Metastasis and bone loss: Advancing treatment and prevention

Tumor metastasis to the skeleton affects over 400,000 individuals in the United States annually, more than any other site of metastasis, including significant proportions of patients with breast, prostate, lung and other solid tumors. Research on the bone microenvironment and its role in metastasis suggests a complex role in tumor growth. Parallel preclinical and clinical investigations into the role of adjuvant bone-targeted agents in preventing metastasis and avoiding cancer therapy-induced bone loss have recently reported exciting and intriguing results. A multidisciplinary consensus conference convened to review recent progress in basic and clinical research, assess gaps in current knowledge and prioritize recommendations to advance research over the next 5 years. The program addressed three topics: advancing understanding of metastasis prevention in the context of bone pathophysiology; developing therapeutic approaches to prevent metastasis and defining strategies to prevent cancer therapy-induced bone loss. Several priorities were identified: (1) further investigate the effects of bone-targeted therapies on tumor and immune cell interactions within the bone microenvironment; (2) utilize and further develop preclinical models to study combination therapies; (3) conduct clinical studies of bone-targeted therapies with radiation and chemotherapy across a range of solid tumors; (4) develop biomarkers to identify patients most likely to benefit from bone-targeted therapies; (5) educate physicians on bone loss and fracture risk; (6) define optimal endpoints and new measures of efficacy for future clinical trials; and (7) define the optimum type, dose and schedule of adjuvant bone-targeted therapy.     

Need to optimise infant feeding counselling: A cross-sectional survey among HIV-positive mothers in Eastern Uganda

Background  

The choice of infant feeding method is important for HIV-positive mothers in order to optimise the chance of survival of their infants and to minimise the risk of HIV transmission. The aim of this study was to investigate feeding practices, including breastfeeding, in the context of PMTCT for infants and children under two years of age born to HIV-positive mothers in Uganda.     

Socio-demographic factors related to periodontal status and tooth loss of pregnant women in Mbale district, Uganda

Background  

Information on the socio-behavioral distribution of periodontal status and tooth loss in pregnancy emanating from sub Saharan Africa is sparse. This study examined periodontal status and tooth loss in pregnant Ugandan women and assessed the relationship with socio-demographics factors, parity, dental care and oral hygiene.     

The effects of individual factors and school environment on mental health and prejudiced attitudes among Norwegian adolescents

Introduction  

The aim was to examine the prevalence of mental health difficulties and prejudices toward mental illness among adolescents, and to analyze possible school and school class effects on these issues.     

Association of maternal HIV-1 severity with dental caries: an observational study of uninfected 5- to 7-yr-old children of HIV-1-infected mothers without severe immune suppression

Treatment programs to prevent perinatal and postnatal HIV-1 transmission have become available in sub-Saharan Africa, leading to an emerging population of HIV-1 exposed uninfected (HEU) children. Exposure to HIV-1 in utero and during breastfeeding may increase the risk of morbidity and mortality in HEU children. This study estimated the association of the severity of maternal HIV-1 infection as assessed by CD4 count and viral load at baseline (7 d postpartum), with  dmft count of their 5- to 7-yr-old HEU offspring. A follow-up study was conducted of HIV-1-infected mother–HEU children pairs (n = 164) from the Ugandan site of the ANRS 12341-PROMISE- PEP trial (ClinicalTrials.gov, number NCT00640263). HIV-1-infected mothers were interviewed and the HEU children were examined for caries using the World Health Organization's survey methods for field conditions and the dmft index. Directed acyclic graphs and negative binomial regression were used for analyses. The prevalence of 1 or more dmft was 48%. Negative binomial regression showed no association between the dmft count and maternal CD4 counts 7 d postpartum but a 10% lower dmft count with longer breastfeeding duration was found. Maternal CD4 count at birth was not associated with the dental caries experience in uninfected children born to women without severe immune suppression, while there appeared to be a protective effect of high viral load and breastfeeding duration.     

Discontinuities in the endothelium of epiphyseal cartilage canals and relevance to joint disease in foals

Cartilage canals have been shown to contain discontinuous blood vessels that enable circulating bacteria to bind to cartilage matrix, leading to vascular occlusion and associated pathological changes in pigs and chickens. It is also inconsistently reported that cartilage canals are surrounded by a cellular or acellular wall that may influence whether bacterial binding can occur. It is not known whether equine cartilage canals contain discontinuous endothelium or are surrounded by a wall. This study aimed to examine whether there were discontinuities in the endothelium of cartilage canal vessels, and whether canals had a cellular or acellular wall, in the epiphyseal growth cartilage of foals. Epiphyseal growth cartilage from the proximal third of the medial trochlear ridge of the distal femur from six healthy foals that were 1, 24, 35, 47, 118 and 122 days old and of different breeds and sexes was examined by light microscopy (LM), transmission electron microscopy (TEM) and immunohistochemistry. The majority of patent cartilage canals contained blood vessels that were lined by a thin layer of continuous endothelium. Fenestrations were found in two locations in one venule in a patent cartilage canal located deep in the growth cartilage and close to the ossification front in the 118‐day‐old foal. Chondrifying cartilage canals in all TEM‐examined foals contained degenerated endothelial cells that were detached from the basement membrane, resulting in gap formation. Thirty‐three percent of all canals were surrounded by a hypercellular rim that was interpreted as contribution of chondrocytes to growth cartilage. On LM, 69% of all cartilage canals were surrounded by a ring of matrix that stained intensely eosinophilic and consisted of collagen fibres on TEM that were confirmed to be collagen type I by immunohistochemistry. In summary, two types of discontinuity were observed in the endothelium of equine epiphyseal cartilage canal vessels: fenestrations were observed in a patent cartilage canal in the 118‐day‐old foal; and gaps were observed in chondrifying cartilage canals in all TEM‐examined foals. Canals were not surrounded by any cellular wall, but a large proportion was surrounded by an acellular wall consisting of collagen type I. Bacterial binding can therefore probably occur in horses by mechanisms that are similar to those previously demonstrated in pigs and chickens.