Bronchiectasis and asthma: Data from the European Bronchiectasis Registry (EMBARC)

\ua9 2024 The AuthorsBackground: Asthma is commonly reported in patients with a diagnosis of bronchiectasis. Objective: The aim of this study was to evaluate whether patients with bronchiectasis and asthma (BE+A) had a different clinical phenotype and different outcomes compared with patients with bronchiectasis without concomitant asthma. Methods: A prospective observational pan-European registry (European Multicentre Bronchiectasis Audit and Research Collaboration) enrolled patients across 28 countries. Adult patients with computed tomography–confirmed bronchiectasis were reviewed at baseline and annual follow-up visits using an electronic case report form. Asthma was diagnosed by the local investigator. Follow-up data were used to explore differences in exacerbation frequency between groups using a negative binomial regression model. Survival analysis used Cox proportional hazards regression. Results: Of 16,963 patients with bronchiectasis included for analysis, 5,267 (31.0%) had investigator-reported asthma. Patients with BE+A were younger, were more likely to be female and never smokers, and had a higher body mass index than patients with bronchiectasis without asthma. BE+A was associated with a higher prevalence of rhinosinusitis and nasal polyps as well as eosinophilia and Aspergillus sensitization. BE+A had similar microbiology but significantly lower severity of disease using the bronchiectasis severity index. Patients with BE+A were at increased risk of exacerbation after adjustment for disease severity and multiple confounders. Inhaled corticosteroid (ICS) use was associated with reduced mortality in patients with BE+A (adjusted hazard ratio 0.78, 95% CI 0.63-0.95) and reduced risk of hospitalization (rate ratio 0.67, 95% CI 0.67-0.86) compared with control subjects without asthma and not receiving ICSs. Conclusions: BE+A was common and was associated with an increased risk of exacerbations and improved outcomes with ICS use. Unexpectedly we identified significantly lower mortality in patients with BE+A

Sexual dysfunction among married couples living in Kumasi metropolis, Ghana

<p>Abstract</p> <p>Background</p> <p>Sexuality and its manifestation constitute some of the most complex of human behaviour and its disorders are encountered in community. Sexual dysfunction is more prevalent in women than in men. While studies examining sexual dysfunction among males and females in Ghana exist, there are no studies relating sexual problems in males and females as dyadic units. This study therefore investigated the prevalence and type of sexual disorders among married couples.</p> <p>Method</p> <p>The study participants consisted of married couples between the ages of 19 and 66 living in the province of Kumasi, Ghana. Socio-demographic information and Golombok-Rust Inventory of Sexual Satisfaction (GRISS) questionnaires were administered to 200 couples who consented to take part in the study. All 28 questions of the GRISS are answered on a five-point (Likert type) scale from "always", through "usually', "sometimes", and "hardly ever", to "never". Responses are summed up to give a total raw score ranging from 28-140. The total score and subscale scores are transformed using a standard nine point scale, with high scores indicating greater problems. Scores of five or more are considered to indicate SD. The study was conducted between July and September 2010.</p> <p>Results</p> <p>Out of a total of 200 married couples, 179 completed their questionnaires resulting in a response rate of 89.5%. The mean age of the participating couples as well as the mean duration of marriage was 34.8 ± 8.6 years and 7.8 ± 7.6 years respectively. The husbands (37.1 ± 8.6) were significantly older (p < 0.0001) than their corresponding wives (32.5 ± 7.9). After adjusting for age, 13-18 years of marriage life poses about 10 times significant risk of developing SD compared to 1-6 years of married life among the wives (OR: 10.8; CI: 1.1 - 49.1; p = 0.04). The total scores (6.0) as well as the percentage above the cut-off (59.2) obtained by the husbands compared to the total score (6.2) and the percentage above cut-off (61.5) obtained by the wives, indicates the likely presence of sexual dysfunction. The prevalence of impotence and premature ejaculation were 60.9% and 65.4% respectively from this study and the prevalence of vaginismus and anorgasmia were 69.3% and 74.9% respectively. The highest prevalence of SD subscales among the men was dissatisfaction with sexual act followed by infrequency, whereas the highest among the women was infrequency followed by anorgasmia. Dissatisfaction with sexual intercourse among men correlated positively with anorgasmia and wife's non-sensuality and infrequency of sex.</p> <p>Conclusion</p> <p>The prevalence of sexual dysfunction in married couples is comparable to prevalence rates in the general male and female population and is further worsened by duration of marriage. This could impact significantly on a couple's self-esteem and overall quality of life.</p

Human difference in the genomic era: Facilitating a socially responsible dialogue

<p>Abstract</p> <p>Background</p> <p>The study of human genetic variation has been advanced by research such as genome-wide association studies, which aim to identify variants associated with common, complex diseases and traits. Significant strides have already been made in gleaning information on susceptibility, treatment, and prevention of a number of disorders. However, as genetic researchers continue to uncover underlying differences between individuals, there is growing concern that observed population-level differences will be inappropriately generalized as inherent to particular racial or ethnic groups and potentially perpetuate negative stereotypes.</p> <p>Discussion</p> <p>We caution that imprecision of language when conveying research conclusions, compounded by the potential distortion of findings by the media, can lead to the stigmatization of racial and ethnic groups.</p> <p>Summary</p> <p>It is essential that the scientific community and with those reporting and disseminating research findings continue to foster a socially responsible dialogue about genetic variation and human difference.</p

A genomic catalog of Earth’s microbiomes

The reconstruction of bacterial and archaeal genomes from shotgun metagenomes has enabled insights into the ecology and evolution of environmental and host-associated microbiomes. Here we applied this approach to >10,000 metagenomes collected from diverse habitats covering all of Earth’s continents and oceans, including metagenomes from human and animal hosts, engineered environments, and natural and agricultural soils, to capture extant microbial, metabolic and functional potential. This comprehensive catalog includes 52,515 metagenome-assembled genomes representing 12,556 novel candidate species-level operational taxonomic units spanning 135 phyla. The catalog expands the known phylogenetic diversity of bacteria and archaea by 44% and is broadly available for streamlined comparative analyses, interactive exploration, metabolic modeling and bulk download. We demonstrate the utility of this collection for understanding secondary-metabolite biosynthetic potential and for resolving thousands of new host linkages to uncultivated viruses. This resource underscores the value of genome-centric approaches for revealing genomic properties of uncultivated microorganisms that affect ecosystem processes

PIK3CA mutations are common in lobular carcinoma in situ, but are not a biomarker of progression

Sample and data collection were funded by Cancer Research UK. Analysis was funded by Breast Cancer Now, the Rosetrees Trust, Guys & St Thomas’ Charity (CanHelp) and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London

Distribution of GABAergic Interneurons and Dopaminergic Cells in the Functional Territories of the Human Striatum

BACKGROUND: The afferent projections of the striatum (caudate nucleus and putamen) are segregated in three territories: associative, sensorimotor and limbic. Striatal interneurons are in part responsible for the integration of these different types of information. Among them, GABAergic interneurons are the most abundant, and can be sorted in three populations according to their content in the calcium binding proteins calretinin (CR), parvalbumin (PV) and calbindin (CB). Conversely, striatal dopaminergic cells (whose role as interneurons is still unclear) are scarce. This study aims to analyze the interneuron distribution in the striatal functional territories, as well as their organization regarding to the striosomal compartment. METHODOLOGY/PRINCIPAL FINDINGS: We used immunohistochemical methods to visualize CR, PV, CB and tyrosine hydroxylase (TH) positive striatal neurons. The interneuronal distribution was assessed by stereological methods applied to every striatal functional territory. Considering the four cell groups altogether, their density was higher in the associative (2120±91 cells/mm(3)) than in the sensorimotor (959±47 cells/mm(3)) or limbic (633±119 cells/mm(3)) territories. CB- and TH-immunoreactive(-ir) cells were distributed rather homogeneously in the three striatal territories. However, the density of CR and PV interneurons were more abundant in the associative and sensorimotor striatum, respectively. Regarding to their compartmental organization, CR-ir interneurons were frequently found in the border between compartments in the associative and sensorimotor territories, and CB-ir interneurons abounded at the striosome/matrix border in the sensorimotor domain. CONCLUSIONS/SIGNIFICANCE: The present study demonstrates that the architecture of the human striatum in terms of its interneuron composition varies in its three functional territories. Furthermore, our data highlight the importance of CR-ir striatal interneurons in the integration of associative information, and the selective role of PV-ir interneurons in the motor territory. On the other hand, the low density of dopaminergic cells casts doubts about their role in the normal human striatum

Cholinergic Interneurons Are Differentially Distributed in the Human Striatum

BACKGROUND: The striatum (caudate nucleus, CN, and putamen, Put) is a group of subcortical nuclei involved in planning and executing voluntary movements as well as in cognitive processes. Its neuronal composition includes projection neurons, which connect the striatum with other structures, and interneurons, whose main roles are maintaining the striatal organization and the regulation of the projection neurons. The unique electrophysiological and functional properties of the cholinergic interneurons give them a crucial modulating function on the overall striatal response. METHODOLOGY/PRINCIPLE FINDINGS: This study was carried out using stereological methods to examine the volume and density (cells/mm(3)) of these interneurons, as visualized by choline acetyltransferase (ChAT) immunoreactivity, in the following territories of the CN and Put of nine normal human brains: 1) precommissural head; 2) postcommissural head; 3) body; 4) gyrus and 5) tail of the CN; 6) precommissural and 7) postcommissural Put. The distribution of ChAT interneurons was analyzed with respect to the topographical, functional and chemical territories of the dorsal striatum. The CN was more densely populated by cholinergic neurons than the Put, and their density increased along the anteroposterior axis of the striatum with the CN body having the highest neuronal density. The associative territory of the dorsal striatum was by far the most densely populated. The striosomes of the CN precommissural head and the postcommissural Put contained the greatest number of ChAT-ir interneurons. The intrastriosomal ChAT-ir neurons were abundant on the periphery of the striosomes throughout the striatum. CONCLUSIONS/SIGNIFICANCE: All these data reveal that cholinergic interneurons are differentially distributed in the distinct topographical and functional territories of the human dorsal striatum, as well as in its chemical compartments. This heterogeneity may indicate that the posterior aspects of the CN require a special integration of information by interneurons. Interestingly, these striatal regions have been very much left out in functional studies

Paleobiology of titanosaurs: reproduction, development, histology, pneumaticity, locomotion and neuroanatomy from the South American fossil record

Fil: García, Rodolfo A.. Instituto de Investigación en Paleobiología y Geología. Museo Provincial Carlos Ameghino. Cipolletti; ArgentinaFil: Salgado, Leonardo. Instituto de Investigación en Paleobiología y Geología. General Roca. Río Negro; ArgentinaFil: Fernández, Mariela. Inibioma-Centro Regional Universitario Bariloche. Bariloche. Río Negro; ArgentinaFil: Cerda, Ignacio A.. Instituto de Investigación en Paleobiología y Geología. Museo Provincial Carlos Ameghino. Cipolletti; ArgentinaFil: Carabajal, Ariana Paulina. Museo Carmen Funes. Plaza Huincul. Neuquén; ArgentinaFil: Otero, Alejandro. Museo de La Plata. Universidad Nacional de La Plata; ArgentinaFil: Coria, Rodolfo A.. Instituto de Paleobiología y Geología. Universidad Nacional de Río Negro. Neuquén; ArgentinaFil: Fiorelli, Lucas E.. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica. Anillaco. La Rioja; Argentin

Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes