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1.
Fam Process ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39118239

RESUMO

Family reactions to coming out can affect the mental health of individuals who disclose their sexual orientation or gender identity. Therefore, it is important to have an appropriate tool to assess them. The Perceived Parental Reactions Scale (PPRS) assessed perceived parental reactions to the disclosure of gay, lesbian, or bisexual sexual orientation by their children. We adapted the PPRS so that it can be answered by any individual belonging to a sexual or gender minority, and can be answered regarding any member of the family, not just parents. A total of 2627 individuals from Spain participated in this study, with a mean age of 31.59 (SD = 11.26). Participants completed the adapted PPRS questionnaire, now named the Family Reaction to Coming Out (FRCO). The FRCO assessed family reactions when disclosing their sexual orientation or gender identity. The majority of participants identified as cisgender men (47.5%) or cisgender women (44.9%), and as gay/lesbian (51.9%). A one-factor model emerged through exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The FRCO displayed excellent internal consistency and demonstrated good levels of invariance for participants' gender (male vs female vs nonbinary gender), family member's gender (male vs female), and type of family member (parents vs other family member). Supporting convergent validity, the FRCO has shown a positive correlation with fear of family reaction to coming out. These findings support the validity and reliability of the FRCO tool in assessing the reactions of any family member within the Spanish context.

2.
Menopause ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39137107

RESUMO

OBJECTIVE: To evaluate the association between menopausal symptoms and cognitive decline in postmenopausal women. METHODS: This was a subanalysis of a cross-sectional, observational study conducted among women attending gynecological consultations across nine Latin American countries. The survey involved late postmenopausal women who were asked to complete a general questionnaire and the Menopause Rating Scale (MRS) to assess menopausal symptoms, with the Montreal Cognitive Assessment used to evaluate cognitive function as an outcome. A Montreal Cognitive Assessment score of less than 21 was used to define women with mild cognitive impairment (MCI). RESULTS: The study included 1,287 postmenopausal women with a mean age of 55.5 years and a mean body mass index of 26.3 kg/m2. On average, participants had 13.8 years of education and 2.3 ± 1.8 children, with 72.8% reporting having a partner. Additionally, 36.7% ever used menopausal hormone therapy. Regarding lifestyle factors, 50.3% engaged in a sedentary lifestyle, whereas 70.5% had never smoked. 15.3% of women had MCI exhibited significantly more intense menopausal symptoms compared with those without MCI (MRS total score 15.24 ± 12.58 vs 10.53 ± 8.84, respectively, P < 0.001). Logistic regression analysis revealed a significant association between severe menopausal symptoms (MRS total score ≥14 points) and MCI (odds ratio [OR], 1.74; 95% CI, 1.25-2.42). Conversely, a lower body mass index (OR, 0.96; 95% CI, 0.95-0.98), sexual activity (OR, 0.70; 95% CI, 0.51-0.96), physical exercise (OR, 0.55; 95% CI, 0.39-0.76), menopausal hormone therapy use (OR, 0.36; 95% CI, 0.24-0.55), and higher educational level (OR, 0.31; 95% CI, 0.21-0.46) were associated with lower odds for MCI. CONCLUSION: Severe menopausal symptoms in postmenopausal women were associated with cognitive impairment. This study highlights the intricate interplay between hormonal, lifestyle, and sociodemographic factors and cognitive health.

3.
Cureus ; 16(7): e65184, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39176357

RESUMO

The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) encompasses various autoimmune conditions triggered by exposure to substances with adjuvant activity. Despite its potential relevance to public health, global scientific production on ASIA syndrome is significantly limited. This knowledge gap underscores the need for a comprehensive bibliometric assessment to understand global research in this field. Therefore, this article aims to conduct a bibliometric analysis to identify and evaluate research trends related to ASIA syndrome worldwide. A Scopus search identified scientific documents published between 2010 and 2022. A total of 2,133 articles meeting inclusion criteria were selected and analyzed for scientific production, authors, and institutions. Two-hundred fifty six documents were analyzed, mostly journal articles with multiple authors. The year with the highest publications was 2023, marking a notable increase since 2021. Italy and Israel had the most documents and citations, correlating with authors Yehuda Shoenfeld (Israel) and Carlo Perricone (Italy). Standout journals are "The Journal of Immunologic Research" and "Lupus." Relevant affiliations include Tel-Aviv University and the National Autonomous University of Mexico. This article identifies and analyzes scientific trends associated with ASIA syndrome. Despite increased publications, this field remains controversial and lacks full acceptance within the medical and scientific community, as evidenced by limited scientific production compared to other pathologies. These findings may motivate researchers to generate impactful publications, contributing to the global knowledge expansion on this syndrome.

4.
Biomolecules ; 14(8)2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39199343

RESUMO

Cyclic acid anhydride is a not very widespread structure in nature, but with a determining role in natural products possessing this functionality in their skeleton. To the best of our knowledge, no revision of terpenes containing cyclic anhydrides has been previously reported. The result was that more than 100 terpenic cyclic anhydrides and related compounds were found to be in need of being reported. This review has been systematically organized by terpene skeletons, from the smallest to largest, describing their sources and bioactivities. In addition, different biosynthetic pathways for their final oxidations, namely, routes A, B and C, leading to the formation of these heterocyclic natural products, have been proposed. We have also included the most plausible precursors of these natural products, which mostly happened to be present in the same natural source. Some molecules derived from terpene cyclic anhydrides, such as their natural imide derivatives, have also been described due to their significant biological activity. In this sense, special attention has been paid to cantharidin because of its historical relevance and its broad bioactivity. A plausible biosynthesis of cantharidin has been proposed for the first time. Finally, cyclic anhydride structures that were firstly assigned as anhydrides and later corrected have been also described.


Assuntos
Anidridos , Produtos Biológicos , Terpenos , Terpenos/química , Terpenos/metabolismo , Anidridos/química , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Vias Biossintéticas , Humanos , Animais
5.
J Am Chem Soc ; 146(32): 22711-22723, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39092878

RESUMO

Excitation of iron pentacarbonyl [Fe(CO)5], a prototypical photocatalyst, at 266 nm causes the sequential loss of two CO ligands in the gas phase, creating catalytically active, unsaturated iron carbonyls. Despite numerous studies, major aspects of its ultrafast photochemistry remain unresolved because the early excited-state dynamics have so far eluded spectroscopic observation. This has led to the long-held assumption that ultrafast dissociation of gas-phase Fe(CO)5 proceeds exclusively on the singlet manifold. Herein, we present a combined experimental-theoretical study employing ultrafast extreme ultraviolet transient absorption spectroscopy near the Fe M2,3-edge, which features spectral evolution on 100 fs and 3 ps time scales, alongside high-level electronic structure theory, which enables characterization of the molecular geometries and electronic states involved in the ultrafast photodissociation of Fe(CO)5. We assign the 100 fs evolution to spectroscopic signatures associated with intertwined structural and electronic dynamics on the singlet metal-centered states during the first CO loss and the 3 ps evolution to the competing dissociation of Fe(CO)4 along the lowest singlet and triplet surfaces to form Fe(CO)3. Calculations of transient spectra in both singlet and triplet states as well as spin-orbit coupling constants along key structural pathways provide evidence for intersystem crossing to the triplet ground state of Fe(CO)4. Thus, our work presents the first spectroscopic detection of transient excited states during ultrafast photodissociation of gas-phase Fe(CO)5 and challenges the long-standing assumption that triplet states do not play a role in the ultrafast dynamics.

6.
Pharmacogenomics J ; 24(5): 29, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39179559

RESUMO

African American (AA) kidney transplant recipients (KTRs) have poor outcomes, which may in-part be due to tacrolimus (TAC) sub-optimal immunosuppression. We previously determined the common genetic regulators of TAC pharmacokinetics in AAs which were CYP3A5 *3, *6, and *7. To identify low-frequency variants that impact TAC pharmacokinetics, we used extreme phenotype sampling and compared individuals with extreme high (n = 58) and low (n = 60) TAC troughs (N = 515 AA KTRs). Targeted next generation sequencing was conducted in these two groups. Median TAC troughs in the high group were 7.7 ng/ml compared with 6.3 ng/ml in the low group, despite lower daily doses of 5 versus 12 mg, respectively. Of 34,542 identified variants across 99 genes, 1406 variants were suggestively associated with TAC troughs in univariate models (p-value < 0.05), however none were significant after multiple testing correction. We suggest future studies investigate additional sources of TAC pharmacokinetic variability such as drug-drug-gene interactions and pharmacomicrobiome.


Assuntos
Negro ou Afro-Americano , Imunossupressores , Transplante de Rim , Tacrolimo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Negro ou Afro-Americano/genética , Citocromo P-450 CYP3A/genética , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Imunossupressores/farmacocinética , Variantes Farmacogenômicos , Fenótipo , Tacrolimo/farmacocinética , Tacrolimo/uso terapêutico , Transplantados
7.
J Interpers Violence ; : 8862605241270016, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39135482

RESUMO

Previous research has shown a robust association between different childhood and adolescent vulnerabilities and youth offending. However, these investigations have primarily focused on youths from high-income Western countries. Consequently, the generalizability of these findings to better inform global justice policies remains uncertain. This study aimed to address this gap by examining the relationship between individual, familial, and contextual vulnerabilities and criminal versatility during young adulthood, accounting for sociodemographic factors and cross-national differences. Data were derived from a diverse sample of 4,182 young adults (67% female; mean age = 18.96; SD = 0.81) residing in 10 countries across 5 continents who participated in the International Study of Pro/Antisocial Behavior in Young Adults. The Psychosocial and Family Vulnerability Questionnaire and the Adverse Childhood Experiences questionnaire were used to assess social and family adversity, and past-year criminal diversity was measured with the Criminal Variety Index. Results indicate that child maltreatment, substance abuse, and delinquent peers are global risk factors for criminal variety. Moreover, they are independent across males and females and among youths living in countries that are ranked differently on the Human Development Index (HDI). In addition, some childhood vulnerabilities showed different predictive ability across sexes (e.g., school failure), and across countries ranked differently on the HDI (e.g., family dysfunction). These findings suggest that certain childhood factors contribute to criminal behavior through transcultural mechanisms. Moreover, they highlight the importance of developing evidence-based policies that focus on transcultural risk factors to globally prevent criminal behavior.

9.
J Phys Chem A ; 128(34): 7277-7283, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39140833

RESUMO

In this work, we implement a generalized spin formulation of the doubly occupied configuration interaction methodology using the energy variance of the N-electron Hamiltonian. We perform the optimization of the N-electron wave functions and calculate their corresponding energies, using a unified variational treatment for ground and excited states based on the energy variance, which allows us to describe the entire energy spectra on an equal footing. We analyze the effects produced by the breakdown of the S2 and Sz symmetries in the spectra of model hydrogenic clusters in terms of energies and spin-related quantities, arising from the restricted, unrestricted, and generalized spin methods. The results are compared with other related methods as well as full configuration interaction.

10.
Theriogenology ; 226: 328-334, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38959843

RESUMO

The objective of this study was to compare the plasma (PL) and seminal plasma (SP) pharmacokinetic profile of ceftiofur (CEFT) and desuroylceftiofur acetamide (DFCA) after administration of CEFT crystalline-free acid (CCFA) by SC route in two sites of the ear in beef bulls. Four clinically healthy Hereford bulls received a comprehensive physical exam and subsequently a breeding-soundness examination, CBC, and chemistry profile panel. All bulls were diagnosed healthy and satisfactory potential breeders. In one group (n = 2), a single dose of CCFA was administered SC route at the base of the ear (BOE) at a dose of 6.6 mg/kg of body weight. The second group (n = 2) was also administered by SC route in the middle third of the posterior aspect of the ear (MTE). The concentrations of CEFT and DFCA in PL and SP were determined by a high-performance liquid chromatography mass spectrometry (HPLC-MS). Blood and semen samples were collected before the administration of CCFA and at 12, 24, 36, 48, 72, 96, 120, 144, and 168 h after injection. No levels of CEFT were detected in PL and only in 20 of the 40 SP samples (P = 0.0001). The mean level of CEFT in SP was 0.11 % in comparison with the DFCA level. DFCA was found in all PL and SP samples. Therefore, DFCA was chosen to be utilized in the study of the pharmacokinetics parameters both in PL and SP. There were no differences in the mean PL levels of DFCA for the two sites of SC administration between the BOE (102.9 ± 78.9 ng/mL; X ± SD) and to MTE (116.1 ± 70.2 ng/mL; P = 0.58). The mean SP levels of DFCA after administration in the BOE was 857 ± 747 ng/mL, and for the MTE was 549 ± 488 ng/mL without differences between both sites (P = 0.15). The mean level of DFCA in PL was 109.5 ± 74.0 ng/mL, which was lower than the mean SP levels of 695 ± 103 ng/mL (P = 0.001). Moreover, the PL peak DFCA concentration (Cmax) was 229 ± 46 ng/mL at 36.0 ± 29.4 h (Tmax) post-administration. The SP Cmax was 1851 ± 533 ng/mL at 30.0 ± 28.6 h (Tmax) post-administration. The Cmax between PL and SP were distinctive (P = 0.004) without any differences in Tmax between PL and SP (P = 0.60). The terminal half-life for PL DFCA (47.4 ± 29.3 h) was not different than in SP (53.1 ± 23.6 h; P = 0.77). The PL area under the curve concentration time from the first to the last sample (AUC0-last) was 18,984 ± 4841 ng/mL/h, which was significatively smaller compared with 125,677 ± 59,445 ng/mL/h for SP AUC0-last (P = 0.04). The PL mean residence time from the first to the last sample (MRT0-last) was 69.7 ± 15.1 h, and it was similar than for SP of 66.5 ± 7.7 h (P = 0.69). From the present investigation, based in its pharmacokinetic features, it was concluded that CCFA should be an appropriate antibiotic that could be used for the treatment of bull genital infections when its indication is properly outlined. To study the pharmacokinetics of CCFA in SP, DFCA metabolite was appropriated.


Assuntos
Antibacterianos , Cefalosporinas , Sêmen , Animais , Masculino , Bovinos , Cefalosporinas/farmacocinética , Cefalosporinas/sangue , Cefalosporinas/administração & dosagem , Sêmen/química , Antibacterianos/farmacocinética , Antibacterianos/sangue , Antibacterianos/administração & dosagem
11.
Food Chem ; 460(Pt 1): 140478, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39032302

RESUMO

Southern Chile native potatoes are an interesting raw material to produce novel snacks like colored potato chips. These novel products should be comprehensively evaluated for the presence of undesirable compounds such as acrylamide, 5-hydroxymethylfurfural and furan, the main neoformed contaminants in starchy rich fried foods. This study evaluated the neoformed contaminant levels and oil content on chips made from eleven Chilean potato accessions and compared them with commercial samples. The neoformed contaminant contents were related to Maillard reaction precursor levels (reducing sugars and asparagine) and secondary metabolites (phenolic compounds and carotenoids). Neoformed contaminants correlated well among them and were weakly correlated with reducing sugars and asparagine. Acrylamide level in native potato chips ranged from 738.2 to 1998.6 µg kg-1 while from 592.6 to 2390.5 µg kg-1 in commercial samples. Thus, there is need to implement neoformed contaminant mitigation strategies at different steps of the production chain of colored potato chips.

12.
Sensors (Basel) ; 24(14)2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39065850

RESUMO

This paper describes and validates an advanced synthesis design process of Frequency-Selective Surfaces (FSSs) with elliptic band-stop responses. A systematic procedure based on the Generalized Chebyshev Function and the extracted pole technique enables control of the position of the transmission zeros and the attenuation level to obtain an equiripple rejection response. A systematic process is followed to obtain the lumped LC values of the resonator circuits extracted as poles and the impedance inverters. Then, equivalent dipoles and transmission lines are obtained to carry out the electromagnetic design at normal incidence for a linearly polarized field. The impact of the higher-order modes of the periodic structure on the electrical response of the FSS, which can be relevant due to the stringent selected specifications, has been also analyzed. A fourth-order band-stop filter with a 3 GHz bandwidth centered at 30 GHz and its attenuation at 50 dB has been designed considering three different implementations: two filters using a vacuum as a transmission line with different connection lengths and a third one using a dielectric substrate to enable its manufacturing. In order to verify the design procedure using experimental results, the third filter with printed dipoles in the dielectric substrate has been manufactured and measured, thus validating the developed process.

14.
Nat Med ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965435

RESUMO

Differential diagnosis of dementia remains a challenge in neurology due to symptom overlap across etiologies, yet it is crucial for formulating early, personalized management strategies. Here, we present an artificial intelligence (AI) model that harnesses a broad array of data, including demographics, individual and family medical history, medication use, neuropsychological assessments, functional evaluations and multimodal neuroimaging, to identify the etiologies contributing to dementia in individuals. The study, drawing on 51,269 participants across 9 independent, geographically diverse datasets, facilitated the identification of 10 distinct dementia etiologies. It aligns diagnoses with similar management strategies, ensuring robust predictions even with incomplete data. Our model achieved a microaveraged area under the receiver operating characteristic curve (AUROC) of 0.94 in classifying individuals with normal cognition, mild cognitive impairment and dementia. Also, the microaveraged AUROC was 0.96 in differentiating the dementia etiologies. Our model demonstrated proficiency in addressing mixed dementia cases, with a mean AUROC of 0.78 for two co-occurring pathologies. In a randomly selected subset of 100 cases, the AUROC of neurologist assessments augmented by our AI model exceeded neurologist-only evaluations by 26.25%. Furthermore, our model predictions aligned with biomarker evidence and its associations with different proteinopathies were substantiated through postmortem findings. Our framework has the potential to be integrated as a screening tool for dementia in clinical settings and drug trials. Further prospective studies are needed to confirm its ability to improve patient care.

15.
Interdiscip Sci ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954232

RESUMO

The electrical activity of the neural processes involved in cognitive functions is captured in EEG signals, allowing the exploration of the integration and coordination of neuronal oscillations across multiple spatiotemporal scales. We have proposed a novel approach that combines the transformation of EEG signal into image sequences, considering cross-frequency phase synchronisation (CFS) dynamics involved in low-level auditory processing, with the development of a two-stage deep learning model for the detection of developmental dyslexia (DD). This deep learning model exploits spatial and temporal information preserved in the image sequences to find discriminative patterns of phase synchronisation over time achieving a balanced accuracy of up to 83%. This result supports the existence of differential brain synchronisation dynamics between typical and dyslexic seven-year-old readers. Furthermore, we have obtained interpretable representations using a novel feature mask to link the most relevant regions during classification with the cognitive processes attributed to normal reading and those corresponding to compensatory mechanisms found in dyslexia.

16.
Med Vet Entomol ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039827

RESUMO

Among mammals, bats harbour the greatest taxonomic diversity of ectoparasitic arthropods. This is mainly due to their high mobility, wide distribution range and gregarious social behaviour. In Chile, 17 species of bats have been reported; however, their ectoparasitic arthropofauna has been little studied. There are currently 12 taxa recorded, belonging to two classes and associated with only four species of bats. This study aimed to investigate the diversity of parasitic flies associated with bats in three ecoregions: Atacama Desert, Chilean Matorral and Valdivian temperate forest. During 2021, using mist nets, bats were captured in Anzota caves (Atacama Desert ecoregion), Huelquén and Alto Jahuel (Chilean Matorral ecoregion), Cherquenco and San Patricio (Valdivian temperate forest). Each bat was carefully checked during a 15-min interval for the collection of ectoparasites. The arthropods were deposited in vials with 96% ethanol. A total of 26 bats corresponding to three species (Vespertilionidae: Histiotus magellanicus Philippi, 1866, Myotis arescens (Osgood, 1943); Phyllostomidae: Desmodus rotundus (Geoffroy, 1810)) were captured from which a total of 142 ectoparasitic arthropods were collected. Bat flies were separated/identified under a stereomicroscope. Additionally, from the fieldwork, we report the presence of other ectoparasites associated with Chilean bats. In our study, we report new host-parasite associations between Trichobius parasiticus Gervais, 1844 (Diptera: Streblidae) on D. rotundus, and Basilia silvae (Brèthes, 1913) (Diptera: Nycteribiidae) in M. arescens in Chile. Our study extended the latitudinal range of distribution for B. silvae to Araucanía region, and we report for first time T. parasiticus in the country. Additionally, partial sequences of the cytochrome c oxidase I gene were obtained from these specimens. Although there is slight morphological variation in the specimens of T. parasiticus, phylogenetic analyses suggest that they correspond to the same species. The sequences generated for B. silvae represent the first for the species. Authors recommend the use of an integrative approach in the identification of ectoparasites in poorly studied ecoregions and hosts. The integration of different markers is necessary to determine more precisely the phylogenetic relationships between South American populations and species of the genera Basilia and Trichobius.

17.
J Nematol ; 56(1): 20240023, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38975564

RESUMO

Recombinase polymerase amplification (RPA) is an isothermal in vitro nucleic acid amplification technique that has been adopted for simple, robust, rapid, reliable diagnostics of nematodes. In this study, the real-time RPA assay and RPA assay combined with lateral flow dipsticks (LF-RPA) have been developed targeting the ITS rRNA gene of the British root-knot nematode, Meloidogyne artiellia. The assay provided specific and rapid detection of this root-knot nematode species from crude nematode extracts without a DNA extraction step with a sensitivity of 0.125 second-stage juvenile (J2) specimen per a reaction tube for real-time RPA during 11 min and a sensitivity of 0.5 J2 specimens per a reaction tube for LF-RPA during 25 min. The RPA assays were validated with a wide range of non-target root-knot nematodes. The LF-RPA assay has great potential for nematode diagnostics in the laboratory having minimal available equipment.

18.
J Phys Chem A ; 128(29): 6026-6032, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38985992

RESUMO

We introduce a new method to remove the one-electron self-interaction error in approximate density functional calculations on an orbital-by-orbital basis, as originally proposed by Perdew and Zunger [Phys. Rev. B 1981, 23, 5048]. This method is motivated by a recent proposal by Pederson et al. [J. Chem. Phys. 2014, 140, 121103] to remove self-interaction that employs orbitals derived from the real-space density matrix, known as FLOSIC (Fermi Löwdin orbitals self-interaction correction). However, instead of Fermi Löwdin orbitals, our scheme utilizes columns of the density matrix to determine localized orbitals, like the localization procedure proposed by Fuemmeler et al. [J. Chem. Theory Comput. 2023, 19, 8572]. The new method, dubbed DOCSIC for density matrix as orbital coefficients self-interaction correction, contrasts with traditional Perdew-Zunger or FLOSIC in that it does not incorporate additional optimization parameters, and, unlike the average density self-interaction correction of Ciofini et al. [Chem. Phys. Lett. 2003, 380, 12], it makes use of localized orbitals. Another advantage of DOCSIC is that it can be implemented as a mean-field formalism. We show details of the self-consistent generalized Kohn-Sham implementation, some illustrative results, and we finally highlight its advantages and limitations.

20.
Eur Respir J ; 64(2)2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38871375

RESUMO

BACKGROUND: Primary ciliary dyskinesia (PCD) represents a group of rare hereditary disorders characterised by deficient ciliary airway clearance that can be associated with laterality defects. We aimed to describe the underlying gene defects, geographical differences in genotypes and their relationship to diagnostic findings and clinical phenotypes. METHODS: Genetic variants and clinical findings (age, sex, body mass index, laterality defects, forced expiratory volume in 1 s (FEV1)) were collected from 19 countries using the European Reference Network's ERN-LUNG international PCD Registry. Genetic data were evaluated according to American College of Medical Genetics and Genomics guidelines. We assessed regional distribution of implicated genes and genetic variants as well as genotype correlations with laterality defects and FEV1. RESULTS: The study included 1236 individuals carrying 908 distinct pathogenic DNA variants in 46 PCD genes. We found considerable variation in the distribution of PCD genotypes across countries due to the presence of distinct founder variants. The prevalence of PCD genotypes associated with pathognomonic ultrastructural defects (mean 72%, range 47-100%) and laterality defects (mean 42%, range 28-69%) varied widely among countries. The prevalence of laterality defects was significantly lower in PCD individuals without pathognomonic ciliary ultrastructure defects (18%). The PCD cohort had a reduced median FEV1 z-score (-1.66). Median FEV1 z-scores were significantly lower in CCNO (-3.26), CCDC39 (-2.49) and CCDC40 (-2.96) variant groups, while the FEV1 z-score reductions were significantly milder in DNAH11 (-0.83) and ODAD1 (-0.85) variant groups compared to the whole PCD cohort. CONCLUSION: This unprecedented multinational dataset of DNA variants and information on their distribution across countries facilitates interpretation of the genetic epidemiology of PCD and indicates that the genetic variant can predict diagnostic and phenotypic features such as the course of lung function.


Assuntos
Estudos de Associação Genética , Genótipo , Fenótipo , Humanos , Masculino , Feminino , Adulto , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Europa (Continente) , Sistema de Registros , Dineínas do Axonema/genética , Volume Expiratório Forçado , Pré-Escolar , Síndrome de Kartagener/genética , Síndrome de Kartagener/fisiopatologia , Variação Genética , Mutação , Idoso , Lactente , Proteínas do Citoesqueleto , Proteínas
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