Risk assessment of N-nitrosodiethylamine (NDEA) and N-nitrosodiethanolamine (NDELA) in cosmetics

N-nitrosamines and their precursors found in cosmetics may be carcinogenic in humans. Thus the aim of this study was to carry out risk assessment for N-nitrosamines (N-nitrosodiethanolamine [NDELA], N-nitrosodiethylamine [NDEA]) and amines (triethanolamine [TEA], diethanolamine [DEA]) levels in cosmetics determined using validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) procedures. NDELA and NDEA concentrations were present at levels of “not detected” (N.D.) to 596.5 μg/kg and N.D. to 40.9 μg/kg, respectively. TEA and DEA concentrations ranged from N.D. to 860 μg/kg and N.D. to 26.22 μg/kg, respectively. The nitrite concentration (3–2250 mg/l), number of nitrosating agents to a maximum 5, and pH (3.93–10.09) were also assessed. The impact of N-nitrosamine formation on the levels of TEA, DEA, nitrite, and other nitrosating agents was also examined. N-nitrosamine concentrations correlated with the number of nitrosating agents and nitrite concentrations. Data demonstrated that higher nitrite concentrations and a greater number of nitrosating agents increased NDELA and NDEA yields. Further, the presence of TEA and DEA exerted a significant influence on N-nitrosamine formation. Risk assessments, including the margin of exposure (MOE) and lifetime cancer risk (LCR) for N-nitrosamines and margin of safety (MOS) for amines, were calculated using product type, use pattern, and concentrations. Exposure to maximum amounts of NDELA and NDEA resulted in MOE > 10,000 (based upon the benchmark dose lower confidence limit 10%) and LCR <1 × 10^?5, respectively. In addition, TEA and DEA concentrations in cosmetic samples resulted in MOS values >100. Therefore, no apparent safety concerns were associated with cosmetic products containing NDELA, NDEA, TEA, and DEA in this study. However, since amines and nitrosating agents produce carcinogenic nitrosamines, their use in cosmetics needs to be minimized to levels as low as technically feasible.     

Biallelic variants in COX4I1 associated with a novel phenotype resembling Leigh syndrome with developmental regression,intellectual disability,and seizures

Autosomal recessive COX4I1 deficiency has been previously reported in a single individual with a homozygous pathogenic variant in COX4I1, who presented with short stature, poor weight gain, dysmorphic features, and features of Fanconi anemia. COX4I1 encodes subunit 4, isoform 1 of cytochrome c oxidase. Cytochrome c oxidase is a respiratory chain enzyme that plays an important role in mitochondrial electron transport and reduces molecular oxygen to water leading to the formation of ATP. Defective production of cytochrome c oxidase leads to a variable phenotypic spectrum ranging from isolated myopathy to Leigh syndrome. Here, we describe two siblings, born to consanguineous parents, who presented with encephalopathy, developmental regression, hypotonia, pathognomonic brain imaging findings resembling Leigh‐syndrome, and a novel homozygous variant on COX4I1, expanding the known clinical phenotype associated with pathogenic variants in COX4I1.     

Genomic characterisation of breast fibroepithelial lesions in an international cohort

Fibroepithelial lesions (FELs) are a heterogeneous group of tumours comprising fibroadenomas (FAs) and phyllodes tumours (PTs). Here we used a 16-gene panel that was previously discovered to be implicated in pathogenesis and progression, to characterise a large international cohort of FELs via targeted sequencing. The study comprised 303 (38%) FAs and 493 (62%) PTs which were contributed by the International Fibroepithelial Consortium. There were 659 (83%) Asian and 109 (14%) non-Asian FELs, while the ethnicity of the rest was unknown. Genetic aberrations were significantly associated with increasing grade of PTs, and were detected more in PTs than FAs for MED12, TERT promoter, RARA, FLNA, SETD2, TP53, RB1, EGFR, and IGF1R. Most borderline and malignant PTs possessed ≥ 2 mutations, while there were more cases of FAs with ≤ 1 mutation compared to PTs. FELs with MED12 mutations had significantly higher rates of TERT promoter, RARA, SETD2, EGFR, ERBB4, MAP3K1, and IGF1R aberrations. However, FELs with wild-type MED12 were more likely to express TP53 and PIK3CA mutations. There were no significant differences observed between the mutational profiles of recurrent FAs, FAs with a history of subsequent ipsilateral recurrence or contralateral occurrence, and FAs without a history of subsequent events. We identified recurrent mutations which were more frequent in PTs than FAs, with borderline and malignant PTs harbouring cancer driver gene and multiple mutations. This study affirms the role of a set of genes in FELs, including its potential utility in classification based on mutational profiles. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Assessment of Physical Activity of Hospitalised Older Adults: A Systematic Review

Background

The assessment of physical activity levels of hospitalised older people requires accurate and reliable measures. Physical activities that older people in hospital commonly engage in include exercises and walking. Measurement of physical activity levels of older inpatients is essential to evaluate the impact of interventions to improve physical activity levels and to determine associations between physical activity in hospital and other health-related outcome measures.

Objective

To determine which measures are used to measure physical activity of older people in hospital, and to describe their properties and applications.

Method

A systematic review of four databases: Medline, Embase, CINAHL and AMED was conducted for papers published from 1996 to 2016. Inclusion criteria were participants aged ≥ 65 years and studies which included measures of physical activity in the acute medical inpatient setting. Studies which specifically assessed the activity levels of surgical patients or patients with neurological conditions such as stroke or brain injury were excluded. All study designs were included in the review.

Results

18 studies were included from 127 articles selected for full review. 15 studies used objective measures to measure the physical activity of older inpatients: 11 studies used accelerometers and four used direct systematic observations. Seven accelerometers were identified including the StepWatch Activity Monitor, activPAL, GENEActiv, Kenz Lifecorder EX, Actiwatch-L, Tractivity and AugmenTech Inc. Pittsburgh accelerometer. Three studies used a subjective measure (interviews with nurses and patients) to classify patients into low, intermediate and high mobility groups. The StepWatch Activity Monitor was reported to be most accurate at step-counting in patients with slow gait speed or altered gait. The activPAL was reported to be highly accurate at classifying postures.

Conclusion

Physical activity levels of older inpatients can be measured using accelerometers. The accuracy of the accelerometers varies between devices and population-specific validation studies are needed to determine their suitability in measuring physical activity levels of hospitalised older people. Subjective measures are less accurate but can be a practical way of measuring physical activity in a larger group of patients.

     

Vitamin D Binding Protein and Vitamin D Levels in Multi-Ethnic Population

Introduction

Low levels of 25-hydroxyvitamin D (25(OH)D) has been associated with many negative health outcomes including falls and fractures. 25(OH)D is largely bound to vitamin D binding protein (VDBP). There is increasing evidence that free or bioavailable 25(OH)D may be a better measure of vitamin D deficiency.

Objective

To determine the prevalence of 25(OH)D deficiency and VDBP levels in multi-ethnic population, and its impact on muscle strength.

Design and methods

Cross-sectional study of older adults in Western region of Singapore. 295 participants from three ethnic groups were selected from the Healthy Older People Everyday (HOPE) cohort for measurements of total 25(OH)D and VDBP levels. Total 25(OH)D, VDBP, frailty status, Timed-Up-and-Go (TUG) and grip strength (GS) were assessed. Albumin, free and bioavailable 25(OH)D were only available for 256 participants.

Results

53% of Malay and 55% of Indians were deficient in 25(OH)D compared with 18.2% of ethnic Chinese participants. Chinese also had higher total 25(OH)D concentrations with a mean of 29.1 ug/l, (p = <0.001). Chinese had the lowest level of VDBP (169.6ug/ml) followed by Malay (188.8 ug/ml) and Indian having the highest (220.1 ug/ml). Calculated bioavailable and free 25(OH)D levels were significantly higher in Chinese, followed by Malays and Indians, which also correlated with better grip strength measures amongst the Chinese.

Conclusion

The Malays and Indians had overall lower free, bioavailable and total 25(OH)D compared with ethnic Chinese. Chinese ethnic group also had the lowest VDBP and better overall grip strength.

     

Small area estimation of under-5 mortality in Bangladesh,Cameroon, Chad,Mozambique, Uganda,and Zambia using spatially misaligned data

Background

The under-5 mortality rate (U5MR) is an important metric of child health and survival. Country-level estimates of U5MR are readily available, but efforts to estimate U5MR subnationally have been limited, in part, due to spatial misalignment of available data sources (e.g., use of different administrative levels, or as a result of historical boundary changes).

Methods

We analyzed all available complete and summary birth history data in surveys and censuses in six countries (Bangladesh, Cameroon, Chad, Mozambique, Uganda, and Zambia) at the finest geographic level available in each data source. We then developed small area estimation models capable of incorporating spatially misaligned data. These small area estimation models were applied to the birth history data in order to estimate trends in U5MR from 1980 to 2015 at the second administrative level in Cameroon, Chad, Mozambique, Uganda, and Zambia and at the third administrative level in Bangladesh.

Results

We found substantial variation in U5MR in all six countries: there was more than a two-fold difference in U5MR between the area with the highest rate and the area with the lowest rate in every country. All areas in all countries experienced declines in U5MR between 1980 and 2015, but the degree varied both within and between countries. In Cameroon, Chad, Mozambique, and Zambia we found areas with U5MRs in 2015 that were higher than in other parts of the same country in 1980. Comparing subnational U5MR to country-level targets for the Millennium Development Goals (MDG), we find that 12.8% of areas in Bangladesh did not meet the country-level target, although the country as whole did. A minority of areas in Chad, Mozambique, Uganda, and Zambia met the country-level MDG targets while these countries as a whole did not.

Conclusions

Subnational estimates of U5MR reveal significant within-country variation. These estimates could be used for identifying high-need areas and positive deviants, tracking trends in geographic inequalities, and evaluating progress towards international development targets such as the Sustainable Development Goals.

     

Effect of filler fraction and filler surface treatment on wear of microfilled composites.

OBJECTIVES: The aim of this study was to determine the effect of filler content and surface treatment on the wear of microfilled composites. METHODS: Four microfilled composites with different filler contents (A=20, B=25, C=30, and D=35 vol.%) were made with a light-cured resin (Bis-GMA/UDMA/TEGDMA). The surface treatment of the colloidal silica in each varied: F=functional silane, NF=non-functional silane, U=untreated. Silux Plus served as a control. Specimens were made in steel molds and cured in a light curing unit Triad II (40s/side). Abrasion and attrition wear were evaluated in vitro in a wear tester (OHSU oral wear simulator) with an abrasive slurry (poppy seeds + PMMA) and a human enamel antagonist. The average of five specimens was computed and compared using a ANOVA/Tukey's test at P < or = 0.05. The surface of the wear patterns and the distribution of filler particles were examined using a scanning electron microscope and digital imaging. RESULTS: As filler volume increased, wear was reduced regardless of filler treatment. Amounts of wear for specimens C and D were significantly lower than specimens A and B. Composites with functional silane treated microfiller (Group F) produced significantly less wear than those with non-functional microfiller (Group NF) at 30 and 35 vol.%, and less than the untreated microfiller (Group U) at 30 vol.%. Scanning electron microscopy of specimens of group NF showed large filler agglomerates (size > 1 microm) in the resin matrix, while specimens of group F and U showed fewer agglomerates. Digital imaging analysis revealed small filler clusters (size < or = 1 microm) in the resin matrix of all specimens. SIGNIFICANCE: Wear resistance of microfilled composites is enhanced by higher filler volumes irrespective of surface treatment, but good filler/matrix adhesion is needed to minimize wear.