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Systemic administration of interleukin (IL)-12 induces potent anti-tumor immune responses in preclinical cancer models through the systemic activation of effector immune cells and release of proinflammatory cytokines. IL-12-loaded PLGA nanospheres (IL12ns) are hypothesized to improve therapeutic efficacy and thwart unwanted side effects observed in previous human clinical trials. Through the investigation of peripheral blood and local tissue immune responses in healthy BALB/c mice, the immune-protective pharmacodynamics of IL12ns were suggested. Nanospheres increased pro-inflammatory plasma cytokines/chemokines (IFN-γ, IL-6, TNF-α, and CXCL10) without inducing maladaptive transcriptomic signatures in circulating peripheral immune cells. Gene expression profiling revealed activation of pro-inflammatory signaling pathways in systemic tissues, the likely source of these effector cytokines. These data support that nanosphere pharmacodynamics, including shielding IL-12 from circulating immune cells, depositing peripherally in systemic immune tissues, and then slowly eluting bioactive cytokine, thereafter, are essential to safe immunostimulatory therapy., Competing Interests: B.A.L., is founder and Chief Scientific Officer of ICaPath Inc., which holds the worldwide exclusive license to the technology presented from West Virginia University Research Corporation (Patent: PROTEIN-LOADED PLGA NANOSPHERES. PCT/US2020/063314. WO2021/113638A1). All other authors declare no competing interests., (© 2024 The Authors.)

Background: Elevated mental illness prevalence complicates efforts designed to address the opioid crisis in Appalachia. The recovery community acknowledges that loneliness impacts mood and engagement in care factors; however, the predictive relationship between loneliness and retention in medication-assisted outpatient treatment programs has not been explored. Our objectives were to identify associations between mental health factors and retention in treatment and elucidate treatment retention odds. Data were collected from eighty participants ( n = 57 retained, n = 23 not retained) of a mindfulness-based relapse prevention (MBRP) intervention for individuals receiving medication for opioid use disorder (MOUD) in Appalachia. Loneliness, depression, and anxiety did not differ between the retained and not retained, nor did they predict not being retained; however, mindfulness was significantly lower among those not retained in treatment compared to those retained (OR = 0.956, 95% CI (0.912-1.00), and p < 0.05). Preliminary findings provide evidence for mindfulness training integration as part of effective treatment, with aims to further elucidate the effectiveness of mindfulness therapies on symptom reduction in co-occurring mental health disorders, loneliness, and MOUD treatment retention.

Loneliness is a significant risk factor for substance use, however, impacts of treatments on loneliness are relatively unexplored. Living in a rural location is a greater risk factor for loneliness. This study examined data from a quasi-experimental study in rural Appalachia, comparing the effectiveness of Mindfulness-Based Relapse Prevention (MBRP) versus Treatment as Usual (TAU) among adults receiving MOUD in outpatient therapy. Our objective was to determine whether observed reductions in self-reported craving, anxiety, depression, and increased perceived mindfulness would also improve loneliness reports. Eighty participants (n = 35 MBRP; n = 45 TAU) were included in the analysis from a group-based Comprehensive Opioid Addiction Treatment program. Outcomes tracked included craving, anxiety, depression, mindfulness, and loneliness as measured by the Revised UCLA Loneliness Scale (R-UCLA). A linear mixed model ANOVA determined the significance of the treatments on changes in loneliness scores at baseline, 12 weeks, 24 weeks, and 36 weeks post-recruitment. Both groups reported significantly reduced loneliness over the course of the study (F = 16.07, p < 0.01), however there were no significant differences between groups. Loneliness was also significantly positively ( p < 0.01) correlated with anxiety (0.66), depression (0.59), and craving (0.38), and significantly ( p < 0.01) inversely correlated (-0.52) with mindfulness. Results suggest that participation in MOUD group-based outpatient therapy has the potential to diminish loneliness and associated poor psychological outcomes. Thus, it is possible that a more targeted intervention for loneliness would further diminish loneliness, which is important as loneliness is linked to risk for relapse.

Background: Accurate aneurysm measurements are important for selecting the WEB device. The objective was to validate a cloud-based platform, SurgicalPreview (SP) against manual measurements for aneurysm analysis., Methods: Two sets of measurements each for SP and manual methods were obtained for 40 aneurysms. Reliability and agreement were assessed with intra-class correlation coefficient (ICC) and Bland-Altman plots respectively. Kappa coefficient was used to assess agreement for predicting WEB size., Results: There was good reliability for repeat SP measurements: aneurysm diameter (ICC-1, 95%CI 0.98-1), height (ICC-1, 95%CI 0.99-1) and neck diameter (ICC-0.96, 95%CI 0.93-0.98). There was good reliability for the two manual diameter (ICC-0.97, 95%CI 0.9-0.97) and height (ICC-0.93, 95%CI 0.87-0.96) measurements and moderate for neck diameter (ICC-0.76, 95%CI 0.54-0.87). There was greater agreement for SP versus manual repeat measurements on Bland-Altman plots. Reliability between the SP and manual methods was good for aneurysm diameter (ICC-0.98, 95%CI 0.95-1) and height (ICC-0.96, 95%CI-0.93-0.98) and moderate for neck. (ICC-0.6, 95%CI -0.22-0.87). The Bland-Altman plots confirmed better agreement between the two methods for the aneurysm diameter and height than the neck. There was strong agreement between the methods for predicting the WEB diameter (Kappa-0.84, 95%CI 0.71-0.97) and moderate for predicting WEB height (Kappa-0.66, 95%CI 0.43-0.89). There was moderate agreement for predicted versus deployed WEB diameter: SP (Kappa-0.56, 95%CI 0.38-0.74), Manual (Kappa-0.53, 95%CI 0.34-0.71)., Conclusion: The SurgicalPreview® had greater agreement for repeat measurements. There was good reliability between the two methods for predicting WEB diameter and height and moderate agreement between predicted versus deployed WEB diameter.

Chlorpyrifos (CPF) is one of the most widely-used pesticides globally for agricultural purposes. Certain occupations (e.g., farmers, military) are at an increased risk for high-dose exposure to CPF, which can lead to seizures and irreversible brain injury. Workers with the highest risk of exposure typically experience increased circulating cortisol levels, which is related to physiological stress. To better represent this exposure scenario, a mouse model utilized exogenous administration of corticosterone (CORT; high physiologic stress mimic) in combination with chlorpyrifos oxon (CPO; oxon metabolite of CPF); this combination increases neuroinflammation post-exposure. In the present study adult male C57BL/6J mice were given CORT (200 μg/mL) in drinking water for seven days followed by a single intraperitoneal injection of CPO (8.0 mg/kg) on day eight, and euthanized 0.5, 2, and 24 h post-injection. Ten post-translationally modified proteins were measured in the frontal cortex and striatum to evaluate brain region-specific effects. The spatiotemporal response to CORT + CPO sequentially activated phosphoproteins (p-ERK1/2, p-MEK1/2, p-JNK) involved in mitogen-activated protein kinase (MAPK) signaling. Observed p-ZAP70 responses further integrated MAPK signaling and provided a spatiotemporal connection between protein phosphorylation and neuroinflammation. This study provides insight into the spatiotemporal cellular signaling cascade following CORT + CPO exposure that represent these vulnerable populations., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The purpose of this study is to evaluate survivorship and outcomes of high-activity patients compared to low-activity patients after total hip arthroplasty., Methods: A retrospective review identified 2002 patients (2532 hip) that underwent a primary total hip arthroplasty with vitamin E-infused highly crosslinked polyethylene liner. Patients were divided into 2 groups based on their University of California Los Angeles (UCLA) activity level: low activity (LA) (UCLA ≤5) and high activity (HA) (UCLA ≥6). Outcomes included Harris Hip Score, UCLA activity score, and reoperations. A multivariate nominal regression analysis was performed to evaluate the significance of postoperative activity level on survivorship., Results: The mean follow-up duration was 4.5 years (range, 0.3 to 9.9 years). HA group had significantly higher improvements in Harris Hip Score (HHS) ( P < .001) and UCLA activity score ( P < .001). Aseptic revisions were performed in 2.1% of the LA group and in 0.4% hips of the HA group ( P < .001). After controlling for age, gender, preoperative pain, HHS, and body mass index, a higher postoperative activity level remained a significant factor for improved aseptic survivorship with an odds ratio of 4.9 (95% confidence interval, 1.1 to 21.2, P  = .03). The all-cause 5-year survivorship was 99% for the HA group and 96% to for the LA group ( P < .001). The aseptic 5-year survivorship was 99.6% for the HA group and 98% for the LA group ( P < .001)., Conclusions: This study found that a higher activity level after primary THA was not deleterious to survivorship at short to midterm follow-up with modern implants., (© 2021 The Authors.)

Aims: Veterans from the 1990-91 Gulf War were exposed to acetylcholinesterase inhibitors (AChEIs), and, following service, an estimated one-third began suffering from a medically unexplained, multi-symptom illness termed Gulf War Illness (GWI). Previous research has developed validated rodent models that include exposure to exogenous corticosterone (CORT) and AChEIs to simulate high stress and chemical exposures encountered in theater. This combination of exposures in mice resulted in a marked increase in neuroinflammation, which is a common symptom of veterans suffering from GWI. To further elucidate the mechanisms associated with these mouse models of GWI, an investigation into intracellular responses in the cortex were performed to characterize the early cellular signaling changes associated with this exposure-initiated neuroinflammation., Main Methods: Adult male C57BL/6J mice were exposed to CORT in the drinking water (200 μg/mL) for 7 days followed by a single intraperitoneal injection of diisopropyl fluorophosphate (DFP; 4.0 mg/kg) or chlorpyrifos oxon (CPO; 8.0 mg/kg), on day 8 and euthanized 0.5, 2, and 24 h post-injection. Eleven post-translationally modified protein targets were measured using a multiplexed ELISA., Key Findings: Phosphoprotein responses were found to be exposure specific following AChEI insult, with and without CORT. Specifically, CORT + CPO exposure was found to sequentially activate several phosphoproteins involved in mitogen activated protein kinase signaling (p-MEK1/2, p-ERK1/2, and p-JNK). DFP alone similarly increased proteins in this pathway (p-RPS6, and p-JNK), but the addition of CORT ameliorated these affects., Significance: The results of this study provide insight into differentially activated pathways depending on AChEI in these GWI models., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Published by Elsevier Ltd.)

Background: Perfluoroalkyl substances (PFASs) have been associated with decreased immunity to childhood tetanus and diphtheria immunizations. If these vaccinations are vulnerable to influence from PFASs, questions arise about associations with other common inoculations., Objective: To examine whether serum PFASs were associated with reduced immunity to rubella immunization, and whether interactions with sex or ethnicity warranted analytic stratification. Usually, toxicology analyses are calculated controlling for race and sex. However, sex differences in immune function have been reported and a reduction of immunity to rubella in women could pose risks such miscarriage., Methods: We analyzed a nationally representative sample of individuals ≥ 12 years from the National Health and Nutrition Examination Survey (NHANES) for years 1999-2000 and 2003-2004 for whom PFAS measures were available. Our analytic strategy was to start with separate analyses for youth and adults controlling for several covariates including ethnicity and sex, as well as the interaction of these terms with PFASs. If there was a main effect of PFASs and an interaction term, we would stratify analyses of effect size. The outcome variable was Rubella IgG titers by quartile of perfluoroalkyl substances., Results: After exclusion for missing data, the analyzed sample contained 581 adult women, 621 adult men, and 1012 youth. There was no significant effect of PFASs on immunity in youths but a significant effect of both PFOA and PFOS in adults, as well as a significant interaction of PFOA x sex and a borderline significant interaction of PFOS x sex. When effect size analyses were stratified by sex, a significant association between rubella titres and PFOA was found in men but not women and PFOS was not significant in either sex., Conclusions: These results support our earlier studies showing sex specific responses to PFASs and indicate the importance of thinking carefully about analytic strategies in population based toxicology research., Competing Interests: The authors have declared that no competing interests exist.

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., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The 21st-century epidemic of pharmaceutical and other drug-intoxication deaths in the United States (US) has likely precipitated an increase in misclassified, undercounted suicides. Drug-intoxication suicides are highly prone to be misclassified as accident or undetermined. Misclassification adversely impacts suicide and other injury mortality surveillance, etiologic understanding, prevention, and hence clinical and public health policy formation and practice., Objective: To evaluate whether observed variation in the relative magnitude of drug-intoxication suicides across US states is a partial artifact of the scope and quality of toxicological testing and type of medicolegal death investigation system., Methods: This was a national, state-based, ecological study of 111,583 drug-intoxication fatalities, whose manner of death was suicide, accident, or undetermined. The proportion of (nonhomicide) drug-intoxication deaths classified by medical examiners and coroners as suicide was analyzed relative to the proportion of death certificates citing one or more specific drugs and two types of state death investigation systems. Our model incorporated five sociodemographic covariates. Data covered the period 2008-2010, and derived from NCHS's Multiple Cause-of-Death public use files., Results: Across states, the proportion of drug-intoxication suicides ranged from 0.058 in Louisiana to 0.286 in South Dakota and the rate from 1 per 100,000 population in North Dakota to 4 in New Mexico. There was a low correlation between combined accident and undetermined drug-intoxication death rates and corresponding suicide rates (Spearman's rho = 0.38; p<0.01). Citation of 1 or more specific drugs on the death certificate was positively associated with the relative odds of a state classifying a nonhomicide drug-intoxication death as suicide rather than accident or undetermined, adjusting for region and type of state death investigation system (odds ratio, 1.062; 95% CI,1.016-1.110). Region, too, was a significant predictor. Relative to the South, a 10% increase in drug citation was associated with 43% (95% CI,11%-83%), 41% (95% CI,7%-85%), and 33% (95% CI,1%-76%) higher odds of a suicide classification in the West, Midwest, and Northeast, respectively., Conclusion: Large interstate variation in the relative magnitude of nonhomicide drug-intoxication deaths classified as suicide by medical examiners and coroners in the US appears partially an artifact of geographic region and degree of toxicological assessment in the case ascertainment process. Etiologic understanding and prevention of drug-induced suicides and other drug-intoxication deaths first require rigorous standardization involving accurate concepts, definitions, and case ascertainment.

The accurate determination of time since death, or postmortem interval (PMI), can be critical in the investigation of suspicious deaths. Knowing when a suspicious death occurred can limit the number of potential suspects to those without a viable alibi for the time of the crime. The forensic techniques currently employed to determine PMI: pathology, entomology, and anthropology, are accurate over different time periods following death. A large gap in time exists between the capabilities of forensic entomology and traditional anthropology, leaving a period in which PMI is difficult to estimate. In this study, time-dependent differences in RNA decay rates were examined to extend the time frame over which early PMI estimates can be made. Comparing the decay rates of a large, labile segment of β-actin RNA and a smaller, more stable, non-overlapping segment of the same RNA from tooth pulp, we were able to estimate PMI values of pigs buried within a shallow grave for up to 84 days. This compares favorably to an estimate of PMI using insect data. Full skeletonization and loss of insect activity was observed by day 28 of our study. In addition to differences in RNA decay rates, morphological changes were observed in the pulp as it aged postmortem. To provide a quantitative measure of progressive color changes, analysis of digital photographs of each tooth's pulp were used to construct a simple colorimetric assay. This assay was then used to cluster ages of pulp samples by color. The two assays, used in combination with one another, can create a more precise estimate of PMI. The potential advantages of this molecular means of estimating PMI include extending the time frame for such estimates, is applicable to samples collected worldwide (no specialized knowledge of local insect fauna is required), is relatively fast, and inexpensive., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: Gastrochisis is a congenital condition resulting in significant morbidity and mortality. Multiple studies have been done to evaluate the value of prognostic indicators with conflicting results. The aim of this study was to evaluate the role of ultrasound in this condition at a single institution while limiting the provider variables that may affect neonatal outcome., Methods: The antepartum charts of expectant mothers of affected fetuses as well as the neonatal hospital charts were reviewed at length. The cases were identified over a period of 4 years from April 1998 to February 2002. In addition, the archived photographs of ultrasounds performed on these fetuses were also reviewed and reread by two independent providers who were blinded to the outcome. Adverse neonatal outcome, including death and time to feeding (amongst many other variables) were assessed against the different ultrasound parameters including bowel thickness and dilation., Results: 25 patients were identified in the stated time frame. Six cases had to be dropped from the final analysis due to incomplete data including the transfer of 3 babies. There were 4 neonatal deaths. The mean birth weight was 2384 grams. There was a significant association with dilation and delta dilation (defined as the difference in bowel dilation from the final ultrasound from the baseline ultrasound cutoff of 4 mm) and time to feeding, time on ventilator and hospital stay. (P< 0.005). Other ultrasound parameters were not significantly correlated with neonatal outcome., Conclusion: Most ultrasound parameters do not help prognosticate the neonatal outcome in babies affected with this condition except for dilation and delta dilation, which are strong predictors of morbidity in the post delivery period. This information may be helpful to providers and parents of affected fetuses.

Aminoglycoside dosing has been studied in the obese population, typically recommending an adjusted weight utilizing a 40% dosing weight correction factor (IBW + 0.4 × (TBW-IBW)). These studies included limited numbers of morbidly obese patients and were not done in the era of extended interval aminoglycoside dosing. Here, we report a retrospective evaluation of morbidly obese patients receiving gentamicin or tobramycin at our hospital. The objective of this study was to evaluate the accuracy of the commonly recommended adjusted weight for weight-based dosing. There were 31 morbidly obese patients who received gentamicin or tobramycin 5-7 mg/kg every 24 hours using a 40% dosing weight correction factor. Our institution utilizes 16-hour postdose concentrations to monitor extended interval aminoglycosides. Twenty-two of the 31 patients (71%) achieved an appropriate serum drug concentration. Four patients (13%) were found to be supratherapeutic and 5 patients (16%) subtherapeutic. The only variable that correlated with supratherapeutic levels was older age (P = 0.0378). Our study helps to validate the current dosing weight correction factor (40%) in the morbidly obese population. We recommend caution when dosing aminoglycosides in morbidly obese patients who are of older age.

A stress-induced myocardial perfusion abnormality (MPS), in the absence of angiographically significant epicardial coronary artery disease, is considered a "false-positive" test result. We hypothesized that echocardiography would provide complementary prognostic and pathophysiologic data relevant to the management of patients with MPS and normal coronary angiograms. Accordingly, left atrial volume index (LAVi) was assessed by echocardiography in 38 patients with false positive MPS as defined by normal coronary angiograms and 26 patients with true negative MPS from a total of 1,356 patients stressed from July 2006-May 2008. Pathologically abnormal elevation of LAVi (≥ 32 mL/m(2)) was observed in 16 of 19 women (84%) and 11 of 19 men (58%) in the false positive MPS (FPMPS) group while none of the patients in the true negative MPS (TNMPS) group had elevated LAVi. In the FPMPS group mean LAVi was significantly higher in women than men (40.64 ± 11.4 mL/m(2) versus 32.6 ± 10.5 mL/m(2), P = 0.01). The mean LAVi in the FPMPS group was significantly different from the TNMPS group (36.6 ± 11.6 versus 21 ± 7 mL/m(2), P = 0.000). A stepwise logistic regression determined BSA, LAV and LAVi as useful in predicting false positive and true negative MPS. All three were significant predictors (P < 0.01) and the area under the ROC curve was 0.91. Our findings in this relatively small cohort suggest that patients with false positive MPS have a greater increased LAVi.

Potential ethical issues can arise during the process of epidemiological classification. For example, unnatural infant deaths are classified as accidental deaths or homicides. Societal sensitivity to the physical abuse and neglect of children has increased over recent decades. This enhanced sensitivity could impact reported infant homicide rates. Infant homicide and accident mortality rates in boys and girls in the USA from 1940 to 2005 were analysed. In 1940, infant accident mortality rates were over 20 times greater than infant homicide rates in both boys and girls. After about 1980, when the ratio of infant accident mortality rates to infant homicide rates decreased to less than five, and the sum of infant accident and homicide rates became relatively constant, further decreases in infant accident mortality rates were associated with increases in reported infant homicide rates. These findings suggest that the dramatic decline of accidental infant mortality and recent increased societal sensitivity to child abuse may be related to the increased infant homicide rates observed in the USA since 1980 rather than an actual increase in societal violence directed against infants. Ethical consequences of epidemiological classification, involving the principles of beneficence, non-maleficence and justice, are suggested by observed patterns in infant accidental deaths and homicides in the USA from 1940 to 2005.

Objectives: We investigated the relation between respiratory symptoms and exposure to water-damaged homes and the effect of respirator use in posthurricane New Orleans, Louisiana., Methods: We randomly selected 600 residential sites and then interviewed 1 adult per site. We created an exposure variable, calculated upper respiratory symptom (URS) and lower respiratory symptom (LRS) scores, and defined exacerbation categories by the effect on symptoms of being inside water-damaged homes. We used multiple linear regression to model symptom scores (for all participants) and polytomous logistic regression to model exacerbation of symptoms when inside (for those participating in clean-up)., Results: Of 553 participants (response rate = 92%), 372 (68%) had participated in clean-up; 233 (63%) of these used a respirator. Respiratory symptom scores increased linearly with exposure (P < .05 for trend). Disposable-respirator use was associated with lower odds of exacerbation of moderate or severe symptoms inside water-damaged homes for URS (odds ratio (OR) = .51; 95% confidence interval (CI) = 0.24, 1.09) and LRS (OR = 0.33; 95% CI = 0.13, 0.83)., Conclusions: Respiratory symptoms were positively associated with exposure to water-damaged homes, including exposure limited to being inside without participating in clean-up. Respirator use had a protective effect and should be considered when inside water-damaged homes regardless of activities undertaken.

Unlabelled: Staffing of rural emergency departments (ED) with residency-trained, board certified emergency physicians has been an ongoing challenge in the field of Emergency Medicine., Objectives: To describe the West Virginia (WV) emergency medicine (EM) workforce and make comparisons with the most recent (1999) national EM workforce study and the 1996 WV rural EM workforce study., Methods: A cross sectional mail survey of all non-governmental emergency departments (EDs) in WV was performed from 10/04-12/04. Subgroup analysis of rural EDs using the 1996 WV rural EM study criteria was conducted. Data collected included: number of physicians, residency training, board certification, ED volume, and the number and type of specialty services available., Results: Surveys were mailed to 55 EDs, with a 71% response rate (N=39) describing 310 physicians. Overall, 51% of physicians were either trained and/or board certified in EM, versus 62% in the 1999 national study. In the rural subgroup, 32% were either residency trained and/or board certified in EM, versus 12% in the 1996 WV study., Conclusions: Just over half of all physicians staffing WV's EDs are residency trained or board certified in EM, a number that lags well behind the national average. Rural EDs report even lower numbers, although the proportion has increased since the 1996 WV study. WV EM practitioners, particularly in more rural locations, continue to provide emergency care with less formal training, certification credentials, and specialty back-up.

A retrospective analysis was conducted of 79 consecutive patients who underwent enhanced external counterpulsation (EECP) at West Virginia University Hospitals during the period of November 1998 to September 2005 to determine its efficacy and safety in treating angina. A chart review and/or phone survey was performed to analyze pertinent clinical data (sublingual nitroglycerin use and angina class) pre and post EECP. A total of 60 (76%) patients who were referred for EECP successfully finished the 35 treatments. Seventy-five percent of the patient population improved at least one angina class after a full course of treatment. Therapy was discontinued due to adverse effects in 12 (15%) patients. Statistically significant improvements in angina class and reduction in anti-angina medications were observed in every co-morbid subgroup analyzed, including patients with peripheral vascular disease, diabetes, hyperlipidemia, hypertension, smoking, Post-MI, and LVEF < 40% (P < .05, Wilcoxon Signed-Rank test). Overall, EECP was effective in improving angina as reflected in a substantial reduction in antiangina medications in 59 (75%) patients.

DNA allows for the unambiguous identification of the person from whom a biological sample was derived but provides little information about when the sample was deposited. This information only indicated that the biological material was deposited at the crime scene prior to the collection of evidence. The ability to determine the age of a biological sample would greatly benefit the forensic science community. If there were independent evidence that the biological sample was deposited at the time of the crime, then its age would reveal when the crime occurred. If the time of the crime were known through another means, then the age of the biological sample could potentially exclude the human source as a suspect. We have used real-time reverse transcriptase PCR to show that the ratio between different types of RNA (mRNA versus rRNA) changes over time in a linear fashion when dried human blood from eight individuals was examined over the course of 150 days. Although other approaches have been used in the past to estimate the age of a biological sample, our approach offers the following advantages: enhanced detectability of small samples, simultaneous isolation of DNA and RNA from the same sample, species-specific probes, and an increased window of usefulness.

The present study was performed to determine whether nitric oxide overproduction is associated with deterioration in peripheral nerve function in type 1 diabetes. We measured peripheral nerve function and biochemical indicators of nitrosative stress annually for 3 years in 37 patients with type 1 diabetes. Plasma nitrite and nitrate (collectively NO(x)) were 34.0 +/- 4.9 micro mol/l in the control subjects and 52.4 +/- 5.1, 50.0 +/- 5.1, and 49.0 +/- 5.2 in the diabetic patients at the first, second, and third evaluations, respectively (P < 0.01). Nitrotyrosine (NTY) was 13.3 +/- 2.0 micro mol/l in the control subjects and 26.8 +/- 4.4, 26.1 +/- 4.3, and 32.7 +/- 4.3 in the diabetic patients (P < 0.01). Uric acid was suppressed by 20% in the diabetic patients (P < 0.001). Composite motor nerve conduction velocity for the median, ulnar, and peroneal nerves was decreased in patients with high versus low NTY (mean Z score -0.522 +/- 0.25 versus 0.273 +/- 0.22; P < 0.025). Patients with high NO(x) had decreased sweating, and those with suppressed uric acid had decreased autonomic function. In conclusion, nitrosative stress in early diabetes is associated with suppressed uric acid and deterioration in peripheral nerve function.

Patients with diabetic neuropathy typically have decreased sweating in the feet but excessive sweating in the upper body. Previous studies of sudomotor function in diabetes have included patients with longstanding disease. The present study was designed to test for the early presence of sudomotor dysfunction and to characterize its relation to glycemic control and other aspects of peripheral nerve function. A total of 37 patients (10 males, 27 females) enrolled in a longitudinal study, in which autonomic function was evaluated annually for 3 years. Patients enrolled 2-22 months after the diagnosis of type 1 diabetes. Forty-one age- and sex-matched healthy control subjects were also studied. Sweat production in response to acetylcholine stimulation was dramatically increased in the forearm at the time of the first evaluation (1.67 +/- 0.24 micro/cm2 in the diabetic patients vs. 1.04 +/- 0.14 microl/cm2 in the control subjects, P < 0.05). Likewise, the ratio of sweating in the forearm to sweating below the waist was higher in the diabetic patients (0.553 +/- 0.07 microl/cm2) than in the control subjects (0.385 +/- 0.04 microl/cm2, P < 0.05). Forearm sweat was negatively associated with the renin-toprorenin ratio and vanillylmandelic acid (VMA) excretion (P < 0.025), tests of sympathetic nerve function. The ratio of sweating in the forearm to sweating in the foot was likewise increased in diabetic patients with poor glycemic control. We interpret this redistribution of sudomotor responses to be indicative of sympathetic nerve injury and conclude 1) that the sympathetic nervous system is especially vulnerable to the adverse effects of chronic hyperglycemia and 2) that sympathetic dysfunction can be detected very early in type 1 diabetes.

This article reports the psychophysical assessment of nine battery-powered lifts, a sliding board, a walking belt, and a baseline manual method for transferring nursing home patients/residents from a bed to a chair. A separate article reports the biomechanical evaluation of the same task and devices. The objectives of the psychophysical assessment were to investigate the effects of resident-transferring methods on the psychophysical stress to nursing assistants performing the transferring task, and to identify transfer methods that could reduce the psychophysical stress reported by nursing assistants. Nine nursing assistants served as test subjects. Two elderly persons participated as residents. The results indicated that the psychophysical stresses on nursing assistants were significantly lower when performing resident transfers with some of the assistive devices than when performing transfers with the baseline manual transfer method. The nursing assistants generally preferred the basket-sling lift and stand-up lift to other methods. The residents' comfort and security ratings indicated the comfort and security with most of the assistive devices were greater than or equal to the baseline manual method. Most of the comments of the nursing assistants and residents on the assistive devices were favourable.

This is the first of two articles to report a biomechanical evaluation and psychophysical assessment of nine battery-powered lifts, a sliding board, a walking belt, and a baseline manual method for transferring nursing home residents from a bed to a chair. The objectives of the biomechanical evaluation were: (1) to investigate the effects of transfer method and resident weight on the biomechanical stress to nursing assistants performing the transferring task, and (2) to identify resident-transferring methods that could reduce the biomechanical stress to the nursing assistants. Nine nursing assistants served as test subjects; two elderly persons participated as residents. A four-camera motion analysis system, two force platforms, and a three-dimensional biomechanical model were used to measure biomechanical load. The results indicate that transfer method and resident weight affect a nursing assistant's low-back loading. The basket-sling and overhead lift devices significantly reduced the nursing assistants' back-compressive forces during the preparation phase of a resident transfer. In addition, the use of basket-sling, overhead, and stand-up lifts removed about two-thirds of the exposure to low-back stress (lifting activities per transfer) as compared to the baseline manual method. Thus, the use of these devices reduces biomechanical stress, and thereby will decrease the occurrence of resident-handling-related low-back injuries. Furthermore, lifting device maneuvering forces were found to be significantly different and a number of design/use problems were identified with various assistive devices. The second article will detail the psychophysical assessment of the same resident-transferring methods.

To obtain an estimate of prostate cancer prevalence when screening is applied to a workforce, we conducted a search of the English world literature from West Virginia University. Thirty-one papers which met selection criteria for screening were followed by histopathologic diagnosis. Publications using Prostate Specific Antigen (PSA) as a screening test were reviewed. The data from these papers were combined. Population characteristics were then selected to represent the demographics of a working population. Prostate cancer prevalence estimates for the demographics of a working population were calculated using a weighted mean after relevant studies lacked homogeneity and therefore failed meta-analysis. The expected prevalence of prostate cancer in a workplace surveillance population is 2.03% (95% C.I. from 1.69% to 2.37%). This information is useful to entities considering workplace surveillance. Selection bias, geographic location, and uncertainty in prediction of a representative workforce population may strongly influence estimates.

Objective: To examine the influence of gestational age on seizures in the neonatal intensive care unit., Study Design: A cohort of 4165 neonates admitted to a university intensive care unit between 1986 and 1995. The incidence, time of onset, and etiology of neonatal seizures in the cohort were distributed by gestational age. Logistic regression and t test were used to examine the relationship between gestational age and seizures in the neonatal intensive care unit., Results: Seizures occurred in 356 (8.6%) infants. The seizure rate was parabolically related to gestational age, such that infants at 30 to 36 weeks' gestation had a 4.8% rate compared with 11.9% and 14.1% rates for infants < 30 and > 36 weeks, respectively (p < 0.001). Seizures manifested earlier in infants < 30 weeks (2.3 +/- 5.6 days of life) and > 36 weeks (3.7 +/- 8.7 days) gestational age compared with neonates 30 to 36 weeks (10.4 +/- 14.5 days) (p < 0.001). Intraventricular hemorrhage was the principal etiology underlying the higher seizure rate for infants < 30 weeks (p < 0.001). Hypoxic-ischemic encephalopathy and congenital malformations were primary factors for infants > 36 weeks (p < 0.01). Nervous system infections were evenly distributed across gestational age., Conclusion: Gestational age exerts a considerable influence on the incidence, onset, and etiology of neonatal seizures.

Escherichia coli strain JM107/pQR700 possesses the vector pBGS18, a high copy number plasmid carrying kanamycin resistance, into which a 4.4 kb fragment containing the transketolase gene had been cloned. The bacterium was grown at 20 and 1000 1 scale for the production of transketolase. The specific growth rate was maintained at 0.15 h-1 until the bacterial concentration reached 20 g dry wt per litre at which point the culture was harvested. The clarified cell extract obtained after disruption of the bacteria in a high-pressure homogeniser contained about 230 U ml-1 of the enzyme, which represented about 40% of the total protein released. No further purification was done at large scale as the clarified cell extract could be used satisfactorily for biotransformations.