percent favored either tax incentives or penalties to encourage the purchase of medical insurance, and 42% preferred a government-run, taxpayer-financed single-payer national health insurance program. The majority of respondents believed that all Americans should receive needed medical care regardless of ability to pay (89%); 33% believed that the uninsured currently have access to needed care. Nearly one fifth of respondents (19.3%) believed that even the insured lack access to needed care. Views about access were independently associated with support for single-payer national health insurance. Conclusions: The vast majority of physicians surveyed supported a change in the health care financing system. While a plurality support the use of financial incentives, a substantial proportion support single payer national health insurance. These findings challenge the perception that fundamental restructuring of the U.S. health care financing system receives little acceptance by physicians

How do validated measures of functional outcome compare with commonly used outcomes in administrative database research for lumbar spinal surgery?

Clinical interpretation of health services research based on administrative databases is limited by the lack of patient-reported functional outcome measures. Reoperation, as a surrogate measure for poor outcome, may be biased by preferences of patients and surgeons and may even be planned a priori. Other available administrative data outcomes, such as postoperative cross sectional imaging (PCSI), may better reflect changes in functional outcome. The purpose was to determine if postoperative events captured from administrative databases, namely reoperation and PCSI, reflect outcomes as derived by validated functional outcome measures (short form 36 scores, Oswestry disability index) for patients who underwent discretionary surgery for specific degenerative conditions of the lumbar spine such as disc herniation, spinal stenosis, degenerative spondylolisthesis, and isthmic spondylolisthesis. After reviewing the records of all patients surgically treated for disc herniation, spinal stenosis, degenerative spondylolisthesis, and isthmic spondylolisthesis at our institution, we recorded the occurrence of PCSI (MRI or CT-myelograms) and reoperations, as well as demographic, surgical, and functional outcome data. We determined how early (within 6 months) and intermediate (within 18 months) term events (PCSI and reoperations) were associated with changes in intermediate (minimum 1 year) and late (minimum 2 years) term functional outcome, respectively. We further evaluated how early (6–12 months) and intermediate (12–24 months) term changes in functional outcome were associated with the subsequent occurrence of intermediate (12–24 months) and late (beyond 24 months) term adverse events, respectively. From 148 surgically treated patients, we found no significant relationship between the occurrence of PCSI or reoperation and subsequent changes in functional outcome at intermediate or late term. Similarly, earlier changes in functional outcome did not have any significant relationship with subsequent occurrences of adverse events at intermediate or late term. Although it may be tempting to consider administrative database outcome measures as proxies for poor functional outcome, we cannot conclude that a significant relationship exists between the occurrence of PCSI or reoperation and changes in functional outcome

Pin1 Modulates the Type 1 Immune Response

BACKGROUND/ABSTRACT: Immune responses initiated by T cell receptor (TCR) and costimulatory molecule mediated signaling culminate in maximal cytokine mRNA production and stability. The transcriptional responses to co-stimulatory T cell signalling involve calcineurin and NF-AT, which can be antagonized by interference with the cis-trans peptidyl-prolyl isomerases (PPIase), cyclophilin A and FKBP. Signalling molecules downstream of CD28 which are essential for the stabilization of cytokine mRNAs are largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: We now show that Pin1, a third member of the PPIase family mediates the post-transcriptional regulation of Th1 cytokines by activated T cells. Blockade of Pin1 by pharmacologic or genetic means greatly attenuated IFN-γ, IL-2 and CXCL-10 mRNA stability, accumulation and protein expression after cell activation. In vivo, Pin1 blockade prevented both the acute and chronic rejection of MHC mismatched, orthotopic rat lung transplants by reducing the expression of IFN-γ and CXCL-10. Combined transcriptional and post-transcriptional blockade with cyclosporine A and the Pin1 inhibitor, juglone, was synergistic. CONCLUSIONS/SIGNIFICANCE: These data suggest Pin1 inhibitors should be explored for use as immunosuppressants and employed with available calcineurin inhibitors to reduce toxicity and enhance effectiveness

FMRP Mediates mGluR(5)-Dependent Translation of Amyloid Precursor Protein

Amyloid precursor protein (APP) facilitates synapse formation in the developing brain, while beta-amyloid (Aβ) accumulation, which is associated with Alzheimer disease, results in synaptic loss and impaired neurotransmission. Fragile X mental retardation protein (FMRP) is a cytoplasmic mRNA binding protein whose expression is lost in fragile X syndrome. Here we show that FMRP binds to the coding region of APP mRNA at a guanine-rich, G-quartet–like sequence. Stimulation of cortical synaptoneurosomes or primary neuronal cells with the metabotropic glutamate receptor agonist DHPG increased APP translation in wild-type but not fmr-1 knockout samples. APP mRNA coimmunoprecipitated with FMRP in resting synaptoneurosomes, but the interaction was lost shortly after DHPG treatment. Soluble Aβ(40) or Aβ(42) levels were significantly higher in multiple strains of fmr-1 knockout mice compared to wild-type controls. Our data indicate that postsynaptic FMRP binds to and regulates the translation of APP mRNA through metabotropic glutamate receptor activation and suggests a possible link between Alzheimer disease and fragile X syndrome