Polycyclic aromatic hydrocarbons modify DNA methylation in animals and humans

Human exposure to the ubiquitous environmental carcinogens polycyclic aromatic hydrocarbons (PAHs) occurs predominantly through the diet, tobacco smoke, and air pollution. While the genotoxic effects of these compounds have been well characterised, it was hypothesised that DNA methylation changes induced by PAHs could be a potential mechanism of their carcinogenicity. This study aimed to identify DNA methylation changes associated with PAH exposure in a mouse model and in human cohorts. Reduced representation bisulphite sequencing was carried out on lung tissue from Benzo[a]pyrene exposed mice. Additionally, PAH8 exposure from air and dietary sources estimated from land use regression models and food frequency questionnaires were used with data from Illumina Infinium HumanMethylation450 in EPIC-Italy (Training subset: N = 493; Testing subset: N = 208) and EPIC-NL (N = 132) cohorts. Several differentially methylated CpG sites (Treated vs Untreated: N = 430; p 25%), 500 b.p. windows (Treated vs Untreated: N = 1780; p 25%), and probes (Air PAH8 exposure: N = 204; Dietary PAH8 exposure: N = 171; Combined air and dietary PAH8 exposure: N = 274; FDR q < 0.05) were identified in the analyses carried out. Although there were little to no overlaps between mouse and human studies at the CpG or gene level, in both the mouse and human analyses significantly fewer changes than expected by chance occurred at promoter regions. Additionally, the three human EWAS showed that different routes of PAH exposure may have different effects on DNA methylation, and when these exposures were combined, the methylation changes observed represented the separate exposures. These observations require further validation, but the results suggest that PAH-DNA adduct formation, which does not occur in a gene-specific manner, could be driving DNA methylation changes.Open Acces

Are local guidelines on investigations in children admitted with acute gastroenteritis being adhered to?

The aim of this article is to assess adherence to local guidelines on the investigation of children admitted with acute gastroenteritis. Children admitted to Mater Dei Hospital with a diagnosis of gastroenteritis between December 2012 and February 2013 were selected. Their investigations were retrospectively assessed in relation to the degree of dehydration and the type of management given. Hospital guidelines relating to investigations performed in children admitted with gastroenteritis were reviewed and compliance was assessed. A total of 411 investigations were carried out in 76 children with the most common investigations being serum electrolytes, urea and creatinine and random blood glucose. Guidelines were met in 4/76 (5.3%) of the study population. Serum electrolytes had the greatest impact on management. The conclusion is that the local guideline on gastroenteritis is not being adhered to in the vast majority of cases. There is an urgent need to raise awareness about the availability and utilisation of this guideline amongst doctors working in paediatrics.peer-reviewe

A case of metastatic Wilms’ tumour with reversible distortion of mediastinal anatomy : a diagnostic challenge for the echocardiographer

Delineation and documentation of anatomy in the presence of significant mass pathology presents a diagnostic challenge. This often necessitates the implementation of more than one imaging modality in order to perform an adequate assessment. We present a three-year old boy with extensive distortion of mediastinal anatomy secondary to pleural metastases from a Wilms tumour. This limited the ability to accurately assess mediastinal anatomy and cardiac function at baseline. Reassessment following initiation of chemotherapy showed a significant reduction in size of metastases with complete resolution of the mediastinal distortion.peer-reviewe

Distribution of Tylos spp. (Crustacea, Isopoda) on Maltese sandy beaches and observations on Tylos Europaeus

The occurrence of Tylos europaeus and T. sardous on 10 Maltese beaches was investigated. T. europaeus occurred on two beaches on Gozo and T. sardous on a single beach on Malta. The largest population was of T. europaeus at Ramla l-Hamra on Gozo, but even here the isopods occupied a limited zone close to sea-level. The diurnal and nocturnal distribution of this population as well as temporal changes in distribution pattern over two years were studied in order to provide baseline information for the conservation of this rare psammophile in the Maltese Islands.peer-reviewe

Distribution of Tylos spp. in the Maltese Islands and population dynamics of Tylos europaeus

Two species of the oniscid genus Tylos occur in the Maltese Islands, T. sardous and T. europaeus, which are allopatric and restricted to just one and two sandy beaches, respectively. The dynamics of the largest locallyoccurring T. europaeus population were investigated during the period 2001-2003. Seasonal variation in the sex ratio, length of the 5th segment of the pereion as a proxy for age, and the proportion of adults and juveniles in the population were assessed during each calendar season. The vertical distribution of male, female and juvenile individuals in the sand was determined in the field during summer 2003. Laboratory experiments were made to test sand moisture preferences. The surface activity of the isopods was studied by means of pitfall trap constellations whilst zonation on the beach was studied by sieving sand collected from quadrats placed at regular intervals along a shore-normal transect starting from mean sea-level (MSL), and counting the number of individuals in each sample. For the Tylos europaeus population studied, males outnumbered females in seven of eight seasonal sampling sessions, with a mean male:female ratio of 1.46, although differences between the abundances of adult males and females were only statistically significantly different during the two spring seasons. Juveniles were consistently more abundant than adults, abundances ranging between 220-450 individuals/m3 for juveniles and between 450-3200 individuals/m3 for adults. Males consistently exhibited larger pereion sizes than females: mean pereion length was 1.91mm (± 0.43mm) for males and 1.79mm (± 0.39mm) for females.peer-reviewe

Integrating Survey and Molecular Approaches to Better Understand Wildlife Disease Ecology

Infectious wildlife diseases have enormous global impacts, leading to human pandemics, global biodiversity declines and socio-economic hardship. Understanding how infection persists and is transmitted in wildlife is critical for managing diseases, but our understanding is limited. Our study aim was to better understand how infectious disease persists in wildlife populations by integrating genetics, ecology and epidemiology approaches. Specifically, we aimed to determine whether environmental or host factors were stronger drivers of Salmonella persistence or transmission within a remote and isolated wild pig (Sus scrofa) population. We determined the Salmonella infection status of wild pigs. Salmonella isolates were genotyped and a range of data was collected on putative risk factors for Salmonella transmission. We a priori identified several plausible biological hypotheses for Salmonella prevalence (cross sectional study design) versus transmission (molecular case series study design) and fit the data to these models. There were 543 wild pig Salmonella observations, sampled at 93 unique locations. Salmonella prevalence was 41% (95% confidence interval [CI]: 37-45%). The median Salmonella DICE coefficient (or Salmonella genetic similarity) was 52% (interquartile range [IQR]: 42-62%). Using the traditional cross sectional prevalence study design, the only supported model was based on the hypothesis that abundance of available ecological resources determines Salmonella prevalence in wild pigs. In the molecular study design, spatial proximity and herd membership as well as some individual risk factors (sex, condition score and relative density) determined transmission between pigs. Traditional cross sectional surveys and molecular epidemiological approaches are complementary and together can enhance understanding of disease ecology: abundance of ecological resources critical for wildlife influences Salmonella prevalence, whereas Salmonella transmission is driven by local spatial, social, density and individual factors, rather than resources. This enhanced understanding has implications for the control of diseases in wildlife populations. Attempts to manage wildlife disease using simplistic density approaches do not acknowledge the complexity of disease ecology

The national helpline during the COVID-19 pandemic : a pillar of support for the public

Soon after the onset of the COVID-19 pandemic in Malta in March 2020, the number of calls from the public escalated so much that a helpline service, Helpline 111, was set at a private call centre. Calls from the public were answered by a team of trained agents, supported onsite by officials from the Public Health Response Team. The reasons for the calls varied and guidelines for answering the calls were continuously updated in line with the current standards and mitigation measures.peer-reviewe

A longitudinal analysis of trends in the number of positive cases and swabbing activities during the first eighteen months of the COVID-19 pandemic in Malta

In March 2020, at the onset of the COVID-19 pandemic teams were set up to execute the processes needed to implement COVID-19 related activities. The Helpline team was responsible for the booking of appointments for swabbing, the first step in the process. The Helpline also received calls from the public for other reasons.peer-reviewe

Role of T198 Modification in the Regulation of p27Kip1 Protein Stability and Function

The tumor suppressor gene p27Kip1 plays a fundamental role in human cancer progression. Its expression and/or functions are altered in almost all the different tumor histotype analyzed so far. Recently, it has been demonstrated that the tumor suppression function of p27 resides not only in the ability to inhibit Cyclins/CDKs complexes through its N-terminal domain but also in the capacity to modulate cell motility through its C-terminal portion. Particular interest has been raised by the last amino-acid, (Threonine 198) in the regulation of both protein stability and cell motility

SINEUP non-coding RNAs rescue defective frataxin expression and activity in a cellular model of Friedreich's Ataxia

Friedreich's ataxia (FRDA) is an untreatable disorder with neuro- and cardio-degenerative progression. This monogenic disease is caused by the hyper-expansion of naturally occurring GAA repeats in the first intron of the FXN gene, encoding for frataxin, a protein implicated in the biogenesis of iron-sulfur clusters. As the genetic defect interferes with FXN transcription, FRDA patients express a normal frataxin protein but at insufficient levels. Thus, current therapeutic strategies are mostly aimed to restore physiological FXN expression. We have previously described SINEUPs, natural and synthetic antisense long non-coding RNAs, which promote translation of partially overlapping mRNAs through the activity of an embedded SINEB2 domain. Here, by in vitro screening, we have identified a number of SINEUPs targeting human FXN mRNA and capable to up-regulate frataxin protein to physiological amounts acting at the post-transcriptional level. Furthermore, FXN-specific SINEUPs promote the recovery of disease-associated mitochondrial aconitase defects in FRDA-derived cells. In summary, we provide evidence that SINEUPs may be the first gene-specific therapeutic approach to activate FXN translation in FRDA and, more broadly, a novel scalable platform to develop new RNA-based therapies for haploinsufficient diseases