MUSICAL TIMES最新文献

Persons with multiple sclerosis (MS) experience cognitive and physical decline despite more effective disease-modifying therapies (DMTs), and symptomatic treatments currently have limited efficacy. The best treatment of MS disability may, therefore, be prevention of decline. Here, we present a working model of reserve and brain maintenance, with a focus on modifiable risk and protective factors. At disease onset, patients have varying degrees of reserve, broadly conceptualized as the dynamic availability of cerebral resources to support functional capacity. A clinical focus on prevention aims to minimize factors that deplete reserve (e.g. disease burden, comorbidities) and maximize factors that preserve reserve (e.g. DMTs, cardiovascular health). We review evidence for cardiovascular health, diet, and sleep as three potentially important modifiable factors that may modulate cerebral reserve generally, but also in disease-specific ways. We frame the brain as a limited capacity system in which inefficient usage of available cerebral capacity (reserve) leads to or exacerbates functional deficits, and we provide examples of factors that may lead to such inefficiency (e.g. poor mood, obesity, cognitive-motor dual-tasking). Finally, we discuss the challenges and responsibilities of MS neurologists and patients in pursuing comprehensive brain maintenance as a preventive approach.

Introduction: An atrophic dermatofibroma is a benign fibrohistiocytic neoplasm. It typically presents as an asymptomatic patch with a depressed central area.

Methods: The PubMed database was used to search the following words: atrophic, dermatofibroma, elastic and fibers. The relevant papers and their references generated by the search were reviewed. Images of the clinical and pathological features of two patients with an atrophic dermatofibroma are presented. In addition, a comprehensive review of the characteristics of this unique dermatofibroma is provided.

Results: An atrophic dermatofibroma has been reported in 102 patients: 53 women, 11 men and 38 individuals whose gender was not provided. It typically appeared as an asymptomatic solitary patch with a central umbilication-most commonly on the shoulder or lower extremity or back-of women aged 48 years or older. Dermoscopy typically showed white scar-like patches; a patchy pigment network was also noted in some lesions. The pathology of an atrophic dermatofibroma has the same features that can be observed in a common fibrous dermatofibroma; there is acanthosis, basal layer hyperpigmentation, and induction of basal cell carcinoma-like features, hair follicle formation or sebaceous hyperplasia in the epidermis and a proliferation of spindle-shaped fibroblasts in the dermis. However, atrophic dermatofibromas also demonstrate depression of the central surface and thinning of the dermis; in many cases, the dermal atrophy is at least 50%. Elastic fibers are either decreased or absent. Similar to non-atrophic dermatofibromas, the immunoperoxidase profile of atrophic dermatofibromas is factor XIIIa-positive and cluster of differentiation 34 (CD34)-negative. The pathogenesis of atrophic dermatofibromas remains to be established.

Conclusion: An atrophic dermatofibroma is an uncommon benign variant of a dermatofibroma. The diagnosis can be suspected based on clinical features and dermatoscopic findings. A biopsy of the lesion will confirm the diagnosis. Periodic evaluation of the lesion site is a reasonable approach to the management of the residual tumor.

Idiopathic pulmonary fibrosis (IPF), the prototypic progressive fibrotic interstitial lung disease, is thought to be a consequence of repetitive micro-injuries to an ageing, susceptible alveolar epithelium. Ageing is a risk factor for IPF and incidence has been demonstrated to increase with age. Decreased (macro)autophagy with age has been reported extensively in a variety of systems and diseases, including IPF. However, it is undetermined whether the role of faulty autophagy is causal or coincidental in the context of IPF. Here, we report that in alveolar epithelial cells inhibition of autophagy promotes epithelial-mesenchymal transition (EMT), a process implicated in embryonic development, wound healing, cancer metastasis and fibrosis. We further demonstrate that this is attained, at least in part, by increased p62/SQSTM1 expression that promotes p65/RELA mediated-transactivation of an EMT transcription factor, Snail2 (SNAI2), which not only controls EMT but also regulates the production of locally acting profibrogenic mediators. Our data suggest that reduced autophagy induces EMT of alveolar epithelial cells and can contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

Hypercapnia challenge (e.g. inhalation of CO₂) has been used in calibrated fMRI as well as in the mapping of vascular reactivity in cerebrovascular diseases. An important assumption underlying these measurements is that CO₂ is a pure vascular challenge but does not alter neural activity. However, recent reports have suggested that CO₂ inhalation may suppress neural activity and brain metabolic rate. Therefore, the goal of this study is to propose and test a gas challenge that is truly "iso-metabolic," by adding a hypoxic component to the hypercapnic challenge, since hypoxia has been shown to enhance cerebral metabolic rate of oxygen (CMRO₂). Measurement of global CMRO₂ under various gas challenge conditions revealed that, while hypercapnia (P = 0.002) and hypoxia (P = 0.002) individually altered CMRO₂ (by -7.6 ± 1.7% and 16.7 ± 4.1%, respectively), inhalation of hypercapnic-hypoxia gas (5% CO₂/13% O₂) did not change brain metabolism (CMRO₂ change: 1.5 ± 3.9%, P = 0.92). Moreover, cerebral blood flow response to the hypercapnic-hypoxia challenge (in terms of % change per mmHg CO₂ change) was even greater than that to hypercapnia alone (P = 0.007). Findings in this study suggest that hypercapnic-hypoxia gas challenge may be a useful maneuver in physiological MRI as it preserves vasodilatory response yet does not alter brain metabolism.

Background: Evidence of anticancer properties of garlic for different cancer sites has been reported previously in in vitro and in vivo experimental studies but there is limited epidemiologic evidence on the association between garlic and lung cancer.

Methods: We examined the association between raw garlic consumption and lung cancer in a case-control study conducted between 2005 and 2007 in Taiyuan, China. Epidemiologic data was collected by face-to-face interviews from 399 incident lung cancer cases and 466 healthy controls. We used unconditional logistic regression models to estimate crude and adjusted ORs (aOR) and their 95% confidence intervals (CI). Adjusted models controlled for age, sex, average annual household income 10 years ago, smoking, and indoor air pollution.

Results: Compared with no intake, raw garlic intake was associated with lower risk of development of lung cancer with a dose-response pattern (aOR for <2 times/week = 0.56; 95% CI, 0.39-0.81 and aOR for ≥2 times/week = 0.50; 95% CI, 0.34-0.74; Ptrend = 0.0002). Exploratory analysis showed an additive interaction of raw garlic consumption with indoor air pollution and with any supplement use in association with lung cancer.

Conclusions: The results of the current study suggest that raw garlic consumption is associated with reduced risk of lung cancer in a Chinese population.

Impact: This study contributes to the limited research in human population on the association between garlic and lung cancer and advocates further investigation into the use of garlic in chemoprevention of lung cancer. Cancer Epidemiol Biomarkers Prev; 25(4); 624-33. ©2016 AACR.

Background: Several widely used risk scores for cardiovascular disease (CVD) incorporate sex effects, yet there has been no systematic summary of the role of sex in clinical prediction models (CPMs). To better understand the potential of these models to support sex-specific care, we conducted a field synopsis of sex effects in CPMs for CVD.

Methods and results: We identified CPMs in the Tufts Predictive Analytics and Comparative Effectiveness CPM Registry, a comprehensive database of CVD CPMs published from January 1990 to May 2012. We report the proportion of models including sex effects on CVD incidence or prognosis, summarize the directionality of the predictive effects of sex, and explore factors influencing the inclusion of sex. Of 592 CVD-related CPMs, 193 (33%) included sex as a predictor or presented sex-stratified models. Sex effects were included in 78% (53/68) of models predicting incidence of CVD in a general population, versus only 35% (59/171), 21% (12/58), and 17% (12/72) of models predicting outcomes in patients with coronary artery disease, stroke, and heart failure, respectively. Among sex-including CPMs, women with heart failure were at lower mortality risk in 8 of 8 models; women undergoing revascularization for coronary artery disease were at higher mortality risk in 10 of 12 models. Factors associated with the inclusion of sex effects included the number of outcome events and using cohorts at-risk for CVD (rather than with established CVD).

Conclusions: Although CPMs hold promise for supporting sex-specific decision making in CVD clinical care, sex effects are included in only one third of published CPMs.