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Background Increased understanding of whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection is an urgent requirement. We aimed to investigate whether antibodies against SARS-CoV-2 were associated with a decreased risk of symptomatic and asymptomatic reinfection. Methods A large, multicentre, prospective cohort study was done, with participants recruited from publicly funded hospitals in all regions of England. All health-care workers, support staff, and administrative staff working at hospitals who could remain engaged in follow-up for 12 months were eligible to join The SARS-CoV-2 Immunity and Reinfection Evaluation study. Participants were excluded if they had no PCR tests after enrolment, enrolled after Dec 31, 2020, or had insufficient PCR and antibody data for cohort assignment. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2–4 weeks) and completed questionnaires every 2 weeks on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive, or previous positive PCR or antibody test) or negative cohort (antibody negative, no previous positive PCR or antibody test). The primary outcome was a reinfection in the positive cohort or a primary infection in the negative cohort, determined by PCR tests. Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, or possible) and symptom-status, depending on the hierarchy of evidence. Primary infections in the negative cohort were defined as a first positive PCR test and seroconversions were excluded when not associated with a positive PCR test. A proportional hazards frailty model using a Poisson distribution was used to estimate incidence rate ratios (IRR) to compare infection rates in the two cohorts. Findings From June 18, 2020, to Dec 31, 2020, 30 625 participants were enrolled into the study. 51 participants withdrew from the study, 4913 were excluded, and 25 661 participants (with linked data on antibody and PCR testing) were included in the analysis. Data were extracted from all sources on Feb 5, 2021, and include data up to and including Jan 11, 2021. 155 infections were detected in the baseline positive cohort of 8278 participants, collectively contributing 2 047 113 person-days of follow-up. This compares with 1704 new PCR positive infections in the negative cohort of 17 383 participants, contributing 2 971 436 person-days of follow-up. The incidence density was 7·6 reinfections per 100 000 person-days in the positive cohort, compared with 57·3 primary infections per 100 000 person-days in the negative cohort, between June, 2020, and January, 2021. The adjusted IRR was 0·159 for all reinfections (95% CI 0·13–0·19) compared with PCR-confirmed primary infections. The median interval between primary infection and reinfection was more than 200 days. Interpretation A previous history of SARS-CoV-2 infection was associated with an 84% lower risk of infection, with median protective effect observed 7 months following primary infection. This time period is the minimum probable effect because seroconversions were not included. This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals. Funding Department of Health and Social Care of the UK Government, Public Health England, The National Institute for Health Research, with contributions from the Scottish, Welsh and Northern Irish governments.

BACKGROUND Identifying early stages of hypersensitivity pneumonitis (HP) is hampered by variable presentation, heterogeneous or undetected causal antigens and lack of gold-standard biomarkers. Krebs von den Lungen (KL)-6 is pathophysiological biomarker of alveolar epithelial damage. Pigeon fanciers, susceptible to HP, provide a model to investigate early HP. OBJECTIVE To test the hypothesis that plasma concentrations of KL-6 are increased in early-stage acute HP. METHODS Clinical history, spirometry and blood samples were obtained from pigeon fanciers, 20 with intermittent acute symptoms indicative of developing HP, 27 with no symptoms and 10 healthy subjects with no avian exposure. Plasma KL-6 (units/mL) and pigeon antigen-specific IgG antibody were quantified by enzyme immunoassay. Blood lymphocytes were quantified by flow cytometry and antigen specificity by in vitro cytokine production. RESULTS KL-6 was higher in fanciers than controls, median (IQR) 452 (244, 632) vs 274 (151, 377), P = .01. Although fanciers with symptoms had similar antigen exposure and lung function, they had higher KL-6 than those without, 632 (468, 1314) vs 320 (200, 480), P

White adipose tissue (WAT), once regarded as morphologically and functionally bland, is now recognized to be dynamic, plastic, heterogenous, and involved in a wide array of biological processes including energy homeostasis, glucose and lipid handling, blood pressure control, and host defense1. High fat feeding and other metabolic stressors cause dramatic changes in adipose morphology, physiology, and cellular composition1, and alterations in adiposity are associated with insulin resistance, dyslipidemia, and type 2 diabetes (T2D)2. Here, we provide detailed cellular atlases of human and murine subcutaneous and visceral white fat at single cell resolution across a range of body weight. We identify subpopulations of adipocytes, adipose stem and progenitor cells (ASPCs), vascular, and immune cells and demonstrate commonalities and differences across species and dietary conditions. We link specific cell types to increased risk of metabolic disease, and we provide an initial blueprint for a comprehensive set of interactions between individual cell types in the adipose niche in leanness and obesity. These data comprise an extensive resource for the exploration of genes, traits, and cell types in the function of WAT across species, depots, and nutritional conditions.

Summary Background BNT162b2 mRNA and ChAdOx1 nCOV-19 adenoviral vector vaccines have been rapidly rolled out in the UK from December, 2020. We aimed to determine the factors associated with vaccine coverage for both vaccines and documented the vaccine effectiveness of the BNT162b2 mRNA vaccine in a cohort of health-care workers undergoing regular asymptomatic testing. Methods The SIREN study is a prospective cohort study among staff (aged ≥18 years) working in publicly-funded hospitals in the UK. Participants were assigned into either the positive cohort (antibody positive or history of infection [indicated by previous positivity of antibody or PCR tests]) or the negative cohort (antibody negative with no previous positive test) at the beginning of the follow-up period. Baseline risk factors were collected at enrolment, symptom status was collected every 2 weeks, and vaccination status was collected through linkage to the National Immunisations Management System and questionnaires. Participants had fortnightly asymptomatic SARS-CoV-2 PCR testing and monthly antibody testing, and all tests (including symptomatic testing) outside SIREN were captured. Data cutoff for this analysis was Feb 5, 2021. The follow-up period was Dec 7, 2020, to Feb 5, 2021. The primary outcomes were vaccinated participants (binary ever vacinated variable; indicated by at least one vaccine dose recorded by at least one of the two vaccination data sources) for the vaccine coverage analysis and SARS-CoV-2 infection confirmed by a PCR test for the vaccine effectiveness analysis. We did a mixed-effect logistic regression analysis to identify factors associated with vaccine coverage. We used a piecewise exponential hazard mixed-effects model (shared frailty-type model) using a Poisson distribution to calculate hazard ratios to compare time-to-infection in unvaccinated and vaccinated participants and estimate the impact of the BNT162b2 vaccine on all PCR-positive infections (asymptomatic and symptomatic). This study is registered with ISRCTN, number ISRCTN11041050, and is ongoing. Findings 23 324 participants from 104 sites (all in England) met the inclusion criteria for this analysis and were enrolled. Included participants had a median age of 46·1 years (IQR 36·0–54·1) and 19 692 (84%) were female; 8203 (35%) were assigned to the positive cohort at the start of the analysis period, and 15 121 (65%) assigned to the negative cohort. Total follow-up time was 2 calendar months and 1 106 905 person-days (396 318 vaccinated and 710 587 unvaccinated). Vaccine coverage was 89% on Feb 5, 2021, 94% of whom had BNT162b2 vaccine. Significantly lower coverage was associated with previous infection, gender, age, ethnicity, job role, and Index of Multiple Deprivation score. During follow-up, there were 977 new infections in the unvaccinated cohort, an incidence density of 14 infections per 10 000 person-days; the vaccinated cohort had 71 new infections 21 days or more after their first dose (incidence density of eight infections per 10 000 person-days) and nine infections 7 days after the second dose (incidence density four infections per 10 000 person-days). In the unvaccinated cohort, 543 (56%) participants had typical COVID-19 symptoms and 140 (14%) were asymptomatic on or 14 days before their PCR positive test date, compared with 29 (36%) with typical COVID-19 symptoms and 15 (19%) asymptomatic in the vaccinated cohort. A single dose of BNT162b2 vaccine showed vaccine effectiveness of 70% (95% CI 55–85) 21 days after first dose and 85% (74–96) 7 days after two doses in the study population. Interpretation Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort was vaccinated when the dominant variant in circulation was B1.1.7 and shows effectiveness against this variant. Funding Public Health England, UK Department of Health and Social Care, and the National Institute for Health Research.

OBJECTIVE In surgical training, most assessment tools focus on advanced clinical decision-making or operative skill. Available tools often require significant investment of resources and time. A high stakes oral examination is also required to become board-certified in surgery. We developed Individual Clinical Evaluation (ICE) to evaluate intern-level clinical decision-making in a time- and cost-efficient manner, and to introduce the face-to-face evaluation setting. DESIGN Intern-level ICE consists of 3 clinical scenarios commonly encountered by surgical trainees. Each scenario was developed to be presented in a step-by-step manner to an intern by an attending physician or chief resident. The interns had 17 minutes to complete the face-to-face evaluation and 3 minutes to receive feedback on their performance. The feedback was transcribed and sent to the interns along with incorrect answers. Eighty percent correct was set as a minimum to pass each scenario and continue with the next one. Interns who failed were retested until they passed. Frequency of incorrect response was tracked by question/content area. After passing the 3 scenarios, interns completed a survey about their experience with ICE. SETTING Beth Israel Deaconess Medical Center, an academic tertiary care facility located in Boston, Massachusetts. PARTICIPANTS All first-year surgery residents in our institution (n = 17) were invited to complete a survey. RESULTS All 2016-2017 surgical interns (17) completed the ICEs. A total of $171 (US) was spent conducting the ICEs, and an average of 17 minutes was used to complete each evaluation. In total, 5 different residents failed 1 scenario, with the most common mistake being: failing to stabilize respiration before starting management. After completing the 3 clinical scenarios, more than 90% of respondents agreed or strongly agreed that the evaluations were appropriately challenging for training level, and that the evaluations helped to identify personal strengths and weaknesses in skill and knowledge. The majority believed their knowledge improved as a result of the ICE and felt better prepared to manage these scenarios (88% and 76%, respectively). CONCLUSIONS The ICE is an inexpensive and time efficient way to introduce interns to board type examinations and assess their preparedness for perioperative patient care issues. Common errors were identified which were able to inform educational efforts. ICEs were well accepted by residents. Next steps include extension of the ICE to PGY2 and PGY3 residents.

Background Fat grafting is a common procedure in plastic surgery. A major limitation is unpredictable graft retention, in part caused by inadequate oxygen delivery during the early posttransfer period. Methods The authors present a bioengineered approach to the design of a fat graft based on mathematical theory, which can estimate the limitations of oxygen delivery. To simplify the problem, four variables were defined: (1) recipient-site oxygen partial pressure; (2) adipose tissue oxygen permeability; (3) adipose tissue oxygen consumption rate; and (4) fat graft size. Recipient-site oxygen partial pressure and adipose tissue oxygen permeability were estimated from literature, whereas adipose tissue oxygen consumption rate was measured using stirred microchamber technology. Calculations were performed in both spherical and planar geometry to calculate the maximum allowable fat graft size from an oxygen delivery standpoint. Results As expected, planar geometry is less favorable for oxygenation but represents a realistic configuration for a fat graft. Maximum allowable fat graft thickness is only approximately 1 to 2 mm at external oxygen partial pressures of 10 to 40 mm Hg; any thicker and an anoxic or necrotic core likely develops. Given a reasonably large surface area and assuming several planes of injection, the maximum allowable fat graft volume is tens of milliliters. Conclusions A systematic bioengineered approach may help better design a fat graft. Applying principles of mass transfer theory can predict whether a fat graft has a favorable chance of surviving from an oxygen delivery standpoint and can direct the development of strategies for improved fat graft oxygenation.

Bdellovibrio bacteriovorus is a predator of Gram-negative bacteria and there is limited research on its utility for decontamination of post-harvest produce. The objective of this research was to determine reduction of E. coli O157:H7 and Salmonella on lettuce and carrot by B. bacteriovorus 109 (Bb109) and evaluate its survival and E. coli in buffer and on lettuce following gamma radiation exposure. Bb109 was cultured on ML35, filtered, and predator cells were suspended in buffer. Produce and buffer were co-inoculated with E. coli and Salmonella, separately; and Bb109 applied. In a separate experiment, Bb109 were inoculated on lettuce and suspended in buffer, then irradiated at 0.25–1.0 kGy treatments. E. coli and Salmonella in buffer were reduced by Bb109 0.4–3.9 and 0.9–2.6 logs, respectively. The predation of E. coli by Bb109 on carrot and lettuce resulted in 0.3–1.8 log reductions, and for Salmonella on the same produce, they were 0.9 and 1.2 logs, respectively. In radiation sensitivity assays, Bb109 populations in buffer and lettuce were inactivated by 3–5 logs (0.5 kGy). Bdellovibrio could aid the mortality of pathogenic bacteria during post-harvest treatment or in hurdle interventions of post-harvest produce. No previous data on Bdellovibrio exposure to radiation is available.

Control of foodborne pathogens on post-harvest produce may be improved by combined treatments. Hurdle applications may enhance the lethal effects of non-thermal interventions on pathogenic bacteria. We evaluated the effects of gamma radiation (0.5 kGy), nisin-based sanitizer (100%), and competitive biocontrol microbes (non-pathogenic Pseudomonas fluorescens) on the survival of Listeria monocytogenes on post-harvest tomato and carrot. Produce storage temperatures (5 and 20 °C) and days (0 and 7), with single, two or three treatment combinations of radiation (R), sanitizer (S) and biocontrol (B) were investigated for pathogen survival. Significant differences (P radiation > biocontrol. Inactivation of Listeria on post-harvest produce may be improved by treatment combinations as hurdle applications could enhance the safety of post-harvest carrot and tomato.

We evaluated knowledge of gynecologic cancer screening recommendations, screening behaviors, and communication with providers among women with Lynch syndrome (LS). Women aged ≥25 years who were at risk for LS-associated cancers completed a semi-structured interview and a questionnaire. Of 74 participants (mean age 40 years), 61% knew the appropriate age to begin screening, 75-80% correctly identified the recommended screening frequency, and 84% reported no previous screening endometrial biopsy. Women initiated discussions with their providers about their LS cancer risks, but many used nonspecific terms or relied on family history. Most were not offered high-risk screening options. While many women were aware of risk-appropriate LS screening guidelines, adherence was suboptimal. Improving communication between women and their providers regarding LS-related gynecologic cancer risk and screening options may help improve adherence.

The CETP inhibitor, torcetrapib, was prematurely terminated from phase 3 clinical trials due to an increase in cardiovascular and noncardiovascular mortality. Because nearly half of the latter deaths involved patients with infection, we have tested torcetrapib and other CETPIs to see if they interfere with lipopolysaccharide binding protein (LBP) or bactericidal/permeability increasing protein (BPI). No effect of these potent CETPIs on LPS binding to either protein was detected. Purified CETP itself bound weakly to LPS with a Kdor= 25 microM compared with 0.8 and 0.5 nM for LBP and BPI, respectively, and this binding was not blocked by torcetrapib. In whole blood, LPS induced tumor necrosis factor-alpha normally in the presence of torcetrapib. Furthermore, LPS had no effect on CETP activity. We conclude that the sepsis-related mortality of the ILLUMINATE trial was unlikely due to a direct effect of torcetrapib on LBP or BPI function, nor to inhibition of an interaction of CETP with LPS. Instead, we speculate that the negative outcome seen for patients with infections might be related to the changes in plasma lipoprotein composition and metabolism, or alternatively to the known off-target effects of torcetrapib, such as aldosterone elevation, which may have aggravated the effects of sepsis.

A model of coping with stress is proposed in which coping mediates the relationship among organizational stressors and personal characteristics, and job-related strains and organizational outcomes. Study results, based on a sample of professional salespeople, provide overall support for most of the hypothesized relationships among work-related stressors, personal characteristics, and coping styles. Findings also support the influence of emotion-focused coping on the psychological outcomes of emotional exhaustion and job-induced anxiety; which in turn are found to influence job satisfaction and intention to withdraw. While problem-focused coping had no effect on job-induced anxiety, problem-focused coping did effect emotional exhaustion, which in turn influences job satisfaction and intention to withdraw. Minor differences were found when the proposed model was applied to saleswomen versus salesmen. Overall, however, the model was robust across both genders.

Novel fluorescent derivatives of serotonin have been synthesized and used as tracers for the development of a 5-HT2C fluorescence polarization assay. Serotonin analogs that feature a fluorescent probe attached through an ether linkage at the tryptamine 5-position have high affinity for the 5-HT2C receptor, and affinity is dependent on both linker length and pendent dye. These variables have been optimized to generate Cy3B derivative 5a, which has 10-fold higher 5-HT2C affinity relative to serotonin (Kd=0.23 nM). In receptor activation experiments, 5a acts as a full agonist of 5-HT2C. Upon binding to 5-HT2C cell membranes, 5a shows a robust increase in fluorescence polarization (FP) signal. In an FP binding assay using 5a as a tracer ligand, Ki values for known 5-HT2C agonists and antagonists showed excellent agreement with Ki values from radioligand binding (r2=0.93). The FP ligand assay is suitable for high-throughput drug screening applications with respect to speed of analysis, displaceable signal, precision, and sensitivity to various reagents. A 384-well-based high-throughput assay that is rapid, economical, and predictive of test compounds' ability to bind to the 5-HT2C receptor has been compiled and validated.

BACKGROUND. Women with Lynch syndrome (hereditary nonpolyposis colorectal cancer) have an increased lifetime risk for endometrial and ovarian cancer. Screening and prophylactic surgery have been recommended as prevention strategies. In this study, the authors estimated the net health benefits and cost-effectiveness of these strategies in a Markov decision-analytic model. METHODS. Five strategies were compared for a hypothetical cohort of women with Lynch syndrome: 1) no prevention (‘reference’); 2) prophylactic surgery (hysterectomy and bilateral salpingo-oophorectomy) at age 30 years; 3) prophylactic surgery at age 40 years; 4) annual screening with endometrial biopsy, transvaginal ultrasound, and CA 125 from age 30 years; and 5) annual screening from age 30 years until prophylactic surgery at age 40 years (combined strategy). Net health benefit was measured in quality-adjusted life years (QALYs), and the primary outcome measured was the incremental cost-effectiveness ratio (ICER). Baseline and transition probabilities were obtained from published literature, and costs were from the U.S. Department of Health and Human Services and Agency for Health Care Quality and Research. Sensitivity analyses were performed for uncertainty around various parameters. RESULTS. The combined strategy provided the highest net health benefit (18.98 QALYs) but had an ICER of $194,650 per QALY relative to the next best strategy (prophylactic surgery at age 40 years). Prophylactic surgery at age 30 years and annual screening were dominated by alternate strategies. CONCLUSIONS. Annual screening followed by prophylactic surgery at age 40 years was the most effective gynecologic cancer prevention strategy, but the incremental benefit over prophylactic surgery alone was attained at substantial cost. The ICER would become favorable by improving the effectiveness and reducing the costs of screening in this population. Cancer 2008. © 2008 American Cancer Society.

Objective To test the hypothesis that an acute reduction in circulating insulin affects LH secretion in women with polycystic ovary syndrome (PCOS). Design Prospective study in normal and PCOS women. Setting General Clinical Research Centers at the University of Virginia, the Medical College of Virginia, and the Massachusetts General Hospital. Patient(s) Six normal women and five women with PCOS. Intervention(s) Administration of diazoxide to lower circulating insulin concentrations. Main Outcome Measure(s) Characteristics of LH secretion as appraised by multiparameter deconvolution and estimation of approximate entropy. Result(s) Short-term administration of diazoxide had no effect on the secretion of LH in women with PCOS. Conclusion(s) Hyperinsulinemia resulting from insulin resistance in women with PCOS may not have a direct effect on gonadotropin secretion.

Novel fluorescent derivatives of dofetilide (1) have been synthesized. Analogues that feature a fluorescent probe attached through an aliphatic spacer to the central tertiary nitrogen of 1 have high affinity for the hERG channel, and affinity is dependent on both linker length and pendent dye. These variables have been optimized to generate Cy3B derivative 10e, which has hERG channel affinity equivalent to that of dofetilide. When bound to cell membranes expressing the hERG channel, 10e shows a robust increase in fluorescence polarization (FP) signal. In a FP binding assay using 10e as tracer ligand, Ki values for several known hERG channel blockers were measured and excellent agreement with the literature Ki values was observed over an affinity range of 2 nM to 3 muM. 10e blocks hERG channel current in electrophysiological patch clamp experiments, and computational docking experiments predict that the dofetilide core of 10e binds hERG channel in a conformation similar to that previously predicted for 1. These analogues enable high-throughput hERG channel binding assays that are rapid, economical, and predictive of test compounds' potential for prolonged QT liabilities.

Nerve growth factor (NGF) is a neurotrophic cytokine with immunomodulatory activity. NGF contributes to neurogenic inflammation and has been described in asthma and idiopathic pulmonary fibrosis.To identify and quantify NGF in serum and peripheral blood lymphocyte cultures from pigeon fanciers, and to investigate an association with the immune response to inhaled avian antigens, and with symptoms of acute hypersensitivity pneumonitis (HP).NGF was quantified and compared with serum IgG antibody against inhaled avian antigens, with serum C-reactive protein (CRP), and with KL-6, a marker of lung interstitial inflammation. These were measured using enzyme-linked immunoassay. Levels were compared with symptom history in 55 pigeon fanciers (26 subjects with acute HP but symptom-free at the time of testing) and 15 subjects with no avian exposure.Pigeon fanciers had higher-than-normal serum IgG antibody, CRP, and KL-6 levels (p0.01 each). These measures were unrelated to HP symptom category; instead, in all pigeon fanciers, the concentrations of CRP and KL-6 correlated with each other and with the antibody titers (p0.01 each). Serum NGF levels were normal; however, NGF production by mitogen-activated lymphocytes was higher than normal, and correlated with IgG antibody titer (p0.05) and with serum CRP (p0.05).Serum NGF was normal in pigeon fanciers; however, their blood lymphocytes ex vivo synthesized increased NGF in concentrations that correlated with the titer of serum IgG antibody to inhaled avian antigens. These also correlated with CRP and KL-6 levels, suggesting that antigen exposure in seropositive subjects is associated with subclinical inflammation involving coordinated synthesis of neurotrophin and immune mediators.

INTRODUCTION: Reduced regenerative capacity of chronically axotomized neurons and reduced growth support by atrophic Schwann cells are key factors that account for the poor functional outcomes after proximal nerve injuries. In this study we examine two strategies aimed to circumvent deleterious effects of chronic axotomy and chronic denervation on axonal regeneration: (1) exogenous application of neurotrophic factors to chronically axotomized motoneurons to reverse time-related decline in regenerative capacity and (2) intracellular elevations of cyclic AMP (via exogenous application of forskolin and transforming growth factor β [TGF-β]) to induce atrophic dormant Schwann cells to proliferate and re-enter the nonmyelinating growth-supportive phenotype that normally supports axonal regeneration. METHODS: (1) Rat tibial motoneurons were chronically axotomized for 2 months and brain-derived neurotrophic factor (BDNF) and/or glia-derived neurotrophic factor (GDNF) supplied exogenously prior to enumeration of retrogradely labeled neurons that regenerate their axons. (2) Sciatic nerve Schwann cells were chronically denervated for 24 weeks prior to preparation and 48 h in vitro incubation of the nerve explants with saline or forskolin/TGF-β and reinsertion in a 1 cm long silastic sheath between cut tibial nerve stumps in vivo. Motoneurons that regenerated axons were enumerated 6 months later by retrograde labeling. RESULTS: (1) Low-dose but not high-dose BDNF and/or GDNF significantly increased the numbers of TIB motoneurons that regenerated axons after chronic but not immediate axotomy. The BDNF positive effect was mediated via trkB receptors, the inhibitory effects of high-dose BDNF being blocked by a p75-blocking antibody. (2) Treatment of chronically denervated Schwann cells with forskolin/TGF-β more than doubled the number of motoneurons that regenerated their axons through the treated Schwann cells. Regenerated axons were also well myelinated. DISCUSSION: Deleterious effects of chronic axotomy and Schwann cell denervation may be reversed by exogenous application of neurotrophic factors and by cytokines, respectively. Such experimental approaches may translate into strategies to promote functional recovery after nerve repair of the injured peripheral nervous system.

Genomic imprinting is a process that determines differential expression of genes according to their parental origin. Most imprinted genes play roles in growth, development and tumour suppression. Angelman syndrome is one of the most studied human diseases related to a gene that is expressed on the maternal chromosome only (at least in certain brain cells). It is caused by inactivation of the UBE3A gene in the brain due to various abnormalities of chromosome 15q11-q13 inherited from the mother. Its phenotype includes developmental delay, absent speech, motor impairment, a typical electroencephalogram, seizures and a peculiar behaviour. Lack of UBE3A expression may result from deletion of the 15q11-q13 region where this gene and GABRB3 are located, paternal uniparental disomy, imprinting defect or UBE3A mutation. Animal models corresponding to the different molecular classes have been generated. An integrative hypothesis for the molecular pathophysiology of the syndrome suggests dysregulation of synaptic neurotransmission through UBE3A-related modulation of functional GABAA receptors and GABRB3-related amount of β3 sub-unit in these receptors. This would account for developmental changes as well as for the differences in severity between deletion and non- deletion cases. In addition to rehabilitation programmes adapted to the patients' individual needs, promising management approaches may include pharmacological agents interfering with GABAA receptors, increasing GABRB3 expression or altering DNA methylation.

Studies have shown that implanting olfactory ensheathing cells (OECs) may be a promising therapeutic strategy to promote functional recovery after spinal cord injury. Several fundamental questions remain, however, regarding their in vivo interactions in the damaged spinal cord. We have induced a clip compression injury at the T10 level of the spinal cord in adult rats. After a delay of 1 week, OECs isolated from embryonic day 18 rats were implanted into the cystic cavity that had formed at the site of injury. Before implantation, OECs were infected with a LacZ-expressing retrovirus. At 3 weeks after implantation, LacZ -expressing OECs survived the implantation procedure and remained localized to the cystic cavity. At the electron microscopic level, the cystic cavity had clusters of LacZ -expressing OECs and numerous Schwann cells lacking LacZ expression. Although labeled OECs made no direct contact with axons, unlabeled Schwann cells were associated with either a single myelinated axon or multiple unmyelinated axons. Positively labeled OEC processes often enveloped multiple Schwann cell-axon units. These observations suggest that the role of OECs as the primary mediators of the beneficial effects on axon growth, myelination, and functional recovery after spinal cord injury may require re-evaluation.

The effects of pH (4.0–5.5), acid identity (acetic, citric, lactic, malic, and hydrochloric), and the induction of pH-dependent stationary phase acid resistance on the radiation resistance of E. coli O157:H7 Ent-C9490 was studied using cells grown in Tryptic Soy Broth with and without dextrose (induced and non-induced to acid resistance) and then resuspended in brain–heart infusion broth containing 5 g/l of an organic acid and acidified with concentrated hydrochloric acid. After treatment with gamma radiation, the number of survivors was determined by plating on brain–heart infusion agar (injured and non-injured cells) and MacConkey agar (non-injured cells), and the data used to calculate radiation D -values. The induction of pH-dependent stationary phase acid resistance consistently provided the enterohemorrhagic E. coli strain cross-protection from subsequent irradiation, increasing radiation D -values by 1.2–3.3-fold, depending on the organic acid present. The radiation resistance of E. coli varied with acid identity, but was largely unaffected by pH within the range examined. The results indicate that induction of cross-protection resulting from induction of acid resistance is a factor that should be considered to accurately determine the radiation dose needed to inactivate enterohemorrhagic E. coli in foods.

In contrast to injuries in the central nervous system, injured peripheral neurons will regenerate their axons. However, axotomized motoneurons progressively lose their ability to regenerate their axons, following peripheral nerve injury often resulting in very poor recovery of motor function. A decline in neurotrophic support may be partially responsible for this effect. The initial upregulation of glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) by Schwann cells of the distal nerve stump after nerve injury has led to the speculation that they are important for motor axonal regeneration. However, few experiments directly measure the effects of exogenous BDNF or GDNF on motor axonal regeneration. This study provided the first direct and quantitative evidence that long-term continuous treatment with exogenous GDNF significantly increased the number of motoneurons which regenerate their axons, completely reversing the negative effects of chronic axotomy. The beneficial effect of GDNF was not dose-dependent. A combination of exogenous GDNF and BDNF on motor axonal regeneration was significantly greater than either factor alone, and this effect was most pronounced following long-term continuous treatment. The ability of GDNF, either alone or in combination with BDNF, to increase the number of motoneurons that regenerated their axons correlated well with an increase in axon sprouting within the distal nerve stump. Thus long-term continuous treatment with neurotrophic factors, such as GDNF and BDNF, can be used as a viable treatment to sustain motor axon regeneration.

Angelman syndrome is characterised by neurodevelopmental impairment (with or without epileptic seizures) associated with functional deficit of the UBE3A gene. Different mechanisms of UBE3A inactivation correlate with clinical phenotypes of varying severity. However, three distinctive, highly consistent electroencephalographic rhythmic patterns can be observed in almost all patients irrespective of genotype, clinical severity and the presence or severity of a seizure disorder. Pattern I consists of runs of high amplitude 2 - 3/s rhythmic activity predominating over the frontal regions. Pattern II consists of more diffuse runs of 4 - 6/s rhythmic activity. Pattern III consists of bursts or runs of high amplitude 3 - 5/s rhythmic activity, maximal over the occipital region, sometimes containing small spikes and facilitated by eye closure. We review the available neurophysiological evidence from human and animal studies in the light of recent molecular advances. Electroencephalographic features in both patients and various mouse models point to two separable categories: characteristic rhythmic patterns, which are not related to epilepsy, and less specific epilepsy-related discharge activity. These features are consistent with a model of cortical and thalamo-cortical dysfunction resulting from dysregulation of synaptic GABAergic neurotransmission by (1) deficient recruitment of functional GABA (A) receptors related to reduced UBE3A gene expression in all cases and (2) decreased amount of beta3 sub-unit in these receptors related to reduced GABRB3 gene expression in deletion cases.

Samples of alfalfa seeds inoculated with Salmonella Mbandaka isolated from a naturally contaminated lot were γ-irradiated to 1 of 8 doses between 0 and 2.8 kGy, producing a maximum inactivation of 3.3 logs CFU/g. Analysis of the data indicates that the γ-radiation D value is 0.81 ± 0.02 kGy. An absorbed dose of 4 kGy, but not 3 kGy, eliminated viable S. Mbandaka from naturally contaminated seeds. Results of experiments with different percentages of inoculated seeds indicate that the dose required to inactivate a contaminating pathogen on alfalfa seeds is dependent upon the maximum contamination per seed, not the mean contamination of the lot.

Olfactory ensheathing cells (OECs) are the glial cells that ensheath the axons of the first cranial nerve. They are attracting increasing attention from neuroscientists as potential therapeutic agents for use in the repair of spinal cord injury and as a source of myelinating glia for use in remyelinating axons in demyelinating diseases such as multiple sclerosis. This review mainly addresses the cell biological aspects of OECs pertinent to addressing two questions. Namely, where do OECs fit into the groupings of central nervous system (CNS)/peripheral nervous system (PNS) glial cells and should OECs be viewed as a clinically relevant alternative to Schwann cells in the treatment of spinal cord injury? The evidence indicates that OECs are indeed a clinically relevant alternative to Schwann cells. However, much more work needs to be done before we can even come close to answering the first question as to the lineage and functional relationship of OECs to the other types of CNS and PNS glial cells.

Improvements in neuroimaging techniques have highlighted the role of cerebral dysplasia in developmental disorders and in epilepsy. The current classification is founded on the presumed timing of the first insult as deduced from the imaging appearances. Although clinical neurophysiological findings are often non-specific, several unusual patterns have been reported in association with certain types of malformation. These include the high amplitude rhythmic activities of lissencephaly, and focal rhythmic spikes. In this general review, we describe the electroence-phalographic and evoked potential findings in a wide range of cerebral dysplasias, including our personal experience of rare conditions such as Ramer-Lin syndrome. We focus on their role in assessment and on potential insights into pathophysiology.

The time-dependent decline in the ability of motoneurons to regenerate their axons after axotomy is one of the principle contributing factors to poor functional recovery after peripheral nerve injury. A decline in neurotrophic support may be partially responsible for this effect. The up-regulation of BDNF after injury, both in denervated Schwann cells and in axotomized motoneurons, suggests its importance in motor axonal regeneration. In adult female Sprague-Dawley rats, we counted the number of freshly injured or chronically axotomized tibial motoneurons that had regenerated their axons 1 month after surgical suture to a freshly denervated common peroneal distal nerve stump. Motor axonal regeneration was evaluated by applying fluorescent retrograde neurotracers to the common peroneal nerve 20 mm distal to the injury site and counting the number of fluorescently labelled motoneurons in the T11-L1 region of the spinal cord. We report that low doses of BDNF (0.5-2 microg/day for 28 days) had no detectable effect on axonal regeneration after immediate nerve repair, but promoted axonal regeneration of motoneurons whose regenerative capacity was reduced by chronic axotomy 2 months prior to nerve resuture, completely reversing the negative effects of delayed nerve repair. In contrast, high doses of BDNF (12-20 microg/day for 28 days) significantly inhibited motor axonal regeneration, after both immediate nerve repair and nerve repair after chronic axotomy. The inhibitory actions of high dose BDNF could be reversed by functional blockade of p75 receptors, thus implicating these receptors as mediators of the inhibitory effects of high dose exogenous BDNF.

Recent progress on designs of flexible circuits for the ATLAS pixel detector will be discussed. Thin flexible circuits can be used to provide power and signal connections between front-end (FE) readout chips and data acquisition chips on the pixel detector module. Fabrication of a prototype design has been completed and test beam measurements with a 16 FE chip flex module gave an efficiency of 98.4% and a position resolution of 13.8 μm for clusters consisting of one or two pixels.

Two diketopiperazines, cyclo-(L-prolyl-L-glycine) and cyclo-(L-phenylalanyl-4R-hydroxy-L-proline), and 2,4-dibromo-6-chlorophenol were isolated from cultures of the marine bacterium, Pseudoalteromonas luteoviolacea. Cyclo-(L-prolyl-L-glycine) and cyclo-(L-phenylalanyl-4R-hydroxy-L-proline) stimulated antibiotic production in this strain. 2,4-Dibromo-6-chlorophenol showed antibacterial activity against methicillin resistant Staphylococcus aureus (MRSA) and the cystic fibrosis associated pathogen Burkholderia cepacia.

Background Inhaled antigens from pigeons can cause extrinsic allergic alveolitis (EAA); a model disease of pulmonary inflammation. Among pigeon breeders, serum antibody and sensitized lymphocytes specific for these antigens have been described primarily, but not always, with disease. Antibody activity within the lung may have a closer association with disease, however, sampling by alveolar lavage at bronchoscopy is impractical for screening, therefore we used saliva to quantify the mucosal antibody response. Objective To establish: (a) if antibody activity against inhaled avian antigens was detectable in the saliva of pigeon breeders, (b) if the distribution of saliva antibody and total immunoglobulin levels were quantitatively or qualitatively different from serum, and (c) whether the hypersensitivity symptoms of EAA were associated more with the mucosal or the systemic humoral immune response. Measures Saliva and serum total and avian antigen-specific IgG, IgA (IgA1 and IgA2) antibody activity in 87 pigeon breeders and 24 control subjects with no avian exposure. Albumin levels were used as a protein reference and cotinine levels confirmed smoking status. Specific hypersensitivity symptoms and various exposure indices to pigeons were established by interview. Results Absolute levels and relative proportions (vs albumin) of IgG, IgA and IgA1 in saliva, and IgG in serum, were significantly higher in pigeon breeders compared with controls, suggesting mucosal inflammation. Avian antigen-specific antibody of all isotypes was readily demonstrable in saliva (predominantly IgA) and serum (predominantly IgG) from pigeon breeders, and there were no significant titres in controls. The levels of IgG antibody in saliva and in serum correlated significantly (r = 0.52, P

OBJECTIVES: To evaluate the EEG changes during seizures in children with drug resistant focal epilepsy who demonstrate hypoperfusion at the "seizure focus" interictally, but no perfusion change during the seizure. METHODS: Ictal EEG findings of six children with focal epilepsy who demonstrated hypoperfusion on rCBF SPECT after an interictal injection of (99)Tc(m) HMPAO concordant with the seizure focus, but who did not demonstrate rCBF change after an ictal injection (group 1) were reviewed. These were contrasted with the EEG data of six children matched as closely as possible for age, type of epilepsy, and pathology who did show hyperperfusion at the seizure focus on ictal scan when compared with the interictal study (group 2). RESULTS: The children in group 1 showed slowing of the EEG at the time of the (99)Tc(m) HMPAO injection relative to that seen at the onset of the seizure. Those in group 2 showed rhythmic activity, or sharp waves, or both on EEG at the time of injection. This last change was also seen consistently when the EEG data of a further 13 children who also showed ictal hyperperfusion at the seizure focus were reviewed. CONCLUSION: Ictal rCBF does not invariably increase at the seizure focus in patients with drug resistant focal epilepsy.

Summary Background Previous studies on allergy to feathers have not adddressed whether orgatiisms living on feathers (mites. lice, moulds) are a source of allergens. Objective To investigate whether feather mites produced allergens of clinical relevance to bird keepers. Methods We examined serum IgE responses of 96 pigeon breeders to an extract of feather mites from pigeons (predominantly Diplaegidia columbae). using Western blotting, specific IgE assay using AlaSTAT EIA and RAST inhibition. Results Feather mites are a major source of soluble proteins derived from feathers, accounting for up to 10% of the total weight of the feather. Forty-three sera had a negative score (0) for anti-feather mite IgE. 27 were weakly positive (1–2) and 26 had strongly positive scores (3–4). Fewer pigeon breeders with scores ± 3 were asymptomatic than those with negative scores (12 versus 40%). more had late onset symptoms (with or without early onset symptoms; 77% versus 44%) and had IgE antibody against house dust mite (89% versus 23%). Western blotting of eight sera against the extract of Diplaegidia columbae revealed 20 IgE-binding components ranging from 22 to 200 kDa. A high diversity of components was recognized by each serum: arithmetic mean 7 (range 2 14). RAST inhibition indicated feather mites had species-specific epitopes as well as ones that cross-reacted with Dermatophagoides pteronyssinus. Conclusion Strongly-positive AlaSTAT scores to pigeon leather mite were associated with allergic symptoms of late onset in pigeon breeders. We conclude that feather mites are a major source of clinically-relevant allergens for pigeon breeders.

We performed the present studies to determine whether a proximal renal tubular dopamine D 1 -like receptor defect exists in human essential hypertension. Twenty-four subjects were studied (13 normotensive and 11 hypertensive) in a randomized, double-blind, vehicle-controlled study using fenoldopam, a selective D 1 -like receptor agonist. Subjects were studied in sodium metabolic balance at 300 mEq/d, after which the salt sensitivity of their blood pressure was determined. Fenoldopam at peak doses of 0.1 to 0.2 μg/kg per minute decreased mean arterial pressure in hypertensive subjects but did not change mean pressure in normotensive subjects. Fenoldopam increased renal plasma flow to a greater extent in hypertensive than normotensive subjects. Fenoldopam increased both urinary and fractional sodium excretions in the hypertensive and normotensive groups. In normotensive but not hypertensive subjects, fenoldopam increased the fractional excretion of lithium and distal sodium delivery. In contrast, both distal fractional sodium reabsorption and sodium-potassium exchange fell significantly in hypertensive subjects. We conclude that human essential hypertension is associated with a reduction in the proximal tubular response to D 1 -like receptor stimulation compared with normotensive subjects. Hypertensive subjects appear to have a compensatory upregulation of renal vascular and distal tubular D 1 -like receptor function that offsets the proximal tubular defect, resulting in an enhanced natriuretic response to D 1 -like receptor stimulation.

A girl aged 9 years with Rasmussen's encephalitis previously treated by left temporal lobectomy suddenly developed prolonged attacks of extremely rapid respirations associated with poverty of body movements and greatly reduced facial movements with loss of speech. Her comprehension appeared intact and she responded to certain requests. Her eye gaze behaviour suggested a high degree of vigilance. The attacks would last from minutes to hours and were repeated up to a dozen times daily. In the context of the stress generated by the illness and other family problems the attacks had been mistaken for an hysterical elaboration. Their ictal nature was confirmed by EEG/video monitoring. Possible links with other developmental language disorders associated with epilepsy are discussed, including a model of autism.

Insulin-stimulated glucose transport has been shown to decline during maturation in lean rats. To determine whether this maturation-induced decrease occurred in the muscle of obese rats and whether the contraction-stimulated pathway for glucose transport was similarly affected, glucose transport rates were measured in insulin- and electrically stimulated skeletal muscle during hindlimb perfusion of 10- and 29-wk-old lean and obese male Zucker rats. Glucose transporter (GLUT-4) protein was also measured. Insulin-stimulated glucose transport rates were significantly decreased (36–56%) in 29-wk compared with 10-wk-old lean rats. There was no maturation-related decrease in GLUT-4. Insulin-mediated glucose transport was unaltered by maturation in skeletal muscle of obese rats. Differential effects of maturation on lean and obese rats caused the effect of obesity on maximally insulin-stimulated glucose transport to be much greater in 10- than 29-wk-old animals. Maturation had no effect on contraction-stimulated glucose transport rates in either lean or obese animals. The combined effect of maximal insulin plus contraction was not altered with maturity in lean animals but was significantly increased in 29- compared with 10-wk-old obese rats. Absence of a change in GLUT-4 content together with uncompromised contraction-stimulated glucose transport suggests that the maturation-induced decrease in insulin-stimulated glucose transport in lean rats is due to a defect in the insulin signaling pathway.

Longissimus dorsi from beef was inoculated with Listeria monocytogenes and the effect of gamma irradiation on the survival of this pathogen at -60 to +15 o C was determined. Radiation D-values were determined for inactivation of L. monocytogenes at 5 o C intervals from -20 to 5 o C. These data were used to develop an equation to predict the response to gamma radiation within that range. An abrupt increase in resistance occurred at -5 o C. The radiation D-value was 0.45 kGy at 0 o C, 0.77 kGy at -5 o C and 1.21 kGy at -20 o C. A straight line was obtained when the log 10 of the D-values from -5 to -20 o C was plotted vs the reciprocal of the absolute temperature. This led us to calculate a value analogous to the Arrhenius activation energy for inactivation of L. monocytogenes by gamma radiation

The spectrum of cancers seen in a hospital based Lynch syndrome registry of mismatch repair gene mutation carriers was examined to determine the distribution of cancers and examine excess cancer risk. Overall there were 504 cancers recorded in 368 mutation carriers from 176 families. These included 236 (46.8 %) colorectal and 268 (53.2 %) extracolonic cancers. MLH1 mutation carriers had a higher frequency of colorectal cancers whereas MSH2, MSH6 and PMS2 mutation carriers had more extracolonic cancers although these differences were not statistically significant. Men had fewer extracolonic cancers than colorectal (45.3 vs. 54.7 %), whereas women had more extracolonic than colorectal cancers (59.0 vs. 41.0 %). The mean age at diagnosis overall for extracolonic cancers was older than for colorectal, 49.1 versus 44.8 years (P ≤ 0.001). As expected, the index cancer was colorectal in 58.1 % of patients and among the extracolonic index cancers, endometrial was the most common (13.8 %). A significant number of non-Lynch syndrome index cancers were recorded including breast (n = 5) prostate (n = 3), thyroid (n = 3), cervix (n = 3), melanoma (n = 3), and 1 case each of thymoma, sinus cavity, and adenocarcinoma of the lung. However, standardized incidence ratios calculated to assess excess cancer risk showed that only those cancers known to be associated with Lynch syndrome were significant in our sample. We found that Lynch syndrome patients can often present with cancers that are not considered part of Lynch syndrome. This has clinical relevance both for diagnosis of Lynch syndrome and surveillance for cancers of different sites during follow-up of these patients.

The purpose of this study was to compare the thickness of the compressed breast between mediolateral oblique and craniocaudal mammograms and to relate these differences in thickness to image quality and radiation dose. These differences may partially explain why some subtle tumors are better visualized on the craniocaudal view.The study population consisted of 250 paired mediolateral oblique and craniocaudal mammograms obtained on one mammographic unit by seven certified mammography technologists during a 2-month period. Only women with breast implants, prior lumpectomy and radiotherapy, or chest wall deformity were excluded. The digital readout of compressed breast thickness and applied compression force was recorded. Mammographic positioning was assessed using standard criteria. Absorbed radiation dose at different thicknesses was measured with a BR-12 breast phantom. Image quality differences for geometric unsharpness and contrast were calculated for the observed breast thickness differences between mediolateral oblique and craniocaudal mammograms.The mean thickness of the compressed breast on the craniocaudal view was less than the mean thickness on the mediolateral oblique view (4.4 versus 4.8 cm, p.0001) despite the greater force used to compress the breast for mediolateral oblique than for craniocaudal views (93 versus 86 newtons, p.0001). The breast thickness on the mediolateral oblique view exceeded that on the craniocaudal view in 98 (84%) of 117 pairs that differed in thickness by 5 mm or more and 46 (94%) of 49 pairs that differed by 10 mm or more (p.0001). Geometric unsharpness increased by 8% and 19% when a 4.4-cm-thick breast was compared to a 4.8- and 5.4-cm-thick breast, respectively. A 5% and 12% loss of contrast was noted when a 4.4-cm-thick breast was compared to a 4.8- and 5.4-cm-thick breast. Mean glandular radiation dose at 4.4, 4.8, and 5.4 cm was 1.40, 1.70, and 2.33 mGy, respectively.The compressed breast is 8% thicker on mediolateral oblique than on craniocaudal mammograms, a small but statistically significant difference. This difference results in a small loss of spatial and contrast resolution on the mediolateral oblique views and an increase in radiation dose. These image quality differences may partially explain why some subtle carcinomas are better visualized on the craniocaudal view.

The increased use of inhaled corticosteroids, particularly in higher doses in the treatment of asthma, has led to a recurrence of the concerns over possible side-effects associated with their long-term use. One area of concern is the possible long-term adverse effect on bone metabolism. Corticosteroids can affect bones by influencing their turnover and metabolism with resulting loss of bone mass and therefore the potential clinical outcome of osteoporosis (1). In order to understand how corticosteroids administered by the inhaled route might exert an effect on bones and to assess whether or not there is clinical relevance of such action, it is necessary to begin with an understanding of the basic processes of bone metabolism.

A micromechanics method based on the Mori-Tanaka averaging scheme is used to predict the effective thermomechanical properties of composite materials reinforced by Shape Memory Alloy (SMA) fibers. Both elastic stiffness changes and transformation strains are taken into account in the constitutive modelling of the SMA fibers. Isothermal longitudinal and transverse stress input and stress-free thermal loading are imposed on the composite, and the composite transformation stress, the maximum transformation strain, and the hysteresis are computed. In con trast to a monolithic SMA, stress-free thermal loading of a shape memory composite is shown to produce transformation strains due to thermal stress induced phase transformation. Closed form solutions for the effective martensite and austenite start temperatures indicate that these temperatures are higher than those of the monolithic SMA material and they depend on the composite processing temperature.

The clinical, radiologic, neurophysiologic, and pathologic findings in 10 children with histologically proven Alexander's disease are described, and the presence of two broad clinical subgroups is confirmed. Macrocephaly, regression, and seizures are found in the infantile form, whereas bulbar signs predominate the so-called juvenile form. None of the clinical or neurophysiologic findings is pathognomonic, and radiologic features suggesting the diagnosis are not present in all cases. However, the combination of abnormalities may suggest the diagnosis and justify histologic confirmation. ( J Child Neurol 1993;8:134-144).

The tantalizing problem of the “quenching” of the Coulomb sum rule observed in medium weight nuclei is investigated in light nuclei at high momentum transfer. Inclusive electron scattering cross sections for 3,4He have been measured in the quasielastic region at electron energies between 0.9 GeV and 4.3 GeV, and scattering angles of 15° and 85°. Longitudinal (RL) and transverse (RT) response functions have been extracted using a Rosenbluth separation at constant ‖ q ‖ of 1.050 (GeV/c). The ratio of the longitudinal to the transverse reduced response functions in the negative y region reaches unity. The experimental Coulomb sum rule although with large uncertainty and conversly to the case of medium weight nuclei, saturates at high momentum to the He nucleus total charge namely Z=2.

Endometrial and colorectal cancers are the most common cancers in Lynch syndrome. Consensus guidelines recommend annual endometrial biopsy (EMB) and regular colonoscopies. We assessed the feasibility of concurrently performing EMB and colonoscopy and evaluated women's perception of pain, satisfaction, and acceptability.From July 2002 to December 2009, women who had a gene mutation for Lynch syndrome, met the Amsterdam II criteria, or had a high-risk situation that required screening were prospectively enrolled. After conscious sedation, the procedures were sequentially performed. Patients completed pre- and postprocedure questionnaires assessing pain, level of satisfaction, and acceptability. The Wilcoxon rank test and Mann-Whitney test were used to compare pain scores.Forty-two women completed the study. Median age was 37 years (range, 25 to 73). Nineteen had previously had an EMB in the office setting. Women reported significantly lower median levels of pain in the combined procedure compared with previous office setting biopsies (P.001). Regardless of parity, women reported significantly less pain for an EMB as part of the combined screen compared with an office EMB (parous, P = .003; nulliparous, P = .026). Women also reported a high level of satisfaction and more convenience in the combined procedure. All participants preferred combined to separately scheduled procedures and would recommend the combined procedure to their relatives.Combined colon and endometrial cancer screening is a patient-centered approach that is feasible, acceptable, and may improve adherence to Lynch syndrome screening recommendations.

When a patient presents with wheezing, pulmonary embolism is not usually considered as a possible cause. However, undoubtedly bronchoconstriction can be caused by pulmonary emboli and occasionally wheezing may be so obvious as to suggest a diagnosis of bronchial asthma. Eleven cases are reported in which wheezing was attributable to recurrent pulmonary emboli and one in which it was a clamant feature after a single embolic incident.

Summary A detailed comparative seroepidemiological study of antibody responses was performed in 271 pigeon fanciers and 100 farmers. Overall 73 % of pigeon fanciers had IgG antibodies at a titre ⩾ 16 to Chlamydia pneumoniae , 39% to Chlamydia psittaci , and 6·6% to Chlamydia trachomatis . The prevalence of chlamydial antibodies was significantly lower in the farmers at 47% for C. pneumoniae , 6% for C. psittaci , and 2% for C. trachomatis . Both populations were exposed to complex microbiological and antigenic environments: 50·5 % of the pigeon fanciers had antibodies to pigeon antigens, 34% to egg membrane, and 0·73% to yolk sac antigen, and 59% of the farmers had antibodies to Micropolyspora faeni , but the high prevalence of chlamydial antibodies could not be attributed to interactions with these antigens. There was considerable overlap of chlamydial antibody responses in the pigeon fanciers but not in the farmers: 36 % of the pigeon fanciers had antibodies to C. pneumoniae alone, 5% to C. psittaci alone, and 31% to both agents, whereas only 3% of farmers had antibodies to both C. pneumoniae and C. psittaci . The high prevalence of antibodies to C. psittaci in the pigeon fanciers is compatible with the known avian reservoir for this infection. The particularly high prevalence of antibodies to C. pneumoniae suggests that complex interactions may be occurring in a population exposed to two chlamydial organisms, whereby infection with one species may provoke an anamnestic response against other chlamydial organisms with which the subject has previously been infected.

We conducted a multicentre, randomized, double-blind, placebo-controlled, parallel group study to determine the efficacy of controlled release salbutamol (SCR) tablets in clinically stable patients with predominantly non-reversible chronic airflow obstruction (CAO). Patients received either 8 mg SCR or matching placebo tablets twice daily for 6 weeks. Fifty-eight patients (30 on SCR and 28 on placebo) completed the study. Outcome measurements included FEV 1 , FVC, 6-min walking distance, and patient assessment of efficacy recorded at the clinic visits and twice daily PEFR measurements plus daytime symptom score recorded in diary cards. The absolute change between baseline and 6-week measurements with SCR was compared to that with placebo. Favourable trends were observed with SCR for all variables tested except FVC. The only significant difference between SCR and placebo was in FEV 1 where there was a small net change of 95 ml in favour of SCR. We conclude, therefore, that the effects of lung function of long-term bronchodilator therapy with SCR in patients with stable non-reversible CAO are slight, and are likely to be of limited clinical benefit.