ABSTRACT
PURPOSE: This questionnaire aimed to explore how general dentists in the Republic of Ireland perceive and manage hypomineralised second primary molars (HSPM). METHODS: Following ethical approval, a validated structured questionnaire containing 19 questions was sent to Irish dentists using Survey Monkey. Questions on awareness, dentist's experience, barriers to care and clinical scenarios with different treatment options were included. Binary outcomes and independent variables were compared using logistic regression analysis (α = 5%). RESULTS: Responses from 279 general dentists were analysed. The majority of dentists were aware of HSPM (72%) and most dentists felt confident in diagnosing HSPM (71%). Dentists who had practiced for ≥ 15 years were significantly more likely to document HSPM frequently compared to those with less experience (OR 0.29; p = 0.012). No significant association was found between confidence in HSPM diagnosis and other variables, such as age group, years of practice and workplace. Dentists not working in private practice reported to be less comfortable in the management of HSPM (OR 0.49; p = 0.030). The most cited barrier to management of HSPM was child's behaviour. A broad variation was observed in the clinical scenarios, in particular when treatment planning more severe HSPM. CONCLUSIONS: In general, Irish dentists are aware of HSPM and are confident in diagnosis and management. Variation existed in treatment options reflecting the disparity that exists in clinical management.
Subject(s)
Dental Enamel Hypoplasia , Child , Humans , Ireland , Molar , Surveys and Questionnaires , DentistsABSTRACT
BACKGROUND: Achieving pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) improves survival outcomes for breast cancer patients. Currently, conventional histopathological biomarkers predicting such responses are inconsistent. Studies investigating radiomic texture analysis from breast magnetic resonance imaging (MRI) to predict pCR have varied radiomic protocols introducing heterogeneity between results. Thus, the efficacy of radiomic profiles compared to conventional strategies to predict pCR are inconclusive. PURPOSE: Comparing the predictive accuracy of different breast MRI radiomic protocols to identify the optimal strategy in predicting pCR to NAC. MATERIAL AND METHODS: A systematic review and network meta-analysis was performed according to PRISMA guidelines. Four databases were searched up to October 4th, 2021. Nine predictive strategies were compared, including conventional biomarker parameters, MRI radiomic analysis conducted before, during, or after NAC, combination strategies and nomographic methodology. RESULTS: 14 studies included radiomic data from 2,722 breast cancers, of which 994 were used in validation cohorts. All MRI derived radiomic features improved predictive accuracy when compared to biomarkers, except for pre-NAC MRI radiomics (odds ratio [OR]: 0.00; 95 % CI: -0.07-0.08). During-NAC and post-NAC MRI improved predictive accuracy compared to Pre-NAC MRI (OR: 0.14, 95 % CI: 0.02-0.26) and (OR: 0.26, 95 % CI: 0.07-0.45) respectively. Combining multiple MRIs did not improve predictive performance compared to Mid- or Post-NAC MRIs individually. CONCLUSION: Radiomic analysis of breast MRIs improve identification of patients likely to achieve a pCR to NAC. Post-NAC MRI are the most accurate imaging method to extrapolate radiomic data to predict pCR.
Subject(s)
Breast Neoplasms , Neoadjuvant Therapy , Humans , Female , Neoadjuvant Therapy/methods , Network Meta-Analysis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast/diagnostic imaging , Breast/pathology , Magnetic Resonance Imaging/methods , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Retrospective StudiesABSTRACT
OBJECTIVES: Our principle objective was to examine the personal and professional impact of service user (SU) suicide on mental health professionals (MHPs). We also wished to explore putative demographic or clinical factors relating to SUs or MPHs that could influence the impact of SU suicide for MHPs and explore factors MHPs report as helpful in reducing distress following SU suicide. METHODS: A mixed-method questionnaire with quantitative and thematic analysis was utilised. RESULTS: Quantitative data indicated SU suicide was associated with personal and professional distress with sadness (79.5%), shock (74.5%) and surprise (68.7%) particularly evident with these phenomena lasting less than a year for more than 90% of MHPs. MHPs also reported guilt, reduced self-confidence and a fear of negative publicity. Thematic analysis indicated that some MHPs had greater expertise when addressing SU suicidal ideation and in supporting colleagues after experiencing a SU suicide. Only 17.7% of MHPs were offered formal support following SU suicide. CONCLUSION: SU suicide impacts MHPs personally and professionally in both a positive and negative fashion. A culture and clear pathway of formal support for MHPs to ascertain the most appropriate individualised support dependent on the distress they experience following SU suicide would be optimal.
Subject(s)
Mental Health , Suicide , Health Personnel/psychology , Humans , Self Concept , Suicide/psychology , Surveys and QuestionnairesABSTRACT
OBJECTIVES: The aim of the study was to evaluate completeness and timeliness of the rapidly developed surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in England using patient-level data. STUDY DESIGN: This is an observational study wherein public health surveillance systems are evaluated. METHODS: Data were collected in the Public Health England's Second-Generation Surveillance System through routine laboratory reporting processes, as well as via enhanced testing in collaboration with commercial partners. Three periods were chosen to present developments in disease surveillance around the first pandemic wave in England. Completeness of valid entries for key demographic and epidemiological fields was summarised. Timeliness was assessed using recorded date intervals: from sample collection to the laboratory reporting a positive result, the positive result being received by the national surveillance system and the data being available for epidemiological analysis. RESULTS: In each period, demographic variables were more than 95% complete and enhanced ethnicity more than 85%, allowing a rich understanding of the general characteristics of COVID-19 cases in England. The proportion of cases completing all reporting stages of the national system within 3 days of when the specimen was taken increased from 69.1% in period 1 to 76.6% in period 3. In period 3, the median number of days to complete all reporting stages decreased to 2, from 3 in previous periods. Analysis of each reporting stage offers suggestive evidence that timeliness of the system has improved as reporting has become established over time. CONCLUSIONS: Timely processing of data for epidemiological use was consistent and rapid once received by the national system. Delays in timeliness were most likely to occur in the first stage of the reporting process, before laboratory input to the surveillance platform. Existing national surveillance mechanisms enhanced during the response have succeeded in providing rapid collection and reporting of case data to facilitate epidemiological monitoring and analysis and guide public health policy and strategy.
Subject(s)
COVID-19 Testing/methods , COVID-19/epidemiology , Laboratories , Public Health Surveillance , COVID-19/diagnosis , England/epidemiology , Epidemiological Monitoring , Humans , Pandemics , SARS-CoV-2/isolation & purificationABSTRACT
Bilateral basal ganglia hemorrhage is exceedingly rare. To our knowledge, our patient is the first reported case of a confirmed coronavirus disease 2019 (COVID-19) patient who had bilateral basal ganglia hemorrhage. In the absence of other risk factors for bilateral deep cerebral involvement, we suspect that COVID-19 may be contributing to these rare pathologies. Most published data represent a correlation between COVID-19 and neurologic complications, and more research is still needed to prove causation.
Subject(s)
Basal Ganglia Hemorrhage/diagnostic imaging , Basal Ganglia Hemorrhage/etiology , Betacoronavirus , Coronavirus Infections/complications , Pneumonia, Viral/complications , COVID-19 , Female , Humans , Magnetic Resonance Imaging , Multimodal Imaging , Pandemics , SARS-CoV-2 , Tomography, X-Ray ComputedABSTRACT
OBJECTIVE: This study aimed to evaluate management practices for glucocorticoid (GC)-induced osteoporosis (GIOP) in systemic lupus erythematosus (SLE) patients using 2017 American College of Rheumatology guidelines as a gold standard. METHODS: We conducted a retrospective cohort study using a clinical database from the years 2011 to 2016. SLE cases with >90 days continuous prednisone use at doses of ≥7.51 mg daily were identified. Osteoporosis risk factors were assessed via chart review. The Fracture Risk Assessment (FRAX) score was estimated for patients > 40 years of age. Vitamin D, bisphosphonate prescriptions, and osteoporotic (OP) fractures were ascertained through chart review. A classification tree was used to identify the key patient-related predictors of bisphosphonate prescription. RESULTS: A total of 203 SLE patients met the inclusion criteria. The recommended dose of vitamin D supplement was prescribed to 58.9% of patients < 40 years of age and 61.5% of patients ≥ 40 years of age. Among patients aged ≥ 40 years, 25% were prescribed bisphosphonates compared to 36% who met indications for bisphosphonates per the ACR guidelines. Another 10% were prescribed a bisphosphonate, despite not having indication per the ACR guidelines, which was considered as overtreatment. Among patients aged ≥ 40 years, older age and a higher FRAX score for major OP fracture and hip fracture predicted bisphosphonate prescription. In a classification tree analysis, patients with FRAX scores (for major OP fracture) of ≥ 23.5% predicted bisphosphonate prescription in this SLE population. Among patients who had OP fractures in the follow-up period, nine (6.50%) were inpatients receiving appropriate GIOP care versus 12 (13.6%) who were inpatients not receiving ACR-appropriate care (p = 0.098). CONCLUSIONS: In clinical practice, fewer SLE patients with or at risk for GIOP are prescribed vitamin D and bisphosphonates than recommended by the 2017 ACR guidelines. Also, in this study, another 10% were prescribed a bisphosphonate, despite not having an indication per the ACR guidelines. Patients were most likely to receive a bisphosphonate prescription if they had a major OP FRAX score of > 23.5%.
Subject(s)
Diphosphonates/therapeutic use , Glucocorticoids/adverse effects , Lupus Erythematosus, Systemic/drug therapy , Osteoporosis/prevention & control , Vitamin D/therapeutic use , Adult , Bone Density Conservation Agents/therapeutic use , Female , Humans , Male , Middle Aged , Minnesota/epidemiology , Osteoporosis/chemically induced , Osteoporotic Fractures/epidemiology , Prednisone/adverse effects , Retrospective Studies , Rheumatology/methods , Risk Factors , Vitamins/therapeutic use , Young AdultABSTRACT
Influenza and Pertussis are vaccine preventable diseases carrying significant morbidity and mortality in pregnant women and infants. The uptake of these vaccinations in pregnancy is suboptimal. Our study aimed to identify factors influencing our pregnant patient's knowledge, beliefs and perceptions. A self-administered, specifically devised, 34-point questionnaire was taken by antenatal patients in a primary care setting from November 2015 to March 2016. A majority believe both diseases are serious during pregnancy or infancy but many are unsure on vaccination safety. A majority of respondents at 80/88 (91%) consider their GP's advice reliable on this matter. Our key message is that health care provider recommendation is the most powerful tool to improve vaccination uptake. Our research clearly identifies GP's as the most trusted source of information, making it crucial to deliver accurate information to this high-risk group.
Subject(s)
Culture , Health Personnel , Health Promotion/methods , Influenza Vaccines , Knowledge , Perception , Pertussis Vaccine , Pregnancy/psychology , Pregnancy/statistics & numerical data , Vaccination/statistics & numerical data , Adolescent , Adult , Female , Humans , Safety , Surveys and Questionnaires , Time Factors , Young AdultABSTRACT
BACKGROUND: Mutation of the IL2RG gene results in a form of severe combined immune deficiency (SCID-X1), which has been treated successfully with hematopoietic stem cell gene therapy. SCID-X1 gene therapy results in reconstitution of the previously lacking T cell compartment, allowing analysis of the roles of T cell immunity in humans by comparing before and after gene correction. METHODS: Here we interrogate T cell reconstitution using four forms of high throughput analysis. (1) Estimation of the numbers of transduced progenitor cells by monitoring unique positions of integration of the therapeutic gene transfer vector. (2) Estimation of T cell population structure by sequencing of the recombined T cell receptor (TCR) beta locus. (3) Metagenomic analysis of microbial populations in oropharyngeal, nasopharyngeal, and gut samples. (4) Metagenomic analysis of viral populations in gut samples. RESULTS: Comparison of progenitor and mature T cell populations allowed estimation of a minimum number of cell divisions needed to generate the observed populations. Analysis of microbial populations showed the effects of immune reconstitution, including normalization of gut microbiota and clearance of viral infections. Metagenomic analysis revealed enrichment of genes for antibiotic resistance in gene-corrected subjects relative to healthy controls, likely a result of higher healthcare exposure. CONCLUSIONS: This multi-omic approach enables the characterization of multiple effects of SCID-X1 gene therapy, including T cell repertoire reconstitution, estimation of numbers of cell divisions between progenitors and daughter T cells, normalization of the microbiome, clearance of microbial pathogens, and modulations in antibiotic resistance gene levels. Together, these results quantify several aspects of the long-term efficacy of gene therapy for SCID-X1. This study includes data from ClinicalTrials.gov numbers NCT01410019, NCT01175239, and NCT01129544.
Subject(s)
Genetic Therapy , Microbiota , T-Lymphocytes/immunology , X-Linked Combined Immunodeficiency Diseases/immunology , X-Linked Combined Immunodeficiency Diseases/therapy , Cell Division , Child, Preschool , Complementarity Determining Regions/genetics , Humans , Receptors, Antigen, T-Cell, alpha-beta/metabolism , X-Linked Combined Immunodeficiency Diseases/microbiology , X-Linked Combined Immunodeficiency Diseases/virologyABSTRACT
BACKGROUND AND PURPOSE: Prehospital stroke scales may help identify patients likely to have large-vessel occlusion to facilitate rapid triage to thrombectomy-capable stroke centers. Scale misclassification may result in inaccurate decisions and possible harm. Pre-existing leukoaraiosis has been shown to attenuate the association between deficit type and stroke severity. We sought to determine whether leukoaraiosis affects the predictive ability of 5 commonly used large-vessel occlusion scales. MATERIALS AND METHODS: We retrospectively analyzed 274 consecutive patients with stroke with available brain MR imaging and vessel imaging. We used the following large-vessel occlusion scales: the 3-Item Stroke Scale; Field Assessment Stroke Triage for Emergency Destination; Rapid Arterial Occlusion Evaluation; Vision, Aphasia, Neglect score; and Cincinnati Prehospital Stroke Severity Scale. For diagnostic scale accuracy, we assessed sensitivity, specificity, positive predictive value, negative predictive value, and κ. Multivariable logistic regression was used to determine the predictive ability of the scales after adjustment for leukoaraiosis and potential confounders. RESULTS: In unadjusted analyses, all scales predicted the presence of large-vessel occlusion (n = 46, P < .01 each), though diagnostic accuracy was attenuated among patients with moderate-to-severe leukoaraiosis. After adjustment, the Field Assessment Stroke Triage for Emergency Destination (OR = 3.2; 95% CI, 1.1-9.5; P = .033) and Rapid Arterial Occlusion Evaluation (OR = 3.7; 95% CI, 1.3-10.8; P = .015), but not the 3-Item Stroke Scale (OR = 5.4; 95% CI, 0.86-33.9; P = .073), Vision, Aphasia, Neglect score (OR = 2.5; 95% CI, 0.8-7.2), and Cincinnati Prehospital Stroke Severity Scale (OR = 2.8; 95% CI, 1.0-8.0), predicted large-vessel occlusion. CONCLUSIONS: The diagnostic accuracy of the tested large-vessel occlusion scales was attenuated in the presence of moderate-to-severe leukoaraiosis. This information that may aid the design of future studies that require large-vessel occlusion scale screening of patients who are likely to have concomitant leukoaraiosis.
Subject(s)
Leukoaraiosis/complications , Stroke/complications , Stroke/diagnosis , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Severity of Illness Index , Triage/methodsABSTRACT
BACKGROUND: Combination chemotherapy is associated with improved outcomes in trials of selected fit patients with advanced colorectal cancer (acrc). For older or less-fit patients, combination chemotherapy is associated with greater toxicity and less benefit. Capecitabine monotherapy is a reasonable option for those patients, but the optimal dose remains controversial. METHODS: A multicentre phase i/ii trial of reduced-dose capecitabine (2000 mg/m2, days 1-14 every 21 days) was conducted in 221 patients representing one or more of the following subsets: age greater than 65 years (n = 167), Eastern Cooperative Oncology Group (ecog) performance status of 1 or greater (n = 139), elevated lactate dehydrogenase (ldh) (n = 105), or prior pelvic radiation (n = 54). Based on phase i results, patients with prior pelvic radiation received capecitabine 750 mg/m2 twice daily. The goal was to ascertain efficacy in a design that was unlikely to cause high levels of toxicity. RESULTS: Median age in the patient cohort was 72 years. A median of 5 and a mean of 8 capecitabine cycles were given (range: 0-50 cycles). Grade 3 or 4 toxicity occurred in 25% of patients during the first 3 cycles (8.1% hand-foot syndrome, 7.7% diarrhea). The response rate was 13.6%, with a 69.7% disease control rate. Median progression-free survival (pfs) was 5.6 months. Post progression, 56 patients received further capecitabine monotherapy (median of 4 additional cycles). Median overall survival duration for the patients was 14.3 months. Median survival was significantly higher for those who, at baseline, had an ecog performance status of 0 (compared with 1 or more) and normal ldh (compared with elevated ldh). CONCLUSIONS: Toxicity is less with dose-reduced capecitabine than with historical full-dose capecitabine, with only a small trade-off in efficacy, seen as a lower objective response rate. The improved tolerability could lead to an increased number of cycles of therapy, and pfs appears to be consistently higher at the lower dose. Those observations should, in the absence of a head-to-head clinical trial, be viewed as compelling evidence that 1000 mg/m2, or even 750 mg/m2, twice daily is an appropriate dose in elderly or frail patients with acrc.
ABSTRACT
The objective of this study was to investigate the effects of storage temperature and duration on the composition and functional properties of bulk tank milk when fresh milk was added to the bulk tank twice daily. The bulk tank milk temperature was set at each of 3 temperatures (2, 4, and 6°C) in each of 3 tanks on 2 occasions during two 6-wk periods. Period 1 was undertaken in August and September when all cows were in mid lactation, and period 2 was undertaken in October and November when all cows were in late lactation. Bulk tank milk stored at the 3 temperatures was sampled at 24-h intervals during storage periods of 0 to 96 h. Compositional parameters were measured for all bulk tank milk samples, including gross composition and quantification of nitrogen compounds, casein fractions, free amino acids, and Ca and P contents. The somatic cell count, heat stability, titratable acidity, and rennetability of bulk tank milk samples were also assessed. Almost all parameters differed between mid and late lactation; however, the interaction between lactation, storage temperature, and storage duration was significant for only 3 parameters: protein content and concentrations of free cysteic acid and free glutamic acid. The interaction between storage temperature and storage time was not significant for any parameter measured, and temperature had no effect on any parameter except lysine: lysine content was higher at 6°C than at 2°C. During 96 h of storage, the concentrations of some free amino acids (glutamic acid, lysine, and arginine) increased, which may indicate proteolytic activity during storage. Between 0 and 96 h, minimal deterioration was observed in functional properties (rennet coagulation time, curd firmness, and heat stability), which was most likely due to the dissociation of ß-casein from the casein micelle, which can be reversed upon pasteurization. Thus, this study suggests that blended milk can be stored for up to 96 h at temperatures between 2°C and 6°C with little effect on its composition or functional properties.
Subject(s)
Caseins , Milk/chemistry , Animals , Cattle , Cell Count , Female , Lactation , PasteurizationABSTRACT
Pertussis has a disproportionately higher morbidity and mortality in infants less than 3 months of age. International and national guidelines recommend pertussis vaccination during pregnancy, as a safe and effective way to protect these infants. Antenatal pertussis vaccination uptake rates remain suboptimal, with many health care professionals (HCPs) still not recommending it. The reasons underlying this reluctance on behalf of HCPs have not been fully established. This study aims to evaluate the current practice and attitudes of General Practitioners (GPs) with regard to antenatal pertussis vaccination. An embedded mixed method design was used. The response rate was 41% (n=109). 54% of GPs who responded (n=59) routinely recommend antenatal pertussis vaccination. Safety concerns and a sense of isolation emerged as the major qualitative themes. More safety data, adequate funding from the Health Service Executive (HSE) and support from secondary care may help to increase the GP recommendation rate and enhance vaccination uptake in pregnancy.
Subject(s)
Attitude of Health Personnel , General Practitioners , Pertussis Vaccine/administration & dosage , Prenatal Care , Whooping Cough/prevention & control , Female , Humans , Infant , Pregnancy , VaccinationABSTRACT
BACKGROUND: Adverse inpatient events may diminish with earlier response to clinical deterioration. Observation and response charts with a tiered escalation response are recommended for use. AIMS: To examine the impact of an observation and response chart and altered calling criteria on rapid response team (RRT) calls, cardiac arrests and intensive care unit (ICU) admissions from the ward and hospital deaths. METHODS: Linked administrative and clinical data from an Australian, adult tertiary hospital for August 2007 to June 2013 (pre-chart) and July 2013 to December 2014 (post-chart) and analysed using interrupted time series analysis. RESULTS: Pre-chart RRT calls were increasing by 1.7 calls per 10 000 hospital admissions per month, whilst ICU admissions from the ward, deaths and cardiac arrests were decreasing by 0.3, 0.25 and 0.079 per 10 000 admissions per month respectively. Immediately upon chart introduction, the RRT call rate increased by 82% (66-98% CI; P < 0.01), the ward admissions to ICU rate increased by 41% (14-67% CI; P < 0.01) and the rates of deaths and cardiac arrests did not change. In the post chart period, both the pre-chart increasing trend in the rate of RRT and decreasing trend in the rate of ICU admissions changed significantly to become constant. The pre chart trends in the cardiac arrest rate and hospital mortality did not change. CONCLUSION: Observation and response charts increased RRT and ICU workload without improving cardiac arrest rate or mortality. Future chart evaluation should identify features beneficial to patient outcomes and refine those that consume critical care resources that are not associated with improved patient outcomes.
Subject(s)
Heart Arrest/mortality , Hospital Mortality/trends , Hospital Rapid Response Team/organization & administration , Medical Records , Workload , Answering Services , Humans , Inpatients , Intensive Care Units , Patient Admission , Regression Analysis , South Australia , Tertiary Care CentersABSTRACT
The dairy industry in Ireland is currently undergoing a period of expansion and, as a result, it is anticipated that milk may be stored in bulk tanks on-farm for periods greater than 48 h. The objective of this study was to investigate the effects of storage temperature and duration on microbial quality of bulk tank milk when fresh milk is added to the bulk tank twice daily. Bulk tank milk stored at 3 temperatures was sampled at 24-h intervals during storage periods of 0 to 96 h. Bulk tank milk samples were analyzed for total bacterial count (TBC), psychrotrophic bacterial count (PBC), laboratory pasteurization count (LPC), psychrotrophic-thermoduric bacterial count (PBC-LPC), proteolytic bacterial count, lipolytic bacterial count, presumptive Bacillus cereus, sulfite-reducing Clostridia (SRC), and SCC. The bulk tank milk temperature was set at each of 3 temperatures (2°C, 4°C, and 6°C) in each of 3 tanks on 2 occasions during two 6-wk periods. Period 1 was undertaken in August and September, when all cows were in mid lactation, and period 2 was undertaken in October and November, when all cows were in late lactation. None of the bulk tank bacterial counts except the proteolytic count were affected by lactation period. The proteolytic bacterial count was greater in period 2 than in period 1. The TBC and PBC of milk stored at 6°C increased as storage duration increased. The TBC did not increase with increasing storage duration when milk was stored at 2°C or 4°C but the PBC of milk stored at 4°C increased significantly between 0 and 96 h. The numbers of proteolytic and lipolytic bacteria, LPC, or PBC-LPC in bulk tank milk were not affected by temperature or duration of storage. Presumptive B. cereus were detected in 10% of all bulk tank milk samples taken over the two 6-wk periods, with similar proportions observed in both. In bulk tank milk samples, a greater incidence of SRC was observed in period 2 (20%) compared with period 1 (3%). Milk produced on-farm with minimal bacterial contamination can be successfully stored at 2°C and 4°C for up to 96h with little effect on its microbial quality.
Subject(s)
Food Preservation/methods , Milk/microbiology , Temperature , Animals , Bacteria/isolation & purification , Bacterial Load , Cattle , Dairying/methods , Dairying/trends , Female , Ireland , Lactation , Milk/cytology , Pasteurization , Seasons , Time FactorsABSTRACT
Paenibacillus larvae bacteriophage Tripp was isolated from an American foulbrood diseased honey bee hive in North Carolina, USA. The 54,439-bp genome is 48.3% G+C, encodes 92 proteins, no tRNAs, and has 378-bp direct terminal repeats. It is currently unique in Genbank.
ABSTRACT
Glioblastoma (GBM) remains the most common and lethal intracranial tumor. In a comparison of gene expression by A2B5-defined tumor-initiating progenitor cells (TPCs) to glial progenitor cells derived from normal adult human brain, we found that the F2R gene encoding PAR1 was differentially overexpressed by A2B5-sorted TPCs isolated from gliomas at all stages of malignant development. In this study, we asked if PAR1 is causally associated with glioma progression. Lentiviral knockdown of PAR1 inhibited the expansion and self-renewal of human GBM-derived A2B5(+) TPCs in vitro, while pharmacological inhibition of PAR 1 similarly slowed both the growth and migration of A2B5(+) TPCs in culture. In addition, PAR1 silencing potently suppressed tumor expansion in vivo, and significantly prolonged the survival of mice following intracranial transplantation of human TPCs. These data strongly suggest the importance of PAR1 to the self-renewal and tumorigenicity of A2B5-defined glioma TPCs; as such, the abrogation of PAR1-dependent signaling pathways may prove a promising strategy for gliomas.
Subject(s)
Brain Neoplasms/genetics , Cell Self Renewal , Glioma/genetics , Neoplastic Stem Cells/metabolism , Receptor, PAR-1/genetics , Adult , Animals , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cell Survival/genetics , Gangliosides/metabolism , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Glioma/metabolism , Glioma/pathology , Humans , Mice , Neoplastic Stem Cells/pathology , RNA Interference , Receptor, PAR-1/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/genetics , Transplantation, HeterologousABSTRACT
The objectives of this study were to evaluate annual and seasonal trends in bulk tank somatic cell count (SCC), total bacterial count (TBC), and laboratory pasteurization count (LPC) in Ireland between 2007 and 2011 (inclusive), and to compare trends based on herd type and herd size. The unadjusted median SCC and TBC of all records were 266,000 and 17,000 cfu/mL, respectively. Data were transformed to log values and analyzed using a mixed model. Fixed effects included milk processor, year, month, and total monthly milk volume; milk producer was fitted as a random variable. After analysis, means were back transformed for interpretation. Annual SCC increased slightly from 259,000 cells/mL in 2007 to a peak of 272,647 cells/mL in 2009 and then declined slightly thereafter. Although statistically significant changes in annual TBC are probably not biologically relevant, values ranged between 23,922 and 26,290 cfu/mL. Annual LPC peaked in 2008 (265 cfu/mL), declined in 2009, and increased thereafter. Monthly mean SCC of all records increased from April onward, with the greatest increases seen from October to December, when the majority of cows entered late lactation. Monthly mean TBC exhibited a seasonal trend, whereby TBC was greatest at the beginning and end of the year, coinciding with winter housing. Seasonal milk production herds (n=8,002 herds) calve all cows in spring (February to April), whereas split-calving herds (n=1,829 herds) calve cows in the spring and autumn. From February to September, monthly SCC was lower for seasonal herds than for split-calving herds, whereas SCC was lower for split-calving herds for the remaining months. During winter (October to March), split-calving herds had lower monthly TBC than seasonal herds, most likely because of stricter regulations imposed upon them. Herd size was approximated using total annual milk production figures. Across all months, larger herds had lower SCC and TBC compared with smaller herds. No obvious improvements in milk quality were seen between 2007 and 2011. Farmers have the opportunity to improve milk quality by reducing bulk tank SCC in late lactation and by imposing stricter hygiene practices at the beginning and end of the year to overcome the seasonal variation of bulk tank TBC.
Subject(s)
Cattle , Milk/cytology , Milk/microbiology , Pasteurization , Seasons , Animals , Bacterial Load/trends , Cell Count/trends , Cell Count/veterinary , Dairying , Female , Food Quality , Hygiene , Ireland , LactationABSTRACT
AIM: To evaluate baseline knowledge and behaviour of parents with regard to the oral and dental health of their young children. METHODS: Following ethical approval, six urban and rural schools were identified. Questionnaires were distributed to the parents of pupils (children aged 4-6 years). The questionnaire included several questions evaluating parental knowledge and behaviour of oral and dental health issues in their children. Each question was assigned a score of either 0 or 1 being inconsistent or consistent with current paediatric guidelines giving a maximum score of 6 for knowledge and 7 for behaviour. Chi-square analysis was used to analyse associations among variables. RESULTS: Parental knowledge varied widely among parents and across questions; however, 70.2 % of parents had scores greater than 3 (range 0-6). The majority of parents (65.8 %) also had scores greater than 3 (range 0-7) for behaviour. Deficiencies were noted in oral hygiene practices; very few parents brushed their child's teeth and were not aware of the recommended age of the first dental visit at 1 year (Age 1 visit). Parents without free medical care demonstrated high levels of knowledge (P < 0.05). Almost half of the parents thought that the information available to them on the oral health of their young children was insufficient. CONCLUSION: Parents appeared to have limited knowledge regarding the dental and oral health of their young children. This study indicates a need for improved education for parents, particularly in toothbrushing behaviour and use of toothpaste. Education strategies tailored to the Irish population should be explored.
Subject(s)
Attitude to Health , Child Health , Health Knowledge, Attitudes, Practice , Oral Health , Parents/psychology , Age Factors , Child , Child, Preschool , Dental Care/psychology , Feeding Behavior/psychology , Fluoridation/psychology , Health Behavior , Humans , Rural Health , Snacks/psychology , Tooth Discoloration/psychology , Tooth Eruption/physiology , Tooth Injuries/psychology , Tooth, Deciduous/physiology , Toothbrushing/psychology , Toothpastes/therapeutic use , Urban HealthABSTRACT
BACKGROUND: The penultimate stage in endoscope reprocessing is the final rinse with water following terminal disinfection. This requires a degree of microbiological and chemical control of the quality of the final rinse water. AIM: To report experience gained over five years of testing, reporting and managing the quality of final rinse water for endoscopic devices. METHODS: Three endoscope reprocessing units, each comprising five endoscope washer-disinfectors (EWDs) supplied by two reverse osmosis (RO) water units, were subjected to weekly monitoring and control of final rinse water quality. EWDs were subjected to nightly thermal self-disinfection, and RO units were subjected to periodic sanitization with peracetic acid. Final rinse water samples were processed periodically for total viable counts (TVCs), Pseudomonas spp., endotoxins, conductivity, environmental mycobacteria and Legionella spp. FINDINGS: Over the five-year study period (2008-2013), no Pseudomonas spp., environmental mycobacteria or Legionella spp. were isolated from endoscopy rinse water. All conductivity readings were below 30 µs/cm. Endotoxin levels fluctuated over the recommended cut-off of 0.25 EU/mL, with no correlation with TVCs. Trend analysis of TVCs established alert and action limits. Apart from the supply water of one EWD becoming contaminated with Aspergillus spp., there have been no interruptions to operational capacity of the endoscope reprocessing units. CONCLUSIONS: Quality control principles coupled with appropriate thermal and chemical disinfection of EWDs resulted in the achievement of microbiological standards for final rinse water. A co-ordinated team approach between the microbiology department, infection control department, endoscope unit managers and estates department is required to achieve this degree of success.
Subject(s)
Disinfection/methods , Endoscopes/microbiology , Equipment Contamination/prevention & control , Water Supply/standards , Colony Count, Microbial , Cross Infection , Endoscopy , Endotoxins/analysis , Infection Control/methods , Legionella/isolation & purification , Microbial Viability , Mycobacterium/isolation & purification , Pseudomonas/isolation & purification , Quality ControlABSTRACT
Many stainless steel crowns (SSCs) disrupt the occlusion in children, but stabilisation appears to occur within a short period post-placement. The extent and mechanism of these short-term occlusal changes in children are unknown. This study sought to determine whether placement of a SSC changes the maximum intercuspation position (MIP) in children, whether the MIP returns to normal within 4 weeks and whether local anaesthesia had an effect on the child's ability to achieve MIP. The T-Scan(®) III was used for the measurement of occlusal contacts. Reliability and reproducibility of the system was determined using a calibration exercise where MIP recordings were taken of eleven children not undergoing any dental treatment. For the main study, the percentage of total occlusal force on each tooth was recorded in 20 children preoperatively, after local anaesthesia, after SSC placement and 4 weeks postoperatively. There was no significant difference in MIP (P = 0·435) preoperatively and post-administration of local anaesthesia. There was a significant difference between the preoperative force on a tooth and the reading after crown placement (P = 0·0013, Wilcoxon test). By 4 weeks, there was no significant difference overall between post-SSC placement and the preoperative value for the tooth (P = 0·3). Administration of local anaesthesia did not affect the ability of a child to attain MIP. Maximum intercuspation position was disturbed by the placement of a SSC in seven of 20 cases. When MIP was disturbed, in most cases, it returned to preoperative status within 4 weeks of crown placement.