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1.
Cells ; 8(11)2019 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-31731497

RESUMO

Androgens are not only essential for bone development but for the maintenance of bone mass. Therefore, conditions with androgen deficiency, such as male hypogonadism, androgen-insensitive syndromes, and prostate cancer with androgen deprivation therapy are strongly associated with bone loss and increased fracture risk. Here we summarize the skeletal effects of androgens-androgen receptors (AR) actions based on in vitro and in vivo studies from animals and humans, and discuss bone loss due to androgens/AR deficiency to clarify the molecular basis for the anabolic action of androgens and AR in bone homeostasis and unravel the functions of androgen/AR signaling in healthy and disease states. Moreover, we provide evidence for the skeletal benefits of androgen therapy and elucidate why androgens are more beneficial than male sexual hormones, highlighting their therapeutic potential as osteoanabolic steroids in improving bone fracture repair. Finally, the application of selective androgen receptor modulators may provide new approaches for the treatment of osteoporosis and fractures as well as building stronger bones in diseases dependent on androgens/AR status.

2.
BMJ Open ; 9(11): e032779, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740474

RESUMO

OBJECTIVES: To detect the combined effects of lifestyle factors on work-related burnout (WB) and to analyse the impact of the number of weekend catch-up sleep hours on burnout risk in a medical workplace. DESIGN: Cross-sectional study. SETTING: Hospital-based survey in Taiwan. PARTICIPANTS: In total, 2746 participants completed the hospital's Overload Health Control System questionnaire for the period from the first day of January 2016 to the end of December 2016, with a response rate of 70.5%. The voluntary participants included 358 physicians, 1406 nurses, 367 medical technicians and 615 administrative staff. PRIMARY AND SECONDARY OUTCOME MEASURES: All factors that correlated significantly with WB were entered into a multinomial logistic regression after adjustment for other factors. The dose-response relationship of combined lifestyle factors and catch-up sleep hours associated with WB was explored by logistic regression. RESULTS: Abnormal meal time (adjusted OR 2.41, 95% CI 1.85 to 3.15), frequently eating out (adjusted OR 1.49, 95% CI 1.12 to 1.97), lack of sleep (adjusted OR 5.13, 95% CI 3.94 to 6.69), no exercise (adjusted OR 1.41, 95% CI 1.10 to 1.81) and >40 work hours (adjusted OR 2.72, 95% CI 2.08-3.57) were independently associated with WB (for high level compared with low level). As the number of risk factors increased (1-5), so did the proportion of high severity of WB (adjusted OR 1.39, 95% CI 0.45 to 4.27, to adjusted OR 32.98, 95% CI 10.78 to 100.87). For those with more than 7 hours' sleep on workdays, weekend catch-up sleep (≤0/>0 and ≤2/>2 hours) was found to be related to an increase of burnout risk (adjusted OR 4.91, 95% CI 2.24 to 10.75/adjusted OR 4.94, 95% CI 2.54 to 9.63/adjusted OR 6.74, 95% CI 2.94 to 15.46). CONCLUSION: WB in the medical workplace was affected by five unhealthy lifestyle factors, and combinations of these factors were associated with greater severity of WB. Weekend catch-up sleep was correlated with lower burnout risk in those with a short workday sleep duration (less than 7 hours). Clinicians should pay particular attention to medical staff with short sleep duration without weekend catch-up sleep.

5.
Int J Mol Sci ; 19(9)2018 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-30150594

RESUMO

Previous studies have suggested that cancer stem cells (CSCs) resisted radiotherapy and chemotherapy. P16INK4A is a biomarker for cervical carcinogenesis and reduces proliferation of stem cells. We aimed to investigate the expression and clinical significance of cyclin-dependent kinase inhibitor 2A (P16INK4A), sex determining region Y-box 2 (SOX2), and Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1) in cervical cancer treated with radiotherapy and cervical cell line models. The expressions of P16INK4A, SOX2, and ALDH1A1 were performed by immunohistochemical staining of tumor samples from 139 cervical cancer patients with International Federation of Gynecology and Obstetrics stages Ib to IV. The staining showed high expression in 100, 107, and 13 patients with P16INK4A (>80%), SOX2 (≥10%), and ALDH1A1 (50%), respectively. The high-P16INK4A group had a higher five-year overall survival (OS) rate and disease-free survival (DFS) than the low-P16INK4A group (OS: 62.0% and 35.2%, p = 0.016; DFS: 60.0% and 31.2%, p = 0.002). The low-P16INK4A/high-SOX2 and low-P16INK4A/high-ALDH1A1 groups had a worse five-year OS and DFS rate than the high-P16INK4A/low-SOX2 and high-P16INK4A/low-ALDH1A1 groups, respectively. Depletion of P16INK4A promoted chemoresistance and radioresistance of cervical cancer cells increased the expression of SOX2 and ALDH1A1 and exhibited higher self-renewal ability. These results suggest that lower P16INK4A expression associated with higher CSC markers predicts poor prognostic outcomes and is a promising target in patients with cervical cancer.


Assuntos
Biomarcadores Tumorais/biossíntese , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Células-Tronco Neoplásicas/efeitos da radiação , Neoplasias do Colo do Útero/radioterapia , Aldeído Desidrogenase/biossíntese , Aldeído Desidrogenase/genética , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Inibidor p16 de Quinase Dependente de Ciclina/genética , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Prognóstico , Retinal Desidrogenase , Fatores de Transcrição SOXB1/biossíntese , Fatores de Transcrição SOXB1/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo
6.
PLoS One ; 13(3): e0193783, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29499067

RESUMO

BACKGROUND: Idiopathic Parkinson's disease (IPD) is a progressive neurodegenerative disorder characterized by typical motor impairment. However, lower urinary tract symptoms, including urinary urgency or frequency, which are non-motor phenomena, occur frequently among patients with IPD. In this study, we assess the risk of overactive bladder (OAB) in patients with IPD. METHODS: The National Health Insurance Research Database of Taiwan was used to identify patients with IPD (IPD cohort) and four-fold controls (non-IPD cohort) from 2000 to 2010. The non-IPD cohort was matched according to age, sex, and baseline comorbidities, including benign prostate hyperplasia, stress incontinence, diabetes, and cerebrovascular diseases. The occurrence of OAB was monitored until the end of 2011. Hazard ratios of OAB were estimated using Cox proportional hazards regression models. RESULTS: In total, 4,571 and 18,255 patients were included in IPD and non-IPD cohorts, respectively. Results showed a significantly higher overall incidence rate of OAB in the IPD cohort compared with the non-IPD cohort (14.5 vs. 6.37 per 10,000 person-years), with a 2.3-fold increased risk of OAB (95% confidence interval [CI] = 1.51-3.51) after controlling for benign prostate hyperplasia and stress incontinence. The mean follow-up period for the IPD cohort was 5.0 years. This cohort study showed that the cumulative incidence of OAB was 0.65% at the fifth year and 1.54% at the tenth year after IPD diagnosis; this risk was highest in the age group 65-74 years. CONCLUSION: This study reveals that IPD is independently associated with an increased risk of OAB in patients with IPD. The probability of OAB was 1.54% over a 10-year period after IPD diagnosis; the risk of OAB is considered to be age-dependent and most substantial in patients aged 65-74 years.


Assuntos
Doença de Parkinson/epidemiologia , Bexiga Urinária Hiperativa/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
8.
Int J Dermatol ; 56(6): 623-629, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28295235

RESUMO

BACKGROUND: Deep cutaneous fungal infections, including subcutaneous mycoses and systemic fungal infection with cutaneous involvement, cause significant morbidity and mortality in light of increasing immunocompromised patients and global warming. Although a few studies reviewed deep fungal infections in temperate regions, a relevant study in tropical regions is lacking. We evaluated features of deep cutaneous fungal infections in southern Taiwan among the tropical regions. METHODS: We retrospectively reviewed all histopathological specimens with deep cutaneous fungal infections in a single referral center from 2001 to 2014 and successfully identified 23 cases. Medical chart review revealed patient demographic data, clinical presentation, underlying disease, microbiological culture reports, and treatment outcomes. RESULTS: The average patient age was 52 years. Fourteen cases had primary subcutaneous mycoses, and nine had systemic mycoses. Fifteen patients were immunocompromised, including hematological malignancies. Acquired immune deficiency syndrome (AIDS) and long-term steroid use were most commonly associated with deep fungal infections. The positive culture growth rate was 63%. Fonsecaea sp. was most frequently identified by tissue culture. Aspergillosis, mucormycosis, and disseminated cryptococcosis were particularly fatal. CONCLUSIONS: Diabetes and long-term steroid use appear as major risk factors for advanced mycoses in this region. Rapid diagnosis with skin biopsy and tissue culture along with appropriate treatment of deep cutaneous fungal infection are necessary.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Corticosteroides/uso terapêutico , Dermatomicoses/microbiologia , Complicações do Diabetes/complicações , Hospedeiro Imunocomprometido , Antifúngicos/uso terapêutico , Ascomicetos , Aspergilose/complicações , Criptococose/complicações , Dermatomicoses/tratamento farmacológico , Dermatomicoses/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucormicose/complicações , Estudos Retrospectivos , Fatores de Risco , Tela Subcutânea/microbiologia , Taiwan , Resultado do Tratamento , Clima Tropical
9.
Biomed Res Int ; 2016: 7682917, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27652267

RESUMO

Background. In Asians, most basal cell carcinomas (BCCs) are pigmented with clear borders. The consensus of 4 mm surgical margin for BCC largely depends on studies in nonpigmented BCCs in Caucasians. However, little is known about recurrences of pigmented BCCs with a narrower surgical margin. We aimed to investigate 5-year recurrence of BCCs, either pigmented or nonpigmented, in Taiwanese with 3 mm surgical margin. Materials and Methods. 143 patients with BCC (M/F = 66/77, average 64 years) were confirmed pathologically from 2002 to 2013. Based on the pathological margin (>1 mm, ≤1 mm, and involved), patients were categorized into the complete excision group (n = 77), histology with close proximity group (n = 43), and unclear surgical margin group (n = 23). Results. Among 143 cases, 105 were pigmented. With standard 3 mm excision, there were 7 recurrences, with 6 of them from nonpigmented BCC group. Logistic regression showed that pigmentation was associated with lower recurrence. Interestingly, 5-year recurrence of completely excised and histology with close proximity BCC (0/77 versus 1/43) was not different statistically. Conclusions. A 3 mm surgical margin is adequate for pigmented BCC. A "wait and see" approach rather than further wide excision is appropriate for BCC with <1 mm free margin.


Assuntos
Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Idoso , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Carcinoma Basocelular/diagnóstico por imagem , Carcinoma Basocelular/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia
10.
Oncotarget ; 7(28): 44047-44061, 2016 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-27317767

RESUMO

Although radiation therapy was known to be effective to cervical cancer, loco-regional recurrences are frequently found in patients. We aimed to identify a molecular marker predicting the response of cervical cancer to radiotherapy. We included the patients (n = 149) with cervical cancer who had undergone radiotherapy from 2004 to 2006. Tumor samples were collected to examine the association between the expression of S-phase kinase-associated protein 2 (SKP2) and prognosis in cervical cancer. We found higher expression of SKP2 associated with recurrence (HRs: 2.52, p < 0.001), death (HRs: 2.01, p < 0.001) and higher locoregional recurrence rate (HRs: 3.76, p < 0.001). Cervical cancer cell lines with higher expression of SKP2 showed higher colony formation, cell survival rate and fewer DNA damages after irradiation. SKP2-C25, an inhibitor for SKP2 activity, dose-dependently decreased cell viability after irradiation and knockdown of SKP2 impaired DNA-damage response and sensitized the cervical cancer cells to irradiation. Our data showed the SKP2 represents a promising tool to identify patients with cervical cancer who have a higher risk of locoregional recurrence after radiotherapy. Targeting SKP2 may serve as a potential radiosensitizer for developing effective therapeutic strategies against cervical cancer.


Assuntos
Dano ao DNA , Proteínas Quinases Associadas a Fase S/biossíntese , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/radioterapia , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Sobrevivência Celular/efeitos da radiação , Reparo do DNA , Feminino , Células HeLa , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Interferência de RNA , Proteínas Quinases Associadas a Fase S/genética , Transdução de Sinais/genética , Neoplasias do Colo do Útero/genética
11.
Biomed Res Int ; 2014: 504279, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24678508

RESUMO

Acne is a common disease in adolescence with female preponderance. It could cause poor self-esteem and social phobia. Previous studies based on questionnaires from several thousands of adolescents showed that acne is associated with major depression and suicide. However, the gender- and age-specific risk of depression and suicide in patients with acne remain largely unknown. Using a database from the National Health Insurance, which included 98% of the population of Taiwan in 2006, we identified patients of acne, major depression, and suicide based on ICD-9-CM codes. Totally 47111 patients with acne were identified (16568 males and 30543 females) from 1 million subjects. The youths of 7-12 years had the highest prevalence of acne (14.39%). Major depression was more common in those with acne (0.77%) than controls (0.56% , P < 0.0001) regardless of gender. Multiple logistic regression showed an increased risk of major depression in women without acne (OR = 1.85, 95% CI 1.75-1.96). The risk is additive in women with acne (OR = 2.78, 95% CI 2.43-3.17). Similar additive risk of suicide was noticed in women with acne. In conclusion, acne and gender, independently and jointly, are associated with major depression and suicide. Special medical support should be warranted in females with acne for the risk of major depression and suicide.


Assuntos
Acne Vulgar/complicações , Acne Vulgar/epidemiologia , Transtorno Depressivo Maior/etiologia , Suicídio/estatística & dados numéricos , Adolescente , Feminino , Humanos , Masculino , Fatores de Risco , Fatores Sexuais , Taiwan/epidemiologia
12.
PLoS One ; 8(11): e79434, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24244503

RESUMO

The dermal papilla, located in the hair follicle, expresses androgen receptor and plays an important role in hair growth. Androgen/Androgen receptor actions have been implicated in the pathogenesis of androgenetic alopecia, but the exact mechanism is not well known. Recent studies suggest that balding dermal papilla cells exhibit premature senescence, upregulation of p16(INK4a), and nuclear expression of DNA damage markers. To investigate whether androgen/AR signaling influences the premature senescence of dermal papilla cells, we first compared frontal scalp dermal papilla cells of androgenetic alopecia patients with matched normal controls and observed that premature senescence is more prominent in the dermal papilla cells of androgenetic alopecia patients. Exposure of androgen induced premature senescence in dermal papilla cells from non-balding frontal and transitional zone of balding scalp follicles but not in beard follicles. Overexpression of the AR promoted androgen-induced premature senescence in association with p16(INK4a) upregulation, whereas knockdown of the androgen receptor diminished the effects of androgen. An analysis of γ-H2AX expression in response to androgen/androgen receptor signaling suggested that DNA damage contributes to androgen/androgen receptor-accelerated premature senescence. These results define androgen/androgen receptor signaling as an accelerator of premature senescence in dermal papilla cells and suggest that the androgen/androgen receptor-mediated DNA damage-p16(INK4a) axis is a potential therapeutic target in the treatment of androgenetic alopecia.


Assuntos
Senescência Celular , Dano ao DNA , Folículo Piloso/citologia , Folículo Piloso/metabolismo , Receptores Androgênicos/metabolismo , Adulto , Alopecia/genética , Alopecia/metabolismo , Androgênios/farmacologia , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Folículo Piloso/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Androgênicos/genética , Transdução de Sinais , Adulto Jovem
13.
Dermatol Surg ; 36(6): 894-8, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20482735

RESUMO

BACKGROUND: Epidermal inclusion cysts (EICs) are a common cutaneous disorder in adults. The etiology of EICs remains obscure. Our clinical experience suggests that smoking may be a risk factor for the development of EICs. OBJECTIVE To determine whether the number and sites of EICs are related to smoking behavior and quantity. METHODS AND MATERIALS: We retrospectively surveyed patients pathologically diagnosed with EICs at our hospital. A control group comprised patients who underwent surgical procedures for diagnoses other than EICs. Smoking history was obtained through telephone or clinical interviews. RESULTS: Three hundred one patients with EICs were identified in our archives: 217 men (mean age 37.1, range 9-77) and 84 women (mean age 41.3, range 9-82). Detailed medical records and smoking history were available for 225 patients. Two hundred twenty-five age- and sex-matched patients were enrolled in the control group. Results showed that a higher percentage of men with facial EICs than of control subjects were smokers (p<.01). No such association was found in women with EICs. CONCLUSION: Smoking may contribute to the development of EICs.


Assuntos
Cisto Epidérmico/patologia , Cisto Epidérmico/psicologia , Dermatoses Faciais/patologia , Dermatoses Faciais/psicologia , Fumar/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Cisto Epidérmico/etiologia , Dermatoses Faciais/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Fumar/efeitos adversos , Fumar/patologia , Adulto Jovem
14.
Dermatology ; 213(3): 236-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17033175

RESUMO

In a 15-year-old Taiwanese girl, multiple purple punctate lesions arranged in a systematized, segmental pattern had developed since childhood, beginning from the right thigh and gradually progressing upwards to the right buttock, the left side of the abdomen, circumventing to the left side of the back, and extending to the right arm as well as to the posterolateral aspect of the left leg. Histopathological examination showed dilated capillaries in the uppermost part of the dermal papillae characteristic of angioma serpiginosum. The systematized, segmental and asymmetric arrangement of lesions as noted in the present case suggest that angioma serpiginosum reflects genetic mosaicism.


Assuntos
Mosaicismo , Dermatopatias Vasculares/diagnóstico , Telangiectasia/diagnóstico , Adolescente , Feminino , Humanos , Dermatopatias Vasculares/genética , Telangiectasia/genética
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