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1.
Sleep Med ; 121: 295-302, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39047303

RESUMO

OBJECTIVE: Obstructive sleep apnea (OSA) is a complex, heterogeneous disease. Categorizing the disorder into phenotypes can help us better understand its pathology and guide us toward more personalized treatment approaches. Nevertheless, most of the previous cluster analysis (CA) studies in OSA predominantly included middle-aged to older men and may not adequately represent the heterogeneity of OSA phenotypes in women. Our aim is to identify these phenotypes in women using an extensive, exclusively female cohort. METHODS: Cross-sectional study of 1886 women diagnosed with OSA (apnea-hypopnea index >5 events/h) by PSG (polysomnography) and RP (respiratory polygraphy) at a tertiary hospital Sleep Unit. A CA was performed including general data, clinical variables, comorbidities and sleep study results. RESULTS: Four phenotypic subtypes were identified: Cluster 1 "Middle-aged paucisymptomatic women without cardiovascular risk factors" (507 patients, 27 %); Cluster 2 "Older paucisymptomatic women with established cardiovascular disease and severe OSA" (228 patients, 12 %); Cluster 3 "Middle-aged women with "classic" symptoms and cardiovascular risk factors" (892 patients, 47 %), and Cluster 4 ″Middle-aged women with mood disorders, nonrestorative sleep and cardiovascular risk factors" (259 patients, 14 %). CONCLUSIONS: Conducting a CA exclusively within a female cohort reveals a heterogeneous presentation of OSA in women, similar to what has been previously reported in the literature for men. The "classical" presentation is notably the most prevalent, while the "atypical" presentation, which was previously more frequently associated with women, is less prevalent. Additionally, paucisymptomatic presentations, with or without associated comorbidities, are also present.


Assuntos
Fenótipo , Polissonografia , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Estudos de Coortes , Adulto , Fatores de Risco , Doenças Cardiovasculares/epidemiologia , Comorbidade , Análise por Conglomerados , Idoso
2.
Vet Res Commun ; 48(4): 2663-2669, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38630425

RESUMO

Canine leishmaniosis is a vector-borne disease caused by Leishmania infantum, and clinical manifestations of infection range from absent or severe to fatal and result from immune-mediated mechanisms. In dogs, the most common clinical signs of leishmaniosis include skin lesions and lymphadenomegaly. However, the presence of other nontypical signs has been described, and diagnosing these cases can be challenging. The aim of the present short communication was to describe the impact of the formation of circulating immunocomplexes due to L. infantum in a dog with leishmaniosis affected by a massive venous thrombus of the caudal vena cava and external iliac veins. On admission, the dog presented bilateral cutaneous vasculopathy of the thigh and renal disease due to L. infantum infection. Two weeks after starting anti-Leishmania treatment based on meglumine antimoniate and allopurinol administration, the animal developed acute claudication of the hind limbs with the presence of a thrombus in the caudal vena cava and the external iliac veins and a high level of circulating immunocomplexes detected by enzyme-linked immunosorbent assay. Exacerbation of the humoral immune response, along with deposition of circulating immune complexes in the tissues and the concurrent presence of kidney and liver damage, might have contributed to an imbalance in haemostasis in this patient. Future studies should evaluate and analyse the pathological mechanisms contributing to thrombosis in dogs with leishmaniosis.


Assuntos
Doenças do Cão , Leishmania infantum , Leishmaniose Visceral , Animais , Cães , Doenças do Cão/parasitologia , Leishmaniose Visceral/veterinária , Leishmaniose Visceral/complicações , Leishmaniose Visceral/patologia , Leishmaniose Visceral/parasitologia , Masculino , Antimoniato de Meglumina/uso terapêutico , Alopurinol/uso terapêutico , Antiprotozoários/uso terapêutico , Feminino
3.
J Comp Pathol ; 211: 8-11, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38636282

RESUMO

The aortic lumen in healthy animals is characterized by a smooth, whitish surface, but sheep have macroscopic corrugation of the intimal surface in the thoracic aorta (TA). Our aim was to determine if this finding was pathological or physiological. Thirteen sheep aortas were included in this work together with aortas from cattle (n = 3), a goat (n = 1), horses (n = 4), dogs (n = 2), rabbits (n = 2) and a pig (n = 1). A corrugated intimal surface in the TA was seen in all the sheep and the goat but was less evident in the cattle. Histologically, in sheep the TA intimal surface was seen to have multifocal bulging areas that protruded into the lumen. The outer half of the tunica media had numerous, randomly distributed muscle islands that disrupted the arrangement of the elastic lamella, displacing them towards the lumen. We conclude that the intimal corrugation of the TA in sheep is physiological and must not be misinterpreted as pathological.


Assuntos
Cabras , Túnica Íntima , Animais , Ovinos , Túnica Íntima/patologia , Coelhos , Suínos , Cães , Bovinos , Cavalos , Aorta Torácica/patologia
4.
Enferm. nefrol ; 27(1): 72-77, ene.-mar. 2024. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-232077

RESUMO

Introducción: El trasplante renal precisa de un tratamiento inmunosupresor para evitar el rechazo del injerto, pero éste aumenta el riesgo de contraer una infección. Este riesgo se agrava, aún más, cuando el paciente es portador de una ureterostomía cutánea por la manipulación de las sondas. Descripción Caso Clínico: Varón que ingresa para realización de primer trasplante renal y ureterostomía cutánea. Como antecedentes personales encontramos nefrectomía derecha en 2014 y nefrectomía izquierda y cistectomía radical en 2019, momento en el que comienza en programa de hemodiálisis. Descripción del plan de cuidados: Se realizó valoración inicial y cada 7 días según patrones funcionales de Marjory Gordon. De los diagnósticos identificados a los 15 días se establecieron como prioritarios: Disposición para mejorar los conocimientos, Complicación potencial la infección y Disposición para mejorar el afrontamiento. Evaluación del plan de cuidados: Semanalmente, se revisó el plan de cuidados, cerrando aquellos diagnósticos resueltos. Al alta, tras 33 días ingresado, se alcanzaron los objetivos establecidos, aunque la gran mayoría de ellos se continuaron reevaluando en la Consulta de Enfermería post-trasplante, como fue el diagnóstico de Disposición para mejorar los conocimientos. Conclusiones: Una correcta educación para la salud y la intervención de un equipo interdisciplinar permite un adecua-do aprendizaje de los cuidados fomentando la adherencia terapéutica y una buena prevención y detección precoz de las complicaciones que pueda conllevar la derivación en un paciente trasplantado. Además, ayudar al paciente y a su familia a aceptar esta nueva etapa que conlleva cambios a nivel físico, emocional y social. (AU)


Introduction: Renal transplant requires immunosuppressive treatment to prevent graft rejection, but this increases the risk of infection. This risk is further exacerbated when the patient has a cutaneous ureterostomy due to catheter manipulation. Clinical case description: A male patient was admitted for his first renal transplant and cutaneous ureterostomy. Past medical history includes a right nephrectomy in 2014, a left nephrectomy, and a radical cystectomy in 2019, which led to the initiation of hemodialysis. Nursing care plan description: Initial assessment was conducted, with subsequent evaluations every seven days based on Marjory Gordon’s functional patterns. At the 15-day mark, the following diagnoses were prioritized: Readiness for Enhanced Knowledge, Potential Infection Complication, and Readiness for Enhanced Coping. Evaluation of care plan: The care plan was reviewed weekly, closing out resolved diagnoses. Upon discharge after 33 days of hospitalization, established goals were achieved, with an ongoing revaluation of most of them in the post-transplant Nursing Consultation, particularly the Readiness for Enhanced Knowledge diagnosis. Conclusions: Proper health education and involvement of an interdisciplinary team enable effective learning of care practices, promoting therapeutic adherence and facilitating early prevention and detection of complications that may arise in transplant patients. Additionally, assisting the patient and family in accepting this new phase, which entails physical, emotional, and social changes, is crucial.


Assuntos
Humanos , Masculino , Idoso , Transplante de Rim/enfermagem , Ureterostomia , Cuidados de Enfermagem
5.
Front Immunol ; 15: 1352929, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545116

RESUMO

Background: HBe-antigen(Ag)-negative chronic hepatitis B virus (HBV) infection is characterized by little liver fibrosis progression and vigorous HBV-multispecific CD8+ T-cell response. Aims: To assess whether HBsAg level could discriminate different HBeAg-negative chronic HBV infection subtypes with dissimilar quality of HBV-specific CD8+ T-cell response. Methods: We recruited 63 HBeAg-negative chronic HBV infection patients in which indirect markers of liver inflammation/fibrosis, portal pressure, viral load (VL), and HBV-specific CD8+ cell effector function were correlated with HBsAg level. Results: A positive linear trend between HBsAg level and APRI, liver stiffness (LS), liver transaminases, and HBV VL, and a negative correlation with platelet count were observed. Frequency of cases with HBV-specific CD8+ T-cell proliferation against at least two HBV epitopes was higher in HBsAg < 1,000 IU/ml group. CD8+ T-cell expansion after HBVpolymerase456-63-specific stimulation was impaired in HBsAg > 1,000 IU/ml group, while the response against HBVcore18-27 was preserved and response against envelope183-91 was nearly abolished, regardless of HBsAg level. Cases with preserved HBVpolymerase456-63 CD8+ cell response had lower LS/duration of infection and APRI/duration of infection rates. HBV-polymerase456-63-specific CD8+ T-cell proliferation intensity was negatively correlated with LS/years of infection ratio. Conclusion: HBsAg > 1,000 IU/ml HBeAg-negative chronic HBV infection group shows indirect data of higher degree of inflammation, liver stiffness, and fibrosis progression speed, which are related to an impaired HBV-polymerase-specific CD8+ T-cell response.


Assuntos
Produtos do Gene pol , Hepatite B Crônica , Humanos , Vírus da Hepatite B/fisiologia , Antígenos de Superfície da Hepatite B/genética , Antígenos E da Hepatite B/genética , Inflamação , Cirrose Hepática , Linfócitos T CD8-Positivos , Alanina Transaminase , Fenótipo
6.
Vet Pathol ; 61(4): 604-608, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38440930

RESUMO

Mannheimia haemolytica-associated abomasitis has been clinically described as a cause of sudden death in lambs, but it is poorly characterized. We describe the pathological features of a severe fibrinonecrotizing abomasitis in 3 lambs that died suddenly. All 3 abomasums had a thickened submucosa due to edema and necrotic areas delimited by bands of degenerate neutrophils with slender nuclei (oat cells) and angiocentric distributions. The overlying mucosa was congested. Myriads of gram-negative coccobacilli were observed within the oat cell bands. M. haemolytica was isolated from the abomasum in all 3 animals and was serotyped as A2 in one of them. Pericarditis and pleuritis were observed in 2 of the lambs. Clostridium spp. were isolated in 1 lamb and detected by immunohistochemistry in the 3 animals, suggesting clostridial co-infection. M. haemolytica should be considered among the differential diagnoses of necrotizing abomasitis in lambs.


Assuntos
Abomaso , Mannheimia haemolytica , Necrose , Infecções por Pasteurellaceae , Doenças dos Ovinos , Animais , Mannheimia haemolytica/isolamento & purificação , Doenças dos Ovinos/patologia , Doenças dos Ovinos/microbiologia , Ovinos , Abomaso/patologia , Abomaso/microbiologia , Infecções por Pasteurellaceae/veterinária , Infecções por Pasteurellaceae/patologia , Infecções por Pasteurellaceae/microbiologia , Necrose/veterinária , Necrose/patologia , Necrose/microbiologia , Gastropatias/veterinária , Gastropatias/patologia , Gastropatias/microbiologia , Masculino , Feminino , Imuno-Histoquímica/veterinária
7.
J Mol Cell Biol ; 16(1)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38253401

RESUMO

Alternative splicing is one of the major cellular processes that determine the tissue-specific expression of protein variants. However, it remains challenging to identify physiologically relevant and tissue-selective proteins that are generated by alternative splicing. Hence, we investigated the target spectrum of the splicing factor Rbfox1 in the cardiac muscle context in more detail. By using a combination of in silico target prediction and in-cell validation, we identified several focal adhesion proteins as alternative splicing targets of Rbfox1. We focused on the alternative splicing patterns of vinculin (metavinculin isoform) and paxillin (extended paxillin isoform) and identified both as potential Rbfox1 targets. Minigene analyses suggested that both isoforms are promoted by Rbfox1 due to binding in the introns. Focal adhesions play an important role in the cardiac muscle context, since they mainly influence cell shape, cytoskeletal organization, and cell-matrix association. Our data confirmed that depletion of Rbfox1 changed cardiomyoblast morphology, cytoskeletal organization, and multinuclearity after differentiation, which might be due to changes in alternative splicing of focal adhesion proteins. Hence, our results indicate that Rbfox1 promotes alternative splicing of focal adhesion genes in cardiac muscle cells, which might contribute to heart disease progression, where downregulation of Rbfox1 is frequently observed.


Assuntos
Processamento Alternativo , Adesões Focais , Miócitos Cardíacos , Paxilina , Fatores de Processamento de RNA , Processamento Alternativo/genética , Fatores de Processamento de RNA/metabolismo , Fatores de Processamento de RNA/genética , Adesões Focais/metabolismo , Adesões Focais/genética , Animais , Paxilina/metabolismo , Paxilina/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/citologia , Camundongos , Vinculina/metabolismo , Vinculina/genética , Humanos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/genética
8.
Ann Hematol ; 103(2): 583-591, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37923805

RESUMO

Although it is known that increasing age is associated with increased morbidity and mortality in allogeneic transplantation (allo-HSCT), individualization of the process may allow to perform it in progressively older patients.This study analyzed the outcome of 97 patients older than 60 years with a first allo-HSCT performed at our institution between 2011 and 2019.Median age was 66 years (range 60-79) and 15.4% were older than 70 years. The most frequent diagnosis was acute leukemia (50.5%), and 58.8% received a myeloablative conditioning. With a median follow-up of 33.9 months (range 7.9-111.5), at 3-years overall survival (OS) was 50%; progression-free survival (PFS), 46%; cumulative incidence of relapse, 22%; and non-relapse mortality (NRM), 32%. There were no significant differences in OS (p = 0.415), PFS (p = 0.691), cumulative incidence of relapse (p = 0.357) or NRM (p = 0.658) between patients of 60-64 years (n = 37), 65-69 (n = 45) and ≥ 70 years (n = 15). No differences were observed either depending on the intensity of the conditioning regimen in terms of OS (p = 0.858), PFS (p = 0.729), cumulative incidence of relapse (p = 0.416) or NRM (p = 0.270).In conclusion, older adults can safely and effectively undergo allo-HSCT with proper patient selection and individualized transplantation procedures.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Idoso , Pessoa de Meia-Idade , Estudos de Viabilidade , Estudos Retrospectivos , Leucemia Mieloide Aguda/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Recidiva , Condicionamento Pré-Transplante/métodos , Doença Enxerto-Hospedeiro/etiologia
9.
Ann Pharmacother ; 58(2): 140-147, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37131300

RESUMO

BACKGROUND: The evaluation of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) in clinical trials has shown high rates of virological suppression but information about its use in real-life settings is scarce. OBJECTIVE: To evaluate the effectiveness, safety, durability, and predictive variables of therapeutic failure of BIC/FTC/TAF in a real-life cohort. METHODS: This observational, retrospective, multicentered cohort study included treatment-naive (TN) and treatment-experienced (TE) adult patients living with HIV (PLWH) who started treatment with BIC/FTC/TAF from January 1, 2019, to January 31, 2022. Treatment effectiveness (based on intention-to-treat [ITT], modified ITT [mITT], and on-treatment [OT]), tolerability, and safety were evaluated in all patients who started BIC/FTC/TAF antiretroviral therapy. RESULTS: We included a total of 505 PLWH of whom 79 (16.6%) were TN and 426 (83.4%) were TE. Patients were followed up for a median (interquartile range [IQR]) of 19.6 (9.6-27.3) months, and 76% and 56% of PLWH reached month 6 and month 12 of treatment, respectively. Rates of TN PLWH with HIV-RNA <50 copies/mL in the OT, mITT, and ITT groups were 94%, 80%, and 62%, respectively, after 12 months of BIC/FTC/TAF treatment. Rates of TE PLWH with HIV-RNA <50 copies/mL were 91%, 88%, and 75% at month 12. The multivariate analysis revealed that neither age, sex, CD4 cell count <200 cells/µL, or viral load >100 000 copies/mL were associated with therapeutic failure. CONCLUSION AND RELEVANCE: Our real-life data showed that BIC/FTC/TAF is effective and safe for use in the treatment of both TN and TE patients in clinical practice.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adulto , Humanos , Espanha , Estudos de Coortes , Estudos Retrospectivos , Tenofovir/uso terapêutico , Combinação de Medicamentos , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Emtricitabina/uso terapêutico , RNA , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis
10.
iScience ; 27(1): 108666, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38155778

RESUMO

A rebalance between energy supply and demand in HBV-specific-CD8+ activated progenitor (AP) cells could restore the functionality of proliferative progeny (PP) in e-antigen(Ag)-negative chronic hepatitis B (CHBe(-)). We observed that quiescent progenitor (QP [TCF1+/FSClow]) HBVcore-specific-CD8+ cells displayed a memory-like phenotype. Following Ag-encounter, the generated AP [TCF1+/FSChigh] subset maintained the PD1+/CD127+ phenotype and gave rise to proliferative progeny (PP [ TCF1-/FSChigh]). In AP cells, IL-15 compared to IL2 decreased the initial mTORC1 boost, but maintained its activation longer linked to a catabolic profile that correlated with enhanced PP effector abilities. In nucleos(t)ide analogue (NUC)-treated CHBe(-), AP subset showed an anabolic phenotype associated with a dysfunctional PP pool. In CHBe(-) cases with low probability of HBVcore-specific-CD8+ cell on-NUC-treatment restoration, according to a clinical predictive model, IL-15/anti-PD-L1 treatment re-established their reactivity. Therefore, IL-15 could improve AP pool energy balance by decreasing intensity but extending T cell activation and by inducing a more catabolic metabolism.

11.
J Comp Pathol ; 205: 33-37, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37647838

RESUMO

Malakoplakia is a rare chronic granulomatous disease usually affecting the urinary bladder and other locations. In humans, the gastrointestinal tract is the second most common location but there are no reports of intestinal malakoplakia in animals. A 10-month-old female French Bulldog was presented with chronic haemorrhagic diarrhoea and anorexia with normochromic-normocytic anaemia and hypoalbuminaemia. Grossly, there was mucosal thickening and ulceration of the caecum, colon and rectum. Microscopically, transmural sheets of foamy macrophages were seen in these tissues. Macrophages were periodic acid-Schiff, vimentin and ionized calcium-binding adaptor molecule 1 positive and contained von Kossa- and Prussian blue-positive Michaelis-Gutmann bodies. Giemsa staining revealed rod-shaped bacterial colonies and fluorescence in-situ hybridization demonstrated Escherichia coli within macrophages. This is the first reported case of intestinal malakoplakia in domestic animals. Pathological features of intestinal malakoplakia share many similarities with ulcerative histiocytic colitis in dogs but it is unclear if they are different forms of the same pathological process or distinct entities.


Assuntos
Colite Ulcerativa , Doenças do Cão , Malacoplasia , Humanos , Animais , Cães , Feminino , Malacoplasia/veterinária , Intestinos , Colite Ulcerativa/veterinária
12.
J Comp Pathol ; 205: 24-26, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37597496

RESUMO

Feline osteochondromatosis is a spontaneous osteocartilaginous exostosis associated with feline leukaemia virus (FeLV) infection or due to a frameshift variant in the exostosin glycosyltransferase 1 (EXT1) gene. Osteochondromatosis was diagnosed in an indoor-only, 12-year-old, neutered female, Russian Blue cat. Radiographs revealed bilateral calcified proliferations in the elbow, costochondral and sternochondral joints, which distorted the normal skeletal structure. Grossly, the proliferated joints presented with consistent, rounded masses, causing complete ankylosis. The main histopathological finding was an osteocartilaginous proliferation composed of multiple irregular islands of well-differentiated hyaline cartilage surrounded and delimited by osteoid tissue. Immunohistochemistry of the osteochondromas, bone marrow and mediastinal lymph nodes, using a primary anti-FeLV gp70 antibody, and FeLV proviral DNA real-time polymerase chain reaction on bone marrow were negative. Sequencing of exon 6 of the EXT1 gene was performed and nucleotide BLAST analysis demonstrated the absence of a frameshift variant. This study reports the only case of spontaneous feline osteochondromatosis in an animal more than 10 years old.


Assuntos
Anquilose , Doenças do Gato , Leucemia Felina , Osteocondromatose , Feminino , Gatos , Animais , Vírus da Leucemia Felina , Osteocondromatose/veterinária , Éxons , Anquilose/veterinária
13.
Microorganisms ; 10(11)2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36422371

RESUMO

Arthropod vectors and parasites are identified morphologically or, more recently, by molecular methods. Both methods are time consuming and require expertise and, in the case of molecular methods, specific devices. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) identification of bacteria has meant a major change in clinical microbiology laboratories because of its simplicity, speed and specificity, and its capacity to identify microorganisms, in some cases, directly from the sample (urine cultures, blood cultures). Recently, MALDI-TOF MS has been shown as useful for the identification of some parasites. On the other hand, the identification of vector arthropods and the control of their populations is essential for the control of diseases transmitted by arthropods, and in this aspect, it is crucial to have fast, simple and reliable methods for their identification. Ticks are blood-sucking arthropods with a worldwide distribution, that behave as efficient vectors of a wide group of human and animal pathogens, including bacteria, protozoa, viruses, and even helminths. They are capable of parasitizing numerous species of mammals, birds and reptiles. They constitute the second group of vectors of human diseases, after mosquitoes. MALDI-TOF MS has been shown as useful for the identification of different tick species, such as Ixodes, Rhipicephalus and Amblyomma. Some studies even suggest the possibility of being able to determine, through MALDI-TOF MS, if the arthropod is a carrier of certain microorganisms. Regarding mosquitoes, the main group of vector arthropods, the possibility of using MALDI-TOF MS for the identification of different species of Aedes and Anopheles has also been demonstrated. In this review, we address the possibilities of this technology for the identification of parasites and arthropod vectors, its characteristics, advantages and possible limitations.

14.
Cell Mol Life Sci ; 79(8): 449, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35882686

RESUMO

Intrinsically disordered proteins and regions (IDPs and IDRs) and their importance in biology are becoming increasingly recognized in biology, biochemistry, molecular biology and chemistry textbooks, as well as in current protein science and structural biology curricula. We argue that the sequence → dynamic conformational ensemble → function principle is of equal importance as the classical sequence → structure → function paradigm. To highlight this point, we describe the IDPs and/or IDRs behind the discoveries associated with 17 Nobel Prizes, 11 in Physiology or Medicine and 6 in Chemistry. The Nobel Laureates themselves did not always mention that the proteins underlying the phenomena investigated in their award-winning studies are in fact IDPs or contain IDRs. In several cases, IDP- or IDR-based molecular functions have been elucidated, while in other instances, it is recognized that the respective protein(s) contain IDRs, but the specific IDR-based molecular functions have yet to be determined. To highlight the importance of IDPs and IDRs as general principle in biology, we present here illustrative examples of IDPs/IDRs in Nobel Prize-winning mechanisms and processes.


Assuntos
Proteínas Intrinsicamente Desordenadas , Prêmio Nobel , Proteínas Intrinsicamente Desordenadas/química , Conformação Proteica
15.
Rev Esp Enferm Dig ; 114(8): 441-444, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35866227

RESUMO

This editorial discusses current challenges in treatment stop in e-antigen-negative chronic hepatitis B, with attention to immunologic and virologic markers associated with functional cure, new therapeutic options for those cases unsuitable for treatment discontinuation, and safety after treatment withdrawal.


Assuntos
Hepatite B Crônica , Hepatite B , Biomarcadores , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B/uso terapêutico , Vírus da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Humanos
16.
Nurse Educ Pract ; 63: 103394, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35797831

RESUMO

AIM: To analyze the attitude of university nursing students at Spanish universities toward organ donation and transplantation and the factors affecting to their attitude. BACKGROUND: The opinion of future nurses toward organ transplant donation could have an important influence on the population. Knowing that opinion and what factors influence it is important to improve the attitude towards organ donation and transplantation. DESIGN: A multicenter, sociological, interdisciplinary and observational study including university nursing diploma students in a complete academic year. METHODS: Selected and randomized sample was taken of students from 52 of the 111 faculties and nursing schools and faculties in Spain with teaching activity PARTICIPANTS: A sample of 10,566 students was selected stratified by geographical area and year. MEASUREMENT INSTRUMENT: The instrument used was a validated questionnaire of attitude toward organ donation and transplantation, self-administered and completed anonymously. RESULTS: Completion rate: 85 % (n = 9001). Of the students surveyed, 78 % (n = 7040) would donate their organs after dying. Variables related to a favourable attitude: (1) Interest in listening to a talk about organ donation and transplantation [Odds ratio 1.66, 95 % confidence interval 2.05-1.35]; (2) Family discussion [Odds ratio 2.30, 95 % confidence interval 2.79-1.90] or discussion with friends about organ donation and transplantation [Odds ratio 1.56, 95 % confidence interval 1.86-1.31]; (3) Knowing that one's father [Odds ratio 1.54, 95 % confidence interval 1.94-1.22], mother's [Odds ratio 1.44, 95 % confidence interval 1.82-1.13] or partner [Odds ratio 1.28, 95 % confidence interval 1.60-1.03] has a favourable opinion; (4) Having a good self-assessment of information about organ donation and transplantation [Odds ratio 2.94, 95 % confidence interval 4.90-1.78]; (5) Not being worried about possible mutilation of the body after donation [Odds ratio 2.73, 95 % confidence interval 3.36-1.72]. CONCLUSIONS: Nursing students in Spain tend to have a favourable attitude toward organ donation and transplantation although more than 20 % of those surveyed are not in favour. TWEETABLE ABSTRACT: To maintain a high rate of organ donation for organ transplantation, it is necessary to improve the social awareness of future generations of nurses towards organ donation.


Assuntos
Transplante de Órgãos , Estudantes de Enfermagem , Obtenção de Tecidos e Órgãos , Atitude , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Inquéritos e Questionários
17.
Hepatology ; 76(5): 1259-1274, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35395098

RESUMO

BACKGROUND AND AIMS: A variant (p.Arg225Trp) of peroxisomal acyl-CoA oxidase 2 (ACOX2), involved in bile acid (BA) side-chain shortening, has been associated with unexplained persistent hypertransaminasemia and accumulation of C27-BAs, mainly 3α,7α,12α-trihydroxy-5ß-cholestanoic acid (THCA). We aimed to investigate the prevalence of ACOX2 deficiency-associated hypertransaminasemia (ADAH), its response to ursodeoxycholic acid (UDCA), elucidate its pathophysiological mechanism and identify other inborn errors that could cause this alteration. METHODS AND RESULTS: Among 33 patients with unexplained hypertransaminasemia from 11 hospitals and 13 of their relatives, seven individuals with abnormally high C27-BA levels (>50% of total BAs) were identified by high-performance liquid chromatography-mass spectrometry. The p.Arg225Trp variant was found in homozygosity (exon amplification/sequencing) in two patients and three family members. Two additional nonrelated patients were heterozygous carriers of different alleles: c.673C>T (p.Arg225Trp) and c.456_459del (p.Thr154fs). In patients with ADAH, impaired liver expression of ACOX2, but not ACOX3, was found (immunohistochemistry). Treatment with UDCA normalized aminotransferase levels. Incubation of HuH-7 hepatoma cells with THCA, which was efficiently taken up, but not through BA transporters, increased reactive oxygen species production (flow cytometry), endoplasmic reticulum stress biomarkers (GRP78, CHOP, and XBP1-S/XBP1-U ratio), and BAXα expression (reverse transcription followed by quantitative polymerase chain reaction and immunoblot), whereas cell viability was decreased (tetrazolium salt-based cell viability test). THCA-induced cell toxicity was higher than that of major C24-BAs and was not prevented by UDCA. Fourteen predicted ACOX2 variants were generated (site-directed mutagenesis) and expressed in HuH-7 cells. Functional tests to determine their ability to metabolize THCA identified six with the potential to cause ADAH. CONCLUSIONS: Dysfunctional ACOX2 has been found in several patients with unexplained hypertransaminasemia. This condition can be accurately identified by a noninvasive diagnostic strategy based on plasma BA profiling and ACOX2 sequencing. Moreover, UDCA treatment can efficiently attenuate liver damage in these patients.


Assuntos
Ácidos e Sais Biliares , Ácido Ursodesoxicólico , Humanos , Ácido Ursodesoxicólico/farmacologia , Ácido Ursodesoxicólico/uso terapêutico , Acil-CoA Oxidase/genética , Espécies Reativas de Oxigênio , Transaminases , Sais de Tetrazólio , Oxirredutases
18.
Rev Esp Geriatr Gerontol ; 57(2): 79-84, 2022.
Artigo em Espanhol | MEDLINE | ID: mdl-35339302

RESUMO

OBJECTIVE: Describe the usability, actionability and understanding of videos to promote exercise at home online during the COVID-19 pandemic, analyzing the characteristics of the population, their satisfaction, adherence and barriers to physical exercise. MATERIAL AND METHODS: A descriptive, non-experimental and cross-sectional observational design study, with a quantitative approach. Home-based videos of physical exercise and education about pain were created for people over 60 years old and distributed in the Metropolitan Region (Chile) during the months of October to December 2020. Participants had to use these videos independently at home during 4 weeks. A sample who received these videos were then voluntarily surveyed. RESULTS: Thirty-four participants rated the videos as understandable and actionable. Usability was lower in people who perceived a lower level of technological management. Average adherence was 2 days a week for 2.5 weeks. The main perceived barrier was the lack of will, which showed a greater tendency in people who performed physical exercise in a group way before the restrictions due to the COVID-19 pandemic. CONCLUSIONS: The videos were well evaluated by the elderly population, however the technological gap can be a limitation to favor an easy and simple use. Among the strategies, interventions that favor social interaction should be considered to promote interpersonal motivation, especially in people who prefer group modalities of exercise.


Assuntos
COVID-19 , Exercício Físico , Promoção da Saúde , Gravação em Vídeo , Idoso , COVID-19/epidemiologia , Chile/epidemiologia , Estudos Transversais , Humanos , Pandemias
19.
Rev. esp. geriatr. gerontol. (Ed. impr.) ; 57(2): 79-84, mar. - abr. 2022. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-205495

RESUMO

Objetivo: Describir la usabilidad, la accionabilidad y la comprensión de videos para promover el ejercicio en el hogar de manera online durante la pandemia COVID-19, analizando las características de la población, su satisfacción, adherencia y barreras para realizar ejercicio físico.Material y métodos: Estudio de diseño observacional descriptivo, no experimental y transversal, con enfoque cuantitativo. Se crearon videos de ejercicio físico y educación sobre dolor para personas mayores de 60 años, y fueron distribuidos en la Región Metropolitana (Chile) durante los meses de octubre a diciembre del 2020. La intervención consistió en el uso independiente en el hogar de estos videos, y tuvo una duración de 4 semanas. Luego, una muestra que recibió estos videos contestó una encuesta voluntariamente.Resultados: Treinta y cuatro participantes evaluaron los videos como comprensibles y accionables. La usabilidad fue menor en las personas que percibían un nivel de manejo tecnológico menor. La adherencia promedio fue de 2 días a la semana durante 2,5 semanas. La principal barrera percibida fue la falta de voluntad, la cual mostró una mayor tendencia en las personas que realizaban ejercicio físico de manera grupal antes de las restricciones por la pandemia COVID-19.Conclusiones: Los videos desarrollados fueron una herramienta bien evaluada por parte de la población mayor, sin embargo, la brecha tecnológica puede ser una limitante para favorecer un uso fácil y sencillo. Dentro de las estrategias se deberían considerar intervenciones que favorezcan la interacción social para promover la motivación interpersonal, en especial en las personas que prefieren modalidades grupales de ejercicio. (AU)


Objective: Describe the usability, actionability and understanding of videos to promote exercise at home online during the COVID-19 pandemic, analyzing the characteristics of the population, their satisfaction, adherence and barriers to physical exercise.Material and methods: A descriptive, non-experimental and cross-sectional observational design study, with a quantitative approach. Home-based videos of physical exercise and education about pain were created for people over 60 years old and distributed in the Metropolitan Region (Chile) during the months of October to December 2020. Participants had to use these videos independently at home during 4 weeks. A sample who received these videos were then voluntarily surveyed.Results: Thirty-four participants rated the videos as understandable and actionable. Usability was lower in people who perceived a lower level of technological management. Average adherence was 2 days a week for 2.5 weeks. The main perceived barrier was the lack of will, which showed a greater tendency in people who performed physical exercise in a group way before the restrictions due to the COVID-19 pandemic.Conclusions: The videos were well evaluated by the elderly population, however the technological gap can be a limitation to favor an easy and simple use. Among the strategies, interventions that favor social interaction should be considered to promote interpersonal motivation, especially in people who prefer group modalities of exercise. (AU)


Assuntos
Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Exercício Físico , Recursos Audiovisuais , Infecções por Coronavirus , Epidemiologia , Pandemias , Estudos Transversais , Epidemiologia Descritiva , Chile
20.
Sci Rep ; 11(1): 23751, 2021 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-34887500

RESUMO

The homeostatic and regenerative potential of the skin is critically impaired by an increasing accumulation of air pollutants in human ecosystems. These toxic compounds are frequently implicated in pathological processes such as premature cutaneous ageing, altered pigmentation and cancer. In this scenario, innovative strategies are required to tackle the effects of severe air pollution on skin function. Here we have used a Human Skin Organotypic Culture (HSOC) model to characterize the deleterious effects of an acute topic exposure of human skin to moderately high concentrations of common ambient pollutants, including As, Cd, Cr, dioxins and tobacco smoke. All these toxic compunds inflict severe damage in the tissue, activating the AHR-mediated response to xenobiotics. We have further evaluated the potential of an aqueous leaf extract of the polyextremophile plant Deschampsia antarctica (Edafence) to protect human skin against the acute exposure to toxic pollutants. Our results indicate that pre-treatment of HSOC samples with this aqueous extract conuterbalances the deleterious effects of the exposure to toxic comunds and triggers the activation of key genes invoved in the redox system and in the pro-inflammatory/wound healing response in the skin, suggesting that this natural compound might be effectively used in vivo to protect human skin routinely in different daily conditions.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Exposição Ambiental , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Pele/efeitos dos fármacos , Poluição do Ar , Biomarcadores , Proliferação de Células/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Pele/metabolismo , Pele/patologia , Técnicas de Cultura de Tecidos
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