137 research outputs found

    Return to Sport after Surgical Treatment of Lisfranc Injuries in Athletes: A Retrospective Case Series

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    Introduction A Lisfranc injury can be a devastating injury in athletes,and if inadequately treated, may lead to chronic pain and lossof function. The purpose of this study was to determine the rate andtime until return to sport after surgical fixation for a ligamentous Lisfrancinjury. We hypothesized that open reduction and screw fixationof a ligamentous Lisfranc injury can be a successful treatment in theathletic population and allow patients to return to sport at close totheir preinjury level of play. Methods All patients who were analyzed underwent repair of aligamentous Lisfranc injury with open reduction and screw fixationby a single surgeon, were between 18 - 40 years old at time of theirfinal follow up, and were identified as being an athlete (either recreationalor competitive). Eligible patients were given a questionnairethat included if they were able to return to sport, time until return tosport, subjective percentage of pre-injury level of play, current pain(0 - 10), and complications. Results Eleven patients were identified as athletes. Ten (91%) wereavailable for follow-up with a mean of 36.5 months (range, 14 - 60).The average age was 25.4 years (range, 15 - 37) at time of surgery.Eighty percent (8/10) were able to return to sport. The average timeuntil return to sport was 29.4 weeks (range, 22 - 52) with an averagesubjective value of their pre-injury level of play of 87% (range, 70 -100%). However, 67% (6/9) of the athletes had occasional pain withsport with an average pain level of 2.1 (range, 0 - 5). Two patientshad complications, a superficial infection and a deep vein thrombosis. Conclusion Most athletes were able to return to sport after undergoingopen reduction and internal fixation of a ligamentous Lisfrancinjury by less than 30 weeks post-surgery with a subjective value of87% of their previous function. However, the majority of the patientsalso experienced some residual pain with their respective sport.These findings suggested that athletes with a ligamentous Lisfrancinjury can have reliably good outcomes with operative repair

    Greater incidence of depression with hypnotic use than with placebo

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    Abstract Background Although it has been claimed that insomnia causes an increased risk for depression, adequate controlled trials testing this hypothesis have not been available. This study contrasted the incidence of depression among subjects receiving hypnotics in randomized controlled trials versus those receiving placebo. Methods The incidence of depression among patients randomized to hypnotic drugs or placebo was compiled from prescribing information approved by the United States Food and Drug Administration (FDA) and from FDA New Drug Application documents. Available data for zolpidem, zaleplon, eszopiclone, and ramelteon were accessed. Results Data for 5535 patients randomized to a hypnotic and for 2318 randomized to placebo were compiled. The incidence of depression was 2.0% among participants randomized to hypnotics as compared to 0.9% among those randomized in parallel to placebo (p Conclusion Modern hypnotics were associated with an increased incidence of depression in data released by the FDA. This suggests that when there is a risk of depression, hypnotics may be contra-indicated. Preventive treatments such as antidepressant drugs, cognitive-behavioral therapy, or bright light might be preferred. Limitations in the FDA data prevented a formal meta-analysis, and there was a lack of information about drop-out rates and definitions of depression. Trials specifically designed to detect incident depression when treating insomnia with hypnotic drugs and better summarization of adverse events in trials submitted to the FDA are both necessary.</p

    Induction of Inflammation by West Nile virus Capsid through the Caspase-9 Apoptotic Pathway

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    West Nile virus (WNV) is a member of the Flaviviridae family of vector-borne pathogens. Clinical signs of WNV infection include neurologic symptoms, limb weakness, and encephalitis, which can result in paralysis or death. We report that the WNV-capsid (Cp) by itself induces rapid nuclear condensation and cell death in tissue culture. Apoptosis is induced through the mitochondrial pathway resulting in caspase-9 activation and downstream caspase-3 activation. Capsid gene delivery into the striatum of mouse brain or interskeletal muscle resulted in cell death and inflammation, likely through capsid-induced apoptosis in vivo. These studies demonstrate that the capsid protein of WNV may be responsible for aspects of viral pathogenesis through induction of the apoptotic cascade

    Public Health Emergency Preparedness and Response Communications with Health Care Providers: A Literature Review

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    <p>Abstract</p> <p>Background</p> <p>Health care providers (HCPs) play an important role in public health emergency preparedness and response (PHEPR) so need to be aware of public health threats and emergencies. To inform HCPs, public health issues PHEPR messages that provide guidelines and updates, and facilitate surveillance so HCPs will recognize and control communicable diseases, prevent excess deaths and mitigate suffering. Public health agencies need to know that the PHEPR messages sent to HCPs reach their target audience and are effective and informative. Public health agencies need to know that the PHEPR messages sent to HCPs reach their target audience and are effective and informative. We conducted a literature review to investigate the systems and tools used by public health to generate PHEPR communications to HCPs, and to identify specific characteristics of message delivery mechanisms and formats that may be associated with effective PHEPR communications.</p> <p>Methods</p> <p>A systematic review of peer- and non-peer-reviewed literature focused on the following questions: 1) What public health systems exist for communicating PHEPR messages from public health agencies to HCPs? 2) Have these systems been evaluated and, if yes, what criteria were used to evaluate these systems? 3) What have these evaluations discovered about characterizations of the most effective ways for public health agencies to communicate PHEPR messages to HCPs?</p> <p>Results</p> <p>We identified 25 systems or tools for communicating PHEPR messages from public health agencies to HCPs. Few articles assessed PHEPR communication systems or messaging methods or outcomes. Only one study compared the effectiveness of the delivery format, device or message itself. We also discovered that the potential is high for HCPs to experience "message overload" given redundancy of PHEPR messaging in multiple formats and/or through different delivery systems.</p> <p>Conclusions</p> <p>We found that detailed descriptions of PHEPR messaging from public health to HCPs are scarce in the literature and, even when available are rarely evaluated in any systematic fashion. To meet present-day and future information needs for emergency preparedness, more attention needs to be given to evaluating the effectiveness of these systems in a scientifically rigorous manner.</p

    Dissection of Hypothalamic-Pituitary-Adrenal Axis Pathology in 1-Month-Abstinent Alcohol-Dependent Men, Part 2: Response to Ovine Corticotropin-Releasing Factor and Naloxone

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    Pituitary and adrenal responsiveness is suppressed in abstinent alcohol-dependent individuals. To clarify the specific organizational disruption in hypothalamic-pituitary-adrenal functioning during early abstinence, the authors separately assessed each level of the stress-response axis. In this second of a two-part study, ovine corticotropin-releasing factor (oCRH) was used to stimulate the pituitary corticotrophs, and naloxone was used to activate the axis at the hypothalamic level. In addition, pulsatile characteristics of corticotropin and cortisol were assessed over a 12-hr period (0800 to 2000 hr). Methods : Eleven abstinent alcohol-dependent men and 10 healthy comparison participants were assessed. All participants were between the ages of 30 and 50 years, and alcohol-dependent patients were abstinent from 4 to 6 weeks. Basal concentrations of corticotropin and cortisol were obtained every 10 min from 0800 to 2000 hr and subjected to pulsatile analysis. Plasma corticotropin and cortisol concentrations were then obtained every 5 to 10 min after low-dose, intravenously administered doses of oCRH (0.4 μg/kg) or naloxone (0.125 mg/kg). Medications were administered at 2000 hr and the two challenge studies were separated by 48 hr. Results : Pulsatile analysis revealed that the mean corticotropin amplitude was increased in alcohol-dependent patients relative to controls ( p < 0.05). Other pulsatile characteristics of corticotropin and all cortisol pulsatile measures were not significantly different between the two groups. The integrated cortisol response to oCRH was significantly lower in alcohol-dependent patients compared with controls ( p < 0.01), but the integrated corticotropin response was not significantly different. In contrast, neither the corticotropin nor the cortisol response to naloxone was significantly different between groups. Conclusions : Adrenocorticoid hyposensitivity persists after oCRH infusion for at least 1 month after cessation of drinking, whereas hyporesponsiveness of the pituitary corticotrophs to CRH seems to resolve with continued abstinence. The authors suggest that adrenocortical hyporesponsiveness during prolonged abstinence may impact relapse risk.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65174/1/01.ALC.0000158939.25531.EE.pd

    Glucose-6-Phosphate Dehydrogenase Protects Escherichia coli from Tellurite-Mediated Oxidative Stress

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    The tellurium oxyanion tellurite induces oxidative stress in most microorganisms. In Escherichia coli, tellurite exposure results in high levels of oxidized proteins and membrane lipid peroxides, inactivation of oxidation-sensitive enzymes and reduced glutathione content. In this work, we show that tellurite-exposed E. coli exhibits transcriptional activation of the zwf gene, encoding glucose 6-phosphate dehydrogenase (G6PDH), which in turn results in augmented synthesis of reduced nicotinamide adenine dinucleotide phosphate (NADPH). Increased zwf transcription under tellurite stress results mainly from reactive oxygen species (ROS) generation and not from a depletion of cellular glutathione. In addition, the observed increase of G6PDH activity was paralleled by accumulation of glucose-6-phosphate (G6P), suggesting a metabolic flux shift toward the pentose phosphate shunt. Upon zwf overexpression, bacterial cells also show increased levels of antioxidant molecules (NADPH, GSH), better-protected oxidation-sensitive enzymes and decreased amounts of oxidized proteins and membrane lipids. These results suggest that by increasing NADPH content, G6PDH plays an important role in E. coli survival under tellurite stress

    Transcriptomics in Interferon-α-Treated Patients Identifies Inflammation-, Neuroplasticity- and Oxidative Stress-Related Signatures as Predictors and Correlates of Depression

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    Owing to the unique opportunity to assess individuals before and after they develop depression within a short timeframe, interferon-α (IFN-α) treatment for chronic hepatitis C virus (HCV) infection is an ideal model to identify molecular mechanisms relevant to major depression, especially in the context of enhanced inflammation. Fifty-eight patients were assessed prospectively, at baseline and monthly over 24 weeks of IFN-α treatment. New-onset cases of depression were determined using the Mini International Neuropsychiatric Interview (MINI). Whole-blood transcriptomic analyses were conducted to investigate the following: (1) baseline gene expression differences associated with future development of IFN-α-induced depression, before IFN-α, and (2) longitudinal gene expression changes from baseline to weeks 4 or 24 of IFN-α treatment, separately in those who did and did not develop depression. Transcriptomics data were analyzed using Partek Genomics Suite (1.4-fold, FDR adjusted pless than or equal to0.05) and Ingenuity Pathway Analysis Software. Twenty patients (34%) developed IFN-α-induced depression. At baseline, 73 genes were differentially expressed in patients who later developed depression compared with those who did not. After 4 weeks of IFN-α treatment, 592 genes were modulated in the whole sample, representing primarily IFN-α-responsive genes. Substantially more genes were modulated only in patients who developed depression (n=506, compared with n=70 in patients who did not), with enrichment in inflammation-, neuroplasticity- and oxidative stress-related pathways. A similar picture was observed at week 24. Our data indicate that patients who develop IFN-α-induced depression have an increased biological sensitivity to IFN-α, as shown by larger gene expression changes, and specific signatures both as predictors and as correlates

    A comparison of low-dose risperidone to paroxetine in the treatment of panic attacks: a randomized, single-blind study

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    <p>Abstract</p> <p>Background</p> <p>Because a large proportion of patients with panic attacks receiving approved pharmacotherapy do not respond or respond poorly to medication, it is important to identify additional therapeutic strategies for the management of panic symptoms. This article describes a randomized, rater-blind study comparing low-dose risperidone to standard-of-care paroxetine for the treatment of panic attacks.</p> <p>Methods</p> <p>Fifty six subjects with a history of panic attacks were randomized to receive either risperidone or paroxetine. The subjects were then followed for eight weeks. Outcome measures included the Panic Disorder Severity Scale (PDSS), the Hamilton Anxiety Scale (Ham-A), the Hamilton Depression Rating Scale (Ham-D), the Sheehan Panic Anxiety Scale-Patient (SPAS-P), and the Clinical Global Impression scale (CGI).</p> <p>Results</p> <p>All subjects demonstrated a reduction in both the frequency and severity of panic attacks regardless of treatment received. Statistically significant improvements in rating scale scores for both groups were identified for the PDSS, the Ham-A, the Ham-D, and the CGI. There was no difference between treatment groups in the improvement in scores on the measures PDSS, Ham-A, Ham-D, and CGI. Post hoc tests suggest that subjects receiving risperidone may have a quicker clinical response than subjects receiving paroxetine.</p> <p>Conclusion</p> <p>We can identify no difference in the efficacy of paroxetine and low-dose risperidone in the treatment of panic attacks. Low-dose risperidone appears to be tolerated equally well as paroxetine. Low-dose risperidone may be an effective treatment for anxiety disorders in which panic attacks are a significant component.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: NCT100457106</p

    In Search of HPA Axis Dysregulation in Child and Adolescent Depression

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    Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis in adults with major depressive disorder is among the most consistent and robust biological findings in psychiatry. Given the importance of the adolescent transition to the development and recurrence of depressive phenomena over the lifespan, it is important to have an integrative perspective on research investigating the various components of HPA axis functioning among depressed young people. The present narrative review synthesizes evidence from the following five categories of studies conducted with children and adolescents: (1) those examining the HPA system’s response to the dexamethasone suppression test (DST); (2) those assessing basal HPA axis functioning; (3) those administering corticotropin-releasing hormone (CRH) challenge; (4) those incorporating psychological probes of the HPA axis; and (5) those examining HPA axis functioning in children of depressed mothers. Evidence is generally consistent with models of developmental psychopathology that hypothesize that atypical HPA axis functioning precedes the emergence of clinical levels of depression and that the HPA axis becomes increasingly dysregulated from child to adult manifestations of depression. Multidisciplinary approaches and longitudinal research designs that extend across development are needed to more clearly and usefully elucidate the role of the HPA axis in depression
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