The mediating role of C-reactive protein and handgrip strength between obesity and walking limitation

OBJECTIVES: To study the association between different obesity indicators and walking limitation and to examine the role of C‐reactive protein (CRP) and handgrip strength in that association. DESIGN: A cross‐sectional, population‐based study. SETTING: The Health 2000 Survey with a representative sample of the Finnish population. PARTICIPANTS: Subjects aged 55 and older with complete data on body composition, CRP, handgrip strength, and walking limitation (N=2,208). MEASUREMENTS: Body composition, anthropometrics, CRP, medical conditions, handgrip strength, and maximal walking speed were measured in the health examination. Walking limitation was defined as maximal walking speed less than 1.2 m/s or difficulty walking half a kilometer. RESULTS: The two highest quartiles of body fat percentage and CRP and the two lowest quartiles of handgrip strength were all significantly associated with greater risk of walking limitation when chronic diseases and other covariates were taken into account. In addition, high CRP and low handgrip strength partially explained the association between high body fat percentage and walking limitation, but the risk of walking limitation remained significantly greater in persons in the two highest quartiles than in those in the lowest quartile of body fat percentage (odds ratio (OR)=1.75, 95% confidence interval (CI)=1.19–2.57 and OR=2.80, 95% CI 1.89–4.16). The prevalence of walking limitation was much higher in persons who simultaneously had high body fat percentage and low handgrip strength (61%) than in those with a combination of low body fat percentage and high handgrip strength (7%). Using body mass index and waist circumference as indicators of obesity yielded similar results as body fat percentage. CONCLUSION: Low‐grade inflammation and muscle strength may partially mediate the association between obesity and walking limitation. Longitudinal studies and intervention trials are needed to verify this pathway.     

信息-动机-行为技巧模型在抑郁症患儿父母健康教育中的应用效果研究

背景　青少年抑郁症常症状不典型,患儿、患儿家属及社会对该病认识普遍不足,难以正确意识疾病危害,即便青少年想要接受治疗,也常受到家属的阻挠,导致无法规范治疗。目的　探究信息-动机-行为技巧模型在抑郁症患儿父母健康教育中的应用效果。方法　选取2018年6-12月在南昌大学第二附属医院心身医学科治疗的90例抑郁症患儿的父母为研究对象。采用随机数字表法将其分为A组（接受常规健康宣教）和B组（接受信息-动机-行为技巧模型指导下健康教育）,各45例。于基线时和干预12周后采用焦虑自评量表、抑郁自评量表、自我感受负担量表调查两组患儿父母负性情绪和自我感受负担,于干预12周后采用自行设计的调查表调查两组患儿父母抑郁症疾病知识掌握情况。结果　基线时,两组焦虑自评量表、抑郁自评量表标准分比较,差异均无统计学意义（P>0.05）;干预12周后,B组焦虑自评量表、抑郁自评量表标准分均低于A组（P<0.05）。两组干预12周后焦虑自评量表、抑郁自评量表标准分均低于基线时（P<0.05）。基线时,两组患儿父母照护体力负担、经济负担、情感负担、家庭负担、社会负担、心理负担得分比较,差异均无统计学意义（P>0.05）;干预12周后,B组患儿父母照护体力负担、经济负担、情感负担、家庭负担、社会负担、心理负担得分均低于A组（P<0.05）。两组干预12周后照护体力负担、经济负担、情感负担、家庭负担、社会负担、心理负担得分均低于基线时（P<0.05）。干预12周后,B组患儿父母疾病知识、家庭管理技术和复诊要求得分均高于A组（P<0.05）。结论　信息-动机-行为技巧模型指导下健康教育能够改善患儿父母负性情绪,减轻其自我感受负担,极大促进患儿父母掌握抑郁症疾病知识,提升抑郁症患儿父母管理技能,优化抑郁症患儿家庭管理方案,有更高的复诊意愿。     

抑郁症自杀行为简易预测模型构建及其预测价值研究

背景　抑郁症作为最常见的心境障碍之一,具有患病率高、复发率高、致残率高和致死率高等特点,给患者造成巨大的疾病负担,甚至出现自杀行为。但是,目前快速筛查抑郁症患者自杀行为的手段相对有限。目的　调查影响抑郁症患者出现自杀行为的心理社会因素,建立抑郁症患者自杀行为简易预测模型,为抑郁症患者自杀防治工作提供参考依据。方法　采用整群抽样方法选择2018年1-12月在南昌大学第二附属医院和南昌大学第一附属医院就诊的抑郁症患者为调查对象,采用一般情况问卷、抑郁自评量表（SDS）、焦虑自评量表（SAS）和Landeiman社会支持量表进行调查,采用多因素Logistic回归分析探讨抑郁症患者出现自杀行为的影响因素,Risk score法构建抑郁症患者自杀行为简易预测模型,并检测其预测效果。结果　共发放问卷2 233份,回收有效问卷2 090份,问卷有效回收率为93.60%。2 090例抑郁症患者中,142例（6.79%）出现自杀行为。经常吸烟、重度饮酒、既往抑郁发作次数≥1次、既往因抑郁症住院次数≥1次、伴焦虑症状、伴精神病性症状、伴自杀意念、有精神障碍家族史、正在用抗抑郁药物、有其他内外科疾病的抑郁症患者自杀行为比例高（P<0.05）。多因素Logistic回归分析结果显示,既往抑郁发作次数≥1次〔OR=4.308,95%CI（3.547,5.232）〕、伴焦虑症状〔OR=2.329,95%CI（1.201,4.518）〕、伴精神病性症状〔OR=2.492,95%CI（1.448,4.287）〕、伴自杀意念〔OR=4.044,95%CI（2.305,7.096）〕、SAS标准分高〔OR=1.036,95%CI（1.003,1.071）〕均是抑郁症患者自杀行为的危险因素（P<0.05）,正在用抗抑郁药物〔OR=0.110,95%CI（0.057,0.212）〕是抑郁症患者自杀行为的保护因素（P<0.05）。基于Logistic回归建立的Risk score预测模型为：Risk score=40.56×既往抑郁发作次数+23.50×伴焦虑症状+25.36×伴精神病性症+38.81×伴自杀意念-61.25×正在用抗抑郁药物+1.00×SAS标准分。按照Risk score预测模型绘制的受试者工作特征曲线（ROC）下面积（AUC）为0.920〔95%CI（0.907,0.931）〕,Youden指数最大时为0.7,截断值为193.23分,灵敏度为76.8%,特异度为94.2%。结论　抑郁症患者自杀行为发生率较高,既往抑郁发作次数≥1次、伴焦虑症状、伴精神病性症状、伴自杀意念、SAS标准分高均为抑郁症患者自杀行为的危险因素。基于Logistic回归建立的Risk score预测模型预测抑郁症患者自杀行为的灵敏度为76.8%,特异度为94.2%。     

Exome sequencing identifies FANCM as a susceptibility gene for triple-negative breast cancer

Inherited predisposition to breast cancer is known to be caused by loss-of-function mutations in BRCA1, BRCA2, PALB2, CHEK2, and other genes involved in DNA repair. However, most families severely affected by breast cancer do not harbor mutations in any of these genes. In Finland, founder mutations have been observed in each of these genes, suggesting that the Finnish population may be an excellent resource for the identification of other such genes. To this end, we carried out exome sequencing of constitutional genomic DNA from 24 breast cancer patients from 11 Finnish breast cancer families. From all rare damaging variants, 22 variants in 21 DNA repair genes were genotyped in 3,166 breast cancer patients, 569 ovarian cancer patients, and 2,090 controls, all from the Helsinki or Tampere regions of Finland. In Fanconi anemia complementation gene M (FANCM), nonsense mutation c.5101C>T (p.Q1701X) was significantly more frequent among breast cancer patients than among controls [odds ratio (OR) = 1.86, 95% CI = 1.26–2.75; P = 0.0018], with particular enrichment among patients with triple-negative breast cancer (TNBC; OR = 3.56, 95% CI = 1.81–6.98, P = 0.0002). In the Helsinki and Tampere regions, respectively, carrier frequencies of FANCM p.Q1701X were 2.9% and 4.0% of breast cancer patients, 5.6% and 6.6% of TNBC patients, 2.2% of ovarian cancer patients (from Helsinki), and 1.4% and 2.5% of controls. These findings identify FANCM as a breast cancer susceptibility gene, mutations in which confer a particularly strong predisposition for TNBC.Breast cancer is the most common cancer affecting women worldwide. It is also the principal cause of death from cancer among women globally, accounting for 14% of all cancer deaths (1). The etiology of breast cancer is multifactorial, and the risk depends on various factors like age, family history, and reproductive, hormonal, or dietary factors. The majority of breast cancers are sporadic, but approximately 15% of cases show familial aggregation (2, 3). Since the identification of the first breast and ovarian cancer susceptibility genes breast cancer 1 and 2 (BRCA1 and BRCA2, respectively) by linkage analysis and positional cloning, several breast cancer susceptibility genes and alleles with different levels of risk and prevalence in the population have been recognized. BRCA1 and BRCA2 mutation carriers have more than 10-fold increased risk of breast cancer compared with women in the general population, and mutations in TP53, PTEN, STK11, and CDH1 have also been associated with a high lifetime risk of breast cancer in the context of rare inherited cancer syndromes (4). In addition, rare variants in genes such as checkpoint kinase 2 (CHEK2), ataxia telangiectasia mutated (ATM), and BRCA1 interacting helicase BRIP1, that confer a two- to fourfold increased risk, and in partner and localizer of BRCA2 (PALB2), with even higher risk estimates, have been found with candidate gene approaches (5, 6), and an increasing number of common low-risk loci with modest odds ratios (ORs; as much as 1.26-fold increased risk for heterozygous carriers) have been identified by genome-wide association studies (7).However, the major portion of hereditary breast cancer still remains unexplained, and many susceptibility loci are yet to be found. Exome sequencing combined with genotyping of the identified variants in case-control analysis is an effective method to recognize novel risk alleles, based on the assumption that disease-causing variants are rare and often accumulate in the protein-coding areas of the genome (8–10).Since the discovery that proteins encoded by the BRCA1 and BRCA2 breast/ovarian cancer susceptibility genes are directly involved in homologous recombination repair of DNA double-strand breaks, it has been evident that other genes involved in DNA repair are attractive breast cancer susceptibility candidates (4). Biallelic mutations in ATM gene cause rare ataxia telangiectasia disease and are associated with an increased risk for breast cancer as a result of improper DNA damage response (11). Fanconi anemia (FA) is a rare genetic disorder caused by biallelic mutations in FA genes that also participate in DNA repair. At least 15 FA genes have been identified (12). Patients with heterozygous mutations in certain FA genes have an elevated risk for various cancers, and monoallelic mutations in at least four of these genes [BRCA2, BRIP1, PALB2, and RAD51 paralog C (RAD51C)] are associated with an increased risk of breast or ovarian cancer (12, 13). Recurrent founder mutations in several cancer susceptibility genes, including the BRCA2, PALB2, and RAD51C FA genes, have been identified in the Finnish population (14–16). The PALB2 and RAD51C founder mutations have been detected at 2% frequency in Finnish breast or ovarian cancer families (15–17), whereas, in other populations, mutations in these genes are rare and often unique for each family. Founder effects in the isolated populations such as Finland or Iceland may enrich certain mutations and thus explain a significant proportion of all mutations in certain genes (18, 19). This provides an advantage in the search for novel susceptibility genes and alleles.In this study, we used exome sequencing to uncover previously unidentified recurrent breast or ovarian cancer predisposing variants in the Finnish population with a focus on DNA repair genes. Selected variants were further genotyped in a large case-control sample set. Our investigation revealed an association of a nonsense mutation (rs147021911) in an FA complementation gene, FANCM, with breast cancer, especially with triple-negative (TN) breast cancer (TNBC).     

Prospective study on burns treated with Integra,a cellulose sponge and split thickness skin graft: Comparative clinical and histological study—Randomized controlled trial

Background

The aim of this study was to compare three different methods to cover excised burn wounds in a randomized controlled trial.

Methods

Fascially excised burn wounds, measuring 10 cm × 5 cm, were covered with Integra^®, split thickness skin graft (STSG), and a viscose cellulose sponge Cellonex™ in each of ten adult patients. Integra^® and Cellonex™ treated areas were covered with thin STSG on day 14. Biopsies were taken 3, 7, 14, and 21 days, 3 months, and 12 months after surgery, and samples were subjected to a range of immunohistochemical stains, in addition to hematoxylin and eosin (HE). Scar assessment was performed 3 and 12 months post-operatively with the Vancouver Scar Scale (VSS).

Results

Inflammation was not substantial in any of the study areas, but Cellonex™ had the most neutrophils, histiocytes, and lymphocytes with significant differences on days 7 and 14. Complete vascularization of Integra^® seemed to occur later compared to the other materials. STSG had the most myofibroblasts on day 14 (p = 0.012). In VSS the quality of the scar improved in all materials from 3 to 12 months.

Conclusions

The final results for all treatments after 12 months demonstrate equal clinical appearance, as well as histological and immunohistochemical findings.     

Ruling Out Myocardial Infarction with Troponin T and Creatine Kinase MB Mass: Diagnostic and Prognostic Aspects

Objective - To investigate the time window for ruling out myocardial infarction (MI) with troponin T (TnT) and creatine kinase isoenzyme MB mass (CK-MBm) and the prognosis of patients with ruled-out MI diagnosis. Design - The study was based on 397 patients admitted with a suspected acute coronary syndrome but with relief of symptoms within 24 h. Results - MI diagnosis was confirmed with elevated TnT (> 0.10 µg/l) in 108 patients, in 91% within 12-24 h from the onset of symptoms, and in 99% within 12 h from admission. In 94 of these patients CK-MBm became elevated (> 5.0 µg/l), in 95% within 10-12 h from the onset of symptoms, and in 99% within 6 h from admission. Among patients with ruled-out MI diagnosis, the 1-year incidence of recurrent coronary events was 29% in those with positive history of coronary heart disease (CHD) but only 7% in those without prior CHD ( p < 0.001). Conclusion - Using TnT or CK-MBm, MI can be ruled out within 12 h from admission in the majority of patients. Among patients with ruled-out MI diagnosis, positive history of CHD is an important determinant of prognosis.