Association of behavioural and social-communicative profiles in children with 16p11.2 copy number variants: a multi-site study.

BACKGROUND: Despite the established knowledge that recurrent copy number variants (CNVs) at the 16p11.2 locus BP4-BP5 confer risk for behavioural and language difficulties, limited research has been conducted on the association between behavioural and social-communicative profiles. The current study aims to further delineate the prevalence, nature and severity of, and the association between, behavioural and social-communicative features of school-aged children with 16p11.2 deletion syndrome (16p11.2DS) and 16p11.2 duplication (16p11.2Dup). METHODS: A total of 68 individuals (n = 47 16p11.2DS and n = 21 16p11.2Dup) aged 6-17 years participated. Standardised intelligence tests were administered, and behavioural and social-communicative skills were assessed by standardised questionnaires. Scores of both groups were compared with population norms and across CNVs. The influence of confounding factors was investigated, and correlation analyses were performed. RESULTS: Compared with the normative sample, children with 16p11.2DS showed high rates of social responsiveness (67%) and communicative problems (69%), while approximately half (52%) of the patients displayed behavioural problems. Children with 16p11.2Dup demonstrated even higher rates of social-communicative problems (80-90%) with statistically significantly more externalising and overall behavioural challenges (89%). In both CNV groups, there was a strong positive correlation between behavioural and social-communicative skills. CONCLUSIONS: School-aged children with 16p11.2 CNVs show high rates of behavioural, social responsiveness and communicative problems compared with the normative sample. These findings point to the high prevalence of autistic traits and diagnoses in these CNV populations. Moreover, there is a high comorbidity between behavioural and social-communicative problems. Patients with difficulties in both domains are vulnerable and need closer clinical follow-up and care.

A qualitative exploration of the feasibility and acceptability of Meaning-Centered Psychotherapy for Cancer Caregivers.

OBJECTIVE: Caregivers of patients with cancer are at significant risk for existential distress. Such distress negatively impacts caregivers' quality of life and capacity to serve in their role as healthcare proxies, and ultimately, contributes to poor bereavement outcomes. Our team developed Meaning-Centered Psychotherapy for Cancer Caregivers (MCP-C), the first targeted psychosocial intervention that directly addresses existential distress in caregivers. METHOD: Nine caregivers of patients with glioblastoma multiforme (GBM) enrolled in a pilot randomized controlled trial evaluating the feasibility, acceptability, and effects of MCP-C, and completed in-depth interviews about their experience in the therapy. One focus group with three MCP-C interventionists was also completed. RESULTS: Four key themes emerged from interviews: (1) MCP-C validated caregivers' experience of caregiving; (2) MCP-C helped participants reframe their "caregiving identity" as a facet of their larger self-identity, by placing caregiving in the context of their life's journey; (3) MCP-C enabled caregivers to find ways to assert their agency through caregiving; and (4) the structure and sequence of sessions made MCP-C accessible and feasible. Feedback from interventionists highlighted several potential manual changes and overall ways in which MCP-C can help facilitate caregivers' openness to discussing death and engaging in advanced care planning discussions with the patient. SIGNIFICANCE OF RESULTS: The overarching goal of MCP-C is to allow caregivers to concurrently experience meaning and suffering; the intervention does not seek to deny the reality of challenges endured by caregivers, but instead to foster a connection to meaning and purpose alongside their suffering. Through in-depth interviews with caregivers and a focus group with MCP interventionists, we have refined and improved our MCP-C manual so that it can most effectively assist caregivers in experiencing meaning and purpose, despite inevitable suffering.

Bivalent engagement of endothelial surface antigens is critical to prolonged surface targeting and protein delivery in vivo.

Targeted drug delivery to the endothelium has the potential to generate localized therapeutic effects at the blood-tissue interface. For some therapeutic cargoes, it is essential to maintain contact with the bloodstream to exert protective effects. The pharmacokinetics (PK) of endothelial surface-targeted affinity ligands and biotherapeutic cargo remain a largely unexplored area, despite obvious translational implications for this strategy. To bridge this gap, we site-specifically radiolabeled mono- (scFv) and bivalent (mAb) affinity ligands specific for the endothelial cell adhesion molecules, PECAM-1 (CD31) and ICAM-1 (CD54). Radiotracing revealed similar lung biodistribution at 30 minutes post-injection (79.3% ± 4.2% vs 80.4% ± 10.6% ID/g for αICAM and 58.9% ± 3.6% ID/g vs. 47.7% ± 5.8% ID/g for αPECAM mAb vs. scFv), but marked differences in organ residence time, with antibodies demonstrating an order of magnitude greater area under the lung concentration vs. time curve (AUCinf 1698 ± 352 vs. 53.3 ± 7.9 ID/g*hrs for αICAM and 1023 ± 507 vs. 114 ± 37 ID/g*hrs for αPECAM mAb vs scFv). A physiologically based pharmacokinetic model, fit to and validated using these data, indicated contributions from both superior binding characteristics and prolonged circulation time supporting multiple binding-detachment cycles. We tested the ability of each affinity ligand to deliver a prototypical surface cargo, thrombomodulin (TM), using one-to-one protein conjugates. Bivalent mAb-TM was superior to monovalent scFv-TM in both pulmonary targeting and lung residence time (AUCinf 141 ± 3.2 vs 12.4 ± 4.2 ID/g*hrs for ICAM and 188 ± 90 vs 34.7 ± 19.9 ID/g*hrs for PECAM), despite having similar blood PK, indicating that binding strength is more important parameter than the kinetics of binding. To maximize bivalent target engagement, we synthesized an oriented, end-to-end anti-ICAM mAb-TM conjugate and found that this therapeutic had the best lung residence time (AUCinf 253 ± 18 ID/g*hrs) of all TM modalities. These observations have implications not only for the delivery of TM, but also potentially all therapeutics targeted to the endothelial surface.

Oral health care and service utilisation in individuals with Rett syndrome: an international cross-sectional study.

BACKGROUND: There is a dearth of literature available on the comparative oral health status of those with Rett syndrome (RTT) despite diurnal bruxism being a supportive diagnostic criterion for the disorder. This study was designed to investigate the dental experiences of individuals with RTT in terms of perceived at-home and professional dental care. METHODS: Using data in the InterRett database, provided by English-speaking families of individuals with a confirmed MECP2 genetic mutation, the study investigated relationships between dental problems, oral care, child factors including bruxism and use of gastrostomy, and socioeconomic indicators. The study also explored relationships between dental presentations and socioeconomic, child, and family-related factors. RESULTS: Individuals with RTT exhibiting bruxism were more likely to access dental treatment. Those who had full oral feeding had a higher incidence rate of dental treatment than those with full tube feeding. A conservative (under) estimation of the overall dental caries progression rate revealed that this may be similar to that of the normal population. CONCLUSIONS: Drivers for dental treatment in RTT include bruxism as well as dental caries. Those who have full oral feeding experience more dental treatment than those with full tube feeding. A higher maternal education level may confer a protective effect for oral health outcomes in those with RTT. Nevertheless, families generally tended to value the importance of oral health despite reported difficulties in day-to-day mouth care.

From an assessment of multiple chelators, clodronate has potential for use in continuous chelation.

AIM: To identify chelators which when mixed with sodium hypochlorite (NaOCl) are stable, exhibiting minimal loss of free available chlorine (FAC) over 80 min and to further investigate potential mixtures by assessing FAC over 18 h and the capacity to remove smear layer. METHODOLOGY: 0.25 mol L-1 EDTA (10%), 0.25 mol L-1 EGTA (egtazic acid), 0.25 mol L-1 CDTA (cyclohexanediaminetetraacetic acid), 0.25 mol L-1 DTPA (pentetic acid), 0.5 mol L-1 ATMP (aminotri(methylene phosphonic acid)) and 1 mol L-1 HPAA, (hydroxyphosphonoacetic acid), all at alkaline pH, were mixed equally with 5% NaOCl. 0.5 mol L-1 alkaline clodronate and 0.5 mol L-1 Na4 etidronate (15%) were mixed equally with 10% NaOCl. For all mixtures, the pH and temperature were measured over 80 min and additionally for the clodronate mixture over 18 h. Iodometric titration was used to measure the FAC of all mixtures except for HPAA. The following were compared with respect to their ability to remove smear layer: 1 mol L-1 clodronate + 10% NaOCl, 0.5 mol L-1 clodronate + 10% NaOCl, 1 mol L-1 etidronate + 10% NaOCl, 0.5 mol L-1 clodronate + 10% NaOCl and the sequences 5% NaOCl/17% EDTA/5% NaOCl and 5% NaOCl/17% EDTA. The area fraction occupied by open dentinal tubules as a percentage of the total area (% AF) from scanning electron microscopy micrographs was calculated using Image J. The results were statistically analysed with alpha set at 0.05. RESULTS: Compared to its control, the mixture 0.5 mol L-1 clodronate + 10% NaOCl lost no FAC over 18 h (P > 0.05). The FAC of 0.25 mol L-1 CDTA mixed with 5% NaOCl fell to 96%, 92%, 75% and 4.9% at 20, 40, 60 and 80 min, respectively. Temperature rises were observed in all cases except in the etidronate and clodronate mixtures. Only in the clodronate mixture did the pH remain above pH 12 for the whole experiment. Although smear layer was removed, the % AF in 1 mol L-1 clodronate + 10% NaOCl, 0.5 mol L-1 clodronate + 10% NaOCl, 1 mol L-1 etidronate + 10% NaOCl was less than for 0.5 mol L-1 etidronate + 10% NaOCl and 5% NaOCl/17% EDTA/5% NaOCl and 5% NaOCl/17% EDTA. CONCLUSION: Alkaline 0.5 mol L-1 clodronate mixed equally with 10% NaOCl has potential for use in continuous chelation, based on this assessment of stability and smear layer removal. Further research is needed to establish its efficacy and safety.

Estimating the Effect of Preventable Treatment Discontinuation on Health Outcomes.

BACKGROUND: There is increased interest in studying the effects of medication adherence on health outcomes. However, if patients appropriately stop treatment because of side effects and treatment failure, it is neither possible nor clinically meaningful to estimate the effect of full medication adherence. METHODS: We present an analysis designed to estimate the effect of nonmedical (preventable) discontinuation of cinacalcet, an oral medication approved to treat secondary hyperparathyroidism in patients with end-stage renal disease on dialysis on mortality and heart failure. The approach involves artificially censoring patients who discontinue treatment for a reason that does not appear to be related to an adverse effect of treatment. We address potential bias from informative censoring through inverse-probability of censoring weighted estimation. RESULTS: Although the analysis is subject to possible residual confounding by the healthy adherer effect and other limitations, we find that potentially preventable discontinuation associates with 2.9 excess deaths at 1 year per 100 patients treated (95% confidence interval, 2.4, 3.5), and 4.6 excess deaths at 2 years (95% confidence interval, 3.5, 5.5). The association between cinacalcet persistence and heart failure hospitalization risk was sensitive to the outcome definition. CONCLUSIONS: Inverse-probability of censoring weighted estimation can be used to estimate the effect of potentially preventable treatment discontinuation in populations where treatment can be stopped for both medical and nonmedical reasons. Estimates from such approaches may represent an upper bound of what would be achievable by an adherence improvement intervention.

Nutritional monitoring of patients post-bariatric surgery: implications for smartphone applications.

BACKGROUND: Optimal results from bariatric surgery are contingent on patient commitment to dietary and lifestyle changes and follow-up care. The present study aimed to investigate the attitudes and use of mobile health (mHealth) smartphone applications (apps) as a potential tool for maintaining connectivity between dietitians and patients post-bariatric surgery. METHODS: A cross-sectional online survey was developed and distributed to a purposeful sample of bariatric dietitians and bariatric patients in Australia. The survey questions explored technology penetration (smartphone and app use), communication preferences, nutrition monitoring methods, professional relationship expectations and reasons for loss to follow-up. RESULTS: Survey completion rate was 85% (n = 50/59) for dietitians and 80% (n = 39/49) for patients. Smartphone ownership was 98% and 95% for dietitians and patients, respectively. Common reasons given for losing patients to follow-up suggest that a traditional in-clinic practice setting could be a barrier for some. Most dietitians (n = 48; 91%) prefer to see patients face-to-face in their clinic, whereas patient preferences extended to e-mail and mobile messaging. Sixty-eight percent of bariatric patients were receptive to two-way communication with dietitians via an app between clinic visits. Both cohorts recognised the potential for emerging technologies to be used in practice, although there was no single routinely recommended mHealth app. CONCLUSIONS: The present study provides the first insight into the use of mobile devices and apps by post-bariatric patients and the dietitians who support them. A mixture of traditional methods and smartphone technology is desirable to both dietitians and patients. The utility and effectiveness of such technologies should be confirmed in future intervention studies.

Implications of recent epidemiologic studies for the linear nonthreshold model and radiation protection.

The recently published NCRP Commentary No. 27 evaluated the new information from epidemiologic studies as to their degree of support for applying the linear nonthreshold (LNT) model of carcinogenic effects for radiation protection purposes (NCRP 2018 Implications of Recent Epidemiologic Studies for the Linear Nonthreshold Model and Radiation Protection, Commentary No. 27 (Bethesda, MD: National Council on Radiation Protection and Measurements)). The aim was to determine whether recent epidemiologic studies of low-LET radiation, particularly those at low doses and/or low dose rates (LD/LDR), broadly support the LNT model of carcinogenic risk or, on the contrary, demonstrate sufficient evidence that the LNT model is inappropriate for the purposes of radiation protection. An updated review was needed because a considerable number of reports of radiation epidemiologic studies based on new or updated data have been published since other major reviews were conducted by national and international scientific committees. The Commentary provides a critical review of the LD/LDR studies that are most directly applicable to current occupational, environmental and medical radiation exposure circumstances. This Memorandum summarises several of the more important LD/LDR studies that incorporate radiation dose responses for solid cancer and leukemia that were reviewed in Commentary No. 27. In addition, an overview is provided of radiation studies of breast and thyroid cancers, and cancer after childhood exposures. Non-cancers are briefly touched upon such as ischemic heart disease, cataracts, and heritable genetic effects. To assess the applicability and utility of the LNT model for radiation protection, the Commentary evaluated 29 epidemiologic studies or groups of studies, primarily of total solid cancer, in terms of strengths and weaknesses in their epidemiologic methods, dosimetry approaches, and statistical modelling, and the degree to which they supported a LNT model for continued use in radiation protection. Recommendations for how to make epidemiologic radiation studies more informative are outlined. The NCRP Committee recognises that the risks from LD/LDR exposures are small and uncertain. The Committee judged that the available epidemiologic data were broadly supportive of the LNT model and that at this time no alternative dose-response relationship appears more pragmatic or prudent for radiation protection purposes.

Lung cancer risk at low radon exposure rates in German uranium miners.

BACKGROUND: A determination of the risk of lung cancer at low levels of radon exposure is important for occupational radiation protection. METHODS: The risk of death from lung cancer at low radon exposure rates was investigated in the subcohort of 26,766 German uranium miners hired in 1960 or later. RESULTS: A clear association between lung cancer mortality (n=334 deaths) and cumulative exposure to radon in working level months (WLM) was found. The excess relative risk per WLM was 0.013 (95% confidence intervals: 0.007; 0.021). CONCLUSIONS: The present findings provide strong evidence for an increased lung cancer risk after long-term exposure to low radon exposure rates among Wismut miners. The results are compatible to those from residential radon studies and miner studies restricted to low levels.

Mortality from internal and external radiation exposure in a cohort of male German uranium millers, 1946-2008.

PURPOSE: To examine exposure-response relationships between ionizing radiation and several mortality outcomes in a subgroup of 4,054 men of the German uranium miner cohort study, who worked between 1946 and 1989 in milling facilities, but never underground or in open pit mines. METHODS: Mortality follow-up was from 1946 to 2008, accumulating 158,383 person-years at risk. Cumulative exposure to radon progeny in working level months (WLM) (mean = 8, max = 127), long-lived radionuclides from uranium ore dust in kBqh/m(3) (mean = 3.9, max = 132), external gamma radiation in mSv (mean = 26, max = 667) and silica dust was estimated by a comprehensive job-exposure matrix. Internal Poisson regression models were applied to estimate the linear excess relative risk (ERR) per unit of cumulative exposure. RESULTS: Overall, a total of 457, 717 and 111 deaths occurred from malignant cancer, cardiovascular diseases and non-malignant respiratory diseases, respectively. Uranium ore dust and silica dust were not associated with mortality from any of these disease groups. A statistically significant relationship between cumulative radon exposure and mortality from all cancers (ERR/100 WLM = 1.71; p = 0.02), primarily due to lung cancer (n = 159; ERR/100 WLM = 3.39; p = 0.05), was found. With respect to cumulative external gamma radiation, an excess of mortality of solid cancers (n = 434; ERR/Sv = 1.86; p = 0.06), primarily due to stomach cancer (n = 49, ERR/Sv = 10.0; p = 0.12), was present. CONCLUSION: The present findings show an excess mortality from lung cancer due to radon exposure and from solid cancers due to external gamma radiation in uranium millers that was not statistically significant. Exposure to uranium was not associated with any cause of death, but absorbed organ doses were estimated to be low.

Factors affecting the rate of oxidation and resultant discolouration of tetracyclines contained in endodontic medicaments and irrigants.

AIM: To determine the effect of pH, oxygen levels and ions on tetracycline oxidation and resultant discolouration. METHODOLOGY: Solutions of demeclocycline hydrochloride or doxycycline hyclate were prepared and exposed to different pH conditions, pure oxygen or carbon dioxide, ascorbic acid or various ions (from calcium chloride, calcium nitrate, strontium chloride, magnesium chloride, zinc chloride, and bismuth nitrate). Subsequently, they were exposed to intense visible blue light (470 ± 15 nm) for 24 h. Colour change was monitored using standardized digital photography. Parametric statistical analysis employing the Wilcoxon matched-pairs signed-rank test was performed to compare the mean change in different colour channels, assessing the discolouration effect of the modified conditions. RESULTS: An acidic pH reduced discolouration, whilst alkaline pH increased it. A higher oxygen tension resulted in more discolouration, as did the presence of calcium, strontium, and bismuth ions, all of which bind to tetracyclines. Conversely, zinc and magnesium ions had a mild photoprotective effect. Ascorbic acid, an anti-oxidant, reduced the level of discolouration. CONCLUSIONS: The tendency of these tetracyclines to undergo photo-oxidation is increased by common variables present in the clinical environment. There are potential benefits from using photoprotectors and anti-oxidants in these materials, to reduce the possibility of discolouration.

Biocompatibility and acid resistance of preformed crowns in children: an in vitro study.

PURPOSE: To investigate the in vitro biocompatibility of human gingival fibroblasts with preformed paediatric crowns and resistance to acid exposure at levels that simulate the oral environment. METHODS: This laboratory study investigated primary HGFs viability, metabolic activity, cytotoxicity, and apoptotic events on preformed metal crown discs, composite resin-coated wells, and monolithic zirconia fragments at 24, 48, and 72 h using the ApoTox-Glo Triplex assay. The PPCs were also immersed in 0.1% lactic acid, 0.2% phosphoric acid, or 10% citric acid for 7 days at 37 °C to reproduce conditions associated with dietary intake or gastric reflux. Samples were then subject to inductively coupled plasma optical emission spectrometry to quantitate the release of ions. RESULTS: The viability of HGFs on stainless steel and CR significantly declined at 48 and 72 h, representing potential cytotoxicity (p < 0.05). Cytotoxicity of HGFs was also higher for stainless steel and ZR compared to control (p < 0.05). PMCs and ZR crowns gave minimal ion release. Meanwhile, significant quantities of metallic ions, including copper (Cu), iron (Fe), nickel (Ni), and zinc (Zn), were present in eluates from veneered-preformed metal crowns. CONCLUSION: As PPCs can be exposed to highly acidic environments for many years, thus the release of metallic ions from V-PMCs should form the further investigation in future studies.

Tooth Discoloration from 2 Silver Fluorides Used in Adults with Special Needs: A Randomized Trial.

BACKGROUND: Discoloration of carious lesions after application of silver diamine fluoride lowers patient acceptance and limits its wider use for caries arrest. OBJECTIVE: To assess lesion and tooth color changes from 2 novel silver fluoride (AgF) products and its relationship to caries activity (clinical visuo-tactile scores) and bacterial load (using laser fluorescence with the DIAGNOdent). METHODS: A split-mouth design was followed, with matched smooth surface carious lesions in the same arch in adults with special needs randomized for 1-min treatments with AgF/potassium iodide (KI) (Riva Star Aqua, SDI) and AgF/stannous fluoride (SnF2) (Caries Status Disclosing Solution; Whiteley). Standardized images taken at baseline, immediately postoperatively, and at 3-mo review were subjected to digital image analysis to calculate delta-E and to track changes in luminosity of carious lesions. RESULTS: Twelve participants were recruited in the study. A total of 56 teeth (28 pairs) were included. Significantly greater changes were seen in treated lesions than in the adjacent noncarious natural tooth structure, both immediately after treatment and at the 3-mo review (P < 0.0001). Color change and caries activity were not affected by tooth type, tooth location, plaque status, salivary status, or special needs condition. AgF/SnF2 caused transitory darkening immediately on application, while AgF/KI caused the immediate formation of yellow deposits (silver iodide). Both products caused significant darkening of treated lesions at 3 mo (P = 0.0009; P = 0.0361), with no differences between them (P = 0.506). Responding lesions showed larger and more perceptible color changes immediately after either AgF application (P = 0.002; P = 0.024). CONCLUSIONS: Both AgF products were highly effective for caries arrest in this patient population. Despite minor differences in the appearance of treated lesions at the time of application, both products lead to similar darkening of treated sites at 3 mo. KNOWLEDGE TRANSFER STATEMENT: This study shows the usefulness of silver fluoride used in conjunction with potassium iodide or stannous fluoride for achieving caries arrest in smooth surface lesions in adults with special needs. Patients need to be informed that long-term staining of the lesion occurs with both, similar to silver diamine fluoride.

Comparison of fidaxomicin, thuricin CD, vancomycin and nisin highlights the narrow spectrum nature of thuricin CD.

Vancomycin and metronidazole are commonly used treatments for Clostridioides difficile infection (CDI). However, these antibiotics have been associated with high levels of relapse in patients. Fidaxomicin is a new treatment for CDI that is described as a narrow spectrum antibiotic that is minimally active on the commensal bacteria of the gut microbiome. The aim of this study was to compare the effect of fidaxomicin on the human gut microbiome with a number of narrow (thuricin CD) and broad spectrum (vancomycin and nisin) antimicrobials. The spectrum of activity of each antimicrobial was tested against 47 bacterial strains by well-diffusion assay. Minimum inhibitory concentrations (MICs) were calculated against a select number of these strains. Further, a pooled fecal slurry of 6 donors was prepared and incubated for 24 h with 100 µM of each antimicrobial in a mini-fermentation system together with a no-treatment control. Fidaxomicin, vancomycin, and nisin were active against most gram positive bacteria tested in vitro, although fidaxomicin and vancomycin produced larger zones of inhibition compared to nisin. In contrast, the antimicrobial activity of thuricin CD was specific to C. difficile and some Bacillus spp. The MICs showed similar results. Thuricin CD exhibited low MICs (<3.1 µg/mL) for C. difficile and Bacillus firmus, whereas fidaxomicin, vancomycin, and nisin demonstrated lower MICs for all other strains tested when compared to thuricin CD. The narrow spectrum of thuricin CD was also observed in the gut model system. We conclude that the spectrum of activity of fidaxomicin is comparable to that of the broad-spectrum antibiotic vancomycin in vitro and the broad spectrum bacteriocin nisin in a complex community.

qPCR assay optimisation for a clinical study comparing oral health risk in Rett syndrome.

PURPOSE: This study aimed to validate qPCR assays for specific microbiota, for use on dental plaque samples stored on Whatman FTA cards to compare relative oral health risk in Rett syndrome. METHODS: Supragingival dental plaque samples were collected, using a sterile swab, (COPAN FLOQswab™) swabbed onto Whatman FTA™ cards. DNA extraction was performed using a modified Powersoil™ protocol. Where published assays were unsuitable, species-specific qPCR assays for caries-associated, gingivitis-associated and oral-health-associated bacteria were designed using multiple sequence alignment, Primer3Plus and PrimerQuest. Assays were run using absolute quantification. Limit of detection (LOD) and limit of quantification (LOQ) were calculated, and PCR products verified by Sanger sequencing. RESULTS: Most assays allowed detection using real-time qPCR with high specificity on samples collected on FTA cards. Several assays showed low or even single gene copy numbers on the test samples. CONCLUSION: Assays were optimised for detection and evaluation of oral health risk in dental plaque samples stored on FTA cards when cold storage is not feasible, except for F. nucleatum. Several assays showed gene copy numbers less than the LOQ or outside the range of the standard curve, so there is merit in optimising these assays using digital droplet PCR.

Silica dust, radon and death from non-malignant respiratory diseases in German uranium miners.

OBJECTIVE: To quantify the relationship between death from non-malignant respiratory diseases (NMRD) and exposure to silica dust or radon in a cohort of 58,690 former German uranium miners. METHODS: In the follow-up period from 1946 to 2008, a total of 2336 underlying deaths from NMRDs occurred, including 715 deaths from chronic obstructive pulmonary diseases (COPD) and 975 deaths from silicosis or other pneumoconiosis. Exposure to respirable crystalline silica and radon was individually assessed by means of a comprehensive job-exposure matrix. Risk analyses were based on a linear Poisson regression model with the baseline stratified by age, calendar year and duration of employment. RESULTS: There was no increase in risk of death from COPDs or any other NMRDs in relation to cumulative exposure to silica (mean=5.9, max=56 mg/m(3)-years), except in the group of deaths from silicosis or other pneumoconiosis. Here, a strong non-linear increase in risk was observed. Cumulative radon exposure (mean=280; max=3224 Working Level Months) was not related to death from COPDs or any other NMRDs. CONCLUSIONS: The present findings do not indicate a relationship between mortality from COPD with silica dust or radon. However, validity of cause of death and lack of control for smoking remain potential sources of bias.

A longitudinal case-control study of caries development from birth to 36 months.

BACKGROUND/AIMS: The aim of this longitudinal case-control study was to investigate variables associated with caries development from birth to 36 months. METHODS: Children (n = 1,017) who were followed up every 6 months from birth to 36 months were grouped into those that developed caries by age 30 and 36 months, respectively, and compared with children without caries. RESULTS: By 30 months (n = 608) there were 24 children (4%) who had caries and an additional 23 developed first caries at 36 months (n = 552), giving a total prevalence of 47 children with caries (9%) at 36 months. Children who showed caries by 30 months were more likely to be mutans streptococci (MS) colonised by 18 months (p = 0.001) compared to those who developed caries at 36 months, and showed the following variables: MS counts of >10(5) CFU/ml at 12 months (p = 0.005), missing enamel (p = 0.001), sugar in pacifier at 18 months (p = 0.02), child sleeping next to mother at 6, 18 and 24 months (p = 0.001 to p = 0.02), and exposure to household cigarette smoke at 24 months (p = 0.02). Caries at 36 months was associated with pregnancy problems (p = 0.024), mother having dental cavitations (p = 0.001) and MS presence at 36 months (adjusted odds ratio, AOR = 0.1, p = 0.01 for counts <10(5) CFU/ml). Caries at both 30 and 36 months was associated with MS presence at 18 months (AOR = 6.3, p = 0.005 and AOR = 4.9, p = 0.01). CONCLUSIONS: Children who developed caries by 30 months are colonised by MS at younger ages and with higher MS counts compared with children who develop caries at 36 months.

External gamma radiation and mortality from cardiovascular diseases in the German WISMUT uranium miners cohort study, 1946-2008.

It is currently unclear whether exposure of the heart and vascular system, at lifetime accumulated dose levels relevant to the general public (<500 mGy), is associated with an increased risk of cardiovascular disease. Therefore, data from the German WISMUT cohort of uranium miners were investigated for evidence of a relationship between external gamma radiation and death from cardiovascular diseases. The cohort comprises 58,982 former employees of the Wismut company. There were 9,039 recorded deaths from cardiovascular diseases during the follow-up period from 1946 to 2008. Exposures to external gamma radiation were estimated using a detailed job-exposure matrix. The exposures were based on expert ratings for the period 1946-1954 and measurements thereafter. The excess relative risk (ERR) per unit of cumulative gamma dose was obtained with internal Poisson regression using a linear ERR model with baseline stratification by age and calendar year. The mean cumulative gamma dose was 47 mSv for exposed miners (86 %), with a maximum of 909 mSv. No evidence for an increase in risk with increasing cumulative dose was found for mortality from all cardiovascular diseases (ERR/Sv = -0.13; 95 % confidence interval (CI): -0.38; 0.12) and ischemic heart diseases (n = 4,613; ERR/Sv = -0.03; 95 % CI: -0.38, 0.32). However, a statistically insignificant increase (n = 2,073; ERR/Sv = 0.44; 95 % CI: -0.16, 1.04) for mortality from cerebrovascular diseases was observed. Data on smoking, diabetes, and overweight are available for subgroups of the cohort, indicating no major correlation with cumulative gamma radiation. Confounding by these factors or other risk factors, however, cannot be excluded. In conclusion, the results provide weak evidence for an increased risk of death due to gamma radiation only for cerebrovascular diseases.