Hospitals between present and future

What role will hospitals play in the future of the healthcare system, and how this role will be changing? Hospitals of the future will confront difficult challanges: new kinds of disease, rapidly evolving medical technologies, aging of the population and evolving budget restrictions. All features that make it difficult to foresee the hospital of the future. The aim of this paper is to analyze the different challanges that hospital have to face in a modern scenario of evolution of public health services.     

How do cancer patients receiving palliative care at home die? A descriptive study

Context

Data regarding the circumstances of the process of death of terminally ill patients followed at home are lacking.

Objectives

The aim of this study was to describe the characteristics and assess the circumstances of the process of death of terminally ill patients followed at home.

Methods

This was a prospective survey to assess the dying process of advanced cancer patients followed at home. Within a week after death, the principal caregiver was interviewed. Information from the palliative home care team and the caregiver about expectation of death, time of death, professional and nonprofessional people present at time of death, emergency admission to hospital, and administration of drugs to resuscitate was gathered. The principal clinical issues in the last two hours also were recorded.

Results

In total, 181 of 222 caregivers provided information. Most deaths were expected. Palliative home care team physicians and nurses visited the patient on the day of death but were occasionally present at the moment of death. More than three people were generally present at time of death. More than two-thirds of patients died peacefully, without apparent suffering, and 35.7% of them received palliative sedation before dying. In the last two hours, the most frequent clinical issues were ranked as death rattle, dyspnea, and agitation. In 10 cases, emergency drugs for resuscitation were administered.

Conclusion

This study has shown how advanced cancer patients die at home and that palliative home care may be helpful in allowing a death at home, particularly when relatives are actively involved.     

Cell cycle-specific cleavage of Scc2 regulates its cohesin deposition activity

Sister chromatid cohesion (SCC), efficient DNA repair, and the regulation of some metazoan genes require the association of cohesins with chromosomes. Cohesins are deposited by a conserved heterodimeric loading complex composed of the Scc2 and Scc4 proteins in Saccharomyces cerevisiae, but how the Scc2/Scc4 deposition complex regulates the spatiotemporal association of cohesin with chromosomes is not understood. We examined Scc2 chromatin association during the cell division cycle and found that the affinity of Scc2 for chromatin increases biphasically during the cell cycle, increasing first transiently in late G₁ phase and then again later in G₂/M. Inactivation of Scc2 following DNA replication reduces cellular viability, suggesting that this post S-phase increase in Scc2 chromatin binding affinity is biologically relevant. Interestingly, high and low Scc2 chromatin binding levels correlate strongly with the presence of full-length or amino-terminally cleaved forms of Scc2, respectively, and the appearance of the cleaved Scc2 species is promoted in vitro either by treatment with specific cell cycle-staged cellular extracts or by dephosphorylation. Importantly, Scc2 cleavage eliminates Scc2–Scc4 physical interactions, and an scc2 truncation mutant that mimics in vivo Scc2 cleavage is defective for cohesin deposition. These observations suggest a previously unidentified mechanism for the spatiotemporal regulation of cohesin association with chromosomes through cell cycle regulation of Scc2 cohesin deposition activity by Scc2 dephosphorylation and cleavage.Multisubunit, ring-shaped cohesin complexes play key roles in chromosome morphogenesis that are required for faithful chromosome transmission to daughter cells. Newly replicated sister chromatids become tethered together by cohesins during S phase, which promotes chromosome biorientation on mitotic spindles (1). Cohesins also mediate efficient DNA double-strand break repair by homologous recombination (2, 3) and the formation or stabilization of chromatin loops that affect various nuclear processes, such as gene expression and Ig gene rearrangements (reviewed in refs. 4 and 5). Altered gene expression resulting from defective cohesin-mediated chromatin looping is likely responsible for the pathogenesis of Cornelia de Lange Syndrome (CdLS), a dominantly inherited human developmental disorder (6).Sister chromatid cohesion (Scc) proteins form a heterodimeric cohesin deposition complex, but the complex''s activity in deposition is not understood (7). Cohesins copurify with Scc2/Scc4, suggesting that Scc2/Scc4 plays a direct role in deposition (8–11). In the absence of either loader complex subunit, cohesin rings assemble, but fail to be deposited (7, 12, 13). ATP hydrolysis by cohesin’s structural maintenance of chromosome (SMC) subunits is required for cohesin loading, and deposition is inhibited when SMC hinge domains, which mediate Smc1/3 interactions within cohesin, are artificially tethered (8, 14, 15). Thus, Scc2/Scc4 may activate cohesin’s ATPase activity or facilitate a conformational change in cohesin structure that promotes its loading, perhaps by permitting transient hinge opening to allow chromatin to enter cohesin rings or by promoting cohesin oligomerization (14, 16).Factors that regulate Scc2/Scc4 chromatin association are only beginning to be elucidated. Interactions of Scc2 and Scc4 orthologs from Xenopus and humans, and their stable association with chromatin, require the amino termini of both proteins (10, 13, 17, 18). In contrast, the fission yeast Scc2 ortholog alone binds nonchromatinized DNA, but does not exhibit an expected preference for sequences shown to associate with Scc2/Scc4 in vivo (19). Xenopus Scc2/Scc4 chromatin association requires prereplication complexes and Drf1-dependent kinase (DDK) activity (10, 12, 20), although this scenario is not the case in budding yeast (21). Scc2/Scc4 interactions with histone deacetylases and an ATP-dependent chromatin remodeler suggest that underlying chromatin structure also influences Scc2/Scc4 chromatin association (22–26). Whether Scc2/Scc4 plays a role in chromatin remodeling or merely deposits cohesins at remodeled sites is unknown, however.The chromatin association of Scc2/Scc4 and its orthologs is also regulated temporally during the cell cycle, although the specifics of association vary across species. Scc2/Scc4 associates with chromatin in late mitosis of the previous cell cycle in metazoans (12, 13) and in late G₁ in budding yeast, but in all cases, this association precedes DNA replication initiation so that cohesins are deposited in time to tether newly replicated sister chromatids together. Surprisingly, budding yeast Scc2/Scc4 chromatin association is more robust in mitotically arrested cells than in G₁-staged cells. Reduced G₁ Scc2/Scc4 chromatin association is not due to the absence of either loader subunit, because Scc2 and Scc4 protein levels vary little during the cell cycle, or by a lack of assembled cohesin complexes in G₁, because Scc2/Scc4 chromatin association occurs independently of cohesins (18, 27, 28). Scc2/Scc4 removal from chromatin is also regulated and occurs during mitosis in Xenopus and, more specifically, during prophase in humans (12, 13). Although factors responsible for regulating Scc2/Scc4 chromatin association/dissociation during the cell cycle remain enigmatic, evidence that multiple Scc2 orthologs are phosphorylated suggests the intriguing possibility that Scc2 posttranslational modifications regulate Scc2/Scc4 chromatin association (29–31).Here, we describe our efforts to understand how budding yeast Scc2/Scc4 chromatin binding is regulated during the cell cycle. Our results demonstrate the existence of multiple Scc2 protein species in vivo and that a specific cleaved form of Scc2 accumulates at cell cycle periods when Scc2 chromatin binding is weak. The appearance of this cleaved Scc2 species is strongly correlated with Scc2 dephosphorylation, suggesting that the phosphorylation state of Scc2 is critical for the regulation of its stability. Scc2 cleavage is also correlated with the loss of Scc2–Scc4 interactions, and an scc2 truncation mutant that mimics cleaved Scc2 is defective in cohesin deposition. These observations suggest that Scc2–Scc4 interactions and, therefore, the function of the complex in cohesin deposition, may be influenced by dephosphorylation-induced Scc2 cleavage.     

Transient involuntary mirror writing triggered by anxiety

Mirror writing (MW) has mainly been observed in left-hemisphere-damaged patients writing with the left hand. This study evaluated the presence of MW in 24 patients with mild cognitive impairment (MCI). We found that MW is not a typical feature of MCI. However, one woman (FC), mislabeled initially with MCI but in fact affected by anxiety, showed florid MW when writing with her left hand, which resolved as her anxiety receded. This case study supports anecdotal reports of MW triggered by anxiety, and the features of FC’s performance indicate a motor rather than a perceptual basis for the phenomenon.     

The Italian validation of the Communicative Effectiveness Index Questionnaire: a multicentric study

Neurological Sciences - Common assessment tools for aphasia evaluate single language impairments but not their functional impact on patient’s communication skills in daily life. The lack of...     

Influence of Interferon beta treatment on quality of life in multiple sclerosis patients

Background

The individual growth model is a relatively new statistical technique now widely used to examine the unique trajectories of individuals and groups in repeated measures data. This technique is increasingly used to analyze the changes over time in quality of life (QOL) data. This study examines the change from adolescence to adulthood in physical health as an aspect of QOL as an illustration of the use of this analytic method.

Methods

Employing data from the Children in the Community (CIC) study, a prospective longitudinal investigation, physical health was assessed at mean ages 16, 22, and 33 in 752 persons born between 1965 and 1975.

Results

The analyses using individual growth models show a linear decline in average physical health from age 10 to age 40. Males reported better physical health and declined less per year on average. Time-varying psychiatric disorders accounted for 8.6% of the explained variation in mean physical health, and 6.7% of the explained variation in linear change in physical health. Those with such a disorder reported lower mean physical health and a more rapid decline with age than those without a current psychiatric disorder. The use of SAS PROC MIXED, including syntax and interpretation of output are provided. Applications of these models including statistical assumptions, centering issues and cohort effects are discussed.

Conclusion

This paper highlights the usefulness of the individual growth model in modeling longitudinal change in QOL variables.