Developing a Brief Neuropsychological Battery for Early Diagnosis of Cognitive Impairment

ObjectivesEarly diagnosis of cognitive impairment is increasingly emphasized in the literature to facilitate timely preventive interventions. Although bedside cognitive tests such as the Montreal Cognitive Assessment (MoCA) are widely used for such early diagnostic purposes, they may not have comparable performance to a full neuropsychological battery (FNB) in diagnosing early cognitive impairment. This study investigated whether a small subset of neuropsychological tests can be added on to MoCA to match its performance to that of the FNB in discriminating mild cognitive impairment and dementia (MCI/dementia) from normal cognition.DesignCross-sectional diagnostic study.SettingAlzheimer's Disease Centers across the United States.ParticipantsOlder participants (≥50 years) who completed MoCA and the FNB (N = 9187).MeasuresThe study sample was split into two: the derivation sample (n = 1837) was used to develop a brief neuropsychological battery that best discriminated MCI/dementia (using the best-subset approach with 10-fold cross-validation); while the validation sample (n = 7350) verified its actual performance in discriminating MCI/dementia.ResultsA 3-item neuropsychological battery was identified, comprising MoCA, Benson Complex Figure Recall, and Craft Story 21 Delayed Recall. It had excellent performance in discriminating MCI/dementia from normal cognition (area under the receiver operating characteristic curve [AUROC] 90.0%, 95% confidence interval [CI] 89.2%-90.7%), which was comparable to that of the FNB (AUROC 88.4%, 95% CI 87.6%-89.2%). By contrast, MoCA alone had significantly worse AUROC (86.9%, 95% CI 86.0%-87.7%) than that of the FNB.Conclusions/ImplicationsUsing rigorous methods, this study developed a brief neuropsychological battery that maintained the brevity of a bedside cognitive test, while rivaling the diagnostic performance of an FNB in early cognitive impairment. This brief battery offers a viable alternative when the FNB is needed but cannot be feasibly administered in nonspecialty clinics. It can have a wider health systems effect of improving patients’ access to accurate diagnosis in early cognitive impairment and facilitating timely interventions to delay the progression of cognitive impairment.     

The effects of d-cycloserine and MK-801 on the performance of rats in two spatial learning and memory tasks

The present study was undertaken to investigate the effects of modulation of the View the MathML source" title="View the MathML source" src="http://binary-services.sciencedirect.com/content/image/1-s2.0-0924977X9580004L-si1.gif"> (NMDA) receptor on learning and memory. Thus, the performance of rats treated with d-cycloserine, a partial agonist at the glycine recognition site of the NMDA receptor complex, and MK-801, a noncompetitive NMDA receptor antagonist, either alone or concurrently were assessed in radial arm maze and water maze tasks. Administration of MK-801 (0.1 mg/kg, i.p.) impaired acquisition in the water maze (increased escape latency and distance) and working memory in the radial arm maze (increased re-entries) in rats. Moreover, in the radial arm maze, MK-801 disrupted locomotion (increased latencies and decreased arm entries per minute) and impaired the acquisition of reference memory (increased number of errors) performance of rats. d-Cycloserine (0.03, 0.3, 1.0, 3.0, 10 mg/kg, i.p.) had no effects on acquisition or memory performance of control or MK-801-treated rats in either of these tasks. However, d-cycloserine (0.03, 0.3, 3.0 mg/kg) reversed the MK-801-induced disruption in locomotion. Furthermore, 3.0 mg/kg d-cycloserine increased behavioral activity and also decreased the time needed to complete the task in control animals. To conclude, our results suggest that the consequences of NMDA receptor modulation on learning and memory processes and sensorimotor functions may be functionally different or have distinct anatomical locations.     

Mast cell degranulation during abdominal surgery initiates postoperative ileus in mice

BACKGROUND & AIMS: Inflammation of the intestinal muscularis following manipulation during surgery plays a crucial role in the pathogenesis of postoperative ileus. Here, we evaluate the role of mast cell activation in the recruitment of infiltrates in a murine model. METHODS: Twenty-four hours after control laparotomy or intestinal manipulation, gastric emptying was determined. Mast cell degranulation was determined by measurement of mast cell protease-I in peritoneal fluid. Intestinal inflammation was assessed by determination of tissue myeloperoxidase activity and histochemical staining. RESULTS: Intestinal manipulation elicited a significant increase in mast cell protease-I levels in peritoneal fluid and resulted in recruitment of inflammatory infiltrates to the intestinal muscularis. This infiltrate was associated with a delay in gastric emptying 24 hours after surgery. Pretreatment with mast cell stabilizers ketotifen (1 mg/kg, p.o.) or doxantrazole (5 mg/kg, i.p.) prevented both manipulation-induced inflammation and gastroparesis. Reciprocally, in vivo exposure of an ileal loop to the mast cell secretagogue compound 48/80 (0.2 mg/mL for 1 minute) induced muscular inflammation and delayed gastric emptying. The manipulation-induced inflammation was dependent on the presence of mast cells because intestinal manipulation in mast cell-deficient Kit/Kitv mice did not elicit significant leukocyte recruitment. Reconstitution of Kit/Kitv mice with cultured bone marrow-derived mast cells from congenic wild types restored the manipulation-induced inflammation. CONCLUSIONS: Our results show that degranulation of connective tissue mast cells is a key event for the establishment of the intestinal infiltrate that mediates postoperative ileus following abdominal surgery.     

产前超声五趾-跖-跟骨足底平面筛查足畸形的价值

目的 探讨产前超声五趾-跖-跟骨足底平面在筛查胎儿足畸形中的价值。方法 连续性选取10 015胎14~40孕周高危胎儿作为研究对象,产前超声检查采用五趾-跖-跟骨足底平面筛查足畸形,并与随访结果进行比较。结果 胎儿足长随孕周增加而增大(F=8.2,P<0.01),单纯先天性马蹄内翻足胎儿的患侧足长变短(χ²=49.1,P <0.01)。五趾-跖-跟骨足底平面超声诊断胎儿足畸形准确率为99.60%(9975/10 015),敏感度为85.29%(116/136),特异度为99.80%(9859/9879),阳性预测值为85.29%(116/136),阴性预测值为99.80%(9859/9879)。结论 五趾-跖-跟骨足底平面可用于胎儿足畸形的产前超声筛查,并可提高诊断水平。     

Brachytherapy: A critical component of primary radiation therapy for cervical cancer: From the Society of Gynecologic Oncology (SGO) and the American Brachytherapy Society (ABS)

Brachytherapy is well-established as an integral component in the standard of care for treatment of patients receiving primary radiotherapy for cervical cancer. A decline in brachytherapy has been associated with negative impacts on survival in the era of modern EBRT techniques. Conformal external beam therapies such intensity modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT) should not be used as alternatives to brachytherapy in patients undergoing primary curative-intent radiation therapy for cervical cancer. Computed tomography or magnetic resonance image-guided adaptive brachytherapy is evolving as the preferred brachytherapy method. With careful care coordination EBRT and brachytherapy can be successfully delivered at different treatment centers without compromising treatment time and outcome in areas where access to brachytherapy maybe limited.     

Metabolic clues regarding the enhanced performance of elite endurance athletes from orchiectomy-induced hormonal changes

This article examines the metabolic performance of an elite cyclist, Lance Armstrong, before and after his diagnosis with testicular cancer. Although a champion cyclist in 1-day events prior to his diagnosis of testicular cancer at age 25, he was not a contender in multi-day endurance cycle races such as the 3-week Tour de France. His genetic makeup and physiology (high VO2max, long femur, strong heavy build) coupled with his ambition and motivation enabled him at an early age to become one of the best 1-day cyclists in the world. Following his cancer diagnosis, he underwent a unilateral orchiectomy, brain surgery and four cycles of chemotherapy. After recovering, he returned to cycling and surprisingly excelled in the Tour de France, winning this hardest of endurance events 7 years running. This dramatic transformation from a 1-day to a 3-week endurance champion has led many to query how this is possible, and under the current climate, has led to suggestions of doping as to the answer to this metamorphosis. Physiological tests following his recovery indicated that physiological parameters such as VO2max were not affected by the unilateral orchiectomy and chemotherapy. We propose that his dramatic improvement in recovery between stages, the most important factor in winning multi-day stage races, is due to his unilateral orchiectomy, a procedure that results in permanent changes in serum hormones. These hormonal changes, specifically an increase in gonadotropins (and prolactin) required to maintain serum testosterone levels, alter fuel metabolism; increasing hormone sensitive lipase expression and activity, promoting increased free fatty acid (FFA) mobilization to, and utilization by, muscles, thereby decreasing the requirement to expend limiting glycogen stores before, during and after exercise. Such hormonal changes also have been associated with ketone body production, improvements in muscle repair and haematocrit levels and may facilitate the loss of body weight, thereby increasing power to weight ratio. Taken together, these hormonal changes act to limit glycogen utilization, delay fatigue and enhance recovery thereby allowing for optimal performances on a day-to-day basis. These insights provide the foundation for future studies on the endocrinology of exercise metabolism, and suggest that Lance Armstrong's athletic advantage was not due to drug use.     

形神及形神一体观的源流考辨

文章通过检索从先秦时期至清代的古代文献,梳理形神字义、形神含义及形神一体观的历史演变过程("鬼魂论"-散在的"形神说"-较系统的"形神观"-形神观与医学有机结合),正本清源,揭示形、神、形神一体的内涵,以期更好地将其运用于医学领域,用以阐发人类生命活动,并指导临床的诊断和防治.