微小染色体维持蛋白5和细胞增殖核抗原在肺癌组织中的表达及其临床意义

目的:检测MCM5蛋白和PCNA在肺癌组织中的表达,探讨两者与肺癌各临床病理因素之间的关系及两者相互的联系,从而为评估肺癌的发生发展、预后及治疗提供理论依据。方法:运用免疫组织化学技术分别检测MCM5蛋白和PCNA在68例肺癌组织和20例正常组织中的表达情况,分析其与临床病理因素之间的关系及两者相互的联系。结果:MCM5表达的阳性信号位于细胞核,胞浆无着色。在正常肺组织中,MCM5的表达局限在上皮基底部的1/3至1/2的细胞,在肺癌组织中,MCM5的表达分布广泛,靠近上皮表面的细胞也可见大量表达。(1)正常肺组织和肺癌组织的MCM5的表达的差别有统计学意义(P<0.01)。(2)肺癌中MCM5表达与分化程度、淋巴结转移有显著相关性(P<0.05),与病人年龄、性别无显著相关性(P>0.05)。(3)PCNA的表达与肺癌的分化程度无显著相关性(P>0.05)。(4)在肺正常组织中,PCNA标记指数高于MCM5标记指数,两者具有显著差异性(P<0.05)。在肺癌组织中,PCNA与MCM5标记指数无显著差异性(P>0.05)。结论:(1)在肺组织中,微小染色体维持蛋白5(MCM5)是一种可靠的细胞增殖标志物。根据MCM5染色的组织结构差异和平均光密度能比较准确区分肺正常组织和癌组织。MCM5表达与肺癌的分化程度显著相关,因此MCM5表达可以提示肺癌的恶性程度,有助于临床判断病人的预后以及选择合适的治疗方法。MCM5与其他增殖标志PCNA相比是一种更好的细胞增殖标志物,是肺癌细胞的更好标志和分级指标。(2)PCNA在肺癌组织中过表达,提示PCNA的过表达与肺癌的发生发展关系密切。     

Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: a double-blind, sham-controlled study

BACKGROUND: Functional neuroimaging studies have shown that specific brain areas are associated with alcohol craving including the dorsolateral prefrontal cortex (DLPFC). We tested whether modulation of DLPFC using transcranial direct current stimulation (tDCS) could alter alcohol craving in patients with alcohol dependence while being exposed to alcohol cues. METHODS: We performed a randomized sham-controlled study in which 13 subjects received sham and active bilateral tDCS delivered to DLPFC (anodal left/cathodal right and anodal right/cathodal left). For sham stimulation, the electrodes were placed at the same positions as in active stimulation; however, the stimulator was turned off after 30s of stimulation. Subjects were presented videos depicting alcohol consumption to increase alcohol craving. RESULTS: Our results showed that both anodal left/cathodal right and anodal right/cathodal left significantly decreased alcohol craving compared to sham stimulation (p<0.0001). In addition, we found that following treatment, craving could not be further increased by alcohol cues. CONCLUSIONS: Our findings showed that tDCS treatment to DLPFC can reduce alcohol craving. These findings extend the results of previous studies using noninvasive brain stimulation to reduce craving in humans. Given the relatively rapid suppressive effect of tDCS and the highly fluctuating nature of alcohol craving, this technique may prove to be a valuable treatment strategy within the clinical setting.     

Successful immune tolerance induction by FVIII in hemophilia A patients with inhibitor may occur without deletion of FVIII‐specific T cells

Summary. Background: The development of an inhibitor is the major complication facing patients with hemophilia A treated by administration of factor (F) VIII concentrates. Restoration of tolerance to FVIII can be achieved by prolonged administration of FVIII (immune tolerance induction, ITI). Although ITI has been used for more than 30 years in patients with hemophilia A and inhibitor, its mechanism of action is still poorly understood. Objectives: As administration of high doses of antigen can induce the apoptosis of the T cells recognizing the antigen, a potential mechanism of action of ITI may be the deletion of FVIII‐specific T cells. Patients/Methods: We studied the CD4+ T‐cell response to FVIII in five (one mild, one moderate and three severe) patients successfully desensitized by administration of FVIII and in control subjects. Results: Following repeated stimulation with autologous dendritic cells loaded with FVIII, FVIII‐specific T oligoclonal cell lines were expanded from the blood of one of the successfully desensitized patients. The FVIII‐specific T cells produced IL‐5, IL‐13 and IL‐2. By contrast, FVIII‐specific T‐cell lines could not be derived from three patients with mild hemophilia A without inhibitor or from four normal control subjects. Conclusions: These data represent the first analysis of the cellular mechanisms regulating the induction of tolerance to FVIII. They demonstrate that successful tolerance induction may occur without deletion of FVIII‐specific T cells.     

Transcranial direct current stimulation of the prefrontal cortex modulates the desire for specific foods

We aimed to assess whether modulation of the dorsolateral prefrontal cortex (DLFPC) with noninvasive brain stimulation, namely transcranial direct current stimulation (tDCS), modifies food craving in healthy subjects. We performed a randomized sham-controlled cross-over study in which 23 subjects received sham and active tDCS (anode left/cathode right and anode right/cathode left) of the DLPFC. Subjects were exposed to food and also watched a movie of food associated with strong craving. Desire for food consumption was evaluated by visual analogue scales (VAS) and food consumption before and after treatment. In addition we measured visual attention to food using an eye tracking system. Craving for viewed foods as indexed by VAS was reduced by anode right/cathode left tDCS. After sham stimulation, exposure to real food or food-related movie increased craving; whereas after anode left/cathode right tDCS, the food-related stimuli did not increase craving levels, as revealed by the VAS scale. Moreover, compared with sham stimulation, subjects fixated food-related pictures less frequently after anode right/cathode left tDCS and consumed less food after both active stimulation conditions. These changes were not related to mood changes after any type of tDCS treatment. The effects of tDCS on food craving might be related to a modulation of neural circuits associated with reward and decision-making.     

Assessing deaf and hearing children's communication in Brazil

In Brazil there are no specific tests for either signed or spoken language for deaf children. A protocol evaluating communicative abilities independent of modality of communication (sign language or spoken language), and comprising assessments of (a) pragmatic profile; (b) modality of communication and linguistic level; (c) complexity of communication; and (d) style and efficacy of communication between parent and child was administered to 127 deaf and hearing children. The children, aged 3-6 years old, were distributed in three groups: 20 with severe hearing loss, 40 with profound hearing loss and 67 normally hearing. Deaf children were found to be delayed, independent of their linguistic level and preferred modality of communication. The protocol in this study proved to be an useful instrument for gathering relevant information about the three groups of preschool children's communicative abilities, and particularly suitable for use in countries where standardized assessments are not available. Learning outcomes: The reader will be introduced to the use of an assessment protocol comprising its development, application and data analysis. The reader will be informed about assessment of deaf children's preferred modality of communication, by the participation of a bilingual (sign language user) professional. Communication abilities can be assessed independently of the linguistic modality. In developing countries in general, where simple and easy to administer assessments tools are scarce, such a protocol is of specific value.     

Text messaging as a new method for injury registration in sports: A methodological study in elite female football

Methodological differences in epidemiologic studies have led to significant discrepancies in injury incidences reported. The aim of this study was to evaluate text messaging as a new method for injury registration in elite female football players and to compare this method with routine medical staff registration. Twelve teams comprising 228 players prospectively recorded injuries and exposure through one competitive football season. Players reported individually by answering three text messages once a week. A designated member of the medical staff conducted concurrent registrations of injuries and exposure. Injuries and exposure were compared between medical staff registrations from nine teams and their 159 affiliated players. During the football season, a total of 232 time‐loss injuries were recorded. Of these, 62% were captured through individual registration only, 10% by the medical staff only, and 28% were reported through both methods. The incidence of training injuries was 3.7 per 1000 player hours when calculated from individual registration vs 2.2 from medical staff registration [rate ratio (RR): 1.7, 1.2–2.4]. For match injuries, the corresponding incidences were 18.6 vs 5.4 (RR: 3.4, 2.4–4.9), respectively. There was moderate agreement for severity classifications in injury cases reported by both methods (kappa correlation coefficient: 0.48, confidence interval: 0.30–0.66).     

Mechanical determinants of early acute ventilatory failure in COPD patients: a physiologic study

Objective  The purpose of this study is to investigate the respiratory mechanics, breathing pattern, and pressure-generating capacity of respiratory muscles during the early phases of an acute exacerbation of COPD. Design  Prospective study. Setting  Division of Emergency Critical Care and Chronic Ventilator Unit. Patients  A total of 24 COPD patients: nine patients requiring ventilatory support because of acute respiratory acidosis due to COPD exacerbation (NPPV group, pH 7.28 ± 0.02); seven patients successfully managed with medical therapy only (SB group, pH 7.39 ± 0.04); eight clinically stable, long term mechanically ventilated, COPD patients (IPPV group). Measurements  Respiratory mechanics during a period of unsupported breathing. Results  A rapid shallow breathing, in the presence of a high drive to breath and a high diaphragmatic tension-time index (TT_di), was found in NPPV and IPPV groups compared to the SB group (f/V _T ratio: 118 ± 43 and 137 ± 65, respectively, versus 37 ± 12 breaths/min/L; P _0.1: 5.0 ± 1.0 and 5.4 ± 1.4, respectively, versus 2.2 ± 0.2 cmH₂O, TT_di: 0.168 ± 0.035 and 0.161 ± 0.039, respectively, versus 0.057 ± 0.033); at variance, PEEPi_dyn was greater in IPPV compared to the other two groups. A significant relationship was observed between TT_di ratio and f/V _T (Rho 0.756). Conclusion  During the early phases of an acute exacerbation, patients with COPD and acute respiratory failure had an imbalance between the decreased capacity of the respiratory muscles to generate pressure and the increased respiratory load. This imbalance was similar to that recorded in patients with COPD and chronic ventilatory failure. In both groups, the imbalance was associated with rapid shallow breathing. Among the mechanical constraints to ventilation, only PEEPi,dyn was different between acute and chronic patients with ventilatory failure. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Participation of older newly-diagnosed cancer patients in an observational prospective pilot study: an example of recruitment and retention

Background  

There have been few prospective observational studies which recruited older newly-diagnosed cancer patients, and of these only some have reported information on the number needed to screen to recruit their study sample, and the number and reasons for refusal and drop-out. This paper reports on strategies to recruit older newly-diagnosed cancer patients prior to treatment into an observational prospective pilot study and to retain them during a six-month period.