Myositis and Its Mimics: Guideline Updates, MRI Characteristics, and New Horizons.

Myositis is defined as inflammation within skeletal muscle and is a subcategory of myopathy, which is more broadly defined as any disorder affecting skeletal muscle. Myositis may be encountered as a component of autoimmune and connective tissue disease, where it is described as idiopathic inflammatory myopathy. Myositis can also be caused by infections, as well as toxins and drugs, including newer classes of medications. MRI plays an important role in the diagnosis and evaluation of patients with suspected myositis, but many entities may have imaging features similar to myositis and can be considered myositis mimics. These include muscular dystrophies, denervation, deep venous thrombosis, diabetic myonecrosis, muscle injury, heterotopic ossification, and even neoplasms. In patients with suspected myositis, definitive diagnosis may require integrated analysis of imaging findings with clinical, laboratory, and pathology data. The objectives of this article are to review the fundamental features of myositis, including recent updates in terminology and consensus guidelines for idiopathic inflammatory myopathies, the most important MRI differential diagnostic considerations for myositis (i.e., myositis mimics), and new horizons, including the potential importance of artificial intelligence and multimodal integrated diagnostics in the evaluation of patients with muscle disorders.

DIETARY REGULATION OF SILENT SYNAPSES IN THE DORSOLATERAL STRIATUM.

Obesity results in circuit adaptations that closely resemble those induced by drugs of abuse. AMPA-lacking 'silent' synapses are critical in circuit generation during early development, but largely disappear by adulthood. Drugs of abuse increase silent synapses during adulthood and may facilitate the reorganization of brain circuits around drug-related experience, facilitating addiction and relapse Whether obesity causes addiction-related synaptic circuit reorganization via alterations in silent synapse expression has not been examined. Using a dietary-induced obesity paradigm, we show that mice that chronically consumed high-fat diet (HFD) exhibit upregulated silent synapses in both direct and indirect pathway medium spiny neurons in the dorsolateral striatum. Both the onset of silent synapses and their re-silencing after HFD withdrawal occur on an extended time scale of weeks rather than days. Our data suggest that HFD-related silent synapses likely arise from AMPA receptor internalization rather than through de novo synaptogenesis of NR2B-containing NMDA receptors. These data demonstrate that chronic consumption of high-fat diet can alter mechanisms of circuit plasticity, likely facilitating neural reorganization analogous to that observed with drugs of abuse.

Does the presence of macroscopic intralesional fat exclude malignancy? An analysis of 613 histologically proven malignant bone lesions.

OBJECTIVE: To determine if macroscopic intralesional fat detected in bone lesions on CT by Hounsfield unit (HU) measurement and on MRI by macroscopic assessment excludes malignancy. MATERIALS AND METHODS: All consecutive CT-guided core needle biopsies (CNB) of non-spinal bone lesions performed at a tertiary center between December 2005 and September 2021 were reviewed. Demographic and histopathology data were recorded. All cases with malignant histopathology were selected, and imaging studies were reviewed. Two independent readers performed CT HU measurements on all bone lesions using a circular region of interest (ROI) to quantitate intralesional fat density (mean HU < -30). MRI images were reviewed to qualitatively assess for macroscopic intralesional fat signal in a subset of patients. Inter-reader agreement was assessed with Cronbach's alpha and intraclass correlation coefficient. RESULTS: In 613 patients (mean age 62.9 years (range 19-95 years), 47.6% female), CT scans from the CNB of 613 malignant bone lesions were reviewed, and 212 cases had additional MRI images. Only 3 cases (0.5%) demonstrated macroscopic intralesional fat on either CT or MRI. One case demonstrated macroscopic intralesional fat density on CT in a case of metastatic prostate cancer. Two cases demonstrated macroscopic intralesional fat signal on MRI in cases of chondrosarcoma and osteosarcoma. Inter-reader agreement was excellent (Cronbach's alpha, 0.95-0.98; intraclass correlation coefficient, 0.90-0.97). CONCLUSION: Malignant lesions rarely contain macroscopic intralesional fat on CT or MRI. While CT is effective in detecting macroscopic intralesional fat in primarily lytic lesions, MRI may be better for the assessment of heterogenous and infiltrative lesions with mixed lytic and sclerotic components. CLINICAL RELEVANCE STATEMENT: Macroscopic intralesional fat is rarely seen in malignant bone tumors and its presence can help to guide the diagnostic workup of bone lesions. KEY POINTS: • Presence of macroscopic intralesional fat in bone lesions has been widely theorized as a sign of benignity, but there is limited supporting evidence in the literature. • CT and MRI are effective in evaluating for macroscopic intralesional fat in malignant bone lesions with excellent inter-reader agreement. • Macroscopic intralesional fat is rarely seen in malignant bone lesions.

MRI of patellar stabilizers: Anatomic visibility, inter-reader reliability, and intra-reader reproducibility of primary and secondary ligament anatomy.

OBJECTIVE: To compare MRI features of medial and lateral patellar stabilizers in patients with and without patellar instability. METHODS: Retrospective study of 196 patients (mean age, 33.1 ± 18.5 years; 119 women) after diagnosis of patellar instability (cohort-1, acute patellar dislocation; cohort-2, chronic patellar maltracking) or no patellar instability (cohort-3, acute ACL rupture; cohort-4, chronic medial meniscus tear). On MRI, four medial and four lateral stabilizers were evaluated for visibility and injury by three readers independently. Inter- and intra-reader agreement was determined. RESULTS: Medial and lateral patellofemoral ligaments (MPFL and LPFL) were mostly or fully visualized in all cases (100%). Of the secondary patellar stabilizers, the medial patellotibial ligament was mostly or fully visualized in 166 cases (84.7%). Other secondary stabilizers were mostly or fully visualized in only a minority of cases (range, 0.5-32.1%). Injury scores for all four medial stabilizers were higher in patients with acute patellar dislocation than the other 3 cohorts (p < .05). Visibility inter- and intra-reader agreement was good for medial stabilizers (κ 0.61-0.78) and moderate-to-good for lateral stabilizers (κ 0.40-0.72). Injury inter- and intra-reader agreement was moderate-to-excellent for medial stabilizers (κ 0.43-0.90) and poor-to-moderate for lateral stabilizers (κ 0-0.50). CONCLUSION: The MPFL and LPFL were well visualized on MRI while the secondary stabilizers were less frequently visualized. The secondary stabilizers were more frequently visualized medially than laterally, and patellotibial ligaments were more frequently visualized compared to the other secondary stabilizers. Injury to the medial stabilizers was more common with acute patellar dislocation than with chronic patellar maltracking or other knee injuries.

The Impact of Heroin Self-Administration and Environmental Enrichment on Ventral Tegmental CRF1 Receptor Expression.

BACKGROUND: There is a strong link between chronic stress and vulnerability to drug abuse and addiction. Corticotropin releasing factor (CRF) is central to the stress response that contributes to continuation and relapse to heroin abuse. Chronic heroin exposure can exacerbate CRF production, leading to dysregulation of the midbrain CRF-dopamine-glutamate interaction. METHODS: Here we investigated the role of midbrain CRF1 receptors in heroin self-administration and assessed neuroplasticity in CRF1 receptor expression in key opioid addiction brain regions. RESULTS: Infusions of antalarmin (a CRF1 receptor antagonist) into the ventral tegmental area (VTA) dose dependently reduced heroin self-administration in rats but had no impact on food reinforcement or locomotor activity in rats. Using RNAscope in situ hybridization, we found that heroin, but not saline, self-administration upregulated CRF1 receptor mRNA in the VTA, particularly on dopamine neurons. AMPA GluR1 and dopamine reuptake transporter mRNA in VTA neurons were not affected by heroin. The western-blot assay showed that CRF1 receptors were upregulated in the VTA and nucleus accumbens. No significant changes in CRF1 protein expression were detected in the prefrontal cortex, insula, dorsal hippocampus, and substantia nigra. In addition, we found that 15 days of environmental enrichment implemented after heroin self-administration does not reverse upregulation of VTA CRF1 receptor mRNA but it downregulates dopamine transporter mRNA. CONCLUSIONS: Overall, these data suggest that heroin self-administration requires stimulation of VTA CRF1 receptors and upregulates their expression in brain regions involved in reinforcement. Such long-lasting neuroadaptations may contribute to continuation of drug use and relapse due to stress exposure and are not easily reversed by EE exposure.

Environmental enrichment facilitates electric barrier induced heroin abstinence after incubation of craving in male and female rats.

BACKGROUND: Treatment strategies that aim to promote abstinence to heroin use and reduce vulnerability to drug-use resumption are limited in sustainability and long-term efficacy. We have previously shown that environmental enrichment (EE), when implemented after drug self-administration, reduces drug-seeking and promotes abstinence to cocaine and heroin in male rats. Here, we tested the effects of EE on abstinence in an animal conflict model in males and females, and after periods where incubation of craving may occur. METHODS: Male and female rats were trained to self-administer heroin followed by 3 or 21 days of a no-event-interval (NEI). Following NEI, rats were permanently moved to environmental enrichment (EE) or new standard (nEE) housing 3 days prior to resuming self-administration in the presence of an electric barrier adjacent to the drug access lever. Electric barrier current was increased daily until rats ceased self-administration. RESULTS: We found that 21 days of NEI led to significantly greater heroin self-administration and a trend toward shorter latencies to emit the first active lever press in the first abstinence session compared to 3 days of NEI. EE, when compared to nEE, led to longer latencies in the first abstinence session. Also, EE groups of both sexes and in both NEIs achieved abstinence criteria in significantly fewer numbers of sessions. CONCLUSIONS: EE facilitates abstinence in males and females and after periods where incubation of craving may occur. This suggests that EE may benefit individuals attempting to abstain from heroin use and may aid in the development of long term treatment strategies.

Muscarinic and NMDA Receptors in the Substantia Nigra Play a Role in Reward-Related Learning.

BACKGROUND: Reward-related learning, where animals form associations between rewards and stimuli (i.e., conditioned stimuli [CS]) that predict or accompany those rewards, is an essential adaptive function for survival. METHODS: In this study, we investigated the mechanisms underlying the acquisition and performance of conditioned approach learning with a focus on the role of muscarinic acetylcholine (mACh) and NMDA glutamate receptors in the substantia nigra (SN), a brain region implicated in reward and motor processes. RESULTS: Using RNAscope in situ hybridization assays, we found that dopamine neurons of the SN express muscarinic (mACh5), NMDA2a, NMDA2b, and NMDA2d receptor mRNA but not mACh4. NMDA, but not mACh5, receptor mRNA was also found on SN GABA neurons. In a conditioned approach paradigm, rats were exposed to 3 or 7 conditioning sessions during which light/tone (CS) presentations were paired with delivery of food pellets, followed by a test session with CS-only presentations. Intra-SN microinjections of scopolamine (a mACh receptor antagonist) or AP-5 (a NMDA receptor antagonist) were made either prior to each conditioning session (to test their effects on acquisition) or prior to the CS-only test (to test their effects on expression of the learned response). Scopolamine and AP-5 produced dose-dependent significant reductions in the acquisition, but not performance, of conditioned approach. CONCLUSIONS: These results suggest that SN mACh and NMDA receptors are key players in the acquisition, but not the expression, of reward-related learning. Importantly, these findings redefine the role of the SN, which has traditionally been known for its involvement in motor processes, and suggest that the SN possesses attributes consistent with a function as a hub of integration of primary reward and CS signals.

Taurine-Derived Compounds Produce Anxiolytic Effects in Rats Following Developmental Lead Exposure.

Lead (Pb2+) is a developmental neurotoxicant that disrupts the GABA-shift and subsequently causes alterations in the brain's excitation-to-inhibition (E/I) balance. Taurine is a well-established neuroprotective and inhibitory compound for regulating brain excitability. Since mechanistically taurine can facilitate neuronal inhibition through the GABA-AR, the present study examined the anxiolytic potential of taurine derivatives. Treatment groups consisted of the following developmental Pb2+-exposures: Control (0 ppm) and Perinatal (150 ppm or 1,000 ppm lead acetate in the drinking water). Rats were scheduled for behavioral tests between postnatal days (PND) 36-45 with random drug assignments to either saline, taurine, or taurine-derived compound (TD-101, TD-102, or TD-103) to assess the rats' responsivity to each drug in mitigating the developmental Pb2+-exposure and anxiety-like behaviors through the GABAergic system. Long-Evans hooded rats were assessed using an open field (OF) test for preliminary locomotor assessment. Twenty-four hours later, the same rats were exposed to the elevated plus maze (EPM) and were given an i.p. injection of 43 mg/Kg of the saline, taurine, or TD drugs 15 min prior to testing. Each rat was tested using the triple-blind random assignment method for each drug condition. The OF data revealed that Control female rats had increased locomotor activity over Control male rats, and the Pb2+-exposed males and females had increased locomotor activity when compared to the Control male and female rats. However, in the EPM, the Control female rats exhibited more anxiety-like behaviors over Control male rats, and the Pb2+-exposed male and female rats showed selective responsivity to TD drugs when compared to taurine. For Pb2+-exposed males, TD-101 showed consistent recovery of anxiety-like behaviors similar to that of taurine regardless of Pb2+ dose, whereas in Pb2+-exposed females TD-101 and TD-103 showed greater anxiolytic responses in the EPM. The results from the present psychopharmacological study suggests that taurine and its derivatives are interesting drug candidates to explore sex-specific mechanisms and actions of taurine and the associated GABAergic receptor properties by which these compounds alleviate anxiety as a potential behavioral pharmacotherapy for neurodevelopmental Pb2+ exposure.

Distant migration of gluteal augmentation fat presenting as a soft tissue knee mass.

Gluteal augmentation with autologous fat grafting is an increasingly popular procedure. While complication rates are low, the clinical and imaging evaluation of the various complications can be challenging. We report a case of distal migration of a failed gluteal fat graft in a young female patient presenting as a soft tissue mass in the knee, mimicking a soft tissue sarcoma. Surgical resection of the migrated fat graft confirmed the diagnosis. The diagnosis was challenging as the patient was initially reluctant to disclose her surgical history due to perceived negative social stigmas related to cosmetic contouring procedures. This case highlights the imaging findings of a rare complication following autologous fat grafting for gluteal augmentation and the importance of obtaining a thorough medical history.

Environmental enrichment reduces heroin seeking following incubation of craving in both male and female rats.

BACKGROUND: Contemporary treatments for heroin use disorder demonstrate only limited efficacy when the goals are long term abstinence and prevention of relapse. We have demonstrated that environmental enrichment (EE) reduces cue-induced heroin reinstatement in male rats. The present study is an attempt to extend the "anti-relapse" effects of EE to female rats and to periods where incubation of craving is hypothesized to occur. METHODS: This experiment implemented a 3-phase procedure. In Phase 1, male and female rats were trained to self-administer heroin for 15 days. Phase 2 consisted of a 3- or 15-day forced abstinence (FA) period. In Phase 3 half of the rats were placed into EE and the other half in non-EE housing and subsequently tested for responding in extinction (no heroin or cues) for 15 days followed by a cue-induced reinstatement test. RESULTS: We found that rats in the 15 days FA condition showed significantly enhanced drug seeking during extinction, irrespective of sex. We also found that EE significantly reduced this effect. During reinstatement, EE significantly reduced drug seeking in male and female rats and in both 3- and 15-day FA groups. CONCLUSIONS: EE, with or without prolonged FA, effectively reduced heroin seeking in male and female rats. These findings indicate that EE can reduce drug-seeking in males and females and when putative incubation of craving (i.e., prolonged abstinence period) has occurred and suggest that it may aid in the development of future long-term behavioral treatments for individuals at risk for heroin relapse.

Therapeutic efficacy of environmental enrichment for substance use disorders.

Addiction to drug and alcohol is regarded as a major health problem worldwide for which available treatments show limited effectiveness. The biggest challenge remains to enhance the capacities of interventions to reduce craving, prevent relapse and promote long-term recovery. New strategies to meet these challenges are being explored. Findings from preclinical work suggest that environmental enrichment (EE) holds therapeutic potential for the treatment of substance use disorders, as demonstrated in a number of animal models of drug abuse. The EE intervention introduced after drug exposure leads to attenuation of compulsive drug taking, attenuation of the rewarding (and reinforcing) effects of drugs, reductions in control of behavior by drug cues, and, very importantly, relapse prevention. Clinical work also suggests that multidimensional EE interventions (involving physical activity, social interaction, vocational training, recreational and community involvement) might produce similar therapeutic effects, if implemented continuously and rigorously. In this review we survey preclinical and clinical studies assessing the efficacy of EE as a behavioral intervention for substance use disorders and address related challenges. We also review work providing empirical evidence for EE-induced neuroplasticity within the mesocorticolimbic system that is believed to contribute to the seemingly therapeutic effects of EE on drug and alcohol-related behaviors.

Assessing the Anxiolytic Properties of Taurine-Derived Compounds in Rats Following Developmental Lead Exposure: A Neurodevelopmental and Behavioral Pharmacological Pilot Study.

Lead (Pb2+) is a developmental neurotoxicant that causes alterations in the brain's excitation-to-inhibition (E/I) balance. By increasing chloride concentration through GABA-ARs, taurine serves as an effective inhibitory compound for maintaining appropriate levels of brain excitability. Considering this pharmacological mechanism of taurine facilitated inhibition through the GABA-AR, the present pilot study sought to explore the anxiolytic potential of taurine derivatives. Treatment groups consisted of the following developmental Pb2+-exposures: Control (0 ppm) and Perinatal (150 ppm or 1000 ppm lead acetate in the drinking water). Rats were scheduled for behavioral tests between postnatal days (PND) 36-45 with random assignments to either solutions of Saline, Taurine, or Taurine Derived compounds (i.e., TD-101, TD-102, or TD-103) to assess the rats' responsiveness to each drug in mitigating the developmental Pb2+-exposure through the GABAergic system. Long Evans Hooded rats were assessed using an Open Field (OF) test for preliminary locomotor assessment. Approximately 24-h after the OF, the same rats were exposed to the Elevated Plus Maze (EPM) and were given an i.p. injection of 43 mg/Kg of the Saline, Taurine, or TD drugs 15-min prior to testing. Each rat was tested using the random assignment method for each pharmacological condition, which was conducted using a triple-blind procedure. The OF data revealed that locomotor activity was unaffected by Pb2+-exposure with no gender differences observed. However, Pb2+-exposure induced an anxiogenic response in the EPM, which interestingly, was ameliorated in a gender-specific manner in response to taurine and TD drugs. Female rats exhibited more anxiogenic behavior than the male rats; and as such, exhibited a greater degree of anxiety that were recovered in response to Taurine and its derivatives as a drug therapy. The results from the present psychopharmacological pilot study suggests that Taurine and its derivatives could provide useful data for further exploring the pharmacological mechanisms and actions of Taurine and the associated GABAergic receptor properties by which these compounds alleviate anxiety as a potential behavioral pharmacotherapy for treating anxiety and other associated mood disorders.

Early Neurodevelopmental Exposure to Low Lead Levels Induces Fronto-executive Dysfunctions That Are Recovered by Taurine Co-treatment in the Rat Attention Set-Shift Test: Implications for Taurine as a Psychopharmacotherapy Against Neurotoxicants.

Lead (Pb2+) is a developmental neurotoxicant that causes lifelong cognitive dysfunctions. In particular, Pb2+-induced frontoexecutive dysfunctions emerge later in life when the cortex is fully myelinated, thereby permitting the ability to assess the extent to which Pb2+ has developmentally impacted higher order cognitive and behavioral systems. The present study evaluated the effects of developmental Pb2+-exposure (150 ppm lead acetate in the drinking water) in Long Evans Hooded rats through the Attention Set-Shift Test (ASST) between postnatal days (PND) 60-90. Treatment groups were comprised of Control (0 ppm), Perinatal (150 ppm), and Perinatal+Taurine (150 ppm + 0.05% Taurine in the drinking water) rats (N = 36; n = 6 per treatment group for each sex). Frontoexecutive functions were evaluated based on trials-to-criterion (TTC) and errors-to-criterion (ETC) measures for simple and complex discriminations (SD & CD), intradimensional and extradimensional shifts (ID & ED), as well as reversals (Rev) of the CD, I-, and ED stages, respectively. Post-testing, the prelimbic (PrL), infralimbic (IL), orbital ventral frontal (OV), orbital ventro-lateral (OVL), and hippocampal (HP) brain regions were extracted and processed through Liquid Chromatography/Mass Spectrophotometry (LC/MS) for determining the GABA and Taurine ratios relative to Glutamate, Dopamine, Norepinephrine, Epinephrine, and Serotonin. The ASST data revealed that Perinatal rats are negatively impacted by developmental Pb2+-exposures evidenced by increased TTC and ETC to learn the SD, ID, and ID-Rev with unique sex-based differences in frontoexecutive dysfunctions. Moreover, Perinatal+Taurine co-treated rats exhibited a recovery of the frontoexecutive dysfunctions observed in Perinatal rats to levels equivalent to Control rats across both sexes. The LC/MS data revealed altered brain sub-region specific patterns across the PrL, IL, OV, OVL, and HP in response to developmental Pb2+-exposure that produced an altered neurochemical signaling profile in a sex-dependent manner, which may underlie the observed frontoexecutive dysfunctions, cognitive inflexibility, and associated motivation deficits. When taurine co-treatment was administered concurrently for the duration of developmental Pb2+-exposure, the observed frontoexecutive dysfunctions were significantly reduced in both ASST task performance and neurochemical ratios that were comparable to Control levels for both sexes. Altogether, the data suggest that taurine co-treatment may facilitate neuroprotection, mitigate neurotransmitter excitability balancing, and perhaps ameliorate against neurotoxicant exposures in early development as a potential psychopharmacotherapy.

Undersized Rigid Nonplanar Annuloplasty: The Key to Effective and Durable Repair of Functional Tricuspid Regurgitation.

BACKGROUND: Previous clinical experiences have demonstrated high early and late recurrence rates after repair of functional tricuspid regurgitation (TR). We investigated the results of functional TR repair with undersized rigid nonplanar annuloplasty rings. METHODS: From January 2007 to December 2013, 216 consecutive patients with moderate or greater functional TR were treated with undersized (size 26 mm or 28 mm) rigid nonplanar annuloplasty rings. RESULTS: The mean age was 69 ± 13 years. There was a previous history of cardiac operation in 25% (54 of 216 patients). Tricuspid regurgitation was graded as severe in 47% (102 of 216) and moderate in 53% (114 of 216). Concomitant operations included mitral valve procedures in 92% (198 of 216), coronary artery bypass grafting in 21% (45 of 216), aortic valve procedures in 9% (20 of 216), and cryomaze procedures in 35% (76 of 216). Size 26 mm rings were used in 38% of patients (81 of 216), and size 28 mm in 62% (135 of 216). The perioperative mortality rate was 6% (14 of 216). On predischarge echocardiography, TR grade was none or mild in 94% (176 of 187 patients), moderate in 4% (7 of 187), and severe in 2% (4 of 187). At a mean follow-up of 33.0 ± 24.0 months, TR grade was none or mild in 81% of patients (130 of 160), moderate in 16% (26 of 160), and severe in 2% (4 of 160). There were no reoperations for recurrent TR, and no patients have had tricuspid stenosis or annuloplasty ring dehiscence. CONCLUSIONS: Treatment of functional TR with undersized (26 mm or 28 mm) nonplanar rigid annuloplasty rings is safe and highly effective, with a near absence of recurrent severe TR at midterm follow-up.

Microbubble and ultrasound radioenhancement of bladder cancer.

BACKGROUND: Tumour vasculature is an important component of tumour growth and survival. Recent evidence indicates tumour vasculature also has an important role in tumour radiation response. In this study, we investigated ultrasound and microbubbles to enhance the effects of radiation. METHODS: Human bladder cancer HT-1376 xenografts in severe combined immuno-deficient mice were used. Treatments consisted of no, low and high concentrations of microbubbles and radiation doses of 0, 2 and 8 Gy in short-term and longitudinal studies. Acute response was assessed 24 h after treatment and longitudinal studies monitored tumour response weekly up to 28 days using power Doppler ultrasound imaging for a total of 9 conditions (n=90 animals). RESULTS: Quantitative analysis of ultrasound data revealed reduced blood flow with ultrasound-microbubble treatments alone and further when combined with radiation. Tumours treated with microbubbles and radiation revealed enhanced cell death, vascular normalisation and areas of fibrosis. Longitudinal data demonstrated a reduced normalised vascular index and increased tumour cell death in both low and high microbubble concentrations with radiation. CONCLUSION: Our study demonstrated that ultrasound-mediated microbubble exposure can enhance radiation effects in tumours, and can lead to enhanced tumour cell death.

The metabolic syndrome and cardiovascular risk: implications for clinical practice.

OBJECTIVE: The clinical importance of the metabolic syndrome (MeS) is confused by the existence of at least three different definitions proposed by prominent organizations, and by a lack of information about the prognostic value of diagnosing a person as having the syndrome by any of the definitions. DESIGN AND SUBJECTS: We used the US National Health and Nutrition Evaluation Survey (NHANES) to determine the prevalence in the United States of the variables used to define the MeS and cardiovascular disease (CVD), and to create a simulated population that matched the US population with respect to all the important characteristics, risk factors and treatments for CVD. We then used the Archimedes model to calculate the long-term CVD outcomes for each person in the simulated population. RESULTS: The definitions implied an increased risk of CVD of 1.5-1.6. The definitions varied considerably in their ability to identify people at risk of myocardial infarctions (MIs); the proportion of people destined to have a future MI captured by the different definitions varied from 57 to 77%. The definitions also varied widely in how well they ruled out future MIs; failure to have MeS by a definition still left a chance of a future MI ranging from 23 to 42%. The definitions differed importantly in which people they identified as having MeS; 34% of those who met the ATP definition did not meet the WHO definition, 30% of those who met the WHO definition did not meet the ATP definition and 28% of those who met the IDF definition did not meet the ATP definition. Of the components of the definitions, the most important single factor for identifying a person at risk of future CVD was high glucose, with hypertension, obesity, high triglycerides and low HDL following in that order. High glucose, by itself, was as good as any definition of the MeS in predicting risk of future MI. Whichever definition was used, individuals who met the definition varied widely in their risk of CVD. CONCLUSIONS: For assessing a particular person's risk of future CVD and for making treatment decisions a diagnosis of MeS by any of the definitions added little if anything to assessing each person's risk factors.

Effect of exercise and fluid consumption on salivary flow and pH.

Recent claims have been made regarding the putative erosive effects of regularly ingesting low-pH beverages on the integrity of tooth enamel. The purpose of this study was to determine whether fluid consumption during exercise affects the body's defenses against enamel erosion: saliva flow and salivary pH. Males and females (n=50) exercised in the heat (26.7 degrees C, 40 % RH) for 75 min on four occasions. Within each session, subjects consumed ad-lib either water, a sports drink (Gatorade), diluted orange juice, or a homemade sports drink, with the latter three fluids all having low pH values (3.0 to 4.0). Prior to and following exercise, subjects performed a standard stimulated saliva collection procedure. Immediately following collection, saliva flow rate and pH were determined for each sample. Repeated-measures ANOVA were used to evaluate the data. Compared to pre-exercise salivary flow rates (2.6+/- 0.8 ml/min), the post-exercise rate was not different when consuming the sports drink (2.6+/- 0.9 ml/min), but decreased when water or the homemade sports drink was ingested (2.4+/- 0.9 ml/min; p<0.05). A time-by-drink interaction (p<0.05) revealed slight differences in saliva pH after exercise, depending on the beverage consumed; post-exercise saliva pH was highest for water (7.2+/- 0.2) and lowest for the homemade sports drink (7.1+/- 0.2), with the sports drink and diluted orange juice values falling in between. The results suggest that minimal changes occur in saliva pH and the rate of stimulated saliva flow with beverage consumption during exercise. Subsequent research is needed to determine whether maintenance of saliva production by drinking beverages during exercise influences the body's defenses against dental erosion via saliva production.

Earlier intervention in type 2 diabetes: the case for achieving early and sustained glycaemic control.

In type 2 diabetes, the onset and progression of complications is significantly delayed by improving glycaemic control. However, the proportion of patients reaching and sustaining guideline recommendations for glycaemic targets remains unacceptably low. Recent clinical trials and predictive physiologically based mathematical simulations (Archimedes model) indicate that benefits can be enhanced with earlier intervention and timely achievement of glycaemic targets. This article reviews the evidence for early intervention, showing that intensive approaches, including earlier introduction of combination therapy, allow more patients to achieve glycaemic targets and hence reduce complications and delay disease progression.

Endovascular stent graft repair of a persistent sciatic artery aneurysm.

An 88-year-old female presented with a large, painful, pulsatile buttock mass. Computed tomographic angiogram with three-dimensional reconstruction and lower extremity arteriogram revealed a 5 cm sciatic artery aneurysm. We report a case of successful repair of a sciatic artery aneurysm with endovascular stent graft.