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1.
Clin Infect Dis ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38769593

RESUMO

Point-of-Care Ultrasound (POCUS) is a safe, non-invasive technique performed at the patient's bedside, providing immediate results to the operator. It complements physical examination and facilitates clinical decision-making. In infectious diseases, POCUS is particularly valuable, offering an initial assessment in cases of suspected infection. It often leads to an early tentative diagnosis enabling the prompt initiation of antimicrobial treatment without the delay associated with traditional radiology. POCUS provides direct visualization of affected organs, assists in evaluating fluid balance and facilitates various interventions, all while reducing patient discomfort. For infectious disease specialists, becoming proficient in POCUS is a critical future challenge, requiring dedicated training for effective utilization.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38662335

RESUMO

Three-dimensional (3D) bioprinting is considered one of the most advanced tools to build up materials for tissue engineering. The aim of this work was the design, development and characterization of a bioink composed of human mesenchymal stromal cells (hMSC) for extrusion through nozzles to create these 3D structures that might potentially be apply to replace the function of damaged natural tissue. In this study, we focused on the advantages and the wide potential of biocompatible biomaterials, such as hyaluronic acid and alginate for the inclusion of hMSC. The bioink was characterized for its physical (pH, osmolality, degradation, swelling, porosity, surface electrical properties, conductivity, and surface structure), mechanical (rheology and printability) and biological (viability and proliferation) properties. The developed bioink showed high porosity and high swelling capacity, while the degradation rate was dependent on the temperature. The bioink also showed negative electrical surface and appropriate rheological properties required for bioprinting. Moreover, stress-stability studies did not show any sign of physical instability. The developed bioink provided an excellent environment for the promotion of the viability and growth of hMSC cells. Our work reports the first-time study of the effect of storage temperature on the cell viability of bioinks, besides showing that our bioink promoted a high cell viability after being extruded by the bioprinter. These results support the suggestion that the developed hMSC-composed bioink fulfills all the requirements for tissue engineering and can be proposed as a biological tool with potential applications in regenerative medicine and tissue engineering.

3.
Eur J Clin Microbiol Infect Dis ; 43(5): 999-1002, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38376633

RESUMO

This case report details the management of a 79-year-old male with recurrent methicillin-resistant Staphylococcus capitis bacteremia and endocarditis. The patient's clinical journey encompassed multiple hospital admissions, with challenges in managing endocarditis, pacemaker replacements, and potential cutaneous sources of infection. The treatment regimen included intravenous antibiotic therapy during hospitalization and suppressive antibiotic treatment upon discharge, alongside a decolonization strategy for his scalp lesions.


Assuntos
Antibacterianos , Bacteriemia , Endocardite Bacteriana , Staphylococcus capitis , Humanos , Masculino , Idoso , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Antibacterianos/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/diagnóstico , Staphylococcus capitis/efeitos dos fármacos , Staphylococcus capitis/isolamento & purificação , Staphylococcus capitis/genética , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/diagnóstico , Recidiva
4.
Medicina (B Aires) ; 84(1): 125-137, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-38271939

RESUMO

The Argentine Osteoporosis Society convened renowned specialists in the care of transgender people to prepare the first local position on the evaluation of bone health in this population. Law 26.743 on "Gender Identity" recognize all identities and guarantees free care throughout the health system. The impact of different gender affirmation treatments on bone mass has been topic of international debate. To date the evidence remains limited and different societies have issued suggestions and recommendations. For this reason, we believe it is relevant to mention our experience, capturing through this document a series of suggestions to be used in medical care.


La Sociedad Argentina de Osteoporosis convocó a especialistas reconocidos en la atención de personas transgénero para la elaboración del primer posicionamiento local sobre la evaluación de la salud ósea en esta población. La ley 26.743 de "Identidad de género" reconoce todas las identidades y garantiza su atención de manera gratuita en el sistema de salud. El impacto de los diferentes tratamientos de afirmación de género sobre la masa ósea ha sido tópico de debate internacional. Hasta la fecha la evidencia sigue siendo limitada y diferentes sociedades han emitido sugerencias y recomendaciones. Por tal motivo, creemos relevante mencionar nuestra experiencia plasmando mediante este documento una serie de sugerencias para ser utilizadas en la atención médica.


Assuntos
Osteoporose , Pessoas Transgênero , Humanos , Densidade Óssea , Identidade de Gênero , Osteoporose/diagnóstico
5.
Cureus ; 15(11): e48735, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38094526

RESUMO

Background Clostridioides difficile infection (CDI) is a major cause of diarrhea in hospitalized adult patients. This study aims to evaluate the clinical characteristics, clinical cure, recurrence and mortality in patients with CDI treated with either fidaxomicin or vancomycin. Methods A retrospective case-control study was conducted on patients with CDI treated with either fidaxomicin or vancomycin at a hospital from January 2019 to March 2022. Results We assessed 140 patients with CDI episodes, 70 patients treated with fidaxomicin and 70 with vancomycin. Seventy (50%) were male. Median age was 70 years old (IQR: 56-81). Fidaxomicin group had more recurrent CDI episodes within six months (59% vs 11%, p ≤ 0.001), more severity (43% vs 16%, p ≤ 0.001) and less treatment response (84% vs 100%, p ≤ 0.002) compared with vancomycin group. Recurrence and mortality rates in the follow-up period did not differ in both groups. Conclusions Our study found fidaxomicin treatment had worse outcomes due to restricted usage, potentially impacting its effectiveness in CDI. This finding is especially significant for patients with severe or recurrent CDI, as prescribing of the drug was limited until May 2022 in Spain with the lifting of this restriction, further research is necessary to better understand the potential benefits of fidaxomicin in treating CDI.

6.
Pediatr. aten. prim ; 25(100): 411-414, Oct.-Dic. 2023. tab
Artigo em Espanhol | IBECS | ID: ibc-228832

RESUMO

La sensibilidad química múltiple (SQM) es una entidad escasamente comprendida y controvertida. La SQM es un síndrome polisintomático y multisistémico. Los sujetos con SQM muestran una sintomatología compleja debido a la intolerancia a los agentes químicos. Los síntomas incluyen malestar general, inestabilidad cardiovascular, irritación de órganos de los sentidos, desórdenes respiratorios, con hipersensibilidad que afecta a piel, recubrimiento epitelial de intestino, garganta y pulmones. Se presenta un caso de una mujer de 8 años, valorada por sensibilización química con síntomas inhalatorios y faríngeos, conjuntivitis, disfonía y accesos de tos con sensación de dificultad respiratoria. El seguimiento se ha realizado durante 6 años, durante los cuales se ha repetido el test inhalatorio en dos ocasiones con los mismos resultados concluyentes para el diagnóstico de SQM. El caso comunicado reúne los criterios de SQM, siendo excepcional el inicio de los síntomas a una edad tan temprana. (AU)


Multiple chemical sensitivity (MCS) is a controversial little understood entity. MCS is a multisystem and poly-symptomatic syndrome. MCS subjects display a complex symptomatology due to the intolerance of chemical agents. Symptoms include general discomfort, cardiovascular instability, sensory organs irritation, breath disorders, hypersensitivity affecting the skin and epithelial lining of the gut, throat and lungs. We report the case of an 8 years old female, assessed in medical consultation for chemical sensitization when presenting inhalation and pharyngeal symptoms, conjunctivitis, dysphonia, coughing spells and respiratory distress. A 6-year follow-up was carried out and the provocation inhaler test which was performed twice among that period obtained the same conclusive results for the diagnosis of MCS. The case submitted meets the criterion of MCS, being exceptional a debut of the symptons at such an early age. (AU)


Assuntos
Humanos , Feminino , Criança , Sensibilidade Química Múltipla/diagnóstico , Sensibilidade Química Múltipla/terapia , Transtornos do Olfato
7.
Arch Rheumatol ; 38(4): 542-548, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38125061

RESUMO

Objectives: This study aimed to evaluate the clinical and serological profile in systemic sclerosis (SSc) by comparing females and males. Patients and methods: This retrospective study was conducted with 215 SSc patients (193 females, 22 males; mean age: 50.1±14.5 years; range, 16 to 88 years) between September 2005 and September 2020. Disease severity was calculated by the Medsger severity score. Males and females were compared for clinical and serological markers. Results: Females more frequently had esophageal involvement (p=0.003), telangiectasias (p=0.03), and antinuclear antibodies (p=0.04). Males more frequently had fingertip scars (p=0.03), digital ulcers (p=0.006), and a worse median Medsger severity score (6 in males vs. 4 in females, p=0.05). Conclusion: In the studied sample, males had more severe disease than females with greater repercussions in periferic circulatory system.

8.
Int J Pharm ; 647: 123535, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-37865132

RESUMO

Wound healing is a natural physiological reaction to tissue injury. Hydrogels show attractive advantages in wound healing not only due to their biodegradability, biocompatibility and permeability but also because provide an excellent environment for cell migration and proliferation. The main objective of the present study was the design and characterization of a hydrogel loaded with human mesenchymal stromal cells (hMSCs) for use in would healing of superficial skin injures. Poloxamer 407® was used as biocompatible biomaterial to embed hMSCs. The developed hydrogel containing 20 % (w/w) of polymer resulted in the best formulation with respect to physical, mechanical, morphological and biological properties. Its high swelling capacity confirmed the hydrogel's capacity to absorb wounds' exudate. LIVE/DEAD® assay confirm that hMSCs remained viable for at least 48 h when loaded into the hydrogels. Adding increasing concentrations of hMSCs-loaded hydrogel to the epithelium did not affect keratinocytes' viability and healing capacity and all wound area was closed in less than one day. Our study opens opportunities to exploit poloxamer hydrogels as cell carriers for the treatment of skin superficial wound.


Assuntos
Hidrogéis , Células-Tronco Mesenquimais , Humanos , Poloxâmero , Cicatrização , Pele
9.
J Cell Sci ; 136(11)2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37288673

RESUMO

Gap junction channels, composed of connexins, allow direct cell-to-cell communication. Connexin 43 (Cx43; also known as GJA1) is widely expressed in tissues, including the epidermis. In a previous study of human papillomavirus-positive cervical epithelial tumour cells, we identified Cx43 as a binding partner of the human homologue of Drosophila Discs large (Dlg1; also known as SAP97). Dlg1 is a member of the membrane associated-guanylate kinase (MAGUK) scaffolding protein family, which is known to control cell shape and polarity. Here, we show that Cx43 also interacts with Dlg1 in uninfected keratinocytes in vitro and in keratinocytes, dermal cells and adipocytes in normal human epidermis in vivo. Depletion of Dlg1 in keratinocytes did not alter Cx43 transcription but was associated with a reduction in Cx43 protein levels. Reduced Dlg1 levels in keratinocytes resulted in a reduction in Cx43 at the plasma membrane with a concomitant reduction in gap junctional intercellular communication and relocation of Cx43 to the Golgi compartment. Our data suggest a key role for Dlg1 in maintaining Cx43 at the plasma membrane in keratinocytes.


Assuntos
Conexina 43 , Proteína 1 Homóloga a Discs-Large , Queratinócitos , Humanos , Comunicação Celular , Membrana Celular/metabolismo , Conexina 43/genética , Conexina 43/metabolismo , Junções Comunicantes/metabolismo , Guanilato Quinases/metabolismo , Queratinócitos/metabolismo , Proteína 1 Homóloga a Discs-Large/genética , Proteína 1 Homóloga a Discs-Large/metabolismo
10.
mSphere ; 8(2): e0068022, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-36877023

RESUMO

Klebsiella pneumoniae, a Gram-negative bacterium, has been listed as a critical pathogen for urgent intervention by the World Health Organization. With no licensed vaccine and increasing resistance to antibiotics, Klebsiella pneumoniae causes a high incidence of hospital- and community-acquired infections. Recently, there has been progress in anti-Klebsiella pneumoniae vaccine development, which has highlighted the lack of standardized assays to measure vaccine immunogenicity. We have developed and optimized methods to measure antibody level and function after vaccination with an in-development Klebsiella pneumoniae O-antigen vaccine. We describe the qualification of a Luminex-based multiplex antibody binding assay and both an opsonophagocytic killing assay and serum bactericidal assay to measure antibody function. Serum from immunized animals were immunogenic and capable of binding to and killing specific Klebsiella serotypes. Cross-reactivity was observed but limited among serotypes sharing antigenic epitopes. In summary, these results demonstrate the standardization of assays that can be used to test new anti-Klebsiella pneumoniae vaccine candidates, which is important for moving them into clinical trials. IMPORTANCE There is no licensed vaccine for the prevention of Klebsiella pneumoniae infections, and increasing levels of antibiotic resistance make this pathogen a high priority for vaccine and therapeutic development. Standardized assays for testing vaccine immunogenicity are paramount for the development of vaccines, and so in this study, we optimized and standardized both antibody-level and function assays for evaluating in-development K. pneumoniae bioconjugate vaccine response in rabbits.


Assuntos
Klebsiella pneumoniae , Antígenos O , Animais , Coelhos , Anticorpos Antibacterianos , Fagocitose , Vacinas Bacterianas
11.
Int J Mol Sci ; 24(5)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36902203

RESUMO

Hyaluronic acid (HA) and proteoglycans (such as dermatan sulphate (DS) and chondroitin sulphate (CS)) are the main components of the extracellular matrix of the skin, along with collagen and elastin. These components decrease with age, which implies a loss of skin moisture causing wrinkles, sagging and aging. Currently, the external and internal administration of effective ingredients that can reach the epidermis and dermis is the main alternative for combating skin aging. The objective of this work was to extract, characterise and evaluate the potential of an HA matrix ingredient to support anti-aging. The HA matrix was isolated and purified from rooster comb and characterised physicochemically and molecularly. In addition, its regenerative, anti-aging and antioxidant potential and intestinal absorption were evaluated. The results show that the HA matrix is composed of 67% HA, with an average molecular weight of 1.3 MDa; 12% sulphated glycosaminoglycans, including DS and CS; 17% protein, including collagen (10.4%); and water. The in vitro evaluation of the HA matrix's biological activity showed regenerative properties in both fibroblasts and keratinocytes, as well as moisturising, anti-aging and antioxidant effects. Furthermore, the results suggest that the HA matrix could be absorbed in the intestine, implying a potential oral as well as topical use for skin care, either as an ingredient in a nutraceutical or a cosmetic product.


Assuntos
Antioxidantes , Ácido Hialurônico , Regeneração , Envelhecimento da Pele , Pele , Animais , Masculino , Antioxidantes/metabolismo , Galinhas , Sulfatos de Condroitina/metabolismo , Colágeno/metabolismo , Fibroblastos/metabolismo , Glicosaminoglicanos/metabolismo , Ácido Hialurônico/metabolismo , Pele/metabolismo , Envelhecimento da Pele/fisiologia
12.
Nutrients ; 15(6)2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36986062

RESUMO

Osteoarthritis (OA) is the most common joint disease, generating pain, disability, and socioeconomic costs worldwide. Currently there are no approved disease-modifying drugs for OA, and safety concerns have been identified with the chronic use of symptomatic drugs. In this context, nutritional supplements and nutraceuticals have emerged as potential alternatives. Among them, collagen is being a focus of particular interest, but under the same term different types of collagens coexist with different structures, compositions, and origins, leading to different properties and potential effects. The aim of this narrative review is to generally describe the main types of collagens currently available in marketplace, focusing on those related to joint health, describing their mechanism of action, preclinical, and clinical evidence. Native and hydrolyzed collagen are the most studied collagen types for joint health. Native collagen has a specific immune-mediated mechanism that requires the recognition of its epitopes to inhibit inflammation and tissue catabolism at articular level. Hydrolyzed collagen may contain biologically active peptides that are able to reach joint tissues and exert chondroprotective effects. Although there are preclinical and clinical studies showing the safety and efficacy of food ingredients containing both types of collagens, available research suggests a clear link between collagen chemical structure and mechanism of action.


Assuntos
Osteoartrite , Humanos , Osteoartrite/metabolismo , Colágeno , Dor , Inflamação , Suplementos Nutricionais
13.
Biotechnol Bioeng ; 120(9): 2717-2724, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36919270

RESUMO

Three dimensional (3D) bioprinting is an emerging technology that enables complex spatial modeling of cell-based tissue engineering products, whose therapeutic potential in regenerative medicine is enormous. However, its success largely depends on the definition of a bioprintable zone, which is specific for each combination of cell-loaded hydrogels (or bioinks) and scaffolds, matching the mechanical and biological characteristics of the target tissue to be repaired. Therefore proper adjustment of the bioink formulation requires a compromise between: (i) the maintenance of cellular critical quality attributes (CQA) within a defined range of specifications to cell component, and (ii) the mechanical characteristics of the printed tissue to biofabricate. Herein, we investigated the advantages of using natural hydrogel-based bioinks to preserve the most relevant CQA in bone tissue regeneration applications, particularly focusing on cell viability and osteogenic potential of multipotent mesenchymal stromal cells (MSCs) displaying tripotency in vitro, and a phenotypic profile of 99.9% CD105+ /CD45,- 10.3% HLA-DR,+ 100.0% CD90,+ and 99.2% CD73+ /CD31- expression. Remarkably, hyaluronic acid, fibrin, and gelatin allowed for optimal recovery of viable cells, while preserving MSC's proliferation capacity and osteogenic potency in vitro. This was achieved by providing a 3D structure with a compression module below 8.8 ± 0.5 kPa, given that higher values resulted in cell loss by mechanical stress. Beyond the biocompatibility of naturally occurring polymers, our results highlight the enhanced protection on CQA exerted by bioinks of natural origin (preferably HA, gelatin, and fibrin) on MSC, bone marrow during the 3D bioprinting process, reducing shear stress and offering structural support for proliferation and osteogenic differentiation.


Assuntos
Bioimpressão , Células-Tronco Mesenquimais , Hidrogéis/química , Osteogênese , Gelatina/química , Engenharia Tecidual/métodos , Fibrina/metabolismo , Alicerces Teciduais/química , Bioimpressão/métodos , Impressão Tridimensional
14.
Eur J Hosp Pharm ; 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36737227

RESUMO

Severe asthma has an important impact on patients and healthcare resources. Recently, the new specific treatments have defined a new scenario in which person-focused care and specialist multidisciplinary teams are necessary. Our Severe Asthma Unit (SAU) started the ASfarMA project along with an external human-centered design company to understand patients' vision of their illness, treatment, and healthcare experience, and to define the ideal SAU by performing a core group session, in-depth semistructured interviews and co-creation workshop. Herein, a series of tips classified as either 'transformative solutions' or 'quick wins', according to a value versus effort matrix are presented. Successful implementation of the proposed solutions will be valuable for patients and healthcare professionals, optimising patient care and resources. These findings can also be helpful to other SAUs or other humanisation projects involving complex, chronic and multidisciplinary pathologies.

15.
EBioMedicine ; 88: 104434, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36640455

RESUMO

BACKGROUND: Previous epigenome-wide association studies have shown that HIV infection can disrupt the host DNA methylation landscape. However, it remains unclear how antiretroviral therapy (ART) affects the HIV-induced epigenetic modifications. METHODS: 184 individuals with HIV from the NEAT001/ANRS143 clinical trial (with pre-ART and post-ART samples [96 weeks of follow-up]) and 44 age-and-sex matched individuals without HIV were included. We compared genome-wide DNA methylation profiles in whole blood between groups adjusting for age, sex, batch effects, and DNA methylation-based estimates of leucocyte composition. FINDINGS: We identified 430 differentially methylated positions (DMPs) between HIV+ pre-ART individuals and HIV-uninfected controls. In participants with HIV, ART initiation modified the DNA methylation levels at 845 CpG positions and restored 49.3% of the changes found between HIV+ pre-ART and HIV-uninfected individuals. We only found 15 DMPs when comparing DNA methylation profiles between HIV+ post-ART individuals and participants without HIV. The Gene Ontology enrichment analysis of DMPs associated with untreated HIV infection revealed an enrichment in biological processes regulating the immune system and antiviral responses. In participants with untreated HIV infection, DNA methylation levels at top HIV-related DMPs were associated with CD4/CD8 ratios and viral loads. Changes in DNA methylation levels after ART initiation were weakly correlated with changes in CD4+ cell counts and the CD4/CD8 ratio. INTERPRETATION: Control of HIV viraemia after 96 weeks of ART initiation partly restores the host DNA methylation changes that occurred before antiretroviral treatment of HIV infection. FUNDING: NEAT-ID Foundation and Instituto de Salud Carlos III, co-funded by European Union.


Assuntos
Metilação de DNA , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Epigênese Genética , Contagem de Linfócito CD4 , Relação CD4-CD8 , DNA , Antirretrovirais/uso terapêutico
16.
Facial Plast Surg ; 39(4): 417-426, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36706784

RESUMO

Managing the nasal septum (NS) position is crucial in septorhinoplasty. The analysis and the preparation of the anterior nasal spine and the quadrangular cartilage as well as the strategy defined to efficiently stabilize the septum will dictate considerably the success of the result. Moreover, what we see in the surgical table can suffer modifications during the healing process because of poor fixation or the cheese-wire effect of the cartilage. We will present a logical sequence and tools to achieve a proper and stable position of the NS and the nasal pyramid. The sublaminar (supraperichondral) dissection of the quadrangular cartilage as an option to the subperichondral one and the use of cable and mirror sutures to three-dimensionally positioning and stabilizing the NS will be described.


Assuntos
Septo Nasal , Rinoplastia , Humanos , Septo Nasal/cirurgia , Cartilagem , Suturas
17.
Nutrients ; 16(1)2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38201844

RESUMO

(1) Background: Hospital malnutrition and sarcopenia are common in inpatients and are associated with worse prognosis. Our objective is to determine the association of the positivity of CIPA (Control of Intakes, Proteins and Anthropometry) nutrition screening tool and sarcopenia and evaluate its prognostic implications (length of stay, readmissions and mortality) as well as different components of body composition. (2) Methodology: Cross-sectional single-center study and prospective six months follow-up for prognostic variables. On admission, CIPA and EWGSOP2 criteria were assessed. (3) Results: Four hundred inpatients, a median of 65.71 years old and 83.6% with high comorbidity, were evaluated. In total, 34.8% had positive CIPA and 19.3% sarcopenia. Positive CIPA and sarcopenia had worse results in body composition (fat mass (FM), fat-free mass (FFM) and appendicular skeletal muscle mass index (ASMI)) and dynamometry. Positive CIPA is significantly associated with worse prognosis (mortality (OR = 1.99), readmissions (OR = 1.86) and length of stay (B = 0.19)). Positive CIPA and sarcopenia combined are associated with a tendency to higher mortality (OR = 2.1, p = 0.088). Low hand grip strength (HGS) is significantly related to a higher length of stay (B = -0.12). (4) Conclusions: In hospitalized patients, malnutrition independently and combined with sarcopenia is associated with a worse prognosis but not body composition. Low HGS is related to a higher length of stay.


Assuntos
Indóis , Desnutrição , Propionatos , Sarcopenia , Humanos , Idoso , Estudos Transversais , Força da Mão , Avaliação Nutricional , Estudos Prospectivos , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Estado Nutricional , Antropometria , Composição Corporal , Desnutrição/diagnóstico , Desnutrição/epidemiologia
18.
Int J Mol Sci ; 23(20)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36293511

RESUMO

Cutaneous fibrosis is one of the main features of systemic sclerosis (SSc). Recent findings correlated abnormal collagen V (Col V) deposition in dermis with skin thickening and disease activity in SSc. Considering that Col V is an important regulator of collagen fibrillogenesis, understanding the role of Col V in the first two years of the skin fibrosis in SSc (early SSc) can help to determine new targets for future treatments. In this study, we analyzed the morphological, ultrastructural and molecular features of α1(V) and α2(V) chains and the expression of their coding genes COL5A1 and COL5A2 in collagen fibrillogenesis in early-SSc. Skin biopsies were obtained from seven consecutive treatment-naïve patients with SSc-related fibrosis and four healthy controls. Our data showed increased α1(V) and α2(V) chain expression in the reticular dermis of early-SSc patients; however, immunofluorescence and ultrastructural immunogold staining determined a significant decreased expression of the α1(V) chain along the dermoepidermal junction in the papillary dermis from early-SSc-patients in relation to the control (12.77 ± 1.34 vs. 66.84 ± 3.36; p < 0.0001). The immunoblot confirmed the decreased expression of the α1(V) chain by the cutaneous fibroblasts of early-SSc, despite the increased COL5A1 and COL5A2 gene expression. In contrast, the α2(V) chain was overexpressed in the small vessels (63.18 ± 3.56 vs. 12.16 ± 0.81; p < 0.0001) and capillaries (60.88 ± 5.82 vs. 15.11 ± 3.80; p < 0.0001) in the reticular dermis of early-SSc patients. Furthermore, COLVA2 siRNA in SSc cutaneous fibroblasts resulted in a decreased α1(V) chain expression. These results highlight an intense decrease in the α1(V) chain along the dermoepidermal junction, suggesting an altered molecular histoarchitecture in the SSc papillary dermis, with a possible decrease in the expression of the α1(V)3 homotrimeric isoform, which could interfere with the thickening and cutaneous fibrosis related to SSc.


Assuntos
Derme , Escleroderma Sistêmico , Humanos , RNA Interferente Pequeno/metabolismo , Estrutura Molecular , Derme/metabolismo , Escleroderma Sistêmico/patologia , Fibrose , Colágeno/metabolismo , Pele/metabolismo , Fibroblastos/metabolismo
19.
Mol Ther Nucleic Acids ; 29: 769-786, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36159592

RESUMO

Satellite cells (SCs), muscle stem cells, display functional heterogeneity, and dramatic changes linked to their regenerative capabilities are associated with muscle-wasting diseases. SC behavior is related to endogenous expression of the myogenic transcription factor MYF5 and the propensity to enter into the cell cycle. Here, we report a role for miR-106b reinforcing MYF5 inhibition and blocking cell proliferation in a subset of highly quiescent SC population. miR-106b down-regulation occurs during SC activation and is required for proper muscle repair. In addition, miR-106b is increased in dystrophic mice, and intramuscular injection of antimiR in injured mdx mice enhances muscle regeneration promoting transcriptional changes involved in skeletal muscle differentiation. miR-106b inhibition promotes the engraftment of human muscle stem cells. Furthermore, miR-106b is also high in human dystrophic muscle stem cells and its inhibition improves intrinsic proliferative defects and increases their myogenic potential. This study demonstrates that miR-106b is an important modulator of SC quiescence, and that miR-106b may be a new target to develop therapeutic strategies to promote muscle regeneration improving the regenerative capabilities of injured dystrophic muscle.

20.
Int J Ment Health Nurs ; 31(6): 1457-1466, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35938942

RESUMO

The aim of this study was to measure and analyse the association of emotional burnout and resilience with the psychological distress of students who finished their nursing studies after the peak of the COVID-19 pandemic. The mental health of nursing students was affected during the pandemic, and resilience seems to counteract the negative effects. This is a cross-sectional study. The data (quantitative) were gathered at the beginning of the second term of the academic year 2020/2021. The study was carried out in the Spanish university context. Self-reported measures were gathered using three one-dimensional, valid, and reliable scales: the Psychological Distress Scale (K-10), the Emotional Burnout Scale (EBS), and the short version of the Connor-Davidson Resilience Scale (CD-RISC10). A total of 393 students of different Spanish universities participated in this study. A valid linear regression model was obtained, which allowed verifying that psychological distress is explained, with 37% variance, by emotional burnout and resilience. The total score in emotional burnout has more relevance than the total score in resilience, and the latter has a negative tendency. Facing the factors that generate emotional burnout in students in the academic scope and promoting resilience in them are fundamental aspects that contribute to their psychological well-being. The reflection should be extended to clinical practices. Universities are urged to think about last-year students, their experiences, perceptions, and feelings, to determine how their susceptibility to emotional burnout and psychological distress can be minimized in their future clinical practices. Strategies to promote their resilience should also be studied.


Assuntos
Esgotamento Profissional , COVID-19 , Angústia Psicológica , Resiliência Psicológica , Estudantes de Enfermagem , Humanos , Estudantes de Enfermagem/psicologia , Pandemias , Estudos Transversais , Esgotamento Profissional/psicologia , Emoções
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