Relative rates of cancers and deaths in Australian communities with PFAS environmental contamination associated with firefighting foams: A cohort study using linked data.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants that are potentially harmful to health. We examined if rates of selected cancers and causes of deaths were elevated in three Australian communities with local environmental contamination caused by firefighting foams containing PFAS. The affected Australian communities were Katherine in Northern Territory, Oakey in Queensland and Williamtown in New South Wales. METHODS: All residents identified in the Medicare Enrolment File (1983-2019)-a consumer directory for Australia's universal healthcare-who ever lived in an exposure area (Katherine, Oakey and Williamtown), and a sample of those who ever lived in selected comparison areas, were linked to the Australian Cancer Database (1982-2017) and National Death Index (1980-2019). We estimated standardised incidence ratios (SIRs) for 23 cancer outcomes, four causes of death and three control outcomes, adjusting for sex, age and calendar time of diagnosis. FINDINGS: We observed higher rates of prostate cancer (SIR=1·76, 95 % confidence interval (CI) 1·36-2·24) in Katherine; laryngeal cancer (SIR=2·71, 95 % CI 1·30-4·98), kidney cancer (SIR=1·82, 95 % CI 1·04-2·96) and coronary heart disease (CHD) mortality (SIR=1·81, 95 % CI 1·46-2·33) in Oakey; and lung cancer (SIR=1·83, 95 % CI 1·39-2·38) and CHD mortality (SIR=1·22, 95 % CI 1·01-1·47) in Williamtown. We also saw elevated SIRs for control outcomes. SIRs for all other outcomes and overall cancer were similar across exposure and comparison areas. INTERPRETATION: There was limited evidence to support an association between living in a PFAS exposure area and risks of cancers or cause-specific deaths.

Mini-review of waste sector greenhouse gas and short-lived climate pollutant emissions in Tyre Caza, Lebanon, using the Solid Waste Emissions Estimation Tool ('SWEET').

In 2020, International Solid Waste Association's (ISWA) Task Force on Closing Dumpsites completed a study of waste sector short-lived climate pollutants (SLCPs) and other greenhouse gas (GHG) emissions in Tyre Caza, Lebanon, using the Solid Waste Emissions Estimation Tool (SWEET). SWEET model runs used data on municipal solid waste (MSW) generation, collection, disposal, and diversion under existing and potential alternative management scenarios proposed in an Integrated Waste Management Plan (IWMP) for Tyre Caza. Waste sector emissions reductions exceeding 45% of baseline levels are achievable by 2030 if all dumpsites are closed and remediated, waste burning stopped, and a new sanitary landfill developed with 60% methane collection and combustion. Additional emissions reduction accrues from implementing the IWMP and upgrading existing waste treatment facilities to increase waste diversion rates from current levels (22% including informal sector recycling) to 40%. Estimates of all of Lebanon's waste sector emissions using SWEET were developed for this mini-review article using published data on the amounts of MSW collected, disposed, and diverted, with adjustments to account for indirect GHG reductions from composting and anaerobic digestion (AD). A 50% reduction in emissions from baseline levels can be achieved by 2034, if by 2025 diversion of collected wastes to recycling, composting, and AD facilities is increased from 14% to 28%, and all residual MSW is disposed in sanitary landfills with 65% methane recovery.

Safety and effectiveness of switching to Abacavir/Lamivudine plus rilpivirine for maintenance therapy in virologically suppressed HIV-1 individuals in Singapore (SEALS).

BACKGROUND: The efficacy and tolerability of an antiretroviral regimen are important considerations for selection of HIV-1 infection maintenance therapy. Abacavir/lamivudine plus rilpivirine (ABC/3TC + RPV) has been shown in international studies to be effective and well-tolerated in virologically suppressed individuals. This study evaluated the effectiveness and safety of switching to ABC/3TC + RPV as maintenance therapy in virologically suppressed HIV-1 infected individuals in Singapore. METHODS: In this retrospective, single-centre study, we included individuals who were prescribed ABC/3TC + RPV, had HIV-1 viral load (VL) < 50 copies/ml immediately pre-switch, and had no documented history of resistance mutations or virologic failure to any of the components. The follow-up period was 48 ± 12 weeks. The primary outcome was the proportion of individuals who maintained virologic suppression of HIV-1 VL < 50 copies/ml at the end of follow-up period based on on-treatment analysis. The secondary outcomes were the resistance profiles associated with virologic failure, changes in immunologic and metabolic parameters, and the safety profile of ABC/3TC + RPV. RESULTS: A total of 222 individuals were included in the study. The primary outcome was achieved in 197 individuals [88.8%, 95% confidence interval: 83.7-92.4%]. There were 21 individuals (9.5%) who discontinued treatment for non-virologic reasons. The remaining 4 individuals experienced virologic failure, of whom, 3 of these individuals had developed emergent antiretroviral resistance and had HIV-1 VL > 500 copies/ml at the end of the 48 ± 12 weeks follow-up period. The remaining individual experienced sustained low level viremia and subsequently achieved viral suppression without undergoing resistance testing. A total of 49 adverse events were observed in 31 out of 222 individuals (14.0%), which led to 13 individuals discontinuing therapy. Neuropsychiatric adverse events were most commonly observed (53.1%). A statistically significant increase in CD4 was observed (p < 0.01), with a median absolute change of 31 cells/uL (interquartile range: - 31.50 to 140.75). No significant changes in lipid profiles were detected. CONCLUSION: ABC/3TC + RPV is a safe and effective switch option for maintenance therapy in virologically suppressed HIV-1 individuals with in Singapore.

Inequalities in life expectancy in Australia according to education level: a whole-of-population record linkage study.

BACKGROUND: Life expectancy in Australia is amongst the highest globally, but national estimates mask within-country inequalities. To monitor socioeconomic inequalities in health, many high-income countries routinely report life expectancy by education level. However in Australia, education-related gaps in life expectancy are not routinely reported because, until recently, the data required to produce these estimates have not been available. Using newly linked, whole-of-population data, we estimated education-related inequalities in adult life expectancy in Australia. METHODS: Using data from 2016 Australian Census linked to 2016-17 Death Registrations, we estimated age-sex-education-specific mortality rates and used standard life table methodology to calculate life expectancy. For men and women separately, we estimated absolute (in years) and relative (ratios) differences in life expectancy at ages 25, 45, 65 and 85 years according to education level (measured in five categories, from university qualification [highest] to no formal qualifications [lowest]). RESULTS: Data came from 14,565,910 Australian residents aged 25 years and older. At each age, those with lower levels of education had lower life expectancies. For men, the gap (highest vs. lowest level of education) was 9.1 (95 %CI: 8.8, 9.4) years at age 25, 7.3 (7.1, 7.5) years at age 45, 4.9 (4.7, 5.1) years at age 65 and 1.9 (1.8, 2.1) years at age 85. For women, the gap was 5.5 (5.1, 5.9) years at age 25, 4.7 (4.4, 5.0) years at age 45, 3.3 (3.1, 3.5) years at 65 and 1.6 (1.4, 1.8) years at age 85. Relative differences (comparing highest education level with each of the other levels) were larger for men than women and increased with age, but overall, revealed a 10-25 % reduction in life expectancy for those with the lowest compared to the highest education level. CONCLUSIONS: Education-related inequalities in life expectancy from age 25 years in Australia are substantial, particularly for men. Those with the lowest education level have a life expectancy equivalent to the national average 15-20 years ago. These vast gaps indicate large potential for further gains in life expectancy at the national level and continuing opportunities to improve health equity.

Behavioural insights and attitudes on community masking during the initial spread of COVID-19 in Hong Kong.

INTRODUCTION: Community face mask use during the coronavirus disease 2019 (COVID-19) pandemic has considerably differed worldwide. Generally, Asians are more inclined to wear face masks during disease outbreaks. Hong Kong has emerged relatively unscathed during the initial outbreak of COVID-19, despite its dense population. Previous infectious disease outbreaks influenced the local masking behaviour and response to public health measures. Thus, local behavioural insights are important for the successful implementation of infection control measures. This study explored the behaviour and attitudes of wearing face masks in the community during the initial spread of COVID-19 in Hong Kong. METHODS: We observed the masking behaviour of 10 211 pedestrians in several regions across Hong Kong from 1 to 29 February 2020. We supplemented the data with an online survey of 3199 respondents' views on face mask use. RESULTS: Among pedestrians, the masking rate was 94.8%; 83.7% wore disposable surgical masks. However, 13.0% wore surgical masks incorrectly with 42.5% worn too low, exposing the nostrils or mouth; 35.5% worn 'inside-out' or 'upside-down'. Most online respondents believed in the efficacy of wearing face mask for protection (94.6%) and prevention of community spread (96.6%). Surprisingly, 78.9% reused their mask; more respondents obtained information from social media (65.9%) than from government websites (23.2%). CONCLUSIONS: In Hong Kong, members of the population are motivated to wear masks and believe in the effectiveness of face masks against disease spread. However, a high mask reuse rate and errors in masking techniques were observed. Information on government websites should be enhanced and their accessibility should be improved.

IglC and PdpA are important for promoting Francisella invasion and intracellular growth in epithelial cells.

The highly infectious bacteria, Francisella tularensis, colonize a variety of organs and replicate within both phagocytic as well as non-phagocytic cells, to cause the disease tularemia. These microbes contain a conserved cluster of important virulence genes referred to as the Francisella Pathogenicity Island (FPI). Two of the most characterized FPI genes, iglC and pdpA, play a central role in bacterial survival and proliferation within phagocytes, but do not influence bacterial internalization. Yet, their involvement in non-phagocytic epithelial cell infections remains unexplored. To examine the functions of IglC and PdpA on bacterial invasion and replication during epithelial cell infections, we infected liver and lung epithelial cells with F. novicida and F. tularensis 'Type B' Live Vaccine Strain (LVS) deletion mutants (ΔiglC and ΔpdpA) as well as their respective gene complements. We found that deletion of either gene significantly reduced their ability to invade and replicate in epithelial cells. Gene complementation of iglC and pdpA partially rescued bacterial invasion and intracellular growth. Additionally, substantial LAMP1-association with both deletion mutants was observed up to 12 h suggesting that the absence of IglC and PdpA caused deficiencies in their ability to dissociate from LAMP1-positive Francisella Containing Vacuoles (FCVs). This work provides the first evidence that IglC and PdpA are important pathogenic factors for invasion and intracellular growth of Francisella in epithelial cells, and further highlights the discrete mechanisms involved in Francisella infections between phagocytic and non-phagocytic cells.

Outcomes of non-surgical periodontal treatment by dental hygienists in training: impact of site- and patient-level factors.

OBJECTIVES: To investigate the site- and patient-level factors that impact on the response to non-surgical periodontal therapy in patients with chronic periodontitis. METHODS: A retrospective evaluation of clinical outcomes following non-surgical periodontal therapy delivered by dental hygienists in training was undertaken. Case notes from 195 patients with chronic periodontitis were reviewed and clinical data pre- and post-treatment abstracted. Patients were categorized as 'responders' or 'non-responders' according to defined outcome criteria, and the relationship between clinical and demographic variables and treatment outcomes was assessed. RESULTS: Overall, there was a good response to the periodontal treatment. At deep sites (those with pretreatment probing depth ≥5 mm), the mean probing depth reduction was 1.6 ± 0.9 mm. Seventy-one (36%) patients were classified as non-responders (indicating that at least 30% of their deep sites did not improve by at least 2 mm following treatment). The non-responding group contained a significantly greater proportion of smokers (28%) than the responding group (16%). Plaque scores did not differ significantly between responders or non-responders either pre- or post-treatment. Regression analyses indicated that smoking status (odds ratio, OR: 2.04), mean pretreatment probing depth (OR: 1.49) and percentage of deep sites ≥5 mm at pretreatment (OR: 1.02) were significantly associated with response to treatment. CONCLUSION: This study supports the benefits of non-surgical therapy in the treatment of chronic periodontitis by dental hygienists in training. Better responses to treatment tend to be observed in non-smokers and in those with less advanced periodontitis at baseline.

Examination of in vitro epithelial cell lines as models for Francisella tularensis non-phagocytic infections.

Francisella tularensis (F. tularensis), the causative agent of tularemia, has long been known to invade and occupy non-phagocytic epithelial cells. Many epithelial cell infection models have been developed to study this process; however, due to the lack of consensus on infection methods and precise experimental procedures to evaluate invasion and replication, selection of appropriate models to use based on the literature is challenging. To evaluate in vitro non-phagocytic cell infection models, we chose 8 epithelial cultured cell lines from published models to infect with F. tularensis subspecies novicida (F. novicida) and compared the results to a recently developed model that used the mouse hepatocyte BNL CL.2 cell line. We utilized classical gentamicin-based invasion assays to determine total intracellular bacterial loads and employed microscopic examination with staining techniques that distinguished between intracellular and extracellular bacteria to provide an accurate assessment of the proportion of invaded host cells and the degree of bacterial replication. We found that COS-7 cells exhibited the greatest invasion rates; CMT-93 cells contained the largest intracellular bacterial loads; ad HEK-293s were capable of invasion and replication rates at high levels, but required shorter infection incubation times. Although COS-7, CMT-93 and HEK-293 cell lines may be suited to study certain aspects of invasion or replication, we found that BNL CL.2 cells appeared the most appropriate to study the overall pathogenesis of F. novicida when examined in toto.

Percutaneous endoscopic gastrostomy in patients with ventriculoperitoneal shunt.

INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) placement in patients with ventriculo-peritoneal shunt (VPS) may be associated with complications. This study reports our experience of PEG in patients with VPS. MATERIALS AND METHODS: Consecutive patients undergoing PEG insertion in a gastroenterology unit over 18 month's period were retrospectively analyzed. All patients were evaluated by an attending gastroenterologist for fitness for procedure. Instructions were given for routine antibiotic prophylaxes before the procedure and continued for 48 hours. Patients were followed for immediate complications in particular, wound infection, signs of meningitis, deterioration in neurological state and shunt malfunction. Post discharge, patients were given routine follow-up for review. RESULTS: Of 86 patients who had PEG inserted during the study period, 14 had VPS including 2 of which had VPS after PEG. The main common indications for VPS were intracerebral bleed and head trauma and for PEG were requirement of long term enteral feeding. Twelve patients had PEG at a mean interval of 61 days (range 1-187 days) after VPS. Of these, eight received prophylactic antibiotic or were on antibiotic for other indications before PEG. Two patients developed mild PEG site infections within a week of insertions, including one patient who was not given antibiotic prophylaxis, both treated successfully with antibiotics. The latter patient developed worsening hydrocephalus secondary to VPS blockage. At a mean follow-up period was 140 days (range 20-570 days), there were no death or further complications encountered. CONCLUSIONS: Although safe in the majority of patients with VPS, PEG infection can lead to intracranial complications. We recommend antibiotic prophylaxis for VPS patients before PEG.

Association of common genetic variants with breast cancer risk and clinicopathological characteristics in a Chinese population.

Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations, and thus GWAS-identified single nucleotide polymorphisms (SNPs) in one population may not be of significance in another population. In order to explore the role of breast cancer susceptibility variants in a Chinese population of Southern Chinese descent, we analyzed 22 SNPs for 1,191 breast cancer cases and 1,534 female controls. Associations between the SNPs and clinicopathological features were also investigated. In addition, we evaluated the combined effects of associated SNPs by constructing risk models. Eight SNPs were associated with an elevated breast cancer risk. Rs2046210/6q25.1 increased breast cancer risk via an additive model [per-allele odds ratio (OR) = 1.43, 95 % confidence interval (CI) = 1.26-1.62], and was associated with estrogen receptor (ER)-positive (per-allele OR = 1.39, 95 % CI = 1.20-1.61) and ER-negative (per-allele OR = 1.55, 95 % CI = 1.28-1.89) disease. Rs2046210 was also associated with stage 1, stage 2, and stage 3 disease, with per-allele ORs of 1.38 (1.14-1.68), 1.48 (1.25-1.74), and 1.58 (1.28-1.94), respectively. Four SNPs mapped to 10q26.13/FGFR2 were associated with increased breast cancer risk via an additive model with per-allelic risks (95 % CI) of 1.26 (1.12-1.43) at rs1219648, 1.22 (1.07-1.38) at rs2981582, 1.21 (1.07-1.36) at rs2981579, and 1.18 (1.04-1.35) at rs11200014. Variants of rs7696175/TLR1, TLR6, rs13281615/8q24, and rs16886165/MAP3K1 were also associated with increased breast cancer risk, with per-allele ORs (95 % CI) of 1.16 (1.00-1.34), 1.15 (1.02-1.29), and 1.15 (1.01-1.29), respectively. Five SNPs associated with breast cancer risk predominantly among ER-positive tumors (rs2981582/FGFR2, rs4415084/MRPS30, rs1219648/FGFR2, rs2981579/FGFR2, and rs11200014/FGFR2). Among our Chinese population, the risk of developing breast cancer increased by 90 % for those with a combination of 6 or more risk alleles, compared to patients with ≤3 risk alleles.

Nexilin is a dynamic component of Listeria monocytogenes and enteropathogenic Escherichia coli actin-rich structures.

The bacterial pathogens Listeria monocytogenes and enteropathogenic Escherichia coli (EPEC) generate motile actin-rich structures (comet tails and pedestals) as part of their infectious processes. Nexilin, an actin-associated protein and a component of focal adhesions, has been suggested to be involved in actin-based motility. To determine whether nexilin is commandeered during L. monocytogenes and EPEC infections, we infected cultured cells and found that nexilin is crucial for L. monocytogenes invasion as levels of internalized bacteria were significantly decreased in nexilin-targeted siRNA-treated cells. In addition, nexilin is a component of the machinery that drives the formation of L. monocytogenes comet tails and EPEC pedestals. Nexilin colocalizes with stationary bacteria and accumulates at the distal portion of comet tails and pedestals of motile bacteria. We also show that nexilin is crucial for efficient comet tail formation as cells pre-treated with nexilin siRNA generate malformed comet tails, whereas nexilin is dispensable during EPEC pedestal generation. These findings demonstrate that nexilin is required for efficient infection with invasive and adherent bacteria and is key to the actin-rich structures these microbes generate.

Urogynaecological problems in pregnancy.

The majority of urogynaecological problems can manifest during pregnancy or as a direct result of pregnancy and delivery. Those most commonly occurring during pregnancy are urinary tract infection, filling and voiding disorders, urinary incontinence, pelvic organ prolapse and faecal incontinence. The development of these may be as a result of physiological changes that occur in pregnancy or as a result of previous pregnancies. There may also be urogynaecological sequelae that occur as a result of trauma sustained during delivery. These include perineal and anal sphincter trauma, bladder or ureteric injuries during caesarean section or operative deliveries, and the development of vesico-vaginal or recto-vaginal fistulae.

Francisella tularensis uses cholesterol and clathrin-based endocytic mechanisms to invade hepatocytes.

Francisella tularensis are highly infectious microbes that cause the disease tularemia. Although much of the bacterial burden is carried in non-phagocytic cells, the strategies these pathogens use to invade these cells remains elusive. To examine these mechanisms we developed two in vitro Francisella-based infection models that recapitulate the non-phagocytic cell infections seen in livers of infected mice. Using these models we found that Francisella novicida exploit clathrin and cholesterol dependent mechanisms to gain entry into hepatocytes. We also found that the clathrin accessory proteins AP-2 and Eps15 co-localized with invading Francisella novicida as well as the Francisella Live Vaccine Strain (LVS) during hepatocyte infections. Interestingly, caveolin, a protein involved in the invasion of Francisella in phagocytic cells, was not required for non-phagocytic cell infections. These results demonstrate a novel endocytic mechanism adopted by Francisella and highlight the divergence in strategies these pathogens utilize between non-phagocytic and phagocytic cell invasion.

The influence of ATP-binding cassette sub-family B member -1 (ABCB1) genetic polymorphisms on acute and chronic pain after intrathecal morphine for caesarean section: a prospective cohort study.

BACKGROUND: Polymorphisms of the ATP-binding cassette sub-family B member -1 (ABCB1) gene that codes for P-glycoprotein could influence the efflux of morphine from the central nervous system affecting its analgesic action. We investigated the effect of ABCB1 gene polymorphisms on analgesia and the development of persistent pain in post caesarean patients. METHODS: Women of Chinese descent who received spinal anaesthesia with intrathecal morphine for elective caesarean section were recruited. They were given intravenous morphine via a patient-controlled analgesia pump for postoperative analgesia. Blood samples were collected and analysed for the presence of C1236T, G2677T/A and C3435T single nucleotide polymorphisms of the ABCB1 gene. We primarily investigated the association between ABCB1 polymorphisms and the effect of morphine. In a postpartum phone survey of the subjects six months after surgery, the occurrence of persistent abdominal wound scar pain was established. RESULTS: We found no significant statistical difference in total morphine consumption, pain scores and side effects among the various genotypes. For C3435T polymorphism, there was a trend towards the association of the T allele and persistent pain for three months after surgery but this did not reach statistical significance (P=0.07). The TT genotype had the longest mean survival time of wound pain in comparison with CT and CC genotypes (P=0.004 and P=0.014, respectively). CONCLUSION: Polymorphisms of ABCB1 were not associated with differences in morphine use in the first 24h after surgery. Women with the T allele of C3435T polymorphism showed a trend towards a higher risk of developing persistent postoperative pain.

Meteorological factors and aneurysmal subarachnoid haemorrhage in Hong Kong.

OBJECTIVE: To evaluate the influence of meteorological factors on the onset of aneurysmal subarachnoid haemorrhage in Hong Kong. DESIGN: Retrospective review of prospectively collected data. SETTING: University teaching hospital, Hong Kong. PATIENTS: A total of 135 consecutive patients with acute aneurysmal subarachnoid haemorrhage presenting to the hospital within 48 hours after ictus from October 2002 to October 2006. MAIN OUTCOME MEASURES: Occurrence of aneurysmal subarachnoid haemorrhage in relation to daily changes in atmospheric pressure, temperature, and humidity. RESULTS: The peak incidence of aneurysmal subarachnoid haemorrhage occurred in winter (December to February), especially January. The mean (+/-standard deviation) daily atmospheric pressure change was significantly higher on days with aneurysmal subarachnoid haemorrhage onset as opposed to days without (1.75+/-1.47 hPa vs 1.48+/-1.28 hPa; P=0.032). CONCLUSIONS: A seasonal variation and relationship to atmospheric pressure change in aneurysmal subarachnoid haemorrhage was noted in the current study carried out in Hong Kong. The mechanism linking atmospheric pressure change and aneurysmal rupture remained to be explored.