Comorbidity patterns in patients with chronic diseases in general practice

Introduction

Healthcare management is oriented toward single diseases, yet multimorbidity is nevertheless the rule and there is a tendency for certain diseases to occur in clusters. This study sought to identify comorbidity patterns in patients with chronic diseases, by reference to number of comorbidities, age and sex, in a population receiving medical care from 129 general practitioners in Spain, in 2007.

Methods

A cross-sectional study was conducted in a health-area setting of the Madrid Autonomous Region (Comunidad Autónoma), covering a population of 198,670 individuals aged over 14 years. Multiple correspondences were analyzed to identify the clustering patterns of the conditions targeted.

Results

Forty-two percent (95% confidence interval [CI]: 41.8–42.2) of the registered population had at least one chronic condition. In all, 24.5% (95% CI: 24.3–24.6) of the population presented with multimorbidity.In the correspondence analysis, 98.3% of the total information was accounted for by three dimensions. The following four, age- and sex-related comorbidity patterns were identified: pattern B, showing a high comorbidity rate; pattern C, showing a low comorbidity rate; and two patterns, A and D, showing intermediate comorbidity rates.

Conclusions

Four comorbidity patterns could be identified which grouped diseases as follows: one showing diseases with a high comorbidity burden; one showing diseases with a low comorbidity burden; and two showing diseases with an intermediate comorbidity burden.     

Activation of NMDA receptors induces protein kinase A-mediated phosphorylation and degradation of matrin 3. Blocking these effects prevents NMDA-induced neuronal death

Activation of NMDA receptors leads to activation of cAMP-dependent protein kinase (PKA). The main substrates phosphorylated by PKA following NMDA receptor activation remain unidentified. The aim of this work was to identify a major substrate phosphorylated by PKA following NMDA receptor activation in cerebellar neurones in culture, and to assess whether this phosphorylation may be involved in neuronal death induced by excessive NMDA receptor activation. The main PKA substrate following NMDA receptor activation was identified by MALDI-TOFF fingerprinting as the nuclear protein, matrin 3. PKA-mediated phosphorylation of matrin 3 is followed by its degradation. NMDA receptor activation in rat brain in vivo by ammonia injection also induced PKA-mediated matrin 3 phosphorylation and degradation in brain cell nuclei. Blocking NMDA receptors in brain in vivo with MK-801 reduced basal phosphorylation of matrin 3, suggesting that it is modulated by NMDA receptors. Inhibition of PKA with H-89 prevents NMDA-induced phosphorylation and degradation of matrin 3 as well as neuronal death. These results suggest that PKA-mediated phosphorylation of matrin 3 may serve as a rapid way of transferring information from synapses containing NMDA receptors to neuronal nuclei under physiological conditions, and may contribute to neuronal death under pathological conditions.     

Sugarcane glycoproteins may act as signals for the production of xanthan in the plant-associated bacterium Xanthomonas albilineans

Visual symptoms of leaf scald necrosis in sugarcane (Saccharum officinarum) leaves develop in parallel to the accumulation of a fibrous material invading exocellular spaces and both xylem and phloem. These fibers are produced and secreted by the plant-associated bacterium Xanthomonas albilineans. Electron microscopy and specific staining methods for polysaccharides reveal the polysaccharidic nature of this material. These polysaccharides are not present in healthy leaves or in those from diseased plants without visual symptoms of leaf scald. Bacteria in several leaf tissues have been detected by immunogold labeling. The bacterial polysaccharide is not produced in axenic culture but it is actively synthesized when the microbes invade the host plant. This finding may be due to the production of plant glycoproteins, after bacteria infection which inhibit microbial proteases. In summary, our data are consistent with the existence of a positive feedback loop in which plant-produced glycoproteins act as a cell-to-bacteria signal that promotes xanthan production, by protecting some enzymes of xanthan biosynthesis against from bacterial proteolytic degradation.Key words: leaf scald, infectivity, Saccharum officinarum (L.) cv. mayarí 55-14, sugarcane glycoproteins, xanthan-like polysaccharide, Xanthomonas albilineans     

Multifunctional roles for the N-terminal basic motif of Alfalfa mosaic virus coat protein: nucleolar/cytoplasmic shuttling, modulation of RNA-binding activity, and virion formation

In addition to virion formation, the coat protein (CP) of Alfalfa mosaic virus (AMV) is involved in the regulation of replication and translation of viral RNAs, and in cell-to-cell and systemic movement of the virus. An intriguing feature of the AMV CP is its nuclear and nucleolar accumulation. Here, we identify an N-terminal lysine-rich nucleolar localization signal (NoLS) in the AMV CP required to both enter the nucleus and accumulate in the nucleolus of infected cells, and a C-terminal leucine-rich domain which might function as a nuclear export signal. Moreover, we demonstrate that AMV CP interacts with importin-α, a component of the classical nuclear import pathway. A mutant AMV RNA 3 unable to target the nucleolus exhibited reduced plus-strand RNA synthesis and cell-to-cell spread. Moreover, virion formation and systemic movement were completely abolished in plants infected with this mutant. In vitro analysis demonstrated that specific lysine residues within the NoLS are also involved in modulating CP-RNA binding and CP dimerization, suggesting that the NoLS represents a multifunctional domain within the AMV CP. The observation that nuclear and nucleolar import signals mask RNA-binding properties of AMV CP, essential for viral replication and translation, supports a model in which viral expression is carefully modulated by a cytoplasmic/nuclear balance of CP accumulation.     

Modulation of K+ translocation by AKT1 and AtHAK5 in Arabidopsis plants

Root cells take up K⁺ from the soil solution, and a fraction of the absorbed K⁺ is translocated to the shoot after being loaded into xylem vessels. K⁺ uptake and translocation are spatially separated processes. K⁺ uptake occurs in the cortex and epidermis whereas K⁺ translocation starts at the stele. Both uptake and translocation processes are expected to be linked, but the connection between them is not well characterized. Here, we studied K⁺ uptake and translocation using Rb⁺ as a tracer in wild‐type Arabidopsis thaliana and in T‐DNA insertion mutants in the K⁺ uptake or translocation systems. The relative amount of translocated Rb⁺ to the shoot was positively correlated with net Rb⁺ uptake rates, and the akt1 athak5 T‐DNA mutant plants were more efficient in their allocation of Rb⁺ to shoots. Moreover, a mutation of SKOR and a reduced plant transpiration prevented the full upregulation of AtHAK5 gene expression and Rb⁺ uptake in K⁺‐starved plants. Lastly, Rb⁺ was found to be retrieved from root xylem vessels, with AKT1 playing a significant role in K⁺‐sufficient plants. Overall, our results suggest that K⁺ uptake and translocation are tightly coordinated via signals that regulate the expression of K⁺ transport systems.     

Characterization of heterotrophic growth and sesquiterpene production by Rhodobacter sphaeroides on a defined medium

Rhodobacter sphaeroides is a metabolically versatile bacterium capable of producing terpenes natively. Surprisingly, terpene biosynthesis in this species has always been investigated in complex media, with unknown compounds possibly acting as carbon and nitrogen sources. Here, a defined medium was adapted for R. sphaeroides dark heterotrophic growth, and was used to investigate the conversion of different organic substrates into the reporter terpene amorphadiene. The amorphadiene synthase was cloned in R. sphaeroides, allowing its biosynthesis via the native 2-methyl-d-erythritol-4-phosphate (MEP) pathway and, additionally, via a heterologous mevalonate one. The latter condition increased titers up to eightfold. Consequently, better yields and productivities to previously reported complex media cultivations were achieved. Productivity was further investigated under different cultivation conditions, including nitrogen and oxygen availability. This novel cultivation setup provided useful insight into the understanding of terpene biosynthesis in R. sphaeroides, allowing to better comprehend its dynamics and regulation during chemoheterotrophic cultivation.

     

Ecological and phenotypic divergence in Iberian shrews (Soricidae)

There are examples of coexisting species with similar morphology and ecology, in apparent contradiction to competition theory. Shrews (Soricidae) are a paradigmatic example of this because members of this group exhibit a conserved body form, relatively low variability in lifestyle, and, in many cases, a sympatric distribution. Here, we combined geometric morphometrics and ecological niche modeling to test whether diversification of soricid species inhabiting the Iberian Peninsula has been driven by niche divergence or, conversely, whether niche conservatism has played a paramount role in this process. We also examined whether pairwise morphological distances increase as the degree of niche overlap between species becomes greater, as would be expected if interspecific competition promotes morphological differentiation. Our results showed that water shrews (Neomys), white‐toothed shrews (Crocidurinae), and red‐toothed shrews (Soricinae) are clearly differentiated in terms of both skull shape and mandible shape. However, we found a lack of phylogenetic signal in most morphological traits, indicating that closely related species are not more similar than expected by random chance. Notably, water shrews show a more “triangular” or sharp skull than white‐toothed and red‐toothed shrews, probably as an adaptation to their semiaquatic lifestyle. In agreement with the phenotypic data, climatic traits (mean annual temperature and annual precipitation) were highly labile and sister taxa showed extensive differentiation in their realized niche space. Finally, we found that phenotypic distances between species tend to increase as the degree of niche overlap increases, suggesting that interspecific competition is an important factor in determining the level of morphological resemblance among relatives. Overall, our results indicate that the existence of limited morphological disparity in a given group does not necessarily imply the existence of a niche conservatism signature.     

Scoring System for Mortality in Patients Diagnosed with and Treated Surgically for Differentiated Thyroid Carcinoma with a 20-Year Follow-Up

Background

Differentiated thyroid carcinoma (DTC) is associated with an increased mortality. Few studies have constructed predictive models of all-cause mortality with a high discriminating power for patients with this disease that would enable us to determine which patients are more likely to die.

Objective

To construct a predictive model of all-cause mortality at 5, 10, 15 and 20 years for patients diagnosed with and treated surgically for DTC for use as a mobile application.

Design

We undertook a retrospective cohort study using data from 1984 to 2013.

Setting

All patients diagnosed with and treated surgically for DTC at a general university hospital covering a population of around 200,000 inhabitants in Spain.

Participants

The study involved 201 patients diagnosed with and treated surgically for DTC (174, papillary; 27, follicular).

Exposures

Age, gender, town, family history, type of surgery, type of cancer, histological subtype, microcarcinoma, multicentricity, TNM staging system, diagnostic stage, permanent post-operative complications, local and regional tumor persistence, distant metastasis, and radioiodine therapy.

Main outcome measure

All-cause mortality.

Methods

A Cox multivariate regression model was constructed to determine which variables at diagnosis were associated with mortality. Using the model a risk table was constructed based on the sum of all points to estimate the likelihood of death. This was then incorporated into a mobile application.

Results

The mean follow-up was 8.8±6.7 years. All-cause mortality was 12.9% (95% confidence interval [CI]: 8.3–17.6%). Predictive variables: older age, local tumor persistence and distant metastasis. The area under the ROC curve was 0.81 (95% CI: 0.72–0.91, p<0.001).

Conclusion

This study provides a practical clinical tool giving a simple and rapid indication (via a mobile application) of which patients with DTC are at risk of dying in 5, 10, 15 or 20 years. Nonetheless, caution should be exercised until validation studies have corroborated our results.