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1.
Endocrine ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008201

RESUMEN

PURPOSE: One of the key functions of brown adipose tissue is its positive impact on metabolism. This study aimed to examine the potential involvement of brown fat-related hormones in the development of metabolically healthy obesity. Specifically, we sought to compare the levels of NRG4, FGF21, and irisin between metabolically healthy and unhealthy individuals with obesity. METHODS: Patients with BMI ≥ 30 kg/m2 and aged between 20 and 50 years were included in the study. Among these patients, those who did not have any metabolic syndrome criteria except for increased waist circumference were defined as metabolically healthy obese. Age, gender, BMI, body fat, and muscle mass, matched metabolically healthy and unhealthy obese groups were compared in terms of FGF21, irisin, and NRG4 levels. RESULTS: Metabolically healthy and unhealthy obese groups were similar in terms of age and gender. There was no difference between the two groups in terms of BMI, weight, total body fat, muscle, fat-free mass, distribution of body fat and muscle mass. No statistically significant difference was found between irisin, NRG4, and FGF21 levels between metabolically healthy and unhealthy individuals with obesity. It was found that irisin had a significant inverse correlation with BMI and body fat percentage. CONCLUSION: The present study showed no difference between metabolically healthy and unhealthy obese individuals in terms of irisin, FGF21, and NRG4 levels. The weak association between irisin and BMI and body fat percentage may suggest a potential link between irisin with metabolic health.

2.
Int. j. morphol ; 42(3)jun. 2024.
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1564598

RESUMEN

SUMMARY: Prior research on post-COVID-19 or long COVID primarily focused on the presence of SARS-CoV-2 mostly in symptomatic patients. This study aimed to investigate the persistence of SARS-CoV-2 after 1 year of asymptomatic or mild COVID-19. SARS-CoV-2 infected and control K18-hACE2 transgenic mice (n=25) were studied. Moderate and severe symptomatic subjects were sacrificed after eight days, while mild or asymptomatic mice were kept in BSL-III for twelve months. Analyses included general condition, histochemistry, immunohistochemistry, transmission electron microscopy, and qRT-PCR. Lungs from the twelve-month group showed thickening of alveolar walls, with some lungs exhibiting the recruitment of inflammatory cells, the presence of SARS- CoV-2 mRNA, immunopositivity for the SARS-CoV-2 spike protein, and TEM showed viruses (60-125 nm) within vesicles, indicating continued replication. Certain lung samples showed persistent SARS-CoV-2 presence in Club cells, endothelial cells, and macrophages. The eight-day group exhibited viral interstitial pneumonitis, SARS-CoV-2 immunopositivity, and mRNA. The eight-day hearts displayed viral mRNA, while the twelve-month hearts tested negative. Some asymptomatic twelve-month subjects presented reduced surfactant, basal membrane thickening, fibrosis, and mild autonomic nerve degeneration. In this study conducted on mice, findings indicate the potential for chronic persistence of SARS-CoV-2 in the lungs one year post initial mild or asymptomatic infection, which could suggest the possibility of recurrent episodes in similar human conditions. The observed thickening of alveolar walls and potential fibrotic areas in these mice may imply an increased risk of post-COVID fibrosis in humans. Furthermore, the presence of SARS-CoV-2-positive inflammatory cells in some asymptomatic murine cases could herald a progression toward ongoing inflammation and chronic lung disease in humans. Therefore, the necessity for further studies in human subjects and vigilant monitoring of high-risk human populations is underscored.


Investigaciones anteriores sobre COVID-19 o COVID prolongado se centraron principalmente en la presencia de SARS-CoV-2 principalmente en pacientes sintomáticos. Este estudio tuvo como objetivo investigar la persistencia del SARS-CoV-2 después de 1 año de COVID-19 asintomático o leve. Se estudiaron ratones transgénicos K18-hACE2 infectados con SARS-CoV-2 y de control (n=25). Los animales con síntomas moderados y graves se sacrificaron después de ocho días, mientras que los ratones con síntomas leves o asintomáticos se mantuvieron en BSL-III durante doce meses. Los análisis incluyeron estado general, histoquímica, inmunohistoquímica, microscopía electrónica de transmisión y qRT- PCR. Los pulmones del grupo de doce meses mostraron engrosamiento de las paredes alveolares, y algunos pulmones exhibieron reclutamiento de células inflamatorias, presencia de ARNm del SARS-CoV-2, inmunopositividad para la proteína de la espícula del SARS-CoV-2 y TEM mostró virus (60 -125 nm) dentro de las vesículas, lo que indica una replicación continua. Ciertas muestras de pulmón mostraron una presencia persistente de SARS- CoV-2 en exocrinocitos bronquiolares, células endoteliales y macrófagos. El grupo de ocho días presentó neumonitis intersticial viral, inmunopositividad al SARS-CoV-2 y ARNm. Los corazones de ocho días mostraron ARNm viral, mientras que los corazones de doce meses dieron negativo. Algunos animales asintomáticos de doce meses presentaron disminución del surfactante, engrosamiento de la membrana basal, fibrosis y degeneración leve del nervio autónomo. En este estudio realizado en ratones, los hallazgos indican la posibilidad de persistencia crónica del SARS-CoV-2 en los pulmones un año después de la infección inicial leve o asintomática, lo que podría sugerir la posibilidad de episodios recurrentes en condiciones humanas similares. El engrosamiento observado de las paredes alveolares y las posibles áreas fibróticas en estos ratones puede implicar un mayor riesgo de fibrosis post-COVID en humanos. Además, la presencia de células inflamatorias positivas para SARS- CoV-2 en algunos casos murinos asintomáticos podría presagiar una progresión hacia una inflamación continua y una enfermedad pulmonar crónica en humanos. Por lo tanto, se subraya la necesidad de realizar más estudios en seres humanos y realizar un seguimiento atento de las poblaciones humanas de alto riesgo.

3.
Environ Sci Pollut Res Int ; 30(47): 104805-104813, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37707728

RESUMEN

In this study, it was aimed to investigate the effects of melamine exposure since the weaning period on ovarian tissue and ovarian reserve. Melamine is illegally added to milk and formula to provide high false protein positivity. Female rats (the weaning period = 21 days old, n = 18) were divided into 3 groups. 0.1 mL saline was applied to the control group by gavage for 21 days. Fifty mg/kg and seventy-five mg/kg melamine was dissolved in 0.1 mL of saline and applied by gavage for 21 days, respectively. At the end of the experiment, plasma anti-Mullerian hormone (AMH) was measured, follicle count and ovarian diameter measurement were performed in the right ovaries, and flow cytometric analysis for apoptosis was performed in the left ovaries. While a statistically significant decrease was not observed in the number of the follicle and ovarian diameter between the control and melamine-treated groups (p > 0.05), a significant decrease in the corpus luteum and a significant increase in the number of atretic follicles were observed (p < 0.05). Apoptosis (Annexin V) increased in both melamine groups and AMH plasma level decreased significantly in the 75 mg/kg group (p < 0.05). Melamine exposure from the weaning (early postnatal) period may cause a decrease in ovarian reserve in parallel with a dose increase.


Asunto(s)
Reserva Ovárica , Ratas , Femenino , Animales , Destete , Folículo Ovárico , Ovario , Hormona Antimülleriana/metabolismo , Hormona Antimülleriana/farmacología
4.
J Cancer Res Ther ; 19(2): 394-402, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37313915

RESUMEN

Background: Prostate cancer (PC) is one of the most common cancer types in men. In addition to androgen-deprivation therapy (ADT), new generation agents have provided survival advantages to patients with metastatic hormone-sensitive PC (mHSPC). In this analysis, we aimed to determine the most effective approach for treating and suppressing mHSPC using network meta-analysis (NMA). Materials and Methods: A total of 10 trials investigating different treatment modalities were conducted using NMA. The analysis was performed for all mHSPC cases as well as for low- and high-volume and docetaxel-naive subgroups. Results: In combination with ADT, abiraterone acetate (AA) in the general-population and high-volume-disease subgroups, and enzalutamide in docetaxel-naive and low-volume-disease subgroups have the highest probability of being the best treatment modalities in terms of overall survival. In addition, in the low-volume and docetaxel-naive settings, enzalutamide was superior to ADT (hazard ratio [HR] = 0.429, 95% CrI: 0.258-0.714 and HR = 0.533, 95% CrI: 0.375-0.756, respectively). In addition, in the high-volume and general-population settings (all trials and cases), AA was superior to ADT (HR = 1.568, 95% CrI: 1.378-1.773 and HR = 1.164, 95%CrI: 1.348-1.924, respectively). Conclusion: The volume status based on the CHAARTED trial should be taken into account to determine an appropriate treatment strategy for mHSPC. AA plus prednisone in high-risk and high-volume-mHSPC patients and enzalutamide in low-volume-mHSPC patients could be favorable options in combination with ADT. Depending on the patient's tolerance, in high-volume mHSPC, docetaxel, or apalutamide in combination with ADT could be alternatives for AA, whereas in the low-volume mHSPC, local radiotherapy plus ADT or ADT alone could be utilized in place of enzalutamide.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Docetaxel , Metaanálisis en Red , Antagonistas de Andrógenos/uso terapéutico , Acetato de Abiraterona/uso terapéutico , Hormonas
5.
J Cancer Res Ther ; 19(Supplement): S6-S11, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37147977

RESUMEN

Background: Small-cell lung cancer (SCLC) has a poor prognosis. For the last 30 years, first-line systemic treatment has remained unaltered. After the integration of immunotherapy, a new first-line gold standard, atezolizumab in combination with carboplatin plus etoposide, was approved in extensive-disease SCLC (ED-SCLC) in 2019. Materials and Methods: First-line randomized controlled studies that investigated anti-programmed cell death protein 1 (PD-1)/PD-1 ligand-1 (PD-L1) and anti-T-lymphocyte-associated protein 4 (CTLA-4) agents in combination with platinum plus etoposide (EP) were scoured. A total of six studies (two - anti-CTLA-4 and four - anti-PD1/PD-L1) were included and classic and network meta-analyses (NMAs) were performed. Results: Fixed model for overall survival (OAS) in the PD-1- or PD-L1-treated subgroup yielded a hazard ratio (HR) of 0.746 with a 95% confidence interval (CI) =0.662-0.840 and in the CTLA-4-treated subgroup a HR of 0.941 with a 95% CI = 0.816-1.084 for the immune therapy + chemotherapy versus chemotherapy comparison (CTLA-4-based versus PD-1- or PD-L1-based groups' comparison of OAS effect Q = 6.05, df = 1, P = 0.014). NMA showed that all chemotherapy + immunotherapy combinations were equally potent and more efficient than PE in terms of OAS and progression-free survival (PFS). Rank probability plots demonstrated nivolumab + EP as the most probable effective treatment modality in terms of OAS and PFS. Conclusion: The usage of anti-PD1/PD-L1 immunotherapy agents results in significant OAS advantage, and anti-PD1/PD-L1 agents are superior to anti-CTLA-4 approach in combination with platinum plus etoposide regimen in ED-SCLC.


Asunto(s)
Antineoplásicos Inmunológicos , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Pulmonares/terapia , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptor de Muerte Celular Programada 1 , Metaanálisis en Red , Etopósido/uso terapéutico , Antígeno B7-H1 , Platino (Metal)/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carboplatino/uso terapéutico
6.
Exp Dermatol ; 31(9): 1355-1363, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35538739

RESUMEN

Vitiligo is a depigmentation disease which affects skin and hair follicles with a prevalence of 0.5%-1% worldwide. In this study, we aimed to investigate treatmental potential of dermis-derived cells in monobenzone (MBEH)-induced mouse vitiligo model with light and electron microscopy. MBEH (40%) cream was topically applied to C57BL/6 mice until depigmentation occured in vitiligo and experimental groups. In experimental groups, dermis-derived cells obtained from back skin biopsy samples before induction of vitiligo, were injected intradermally to vitiligo mice. On Days 3 and 15 after cell transplantation to experimental groups, skin biopsies were compared with biopsies of control and vitiligo groups. Dermis-derived cells obtained from back skin biopsy samples of experimental groups showed nestin and versican immunoreactivity. Melanin in hair follicles of control group was detected by histochemical stainings (Haematoxylin and eosin and Fontana-Masson) whereas sparse melanin granules were observed in hair follicles of vitiligo group. In experimental groups, there was an increase in the number of hair follicles with melanin compared with vitiligo group. We observed MART-1 immunoreactive cells mostly around the hair follicles in control group and within dermis in vitiligo group. Electron microscopic investigation showed presence of melanosomes in hair follicles of control group and lacking in vitiligo group. In experimental groups, both type of hair follicles were observed with electron microscope. Our data suggest that autologously transplanted dermis-derived cells may be effective in vitiligo treatment by contrubuting to melanin production.


Asunto(s)
Hipopigmentación , Vitíligo , Animales , Dermis/metabolismo , Modelos Animales de Enfermedad , Folículo Piloso/metabolismo , Hidroquinonas , Melaninas/metabolismo , Ratones , Ratones Endogámicos C57BL , Vitíligo/patología
7.
Support Care Cancer ; 30(3): 2621-2629, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34816328

RESUMEN

PURPOSE: Febrile neutropenia resulting from chemotherapy is a significant cause of morbidity and mortality in cancer patients. We had previously published the associates of the risk of febrile neutropenia, and this study now extends and modifies the previous model as well as tests its external validity. METHODS: We have recruited documented febrile neutropenia cases with solid tumors, in addition to a selected control group of cancer patients from one institution treated between 2015 and 2019. We then united our sample with our previously published original derivation group, to modify and update our previous model by logistic regression analysis. Additionally, consecutive cancer patients from 5 institutions were recruited in 2020 to test external validity of the resultant algorithm. RESULTS: A total of 4075 cycles of chemotherapy in 1282 cases were recruited in the updated, new model derivation group, and a total of 8 variables were selected for the updated algorithm. In the new external validation group, 653 cycles of chemotherapy in 624 patients were analyzed, to indicate that after cycles without prophylactic granulocyte colony-stimulating factor (GCSF) usage, the algorithm yielded a sensitivity value of 91%, specificity of 40%, and an area under curve (AUC) figure of 0.78, when a risk cutoff threshold value of ≥ 0.20 is chosen. This algorithm is now embedded in a web application for free clinical use. CONCLUSION: Our algorithm identifies and quantifies the risk of febrile neutropenia in cancer patients. Further studies are required to improve this model with additional predictors.


Asunto(s)
Neutropenia Febril , Neoplasias , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica , Neutropenia Febril/inducido químicamente , Neutropenia Febril/epidemiología , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Neoplasias/tratamiento farmacológico , Estudios Prospectivos
8.
Disaster Med Public Health Prep ; 16(4): 1341-1345, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34176545

RESUMEN

OBJECTIVE: The objective of this study was to determine whether coordination of prehospital emergency health services and Disaster and Emergency Management Presidency (DEMP) and being prepared for disasters, such as building collapses, allow quick evaluation and fast intervention. METHODS: The information flow, hierarchy, treatment, and rehabilitation processes, and rescue organization and planning during the rescue attempt for 35 people who needed help due to this building collapse were reviewed. RESULTS: Of the 43 people who lived in this 8-story building, 35 were inside the building during the collapse; 40% of them were assessed as injured and 60% as exitus. Almost two-thirds (64.3%) of the injured individuals who were rescued were women. The mean duration until rescue was 330 (57.0-512.0) min. CONCLUSIONS: Leading and important factors that can increase the success rate in search and rescue interventions are informing official authorities as first early warning by individuals who can clearly define the situation, early security measures by security forces arriving before the health and search-rescue teams, accurate identification of estimated numbers of injured victims, and identifying and informing appropriate hospitals which victims rescued from the debris will be transferred to there.


Asunto(s)
Planificación en Desastres , Desastres , Servicios Médicos de Urgencia , Colapso de la Estructura , Femenino , Humanos , Masculino
9.
Ultrastruct Pathol ; 45(6): 384-390, 2021 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-34875974

RESUMEN

Monobenzyl ether of hydroquinone (MBEH) is a topical depigmentation agent used by vitiligo patients to even the skin tone. We aimed to investigate the effects of MBEH on 3T3 mouse fibroblasts. Fibroblasts were treated with 250 µM, 500 µM, and 750 µM MBEH and vehicle (EtOH:DMSO) for 24 hours. Cell numbers of 250 µM, 500 µM, and 750 µM MBEH treated and vehicle groups decreased significantly compared to control group. TUNEL positive cell rate increased with MBEH concentration. In electron microscopic examination, control and vehicle groups showed active cells features, while mitochondrial swelling and cristae loss were seen in 250 µM MBEH-treated group. In cytoplasm of 500 µM MBEH-treated group, there were many multivesicular bodies and autophagic vacuoles. As an indication of apoptosis, cell membrane blebs and reduction in cell size were observed. In 750 µM MBEH-treated group, cells were completely degenerated. Our findings show that MBEH, which is used as a depigmentation agent to lighten the skin by destroying melanocytes, may also have dose-dependent negative effects on the viability of 3T3 mouse fibroblasts, and these may be mediated through autophagic and apoptotic cell death mechanisms.


Asunto(s)
Hidroquinonas , Vitíligo , Animales , Apoptosis , Éteres , Fibroblastos , Humanos , Hidroquinonas/toxicidad , Melanocitos , Ratones
10.
Toxicol Res (Camb) ; 10(3): 418-424, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34141155

RESUMEN

This study aims to investigate the effects of melamine exposure from the weaning period (21st postnatal days in rats) on liver tissue. Female Wistar albino rats (n = 18) were divided into three groups. About 0.1-ml saline was applied to the control group by gavage for 21 days from the postnatal 21st day. The second group was taken 50-mg/kg melamine (in 0.1-ml saline) and the third group was taken 75-mg/kg melamine (in 0.1-ml saline) p.o. On the postnatal 45th day, all rats were sacrificed under anesthesia. Then, liver tissues were cut into three parts and two of them placed in neutral formalin for histopathological and flow cytometric analysis, and one of them placed in 2.5% glutaraldehyde. Histopathological analysis was performed with hematoxylin & eosin, Masson trichrome, periodic acid Schiff stained sections, and also with transmission electron microscopy. Apoptosis (Annexin V positivity) was analyzed by flow cytometry. According to histopathological analysis, hepatocyte damage, sinusoidal dilatation, and inflammatory cell infiltration significantly increased in both melamine groups compared with the control group. Apoptosis significantly increased in the 50 and 75-mg melamine groups compared with the control group. In the results of transmission electron microscopy analysis, there was abnormal chromatin distribution in the hepatocyte nuclei, loss in the cristae of the mitochondria, and organelle loss in large areas in the cytoplasm in both melamine exposure groups. As result, melamine exposure from the weaning period causes liver damage with increasing doses.

11.
J Oncol Pharm Pract ; 27(2): 405-413, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33040676

RESUMEN

BACKGROUND: Programmed Death-1 (PD-1) and Programmed Death Ligand-1 (PDL-1) inhibitors have improved survival over chemotherapy in advanced Non- Small Cell Lung Cancer (NSCLC). However, it is unclear if there are class specific differences in the efficacy of Checkpoint Inhibitors (CPIs) in NSCLC, and this paper is designed to answer these clinical questions. METHODS: For this Meta-analysis, we searched PubMed, Science of Web, "Clinicaltrials.gov" and online sources for trials comparing PD-1 and PDL-1 CPIs in advanced NSCLC. The data for Hazard Ratio (HR) and their Confidence Intervals (CI) for Overall Survival (OS) was extracted. RESULTS: A sum of 9739 patients from 16 trials were included in the efficacy evaluation. For the OS endpoint, both PD-1 inhibitors (HR = 0.76, 95%CI = 0.69-0.83, P < 0.001) and PDL-1 inhibitors (HR = 0.84, 95%CI = 0.74-0.95, P < 0.001) were superior to chemotherapy in treatment naïve (upfront) patients, the results were similar in treatment refractory patients (PD-1 inhibitors (HR = 0.67, 95%CI = 0.60-0.75, P < 0.001) and PDL-1 inhibitors (HR = 0.78, 95%CI = 0.69-0.88, P < 0.001) were superior to chemotherapy). There was no difference in the effect of PD-1 and PDL-1 classes of CPIs over chemotherapy in treatment naïve and treatment refractory settings (Q = 1.88, df = 1, P = 0.017, and, Q = 3.27, df = 1, P = 0.070, respectively). CONCLUSION: Efficacy of PD-1 and PDL-1 class of CPIs was not different, although differences among individual CPIs or their combinations cannot be excluded. We were also able to compute pooled efficacy data, as compared to chemotherapy alone, for trials where these groups of CPIs were utilized.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Antígeno B7-H1/antagonistas & inhibidores , Humanos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Retratamiento , Tasa de Supervivencia
12.
J Biomed Mater Res B Appl Biomater ; 109(2): 227-237, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32770599

RESUMEN

Magnesium (Mg) based implants such as plates and screws are often preferred to treat bone defects because of the positive effects of magnesium in bone growth and healing. Their low corrosion resistance, however, leads to fast degradation and consequently failure before healing was completed. Previously, we developed Mg doped titanium nitrate (TiN) thin film coatings to address these limitations and demonstrated that <10 at% Mg doping led to enhanced mineralization in vitro. In the present study, in vivo performance of (Ti,Mg)N coated Ti6Al4V based plates and screws were studied in the rabbit model. Bone fractures were formed on femurs of 16 rabbits and then fixed with either (Ti,Mg)N coated (n = 8) or standard TiN coated (n = 8) plates and screws. X-ray imaging and µCT analyses showed enhanced bone regeneration on fracture sites fixed with (Ti,Mg)N coated plates in comparison with the Mg free ones. Bone mineral density, bone volume, and callus volume were also found to be 11.4, 23.4, and 42.8% higher, respectively, in accordance with µCT results. Furthermore, while TiN coatings promoted only primary bone regeneration, (Ti,Mg)N led to secondary bone regeneration in 6 weeks. These results indicated that Mg presence in the coatings accelerated bone regeneration in the fracture site. (Ti,Mg)N coating can be used as a practical method to increase the efficiency of existing bone fixation devices of varying geometry.


Asunto(s)
Aleaciones/química , Placas Óseas , Tornillos Óseos , Materiales Biocompatibles Revestidos/química , Fracturas del Fémur/cirugía , Curación de Fractura , Magnesio/química , Titanio/química , Animales , Modelos Animales de Enfermedad , Masculino , Conejos
13.
J Cancer Res Ther ; 16(4): 828-837, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32930126

RESUMEN

BACKGROUND: Checkpoint inhibitors (CPIs) have improved survival compared to chemotherapy alone in advanced nonsmall-cell lung cancer (NSCLC). This article aims to compare indirect evidence and rank the effect of different CPIs in this setting. MATERIALS AND METHODS: In this network meta-analysis, we searched for trials comparing CPIs in advanced NSCLC. Figures for survival endpoints were extracted. In addition, a network meta-regression analysis was carried out. RESULTS: A total of 9220 patients from 16 trials were included in the analysis. In the first-line setting, for the overall survival endpoint, the chemotherapy + Pembrolizumab combination had the highest effectivity rank probability as compared to chemotherapy (hazard ratio = 0.788, 95% credential interval = 0.728-0.855). For the second-line setting, and also for the efficacy in terms of progression-free survival, various CPIs and their combinations were ranked. CONCLUSION: Some degree of differences in terms of efficacy exists between different types, dosages, settings, and combinations of CPI. We quantify these differences to guide clinical practice.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Teorema de Bayes , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Ensayos Clínicos como Asunto , Humanos , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto
14.
Acta Histochem ; 122(5): 151552, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32622425

RESUMEN

Healing of diabetic wounds are delayed due to late initiation and prolongation of the inflammatory phase, and inadequate growth factor synthesis, which may lead to chronic ulcers that may cause limb amputation, besides making the patients vulnerable to infections. In recent years, it has been extensively discussed whether different cell types transplanted to diabetic wound models accelerate wound healing. In this study, the effect of dermis-derived cells on Streptozotocin (STZ) induced experimental diabetic Sprague-Dawley rats were investigated. Animals were divided into 3 groups. First group was control, second group included diabetic animals with wounds. In the third group, firstly, skin specimens were obtained from animal's back, and then primary explant culture was performed. STZ induced experimental diabetes was applied to these animals and then wound was opened. The cells grown in primary culture were transplanted autologously. In all three groups, the samples taken from the wound areas on the 5th and 15th days of the wound were examined at the level of histochemical and immunohistochemical and electron microscopy. In the study, it was observed that the decreasing α-SMA and KGF (FGF-7) expression in the early period especially in the case of experimental diabetes increased as a result of cell transplantation, and in the sections belonging to the experimental diabetic group, a large number of inflammatory cells in the wound area were removed from the environment. In the cell transplanted group, the collagen fiber bundles as if in the control group. As a result, healthy cells of dermis can act as mesenchymal stem cells under certain conditions and have a positive effect on diabetic wound healing.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Fibroblastos/efectos de los fármacos , Estreptozocina/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Diabetes Mellitus Experimental/inducido químicamente , Modelos Animales de Enfermedad , Fibroblastos/metabolismo , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Ratas Sprague-Dawley
15.
Medeni Med J ; 35(4): 281-289, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33717619

RESUMEN

OBJECTIVE: Lifelong Learning is a voluntary and self-motivated form of learning that lasts from birth to death for personal and professional reasons. As medical science has a dynamic nature, the knowledge gained in the faculty of medicine mostly will not be enough in the later professional life. The aim of this study is to determine the validity and reliability of the JeffSPLL-MS© in Turkish. METHOD: Linguistic equivalence analysis was applied first, and confirmatory factor analysis (CFA) was utilized in order to test the construct validity. Concurrent validity was tested by simultaneous administration of Lifelong Learning Trends Scale (LLTS) and JeffSPLL-MS©. Finally, internal consistency and test-retest reliability of the scores gathered from the scales in the study were calculated. RESULTS: Linguistic equivalence study supplied that there is a strong relationship (r=.873, p=.001) between Turkish and English forms of the scale. For CFA, Kaiser Meyer Olkin (KMO) value was .863 and the results of Bartlett Sphericity Test were appropriate (X2 = 1173,6; p=.001, df=91); model-data fit indices for JeffSPLL-MS© with 14 items in three factors were also satisfactory ((X2/df =1,51); RMSEA=0,046; NFI=0,918; RFI=0,902; CFI=0,971) and factor loadings of items were ranging between.522 and.764. The Pearson correlation coefficient as the indicator of concurrent validity of the scales LLTS and JeffSPLL-MS© was calculated as .624 (p=.001). The internal consistency (Cronbach alpha) of the total scores gathered from JeffSPLL-MS© is .843 and stratified alpha coefficient is .892. Cronbach alpha values for the subscales are as follows: .830 (F1=Learning beliefs and motivation), .719 (F2=Skills in seeking information), .721 (F3=Attention to learning opportunities). The test-retest reliability values for the scale, and its subscales were ranged between.709 and.812 within a four-week period. CONCLUSION: It is concluded that JeffSPLL-MS© can be used as a valid and reliable measurement instrument for medical education studies in Turkey.

16.
J Cancer Res Ther ; 15(Supplement): S170-S172, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30900642

RESUMEN

Renal pelvis squamous cell carcinoma (RSCC) is a rare tumor. It starts with nonspecific symptoms and it is usually at an advanced stage with a poor prognosis at the time of diagnosis. SCC-associated hypercalcemia is a well-known paraneoplastic syndrome; however RSCC-associated hypercalcemia is a rare condition. Our patient is a 57-year-old-male patient with no bone metastases. Based on the literature screening on PubMed Database for paraneoplastic malignant hypercalcemia-associated RSCC, we found a few cases.


Asunto(s)
Carcinoma de Células Escamosas/complicaciones , Hipercalcemia/etiología , Neoplasias Renales/complicaciones , Pelvis Renal/patología , Síndromes Paraneoplásicos/etiología , Calcio/sangre , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Humanos , Hipercalcemia/sangre , Neoplasias Renales/sangre , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Pelvis Renal/cirugía , Masculino , Persona de Mediana Edad , Nefrectomía , Síndromes Paraneoplásicos/sangre , Resultado del Tratamiento
17.
J Cancer Res Ther ; 14(3): 619-624, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29893329

RESUMEN

OBJECTIVE: Increased tumor-infiltrating lymphocytes (TILs) in breast carcinoma tissues is an independent predictive factor for pathologic complete response (pCR). The increased intratumoral and stromal TILs (sTILs) in breast cancer (BC) have significant prognostic effects. In this study, we evaluated whether pCR rates to neoadjuvant chemotherapy (NACT) are higher in tumors with increased number of TILs in the pretreatment biopsy. MATERIALS AND METHODS: We retrospectively evaluated the number of TILs in intratumoral TILs (iTILs) and sTILs compartments from pretreatment full-face hematoxylin and eosin-stained sections of 62 patients with locally advanced BC (LABC) who received NACT. The capacity of sTILs and iTILs in predicting pCR to NACT in LABC analyzed using receiver operating characteristic (ROC) curve analysis. RESULTS: According to ROC curve analysis, the optimum sTILs and iTILs cut-off points (the number of positive cells per square millimeter of tissue) for patients with LABC patients with pCR (+) were 19 (area under the curve (AUC): 0.668, 95% confidence interval [CI] [0.501-0.835],P = 0.064) and 4 (AUC: 0.786, 95%CI [0.666-0.907],P = 0.002), respectively. Of the 62 patients, 26 had sTILs >19 and 25 had iTILs >4. The patients were divided into two according to percent of sTILs (sTILs >19 and sTILs ≤19 groups) and iTILs (iTILs >4 and iTILs ≤4 groups). Both sTILs >19 and iTILs >4 patients were associated with development higher pCR. While pCR was significantly higher in iTILs >4 patients (P = 0.002), it was not significantly in sTILs >19 patients (P = 0.107). CONCLUSIONS: There is significantly an association between pCR and increased number of intratumoral TILs (>4 cells/mm 2 of tissue) in BC who received NACT.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Linfocitos Infiltrantes de Tumor/inmunología , Terapia Neoadyuvante , Células del Estroma/inmunología , Microambiente Tumoral/inmunología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/inmunología , Quimioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Curva ROC , Estudios Retrospectivos , Células del Estroma/efectos de los fármacos , Células del Estroma/patología , Microambiente Tumoral/efectos de los fármacos
18.
J Orthop Trauma ; 32(8): 425-430, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29781943

RESUMEN

OBJECTIVES: We aimed to study the effects of repeated sterilization, using different methods, on the carbon fiber rods of external fixator systems. METHODS: We used a randomized set of 44 unused, unsterilized, and identical carbon fiber rods (11 × 200 mm), randomly assigned to 2 groups: unsterilized (4 rods) and sterilized (40 rods). The sterilized rods were divided into 2 groups, those sterilized in an autoclave and those sterilized using hydrogen peroxide. These were further divided into 5 subgroups based on the number of sterilization repetition to which the fibers were subjected (25, 50, 75, 100, and 200). A bending test was conducted to measure the maximum bending force, maximum deflection, flexural strength, maximum bending moment and bending rigidity. We also measured the surface roughness of the rods. RESULTS: An increase in the number of sterilization repetition led to a decrease in maximum bending force, maximum bending moment, flexural strength, and bending rigidity, but increased maximum deflection and surface roughness (P < 0.01). The effect of the number of sterilization repetition was more prominent in the hydrogen peroxide group. CONCLUSIONS: This study revealed that the sterilization method and number of sterilization repetition influence the strength of the carbon fiber rods. Increasing the number of sterilization repetition degrades the strength and roughness of the rods.


Asunto(s)
Fibra de Carbono , Fijadores Externos , Ensayo de Materiales/métodos , Prótesis e Implantes , Esterilización/métodos , Materiales Biocompatibles , Humanos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Estrés Mecánico
19.
Psychooncology ; 27(4): 1277-1283, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29466609

RESUMEN

OBJECTIVE: Research examining the relationship between metacognitions and cancer has only recently begun to emerge. This study attempted to compare the metacognitions of the patients with and without cancer. The effects of stage of cancer, type of cancer, and treatment modality (chemotherapy, radiotherapy, operation) on metacognitions were investigated. Patients with cancer were hypothesized to have higher levels of negative metacognitions. METHODS: Participants were patients with cancer (N = 279) and patients without cancer (control group, N = 212). The Metacognition Questionnaire-30 was administered to all participants. Results were analyzed according to demographic and histopathological characteristics of the patients. RESULTS: The results showed that patients with different cancer diagnoses scored higher than the controls on all subscales of the MCQ-30. Those who received chemotherapy scored the highest on the MCQ-30. The patients who were in early stages of cancer had higher levels of negative metacognitions. Patients who did not have operation but had chemotherapy had the highest levels of negative metacognitions. Patients who were in locally advanced stage, did not have operation but had received or was receiving chemotherapy had the highest levels of negative metacognitions. CONCLUSIONS: Patients who were in early stages of cancer appeared to be in greater need for psychological help and access to services. Findings indicated a need for psychological support for patients who undergo chemotherapy.


Asunto(s)
Ansiedad/psicología , Cognición/fisiología , Metacognición , Neoplasias/psicología , Adulto , Ansiedad/diagnóstico , Grupos Control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios
20.
Scott Med J ; 62(4): 156-158, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29226770

RESUMEN

Introduction Central venous catheterisation is an essential component of patient care in hospital. A forgotten complete guide-wire is a rare complication, although the reported incidence has increased rapidly over the last decade. Case report We report a 72-year-old man with a complete guide-wire inadvertently overlooked during catheter insertion. A central venous catheter had been inserted for total parental nutrition during treatment for pancreatitis. Five years later, the patient was readmitted with a painful lesion on his neck and the sensation of a sharp object under his skin. He was discharged without complication following removal of the free part of the guide-wire that had not become attached to the endothelial layer. Conclusion Inattention, inexperience and lack of supervision by a more experienced clinician are considered the most important contributing factors to this complication. Ultrasonography assistance during the procedure, senior supervision, a set count and a chest X-ray after the procedure are recommended in order to prevent forgotten guide-wires.


Asunto(s)
Cateterismo Venoso Central/efectos adversos , Competencia Clínica/normas , Cuerpos Extraños/diagnóstico por imagen , Adhesión a Directriz , Venas Yugulares/diagnóstico por imagen , Dolor de Cuello/diagnóstico por imagen , Anciano , Competencia Clínica/estadística & datos numéricos , Remoción de Dispositivos , Humanos , Enfermedad Iatrogénica , Masculino , Dolor de Cuello/cirugía , Guías de Práctica Clínica como Asunto , Radiografía Torácica
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