QEEG Correlates of Auditory-Visual Entrainment Treatment Efficacy of Refractory Depression

Introduction. It is well established that the number of people diagnosed and suffering from depression is on the increase. Many of these patients are not responsive to first-line pharmacological intervention or simply cannot use medications for other reasons. As such, there has been a growing need for nonmedication approaches to treatment. The purpose of this study was to examine the use of auditory-visual EEG entrainment (AVE) at a 14 Hz (beta) frequency to decrease symptoms of depression with corresponding changes in neurophysiology.

Method. Sixteen participants ranged in age from 20 to 67 years and were screened utilizing the Beck Depression Inventory–II (BDI–II) and broken into two groups of 8 (simulated, AVE treatment groups), with a cross-over design. Both groups were given the BDI–II and QEEG testing at baseline, 4 weeks following either AVE or simulated treatment, and then again after an additional 4 weeks and a switch in treatment in the cross-over design.

Results. Results revealed significant reduction of depression only after the 4 weeks on AVE therapy of the BDI–II scores (p > .01). QEEG scores adjusted for normal age deviations demonstrate significant EEG change scores over time in cortical regions associated with mood regulation.

Conclusion. The findings indicate that AVE therapy may be a viable nonmedication therapeutic intervention.     

Seasonal variation of serotonin turnover in human cerebrospinal fluid,depressive symptoms and the role of the 5-HTTLPR

Studying monoaminergic seasonality is likely to improve our understanding of neurobiological mechanisms underlying season-associated physiological and pathophysiological behavior. Studies of monoaminergic seasonality and the influence of the serotonin-transporter-linked polymorphic region (5-HTTLPR) on serotonin seasonality have yielded conflicting results, possibly due to lack of power and absence of multi-year analyses. We aimed to assess the extent of seasonal monoamine turnover and examined the possible involvement of the 5-HTTLPR. To determine the influence of seasonality on monoamine turnover, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured in the cerebrospinal fluid of 479 human subjects collected during a 3-year period. Cosine and non-parametric seasonal modeling were applied to both metabolites. We computed serotonin (5-HT) seasonality values and performed an association analysis with the s/l alleles of the 5-HTTLPR. Depressive symptomatology was assessed using the Beck Depression Inventory-II. Circannual variation in 5-HIAA fitted a spring-peak cosine model that was significantly associated with sampling month (P=0.0074). Season of sampling explained 5.4% (P=1.57 × 10⁻⁷) of the variance in 5-HIAA concentrations. The 5-HTTLPR s-allele was associated with increased 5-HIAA seasonality (standardized regression coefficient=0.12, P=0.020, N=393). 5-HIAA seasonality correlated with depressive symptoms (Spearman''s rho=0.13, P=0.018, N=345). In conclusion, we highlight a dose-dependent association of the 5-HTTLPR with 5-HIAA seasonality and a positive correlation between 5-HIAA seasonality and depressive symptomatology. The presented data set the stage for follow-up in clinical populations with a role for seasonality, such as affective disorders.     

Comparison of conventional and highly-sensitive troponin I measurement in ultra-marathon runners

Cardiac troponins are a mainstay in the diagnostic approach of patients with suspected acute coronary syndrome. Along with other causes of cardiac injury, strenuous aerobic exercise is an important source of troponin leakage from myocardium. Due to recent immunoassays development, there is no information on variation of highly-sensitive (HS) troponin I (TnI) in ultra-marathon runners. We studied 15 healthy trained Caucasian athletes before and immediately after completion of a 60 km, ultra-marathon. TnI was measured with both the conventional AccuTnI and the novel HS-AccuTnI immunoassays. At the end of the ultra-marathon the concentration of HS-AccuTnI significantly increased from the baseline value (19.2 ± 4.2 vs. 5.2 ± 0.8 ng/l; P = 0.001). The number of athletes displaying HS-AccuTnI values exceeding the 99th percentile of the reference limit was 2 (13%) pre-exercise, increasing significantly to 12 (80%; P < 0.001) post-exercise. Measurable value of AccuTnI were found in 1 (7%) and 12 (80%; P < 0.001) athletes pre- and post exercise, respectively. All AccuTnI values were below the 99th percentile reference limit pre-exercise, whereas this cut-off was overcome in 20% of athletes, post-exercise. These results suggest that the myocardium release of TnI during strenuous aerobic exercise mirrors that of troponin T. Moreover, the improved sensitivity of the HS-AccuTnI over the conventional assay makes it more suited for detecting even minor elevations of TnI in blood.     

A systematic review of comparative studies on bone graft alternatives for common spine fusion procedures

Background

The increased prevalence of spinal fusion surgery has created an industry focus on bone graft alternatives. While autologous bone graft remains the gold standard, the complications and morbidity from harvesting autologous bone drives the search for reliable and safe bone graft substitutes. With the recent information about the adverse events related to bone morhogenetic protein use, it is appropriate to review the literature about the numerous products that are not solely bone morphogenetic protein.

Purpose

The purpose of this literature review is to determine the recommendations for use of non-bone morphogenetic protein bone graft alternatives in the most common spine procedures based on a quantifiable grading system.

Study design

Systematic literature review.

Methods

A literature search of MEDLINE (1946–2012), CINAHL (1937–2012), and the Cochrane Central Register of Controlled Trials (1940–April 2012) was performed, and this was supplemented by a hand search. The studies were then evaluated based on the Guyatt criteria for quality of the research to determine the strength of the recommendation.

Results

In this review, more than one hundred various studies on the ability of bone graft substitutes to create solid fusions and good patient outcomes are detailed.

Conclusion

The recommendations for use of bone graft substitutes and bone graft extenders are based on the strength of the studies and given a grade.     

Frequency and Intensity of Postoperative Surveillance After Curative Treatment of Pancreatic Cancer: A Cost-Effectiveness Analysis

Background

Few data exist to guide oncologic surveillance following curative treatment of pancreatic cancer. We sought to identify a rational, cost-effective postoperative surveillance strategy.

Methods

We constructed a Markov model to compare the cost-effectiveness of 5 postoperative surveillance strategies. No scheduled surveillance served as the baseline strategy. Clinical evaluation and carbohydrate antigen (CA) 19-9 testing without/with routine computed tomography and chest X-ray at either 6- or 3-month intervals served as the 4 comparison strategies of increasing intensity. We populated the model with symptom, recurrence, treatment, and survival data from patients who had received intensive surveillance after multimodality treatment at our institution between 1998 and 2008. Costs were based on Medicare payments (2011 US dollars).

Results

The baseline strategy of no scheduled surveillance was associated with a postoperative overall survival (OS) of 24.6 months and a cost of $3837/patient. Clinical evaluation and CA 19-9 assay every 6 months until recurrence was associated with a 32.8-month OS and a cost of $7496/patient, with an incremental cost-effectiveness ratio (ICER) of $5364/life-year (LY). Additional routine imaging every 6 months incrementally increased total cost by $3465 without increasing OS. ICERs associated with clinic visits every 3 months without/with routine imaging were $127,680 and $294,696/LY, respectively. Sensitivity analyses changed the strategies’ absolute costs but not the relative ranks of their ICERs.

Conclusions

Increasing the frequency and intensity of postoperative surveillance of patients after curative therapy for pancreatic cancer beyond clinical evaluation and CA 19-9 testing every 6 months increases cost but confers no clinically significant survival benefit.     

Resistance exercise in chronic heart failure: hemodynamic and metabolic adjustments

The aim of this study was to characterize hemodynamic and metabolic responses to dynamic resistance exercise in chronic heart failure patients (CHF) compared to healthy older men (CTR). We hypothesized that in controlled conditions; pharmacologically treated CHF should show the adaptations to the strength exercises similar to healthy subjects, demonstrating therefore the compatibility with the practical on field. We addressed the acute effects of dynamic resistance exercise in eight CHF patients and eleven age-matched CTRs, instrumented for expiratory gas and cardiovascular analysis. All subjects performed two series with up to twelve repetitions at 70 % of 1RM on a leg press machine. Arterial pressure and heart rate progressively increased throughout the movements and decreased on cessation, while stroke volume (Modelflow software) decreased by 30 % at the start and increased by 10 % at cessation. Cardiac output increased at cessation only. All values were lower in CHF, but the changes during the exercises were not significantly different from those of CTR. Oxygen consumption increased during the exercises and continued increasing thereafter up to 60–70 % V’O_2max (absolute changes were smaller in CHF). We concluded that the response to dynamic resistance exercise is characterized by a sharp hindrance to the output of blood from the heart, which reduces stroke volume and enhances arterial pressure in CHF as well as in CTR. The simultaneous increase in heart rate kept cardiac output unaltered. The most important differences concerned a reduced metabolic response during exercise in CHF, even more evident in rest. Chronic heart failure syndrome and its treatment do not interfere with the cardiovascular responses to these kinds of physical activities. This finding can be considered a step forward in demonstrating that patients with chronic heart failure can, in controlled conditions, safely practice these essential exercises to preserve their muscle integrity.     

Loss of nuclear p21(Cip1/WAF1) during neoplastic progression to metastasis in gamma-irradiated p21 hemizygous mice

p21(Cip1/WAF1) localizes to the nucleus in response to gamma-irradiation induced DNA damage and mediates a G(1) checkpoint arrest. Although gamma-irradiated p21(+/-) mice develop a broad spectrum of tumors, gamma-irradiated p21(-/-) mice develop significantly more metastatic cancers. To evaluate the expression of p21 in tissues prone or resistant to tumorigenesis as a function of gamma-irradiation, and to determine whether phenotypic loss of p21 heterozygosity occurs during tumor progression in p21(+/-) mice, tissues and tumors from gamma-irradiated mice were evaluated immunohistochemically. The percentage of tumors in p21(+/-) mice that were nuclear p21-positive declined with progression to metastasis (p<0.0001). Benign tumors were more often p21-positive and comprised of larger subsets of nuclear p21-positive cells than were malignant tumors of the same histopathological type, while metastatic cancers were nuclear p21-negative (p=0.0003). Even when a primary cancer was comprised of a subset of nuclear p21-positive cells, the metastatic foci of that same cancer were nuclear p21-negative. Mesenchymal tumors, though rare, were more likely metastatic than were epithelial tumors (p=0.0004), and these were invariably nuclear p21-negative. Prepubescent epithelial tissues from which most tumors later originated in mice with reduced p21 gene dosage (i.e., harderian gland, ovary, small intestine, and lung) were p21 expressive within 4 h of gamma-irradiation (p=0.0625), so that p21/Ki67 ratios increased post-gamma-irradiation (p=0.03). In contrast, p21 did not localize to nuclei of cortical thymocytes, a tissue where tumorigenesis was not augmented by reduced p21 gene dosage. Cellular subclones of malignant tumors, especially those of mesenchymal cell origin, which lack nuclear p21 may more readily acquire the genetic alterations of the metastatic phenotype.     

Transient neonatal hemolytic anemia due to the novel gamma globin gene mutation HBG2:C.290T>C,p.Leu97Pro (hemoglobin Wareham)

Unstable gamma globin variants can cause transient neonatal hemolytic anemia. We have identified a novel variant in a newborn who presented with jaundice and anemia requiring phototherapy and red blood cell transfusion. The patient was found to be heterozygous for the mutation HGB2:c.290T>C, p.Leu97Pro, which we have termed hemoglobin (Hb) Wareham. This substitution is expected to generate an unstable hemoglobin with increased oxygen affinity based on the homologous mutation previously described in the beta globin gene, which is termed as Hb Debrousse. The patient fully recovered by 9 months of age as expected with the transition from fetal to adult hemoglobin.