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.     

The TT Genotype of the STAT4 rs7574865 Polymorphism Is Associated with High Disease Activity and Disability in Patients with Early Arthritis

Background

The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis.

Methodology and Results

We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5′ allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01–0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = −0.27 [−0.56– −0.01], p = 0.042; TT genotype = −0.68 [−1.64– −0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype.

Conclusions

Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.     

Properties of Ca2+ sparks revealed by four-dimensional confocal imaging of cardiac muscle

Parameters (amplitude, width, kinetics) of Ca(2+) sparks imaged confocally are affected by errors when the spark source is not in focus. To identify sparks that were in focus, we used fast scanning (LSM 5 LIVE; Carl Zeiss) combined with fast piezoelectric focusing to acquire x-y images in three planes at 1-μm separation (x-y-z-t mode). In 3,000 x-y scans in each of 34 membrane-permeabilized cat atrial cardiomyocytes, 6,906 sparks were detected. 767 sparks were in focus. They had greater amplitude, but their spatial width and rise time were similar compared with all sparks recorded. Their distribution of amplitudes had a mode at ΔF/F(0) = 0.7. The Ca(2+) release current underlying in-focus sparks was 11 pA, requiring 20 to 30 open channels, a number at the high end of earlier estimates. Spark frequency was greater than in earlier imaging studies of permeabilized ventricular cells, suggesting a greater susceptibility to excitation, which could have functional relevance for atrial cells. Ca(2+) release flux peaked earlier than the time of peak fluorescence and then decayed, consistent with significant sarcoplasmic reticulum (SR) depletion. The evolution of fluorescence and release flux were strikingly similar for in-focus sparks of different rise time (T). Spark termination involves both depletion of Ca(2+) in the SR and channel closure, which may be synchronized by depletion. The observation of similar flux in sparks of different T requires either that channel closure and other termination processes be independent of the determinants of flux (including [Ca(2+)](SR)) or that different channel clusters respond to [Ca(2+)](SR) with different sensitivity.     

Development of a panel of genome-wide ancestry informative markers to study admixture throughout the Americas

Most individuals throughout the Americas are admixed descendants of Native American, European, and African ancestors. Complex historical factors have resulted in varying proportions of ancestral contributions between individuals within and among ethnic groups. We developed a panel of 446 ancestry informative markers (AIMs) optimized to estimate ancestral proportions in individuals and populations throughout Latin America. We used genome-wide data from 953 individuals from diverse African, European, and Native American populations to select AIMs optimized for each of the three main continental populations that form the basis of modern Latin American populations. We selected markers on the basis of locus-specific branch length to be informative, well distributed throughout the genome, capable of being genotyped on widely available commercial platforms, and applicable throughout the Americas by minimizing within-continent heterogeneity. We then validated the panel in samples from four admixed populations by comparing ancestry estimates based on the AIMs panel to estimates based on genome-wide association study (GWAS) data. The panel provided balanced discriminatory power among the three ancestral populations and accurate estimates of individual ancestry proportions (R2 > 0.9 for ancestral components with significant between-subject variance). Finally, we genotyped samples from 18 populations from Latin America using the AIMs panel and estimated variability in ancestry within and between these populations. This panel and its reference genotype information will be useful resources to explore population history of admixture in Latin America and to correct for the potential effects of population stratification in admixed samples in the region.     

Network dynamics in nociceptive pathways assessed by the neuronal avalanche model

ABSTRACT: BACKGROUND: Traditional electroencephalography provides a critical assessment of pain responses. The perception of pain, however, may involve a series of signal transmission pathways in higher cortical function. Recent studies have shown that a mathematical method, the neuronal avalanche model, may be applied to evaluate higher-order network dynamics. The neuronal avalanche is a cascade of neuronal activity, the size distribution of which can be approximated by a power law relationship manifested by the slope of a straight line (i.e., the alpha value). We investigated whether the neuronal avalanche could be a useful index for nociceptive assessment. FINDINGS: Neuronal activities were recorded with 4 X 8 multichannel electrode arrays in the primary somatosensory cortex (S1) and anterior cingulate cortex (ACC). Under light anesthesia, peripheral pinch stimulation increased the slope of the alpha value in both the ACC and S1, whereas brush stimulation increased the alpha value only in the S1. The increase in alpha values was blocked in both regions under deep anesthesia. The increase in alpha values in the ACC induced by peripheral pinch stimulation was blocked by medial thalamic lesion, but the increase in alpha values in the S1 induced by brush and pinch stimulation was not affected. CONCLUSIONS: The neuronal avalanche model shows a critical state in the cortical network for noxious-related signal processing. The alpha value may provide an index of brain network activity that distinguishes the responses to somatic stimuli from the control state. These network dynamics may be valuable for the evaluation of acute nociceptive processes and may be applied to chronic pathological pain conditions.     

Differences in the inflammatory response induced by acute pancreatitis in different white adipose tissue sites in the rat

Background

There is increasing evidence of the role of adipose tissue on the systemic effects of acute pancreatitis. Patients with higher body mass index have increased risk of local and systemic complications and patients with android fat distribution and higher waist circumference are at greater risk for developing the severe form of the disease. Here we evaluated the changes on different areas of adipose tissue and its involvement on the inflammatory response in an experimental model of acute pancreatitis.

Methods

Pancreatitis was induced in male Wistar rats by intraductal administration of sodium taurocholate. Orlistat was administered to inhibit lipase activity. Activation of peritoneal macrophages was evaluated by measuring IL1β and TNFα expression. Inflammation was evaluated by measuring myeloperoxidase activity in mesenteric, epididymal and retroperitoneal areas of adipose tissue. Changes in the expression of inflammatory mediator in these areas of adipose tissue were also evaluated by RT-PCR.

Results

Pancreatitis induces the activation of peritoneal macrophages and a strong inflammatory response in mesenteric and epididymal sites of adipose tissue. By contrast, no changes were found in retroperitoneal adipose tissue. Inhibition of lipase prevented the activation of macrophages and the local inflammation in adipose tissue.

Conclusions

Our results confirm the involvement of adipose tissue on the progression of systemic inflammatory response during acute pancreatitis. However, there is a considerable diversity in different adipose tissue sites. These differences need to be taken into account in order to understand the progression from local pancreatic damage to systemic inflammation during acute pancreatitis.     

Methods to quantify soft-tissue based facial growth and treatment outcomes in children: a systematic review

Context

Technological advancements have led craniofacial researchers and clinicians into the era of three-dimensional digital imaging for quantitative evaluation of craniofacial growth and treatment outcomes.

Objective

To give an overview of soft-tissue based methods for quantitative longitudinal assessment of facial dimensions in children until six years of age and to assess the reliability of these methods in studies with good methodological quality.

Data Source

PubMed, EMBASE, Cochrane Library, Web of Science, Scopus and CINAHL were searched. A hand search was performed to check for additional relevant studies.

Study Selection

Primary publications on facial growth and treatment outcomes in children younger than six years of age were included.

Data Extraction

Independent data extraction by two observers. A quality assessment instrument was used to determine the methodological quality. Methods, used in studies with good methodological quality, were assessed for reliability expressed as the magnitude of the measurement error and the correlation coefficient between repeated measurements.

Results

In total, 47 studies were included describing 4 methods: 2D x-ray cephalometry; 2D photography; anthropometry; 3D imaging techniques (surface laser scanning, stereophotogrammetry and cone beam computed tomography). In general the measurement error was below 1 mm and 1° and correlation coefficients range from 0.65 to 1.0.

Conclusion

Various methods have shown to be reliable. However, at present stereophotogrammetry seems to be the best 3D method for quantitative longitudinal assessment of facial dimensions in children until six years of age due to its millisecond fast image capture, archival capabilities, high resolution and no exposure to ionizing radiation.     

Considerations on bacterial nucleoids

The classic genome organization of the bacterial chromosome is normally envisaged with all its genetic markers linked, thus forming a closed genetic circle of duplex stranded DNA (dsDNA) and several proteins in what it is called as “the bacterial nucleoid.” This structure may be more or less corrugated depending on the physiological state of the bacterium (i.e., resting state or active growth) and is not surrounded by a double membrane as in eukayotic cells. The universality of the closed circle model in bacteria is however slowly changing, as new data emerge in different bacterial groups such as in Planctomycetes and related microorganisms, species of Borrelia, Streptomyces, Agrobacterium, or Phytoplasma. In these and possibly other microorganisms, the existence of complex formations of intracellular membranes or linear chromosomes is typical; all of these situations contributing to weakening the current cellular organization paradigm, i.e., prokaryotic vs eukaryotic cells.     

Range expansion and ancestral niche reconstruction in the Mediterranean diving beetle genus Meladema (Coleoptera,Dytiscidae)

Species of the genus Meladema (Dytiscidae, Colymbetinae) are some of the largest macroinvertebrates in the western Palearctic region, being top predators in fishless streams. Two of the three described species, Meladema imbricata (Wollaston, 1871) and Meladema lanio (Fabricius, 1775) are Macaronesian endemics from the Canary Islands and Madeira, respectively, while the third, Meladema coriacea Laporte, 1835, is widely distributed from Morocco and the Iberian Peninsula to Turkey, including the Canary Islands. Previous phylogenetic analysis using only mitochondrial markers revealed the existence of two cryptic lineages within M. coriacea, one restricted to Corsica and the other including the rest of sampled populations. We reconstruct here the evolutionary history of the species of Meladema using a more comprehensive sampling covering its whole geographical range, adding nuclear markers and Bayesian molecular dating. Using environmental niche modelling, we test for possible differences in climatic preferences among lineages and reconstruct their ancestral climatic niche. Our results strongly supported the existence of four monophyletic lineages represented by the three recognized species plus a fourth cryptic lineage with populations of M. coriacea from the Tyrrhenian islands (Corsica, Sardinia and Montecristo). This pattern is not likely to be the result of mitochondrial artefacts due to Wolbachia infection, as all 11 tested individuals were negative for this parasite. Dating analysis placed the origin of Meladema in the Middle Miocene although diversification among extant Meladema lineages started in the early Pleistocene and took place in a relatively short time period. Phylogeographic analysis inferred a continental origin of Meladema, with an independent colonization of the Macaronesian and Mediterranean islands. From the south‐western Mediterranean region, the continental M. coriacea expanded its range up to Bulgaria and Turkey in the northern basin and to Tunisia in the southern. Results of niche modelling showed that seasonality is the critical factor in shaping the current distribution of Meladema. Island lineages (M. imbricata, M. lanio and the Tyrrhenian lineage of M. coriacea) occur in sites with low seasonality, within the range of the reconstructed ancestral climatic niche of the genus. On the contrary, continental M. coriacea expanded its range to localities outside the ancestral climatic range of the genus, with a higher seasonality and aridity.