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1.
Sleep Breath ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898191

RESUMO

OBJECTIVES: To examine the efficacy of a 24-week Baduanjin exercise program on self-reported sleep quality and quality of life in community-dwelling elderly subjects with sleep disturbances. METHODS: Community-dwelling elderly men and women meeting criteria for sleep disturbances (i.e., Pittsburgh Sleep Quality of Index (PSQI) score ≥ 5) were recruited and randomized to a Baduanjin exercise intervention group or a control group. Participants in the intervention group completed five 45-min exercise sessions per week for 24 weeks, while those in control group were instructed to maintain their usual lifestyle behaviors. RESULTS: A total of 139 participants were enrolled and randomized. Sixty-two of 67 participants in the intervention group (response rate of 92.5%) and 57 of 72 participants (response rate of 79.6%) in the control group completed intervention and follow-up. The intervention group reported significant improvements in overall sleep quality after 24 weeks compared with those randomized to control (PSQI endpoint-to-baseline change = - 2.6 ± 4.0 vs. - 0.5 ± 4.2, time × group interaction p = 0.007). Intervention group participants had higher response rates at both week 12 (23.9% vs. 9.7%, p = 0.025) and week 24 (40.3% vs. 15.3%, p = 0.001) when compared with the control group. There was a trend that the intervention group had increased quality of life (The Short Form Health Survey [SF-36] endpoint=tobaseline change 6.3 ± 10.9 vs. 2.2 ± 10.9, time × group interaction p = 0.06) when compared with the control group. CONCLUSIONS: Baduanjin exercise is an effective and feasible approach to improve self-reported sleep quality but less likely the quality of life in community-dwelling elderly men and women with sleep disturbances. TRIAL REGISTRATION: Effect of Baduanjin Exercise on the Elderly's Sleep; http://www.chictr.org.cn/listbycreater.aspx; ChiCTR1800014706, registered 1 January 2018.

2.
Sci China Life Sci ; 62(12): 1638-1654, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31820200

RESUMO

Staurosporine, belonging to indolocarbazole compounds, is regarded as an excellent lead compound for synthesizing antitumor agents as a potent inhibitor against various protein kinases. In this study, two separate clusters (cluster A and cluster B), corresponding to biosyntheses of K-252c (staurosporine aglycone) and sugar moiety, were identified in Streptomyces fradiae CGMCC 4.576 and heterologously expressed in Streptomyces coelicolor M1146 separately or together. StaR, a cluster-situated LAL family regulator, activates staurosporine biosynthesis by binding to the promoter regions of staO-staC and staG-staN. The conserved sequences GGGGG and GCGCG were found through gradually truncating promoters of staO and staG, and further determined by mutational experiments. Overexpression of staR with the supplementation of 0.01 g L-1 FeSO4 increased staurosporine production to 5.2-fold compared with that of the parental strain Streptomyces fradiae CGMCC 4.576 in GYM medium. Our results provided an approach for improvement of staurosporine production mediated by a positive regulator and established the basis for dissecting the regulatory mechanisms of other indolocarbazole compounds with clinical application value.

3.
BMJ Open ; 9(11): e033457, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31740476

RESUMO

INTRODUCTION: Previous evidence suggested that online self-guided sleep intervention is efficacious in improving treatment outcomes in patients with persistent insomnia. However, research on online sleep interventions targeting episodic insomnia has been scarce. This study aims to evaluate the effectiveness of brief e-aid cognitive behavioural therapy for insomnia (eCBTI) in preventing transition from episodic insomnia to persistent insomnia. METHODS AND ANALYSIS: This is a pragmatic two-arm multicentre, randomised controlled trial comparing eCBTI with treatment as usual (TAU) in outpatients. Two hundred patients with episodic insomnia (as defined by DSM-5) will be recruited. Patients will be randomly assigned to receive 1 week eCBTI via a Smartphone application, or to receive TAU. Treatment effects will be assessed at 1 week and 3 months after intervention. The primary outcome of the study, whether the eCBTI program is sufficient in preventing transition from short-term to persistent insomnia, is measured by the Insomnia Severity Index. Secondary outcome measurements include the Dysfunctional Beliefs and Attitudes about Sleep Scale, Ford Insomnia Response to Stress Test, Sleep Hygiene and Practices Scale, Pre-sleep Arousal Scale and Epworth Sleepiness Scale. Additionally, the Hospital Anxiety and Depression Scale and the Short-Form 12-Item Health Survey will be used for measurement of mood symptoms and quality of life. ETHICS AND DISSEMINATION: Ethical approval for the study has been obtained from the Ethics Committee of Southern Medical University (reference number: NFEC-2017-131). The results of the investigation will be published in scientific papers. The data from the investigation will be made available online if necessary. TRIAL REGISTRATION: NCT03302455 (clinicaltrials.gov). Date of registration: October 5, 2017.

4.
J Clin Sleep Med ; 15(11): 1561-1570, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31739845

RESUMO

STUDY OBJECTIVES: Previous studies suggest the presence of familial aggregation of obstructive sleep apnea (OSA) in adults. However, similar data on childhood OSA are limited. This family study aimed to investigate the heritability and familial aggregation of childhood OSA and to examine whether significant differences existed between patients of normal weight and overweight. METHODS: Children aged 6 to 18 years were recruited as probands either from attendants to sleep clinic (with habitual snoring) or the community (without habitual snoring). Parents and siblings of the probands were also invited to participate. All participants underwent nocturnal sleep study. RESULTS: A total of 229 probands took part, of whom 33 had moderate to severe OSA, 70 had mild disease, and 126 had no OSA. A total of 412 relatives were also recruited. Although the overall heritability of obstructive apnea-hypopnea index (OAHI) was not significant (h² ± SE = 0.03 ± 0.09, P = .37), it was significant in overweight individuals on subgroup analysis (h² ± SE = 0.43 ± 0.24, P = .032). Significant interaction effect of overweight was demonstrated in both heritability and familial aggregation analyses. Bivariate genetic analysis found that the genetic correlation between OAHI and body mass index in overweight individuals (ρg ± SE = 0.63 ± 0.18) was significantly different from both 0 (P = .005) and 1 (P = .025). CONCLUSIONS: The differential results of heritability and familial aggregation of OSA in normal weight and overweight subgroups substantiated the recommendation of separating childhood OSA into normal weight and overweight subtypes. In the overweight subgroup, there may be obesity-independent components involved in the genetic variance of OAHI, although a significant proportion of the genetic variance is shared with obesity.

5.
J Clin Sleep Med ; 15(10): 1495-1502, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31596215

RESUMO

STUDY OBJECTIVES: To compare the secular trends of sleep/wake patterns in school-aged children in Hong Kong and Shanghai, two major metropolitan cities in China with two different policies that school start time was delayed in Shanghai, but advanced in Hong Kong in 10 years' time. METHODS: Participants were from two waves of cross-sectional school-based surveys of children aged 6 to 11 years. In Shanghai, 4,339 and 13,795 children participated in the 2005 and 2014 surveys, respectively. In Hong Kong, 6,231 and 4,585 children participated in the 2003 and 2012 surveys, respectively. Parents reported their children's bedtime and wakeup time, and thus sleep duration, short sleep (≤ 9 hours) and weekend oversleep (difference in sleep duration between weekday and weekend > 2 hours) were determined. RESULTS: Hong Kong children had later bedtime and wakeup time and slept consistently less than their Shanghai counterparts at both survey time points. The shorter sleep duration was particularly marked during weekdays. Over the interval period, weekday sleep duration significantly decreased from 9.2 to 8.9 hours as wakeup time became earlier for Hong Kong children, but increased from 9.4 to 9.6 hours as wakeup time became later for children in Shanghai. Children from both cities slept longer on the weekends. Prevalence of weekend oversleep significantly increased in Hong Kong children, but no interval change was found in Shanghai children. CONCLUSIONS: The findings indicate subcultural differences in sleep/wake patterns in Shanghai and Hong Kong school-aged children. In particular, sleep duration had increased for Shanghai children, but decreased for Hong Kong children over 10 years. The benefits and barriers of delaying school start time for optimizing sleep health in school-aged children should be further explored.

6.
Sleep Med ; 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-31607435

RESUMO

OBJECTIVE: Cataplexy is a pathognomonic symptom of narcolepsy type 1. This study was conducted to clarify the clinical characteristics of cataplexy by staging, and to further analyse the correlations of clinical features and cataplectic stages in patients with narcolepsy type 1 (NT1). METHODS: We experimentally triggered patients with NT1 into cataplexy while under video-polysomnography (v-PSG) monitoring in the sleep lab. The most serious cataplectic attack from each patient was analysed. Each cataplectic episode was segmented into four stages according to the v-PSG. Correlations were analysed between cataplectic stages in pairs, and between cataplectic stages and other clinical features. RESULTS: We observed 81 cataplectic episodes in 21 patients with diverse triggers, including humorous or exciting videos, tickling, recalling horrible memories and exercising. Nine patients (43%) went through complete cataplectic attacks while the others experienced partial attacks. Four cataplectic stages (ie, triggering, resisting, atonic, and recovering) were identified according to clinical and electromyograms characteristics. Resisting stage is predominant (56.4%) in cataplexy, while atonic stage is most related with the total duration of cataplexy. The Epworth Sleepiness Scale score (ESS) has a positive correlation with the total duration of cataplexy. Both duration of cataplexy and ESS score are negatively correlated with disease course. However, medication history seems have no influence on either cataplexy duration or ESS score. CONCLUSION: Four-stage segmentation shows the dynamic process of the cataplectic attack, which is different from the traditional classification of complete or partial cataplexy. Resisting stage is necessary for every cataplexy and might reflect the compensation mechanism, while atonic stage may be omitted in some patients. The severity of narcolepsy reduces with the extension of natural course regardless of medication history.

7.
Sleep Med Rev ; 48: 101210, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31518950

RESUMO

Polysomnographic studies have been performed to examine sleep abnormalities in posttraumatic stress disorder (PTSD), but clear associations between PTSD and sleep disturbances have not been established. A systematic review of the evidence examining the polysomnographic changes in PTSD patients compared with controls was conducted using MEDLINE, EMBASE, All EBM databases, PsycINFO, and CINAHL databases. Meta-analysis was undertaken where possible. The searches identified 34 studies, 31 of which were appropriate for meta-analysis. Pooled results indicated decreased total sleep time, slow wave sleep and sleep efficiency, and increased wake time after sleep onset in PTSD patients compared with healthy controls. PTSD severity was associated with decreased sleep efficiency and slow wave sleep percentage. Rapid eye movement (REM) sleep percentage was significantly decreased in PTSD patients compared with controls in studies including participants with mean age below 30 y, but not in studies with other mean age groups (30-40 y and >40 y). Our study shows that polysomnographic abnormalities are present in PTSD. Sex, age, PTSD severity, type of controls, medication status, adaptation night, polysomnographic scoring rules and study location are several of the demographic, clinical and methodological factors that contribute to heterogeneity between studies.

8.
Zhongguo Gu Shang ; 32(7): 630-635, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31382721

RESUMO

OBJECTIVE: To explore the efficacy of bilateral sagittal cross percutaneous kyphoplasty(PKP) for preventing recurrent fracture of the cemented vertebrae. METHODS: From January 2017 to June 2017, 85 patients with single-segment osteoporotic vertebral compression fractures(OVCFs) were treated by bilateral sagittal cross PKP(cross group). There were 35 males and 50 females with an average age of (70.1±8.3) years old in cross group. Another 85 patients with single-segment OVCFs were treated by traditional PKP (traditional group). There were 37 males and 48 females with an average age of (73.3±9.5) years old in traditional group. The cement distribution condition, recurrent fracture of the cemented vertebrae, the anterior vertebral body height and sagittal Cobb angle, visual analogue scale(VAS) were observed in two groups. RESULTS: All patients underwent operation successfully. The follow-up time were (11.8±4.5) months in cross group and (12.1±3.7) months in traditional group. In cross group, all patients' bone cement touched the upper and lower endplates of the vertebral body while 67 cases (78.8%) in traditional group did with significant difference between two groups (P<0.05). No patient in cross group suffered recurrent fracture of the cemented vertebrae while 10 cases (11.8%) in traditional group did with significant difference between two groups(P<0.05). The anterior vertebral body height, sagittal Cobb angle and VAS in both groups were obvious improved at 2 days after operation (P<0.05) and there were no significant difference between two groups at 2 days after operation and the final follow-up(P>0.05). CONCLUSIONS: Bilateral sagittal cross PKP was a simple, safe and effective technique which can make bone cement distribute in the fractured vertebral body and contact the upper and lower endplates of the vertebral body, thus preventing the recurrent fracture of the cemented vertebrae.


Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
9.
Zhongguo Gu Shang ; 32(6): 524-530, 2019 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-31277535

RESUMO

OBJECTIVE: The 3D model of lumbar spine was established by using Mimics software. To observe the applicability and needling parameters of lumbar vertebral kyphoplasty with unilateral puncture by backward rotation method using simulated puncture. METHODS: Twenty-four patients (12 males and 12 females) with osteoporotic thoracic fracture in the first time and no signs of lumbar misalignment and bone destruction were scanned by spiral CT on the lumbar spine. The original DICOM file was modeled in 3D with Mimics software, and the vertebral bodies were separated. After being imported into 3-matic software, the posterior wall of the vertebral body was restrained for standardized measurement. A sketch perpendicular to the mid-section of the pedicle and the posterior wall of the vertebral body was drawn. The simulated puncture was performed on the sketch. The angle and distance parameters of the range of motion of the puncture needle were recorded, and the puncture needle was recorded at the top. The crossing points of the anterior, middle and posterior zones of the tangential line of the vertebral body were located at the high extraversion angle, and the results were compared and analyzed. RESULTS: All the data in the left and right sides had no significantly differences(P>0.05). Data of different segments in different gender were significantly differences(P<0.05). The maximal extraversion angle in lumbar spine increased gradually from (33.41±1.31) degree to (56.53±4.71) degree in males, as same as in females from(28.58±2.55) to (53.86±2.68) degree. There was no crossing point in area A, 3.3% of males and 26.67% of females in area B, rest in area C. The distribution areas on gender showed statistically significance (P<0.05). CONCLUSIONS: Backward rotation method can theoretically meet the requirements of puncture point for vertebral compression fracture, especially for males and lower lumbar spine. The determination of the maximum inclination angle is of guiding significance to the backward rotation method.


Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Feminino , Humanos , Vértebras Lombares , Masculino , Punções , Rotação , Vértebras Torácicas , Resultado do Tratamento
10.
Methods Mol Biol ; 2020: 185-205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31177501

RESUMO

House dust mites are globally significant triggers of allergic disease. Notable among their extensive repertoire of allergens are the Group 1 cysteine peptidase allergens which function as digestive enzymes in house dust mites. Compelling evidence suggests that the proteolytic activity of these molecules plays a key role in the development and maintenance of allergic diseases through the activation of innate immune mechanisms which exploit genetic predispositions to allergy. Growing interest in this area creates a requirement for high-quality purified protein, whether natural or recombinantly expressed. It has also identified these allergens as therapeutic targets for a novel approach to allergy treatment through modulation of innate immune responses. The purpose of this chapter is to describe a new method for the purification of Der p 1 and use of the protein produced in a screening assay designed for the discovery of novel inhibitors of Group 1 house dust mite allergens.

12.
Sci Rep ; 9(1): 5881, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30971731

RESUMO

We examined the temporal changes in obesity and sleep habits and their relationship in a prospective cohort of healthy Chinese adolescents. We collected data on anthropometric and questionnaire-measured sleep parameters in 2007-2008. 516 participants returned for examinations in 2013-2015. General obesity was defined as body mass index (BMI) ≥age- and sex-specific 95th percentile or ≥25 kg/m2 for participants aged <18 or ≥18 years, respectively. Central obesity was defined as waist circumference (WC) ≥ age- and sex-specific 90th percentile or using adult cut-offs. After a mean follow-up of 6.2 ± 0.5 years, the mean BMI increased from 18.5 ± 3.1 to 20.9 ± 3.4 kg/m2. The corresponding WC were 63.7 ± 8.9 and 69.8 ± 9.7 cm. General obesity rate increased from 8.3% (95% confidence interval [CI] 6.1-11.1) to 11.3% (8.7-14.4; p = 0.034). Central obesity rate decreased from 16.9% (13.7-20.4) to 13.5% (10.6-16.8; p = 0.034). During follow-up, more participants reported short sleep (<7 hours/day during weekday: 20.5% [17.1-24.2] vs. 15.3% [12.3-18.8]; p = 0.033) and bedtime after midnight (60.5% [56.2-64.8] vs. 16.2% [13.1-19.7]; p < 0.001) than baseline. The relative risk of overweight/obesity in participants with short sleep and late bedtime was 1.30 (0.48-3.47) and 1.46 (0.70-3.05), respectively. Despite rising rates of unhealthy sleep habits and general obesity, their associations were not significant at 6-year of follow-up.

13.
Ann Clin Transl Neurol ; 6(2): 210-221, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30847354

RESUMO

Objective: Cataplexy is a complicated and dynamic process in narcolepsy type 1 (NT1) patients. This study aimed to clarify the distinct stages during a cataplectic attack and identify the changes of the primary motor cortex (PMC) excitability during these stages. Methods: Thirty-five patients with NT1 and 29 healthy controls were recruited to this study. Cataplectic stages were distinguished from a cataplectic attack by video-polysomnogram monitoring. Transcranial magnetic stimulation motor-evoked potential (TMS-MEP) was performed to measure the excitability of PMC during quiet wakefulness, laughter without cataplexy, and each cataplectic stage. Results: Based on the video and electromyogram observations, a typical cataplectic attack (CA) process is divided into four stages: triggering (CA1), resisting (CA2), atonic (CA3), and recovering stages (CA4). Compared with healthy controls, NT1 patients showed significantly decreased intracortical facilitation during quiet wakefulness. During the laughter stage, both patients and controls showed increased MEP amplitude compared with quiet wakefulness. The MEP amplitude significantly increased even higher in CA1 and 2, and then dramatically decreased in CA3 accompanied with prolonged MEP latency compared with the laughter stage and quiet wakefulness. The MEP amplitude and latency gradually recovered during CA4. Interpretation: This study identifies four stages during cataplectic attack and reveals the existence of a resisting stage that might change the process of cataplexy. The fluctuation of MEP amplitude and MEP latency shows a potential participation of PMC and motor control pathway during cataplexy, and the increased MEP amplitude during CA1 and 2 strongly implies a compensatory mechanism in motor control that may resist or avoid cataplectic attack.

14.
Sleep Med Rev ; 45: 1-17, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30844624

RESUMO

Recent investigations have established that patients with obstructive sleep apnea (OSA) and insomnia have greater daytime impairments and reduced quality of life compared to those with either disorder alone. The present study reviewed current data on the co-occurrence prevalence of insomnia and insomnia symptoms with OSA and assessed its worldwide and regional prevalence based on World Health Organization (WHO) regions. A total of 37 studies were included in the analysis. The overall prevalence rates of insomnia, any insomnia complaints, difficulty falling asleep (DFA), difficulty maintaining sleep (DMS) and early morning awakening (EMA) found in OSA patients were 38%, 36%, 18%, 42%, and 21%, respectively. According to the regional classification of the WHO, the rates of DFA, DMS and EMA in OSA patients in the Western Pacific Region were lower than those in the European Region and the Region of the Americas. We also analyzed the pooled prevalence rates of OSA based on different apnea-hypopnea index (AHI) criteria in insomnia patients. The rates were 35% (AHI≥5) and 29% (AHI≥15), respectively. Regional differences of DFA, DMS and EMA in OSA patients may be related to sex, age and body mass index.

15.
Sleep Med ; 56: 128-134, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30852128

RESUMO

OBJECTIVES: To investigate whether baseline electromyography (EMG) activity during rapid eye movement (REM) sleep predicts the development of neurodegenerative diseases over time in patients with idiopathic REM sleep behavior disorder (iRBD). METHODS: A total of 216 patients with polysomnography-confirmed iRBD were recruited from September 1997 to December 2016 with a mean follow-up duration of 5.0 ± 3.7 years (median: 4.0, range: 0.5-19.0). Neurodegenerative diseases were ascertained according to standard diagnostic criteria during follow-up. Time-dependent receiver operating characteristic (ROC) curves were employed to evaluate the dynamic predictive performance of EMG activity over time. Both tonic and phasic EMG activity were dichotomized into 'mild' and 'severe' categories by the ROC curves estimated optimal cut-offs. RESULTS: A total of 58 patients (26.9%) developed neurodegenerative diseases. The predictive performance of tonic EMG activity was stable (area under the curve of approximately 0.68) over time, while the performance of phasic EMG activity was significantly superior to chance only after five years of follow-up. The optimal cut-off for prediction at five years was 15.4% (sensitivity, 0.69; specificity, 0.57) and 7.8% (sensitivity, 0.79; specificity, 0.47) for tonic and phasic EMG activity, respectively. Cox proportional hazards regression analyses further revealed that severe tonic (adjusted HR: 2.76, 95% CI: 1.35-5.62) and phasic EMG activity (adjusted HR: 3.10, 95% CI: 1.10-8.71) were associated with early development of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), respectively. CONCLUSIONS: Tonic but not phasic EMG activity may serve as a stable biomarkers for predicting the progression of neurodegeneration in iRBD.

16.
Sleep Med ; 55: 14-21, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30743205

RESUMO

OBJECTIVE: This prospective cohort study captured the patterns of sleep, sleep-wake activity rhythm, and first-morning urinary melatonin in breast cancer patients undergoing adjuvant chemotherapy. METHODS: Breast cancer patients undergoing adjuvant chemotherapy wore wrist actigraph for 168 h and collected first-morning void urine samples before treatment, during the first, and at the last cycle of chemotherapy. We converted actigraphy data into sleep duration, sleep efficiency, nighttime total wake time, percent rhythm, F-statistic, amplitude, mesor, and acrophase. We then assessed urinary 6-sulfatoxymelatonin (aMT6s) levels. RESULTS: This cohort contained 180 participants. Compared with the baseline, sleep efficiency during the first and last cycle decreased by 10.16% [95% confidence interval (95% CI): 5.85%, 14.47%] and 5.01% (95% CI: 0.50%, 9.53%), respectively. Similarly, percent rhythm decreased by 27.20% (95% CI: 19.95%, 34.45%) during the first cycle and 21.20% (95% CI: 13.52, 28.89) during the last cycle. Taking the baseline as the reference, aMT6s levels during the first and last cycle decreased by 11.27% (95% CI: 0.37%, 22.16%) and 14.74% (95% CI: 2.34, 27.11), respectively. CONCLUSION: The first administration of adjuvant chemotherapy is associated with sleep disturbance and sleep-wake activity rhythm disruption among breast cancer patients, while the disturbance and disruption during the last cycle are less severe; nevertheless, repeated administration of chemotherapy results in progressive impairment of nocturnal melatonin production.

17.
Ann Neurol ; 85(4): 582-592, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30761606

RESUMO

OBJECTIVE: To determine the familial aggregation of idiopathic rapid eye movement sleep behavior disorder (iRBD), neurodegenerative diseases, and related biomarkers. METHODS: A total of 404 and 387 first-degree relatives of 102 patients with iRBD and of 89 controls were recruited, respectively. Among them, 204 and 208 relatives of patients and controls underwent face-to-face clinical assessment, whereas 97 and 75 relatives underwent further video-polysomnographic assessment, respectively. RESULTS: Compared with relatives of controls, relatives of patients demonstrated higher levels of RBD features, including chin tonic electromyography activity (mean = 1.5 ± 7.5 vs 0.3 ± 1.0, p = 0.04) and behavioral events (n [weighted %] = 12 [11.3] vs 2 [1.9], adjusted hazard ratio [aHR] = 7.69, 95% confidence interval [CI] = 1.54-33.33, p = 0.009) during rapid eye movement sleep, probable diagnosis (n [%] = 57 [14.9] vs 20 [4.9], aHR = 3.45, 95% CI = 1.96-6.25, p < 0.001), and definite diagnosis (n [weighted %] = 10 [8.4] vs 2 [1.4], aHR = 5.56, 95% CI = 1.16-25.00, p = 0.03). They also had higher risks of Parkinson disease (3.1% vs 0.5%, aHR = 5.88, 95% CI = 1.37-25.00, p = 0.02), dementia (6.9% vs 2.6%, aHR = 2.44, 95% CI = 1.15-5.26, p = 0.02), constipation (8.3% vs 2.4%, adjusted odds ratio = 4.21, 95% CI = 1.34-13.17, p = 0.01), and motor dysfunction (Movement Disorders Society Unified Parkinson's Disease Rating Scale part III motor score, mean = 1.9 ± 3.2 vs 0.9 ± 2.3, p = 0.002). The unaffected relatives of patients demonstrated a higher likelihood ratio of prodromal Parkinson disease (median [interquartile range] = 0.27 [1.19] vs 0.22 [0.51], p = 0.03). INTERPRETATION: iRBD is familially aggregated from isolated features to full-blown sleep disorder. Relatives of patients carry a higher risk of alpha-synucleinopathy in terms of neurodegenerative diseases and prodromal markers, suggesting a familial aggregation and staging pathology of alpha-synucleinopathy. Ann Neurol 2019;85:582-592.

18.
Sleep ; 42(4)2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30715548

RESUMO

STUDY OBJECTIVES: Insomnia is associated with insulin resistance and type 2 diabetes (T2D) in the general population. However, the associations between insomnia and glycemic control in T2D population are not consistently reported. In this study, we aimed to examine the associations between insomnia and glycemic control, and gender differences in these associations among Hong Kong Chinese patients with T2D. METHODS: This was a cross-sectional study involving T2D patients recruited from the Hong Kong Diabetes Registry between July 2010 and June 2015. Glycemic control was estimated by fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c). Participants with the Insomnia Severity Index score > 14 were considered as having insomnia. RESULTS: A total of 3753 patients were recruited. Compared with patients without insomnia, patients with insomnia had higher levels of FPG and HbA1c. After adjustment for potential confounding factors, insomnia was associated with higher FPG and HbA1c in the entire cohort. There were significant interactions between insomnia and gender for FPG (p = 0.001) and HbA1c (p = 0.025) in the full model. Subgroup analyses found that men with insomnia had higher FPG [8.23 (7.85-8.61) mmol/L versus 7.50 (7.39-7.61) mmol/L, p < 0.001] and HbA1c [7.79 (7.57-8.02)% versus 7.45 (7.39-7.52)%, p = 0.005] than men without insomnia after adjusted for confounding factors, whereas such difference was not observed in women. CONCLUSIONS: T2D patients with insomnia had worse glycemic control than the patients without insomnia. The associations were particularly pronounced in men.

19.
Appl Microbiol Biotechnol ; 103(5): 2263-2275, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30685809

RESUMO

Neomycin, an aminoglycoside antibiotic, is widely used in the livestock husbandry due to its higher antimicrobial activity and availability of feed additives in animals. However, its production yield is relatively low and cannot meet the needs of developing market and clinical application. Here, the entire natural neo cluster was cloned from Streptomyces fradiae CGMCC 4.576 by φBT1 integrase-mediated site-specific recombination. Then, the rational reconstruction of the neo cluster was performed by using λ-Red-mediated PCR targeting for improving neomycin production. In order to coordinate with this attempt, the supplementation of suitable precursors was carried out. The constructed recombinant strain Sf/pKCZ03 has multi-copy of the neo cluster modified by disrupting the negative regulatory gene neoI and replacing the native promoter of the neoE-D with PkasO*. Compared to the yield (1282 mg/L) of Streptomyces fradiae CGMCC 4.576, the engineered strain Sf/pKCZ03 had a 36% enhancement of neomycin production. Quantitative real-time PCR analysis revealed the increased transcription of structural genes (neoE, neoB, neoL, aacC8) and regulatory genes (neoR, neoH) in Sf/pKCZ03. Additionally, under the supplementation of 1 g/L N-acetyl-D-glucosamine and 5 g/L L-glutamine, the yield of engineered strain Sf/pKCZ03 showed 62% and 107% improvements compared to that of the wild-type strain in the original medium, respectively. These findings demonstrated that engineering the antibiotic gene cluster in combination with precursors feeding was an effective approach for strain improvement, and would be potentially extended to other Streptomyces for large-scale production of commercialized antibiotics.


Assuntos
Antibacterianos/biossíntese , Neomicina/biossíntese , Engenharia de Proteínas/métodos , Streptomyces/genética , Streptomyces/metabolismo , Clonagem Molecular/métodos , Testes de Sensibilidade Microbiana , Família Multigênica/genética , Staphylococcus aureus/efeitos dos fármacos
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