Pandemic preparedness from the perspective of Occupational Health professionals.

BACKGROUND: Prior to any infectious disease emergence as a public health concern, early occupational preparedness is crucial for protecting employees from novel pathogens- coronavirus disease 2019 (COVID-19) is no different. AIMS: This study ascertains how occupational safety and health (OSH)/Human Resource (HR) professionals in the Republic of Ireland had managed to prepare their workplaces prior to the advent of COVID-19. METHODS: As part of a larger COVID-19 workplace study, online focus groups were conducted with OSH/HR professionals. Collected data were transcribed verbatim and entered into NVivo for thematic analysis incorporating intercoder reliability testing. RESULTS: Fifteen focus groups were conducted with OSH/HR professionals (n = 60) from various occupational settings. Three levels of organizational preparedness were identified: 'early awareness and preparation'; 'unaware and not ready' and 'aware, but not ready'. Most organizations were aware of the COVID-19 severity, but not fully prepared for the pandemic, especially stand-alone enterprises that may not have sufficient resources to cope with an unanticipated crisis. The experiences shared by OSH professionals illustrate their agility in applying risk management and control skills to unanticipated public/occupational health crises that arise. CONCLUSIONS: General pandemic preparedness such as the availability of work-from-home policies, emergency scenario planning and prior experience in workplace outbreaks of infectious diseases were helpful for workplace-associated COVID-19 prevention. This is the first study conducted with OSH/HR professionals in Ireland regarding COVID-19 preparedness in workplaces, which provides valuable insights into research literature, as well as empirical experience for the preparation of future public health emergencies.

Routine testing of close contacts of confirmed COVID-19 cases - National COVID-19 Contact Management Programme, Ireland, May to August 2020.

OBJECTIVES: The objective of this study was to inform public health practitioners who are designing, adapting and implementing testing and tracing strategies for Coronavirus disease (COVID-19) control. STUDY DESIGN: The study design is monitoring and evaluation of a national public health protection programme. METHODS: All close contacts of laboratory-confirmed cases of COVID-19 identified between the 19th May and 2nd August were included; secondary attack rates and numbers needed to test were estimated. RESULTS: Four thousand five hundred eighty six of 7272 (63%) close contacts of cases were tested with at least one test. The secondary attack rate in close contacts who were tested was 7% (95% Confidence Interval [CI]: 6.3 - 7.8%). At the 'day 0' test, 14.6% (95% CI: 11.6-17.6%) of symptomatic close contacts tested positive compared with 5.2% (95% CI: 4.4-5.9%) of asymptomatic close contacts. CONCLUSIONS: The application of additional symptom-based criteria for testing in this high-incidence population (close contacts) is of limited utility because of the low negative predictive value of absence of symptoms.

Trends in blindness due to diabetic retinopathy among adults aged 18-69years over a decade in Ireland.

AIMS: To describe trends in the incidence of visual impairment and blindness due to diabetic retinopathy among adults aged 18-69years in Ireland between 2004 and 2013. METHODS: Data on visual impairment due to diabetic retinopathy in adults aged 18-69years or over who are registered with the National Council for the Blind of Ireland, (2004-2013) were analysed. Annual incidence rates were calculated for the adult population and the population with diagnosed diabetes. Poisson regression was used to test for changes in rates over time. The relative, attributable and population risk of blindness and visual impairment due to diabetic retinopathy were calculated for 2013. RESULTS: Over the decade, the prevalence of diagnosed diabetes increased from 2.1% to 3.6%. Among people with diagnosed diabetes, the incidence of visual impairment due to diabetic retinopathy increased from 6.4 (95% CI 2.4-13.9) per 100,000 in 2004 to 11.7 (95% CI 5.9-21.0) per 100,000 in 2013. The incidence of blindness due to diabetic retinopathy varied from 31.9 per 100,000 (95% CI 21.6-45.7) in 2004 to 14.9 per 100,000 (95% CI 8.2-25.1) in 2013. CONCLUSIONS: Our findings indicate the need for increased attention to preventive measures for microvascular complications among adults with diabetes in Ireland. Retinopathy screening has been standardised in Ireland, these findings provide useful baseline statistics to monitor the impact of this population-based screening programme.

The prevalence of Type 2 diabetes and related complications in a nationally representative sample of adults aged 50 and over in the Republic of Ireland.

AIM: To investigate the prevalence of diagnosed Type 2 diabetes and its related complications in a nationally representative sample of older adults in the Republic of Ireland. METHODS: Cross-sectional analysis of a population-based sample of adults aged ≥ 50 years from the first wave of The Irish Longitudinal Study on Ageing (TILDA), (2009-2011). Diagnosed Type 2 diabetes prevalence was estimated by self-report or the use of oral hypoglycaemic agents. The prevalence of microvascular and macrovascular complications was determined by self-report. RESULTS: Diagnosed Type 2 diabetes prevalence was 8.4% [95% confidence interval (CI): 7.8-9.0%] and was higher among men [10.3% (95% CI: 9.4-11.2%)] than women [6.6% (95% CI: 5.9-7.5%)]; P ≤ 0.001. Among participants with diagnosed Type 2 diabetes, the overall prevalence of microvascular complications was 26.0% (95% CI: 22.4-30.0%) with no evidence of gender-specific differences (P = 0.7). The overall prevalence of macrovascular complications was 15.1% (95% CI: 12.2-18.4%) and was higher among men [17.8% (95% CI: 14.3-23.1%)] than women [11.4% (95% CI: 7.7-16.4%)]; P ≤ 0.001. CONCLUSIONS: In the absence of a national diabetes register, these findings provide a robust estimate of the national prevalence of diagnosed Type 2 diabetes and level of complications among adults aged 50 years and over in Ireland.

Does contact with a podiatrist prevent the occurrence of a lower extremity amputation in people with diabetes? A systematic review and meta-analysis.

OBJECTIVE: To determine the effect of contact with a podiatrist on the occurrence of Lower Extremity Amputation (LEA) in people with diabetes. DESIGN AND DATA SOURCES: We conducted a systematic review of available literature on the effect of contact with a podiatrist on the risk of LEA in people with diabetes. Eligible studies, published in English, were identified through searches of PubMed, CINAHL, EMBASE and Cochrane databases. The key terms, 'podiatry', 'amputation' and 'diabetes', were searched as Medical Subject Heading terms. Reference lists of selected papers were hand-searched for additional articles. No date restrictions were imposed. STUDY SELECTION: Published randomised and analytical observational studies of the effect of contact with a podiatrist on the risk of LEA in people with diabetes were included. Cross-sectional studies, review articles, chart reviews and case series were excluded. Two reviewers independently assessed titles, abstracts and full articles to identify eligible studies and extracted data related to the study design, characteristics of participants, interventions, outcomes, control for confounding factors and risk estimates. ANALYSIS: Meta-analysis was performed separately for randomised and non-randomised studies. Relative risks (RRs) with 95% CIs were estimated with fixed and random effects models as appropriate. RESULTS: Six studies met the inclusion criteria and five provided data included in meta-analysis. The identified studies were heterogenous in design and included people with diabetes at both low and high risk of amputation. Contact with a podiatrist did not significantly affect the RR of LEA in a meta-analysis of available data from randomised controlled trials (RCTs); (1.41, 95% CI 0.20 to 9.78, 2 RCTs) or from cohort studies; (0.73, 95% CI 0.39 to 1.33, 3 Cohort studies with four substudies in one cohort). CONCLUSIONS: There are very limited data available on the effect of contact with a podiatrist on the risk of LEA in people with diabetes.

Pre-diabetes in adults 45 years and over in Ireland: the Survey of Lifestyle, Attitudes and Nutrition in Ireland 2007.

OBJECTIVES: Pre-diabetes is an important indicator of future diabetes burden and many countries are reporting prevalence estimates of pre-diabetes. To date in Ireland, estimates of the prevalence of pre-diabetes were unavailable. Our objectives were to estimate the prevalence of pre-diabetes in a nationally representative sample of Irish adults and to explore determinants of pre-diabetes. METHODS: The Survey of Lifestyle Attitudes and Nutrition 2007 was a cross-sectional survey on health and lifestyle in a nationally representative sample of Irish adults. Analysis was performed on a subsample of 1132 participants ≥ 45 years who provided blood samples. Determination of pre-diabetes was based on American Diabetes Association HbA1c cut points of 39-46 mmol/mol (5.7-6.4%). To explore determinants, we modelled pre-diabetes prevalence as a function of a set of health system and socio-demographic variables using logistic regression. RESULTS: The overall weighted prevalence estimate of pre-diabetes in participants ≥ 45 years was 19.8% (95% CI 16.4-23.9). There was no significant difference between age or gender-specific prevalence rates. Obesity was significantly associated with pre-diabetes on univariate and multivariate analysis. Population attributable fraction estimates for excess BMI, physical inactivity and poor diet as causes of pre-diabetes were 31.3% (95% CI -3.9 to 54.5), 10.0% (95% CI -2.7 to 21.3) and 6.1% (95% CI -4.9 to 15.9), respectively. CONCLUSIONS: The high levels of pre-diabetes detected in this study are worrying. Population level interventions to address diet and lifestyle factors are needed urgently to prevent progression to diabetes in high-risk individuals.

Evaluation of the direct and diffusion methods for the determination of fluoride content in table salt.

OBJECTIVE: The aim of this study was to assess methods currently used for analyzing fluoridated salt in order to identify the most useful method for this type of analysis. BASIC RESEARCH DESIGN: Seventy-five fluoridated salt samples were obtained. Samples were analyzed for fluoride content, with and without pretreatment, using direct and diffusion methods. Element analysis was also conducted in selected samples. Fluoride was added to ultra pure NaCl and non-fluoridated commercial salt samples and Ca and Mg were added to fluoride samples in order to assess fluoride recoveries using modifications to the methods. RESULTS: Larger amounts of fluoride were found and recovered using diffusion than direct methods (96%-100% for diffusion vs. 67%-90% for direct). Statistically significant differences were obtained between direct and diffusion methods using different ion strength adjusters. Pretreatment methods reduced the amount of recovered fluoride. Determination of fluoride content was influenced both by the presence of NaCl and other ions in the salt. CONCLUSION: Direct and diffusion techniques for analysis of fluoridated salt are suitable methods for fluoride analysis. The choice of method should depend on the purpose of the analysis.

Epidemiology of osteosarcoma and Ewing's sarcoma in childhood: a study of 305 cases by the Children's Cancer Group.

BACKGROUND: The Children's Cancer Group conducted a case-control study to determine the role of a broad range of environmental and familial factors in the etiology of Ewing's sarcoma and osteosarcoma in children. These factors included radiation exposure and, for children with osteosarcoma, parental exposure to beryllium. METHODS: The parents of 152 children with osteosarcoma and 153 children with Ewing's sarcoma were interviewed by telephone. Controls were obtained by random digit dialing and were matched to cases by age and race. RESULTS: Female osteosarcoma patients had earlier onset of breast development (age 11.4 vs. 11.8 years, P=0.03) and menarche (age 12.1 vs. 12.5 years, P=0.002) but no significant differences in growth, whereas male osteosarcoma patients were similar in age at the onset of secondary sexual characteristics but reported significantly less weight gain during their growth spurt (6.6 vs. 11.7 kg, P=0.003). For children with Ewing's sarcoma, the growth spurt began earlier (age 12.1 vs. 12.7 years, P=0.12) and resulted in less weight and height gain (5.2 vs. 9.7 kg, P=0.002, and 10.2 vs. 12.7 cm, P=0.02, respectively) for males, but no differences were observed among females. For factors not related to growth and development (including a wide range of occupational, medical, and household exposures), there was little evidence of an etiologic role with respect to either tumor type. CONCLUSIONS: Differences between cases and controls with respect to growth and development showed no consistent pattern. This study did not identify any important risk factors for either type of childhood bone tumor.

Glutathione S-transferases from the white-rot fungus, Phanerochaete chrysosporium.

A glutathione S-transferase (GST) was purified to homogeneity from the white-rot fungus, Phanerochaete chrysosporium, by affinity chromatography on glutathione-agarose followed by Mono-Q ion-exchange FPLC. This protein immunoblotted with antisera to rat Theta class GST 5-5 and also showed N-terminal sequence similarity to the Theta class, including the presence of a conserved serine residue that has been specifically implicated in catalysis in this class [Wilce, Board, Feil and Parker (1995) EMBO J. 14, 2133-2143] and other residues conserved in plant sequences. Catalytic activity was found to be highly labile in the purified protein, although preliminary evidence for activity (approx. 120 m-units/mg) with 1,2-epoxy-3-(p-nitrophenoxy)propane was obtained in some preparations. The enzyme seems to be a dimer with a subunit molecular mass of 25 kDa by SDS/PAGE. The native molecular masses estimated by non-denaturing electrophoresis and by Superose-12 gel filtration were 58 and 45 kDa respectively. A second protein purified in this study also gave low level of activity with 1,2-epoxy-3-(p-nitrophenoxy)propane and had a subunit molecular mass of 28 kDa (native size 62-63 kDa), but did not immunoblot with any GST class and seemed to be N-terminally blocked.

Concordance for childhood cancer in twins.

The causes of most childhood cancer remain elusive; some children clearly have a genetic predisposition, but in the majority the relative contributions of environmental and host factors are not established. One approach to this question is through twin concordance studies, but only the most common malignancy, acute leukemia, has been studied to date, owing to the rarity of other forms of childhood cancer. The aim of the study was to determine the concordance rates for childhood cancer in twins, in order to clarify the importance of constitutional predisposition for a range of tumor types. Twins with cancer were ascertained through three cooperative clinical trials groups, a cancer-twin registry, and a large pediatric hospital. Subjects were sent a postal questionnaire requesting information on cancer concordance and zygosity. Data were obtained on 556 twins with cancer. Three twin pairs, out of 197 twin pairs (76 monozygous, MZ, twin pairs), were concordant for leukemia, giving an MZ case-wise concordance rate (5%) that is substantially lower than previously reported. The case-wise concordance for non-retinoblastoma solid tumors was 2.2%: Two twin pairs were concordant for CNS tumors, one was concordant for neuroblastoma, and two twin pairs were concordant for cancer but not for the type of cancer. The results of the present study, together with previous data from population studies of siblings and offspring, suggest that there is not in general a strong constitutional genetic component for childhood cancers other than retinoblastoma.

Interaction of the Pseudomonas cepacia DSM3959 lipase with its chaperone, LimA.

The lipA gene of Pseudomonas cepacia DSM3959 requires a downstream gene, limA, in oder to express lipase activity. The product of the lim gene, LimA, is a molecular chaperone required during the folding of lipase in oder for the lipase to adopt an active conformation. The lipase and LimA proteins have been shown to form a complex precipitable with either an anti-lipase or anti-LimA antibody. LimA has been shown to form a 1:1 complex with with prelipase and lipase isolated from "natural" P. cepacia system. The mature lipase (lacking its signal peptide) has been expressed in the presence and absence of LimA in Escherichia coli. LimA can activate mature lipase during a urea denaturation-renaturation experiment, indicating that the signal peptide is not required for the lipase to be activated by LimA. The effects of various reagents on the renaturation of lipase from 8 M urea have been examined. We propose a mechanism for the function of the LimA chaperone during the production of active extracellular lipase.

Possible regulatory role for nonaromatic carbon sources in styrene degradation by Pseudomonas putida CA-3.

Styrene metabolism in styrene-degrading Pseudomonas putida CA-3 cells has been shown to proceed via styrene oxide, phenylacetaldehyde, and phenylacetic acid. The initial step in styrene degradation by strain CA-3 is oxygen-dependent epoxidation of styrene to styrene oxide, which is subsequently isomerized to phenylacetaldehyde. Phenylacetaldehyde is then oxidized to phenylacetic acid. Styrene, styrene oxide, and phenylacetaldehyde induce the enzymes involved in the degradation of styrene to phenylacetic acid by P. putida CA-3. Phenylacetic acid-induced cells do not oxidize styrene or styrene oxide. Thus, styrene degradation by P. putida CA-3 can be subdivided further into an upper pathway which consists of styrene, styrene oxide, and phenylacetaldehyde and a lower pathway which begins with phenylacetic acid. Studies of the repression of styrene degradation by P. putida CA-3 show that glucose has no effect on the activity of styrene-degrading enzymes. However, both glutamate and citrate repress styrene degradation and phenylacetic acid degradation, showing a common control mechanism on upper pathway and lower pathway intermediates.

Chaperone-mediated activation in vivo of a Pseudomonas cepacia lipase.

An extracellular Pseudomonas cepacia lipase, LipA, is inactive when expressed in the absence of the product of the limA gene. Evidence has been presented that LimA is a molecular chaperone. The lipA and limA genes have been cloned in separate and independently inducible expression systems in Escherichia coli. These systems were used to test the molecular chaperone hypothesis by investigating whether LimA could activate presynthesized prelipase and whether presynthesized LimA could activate newly synthesized prelipase. The results show that LimA cannot activate presynthesized prelipase and that presynthesized LimA can activate only a limited number of de novo synthesized prelipase molecules. Co-immunoprecipitation of prelipase/lipase with LimA generated a 1:1 complex of prelipase/lipase and LimA. The results suggest that a 1:1 complex of LipA and LimA is required for prelipase processing and secretion of active lipase.

Ethylbenzene degradation by Pseudomonas fluorescens strain CA-4.

Pseudomonas fluorescens strain CA-4 is a bioreactor isolate capable of ethylbenzene degradation. Transposon mutagenesis and enzyme assays have been performed which allow us to propose the ethylbenzene degradative pathway in operation in this strain. Ethylbenzene is initially converted to 2-phenylethanol. This is degraded to phenylacetaldehyde and then to phenylacetic acid. The major inducer of the pathway is ethylbenzene itself. The pathway is regulated by the presence of non-aromatic carbon sources. Oxidation of ethylbenzene is repressed by glutamate, but not by citrate or glucose. A clone from a chromosomal library has been found to complement a mutant deficient in the ability to convert ethylbenzene to 2-phenylethanol.

Epidemiological characteristics of childhood acute lymphocytic leukemia. Analysis by immunophenotype. The Childrens Cancer Group.

While a number of epidemiological studies of childhood acute lymphocytic leukemia (ALL) have been conducted, separate analysis of risk factors for ALL subtypes has generally not been possible. We report the results of an analysis of data obtained from parents of children with ALL (and a control group of children without cancer), linked to a clinical database. Cases were classified into four ALL subtypes, and odds ratios (OR) were determined for each subtype for a broad range of factors. Numerous significant associations were found, some across all subtypes and others that were subtype-specific. Factors with elevated and/or significant ORs included: (i) for common ALL (n = 286): Down syndrome; family history (FH) of bone/joint diseases; postnatal jaundice; birthweight; MMR vaccination; exposure to gases and insecticides; and parental occupational exposure to insecticides. (ii) for pre-B ALL (n = 38): FH of gastrointestinal, hematological or bone/joint diseases, or allergy; cat ownership; exposure to solvents, fumes, petroleum products, cleaning agents and farm animals; and parental exposure to farm animals, fumes and solvents; (iii) for T-cell ALL (n = 158): FH of gastrointestinal disorders, maternal age, male gender, and parental occupational exposure to metals; (iv) for null-cell ALL (n = 65): FH of congenital heart disorders; measles; and parental occupational exposure to fumes, metals or solvents. This analysis should be considered as a hypothesis-generating process for future case-control interview studies.

Activation of a bacterial lipase by its chaperone.

The gene lipA of Pseudomonas cepacia DSM 3959 encodes a prelipase from which a signal peptide is cleaved during secretion, producing a mature extracellular lipase. Expression of lipase in several heterologous hosts depends on the presence of another gene, limA, in cis or in trans. Lipase protein has been overproduced in Escherichia coli in the presence and absence of the lipase modulator gene limA. Therefore, limA is not required for the transcription of lipA or for the translation of the lipA mRNA. However, no lipase activity is observed in the absence of limA. limA has been overexpressed and encodes a 33-kDa protein, Lim. If lipase protein is denatured in 8 M urea and the urea is removed by dialysis, lipase activity is quantitatively recovered provided Lim protein is present during renaturation. Lip and Lim proteins form a complex precipitable either by an anti-lipase or anti-Lim antibody. The Lim protein has therefore the properties of a chaperone.

The yeast secretory pathway is perturbed by mutations in PMR1, a member of a Ca2+ ATPase family.

The genes for two new P-type ATPases, PMR1 and PMR2, have been identified in yeast. A comparison of the deduced sequences of the PMR proteins with other known ion pumps showed that both proteins are very similar to Ca2+ ATPases. PMR1 is identical to SSC1, a gene previously identified by its effect on secretion of some foreign proteins from yeast. Proteins secreted from pmr1 mutants lack the outer chain glycosylation that normally results from passage through the Golgi. Loss of PMR1 function suppresses the lethality of ypt1-1, a mutation that blocks the secretion pathway. These data suggest that PMR1 functions as a Ca2+ pump affecting transit through the secretory pathway.

Antagonist binding properties of five cloned muscarinic receptors expressed in CHO-K1 cells.

A family of five cholinergic muscarinic receptor genes (m1, m2, m3, m4, and m5) has recently been identified and cloned. In order to investigate the pharmacological properties of the individual muscarinic receptors, we have transfected each of these genes into Chinese hamster ovary cells (CHO-K1) and have established stable cell lines expressing each receptor. In the present study we have examined the antagonist binding properties of each muscarinic receptor. Antagonists were chosen that had previously been proposed to be selective for muscarinic receptor subtypes and included pirenzepine, AF-DX 116, methoctramine, dicyclomine, hexohydrodifenidol, hexahydrosiladifenidol, hexocyclium, and silahexocyclium. m1, m2, and m3 receptors express binding properties similar to those expected of high affinity pirenzepine-type receptors of cerebral cortex ("M1"), low affinity pirenzepine-type receptors of atria ("M2 cardiac type"), and the intermediate affinity pirenzepine-type receptors found in exocrine glands ("M2 glandular type"), respectively. The M1/M2 schema cannot readily accommodate the binding properties of the m4 and m5 receptors. Pirenzepine, methoctramine, and hexahydrosiladifenidol were the most selective agents for the m1, m2, and m3 receptors, respectively. None of the antagonists used in this study were uniquely selective for either the m4 or m5 receptors. The diverse binding profiles of individual cloned receptors and the widespread distribution of m1-m4 mRNAs indicate that radioligand binding studies performed on primary tissues may actually be assessing the composite properties of a heterogeneous mixture of muscarinic receptor subtypes.