The major histocompatibility complex homozygous inbred Babraham pig as a resource for veterinary and translational medicine.

The Babraham pig is a highly inbred breed first developed in the United Kingdom approximately 50 years ago. Previous reports indicate a very high degree of homozygosity across the genome, including the major histocompatibility complex (MHC) region, but confirmation of homozygosity at the specific MHC loci was lacking. Using both direct sequencing and PCR-based sequence-specific typing, we confirm that Babraham pigs are essentially homozygous at their MHC loci and formalise their MHC haplotype as Hp-55.6. This enhances the utility of the Babraham pig as a useful biomedical model for studies in which controlling for genetic variation is important.

Executive Summary: Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis

The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice.

Sequence variations of the locus-specific 5' untranslated regions of SLA class I genes and the development of a comprehensive genomic DNA-based high-resolution typing method for SLA-2.

The genetic diversity of the major histocompatibility complex (MHC) class I molecules of pigs has not been well characterized. Therefore, the influence of MHC genetic diversity on the immune-related traits of pigs, including disease resistance and other MHC-dependent traits, is not well understood. Here, we attempted to develop an efficient method for systemic analysis of the polymorphisms in the epitope-binding region of swine leukocyte antigens (SLA) class I genes. We performed a comparative analysis of the last 92 bp of the 5' untranslated region (UTR) to the beginning of exon 4 of six SLA classical class I-related genes, SLA-1, -2, -3, -4, -5, and -9, from 36 different sequences. Based on this information, we developed a genomic polymerase chain reaction (PCR) and direct sequencing-based comprehensive typing method for SLA-2. We successfully typed SLA-2 from 400 pigs and 8 cell lines, consisting of 9 different pig breeds, and identified 49 SLA-2 alleles, including 31 previously reported alleles and 18 new alleles. We observed differences in the composition of SLA-2 alleles among different breeds. Our method can be used to study other SLA class I loci and to deepen our knowledge of MHC class I genes in pigs.

Ge overlayer and surface alloy structures on Pt(100) studied using alkali ion scattering spectroscopy, x-ray photoelectron spectroscopy and x-ray photoelectron diffraction.

We have investigated surface structures formed by deposition of Ge on a Pt(100) substrate by using a multi-technique approach utilizing alkali ion scattering spectroscopy (ALISS), x-ray photoelectron spectroscopy (XPS), and x-ray photoelectron diffraction (XPD). ALISS was used to distinguish Ge overlayers from incorporated alloy layers for the surface structures reported, and to supply structural information about the surface alloy or 'layer compound' formed by the deposition of 1.5-ML Ge. A Ge adlayer forms following the deposition of 0.2-ML Ge on Pt(100) and annealing at 600 K. ALISS revealed that Ge adatoms in these overlayers had 1D (incomplete c(2 × 2)) Ge-Ge ordering along [010] and equivalent directions, even though this was not directly apparent in observations using LEED and STM. A c(2 × 2)-Ge overlayer was produced after 0.5 ML-Ge deposition on Pt(100) and annealing at 600 K. Deposition of 1.5-ML Ge on Pt(100) and annealing at 600 K caused extensive Ge interdiffusion into the third (subsurface) layer, while the first and second layers remained as a c(2 × 2) Ge overlayer and (1 × 1) Pt layer, respectively. We propose that the Pt(100) substrate thus is 'capped' by an alloy film with the structure of a body-centered tetragonal Pt2Ge layer compound, which is terminated by a pure-Ge layer that is indistinguishable from a c(2 × 2)-Ge adlayer. This explains the apparently 'strange' result that even though extensive Ge interdiffusion was occurring deeply into the Pt bulk during annealing at 900 and 1200 K, a Ge overlayer remained on the surface. XPS spectra showed a +0.5 eV binding energy shift of the Ge 3d core level and a small (0-0.1 eV) positive shift of the Pt 5d core level compared to Ge(100) and Pt(100) surfaces for the c(2 × 2)-Ge overlayer. There was no effect on these binding energies upon formation of the Pt2Ge layer compound at the surface, and this indicates similar Ge-Pt interactions in the two cases. Compared to other overlayers of Group-IV atoms on metal surfaces, the Ge overlayer on Pt(100) was extraordinarily stable.

Molecular characterization of swine leucocyte antigen class II genes in outbred pig populations.

The highly polymorphic swine leucocyte antigen (SLA) genes are among the most important determinants of swine immune responses to disease and vaccines. Accurate and effective SLA genotyping methods are required to understand how SLA gene polymorphisms affect immunity, especially in outbred pigs with diverse genetic backgrounds. In this study, we present a simple and rapid molecular-based typing system for characterizing SLA class II alleles of the DRB1, DQB1 and DQA loci. This system utilizes a set of 47 sequence-specific PCR primers developed to differentiate alleles by groups that share similar sequence motifs. We applied this typing method to investigate the SLA class II diversity in four populations of outbred pigs (n = 206) and characterized a total of 19 SLA class II haplotypes, six of which were shared by at least three of the sampled pig populations. We found that Lr-0.1 (DRB1*01XX-DQB1*01XX-DQA*01XX) was the most prevalent haplotype with a combined frequency of 16.0%, followed by Lr-0.2 (DRB1*02XX-DQB1*02XX-DQA*02XX) with 14.6% and Lr-0.15b (DRB1*04XX-DQB1*0202-DQA*02XX) with 14.1%. Over 70% of the pigs (n = 147) had at least one copy of one of these three haplotypes. The PCR-based typing system described in this study demonstrates a reliable and unambiguous detection method for SLA class II alleles. It will be a valuable tool for studying the influence of SLA diversity on various immunological, pathological and physiological traits in outbred pigs.

Evaluation of erectile dysfunction and associated cardiovascular risk using structured questionnaires in Chinese type 2 diabetic men.

Erectile dysfunction (ED) is not uncommon, but frequently underdiagnosed in type 2 diabetic men. In this study, we aimed to explore the frequency and severity of ED in Chinese type 2 diabetic men using a structured questionnaire. We furthermore sought to investigate the associations of ED with diabetes-related complications and metabolic indices. A consecutive cohort of 313 Chinese type 2 diabetic men aged between 25 and 76 years attending a diabetic centre were recruited between October 2006 and June 2007. Of the study population, the frequency of ED was 39.3% according to the National Institutes of Health (NIH) Consensus Conference criteria, compared with 84.3% (41.7% of them having moderate to severe ED) as diagnosed by International Index of Erectile Function (IIEF-5) questionnaire. After adjusting for potential confounding factors by multivariable logistic regression, ED defined by NIH criterion was associated with advanced age [OR = 1.05 (95% CI 1.01-1.09), p = 0.012], the presence of diabetic retinopathy [OR = 2.43 (95% CI 1.27-4.66), p = 0.008] and coronary heart disease [OR = 2.63 (95% CI 1.21-5.70), p = 0.015]. ED defined by IIEF-5 was associated with advanced age [OR = 1.12 (95% CI 1.06-1.17), p < 0.0001], use of insulin therapy [OR = 2.94 (95% CI 1.12-7.73), p = 0.029] and urinary albumin-creatinine ratio [OR = 2.29 (95% CI 1.05-5.01), p = 0.037]. In conclusion, ED was highly prevalent in Chinese type 2 diabetic men and was associated with multiple cardiovascular risk factors and complications. Advanced age, use of insulin therapy, the existence of microvascular complications such as retinopathy, albuminuria and coronary heart disease were associated with ED. NIH criteria diagnosed a much lower rate of ED compared with IIEF-5. Overall, structured questionnaires are useful and objective tools to detect ED, which should prompt a comprehensive risk assessment in these subjects.

Molecular characterization of swine leucocyte antigen class I genes in outbred pig populations.

The highly polymorphic swine leucocyte antigen (SLA) genes are one of the most important determinants in swine immune responses to infectious diseases, vaccines, and in transplantation success. Study of SLA influence requires accurate and effective typing methods. We developed a simple and rapid method to type alleles at the three classical SLA class I loci (SLA-1, SLA-3 and SLA-2) using the PCR-sequence-specific primer (PCR-SSP) strategy. This typing system relies on 47 discriminatory PCR primer pairs designed to amplify the SLA class I alleles by groups that have similar sequence motifs. We applied this low-resolution group-specific typing method to characterize the SLA class I alleles present in three outbred pig populations (n = 202). Alleles from 24 class I allele groups corresponding to 56 class I genotypes were detected. We also identified 23 low-resolution SLA class I haplotypes in these pigs and found haplotypes Lr-1.0 (SLA-1*01XX-SLA-3*01XX-SLA-2*01XX) and Lr-4.0 (SLA-1*04XX-SLA-3*04XX-SLA-2*04XX) in all three pig populations with a high prevalence. Over 80% of the pigs examined (n = 162) were found to bear at least one of these haplotypes, resulting in a combined haplotype frequency of nearly 50%. This PCR-SSP-based typing system demonstrates a reliable and unambiguous detection of SLA class I alleles, and can be used to effectively investigate the SLA diversity in outbred pig populations. It will help to identify the role of SLA antigens in disease-resistant pigs and may facilitate the development of effective vaccines.

Nomenclature for factors of the SLA system, update 2008.

This report summarizes the new swine leukocyte antigen (SLA) allele sequences and haplotypes designated by the SLA Nomenclature Committee of the International Society for Animal Genetics. There have been 74 new SLA alleles, comprising 18 SLA-1 alleles, 11 SLA-2 alleles, six SLA-3 alleles, two SLA-6 alleles, one SLA-DRA allele, 20 SLA-DRB1 alleles, three SLA-DQA alleles and 13 SLA-DQB1 alleles. Twelve new SLA class I and four new class II haplotypes have also been designated. This is the first official update since the 2005 reports on the nomenclature for factors of the SLA class I and II systems. This report also summarizes recent updates to the Immunopolymorphism Database-Major Histocompatibility Complex (IPD-MHC) website (http://www.ebi.ac.uk/ipd/mhc/sla/). All information has now been integrated to the SLA section of the IPD-MHC database, which serves as the repository for maintaining a list of all recognized SLA genes and their allelic sequences.

Assessing the prevalence of malnutrition with the Mini Nutritional Assessment (MNA) in a nationally representative sample of elderly Taiwanese.

OBJECTIVE: The study was to determine whether the Mini Nutritional Assessment (MNA) could be used as a tool to effectively identify malnourished elderly in a non-Caucasian population. DESIGN: The study was a part of a population-based multistage random sample survey. SETTING: In-home face-to-face interviews. PARTICIPANTS: Randomly selected 1583 men and 1307 women, 65 years or older, in Taiwan. MEASUREMENTS: Assessing nutritional risk status of participants with the Mini Nutritional Assessment. RESULTS: The prevalence of malnutrition is 1.7% in elderly men and 2.4% in elderly women, 65 years or older. The proportion at risk of malnutrition is 13.1%. CONCLUSION: To the best of our knowledge, this is the first study to apply the MNA to estimate the prevalence of malnutrition in the elderly in a nationally representative sample. Results suggest that the MNA can identify malnourished elderly in a non-Caucasian population. However, it appears that the functionality of the instrument can be improved by adapting population-specific anthropometric cutoff standards.

Uncorrected refractive error in Singapore teenagers.

AIM: To study the prevalence rate of uncorrected refractive error and associated risk factors among Singapore schoolchildren aged 12-16 years (grade 7). METHODS: A cross sectional study of 628 participants (participation rate 99.8%) was conducted in two schools. An interviewer led questionnaire asking about sociodemographic variables and risk factors was administered. Refractive errors were measured using a table mounted autorefractor. Participants with habitual visual acuity (VA) of 0.2 logMAR or worse underwent subjective refraction. Uncorrected refractive error was defined as improvement of at least 0.2 logMAR in best corrected visual acuity after subjective refraction. RESULTS: The prevalence rate of uncorrected refractive error was 22.3% (95% confidence interval (CI) 19.0% to 25.5%). The multivariate adjusted odds ratio of uncorrected refractive error in students with the lowest academic ability was 2.24 (95% CI 1.34 to 3.73). Increasing time interval since the last visit to an eye care provider increased the risk of uncorrected refractive error (trend p = 0.001). CONCLUSION: Uncorrected refractive error was a significant problem among Singapore students aged 12-16 years (grade 7). Uncorrected refractive error was more common among students with low academic ability or those who had not visited an eye care provider for a long time.

Nomenclature for factors of the swine leukocyte antigen class II system, 2005.

A systematic nomenclature for the genes and alleles of the swine major histocompatibility complex (MHC) is essential to the development and communication of research in swine immunology. The Swine Leukocyte Antigen (SLA) Nomenclature Committee of the International Society for Animal Genetics (ISAG) has reviewed all of the DNA-sequence information for MHC class II genes, available in GenBank/EMBL/DDBJ databases, and the associated published reports to develop such a systematic nomenclature. This article summarizes the proposed nomenclature, which parallels the World Health Organization's nomenclature for factors of the human MHC. The SLA class II genes expressed on the cell membrane will be noted as SLA-DRA, SLA-DRB1, SLA-DQA, and SLA-DQB1. Nomenclature assignments for all SLA class II GenBank sequences are now noted. The committee will add new SLA class II allele designations, as they are discovered, and will maintain a publicly available list of all recognized genes and alleles using the Immuno Polymorphism Database (IPD). The sequences will be available from the IPD-MHC section of the database which contains non-human MHC sequences (http://www.ebi.ac.uk/ipd/mhc/sla/).

Nomenclature for factors of the SLA class-I system, 2004.

A systematic nomenclature for the genes and alleles of the swine major histocompatibility complex (MHC) is essential to the development and communication of research in swine immunology. The Swine Leucocyte Antigen (SLA) Nomenclature Committee of the International Society for Animal Genetics has reviewed all of the DNA sequence information for MHC class-I genes, available in GenBank/EMBL/DDBJ databases, and the associated published reports in order to develop such a systematic nomenclature. This report summarizes the proposed nomenclature, which parallels the World Health Organization's nomenclature for factors of the human MHC. The classical class-I SLA genes are designated as SLA-1, SLA-2 and SLA-3; the non-classical as SLA-6, SLA-7 and SLA-8. Nomenclature assignments for all SLA class-I GenBank sequences are now noted. The Committee will add new SLA class-I allele designations, as they are discovered, and will maintain a publicly available list of all recognized genes and alleles by using the International ImMunoGeneTics Project and its Immuno Polymorphism Database/MHC (IPD/MHC) sequence database for MHC sequences in veterinary species.

Effects of gender, Helicobacter pylori and hepatitis B virus serology status on cardiovascular and renal complications in Chinese type 2 diabetic patients with overt nephropathy.

BACKGROUND: The aim of this study was to investigate whether chronic infections with Helicobacter pylori and hepatitis B virus (HBV) might affect clinical outcomes in Chinese type 2 diabetic patients with advanced nephropathy. METHODS: A prospective study of 97 type 2 diabetic patients with clinical proteinuria and renal insufficiency (median serum creatinine 200 micro mol/l). RESULTS: During a median follow-up period of 2 years, 34 developed end-stage renal disease (ESRD), 28 had cardiovascular endpoints and 11 patients had died (seven men and four women), and 52.7% developed a combined endpoint. Female patients had longer disease duration, higher blood pressure, lower body weight but higher serum creatinine and spot urine albumin : creatinine ratio as well as lower haemoglobin than male patients. On logistic regression analysis, female gender (hazard ratio: 5.91, p = 0.02), negative H. pylori serology (8.39, p = 0.004), baseline serum creatinine (1.04, p = 0.001) and haemoglobin (1.86, p = 0.01) were independent predictors for ESRD. Systolic blood pressure (1.04, p = 0.003), prior treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists (3.41, p = 0.04) and positive hepatitis B surface antigen (4.88, p = 0.025) were independent predictors for cardiovascular endpoints. Female gender (7.89, p = 0.002) and baseline serum creatinine (1.05, p < 0.001) were independent predictors for combined death and cardio-renal endpoints. CONCLUSIONS: In Chinese type 2 diabetic patients with clinical proteinuria renal insufficiency, there were high rates of death and cardio-renal outcomes. Female gender, low haemoglobin and negative H. pylori serology were important predictors for ESRD, whereas chronic HBV infection was associated with increased cardiovascular risks.