The Inclusion of Practical Urology Skills in Intern Induction: A Pilot Programme.

Introduction Intern is the first postgraduate year of training and gives interns the opportunity to practice skills in real-life settings. We aim to examine the undergraduate exposure to urology across all Irish Medical Schools and assess the impact of a mandatory urology training skills session delivered during induction on the preparedness of interns ahead of starting their intern year. Methods In July 2020 all interns mandated to attend the Dublin/Mid-Leinster (DML) network intern induction underwent a 120-minute urology teaching session. The session comprised of formal teaching, followed by practical training and an informal question and answer session. All interns were asked to complete a survey before and after the session that examined undergraduate urology exposure and confidence around practical skills. Results All interns (n=74) who attended induction completed the survey. Less than half [43% (n=32]) reported a compulsory urology placement in medical school and 57% (n=42) reported previous practical training sessions in urology. There was low level of confidence in the management of urological scenarios with only 45 % (n = 33) reporting confidence in the management of urosepsis and 26 % (n = 19) in the insertion of a male catheter. There was a significant increase in self-reported confidence following the teaching session with 78 % (n = 58) interns reporting confidence in the management of urosepsis and 81 % (n = 60) in the insertion of a male catheter. Conclusion To ensure best patient care interns need to be trained in the management of common urology presentations, but our results suggest the current undergraduate curriculum is not sufficient. A dedicated theory and practical urology teaching session during intern induction was able to improve self-reported confidence and better prepare interns. Therefore we support inclusion of practical urology skills session in network intern induction.

Renal transplantation outcomes following heart and heart-lung transplantation.

BACKGROUND: Chronic kidney disease is a frequent complication following heart and combined heart-lung transplantation. The aim of this study was to analyse the outcome of a subsequent renal transplant in heart, lung and heart-lung transplantation recipients. METHODS: All heart, lung and heart-lung transplant recipients who received a subsequent renal transplant over a 27-year period in a national heart and lung transplant centre were included in this study. RESULTS: A total of 18 patients who had previously undergone heart (n = 6), lung (n = 7) and heart-lung (n = 5) transplantation received a renal transplant. The mean duration to development of end-stage kidney disease (ESKD) was 115 ± 45.9 months. The most common contributor to ESKD was calcineurin inhibitor nephrotoxicity. The 5-year patient survival and graft survival rates were 91.7 and 85.6%, respectively. The median creatinine level at the most recent follow-up was 123 µmol/L, IQR 90.8-147.5. CONCLUSIONS: The overall outcome of renal transplantation following previous non-renal solid organ transplantation is excellent considering the medical complexity and co-morbidities of this patient population. Renal transplantation represents an important treatment option for ESKD in non-renal solid organ transplant recipients.

Genetic polymorphisms in nitric oxide synthase 3 gene and implications for kidney disease: a meta-analysis.

BACKGROUND/AIMS: The NOS3 gene is a biological and positional candidate for diabetic nephropathy. However, the relationship between NOS3 polymorphisms and renal disease is inconclusive. This study aimed to clarify the association of NOS3 variants with nephropathy in individuals with type 1 diabetes. METHODS: We conducted a case-control study examining all common SNPs in the NOS3 gene by a tag SNP approach. Individuals with type 1 diabetes and persistent proteinuria (cases, n = 718) were compared with individuals with type 1 diabetes but no evidence of renal disease (controls, n = 749). Our replication collection comprised 1,105 individuals with type 1 diabetes recruited to a nephropathy case group and 862 control individuals with normal urinary albumin excretion rates. Meta-analysis was conducted for SNPs where more than three genotype datasets were available. RESULTS: A novel association was identified in the discovery collection (rs1800783, p(genotype) = 0.006, p(allele) = 0.002, OR = 1.26, 95% CI: 1.08-1.47) and supported by independent replication using a tag SNP (rs4496877, pairwise r² = 0.96 with rs1800783) in the replication collection (p(genotype) = 0.002, p(allele) = 0.0006, OR = 1.27, 95% CI: 1.10-1.45). CONCLUSION: The A allele of rs1800783 is a significant risk factor for nephropathy in individuals with type 1 diabetes, and further comprehensive studies are warranted to confirm the definitive functional variant in the NOS3 gene.

Investigation of ACE, ACE2 and AGTR1 genes for association with nephropathy in Type 1 diabetes mellitus.

BACKGROUND: Polymorphisms in ACE and AGTR1 genes have been assessed in multiple studies for association with diabetic nephropathy; however, results are conflicting. The ACE2 gene has not been studied extensively for association with diabetic nephropathy. METHODS: We investigated variants in ACE, ACE2 and AGTR1 for association with nephropathy in a case-control group (1467 participants with Type1 diabetes, case subjects n=718; control subjects n=749) of white descent with grandparents born in the British Isles. All recruited individuals were carefully phenotyped and genotyping was performed using Sequenom, Taqman and gel electrophoresis methods. The χ(2) -test for contingency tables was used to compare genotype and allele frequencies in case and control groups. RESULTS: No departure from Hardy-Weinberg equilibrium was observed in cases or controls. Two variants within the ACE gene (rs4293, P(allelic) =0.02, P(genotypic) =0.008; rs4309, P(allelic) =0.02, P(genotypic) =0.01) were significantly associated with nephropathy at the 5% level. No variant remained statistically significant following adjustment for multiple comparisons. No single nucleotide polymorphisms in the ACE2 or AGTR1 genes were significantly associated with nephropathy when analysed either by genotype or allele frequencies. CONCLUSIONS: Our independent case-control study provides no evidence that common variants in ACE, ACE2 and AGTR1 play a major role in genetic susceptibility to diabetic nephropathy in a white population with Type1 diabetes.

Investigation of the association of BMP gene variants with nephropathy in Type 1 diabetes mellitus.

AIMS: Diabetic nephropathy is a leading cause of end-stage renal disease. The transforming growth factor beta-bone morphogenic protein (BMP) pathway is implicated in the pathogenesis of diabetic nephropathy. The BMP2, BMP4 and BMP7 genes are located near linkage peaks for renal dysfunction, and we hypothesize that genetic polymorphisms in these biological and positional candidate genes may be risk factors for diabetic kidney disease. METHODS: The BMP7 gene was screened, variants identified and allele frequencies determined by bidirectionally sequencing 46 individuals to facilitate selection of tag SNPs (n = 4). For BMP2 and BMP4 genes, data were downloaded for 19 single nucleotide polymorphisms (SNPs) from the International HapMap project and six tag SNPs selected. RESULTS: The BMP7 gene was screened for novel genetic polymorphisms, haplotypes were identified, an appropriate subset of variants selected for the investigation of common genetic risk factors, and BMP2, BMP4 and BMP7 genes assessed for association with diabetic nephropathy in 1808 individuals. Thirty-two SNPs were identified, of which 11 were novel, including an amino-acid changing SNP (+63639C>T). No significant differences (P > 0.2) were observed when comparing genotype or allele or haplotype frequencies between 864 individuals with Type 1 diabetes and nephropathy compared with 944 individuals with Type 1 diabetes without nephropathy, stratified by recruitment centre. CONCLUSIONS: Common polymorphisms in these BMP genes do not strongly influence genetic susceptibility to diabetic nephropathy in White individuals with Type 1 diabetes mellitus.

Regulation of the apoptosis-inducing kinase DRAK2 by cyclooxygenase-2 in colorectal cancer.

BACKGROUND: Cyclooxygenase-2 (COX-2) is over-expressed in colorectal cancer (CRC), rendering tumour cells resistant to apoptosis. Selective COX-2 inhibition is effective in CRC prevention, although having adverse cardiovascular effects, thus focus has shifted to downstream pathways. METHODS: Microarray experiments identified genes regulated by COX-2 in HCA7 CRC cells. In vitro and in vivo regulation of DRAK2 (DAP kinase-related apoptosis-inducing kinase 2 or STK17beta, an apoptosis-inducing kinase) by COX-2 was validated by qRT-PCR. RESULTS: Inhibition of COX-2 induced apoptosis and enhanced DRAK2 expression in HCA7 cells (4.4-fold increase at 4 h by qRT-PCR, P=0.001), an effect prevented by co-administration of PGE(2). DRAK2 levels were suppressed in a panel of human colorectal tumours (n=10) compared to normal mucosa, and showed inverse correlation with COX-2 expression (R=-0.68, R2=0.46, P=0.03). Administration of the selective COX-2 inhibitor rofecoxib to patients with CRC (n=5) induced DRAK2 expression in tumours (2.5-fold increase, P=0.01). In vitro silencing of DRAK2 by RNAi enhanced CRC cell survival following COX-2 inhibitor treatment. CONCLUSION: DRAK2 is a serine-threonine kinase implicated in the regulation of apoptosis and is negatively regulated by COX-2 in vitro and in vivo, suggesting a novel mechanism for the effect of COX-2 on cancer cell survival.

Investigation of DNA polymorphisms in SMAD genes for genetic predisposition to diabetic nephropathy in patients with type 1 diabetes mellitus.

AIMS/HYPOTHESIS: SMAD proteins are involved in multiple signalling pathways and are key modulators of gene expression. We hypothesised that genetic variation in selected SMAD genes contributes to susceptibility to diabetic nephropathy. METHODS: We selected 13 haplotype tag (ht) single nucleotide polymorphisms (SNPs) from 67 variants identified by resequencing the SMAD2 and SMAD3 genes. For SMAD1, SMAD4 and SMAD5 genes, genotype data were downloaded for 217 SNPs from Phase II of the International HapMap project. Of these, 85 SNPs met our inclusion criteria, resulting in the selection of 13 tag SNPs for further investigation. A case-control approach was employed, using 267 nephropathic patients and 442 controls with type 1 diabetes from Ireland. Two further populations (totalling 1,407 patients, 2,238 controls) were genotyped to validate initial findings. Genotyping was conducted using iPLEX, TaqMan and gel electrophoresis. RESULTS: The distribution of genotypes was in Hardy-Weinberg equilibrium. Analysis by the chi(2) test of genotype and allele frequencies in patients versus controls in the Irish population (n = 709) revealed evidence for the association of one allele at 5% level of significance (rs10515478, p(uncorrected) = 0.006; p(corrected) = 0.04). This finding represents a relatively small difference in allele frequency of 6.4% in the patient group compared with 10.7% in the control group; this difference was not supported in subsequent investigations using DNA from European individuals with similar phenotypic characteristics. CONCLUSIONS/INTERPRETATION: We selected an appropriate subset of variants for the investigation of common genetic risk factors and assessed SMAD1 to SMAD5 genes for association with diabetic nephropathy. We conclude that common polymorphisms in these genes do not strongly influence genetic susceptibility to diabetic nephropathy in white individuals with type 1 diabetes mellitus.

Investigation of Adducin 2 (beta) DNA polymorphisms in genetic predisposition to diabetic nephropathy in Type 1 diabetes.

AIMS: Adducin 2 (beta) (ADD2) is a biological and positional candidate gene proposed to confer genetic risk for diabetic nephropathy. This study aimed to comprehensively investigate all common and putatively functional polymorphisms in the genomic region encompassing this gene. METHODS: Tag single nucleotide polymorphisms (n = 23) derived from phase II of the International HapMap Project and in silico functional variants (n = 2) were genotyped in 1467 White individuals from the British Isles (cases, n = 718; control subjects, n = 749) by a combination of Sequenom iPLEX and TaqMan technologies. RESULTS: Chi(2) analysis of genotype and allele frequencies in cases vs. control subjects revealed weak evidence for association of one variant at the 5% level of significance (rs10164951, P = 0.02). Adjusting for multiple testing in the present case-control collection negated this association. CONCLUSIONS: We selected an appropriate subset of variants suitable for genetic investigations of the ADD2 gene and report the first investigation of polymorphisms in ADD2 with diabetic nephropathy. Our results suggest that common polymorphisms and putatively functional variants in the ADD2 gene do not strongly influence genetic susceptibility to diabetic nephropathy in this White population with Type 1 diabetes.

Lung tissue storage: optimizing conditions for future use in molecular research.

The quality of tissue studied impacts greatly on oligonucleotide microarray results, emphasizing the importance of harvesting techniques. The analyzed RNA extracted from human lung samples preserved via 4 different storage conditions (RNAlater, phosphate-buffered saline, TRIzol, liquid nitrogen). RNA was assessed by denaturing gel electrophoresis, Agilent bioanalysis, real-time polymerase chain reaction (PCR), and Test3 Affymetrix chip hybridization. Results revealed better quality RNA from RNAlater samples on gel electrophoresis and bioanalysis. RNAlater samples also showed greater yield (r18s via PCR P < .05) and resulted in better Test3 chips hybridization (p < .05), suggesting RNAlater was superior at preserving lung tissue nucleic acid.

Genetic association analyses of non-synonymous single nucleotide polymorphisms in diabetic nephropathy.

AIMS/HYPOTHESIS: Diabetic nephropathy, characterised by persistent proteinuria, hypertension and progressive kidney failure, affects a subset of susceptible individuals with diabetes. It is also a leading cause of end-stage renal disease (ESRD). Non-synonymous (ns) single nucleotide polymorphisms (SNPs) have been reported to contribute to genetic susceptibility in both monogenic disorders and common complex diseases. The objective of this study was to investigate whether nsSNPs are involved in susceptibility to diabetic nephropathy using a case-control design. METHODS: White type 1 diabetic patients with (cases) and without (controls) nephropathy from eight centres in the UK and Ireland were genotyped for a selected subset of nsSNPs using Illumina's GoldenGate BeadArray assay. A chi (2) test for trend, stratified by centre, was used to assess differences in genotype distribution between cases and controls. Genomic control was used to adjust for possible inflation of test statistics, and the False Discovery Rate method was used to account for multiple testing. RESULTS: We assessed 1,111 nsSNPs for association with diabetic nephropathy in 1,711 individuals with type 1 diabetes (894 cases, 817 controls). A number of SNPs demonstrated a significant difference in genotype distribution between groups before but not after correction for multiple testing. Furthermore, neither subgroup analysis (diabetic nephropathy with ESRD or diabetic nephropathy without ESRD) nor stratification by duration of diabetes revealed any significant differences between groups. CONCLUSIONS/INTERPRETATION: The nsSNPs investigated in this study do not appear to contribute significantly to the development of diabetic nephropathy in patients with type 1 diabetes.

Prevalence of 25(OH) vitamin D (calcidiol) deficiency at time of renal transplantation: a prospective study.

25(OH) Vitamin D (calcidiol) is the major circulating form of vitamin D and is considered the most reliable measure of vitamin D status. Adequate vitamin D status is important for bone health but there is increasing evidence that low serum concentrations of calcidiol (<30 ng/mL) are associated with many adverse health outcomes in the general population. Little is known about calcidiol status at the time of renal transplantation, a period when bone loss is greatest and immunosuppression is highest. We prospectively measured serum calcidiol and parathyroid hormone immediately after transplant from March 2005 onwards. Of 112 patients studied, 29% had calcidiol deficiency (<10 ng/mL), 59% had calcidiol insufficiency (10-29 ng/mL) and only 12% of patients had a normal calcidiol concentration (>30 ng/mL). The prevalence of calcidiol deficiency in black recipients was extremely high at 41%. Serum calcidiol tended to be lower in winter than other seasons. In conclusion, the prevalence of 25(OH) vitamin D (calcidiol) deficiency/insufficiency at the time of renal transplant is very high. The clinical effects of this deficiency/insufficiency deserve further study.

Impact evaluation of an oral health intervention amongst primary school children in Ireland.

A pilot oral health programme was developed which aimed to improve dental health knowledge and behaviour amongst Irish school children aged 7-12 years. The programme comprised two integral components: a television campaign, run over a 6-week period, was incorporated into the children's programme 'Den TV' on national television, with video clips of a member of the music band Boyzone promoting key oral health messages; and a Smile of the Year contest. Concurrently, a dental nurse delivered an interactive talk with pupils, showed a video of the Den TV oral health programme and distributed posters and leaflets. The aim of this study was to assess the impact of the overall intervention on school pupils' dental health knowledge and reported behaviour. Thirty-two primary schools in two health board regions in the Republic of Ireland participated in the study. At baseline and after 6 weeks, 1534 school children completed specially developed questionnaires. There was a positive net effect of the dental nurse intervention in all but one question. The percentage of children who reported using the recommended amount of toothpaste and brushing for 3 min appeared to have been further increased having observed the television campaign. These results are in line with the argument that mass media campaigns work to supplement the one-to-one activities of health professionals in order to effect knowledge and behavioural change.

Smoking habits and attitudes of Irish dentists and dental students.

Objective To ascertain firstly the proportions of smokers and ex-smokers among Irish dentists and dental students, secondly their knowledge of the role of tobacco in the aetiology of oral cancer and thirdly the attitudes of dentists to matters of public health policy relating to tobacco. Background Smoking has been associated with various diseases including oral cancer and other oral disease. Dentists are known to be potentially effective health educators and their role in smoking cessation is now appreciated. Study Design A questionnaire was distributed to dental students and a longer questionnaire to dentists; results were examined statistically. Results 14% of dentists were smokers and 45% were ex-smokers; 20% of students were smokers and 15% were ex-smokers. Most smokers declared an intention of ceasing. Almost all dentists were aware of links between smoking and oral cancer. There was strong support from dentists for higher taxes on tobacco and stricter control of advertising and sponsorship. Conclusions Irish dentists and dental students are less likely to smoke than the general public. Dentists are aware of major risk factors in oral cancer and support government intervention to reduce smoking prevalence. Such views should assist public health planners.

The Kilkenny Integrated Oral Health Project.

The Kilkenny Health Project, started in 1985, aims to reduce the level of risk factors in the community for coronary heart disease through health promotion. Dental disease and coronary heart disease share risk factors of tobacco use, alcohol consumption and poor dietary patterns. A baseline oral health survey demonstrated significant levels of dental disease in Kilkenny in the 429 adults and 523 children who were examined there in 1987. Seventy one per cent of adults required treatment for periodontal disease and 49% of children surveyed required treatment for dental decay. The Kilkenny Oral Health Project was developed as a community participation project aiming to reduce the level of common risk factors in the community for coronary heart disease and dental disease. It has run parallel with the main Kilkenny Health Project and is one of the first health promotion projects which has an integrated health message preventing dental disease and coronary heart disease.

ABO blood group and social class: a prospective study in a regional blood bank.

STUDY OBJECTIVE: The aim of the study was to investigate an association previously reported in a retrospective study between the A phenotype and social classes I and II. DESIGN: The study was a prospective survey using a cohort of blood donors. SETTING: Participants were donors at a regional blood bank in southern Ireland servicing a population of approximately 380,000. PARTICIPANTS: Of 2442 donors considered for inclusion in the study, 21 refused to participate, 33 provided insufficient information, and 184 were excluded because they were not wholly of Irish extraction, leaving a total of 2204 subjects, 64% of whom were male. MEASUREMENT AND RESULTS: Occupation, age and birth place were obtained from a short questionnaire given to all potential donors during the study period. Social class was defined according to the United Kingdom Registrar General's criteria. No association between the ABO phenotype and social class could be found, either on the whole sample, or on currently employed persons, or on separate analysis of the sexes. CONCLUSIONS: The balance of current evidence is against a variation in ABO distribution by social class designation.