The threat of the COVID-19 pandemic on reversing global life-saving gains in the survival of childhood cancer: A call for collaborative action from SIOP, IPSO, PROS, WCC, CCI, st jude global, UICC and WHPCA

The COVID-19 pandemic poses an unprecedented health crisis in all socio-economic regions across the globe. While the pandemic has had a profound impact on access to and delivery of health care by all services, it has been particularly disruptive for the care of patients with life-threatening noncommunicable diseases (NCDs) such as the treatment of children and young people with cancer. The reduction in child mortality from preventable causes over the last 50 years has seen childhood cancer emerge as a major unmet health care need. Whilst survival rates of 85% have been achieved in high income countries, this has not yet been translated into similar outcomes for children with cancer in resource-limited settings where survival averages 30%. Launched in 2018, by the World Health Organization (WHO), the Global Initiative for Childhood Cancer (GICC) is a pivotal effort by the international community to achieve at least 60% survival for children with cancer by 2030. The WHO GICC is already making an impact in many countries but the disruption of cancer care during the COVID-19 pandemic threatens to set back this global effort to improve the outcome for children with cancer, wherever they may live. As representatives of the global community committed to fostering the goals of the GICC, we applaud the WHO response to the COVID-19 pandemic, in particular we support the WHO's call to ensure the needs of patients with life threatening NCDs including cancer are not compromised during the pandemic. Here, as collaborative partners in the GICC, we highlight specific areas of focus that need to be addressed to ensure the immediate care of children and adolescents with cancer is not disrupted during the pandemic; and measures to sustain the development of cancer care so the long-term goals of the GICC are not lost during this global health crisis.Fil: Pritchard Jones, Kathy. University College London; Estados UnidosFil: de Abib, Simone C.V.. International Society Of Paediatric Surgical Oncology; Surinam. Universidade Federal de Sao Paulo; BrasilFil: Esiashvili, Natia. University of Emory; Estados UnidosFil: Kaspers, Gertjan J.L.. Princess Máxima Center for Pediatric Oncology; Países BajosFil: Rosser, Jon. No especifíca;Fil: van Doorninck, John A.. Rocky Mountain Hospital for Children; Estados UnidosFil: Braganca, João M.L.. No especifíca;Fil: Hoffman, Ruth I.. No especifíca;Fil: Rodriguez Galindo, Carlos. St Jude Children’s Research Hospital; Estados UnidosFil: Adams, Cary. Union for International Cancer Control; SuizaFil: Connor, Stephen R.. Worldwide Hospice Palliative Care Alliance; Estados UnidosFil: Abdelhafeez, Abdelhafeez H.. International Society of Paediatric Surgical Oncology; Suiza. St. Jude Children’s Research Hospital; Estados UnidosFil: Bouffet, Eric. University Of Toronto. Hospital For Sick Children; Canadá. International Society of Paediatric Surgical Oncology; SuizaFil: Howard, Scott C.. International Society of Paediatric Surgical Oncology; Suiza. University of Tennessee; Estados UnidosFil: Challinor, Julia M.. International Society of Paediatric Surgical Oncology; Suiza. University of California; Estados UnidosFil: Hessissen, Laila. Children Hospital of Rabat; Marruecos. International Society of Paediatric Surgical Oncology; SuizaFil: Dalvi, Rashmi B.. Bombay Hospital Institute of Medical Sciences; India. International Society of Paediatric Surgical Oncology; SuizaFil: Kearns, Pamela. International Society of Paediatric Surgical Oncology; SuizaFil: Chantada, Guillermo Luis. International Society of Paediatric Surgical Oncology; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Frazier, Lindsay A.. International Society of Paediatric Surgical Oncology; Suiza. Dana-Farber Cancer Institute; Estados UnidosFil: Sullivan, Michael J.. University of Melbourne; Australia. International Society of Paediatric Surgical Oncology; SuizaFil: Schulte, Fiona S.M.. University of Calgary; Canadá. International Society of Paediatric Surgical Oncology; SuizaFil: Morrissey, Lisa K.. Boston Children’s Hospital; Estados Unidos. International Society of Paediatric Surgical Oncology; SuizaFil: Kozhaeva, Olga. European Society for Paediatric Oncology; BélgicaFil: Luna Fineman, Sandra. Children’s Hospital Colorado; Estados Unidos. International Society of Paediatric Oncology; SuizaFil: Khan, Muhammad S.. Tawam Hospital; Emiratos Arabes Unido

Diabetic gastroparesis: Therapeutic options

Gastroparesis is a condition characterized by delayed gastric emptying and the most common known underlying cause is diabetes mellitus. Symptoms include nausea, vomiting, abdominal fullness, and early satiety, which impact to varying degrees on the patient’s quality of life. Symptoms and deficits do not necessarily relate to each other, hence despite significant abnormalities in gastric emptying, some individuals have only minimal symptoms and, conversely, severe symptoms do not always relate to measures of gastric emptying. Prokinetic agents such as metoclopramide, domperidone, and erythromycin enhance gastric motility and have remained the mainstay of treatment for several decades, despite unwanted side effects and numerous drug interactions. Mechanical therapies such as endoscopic pyloric botulinum toxin injection, gastric electrical stimulation, and gastrostomy or jejunostomy are used in intractable diabetic gastroparesis (DG), refractory to prokinetic therapies. Mitemcinal and TZP-101 are novel investigational motilin receptor and ghrelin agonists, respectively, and show promise in the treatment of DG. The aim of this review is to provide an update on prokinetic and mechanical therapies in the treatment of DG

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society

A stereological study of the effect of locally administered growth hormone on the microstructure of the tibial growth plate in immature rabbits

Background: The mechanism of growth hormone (GH) effects on growth plate (GP) and its chondrocytes is of utmost importance, thus we have investigated the microstructure of proximal tibial GP of rabbits with designed-based stereological methods. Material and methods: In this experimental study, the tissue came from a study into longitudinal growth using minipumps surgically implanted into the right upper tibial GP of 9 weeks old rabbits, administering GH at 10 and 100 μ g/day for a period of 21 days. Saline only administered and non-operated groups served as controls. The following stereological parameters were investigated: GP volume and height chondrocyte volume, surface and number densities. These direct measurements lead to estimate of chondrocyte total volume, surface and number mean chondrocyte volume and surface in the number-weighted distribution. Data were analyzed using t-test and single factor ANOVA, then if there was any significant difference, Dunnett's multiple comparison test was performed. Results: No significant differences were found between the right and left tibial and saline and control groups in the total quantities. The GP volume and height and chondrocyte total volume showed no significant differences between the treatment and control groups. Conclusion: GH acts on rabbit proximal tibial GP by inducing chondrocyte hyperplasia but not hypertrophy. The operative procedure of implanting a minipump had no detectable effect on any of the parameters measured. GH had an effect on the local cytostructure of the GP on the treated side