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BACKGROUND: Periprosthetic joint infection (PJI) is a significant post-arthroplasty complication for diabetic patients, with uncontrolled diabetes identified as a PJI risk factor. Taiwan's Diabetes Shared Care Program (DSCP) was established for holistic diabetes care. AIM: To evaluate the DSCP's impact on PJI incidence and patients' medical costs. METHODS: Data were analysed from Taiwan's National Health Insurance Research Database from 2010 to 2020, focusing on type 2 diabetes mellitus (DM) patients who had undergone arthroplasty. The study group involved DSCP participants, while a comparison group comprised non-participants with matched propensity scores for age, sex, and comorbidities. The primary outcome was the PJI incidence difference between the groups; the secondary outcome was the medical expense difference. FINDINGS: The study group consisted of 11,908 type 2 DM patients who had arthroplasty and joined the DSCP; PJI occurred in 128 patients. Among non-participants, 184 patients had PJI. The PJI incidence difference between the groups was statistically significant (1.07% vs 1.55%). The study group's medical costs were notably lower, regardless of PJI incidence. Multivariate regression showed higher PJI risk in patients in comparison group, aged >70 years, male, or who had obesity, anaemia. CONCLUSION: The study indicates that DSCP involvement reduces PJI risks and decreases annual medical costs for diabetic patients after arthroplasty. Consequently, the DSCP is a recommendable option for such patients who are preparing for total joint arthroplasty.
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Artroplastia de Reemplazo de Cadera , Diabetes Mellitus Tipo 2 , Infecciones Relacionadas con Prótesis , Humanos , Masculino , Diabetes Mellitus Tipo 2/complicaciones , Factores de Riesgo , Infecciones Relacionadas con Prótesis/complicaciones , Taiwán/epidemiología , Artroplastia de Reemplazo de Cadera/efectos adversos , Estudios RetrospectivosRESUMEN
OBJECTIVE: To evaluate the effects of surface treatment on the phase and fracture strength of yttria-and magnesia-stabilized and its mechanisms. METHODS: One-piece cylindrical screw-type implants were fabricated with yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) and magnesia partially stabilized zirconia (Mg-PSZ) using computer aided design (CAD)/computer aided manufacture (CAM) technique.They were divided into three groups: (1) placed in water for 1 h after final sintering (control group), (2) sandblasting using 110 µm Al2O3 particles, (3) sandblasting plus etching with hydrofluoric acid for 1 h.The surface morphology and roughness of the implants were evaluated.Tetragonal to monoclinic transformation was measured on the surface by X-ray diffraction.Static tests of the zirconia implants were carried out at room temperature following the International Standards Organization (ISO)14801:2014 Standard. RESULTS: Both sandblasting alone and sandblasting plus acid etching significantly increased surface roughness (Ra) of Mg-PSZ and Y-TZP implants (P < 0.01), with sandblasting plus acid etching exhibited the highest surface roughness.No monoclinic band was detected in Mg-PSZ surface.Compared with the control group, the surface monoclinic content of Mg-PSZ had no obvious change after surface treatments.However, strong monoclinic bands appeared in surface modified Y-TZP.Monoclinic content of Y-TZP was higher than that of control group (1.55%) after both sandblasting alone (16.44%) and sandblasting plus acid etching (7.68%).For Mg-PSZ implants, fracture strengths of sandblasting group and sandblasting plus acid etching group were (294.1±3.3) N and (331.3±26.4) N respectively, which were lower than that of control group (458.4±48.7) N with significant differences (P < 0.01).For Y-TZP implants, fracture strength of control group was (827.3±101.6) N.Compared with control group, sandblasting group showed significantly higher fracture strength (P=0.03), which was (1 162.9±116.5) N.While sandblasting plus acid etching group had a fracture strength of (867.2±171.0) N, with no significant difference with control group (P>0.99). CONCLUSION: Sandblasting improved the fracture strength of Y-TZP implants.For the Mg-PSZ implants manufactured in this study, surface treatments with sandblasting and sandblasting plus acid etching resulted in a decrease of fracture strength.
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Resistencia Flexional , Óxido de Magnesio , Ensayo de Materiales , Propiedades de Superficie , Itrio/química , Circonio/químicaRESUMEN
Objective: To observe the treatment response of a two-dose regimen of inotuzumab ozogamicin (inotuzumab), a monoclonal antibody targeting CD22, for patients with heavily treated relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), including those failed or relapsed after chimeric antigen receptor (CAR) -T-cell therapy. Methods: Pediatric and adult patients who received two doses of inotuzumab and who were evaluated after inotuzumab treatment were included. Antibody infusions were performed between March 2020 and September 2022. All patients expressed CD22 antigen as detected by flow cytometry (>80% leukemic cells displaying CD22) before treatment. For adults, the maximum dosage per administration was 1 mg (with a total of two administrations). For children, the maximum dosage per administration was 0.85 mg/m(2) (no more than 1 mg/dose; total of two administrations). The total dosage administered to each patient was less than the standard dosage of 1.8 mg/m(2). Results: Twenty-one patients with R/R B-ALL were included, including five children (<18 years old) and sixteen adults. Seventeen patients presented with 5.0% -99.0% leukemic blasts in the bone marrow/peripheral blood or with extramedullary disease, and four patients were minimal residual disease (MRD) -positive. Fourteen patients underwent both CD19 and CD22 CAR-T-cell therapy, four underwent CD19 CAR-T-cell therapy, and three underwent blinatumomab therapy. Eleven patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). After inotuzumab treatment, 14 of 21 patients (66.7% ) achieved a complete response (CR, one was MRD-positive CR), and all four MRD-positive patients turned MRD-negative. Four of six patients who failed recent CD22 CAR-T-cell therapy achieved a CR after subsequent inotuzumab treatment. Seven patients (33.3% ) demonstrated no response. Grade 1-3 hepatotoxicity occurred in five patients (23.8% ), one child with no response experienced hepatic veno-occlusive disease (HVOD) during salvage transplantation and recovered completely. Conclusion: For patients with heavily treated R/R B-ALL, including those who had undergone allo-HSCT and CD19/CD22 CAR-T-cell therapy, the two-dose regimen of inotuzumab resulted in a CR rate of 66.7%, and the frequency of hepatotoxicity and HVOD was low.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores Quiméricos de Antígenos , Adulto , Humanos , Niño , Adolescente , Inotuzumab Ozogamicina , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Anticuerpos Monoclonales , Proteínas Adaptadoras Transductoras de Señales , Antígenos CD19RESUMEN
Fractures are commonly encountered in clinical practice. Early diagnosis and individualized treatment are the basis for achieving high-quality fracture healing and functional recovery. Radiographic examinations play an important role in the diagnosis and treatment of fractures. In recent years, with the innovation in ultrasonic examination technology and equipment, its application in the diagnosis and treatment of fractures has greatly increased. Long bone, rib, radius and ulnar, metacarpal, cartilage, nasal bone, and occult are common fracture types. Ultrasound has long been used in fracture diagnosis and treatment. This narrative review summarizes and discusses the application of ultrasound in the diagnosis and treatment of fractures.
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Fracturas Óseas , Humanos , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/terapia , Ultrasonografía , Curación de Fractura , Radio (Anatomía)RESUMEN
Cardiovascular diseases (CVD) is an urgent threat to Chinese. It is of primary importance to assess risk for cardiovascular diseases. However, there are some limitations about traditional tools for CVD risk assessment. Recently, numbers of clinical trials demonstrated that CVD risk assessments based on cardiovascular biomarkers would significantly improve sensitivity and specificity of prediction. The comment review the limitations of traditional tools for CVD risk assessment, the application value of novel tools and advances of cardiovascular biomarkers in CVD prediction. It is benefit for precise stratification and management of general population during risk stage. Archieving the strategic goal of"Healthy China"would be promising soon.
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Enfermedades Cardiovasculares , Sistema Cardiovascular , Biomarcadores , Humanos , Medición de Riesgo , Factores de RiesgoRESUMEN
The Quarterly Reports of the Ophthalmic Hospital at Canton written by Rev. Peter Parker, an American protestant missionary in China, were serialised in The Chinese Repository from 1836 to 1850. Each report provided the number of patients treated in the corresponding period and described in detail the treatment of diseases which were difficult to deal with. However, due to historical conditions, these reports were inconsistent in terms of the disease classification standards, let alone the statistical deficiencies. This paper aims to regroup the diseases recorded in the 15 reports according to the classification from the eleventh to fifteenth report and recount the patient number of each disease systematically in different periods, with reliable historical data to support such relevant studies as the history of the Ophthalmic Hospital at Canton and the introduction of Western Medicine into China and the development of International Classification of Diseases.
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Hospitales , Misioneros , Pueblo Asiatico , China , Humanos , EscrituraRESUMEN
Tumour necrosis factor inhibitors (TNFis) are commonly used for treating psoriatic diseases; however, the risk of infection while receiving TNFis remains uncertain. The aim of this study was to investigate the infection risk in patients with psoriatic disease receiving TNFis. A prospectively registered systematic literature search was conducted in Medline (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and the ClinicalTrials.gov databases from inception to December 31, 2021. We included double-blind randomized controlled trials that compared TNFis or other biologics with placebo in adults with psoriasis or psoriatic arthritis. The primary outcomes included overall and serious infection risks, and secondary outcomes included upper respiratory infections and nasopharyngitis risks. The risk ratio of the dichotomous outcome was calculated using the Mantel-Haenszel method with random effects, and heterogeneity was assessed using Cochran's Q statistic and quantified using the I-squared statistic. A total of 48 studies with 15 464 patients with psoriatic diseases were included. The meta-analysis demonstrated a slightly increased overall infection risk (risk ratio = 1.09; 95% confidence interval, 1.02-1.15) but not serious infection risk (risk ratio = 0.95; 95% confidence interval, 0.61-1.49) among patients receiving TNFis. There were also no increased risks of upper respiratory infections (risk ratio = 1.10; 95% confidence interval, 0.94-1.28) or nasopharyngitis (risk ratio = 1.14; 95% confidence interval, 1.00-1.30). In subgroup analyses using the fixed effects model, only etanercept and certolizumab pegol were, respectively, associated with an increased risk of overall infection (RR = 1.14, 95% CI, 1.03-1.27) and upper respiratory infections (RR = 1.42, 95% CI, 1.02-1.98). In conclusion, evidence to date suggests an increased overall infection risk that is generally tolerable in patients with psoriatic diseases receiving TNFis. There are no increased risks of serious infections, upper respiratory infections or nasopharyngitis.
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Nasofaringitis , Inhibidores del Factor de Necrosis Tumoral , Adulto , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Certolizumab Pegol/uso terapéutico , Etanercept/efectos adversosRESUMEN
OBJECTIVE: Enteral nutrition (EN) is the first-choice nutritional support, as it is more in line with normal physiological processes. During EN, the major goals to achieve include accurate confirmation of the feeding tube position, monitoring the gastric residual volume, assessing gastrointestinal motility, and monitoring the nutritional status of patients. With rapid development in technology, point-of-care ultrasound (POCUS) has become a more convenient and effective technical tool for monitoring critically ill patients receiving EN. In this review, we have summarized and discussed the value of POCUS in the implementation, monitoring, and evaluation of EN therapy to provide a reference for nutritional support of critically ill patients in critical care settings. MATERIALS AND METHODS: This is a narrative review. A literature search for Scopus-indexed articles was performed randomly using PubMed and MEDLINE databases as the primary sources. No specific term was used for the search. RESULTS: POCUS can be used for positioning of nasogastric and nasointestinal tubes, evaluation of gastric residuals and gastrointestinal motility as well as monitoring of nutritional status. CONCLUSIONS: POCUS is a real-time, highly repeatable, radiation-free, and non-invasive visual inspection technique, with high application value in assessing the nutritional status of patients receiving EN and guiding the development of further nutritional treatment plans. It is an important diagnostic and monitoring tool that can be used by the clinicians in the ICU.
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Enfermedad Crítica , Nutrición Enteral , Cuidados Críticos/métodos , Enfermedad Crítica/terapia , Nutrición Enteral/métodos , Humanos , Unidades de Cuidados Intensivos , Intubación Gastrointestinal , Sistemas de Atención de PuntoRESUMEN
Resulting from impaired collagen turnover, fibrosis is a hallmark of adipose tissue (AT) dysfunction and obesity-associated insulin resistance (IR). Prolidase, also known as peptidase D (PEPD), plays a vital role in collagen turnover by degrading proline-containing dipeptides but its specific functional relevance in AT is unknown. Here we show that in human and mouse obesity, PEPD expression and activity decrease in AT, and PEPD is released into the systemic circulation, which promotes fibrosis and AT IR. Loss of the enzymatic function of PEPD by genetic ablation or pharmacological inhibition causes AT fibrosis in mice. In addition to its intracellular enzymatic role, secreted extracellular PEPD protein enhances macrophage and adipocyte fibro-inflammatory responses via EGFR signalling, thereby promoting AT fibrosis and IR. We further show that decreased prolidase activity is coupled with increased systemic levels of PEPD that act as a pathogenic trigger of AT fibrosis and IR. Thus, PEPD produced by macrophages might serve as a biomarker of AT fibro-inflammation and could represent a therapeutic target for AT fibrosis and obesity-associated IR and type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Tejido Adiposo/metabolismo , Animales , Diabetes Mellitus Tipo 2/metabolismo , Dipeptidasas , Fibrosis , Inflamación/metabolismo , Resistencia a la Insulina/genética , Macrófagos/metabolismo , Ratones , Obesidad/metabolismoRESUMEN
Lymphoepithelial carcinoma is rare in the salivary glands, with an incidence of 0.4%. The most commonly affected site is the parotid gland, followed by the submandibular gland. Lymphoepithelial carcinoma in the sublingual gland has been reported only four times in the existing English-language literature. Such tumours are characterized by the presence of a poorly differentiated carcinoma that is surrounded and infiltrated by lymphocytes, and they are strongly associated with Epstein-Barr virus infection, patient ethnicity, and prominent radiosensitivity. Wide surgical excision combined with adjuvant therapy has been suggested as the first-choice therapeutic regimen. This report describes the case of a 34-year-old Indonesian woman who was evaluated and treated in Taipei Medical University Hospital. She had a tumour that presented as a painless swelling on the floor of the mouth. The diagnosis was confirmed by conducting an incisional biopsy, and a wide surgical excision with bilateral supraomohyoid neck dissection and free flap reconstruction was performed. The patient also underwent adjuvant chemoradiotherapy. No evidence of local recurrence or distant metastasis was detected during the 6 months of follow-up. Subsequently, the patient returned to her home country, and further follow-ups were not conducted.
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Carcinoma de Células Escamosas , Infecciones por Virus de Epstein-Barr , Adulto , Carcinoma de Células Escamosas/patología , Infecciones por Virus de Epstein-Barr/cirugía , Femenino , Herpesvirus Humano 4 , Humanos , Disección del Cuello , Glándula Sublingual/patologíaRESUMEN
Objective: To explore the associations of platelet parameters platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT) with the risk for stroke in people with different blood pressure levels. Methods: All the participants were from Dongfeng-Tongji cohort, including 38 295 retired employees from Dongfeng Motor Corporation at the first follow-up survey. After excluding participants with coronary heart disease, stroke, cancer, history of platelet influential drug use and those with missed data of platelet parameters or blood pressure or lost to follow-up, finally a total of 21 294 participants were included in this study. All the participants completed baseline questionnaires, physical examinations, clinical biochemical tests, and blood sample collection. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and the corresponding 95% confident intervals (CIs) for the associations between platelet parameters and risk for stroke in people with different blood pressure levels. Results: After a mean follow-up of 8.0 years, 1 578 participants developed incident stroke [1 266 ischemic stroke (IS) cases and 312 hemorrhagic stroke (HS) cases]. Compared with the participants with PLT<188×109/L, those with PLT≥188×109/L among hypertension cases were significantly associated with higher risks for stroke and IS (stroke: HR=1.27, 95%CI: 1.12-1.44; IS: HR=1.39, 95%CI: 1.21-1.60). Among hypertension group, compared with participants with PCT<0.165%, PCT≥0.165% were significantly associated with higher risk for stroke (HR=1.15, 95%CI: 1.01-1.30) and lower risk for HS (HR=0.70, 95%CI: 0.53-0.93); Among non-hypertension and hypertension group, PCT ≥0.165% were significantly associated with higher risks of IS (HR=1.27, 95%CI: 1.05-1.54; HR=1.31, 95%CI: 1.14-1.50). MPV and PDW were not significantly associated with risk for stroke. Risk for stroke increased significantly in hypertension cases with different platelet parameters levels compared with non-hypertension cases with lower levels of each platelet parameters. Conclusion: Higher levels of PLT and PCT could increase the risks for stroke and IS in middle-aged and elderly hypertension patients, and lower levels of PCT could decrease the risk for HS in hypertension patients.
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Volúmen Plaquetario Medio , Accidente Cerebrovascular , Anciano , Plaquetas , Presión Sanguínea , Humanos , Persona de Mediana Edad , Recuento de Plaquetas , Accidente Cerebrovascular/epidemiologíaRESUMEN
Endoscopic prelacrimal recess approach is a promising technique for treating various maxillary sinus diseases because it allows for adequate visualization and wide access to the entire maxillary sinus. However, the incidence of absent prelacrimal recess (PLR) has ranged from 7% to 17.5%, implying that there is a limitation for the application of EPLA in this population. Here, a male patient with concomitant Krouse T2 maxillary inverted papilloma and mycetoma presenting with unilateral nasal obstruction and blood-tinged secretion is described. The presurgical computed tomography showed no recess. By dislocating the nasolacrimal duct from the bony canal and removing the medial maxillary wall sufficiently to extend the surgical corridor; and by preserving the inferior turbinate, nasal mucosa, and nasolacrimal duct, the patient did not experience any postoperative complications. In conclusion, our modified technique may be an effective and safe strategy for treating maxillary sinus disease without prelacrimal recess.
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Neoplasias del Seno Maxilar , Micetoma , Papiloma Invertido , Endoscopía , Humanos , Masculino , Seno Maxilar/diagnóstico por imagen , Seno Maxilar/cirugía , Neoplasias del Seno Maxilar/cirugía , Papiloma Invertido/cirugía , Estudios RetrospectivosRESUMEN
Cerebrospinal fluid (CSF) leak and encephalocele from the middle cranial fossa into the sphenoid sinus lateral recess (SSLR) is a rare condition. It is often associated with obesity, female sex, well-pneumatized sinus, and prolonged intracranial hypertension. Endoscopic repair has emerged as the mainstay treatment with a success rate increasing to over 90% by refining reconstruction methods and controlling intracranial pressure. Here, we describe how a female with SSLR CSF leak and encephalocele successfully managed with endoscopic transpterygoid approach and multilayered repair. The defect was closed using four indifferent tissues, including the duragen patch, sinus mucosal flaps, the middle turbinate bone, and free mucosa flap, from the inside out. The patient had an uneventful postsurgical course and remained disease-free during the 9-month follow-up. To conclude, the technique of using sinus mucosal flaps in the context of multilayered reconstruction might be a useful method to repair CSF leak.
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Pérdida de Líquido Cefalorraquídeo , Hueso Esfenoides , Pérdida de Líquido Cefalorraquídeo/etiología , Pérdida de Líquido Cefalorraquídeo/cirugía , Encefalocele/cirugía , Endoscopía , Femenino , Humanos , Seno Esfenoidal/cirugíaRESUMEN
We report observations of gamma-ray emissions with energies in the 100-TeV energy region from the Cygnus region in our Galaxy. Two sources are significantly detected in the directions of the Cygnus OB1 and OB2 associations. Based on their positional coincidences, we associate one with a pulsar PSR J2032+4127 and the other mainly with a pulsar wind nebula PWN G75.2+0.1, with the pulsar moving away from its original birthplace situated around the centroid of the observed gamma-ray emission. This work would stimulate further studies of particle acceleration mechanisms at these gamma-ray sources.
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Ag50Cu50 films were deposited on glass substrates by a sputtering system. Effects of accumulated energy on nanoparticle formation in pulse-laser dewetting of AgCu films were investigated. The results showed that the properties of the dewetted films were found to be dependent on the magnitude of the energy accumulated in the film. For a low energy accumulation, the two distinct nanoparticles had rice-shaped/Ag60Cu40 and hemispherical/Ag80Cu20. Moreover, the absorption spectra contained two peaks at 700 nm and 500 nm, respectively. By contrast, for a high energy accumulation, the nanoparticles had a consistent composition of Ag60Cu40, a mean diameter of 100 nm and a peak absorption wavelength of 550 nm. Overall, the results suggest that a higher Ag content of the induced nanoparticles causes a blue shift of the absorption spectrum, while a smaller particle size induces a red shift.
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We report, for the first time, the long-awaited detection of diffuse gamma rays with energies between 100 TeV and 1 PeV in the Galactic disk. Particularly, all gamma rays above 398 TeV are observed apart from known TeV gamma-ray sources and compatible with expectations from the hadronic emission scenario in which gamma rays originate from the decay of π^{0}'s produced through the interaction of protons with the interstellar medium in the Galaxy. This is strong evidence that cosmic rays are accelerated beyond PeV energies in our Galaxy and spread over the Galactic disk.
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Diabetic nephropathy (DN) is primary cause of end-stage renal disease. A previous study has shown that miR-32-5p (miR-32) is highly expressed in kidney tissue during chronic allograft dysfunction with interstitial fibrosis and tubular atrophy. However, the role of miR-32-5p (miR-32) in DN is still unclear. In this study, streptozotocin-induced DN rat models and high glucose (HG)-incubated human kidney proximal tubular epithelial (HK-2) cells were established to investigate the role and underlying mechanisms of miR-32 in DN. Results of real-time PCR revealed that miR-32 levels were greatly increased in DN rats and HG-incubated HK-2 cells. Downregulation of miR-32 effectively relieved HG-induced autophagy suppression, fibrosis, epithelial-mesenchymal transition (EMT) and inflammation in HK-2 cells. Besides, miR-32 overexpression significantly down-regulated the expression of mothers against decapentaplegic homolog 7 (SMAD7), whereas knockdown of miR-32 markedly up-regulated the level of SMAD7. Dual-luciferase reporter gene assay confirmed that SMAD7 was a target of miR-32. Reintroduction of SMAD7 expression rescued miR-32-induced HK-2 cells autophagy suppression, EMT and renal fibrosis. Our findings indicate that miR-32 may play roles in the progression of EMT and fibrosis in DN.
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Diabetes Mellitus Experimental , Nefropatías Diabéticas , Transición Epitelial-Mesenquimal , Riñón/patología , MicroARNs , Proteína smad7/metabolismo , Animales , Línea Celular , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Fibrosis , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Ratas Sprague-Dawley , Proteína smad7/genética , Regulación hacia ArribaRESUMEN
Mentoring aims to improve careers and create benefits for the participants' personal and professional lives. Mentoring can be an individual or a shared experience for a group, while the mentor's role remains the same in both models. Mentors should increase confidence, teach, inspire, and set examples, helping the mentees to mould their path, contributing to the pursuit of their personal and professional goals. This study aims to report on the experience of early-career medical physics professionals and postgraduate students participating in a global mentoring program and to assess the impact of this activity on their professional development. The objectives of this mentoring program are to develop leadership roles among young medical physicists and to provide guidance and support. An online questionnaire was administered to the mentee participants. The analysis of their responses is reported in this work and the current status of the programme was examined using a SWOT analysis. In general, the mentoring experience had a positive impact on the mentees. The mentors were found especially helpful in the decision-making situations and in other conflicts that may arise with career development. Additionally, the mentees felt that mentoring contributed to the development of leadership skills required for the job market and assist in personal development. This paper concludes that participation of young medical physicists in a mentoring group program is beneficial to their career and therefore should be encouraged.