Malignant pleural mesothelioma incidence and survival in the Republic of Ireland 1994–2009

ObjectiveMalignant pleural mesothelioma (MPM) is a rare malignancy associated with exposure to asbestos. The protracted latent period of MPM means that its incidence has continued to rise across Europe after the introduction of restrictions on asbestos use. In order to obtain a clearer indication of trends in the Republic of Ireland (ROI), incidence and survival were assessed based on all MPM cases reported since the establishment of the National Cancer Registry of Ireland (NCR).MethodsNCR recorded 337 MPM diagnoses in the ROI during 1994–2009. Survival was assessed for all cases diagnosed with adequate follow-up (n = 330). Crude and European age-standardized incidence rates were calculated for all cases and for 4-year periods. A Cox model of observed (all-cause) survival was used to generate hazard ratios for the effect of: gender; age at diagnosis; diagnosis cohort; region of residence; histological type; and tumour stage. Single P-values for the variables indicated were calculated using either a stratified log-rank test or stratified trend test.ResultsOver the study period the age-standardized MPM incidence in the ROI rose from 4.98 cases per million (cpm) to 7.24 cpm. The 1-year survival rate for all MPM cases was 29.6% (CI 24.7–34.6%). Excess mortality risk was associated with age at diagnosis (75–89 yrs vs. 55–64 yrs, HR 1.88, 95% CI 1.35–2.63, P < 0.001) and tumour stage (III vs. I HR 1.57, 95% CI 1.00–2.48, P < 0.05; IV vs. I HR 1.55, 95% CI 1.08–2.21, P < 0.05). Age showed a significant survival trend (P < 0.001) but tumour stage did not (P = 0.150). There was significant heterogeneity between the survival of patients resident in different regions (P = 0.027).ConclusionMPM incidence and mortality continued to rise in the ROI after the restrictions on asbestos use and the predictors of survival detected in this study are broadly consistent with those identified for other countries.     

Differential regulation of cell death programs in males and females by Poly (ADP-Ribose) Polymerase-1 and 17 β estradiol

Cell death can be divided into the anti-inflammatory process of apoptosis and the pro-inflammatory process of necrosis. Necrosis, as apoptosis, is a regulated form of cell death, and Poly-(ADP-Ribose) Polymerase-1 (PARP-1) and Receptor-Interacting Protein (RIP) 1/3 are major mediators. We previously showed that absence or inhibition of PARP-1 protects mice from nephritis, however only the male mice. We therefore hypothesized that there is an inherent difference in the cell death program between the sexes. We show here that in an immune-mediated nephritis model, female mice show increased apoptosis compared to male mice. Treatment of the male mice with estrogens induced apoptosis to levels similar to that in female mice and inhibited necrosis. Although PARP-1 was activated in both male and female mice, PARP-1 inhibition reduced necrosis only in the male mice. We also show that deletion of RIP-3 did not have a sex bias. We demonstrate here that male and female mice are prone to different types of cell death. Our data also suggest that estrogens and PARP-1 are two of the mediators of the sex-bias in cell death. We therefore propose that targeting cell death based on sex will lead to tailored and better treatments for each gender.     

Trends and inequities in colorectal cancer screening participation in Ontario,Canada, 2005–2011

Background: Participation in screening tests for colorectal cancer (CRC) is generally low in Ontario, Canada. In addition, inequities in participation exist including lower participation among low-income individuals, males and individuals living in rural areas. In April 2008, Colon Cancer Check (CCC) program, the province-wide CRC screening program, was launched in Ontario. This study describes the trends and inequities in CRC screening participation three years before and three years after the CCC, and assesses the effect of the program on CRC screening participation, overall and among certain population groups. Methods: We used administrative data to identify cohorts of individuals eligible for CRC screening in fiscal years 2005–2011. We calculated the age-standardized percent of Fecal Occult Blood Test (FOBT) participation, large bowel endoscopy participation, and being ‘up-to-date’ with CRC screening tests. Results: From 2005 to 2011, FOBT participation increased from 7.6% to 14.8%, large bowel endoscopy participation from 3.4% to 5.7%, and ‘up-to-date’ with CRC screening from 27.2% to 41.3%. Before the launch of the CCC program, the quarterly increase in FOBT participation was 0.07% (p = 0.19), increased immediately after the launch (1.8%, p < 0.01), followed by a decline (?0.08%, p = 0.08), returning to its pre-program increase rate. We noted a significant decrease in FOBT participation every summer (?0.44%, p < 0.01). The CCC program had minimal effect on large bowel endoscopy participation. Before the launch of the CCC program, the quarterly increase in ‘up-to-date’ with CRC screening was 0.9% (p < 0.01), increased immediately after the launch (2.5%, p = 0.05), followed by a modest decline thereafter (?0.59%, p < 0.02). From 2005 to 2011, recent residents living in low-income neighborhoods were consistently and significantly less likely to have a FOBT and be ‘up-to-date’ with CRC screening than long-term residents living in high-income neighborhoods (2.9–4.5%; 14.7–17.3% respectively). Pre-CCC inequities in CRC participation persisted after the launch of the program. Conclusion: CRC testing was increasing in Ontario from 2005. An immediate increase in CRC testing, FOBT in particular, occurred after the launch of the CCC program, followed by a return to its pre-CCC increase rate thereafter. Future efforts are needed to improve screening participation and address inequities.     

Trends in hospital admissions for adverse drug reactions in England: analysis of national hospital episode statistics 1998–2005

Background  

Adverse drug reactions (ADRs) are a frequent cause of mortality and morbidity to patients worldwide, with great associated costs to the healthcare providers including the NHS in England. We examined trends in hospital admissions associated with adverse drug reaction in English hospitals and the accuracy of national reporting.     

β-Hairpin Loop of Eukaryotic Initiation Factor 1 (eIF1) Mediates 40 S Ribosome Binding to Regulate Initiator tRNAMet Recruitment and Accuracy of AUG Selection in Vivo

Recognition of the translation initiation codon is thought to require dissociation of eIF1 from the 40 S ribosomal subunit, enabling irreversible GTP hydrolysis (P_i release) by the eIF2·GTP·Met-tRNA_i ternary complex (TC), rearrangement of the 40 S subunit to a closed conformation incompatible with scanning, and stable binding of Met-tRNA_i to the P site. The crystal structure of a Tetrahymena 40 S·eIF1 complex revealed several basic amino acids in eIF1 contacting 18 S rRNA, and we tested the prediction that their counterparts in yeast eIF1 are required to prevent premature eIF1 dissociation from scanning ribosomes at non-AUG triplets. Supporting this idea, substituting Lys-60 in helix α1, or either Lys-37 or Arg-33 in β-hairpin loop-1, impairs binding of yeast eIF1 to 40 S·eIF1A complexes in vitro, and it confers increased initiation at UUG codons (Sui⁻ phenotype) or lethality, in a manner suppressed by overexpressing the mutant proteins or by an eIF1A mutation (17–21) known to impede eIF1 dissociation in vitro. The eIF1 Sui⁻ mutations also derepress translation of GCN4 mRNA, indicating impaired ternary complex loading, and this Gcd⁻ phenotype is likewise suppressed by eIF1 overexpression or the 17–21 mutation. These findings indicate that direct contacts of eIF1 with 18 S rRNA seen in the Tetrahymena 40 S·eIF1 complex are crucial in yeast to stabilize the open conformation of the 40 S subunit and are required for rapid TC loading and ribosomal scanning and to impede rearrangement to the closed complex at non-AUG codons. Finally, we implicate the unstructured N-terminal tail of eIF1 in blocking rearrangement to the closed conformation in the scanning preinitiation complex.     

Trends in myeloma incidence,mortality and survival in New Zealand (1985–2016)

BackgroundMyeloma, one of the most common haematological malignancies worldwide arises in the bone marrow. Incidence rates vary by age and ethnicity but reasons behind these trends are unknown. Treatment of myeloma has changed significantly over recent decades, resulting in longer survival and decreased mortality.MethodsFrom data supplied by the Ministry of Health, all new registrations of and deaths from myeloma between 1985 and 2016 were extracted. Trends in age-specific rates were assessed using the method of Armitage. Age-standardised rates were calculated, and trends in age-adjusted rates analysed using the Mantel-Haenszel extension chi-square test. Age-adjusted incidence and mortality rate ratios were calculated. Myeloma-specific survival was visualised using Kaplan-Meier curves and multivariable hazard ratios calculated using Cox regression.ResultsBetween 1985 and 2016, 7826 New Zealanders were registered with myeloma. Over this time the age-specific incidence of myeloma increased significantly for men, who had higher rates than women. Myeloma mortality was highest in Maori men. Men had higher mortality rates than women in all time periods. Since 1995–1999, mortality has decreased in women whereas in men it has declined since about 2000–2004. Survival has increased significantly since 1990 but Maori still have a higher risk of death than non-Maori.ConclusionThe patterns of variation in myeloma incidence, mortality and survival, as well as their trends over time may be used to assist research into the causes and management of myeloma in New Zealand.     

National trends in rates of death and hospital admissions related to acute myocardial infarction,heart failure and stroke, 1994–2004

Background

Rates of death from cardiovascular and cerebrovascular diseases have been steadily declining over the past few decades. Whether such declines are occurring to a similar degree for common disorders such as acute myocardial infarction, heart failure and stroke is uncertain. We examined recent national trends in mortality and rates of hospital admission for these 3 conditions.

Methods

We analyzed mortality data from Statistic Canada’s Canadian Mortality Database and data on hospital admissions from the Canadian Institute for Health Information’s Hospital Morbidity Database for the period 1994–2004. We determined age- and sex-standardized rates of death and hospital admissions per 100 000 population aged 20 years and over as well as in-hospital case-fatality rates.

Results

The overall age- and sex-standardized rate of death from cardiovascular disease in Canada declined 30.0%, from 360.6 per 100 000 in 1994 to 252.5 per 100 000 in 2004. During the same period, the rate fell 38.1% for acute myocardial infarction, 23.5% for heart failure and 28.2% for stroke, with improvements observed across most age and sex groups. The age- and sex-standardized rate of hospital admissions decreased 27.6% for stroke and 27.2% for heart failure. The rate for acute myocardial infarction fell only 9.2%. In contrast, the relative decline in the inhospital case-fatality rate was greatest for acute myocardial infarction (33.1%; p < 0.001). Much smaller relative improvements in case-fatality rates were noted for heart failure (8.1%) and stroke (8.9%).

Interpretation

The rates of death and hospital admissions for acute myocardial infarction, heart failure and stroke in Canada changed at different rates over the 10-year study period. Awareness of these trends may guide future efforts for health promotion and health care planning and help to determine priorities for research and treatment.Cardiovascular disease, including stroke, is the leading cause of death globally. Therefore, changes in the incidence and mortality of these disorders have a major impact on the overall health of a country’s population and on the health care system.¹ Rates of death from cardiovascular and cerebrovascular disease have been steadily declining in Western Europe and North America for the past 3 decades.^2,3 Whether this decline is occurring to a similar degree for common conditions such as acute myocardial infarction, heart failure and stroke is uncertain. Although these 3 conditions are associated with several common risk factors, the relative importance of risk factors such as smoking, hypertension and hyperlipidemia differs between them.⁴ Furthermore, the rate of new therapeutic advances for these conditions has varied in both the acute, in-hospital setting and in the outpatient setting, where primary and secondary prevention of events occurs.A comparative evaluation of recent population-based trends in incidence and mortality would provide an assessment of the relative progress achieved in preventing and treating these important conditions. Furthermore, the substantial economic impact of cardiovascular disease, including stroke, on the health care system — estimated at $18 billion per year in direct and indirect costs in Canada in 1998⁵ — underscores the need for continued monitoring of cardiovascular disease and treatment outcomes. A study of temporal trends could also help guide future health promotion activities and health care planning.We conducted a study of recent trends in the rates of death and hospital admissions for acute myocardial infarction, heart failure and stroke in Canada from 1994 to 2004. We also studied whether changes in these trends occurred at similar rates in younger and older Canadians and in both sexes.     

Trends in stage-specific population-based survival of cancer patients in the Czech Republic in the period 2000–2008

BackgroundThe objective of this study was to assess trends in overall and in stage-specific 5-year relative survival rates of the Czech cancer patients between periods 2000–2004 and 2005–2008.MethodsAll Czech cancer patients diagnosed between 1995 and 2008 were included in the analysis. Period analysis was employed to calculate 5-year relative survival for 21 cancers.ResultsSignificant improvements in crude 5-year relative survival for 14 of 21 assessed types of cancer, including the most frequent diagnoses, such as, colorectal, prostate, breast, lung, kidney, pancreatic, and bladder cancer and melanoma, were identified. Moreover, in case of colorectal, lung, and prostate cancer, improvement in stage-specific 5-year relative survival was confirmed as statistically significant for all clinical stages. No diagnosis showed significant decrease in the 5-year relative survival. However, the 5-year relative survival remained poor in patients with metastatic cancers at diagnosis, particularly in case of liver, pancreatic, lung, and oesophageal cancer.ConclusionsThe cancer-specific outcomes in the Czech Republic are improving. Nevertheless, despite the overall significant improvement in 5-year relative survival of most of the cancer diagnoses, the high proportion of patients primarily diagnosed with metastatic cancer still represents a substantial challenge for prevention and early detection.     

Trends in antibiotic resistance in Prevotella species from patients of the University Hospital of Maxillofacial Surgery,Sofia, Bulgaria,in 2003–2009

Head-and-neck infections often involve anaerobes such as Prevotella species. Aim of the present study was to assess the evolution and the factors associated with resistance in Prevotella species to penicillin, clindamycin, metronidazole, tetracycline and β-lactams/β-lactamase inhibitors (BL/BLIs). In total, 192 Prevotella strains, isolated from patients with oral and head-and-neck infections, were evaluated. Common isolates were Prevotella intermedia and Prevotella melaninogenica within the pigmented species as well as Prevotella oris and Prevotella oralis group within the non-pigmented species. Overall resistance was 43.2% for penicillin, 10.9% for clindamycin, 0% for metronidazole. Nonsusceptibility to tetracycline was 29.1% without significant differences in resistance rates between pigmented and other species. Penicillin resistant strains were β-lactamase positive. From 2003–2004 to 2007–2009, penicillin resistance rates increased about four-fold (from 15.4% to 60.6%). Clindamycin resistance did not show evolution, whereas tetracycline nonsusceptibility decreased from 43.3% in 2003–2004 to 20.7% in 2007–2009. Except for one (0.5%) P. oralis strain with intermediate susceptibility to BL/BLIs, the other strains were susceptible to the agents. In conclusion, in Prevotella strains from patients with head-and-neck infections, the resistance rate to penicillin increased, that to clindamycin remained stable and the nonsusceptibility rate to tetracycline decreased during the period. Activity against >99% of Prevotella strains was observed with metronidazole and BL/BLIs. The penicillin resistance and tetracycline nonsusceptibility were associated with the year of study, national antibiotic consumption and possibly with previous treatment (for tetracycline). The evolution of penicillin resistance in Prevotella strains was highly dynamic.     

‘From Death,Lead Me to Immortality’ – Mantra of Ageing Skeletal Muscle

Skeletal muscle is a post-mitotic tissue maintained by repair and regeneration through a population of stem cell-like satellite cells. Following muscle injury, satellite cell proliferation is mediated by local signals ensuring sufficient progeny for tissue repair. Age–related changes in satellite cells as well as to the local and systemic environment potentially impact on the capacity of satellite cells to generate sufficient progeny in an ageing organism resulting in diminished regeneration. ‘Rejuvenation’ of satellite cell progeny and regenerative capacity by environmental stimuli effectors suggest that a subset of age-dependent satellite cell changes may be reversible. Epigenetic regulation of satellite stem cells that include DNA methylation and histone modifications which regulate gene expression are potential mechanisms for such reversible changes and have been shown to control organismal longevity. The area of health and ageing that is likely to benefit soonest from advances in the biology of adult stem cells is the emerging field of regenerative medicine. Further studies are needed to elucidate the mechanisms by which epigenetic modifications regulate satellite stem cell function and will require an increased understanding of stem-cell biology, the environment of the aged tissue and the interaction between the two.     

1H–NMR Metabolomic Biomarkers of Poor Outcome after Hemorrhagic Shock are Absent in Hibernators

Background

Hemorrhagic shock (HS) following trauma is a leading cause of death among persons under the age of 40. During HS the body undergoes systemic warm ischemia followed by reperfusion during medical intervention. Ischemia/reperfusion (I/R) results in a disruption of cellular metabolic processes that ultimately lead to tissue and organ dysfunction or failure. Resistance to I/R injury is a characteristic of hibernating mammals. The present study sought to identify circulating metabolites in the rat as biomarkers for metabolic alterations associated with poor outcome after HS. Arctic ground squirrels (AGS), a hibernating species that resists I/R injury independent of decreased body temperature (warm I/R), was used as a negative control.

Methodology/principal findings

Male Sprague-Dawley rats and AGS were subject to HS by withdrawing blood to a mean arterial pressure (MAP) of 35 mmHg and maintaining the low MAP for 20 min before reperfusing with Ringers. The animals’ temperature was maintained at 37±0.5°C for the duration of the experiment. Plasma samples were taken immediately before hemorrhage and three hours after reperfusion. Hydrophilic and lipid metabolites from plasma were then analyzed via ¹H–NMR from unprocessed plasma and lipid extracts, respectively. Rats, susceptible to I/R injury, had a qualitative shift in their hydrophilic metabolic fingerprint including differential activation of glucose and anaerobic metabolism and had alterations in several metabolites during I/R indicative of metabolic adjustments and organ damage. In contrast, I/R injury resistant AGS, regardless of season or body temperature, maintained a stable metabolic homeostasis revealed by a qualitative ¹H–NMR metabolic profile with few changes in quantified metabolites during HS-induced global I/R.

Conclusions/significance

An increase in circulating metabolites indicative of anaerobic metabolism and activation of glycolytic pathways is associated with poor prognosis after HS in rats. These same biomarkers are absent in AGS after HS with warm I/R.     

Trends in cancer incidence in the Republic of Mauritius, 1991–2015

IntroductionMauritius, a small state, is among the few African countries where cancer registration is population based and nationwide. We reported trends in cancer incidence for twenty five years as well as the mortality to incidence ratio (MIR) as main quality indicator of the Mauritius National Cancer Registry (MNCR).Materials and methodsWe calculated age standardised incidence rates (ASRs) of cancers by sex and by 5 year age group for five successive year periods from 1991 to 2015. The average annual percentage change (AAPC) were determined by sex and cancer sites. MIRs were compared for the period 2001–2004 and 2012–2015.ResultsIn males, the most common cancer sites (in terms of ASRs per 100,000) were those of the colon-rectum (17.0), prostate (16.5), trachea-bronchus-lung (13.0), stomach (8.4) and lip-oral cavity-pharynx (7.7). The AAPC were +3.9%, +4.2%, +0.5%, -0.1% and -1.3% respectively. In females, the most frequent sites were breast (53.7), colon-rectum (13.2), cervix uteri (11.2), corpus uteri (7.7) and ovary (5.7). The AAPC were +3.4%, +4.4%, -2%, +5.2% and -0.1% respectively. The most significant decrease in MIRs among males were liver (1.9 to 1.0), stomach (1.3 to 0.8) and lung (1.7 to 1.2) cancers while among females, they were pancreas (3.4 to 1.3), liver (1.8 to 1.2) and stomach (1.5 to 0.8) cancers.ConclusionThe most common cancers were those associated with 'westernisation' of lifestyle. Our figures contrast with other Sub-Saharan Africa countries where infection related cancers are most predominant. The MNCR has also improved its data quality over time.     

Gastrocopta (Mollusca,Gastropoda, Pupillidae) in?the?Pilbara region of Western Australia

Six species of Gastrocopta have been identified from the Pilbara region, Western Australia, by means of comparative analyses of shell and mtDNA variation. Three of these species, Gastrocopta hedleyi, Gastrocopta larapinta and Gastrocopta servilis, have been recorded in the Pilbara for the first time. Gastrocopta sp. CW1 is probably new to science and might be endemic to the region. By contrast, Gastrocopta hedleyi, Gastrocopta larapinta and Gastrocopta mussoni are shown to be widespread.     

Bellisotoma,a new genus of Isotomidae from North?America (Hexapoda,Collembola)

A new genus of Isotomidae, Bellisotoma gen. n., is described. The new genus is a member of the Proisotoma genus complex and is characterized by a combination of having a bidentate mucro with wide dorsal lamellae that join clearly before the end of mucronal axis without forming a tooth and one strong ventral rib with basal notch that articulates with dens; having abundant chaetotaxy on both faces of dens; and abundant tergal sensilla. Bellisotoma gen. n. shows a furcula adapted to a neustonic mode of life, and may be a Isotopenola-like derivative adapted to neustonic habitats. Subisotoma joycei Soto-Adames & Giordano, 2011 and Ballistura ewingi James, 1933 are transferred to the new genus.     

Identifying the African Wintering Grounds of Hybrid Flycatchers Using a Multi–Isotope (δ 2H, δ 13C, δ 15N) Assignment Approach

Migratory routes and wintering grounds can have important fitness consequences, which can lead to divergent selection on populations or taxa differing in their migratory itinerary. Collared (Ficedula albicollis) and pied (F. hypoleuca) flycatchers breeding in Europe and wintering in different sub-Saharan regions have distinct migratory routes on the eastern and western sides of the Sahara desert, respectively. In an earlier paper, we showed that hybrids of the two species did not incur reduced winter survival, which would be expected if their migration strategy had been a mix of the parent species'' strategies potentially resulting in an intermediate route crossing the Sahara desert to different wintering grounds. Previously, we compared isotope ratios and found no significant difference in stable-nitrogen isotope ratios (δ ¹⁵N) in winter-grown feathers between the parental species and hybrids, but stable-carbon isotope ratios (δ ¹³C) in hybrids significantly clustered only with those of pied flycatchers. We followed up on these findings and additionally analyzed the same feathers for stable-hydrogen isotope ratios (δ ²H) and conducted spatially explicit multi-isotope assignment analyses. The assignment results overlapped with presumed wintering ranges of the two species, highlighting the efficacy of the method. In contrast to earlier findings, hybrids clustered with both parental species, though most strongly with pied flycatcher.