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Twelve years have now passed since the influential WHO Report on the Social Determinants of Health (SDoH) in 2008. A group of senior international public health scholars and decision-makers met in Italy in mid-2019 to review the legacy of the SDoH conceptual framework and its adequacy for the many challenges facing our field as we enter the 2020s. Four major categories of challenges were identified: emerging “exogenous” challenges to global health equity, challenges related to weak policy and practice implementation, more fundamental challenges related to SDoH theory and research, and broader issues around modern research in general. Each of these categories is discussed, and potential solutions offered. We conclude that although the SDoH framework is still a worthy core platform for public health research, policy, and practice, the time is ripe for significant evolution.

Statutory registration of Chinese Medicine (CM) practitioners was introduced in Victoria in 2000. The application assessment process for those who were granted registration during the transitional period (2002-04) was resource intensive, as little was known about their age, education, practice and language proficiency. This study offers insights that may be useful for the planning of national registration to commence in 2012. Data were extracted from registration application forms submitted to the Chinese Medicine Registration Board of Victoria (CMRB) between 2002 and 2004, using pre-defined data collection forms. In 2006, 639 'grandparented' Victorian CM practitioners had been registered, with a median age of 44 years old (range 23-86). There was a higher proportion of younger female, English-speaking, acupuncturists v. a higher proportion of older male, non-English-speaking, Chinese herbalists. There were few CM practitioners in rural areas, particularly herbalists. More than one-third of practitioners had obtained qualifications overseas and almost half of these practitioners provided no evidence of past study in professional issues and medical ethics. Ageing, diversity in qualifications and training, English proficiency, and level of study in professional issues and medical ethics represent major challenges for the implementation of CM national registration in 2012.

Background. Statutory registration of Chinese Medicine (CM) practitioners was introduced in Victoria in 2000. The application assessment process for those who were granted registration during the transitional period (2002-04) was resource intensive, as little was known about their age, education, practice and language proficiency. This study offers insights that may be useful for the planning of national registration to commence in 2012. Methods. Data were extracted from registration application forms submitted to the Chinese Medicine Registration Board of Victoria (CMRB) between 2002 and 2004, using pre-defined data collection forms. Results. In 2006, 639 'grandparented' Victorian CM practitioners had been registered, with a median age of 44 years old (range 23-86). There was a higher proportion of younger female, English-speaking, acupuncturists v. a higher proportion of older male, non-English-speaking, Chinese herbalists. There were few CM practitioners in rural areas, particularly herbalists. More than one-third of practitioners had obtained qualifications overseas and almost half of these practitioners provided no evidence of past study in professional issues and medical ethics. Conclusions. Ageing, diversity in qualifications and training, English proficiency, and level of study in professional issues and medical ethics represent major challenges for the implementation of CM national registration in 2012.

Background. Statutory registration of Chinese Medicine (CM) practitioners was introduced in Victoria in 2000. The application assessment process for those who were granted registration during the transitional period (2002-04) was resource intensive, as little was known about their age, education, practice and language proficiency. This study offers insights that may be useful for the planning of national registration to commence in 2012. Methods. Data were extracted from registration application forms submitted to the Chinese Medicine Registration Board of Victoria (CMRB) between 2002 and 2004, using pre-defined data collection forms. Results. In 2006, 639 'grandparented' Victorian CM practitioners had been registered, with a median age of 44 years old (range 23-86). There was a higher proportion of younger female, English-speaking, acupuncturists v. a higher proportion of older male, non-English-speaking, Chinese herbalists. There were few CM practitioners in rural areas, particularly herbalists. More than one-third of practitioners had obtained qualifications overseas and almost half of these practitioners provided no evidence of past study in professional issues and medical ethics. Conclusions. Ageing, diversity in qualifications and training, English proficiency, and level of study in professional issues and medical ethics represent major challenges for the implementation of CM national registration in 2012.

ObjectiveTo investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA).MethodsIn a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data.ResultsLD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features.ConclusionsA rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.

Ionizing radiation and chemotherapy deplete hematopoietic stem cells and damage the vascular niche wherein hematopoietic stem cells reside. Hematopoietic stem cell regeneration requires signaling from an intact bone marrow (BM) vascular niche, but the mechanisms that control BM vascular niche regeneration are poorly understood. We report that BM vascular endothelial cells secrete semaphorin 3 A (SEMA3A) in response to myeloablation and SEMA3A induces p53 – mediated apoptosis in BM endothelial cells via signaling through its receptor, Neuropilin 1 (NRP1), and activation of cyclin dependent kinase 5. Endothelial cell – specific deletion of Nrp1 or Sema3a or administration of anti-NRP1 antibody suppresses BM endothelial cell apoptosis, accelerates BM vascular regeneration and concordantly drives hematopoietic reconstitution in irradiated mice. In response to NRP1 inhibition, BM endothelial cells increase expression and secretion of the Wnt signal amplifying protein, R spondin 2. Systemic administration of anti - R spondin 2 blocks HSC regeneration and hematopoietic reconstitution which otherwise occurrs in response to NRP1 inhibition. SEMA3A – NRP1 signaling promotes BM vascular regression following myelosuppression and therapeutic blockade of SEMA3A – NRP1 signaling in BM endothelial cells accelerates vascular and hematopoietic regeneration in vivo. Ionizing radiation and chemotherapy deplete haematopoietic stem cells and damage the vascular niche. Here the authors show that irradiation induces SEMA3A secretion from bone marrow endothelial cells (ECs), inducing EC apoptosis via NRP1 and that NRP1 inhibition promotes vascular regeneration and R spondin 2 dependent hematopoietic regeneration.

Dry-eye syndrome (DES) is a general eye disease. Eye drops are the common ophthalmological medication. However, the ocular barrier makes it difficult to attain high drug bioavailability. Nanomedicine is a promising alternative treatment for ocular diseases and may increase drug content in the affected eye. To explore this potential, we constructed nanoparticles (NPs) containing an anti-inflammatory agent for DES treatment. The NPs were made of gelatin-epigallocatechin gallate (EGCG) with surface decoration by hyaluronic acid (HA) and designated \"GEH\". The particle size, surface charge, and morphology were evaluated. The in vitro biocompatibility and anti-inflammation effect of nanoparticles were assayed via culturing with human corneal epithelium cells (HCECs) and in vivo therapeutic effect was examined in a DES rabbit's model. The synthesized GEH NPs had a diameter of approximately 250 nm and were positively charged. A coculture experiment revealed that 20 µg/mL GEH was not cytotoxic to HCECs and that an EGCG concentration of 0.2 µg/mL downregulated the gene expression of and in inflamed HCECs. Large amounts of GEH NPs accumulated in the cytoplasm of HCECs and the ocular surfaces of rats and rabbits, indicating the advantage of GEH NPs for ocular delivery of medication. Twice-daily topical treatment with GEH NPs was performed in a rabbit model of DES. The ocular surface of GEH-treated rabbits displayed normal corneal architecture with no notable changes in inflammatory cytokine levels in the cornea lysate. The treatment improved associated clinical signs, such as tear secretion, and fluorescein staining recovered. We successfully produced GEH NPs with high affinity for HCECs and animal eyes. The treatment can be delivered as eye drops, which retain the drug on the ocular surface for a longer time. Ocular inflammation was effectively inhibited in DES rabbits. Therefore, GEH NPs are potentially valuable as a new therapeutic agent delivered in eye drops for treating DES.

In adults with congenital adrenal hyperplasia, crinecerfont, a corticotropin-releasing factor type 1 receptor antagonist, lowered the mean glucocorticoid dose and decreased the mean androstenedione level.

ObjectiveTo evaluate the effects of denosumab on erosion healing at 2–4 metacarpophalangeal (MCP) head as determined by high-resolution peripheral quantitative CT (HR-pQCT) in patients with rheumatoid arthritis (RA) with stable disease.MethodsThis was a randomised, placebo-controlled, double-blind study. Patients with RA with disease activity score 28 joints (DAS28) ≤5.1 were randomised (1:1) to subcutaneous denosumab 60 mg or placebo once every 6 months for 24 months. The primary outcome was erosion healing at MCP 2–4 on HR-pQCT at 12 months. The effects of denosumab on erosion and joint space parameters on HR-pQCT and radiographs, disease activity and health assessment questionnaire-disability index (HAQ-DI) were also examined.ResultsAt 24 months, HR-pQCT images were analysed in 98 patients. One-third of the patients achieved sustained low disease activity throughout the study. At 12 months, changes in erosion parameters on HR-pQCT were similar between the two groups. At 24 months, new erosions (19% vs 9%, p=0.009) and erosion progression (18% vs 8%, p=0.019) were more common in the placebo group than the denosumab group. Erosion healing was seen in a significantly higher proportion of patients in the denosumab group (20% vs 6%, p=0.045) at 24 months. No significant changes in joint space parameters on HR-pQCT, van der Heijde-Sharp erosion score, DAS28 and HAQ-DI were observed in the two groups at 12 and 24 months.ConclusionAlthough no differences in erosion parameters were observed at 12 months, denosumab was more efficacious than placebo in erosion repair on HR-pQCT after 24 months.Trial registration number NCT03239080.