Diagnostic accuracy of ANCA serology in ANCA-associated vasculitis with renal involvement.

BACKGROUND: Pauci-immune glomerulonephritis (GN) due to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a common cause of crescentic GN. Despite advances in treatment, rates of mortality and progression to end-stage kidney disease remain high. Renal involvement is diagnosed by histological examination of kidney tissue. Serum ANCAs play a significant role in AAV; however, the value of serum ANCA quantification to predict renal involvement is not well-established. AIM: We aimed to evaluate the diagnostic accuracy of serum ANCA titres in diagnosing AAV with renal involvement. METHODS: We conducted a retrospective study of consecutive native kidney biopsies reported at our centre from 2016 to 2021. We included all adults who had both a kidney biopsy and ANCA serology. ANCA serology was tested using indirect immunofluorescence with reporting of titres. Antibodies to proteinase 3 and myeloperoxidase were measured using a chemiluminescent immunoassay. RESULTS: Eight hundred and forty-eight native kidney biopsies were reported during the study period. Five hundred and seven cases were included. The biopsy prevalence of pauci-immune GN in paired samples was 41/507 (8.1%). Most of the cohort had haematuria (66.6%), proteinuria (93.4%) and/or acute kidney injury (65.0%). A positive ANCA at any titre demonstrated a sensitivity of 97.6% and a specificity of 71.2% for a diagnosis of pauci-immune GN. The area under the curve for the receiver operator characteristic was 0.93 (95% confidence interval [CI]: 0.89-0.97). A cutoff ANCA titre of 1:160 provided the optimum balance between a sensitivity of 75.6% (95% CI: 59.7%-87.6%) and a specificity of 94.0% (95% CI: 91.6%-96.0%). CONCLUSIONS: ANCA titres are highly predictive of pauci-immune GN in the appropriate context. While serum ANCA quantitation may not replace renal biopsy, reporting will assist in the decision to start treatment early for patients with organ or life-threatening disease.

COVID-19 Vaccine Boundary Work: The Case of Facebook Comments in Southeast Georgia.

Although much research has considered the worldview of the vaccine hesitant, little attention has been given to the cultural conflict over what it means to be a person who takes vaccines. Through a qualitative content analysis of comments made on the Facebook pages of media outlets serving southeast Georgia, this analysis identifies both motives for rejecting the vaccine and outlines the symbolic boundaries that the vaccine hesitant have erected to distinguish themselves from vaccine advocates. The motives include perfunctory rejections, claims that the vaccine is ineffective, illegitimate, injurious in the short and long term, poisonous, infectious, particularly dangerous for children, and a component of conspiracy theories. These symbolic boundaries include distinguishing vaccine advocates from the vaccine hesitant by personal characteristics such as irrationality and authoritarianism. There are also social boundaries rooted in social locations - namely conservatives vs. liberals and non-elites vs. elites. This study also demonstrates how vaccine proponents engage with these symbolic boundaries. Vaccine proponents both contest and accept these boundaries. Likewise, pro-vaccine comments vary in terms of whether they stigmatize the boundary between vaccine user and non-user. This study adds to the literature on health communication and vaccines by confirming previous reports of the reasons for not taking the COVID-19 vaccine, indicating that public communication on vaccines is not regionally specific, and demonstrating the role that ostensible vaccine advocates might play in contributing to vaccine hesitancy.

Postnatal growth restriction impairs rat lung structure and function.

The negative impact of nutritional deficits in the development of bronchopulmonary dysplasia is well recognized, yet mechanisms by which nutrition alters lung outcomes and nutritional strategies that optimize development and protect the lung remain elusive. Here, we use a rat model to assess the isolated effects of postnatal nutrition on lung structural development without concomitant lung injury. We hypothesize that postnatal growth restriction (PGR) impairs lung structure and function, critical mediators of lung development, and fatty acid profiles at postnatal day 21 in the rat. Rat pups were cross-fostered at birth to rat dams with litter sizes of 8 (control) or 16 (PGR). Lung structure and function, as well as serum and lung tissue fatty acids, and lung molecular mediators of development, were measured. Male and female PGR rat pups had thicker airspace walls, decreased lung compliance, and increased tissue damping. Male rats also had increased lung elastance, increased lung elastin protein abundance, and lysol oxidase expression, and increased elastic fiber deposition. Female rat lungs had increased conducting airway resistance and reduced levels of docosahexaenoic acid in lung tissue. We conclude that PGR impairs lung structure and function in both male and female rats, with sex-divergent changes in lung molecular mediators of development.

Fibrillary and immunotactoid glomerulopathies in the Hunter region: a retrospective cohort study.

BACKGROUND: Fibrillary (FGN) and immunotactoid (IT) glomerulonephritis are uncommon. AIMS: To evaluate the prevalence, clinicopathological correlations and outcomes of FGN and IT in our regional centre in Australia. METHODS: We interrogated a renal biopsy database for cases of FGN and IT from 2000 to 2020. Data included demographics, serum creatinine, haematuria status, proteinuria, comorbidities and histopathological findings. RESULTS: We had 14 cases of FGN and t of IT. The mean presenting age was 59.8 years, and 42.9% were males. No patients with FGN had dysproteinaemia, whereas both patients with IT had chronic lymphocytic leukaemia. At presentation, 75% of patients with FGN and both patients with IT had haematuria; all had proteinuria. Mean albumin-creatinine ratio at presentation was 254 mg/mmol for FGN and 604 mg/mmol for IT. Mean presenting serum creatinine was 149 µmol/L for FGN and 95 µmol/L for IT. Four patients with FGN (28.6%) received immunomodulatory therapy. The prognosis of FGN was poor, with six patients (46.2%) reaching end-stage kidney disease after a median of 42 months (range 1-96 months). All patients presenting with proteinuria <30 mg/mmol entered complete remission; patients with higher-grade proteinuria exhibited progressive chronic kidney disease. Patients with IT had complete remission with treatment of underlying haematological disease. CONCLUSION: FGN is rare, with poor response to immunomodulatory therapy. It carries poor renal prognosis. Less proteinuria at diagnosis may predict a more benign disease course. IT is associated with haematological malignancy and carries better prognosis and response to treatment.

Tbc1d10c is a selective, constitutive suppressor of the CD8 T-cell anti-tumor response.

Cancer immunotherapy approaches target signaling pathways that are highly synonymous between CD4 and CD8 T-cell subsets and, therefore, often stimulate nonspecific lymphocyte activation, resulting in cytotoxicity to otherwise healthy tissue. The goal of our study was to identify intrinsic modulators of basic T lymphocyte activation pathways that could discriminately bolster CD8 anti-tumor effector responses. Using a Tbc1d10c null mouse, we observed marked resistance to a range of tumor types conferred by Tbc1d10c deficiency. Moreover, tumor-bearing Tbc1d10c null mice receiving PD-1 or CTLA-4 monotherapy exhibited a 33% or 90% cure rate, respectively. While Tbc1d10c was not expressed in solid tumor cells, Tbc1d10c disruption selectively augmented CD8 T-cell activation and cytotoxic effector responses and adoptive transfer of CD8 T cells alone was sufficient to recapitulate Tbc1d10c null tumor resistance. Mechanistically, Tbc1d10c suppressed CD8 T-cell activation and anti-tumor function by intersecting canonical NF-κB pathway activation via regulation of Map3k3-mediated IKKß phosphorylation. Strikingly, none of these cellular or molecular perturbations in the NF-κB pathway were featured in Tbc1d10c null CD4 T cells. Our findings identify a Tbc1d10c-Map3k3-NF-κB signaling axis as a viable therapeutic target to promote CD8 T-cell anti-tumor immunity while circumventing CD4 T cell-associated cytotoxicity and NF-κB activation in tumor cells.

Women Gerontologists' Personal Experiences with Aging: Results From the Women in Gerontology Legacy Project.

The Women in Gerontology Legacy (WIGL) Project involved interviewing 46 older women gerontologists between 2014 and 2015. The current study focuses on the WIGL interview questions regarding the interactions between participants' experiences as gerontologists and their own aging. Emergent themes focus on the direction of influence: professional lives influencing personal lives, personal lives informing professional lives and mutuality between personal and professional lives. Thematic findings expand our current understanding of how professional knowledge and experiences contribute to personal aging experiences and the role personal aging experiences can have on the professional lives of women gerontologists. There is a potential for disconnect to occur between our personal experiences and the experiences of others. The current study contributes to our understanding of when and how this occurs, so we can then ensure our messages fall on receptive ears by overcoming the natural tendency to distort or ignore messages that may create anxiety.

The CD200-CD200R Axis Promotes Squamous Cell Carcinoma Metastasis via Regulation of Cathepsin K.

The CD200-CD200R immunoregulatory signaling axis plays an etiologic role in the survival and spread of numerous cancers, primarily through suppression of antitumor immune surveillance. Our previous work outlined a prometastatic role for the CD200-CD200R axis in cutaneous squamous cell carcinoma (cSCC) that is independent of direct T-cell suppression but modulates the function of infiltrating myeloid cells. To identify effectors of the CD200-CD200R axis important for cSCC metastasis, we conducted RNA sequencing profiling of infiltrating CD11B+Cd200R+ cells isolated from CD200+ versus CD200-null cSCCs and identified the cysteine protease cathepsin K (Ctsk) to be highly upregulated in CD200+ cSCCs. CD11B+Cd200R+ cells expressed phenotypic markers associated with myeloid-derived suppressor cell-like cells and tumor-associated macrophages and were the primary source of Ctsk expression in cSCC. A Cd200R+ myeloid cell-cSCC coculture system showed that induction of Ctsk was dependent on engagement of the CD200-CD200R axis, indicating that Ctsk is a target gene of this pathway in the cSCC tumor microenvironment. Inhibition of Ctsk, but not matrix metalloproteinases, significantly blocked cSCC cell migration in vitro. Finally, targeted CD200 disruption in tumor cells and Ctsk pharmacologic inhibition significantly reduced cSCC metastasis in vivo. Collectively, these findings support the conclusion that CD200 stimulates cSCC invasion and metastasis via induction of Ctsk in CD200R+ infiltrating myeloid cells. SIGNIFICANCE: These findings highlight the relationship between CD200-CD200R and cathepsin K in cutaneous squamous cell carcinoma metastasis and suggest that either of these components may serve as a viable therapeutic target in this disease.

The Challenges of Intersectionality in the Lives of Older Adults Living in Rural Areas with Limited Financial Resources.

The objective of this study was to use intersectionality to better understand the challenges of having the combined statuses of being an older adult, living in a rural area and having limited financial resources. Eight focus groups and 38 individual interviews were conducted in southern Georgia. Participants included program participants and staff, community members, and community leaders. Thematic analysis was done using verbatim transcripts from focus groups and interviews. Results demonstrate that the multiplicative and intersecting statuses of the study population create challenges in the areas of transportation, health care, food, and housing. The challenges of these intersectional statuses limit access to services in ways that each individual status did not, thereby compounding challenges. While previous literature describes the challenges of one or two of these statuses, this work explores the multiplicative effects of the combination of the three statuses using intersectionality. Programmatic and policy recommendations and implications are discussed.

The Prevalence and Incidence of Dementia: a Systematic Review and Meta-analysis.

UNLABELLED: Introduction Dementia is a common neurological condition affecting many older individuals that leads to a loss of independence, diminished quality of life, premature mortality, caregiver burden and high levels of healthcare utilization and cost. This is an updated systematic review and meta-analysis of the worldwide prevalence and incidence of dementia. METHODS: The MEDLINE and EMBASE databases were searched for relevant studies published between 2000 (1985 for Canadian papers) and July of 2012. Papers selected for full-text review were included in the systematic review if they provided an original population-based estimate for the incidence and/or prevalence of dementia. The reference lists of included articles were also searched for additional studies. Two individuals independently performed abstract and full-text review, data extraction, and quality assessment of the papers. Random-effects models and/or meta-regression were used to generate pooled estimates by age, sex, setting (i.e., community, institution, both), diagnostic criteria utilized, location (i.e., continent) and year of data collection. RESULTS: Of 16,066 abstracts screened, 707 articles were selected for full-text review. A total of 160 studies met the inclusion criteria. Among individuals 60 and over residing in the community, the pooled point and annual period prevalence estimates of dementia were 48.62 (CI95%: 41.98-56.32) and 69.07 (CI95%: 52.36-91.11) per 1000 persons, respectively. The respective pooled incidence rate (same age and setting) was 17.18 (CI95%: 13.90-21.23) per 1000 person-years, while the annual incidence proportion was 52.85 (CI95%: 33.08-84.42) per 1,000 persons. Increasing participant age was associated with a higher dementia prevalence and incidence. Annual period prevalence was higher in North America than in South America, Europe and Asia (in order of decreasing period prevalence) and higher in institutional compared to community and combined settings. Sex, diagnostic criteria (except for incidence proportion) and year of data collection were not associated with statistically significant different estimates of prevalence or incidence, though estimates were consistently higher for females than males. CONCLUSIONS: Dementia is a common neurological condition in older individuals. Significant gaps in knowledge about its epidemiology were identified, particularly with regard to the incidence of dementia in low- and middle-income countries. Accurate estimates of prevalence and incidence of dementia are needed to plan for the health and social services that will be required to deal with an aging population.

The Prevalence and Incidence of Dementia Due to Alzheimer's Disease: a Systematic Review and Meta-Analysis.

BACKGROUND: Updated information on the epidemiology of dementia due to Alzheimer's disease (AD) is needed to ensure that adequate resources are available to meet current and future healthcare needs. We conducted a systematic review and meta-analysis of the incidence and prevalence of AD. METHODS: The MEDLINE and EMBASE databases were searched from 1985 to 2012, as well as the reference lists of selected articles. Included articles had to provide an original population-based estimate for the incidence and/or prevalence of AD. Two individuals independently performed abstract and full-text reviews, data extraction and quality assessments. Random-effects models were employed to generate pooled estimates stratified by age, sex, diagnostic criteria, location (i.e., continent) and time (i.e., when the study was done). RESULTS: Of 16,066 abstracts screened, 707 articles were selected for full-text review. A total of 119 studies met the inclusion criteria. In community settings, the overall point prevalence of dementia due to AD among individuals 60+ was 40.2 per 1000 persons (CI95%: 29.1-55.6), and pooled annual period prevalence was 30.4 per 1000 persons (CI95%: 15.6-59.1). In community settings, the overall pooled annual incidence proportion of dementia due to AD among individuals 60+ was 34.1 per 1000 persons (CI95%: 16.4-70.9), and the incidence rate was 15.8 per 1000 person-years (CI95%: 12.9-19.4). Estimates varied significantly with age, diagnostic criteria used and location (i.e., continent). CONCLUSIONS: The burden of AD dementia is substantial. Significant gaps in our understanding of its epidemiology were identified, even in a high-income country such as Canada. Future studies should assess the impact of using such newer clinical diagnostic criteria for AD dementia such as those of the National Institute on Aging-Alzheimer's Association and/or incorporate validated biomarkers to confirm the presence of Alzheimer pathology to produce more precise estimates of the global burden of AD.

Social Supports as Enabling Factors in Nursing Home Admissions: Rural, Suburban, and Urban Differences.

This study investigates differences in social support and nursing home admission by rurality of residence. We use discrete-time event history models with longitudinal data from seven waves (1998-2010) of the Health and Retirement Study to prospectively examine the risk of spending 30 or more days in a nursing home (n = 5,913). Results show that elders with a health problem who live in rural areas of the South or Midwest have approximately 2 times higher odds of nursing home entry than elders living in urban areas in the Northeast. Rural elders report somewhat higher social support than non-rural elders, and controlling for these forms of social support does not explain the higher risk of a nursing home stay for Southerners and Midwesterners living in rural areas. Results suggest that social support has a similar association with nursing home entry for rural, suburban, and urban elders.

Patient safety and quality of care in developing countries in Southeast Asia: a systematic literature review.

OBJECTIVE: To establish current knowledge of patient safety and quality of care in developing countries in Southeast Asia, current interventions and the knowledge gaps. STUDY DESIGN: Systematic review and narrative synthesis. DATA SOURCES: Key words, synonyms and subject headings were used to search seven electronic databases in addition to manual searching of relevant journals. DATA SYNTHESIS: Titles and abstracts of publications between 1990 and 2014 were screened by two reviewers and checked by a third. Full text articles were screened against the eligibility criteria. Data on design, methods and key findings were extracted and synthesized. RESULTS: Four inter-related safety and quality concerns were evident from 33 publications: (i) the risk of patient infection in healthcare delivery, (ii) medications errors/use, (iii) the quality and provision of maternal and perinatal care and (iv) the quality of healthcare provision overall. CONCLUSIONS: Large-scale prevalence studies are needed to identify the full range of safety and quality problems in developing countries in Southeast Asia. Sharing lessons learnt from extensive quality and safety work conducted in industrialized nations may contribute to significant improvements. Yet the applicability of interventions utilized in developed countries to the political and social context in this region must be considered. Strategies to facilitate the collection of robust safety and quality data in the context of limited resources and the local context in each country are needed.

Student journals: a means of assessing transformative learning in aging related courses.

In courses where topics are sensitive or even considered taboo for discussion, it can be difficult to assess students' deeper learning. In addition, incorporating a wide variety of students' values and beliefs, designing instructional strategies and including varied assessments adds to the difficulty. Journal entries or response notebooks can highlight reflection upon others' viewpoints, class readings, and additional materials. These are useful across all educational levels in deep learning and comprehension strategies assessments. Journaling meshes with transformative learning constructs, allowing for critical self-reflection essential to transformation. Qualitative analysis of journals in a death and dying class reveals three transformative themes: awareness of others, questioning, and comfort. Students' journal entries demonstrate transformative learning via communication with others through increased knowledge/exposure to others' experiences and comparing/contrasting others' personal beliefs with their own. Using transformative learning within gerontology and geriatrics education, as well as other disciplined aging-related courses is discussed.