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1.
Laryngoscope ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727257

RESUMO

OBJECTIVE: To compare thyroid cancer incidence rates and trends between Korean, non-Korean Asian, and non-Hispanic White populations in the United States, and between the US Korean population and the South Korean population. METHOD: Population-based analysis of cancer incidence data. Cases of thyroid cancer diagnosed during 1999-2014 from the Korean Central Cancer Registry (KCCR) and the Surveillance, Epidemiology, and End Results (SEER) 9 detailed Asian/Pacific Islander subgroup incidence and population dataset were included. Incidence rates were obtained from the datasets, and annual percent change (APC) of the incidence rates was calculated using Joinpoint regression analysis. RESULTS: Thyroid cancer incidence rate for 1999-2014 was significantly higher for South Korea (48.05 [95% CI 47.89-48.22] per 100,000 person-years) than for the US Korean population (11.12 [95% CI 10.49-11.78] per 100,000 person-years), which was slightly higher than the Non-Korean Asian population (10.23 [95% CI 10.02-10.43] per 100,000 person-years), and slightly lower than the Non-Hispanic White population (12.78 [95% CI 12.69-12.87] per 100,000 person-years). Incidence rates in South Korea increased dramatically (average APC 17.9, 95% CI 16.0-19.9), significantly higher than the US Korean population (average APC 5.0, 95% CI 3.1-6.8), which was similar to the non-Korean Asian (average APC 2.5, 95% CI 0.9-4.2) and the non-Hispanic White (average APC 5.1, 95% CI 4.7-5.6) populations. CONCLUSIONS: South Korea's high thyroid cancer incidence rates cannot be attributed to genetic factors, but are likely due to health care system factors. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

2.
Chemistry ; 29(71): e202302548, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-37725661

RESUMO

Dye-dye conjugates have attracted significant interest for their utility in applications such as bioimaging, theranostics, and light-harvesting. Many classes of organic dyes have been employed in this regard; however, building blocks don't typically extend beyond small chromophores. This can lead to minor changes to the optoelectronic properties of the original dye. The exploration of dye-dye structures is impeded by long synthetic routes, incompatible synthetic conditions, or a mismatch of the desired properties. Here, we present the first-of-their-kind dye-dye conjugates of boron difluoride complexes of formazanate and dipyrromethene ligands. These conjugates exhibit dual photoluminescence bands that reach the near-infrared spectral region and implicate anti-Kasha processes. Cyclic voltammetry experiments revealed the generation of polyanionic species that can reversibly tolerate the uptake of up to 6 electrons. Ultimately, we demonstrate that BF2 formazanates can serve as a synthetically accessible platform to build upon new classes of dye-dye conjugates.

3.
Sci Rep ; 13(1): 12714, 2023 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-37543611

RESUMO

Neuroretinal rim (NRR) measurement can aid the diagnosis of glaucoma. A few studies reported that Cirrus optical coherence tomography (OCT) had NRR segmentation errors. The current study investigated segmentation success of NRR in myopic eyes using the Cirrus built-in software and to determine the number of acquisitions required to identify NRR thinning. Right eye of 87 healthy adult myopes had an optic disc scanned using Cirrus HD-OCT for five successive acquisitions. A masked examiner evaluated 36 radial line images of each scan to screen for segmentation errors using the built-in software at the Bruch's membrane opening (BMO) and/or internal limiting membrane (ILM). Participants with three accurate NRR acquisitions had their average NRR thickness determined. This result was compared with average of the two acquisitions and the first acquisition. Among 435 OCT scans of the optic disc (87 eyes × 5 acquisitions), 129 (29.7%) scans had segmentation errors that occurred mainly at the ILM. The inferior-temporal and superior meridians had slightly more segmentation errors than other meridians, independent of axial length, amount of myopia, or presence of peripapillary atrophy. Sixty-five eyes (74.7%) had at least three accurate NRR measurements. The three acquisitions had high reliability in NRR thickness in the four quadrants (intraclass correlation coefficient > 0.990, coefficient of variation < 3.9%). NRR difference between the first acquisition and the average of three acquisitions was small (mean difference 2 ± 13 µm, 95% limits of agreement within ± 30 µm) among the four quadrants. Segmentation errors in NRR measurements appeared regardless of axial length, amount of myopia, or presence of peripapillary atrophy. Cirrus segmentation lines should be manually inspected when measuring NRR thickness.


Assuntos
Miopia , Disco Óptico , Adulto , Humanos , Disco Óptico/diagnóstico por imagem , Disco Óptico/patologia , Tomografia de Coerência Óptica/métodos , Reprodutibilidade dos Testes , Pressão Intraocular , Células Ganglionares da Retina/patologia , Miopia/diagnóstico por imagem , Miopia/patologia , Atrofia/patologia
4.
FEMS Microbiol Lett ; 3702023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36764667

RESUMO

N-acyl homoserine lactones (N-HLs) are signaling molecules used by Gram-negative bacteria in a phenomenon called quorum sensing. Bacteria will detect N-HLs as a way of monitoring their population which, upon reaching a critical level, will express a specific phenotype. An example is the expression of bioluminescence by Vibrio fischeri. Most studies have not considered the chirality of these molecules nor have they used highly sensitive detection methods. Here, the production of d,l-N-HLs are monitored for V. fischeri, Burkholderia cepacia, Pseudomonas fluorescens, and P. putida, using highly sensitive tandem mass spectrometry analysis. Novel N-HLs are reported for both V. fischeri and B. cepacia, including a plethora of previously unknown d-N-HLs, including the first d-N-HLs containing oxo and hydroxy functionalities. Anomalously, N-HLs were not detected in any cultures of P. fluorescens and P. putida, which are species that previously were reported to produce N-HLs. However, it is apparent that differences in the reported occurrence and levels of N-HLs can result from (a) different strains of bacteria, (b) different growth media and environmental conditions, and (c) sometimes false-positive results from detection methodologies. Time studies of V. fischeri suggest the possibility that separate synthetic and elimination pathways exist between d- and l-N-HLs. Possible biological processes that could be the source of d-N-HL production are considered.


Assuntos
Aliivibrio fischeri , Burkholderia cepacia , Aliivibrio fischeri/química , Aliivibrio fischeri/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Percepção de Quorum , Burkholderia cepacia/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , 4-Butirolactona/metabolismo
5.
Int J Low Extrem Wounds ; 22(3): 503-508, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34096804

RESUMO

This study aimed to determine how the muscle mass of the lower leg affects the preservation of the lower extremities in patients with diabetic foot ulcer. This study analyzed patients with diabetic foot ulcer between January 2014 and June 2018 with a follow-up of at least 2 years. Of these 181 patients whose ulcer is located distal to the metatarsophalangeal joint, which was categorized as grade ≤2 by the Wagner classification were classified into 4 grades: grade 0 (treated without amputation), grade 1 (amputation distal to the metatarsophalangeal joint), grade 2 (Ray, transmetatarsal, Lisfranc, and Chopart amputation), and grade 3 (Syme, below-knee, and above-knee amputation) according to the final amputation degree. The muscles of the lower leg were classified into 4 compartments: anterior, lateral, deep posterior, and superficial posterior. The cross-sectional area and attenuation to estimate the muscle volume and density were measured at the axial image of computed tomography (CT) angiography. No significant differences were observed in the sex ratio and mean age among the grades (P = .966 and .962). The cross-sectional area of the anterior, lateral, and posterior compartments demonstrated no significant differences, but that of the superficial posterior compartment exhibited significant differences among the grades (P < .001). Moreover, the attenuation of the anterior, lateral, and deep posterior compartments showed no significant differences, but that of the posterior compartment showed significant differences among the grades (P = .003). The muscle mass of the superficial posterior compartment of the lower leg could be a good indicator of the preservation of the lower extremity in patients with diabetic foot ulcer. Therefore, a strengthening exercise for the triceps surae and plantaris muscles in the early stage could help preserve as much of the lower extremities as possible.


Assuntos
Diabetes Mellitus , Pé Diabético , Humanos , Pé Diabético/diagnóstico , Pé Diabético/cirurgia , Perna (Membro) , , Extremidade Inferior , Músculos
6.
Brain Behav Immun ; 108: 118-134, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36427808

RESUMO

Traumatic brain injury (TBI) leads to lasting brain dysfunction with chronic neuroinflammation typified by nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome activation in microglia. This study probed whether a single intranasal (IN) administration of human mesenchymal stem cell-derived extracellular vesicles (hMSC-EVs) naturally enriched with activated microglia-modulating miRNAs can avert chronic adverse outcomes of TBI. Small RNA sequencing confirmed the enrichment of miRNAs capable of modulating activated microglia in hMSC-EV cargo. IN administration of hMSC-EVs into adult mice ninety minutes after the induction of a unilateral controlled cortical impact injury resulted in their incorporation into neurons and microglia in both injured and contralateral hemispheres. A single higher dose hMSC-EV treatment also inhibited NLRP3 inflammasome activation after TBI, evidenced by reduced NLRP3, apoptosis-associated speck-like protein containing a CARD, activated caspase-1, interleukin-1 beta, and IL-18 levels in the injured brain. Such inhibition in the acute phase of TBI endured in the chronic phase, which could also be gleaned from diminished NLRP3 inflammasome activation in microglia of TBI mice receiving hMSC-EVs. Proteomic analysis and validation revealed that higher dose hMSC-EV treatment thwarted the chronic activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway by IL-18, which decreased the release of proinflammatory cytokines. Inhibition of the chronic activation of NLRP3-p38/MAPK signaling after TBI also prevented long-term cognitive and mood impairments. Notably, the animals receiving higher doses of hMSC-EVs after TBI displayed better cognitive and mood function in all behavioral tests than animals receiving the vehicle after TBI. A lower dose of hMSC-EV treatment also partially improved cognitive and mood function. Thus, an optimal IN dose of hMSC-EVs naturally enriched with activated microglia-modulating miRNAs can inhibit the chronic activation of NLRP3-p38/MAPK signaling after TBI and prevent lasting brain dysfunction.


Assuntos
Lesões Encefálicas Traumáticas , Vesículas Extracelulares , MicroRNAs , Proteína Quinase 14 Ativada por Mitógeno , Animais , Humanos , Camundongos , Encéfalo/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Vesículas Extracelulares/metabolismo , Inflamassomos/metabolismo , Interleucina-18/metabolismo , MicroRNAs/metabolismo , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteômica , Transdução de Sinais , Células-Tronco Mesenquimais
7.
IEEE J Transl Eng Health Med ; 10: 2100711, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304845

RESUMO

OBJECTIVE: A primary goal of acute stroke rehabilitation is to maximize functional recovery and help patients reintegrate safely in the home and community. However, not all patients have the same potential for recovery, making it difficult to set realistic therapy goals and to anticipate future needs for short- or long-term care. The objective of this study was to test the value of high-resolution data from wireless, wearable motion sensors to predict post-stroke ambulation function following inpatient stroke rehabilitation. METHOD: Supervised machine learning algorithms were trained to classify patients as either household or community ambulators at discharge based on information collected upon admission to the inpatient facility (N=33-35). Inertial measurement unit (IMU) sensor data recorded from the ankles and the pelvis during a brief walking bout at admission (10 meters, or 60 seconds walking) improved the prediction of discharge ambulation ability over a traditional prediction model based on patient demographics, clinical information, and performance on standardized clinical assessments. RESULTS: Models incorporating IMU data were more sensitive to patients who changed ambulation category, improving the recall of community ambulators at discharge from 85% to 89-93%. CONCLUSIONS: This approach demonstrates significant potential for the early prediction of post-rehabilitation walking outcomes in patients with stroke using small amounts of data from three wearable motion sensors. CLINICAL IMPACT: Accurately predicting a patient's functional recovery early in the rehabilitation process would transform our ability to design personalized care strategies in the clinic and beyond. This work contributes to the development of low-cost, clinically-implementable prognostic tools for data-driven stroke treatment.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Dispositivos Eletrônicos Vestíveis , Humanos , Pacientes Internados , Caminhada , Acidente Vascular Cerebral/complicações
9.
Sensors (Basel) ; 22(2)2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35062519

RESUMO

A graphene oxide (GO)-based cortisol biosensor was developed to accurately detect cortisol concentrations from sweat samples at point-of-care (POC) sites. A reference electrode, counter electrode, and working electrode make up the biosensor, and the working electrode was functionalized using multiple layers consisting of GO and antibodies, including Protein A, IgG, and anti-Cab. Sweat samples contact the anti-Cab antibodies to transport electrons to the electrode, resulting in an electrochemical current response. The sensor was tested at each additional functionalization layer and at cortisol concentrations between 0.1 and 150 ng/mL to determine how the current response differed. A potentiostat galvanostat device was used to measure and quantify the electrochemical response in the GO-based biosensor. In both tests, the electrochemical responses were reduced in magnitude with the addition of antibody layers and with increased cortisol concentrations. The proposed cortisol biosensor has increased accuracy with each additional functionalization layer, and the proposed device has the capability to accurately measure cortisol concentrations for diagnostic purposes.


Assuntos
Técnicas Biossensoriais , Grafite , Biomarcadores , Técnicas Eletroquímicas , Eletrodos
10.
J Endourol ; 36(1): 1-12, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210171

RESUMO

Background: With recent technological advancement, new and improved endoscopic instruments and laser devices have catapulted flexible ureteroscopy to the forefront, hence making retrograde intrarenal surgery (RIRS) a popular choice for the management of renal stones. However, RIRS has also resulted in an increasing number of work-related musculoskeletal disorders, which can have a detrimental impact on surgeons' physical health and operative lifespan. The aim of our review is to examine the impact and feasibility of ergonomic adjustments and outline future directions and recommendations to improve the awareness of and reduce the prevalence of musculoskeletal injuries among urologists. Methods: This study was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A thorough literature review was conducted of several databases using the following keywords and Medical Subject Headings (MeSH) terms to generate a search strategy: nephrolithiasis, kidney calculus, renal calculus, staghorn calculus, ergonomics, position, fatigue, comfort, tire, physical strain, visual strain, muscle, ureteroscopy, RIRS, laser, and lithotripsy. Studies were chosen for inclusion by reviewers independently, and the data were consolidated for analysis. Results: A total of 1446 articles were identified on initial literature search; 23 were included in the final analysis. The impact of various ergonomic modifications on operative outcomes, surgeons, surgical equipment, and patients, was analyzed. In addition, we summarized all the improvements that resulted in better ergonomics in RIRS. Conclusion: Ergonomics in RIRS is poorly understood and there are currently no formal guidelines for this aspect. While modern endourology armamentarium seems to help with procedural ergonomics, more needs to be done to enhance surgeon comfort, protect surgeon longevity, and prioritize the health and safety of endourologists.


Assuntos
Cálculos Renais , Litotripsia , Ergonomia , Humanos , Cálculos Renais/cirurgia , Litotripsia/métodos , Resultado do Tratamento , Ureteroscopia/métodos , Urologistas
11.
J Adv Pharm Technol Res ; 12(4): 373-377, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34820312

RESUMO

The present study evaluated the physicochemical characterization and cytotoxicity activity of chitosan and chito-oligosaccharides (COSs). The extraction of chitosan and COSs was executed by chemical hydrolysis. The physicochemical characterization and deacetylation (DA) value were determined using an FTIR. The molecular weight was determined by using the Mark-Houwink equation. The physical parameters such as solubility, water-binding capacity (WBC), and fat-binding capacity (FBC) were determination as per equation (i), (ii), and (iii) respectively. The cytotoxic activities of chitosan and COS against MCF-7, HepG2, HeLa-6, and 3T3 were performed by MTS assay. The COS induced enhance cytotoxicity with IC50 0.87 and2.21 mg/ml against MCF-7 and HepG2 respectively. However, COSs seem to be more sensitive toward the cell lines with the relative potential of MCF-7 > HepG2 > HeLa. Hence, the results showed promising future perspectives of chitosan and COS to develop biodegradable, antibacterial, cytotoxic naturally derived polysaccharides for cancer drug delivery and smart wound dressings.

12.
Obstet Gynecol Surv ; 76(8): 504-513, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34449853

RESUMO

IMPORTANCE: There is great concern about the impact of COVID-19 in pregnancy due to the high morbidity and mortality associated with prior coronavirus infections. OBJECTIVE: The objective of this review is to summarize the current literature on the impact of COVID-19 on pregnant women and their newborns. EVIDENCE ACQUISITION: The search terms COVID-19 and pregnancy were used in Medline and Clinical Key databases. Only articles written in English with outcome data on both mothers and their newborns were incorporated. RESULTS: Pregnant women generally experience COVID-19 as a mild-moderate illness. However, approximately 5% become critically ill. Women with underlying comorbidities seem more likely to experience severe morbidity. Newborns also generally have a favorable course. Vertical transmission in the intrauterine period is possible but rare. Infection control measures need to be taken to prevent transmission during the peripartum period. There is a paucity of data on infections in the first and second trimesters, but research from those infected in the third trimester indicates a possible link with preterm birth. There is a significant percentage of asymptomatic cases. Racial disparities are also being noted with disproportionate numbers of racial/ethnic minorities being affected. CONCLUSIONS: COVID-19 is generally experienced by pregnant women and their newborns as a mild to moderate illness, although a minority become critically ill and mortality does occur. This is more likely among those with underlying comorbidities, as in the general population. Asymptomatic cases heighten the need for increased testing and infection control measures. Racial disparities highlight underlying vulnerabilities and the need for increased research and policy changes.


Assuntos
COVID-19/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , SARS-CoV-2
13.
Proteomes ; 9(2)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200203

RESUMO

Hyperphosphorylation of the calcium release channel/ryanodine receptor type 2 (RyR2) at serine 2814 (S2814) is associated with multiple cardiac diseases including atrial fibrillation and heart failure. Despite recent advances, the molecular mechanisms driving pathological changes associated with RyR2 S2814 phosphorylation are still not well understood. Methods: Using affinity-purification coupled to mass spectrometry (AP-MS), we investigated the RyR2 interactome in ventricles from wild-type (WT) mice and two S2814 knock-in mutants: the unphosphorylated alanine mutant (S2814A) and hyperphosphorylated mimic aspartic acid mutant (S2814D). Western blots were used for validation. Results: In WT mouse ventricular lysates, we identified 22 proteins which were enriched with RyR2 pull-down relative to both IgG control and no antibody (beads-only) pull-downs. Parallel AP-MS using WT, S2814A, and S2814D mouse ventricles identified 72 proteins, with 20 being high confidence RyR2 interactors. Of these, 14 had an increase in their binding to RyR2 S2814A but a decrease in their binding to RyR2 S2814D. We independently validated three protein hits, Idh3b, Aifm1, and Cpt1b, as RyR2 interactors by western blots and showed that Aifm1 and Idh3b had significantly decreased binding to RyR2 S2814D compared to WT and S2814A, consistent with MS findings. Conclusion: By applying state-of-the-art proteomic approaches, we discovered a number of novel RyR2 interactors in the mouse heart. In addition, we found and defined specific alterations in the RyR2 interactome that were dependent on the phosphorylation status of RyR2 at S2814. These findings yield mechanistic insights into RyR2 regulation which may guide future drug designs.

14.
Thorac Cancer ; 12(15): 2143-2150, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34121347

RESUMO

BACKGROUND: Brain metastases frequently occur in patients with non-small cell lung cancer (NSCLC) resulting in a poor prognosis. Here, we investigated the association between PD-L1 expression and brain metastasis in patients with NSCLC and its clinical significance. METHODS: A total of 270 patients diagnosed with metastatic NSCLC who underwent PD-L1 testing on their tumor tissue between January 2017 and March 2019 were retrospectively reviewed. The VENTANA PD-L1 (SP263) assay was used, and positive PD-L1 expression was defined as staining in ≥1% of tumor cells. RESULTS: Positive PD-L1 expression was observed in 181 (67.0%) patients, and 74 (27.4%) patients had brain metastasis at diagnosis. Synchronous brain metastases were more frequently observed in PD-L1-positive compared with PD-L1-negative patients (31.5% vs. 19.1%, p = 0.045). Multiple logistic regression analysis identified positive PD-L1 expression (odds ratio [OR]: 2.24, p = 0.012) as an independent factor associated with synchronous brain metastasis, along with the histological subtype of nonsquamous cell carcinoma (OR: 2.84, p = 0.003). However, the incidence of central nervous system (CNS) progression was not associated with PD-L1 positivity, with a two-year cumulative CNS progression rate of 26.3% and 28.4% in PD-L1-positive and PD-L1-negative patients, respectively (log rank p = 0.944). Furthermore, positive PD-L1 expression did not affect CNS progression or overall survival in patients with synchronous brain metastasis (long rank p = 0.513 and 0.592, respectively). CONCLUSIONS: Initial brain metastases are common in NSCLC patients with positive PD-L1 expression. Further studies are necessary to understand the relationship between early brain metastasis and cancer immunity.


Assuntos
Antígeno B7-H1/metabolismo , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Eur J Cancer ; 151: 190-200, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34010788

RESUMO

BACKGROUND: Adding ovarian function suppression (OFS) after chemotherapy improves survival in young women with moderate- and high-risk breast cancer. Assessment of ovarian function restoration after chemotherapy becomes critical for subsequent endocrine treatment and addressing fertility issues. PATIENTS AND METHODS: In the adding OFS after chemotherapy trial, patients who resumed ovarian function up to 2 years after chemotherapy were randomised to receive either 5 years of tamoxifen or adding 2 years of OFS with tamoxifen. Ovarian function was evaluated from enrolment to randomisation, and patients who did not randomise because of amenorrhoea for 2 years received tamoxifen and were followed up for 5 years. Prospectively collected consecutive hormone levels (proportion of patients with premenopausal follicle-stimulating hormone [FSH] levels <30 mIU/mL and oestradiol [E2] levels ≥40 pg/mL) and history of menstruation were available for 1067 patients with breast cancer. RESULTS: Over 5 years of tamoxifen treatment, 69% of patients resumed menstruation and 98% and 74% of patients satisfied predefined ovarian function restoration as per serum FSH and E2 levels, respectively. Menstruation was restored in 91% of patients younger than 35 years at baseline, but in only 33% of 45-year-old patients over 5 years. Among these patients, 41% experienced menstruation restoration within 2 years after chemotherapy and 28% slowly restored menstruation after 2-5 years. Younger age (<35 years) at baseline, anthracycline without taxanes and ≤90 days of chemotherapy were predictors of menstruation restoration. CONCLUSIONS: During 5 years of tamoxifen treatment after chemotherapy, two-thirds of the patients experienced menstruation restoration, especially patients younger than 35 years. Young age, Adriamycin without taxanes and short duration of chemotherapy appeared to have a positive effect on ovarian reserves in the long term. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00912548.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Menstruação/efeitos dos fármacos , Ovário/efeitos dos fármacos , Pré-Menopausa , Tamoxifeno/uso terapêutico , Adulto , Fatores Etários , Antineoplásicos Hormonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores/sangue , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante Humano/sangue , Humanos , Menstruação/sangue , Pessoa de Meia-Idade , Ovário/metabolismo , Ovário/fisiopatologia , Recuperação de Função Fisiológica , República da Coreia , Medição de Risco , Fatores de Risco , Tamoxifeno/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Fam Med ; 53(2): 152, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33566353

Assuntos
Incerteza , Humanos
17.
Z Rheumatol ; 80(9): 889-898, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32970188

RESUMO

An assessment of the relative efficacy and tolerability of tofacitinib, baricitinib, upadacitinib, and filgotinib compared to those of methotrexate (MTX) was performed in disease-modifying antirheumatic drug (DMARD)-naive patients with rheumatoid arthritis (RA). We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) so as to examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib, and MTX in DMARD-naïve RA patients. Four RCTs comprising 2185 patients met the inclusion criteria. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg had the highest probability of achieving the American College of Rheumatology 20% (ACR20) response rate, followed by baricitinib 4 mg, tofacitinib 5 mg, filgotinib 200 mg, and MTX. Tofacitinib, baricitinib, upadacitinib, and filgotinib treatments achieved significantly higher ACR50 and ACR70 responses compared to MTX. Tofacitinib 5 mg had the highest probability of achieving the ACR50 and ACR70 response rates, followed by upadacitinib 15 mg, baricitinib 4 mg, filgotinib 200 mg, and MTX. The safety analysis based on serious adverse events, adverse events (AEs), and withdrawals due to AEs revealed no statistically significant differences between the respective intervention groups. In conclusion, tofacitinib, baricitinib, upadacitinib, and filgotinib were effective treatment options for DMARD-naïve RA patients, suggesting a difference in efficacy and safety among the different JAK inhibitors.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Azetidinas , Teorema de Bayes , Quimioterapia Combinada , Compostos Heterocíclicos com 3 Anéis , Humanos , Metotrexato/efeitos adversos , Piperidinas , Purinas , Pirazóis , Piridinas , Pirimidinas , Sulfonamidas , Resultado do Tratamento , Triazóis
18.
J Clin Invest ; 130(8): 4118-4132, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32597833

RESUMO

Lysosomal enzymes are synthesized in the endoplasmic reticulum (ER) and transferred to the Golgi complex by interaction with the Batten disease protein CLN8 (ceroid lipofuscinosis, neuronal, 8). Here we investigated the relationship of this pathway with CLN6, an ER-associated protein of unknown function that is defective in a different Batten disease subtype. Experiments focused on protein interaction and trafficking identified CLN6 as an obligate component of a CLN6-CLN8 complex (herein referred to as EGRESS: ER-to-Golgi relaying of enzymes of the lysosomal system), which recruits lysosomal enzymes at the ER to promote their Golgi transfer. Mutagenesis experiments showed that the second luminal loop of CLN6 is required for the interaction of CLN6 with the enzymes but dispensable for interaction with CLN8. In vitro and in vivo studies showed that CLN6 deficiency results in inefficient ER export of lysosomal enzymes and diminished levels of the enzymes at the lysosome. Mice lacking both CLN6 and CLN8 did not display aggravated pathology compared with the single deficiencies, indicating that the EGRESS complex works as a functional unit. These results identify CLN6 and the EGRESS complex as key players in lysosome biogenesis and shed light on the molecular etiology of Batten disease caused by defects in CLN6.


Assuntos
Retículo Endoplasmático/enzimologia , Complexo de Golgi/enzimologia , Lisossomos/enzimologia , Proteínas de Membrana/metabolismo , Complexos Multiproteicos/metabolismo , Animais , Retículo Endoplasmático/genética , Complexo de Golgi/genética , Lisossomos/genética , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Complexos Multiproteicos/genética , Lipofuscinoses Ceroides Neuronais/enzimologia , Lipofuscinoses Ceroides Neuronais/genética , Lipofuscinoses Ceroides Neuronais/patologia , Transporte Proteico/genética
19.
Lasers Surg Med ; 52(10): 928-934, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32350899

RESUMO

BACKGROUND AND OBJECTIVES: Combined sequential treatments with multiple modalities such as lasers and soft-tissue fillers are commonly required for the treatment of atrophic acne scars. Recently, fractional treatment with picosecond-domain lasers has proven to be effective for skin rejuvenation and scar treatment. However, little is known about the effects of picosecond-domain fractional laser treatment over hyaluronic acid fillers (HAFs). We aimed to evaluate the in vivo tissue responses to 1064 nm picosecond-domain fractional neodymium:yttrium-aluminum-garnet (Nd:YAG) laser treatments using microlens array (MLA) applied over pre-injected HAF in rats. In addition, we evaluated the efficacy and safety of this combined same-day treatment for atrophic acne scars in patients. STUDY DESIGN/MATERIALS AND METHODS: Sprague-Dawley rats were subjected to 1064 nm picosecond-domain fractional Nd:YAG laser treatment immediately after HAF dermal injection. Skin specimens were histologically evaluated on days 0, 7, and 21. In a clinical study, 36 patients with acne scars were treated concurrently with 1064 nm MLA-type picosecond lasers and HAFs. The patients were scheduled to receive two consecutive treatments at 4-week intervals, with a follow-up visit at 12 weeks after the final treatment. Acne scar photographs were graded using the Goodman and Baron's qualitative and quantitative scales at baseline and 12 weeks post-procedure. RESULTS: Picosecond-domain fractional laser treatment immediately after the dermal injection of HAF into rats did not cause any histological changes in the filler or surrounding skin. In a clinical study, treated subjects (n = 36) achieved significant improvement in acne scars and patient satisfaction. No serious adverse events were observed. CONCLUSIONS: Combined picosecond laser and HAF treatment were proven to be safe and effective based on in vivo and clinical study results. Facial rejuvenation and scar treatment using a picosecond-domain fractional laser may be performed immediately after HAF injection. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.


Assuntos
Acne Vulgar , Lasers de Estado Sólido , Acne Vulgar/complicações , Acne Vulgar/terapia , Animais , Cicatriz/etiologia , Cicatriz/terapia , Humanos , Ácido Hialurônico , Lasers de Estado Sólido/uso terapêutico , Ratos , Ratos Sprague-Dawley
20.
Neuropediatrics ; 51(5): 359-363, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32016944

RESUMO

Poland's syndrome (PS; OMIM 173800) is a rare congenital syndrome which consists of absence or hypoplasia of the pectoralis muscle. Other features can be variably associated, including rib defects. On the affected side other features (such as of breast and nipple anomalies, lack of subcutaneous tissue and skin annexes, hand anomalies, visceral, and vertebral malformation) have been variably documented. To date, association of PS with central nervous system malformation has been rarely reported remaining poorly understood and characterized. We report a left-sided PS patient carrying a de novo 1.5 Mb Xp22.31 duplication diagnosed in addiction to strabismus, optic nerves and chiasm hypoplasia, corpus callosum abnormalities, ectopic neurohypophysis, pyelic ectasia, and neurodevelopmental delay. Since, to our knowledge, this features' association has not been previously reported, we argue that this case may contribute to further widening of the variability of PS phenotype.


Assuntos
Cromossomos Humanos X/genética , Malformações do Sistema Nervoso/etiologia , Malformações do Sistema Nervoso/patologia , Síndrome de Poland/complicações , Síndrome de Poland/genética , Duplicação Cromossômica , Humanos
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