Digitalizing WHO’s Health Emergency Leadership Training During the Pandemic

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Novel therapies for resistant focal segmental glomerulosclerosis (FONT) phase II clinical trial: study design

Abstract Background The lack of adequate randomized clinical trials (RCT) has hindered identification of new therapies that are safe and effective for patients with primary focal segmental glomerulosclerosis (FSGS), especially in patients who fail to respond to corticosteroids and immunosuppressive therapies. Recent basic science advances have led to development of alternative treatments that specifically target aberrant pathways of fibrosis which are relevant to disease progression in FSGS. There is a need for a flexible Phase II study design which will test such novel antifibrotic strategies in order to identify agents suitable for phase III testing. Methods/Design The Novel Therapies for Resistant Focal Segmental Glomerulosclerosis (FONT) project is a multicenter Phase I/II RCT designed to investigate the potential efficacy of novel therapies for resistant FSGS. Adalimumab and galactose will be evaluated against conservative therapy consisting of the combination of lisinopril, losartan and atorvastatin. The sample size is defined to assure that if one of the treatments has a superior response rate compared to that of the other treatments, it will be selected with high probability for further evaluation. Comparison of primary and secondary endpoints in each study arm will enable a choice to be made of which treatments are worthy of further study in future Phase III RCT. Discussion This report highlights the key features of the FONT II RCT including the two-step outcome analysis that will expedite achievement of the study objectives. The proposed phase II study design will help to identify promising agents for further testing while excluding ineffective agents. This staged approach can help to prevent large expenditures on unworthy therapeutic agents in the management of serious but rare kidney diseases Trial Registration ClinicalTrials.gov, NCT0081425

A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome

Steroid-resistant nephrotic syndrome (SRNS) is the second most frequent cause of ESRD in the first two decades of life. Effective treatment is lacking. First insights into disease mechanisms came from identification of single-gene causes of SRNS. However, the frequency of single-gene causation and its age distribution in large cohorts are unknown. We performed exon sequencing of NPHS2 and WT1 for 1783 unrelated, international families with SRNS. We then examined all patients by microfluidic multiplex PCR and next-generation sequencing for all 27 genes known to cause SRNS if mutated. We detected a single-gene cause in 29.5% (526 of 1783) of families with SRNS that manifested before 25 years of age. The fraction of families in whom a single-gene cause was identified inversely correlated with age of onset. Within clinically relevant age groups, the fraction of families with detection of the single-gene cause was as follows: onset in the first 3 months of life (69.4%), between 4 and 12 months old (49.7%), between 1 and 6 years old (25.3%), between 7 and 12 years old (17.8%), and between 13 and 18 years old (10.8%). For PLCE1, specific mutations correlated with age of onset. Notably, 1% of individuals carried mutations in genes that function within the coenzyme Q10 biosynthesis pathway, suggesting that SRNS may be treatable in these individuals. Our study results should facilitate molecular genetic diagnostics of SRNS, etiologic classification for therapeutic studies, generation of genotype-phenotype correlations, and the identification of individuals in whom a targeted treatment for SRNS may be available

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154675/1/art41191.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154675/2/art41191_am.pd

Cinesi d’oltremare. L’insediamento nel Sud-Est asiatico

Il rapido sviluppo economico di Taiwan, Hong Kong e dei paesi dell'ASEAN negli ultimi decenni ha richiamato l'attenzione sul rilevante ruolo svolto in tale processo dai milioni di "cinesi d'oltremare" che popolano il Sud-Est asiatico. Il volume ripercorre la storia della diaspora cinese in Asia sudorientale evidenziandone le differenti dinamiche e i rapporti con le società ospiti.- Indice #6- Prefazione #12- Introduzione, Jamie A. C. Mackie #16- Cap.I Il soggiorno: l’esperienza dei cinesi nel Sud-Est asiatico, Wang Gungwu #38- Cap.II Le oscillazioni dell’interazione cinese con il Sud-Est asiatico sul lungo periodo, Anthony Reid #56- Cap.III Le società cinesi creolizzate nel Sud-Est asiatico, G. William Skinner #96- Cap.IV Ngo Si Lien e gli Annali vietnamiti, Oliver W. Wolters #146- Cap.V Il romanzo dei tre regni e il Sam Kok thai, Craig J. Reynolds #170- Cap.VI Le vicissitudini del commercio marittimo: le lettere del mercante Li Kunhe (1803-09), Leonard Blussé #204- Cap.VII Gli insediamenti cinesi nelle campagne del Sud-Est asiatico: storie mai scritte, Mary F. Somers Heidhues #222- Cap.VIII Templi ancestrali, associazioni funerarie e tentativi di risinificazione nell’India olandese del XIX secolo, Claudine Salmon #246- Cap.IX Jennifer Wayne Cushman (1945-1989): lo studio dei cinesi d’oltremare, Virginia Hooker e Anthony C. Milner #270- Indice analitico #27

An emerging concern: Toxic fumes in airplane cabins

Toxicology is a new science, the complexities of which have been highlighted in the papers contained within this special section. Our understanding of the mechanisms through which various chemicals interfere with nervous system function is constantly evolving and research is unable to keep up with the speed with which new chemicals are produced and put onto the market. Thus there are often controversies surrounding the health-effects of commercially available compounds and disagreement around what constitutes safe exposure limits. This article will introduce readers to an emerging concern in this field, the potential risk to health of toxic fumes in airplane cabins. We explore the challenges and methodological issues encountered by researchers who have tried to investigate this issue and highlight the need for further research on this topic. We hope this article will promote discussion amongst academics and clinicians, and lead to the identification of creative solutions to the methodological issues encountered to date