Recent research suggests that exercise can be effective in reducing pain in animals and humans with neuropathic pain. To investigate mechanisms in which exercise may improve hyperalgesia associated ...with prediabetes, C57Bl/6 mice were fed either standard chow or a high-fat diet for 12 weeks and were provided access to running wheels (exercised) or without access (sedentary). The high-fat diet induced a number of prediabetic symptoms, including increased weight, blood glucose, and insulin levels. Exercise reduced but did not restore these metabolic abnormalities to normal levels. In addition, mice fed a high-fat diet developed significant cutaneous and visceral hyperalgesia, similar to mice that develop neuropathy associated with diabetes. Finally, a high-fat diet significantly modulated neurotrophin protein expression in peripheral tissues and altered the composition of epidermal innervation. Over time, mice that exercised normalized with regards to their behavioral hypersensitivity, neurotrophin levels, and epidermal innervation. These results confirm that elevated hypersensitivity and associated neuropathic changes can be induced by a high-fat diet and exercise may alleviate these neuropathic symptoms. These findings suggest that exercise intervention could significantly improve aspects of neuropathy and pain associated with obesity and diabetes. Additionally, this work could potentially help clinicians determine those patients who will develop painful versus insensate neuropathy using intraepidermal nerve fiber quantification.
This study examined a cohort of retrieved rotating hinge (RH) total knee arthroplasty implants of four different designs with emphasis on the surface damage observed on the polyethylene components. ...Our purpose was to determine if differences in polyethylene damage existed among the designs, and if those differences could be explained by differences in design characteristics.
Seventy-two RH implants from four manufacturers (DePuy LPS/SROM, Zimmer NexGen, Stryker Howmedica MRH, and Biomet Finn-OSS) removed at the time of revision performed between 2002 and 2017 were identified in our institutional retrieval registry. Damage to the surfaces of the polyethylene was assessed using a subjective grading system and evaluated in multiple zones. Design characteristics that were evaluated included the following: location of the dwell point on the polyethylene component, posterior position of the axle, and amount of hyperextension and rotation allowed by the implant.
There were no differences in total damage scores between the four implant groups (P = .45). The Stryker Howmedica MRH group showed the least backside wear of all implants but significantly more articular-sided wear compared with two of the other three groups. All implants except NexGen showed increased total damage scores in implants revised for mechanical (vs nonmechanical) reasons and in implants with a longer duration of implantation.
No single implant design emerged as superior in terms of minimizing polyethylene wear damage. Polyethylene damage existed in various locations but was not different in severity across designs, suggesting that there is no clear superior RH design that minimizes overall articular surface wear compared with other designs.
To conduct a systematic review of published cardiac risk indices relevant to patients undergoing noncardiac surgery and to provide clinically meaningful recommendations to physicians regarding the ...use of these indices.
A literature search of articles published from January 1, 1999, through December 28, 2018, was conducted in Ovid (MEDLINE), PubMed, Embase, CINAHL, and Web of Science. Publications describing models predicting risk of cardiac complications after noncardiac surgery were included and citation chaining was used to identify additional studies for inclusion.
Eleven risk indices involving 2,910,297 adult patients were included in this analysis. Studies varied in size, population, quality, risk of bias, outcome event definitions, risk factors identified, index outputs, accuracy, and clinical usefulness. Studies considered 6 to 83 variables to develop their models. Among the identified models, the factors with the highest predictiveness for adverse cardiac outcomes included congestive heart failure, type of surgery, creatinine, diabetes, history of stroke or transient ischemic attack, and emergency surgery. Substantial data from the large studies also supports advancing age, American Society of Anesthesiology physical status classification, functional status, and hypertension as additional risks.
The risk indices identified generally fell into two groups - those with higher accuracy for predicting a narrow range of cardiac outcomes and those with lower accuracy for predicting a broader range of cardiac outcomes. Using one index from each group may be the most clinically useful approach. Risk factors identified varied widely among studies. In addition to judicious use of predictive indices, reasoned clinical judgment remains indispensable in assessing perioperative cardiac risk.
Ketogenic diets are emerging as protective interventions in preclinical and clinical models of somatosensory nervous system disorders. Additionally, dysregulation of succinyl-CoA 3-oxoacid ...CoA-transferase 1 (SCOT, encoded by Oxct1), the fate-committing enzyme in mitochondrial ketolysis, has recently been described in Friedreich's ataxia and amyotrophic lateral sclerosis. However, the contribution of ketone metabolism in the normal development and function of the somatosensory nervous system remains poorly characterized. We generated sensory neuron-specific, Advillin-Cre knockout of SCOT (Adv-KO-SCOT) mice and characterized the structure and function of their somatosensory system. We used histological techniques to assess sensory neuronal populations, myelination, and skin and spinal dorsal horn innervation. We also examined cutaneous and proprioceptive sensory behaviors with the von Frey test, radiant heat assay, rotarod, and grid-walk tests. Adv-KO-SCOT mice exhibited myelination deficits, altered morphology of putative Aδ soma from the dorsal root ganglion, reduced cutaneous innervation, and abnormal innervation of the spinal dorsal horn compared to wildtype mice. Synapsin 1-Cre-driven knockout of Oxct1 confirmed deficits in epidermal innervation following a loss of ketone oxidation. Loss of peripheral axonal ketolysis was further associated with proprioceptive deficits, yet Adv-KO-SCOT mice did not exhibit drastically altered cutaneous mechanical and thermal thresholds. Knockout of Oxct1 in peripheral sensory neurons resulted in histological abnormalities and severe proprioceptive deficits in mice. We conclude that ketone metabolism is essential for the development of the somatosensory nervous system. These findings also suggest that decreased ketone oxidation in the somatosensory nervous system may explain the neurological symptoms of Friedreich's ataxia.
•Virtually all dorsal root ganglia neurons express SCOT, which is required for ketone oxidation.•Somatosensory neuronal knockout of SCOT results in reduced cutaneous innervation.•Deficits in neuronal ketone oxidation lead to significant impairment of proprioception.•Loss of axonal ketone oxidation results in myelin abnormalities.
Hematopoietic stem cells (HSCs) reside predominantly in bone marrow, but low numbers of HSCs are also found in peripheral blood. We examined the fate of blood-borne HSCs using genetically marked ...parabiotic mice, which are surgically conjoined and share a common circulation. Parabionts rapidly established stable, functional cross engraftment of partner-derived HSCs and maintained partner-derived hematopoiesis after surgical separation. Determination of the residence time of injected blood-borne progenitor cells suggests that circulating HSCs/progenitors are cleared quickly from the blood. These data demonstrate that HSCs rapidly and constitutively migrate through the blood and play a physiological role in, at least, the functional reengraftment of unconditioned bone marrow.
Osseous disease accounts for over half of chronic pathologies, but there is a limited supply of autografts, the gold standard; hence, there is a demand for new synthetic biomaterials. Herein, we ...present the use of a promising, new dairy-derived biomaterial: whey protein isolate (WPI) in the form of hydrogels, modified with the addition of different concentrations of the biotechnologically produced protein-like polymeric substance poly-γ-glutamic acid (γ-PGA) as a potential scaffold for tissue regeneration. Raman spectroscopic analysis demonstrated the successful creation of WPI-γ-PGA hydrogels. A cytotoxicity assessment using preosteoblastic cells demonstrated that the hydrogels were noncytotoxic and supported cell proliferation from day 3 to 14. All γ-PGA-containing scaffold compositions strongly promoted cell attachment and the formation of dense interconnected cell layers. Cell viability was significantly increased on γ-PGA-containing scaffolds on day 14 compared to WPI control scaffolds. Significantly, the cells showed markers of osteogenic differentiation; they synthesised increasing amounts of collagen over time, and cells showed significantly enhanced alkaline phosphatase activity at day 7 and higher levels of calcium for matrix mineralization at days 14 and 21 on the γ-PGA-containing scaffolds. These results demonstrated the potential of WPI-γ-PGA hydrogels as scaffolds for bone regeneration.
Abstract Background The severity and location of adverse local tissue reaction seen in metal-on-polyethylene (MoP) total hip arthroplasty (THA) is not well described. Methods We retrospectively ...reviewed the records of patients who underwent a revision THA using our biomechanics database. We included all patients who underwent revision surgery for the diagnosis of ALTR with THA implants that had modularity solely at the head-neck junction and excluded patients with implant modularity at sites other than the head-neck junction. Magnetic resonance imaging (MRI) was evaluated by a fellowship trained radiologist who specializes in evaluating metal artifact reducing MRI sequences in order to quantify the ALTR lesions. Histology was evaluated for findings of ALTR using the Campbell score. Results We identified eleven patients in the database. Eight patients had a MRI ALTR grade of severe and seven did based on the histology score. The mean synovial volume was 218,658 mm3 (range 23,461-451,435 mm3) with a mean maximal synovial thickness of 15.3 mm (range 3-34.3 mm). A disruptive infiltration of the abductors due to pseudocapsule invasion was seen in 67% of the patients with three not having abductor involvement. Mean preoperative cobalt and chromium levels were 5.4 ppb (range 1-12.3) and 1.1 ppb (range 0.6-2.4) respectively. Conclusion Patients with ALTR from head-neck junction corrosion in MoP THA may present with large pseudotumors that have previously been under appreciated. Mean preoperative serum cobalt and chromium ion levels remained relatively low, and MRI was an effective way to characterize the size and location of these lesions.
Modular connections in total hip arthroplasty (THA) offer surgical advantages, but can contribute to implant fretting and corrosion due to micromotion at the head–stem interface. Previous studies ...implicated lower flexural rigidity as a key contributing factor to THA corrosion and fretting, but none associated flexural rigidity with direct histological evaluation or magnetic resonance imaging (MRI) outcomes. The purpose of this study was to determine how implant flexural rigidity is associated with MRI imaging metrics and histopathological outcomes in patients who have a failed THA.
Patients requiring revision THA surgery underwent preoperative MRIs with 3-dimensional multispectral imaging techniques to suppress metal artifacts. The MRI images were graded for adverse local tissue reactions. For each hip, trunnion flexural rigidity was measured from the retrieved femoral stem, and a periprosthetic tissue sample was retrieved and evaluated using semiquantitative histology. Generalized linear models and analyses of variance were used to assess associations between flexural rigidity and MRI and histology outcomes.
A total of 106 THA stems were retrieved (46 women and 60 men, age: 68 years (range, 60 to 73 years). After adjustment for length of implantation, flexural rigidity was negatively correlated with histologic aseptic lymphocyte-dominant vasculitis-associated lesion severity (β = −26.27, P = .018), Fujishiro lymphocyte grading (β = −13.4, P = .039), perivascular lymphocyte layers (β = −17.8, P = .022), the grade of tissue organization (β = −22.5, P = .009), the presence of diffuse synovitis (β = −66.5, P = .003), and the presence of lymphoid aggregates (β = −75.9, P = .022). No association was found between MRI metrics and flexural rigidity.
Among these implants, decreased trunnion stiffness was associated with increased histologic features of adverse host-mediated soft tissue reactions.
Mild cognitive impairment (MCI) is common in Parkinson's disease patients. However, its underlying mechanism is not well understood, which has hindered new treatment discoveries specific to MCI. The ...aim of this study was to investigate functional connectivity changes of the caudate nucleus in cognitively impaired Parkinson's patients. We recruited 18 Parkinson's disease patients-10 PDNC normal cognition Parkinson's disease; Montreal Cognitive Assessment (MoCA) ≥ 26, 8 PDLC (low cognition Parkinson's disease; MoCA < 26) -and 10 age-matched healthy controls. All subjects were scanned with resting-state functional magnetic resonance imaging (MRI) and perfusion MRI. We analyzed these data for graph theory metrics and Alzheimer's disease-like pattern score, respectively. A strong positive correlation was found between the functional connectivity of the right caudate nucleus and MoCA scores in Parkinson's patient groups, but not in healthy control subjects. Interestingly, PDNC's functional connectivity of the right caudate was significantly higher than both PDLC and healthy controls, while PDLC and healthy controls were not significantly different from each other. We found that Alzheimer's disease-like metabolic/perfusion pattern score correlated with MoCA scores in healthy controls, but not in Parkinson's disease. Increased caudate connectivity may be related to a compensatory mechanism found in cognitively normal patients with Parkinson's disease. Our findings support and complement the dual syndrome hypothesis.
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