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Background: Existing evidence indicates household income as a predictor of health-related quality of life (HRQoL) following a colorectal cancer diagnosis. This association likely varies with neighborhood socioeconomic status (nSES), but evidence is limited. Methods: We included data from 1,355 colorectal cancer survivors participating in the population-based Puget Sound Colorectal Cancer Cohort (PSCCC). Survivors reported current annual household income; we measured HRQoL via the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) tool. Using neighborhood data summarized within a 1-km radial buffer of Census block group centroids, we constructed a multidimensional nSES index measure. We employed survivors' geocoded residential addresses to append nSES score for Census block group of residence. With linear generalized estimating equations clustered on survivor location, we evaluated associations of household income with differences in FACT-C mean score, overall and stratified by nSES. We used separate models to explore relationships for wellbeing subscales. Results: We found lower household income to be associated with clinically meaningful differences in overall FACT-C scores [ Conclusions: Our findings suggest that recently diagnosed lower income colorectal cancer survivors are likely to report lower HRQoL, and modestly more so in lower SES neighborhoods. Impact: The findings from this work will aid future investigators' ability to further consider the contexts in which the income of survivors can be leveraged as a means of improving HRQoL

Mitochondria produce the bulk of the energy used by almost all eukaryotic cells through oxidative phosphorylation (OXPHOS) which occurs on the four complexes of the respiratory chain and the F1–F0 ATPase. Mitochondrial diseases are a heterogenous group of conditions affecting OXPHOS, either directly through mutation of genes encoding subunits of OXPHOS complexes, or indirectly through mutations in genes encoding proteins supporting this process. These include proteins that promote assembly of the OXPHOS complexes, the post-translational modification of subunits, insertion of cofactors or indeed subunit synthesis. The latter is important for all 13 of the proteins encoded by human mitochondrial DNA, which are synthesised on mitochondrial ribosomes. Together the five OXPHOS complexes and the mitochondrial ribosome are comprised of more than 160 subunits and many more proteins support their biogenesis. Mutations in both nuclear and mitochondrial genes encoding these proteins have been reported to cause mitochondrial disease, many leading to defective complex assembly with the severity of the assembly defect reflecting the severity of the disease. This review aims to act as an interface between the clinical and basic research underpinning our knowledge of OXPHOS complex and ribosome assembly, and the dysfunction of this process in mitochondrial disease.

Background Adding additional bicycle and pedestrian paths to an area can lead to improved health outcomes for residents over time. However, quantitatively determining which areas benefit more from bicycle and pedestrian paths, how many miles of bicycle and pedestrian paths are needed, and the health outcomes that may be most improved remain open questions. Objective Our work provides and evaluates a methodology that offers actionable insight for city-level planners, public health officials, and decision makers tasked with the question “To what extent will adding specified bicycle and pedestrian path mileage to a census tract improve residents’ health outcomes over time?” Methods We conducted a factor analysis of data from the American Community Survey, Center for Disease Control 500 Cities project, Strava, and bicycle and pedestrian path location and use data from two different cities (Norfolk, Virginia, and San Francisco, California). We constructed 2 city-specific factor models and used an algorithm to predict the expected mean improvement that a specified number of bicycle and pedestrian path miles contributes to the identified health outcomes. Results We show that given a factor model constructed from data from 2011 to 2015, the number of additional bicycle and pedestrian path miles in 2016, and a specific census tract, our models forecast health outcome improvements in 2020 more accurately than 2 alternative approaches for both Norfolk, Virginia, and San Francisco, California. Furthermore, for each city, we show that the additional accuracy is a statistically significant improvement (P2 weeks of poor physical health days in the census tract within 1.83% (SD 0.57%). For San Francisco (n=49 census tracts), our approach estimates, on average, that the percentage of individuals who had a stroke in the census tract is within 1.81% (SD 0.52%), and the percentage of individuals with diabetes in the census tract is within 1.26% (SD 0.91%). Conclusions We propose and evaluate a methodology to enable decision makers to weigh the extent to which 2 bicycle and pedestrian paths of equal cost, which were proposed in different census tracts, improve residents’ health outcomes; identify areas where bicycle and pedestrian paths are unlikely to be effective interventions and other strategies should be used; and quantify the minimum amount of additional bicycle path miles needed to maximize health outcome improvements. Our methodology shows statistically significant improvements, compared with alternative approaches, in historical accuracy for 2 large cities (for 2016) within different geographic areas and with different demographics.

BACKGROUND Extant evidence links neighborhood walkability with obesity-related health in the general population. This association likely exists in cancer survivors, but research is limited. Furthermore, a disproportionate obesity burden in African American cancer survivors warrants subgroup-specific analyses. METHODS This study analyzed data from 2089 African American cancer survivors participating in the Detroit Research on Cancer Survivors (ROCS) cohort. On the basis of built environment data summarized within 1-km radial buffers around census block centroids, a multidimensional neighborhood walkability index (NWI) was constructed. Survivors' residential addresses at Detroit ROCS enrollment were geocoded, and addresses were linked to NWI scores via the census block of residence. At study enrollment, survivors reported height and weight; these data were used to calculate their body mass index (BMI). Associations between NWI quartiles and BMI overall and by cancer type, biological sex, and physical activity engagement were evaluated. RESULTS BMI was found to be inversely associated with increasing NWI quartile (P for trend < .01). This inverse relationship was observed in men (P for trend < .01) and in survivors reporting any regular physical activity (P for trend < .01). CONCLUSIONS This study's findings suggest that among African American cancer survivors, higher neighborhood walkability is associated with lower BMI. As health care systems in the United States increasingly consider the role of the neighborhood environment in their patients' health, these findings provide additional evidence supporting health systems' incorporation of neighborhood walkability as an obesity-related health indicator for this cancer survivor subgroup and potentially for cancer survivors from other vulnerable populations.

Objective: To identify and assess the criticality for infrastructure assets and better understand their dependencies, interdependencies, and supply chain reliance. Design: This study used a modified mission impact, symbolism, history, accessibility, recognizability, population, and proximity model combined with a deliberative process with regional subject matter experts. Setting: Hampton roads Virginia maritime area. Participants: Emergency managers, US Corps of Engineers, US Coast Guard, law enforcement, railroad industry, intelligence community, Virginia Department of Emergency Management, Virginia Department of Transportation, and Virginia Port. Main outcome: A prioritized list of one-to-n critical assets in the maritime area and identification of up and downstream dependencies. Results: The final most highly critical grouping included 26 out of 277 assets including especially important road bridges and tunnels, rail bridges and choke points, shipping channels, and marine terminals. Conclusions: Subject matter experts identified 277 critical infrastructure assets in the Hampton Roads Maritime Area (HRMA). From these, 26 assets that were deemed to be significantly more critical than others. From this reduced list, 12 were further assessed to be most important. The selection process provided significant support to those responsible for providing protection, mitigating potential damage, and planning recovery and allows informed, objective expenditures of limited funding. Additional key findings include the following: Proximity, or the potential for an asset that has been damaged or destroyed to cause direct harm to adjacent assets in the surrounding community, drives criticality in the HRMA more than any other factor in the model . A small group of 26 out of 277 assets exerts an outsized impact in the HRMA—nearly 20 percent of criticality—due to the potential consequences associated with their destruction or disruption . Road transportation, particularly tunnels, represents the primary dependency among critical assets. Major road and maritime transportation assets rely heavily on federal and state organizations to maintain their function . Supply chain: The critical asset group supports or supplies many missions and industries both nationally and internationally, including defense, manufacturing, commercial enterprise, and the movement of raw commodities .

Importance Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed. Objective To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19. Design, Setting, and Participants This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients. Interventions Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237). Main Outcomes and Measures The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality. Results Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, −0.2% [95% CI, −5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]). Conclusions and Relevance Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults. Trial Registration ClinicalTrials.gov:NCT04332991

OBJECTIVE: To determine whether men with unexplained infertility (UI) and low total testosterone (TT) have abnormal spermatogenesis and lower fecundity. DESIGN: Secondary analysis of the prospective, randomized, multicenter clinical trial: Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS). SETTING: Reproductive Medicine Network infertility clinics. PATIENTS: 900 couples with UI enrolled in AMIGOS. Semen analysis with an ejaculate of at least 5 million total motile sperm was required for enrollment. For inclusion in this secondary analysis, a fasting TT was required. INTERVENTIONS: None MAIN OUTCOME MEASURE: Logistic regression, adjusted for age and BMI, assessed the association between low TT (defined as 264 ng/dL. The odds of live birth decreased by 40% in couples whose male partner had low TT (unadjusted OR 0.60, 95% CI (0.36, 1.00); adjusted OR 0.65, 95% CI (0.38, 1.12)). CONCLUSION: In couples with UI, low TT in the male partner was associated with abnormal sperm morphology and lower live birth rates. CLINICAL TRIAL REGISTRATION NUMBER: NCT01044862

Social dynamics play a critical role in successful pedestrian evacuations. Crowd modeling research has made progress in capturing the way individual and group dynamics affect evacuations; however, few studies have simultaneously examined how individuals and groups interact with one another during egress. To address this gap, the researchers present a conceptual agent-based model (ABM) designed to study the ways in which autonomous, heterogeneous, decision-making individuals negotiate intragroup and intergroup behavior while exiting a large venue. A key feature of this proposed model is the examination of the dynamics among and between various groupings, where heterogeneity at the individual level dynamically affects group behavior and subsequently group/group interactions. ABM provides a means of representing the important social factors that affect decision making among diverse social groups. Expanding on the 2013 work of Vizzari et al., the researchers focus specifically on social factors and decision making at the individual group and group/group levels to more realistically portray dynamic crowd systems during a pedestrian evacuation. By developing a model with individual, intragroup, and intergroup interactions, the ABM provides a more representative approximation of real-world crowd egress. The simulation will enable more informed planning by disaster managers, emergency planners, and other decision makers. This pedestrian behavioral concept is one piece of a larger simulation model. Future research will build toward an integrated model capturing decision-making interactions between pedestrians and vehicles that affect evacuation outcomes.

There is considerable evidence that understanding reasons for using substances is important for understanding patterns of use and related consequences as well as for developing assessment and intervention strategies. Despite increases in prescription opioid use and related problems (e.g., overdose deaths), a comprehensive measure of prescription opioid motives has yet to be developed. As such, the current study sought to develop and provide validation evidence for a measure of prescription opioid motives. One hundred eleven male and 226 female undergraduate students completed an initial pool of motive items based on the current literature and measures of prescription opioid use and related problems. Confirmatory factor analysis results demonstrated that the predicted 4-factor model provided a good fit to the data. The 4 motives-pain, social, enhancement, and coping-each showed differential patterns of associations with prescription opioid-related contextual and use variables. Enhancement motives were associated with quantity of use (past 3 months and maximum use in 1 day), frequency of use, in multiple contexts, misuse, and related problems. Coping motives demonstrated relations with maximum pills (in 1 day), frequency of use, and prescription opioid misuse, consequences, and dependence features. For social motives, significant associations were found with frequency of use (in past 3 months), typical number of pills (in 1 day), dependence features, and use both on weekdays and on weekends; this motive had a negative association with maximum number of pills taken in 1 day. Pain motives were largely related to frequency of use (in past 3 months), consequencess, and dependence features. The present study is the first to present an empirical measure of prescription opioid motives and demonstrates how these motives have important implications for understanding patterns of prescription opioid use and related problems.

Early predictors of massive transfusion (MT) would prevent undertriage of patients likely to require MT. This study validates triggers using the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study.All enrolled patients in PROMMTT were analyzed. The initial emergency department value for each trigger (international normalized ratio [INR], systolic blood pressure, hemoglobin, base deficit, positive result for Focused Assessment for the Sonography of Trauma examination, heart rate, temperature, and penetrating injury mechanism) was compared for patients receiving MT (≥ 10 U of packed red blood cells in 24 hours) versus no MT. Adjusted odds ratios (ORs) for MT are reported using multiple logistic regression. If all triggers were known, a Massive Transfusion Score (MTS) was created, with 1 point assigned for each met trigger.A total of 1,245 patients were prospectively enrolled with 297 receiving an MT. Data were available for all triggers in 66% of the patients including 67% of the MTs (199 of 297). INR was known in 87% (1,081 of 1,245). All triggers except penetrating injury mechanism and heart rate were valid individual predictors of MT, with INR as the most predictive (adjusted OR, 2.5; 95% confidence interval, 1.7-3.7). For those with all triggers known, a positive INR trigger was seen in 49% receiving MT. Patients with an MTS of less than 2 were unlikely to receive MT (negative predictive value, 89%). If any two triggers were present (MTS ≥ 2), sensitivity for predicting MT was 85%. MT was present in 33% with an MTS of 2 greater compared with 11% of those with MTS of less than 2 (OR, 3.9; 95% confidence interval, 2.6-5.8; p0.0005).Parameters that can be obtained early in the initial emergency department evaluation are valid predictors for determining the likelihood of MT.Diagnostic, level II.

Thymosin β4 (Tβ4) is a 43-amino acid signature motif peptide that defines the beta-thymosin (βT) family of proteins. βTs are intrinsically unstructured in their free states and undergo disorder-to-order transitions in carrying out their biological functions. This property poses challenges in determining their 3D structures, mainly favoring structural studies on the complexes formed between βTs and their interaction partners. One of the βTs' primary binding partners is monomeric actin, a major component of the cytoskeleton in eukaryotic cells. Tβ4's role in this system is to maintain the highly concentrated pool of monomeric actin that can be accessed through profilin by actin filament nucleating machineries. Here, we give an account of the structures of βTs that have been illuminated by nuclear magnetic resonance (NMR) and X-ray crystallography. NMR has been the method of choice for probing regions that have intrinsic conformational preference within the largely disordered βTs in their native states in solution. X-ray crystallography has demonstrated at atomic detail how βTs interact with actin. Detailed analysis of these structures highlights the disorder-to-order transition of Tβ4 in binding to actin and its isoform specificity.

SUMMARYThe infection status of angiostrongylosis in Jamaica was assessed in wild rats and molluscs in the 5 years following the major outbreak of eosinophilic meningitis (EM) in 2000. Parasitological analyses of 297 Rattus rattus and 140 Rattus norvegicus, and 777 terrestrial molluscs from all 14 Parishes on the island revealed Angiostrongylus cantonensis in 32·0% of the rats and in 12·5% of the molluscs. Multivariate analyses confirmed that A. cantonensis occurred significantly more frequently in R. rattus (Odds Ratio [OR] = 1·76), while mean infection intensity in R. rattus was also significantly higher (16·8) than R. norvegicus (11·3) (Mann–Whitney U-test: P = 0·01). Third-stage larvae of A. cantonensis were detected in 29% of 86 Pleurodonte spp.; in 20% of five Poteria spp.; in 18·7% of 369 Thelidomus asper; in 11% of 18 Sagda spp.; and in 6% of 24 veronicellid slugs. Most rodent infections occurred in Northeastern Jamaica (OR = 11·66), a region where infected molluscs were also abundant. Given the prevalence of A. cantonensis infection in rats has significantly increased since the 2000 outbreak, and that a survey of human infections revealed at least ten autochthonous cases in the last 15 years, angiostrongylosis persists as an important zoonosis in Jamaica.

Current theories of borderline personality disorder (BPD) suggest that extreme levels of affective instability/emotional dysregulation, impulsivity, or a combination of these traits account for the symptoms of BPD. The present study tested the extent to which personality measures of affective instability and impulsivity could account for BPD features in a nonclinical sample. One hundred forty-one undergraduates completed the Affective Lability Scale, the UPPS Impulsive Behavior Scale, and the Personality Assessment Inventory for Borderlines. Both affective instability and impulsivity were uniquely associated with BPD features. Shifts between euthymia and anger, and between anxiety and depression, were associated with BPD features, as were the urgency and (lack of) premeditation scales. Results indicated that specific BPD features may be differentially accounted for by affective instability vs. impulsivity, consistent with perspectives on BPD emphasizing combinations of affective instability and impulsivity as underlying dimensions of the disorder.

SUMMARY The aplanation principle has been proposed as a basis for a non-invasive method of measuring intracranial pressure in infants with patent anterior fontanelles. With minor adjustments, the method was found to give reproduceable results over the range 5 to 60cm H2O. The mean (± 1 SD) intracranial pressure of 91 infants born at term was 10.7 ± 3.1cm H2O. Babies who had had complicated deliveries were found to have a higher mean intracranial pressure on the first day of life. We suggest this difference is caused by post-hypoxic cerebral oedema. RESUME Mesures non agressives de la pression intra-crânienne chez ies nouveaux-nŕs normaux Le principe de 'aplatissement a ŕtŕ proposŕ a la base dune mŕthode non agressive de la pression intra-crânienne chez les nourrissons avec fontanelles antŕrieures apparentes. Avec quelques ajustements minimes, il a ŕtŕ trouvŕ que la mŕthode donnait des rŕsultats reproductibles sur une ŕtendue de pression de 5–60cm deau. La moyenne a ± 1 SD chez 91 nourrissons nŕs a terme a ŕtŕ trouvŕe de 10,7 ± 3,1cm deau. Chez les nourrissons nŕs aprŕGs accouchement compliquŕ, il a ŕtŕ trouvŕ une pression intra-crânienne moyenne plus ŕlevŕe le premier jour de la vie. Il est suggŕrŕ que cette diffŕrence est causŕe par un oedeme cŕrŕbral post-hypoxique. ZUSAMMENFASSUNG Eine nicht eingreifende Methode zur intracraniellen Druckmessung bei Neugeborenen Bei Kindern mit offener groser Fontanelle wurde das Prinzip der Abflachung als Basis fur eine nicht eingreifende Methode zur intracraniellen Druckmessung vorgeschlagen. Mit geringen Angleichungen ergab die Methode reproduzierbare Ergebnisse im Bereich von funf bis 60cm H2O. Der mittlere intracranielle Druck war bei 91 reifen Neugeborenen 10.7 mit einer ersten Standardabweichung von ± 3.cm H2O. Neugeborene mit komplizierter Geburt hatten am ersten Lebenstag einen hoheren intracraniellen Druck. Es wird angenommen, das diese Druckdifferenz durch ein aufgrund einer Hypoxie entstandenes cerebrales Odem hervorgerufen wird. RESUMEN Mediciones de la presion intracraneal no-invasivas en reciŕn nacidos normales El principio de la aplanacion ha sido propuesto como una base para un mŕtodo no invasivo de medicion de la presiŕn intracraneal en lactantes con fontanelas anteriores patentes. Con ajustes menores se ha hallado que el mŕtodo da resultados reproducibles sobre un margen de 5 – 60cm H2O. El promedio ± 1 SD de la presion intracraneal de 91 lactantes nacidos a tŕrmino fue de 10,7 ± 3,1cm H2O. Se hallo que en ninos nacidos de partos complicados existia una presibn intracraneal media mayor en el primer dia de vida. Se sugiere que esta diferencia esta causada por un edema cerebral post-hipoxico.

Objective: To determine the earliest symptoms of anosognosia in people with Alzheimer’s disease and to validate a criteria-guided strategy to diagnose anosognosia in dementia. Methods: A consecutive series of 750 patients with very mild or probable Alzheimer’s disease attending a memory clinic, as well as their respective care givers, was assessed using a comprehensive psychiatric evaluation. Results: The factors of anosognosia for (1) basic activities of daily living (bADL), (2) instrumental activities of daily living (iADL), (3) depression and (4) disinhibition were produced by a principal component analysis on the differential scores (ie, caregiver score minus patient score) on the anosognosia questionnaire for dementia. A discrepancy of two or more points in the anosognosia-iADL factor was found to have a high sensitivity and specificity to identify clinically diagnosed anosognosia in people with Alzheimer’s disease. By logistic regression analysis, the severity of dementia and apathy were both shown to be noticeably associated with anosognosia in people with Alzheimer’s disease. Conclusion: Anosognosia in those with Alzheimer’s disease is manifested as poor awareness of deficits in iADL and bADL, depressive changes and behavioural disinhibition. The frequency of anosognosia is found to increase considerably with the severity of dementia. The validity of a specific set of criteria to diagnose anosognosia in people with Alzheimer’s disease was shown, which may contribute to the early identification of this condition.

Apathy and depression are the most frequent behavioural and psychiatric disorders in Alzheimer's disease, and may both have a negative impact on the progression of the illness.To examine the clinical correlates of apathy in Alzheimer's disease (AD), and to determine whether apathy is a significant predictor of more rapid cognitive, functional and emotional decline.Using a structured psychiatric evaluation, we examined a consecutive series of 354 subjects meeting clinical criteria for AD. Apathy was assessed by the Apathy Scale, and diagnosed using standardised criteria. Additional measurements included scales for depression, functional impairment, and global cognitive functions. A follow up evaluation was carried out in 247 patients (70% of the total sample) between 1 and 4 years after the baseline evaluation.Apathy was significantly associated with older age (p = 0.009), and a higher frequency of minor and major depression (p0.0001). Apathy at baseline was a significant predictor of depression at follow up (p = 0.01), and was associated with a faster cognitive (p = 0.0007) and functional decline (p = 0.006).Apathy in AD is a behavioural marker of a more aggressive dementia, characterised by a faster progression of cognitive, functional, and emotional impairment.

Summary Background: Management of high-grade dysplasia in Barrett's oesophagus is controversial: surgery carries an appreciable morbidity/mortality, high-grade dysplasia may not progress to cancer and endoscopic ablation is an emerging option. Aim: To review Barrett's oesophagus-related high-grade dysplasia management and outcome over a 10-year period. Methods: This was a retrospective case note review of 36 patients identified from a pathology database. Results: There were 31 men of mean age 67 years. Endoscopic surveillance identified nine. Median follow-up was 21 months. Seven patients had no further intervention because of age/comorbidity. The other 29 had repeat endoscopic biopsies, nine showing cancer (six oesophagectomized). Of the 20 remaining patients with persisting high-grade dysplasia, eight had surgery (histology showed cancer in six), seven continued endoscopic surveillance (high-grade dysplasia regressed in four) and five had ‘curative’ argon ablation. An intensive biopsy protocol was not followed in 55% of endoscopies. Prevalent cancers occurred in 44% with an annual incidence of 5% over 5 years. All cause mortality was 39% (14 of 36, eight of 14 from cancer). Conclusions: Management of high-grade dysplasia was not uniform. Unsuspected cancer was common in high-grade dysplasia patients undergoing surgery but 13% regressed under surveillance. High-grade dysplasia patients have a high mortality but 43% did not die from cancer.

Background The aetiology of bone loss in ulcerative colitis is multifactorial, but corticosteroid treatment is an important risk factor. A novel formulation of Eudragit-L-coated prednisolone metasulphobenzoate (Predocol) has been developed, in order to deliver high mucosal levels of prednisolone within the colon but with little systemic absorption. The aim of this study was to investigate its efficacy, and short-term effects on bone formation and bone mineral density. Methods In a 12-week longitudinal study 13 patients with active colitis were treated with a reducing dose of Predocol. Disease activity scores were recorded and the bone formation marker osteocalcin was measured before, during and after treatment, with hip and spine bone mineral density assessed at baseline and after treatment. Results Eleven of the 13 patients completed the study. Compared with baseline, disease activity scores improved significantly after 4 weeks [difference in means, 6.9; 95% confidence interval (CI), 5.2, 8.7; P < 0.0001 and 12 weeks (difference in means, 5.7; 95% CI, 3.3,8.2; P < 0.0001) of treatment. Osteocalcin did not fall compared with baseline [16.91 mg/l (95% CI, 12.70, 21.12)], after 4 weeks [13.67 mg/l (95% CI, 8.72, 18.60)] (difference in means, 3.25; 95% CI, 2.37, 8.87; P = 0.23) or 12 weeks [23.91 mg/l (95% CI, 16.10, 31.74)] (difference in means, 13.23; 95% Cl, 2.45,16.48; P = 0.13) of treatment. Similarly, bone mineral density at the hip [0.99 g/cm 2 (95% CI, 0.90, 1.09)] did not change after 12 weeks of treatment [1.00 g/cm 2 (95% CI, 0.89,1.11)] (difference in means, 0.01; 95% CI, 0.25, 0.34; P = 0.74). Spine bone mineral density did not fall from pretreatment levels [1.20 g/cm 2 (95% CI, 1.11, 1.30)] after 12 weeks [1.19 g/cm 2 (95% CI, 1.10, 1.29)] (difference in means, 0.01; 95% CI, 0.004, 0.01; P = 0.26). Conclusions These results confirm that Predocol is effective treatment for acute ulcerative colitis and short courses of the steroid have no adverse effects on bone formation and bone mineral density. The encouraging results from this study suggest that Predocol may be a significant advance in preventing corticosteroid induced bone loss in ulcerative colitis.

Osteoporosis is a common medical problem. Lifestyle measures to prevent or help treat existing osteoporosis often only receive lip service. The evidence for the role of exercise in the prevention and treatment of osteoporosis is reviewed.

Group AB plasma, the traditional universal donor plasma product, is a limited resource. We compared outcomes of Group A plasma transfusion in comparison to AB.Analysis of blunt-injured patients who received emergency release plasma from was performed. Multivariable logistic regression was utilized to identify associations with morbidity and mortality.There were 191 patients; 115 Group A and 76 Group AB. No differences were seen in age, sex, plasma transfusions, uncrossmatched red blood cells (RBCs), and Glasgow Coma Scale (GCS). Patients who received Group A plasma had significantly lower Injury Severity Score, chest Abbreviated Injury Scale (AIS), and scene transfer rate but not head AIS, or abdomen AIS. In addition, significant differences were noted in terms of blood products transfused within 24 hours in those receiving Group A over AB. Development of acute respiratory distress syndrome (ARDS), but not mortality, was higher within the AB cohort. No hemolytic or transfusion associated-ARDS reactions were noted in either group. ARDS; RBC transfusion volumes and head AIS were independently associated with mortality.Utilization of Group A plasma for emergency blood resuscitation is a safe option which may alleviate potential shortages of AB plasma.

In recent years, botulinum toxin type A (BT) has been found to be effective in the treatment of various spastic disorders of smooth muscle in the upper and lower gastrointestinal tract. The short-term efficacy of intrasphincteric injection of BT in achalasia is now well established, however, because of the chronic nature of the disease, patients will require repeated injections at regular intervals. In contrast, after a single injection into the anal sphincter, BT has impressively high healing rate with minimal side effects. BT remains a novel therapeutic approach in a range of other gastrointestinal motility disorders including diffuse oesophageal spasm, sphincter of Oddi dysfunction and anismus, and the list of its indications is increasing. BT seems to be safe but as its long-term effects remain unestablished, it should be used with caution in younger patients. In this review we discuss the mechanism of action, indications, efficacy and side-effects of BT with its use in various areas of gastrointestinal tract.

To assess the effect and tolerance of a 6-week course of intravesical valrubicin on a tumour intentionally left in the bladder (marker lesion) following incomplete transurethral resection of the bladder (TURBT).In a prospective phase II study, 40 patients with refractory superficial transitional cell carcinoma (TCC), with or without carcinoma in situ, underwent TURBT at which a tumour1 cm in diameter was deliberately left in the bladder. They were then treated with six instillations of 800 mg valrubicin at weekly intervals. Patients were assessed three months after the initial TURBT by cystoscopy and biopsy. Patients remaining clear of disease underwent repeat cystoscopies at 3-monthly intervals until recurrence or for up 2 years.21/39 (54%) of patients were found to be clinically clear of disease upon cystoscopic examination at 3 months. 18/39 (46%) of patients were considered histologically clear of bladder disease. The current estimate of the mean time to recurrence is 248 days.A 6-week course of intravesical valrubicin has proved effective in ablating a marker tumour left in the bladder after incomplete TURBT and in preventing or delaying recurrence of further tumours in a group of patients with previously treated superficial TCC.

Objective: To develop and assess the efficacy of couples stress management groups offered concurrently with IVF treatment. Design: Couples in IVF treatment were given the option of participating in a biweekly stress management group. Setting: The IVF treatment clinic at Wilford Hall Medical Center, San Antonio, Texas. Patient(s): One or both members of 17 couples participated in the program in one of four group cycles. Intervention(s): A cognitive behavioral treatment model was used to help couples process their feelings and cognitions about the impact of infertility on their life and explore their expectations about their future options for becoming parents. Main Outcome Measure(s): Couples were asked to anonymously evaluate the efficacy of the group after they had completed their IVF cycle. Result(s): Participants reported that the group helped them deal with the stress of infertility and that they valued the social bonds they formed with other group members. Conclusion(s): These data suggest that brief focused group therapy, offered while couples are undergoing IVF, is an effective way to help people deal with the stress of infertility treatment.

Objective.—To assess the prevalence of activating mutations in K-ras and H-ras genes in salivary gland tumors with ductal or acinar differentiation and to evaluate their potential correlation with clinical parameters. Design.—Paraffin-embedded tissue samples of salivary gland carcinomas were investigated by the application of a direct sequence analysis procedure with automated DNA sequencing of polymerase chain reaction–amplified ras sequences. Setting.—Tertiary care teaching hospital. Patients.—Twenty-four patients with salivary gland carcinoma were surgically treated. Nine had adenocarcinoma, 1 had adenosquamous carcinoma, 11 had mucoepidermoid carcinoma, and 3 had acinic cell carcinoma. Results.—Point mutations were detected in 7 (29%) of the 24 carcinomas examined. The K-ras gene was mutated in only 2 samples (8%): a GGC-to-ATC mutation at codon 13 in an adenocarcinoma and a GGC-to-GTC transversion mutation at codon 13 in a mucoepidermoid carcinoma. Five (21%) harbored H-ras mutations: 4 contained a GGC-to-GTC transversion mutation at codon 12 and 1 had 2 distinct mutations, the same G-to-T at codon 12 as was shown in the other cases and a GGT-to-GGA heterozygous mutation at codon 13. All the H-ras mutations were in the group of mucoepidermoid carcinoma lesions (45%; 5/11). Conclusion.—Our data suggest that K-ras gene alteration is probably not an important factor in the oncogenesis of human salivary gland tumors. However, mutational activation of the H-ras gene appears to play a role in the development and/or progression of salivary gland mucoepidermoid carcinomas.

Exposure to high concentrations of radon progeny (radon) produces lung cancer in both underground miners and experimentally exposed laboratory animals. To determine the risk posed by residential radon exposure, the authors performed a population-based, case-control epidemiologic study in Iowa from 1993 to 1997. Subjects were female Iowa residents who had occupied their current home for at least 20 years. A total of 413 lung cancer cases and 614 age-frequency-matched controls were included in the final analysis. Excess odds were calculated per 11 working-level months for exposures that occurred 5-19 years (WLM(5-19)) prior to diagnosis for cases or prior to time of interview for controls. Eleven WLM(5-19) is approximately equal to an average residential radon exposure of 4 pCl/liter (148 Bq/m3) during this period. After adjustment for age, smoking, and education, the authors found excess odds of 0.50 (95% confidence interval: 0.004, 1.81) and 0.83 (95% percent confidence interval: 0.11, 3.34) using categorical radon exposure estimates for all cases and for live cases, respectively. Slightly lower excess odds of 0.24 (95 percent confidence interval: -0.05, 0.92) and 0.49 (95 percent confidence interval: 0.03, 1.84) per 11 WLM(5-19) were noted for continuous radon exposure estimates for all subjects and live subjects only. The observed risk estimates suggest that cumulative ambient radon exposure presents an important environmental health hazard.

We researched epidemiologic associations between environmental and demographic factors and prevalence of Helicobacter pylori infection in a suburban Jamaican community. Using a clustered sampling technique, 22 domestic yards enclosing 60 separate households were randomly selected from a local community. All household members (n = 346) were invited to participate following informed consent; the overall compliance rate was 58.9%. A commercial enzyme immunoassay (HMáCAP) was used to detect IgG antibodies raised against H. pylori. Environmental and demographic information was obtained by questionnaire. The seroprevalence of H. pylori was 69.9% (n = 202). Analysis of the independent variables revealed three major components: Component 1 described, collectively, good personal hygiene and sanitation, indoor water supply and absence of straying animals in the peridomestic area; Component 2 included older age, good personal hygiene and large yard size; Component 3 the presence of domestic animals (cats and dogs) and, again, large yard size. These three complexes explained 42.2% of the variability in the data set. Logistic regression showed that Components 2 and 3 were independently associated with H. pylori seropositivity, indicating that a combination of demographic, environmental and zoonotic factors is involved in the spread of H. pylori infections at the tropical community level.

Over the past 15 years, factors suh as corticosteroid treatment, cytotoxic chemotherapy, excessive use of broad spectrum antibiotics and HIV have led to an increased risk of serious fungal infections in both adults and pediatric patients. This increase in invasive fungal infections poses increasing difficulty in their treatment. Three new lipid formulations of amphotericin B are now available in the U.S.: amphotericin B lipid complex (Abelcet), amphotericin B colloidal dispersion (Amphotec), and liposomal amphotericin B (AmBisome). These newer formulations are substantially more expensive, but allow patients to receive higher doses for longer periods of time with decreased renal toxicity than conventional amphotericin B. The properties of these new agents are summarized in this review. Discussion of current national guidelines as well as those used at our institution are presented to provide guidance for the development of institution specific guidelines for the most cost-effective drug for most patients, some may benefit more from one of the newer lipid formulations.

Familial cases of schizencephaly hitherto have been associated with readily diagnosable metabolic conditions or malformation syndromes. Where such associations are absent, it is usually considered to be a sporadic event without a genetic contribution. Described here are a brother and sister with identical bilateral symmetrical schizencephaly. Genetic counselling must therefore allow for the possibility of an autosomal recessive form of this condition.

SUMMARYMethanol-water (4:1, v/v) crude extracts (50 mg mL−1) of 25 Jamaican medicinal plants were screened in vitro for anthelmintic activity using infective third-stage larvae of Strongyloides stercoralis. The most effective extract was further chemically scrutinized to isolate and identify the source of the bioactivity, and the efficacy of this compound was compared with ivermectin. Eosin exclusion (0·1 mg mL−1) served as the indicator of mortality in all bioassays. A crude extract of Eryngium foetidum (Apiaceae) was significantly (Probit Analysis, P50) of the larvae. Further, the petrol extract of E. foetidum was significantly more effective (Probit Analysis, P50, 4·7 h) than either its methanol–water or dichloromethane extract. The latter two effected less than 1% larval mortality after 120 h. With bioassay-driven column chromatography of the petrol extract, trans-2-dodecenal (eryngial) was identified and chemically isolated as the main anthelmintic compound in E. foetidum. There was a significant difference between the 24 h LD50 values (mm) of trans-2-dodecenal (0·461) and ivermectin (2·251) but there was none between the 48 h LD50 values (mm): trans-2-dodecenal (0·411) and ivermectin (0·499) in vitro.

The proliferation of cholangiocarcinoma cells is suppressed in cell culture by nonsteroidal antiinflammatory drugs (NSAIDs) through the inhibition of cyclo-oxygenase-2 enzyme and also by statins which decrease the production of mediators of the cell cycle. To investigate whether there is an inverse association between NSAIDs, including aspirin, and the development of cholangiocarcinoma and, for the first time in a Western population, between statin use and the development of cholangiocarcinoma. This epidemiological study had a case–control design in which cases of cholangiocarcinoma diagnosed in Norwich between 2004 and 2010 and in Leicester in 2007 were identified from clinical databases. Controls were patients with basal cell carcinomas treated in the respective dermatology departments. The case notes of all subjects were reviewed to confirm diagnoses and obtain information on medication use. The data were analyzed using unconditional logistic regression to calculate odds ratios (OR) with 95 % confidence intervals (CI). In total, 81 cases of cholangiocarcinoma and 275 controls were identified. For all cases there was radiological evidence of cancer and 86 % of the cases involved the extrahepatic biliary system. Aspirin use was inversely associated with the development of cholangiocarcinoma (OR 0.45, 95 % CI 0.22–0.92), but there were no significant associations between the development of cholangiocarcinoma and NSAIDs (OR 0.39; 95 % CI 0.11–1.42) or statins (OR 0.58; 95 % CI 0.28–1.19). The epidemiological data from this study support the biological evidence for aspirin having a protective effect against the development of cholangiocarcinoma. Aspirin use should be measured in future etiological studies and assessed as a chemoprevention agent in those at high risk of developing this type of cancer.

Patient-ventilator synchrony and patient comfort are assumed to go hand in hand, yet few studies provide support for this common sense idea. In reality, synchrony between the patient and ventilator is complex and can be affected by the ventilator settings, type of ventilator, patient-ventilator interface, and sedation. Inspections of airway pressure and flow waveforms are reliable methods for detecting asynchrony, and automated detection seems accurate. A number of types of asynchronies have been defined, and asynchrony during invasive and noninvasive ventilation have different calling cards. There is a clear association between asynchrony, ventilator-induced diaphragmatic dysfunction, and duration of mechanical ventilation. Whether these are cause and effect or simply associated remains to be determined.

There are plausible biological mechanisms for how statins may prevent pancreatic cancer, although the evidence from epidemiological studies in the general population is conflicting. This study aims to clarify whether statins exert their effects in specific sub-groups, namely, gender, smoking status and diabetes. A matched case–control study was conducted in patients diagnosed with pancreatic cancer, and a group of dermatology patients of similar ages and gender, diagnosed with basal cell carcinoma. Participants’ medical records were reviewed for information on statin use prior to diagnosis. Odds ratios and 95 % CIs for the development of pancreatic cancer were estimated using conditional logistic regression. Subgroup analysis was performed in men, women, smokers and those with type 2 diabetes. Two hundred fifty-two cases (median age 71 years, range 48–73 years, 51 % women) and 504 controls were identified, of which 23 % of cases were regular statin users versus 21 % of controls. In the general study population there was no association between pancreatic cancer and regular statin use (OR 0.82, 95 % CI 0.53–1.23, p = 0.33). However, in male smokers, regular statin use was associated with significantly reduced odds of pancreatic cancer compared to male smokers not prescribed a statin (OR 0.11, 95 % CI 0.01–0.96, p = 0.05). In patients with type 2 diabetes statins use was not associated with reduced odds (OR 0.92, 95 % CI 0.35–2.45, p = 0.80), with no gender effects. In male smokers, statins may reduce the odds of pancreatic cancer. Statin use should be measured in aetiological studies of pancreatic cancer but analysed in specific sub-groups. Future work should investigate statins as chemopreventative agents in this high risk sub-group.

PURPOSE This study was designed to assess the anti-tumor activity of topotecan (TPT) in patients with advanced non-small-cell lung cancer (NSCLC) previously untreated with chemotherapy. PATIENTS AND METHODS Patients with stage IIIB or IV NSCLC with measurable disease in nonradiated fields were eligible. Other eligibility criteria were Zubrod performance status (PS) < or = 2 and adequate renal and liver function. TPT was administered at a dose of 1.5 mg/m2/d for 5 days over 30 minutes every 21 days. Of 48 registered patients, 40 were fully assessable. Nineteen patients had adenocarcinoma (AD), 14 squamous carcinoma (SCC), and seven poorly differentiated carcinoma. RESULTS Six patients (15%) achieved a partial remission (PR) (durations: 8, 14, 18, 28, 56, and 61 weeks) and four patients a minor response; 10 patients had stable disease and 20 patients progressive disease. The PR rate was 36% (five of 14 patients) in patients with SCC versus 4% (one of 26 patients) in those with other histologies (P = .014). The overall median survival time was 38 weeks and 30% of patients were alive at 1 year. Grade 3 to 4 granulocytopenia and thrombocytopenia occurred after 76% and 10% of courses administered, respectively. No grade 3 to 4 nonhematologic toxicities were observed. Grade 1 or 2 nonhematologic toxicities consisted of nausea (46% and 5%), vomiting (31% and 7%), and fatigue (53% and 16%). CONCLUSION TPT at the dose and schedule used has moderate antitumor activity in NSCLC; its activity is mostly limited to patients with SCC. TPT is well tolerated, with myelosuppression of short duration being the most common and limiting toxicity.

The effects of low dose high linear energy transfer (LET) radiation on human health are of concern for space, occupational, and clinical exposures. As epidemiological data for such radiation exposures are scarce for making relevant predictions, we need to understand the mechanism of response especially in normal tissues. Our objective here is to understand the effects of heavy ion radiation on tissue homeostasis in a realistic model system. Towards this end, we exposed an in vitro three dimensional skin equivalent to low fluences of neon (Ne) ions (300 MeV u(-1)), and determined the differentiation profile as a function of time following exposure using immunohistochemistry. We found that Ne ion exposures resulted in transient increases in the tissue regions expressing the differentiation markers keratin 10, and filaggrin, and more subtle time-dependent effects on the number of basal cells in the epidermis. We analyzed the data using a mathematical model of the skin equivalent, to quantify the effect of radiation on cell proliferation and differentiation. The agent-based mathematical model for the epidermal layer treats the epidermis as a collection of heterogeneous cell types with different proliferation-differentiation properties. We obtained model parameters from the literature where available, and calibrated the unknown parameters to match the observed properties in unirradiated skin. We then used the model to rigorously examine alternate hypotheses regarding the effects of high LET radiation on the tissue. Our analysis indicates that Ne ion exposures induce rapid, but transient, changes in cell division, differentiation and proliferation. We have validated the modeling results by histology and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The integrated approach presented here can be used as a general framework to understand the responses of multicellular systems, and can be adapted to other epithelial tissues.

Glial hyaluronate-binding protein (GHAP) is a 60 kDa glycoprotein with an amino acid sequence identical to that of the hyaluronate-binding region of versican, a large fibroblast aggregating proteoglycan found in the brain. Both GHAP and versican were identified by immunoblot in bovine brain extracts prepared only minutes after death. Human recombinant collagenase, stromelysin, mouse gelatinase and gelatinases isolated from human brain by affinity chromatography digest versican and give rise to a polypeptide with electrophoretic mobility identical to GHAP. Immunoblot analysis, peptide mapping and C-terminal amino acid sequencing indicate that the polypeptide generated by digestion with human brain gelatinases is identical to GHAP. We suggest that GHAP is a naturally occurring versican degradation product.

Fat necrosis of the breast is a benign condition that most commonly occurs as the result of minor breast trauma. The radiographic and clinical significance of fat necrosis of the breast is that it may mimic a breast malignancy, requiring biopsy for diagnosis. The mammographic appearance of fat necrosis ranges from a lipid cyst to findings suspicious for malignancy, including clustered microcalcifications, a spiculated area of increased opacity, or a focal mass. The changes of fat necrosis may be seen following blunt trauma, cyst aspiration, biopsy, lumpectomy, radiation therapy, reduction mammoplasty, breast reconstruction with a transverse rectus abdominis myocutaneous (TRAM) flap, implant removal, and anticoagulant therapy, as well as in patients without a relevant history. Fat necrosis may also be detected mammographically as an incidental finding in benign lipomas. It is important to recognize the mammographic spectrum of appearances of fat necrosis to avoid unnecessary biopsy and to avoid overlooking breast cancer.

Understanding how human organs respond to ionizing radiation (IR) at a systems biology level and identifying biomarkers for IR exposure at low doses can help provide a scientific basis for establishing radiation protection standards. Little is known regarding the physiological responses to low dose IR at the metabolite level, which represents the end-point of biochemical processes inside cells. Using a full thickness human skin tissue model and GC-MS-based metabolomic analysis, we examined the metabolic perturbations at three time points (3, 24 and 48 h) after exposure to 3, 10 and 200 cGy of X-rays. PLS-DA score plots revealed dose- and time-dependent clustering between sham and irradiated groups. Importantly, delayed metabolic responses were observed at low dose IR. When compared with the high dose at 200 cGy, a comparable number of significantly changed metabolites were detected 48 h after exposure to low doses (3 and 10 cGy) of irradiation. Biochemical pathway analysis showed perturbations to DNA/RNA damage and repair, lipid and energy metabolisms, even at low doses of IR.

Forty-one-, 31-, and 28-kDa proteins of Strongyloides stercoralis filariform larvae have previously been demonstrated to be sensitively and specifically recognized by serum IgG in individuals with strongyloidiasis. Characteristics of these proteins, their immunodominant epitopes, and reactive antibodies are described here. The proteins are soluble in aqueous as well as detergent extracts. The immunodominant epitopes are present in S. stercoralis but not in S. cebus or S. ratti. Epitopes on the three proteins are not shared, as determined by cross-adsorption of serum with each of the size components on nitrocellulose. In most sera from strongyloidiasis patients there was reactivity to each of the proteins by IgG1 and IgG4, but reactivity by IgG2 or IgG3 was detectable only in a minority. A rabbit antiserum raised to a 41-kDa size fraction of S. stercoralis larvae reacted against a doublet of 41-kDa which was distinct from the immunodiagnostic 41-kDa protein.

Recently described enzyme-linked immunosorbent assay (ELISA) and immunoblot methods for the detection of serum IgG against Strongyloides stercoralis larval antigens were prospectively evaluated for the diagnosis of endemic strongyloidiasis. A modification of the ELISA involved preincubation of sera with Onchocerca gutturosa phosphate-buffered saline-soluble extract to remove cross-reactivity with other helminths. The sensitivity of the ELISA increased from 80% to 85% following preincubation. Similarly, there was an increase in specificity from 94% to 97%. The IgG recognition of 41-, 31-, and 28-kD filariform larval components showed sensitivities of 100%, 85%, and 65%, respectively. Both the ELISA following incubation of sera with O. gutturosa extract and serum IgG reactivity to a 41-kD larval component using immunoblotting are sensitive and specific techniques for diagnosing endemic strongyloidiasis.

Pulmonary aspiration of gastric contents results initially from reflux of stomach contents into the esophagus. Small-bore enteral feeding tubes are thought to result in less pulmonary aspiration and less reflux. We prospectively investigated the effect of nasogastric tube size upon gastroesophageal (GE) reflux in normal volunteers in a randomized crossover trial. Reflux was assessed by gastroesophageal scintiscanning, a radioisotopic technique that detects and quantitates GE reflux. A total of 11 subjects were studied three times: control, no nasogastric tube, small-bore (8F) nasogastric tube, and large-bore (14F) nasogastric tube. Reflux was assessed in each subject under each experimental condition by provocative testing in which abdominal pressure was increased from 0 to 100 mm Hg by 20-mm Hg increments with an abdominal pressure device. GE reflux indices were calculated for each measurement and the groups compared. A positive indicator of reflux was defined as a > or = 4% reflux index. Gastroesophageal reflux was not detected at any level of abdominal pressure regardless of the presence or size of a nasogastric tube. With maximum 100 mm Hg abdominal pressure, the reflux index was control, 1.75 +/- 0.45%; small-bore tube, 1.67 +/- 0.28%; and large-bore tube, 1.88 +/- 0.35% (NS). The reflux index was not different between small-bore and large-bore nasogastric tubes. Our data suggest the size of a nasogastric tube is not an important determinant of GE reflux in normal subjects during short-term intubation. Large-bore tubes did not cause more reflux than small-bore tubes. The presence of a nasogastric tube did not cause reflux in normal subjects. These data suggest that factors other than the size of nasogastric tube are more important in GE reflux in normal subjects.

The concern over possible health risks from exposures to low doses of ionizing radiation has been driven largely by the increase in medical exposures, the routine implementation of X-ray backscatter devices for airport security screening, and, most recently, the nuclear incident in Japan. Because of a paucity of direct epidemiological data at very low doses, cancer risk must be estimated from high dose exposure scenarios. However, there is increasing evidence that low and high dose exposures result in different signaling events and may have different response mechanisms than higher doses. We have examined the radiation-induced temporal response after exposure to 10 cGy of an in vitro three dimensional (3D) human skin tissue model using microarray-based transcriptional profiling. Cell type-specific analysis showed significant changes in gene expression with the levels of >1,400 genes altered in the dermis and >400 genes regulated in the epidermis. The two cell layers rarely exhibited overlapping responses at the mRNA level. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) measurements validated the microarray data in both regulation direction and value. Key pathways identified relate to cell cycle regulation, immune responses, hypoxia, reactive oxygen signaling, and DNA damage repair. The proliferation status as well as the expression of PCNA was examined in histological samples. We discuss in particular the role of proliferation, emphasizing how the disregulation of cellular signaling in normal tissue may impact progression toward radiation-induced secondary diseases. Environ. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.

The cases are reported of 13 children seen over a 22 month period who presented with a variety of acute neurological illnesses associated with Mycoplasma pneumoniae infection. Although presentation with a decreased level of consciousness or seizures was common, psychosis, hemiparesis, cranial nerve palsies, and Guillain-Barré syndrome were also seen. In contrast with published reports, only one child had an associated chest infection. Although some children have been left with residual disability, most have made a complete recovery. In this recent experience, M pneumoniae is a not rare cause of neurological illness in childhood and may present in unusual ways.

Commercially available monoclonal antibodies AUA1, BER EP4 and carcinoembryonic antigen (CEA) were applied to cell blocks from 95 serous effusions. AUA1 and BER EP4 were reactive with 89% of effusions known to contain carcinoma cells, and anti-CEA with 71%. They also reacted with cells in two effusions from patients with malignant disease which were regarded as negative on conventional cytological examination of Papanicolaou-stained smears. They were negative in all but one of the benign effusions. Using all three antibodies, 95% of effusions containing carcinoma cells were detected. Use of these antibodies could improve the cytological diagnosis of serous effusions.

Indirect enzyme-linked immunosorbent assay (ELISA) allows sensitive detection of serum immunoglobulin (Ig) G against a soluble extract of Strongyloides stercoralis infective larvae. In this study, 40/40 (100%) human strongyloidiasis sera had high levels of anti-S. stercoralis IgG, but 30/40 (75%) filariasis sera, and 12/40 (30%) necatoriasis sera also had higher levels than control sera from UK residents. In attempts to increase the assay specificity by absorption of cross-reactive IgG, the effectiveness of pre-incubation of sera with extracts of different parasitic nematodes was investigated. One hour of incubation with 20 micrograms/ml aqueous extract of Onchocerca gutturosa absorbed cross-reactive IgG in most filariasis and necatoriasis sera, reducing the proportion with IgG levels above the positivity threshold by more than one-half. Preliminary results suggest that absorption with extracts of other filarial nematodes is equally effective, and that some of the cross-reactive IgG is directed against phosphorylcholine. Cross-reactive IgG in most necatoriasis sera was effectively absorbed with 20 micrograms/ml extract of Necator americanus. Cross-reactive IgG was not effectively absorbed with an extract of Ascaris lumbricoides. Absorption of cross-reactive IgG is an effective means of increasing the specificity of the indirect ELISA, for use in the immunodiagnosis and immuno-epidemiology of S. stercoralis infection.