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1.
J Public Health (Oxf) ; 45(3): e510-e517, 2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-37122205

RESUMO

BACKGROUND: Considering the prolongation of the COVID-19 pandemic, the lack of studies on burnout, particularly in healthcare workers, needs to be addressed. This report aimed to identify the risk factors of burnout by comparing the level of burnout between nurses in general wards and those in COVID-19-dedicated wards in a national university hospital. METHODS: A survey based on the Korean version of Burnout Assessment Tool (BAT-K) was conducted on nurses between 10 January and 31 January 2022. The BAT-K consists of exhaustion, mental distance, cognitive impairment, emotional impairment and secondary symptoms. RESULTS: A total of 165 nurses, including 81 nurses from the COVID-19-dedicated ward, completed the questionnaire. The percentage of general-ward nurses with an emotional impairment score above the clinical cutoff was higher than that of COVID-19 ward nurses. General ward compared to the COVID-19 ward increased the risk of presenting with total-core symptoms. Two factors increased the risk regarding mental distance: short career length and underlying disease. CONCLUSIONS: In contrast to previous studies, the risk of burnout in the COVID-19-ward nurses was lower than that of the general ward nurses. The risk regarding mental distance was correlated with short career length and presence of an underlying disease.


Assuntos
Esgotamento Profissional , COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Pessoal de Saúde/psicologia , Hospitais Universitários , Inquéritos e Questionários
2.
Bone Joint J ; 105-B(2): 190-197, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36722060

RESUMO

AIMS: This study aimed to analyze the accuracy and errors associated with 3D-printed, patient-specific resection guides (3DP-PSRGs) used for bone tumour resection. METHODS: We retrospectively reviewed 29 bone tumour resections that used 3DP-PSRGs based on 3D CT and 3D MRI. We evaluated the resection amount errors and resection margin errors relative to the preoperative plans. Guide-fitting errors and guide distortion were evaluated intraoperatively and one month postoperatively, respectively. We categorized each of these error types into three grades (grade 1, < 1 mm; grade 2, 1 to 3 mm; and grade 3, > 3 mm) to evaluate the overall accuracy. RESULTS: The maximum resection amount error was 2 mm. Out of 29 resection amount errors, 15 (51.7%) were grade 1 errors and 14 (38.3%) were grade 2 errors. Complex resections were associated with higher-grade resection amount errors (p < 0.001). The actual resection margins correlated significantly with the planned margins; however, there were some discrepancies. The maximum guide-fitting error was 3 mm. There were 22 (75.9%), five (17.2%), and two (6.9%) grade 1, 2, and 3 guide-fitting errors, respectively. There was no significant association between complex resection and fitting error grades. The guide distortion after one month in all patients was rated as grade 1. CONCLUSION: In terms of the accurate resection amount according to the preoperative planning, 3DP-PSRGs can be a viable option for bone tumour resection. However, 3DP-PSRG use may be associated with resection margin length discrepancies relative to the planned margins. Such discrepancies should be considered when determining surgical margins. Therefore, a thorough evaluation of the preoperative imaging and surgical planning is still required, even if 3DP-PSRGs are to be used.Cite this article: Bone Joint J 2023;105-B(2):190-197.


Assuntos
Neoplasias Ósseas , Margens de Excisão , Humanos , Estudos Retrospectivos , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Impressão Tridimensional
3.
J Hand Surg Asian Pac Vol ; 27(4): 623-635, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35965369

RESUMO

Background: The treatment of complex transverse olecranon fractures (CTOFs), also known as olecranon fractures with the impacted articular fragments (IAF), was reported recently. We fix IAFs with absorbable pins supported by autologous bone graft followed by olecranon fracture fixation. We have used the arc centre distance (ACD) method to evaluate the congruency of this concentric hinge joint. The aim of this study is to present the outcomes of this fixation technique and evaluate the value of the ACD method. Methods: We reviewed 26 cases of CTOF treated at our hospital from 2014 to 2020. The functional outcome and range of motion of the elbow joint was measured by MEPS (Mayo Elbow Performance Score). We measured the ACD of each fragment of the ulnotrochlear joint [coronoid process (CP), IAF and olecranon process (OP)] with the CT image taken at 15 months postoperatively on average. Results: The mean arc of elbow motion was 3º to 132º. The mean MEPS at 1 year postoperatively was 94, and 25 of 26 cases (96%) achieved a good or excellent outcome. Twelve patients, who took the elbow CT at least more than 3 months post-operatively, were included for ACD measurement. The postoperative joint incongruency of each fragment was as follows, 0.39 ± 0.70, 0.40 ± 0.69 and 0.29 ± 0.72 mm (CP, IAF and OP, respectively) according to the ACD method. The ACD value for each fragment was significantly different before and after the surgery (p < 0.05). Conclusions: Accurate reduction of IAF with absorbable pins completed by tension band wiring with autogenous bone grafting can be an effective technique for CTOF with a large IAF. The restoration of the joint improved ACD. Level of Evidence: Level IV (Therapeutic).


Assuntos
Articulação do Cotovelo , Fraturas Ósseas , Olécrano , Fraturas da Ulna , Transplante Ósseo , Articulação do Cotovelo/diagnóstico por imagem , Articulação do Cotovelo/cirurgia , Humanos , Olécrano/diagnóstico por imagem , Olécrano/cirurgia , Resultado do Tratamento , Fraturas da Ulna/diagnóstico por imagem , Fraturas da Ulna/cirurgia
4.
Clin J Am Soc Nephrol ; 17(6): 827-834, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35383043

RESUMO

BACKGROUND AND OBJECTIVES: Total kidney volume is a validated prognostic biomarker for autosomal dominant polycystic kidney disease. Total kidney volume by magnetic resonance imaging (MRI) and manual segmentation is considered the "reference standard," but it is time consuming and not readily accessible. By contrast, three-dimensional (3D) ultrasound provides a promising technology for total kidney volume measurements with unknown potential. Here, we report a comparative study of total kidney volume measurements by 3D ultrasound versus the conventional methods by ultrasound ellipsoid and MRI ellipsoid. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This single-center prospective study included 142 patients who completed a standardized 3D ultrasound and MRI. Total kidney volumes by 3D ultrasound and ultrasound ellipsoid were compared with those by MRI. We assessed the agreement of total kidney volume measurements by Bland-Altman plots and misclassification of the Mayo Clinic imaging classes between the different imaging methods, and we assessed prediction of Mayo Clinic imaging classes 1C-1E by average ultrasound kidney length >16.5 cm. RESULTS: Compared with MRI manual segmentation, MRI ellipsoid, 3D ultrasound, and ultrasound ellipsoid underestimated total kidney volume (mean difference: -3%, -9%, and -11%, respectively), with Mayo Clinic imaging classes misclassified in 11%, 21%, and 22% of patients, respectively; most misclassified cases by MRI ellipsoid (11 of 16), 3D ultrasound (23 of 30), and ultrasound ellipsoid (26 of 31) were placed into a lower Mayo Clinic imaging class. Predictions of the high-risk Mayo Clinic imaging classes (1C-1E) by MRI ellipsoid, 3D ultrasound, and ultrasound ellipsoid all yielded high positive predictive value (96%, 95%, and 98%, respectively) and specificity (96%, 96%, and 99%, respectively). However, both negative predictive value (90%, 88%, and 95%, respectively) and sensitivity (88%, 85%, and 94%, respectively) were lower for 3D ultrasound and ultrasound ellipsoid compared with MRI ellipsoid. An average ultrasound kidney length >16.5 cm was highly predictive of Mayo Clinic imaging classes 1C-1E only in patients aged ≤45 years. CONCLUSIONS: Total kidney volume measurements in autosomal dominant polycystic kidney disease by 3D ultrasound and ultrasound ellipsoid displayed similar bias and variability and are less accurate than MRI ellipsoid. Prediction of high-risk Mayo Clinic imaging classes (1C-1E) by all three methods provides high positive predictive value, but ultrasound ellipsoid is simpler to use and more readily available.


Assuntos
Rim Policístico Autossômico Dominante , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Imageamento por Ressonância Magnética/métodos , Rim Policístico Autossômico Dominante/diagnóstico por imagem , Rim Policístico Autossômico Dominante/patologia , Estudos Prospectivos , Ultrassonografia
5.
Biotechnol Bioeng ; 119(1): 315-320, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34633065

RESUMO

In anoxic environments, microbial activation of alkanes for subsequent metabolism occurs most commonly through the addition of fumarate to a subterminal carbon, producing an alkylsuccinate. Alkylsuccinate synthases are complex, multi-subunit enzymes that utilize a catalytic glycyl radical and require a partner, activating enzyme for hydrogen abstraction. While many genes encoding putative alkylsuccinate synthases have been identified, primarily from nitrate- and sulfate-reducing bacteria, few have been characterized and none have been reported to be functionally expressed in a heterologous host. Here, we describe the functional expression of the (1-methylalkyl)succinate synthase (Mas) system from Azoarcus sp. strain HxN1 in recombinant Escherichia coli. Mass spectrometry confirms anaerobic biosynthesis of the expected products of fumarate addition to hexane, butane, and propane. Maximum production of (1-methylpentyl)succinate is observed when masC, masD, masE, masB, and masG are all present on the expression plasmid; omitting masC reduces production by 66% while omitting any other gene eliminates production. Meanwhile, deleting iscR (encoding the repressor of the E. coli iron-sulfur cluster operon) improves product titer, as does performing the biotransformation at reduced temperature (18°C), both suggesting alkylsuccinate biosynthesis is largely limited by functional expression of this enzyme system.


Assuntos
Alcanos/metabolismo , Escherichia coli , Engenharia Metabólica , Succinatos/metabolismo , Anaerobiose/genética , Azoarcus/enzimologia , Azoarcus/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Redes e Vias Metabólicas/genética
6.
Genet Sel Evol ; 52(1): 54, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993481

RESUMO

BACKGROUND: In this study, we assessed the accuracy of genomic prediction for carcass weight (CWT), marbling score (MS), eye muscle area (EMA) and back fat thickness (BFT) in Hanwoo cattle when using genomic best linear unbiased prediction (GBLUP), weighted GBLUP (wGBLUP), and a BayesR model. For these models, we investigated the potential gain from using pre-selected single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS) on imputed sequence data and from gene expression information. We used data on 13,717 animals with carcass phenotypes and imputed sequence genotypes that were split in an independent GWAS discovery set of varying size and a remaining set for validation of prediction. Expression data were used from a Hanwoo gene expression experiment based on 45 animals. RESULTS: Using a larger number of animals in the reference set increased the accuracy of genomic prediction whereas a larger independent GWAS discovery dataset improved identification of predictive SNPs. Using pre-selected SNPs from GWAS in GBLUP improved accuracy of prediction by 0.02 for EMA and up to 0.05 for BFT, CWT, and MS, compared to a 50 k standard SNP array that gave accuracies of 0.50, 0.47, 0.58, and 0.47, respectively. Accuracy of prediction of BFT and CWT increased when BayesR was applied with the 50 k SNP array (0.02 and 0.03, respectively) and was further improved by combining the 50 k array with the top-SNPs (0.06 and 0.04, respectively). By contrast, using BayesR resulted in limited improvement for EMA and MS. wGBLUP did not improve accuracy but increased prediction bias. Based on the RNA-seq experiment, we identified informative expression quantitative trait loci, which, when used in GBLUP, improved the accuracy of prediction slightly, i.e. between 0.01 and 0.02. SNPs that were located in genes, the expression of which was associated with differences in trait phenotype, did not contribute to a higher prediction accuracy. CONCLUSIONS: Our results show that, in Hanwoo beef cattle, when SNPs are pre-selected from GWAS on imputed sequence data, the accuracy of prediction improves only slightly whereas the contribution of SNPs that are selected based on gene expression is not significant. The benefit of statistical models to prioritize selected SNPs for estimating genomic breeding values is trait-specific and depends on the genetic architecture of each trait.


Assuntos
Cruzamento/métodos , Bovinos/genética , Estudo de Associação Genômica Ampla/métodos , Carne/normas , Animais , Cruzamento/normas , Bovinos/fisiologia , Perfilação da Expressão Gênica/métodos , Estudo de Associação Genômica Ampla/normas , Polimorfismo de Nucleotídeo Único , Sequenciamento Completo do Genoma/métodos
7.
Br J Ophthalmol ; 104(7): 980-984, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31662310

RESUMO

PURPOSE: To understand the added value of Bruch's membrane opening-minimum rim width (BMO-MRW) measurements to conventional circumpapillary retinal nerve fibre layer (cpRNFL) thickness measurements on optical coherence tomography (OCT) imaging for discriminating between perimetric glaucoma and healthy eyes, evaluated through a qualitative evaluation. METHODS: 384 healthy eyes and 188 glaucoma eyes were evaluated, and glaucoma eyes were categorised as perimetric (n=107) based on a history of ≥3 consecutive abnormal 24-2 visual field tests or suspected glaucoma if they did not (n=81). OCT-derived BMO-MRW and cpRNFL reports were qualitatively evaluated by two experienced graders in isolation at first, and then by using both reports combined. The diagnostic performance (sensitivity at 95% specificity, total and partial area under the receiver operating characteristic curve) of detecting perimetric glaucoma with each method were compared. RESULTS: All diagnostic performance measures for detecting perimetric glaucoma eyes were not significantly different when using either the cpRNFL or BMO-MRW reports alone compared with using both reports combined (p≥0.190), nor when comparing the use of each report in isolation (p≥0.500). CONCLUSIONS: Experienced graders exhibited no difference in discriminating between perimetric glaucoma and healthy eyes when using a cpRNFL report alone, the BMO-MRW report alone or the two reports combined. Therefore, either OCT imaging report of the neuroretinal tissue could be used effectively for detecting perimetric glaucoma, but further studies are needed to determine whether there are specific advantages of each method, or the combination of both, when evaluating eyes that have a greater degree of diagnostic uncertainty.


Assuntos
Lâmina Basilar da Corioide/patologia , Glaucoma de Ângulo Aberto/diagnóstico por imagem , Fibras Nervosas/patologia , Disco Óptico/patologia , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Microscopia com Lâmpada de Fenda , Testes de Campo Visual , Campos Visuais/fisiologia , Adulto Jovem
8.
Ophthalmol Glaucoma ; 2(3): 130-135, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850400

RESUMO

Purpose: To examine the utility of optical coherence tomography (OCT) for studying eyes with advanced glaucoma [i.e., eyes with a 24-2 visual field (VF) mean deviation (MD) worse than -15 dB], we tested the hypothesis that if these eyes had a 10-2 total deviation (TD) map with points better than -8 dB, then the topographically corresponding regions on the circumpapillary retinal nerve fiber layer (cpRNFL) should show a preserved region. Design: Evaluation of technology study. Participants: 39 eyes from 33 patients (mean: 68.8 ± 9.2 years) with a diagnosis of glaucoma had a 24-2 VF with a MD ≤ -15 dB (mean: -18.94 ± 2.95 dB). All eyes additionally had a 10-2 VF and an averaged OCT circle scan. Methods: Each scan was inspected, and preserved cpRNFL regions of the disc associated with the macula (central ±8° were delin eated. Main Outcome Measures: The number of eyes with preserved cpRNFL regions and their association with preserved VF locations (i.e. better than -8 dB) shown in the 10-2 VF TD map. Results: 38 of the 39 eyes had one or more points on the 10-2 VF with TD values that were better than -8 dB (mean: 25.7 ± 12.6 points). For all 39 eyes, there was a preserved portion of the cpRNFL on the circle scan within the disc region associated with the macula. However, for 3 of these eyes, this region was hypodense and could be a challenge for the clinician to identify. Conclusion: OCT scans can be used to assess and potentially follow the preserved regions of cpRNFL associated with the macula in eyes with advanced glaucoma if there is a preserved region on the 10-2 VF better than -8 dB.


Assuntos
Glaucoma/diagnóstico , Pressão Intraocular/fisiologia , Macula Lutea/patologia , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Campos Visuais/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Glaucoma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Disco Óptico/patologia , Índice de Gravidade de Doença , Testes de Campo Visual
9.
J Cell Biochem ; 120(2): 2532-2539, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30206979

RESUMO

Gastric cancer is the fourth most common cancer worldwide. Despite the high incidence of gastric cancer, efficient chemotherapy treatments still need to be developed. In this study, we examined the anticancer effects of endoplasmic reticulum (ER) stress inducer tunicamycin in gastric cancer. Previously, we found that overexpression of WLS1/GPR177 correlated with poor prognosis in patients with gastric cancer. Furthermore, tunicamycin treatment downregulated GPR177 expression in a dose-dependent manner. GPR177 transports WNT ligand from ER to the plasma membrane, mediating its secretion to the extracellular matrix. In gastric cancer cells, GPR177 preferentially localizes to the ER. Small interfering RNA-mediated knockdown of GPR177 leads to sensitization to ER stress and induces apoptosis of cancer cells along with tunicamycin treatment. GPR177 suppression promoted the ER stress-mediated proapoptotic pathway, such as PERK-CHOP cascade. Furthermore, fluorouracil treatment combined with tunicamycin dramatically reduced cancer cell proliferation. Efficacy of tunicamycin chemotherapy treatments depended on GPR177 expression in gastric cancer cell lines. Together, our results indicate that ER stress can potentiate anticancer effects and suggest GPR177 as a potential gastric cancer therapeutic target.

10.
ACS Med Chem Lett ; 8(6): 608-613, 2017 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-28626519

RESUMO

In our continued effort to discover and develop best-in-class Bruton's tyrosine kinase (Btk) inhibitors for the treatment of B-cell lymphomas, rheumatoid arthritis, and systemic lupus erythematosus, we devised a series of novel tricyclic compounds that improved upon the druglike properties of our previous chemical matter. Compounds exemplified by G-744 are highly potent, selective for Btk, metabolically stable, well tolerated, and efficacious in an animal model of arthritis.

11.
Diabetes Obes Metab ; 19(6): 892-896, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28058753

RESUMO

The aim of this study was to evaluate the effect of gemigliptin vs sitagliptin or glimepiride as initial combination therapy with metformin on glycaemic variability and to assess the correlation between glycaemic variability reduction and the dipeptidyl peptidase-4 (DPP-4) inhibition in patients with type 2 diabetes. This multicentre, randomized, active-controlled, open-label exploratory study included 69 patients with HbA1c > 7.5%. Subjects were randomized to receive gemigliptin 50 mg (n = 24), sitagliptin 100 mg (n = 23) or glimepiride 2 mg (n = 22) for 12 weeks. After 12 weeks, the change in mean amplitude of glycaemic excursion (MAGE) compared with baseline was significantly lower in the DPP-4 inhibitor groups compared with that in patients who received glimepiride. Furthermore, the standard deviation (SD) of glucose was significantly lower in patients who received gemigliptin than that in patients who received sitagliptin or glimepiride. The DPP-4 inhibition was significantly correlated with changes in MAGE and SD of glucose. In conclusion, gemigliptin and sitagliptin were more effective than glimepiride in reducing glycaemic variability as initial combination therapy with metformin in patients with type 2 diabetes, and the DPP-4 inhibition was associated with a reduction in glycaemic variability.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Piperidonas/administração & dosagem , Pirimidinas/administração & dosagem , Adulto , Idoso , Diabetes Mellitus Tipo 2/sangue , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Fosfato de Sitagliptina/administração & dosagem , Compostos de Sulfonilureia/administração & dosagem , Resultado do Tratamento , Adulto Jovem
13.
Bioorg Med Chem Lett ; 26(2): 575-579, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26675441

RESUMO

BTK inhibitor GDC-0834 (1) was found to be rapidly metabolized in human studies, resulting in a suspension of clinical trials. The primary route of metabolism was through cleavage of the acyclic amide bond connecting the terminal tetrahydrobenzothiophene with the central linker aryl ring. SAR studies were focused on reducing metabolic cleavage of this amide, and resulted in the identification of several central aryl linker substituents that conferred improved stability. The most promising substituted aryl linkers were then incorporated into an optimized pyridazinone scaffold, resulting in the identification of lead analog 23, possessing improved potency, metabolic stability and preclinical properties.


Assuntos
Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Piridazinas/química , Piridazinas/farmacologia , Pirimidinonas/química , Pirimidinonas/farmacologia , Tiofenos/química , Tiofenos/farmacologia , Tirosina Quinase da Agamaglobulinemia , Animais , Cães , Humanos , Camundongos , Microssomos Hepáticos/metabolismo , Modelos Moleculares , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacocinética , Proteínas Tirosina Quinases/metabolismo , Piridazinas/metabolismo , Piridazinas/farmacocinética , Pirimidinonas/metabolismo , Pirimidinonas/farmacocinética , Ratos , Tiofenos/metabolismo , Tiofenos/farmacocinética
14.
BMC Evol Biol ; 15: 284, 2015 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-26677975

RESUMO

BACKGROUND: The main cattle breed in Korea is the brown Hanwoo, which has been under artificial selection within a national breeding program for several decades. Varieties of the Hanwoo known as Jeju Black and Chikso were not included in the breeding program and remained isolated from the effects of recent artificial selection advancements. We analysed the Jeju Black and Chikso populations in regards to their genetic variability, state of inbreeding, as well as level of differentiation from the mainland Hanwoo population. RESULTS: Jeju Black and Chikso were found to have small estimated effective population sizes (N e ) of only 11 and 7, respectively. Despite a small N e , higher than expected heterozygosity levels were observed (0.303 and 0.306), however, lower allelic richness was found for the two island populations (1.76 and 1.77) compared to the mainland population (1.81). The increase in heterozygosity could be due to environmental disease challenges that promoted maintenance of higher genetic variability; however, no direct proof exists. Increased heterozygosity due to a first generation crossing of genetically different populations is not recorded. The differentiation between the Korean populations had F ST values between 0.014 and 0.036 which is not as high as the differentiation within European beef or dairy cattle breeds (0.047-0.111). This suggests that the three populations have not separated into independent breeds. CONCLUSION: Results agree with an island model of speciation where the brown Hanwoo represents the ancestral breed, whilst the Jeju Black and Chikso diverge from this common ancestor, following different evolutionary trajectories. Nevertheless, differences are minor and whether Jeju Black and Chikso cattle will develop into discrete breeds or reintegrate with the main population has to be seen in the future and will largely depend on human management decisions. This offers a rare opportunity to accompany the development of new breeds but also poses challenges on how to preserve these incipient breeds and ensure their long term viability.


Assuntos
Bovinos/genética , Variação Genética , Modelos Genéticos , Animais , Cruzamento , Bovinos/classificação , Genética Populacional , Endogamia , Ilhas , República da Coreia
15.
Biosens Bioelectron ; 73: 114-122, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26057732

RESUMO

We report results of the studies relating to the fabrication of a paper based sensor comprising of poly (3,4-ethylenedioxythiophene):poly(styrenesulfonate) ( PEDOT: PSS) and reduced graphene oxide (RGO) composite. The effect of various solvents like methanol, ethylene glycol and H2SO4 on the electrical conductivity of PEDOT: PSS coated Whatman paper has been investigated. The conductivity of this solution processed conducting paper significantly increases from ~1.16×10(-4) S cm(-1) up to ~3.57×10(-2) S cm(-1) (~300 times) on treatment with ethylene glycol. The observed significant increase in electrical conductivity is due to conformational rearrangement in the polymer and is due to strong non-covalent cooperative interaction between PEDOT and the cellulose molecules. Further, incorporation of RGO into the conducting paper results in improved electrochemical performance and signal stability. This paper electrode is a promising alternative over the expensive conventional electrodes (ITO, gold and glassy carbon), that are known to have limited application in smart point-of-care (POC) devices. This low cost, flexible and environment friendly conducting paper based biosensor utilized for cancer biomarker (carcinoembryonic antigen, CEA) detection reveals high sensitivity of 25.8 µA ng(-1) mL cm(-2) in the physiological range, 1-10 ng mL(-1).


Assuntos
Técnicas Biossensoriais/instrumentação , Grafite , Neoplasias/diagnóstico , Papel , Antígeno Carcinoembrionário/sangue , Condutividade Elétrica , Desenho de Equipamento , Grafite/química , Humanos , Neoplasias/sangue , Sistemas Automatizados de Assistência Junto ao Leito , Poliestirenos/química , Tiofenos/química
17.
J Invest Dermatol ; 135(9): 2219-2227, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25880702

RESUMO

Protease-activated receptor-2 (PAR-2) functions as innate biosensor for proteases and regulates numerous functions of the skin. However, the expression and physiological role of PAR-2 in sebocytes remain to be elucidated. Here, we identified PAR-2 expression in SZ95 sebocytes at both mRNA and protein levels. Intracellular Ca(2+) mobilization by PAR-2 agonist peptide (PAR-2 AP) or Propionibacterium acnes (P. acnes) culture supernatant was detected, indicating that P. acnes is a potent activator of PAR-2 on sebocytes. The small interfering RNA (siRNA)-mediated PAR-2 knockdown in sebocytes resulted in defective differentiation and lipogenesis. PAR-2 AP treatment enhanced lipogenesis and sterol response element-binding protein-1 (SREBP-1) expression, suggesting a role of PAR-2 in the differentiation and lipogenesis of sebocytes. Moreover, PAR-2 AP induced cytokines and human ß-defensin-2 (hBD-2) transcription in sebocytes. PAR-2 expression was increased in sebaceous glands of acne lesions. PAR-2 silencing by siRNA abrogated the increase in sebaceous lipogenesis and SREBP-1 expression by P. acnes supernatant. PAR-2 knockdown also inhibited the P. acnes supernatant-induced expression of cytokines and hBD-2. In conclusion, PAR-2 is expressed in SZ95 sebocytes and mediates differentiation, lipogenesis, inflammation, and innate immunity in response to P. acnes. Therefore, PAR-2 might be a therapeutic target for sebaceous gland disorders such as acne.


Assuntos
Acne Vulgar/imunologia , Imunidade Inata/genética , Inflamação/genética , Lipogênese/genética , Receptor PAR-2/genética , Glândulas Sebáceas/citologia , Glândulas Sebáceas/metabolismo , Acne Vulgar/microbiologia , Biópsia por Agulha , Células Cultivadas , Regulação da Expressão Gênica , Humanos , Imunidade Inata/fisiologia , Imuno-Histoquímica , Inflamação/imunologia , Lipogênese/imunologia , Propionibacterium acnes/imunologia , RNA Interferente Pequeno/análise , Sensibilidade e Especificidade , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
18.
Bioorg Med Chem Lett ; 25(6): 1333-7, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25701252

RESUMO

SAR studies focused on improving the pharmacokinetic (PK) properties of the previously reported potent and selective Btk inhibitor CGI-1746 (1) resulted in the clinical candidate GDC-0834 (2), which retained the potency and selectivity of CGI-1746, but with much improved PK in preclinical animal models. Structure based design efforts drove this work as modifications to 1 were investigated at both the solvent exposed region as well as 'H3 binding pocket'. However, in vitro metabolic evaluation of 2 revealed a non CYP-mediated metabolic process that was more prevalent in human than preclinical species (mouse, rat, dog, cyno), leading to a high-level of uncertainly in predicting human pharmacokinetics. Due to its promising potency, selectivity, and preclinical efficacy, a single dose IND was filed and 2 was taken in to a single dose phase I trial in healthy volunteers to quickly evaluate the human pharmacokinetics. In human, 2 was found to be highly labile at the exo-cyclic amide bond that links the tetrahydrobenzothiophene moiety to the central aniline ring, resulting in insufficient parent drug exposure. This information informed the back-up program and discovery of improved inhibitors.


Assuntos
Inibidores de Proteínas Quinases/química , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinonas/química , Tiofenos/química , Tirosina Quinase da Agamaglobulinemia , Animais , Benzamidas/química , Benzamidas/metabolismo , Sítios de Ligação , Compostos Bicíclicos Heterocíclicos com Pontes/química , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Cristalografia por Raios X , Cães , Meia-Vida , Humanos , Camundongos , Microssomos Hepáticos/metabolismo , Simulação de Dinâmica Molecular , Ligação Proteica , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacocinética , Estrutura Terciária de Proteína , Proteínas Tirosina Quinases/metabolismo , Pirimidinonas/síntese química , Pirimidinonas/farmacocinética , Ratos , Relação Estrutura-Atividade , Tiofenos/síntese química , Tiofenos/farmacocinética
19.
Int J Dermatol ; 51(6): 733-41, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22607296

RESUMO

BACKGROUND: Retinoids have been used for the treatment of skin disorders such as acne, psoriasis, and photoaging. However, despite their beneficial effects, topical retinoids often cause severe local irritation called retinoid dermatitis. We previously developed a novel vitamin A derivative, retinyl retinoate, which induces less irritation and affords excellent tolerance. In this study, we examined whether co-treatment with topical peroxisome proliferator-activated receptor-α (PPARα) agonists (e.g. WY14643) reduce retinoid dermatitis in hairless mouse skin. METHODS: The effect of concomitant treatment with a PPARα agonist on retinoid dermatitis in hairless mouse epidermis was evaluated by measuring transepidermal water loss, epidermal histology, and cytokine expression. RESULTS: Retinyl retinoate induced less severe retinoid dermatitis than retinoic acid. Topical application of a PPARα agonist improved the stratum corneum structure and function, reduced mRNA expression of interleukin (IL)-1α, tumor necrosis factor-α and IL-8, and inhibited ear edema induced by retinoic acid or retinyl retinoate. CONCLUSIONS: Our results indicate that PPARα agonists can potentially be used to improve retinoid dermatitis. We suggest that co-treatment with retinyl retinoate and a PPARα agonist may reduce or prevent detrimental alterations in retinoid-treated skin.


Assuntos
Dermatite/tratamento farmacológico , PPAR alfa/agonistas , Retinoides/efeitos adversos , Tretinoína/efeitos adversos , Administração Tópica , Animais , Diferenciação Celular , Proliferação de Células , Dermatite/patologia , Inibidores Enzimáticos/farmacologia , Epiderme/patologia , Feminino , Interleucina-1alfa/genética , Interleucina-1alfa/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Ceratolíticos/efeitos adversos , Receptores X do Fígado , Camundongos , Camundongos Pelados , Receptores Nucleares Órfãos/agonistas , Ácido Palmítico/farmacologia , Pirimidinas/farmacologia , RNA Mensageiro/metabolismo , Ésteres de Retinil , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Perda Insensível de Água
20.
J Sleep Res ; 21(5): 569-76, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22463600

RESUMO

This study aimed to explore the association between restless legs syndrome and irritable bowel syndrome in an epidemiological cohort. We included 3365 adults, of whom 1602 were female (age 52.5 ± 7.5 years), who had participated in the Korean Genome and Epidemiology Study (2005-2006). The diagnosis of restless legs syndrome was based on the criteria proposed by the International Restless Legs Syndrome Study Group, and irritable bowel syndrome was defined according to the Rome II criteria. The prevalence of each condition was determined and their association was tested by logistic regression analysis. Age, sex, haemoglobin concentration, renal insufficiency, use of medications and depressive mood were all adjusted for. The prevalence of restless legs syndrome and irritable bowel syndrome was 4.5 and 11.1%, respectively. Irritable bowel syndrome was more prevalent in the group with restless legs syndrome (24.0 versus 10.5%, P < 0.001). Subjects with restless legs syndrome were older (54.2 ± 8.4 versus 52.4 ± 7.4, P = 0.006) and more depressive (26.7 versus 12.5%, P < 0.001), and were predominantly female (57.3 versus 47.2%, P = 0.015), had more frequent insomnia symptoms (44.0 versus 28.2%, P < 0.001), had lower haemoglobin concentration (13.7 ± 1.5 versus 14.1 ± 1.6 g dL(-1) P = 0.004) and higher highly sensitive C-reactive protein (1.8 ± 5.1 versus 1.4 ± 2.9 mg dL(-1), P = 0.08). The adjusted odds ratio of restless legs syndrome in relation to irritable bowel syndrome was 2.59 (1.74-3.85, P < 0.001). Irritable bowel syndrome appeared to be associated with restless legs syndrome independently from other major risk factors for restless legs syndrome. Searching for the mechanisms underlying this association is indicated.


Assuntos
Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/epidemiologia , Síndrome das Pernas Inquietas/complicações , Síndrome das Pernas Inquietas/epidemiologia , Adulto , Afeto , Distribuição por Idade , Idoso , Proteína C-Reativa/análise , Doenças Cardiovasculares/complicações , Estudos de Coortes , Depressão/complicações , Depressão/fisiopatologia , Feminino , Hemoglobinas/análise , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , República da Coreia/epidemiologia , Síndrome das Pernas Inquietas/fisiopatologia , Fatores de Risco , Distribuição por Sexo , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/fisiopatologia
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