The osteoarthritis bone score (OABS): a new histological scoring system for the characterisation of bone marrow lesions in osteoarthritis.

OBJECTIVES: Bone marrow lesions (BMLs) are associated with pain in osteoarthritis (OA), but histological scores for OA focus on cartilage pathology. We developed a new scoring system, the Osteoarthritis Bone Score (OABS), to characterise OA-related BMLs. METHODS: BML/non-BML tissues identified by Magnetic Resonance Imaging (MRI) in 10 knee OA subjects were harvested at total knee replacement (TKR). Osteochondral tissue from a further 140 TKR and 23 post-mortem (PM) cases was assessed. Histological features distinguishing MRI-defined BML/non-BML tissues on qualitative analysis were classified as present (0) or absent (1), summated for the OABS, validated by Rasch analysis and sensitivity to distinguish between sample groups. Immunohistochemistry for PGP9.5 assessed innervation. RESULTS: Subchondral characteristics associated with BML tissues were cysts, fibrosis, hypervascularity, cartilage islands, trabecular thickening, loss of tidemark integrity and inflammatory cell infiltration. PGP9.5 immunoreactive perivascular nerves were associated with BMLs. OABS performed well as a measurement tool, displayed good reliability (Cronbach alpha = 0.68), had a 2-factor structure (trabecular/non-trabecular), with moderate correlation between the two factors (r = 0.56, 95% CI 0.46, 0.65). OABS scores were higher in TKR than PM cases with chondropathy, median difference 1.5 (95% CI -2, 0). OABS and Mankin scores similarly distinguished TKR from non-OA controls, but only OABS was higher in BML than non-BML tissues, median difference -4 (95% CI -5 to -2). CONCLUSIONS: OABS identifies and validly quantifies histopathological changes associated with OA BMLs. Histopathology underlying BMLs may represent 2 inter-related pathological processes affecting trabecular/non-trabecular structures. Increased vascularity/perivascular innervation in BMLs might contribute to pain.

Early inflammation precedes cardiac fibrosis and heart failure in desmoglein 2 murine model of arrhythmogenic cardiomyopathy.

The study of a desmoglein 2 murine model of arrhythmogenic cardiomyopathy revealed cardiac inflammation as a key early event leading to fibrosis. Arrhythmogenic cardiomyopathy (AC) is an inherited heart muscle disorder leading to ventricular arrhythmias and heart failure due to abnormalities in the cardiac desmosome. We examined how loss of desmoglein 2 (Dsg2) in the young murine heart leads to development of AC. Apoptosis was an early cellular phenotype, and RNA sequencing analysis revealed early activation of inflammatory-associated pathways in Dsg2-null (Dsg2-/-) hearts at postnatal day 14 (2 weeks) that were absent in the fibrotic heart of adult mice (10 weeks). This included upregulation of iRhom2/ADAM17 and its associated pro-inflammatory cytokines and receptors such as TNFα, IL6R and IL-6. Furthermore, genes linked to specific macrophage populations were also upregulated. This suggests cardiomyocyte stress triggers an early immune response to clear apoptotic cells allowing tissue remodelling later on in the fibrotic heart. Our analysis at the early disease stage suggests cardiac inflammation is an important response and may be one of the mechanisms responsible for AC disease progression.

Characterisation of hypertensive heart disease: pathological insights from a sudden cardiac death cohort to inform clinical practice.

Hypertensive heart disease refers to changes in the myocardium that result from hypertension. The relationship between hypertensive heart disease and sudden cardiac death is well established, but there are few pathological studies. We examined the clinical and pathological features of hypertensive heart disease in sudden cardiac death victims from a national cardiovascular pathology registry. We investigated 5239 cases of sudden cardiac death between 1994 and 2018. Hearts were examined by two expert cardiac pathologists. Diagnostic criteria included history of hypertension, increased heart weight and left ventricular wall thickness in the absence of other causes. Collagen was quantified using picrosirius red staining and imaging software. Of 75 sudden cardiac death cases due to hypertensive heart disease (age at death: 54 ± 16 years; 56% males), 56 (75%) reported no prior cardiac symptoms. Thirty-four (45%) recorded a BMI ≥ 30. Only two (2.7%) had hypertensive heart disease diagnosed antemortem. Four (5%) were diagnosed clinically with hypertrophic cardiomyopathy, but lacked myocyte disarray at autopsy. All hearts showed concentric left ventricular hypertrophy and myocyte hypertrophy. Fibrosis was identified microscopically in 59 cases (81%). The posterior left ventricular wall showed the greatest increase in the percentage of collagen in hypertensive diseased hearts compared to controls (25.2% vs 17.9%, p = 0.034). Most sudden deaths due to hypertensive heart disease occur without prior cardiac symptoms; thus, clinical risk stratification is challenging. Hypertensive heart disease can be misdiagnosed in life as hypertrophic cardiomyopathy which has major implications for relatives. Pathologists require a history of hypertension and histology for a definitive diagnosis of hypertensive heart disease.

Factors influencing exposure of children to major hazards on family farms.

On family farms, parents are usually knowledgeable of high-risk activities, yet they allow their children to be active participants in (or bystanders to) hazardous work for reasons not well-documented. A two-phase descriptive study, based on the theory of planned behavior and using mail survey research methods, was carried out to understand factors that influence parents' decisions to expose children to major hazards on family farms. A representative sample of 1,255 Wisconsin dairy farm fathers provided data about factors that influence their decisions to expose children younger than 14 years to risks of injury. Multivariate analyses revealed that attitudes, subjective norms, and perceived control accounted for up to three-fourths of the variance in fathers' behavioral intentions. Fathers' attitudes were stronger predictors of behavioral intentions than subjective norms (i.e., perceived social pressure) or perceived control. Grandparents and mothers exerted a limited influence. Other groups, such as health care providers, 4-H, Future Farmers of America, and insurers, exerted only a modest influence on fathers' feelings of social pressure. Few demographic characteristics of the family or farm were predictive of fathers' intentions to expose children to hazards.

Agricultural employers' hiring and safety practices for adolescent workers.

The goal of the "Safety Training for Employers and Supervisors of Adolescent Farmworkers" initiative is to improve the occupational health and safety knowledge and practices of agricultural employers and supervisors responsible for employees, ages 14 to 17 years. Surveys were sent to members of the National Council of Agricultural Employers and the Washington Growers League to measure attitudes regarding adolescent employees, current hiring and training practices, and future intentions. More than half of the respondents hire adolescents. Two-thirds were male, nearly three-quarters of the respondents had college or post-graduate degrees, and more than half were 50 years or older. The majority of respondents had positive perceptions of adolescents in terms of dependability, helpfulness, and work ethic. Among those who currently hire young workers, the most common reasons were to provide a job for children of friends and family and because they can work part-time to fill a labor demand. Among those not hiring adolescents, the most common reason was concern about child labor regulations and associated tasks (e.g., paperwork, monitoring hours). Respondents use a variety of safety training resources, especially posters and safety meetings. For the future, they expect to need more handout materials and training videos. Study results provide insights into barriers to the employment of young workers and suggest methods by which agricultural safety specialists can best assist those employers and producers who are willing to hire adolescents into agricultural work settings.

Medically attended injuries among young children: observations in a suburban area. 1964.

A control study of the effect of public health education on the rate of accidental injuries among children under 7 years of age in a newly developing suburban area provided an opportunity to gain an insight into the nature and extent of the accident problem itself during a one year baseline period preceding the educational phase of the study. An accident was arbitrarily defined as any actual or presumed trauma following an incident for which direct medical or dental attention was obtained. Data were gathered through regular visits of data collectors to physicians, dentists, and hospitals in the area. An annual accident rate of 124 per 1000 children under 7 years of age was found. Two or more accident occurred to 10% of the children. The highest injury rate by age (179 per 1000 children) was found among 2 year old children, with the rate amount 2 year old boys 75% higher than any other age-sex group. The possible relationships of suburban living to the type and location of accidents by age and sex and to the variation in accidents by day of week are also presented.

A controlled study of health education in accident prevention: the Rockland County Child Injury Project. 1966.

The Rockland County Child Injury Prevention Project was designed to test the effects of public health education for parents on the incidence of accidental injuries to children under 7 years of age in a controlled situation. The incidence of accidental injuries, defined as any actual or presumed trauma following an accident for which medical or dental attention was obtained, was determined in a study population before, during, and after exposure to the educational program and in a comparable control group during a corresponding period of time. The study group was exposed to an intensive education program involving neighborhood discussion groups conducted by lay and professional leaders, meetings with organized groups, and a monthly newsletter. The study population was organized into small neighborhood units of about 24 homes within the suburban housing developments. To measure the effect of the education program, accident rates were computed for each three month reporting period, projected on an annual basis. No consistent differences were discernible in the trends in the accident rates between the study and control groups during the three years of the project. On the contrary, the curve for the study group crossed that of the control group on no less than five occasions. There was a sharp decline in accidents during the second half of the education phase. Any conclusions regarding a positive effect of the education program proved untenable in the light of the sharp and disproportionate increase in the accident rate in the study group during the six month phase after education had stopped. After what appeared to be a contrary trend earlier, developments during this period demonstrated vividly the need to continue reporting for a sufficient time in a controlled situation to be sure that fortuitous changes over short periods do not lead to unwarrented conclusion. The flow of reports from hospitals was more consistent than from physicians. This suggested that, in selected control studies, adequate rates for comparative purposes might have been obtained entirely from hospital records.