Medical Conditions of Nursing Home Admissions

<p>Abstract</p> <p>Background</p> <p>As long-term nursing home care is likely to increase with the aging of the population, identifying chronic medical conditions is of particular interest. Although need factors have a strong impact on nursing home (NH) admission, the diseases causing these functional disabilities are lacking or unclear in the residents' file. We investigated the medical reason (primary diagnosis) of a nursing home admission with respect to the underlying disease.</p> <p>Methods</p> <p>This study is based on two independent, descriptive and comparative studies in Belgium and was conducted at two time points (1993 and 2005) to explore the evolution over twelve years. Data from the subjects were extracted from the resident's file; additional information was requested from the general practitioner, nursing home physician or the head nurse in a face-to-face interview. In 1993 we examined 1332 residents from 19 institutions, and in 2005 691 residents from 7 institutions. The diseases at the time of admission were mapped by means of the International Classification of Diseases - 9th edition (ICD-9). Longitudinal changes were assessed and compared by a chi-square test.</p> <p>Results</p> <p>The main chronic medical conditions associated with NH admission were dementia and stroke. Mental disorders represent 48% of all admissions, somatic disorders 43% and social/emotional problems 8%. Of the somatic disorders most frequently are mentioned diseases of the circulatory system (35%) [2/3 sequels of stroke and 1/5 heart failure], followed by diseases of the nervous system (15%) [mainly Parkinson's disease] and the musculoskeletal system (14%) [mainly osteoarthritis]. The most striking evolution from 1993 to 2005 consisted in complicated diabetes mellitus (from 4.3 to 11.4%; p < 0.0001) especially with amputations and blindness. Symptoms (functional limitations without specific disease) like dizziness, impaired vision and frailty are of relevance as an indicator of admission.</p> <p>Conclusion</p> <p>Diseases like stroke, diabetes and mobility problems are only important for institutionalisation if they cause functional disability. Diabetes related complications as cause of admission increased almost three-fold between 1993 and 2005.</p

Functional, Non-Clonal IgMa-Restricted B Cell Receptor Interactions with the HIV-1 Envelope gp41 Membrane Proximal External Region

The membrane proximal external region (MPER) of HIV-1 gp41 has several features that make it an attractive antibody-based vaccine target, but eliciting an effective gp41 MPER-specific protective antibody response remains elusive. One fundamental issue is whether the failure to make gp41 MPER-specific broadly neutralizing antibodies like 2F5 and 4E10 is due to structural constraints with the gp41 MPER, or alternatively, if gp41 MPER epitope-specific B cells are lost to immunological tolerance. An equally important question is how B cells interact with, and respond to, the gp41 MPER epitope, including whether they engage this epitope in a non-canonical manner i.e., by non-paratopic recognition via B cell receptors (BCR). To begin understanding how B cells engage the gp41 MPER, we characterized B cell-gp41 MPER interactions in BALB/c and C57BL/6 mice. Surprisingly, we found that a significant (∼7%) fraction of splenic B cells from BALB/c, but not C57BL/6 mice, bound the gp41 MPER via their BCRs. This strain-specific binding was concentrated in IgMhi subsets, including marginal zone and peritoneal B1 B cells, and correlated with enriched fractions (∼15%) of gp41 MPER-specific IgM secreted by in vitro-activated splenic B cells. Analysis of Igha (BALB/c) and Ighb (C57BL/6) congenic mice demonstrated that gp41 MPER binding was controlled by determinants of the Igha locus. Mapping of MPER gp41 interactions with IgMa identified MPER residues distinct from those to which mAb 2F5 binds and demonstrated the requirement of Fc CH regions. Importantly, gp41 MPER ligation produced detectable BCR-proximal signaling events, suggesting that interactions between gp41 MPER and IgMa determinants may elicit partial B cell activation. These data suggest that low avidity, non-paratopic interactions between the gp41 MPER and membrane Ig on naïve B cells may interfere with or divert bnAb responses

Transcriptional and Linkage Analyses Identify Loci that Mediate the Differential Macrophage Response to Inflammatory Stimuli and Infection

Macrophages display flexible activation states that range between pro-inflammatory (classical activation) and anti-inflammatory (alternative activation). These macrophage polarization states contribute to a variety of organismal phenotypes such as tissue remodeling and susceptibility to infectious and inflammatory diseases. Several macrophage- or immune-related genes have been shown to modulate infectious and inflammatory disease pathogenesis. However, the potential role that differences in macrophage activation phenotypes play in modulating differences in susceptibility to infectious and inflammatory disease is just emerging. We integrated transcriptional profiling and linkage analyses to determine the genetic basis for the differential murine macrophage response to inflammatory stimuli and to infection with the obligate intracellular parasite Toxoplasma gondii. We show that specific transcriptional programs, defined by distinct genomic loci, modulate macrophage activation phenotypes. In addition, we show that the difference between AJ and C57BL/6J macrophages in controlling Toxoplasma growth after stimulation with interferon gamma and tumor necrosis factor alpha mapped to chromosome 3, proximal to the Guanylate binding protein (Gbp) locus that is known to modulate the murine macrophage response to Toxoplasma. Using an shRNA-knockdown strategy, we show that the transcript levels of an RNA helicase, Ddx1, regulates strain differences in the amount of nitric oxide produced by macrophage after stimulation with interferon gamma and tumor necrosis factor. Our results provide a template for discovering candidate genes that modulate macrophage-mediated complex traits

Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse

Leopard complex spotting is a group of white spotting patterns in horses caused by an incompletely dominant gene (LP) where homozygotes (LP/LP) are also affected with congenital stationary night blindness. Previous studies implicated Transient Receptor Potential Cation Channel, Subfamily M, Member 1 (TRPM1) as the best candidate gene for both CSNB and LP. RNA-Seq data pinpointed a 1378 bp insertion in intron 1 of TRPM1 as the potential cause. This insertion, a long terminal repeat (LTR) of an endogenous retrovirus, was completely associated with LP, testing 511 horses (χ²=1022.00, p<<0.0005), and CSNB, testing 43 horses (χ2=43, p<<0.0005). The LTR was shown to disrupt TRPM1 transcription by premature poly-adenylation. Furthermore, while deleterious transposable element insertions should be quickly selected against the identification of this insertion in three ancient DNA samples suggests it has been maintained in the horse gene pool for at least 17,000 years. This study represents the first description of an LTR insertion being associated with both a pigmentation phenotype and an eye disorder.Rebecca R. Bellone … David L. Adelson, Sim Lin Lim … et al

European Courts as Value-Harmonizing 'Motors of Integration'

The paper first deals with the conditions and prerequisites of adopting European law before the former „real-socialist” countries joined the EU. The key role of European Courts is described by showing that they worked as de facto virtual legislators even before accession. It is emphasized that European Courts have provided the courts and antitrust authorities of new Member States with an inestimable value-based orientation. The EU judicial practice enhanced national legal standards and legal culture in the respective countries. The second part of the contribution contrasts with this positive tone. An example of a serious inconsistency in values between the Court of Justice of the EU and the European Commission is shown concerning their divergent views on “uni-sex insurance” and the draft directive on women’s representation in board member positions. There is substantial disagreement in this matter, which weakens and endangers the integrative role of the CJEU and its habitual value-confirming impact. This disparity could to some extent depreciate the role of European Courts as „motors of integration”.Le document traite d'abord sur les conditions et les préalables de l'adoption de la législation européenne avant que les anciens pays «vraiment» socialistes aient rejoint l'UE. Un grand rôle des juridictions européennes est décrit d’une manière suivante: ils travaillaient en réalité comme des législateurs virtuelles même avant l'adhésion. Il est souligné que les tribunaux et les autorités de la concurrence des nouveaux Etats membres de l'UE ont été fournis d’une orientation axée sur la valeur inestimable par les juridictions européennes. La pratique judiciaire de l'UE renforçait des normes juridiques nationales et de la culture juridique dans les pays respectifs. La deuxième partie de la contribution contraste avec ce ton positif. Un exemple d'une grave incohérence de valeur entre la Cour de justice de l'Union européenne (CJUE) et la Commission européenne, concernant la divergence entre la CJUE et la Commission européenne dans une affaire qu'on appelle «l'assurance uni - sexe» et le projet d'une directive sur la représentation des femmes aux postes de membres du conseil d'administration est présenté. Il y a un désaccord important dans cette matière qui affaiblit et met en danger le rôle intégratif de la CJUE et son impact habituel de confirmation de valeur; il pourrait, en quelque sorte, déprécier le rôle des tribunaux européens étant des «moteurs de l'intégration»