3-month Recovery Period Research Articles

Bilateral treatment of the masseter with botulinum toxin: Consequences for mastication, muscle force and the mandibular condyle.

Clinical use of botulinum neurotoxins (BoNTs) in masticatory muscles is usually bilateral, but most studies on the functional consequences of BoNT treatment have used unilaterally treated animals. To test the hypothesis that bilateral BoNT treatment of the rabbit masseter hampers mastication and to assess its effects on bone density of the mandibular condyles. Ten 5-month-old female rabbits received injections of BoNT into both masseter muscles and nine sham animals received saline. Body weight, incisor bite force during masseter tetany, and surface and fine-wire electromyography (EMG) of the masseter and medial pterygoid muscles were assessed at regular intervals. Half the sample was terminated after 4 weeks and the remainder after 12 weeks. Muscles were weighed and mandibular condyles were scanned with microCT to analyse bone density. BoNT rabbits lost weight and required a soft-food diet. Incisor occlusal force plummeted after BoNT injection and remained lower than the shams. The duration of masticatory cycles was increased in the BoNT rabbits for 5 weeks, with most of the increase due to the adductor burst. Masseteric EMG amplitude began to improve at Week 5, but remained low on the working side throughout the experiment. At the 12-week endpoint, masseter muscles were smaller in the BoNT rabbits. Medial pterygoid muscles did not compensate. Condylar bone density was reduced. Bilateral treatment of the rabbit masseter by BoNT severely affected chewing performance. Even after a 3-month recovery period, deficits remained in bite force, muscle size and condylar bone density.

Evaluation of perinatal exposure of glyphosate and its mixture with 2,4-D and dicamba οn liver redox status in Wistar rats

Wide-scale emergence of glyphosate-resistant weeds has led to an increase in the simultaneous application of herbicide mixtures exacerbated by the introduction of crops tolerant to glyphosate plus dicamba or glyphosate plus 2,4-D. This raises serious concerns regarding the environmental and health risks resulting from increased exposure to a mixture of herbicide active ingredients. We evaluated hepatotoxic effects following perinatal exposure to glyphosate alone or in combination with 2,4-D and dicamba from gestational day-6 until adulthood in Wistar rats. Animals were administered with glyphosate at the European Union (EU) acceptable daily intake (ADI; 0.5 mg/kg bw/day) and no-observed-adverse-effect level (NOAEL; 50 mg/kg bw/day). A mixture of glyphosate with 2,4-D (0.3 mg/kg bw/day) and dicamba (0.02 mg/kg bw/day) with each at their EU ADI was evaluated. Redox status was determined by measuring levels of reduced glutathione, decomposition rate of Η2Ο2, glutathione reductase, glutathione peroxidase, total antioxidant capacity, thiobarbituric reactive substances, and protein carbonyls. Gene expression analysis of Nr1d1, Nr1d2, Clec2g, Ier3, and Gadd45g associated with oxidative damage to DNA, was also performed. Analysis of liver samples showed that exposure to the mixture of the three herbicides induced a marked increase in the concentration of glutathione and malondialdehyde indicative of a disturbance in redox balance. Nevertheless, the effect of increased lipid peroxidation was not discernible following a 3-month recuperation period where animals were withdrawn from pesticide exposure post-weaning. Interestingly, toxic effects caused by prenatal exposure to the glyphosate NOAEL were present after the same 3-month recovery period. No statistically significant changes in the expression of genes linked with genotoxicity were observed. Our findings reinforce the importance of assessing the combined effects of chemical pollutants at doses that are asserted by regulatory agencies to be safe individually.

Changes in interstitial cells and gastric excitability in a mouse model of sleeve gastrectomy.

Obesity is a critical risk factor of several life-threatening diseases and the prevalence in adults has dramatically increased over the past ten years. In the USA the age-adjusted prevalence of obesity in adults was 42.4%, i.e., with a body mass index (BMI, weight (kg)/height (m)2) that exceeds 30 kg/m2. Obese individuals are at the higher risk of obesity-related diseases, co-morbid conditions, lower quality of life, and increased mortality more than those in the normal BMI range i.e., 18.5–24.9 kg/m2. Surgical treatment continues to be the most efficient and scientifically successful treatment for obese patients. Sleeve gastrectomy or vertical sleeve gastrectomy (VSG) is a relatively new gastric procedure to reduce body weight but is now the most popular bariatric operation. To date there have been few studies examining the changes in the cellular components and pacemaker activity that occur in the gastric wall following VSG and whether normal gastric activity recovers following VSG. In the present study we used a murine model to investigate the chronological changes of gastric excitability including electrophysiological, molecular and morphological changes in the gastric musculature following VSG. There is a significant disruption in specialized interstitial cells of Cajal in the gastric antrum following sleeve gastrectomy. This is associated with a loss of gastric pacemaker activity and post-junctional neuroeffector responses. Over a 4-month recovery period there was a gradual return in interstitial cells of Cajal networks, pacemaker activity and neural responses. These data describe for the first time the changes in gastric interstitial cells of Cajal networks, pacemaker activity and neuroeffector responses and the time-dependent recovery of ICC networks and normalization of motor activity and neural responses following VSG.

Expression of Renal Vitamin D and Phosphatonin-Related Genes in a Sheep Model of Osteoporosis.

Simple SummaryOsteoporosis is a significant public health issue around the world, with post-menopausal osteoporosis due to estrogen deficiency resulting in approximately ¾ of cases. Treatment with glucocorticoids is another common cause of osteoporosis in humans. Sheep are a well-established model for osteoporosis in humans. In this study, aged sheep had their ovaries removed (ovariectomy) to simulate estrogen deficiency, and some sheep were also treated with glucocorticoids. The results showed that expression of the gene klotho in the kidney had the most marked difference in ovariectomized sheep treated with glucocorticoids for 2 months followed by a recovery period of 3 months. Klotho is known as the “anti-aging” hormone and is an important regulator of calcium and phosphorus metabolism. It may therefore be involved in the recovery of bone mineral density seen in ovariectomized sheep treated with glucocorticoids for 2 months followed by euthanasia at 5 months. As such, it could be an important treatment target for osteoporosis in humans.Osteoporosis is a significant public health issue around the world, with post-menopausal osteoporosis due to estrogen deficiency resulting in approximately ¾ of cases. In this study, 18 aged Merino ewes were ovariectomized, and 10 were controls. Three of the ovariectomized ewes were treated weekly with 400 mg of methylprednisolone for 5 months and three were treated weekly for 2 months, followed by a 3-month recovery period. At 2 months, five control animals and six ovariectomized animals were euthanized. At 5 months, all the remaining ewes were euthanized. Kidney samples were collected postmortem for qPCR analysis of NPT1, PTH1R, NPT2a, NPT2c, Klotho, FGFR1IIIc, VDR, CYP24A1, CYP27B1, TRPV5, TRPV6, CalD9k, CalD28k, PMCA and NCX1. Ovariectomized sheep had significantly greater VDR expression compared with other groups. Ovariectomized sheep treated with glucocorticoids for 2 months followed by euthanasia at 5 months showed significant differences in TRPV5, CYP24A1 and klotho gene expression compared to other groups. Differences in klotho expression were most marked after adjustment for repeated measures (p = 0.1). Klotho is known as the “anti-aging” hormone and is involved in calcium and phosphorus metabolism. Klotho may be involved in the recovery of bone mineral density in ovariectomized sheep treated with glucocorticoids for 2 months followed by euthanasia at 5 months. Further research on the role of klotho is recommended.

Repairing Volumetric Muscle Loss in the Ovine Peroneus Tertius Following a 6-Month Recovery.

Tissue-engineered skeletal muscle is a promising novel therapy for the treatment of volumetric muscle loss (VML). Our laboratory has developed tissue-engineered skeletal muscle units (SMUs) and engineered neural conduits (ENCs), and modularly scaled them to clinically relevant sizes for the treatment of VML in a large animal (sheep) model. In a previous study, we evaluated the effects of the SMUs and ENCs in treating a 30% VML injury in the ovine peroneus tertius muscle after a 3-month recovery period. The goal of the current study was to expand on our 3-month study and evaluate the SMUs and ENCs in restoring muscle function after a 6-month recovery period. Six months after implantation, we found that the repair groups with the SMU (VML+SMU and VML+SMU+ENC) restored muscle mass to a level that was statistically indistinguishable from the uninjured contralateral muscle. In contrast, the muscle mass in the VML-Only group was significantly less than groups repaired with an SMU. Following the 6-month recovery from VML, the maximum tetanic force was significantly lower for all VML injured groups compared with the uninjured contralateral muscle. However, we did demonstrate the ability of our ENCs to effectively regenerate nerve between the distal stump of the native nerve and the repair site in 14 of the 15 animals studied. Impact Statement Volumetric muscle loss (VML) is a clinically relevant problem for which current treatment options are lacking and for which tissue-engineered skeletal muscle presents a promising novel therapeutic option. However, the fabrication of tissues of clinically relevant sizes is necessary for advancement of the technology to the clinic. This study aimed to evaluate the efficacy of our scaled-up tissue-engineered skeletal muscle to treat VML in a large animal (sheep) model after a 6-month recovery.

Limb Muscle Reinnervation with the Nerve-Muscle-Endplate Grafting Technique: An Anatomical Feasibility Study.

Background Peroneal nerve injuries results in tibialis anterior (TA) muscle paralysis. TA paralysis could cause “foot drop,” a disabling condition that can make walking difficult. As current treatment methods result in poor functional recovery, novel treatment approaches need to be studied. The aim of this study was to explore anatomical feasibility of limb reinnervation with our recently developed nerve-muscle-endplate grafting (NMEG) in the native motor zone (NMZ). Methods As the NMEG-NMZ technique involves in nerves and motor endplates (MEPs), the nerve supply patterns and locations of the MEP bands within the gastrocnemius (GM) and TA muscles of rats were investigated using Sihler's stain and whole-mount acetylcholinesterase (AChE) staining, respectively. Five adult rats underwent TA nerve transaction. The denervated TA was reinnervated by transferring an NMEG pedicle from the ipsilateral lateral GM. At the end of a 3-month recovery period, maximal muscle force was measured to document functional recovery. Results The results showed that the TA was innervated by the deep peroneal nerve. A single MEP band was located obliquely in the middle of the TA. The GM was composed of two neuromuscular compartments, lateral (GM-l) and medial (GM-m), each of which was innervated by a separate nerve branch derived from the tibial nerve and had a vertically positioned MEP band. The locations of MEP bands in the GM and TA muscles and nerve supply patterns demonstrated that an NMEG pedicle can be harvested from the GM-l and implanted into the NMZ within the TA muscle. The NMEG-NMZ pilot study showed that this technique resulted in optimal muscle force recovery. Conclusion NMEG-NMZ surgery is feasible for limb reinnervation. Specifically, the denervated TA caused by peroneal nerve injuries can be reinnervated with a NMEG from the GM-l.

Selective Facial Muscle Activation with Acute and Chronic Multichannel Cuff Electrode Implantation in a Feline Model.

Facial paralysis is a debilitating condition with substantial functional and psychological consequences. This feline-model study evaluates whether facial muscles can be selectively activated in acute and chronic implantation of 16-channel multichannel cuff electrodes (MCE). Two cats underwent acute terminal MCE implantation experiments, 2 underwent chronic MCE implantation in uninjured facial nerves (FN) and tested for 6 months, and 2 underwent chronic MCE implantation experiments after FN transection injury and tested for 3 months. The MCE were wrapped around the main trunk of the skeletonized FN, and data collection consisted of EMG thresholds, amplitudes, and selectivity of muscle activation. In acute experimentation, activation of specific channels (ie, channels 1-3 and 6-8) resulted in selective activation of orbicularis oculi, whereas activation of other channels (ie, channels 4, 5, or 8) led to selective activation of levator auris longus with higher EMG amplitudes. MCE implantation yielded stable and selective facial muscle activation EMG thresholds and amplitudes up to a 5-month period. Modest selective muscle activation was furthermore obtained after a complete transection-reapproximating nerve injury after a 3-month recovery period and implantation reoperation. Chronic implantation of MCE did not lead to fibrosis on histology. Field steering was achieved to activate distinct facial muscles by sending simultaneous subthreshold currents to multiple channels, thus theoretically protecting against nerve damage from chronic electrical stimulation. Our proof-of-concept results show the ability of an MCE, supplemented with field steering, to provide a degree of selective facial muscle stimulation in a feline model, even following nerve regeneration after FN injury. N/A.

Investigating White Matter Tract Microstructural Changes at Six-Twelve Weeks following Mild Traumatic Brain Injury: A Combined Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging Study.

Using diffusion-weighted imaging (DWI), research has demonstrated changes suggestive of damage to white matter tracts (WMT) following mild traumatic brain injury (mTBI). Yet due to the predominant use of the diffusion tensor imaging (DTI) model, which has numerous well-established limitations, it has not yet been possible to clearly examine the nature of changes to WMT microstructure following mTBI. This study used a second DWI-based technique, neurite orientation dispersion and density imaging (NODDI), in combination with DTI to measure microstructural changes within the corpus callosum, three long association and one projection WMTs at 6-12 weeks following mTBI, compared with matched trauma controls (TC). Between-groups differences were identified across all WMT for the DTI metric fractional anisotropy (FA), and the NODDI metrics orientation dispersion index (ODI) and isotropic volume fraction (ISO). No statistically significant between-groups differences were found for other DTI and NODDI metrics. Our study revealed that reduced FA was accompanied by increased ODI, suggesting that mTBI results in reduced coherence of axonal fiber bundles within the studied WMTs. These between-groups differences in WMT microstructure were found at 6-12 weeks post-injury, which suggests that structural recovery is not yet complete towards end of the typical 3-month recovery period.

The Effects of Engineered Skeletal Muscle on Volumetric Muscle Loss in The Tibialis Anterior Of Rat After Three Months In Vivo.

Volumetric muscle loss (VML) is traumatic, degenerative, or surgical loss of skeletal muscle that exceeds the regenerative capacity of the remaining muscle, thus resulting in impaired muscle function. In humans, the loss of 30% or more mass of any one muscle will result in permanent structural and functional loss. Current VML repair treatments are limited by donor site morbidity and graft tissue availability, necessitating alternative muscle graft sources. To address this need, our lab has fabricated tissue-engineered skeletal muscle units (SMUs) for implantation into a 30 % VML model in the tibialis anterior (TA) muscle of rat. Previous results showed that after 28 days in vivo, muscle with a 30% VML repaired with our SMUs produced significantly more force than muscle with acute VML. But repair with our SMU did not fully restore muscle force production to that of native muscle. Thus, we hypothesized that more time for in vivo tissue regeneration would allow for greater force recovery. Therefore, the purpose of this study was to examine the long-term (3-month) effects of our SMUs on a 30% VML repair. We also assessed the effects of reinnervation by redirecting a branch of the peroneal nerve to the repair site. Thirty-nine, 2-month old female F344 rats were separated into a nonsurgical control group (n=5) and four surgical experimental groups (VML Only, n=5; VML+Nerve Redirect, n=6; VML+SMU, n=5; VML+SMU+ Nerve Redirect, n=8). Experimental rats were allowed a 3-month recovery period post-surgery before undergoing in situ force testing of the surgical (left) TA. The left TA of the control animals also underwent in situ force testing. Finally, the surgical (left) and contralateral (right) TAs of the experimental animals, as well as the left TA of the control animals, were explanted for histological analysis. Results for specific force showed that while all groups recovered specific forces similar to that of native muscle, the two SMU groups had significantly higher specific forces, on average, compared to the uninjured control group. Histological staining showed small muscle fibers in the repair site in animals that received an SMU. The average cross-sectional area of the native fibers just outside the area of repair (or the equivalent area in control animals) was not significantly different between groups, indicating that hypertrophy of remaining fibers did not contribute to the recovery of force following the VML. Our results suggest that following a 30% VML of the TA muscle, all surgical groups were able to recover TA mass, maximum tetanic and specific force production. Thus, creating a 30% VML in the TA in a rat model is not enough a sufficient VML to produce the sustained VML seen in humans following similar 30% loss of muscle volume.

Pulsed electromagnetic fields promote repair of focal articular cartilage defects with engineered osteochondral constructs.

Articular cartilage injuries are a common source of joint pain and dysfunction. We hypothesized that pulsed electromagnetic fields (PEMFs) would improve growth and healing of tissue-engineered cartilage grafts in a direction-dependent manner. PEMF stimulation of engineered cartilage constructs was first evaluated in vitro using passaged adult canine chondrocytes embedded in an agarose hydrogel scaffold. PEMF coils oriented parallel to the articular surface induced superior repair stiffness compared to both perpendicular PEMF (p = .026) and control (p = .012). This was correlated with increased glycosaminoglycan deposition in both parallel and perpendicular PEMF orientations compared to control (p = .010 and .028, respectively). Following in vitro optimization, the potential clinical translation of PEMF was evaluated in a preliminary in vivo preclinical adult canine model. Engineered osteochondral constructs (∅ 6 mm × 6 mm thick, devitalized bone base) were cultured to maturity and implanted into focal defects created in the stifle (knee) joint. To assess expedited early repair, animals were assessed after a 3-month recovery period, with microfracture repairs serving as an additional clinical control. In vivo, PEMF led to a greater likelihood of normal chondrocyte (odds ratio [OR]: 2.5, p = .051) and proteoglycan (OR: 5.0, p = .013) histological scores in engineered constructs. Interestingly, engineered constructs outperformed microfracture in clinical scoring, regardless of PEMF treatment (p < .05). Overall, the studies provided evidence that PEMF stimulation enhanced engineered cartilage growth and repair, demonstrating a potential low-cost, low-risk, noninvasive treatment modality for expediting early cartilage repair.

Effects of Long-Term Administration of Gardeniae Fructus on Intra-Abdominal Organs of Rats.

Many recent reports have suggested a possible association between Japanese traditional (Kampo) medicines containing Gardeniae Fructus (GF, the fruit of Gardenia jasminoides J. Ellis) and the mesenteric phlebosclerosis (MP). MP is a chronic orphan disease characterized by venous calcification extending from the colonic wall to the mesentery, usually developing in the proximal colon. In the present study, we administered GF to Wistar/ST female rats as 1% and 2% feed in the diet for 11 months to evaluate any calcification and/or fibrosis of veins in the colonic wall and mesentery. The reversibility of GF's effects was examined by feeding a normal diet for an additional 3 months. A significant decrease in body weight gain and food consumption occurred in the 2% GF group. Pigmentation of the liver, kidney, and spleen in macroscopic or histopathological examination was observed after 11-month administration, which disappeared after the 3-month recovery period. Histopathological findings such as fibrous thickening and calcification of vein walls, characteristic of human MP, were not observed. Fibrosis in the colonic lamina propria was observed in the 2% GF group but not in the 1% GF group during the treatment period, but the incidence as well as grade of this type of fibrosis decreased in the recovery period, suggesting that the effects of GF were reversible. In the present study, chronic GF administration did not result in any venous pathological changes but induced pigmentation in the liver, kidneys, and spleen and moderate fibrosis in the colonic lamina propria, all of which being reversible. Further studies are required to determine the association between GF and MP.

Response of tidal marsh vegetation to pulsed increases in flooding and nitrogen

Worldwide, human activities have modified hydrology and nutrient loading regimes in coastal wetlands. Understanding the interplay between these drivers and subsequent response of wetland plant communities is essential to informing wetland management and restoration efforts. Recent restoration strategies in Louisiana proposes to use sediment diversions from the Mississippi River to build land in adjacent wetlands and reduce the rate of land to open water conversion. In conjunction with sediment delivery, diversions can increase nutrient loads and water levels in the receiving basins. We conducted a greenhouse mesocosm experiment in which we exposed three common tidal freshwater and brackish marsh plants (Panicum hemitomon, Sagittaria lancifolia, and Spartina patens) to two nitrate loading rates [high (35 g N m2 year−1) and low (0.25 g N m2 year−1)], and two flooding treatments (with and without diversion pulsing). Experimental units were set at two different elevations within the treatment tanks to simulate both a healthy and degraded marsh. Plant growth metrics and soil physicochemical properties were measured monthly. Final total biomass was determined at the study’s conclusion. Growth responses differed between species but were not significantly influenced by the treatments. Soil redox potential decreased significantly following the increase in flooding associated with the diversion pulse, but recovered to pre-diversion levels after a 3-month recovery period. Our study suggests short flooding pulses with a recovery period may be key for maintaining healthy marshes, however there remains a need for longer-term empirical studies to understand marsh response to pressures associated with river sediment diversions over time.

Brain findings associated with risperidone in rhesus monkeys: magnetic resonance imaging and pathology perspectives.

Brain changes associated with risperidone, a dopamine-2/serotonin-2 receptor antagonist, have been documented in rats and humans, but not in nonhuman primates. This study characterized brain changes associated with risperidone in nonhuman primates. Rhesus monkeys were orally administered risperidone in a dose-escalation paradigm up to a maximum tolerated dose of 0.5 mg/kg/day for 3 weeks, or 3 months followed by a 3-month recovery period. Transient and fully reversible neurological signs consistent with risperidone pharmacology were observed. The results of a magnetic resonance imaging evaluation after 3 months of treatment and at the end of the 3-month recovery period showed no meaningful changes in the brain. There were no risperidone-related brain weight changes or gross findings. Histomorphological evaluation of brain sections stained with hematoxylin and eosin, ionized calcium binding adaptor molecule 1 (Iba1), and luxol fast blue/cresyl violet double staining showed no notable differences between control and risperidone groups. However, evaluation of the brain after glial fibrillary acidic protein (GFAP) immunohistochemical staining revealed increased staining in the cell bodies and processes of astrocytes in the putamen without apparent alterations in numbers or distribution. The increase in GFAP staining was present after 3 weeks and 3 months of treatment, but no increase in staining was observed after the 3-month recovery period, demonstrating the reversibility of this finding. The reversible increase in GFAP expression was likely an adaptive, non-adverse response of astrocytes, associated with the pharmacology of risperidone. These observations are valuable considerations in the nonclinical risk assessment of new drug candidates for psychiatric disorders.

Examining symptom trajectories that predict worse outcomes in post-CABG patients.

Background:Coronary artery bypass grafting is one of the most common interventional revascularisation procedures used to treat coronary artery disease worldwide. With a wide variability in postoperative cardiac symptoms, identification of symptom trajectories during the 3-month postoperative recovery period may improve clinicians’ abilities to support symptom recovery.Aims:To identify distinct trajectories of cardiac symptoms seen over time in a cohort of patients during the 3-month post-coronary artery bypass grafting period, and determine clinical characteristics associated with different symptom trajectories postoperatively.Methods:A prospective trial used the cardiac symptom survey to determine patient symptoms at baseline prior to surgery, and at 1 week, 6 weeks and 3 months following coronary artery bypass grafting. A latent class growth model and multivariate logistic regression analyses were used.Results:Data were obtained from patients (N=198) undergoing coronary artery bypass grafting in six medical centres of Taiwan, through patient medical records and interviews. Based on their frequency, trajectories were explored for the six most common postoperative symptoms including angina, dyspnoea, fatigue, depression, sleep problems and anxiety. We identified two to three distinct classes of trajectories for each symptom. Age, longer intensive care unit stay, fewer vessels bypassed, off-pump coronary artery bypass grafting, smoking history and lack of regular exercise were associated with worse symptom outcome trends over time.Conclusions:Using this unique trajectories-based research method, we are able to achieve a better understanding of symptom recovery patterns over time among coronary artery bypass grafting patients. Recognising risk factors and potential recovery patterns prior to surgery may allow healthcare providers to deliver targeted discharge planning and individualised care after coronary artery bypass grafting.

Longitudinal Resting State Functional Connectivity Predicts Clinical Outcome in Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) affects about 42 million people worldwide. It is often associated with headache, cognitive deficits, and balance difficulties but rarely shows any abnormalities on conventional computed tomography (CT) or magnetic resonance imaging (MRI). Although in most mTBI patients the symptoms resolve within 3 months, 10-15% of patients continue to exhibit symptoms beyond a year. Also, it is known that there exists a vulnerable period post-injury, when a second injury may exacerbate clinical prognosis. Identifying this vulnerable period may be critical for patient outcome, but very little is known about the neural underpinnings of mTBI and its recovery. In this work, we used advanced functional neuroimaging to study longitudinal changes in functional organization of the brain during the 3-month recovery period post-mTBI. Fractional amplitude of low frequency fluctuations (fALFF) measured from resting state functional MRI (rs-fMRI) was found to be associated with symptom severity score (SSS, r = -0.28, p = 0.002). Decreased fALFF was observed in specific functional networks for patients with higher SSS, and fALFF returned to higher values when the patient recovered (lower SSS). In addition, functional connectivity of the same networks was found to be associated with concurrent SSS, and connectivity immediately after injury (<10 days) was capable of predicting SSS at a later time-point (3 weeks to 3 months, p < 0.05). Specific networks including motor, default-mode, and visual networks were found to be associated with SSS (p < 0.001), and connectivity between these networks predicted 3-month clinical outcome (motor and visual: p < 0.001, default-mode: p < 0.006). Our results suggest that functional connectivity in these networks comprise potential biomarkers for predicting mTBI recovery profiles and clinical outcome.

Staged curative treatment of a complex direct carotid-cavernous fistula with a large arterial defect and an 'oversized' internal carotid artery

This is a case of a high-flow, post-traumatic direct carotid-cavernous fistula with a widened arterial defect and a large-diameter internal carotid artery (ICA). The unique aspect of this case is...

Premorbid IQ Predicts Postconcussive Symptoms in OEF/OIF/OND Veterans with mTBI.

Extant literature has demonstrated that symptoms of postconcussive syndrome (PCS) persist well beyond the expected 3-month post-injury recovery period in a minority of individuals with mild traumatic brain injury (mTBI). Suboptimal performance on validity measures and pre- and post-injury psychosocial stressors - rather than actual mTBI or current cognitive functioning - have been identified as predictors of chronic PCS. Whether premorbid IQ has any influence on chronic PCS has been understudied, in the context of established psychogenic etiologies. The sample included 31 veterans, who underwent mTBI neuropsychological evaluations six or more months post-injury in a VA outpatient neuropsychology clinic. A two-step multiple linear regression was conducted to examine the effects on the outcome variable, PCS (Neurobehavioral Symptom Inventory), of the following predictors: cognitive functioning (Repeatable Battery for the Assessment of Neuropsychological Status; Attention, Immediate Memory, and Delayed Memory Indices), performance validity, depression (Beck Depression Inventory-Second Edition), posttraumatic stress disorder (PTSD Checklist, Civilian Version), quality of sleep (Pittsburgh Sleep Quality Index), pain (Brief Pain Inventory), education, and Premorbid IQ (Wechsler Test of Adult Reading). The overall regression model containing all nine predictor variables was statistically significant. Depression (p < .05) and premorbid IQ (p < .05) were the most salient predictors of chronic PCS; in that lower premorbid IQ and greater endorsed symptoms of depression were associated with higher PCS scores. In Step 2 of the multiple linear regression, the WTAR explained an additional 6.7% of the variance in PCS after controlling for psychosocial stressors and current cognitive ability. The findings support premorbid IQ as a unique and relevant predictor of chronic PCS, with significance variance accounted for beyond education, cognitive functioning, and psychosocial variables. Given the predictive relationship between premorbid IQ and PCS, adapting postconcussive interventions to meet the specific needs of individuals with varying levels of intellect may be important in minimizing ongoing symptomatology.

Altered taste preference and loss of limbic-projecting serotonergic neurons in the dorsal raphe nucleus of chronically epileptic rats

Mood disorders and major depression are frequently comorbid with epilepsy. While the nature of this comorbidity is not fully understood, multiple lines of evidence suggest that changes in serotonin (5-HT) neurotransmission may be an underlying mechanism. In this study, we tested the hypothesis that chronic epilepsy in rats can be associated with loss of 5-HT neurons in the dorsal raphe (DR) nuclear complex, the main source of 5-HT projections to the cerebral cortex, which would help to explain respective behavioral deficits. Epilepsy was induced using the kainate model of status epilepticus in adult Wistar rats. After a 3-month recovery period, all kainate-treated rats that had experienced status epilepticus showed spontaneous seizures and reduced sucrose preference (anhedonia), a core symptom of depression. No changes in the forced swim test were detected. The total numbers of 5-HT immunoreactive cells were estimated in all DR subdivisions of control and epileptic rats. Interestingly, epilepsy-related loss of 5-HT neurons (approximately 35%) was observed only in the interfascicular part of the DR complex, which is known to innervate brain regions involved in depression. These findings support the notion that mental health impairments observed in epilepsy may be related to loss of a specific population of the DR 5-HT neurons projecting to limbic brain areas.

Circadian actigraphic rest–activity rhythms following surgery for endometrial cancer: A prospective, longitudinal study

ObjectiveTo investigate (1) circadian rest–activity rhythm disturbances among endometrial cancer patients as they recover from surgery in comparison to a historical reference group of women with no cancer history and (2) health- and treatment-related predictors of dysregulated rest–activity rhythms in endometrial cancer patients. Methods60 endometrial cancer patients participated in a prospective, longitudinal study with actigraphic assessment at 1week, 1month, and 4months post-surgery. 60 women without cancer from an epidemiological sample completed one actigraphic assessment, acting as a reference group. ResultsOn average, results revealed initial significant rest–activity dysregulation at 1week and 1month post-surgery for the endometrial cancer group and then significant recovery in rest–activity patterns at 4months post-surgery. Similarly, the cancer group had significantly more impaired rhythms than the reference group at 1week post-surgery, but demonstrated comparable rhythms by 4months post-surgery. Among the health- and treatment-related variables examined, obesity and receipt of more invasive surgery were found to predict more impaired rhythms at all time points. Conclusion(s)The current study highlights significant disturbances in rest–activity patterns for endometrial cancer patients initially during surgical recovery followed by improvement in these patterns by 4months post-surgery; however, obese patients and those having more invasive surgery demonstrated more impaired rest–activity patterns throughout the 4-month recovery period. Further research is warranted to understand how more impaired rest–activity patterns relate to health and quality of life outcomes.

Noninvasive brain stimulation for persistent postconcussion symptoms in mild traumatic brain injury.

Mild traumatic brain injury (mTBI) is typically followed by various postconcussive symptoms (PCS), including headache, depression, and cognitive deficits. In 15-25% of cases, PCS persists beyond the usual 3-month recovery period, interfering with activities of daily living and responding poorly to pharmacotherapy. We tested the safety, tolerability, and efficacy of repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) for alleviating PCS. Fifteen eligible patients with mTBI and PCS > 3 months postinjury consented to 20 sessions of rTMS (20 × 5-sec trains; 10 Hz at 110% threshold), with clinical and functional magnetic resonance imaging (fMRI) assessments before and after intervention and clinical assessment at 3-month follow-up. Primary outcomes were tolerability, safety, and efficacy, as measured with the PCS Scale. Secondary outcomes included the Cognitive Symptoms Questionnaire, neuropsychological test performance, and working memory task-associated activity as assessed with fMRI. Twelve patients completed all sessions. Three withdrew because of worsening symptoms or for an unrelated event. Stimulation intensity was increased gradually across sessions, and all subjects tolerated the protocol by the sixth session. Commonly reported side effects among completers were increased headache (n = 3) and greater sleep disturbance (n = 3). Participants also reported positive outcomes such as less sleep disturbance (n = 3), and better mental focus (n = 3). On average, PCS scores declined by 14.6 points (p = 0.009) and fMRI task-related activation peaks in the DLPFC increased after rTMS. rTMS is safe, tolerated by most patients with mTBI, and associated with both a reduction in severity of PCS and an increase in task-related activations in DLPFC. Assessment of this intervention in a randomized, control trial is warranted.