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AIM: The aim of this systematic revue of literature is to examine articles dealing with the narrative insight (patient's explanatory models of his difficulties) in patients suffering from schizophrenia. In addition to the theoretical interest of this work, it would make it possible to better adjust the clinical practices concerning the stories of patients about their disorders. METHOD: A study was conducted using the databases ScienceDirect, Medline, PsychInfo and PubPsych using the key words "narrative insight", "cultural insight", "subjective insight", "narrative awareness", "mental illness", and "psychiatric disorder". This search by keywords led to eighty-six results; abstracts of all the articles were consulted. Then the authors selected and studied all articles corresponding to inclusion criteria and compared their results and reached agreement by consensus in case of difference. The theme of the study was to focus on the concept of narrative insight or any other close concept mentioning an explanatory model of mental and/or psychiatric disorders, moving away from the biomedical model. Nine articles were selected based on the inclusion criteria (articles published in peer reviewed journals, where the both the resume and article are accessible; articles dealing with narrative insight of people suffering from schizophrenia). RESULTS: The authors of these articles agree that awareness of mental illness, insight, is a narrative act in which people give a personal meaning to their disorder. The most popular biomedical model used has many limitations and is the subject of many controversies. Results of the conducted study suggest considering narrative insight as adaptive strategies to mental illnesses. Indeed the process of narrative insight essentially consists in the patient adapting his life story to his conceptions and his values. To tell the story of one's own troubles with one's own values and beliefs gives meaning that helps protect identity and give back hope. This concept is considered to be dynamic and multidimensional. In addition, studies highlight its positive effects including the simultaneous presence of several models, which would have a greater favorable impact on the prognosis than the medical explanation alone. CONCLUSION: It seems necessary to take into account the concept of narrative insight in order to evaluate insight of patients suffering from mental illness. This implies that the evaluation methods of insight as well as the clinical practice must evolve to adapt to the culture and subculture of the patient. This could have beneficial effects on the well-being of patients, therapeutic relations, access to treatment as well as psychiatric research, as well as limit controversies around this topic. It would be interesting to confirm this new conception of insight and the therapeutic relations by carrying out new studies as well as by starting to take it into account in patient care.
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Narração , Terapia Narrativa , Psicologia do Esquizofrênico , Humanos , Esquizofrenia/terapia , AutoimagemRESUMO
BACKGROUND: Obese men commonly have reductions in circulating testosterone and report symptoms consistent with androgen deficiency. We hypothesized that testosterone treatment improves constitutional and sexual symptoms over and above the effects of weight loss alone. METHODS: We conducted a pre-specified analysis of a randomized double-blind, placebo-controlled trial at a tertiary referral center. About 100 obese men (body mass index (BMI)⩾30 kg m-2) with a repeated total testosterone level ⩽12 nmol l-1 and a median age of 53 years (interquartile range 47-60) receiving 10 weeks of a very-low-energy diet (VLED) followed by 46 weeks of weight maintenance were randomly assigned at baseline to 56 weeks of intramuscular testosterone undecanoate (n=49, cases) or matching placebo (n=51, controls). Pre-specified outcomes were the between-group differences in Aging Male Symptoms scale (AMS) and international index of erectile function (IIEF-5) questionnaires. RESULTS: Eighty-two men completed the study. At study end, cases showed significant symptomatic improvement in AMS score, compared with controls, and improvement was more marked in men with more severe baseline symptoms (mean adjusted difference (MAD) per unit of change in AMS score -0.34 (95% confidence interval (CI) -0.65, -0.02), P=0.04). This corresponds to improvements of 11% and 20% from baseline scores of 40 and 60, respectively, with higher scores denoting more severe symptoms. Men with erectile dysfunction (IIEF-5⩽20) had improved erectile function with testosterone treatment. Cases and controls lost the same weight after VLED (testosterone -12.0 kg; placebo -13.5 kg, P=0.40) and maintained this at study end (testosterone -11.4 kg; placebo -10.9 kg, P=0.80). The improvement in AMS following VLED was not different between the groups (-0.05 (95% CI -0.28, 0.17), P=0.65). CONCLUSIONS: In otherwise healthy obese men with mild to moderate symptoms and modest reductions in testosterone levels, testosterone treatment improved androgen deficiency symptoms over and above the improvement associated with weight loss alone, and more severely symptomatic men achieved a greater benefit.
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Androgênios/uso terapêutico , Dieta Redutora , Terapia de Reposição Hormonal , Hipogonadismo/tratamento farmacológico , Hipogonadismo/fisiopatologia , Obesidade/fisiopatologia , Testosterona/uso terapêutico , Envelhecimento , Androgênios/sangue , Androgênios/deficiência , Austrália/epidemiologia , Depressão , Dieta Redutora/efeitos adversos , Método Duplo-Cego , Humanos , Hipogonadismo/etiologia , Hipogonadismo/psicologia , Libido/fisiologia , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/psicologia , Qualidade de Vida , Testosterona/sangue , Resultado do TratamentoRESUMO
Quantification of abdominal visceral adipose tissue (VAT) is important to understand obesity-related comorbidities. We hypothesized that dual X-ray absorptiometry (DXA) measurements of VAT would correlate with traditional gold standards of magnetic resonance imaging (MRI) and computed tomography (CT) in older men. Deming regression and Bland-Altman plots were used to assess the agreement between VAT measured simultaneously by DXA and MRI (n=95) in a cohort of older males participating in a randomized trial of testosterone replacement for diabetes. We also correlated DXA with single-slice CT (n=102) in a cohort of older males undergoing testosterone deprivation for prostate cancer. Lunar Prodigy DXA scanners using enCORE software was used to measure VAT. DXA VAT volume strongly correlated with MRI VAT volume (r=0.90, P<0.0001) and CT VAT area (r=0.83, P<0.0001). As DXA assesses VAT volume in a smaller compartment than MRI, Bland-Altman analysis demonstrated DXA systematically underestimated VAT by an approximately 30% proportional bias. DXA VAT volume measured by Lunar Prodigy DXA scanners correlate well with gold standard MRI and CT quantification methods, and provides a low radiation, efficient, cost-effective option. Future clinical studies examining the effects of interventions on body composition and regional fat distribution may find DXA an appropriate volumetric method to quantify VAT.
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Absorciometria de Fóton , Gordura Intra-Abdominal/diagnóstico por imagem , Imageamento por Ressonância Magnética , Obesidade/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adiposidade , Idoso , Austrália/epidemiologia , Índice de Massa Corporal , Comorbidade , Estudos Transversais , Humanos , Gordura Intra-Abdominal/fisiopatologia , Masculino , Obesidade/complicações , Obesidade/fisiopatologia , Reprodutibilidade dos TestesRESUMO
A semiconductor quantum dot can generate highly coherent and indistinguishable single photons. However, intrinsic semiconductor dephasing mechanisms can reduce the visibility of two-photon interference. For an electron in a quantum dot, a fundamental dephasing process is the hyperfine interaction with the nuclear spin bath. Here, we directly probe the consequence of the fluctuating nuclear spins on the elastic and inelastic scattered photon spectra from a resident electron in a single dot. We find the in-plane component of the nuclear Overhauser field leads to detuned Raman scattered photons, broadened over experimental time scales by field fluctuations, which are distinguishable from both the elastic and incoherent components of the resonance fluorescence. This significantly reduces two-photon interference visibility. However, we demonstrate successful screening of the nuclear spin noise, which enables the generation of coherent single photons that exhibit high visibility two-photon interference.
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We report the design of a solid-state, micron-sized hemispherical cavity that yields significantly enhanced extraction efficiency with modest Purcell enhancement from embedded quantum emitters. A simple analytical model provides a guideline for the design and optimization of the structure, while finite-difference time-domain simulations are used for full analysis of the optimum structure. Cavity modes with up to 90% extraction efficiency, a Purcell enhancement factor >2, and a quality factor of ≈50 are achieved. In addition, Gaussian-like far-field beam profiles with low divergence are exhibited for several modes. These monolithic cavities are promising for solid-state emitters buried in a high dielectric environment, such as self-assembled quantum dots and optically active defects in diamond.
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UNLABELLED: In this longitudinal case-control study, acute fracture was associated with low serum testosterone, which was transient in 43% of men. While assessment of gonadal status is part of the assessment of bone fragility, measurement of testosterone in the early period after fracture may overestimate the prevalence of androgen deficiency. INTRODUCTION: Measurement of circulating testosterone is recommended in the evaluation of bone fragility in men. Since acute illness can transiently decrease circulating testosterone, we quantified the association of acute fracture and serum testosterone levels. METHODS: A case-control study was conducted involving 240 men with a radiologically confirmed minimal trauma fracture presenting to a tertiary referral hospital and 89 age-matched men without a history of minimal trauma fracture serving as controls. Follow-up testosterone levels 6 months after baseline were available for 98 cases and 27 controls. Results were expressed as the median and interquartile (IQR) range. RESULTS: Compared to controls, cases had lower total testosterone [TT, 7.2 (3.5, 10.8) vs 13.6 (10.9, 17.1) nmol/L, p < 0.001]. The 143 cases treated as inpatients had lower testosterone levels than the 97 cases treated as outpatients [TT 4.7 (2.3, 8.1) vs 10.3 (7.5, 12.7) nmol/L, p < 0.001]. Group differences in calculated free testosterone (cFT) were comparable to the group differences in TT. At follow-up, in 98 cases, median TT increased from 6.5 nmol/L (3.2, 8.5) to 9.6 nmol/L (6.9, 12.0) p < 0.0001, and SHBG remained unchanged. Of cases with low testosterone, 43% with TT <10 nmol/L and/or cFT <230 pmol/L at presentation were reclassified as androgen sufficient at follow-up. TT was unchanged in the controls. CONCLUSIONS: Low testosterone levels in men presenting with an acute fracture may, at least in part, be due to an acute, fracture-associated, stress response. To avoid over diagnosis, evaluation for testosterone deficiency should be deferred until recovery from the acute event.
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Fraturas por Osteoporose/sangue , Testosterona/sangue , Absorciometria de Fóton/métodos , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/fisiologia , Estudos de Casos e Controles , Comorbidade , Seguimentos , Articulação do Quadril/fisiopatologia , Humanos , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/fisiopatologia , Testosterona/deficiênciaRESUMO
PURPOSE: To (1) determine the characteristics and participation rate of adults with Parkinson disease (PD) in physical therapy (PT) delivered via telehealth, (2) identify the outcome measures and interventions implemented, (3) determine the safety of and (4) patient and therapist satisfaction with PT via telehealth in a clinic specializing in the care of people with PD during the coronavirus pandemic. MATERIALS & METHODS: A retrospective analysis of PT services via telehealth was conducted. Participating patients completed a satisfaction survey. Physical therapists (PTs) who delivered this care were interviewed. Three coders conducted thematic analysis of interviews. Descriptive statistics described the participation rate, demographics, outcome measures, interventions, and safety. RESULTS: There was a 71.4% participation rate. Participants (n = 55) were white (96%), non-Hispanic (100%), older adult (mean = 69.5 years (8.3)) males (65.5%). Non-participants (n = 22) had similar demographics. Therapists selected patient-reported measures more often than performance-based measures. Therapeutic exercise was the most common intervention. All patients (80% response rate) reported satisfaction with their experience. PTs reported the home enhanced specificity of training but impeded evaluation. Therapists endorsed a hybrid model for future practice. CONCLUSIONS: Patients reported satisfaction with PT via telehealth during the pandemic. A hybrid model may support optimal delivery of PT.IMPLICATIONS FOR REHABILITATIONPhysical therapy via telehealth for patients with Parkinson disease was acceptable to patients and physical therapists in our study.Physical therapy via telehealth was safe for people with Parkinson disease in our study, although availability and benefits may not be reaching all populations equitably.Both physical therapists and patients endorse a hybrid model of care (a combination of in-person and remote assessment and treatment) to profit from the strengths of in-person and virtual formats while minimizing barriers to access.
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COVID-19 , Doença de Parkinson , Telemedicina , Masculino , Humanos , Idoso , Pandemias , Doença de Parkinson/terapia , Estudos Retrospectivos , COVID-19/epidemiologia , Modalidades de FisioterapiaRESUMO
AIM: We aimed to compare the precipitants of acute decompensated heart failure (ADHF) among patients admitted with diagnoses inclusive of ADHF (community patients) and patients admitted without ADHF but who developed it during their stay (hospital patients). METHODS: This was a prospective, analytical, observational study undertaken in the Austin Hospital, a major metropolitan teaching hospital (September 2008-February 2010). Consecutive patients admitted to a general medicine unit, and diagnosed and treated for ADHF were enrolled. The unit medical staff completed a specifically designed data collection document. RESULTS: Three hundred and fifty-nine patients were enrolled (42.9% male, mean age 81.9 years). The community (n=312) and hospital (n=47) patient groups did not differ in age, gender, risk variables (living alone, cognitive impairment, multiple medications, compliance), cardiac failure medication use or cause of known heart failure (ischaemia, hypertension, valve dysfunction, 'other') (p>0.05). The ADHF precipitants comprised infection (39.8% patients), myocardial ischaemia (17.3%), tachyarrhythmia (16.2%), non-compliance with fluid and salt restriction (9.2%), non-compliance with medication (6.7%), renal failure (5.8%), medication reduction (5.0%), intravenous fluid complication (3.9%) and 'other' causes (13.9%). Significantly more hospital patients had their ADHF precipitated by intravenous fluid complications (25.5% versus 0.6%, p<0.001). Hospital patients also had a significantly greater death rate (25.5% versus 9.3%, p<0.01). CONCLUSION: Acute decompensated heart failure precipitated in hospital is a dangerous condition with a high mortality. While infection and myocardial ischaemia are the common precipitants, complications of intravenous fluid use, an iatrogenic condition, may be considerable and are potentially avoidable.
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Insuficiência Cardíaca/mortalidade , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Austrália , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Mortalidade Hospitalar , Humanos , Masculino , Estudos Prospectivos , Taxa de SobrevidaRESUMO
OBJECTIVE: Androgen deprivation therapy (ADT) for prostate cancer is associated with increases in fat mass and risk of type 2 diabetes; however, the relationship between sex steroid deficiency and abdominal fat distribution remains controversial. DESIGN: We conducted a 12-month prospective observational study at a tertiary referral centre. PATIENTS AND MEASUREMENTS: We investigated changes in abdominal fat distribution and insulin resistance in 26 men (70.6±6.8 years) with nonmetastatic prostate cancer during the first year of ADT. RESULTS: Twelve months of ADT increased visceral abdominal fat area by 22% (from 160.8±61.7 to 195.9±69.7 cm(2) ; P<0.01) and subcutaneous abdominal fat area by 13% (from 240.7±107.5 to 271.3±92.8 cm(2) ; P<0.01). Fat mass increased by 14% (+3.4 kg; P<0.001) and lean tissue mass decreased by 3.6% (-1·9 kg; P<0.001). Insulin resistance (HOMA-IR) increased by 12% (2.50±1.12 to 2.79±1.31, P<0.05). There was no change in fasting glucose or glycated haemoglobin levels. Total testosterone (TT) was inversely associated with visceral fat area independent of oestradiol (E2), but E2 was not associated with visceral fat area independent of TT. Visceral fat area, not TT or E2, was independently associated with insulin resistance. CONCLUSIONS: ADT for prostate cancer results in accumulation of both visceral and subcutaneous abdominal fat. Increased visceral fat area appears more closely linked to testosterone than oestradiol deficiency. Increased insulin resistance may arise secondary to visceral fat accumulation, rather than as a direct result of sex steroid deficiency.
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Antagonistas de Androgênios/efeitos adversos , Gordura Intra-Abdominal/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Gordura Subcutânea Abdominal/efeitos dos fármacos , Análise de Variância , Antagonistas de Androgênios/uso terapêutico , Estradiol/sangue , Humanos , Imunoensaio/métodos , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Modelos Lineares , Masculino , Estudos Prospectivos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/metabolismo , Medição de Risco , Fatores de Risco , Gordura Subcutânea Abdominal/metabolismo , Testosterona/sangue , Fatores de TempoRESUMO
The fast microwave reflectometer system on the COMPASS tokamak consists of an O-mode polarized K-band (18 GHz-26 GHz), Ka-band (26 GHz-40 GHz), and a part of U-band (40 GHz-54 GHz). The plasma density profile from the edge plasma area is measured using a fast sweeping rate up of to 6 µs of the probing wave. The processing of the reflected signal is realized by the heterodyne detection configuration based on the I/Q modulator. Two different methods of dynamic calibration of the required linear sweep frequency, together with static frequency and dispersion calibration, were used. The electron density profile was reconstructed by a spectrogram-based method with four sweeps on average. The system has the capability to measure the mid-plane low-field side electron density profile in the density range from 4 × 1018 m-3 to 3.6 × 1019 m-3. Experimental results obtained on COMPASS discharges are presented to demonstrate the performance of the diagnostics.
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OBJECTIVE: To assess the association between glycaemic status prior to the first hospital presentation with developing adverse renal outcomes overtime in patients with multiple hospital re-admissions. DESIGN: A prospective observational cohort study. PARTICIPANTS: All inpatients aged ≥54â¯years admitted between 2013 and 16 to a tertiary hospital. MAIN OUTCOMES: We prospectively measured HbA1c levels in all inpatients aged ≥54â¯years admitted between 2013 and 16. Diabetes was defined as prior documented diagnosis of diabetes and/or HbA1c ≥6.5% (47·5â¯mmol/L). Included patients hadâ¯≥â¯two admissions (at least 90â¯days apart), baseline estimated glomerular filtration rate (eGFR) >30â¯ml/min/1·73m2 and no history of renal replacement therapy. We assessed several renal outcomes: (a) 50% decline in eGFR; (b) rapid decline in renal function (eGFR decline >5â¯mL/min/1·73m2/year) and (c) final eGFR<30â¯ml/min/1·73m2. RESULTS: Of 4126 inpatients with a median follow-up of 465â¯days (254, 740), 26% had diabetes. The presence of diabetes was associated with higher odds of (a) 50% decline in eGFR (ORâ¯=â¯1·42;95% CI:1·18-1·70;pâ¯<â¯0·001); (b) rapid decline in renal function (ORâ¯=â¯1·40;95%CI:1·20-1·63;pâ¯<â¯0·001), and (c) reaching eGFR<30â¯ml/min/1.73m2 (ORâ¯=â¯1·25;95%CI:1·03-1·53;pâ¯<â¯0·05). Every 1% (11â¯mmol/L) increase in baseline HbA1c was associated with significantly greater odds of (a) >50% decline in eGFR (ORâ¯=â¯1·07;95% CI:1·01-1·4;pâ¯<â¯0·05) and (b) rapid decline in renal function (ORâ¯=â¯1·11;95% CI:1·05-1·18;pâ¯<â¯0·001). CONCLUSIONS: In patients with ≥two admissions, the presence of diabetes and higher HbA1c levels were strongly and independently associated with adverse renal outcomes at follow up. Such patients are at high risk of relatively rapid deterioration in renal function and a logical target for structured preventive interventions.
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Diabetes Mellitus/diagnóstico , Hemoglobinas Glicadas/metabolismo , Falência Renal Crônica/diagnóstico , Readmissão do Paciente , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/terapia , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Falência Renal Crônica/sangue , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Prognóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
Due to an increased interest in runaway electron (RE) phenomena in tokamak research, the need for diagnostics of runaway electron population in plasma has emerged. A novel diagnostic of the nonthermal electron cyclotron emission from runaway electrons can be utilized for this purpose. It was designed and installed at the COMPASS tokamak based on the available heterodyne radiometer. The vertical ECE (V-ECE) system uses a 16-channel heterodyne radiometer with a vertically placed E2-band horn antenna with a 76.5-90 GHz frequency range front-end. Simulations with the ray-tracing SPECE code have shown a measurement feasibility of the runaway electrons with energies up to 1 MeV. Due to a low optical depth of the plasma in COMPASS during RE discharges, reflected waves from the tokamak wall can be detected as well. First results show strong connection with other RE diagnostics at COMPASS. The V-ECE can obtain important information about RE population evolution and primary generation mechanism.
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Our main purpose was to evaluate the influence of cancer pain on the rewarding properties of morphine. Opioids are very addictive when used by healthy persons, conversely the occurrence of an opioid addiction seems very low when patients suffering from cancer are treated with morphine. We investigated the reinforcing properties of morphine in the place preference paradigm on a new model of mice suffering from a cancer pain induced by syngenic melanoma cells injected in the hind paw. These data were compared with mice suffering either from a short-term- or a chronic-inflammatory pain induced respectively by injection of carrageenan or complete Freund's adjuvant. Remarkably, mice suffering from cancer pain or chronic inflammatory pain did not develop any preference for the environment associated with the injection of morphine. In mice injected with melanoma cells, the specific binding of [(125)I]EYWSLAAPQRF-NH(2), an agonist of neuropeptide FF(2) receptors, was increased in several brain areas involved in the rewarding properties of opiates, including the shell of the nucleus accumbens, the major islands of Calleja, the ventral endopiriform nucleus and the amygdaloid area. Our study is the first to reveal a modification of morphine rewarding properties under cancer pain in rodents. We postulate that anti-opioid neuropeptides might contribute to the suppression of morphine rewarding effects in this murine model of cancer pain.
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Analgésicos Opioides/farmacologia , Inflamação/complicações , Inflamação/psicologia , Morfina/farmacologia , Motivação , Neoplasias/complicações , Neoplasias/psicologia , Dor/tratamento farmacológico , Dor/psicologia , Receptores de Neuropeptídeos/efeitos dos fármacos , Animais , Autorradiografia , Comportamento Animal/efeitos dos fármacos , Doença Crônica , Condicionamento Operante/efeitos dos fármacos , Edema/patologia , Feminino , Pé/patologia , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Neoplasias/patologia , Dor/etiologia , Medição da Dor/efeitos dos fármacosRESUMO
Androgens have anabolic actions in skeletal muscle and could potentially act to: (a) increase proliferation of myoblasts; (b) delay differentiation to myotubes; and (c) induce protein accretion in post-proliferative myofibers. To identify the site of androgens action, we investigated the proliferative response of the C2C12 mouse myoblast cell line to testosterone and dihydrotestosterone (DHT) treatment. Neither androgens affected cell proliferation after up to 7 days treatment, nor was there a synergistic effect of androgens on the proliferative response of C2C12 cells to IGF-I treatment. However, proliferating C2C12 cells expressed 0.1% of the level of androgen receptor (AR) mRNA found in adult mouse gastrocnemius muscle (p<0.01). Therefore, we generated mouse C2C12 myoblast cell lines stably transfected with the mouse AR cDNA driven by the SV40 promoter (C2C12-AR). C2C12-AR cell proliferation, differentiation, and protein content were analyzed in response to androgen treatment. Our data demonstrated that androgen treatment does not alter either proliferation rate or differentiation rate of C2C12-AR cells. However, treatment of differentiated C2C12-AR myotubes with 100 nM DHT for 3 days caused a 20% increase in total protein content vs vehicle treatment (p<0.05). This effect was not observed in control C2C12 cells transfected with empty vector. These data suggest that androgens act via the AR to upregulate myotube protein content. This model cell line will be useful to further investigate the molecular mechanisms via which androgens regulate protein accretion.
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Androgênios/farmacologia , Di-Hidrotestosterona/farmacologia , Fibras Musculares Esqueléticas/metabolismo , Mioblastos/citologia , Testosterona/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Humanos , Camundongos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/crescimento & desenvolvimento , Mioblastos/efeitos dos fármacos , Receptores Androgênicos/fisiologiaRESUMO
Diabetes is an independent risk factor for development of heart failure and has been associated with poor outcomes in these patients. The prevalence of diabetes continues to rise. Using routine HbA1c measurements on inpatients at a tertiary hospital, we aimed to investigate the prevalence of diabetes amongst patients hospitalised with decompensated heart failure and the association of dysglycaemia with hospital outcomes and mortality. 1191 heart failure admissions were identified and of these, 49% had diabetes (HbA1c ≥ 6.5%) and 34% had pre-diabetes (HbA1c 5.7-6.4%). Using a multivariable analysis adjusting for age, Charlson comorbidity score (excluding diabetes and age) and estimated glomerular filtration rate, diabetes was not associated with length of stay (LOS), Intensive Care Unit (ICU) admission or 28-day readmission. However, diabetes was associated with a lower risk of 6-month mortality. This finding was also supported using HbA1c as a continuous variable. The diabetes group were more likely to have diastolic dysfunction and to be on evidence-based cardiac medications. These observational data are hypothesis generating and possible explanations include that more diabetic patients were on medications that have proven mortality benefit or prevent cardiac remodelling, such as renin-angiotensin system antagonists, which may modulate the severity of heart failure and its consequences.
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Diabetes Mellitus/epidemiologia , Hemoglobinas Glicadas/análise , Insuficiência Cardíaca/sangue , Idoso , Idoso de 80 Anos ou mais , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Humanos , Pacientes Internados , Tempo de Internação/estatística & dados numéricos , Masculino , Readmissão do Paciente/estatística & dados numéricos , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Análise de SobrevidaRESUMO
The role of classical genomic androgen receptor (AR) mediated actions in female reproductive physiology remains unclear. Female mice homozygous for an in-frame deletion of exon 3 of the Ar (AR(-/-)) were subfertile, exhibiting delayed production of their first litter (AR(+/+) = 22 d vs. AR(-/-) = 61 d, P < 0.05) and producing 60% fewer pups/litter (AR(+/+): 8.1 +/- 0.4 vs. AR(-/-): 3.2 +/- 0.9, P < 0.01). Heterozygous females (AR(+/-)) exhibited an age-dependent 55% reduction (P < 0.01) in pups per litter, evident from 6 months of age (P < 0.05), compared with AR(+/+), indicating a significant gene dosage effect on female fertility. Ovulation was defective with a significant reduction in corpora lutea numbers (48-79%, P < 0.01) in 10- to 12- and 26-wk-old AR(+/-) and AR(-/-) females and a 57% reduction in oocytes recovered from naturally mated AR(-/-) females (AR(+/+): 9.8 +/- 1.0 vs. AR(-/-): 4.2 +/- 1.2, P < 0.01); however, early embryo development to the two-cell stage was unaltered. The delay in first litter, reduction in natural ovulation rate, and aromatase expression in AR(+/-) and AR(-/-) ovaries, coupled with the restored ovulation rate by gonadotropin hyperstimulation in AR(-/-) females, suggest aberrant gonadotropin regulation. A 2.7-fold increase (AR(+/+): 35.4 +/- 13.4 vs. AR(-/-): 93.9 +/- 6.1, P < 0.01) in morphologically unhealthy antral follicles demonstrated deficiencies in late follicular development, although growing follicle populations and growth rates were unaltered. This novel model reveals that classical genomic AR action is critical for normal ovarian function, although not for follicle depletion and that haploinsufficiency for an inactivated AR may contribute to a premature reduction in female fecundity.
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Envelhecimento/fisiologia , Infertilidade Feminina/fisiopatologia , Folículo Ovariano/fisiologia , Ovulação/fisiologia , Receptores Androgênicos/genética , Envelhecimento/patologia , Animais , Contagem de Células , Modelos Animais de Doenças , Desenvolvimento Embrionário/fisiologia , Estradiol/sangue , Feminino , Fertilidade/fisiologia , Hormônio Foliculoestimulante/sangue , Genótipo , Infertilidade Feminina/patologia , Hormônio Luteinizante/sangue , Camundongos , Camundongos Knockout , Folículo Ovariano/crescimento & desenvolvimento , Folículo Ovariano/patologia , Indução da Ovulação , Fenótipo , Gravidez , Receptores Androgênicos/metabolismo , Testosterona/sangueRESUMO
We have identified different members of one family affected by androgen insensitivity syndrome who have deletions of different exons of the X-linked androgen receptor (AR) gene. Two affected (XY) siblings have a deletion of exon E of the AR gene and their affected (XY) aunt has a normal exon E, but a deletion of exons F and G of the same gene. The mother and maternal grandmother of the children both carry the exon E deletion, but not the exon F, G deletion. Both deletions are 5 kb in length and have one breakpoint within a 200-bp region in intron 5; however, they extend in opposite directions. The probability that these two different deletions have arisen at random is extremely low, but the cause of this intriguing phenomenon remains to be found.
Assuntos
Deleção de Genes , Receptores Androgênicos/genética , Cromossomo X , Adulto , Sequência de Bases , Células Cultivadas , Criança , DNA/sangue , DNA/genética , DNA/isolamento & purificação , Éxons , Feminino , Fibroblastos/metabolismo , Humanos , Íntrons , Cariotipagem , Masculino , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos , Linhagem , Reação em Cadeia da Polimerase/métodos , Valores de Referência , Mapeamento por Restrição , Pele/metabolismo , Cromossomo YRESUMO
The specificities of autoantibodies directed against the acetylcholine receptor (AChR) for embryonic and adult muscle AChR were studied in 22 mothers with myasthenia gravis (MG) and in their newborns using human fetus and normal adult muscle AChR preparations. 12 mothers had transmitted MG to their neonates with, in three cases, antenatal injury. A clear correlation was found between occurrence of neonatal MG (NMG) and the high overall level of anti-AChR antibodies (embryonic or adult muscle AChR). However, a strong correlation was also found between occurrence of NMG and the ratio of anti-embryonic AChR to anti-adult muscle (Te/Ta) AChR antibodies (P < 0.0002). Taken together, these data suggest that autoantibodies directed against the embryonic form of the AChR could play a predominant role in the pathogenesis of NMG. Paradoxically, the three cases with antenatal injury presumably the most severe form of NMG, were not associated with high Te/Ta. At the clinical level, these observations could prove helpful in the prediction of transmission of NMG.
Assuntos
Autoanticorpos/análise , Feto/imunologia , Miastenia Gravis/imunologia , Complicações na Gravidez/imunologia , Receptores Colinérgicos/imunologia , Adolescente , Adulto , Especificidade de Anticorpos , Criança , Feminino , Humanos , Recém-Nascido , GravidezRESUMO
By using an optimized [(35)S]GTPgammaS binding assay, the functional activities (potency and efficacy) of peptides belonging to three members of the RFamide family; Neuropeptide FF (NPFF), prolactin-releasing peptide (PrRP) and 26RFamide, were investigated on NPFF(1) and NPFF(2) receptors stably expressed in Chinese Hamster Ovary (CHO) cells. Despite their large differences in affinity and selectivity, all analogues tested behaved as agonists toward NPFF(1) and NPFF(2) receptors. High NaCl concentration in the assay strongly increased the efficacy toward NPFF(2) receptors and augmented differences among agonists. In low sodium conditions, whereas the potencies of agonists correlated with their affinities for NPFF(1) receptors, NPFF(2) receptors exhibited an extraordinary activity since all compounds tested displayed EC(50) values of GTPgammaS binding lower than their K(I) values. Comparisons of functional values between NPFF(1) and NPFF(2) receptors revealed unexpected potent selective NPFF(2) agonists especially for the PLRFamide and the VGRFamide sequences. By using blocker peptides, we also show that Galpha(i3) and Galpha(s) are the main transducers of NPFF(1) receptors while NPFF(2) are probably coupled with Galpha(i2), Galpha(i3), Galpha(o) and Galpha(s) proteins. Our data indicate that NPPF(1) and NPFF(2) receptors are differently coupled to G proteins in CHO cells.
Assuntos
Guanosina 5'-O-(3-Tiotrifosfato)/metabolismo , Neuropeptídeos/metabolismo , Receptores de Neuropeptídeos/metabolismo , Animais , Células CHO , Membrana Celular/diagnóstico por imagem , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Interações Medicamentosas , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Humanos , Isótopos/farmacocinética , Ligação Proteica/efeitos dos fármacos , Cintilografia , Saponinas/farmacologiaRESUMO
Two synthetic smectites (montmorillonite and beidellite) are studied by a water adsorption technique in order to assess their specific surface areas under atmospheric conditions. A route recently proposed for extracting the thermodynamic data from experimental adsorption isotherms is used. The variation of the specific surface area during water adsorption is obtained, which can be linked to the enlargement of the interlayer space determined using X-ray diffraction. This variation is compared to an idealized specific surface area obtained from TEM and X-ray measurements in agreement with crystallographic models. All these results are also compared with those obtained previously for a natural montmorillonite. A simple view of swelling is proposed.