Citations

Omega-3 fatty acids found in fish oil have been suggested to protect against cardiovascular disease, yet underlying mechanisms remain unclear. Despite the well-documented link between mental stress and cardiovascular risk, no study has examined neural cardiovascular reactivity to mental stress after fish oil supplementation. We hypothesized that fish oil would blunt the blood pressure, heart rate (HR), and muscle sympathetic nerve activity (MSNA) responsiveness to mental stress and/or augment limb vasodilation associated with mental stress. Blood pressure, HR, MSNA, forearm vascular conductance (FVC), and calf vascular conductance (CVC) responses were recorded during a 5-min mental stress protocol in 67 nonhypertensive subjects before and after 8 wk of fish oil ( n = 34) or placebo supplementation ( n = 33). Fish oil blunted HR reactivity to mental stress (group × condition × time interactions, P = 0.012) but did not alter blood pressure reactivity to mental stress (interactions, P > 0.05). Fish oil blunted total MSNA reactivity to mental stress (interaction, P = 0.039) but did not alter MSNA burst frequency and burst incidence reactivity (interactions, P > 0.05). Finally, fish oil significantly blunted CVC reactivity to mental stress (interaction, P = 0.013) but did not alter FVC reactivity (interaction, P > 0.05). In conclusion, 8 wk of fish oil supplementation significantly attenuated both HR and total MSNA reactivity to mental stress and elicited a paradoxical blunting of calf vascular conductance. These findings support and extend the growing evidence that fish oil may have positive health benefits regarding neural cardiovascular control in humans.

Traumatic brain injury (TBI) is a global public health epidemic. In the US alone, more than 3 million people sustain a TBI annually. It is one of the most disabling injuries as it may cause motor and sensory deficits and lead to severe cognitive, emotional, and psychosocial impairment, crippling vital areas of higher functioning. Fueled by the recognition of TBI as the “signature injury” in our wounded soldiers in Iraq and Afghanistan, and its often devastating impact on athletes playing contact sports, interest in TBI and TBI research has increased dramatically. Unfortunately, despite increased awareness of its detrimental consequences, there has been little progress in developing effective TBI interventions. Recent evidence, however, strongly indicates that nutritional intervention may provide a unique opportunity to enhance the neuronal repair process after TBI. To date, two omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have the most promising laboratory evidence for their neuro-restorative capacities in TBI. Although both animal models and human studies of brain injuries suggest they may provide benefits, there has been no clinical trial evaluating the effects of n-3 fatty acids on resilience to, or treatment, of TBI. This article reviews the known functions of n-3 fatty acids in the brain and their specific role in the cellular and biochemical pathways underlying neurotraumatic injury. We also highlight recent studies on the therapeutic impact of enhanced omega 3 intake in vivo , and how this may be a particularly promising approach to improving functional outcome in patients with TBI.

The antihypertensive influence of fish oil is controversial, and the mechanisms remain unclear. Because the inverse relation between fish oil and hypertension appears to be partially dependent on the degree of hypertension, we tested the hypothesis that fish oil would elicit more dramatic reductions in mean arterial pressure (MAP) and muscle sympathetic nerve activity (MSNA) in prehypertensive (PHT) compared with normotensive (NT) subjects. Resting MAP, MSNA, and heart rate (HR) were examined before and after 8 wk of fish oil (9 g/day; 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid) or placebo (olive oil; 9 g/day) in 38 NT (19 fish oil; 19 placebo) and 29 PHT (15 fish oil; 14 placebo) volunteers. Fish oil did not alter resting MAP, MSNA, or HR in either NT (80 ± 1 to 80 ± 1 mmHg; 11 ± 2 to 10 ± 1 bursts/min; 71 ± 2 to 71 ± 2 beats/min) or PHT (88 ± 2 to 87 ± 1 mmHg; 11 ± 2 to 10 ± 2 bursts/min; 73 ± 2 to 73 ± 2 beats/min) subjects. When NT and PHT groups were consolidated, analysis of covariance confirmed that pretreatment resting MAP was not associated with changes in MSNA after fish oil. In contrast, pretreatment resting HR was correlated with changes in MSNA ( r = 0.47; P = 0.007) and MAP ( r = 0.42; P < 0.007) after fish oil but not placebo. In conclusion, fish oil did not alter sympathetic neural control in NT or PHT subjects. However, our findings suggest that fish oil is associated with modest sympathoinhibition in individuals with higher resting heart rates, a finding that is consistent with a recent meta-analysis examining the relations among fish oil, HR, and the risk of cardiovascular disease.

Abstract The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05–1.15; P = 3.49 × 10−5] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13–1.31; P = 2.22 × 10−7). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89–1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18–1.33; P = 3.31 × 10−13]. Thus, 19p13.1 is the first triple-negative–specific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways. Cancer Res; 72(7); 1795–803. ©2012 AACR.

Object Contralateral C-7 nerve transfer has been used clinically for more than 20 years. The increased interest in studies of transfer effectiveness at different target muscles, posttransfer cocontraction, and brain plasticity has prompted the need for an animal model. In addition to the conventional electrophysiological, histomorphometric, and biomechanical evaluation modalities, quantitative functional and behavioral evaluation will be crucial in applying this kind of model. The aim of this study was to establish a C-7 transection animal model and quantify the changes in upper-limb joint movement and muscle power. Methods A C-7 nerve transection model was created in Sprague-Dawley rats, the brachial plexus of which resembles the human brachial plexus. The impact of C-7 transection on donor limb function—namely, strength, movement, and coordination—was evaluated in 6 rats. Muscle strength (power reported in g) was measured as a grasping task. The active range of motion (ROM; angle reported in °) of the elbow, wrist, and metacarpophalangeal joints was quantified by computerized video motion analysis. Antiresistance coordinated movement (speed reported in seconds) was assessed by the vertical rope-climbing test. These tests were carried out before surgery and at 2, 4, 6, 8, 10, 14, 21, and 28 days after C-7 transection. Repeated-measures 1-way analysis of variance was applied for statistical analysis. When the overall probability value was < 0.05, the Dunnett multiple-comparison posttest was used to compare postoperative values with preoperative baseline values. Results Immediately after C-7 transection, the mean ± SD grip strength declined from 378.50 ± 20.55 g to 297.77 ± 15.04 g. Active elbow extension was impaired, as shown by a significant decrease of the elbow extension angle. The speed of vertical rope climbing was also reduced. Elbow flexion, wrist flexion and extension, and metacarpophalangeal joint flexion and extension were not impaired. Fast recovery of motor function was observed thereafter. Grip strength, range of active elbow extension, and speed of rope climbing returned to baseline values at postoperative Days 4, 8, and 8, respectively. Conclusions The ROM and muscle strength of the upper limb in rats can be measured quantitatively in studies that simulate clinical situations. Application of these functional evaluation modalities in a C-7 nerve transection rat model confirmed that transection of C-7 causes only temporary functional dysfunction to the donor limb. The results obtained in this animal model mimic those seen in humans who undergo contralateral C-7 nerve harvesting.

Intraneural ganglion cysts have been considered a curiosity for 2 centuries. Based on a unifying articular (synovial) theory, recent evidence has provided a logical explanation for their formation and propagation. The fundamental principle is that of a joint origin and a capsular defect through which synovial fluid escapes following the articular branch, typically into the parent nerve. A stereotypical, reproducible appearance has been characterized that suggests a shared pathogenesis. In the present report the authors will provide a mechanistic explanation that can then be mathematically tested using a preliminary model created by finite element analysis.

Object Intraneural ganglia are nonneoplastic mucinous cysts contained within the epineurium of peripheral nerves. Their pathogenesis has been controversial. Historically, the majority of authors have favored de novo formation (degenerative theory). Because of their rarity, intraneural ganglia affecting the upper limb have been misunderstood. This study was designed to critically analyze the literature and to test the hypothesis that intraneural ganglia of the upper limb act analogously to those in the lower limb, being derived from an articular source (synovial theory). Methods Two patients with digital intraneural cysts were included in the study. An extensive literature review of intraneural ganglia of the upper limb was undertaken to provide the historical basis for the study. Results In both cases, the digital intraneural ganglia were demonstrated to have joint connections; the one patient in whom an articular branch was not appreciated initially had evidence on postoperative MR images of persistence of intraneural cyst after simple decompression was performed. Eighty-six cases of intraneural lesions were identified in varied locations of the upper limb: the most common sites were the ulnar nerve at the elbow and wrist, occurring 38 and 22 times, respectively. Joint connections were present in only 20% of the cases published by other groups. Conclusions The authors believe that the fundamental principles of the unifying articular (synovial) theory (that is, articular branch connections, cyst fluid following a path of least resistance, and the role of pressure fluxes) previously described to explain intraneural ganglia in the lower limb apply to those cases in the upper limb. In their opinion, the joint connection is often not identified because of the cysts' rarity, radiologists' and surgeons' inexperience, and the difficulty visualizing and demonstrating it because of the small size of the cysts. Furthermore, they believe that recurrence (subclinical or clinical) is not only underreported but also predictable after simple decompression that fails to address the articular branch. In contrast, intraneural recurrence can be eliminated with disconnection of the articular branch.

Object The purpose of this study was to determine the incidence of shunt infection in patients with subarachnoid hemorrhage (SAH) after converting an external ventricular drain (EVD) to a ventriculoperitoneal (VP) shunt using the existing EVD site. The second purpose was to assess the risk of shunt malfunction after converting the EVD to a permanent shunt irrespective of the cerebrospinal fluid (CSF) protein and red blood cell (RBC) counts. Methods Data obtained in 80 consecutive adult patients (18 men and 62 women, mean age 60.8 years, range 33–85 years) who underwent direct conversion of an EVD to a VP shunt for post-SAH hydrocephalus between August 2002 and March 2007 were retrospectively reviewed. In each patient, the existing EVD site was used to pass the proximal shunt catheter. In no patient was VP shunt insertion delayed based on preoperative RBC or protein counts. Results The mean period of external ventricular drainage before VP shunt placement was 14.1 days (range 3–45 days). No patient suffered ventriculitis. The mean perioperative CSF protein level was 124 mg/dl (range 17–516 mg/dl). The mean and median perioperative RBC values in CSF were 14,203 RBCs/mm3 and 4600 RBCs/mm3 (range 119–290,000/mm3), respectively. No patient was lost to follow-up. The mean follow-up duration was 24 months (range 2–53 months). Three patients (3.8%) had shunt malfunction related to obstruction of the shunt system after 15 days, 2 months, and 18 months, respectively. There were no shunt-related infections. No patient suffered a clinically significant hemorrhage from ventricular catheter placement after VP shunt insertion. Conclusions In adult patients with aneurysmal SAH, conversion of an EVD to a VP shunt can be safely done using the same EVD site. In this defined patient population, protein and RBC counts in the CSF do not seem to affect shunt survival adversely. Thus, conversion of an EVD to VP shunt should not be delayed because of an elevated protein or RBC count.