AdamTS proteases control basement membrane heterogeneity and organ shape in Drosophila.

The basement membrane (BM) is an extracellular matrix that plays important roles in animal development. A spatial heterogeneity in composition and structural properties of the BM provide cells with vital cues for morphogenetic processes such as cell migration or cell polarization. Here, using the Drosophila egg chamber as a model system, we show that the BM becomes heterogeneous during development, with a reduction in Collagen IV density at the posterior pole and differences in the micropattern of aligned fiber-like structures. We identified two AdamTS matrix proteases required for the proper elongated shape of the egg chamber, yet the molecular mechanisms by which they act are different. Stall is required to establish BM heterogeneity by locally limiting Collagen IV protein density, whereas AdamTS-A alters the micropattern of fiber-like structures within the BM at the posterior pole. Our results suggest that AdamTS proteases control BM heterogeneity required for organ shape.

Incidence of Tube Feeding in 7174 Newly Admitted Nursing Home Residents With and Without Dementia.

BACKGROUND: Tube feeding is a common form of long-term nutritional support, especially for nursing home residents, of whom many have dementia. OBJECTIVE: Estimating the incidence of feeding tube placement in nursing home residents with and without dementia. METHODS: Using claims data, we studied a cohort of newly admitted nursing home residents aged 65 years and older between 2004 and 2009. Analyses were stratified by dementia. We estimated incidence rates and performed multivariate Cox regression analyses. RESULTS: The study cohort included 7174 nursing home residents. Over a mean follow-up of 1.3 years, 273 people received a feeding tube. The incidence per 1000 person-years was 28.4, with higher estimates for patients with dementia. When adjusting for age, sex, and level of care as a time-dependent covariate, influence of dementia decreased to a nonsignificant hazard ratio. CONCLUSION: It seems that not dementia itself but the overall clinical condition might be a predictor of tube feeding placement.

Phylogeny of haemosporidian blood parasites revealed by a multi-gene approach.

The apicomplexan order Haemosporida is a clade of unicellular blood parasites that infect a variety of reptilian, avian and mammalian hosts. Among them are the agents of human malaria, parasites of the genus Plasmodium, which pose a major threat to human health. Illuminating the evolutionary history of Haemosporida may help us in understanding their enormous biological diversity, as well as tracing the multiple host switches and associated acquisitions of novel life-history traits. However, the deep-level phylogenetic relationships among major haemosporidian clades have remained enigmatic because the datasets employed in phylogenetic analyses were severely limited in either gene coverage or taxon sampling. Using a PCR-based approach that employs a novel set of primers, we sequenced fragments of 21 nuclear genes from seven haemosporidian parasites of the genera Leucocytozoon, Haemoproteus, Parahaemoproteus, Polychromophilus and Plasmodium. After addition of genomic data from 25 apicomplexan species, the unreduced alignment comprised 20,580 bp from 32 species. Phylogenetic analyses were performed based on nucleotide, codon and amino acid data employing Bayesian inference, maximum likelihood and maximum parsimony. All analyses resulted in highly congruent topologies. We found consistent support for a basal position of Leucocytozoon within Haemosporida. In contrast to all previous studies, we recovered a sister group relationship between the genera Polychromophilus and Plasmodium. Within Plasmodium, the sauropsid and mammal-infecting lineages were recovered as sister clades. Support for these relationships was high in nearly all trees, revealing a novel phylogeny of Haemosporida, which is robust to the choice of the outgroup and the method of tree inference.

The Plasmodium falciparum exportome contains non-canonical PEXEL/HT proteins.

The pathogenicity of Plasmodium falciparum is partly due to parasite-induced host cell modifications. These modifications are facilitated by exported P. falciparum proteins, collectively referred to as the exportome. Export of several hundred proteins is mediated by the PEXEL/HT, a protease cleavage site. The PEXEL/HT is usually comprised of five amino acids, of which R at position 1, L at position 3 and E, D or Q at position 5 are conserved and important for export. Non-canonical PEXEL/HTs with K or H at position 1 and/or I at position 3 are presently considered non-functional. Here, we show that non-canonical PEXEL/HT proteins are overrepresented in P. falciparum and other Plasmodium species. Furthermore, we show that non-canonical PEXEL/HTs can be cleaved and can promote export in both a REX3 and a GBP reporter, but not in a KAHRP reporter, indicating that non-canonical PEXEL/HTs are functional in concert with a supportive sequence environment. We then selected P. falciparum proteins with a non-canonical PEXEL/HT and show that some of these proteins are exported and that their export depends on non-canonical PEXEL/HTs. We conclude that PEXEL/HT plasticity is higher than appreciated and that non-canonical PEXEL/HT proteins cannot categorically be excluded from Plasmodium exportome predictions.

Institutionalization in incident dementia cases in comparison to age- and sex- matched controls: a 5-year follow-up from Germany.

BACKGROUND: Dementia is a main reason for nursing home admission. Information on institutionalization is often based on studies of limited methodological quality. We aimed to analyze time until nursing home admission since first coding of dementia diagnosis and factors associated with institutionalization in incident dementia patients compared to non-demented controls. METHODS: We analyzed claims data of a German Health insurance company including a cohort of 1,440 patients with a first diagnosis of dementia and 6,988 age- and sex-matched controls aged 65 years and older. The follow-up was up to 5 years. We used Kaplan-Meier analysis for examining time until nursing home admission and cox regression for estimating crude and adjusted Hazard ratios. RESULTS: Dementia patients and controls were on average 78 years and about 55 % were males. The mean time to nursing home admission was 4.0 years in patients with dementia and 4.6 years for controls. After the 5-years observation-period 62.7 % (95 % CI 59.0-66.1) of dementia patients still lived in the community in comparison to 86.2 % (95 % CI 85.2-87.2) of controls. Cox regression models show that the risk for institutionalization is 3.45 (95 % CI 3.05-3.90) times higher in dementia patients in comparison to controls when adjusted for sex, age, and comorbidity. CONCLUSIONS: Our analysis shows a significant influence of dementia on institutionalization in comparison to age- and sex-matched controls, especially in the youngest age groups. Hence, the results add substantial information on the disease progression of dementia and are, therefore, of great importance for health-care as well as long-term care planning.

Prescribing of antipsychotic drugs in patients with dementia: a comparison with age-matched and sex-matched non-demented controls.

PURPOSE: Since the beginning of the 21st century, serious adverse events and an increased risk of mortality have been documented in patients with dementia treated with antipsychotics. The aim of this study was to assess antipsychotic prescribing in patients with incident dementia compared with a non-demented control group. METHODS: We analysed the claims data of a German health insurance company for incident dementia patients and age-matched and sex-matched non-demented controls aged 65 years and older in 2004 to 2006. The data were used to analyse the prescribing patterns of antipsychotics in the year of dementia incidence. We estimated odds ratios stratified by age, sex, care setting and care dependence and in a multivariate logistic regression. RESULTS: The 1848 patients with and 7385 persons without dementia were on average 78.8 years old (standard deviation: 7.4), and 47.6% were women. A total of 25.4% of the dementia patients received antipsychotics compared with 4.3% of the controls (ORcrude : 7.61; 95%CI: 6.52-8.87). An increase in care level, age, female gender and living in a nursing home is associated with a considerably higher prevalence of at least one prescription for antipsychotics. After adjusting for all these variables, a significant influence of age could no longer be found. CONCLUSIONS: The results show that antipsychotics play an important role in dementia care-despite the risk of adverse events. Further research is needed with regard to safe pharmacological and non-pharmacological approaches for the behavioural and psychological symptoms of dementia in this vulnerable group.

Impact of safety warnings on antipsychotic prescriptions in dementia: nothing has changed but the years and the substances.

Dementia patients suffering from behavioral and psychological symptoms (BPSD) are often treated with antipsychotics. Trial results document an increased risk for serious adverse events and mortality in dementia patients taking these agents. Furthermore, the efficacy of treating BPSD with antipsychotics seems to be only modest. Using data of a German statutory health insurance company, we examined prescription trends of antipsychotics in prevalent dementia patients in the context of official warnings. The study period is 2004-2009. We studied trends in demographics, age and sex, as well as need of care and the intake of typical and atypical antipsychotics. Seeking for linear trends adjusted for age, sex and level of care between 2004 and 2009, we obtained p-values from a multivariate logistic regression. Prescription volumes were calculated by number of packages as well as defined daily doses (DDDs) using multiple linear regressions for trends in prescriptions amount. We included 3460-8042 patients per year (mean age 80 years). The prescription prevalence of antipsychotics decreased from 35.5% in 2004 to 32.5% in 2009 (multivariate analysis for linear trend: p=0.1645). Overall prescriptions for typical antipsychotics decreased (from 27.2% in 2004 to 23.0% in 2009, p<0.0001) and prescriptions for atypical antipsychotics increased from 17.1% to 18.9% (p<0.0001). The mean DDD per treated patient increased from 80.5 to 91.2 (2004-2009; p=0.0047). Our findings imply that warnings of international drug authorities and manufacturers against adverse drug events in dementia patients receiving antipsychotics did not impact overall prescription behavior.

Lag screw osteosynthesis of fractures of the mandibular condyle: potential benefit of preoperative planning using multiplanar CT reconstruction.

OBJECTIVE: The purpose of the study was to develop a method of multiplanar CT reconstruction in fractures of the mandibular condyle in order to evaluate the feasibility of lag screw osteosynthesis. STUDY DESIGN: Angulated axial and sagittal images of the mandibular ramus were calculated using collected CT data. In 183 mandibular rami the optimal position of the screw axis was determined retrospectively. The thickness of the covering bone as well as the degree of screw exposure were measured. RESULTS: Application of the method led to medial (28.4% of cases) or lateral (3.8% of cases) correction of the usual screw axis. In 1.6% of cases an extraosseous position of screws could not be avoided by this correction. CONCLUSIONS: Evaluation of the feasibility of lag screw osteosynthesis by this method is possible. Medial or lateral change of the axis ensures the optimal intraosseous screw position. Intraosseous screw placement is almost always possible.