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Purpose: While there is concern about degenerative tissue effects of exposure to space radiation during deep-space missions, there are no pharmacological countermeasures against these adverse effects. γ-Tocotrienol (GT3) is a natural form of vitamin E that has anti-oxidant properties, modifies cholesterol metabolism, and has anti-inflammatory and endothelial cell protective properties. The purpose of this study was to test whether GT3 could mitigate cardiovascular effects of oxygen ion (16O) irradiation in a mouse model. Materials and methods: Male C57BL/6 J mice were exposed to whole-body 16O (600 MeV/n) irradiation (0.26–0.33 Gy/min) at doses of 0 or 0.25 Gy at 6 months of age and were followed up to 9 months after irradiation. Animals were administered GT3 (50 mg/kg/day s.c.) or vehicle, on Monday – Friday starting on day 3 after irradiation for a total of 16 administrations. Ultrasonography was used to measure in vivo cardiac function and blood flow parameters. Cardiac tissue remodeling and inflammatory infiltration were assessed with histology and immunoblot analysis at 2 weeks, 3 and 9 months after radiation. Results: GT3 mitigated the effects of 16O radiation on cardiac function, the expression of a collagen type III peptide, and markers of mast cells, T-cells and monocytes/macrophages in the left ventricle. Conclusions: GT3 may be a potential countermeasure against late degenerative tissue effects of high-linear energy transfer radiation in the heart.

Intimate partner violence (IPV) remains a devastating public health issue in the United States. Given the high stakes of IPV, it is imperative that treatment provided to perpetrators be efficacious to prevent further victimization and not lull survivors into a false sense of security. Unfortunately, the historically dominant modalities of perpetrator treatment, group-based Duluth and cognitive-behavioral therapy, show small effects at best in deterring re-assault. Because of this, new directions are needed. In this article, we report on a literature review that centered on IPV perpetrator treatment. Results suggest a prominent theme in the literature is a shift from these blanket approaches to treatment based on individual need and co-occurring issues. Specifically, practitioners should be aware of (1) demographic factors affecting treatment completion and re-assault, (2) perpetrator typologies, (3) perpetrator readiness to change and use of motivation-based approaches, and (4) common individual co-occurring concerns, including substance use and mental health issues. For each of these, we discuss treatment implications and make recommendations for future research. We envision a future where the landscape of perpetrator treatment is tailored to individual treatment needs and argue that social work practitioners bring a critical person-centered perspective to IPV perpetrator treatment.

Cardiovascular disease constitutes an important threat to humans after space missions beyond the Earth's magnetosphere. Epigenetic alterations have an important role in the etiology and pathogenesis of cardiovascular disease. Previous research in animal models has shown that protons and 56Fe ions cause long-term changes in DNA methylation and expression of repetitive elements in the heart. However, astronauts will be exposed to a variety of ions, including the smaller fragmented products of heavy ions after they interact with the walls of the space craft. Here, we investigated the effects of 16O on the cardiac methylome and one-carbon metabolism in male C57BL/6 J mice. Left ventricles were examined 14 and 90 days after exposure to space-relevant doses of 0.1, 0.25, or 1 Gy of 16O (600 MeV/n). At 14 days, the two higher radiation doses elicited global DNA hypomethylation in the 5′-UTR of Long Interspersed Nuclear Elements 1 (LINE-1) compared to unirradiated, sham-treated mice, whereas specific LINE-1 elements exhibited hypermethylation at day 90. The pericentromeric major satellites were affected both at the DNA methylation and expression levels at the lowest radiation dose. DNA methylation was elevated, particularly after 90 days, while expression showed first a decrease followed by an increase in transcript abundance. Metabolomics analysis revealed that metabolites involved in homocysteine remethylation, central to DNA methylation, were unaffected by radiation, but the transsulfuration pathway was impacted after 90 days, with a large increase in cystathione levels at the lowest dose. In summary, we observed dynamic changes in the cardiac epigenome and metabolome three months after exposure to a single low dose of oxygen ions.

Cardiovascular disease is a leading cause of morbidity and death among women. Our knowledge of ischemic heart disease has grown tremendously over the past few decades as sex differences in prevalence, presentation, and pathophysiology are increasingly being recognized. Women with ischemic heart disease have less coronary atherosclerosis than men. Coronary endothelial dysfunction and microvascular disease have been proposed as important mechanisms that contribute to the cause and prognosis of ischemic heart disease in women. This review outlines sex-specific issues in ischemic heart disease, including prevalence, prognosis, pathophysiology, traditional and nontraditional risk factors, screening, and diagnostic testing, as well as management strategies.

Purpose Studies are required to determine whether exposures to radiation encountered during manned missions in deep space may have adverse effects on the cardiovascular system. Most of the prior studies on effects of simulated space radiation on the heart and vasculature have been performed in mouse models. To provide data from a second animal species, two studies were performed to assess effects of high-energy charged particle radiation on the heart and abdominal aorta in a rat model. Materials and methods In study A, male Long Evans rats were exposed to whole-body protons (250 MeV, 0.5 Gy) or oxygen ions (16O, 600 MeV/n, 0.5 Gy), and ultrasonography was used to measure in vivo cardiac function and blood flow parameters at 3, 5, 9 and 12 months after radiation, followed by tissue collection at 12 months. In study B, male Long Evans rats were exposed to 16O (1 GeV/n, 0.01-0.25 Gy), and hearts collected at 6 to 7 and 12 months for histology and western-blots. Results Both protons (250 MeV) and 16O (600 MeV/n) caused a decrease in left ventricular posterior wall thickness at 3-5 months, but did not change echocardiographic measures of cardiac function. In Pulsed-wave Doppler assessment of the abdominal aorta, an increase was seen in mean velocity, peak velocity, and velocity time integral at 12 months after 16O (600 MeV/n), suggesting a change in vascular function. There were no significant changes in histopathology or histological quantification of total collagens in heart or aorta. On the other hand, an increase was seen in a 75 kDa peptide of collagen type III in the left ventricle of rats exposed to protons (250 MeV) and 16O (600 MeV/n and 1 GeV/n), suggesting that radiation caused remodeling of existing collagens in the heart. 16O (600 MeV/n and 1 GeV/n) caused increases in left ventricular protein levels of immune cell markers CD2, CD4, CD8, and CD68. Conclusion A single low dose of whole body protons or 16O in male Long Evans rats did not change cardiac function or induce gross pathological changes in the heart or aorta, but induced mild changes in vascular function and remodeling of existing collagens in the heart. Altogether, studies in prior mouse models and the current work in rats indicate minor changes in cardiac function and structure after a low dose of single-ion radiation.

NASA’s Missions to Mars and beyond will expose flight crews to potentially dangerous levels of charged-particle radiation. Of all charged nuclei, 1H is the most abundant charged particle in both the galactic cosmic ray (GCR) and solar particle event (SPE) spectra. There are currently no functional spacecraft shielding materials that are able to mitigate the charged-particle radiation encountered in space. Recent studies have demonstrated cognitive injuries due to high-dose 1H exposures in rodents. Our study investigated the effects of 1H irradiation on neuronal morphology in the hippocampus of adult male mice. 6-month-old mice received whole-body exposure to 1H at 0.5 and 1 Gy (150 MeV/n; 0.35–0.55 Gy/min) at NASA's Space Radiation Laboratory in Upton, NY. At 9-months post-irradiation, we tested each animal's open-field exploratory performance. After sacrifice, we dissected the brains along the midsagittal plane, and then either fixed or dissected further and snap-froze them. Our data showed that exposure to 0.5 Gy or 1 Gy 1H significantly increased animals’ anxiety behavior in open-field testing. Our micromorphometric analyses revealed significant decreases in mushroom spine density and dendrite morphology in the Dentate Gyrus, Cornu Ammonis 3 and 1 of the hippocampus, and lowered expression of synaptic markers. Our data suggest 1H radiation significantly increased exploration anxiety and modulated the dendritic spine and dendrite morphology of hippocampal neurons at a dose of 0.5 or 1 Gy.

Radiation from galactic cosmic rays (GCR) poses a significant health risk for deep-space flight crews. GCR are unique in their extremely high-energy particles. With current spacecraft shielding technology, some of the predominant particles astronauts would be exposed to are 1H + 16O. Radiation has been shown to cause cognitive deficits in mice. The hippocampus plays a key role in memory and cognitive tasks; it receives information from the cortex, undergoes dendritic-dependent processing and then relays information back to the cortex. In this study, we investigated the effects of combined 1H + 16O irradiation on cognition and dendritic structures in the hippocampus of adult male mice three months postirradiation. Six-month-old male C57BL/6 mice were irradiated first with 1H (0.5 Gy, 150 MeV/n) and 1 h later with 16O (0.1 Gy, 600 MeV/n) at the NASA Space Radiation Laboratory (Upton, NY). Three months after irradiation, animals were tested for hippocampus-dependent cognitive performance using the Y-maze. Upon sacrifice, molecular and morphological assessments were performed on hippocampal tissues. During Y-maze testing, the irradiated mice failed to distinguish the novel arm, spending approximately the same amount of time in all three arms during the retention trial relative to sham-treated controls. Irradiated animals also showed changes in expression of glutamate receptor subunits and synaptic density-associated proteins. 1H + 16O radiation compromised dendritic morphology in the cornu ammonis 1 and dentate gyrus within the hippocampus. These data indicate cognitive injuries due to 1H + 16O at three months postirradiation.

From 1991 to 2013, Mississippi was without liver transplant services. In 2013, a new liver transplant program was established at the University of Mississippi Medical Center. Here, we describe our experience with the first 150 transplants over a 4.5-year period. This study is a review of 147 patients who underwent the first 150 liver transplants at the University of Mississippi Medical Center between March 5, 2013, and January 4, 2018. There were no exclusion criteria for this study. Donor, recipient, and outcome variables were analyzed. Recipients were 46% female and 74% white. Age at the time of transplant was 57 [IQR 49–63]. BMI at transplant was 30 [IQR 25–35]. Thirty per cent of transplants were for alcoholic cirrhosis, 25% non-alcoholic steatohepatitis, 24% hepatitis C, and 12% cholestatic. Mean model for end-stage liver disease (MELD) at the time of transplant was 20 [95% confidence interval 19–21] and MELD-Na was 22 [95% confidence interval 20–23]. One-year patient- and graft survival were 89% and 87%, respectively, which were as expected based on Scientific Registry of Transplant Recipient reports after risk adjustment. The data published here verifies it is possible to establish a new liver transplant center in an underserved area previously lacking comprehensive liver care and to achieve results similar to other high-volume centers across the country.

Early hospital readmissions after kidney transplantation pose a significant financial burden and hardship for patients and health-care institutions alike. We sought to identify the risk factors associated with increased likelihood of readmission after transplantation, and examined to determine whether patient socioeconomic demographics impacted the likelihood of perioperative readmissions. We evaluated all deceased donor renal transplants performed at our institution between August 2011 and December 2015. In a cohort of 325 transplant operations that met our inclusion criteria, 117 (36%) were readmitted to the hospital within 90 days of discharge. In univariable analyses, length of stay and pretransplant disabled status were associated with increased likelihood of readmission within 90 days of transplant. When placed into multivariable models, there was a suggestion association with length of stay and disability status. Kidney donor profile index, estimated posttransplant survival, employment, race, age, and payor status were not associated with readmission. In conclusion, the factors associated with posttransplant readmission are not necessarily influenced by socioeconomic factors in our study population. The data collected in this single center study indicate that the factors associated with increased rates of readmission are likely clinical in nature.

We tested the hypothesis that exposure to a short-term (1 h) increase in intraluminal pressure and shear stress (SS), to mimic two mechanical signals associated with a bout of exercise, improves nitric oxide (NO)-mediated endothelium-dependent dilation in aged soleus muscle feed arteries (SFA). In addition, we hypothesized that pressure and SS would interact to produce greater improvements in endothelial function than pressure alone. SFA from young (4 months) and old (24 months) Fischer 344 rats were cannulated and pressurized at 90 (P90) or 130 (P130) cmH2O and exposed to no SS (0 dyn/cm2) or high SS (~65 dyn/cm2) for 1 h. At the end of the 1 h treatment period, pressure in all P130 SFA was set to 90 cmH2O and no SS (0 dyn/cm2) for examination of endothelium-dependent [flow and acetylcholine (ACh)] and endothelium-independent [sodium nitroprusside (SNP)] dilation. To evaluate the contribution of NO, vasodilator responses were assessed in the presence of Nω-nitro- l -arginine (L-NNA). Flow- and ACh-induced dilations were impaired in Old P90 SFA. Treatment with increased pressure + SS for 1 h improved flow- and ACh-induced dilations in old SFA. The beneficial effect of pressure + SS was abolished in the presence of L-NNA and was not greater than treatment with increased pressure alone. These results indicate that short-duration increases in pressure + SS improve NO-mediated endothelium-dependent dilation in aged SFA; however, pressure and SS do not interact to produce greater improvements in endothelial function than pressure alone.

We tested the hypothesis that exposure to a short-duration (1 h) increase in intraluminal pressure, to mimic pressure associated with a bout of exercise, would attenuate age-induced impairments of vascular smooth muscle (VSM) constrictor responses in soleus muscle feed arteries (SFA) via the Rho pathway. SFA from young (4 months) and old (24 months) Fischer 344 rats were cannulated and pressurized to 90 or 130 cmH2O for 1 h. Following the 1-h treatment, pressure in P130 arteries was lowered to 90 cmH2O for examination of vasoconstrictor responses to norepinephrine (NE), angiotensin II (Ang II), and phenylephrine (PE). To assess the role of the Rho pathway, vasoconstrictor responses were assessed in the absence or presence of a RhoA-kinase inhibitor (Y27632) or RhoA-kinase activator (LPA). Vasoconstrictor responses to NE, Ang II, and PE were impaired in old P90 SFA. Pretreatment of old SFA with increased pressure improved vasoconstrictor responses to NE, PE and Ang II. The beneficial effect of the pressure pretreatment in old SFA was eliminated in the presence of Y27632. In the presence of LPA, vasoconstrictor responses to Ang II were improved in old SFA such that responses were not different than young P90 SFA. These results indicate that a short-duration exposure to increased intraluminal pressure, to mimic pressure associated with a bout of exercise, attenuates or reverses the age-related decrement in VSM constrictor responses in SFA and that the beneficial response is mediated through Rho kinase.

Aging induces a progressive decline in vasoconstrictor responses in central and peripheral arteries. This study investigated the hypothesis that vascular smooth muscle (VSM) contractile function declines with age in soleus muscle feed arteries (SFA). Contractile function of cannulated SFA isolated from young (4 months) and old (24 months) Fischer 344 rats was assessed by measuring constrictor responses of denuded (endothelium removed) SFA to norepinephrine (NE), phenylephrine (PE), and angiotensin II (Ang II). In addition, we investigated the role of RhoA signaling in modulation of VSM contractile function. Structural and functional characteristics of VSM cells were evaluated by fluorescence imaging and atomic force microscopy (AFM). Results indicated that constrictor responses to PE and Ang II were significantly impaired in old SFA, whereas constrictor responses to NE were preserved. In the presence of a Rho-kinase inhibitor (Y27632), constrictor responses to NE, Ang II, and PE were significantly reduced in young and old SFA. In addition, the age-group difference in constrictor responses to Ang II was eliminated. ROCK1 and ROCK2 content was similar in young and old VSM cells, whereas pROCK1 and pROCK2 were significantly elevated in old VSM cells. Aging was associated with a reduction in smooth muscle α-actin stress fibers and recruitment of proteins to cell-matrix adhesions. Old VSM cells presented an increase in integrin adhesion to the matrix and smooth muscle γ-actin fibers that was associated with increased cell stiffness. In conclusion, our results indicate that VSM contractile function declined with age in SFA. The decrement in contractile function was mediated in part by RhoA/ROCK signaling. Upregulation of pROCK in old VSM cells was not able to rescue contractility in old SFA. Collectively, these results indicate that changes at the VSM cell level play a central role in the reduced contractile function of aged SFA.

Current research indicates that vasomotor responses are altered with aging in skeletal muscle resistance arteries. The changes in vasomotor function are characterized by impaired vasodilator and vasoconstrictor responses. The detrimental effects of aging on vasomotor function are attenuated in some vascular beds after a program of endurance exercise training. The signals associated with exercise responsible for inducing improvements in vasomotor function have been proposed to involve short-duration increases in intraluminal shear stress and/or pressure during individual bouts of exercise. Here, we review evidence that increases in shear stress and pressure, within a range believed to present in these arteries during exercise, promote healthy vasomotor function in aged resistance arteries. We conclude that available research is consistent with the interpretation that short-duration mechanical stimulation, through increases in shear stress and pressure, contributes to the beneficial effects of exercise on vasomotor function in aged skeletal muscle resistance arteries.

We tested the hypothesis that impaired nitric oxide (NO)-mediated, endothelium-dependent dilation in aged soleus muscle feed arteries (SFA) is due to an age-related decline in the potential for PI3-kinase (PI3K)/protein kinase B (Akt)-dependent phosphorylation of endothelial NO synthase (eNOS) on serine residue 1177 (p-eNOS(ser1177)). SFA from young (4 months) and old (24 months) Fischer 344 rats were cannulated for examination of endothelium-dependent [flow or acetylcholine (ACh)] and endothelium-independent [sodium nitroprusside (SNP)] vasodilator function. To determine the mechanism by which aging affected vasodilation to flow and ACh, vasodilator responses were assessed in the presence of N (ω)-nitro-L-arginine (L-NNA, to inhibit NOS), LY-294002 (to inhibit PI3K), or 1L6-hydroxymethyl-chiro-inositol-2-(R)-2-O-methyl-3-O-octadecyl-sn-glycerocarbonate (AktI, to inhibit Akt). Flow- and ACh-induced vasodilator responses were significantly impaired in old SFA, whereas endothelium-independent dilation to SNP was not compromised. Age-group differences in flow- and ACh-induced dilations were abolished in the presence of L-NNA, LY-294002, or AktI. In a separate experiment, SFA were cannulated and stimulated with ACh (10(-4) M, 3 min), flow (60 μl/min, 5 min), or remained unstimulated (3 min). SFA were removed from the pipettes and immunoblot analysis was used to assess ACh- and flow-stimulated phosphorylation of eNOS on ser(1177). Stimulation with ACh or flow increased phosphorylation of eNOS on ser(1177) in young (not old) SFA. Preincubation of young SFA with LY-294002, abolished the ACh-induced phosphorylation of eNOS in young SFA. Collectively, these results indicate that impaired NO-mediated, endothelium-dependent dilation in old SFA is due, in part, to an impaired potential for PI3K/Akt-dependent phosphorylation of eNOS on ser(1177).

We tested the hypothesis that age-related endothelial dysfunction in rat soleus muscle feed arteries (SFA) is mediated in part by NAD(P)H oxidase-derived reactive oxygen species (ROS). SFA from young (4 mo) and old (24 mo) Fischer 344 rats were isolated and cannulated for examination of vasodilator responses to flow and acetylcholine (ACh) in the absence or presence of a superoxide anion (O2−) scavenger (Tempol; 100 μM) or an NAD(P)H oxidase inhibitor (apocynin; 100 μM). In the absence of inhibitors, flow- and ACh-induced dilations were attenuated in SFA from old rats compared with young rats. Tempol and apocynin improved flow- and ACh-induced dilation in SFA from old rats. In SFA from young rats, Tempol and apocynin had no effect on flow-induced dilation, and apocynin attenuated ACh-induced dilation. To determine the role of hydrogen peroxide (H2O2), dilator responses were assessed in the absence and presence of catalase (100 U/ml) or PEG-catalase (200 U/ml). Neither H2O2 scavenger altered flow-induced dilation, whereas both H2O2 scavengers blunted ACh-induced dilation in SFA from young rats. In old SFA, catalase improved flow-induced dilation whereas PEG-catalase improved ACh-induced dilation. Compared with young SFA, in response to exogenous H2O2 and NADPH, old rats exhibited blunted dilation and constriction, respectively. Immunoblot analysis revealed that the NAD(P)H oxidase subunit gp91phox protein content was greater in old SFA compared with young. These results suggest that NAD(P)H oxidase-derived reactive oxygen species contribute to impaired endothelium-dependent dilation in old SFA.

Context—Clinical pathways have been used in many acute hospital settings.Objectives—To develop a systematic approach to postoperative care of adult recipients of deceased donor kidney transplants at the University of Mississippi Medical Center.Design and Setting—A pilot quality improvement project that uses implementation of a clinical pathway 24 hours after surgery for adult recipients of a deceased donor kidney transplant for 7 months. Charts from the same 7 months of the preceding year were retrospectively reviewed for comparison. The project occurred on the transplant floor in an acute care hospital and did not include any patients admitted to the intensive care unit.Main Outcome Measures—To demonstrate that clinical pathways can (1) promote a method for standardizing postoperative care, (2) decrease postoperative length of stay, and (3) contain costs by minimizing hospital charges related to laboratory and room fees and promote efficient medication use in adult recipients of a deceased donor kidney t...

The Page kidney phenomenon is a well recognized entity where an extrinsically compressed kidney results in hypertension and loss of function. This compression is usually caused by a subcapsular hematoma secondary to blunt abdominal trauma or an invasive procedure such as a renal biopsy. We describe an unusual case involving the spontaneous development of a Page kidney 24 days after renal transplantation without any history of preceding trauma. The subcapsular hematoma was detected by a computerized tomographic scan performed as part of the work-up for acute allograft dysfunction. Prompt recognition and early intervention are essential if renal function is to be restored before irreversible damage occurs.

Feline idiopathic cystitis (FIC), is the most common medical cause of elimination change in the cat, and hence is an important differential when working up cats presenting with inappropriate elimination. A recent case-control study found that case cats were more likely than the control population to be male, overweight, and pedigreed, but the study also found that several stress factors were "flare factors" associated with the onset of a bout of clinical signs. A 5-year-old male, neutered, domestic shorthaired cat presented with recurrent bouts of dysuria and hematuria. A full medical work up eliminated other causes, leading to the diagnosis of FIC. On behavioral assessment, the cat was found to be one of 6 within the household. He showed no signs of regarding any of the other cats as part of his social group. A program of behavior therapy was instituted, which involved ensuring the patient had a separate "core area" and easy access to important resources. In addition, visual access to cats from outside the household was restricted. The cat was followed up for a period of 7 months. There was no further recurrence of clinical signs for 6 months, after which clinical signs returned. Further investigation revealed that this outbreak occurred 2 days after the owner confined the cats in close proximity again. This case provides an interesting example of how bouts of clinical signs in FIC cats can often be linked to specific "stressful" events, and how such outbreaks can be reduced or prevented through the implementation of a specific program of behavior therapy.

Objective: To determine the mechanism of exercise-induced attenuation of the detrimental effects of aging on endothelial function. We tested the hypothesis that exercise-like mechanical stimulation...

Exposure of the heart to ionizing radiation can cause adverse myocardial remodeling. In small animal models, local heart irradiation causes persistent alterations in cardiac mitochondrial function and swelling. POLY-MVA is a dietary supplement that contains a palladium lipoic acid complex that targets mitochondrial complex I and has been demonstrated to have greater redox potential than lipoic acid alone. POLY-MVA improves mitochondrial function and anti-oxidant enzyme activity in the aged rat heart. In this study, we tested whether POLY-MVA can mitigate cardiac effects of ionizing radiation. Adult male rats were exposed to local heart X rays with a daily dose of 9 Gy for 5 consecutive days. Eighteen weeks after irradiation, POLY-MVA was administered orally at 1 ml/kg bodyweight per day during weekdays, for 6 weeks. Alterations in cardiac function as measured with echocardiography coincided with enhanced mitochondrial swelling, a reduction in mitochondrial expression of complex II, manifestations of adverse remodeling such as a reduction in myocardial microvessel density and an increase in collagen deposition and mast cell numbers. POLY-MVA enhanced left ventricular expression of superoxide dismutase 2, but only in sham-irradiated animals. In irradiated animals, POLY-MVA caused a reduction in markers of inflammatory infiltration, CD2 and CD68. Moreover, POLY-MVA mitigated the effects of radiation on mitochondria. Nonetheless, POLY-MVA did not mitigate adverse cardiac remodeling, suggesting that this tissue remodeling may not be alleviated by altering cardiac mitochondria alone. However, we cannot exclude the possibility that an earlier onset of POLY-MVA administration may have more profound effects on radiation-induced cardiac remodeling.

Objectives Aspirin is recommended for cardiovascular disease (CVD) prevention in patients who are at high risk for CVD. The objective of this study was to compare agreement between two American Diabetes Association-endorsed CVD risk calculators in identifying candidates for aspirin therapy. Methods Adult patients with diabetes mellitus (n = 238) were studied for 1 year in a family medicine clinic. Risk scores were calculated based on the United Kingdom Prospective Diabetes Study Risk Engine and the Atherosclerosis Risk in Communities Coronary Heart Disease Risk Calculator. Analyses included χ(2), κ scores, and logistic regressions. Results The Atherosclerosis Risk in Communities Coronary Heart Disease Risk Calculator identified 50.4% of patients as high risk versus 23.5% by the United Kingdom Prospective Diabetes Study Risk Engine. κ score for agreement identifying high-risk status was 0.3642. Among patients at high risk, African Americans (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.24-0.86) and those with uncontrolled diabetes (OR 0.30, 95% CI 0.16-0.56) had lower odds of disagreement, whereas nonsmokers had higher odds (OR 2.98, 95% CI 1.57-5.69). Among patients at low risk, women (OR 3.83, 95% CI 1.64-8.91), African Americans (OR 5.96, 95% CI 3.07-11.59), and those with high high-density lipoprotein (OR 2.82, 95% CI 1.48-5.37) showed greater odds of disagreement. Conclusions Improved risk assessment methods are needed to identify patients with diabetes mellitus who benefit from aspirin for the primary prevention of CVD. Prospective trials are needed to provide additional evidence for aspirin use in this population.

We tested the hypothesis that exposure to an acute increase in intraluminal pressure, to mimic pressure associated with a bout of exercise, improves nitric oxide (NO)-mediated endothelium-dependent dilation in aged soleus muscle feed arteries (SFA) and that improved endothelial function would persist after a 2 h recovery period. SFA from young (4-month) and old (24-month) Fischer 344 rats were cannulated and pressurized at 90 (P90) or 130 (P130) cmH2O for 60 min. At the end of the treatment period, pressure in the P130 SFA was lowered to 90 cmH2O for examination of endothelium-dependent [flow or acetylcholine (ACh)] and endothelium-independent [sodium nitroprusside (SNP)] vasodilation. To determine the role of NO, vasodilator responses were assessed in the presence of N ω-nitro-l-arginine (L-NNA). To determine whether the effects of pressure persisted following a recovery period at normal pressure, SFA were pressurized to 130 cmH2O for 60 min and subsequently lowered to 90 cmH2O for 2 h before assessing function. ACh- and flow-induced dilations were impaired in old SFA. Treatment with increased pressure for 60 min improved ACh- and flow-induced dilations in old SFA. SNP-induced dilation was improved in old and young SFA. The beneficial effect of pressure treatment on ACh- and flow-induced dilation in old SFA was blocked by L-NNA and was not present following a 2 h recovery period. These results indicate that an acute increase in intraluminal pressure improves NO-mediated endothelium-dependent dilation in aged SFA; however, the beneficial effect does not persist after 2 h.

Radiolabelled C-14 cylindrospermopsin (CYN) has been prepared and used to investigate the distribution and excretion of CYN in vivo in male Quackenbush mice. At a dose of 0.2 mg/kg (i.e., approx. median lethal dose) the following mean (SID) urinary and faecal recoveries (cumulative) were obtained, respectively: (0-6 hours, n = 4) 48.2 (29.3)%, 11.9 (21.4)%; (0-12 hours, n = 12) 66.0 (27.1)%, 5.7 (5.6)%; (0-24 hours, n = 12) 68.4 (26.7)%, 8.5 (8.1)%. Mean (SD) recoveries from livers at 6 hours were 20.6 (6.4)% (n = 4), at 48 hours 13.1 (7.7)% (n = 8), and 5-7 days were 2.1 (2.1)% (n = 8). A substantial amount (up to 23%) can be retained in the liver for up to 48 hours with a lesser amount retained in the kidneys. The excretion patterns show substantial interindividual variability between predominantly faecal or urinary excretion, but these patterns are not related in any simple manner to the outcome in terms of toxicity. There is at least one methanol-extractable metabolite as well as a nonmethanol-extractable metabolite in the liver. The methanol-extractable metabolite was not found in the kidney and is more hydrophilic than CYN itself on reverse phase. (C) 2001 by John Wiley & Sons, Inc.

The objective of this article is to increase awareness among public health personnel of the complexities involved in integrating existing data systems. This article describes the electronic importing feature of the Centers for Disease Control and Prevention (CDC) software package called staffTRAK-TB, and users' experience with it.

Purpose: To report the results of treatment of a series of patients with superior oblique overaction using the superior oblique silicone tendon-expander technique. Methods: A chart review of 17 patients with superior oblique overaction who had a total of 26 silicone tendonexpander procedures was conducted. Results: Mean preoperative degree of superior oblique overaction was +2.7. 92% of eyes had mild (+1) or no residual overaction at last postoperative assessment (follow-up range: 6 to 59 months). Of 15 patients with preoperative ?-pattern of 10 prism diopter (A) or more, only two patients (1 3%) had ?-pattern of 1 0 ? or more at last assessment. Of 13 patients with preoperative hypotropia in primary position, five patients (38%) had no vertical deviation in primary position, and seven patients (54%) had persistent, but less vertical deviation in primary position at last assessment (mean reduced from 11Δ to 4Δ). No patient manifested superior oblique palsy at their last postoperative assessment. Conclusions: We believe that the superior oblique tendon-expander technique should be strongly considered for the treatment of superior oblique overaction associated with ?-pattern or hypotropia In primary position, because it has a high success rate and a low incidence of postoperative complications. Consecutive superior oblique underaction did not occur In this series.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) and transforming growth factor-β (TGF-β) are both important regulators of chondrocyte growth and differentiation. We report here that 1,25(OH)2D3 differentially regulates the expression of the genes for TGF-β1 to -β3 and the secretion of the corresponding proteins in cultured chick chondrocytes. Confluent growth plate chondrocytes were serum-deprived and cultured in varying concentrations of 1,25(OH)2D3. Cells were assayed for TGF-β mRNA and conditioned medium was assayed for TGF-β activity and isoform composition. Active TGF-β was only detected in 10−8m 1,25(OH)2D3-treated cultures (8·37 ng active TGF-β/mg protein). There was a significant decrease in total (latent+active) TGF-β activity in conditioned medium of 10−12 m (23·4%; P−10 m (20·7%; P2D3-treated cultures but 10−8 m 1,25(OH)2D3 significantly increased (30·9%; P−10 or 10−12m 1,25(OH)2D3-treated cultures but the conditioned medium of 10−8 m 1,25(OH)2D3-treated cultures contained significantly higher amounts of all three isoforms. Quantification of TGF-β mRNA demonstrated differential control of TGF-β gene expression with TGF-β1 and -β3 mRNA levels reduced by all concentrations of 1,25(OH)2D3 examined (10−8, 10−10 and 10−12 m) whilst TGF-β2 mRNA concentrations were elevated. Our results indicated that 1,25(OH)2D3 regulates chick growth plate chondrocyte TGF-β secretion and mRNA expression in a concentration-dependent and isoform-specific manner. This interaction may be important in the regulation of chondrocyte metabolism and endochondral bone growth. Journal of Endocrinology (1996) 149, 277–285

Tibial dyschondroplasia (TD) is a disorder of endochondral bone growth and results in the retention of a mass of unmineralized, avascular cartilage extending into the metaphysis. We have studied various parameters of chondrocyte differentiation, both in isolated chick chondrocytes and growth plate sections, in an attempt to determine whether the inhibition in chondrocyte differentiation seen in TD is a consequence of an inherent incapability of chondrocytes to differentiate terminally and mineralize. Results from in vitro experiments indicated that both normal and lesion chondrocytes synthesized a matrix that stained with antibodies to types II and X collagen and displayed foci of mineralization. Alkaline phosphatase activity in lesion chondrocytes was significantly increased in comparison to that in normal hypertrophic chondrocytes. In addition, normal and lesion chondrocytes in culture synthesized transforming growth factor-beta and 24,25(OH)2D3 but not 1,25(OH)2D3. There was no significant difference in the production rate of these growth regulators between normal and lesion chondrocytes. In contrast, in growth plate sections, alkaline phosphatase activity was markedly reduced in the lesion chondrocytes and sites of mineralization were not evident. Type II collagen was located throughout the growth plate and lesion, but type X collagen was not present within the lesion except at sites of vascularization. These results indicate that, in culture, lesion chondrocytes have the ability to differentiate terminally and mineralize, and suggest that the primary abnormality in TD is related to a developmental fault which is only operative in vivo. This may include a defect in cartilage vascularization and/or impairment of chondrocyte differentiation by mechanisms that have not yet been elucidated but may involve the abnormal production of regulatory factors.

We tested the hypothesis that impaired nitric oxide (NO)-mediated, endothelium-dependent dilation in aged soleus muscle feed arteries (SFA) is due to an age-related decrement in PI3-kinase(PI3K)/protein kinase B (Akt)-dependent phosphorylation of endothelial NO synthase (eNOS) on serine residue 1177 (peNOSser1177). SFA from young (4 mo) and old (24 mo) Fischer 344 rats were cannulated for examination of endothelium-dependent vasodilator responses to acetylcholine (ACh). To determine the mechanism by which aging affected vasodilation to ACh, vasodilator responses were assessed in the absence and presence of Nw-nitro-L-arginine (L-NNA, to inhibit NOS), LY-294002 (to inhibit PI3K), or 1L6hydroxymethyl-chiro-inositol-2-(R)-2-O-methyl-3-O-octadecyl-sn-glycerocarbonate (AktI, to inhibit Akt). Results indicate that ACh-induced vasodilation was significantly blunted in old SFA, whereas dilation to sodium nitroprusside (a NO donor) was not compromised. The age-group difference in ACh-induced dilation was abolished in the presence of L-NNA, LY-294002, or AktI. In a separate set of experiments, ACh-induced vasodilation was assessed in SFA from young and old rats. SFA were subsequently removed from the pipettes, snap frozen, and immunoblot analysis was used to assess p-AktSer473, peNOSser1177, total Akt and total eNOS protein content. ACh-induced vasodilation was blunted in old SFA; however, the p-AktSer473/Akt and p-eNOSser1177/eNOS ratios were similar in young and old SFA. Collectively, these results indicate that NO-mediated dilation is impaired in old SFA; however, the decrement in endothelial function is not due to reduced PI3K/Akt-dependent phosphorylation of eNOS on serine residue 1177. Research supported by AHA 0765043Y (CRW), AHA 4150031 (CRW), and Sydney and J.L. Huffines Institute of Sports Medicine Graduate Student Research Grants (MJL, JWS, and DWT).

A foal, small and jaundiced from birth, succumbed after two months to chronic hepatic damage which was characterised by fibrosis, biliary ductular hyperplasia and the presence of pleomorphic hepatocytes containing either a single large nucleus or multiple nuclei. The fixed liver contained sulfur-bound pyrroles, which are derived from pyrrolizidine alkaloids. During pregnancy the pasture was heavily infested with the pyrrolizidine alkaloid-containing plant, Senecio madagascariensis. The hepatic disease affecting the foal appears to have been initiated by consumption of the alkaloids by the mare during gestation, and to represent a rare case of congenital pyrrolizidine alkaloidosis.

Parathyroid hormone-related peptide (PTHrP) has a key role in the growth of long bones, as it is a negative regulator of growth plate chondrocyte terminal differentiation. We have examined the distribution and gene expression levels of PTHrP in the growth plates of broiler chickens with tibial dyschondroplasia (TD) in order to determine whether increased expression of PTHrP is responsible for the delayed chondrocyte differentiation that is characteristic of this skeletal disorder. PTHrP protein distribution and gene expression levels were assessed by immunocytochemistry and reverse transcriptase-polymerase chain reaction, respectively. In growth plates of normal birds, PTHrP was found to be distributed throughout all maturational zones of the growth plate. In cartilage proximal to the TD lesion, PTHrP immunostaining and the level of PTHrP gene expression were similar to that observed in normal birds. In contrast, many chondrocytes within the centre of the TD lesion stained poorly for PTHrP and this was reflected in the lower levels of PTHrP mRNA detected in lesion cells. These results suggest that alterations in PTHrP distribution and gene expression are not primarily responsible for the delayed chondrocyte differentiation and hypertrophy noted in dyschondroplasia, but are a result of secondary changes due to the pathology of the condition.

Diagnosis of anorexia nervosa (AN) and bulimia nervosa (BN), while including such physiological data as weight and the reproductive status of the individual, are primarily based on questionnaires and interviews that rely on self-report of both body-related concerns and eating-related behaviors. While some key components of eating disorders are psychological and thus introspective in nature, reliance on self-report for the assessment of eating-related behaviors and nutritional status lacks the objectivity that a physiologically based measure could provide. The development of a more physiologically informed diagnosis for AN and BN would provide a more objective means of diagnosing these disorders, provide a sound physiological basis for diagnosing subclinical disorders and could also aid in monitoring the effectiveness of treatments for these disorders. Empirically supported, physiologically based methods for diagnosing AN and BN are reviewed herein as well as promising physiological measures that may potentially be used in the diagnosis of AN and BN.

Phytochemicals have provided an abundant and effective source of therapeutics for the treatment of cancer. Here we describe the characterization of a novel plant toxin, persin, with in vivo activity in the mammary gland and a p53-, estrogen receptor–, and Bcl-2-independent mode of action. Persin was previously identified from avocado leaves as the toxic principle responsible for mammary gland–specific necrosis and apoptosis in lactating livestock. Here we used a lactating mouse model to confirm that persin has a similar cytotoxicity for the lactating mammary epithelium. Further in vitro studies in a panel of human breast cancer cell lines show that persin selectively induces a G2-M cell cycle arrest and caspase-dependent apoptosis in sensitive cells. The latter is dependent on expression of the BH3-only protein Bim. Bim is a sensor of cytoskeletal integrity, and there is evidence that persin acts as a microtubule-stabilizing agent. Due to the unique structure of the compound, persin could represent a novel class of microtubule-targeting agent with potential specificity for breast cancers. [Mol Cancer Ther 2006;5(9):2300–9]

Glucocorticoids (GC) are used extensively in children and may cause growth retardation, which is in part due to the direct effects of GC on the growth plate. We characterised the ATDC5 chondrocyte cell line, which mimics the in vivo process of longitudinal bone growth, to examine the effects of dexamethasone (Dex) and prednisolone (Pred) during two key time points in the chondrocyte life cycle - chondrogenesis and terminal differentiation. Additionally, we studied the potential for recovery following Dex exposure. During chondrogenesis, Dex and Pred exposure at 10(-8) M, 10(-7) M and 10(-6) M resulted in a significant mean reduction in cell number (28% vs 20%), cell proliferation (27% vs 24%) and proteoglycan synthesis (47% vs 43%) and increased alkaline phosphatase (ALP) activity (106% vs 62%), whereas the incidence of apoptosis was unaltered. Minimal effects were noted during terminal differentiation with both GC although all concentrations of Dex lowered apoptotic cell number. To assess catch-up growth the cells were incubated for a total of 14 days which included 1, 3, 7, 10 or 14 days exposure to 10(-6) M Dex, prior to the recovery period. Recovery of proteoglycan synthesis was irreversibly impaired following just one day exposure to Dex. Although cell number showed a similar pattern, significant impairment was only achieved following 14 days exposure. Irreversible changes in ALP activity were only noticed following 10 days exposure to Dex. In conclusion, GC have maximal effects during chondrogenesis; Dex is more potent than Pred and cells exposed to Dex recover but this may be restricted due to differential effects of GC on specific chondrocyte phenotypes.

Chondrocyte differentiation during embryonic bone growth is controlled by interactions between PTHrP and Indian hedgehog. We have now determined that the major components of this signaling pathway are present in the postembryonic growth plate. PTHrP was immunolocalized throughout the growth plate, and semiquantitative RT-PCR analysis of maturationally distinct chondrocyte fractions indicated that PTHrP, Indian hedgehog, and the PTH/PTHrP receptor were expressed at similar levels throughout the growth plate. However, patched, the hedgehog receptor, was more highly expressed in proliferating chondrocytes. Although all fractionated cells responded to PTHrP in culture by increasing thymidine incorporation and cAMP production and decreasing alkaline phosphatase activity, the magnitude of response was greatest in the proliferative chondrocytes. Bone morphogenetic proteins are considered likely intermediates in PTHrP signaling. Expression of bone morphogenetic protein-2 and 4--7 was detected within the growth plate, and PTHrP inhibited the expression of bone morphogenetic protein-4 and 6. Although organ culture studies indicated a possible paracrine role for epiphyseal chondrocyte-derived PTHrP in regulating growth plate chondrocyte differentiation, the presence within the postembryonic growth plate of functional components of the PTHrP-Indian hedgehog pathway suggests that local mechanisms intrinsic to the growth plate exist to control the rate of endochondral ossification.

Reduced availability of tetrahydrobiopterin (BH4) contributes to the age-related decline of nitric oxide (NO)-mediated vasodilatation of soleus muscle arterioles. Depending on availability of substrate and/or necessary co-factors, endothelial nitric oxide synthase (eNOS) can generate NO and/or superoxide (O2−). We evaluated the effects of age and chronic exercise on flow-induced vasodilatation and levels of NO and O2− in soleus muscle arterioles. Young (3 months) and old (22 months) male rats were exercise trained or remained sedentary (SED) for 10 weeks. Flow-stimulated NO and O2−, as well as BH4 and l-arginine content, were determined in soleus muscle arterioles. Flow-induced vasodilatation was assessed under control conditions and during the blockade of O2− and/or hydrogen peroxide. Exercise training enhanced flow-induced vasodilatation in arterioles from young and old rats. Old age reduced, and exercise training restored, BH4 content and flow-stimulated NO availability. Flow-stimulated, eNOS-derived O2− levels were higher in arterioles from old SED compared to those from young SED rats. Exercise training increased flow-stimulated eNOS-derived O2− levels in arterioles from young but not old rats. O2− scavenging with Tempol reduced flow-induced vasodilatation from all groups except young SED rats. Addition of catalase to Tempol-treated arterioles eliminated flow-induced vasodilatation in arterioles from all groups. Catalase reduced flow-induced vasodilatation from all groups. In Tempol-treated arterioles, flow-induced vasodilatation was restored by deferoxamine, an iron chelator. These data indicate that uncoupling of eNOS contributes to the age-related decline in flow-induced vasodilatation; however, reactive oxygen species are required for flow-induced vasodilatation in soleus muscle arterioles from young and old rats.

The Centers for Disease Control and Prevention (CDC) recommends periodic tuberculin skin testing of healthcare workers with potential exposure to Mycobacterium tuberculosis. However, many healthcare facilities have neither a system to identify workers due for their skin test nor a means of analyzing aggregate data. To illustrate some of the complexities involved in tuberculin skin test (TST) tracking and analysis, and how these might be addressed, this report describes a software package called staffTRAK-TB, developed by the CDC to facilitate surveillance of tuberculosis infection in healthcare workers. staffTRAK-TB records data for each healthcare worker, including demographic information, occupation, work location, multiple TST results, and results of evaluations to determine if clinically active tuberculosis is present. Programmed reports include lists of workers due and overdue for skin tests, and skin test conversion rates by occupation or worksite. Standardization of types of occupations and locations allows data from multiple facilities to be aggregated and compared. Data transfer to the CDC can be performed via floppy diskettes. staffTRAK-TB illustrates important issues in software structure, standardization of occupation and work-location information, relevant data items, and reports and analyses that would be useful in practice. Developing software that adequately addresses the epidemiological issues is complex, and the lessons learned may serve as a model for hospital epidemiologists, infection control personnel, occupational health personnel, and computer programmers considering software development in this area or trying to optimize their facility's TST surveillance.

Background: Intraocular cilia present clinical perplexity due to their radiolucency, the extremely variable ocular response to such cilia, and the inadvisability of using MRI in cases of suspected metallic intraocular foreign bodies (IOFB). Methods: Two cases of intravitreal cilia associated with phakic penetrating eye injury are described where preoperative CT scan revealed no retained IOFB. Results: B-scan ultrasonography detected intravitreal cilia in one patient and raised this suspicion in the other. One patient presented with endophthalmitis unresponsive to intravitreal antibiotics, the other with culture-negative anterior uveitis. Both underwent vitrectomy and removal of cilia. Conclusions: Intravitreal cilia should be considered in penetrating eye injuries even in phakic eyes with no radiological evidence of IOFB, especially if associated with endophthalmitis. B-scan ultrasonography may aid detection of intravitreal cilia and thus alter clinical management.

Background: Orbital venous anomalies can result in significant morbidity and have been reported in association with other venous anomalies, some with the potential for serious complication. Methods/results: We present a case of an orbital venous anomaly coexistent with a large cerebellar venous angioma and a linear sebaceous naevus. Clinical features, associations, complications .and management principles are presented. Conclusion: Upon clinical recognition of an orbital venous anomaly, brain imaging and appropriate clinical assessment should be considered in light of the possibility of coexistence of potentially life-threatening lesions.