Relationship between in feed drugs, antibiotics and organic enrichment in marine sediments at Canadian Atlantic salmon aquaculture sites.

The presence of in-feed anti-sea lice drugs and their relationship with organic enrichment is poorly understood in sediment surrounding salmon farms. Using data from an aquaculture monitoring program (2018-2020), we describe this relationship at ten sites in four Canadian provinces. Three anti-sea lice pesticides (lufenuron, teflubenzuron, emamectin benzoate and metabolite desmethyl emamectin benzoate), and one antibiotic (oxytetracycline) were detected. Concentrations were often below limits of quantification. Values are also lower than those reported in other aquaculture salmon-producing countries. Highest concentrations, along with organic enrichment, were observed ~200 m of cages with lower concentrations detected up to 1.5 km away. Most samples had at least two drugs present: 75.2 % (British Columbia), 91.4 % (Newfoundland), and 54.8 % (New Brunswick/Nova Scotia) highlighting the potential for cumulative effects. Emamectin benzoate and oxytetracycline were detected four and three years respectively after last known treatments, demonstrating the need for research on overall persistence of compounds.

Assessing trace-elements as indicators of marine finfish aquaculture across three distinct Canadian coastal regions.

Several trace-elements have been identified as indicators of finfish aquaculture organic enrichment. In this study, sediment sampling at finfish farms was completed as part of an Aquaculture Monitoring Program in three distinct Canadian regions. Despite diverse datasets, multivariate analyses show a consistent clustering of known direct (Cu and Zn) and indirect (Cd, Mo and U) tracers of aquaculture activities with sediment organic matter (OM) and/or total dissolved sulfides concentrations. OM content was also a predictor of Cu, Zn, Mo and U concentrations according to decision tree analyses. Distance from cages did not emerge as a strong driver of differences among sampling points; however, a tendency towards negative associations is clear especially for Zn. Enriched stations as determined after geochemical normalization were mostly localized within 150 m of net-pens. Selected trace-elements (in particular Zn) can be useful indicators of aquaculture organic enrichment in different ecosystems and valuable tools for monitoring programs.

Workplace injury data reported by occupational physicians and general practitioners.

BACKGROUND: Accurate workplace injury data are useful in the prioritization of prevention strategies. In the UK, physicians report workplace ill-health data within The Health and Occupation Research (THOR) network, including injury case reports. AIMS: To compare workplace injury data reported by occupational physicians (OPs) and general practitioners (GPs) to THOR. METHODS: Injury cases reported by OPs and GPs, reported to THOR between 2006 and 2012 were analysed. Demographics, industrial groups, nature of injury, kind of accident and site of injury were compared. Data on sickness absence for workplace injuries reported by GPs were investigated. RESULTS: In total, 2017 workplace injury cases were reported by OPs and GPs. Males were more likely to sustain a workplace accident than females. Sprains and strains were reported most often, with the upper limbs being affected most frequently. Slips, trips and falls were identified as important causal factors by both OPs and GPs. Psychological injuries also featured in THOR reporting, with a higher proportion reported by OPs (21%) than by GPs (3%). The proportion of people classified as 'unfit' by GPs reduced following the introduction of the 'fit' note. CONCLUSIONS: THOR reports returned by OPs and GPs provide a valuable source of information of workplace injury data, and complement other sources of information, such as the Reporting of Injuries, Diseases and Dangerous Occurrences Regulations and the Labour Force Survey.

Family to work conflict and the usefulness of workplace support.

BACKGROUND: While much is known about the effect of work stress on an employee's home life, less is known about the opposite effect, that of domestic worries upon work performance. AIMS: To investigate employee perceptions about the effect of family to work conflict (FWC) on work. METHODS: An online anonymous survey tool was developed and sent to all employees reporting to a single onsite human resources (HR) department at a UK research and development plant. FWC included family and other domestic stressors. Work effects studied included those on business travel, work performance and the awareness and usefulness of work-provided support. RESULTS: The sample size was 286 and response rate was 58%. Approximately two-thirds of respondents reported requiring time away from work for domestic reasons in the previous 5 years. The role of domestic stressors not related to care giving was significant. Support from line-managers and colleagues was important, and the perceived usefulness of in-house occupational health (OH) by business travellers was significant. Only 53% of the workforce said they knew of the Employee Assistance Programme (EAP), although 70% of users found it beneficial and usage was higher in females. CONCLUSIONS: All forms of FWC affected work performance, including when on business travel. FWC arose from caring responsibilities but also from financial and relationship problems, which are potentially amenable to help from EAPs. Line-managers and colleagues were the primary sources of workplace support. The in-house OH service and the EAP were underutilized and they may require popularizing with employees.

[Maxillar osteonecrosis associated with bisphosphonate treatment and dental implants]. / Ostéonécrose maxillaire sous bisphosphonates et implants dentaires.

INTRODUCTION: Bisphosphosnates are reference products used to treat osteoporosis, malignant bone disease, Paget's disease, and hypercalcemia. However these drugs seem to induce osteonecrosis of the jaws. This osteonecrosis is frequently observed and must be evoked in patients presenting with oral ulceration under bisphosphonate therapy. OBSERVATION: We report the case of a long-term fully dental implanted patient treated by bisphosphonates who presented a maxillar ostenecrosis with no previous radiotherapy. DISCUSSION: The risk factors and mechanism of this induced osteonecrosis are described. But could long term osseo-integrated dental implants be a triggering factor?

Hydrographics and the timing of infectious salmon anemia outbreaks among Atlantic salmon (Salmo salar L.) farms in the Quoddy region of Maine, USA and New Brunswick, Canada.

Infectious salmon anemia (ISA) has caused severe morbidity and mortality in farmed Atlantic salmon in North America, Norway, Scotland and the Faroe Islands. The Quoddy region of Maine, United States of America (USA), and New Brunswick (NB), Canada is characterized by extensive tidal mixing and close proximity between farms. This region is also prone to recurrent appearances of ISA, though control measures limit disease spread and severity on infected farms. We conducted a retrospective longitudinal analysis of the apparent impact of hydrographics on the incidence and timing of ISA outbreaks on Atlantic salmon (Salmo salar L.) farms in the Quoddy region from May 2002 to August 2004. A time-series cross-sectional regression of 32 farms over 28 months demonstrated a limited, but statistically significant, spatio-temporal clustering of ISA outbreaks linked hydrographically. New outbreaks correlated temporally with those occurring on-site 1 and 3 months prior, and those occurring within one tidal-excursion upstream the same month. Other risk factors included holdover of previous year-class fish, wharf sharing, and possibly harvests of cages infected in previous months. Conclusions suggest that tidal dispersion does play a role in ISAV transmission in the Quoddy region. Dispersal of free virus and/or tidal distribution of lice or other hydrographically influenced vectors or fomites could all contribute to the spatio-temporal patterns described.

The effect of transdermal nicotine patches on sleep and dreams.

This study was undertaken to determine the effect of 24-h transdermal nicotine patches on sleep and dream mentation in 15 smokers aged 20 to 33. Utilising a repeated measures design, it was found that more time awake and more ASDA micro-arousals occurred while wearing the nicotine patch compared to placebo. Also, the percentage of REM sleep decreased, but REM latency and the proportion of time spent in NREM sleep stages did not change significantly. Dream reports containing visual imagery, visual imagery ratings and the number of visualizable nouns were significantly greater from REM compared to Stage 2 awakenings, regardless of patch condition. However, a general interaction effect was observed. Stage 2 dream variables remained equivalent across nicotine and placebo conditions. Within REM sleep, more dream reports containing visual imagery occurred while wearing the nicotine patch, and these were rated as more vivid. The greater frequency of visual imagery reports and higher imagery ratings specifically from REM sleep suggests that previously reported dreaming side effects from 24-h nicotine patches may be specific to REM sleep. Combined with previous animal studies showing that transdermally delivered nicotine blocks PGO activity in REM sleep, the current results do no appear consistent with PGO-based hypotheses of dreaming, such as the Activation-Synthesis (AS) or Activation, Input and Modulation (AIM) models.

Repair of 8-oxoguanine and Ogg1-incised apurinic sites in a CHO cell line.

The repair mechanisms involved in the removal of 8-oxo-7,8-dihydroguanine (8-oxoG) in damaged DNA have been investigated using cell-free extracts or purified proteins. However, in vivo repair assays are required to further dissect mechanisms involved in the repair of 8-oxoG in the cellular context. In this study, we analyzed the removal of 8-oxoG from plasmids that contain a single 8-oxoG.C base pair in a sequence that can be transcribed (TS) or nontranscribed (NTS) in a chinese hamster ovary (CHO) cell line. The results show that 8-oxoG located in a TS is removed faster than in a NTS, indicating transcription-coupled repair (TCR) of 8-oxoG in rodent cells. The results also show that CHO cells efficiently repair DNA molecules that contain an Ogg1-incised AP site, which is the first intermediate in the course of base excision repair of 8-oxoG.

Dispersion and toxicity to non-target aquatic organisms of pesticides used to treat sea lice on salmon in net pen enclosures.

Pesticides are used extensively in the finfish aquaculture industry to control sea lice infestations on farmed salmon. The most prevalent method of use is to enclose a net pen with an impervious tarpaulin and mix a pesticide solution within that enclosure. After treatment for short periods (1 h) the pesticide solution is released to the environment. Concerns have been raised that there is a potential risk to non-target aquatic organisms from those releases. The fate of dispersing pesticide solutions was measured after six simulated treatments in the Lower Bay of Fundy, New Brunswick. Three simulated treatments were done with azamethiphos and three with cypermethrin. Rhodamine dye was added to all pesticide solutions in order to facilitate tracking of the dispersing plume through real-time measurements of dye concentrations by a flow-through fluorometer coupled with a differential global positioning system (DGPS). Water samples were obtained from within the plumes at various times after release and analysed for pesticide content and toxicity to a benthic amphipod Eohaustorius estuaris. Dye concentrations were detectable for time periods after release which varied from 2 to 5.5 h. Distances travelled by the dye patches ranged from 900 to 3000 m and the dye concentrations at the final sampling period were generally 1/200-1/3000 the pre-release concentrations and cypermethrin concentrations were generally 1/1000-1/2000 the pre-release concentrations. Cypermethrin concentrations in water samples were closely correlated with dye concentrations, indicating that dye analyses were an accurate surrogate for cypermethrin concentrations. Most samples taken after the releases of azamethiphos were not toxic to test organisms in 48 h exposures and none were beyond 20 min post-release. By contrast, almost all samples taken after the release of cypermethrin, even up to 5-h post-release, were toxic. Data indicate the potential to cause toxic effects over areas of hectares from a single release of cypermethrin.

Osmoregulated periplasmic glucan synthesis is required for Erwinia chrysanthemi pathogenicity.

Erwinia chrysanthemi is a phytopathogenic enterobacterium causing soft rot disease in a wide range of plants. Osmoregulated periplasmic glucans (OPGs) are intrinsic components of the gram-negative bacterial envelope. We cloned the opgGH operon of E. chrysanthemi, encoding proteins involved in the glucose backbone synthesis of OPGs, by complementation of the homologous locus mdoGH of Escherichia coli. OpgG and OpgH show a high level of similarity with MdoG and MdoH, respectively, and mutations in the opgG or opgH gene abolish OPG synthesis. The opg mutants exhibit a pleiotropic phenotype, including overproduction of exopolysaccharides, reduced motility, bile salt hypersensitivity, reduced protease, cellulase, and pectate lyase production, and complete loss of virulence. Coinoculation experiments support the conclusion that OPGs present in the periplasmic space of the bacteria are necessary for growth in the plant host.

BRCA1 and BRCA2 are necessary for the transcription-coupled repair of the oxidative 8-oxoguanine lesion in human cells.

The breast and ovarian cancer susceptibility genes, BRCA1 and BRCA2, are likely to participate in DNA lesion processing. Oxidative lesions, such as 8-oxoguanine, occur in DNA after endogenous or exogenous oxidative stress. We show that deficiency for either BRCA1 or BRCA2 in human cancer cells leads to a block of the RNA polymerase II transcription machinery at the 8-oxoguanine site and impairs the transcription-coupled repair of the lesion, leading to a high mutation rate. Expression of wild-type BRCA1 from a recombinant adenovirus fully complements the repair defect in BRCA1-deficient cells. These results represent the first demonstration of the essential contribution of BRCA1 and BRCA2 gene products in the repair of the 8-oxoguanine oxidative damage specifically located on the transcribed strand in human cells. This suggests that cells from individuals predisposed to breast and/or ovarian cancer may undergo a high rate of mutations because of the deficiency of this damage repair pathway after oxidative stress.

Transcription coupled repair of 8-oxoguanine in murine cells: the ogg1 protein is required for repair in nontranscribed sequences but not in transcribed sequences.

To assess the role of the Ogg1 DNA glycosylase in the transcription-coupled repair (TCR) of the mutagenic lesion, 7, 8-dihydro-8oxoguanine (8-OxoG), we have investigated the removal of this lesion in wild-type and ogg1(-/-) null mouse embryo fibroblast (MEF) cell lines. We used nonreplicating plasmids containing a single 8-OxoG.C base pair in a different assay that allowed us to study the removal of 8-OxoG located in a transcribed sequence (TS) or in a nontranscribed sequence (NTS). The results show that the removal of 8-OxoG in a wild-type MEF cell line is faster in the TS than in the NTS, indicating TCR of 8-OxoG in murine cells. In the homozygous ogg1(-/-) MEF cell line, 8-OxoG was not removed from the NTS whereas there was still efficient 8-OxoG repair in the TS. Expression of the mouse Ogg1 protein in the homozygous ogg1(-/-) cell line restored the ability to remove 8-OxoG in the NTS. Therefore, we have demonstrated that Ogg1 is essential for the repair of 8-OxoG in the NTS but is not required in the TS. These results indicate the existence of an Ogg1-independent pathway for the TCR of 8-OxoG in vivo.

Mutation spectra induced by replication of two vicinal oxidative DNA lesions in mammalian cells.

Ionizing radiations often induce multiple and clustered DNA lesions at the site of DNA interaction. As a model, we have studied the toxicity and the mutagenicity of two adjacent oxidative bases as clustered DNA lesions in mammalian cells using shuttle vectors. The chosen oxidative lesions were 8-oxo-7,8-dihydroguanine, the formylamine residue resulting from the oxidation of a pyrimidine base and the tandem lesion 8-oxo-7,8-dihydroguanine/formylamine where both modifications are located at a vicinal position. A single-stranded DNA shuttle vector carrying a unique DNA lesion was constructed, transfected into simian COS7 cells and mutations induced after replication in mammalian cells were screened in bacteria. 8-oxo-7,8-dihydroguanine, as expected, does not affect greatly survival (70% bypass) whereas formylamine and the tandem lesions are blocking alterations, DNA polymerase bypass being of 45% and 17%, respectively. Base insertion opposite the lesion was studied. Under our experimental conditions, replication of 8-oxo-7, 8-dihydroguanine finally gives rise to guanine:cytosine pairing, rendering this lesion only slightly mutagenic. This is not the case for the formylamine that codes preferentially for adenine (71%). In addition, one-base deletions were observed targeted to the site to the lesion. Cytosine and thymine were inserted opposite the lesion with similar but low frequencies. Thus, coding properties of the formylamine render this residue very mutagenic when coming from the oxidative alteration of a cytosine. The coding properties of the tandem damage are a combination of the contribution of the two isolated lesions with a very high percentage of adenine insertion (94%) opposite the formylamine residue of the tandem lesion. The toxicity as well as the mutation spectrum of the tandem lesion allow us to speculate about the molecular mechanism with which the DNA polymerase replicates these two lesions.

Transcription-coupled repair of 8-oxoguanine: requirement for XPG, TFIIH, and CSB and implications for Cockayne syndrome.

Analysis of transcription-coupled repair (TCR) of oxidative lesions here reveals strand-specific removal of 8-oxo-guanine (8-oxoG) and thymine glycol both in normal human cells and xeroderma pigmentosum (XP) cells defective in nucleotide excision repair. In contrast, Cockayne syndrome (CS) cells including CS-B, XP-B/CS, XP-D/CS, and XP-G/CS not only lack TCR but cannot remove 8-oxoG in a transcribed sequence, despite its proficient repair when not transcribed. The XP-G/CS defect uniquely slows lesion removal in nontranscribed sequences. Defective TCR leads to a mutation frequency at 8-oxoG of 30%-40% compared to the normal 1%-4%. Surprisingly, unrepaired 8-oxoG blocks transcription by RNA polymerase II. These data imply that TCR is required for polymerase release to allow repair and that CS results from defects in TCR of oxidative lesions.

A phase I/II study of intensive dose escalation of cytarabine in combination with idarubicin and etoposide in induction and consolidation treatment of adult acute myeloid leukemia. Australian Leukaemia Study Group (ALSG).

To determine the safety and efficacy of the combination of idarubicin, cytarabine and etoposide ("ICE") for induction and consolidation treatment of acute myeloid leukemia (AML), and of dose-intensification of cytarabine in this setting, 54 previously untreated patients in three cohorts were studied by sequential dose escalation of cytarabine, in combination with standard doses of idarubicin and etoposide. Cytarabine was given to Cohort 1 at the conventional dosage of 100 mg/m2 per day by continuous infusion for 7 days in induction and 5 days in consolidation; to Cohort 2 at high-dose (HiDAC) (3 g/m2 intravenously twice daily on days 1, 3, 5 and 7) during induction with conventional dosage during consolidation; to Cohort 3 HiDAC was given for both induction and consolidation. In addition, Cohort 3 patients received lenograstim (Granocyte; rHuG-CSF) after both induction and consolidation courses. We found that there was no significant difference between the three cohorts in hematological toxicity in induction, but that HiDAC was associated with a greater incidence of gastro-intestinal toxicities. There was no difference in induction mortality between the three cohorts, which was 11% overall. Consolidation with HiDAC led to a significant increase in hematological toxicity. Overall, the complete remission (CR) rate was 80% with no significant difference between the three regimens. The estimated disease free survival at 3 years was 28%, 67% and 54% respectively for Cohorts 1, 2 and 3 with an estimated overall survival of 38%, 63% and 47%. We conclude that cytarabine dosage can be escalated safely in combination with idarubicin and etoposide in both induction and consolidation. The combination is effective for induction treatment of AML and its side-effects appear similar to those of standard regimens. Whether its use offers long-term benefits compared with standard regimens is the subject of ongoing controlled randomized studies.

Repair and mutagenesis survey of 8-hydroxyguanine in bacteria and human cells.

8-Hydroxyguanine is one of the major products formed by the reactive oxygen species which are generated in living cells as a consequence of either the normal metabolic pathways or an exogeneous chemical or physical stress. The production of the oxidative damage is described and the different repair pathways of the oxidative lesions are analyzed from bacteria to human cells. Analysis of repair in human cells harboring different deficiencies in the nucleotide excision repair mechanism such as xeroderma pigmentosum cells from different complementation groups and cells from Cockayne's syndrome patients allows us to emphasize the possibility of the intervention of this repair mechanism on the elimination of oxidative damages. Finally, a repair model of oxidative lesions is proposed.

A review of mental health morbidity associated with OFSTED inspections of schools in one metropolitan local authority.

Anecdotally there appeared to be a relationship between OFSTED inspections and mental health morbidity. This study was set up to examine this relationship in one metropolitan local authority. Inspected schools were matched with schools from the same local authority that were not inspected. The rate of sickness absence per 100 whole time equivalent staff in inspected schools was 5.4 as compared with 2.1 in matched schools. The relative risk of a spell of sickness absence due to mental ill-health in an inspected versus an uninspected school was 2.52 (95% confidence interval = 1.19-5.31). The study indicates that there may be a relationship between the OFSTED inspection process and mental health morbidity. Some recommendations are made.

Repair and mutagenic potency of 8-oxoG:A and 8-oxoG:C base pairs in mammalian cells.

Replication of the oxidative lesion 8-oxo-7,8-dihydroguanine (GO) leads to the formation of both 8-oxo-7,8-dihydroguanine:adenine (GO:A) and 8-oxo-7,8-di-hydroguanine:cytosine (GO:C) pairs. The repair and mutagenic potency of these two kinds of base pairs were studied in simian COS7 and human MRC5V1 cells using the shuttle vector technology. Shuttle vectors carrying a unique GO residue opposite either a C or an A were constructed, then transfected into recipient mammalian cells. DNA repair resulting in G:C pairs and mutation frequency, were determined using resistance to digestion by the Ngo MI restriction enzyme for screening and DNA sequencing of suspect mutants. Results showed that the GO:C mismatch was well repaired since almost no mutations were detected in the plasmid progeny obtained 72 h after cell transfection. The GO:A pair was poorly repaired since only 32-34% of the plasmid progeny contained G:C whereas two thirds contained A:T at the original site. Repair kinetics measured with a non-replicating vector deleted by 13 bp at the SV40 replication origin, showed that GO:A was slowly repaired. Only 30% of the mispairs were corrected in 12 h. During this time 100% of the plasmids containing GO:A pairs were replicated as seen by the replication kinetics in a vector with an intact SV40 replication origin. These results show that, under our experimental conditions, replication is occurring before completion of DNA repair which explains the high mutagenic potency of the GO:A mispair.