The effects of strength,aerobic, and concurrent exercise on skeletal muscle damage in rats

Introduction: In this study we examined oxidative stress and skeletal muscle damage resulting from acute strength, aerobic, or concurrent exercise in rats. Methods: The animals were divided into control (C), strength (SE), aerobic (AE), and combined (CE) exercise groups. They were euthanized at 3 different time‐points (6, 24, and 48 h) after acute exercise. Results: SE exercise rats had increased dichlorofluorescein oxidation at 6 h post‐exercise and decreased superoxide dismutase activity at all time‐points. Glutathione peroxidase activity and sulfhydryl levels were increased in the AE group at 48 h post‐exercise. Serum lactate dehydrogenase activity was increased in the SE and CE groups at 24 h and in the AE group at 48 h. Echo intensity was elevated at 24 h for all groups. Conclusions: Forty‐eight hours was sufficient for complete recovery from oxidative stress and muscle damage in the SE and CE groups, but not in the AE group. Muscle Nerve 50 : 79–86, 2014     

No difference in postoperative complications,pain, and functional outcomes up to 2 years after incidental durotomy in lumbar spinal fusion: a prospective,multi-institutional,propensity-matched analysis of 1,741 patients

BackgroundIncidental durotomies occur in up to 17% of spinal operations. Controversy exists regarding the short- and long-term consequences of durotomies.PurposeThe primary aim of this study was to assess the effect of incidental durotomies on the immediate postoperative complications and patient-reported outcome measures.Study designProspective study.Patient sampleA total of 1,741 patients undergoing index lumbar spine fusion were selected from a multi-institutional prospective data registry.Outcome measuresPatient-reported outcome measures used in this study included back pain (BP-Visual Analog Scale), leg pain (LP-Visual Analog Scale), and Oswestry Disability Index.MethodsA total of 1,741 patients were selected from a multi-institutional prospective data registry, who underwent primary lumbar fusion for low back pain and/or radiculopathy between January 2003 and December 2010. We collected and analyzed data on patient demographics, postoperative complications, back pain, leg pain, and functional disability over 2 years, with risk-adjusted propensity score modeling.ResultsIncidental durotomies occurred in 70 patients (4%). Compared with the control group (n=1,671), there was no significant difference in postoperative infection (p=.32), need for reoperation (p=.85), or symptomatic neurologic damage (p=.66). At 1- and 2-year follow-up, there was no difference in patient-reported outcomes of back pain (BP-Visual Analog Scale), leg pain (LP-Visual Analog Scale), or functional disability (Oswestry Disability Index) (p>.3), with results remaining consistent in the propensity-matched cohort analysis (p>.4).ConclusionWithin the context of an on-going debate on the consequences of incidental durotomy, we found no difference in neurologic symptoms, infection, reoperation, back pain, leg pain, or functional disability over a 2-year follow-up period.     

ASB Clinical Biomechanics Award Paper 2010 Virtual pre-operative reconstruction planning for comminuted articular fractures

Background

Highly comminuted intra-articular fractures are complex and difficult injuries to treat. Once emergent care is rendered, the definitive treatment objective is to restore the original anatomy while minimizing surgically induced trauma. Operations that use limited or percutaneous approaches help preserve tissue vitality, but reduced visibility makes reconstruction more difficult. A pre-operative plan of how comminuted fragments would best be re-positioned to restore anatomy helps in executing a successful reduction.

Methods

In this study, the methods for virtually reconstructing a tibial plafond fracture were developed and applied to clinical cases. Building upon previous benchtop work, novel image analysis techniques and puzzle solving algorithms were developed for clinical application. Specialty image analysis tools were used to segment the fracture fragment geometries from CT data. The original anatomy was then restored by matching fragment native (periosteal and subchondral) bone surfaces to an intact template, generated from the uninjured contralateral limb.

Findings

Virtual reconstructions obtained for ten tibial plafond fracture cases had average alignment errors of 0.39 (0.5 standard deviation) mm. In addition to precise reduction planning, 3D puzzle solutions can help identify articular deformities and bone loss.

Interpretation

The results from this study indicate that 3D puzzle solving provides a powerful new tool for planning the surgical reconstruction of comminuted articular fractures.     

Expanding the taxonomy of the diagnostic criteria for temporomandibular disorders

There is a need to expand the current temporomandibular disorders' (TMDs) classification to include less common but clinically important disorders. The immediate aim was to develop a consensus‐based classification system and associated diagnostic criteria that have clinical and research utility for less common TMDs. The long‐term aim was to establish a foundation, vis‐à‐vis this classification system, that will stimulate data collection, validity testing and further criteria refinement. A working group [members of the International RDC/TMD Consortium Network of the International Association for Dental Research (IADR), members of the Orofacial Pain Special Interest Group (SIG) of the International Association for the Study of Pain (IASP), and members from other professional societies] reviewed disorders for inclusion based on clinical significance, the availability of plausible diagnostic criteria and the ability to operationalise and study the criteria. The disorders were derived from the literature when possible and based on expert opinion as necessary. The expanded TMDs taxonomy was presented for feedback at international meetings. Of 56 disorders considered, 37 were included in the expanded taxonomy and were placed into the following four categories: temporomandibular joint disorders, masticatory muscle disorders, headache disorders and disorders affecting associated structures. Those excluded were extremely uncommon, lacking operationalised diagnostic criteria, not clearly related to TMDs, or not sufficiently distinct from disorders already included within the taxonomy. The expanded TMDs taxonomy offers an integrated approach to clinical diagnosis and provides a framework for further research to operationalise and test the proposed taxonomy and diagnostic criteria.     

Interneuron precursor transplants in adult hippocampus reverse psychosis-relevant features in a mouse model of hippocampal disinhibition

GABAergic interneuron hypofunction is hypothesized to underlie hippocampal dysfunction in schizophrenia. Here, we use the cyclin D2 knockout (Ccnd2^−/−) mouse model to test potential links between hippocampal interneuron deficits and psychosis-relevant neurobehavioral phenotypes. Ccnd2^−/− mice show cortical PV⁺ interneuron reductions, prominently in hippocampus, associated with deficits in synaptic inhibition, increased in vivo spike activity of projection neurons, and increased in vivo basal metabolic activity (assessed with fMRI) in hippocampus. Ccnd2^−/− mice show several neurophysiological and behavioral phenotypes that would be predicted to be produced by hippocampal disinhibition, including increased ventral tegmental area dopamine neuron population activity, behavioral hyperresponsiveness to amphetamine, and impairments in hippocampus-dependent cognition. Remarkably, transplantation of cells from the embryonic medial ganglionic eminence (the major origin of cerebral cortical interneurons) into the adult Ccnd2^−/− caudoventral hippocampus reverses these psychosis-relevant phenotypes. Surviving neurons from these transplants are 97% GABAergic and widely distributed within the hippocampus. Up to 6 mo after the transplants, in vivo hippocampal metabolic activity is lowered, context-dependent learning and memory is improved, and dopamine neuron activity and the behavioral response to amphetamine are normalized. These findings establish functional links between hippocampal GABA interneuron deficits and psychosis-relevant dopaminergic and cognitive phenotypes, and support a rationale for targeting limbic cortical interneuron function in the prevention and treatment of schizophrenia.Precursors of most γ-aminobutyric acid (GABA)-releasing interneurons of the cerebral cortex and the hippocampus originate in the embryonic medial ganglionic eminence (MGE) (1–3). A subpopulation of MGE-derived cells differentiates into fast-spiking, parvalbumin-expressing (PV⁺) interneurons that tightly regulate the activity and synchronization of cortical projection neurons (2, 4). Structural and functional deficits in PV⁺ interneurons are hypothesized as a pathophysiological mechanism in schizophrenia and psychotic disorders (4–6).Although psychotic disorders are clearly heterogeneous in etiology, disinhibition within temporolimbic cortical circuits is postulated as a core pathophysiology underlying positive symptoms (e.g., delusions and hallucinations) and a subset of cognitive disturbances that manifest with psychosis (4, 5, 7). Postmortem studies of brains from individuals with psychotic disorders show reduced molecular markers of the number and/or function of PV⁺ interneurons in the hippocampus (6, 8). Consistent with these observations, basal metabolic activity in the hippocampus, as measured with functional magnetic resonance imaging (fMRI), is increased in schizophrenia, a phenotype that predicts psychosis and positive symptom severity (5, 7). This abnormal resting activity is postulated to underlie abnormal recruitment of hippocampal circuits during cognitive performance (5, 9). Striatal dopamine (DA) release capacity is also increased and correlated with positive symptoms in schizophrenia and its risk states (10, 11). Importantly, hippocampal hyperactivity may contribute to DA dysregulation (12), because rodent studies show that caudoventral hippocampal (in the primate, anterior hippocampal) efferents regulate the activity of DA neurons and medial striatal DA release (13, 14).Thus, converging evidence implicates hippocampal disinhibition in the abnormal striatal DA transmission and cognitive impairment in schizophrenia. However, the role of hippocampal inhibitory interneurons in psychosis-relevant circuitry remains to be established. To this end, we used the cyclin D2 (Ccnd2) knockout mouse model (15), which displays a relatively selective deficit in cortical PV⁺ interneurons, and transplantation of interneuron precursors from the MGE to elucidate relationships between reduced hippocampal GABA interneuron function and multiple psychosis-relevant phenotypes, and to explore a novel treatment strategy for psychosis.     

Panostotic Expansile Bone Disease With Massive Jaw Tumor Formation and a Novel Mutation in the Signal Peptide of RANK

Precise regulation of bone resorption is critical for skeletal homeostasis. We report a 32‐year‐old man with a panostotic expansile bone disease and a massive hemorrhagic mandibular tumor. Originally from Mexico, he was deaf at birth and became bow‐legged during childhood. There was no family history of skeletal disease. Puberty occurred normally, but during adolescence he experienced difficulty straightening his limbs, sustained multiple fractures, and developed a bony tumor on his chin. By age 18 years, all limbs were misshapen. The mandibular mass grew and protruded from the oral cavity, extending to the level of the lower ribs. Other bony defects included a similar maxillary mass and serpentine limbs. Upon referral at age 27 years, biochemical studies showed serum alkaline phosphatase of 1760 U/L (Nl: 29‐111) and other elevated bone turnover markers. Radiography of the limbs showed medullary expansion and cortical thinning with severe bowing. Although the jaw tumors were initially deemed inoperable, mandibular mass excision and staged partial maxillectomy were eventually performed. Tumor histopathology showed curvilinear trabeculae of woven bone on a background of hypocellular fibrous tissue. Fibrous dysplasia of bone was suspected, but there was no mutation in codon 201 of GNAS in samples from blood or tumor. His clinical and radiographic findings, elevated serum markers, and disorganized bone morphology suggested amplified receptor activator of NF‐κB (RANK) signaling, even though his disorder differed from conditions with known constitutive activation of RANK signaling (eg, familial expansile osteolysis). We found a unique 12‐base pair duplication in the signal peptide of TNFRSF11A, the gene that encodes RANK. No exon or splice site mutations were found in the genes encoding RANK ligand or osteoprotegerin. Alendronate followed by pamidronate therapies substantially decreased his serum alkaline phosphatase activity. This unique patient expands the phenotypes and genetic basis of the mendelian disorders of RANK signaling activation. © 2014 American Society for Bone and Mineral Research.