Genetic diversity of the Leptospiral immunoglobulin-like (Lig) genes in pathogenic Leptospira spp.

Recent serologic, immunoprotection, and pathogenesis studies identified the Lig proteins as key virulence determinants in interactions of leptospiral pathogens with the mammalian host. We examined the sequence variation and recombination patterns of ligA, ligB, and ligC among 10 pathogenic strains from five Leptospira species. All strains were found to have intact ligB genes and genetic drift accounting for most of the ligB genetic diversity observed. The ligA gene was found exclusively in L. interrogans and L. kirschneri strains, and was created from ligB by a two-step partial gene duplication process. The aminoterminal domain of LigB and the LigA paralog were essentially identical (98.5 ± 0.8% mean identity) in strains with both genes. Like ligB, ligC gene variation also followed phylogenetic patterns, suggesting an early gene duplication event. However, ligC is a pseudogene in several strains, suggesting that LigC is not essential for virulence. Two ligB genes and one ligC gene had mosaic compositions and evidence for recombination events between related Leptospira species was also found for some ligA genes. In conclusion, the results presented here indicate that Lig diversity has important ramifications for the selection of Lig polypeptides for use in diagnosis and as vaccine candidates. This sequence information will aid the identification of highly conserved regions within the Lig proteins and improve upon the performance characteristics of the Lig proteins in diagnostic assays and in subunit vaccine formulations with the potential to confer heterologous protection.     

Using aggregated mobile phone location data to compare the realised foodscapes of different socio-economic groups.

The foodscape (the built food environment) is considered one of the driving factors of the higher burden of obesity and chronic disease observed in low socio-economic status (SES) groups. Traditional data collection methods struggle to accurately capture actual access and exposure to the foodscape (realised foodscape). We assess the use of anonymised mobile phone location data (location data) in foodscape studies by applying them to a case study in Perth, Western Australia to test the hypothesis that lower SES groups have poorer realised foodscapes than high SES groups. Kernel density estimation was used to calculate realised foodscapes of different SES groups and home foodscape typologies, which were compared to home foodscapes of the different groups. The location data enabled us to measure realised foodscapes of multiple groups over an extended period and at the city scale. Low SES groups had poor availability of food outlets, including unhealthy outlets, in their home and realised foodscapes and may be more susceptible to a poor home foodscape because of low mobility.     

Towards an integrated theoretical framework for understanding water insecurity and gender-based violence in Low-and middle-income countries (LMICs)

Disparities in access to basic needs and resources such as water is largely borne out of power imbalance across scale. In examining these power dynamics in the context of health inequalities, scholars have deployed Feminist political ecology analytical framework to situate gender and other forms of vulnerability as emerging from unequal power relations, and political ecology of health to emphasise the health implications of inherent relational power in the distribution of resources. Although appealing, the two theoretical frameworks over time have proven to be limiting in the study of intersectional vulnerabilities such as gender-based violence and water insecurity which reflect multiple dimensions of unequal power structures. This study expands the theoretical space for the study of inequalities in health geography by demonstrating the utility of incorporating feminist political ecology with political ecology of health to form an integrated theoretical framework – Feminist Political Ecology of Health (FPEH). This proposed theoretical framework gives guidance for engaging with a suite of questions and methods related to multifaceted problems such as water insecurity and gender based-violence. The paper highlights these theoretical issues and then discusses how FPEH can enrich research on water security and gender-based violence in Low-and middle-income countries (LMICs).     

Assessing Residents’ Perceptions of Their Relocation to Long-Term Care: Psychometric Validation of the View of Relocation Scale

ObjectivesRelocation to long-term care is a major challenge for older people. The View of Relocation Scale (VRS) was developed to address the need for a brief instrument to assess residents’ perceptions of the relocation.DesignSecondary analysis of data collected in a cluster randomized trial. The psychometric properties of the VRS examined in this study included factorial structure (using exploratory factor analysis), unidimensionality (Rasch modeling), internal consistency reliability (Kuder-Richardson Formula 20, squared multiple correlations, and item-total correlations), and known groups validity (analysis of variance). The results were used to identify the psychometrically most robust items for inclusion into the final version of the instrument.Setting and ParticipantsParticipants were 202 long-term care residents in Melbourne, Australia (mean age = 85.52 years, standard deviation = 7.33), who had relocated to the facility a mean of 4.4 weeks previously. Residents with moderately severe and severe dementia were excluded.MeasuresThe VRS was developed following a review of the literature describing residents’ views of relocation and was designed for administration shortly after their relocation.ResultsThere was support for a 2-factor, 10-item solution, with separate subscales assessing Perceived Control (degree of control in the decision making and planning for the relocation) and Perceived Need (perceived need for the relocation to long-term care). Participants who were admitted directly from hospital reported higher perceived need but lower perceived control than those admitted to the facility from home.Conclusion and ImplicationsThe VRS can be used to understand the impact of older people's perceptions of relocation to long-term care on their subsequent adjustment and well-being, and to identify those who may benefit from tailored support.     

Characteristics of injuries among infants who fall from bed

IntroductionAccidental falls are the most common causes of injury among infants. Due to their limited ability to move independently, falling from bed or other types of furniture (such as sofas or armchairs) is considered the most common reason for such injury. However, little is known about the frequency and types of injury associated with this type of fall among infants. This study aimed to determine the incidence and characteristics of injury among infants presented at emergency departments (ED) after falling from bed or similar furniture.MethodsThe retrospective analysis of infants under one year old presenting at ED after falling from bed (or similar furniture) was performed over a four-year period (2016–2019). Patient demographics, incidence and patterns of injury, outcomes, and ED resources use were evaluated as part of the study.ResultsIn total, 1,439 infants were included in the study, of whom 782 (54.3%) were male and 657 (45.7%) female. The median age of the patients was 7 months (interquartile range [IQR]: 6–9 months). More than half the infants (n = 812, 56.4%) had minor injuries, such as abrasions, bruising, contusions, and lacerations. There were significant injuries for 135 (9.4%) infants. The most common fracture was skull fracture (n = 59, 4.1%), followed by proximal fracture of the upper extremities (n = 26, 1.8%). Six (0.4%) patients had radial head subluxation. Traumatic brain injury featured for 30 (2.1%) infants (intracranial hemorrhage/cerebral contusion). While the majority of patients (n = 1352, 94%) were discharged from ED, 86 (6%) infants were hospitalized, all due to head injuries. A neurosurgical intervention was performed with three (0.2% of all patients) of the hospitalized patients.ConclusionFalling from bed causes skull fractures, traumatic brain injury, and long bone fractures among infants. Therefore, campaigns should be organized to raise awareness of these risks among parents and caregivers of infants. In addition, the use of safety equipment (such as bed rails) and creating a safe environment can help prevent significant injuries.     

Tobacco smoke exposure limits the therapeutic benefit of tezacaftor/ivacaftor in pediatric patients with cystic fibrosis

ObjectivesTobacco smoke exposure reduces CFTR functional expression in vitro and contributes to acquired CFTR dysfunction. We investigated whether it also inhibits the clinical benefit of CFTR modulators, focusing on tezacaftor/ivacaftor, approved in February 2018 for individuals with CF age ≥12 years.MethodsA retrospective longitudinal analysis of encounter-based data from the CF Foundation Patient Registry (2016–2018) compared the slope of change in lung function (GLI FEV₁% predicted) before and after tezacaftor/ivacaftor initiation in smoke-exposed vs unexposed age-eligible pediatric patients. Tobacco smoke exposure (Ever/Never) was determined from caregiver self-report. Statistical analyses used hierarchical linear mixed modeling and fixed effects regression modeling.ResultsThe sample included 6,653 individuals with a total of 105,539 person-period observations. Tezacaftor/ivacaftor was prescribed to 19% (1,251) of individuals, mean age 17 years, mean baseline ppFEV₁ 83%, 28% smoke-exposed. Tezacaftor/ivacaftor users who were smoke-exposed had a lower baseline ppFEV₁ and experienced a greater lung function decline. Over two years, the difference in ppFEV₁ by smoke exposure among tezacaftor/ivacaftor users increased by 1.2% (7.6% to 8.8%, p<0.001). In both mixed effects and fixed effects regression models, tezacaftor/ivacaftor use was associated with improved ppFEV₁ among unexposed individuals (1.2% and 1.7%, respectively; p<0.001 for both) but provided no benefit among smoke-exposed counterparts (0.3%, p = 0.5 and 0.6%, p = 0.07, respectively).ConclusionTobacco smoke exposure nullifies the therapeutic benefit of tezacaftor/ivacaftor among individuals with CF aged 12–20 years old. To maximize the therapeutic opportunity of CFTR modulators, every effort must be taken to eliminate smoke exposure in CF.     

Factors affecting antibody responses to immunizations in infants born to women immunized against pertussis in pregnancy and unimmunized women: Individual-Participant Data Meta-analysis

BackgroundExploring factors that affect immune responses to immunizations in infants born to women immunized with tetanus-diphtheria-acellular-pertussis (Tdap) in pregnancy compared with unimmunized women is important in designing immunization programs.MethodsIndividual-participant data meta-analysis of 8 studies reporting post-immunization immunoglobulin G (IgG) levels to vaccine antigens in infants born to either women immunized with Tdap in pregnancy or unimmunized women, using mixed-effects models.ResultsIn infants of Tdap-immunized women, two-fold higher levels of anti-pertussis toxin (PT) and anti-diphtheria-toxoid (DT) IgG pre-primary immunization were associated with 9% and 10% lower post-primary immunization levels, (geometric mean ratio [GMR], PT: 0.91; 95% CI, 0.88–0.95,n = 494, DT: 0.9; 0.87–0.93,n = 519). Timing of immunization in pregnancy did not affect post-primary immunization anti-Bordetella pertussis, anti-tetanus-toxoid (TT) and anti-DT IgG levels. Spacing of infant immunization did not affect post-primary immunization anti-B. pertussis and anti-DT levels. In infants of Tdap-immunized women, two-fold higher levels of anti-PT and anti-filamentous haemagglutinin (FHA) IgG pre-primary immunization were associated with lower post-booster immunization levels, (GMR, PT: 0.91; 0.85–0.97,n = 224, FHA: 0.92; 0.85–0.99,n = 232). Timing of immunization in pregnancy did not affect post-booster immunization anti-Bordetella pertussis, anti-tetanus-toxoid (TT) and anti-DT IgG levels. Spacing of infant immunization did not affect post-booster immunization anti-PT, anti-pertactin (PRN), anti-TT and anti-DT IgG levels.In infants of unimmunized women, two-fold higher IgG levels of some vaccine antigens pre-primary immunization were associated with 8–17% lower post-primary immunization levels (GMR, PT 0.92, 95% CI:0.88–0.97, n = 373; FHA:0.88, 95% CI:0.85–0.92,n = 378; PRN:0.84, 95% CI:0.81–0.88, n = 367; TT:0.88, 95% CI:0.83–0.93, n = 241; DT: 0.83, 95% CI:0.79–0.87,n = 278). Two-fold higher levels of anti-FHA IgG pre-primary immunization were associated with 8% lower post-booster immunization levels (GMR, 0.92; 95% CI: 0.86–0.99,n = 138).DiscussionIncreased IgG levels pre-primary immunization is associated with reduced post-primary and post-booster immunization levels for some antigens in infants of women immunized or unimmunized in pregnancy, but their clinical significance is uncertain.     

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10^–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.