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Aims: Post-infarction ventricular septal defect (PIVSD) is a mechanical complication of acute myocardial infarction (AMI) with a poor prognosis. Surgical repair is the mainstay of treatment, although percutaneous closure is increasingly undertaken., Methods and Resuts: Patients treated with surgical or percutaneous repair of PIVSD (2010-2021) were identified at 16 UK centres. Case note review was undertaken. The primary outcome was long-term mortality. Patient groups were allocated based upon initial management (percutaneous or surgical). Three-hundred sixty-two patients received 416 procedures (131 percutaneous, 231 surgery). 16.1% of percutaneous patients subsequently had surgery. 7.8% of surgical patients subsequently had percutaneous treatment. Times from AMI to treatment were similar [percutaneous 9 (6-14) vs. surgical 9 (4-22) days, P = 0.18]. Surgical patients were more likely to have cardiogenic shock (62.8% vs. 51.9%, P = 0.044). Percutaneous patients were substantially older [72 (64-77) vs. 67 (61-73) years, P < 0.001] and more likely to be discussed in a heart team setting. There was no difference in long-term mortality between patients (61.1% vs. 53.7%, P = 0.17). In-hospital mortality was lower in the surgical group (55.0% vs. 44.2%, P = 0.048) with no difference in mortality after hospital discharge (P = 0.65). Cardiogenic shock [adjusted hazard ratio (aHR) 1.97 (95% confidence interval 1.37-2.84), P < 0.001), percutaneous approach [aHR 1.44 (1.01-2.05), P = 0.042], and number of vessels with coronary artery disease [aHR 1.22 (1.01-1.47), P = 0.043] were independently associated with long-term mortality., Conclusion: Surgical and percutaneous repair are viable options for management of PIVSD. There was no difference in post-discharge long-term mortality between patients, although in-hospital mortality was lower for surgery., Competing Interests: Conflict of interest: B.R.C. has received speaking fees from Abbott Vascular. P.M. has provided expert testimony and worked as a speaker for Edwards Lifesciences. J.B. has worked as a proctor for Abbott Vascular. M.S.T. has worked as a consultant and received educational grants from Occlutech. He has worked as a consultant and proctor for Abbott Vascular. D.B.N. has worked as a proctor for Abbott Vascular. D.H.-S. has received travel support and worked as a proctor for Abbott Vascular and Boston Scientific; he has received consulting fees and participated in a data and safety monitoring board for Abbott Vascular. M.A.M. has received non-restrictive educational grants from Abbott Vascular and Terumo, and worked as a consultant for Daiichi Sankyo and Terumo. P.A.C. has worked as a proctor for Abbott Vascular, Gore Medical and Occlutech., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Launching an academic career in breast imaging presents both challenges and opportunities for the newly graduated trainee. A strategic plan aligned with one's personal strengths and interests facilitates career success and professional satisfaction. Academic departments offer multiple tracks to accommodate diverse faculty goals. The specific requirements of various tracks vary across institutions. The clinician-educator track typically encourages a focus on medical education and educational scholarship. The clinician-investigator or clinician-scholar track supports original research and grant-funded clinical trials. Finally, the clinical and clinician-administrator tracks allow for emphasis on clinical program development and leadership. As definitions of scholarship broaden, many opportunities are accessible to demonstrate excellence in the traditional areas of clinical practice, education, and research, as well as the broader fields of leadership and administration. Departmental and national society resources that advance knowledge in one's chosen area of interest are available and should be explored. Mentorship and sponsorship can provide valuable insight into identifying such resources and devising a plan for sustainable career success and work-life integration., (© Society of Breast Imaging 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To understand the genetics involved in surface attachment and biofilm formation of Listeria monocytogenes., Methods and Results: An in vitro screen of a Himar1 transposon library of L. monocytogenes strain 15G01 identified three transposants that produced significantly different biofilm levels when compared to the wild-type strain; two mutants exhibited enhanced biofilm formation and one produced less biofilm biomass than the wild-type. The mutant 15G01 mprF::Himar1, which had a transposon insertion in the mprF gene, was selected for further analysis. The mutant produced a more densely populated biofilm on solid surfaces such as stainless steel and polystyrene, as determined using scanning electron and light microscopy. The 15G01 mprF::Himar1 mutant remained viable in biofilms, but showed an increase in sensitivity to the cationic antimicrobial gallidermin. The mutant also displayed reduced invasiveness in CaCo-2 intestinal cells, suggesting virulence properties are compromised by the inactivation of mprF., Conclusions: Biofilm formation and gallidermin resistance of L. monocytogenes is influenced by mprF, but this trait is associated with a compromise in invasiveness., Significance and Impact of the Study: The presence of pathogenic microorganisms in the food processing environment can cause a significant problem, especially when these microorganisms are established as biofilms. This study shows that the inactivation of the mprF gene results in enhanced biofilm formation and abiotic surface attachment of L. monocytogenes., (© 2020 The Society for Applied Microbiology.)

Lung ultrasound has been described for over a decade and international protocols exist for its application. It is a controversial area among pulmonologists and has had more uptake with emergency as well as intensive care physicians. We discuss the basics and evidence behind the use of lung ultrasound in respiratory failure, and what role we see it playing in the current 2019 novel coronavirus pandemic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Barrett's esophagus (BE), a consequence of gastroesophageal reflux disease (GERD), is a premalignant condition for esophageal adenocarcinoma. Impaired gastric emptying leads to increased gastric volume and therefore more severe reflux. We seek to investigate the association between gastroparesis and BE and the predictors of BE among patients with gastroparesis. This is a retrospective review of patients seen at Cleveland Clinic between 2011 and 2016 who had an upper endoscopy and a gastric emptying study. Demographics, symptoms, medications, endoscopic and histological findings, and therapeutic interventions were abstracted. Risk of BE among gastroparesis group and control group was assessed, and logistic regression analysis was performed to identify predictors of BE among gastroparesis patients. Of the 4,154 patients, 864 (20.8%) had gastroparesis and 3, 290 (79.2%) had normal gastric emptying. The mean age was 51.4 ± 16.4 years, 72% were women and 80% were Caucasians. Among the gastroparesis group, 18 (2.1%) patients had BE compared to 71 (2.2%) cases of BE in the control group, P = 0.89. There were no differences in gender, race, reflux symptoms, or esophageal findings between the two groups. Among gastroparesis group, predictors of developing BE were a history of alcohol use (odds ratio [OR] 6.76; 95% confidence intervals [CI]: 1.65-27.67, P = 0.008), history of pyloroplasty (OR: 8.228; CI: 2.114-32.016, P = 0.002), and hiatal hernia (OR: 8.014; CI: 2.053-31.277, P = 0.003). Though gastroparesis is a known contributing factor for GERD, there was no increased prevalence of BE in gastroparesis. Among patients with gastroparesis, predictors of BE are history of alcohol use, hiatal hernia, and pyloroplasty., (© The Author(s) 2020. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Mammographic screening guidelines in women aged 75 and older are inconsistent due to a lack of data from prospective randomized controlled trials, such as those that exist for women between 40-74 years of age. In addition, older women are perceived as less likely to benefit from early detection due to increased comorbidities and a greater proportion of biologically favorable cancers. With increasing life expectancy and quality of life in the elderly, the question of when to stop mammographic screening merits renewed discussion. Observational data support a survival benefit from regular screening in older women with no severe comorbidities. In addition, screening mammography in this age group has been shown to perform better than in younger age groups, tipping the balance toward greater benefits than harms. Early studies of digital breast tomosynthesis (DBT) in older women suggest that performance metrics are further improved with DBT screening. While a biennial schedule in older women preserves some of the benefit of screening, annual mammography achieves the greatest reductions in breast cancer mortality and morbidity. As the medical community strives to offer personalized care for all age groups, health care providers are well positioned to offer shared decision-making based on existing data and tailored to each woman's individual risk profile, comorbid conditions, and personal values., (© Society of Breast Imaging 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The PathoSystems Resource Integration Center (PATRIC) is the bacterial Bioinformatics Resource Center funded by the National Institute of Allergy and Infectious Diseases (https://www.patricbrc.org). PATRIC supports bioinformatic analyses of all bacteria with a special emphasis on pathogens, offering a rich comparative analysis environment that provides users with access to over 250 000 uniformly annotated and publicly available genomes with curated metadata. PATRIC offers web-based visualization and comparative analysis tools, a private workspace in which users can analyze their own data in the context of the public collections, services that streamline complex bioinformatic workflows and command-line tools for bulk data analysis. Over the past several years, as genomic and other omics-related experiments have become more cost-effective and widespread, we have observed considerable growth in the usage of and demand for easy-to-use, publicly available bioinformatic tools and services. Here we report the recent updates to the PATRIC resource, including new web-based comparative analysis tools, eight new services and the release of a command-line interface to access, query and analyze data., (Published by Oxford University Press on behalf of Nucleic Acids Research 2019.)

The order of enzymatic activity across Golgi cisternae is essential for complex molecule biosynthesis. However, an inability to separate Golgi cisternae has meant that the cisternal distribution of most resident proteins, and their underlying localization mechanisms, are unknown. Here, we exploit differences in surface charge of intact cisternae to perform separation of early to late Golgi subcompartments. We determine protein and glycan abundance profiles across the Golgi; over 390 resident proteins are identified, including 136 new additions, with over 180 cisternal assignments. These assignments provide a means to better understand the functional roles of Golgi proteins and how they operate sequentially. Protein and glycan distributions are validated in vivo using high-resolution microscopy. Results reveal distinct functional compartmentalization among resident Golgi proteins. Analysis of transmembrane proteins shows several sequence-based characteristics relating to pI, hydrophobicity, Ser abundance, and Phe bilayer asymmetry that change across the Golgi. Overall, our results suggest that a continuum of transmembrane features, rather than discrete rules, guide proteins to earlier or later locations within the Golgi stack., (© 2019 American Society of Plant Biologists. All rights reserved.)

Background: The effect of a weekend compared with a weekday hospital admission on patient outcomes after an acute coronary syndrome is unclear. This study aims to determine whether collectively there is a weekend effect in acute coronary syndrome., Method: We conducted a systematic review and meta-analysis of cohort studies examining the association between weekend compared to weekday admission at any time of the day and early mortality (in-hospital or 30-day). A search was performed on Medline and Embase and relevant studies were pooled using random effects meta-analysis for risk of early mortality. Additional analyses were performed considering only more recent studies (conducted after 2005) and by patient group (ST-elevation myocardial infarction [STEMI] or non-STEMI [NSTEMI]), as well as meta-regression according to starting year and mean year of study., Results: A total of 18 studies were included with over 14 million participants incorporating 3 million weekend and over 11.5 million weekday admissions and the rates of mortality were 19.2% and 23.4%, respectively. The pooled results of all 18 studies suggest that weekend admission was associated with a small increased risk of early mortality (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.03-1.09). The results for subgroups of STEMI and NSTEMI cohorts were not statistically significant and timing of admission after 2005 had minimal influence on the results (OR 1.06, 95% CI 0.95-1.17)., Conclusions: There is a small weekend effect for admission with acute coronary syndrome that has persisted over time.

Digital breast tomosynthesis (DBT) is increasingly recognized as a superior breast imaging technology compared with 2D digital mammography (DM) alone. Accumulating data confirm increased sensitivity and specificity in the screening setting, resulting in higher cancer detection rates and lower abnormal interpretation (recall) rates. In the diagnostic environment, DBT simplifies the diagnostic work-up and improves diagnostic accuracy. Initial concern about increased radiation exposure resulting from the DBT acquisition added onto a 2D mammogram has been largely alleviated by the development of synthesized 2D mammography (SM). Continued research is underway to reduce artifacts associated with SM, and improve its comparability to DM. Breast cancers detected with DBT are most often small invasive carcinomas with a preponderance for grade 1 histology and luminal A molecular characteristics. Recent data suggest that higher-grade cancers are also more often node negative when detected with DBT. A meta-analysis of early single-institution studies of the effect of DBT on interval cancers has shown a modest decrease when multiple data sets are combined. Because of the greater conspicuity of lesions on DBT imaging, detection of subtle architectural distortion is increased. Such findings include both spiculated invasive carcinomas and benign etiologies such as radial scars. The diagnostic evaluation of architectural distortion seen only with DBT can pose a challenge. When no sonographic correlate can be identified, DBT-guided biopsy and/or localization capability is essential. Initial experience with DBT-guided procedures suggests that DBT biopsy equipment may improve the efficiency of percutaneous breast biopsy with less radiation., (© Society of Breast Imaging 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To examine community pharmacists' perspectives on CMs regulation in New Zealand, where proposals for CMs regulations had recently been suspended and where, currently, CMs are only weakly regulated., Methods: Qualitative, in-depth, semi-structured interviews with New Zealand practising community pharmacists are identified through purposive and convenience sampling. Data were analysed using a general inductive approach., Key Findings: Participants held mixed views regarding harmonisation of CMs regulations across Australia and NZ; some supported an NZ national regulatory framework for CMs, based on the Australian system. Participants recognised the current CMs regulatory framework in NZ as inadequate, that regulation was required to some extent, and that mandatory regulation was not necessarily required. A key reason given in support of CMs regulations was the need for greater assurances around quality of CMs. Participants also supported a regulatory framework that incorporated assessment of the safety of CMs, but were less convinced of the need for, or feasibility of, requiring evidence of efficacy from clinical trials. Participants believed that regulation of CMs practitioners, such as herbalists, and CMs retailers was important, although there were mixed views as to whether regulation should be statutory or whether self-regulation would be adequate., Conclusions: On the basis of these findings, pharmacists would be expected to welcome proposals for national regulations for CMs in NZ: such regulations should address concerns regarding product quality, inappropriate health claims and supporting evidence, and therefore should support pharmacists in meeting their obligations under the NZ Pharmacy Council's Code of Ethics., (© 2018 Royal Pharmaceutical Society.)

Hodgkin lymphoma and lymphomatoid granulomatosis (LYG) are entities that contain a small number of large, variably Epstein-Barr virus (EBV)-positive neoplastic cells scattered within background non-neoplastic mixed inflammatory infiltrate. The 2 entities can typically be distinguished histologically by the angiocentric and angiodestructive pattern of lymphomatoid granulomatosis (LYG); also, they differ in overall prognosis. Herein, we report a case of Hodgkin lymphoma in a 64-year-old Caucasian woman, diagnosed at autopsy with unusual histologic features and aggressive clinical course that mimicked LYG., (© American Society for Clinical Pathology 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Poliovirus importations and related outbreaks continue to occur in polio-free countries, including those in the World Health Organization (WHO) European Region. National preparedness plans for responding to poliovirus introduction are insufficient in many countries of the European Region. We describe a series of polio outbreak simulation exercises that were implemented to formally test polio outbreak preparedness plans in the European Region., Methods: We designed and implemented the exercises, reviewed the results, made recommendations, and assessed the role of outbreak simulation exercises in maintaining regional polio-free status. In addition, we performed a comprehensive review of the national plans of all WHO Member States in the European Region., Results: Three exercises, delivered during 2011-2013 (for the Balkans, United Kingdom, and the Caucasus and Ukraine), revealed that participating countries were generally prepared for poliovirus introduction, but the level of preparedness needed improvement. The areas in particular need of strengthening were national preparedness plans, initial response, plans for securing vaccine supply, and communications., Conclusions: Polio outbreak simulation exercises can be valuable tools to help maintain polio-free status and should be extended to other high-risk countries and subnational areas in the European Region and elsewhere., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: The European region, certified as polio free in 2002, had recent wild poliovirus (WPV) introductions, resulting in a major outbreak in Central Asian countries and Russia in 2010 and in current widespread WPV type 1 circulation in Israel, which endangered the polio-free status of the region., Methods: We assessed the data on the major determinants of poliovirus transmission risk (population immunity, surveillance, and outbreak preparedness) and reviewed current threats and measures implemented in response to recent WPV introductions., Results: Despite high regional vaccination coverage and functioning surveillance, several countries in the region are at high or intermediate risk of poliovirus transmission. Coverage remains suboptimal in some countries, subnational geographic areas, and population groups, and surveillance (acute flaccid paralysis, enterovirus, and environmental) needs further strengthening. Supplementary immunization activities, which were instrumental in the rapid interruption of WPV1 circulation in 2010, should be implemented in high-risk countries to close population immunity gaps. National polio outbreak preparedness plans need strengthening. Immunization efforts to interrupt WPV transmission in Israel should continue., Conclusions: The European region has successfully maintained its polio-free status since 2002, but numerous challenges remain. Staying polio free will require continued coordinated efforts, political commitment and financial support from all countries., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Frontotemporal dementia and amyotrophic lateral sclerosis are closely related clinical syndromes with overlapping molecular pathogenesis. Several families have been reported with members affected by frontotemporal dementia, amyotrophic lateral sclerosis or both, which show genetic linkage to a region on chromosome 9p21. Recently, two studies identified the FTD/ALS gene defect on chromosome 9p as an expanded GGGGCC hexanucleotide repeat in a non-coding region of the chromosome 9 open reading frame 72 gene (C9ORF72). In the present study, we provide detailed analysis of the clinical features and neuropathology for 16 unrelated families with frontotemporal dementia caused by the C9ORF72 mutation. All had an autosomal dominant pattern of inheritance. Eight families had a combination of frontotemporal dementia and amyotrophic lateral sclerosis while the other eight had a pure frontotemporal dementia phenotype. Clinical information was available for 30 affected members of the 16 families. There was wide variation in age of onset (mean = 54.3, range = 34-74 years) and disease duration (mean = 5.3, range = 1-16 years). Early diagnoses included behavioural variant frontotemporal dementia (n = 15), progressive non-fluent aphasia (n = 5), amyotrophic lateral sclerosis (n = 9) and progressive non-fluent aphasia-amyotrophic lateral sclerosis (n = 1). Heterogeneity in clinical presentation was also common within families. However, there was a tendency for the phenotypes to converge with disease progression; seven subjects had final clinical diagnoses of both frontotemporal dementia and amyotrophic lateral sclerosis and all of those with an initial progressive non-fluent aphasia diagnosis subsequently developed significant behavioural abnormalities. Twenty-one affected family members came to autopsy and all were found to have transactive response DNA binding protein with M(r) 43 kD (TDP-43) pathology in a wide neuroanatomical distribution. All had involvement of the extramotor neocortex and hippocampus (frontotemporal lobar degeneration-TDP) and all but one case (clinically pure frontotemporal dementia) had involvement of lower motor neurons, characteristic of amyotrophic lateral sclerosis. In addition, a consistent and relatively specific pathological finding was the presence of neuronal inclusions in the cerebellar cortex that were ubiquitin/p62-positive but TDP-43-negative. Our findings indicate that the C9ORF72 mutation is a major cause of familial frontotemporal dementia with TDP-43 pathology, that likely accounts for the majority of families with combined frontotemporal dementia/amyotrophic lateral sclerosis presentation, and further support the concept that frontotemporal dementia and amyotrophic lateral sclerosis represent a clinicopathological spectrum of disease with overlapping molecular pathogenesis.

Inflammatory bowel disease (IBD) is a chronic relapsing disorder that is increasing in prevalence in Western society and has been linked to the development of colorectal cancer. There remains no definitive treatment for IBD, hence recent investigations have focused on the development of new therapeutics, including probiotics, which can reduce intestinal inflammation and restore balance to the gastrointestinal microbiota. Probiotics are currently being studied in greater detail, albeit predominantly in animal models of IBD. Clinical studies have yielded promising findings and justify further investigation. Furthermore, the use of inactivated probiotics as well as the soluble products produced by these bacteria has demonstrated therapeutic potential, and may in fact be more suitable, as there is no risk of sepsis associated with their administration and they can be manufactured with greater quality control. Further research is essential to define the mechanism and source of probiotic action, and to identify more efficacious strains, while future clinical trials must focus on determining whether the bacterial and genetic profiles of IBD patients influence the effectiveness of treatment., (Copyright © 2009 Crohn's & Colitis Foundation of America, Inc.)

VectorBase (http://www.vectorbase.org) is an NIAID-funded Bioinformatic Resource Center focused on invertebrate vectors of human pathogens. VectorBase annotates and curates vector genomes providing a web accessible integrated resource for the research community. Currently, VectorBase contains genome information for three mosquito species: Aedes aegypti, Anopheles gambiae and Culex quinquefasciatus, a body louse Pediculus humanus and a tick species Ixodes scapularis. Since our last report VectorBase has initiated a community annotation system, a microarray and gene expression repository and controlled vocabularies for anatomy and insecticide resistance. We have continued to develop both the software infrastructure and tools for interrogating the stored data.

Objective: To investigate the psychological problems associated with bedwetting and combined (day and night) wetting in children aged around 7(1/2) years., Methods: Participants were a cohort of over 8000 children enrolled in the population-based Avon Longitudinal Study of Parents and Children. Parents completed postal questionnaires assessing common childhood psychological problems, and children were asked about behavior, friendships, bullying, and self-esteem in clinical interviews. The rates of psychological problems were compared in children with bedwetting, combined wetting, and in children with no wetting problems., Results: The study found a higher rate of parent-reported psychological problems in children with bedwetting and combined wetting compared with those with no wetting problems. Children with combined wetting were particularly at risk for externalizing problems. There was little difference with the child-reported measures., Conclusions: Bedwetting and combined wetting are associated with parent-reported psychological problems and combined wetting confers an increased risk for externalizing problems.

VectorBase (http://www.vectorbase.org/) is a web-accessible data repository for information about invertebrate vectors of human pathogens. VectorBase annotates and maintains vector genomes providing an integrated resource for the research community. Currently, VectorBase contains genome information for two organisms: Anopheles gambiae, a vector for the Plasmodium protozoan agent causing malaria, and Aedes aegypti, a vector for the flaviviral agents causing Yellow fever and Dengue fever.

Aims: To determine the effect of chlorine on mixed bacterial biofilms on stainless steel (SS) and conveyor belt surfaces., Methods and Results: Biofilms were exposed to pH-adjusted (6.5) and non-pH-adjusted solutions of chlorine (200, 400 and 600 ppm) for either 2, 10 or 20 min and survivors enumerated. There were significant differences in cell death relating to chlorine concentration and exposure time for the cells attached to the SS, with solutions adjusted to pH 6.5 being more effective at reducing numbers. In contrast, on conveyor belt surfaces cell numbers decreased by less than two logs after 20 min regardless of treatment., Conclusions: Chlorine effectiveness is dependent on its concentration, solution pH, exposure time, the nature of the surface and the microbial species present. SIGNIFICANCE AND IMPACT OF THE STUDY the interests of food safety it is important that sanitizer users are aware of the conditions that effect their performance.

Objective: To examine the relationship between family communication and HIV risk reduction behaviors among a multisite sample of 125 male youths (ages 12-25) with hemophilia and HIV- infection, as well as their parents., Methods: Participants completed self-report surveys assessing communication and attitudes regarding HIV risk reduction interventions; adolescents also provided data about their sexual behaviors., Results: Adolescents with parents who discuss sexual issues were more likely to report HIV status disclosure to sexual partners. Most parents were supportive of HIV risk reduction interventions for their adolescents, but the youths themselves tended to endorse only interventions that offered opportunities for recreational activities and socialization with peers., Conclusions: Findings are discussed in terms of intervention implications and the need for family systems-based programs.

Determination of intestinal permeability by measuring nonmetabolized sugars has been used to assess the integrity of intestinal mucosa. We have developed and validated a modified HPLC method for determining the concentration of L-rhamnose, mannitol, and lactulose in urine, using an amine-modified silica column and refractive index detection. Probe sugars are simultaneously resolved within 18 min. The calibration curve for each sugar is linear to 20 mmol/L. The minimum detectable concentration of lactulose is 0.05 mmol/L. Recovery of probe sugars is between 99.3% and 105.1%. Overall precision (CV) of estimation of probe sugars ranges from 4.2% to 6.5%. In 14 urine samples from healthy children who ingested the test solution containing 1 g of L-rhamnose, 1 g of mannitol, and 5 g of lactulose, the 5-h urinary excretion ratios of lactulose/rhamnose and lactulose/mannitol were 0.047 +/- 0.018 and 0.021 +/- 0.010 (mean +/- SD), respectively. This method presents a rapid, convenient, and practical technique for determining intestinal permeability in clinical pediatric practice.

The cloning of large DNA fragments of hundreds of kilobases in Yeast artificial chromosomes, has simplified the analysis of regions of the genome previously cloned by cosmid walking. The mapping of expressed sequences within cosmid contigs has relied on the association of genes with sequence motifs defined by rare-cutting endonucleases, and the identification of sequence conservation between species. We reasoned that if the contribution of repetitive sequences to filter hybridizations could be minimised, then the use of large cloned DNAs as hybridisation probes to screen cDNA libraries would greatly simplify the characterisation of hitherto unidentified genes. In this paper we demonstrate the use of this approach by using a YAC, containing 180 kb of human genomic DNA including the aldose reductase gene, as a probe to isolate an aldose reductase cDNA from a lambda gt11 human foetal liver cDNA library.

The recent development of yeast artificial chromosome (YAC) vectors has provided a system for cloning fragments that are over ten times larger than those that can be cloned in more established systems. We have developed a method for the rapid isolation of terminal sequences from YAC clones. The YAC clone is digested with a range of restriction enzymes, a common linker is ligated to the DNA fragments and terminal sequences are amplified using a vector specific primer and a linker specific primer. Sequence data derived from these terminal specific products can be used to design primers for a further round of screening to isolate overlapping clones. The method also provides a convenient method of generating Sequence Tagged Sites for the mapping of complex genomes.

The construction of a yeast artificial chromosome (YAC) primary gridded library of 35,000 clones from human lymphoblastoid (48,XXXX) cell line DNA is described. The average YAC size is approximately 350kb representing a greater than 3.5 times coverage of the genome. The library is stored at -70 degrees C as gridded clones on nylon filters impregnated with 20% glycerol and as glycerol suspensions of individual clones in microtitre plates providing a prolonged multi-user potential. To date we have used 14 single copy probes to screen this library by colony hybridisation as well as PCR and have isolated between 1 and 5 YAC clones for every probe.

An outbreak of diarrheal disease due to Yersinia enterocolitica serotype 0:5 , biotype 1, involved nine hospitalized patients. The possible source of this infection was two patients who were both hospitalized with a history of several weeks of intermittent diarrhea. Person-to-person contact was the probable mode of transmission of the disease. The present report describes the second known nosocomial outbreak of infection due to Y. enterocolitica, Serotype 0:5 of Y. enterocolitica is not commonly encountered, and its involvement in an outbreak of gastroenteritis has not been previously reported. The importance of the enrichment technique in the isolation of Y. enterocolitica is demonstrated.

Live Mycobacterium lepraemurium or 60Co-gamma-irradiated organisms stimulated a very weak oxidative burst compared with similar numbers of heat-killed organisms or with live M. microti. This was found to reflect the poor uptake of the living organisms rather than an absolute failure to stimulate an oxidative burst. It is possible, however, that phagocytosis of fewer than 3-4 bacteria may not trigger the respiratory burst. Pre-incubating live M. lepraemurium with sera from infected mice, but not with fresh normal mouse sera, resulted in enhanced phagocytosis with a concomitant increase in the oxidative burst. The level of opsonic activity correlated with the M. lepraemurium specific antibody titres. The opsonic activity appeared to be mediated by antigen-antibody activation of the classical complement pathway as heat-inactivation destroyed the activity.