Riviste scientifiche

[Obituary] Gordon Ostlere, alias Richard Gordon

The Lancet - Sa, 09/09/2017 - 00:00
Anaesthetist and author of the successful series of Doctor books. Born in London on Sept 15, 1921, he died after a stroke in Kent, UK, on Aug 11, 2017, aged 95 years.

[Correspondence] The physician as dictator

The Lancet - Sa, 09/09/2017 - 00:00
In the wake of the atrocities committed by the regime of ophthalmologist-cum-dictator Bashar al-Assad, the medical community has been horrified by the devastation caused by one of its own.1 Considering the frequent criticisms of the hierarchical power structure in medicine, we sought to establish whether physicians disproportionately tend to be the leaders of autocracies. We analysed the governments of 176 countries over 71 years (1945–2015), identifying the de-facto ruler of every country for each year.

[Correspondence] The Global Gag Rule: placing the health and lives of women and girls at risk

The Lancet - Sa, 09/09/2017 - 00:00
The Lancet Editorial (July 1, p 1)1 and Obituary (July 1, p 24)2 published following the death of Babatunde Osotimehin—the Executive Director of the UN Population Fund—gave a fitting tribute to his huge contribution to sexual and reproductive health and rights, but also provided a timely reminder of how the current political climate in the USA threatens to undermine gender equality, jeopardise the health, rights, and wellbeing of girls and women, and reverse years of hard work and progress.

[Correspondence] Life-sustaining technologies in resource-limited settings

The Lancet - Sa, 09/09/2017 - 00:00
Vivekanand Jha and colleagues (Feb 23, p 1851)1 highlighted several issues on global dialysis. As stated in their Health Policy paper, more than 2 million people died in 2010 because of insufficient access to dialysis, most of whom were from resource-limited settings.2 However, several issues remain unaddressed, particularly factors related to dialysis in resource-limited settings, where more than 80% of people affected by kidney diseases live.3,4

[Correspondence] Life-sustaining technologies in resource-limited settings – Authors' reply

The Lancet - Sa, 09/09/2017 - 00:00
The achievement of equity in the distribution of renal replacement therapies and nephrology care for patients with end-stage kidney disease in resource-limited settings is a complex ethical and clinical problem.1 John W Stanifer and Abhinav Sharma draw attention to the substantial burden of mortality associated with acute kidney injury in such settings, the demographic factors that can distinguish between populations requiring dialysis for acute or chronic kidney failure, and the consequences of the non-availability of dialysis for the two groups.

[Correspondence] Conscious sedation or general anaesthesia for lumbar puncture in children in Poland

The Lancet - Sa, 09/09/2017 - 00:00
Children with acute lymphoblastic leukaemia who are treated according to the intercontinental ALL-IC-BFM-2009 protocol have between 15 and 22 lumbar punctures with intrathecal drug administration during the first 12 months of therapy, depending on risk group and central nervous system involvement. Families in Poland are putting considerable pressure on paediatric oncology centres to do lumbar punctures under general anaesthesia, instead of using conscious sedation alone. Conscious sedation is usually done with midazolam, analgesics, and topical anaesthetic ointment.

[Articles] Partial pancreatoduodenectomy versus duodenum-preserving pancreatic head resection in chronic pancreatitis: the multicentre, randomised, controlled, double-blind ChroPac trial

The Lancet - Sa, 09/09/2017 - 00:00
No differences in quality of life after surgery for chronic pancreatitis were seen between the interventions. Results from single-centre trials showing superiority for DPPHR were not confirmed in the multicentre setting.

[Series] Advances in paediatric urology

The Lancet - Sa, 09/09/2017 - 00:00
Paediatric urological surgery is often required for managing congenital and acquired disorders of the genitourinary system. In this Series paper, we highlight advances in the surgical management of six paediatric urological disorders. The management of vesicoureteral reflux is evolving, with advocacy ranging from a less interventional assessment and antimicrobial prophylaxis to surgery including endoscopic injection of a bulking agent and minimally invasive ureteric reimplantation. Evidence supports early orchidopexy to improve fertility and reduce malignancy in boys with undescended testes.

[Series] Advances in paediatric gastroenterology

The Lancet - Sa, 09/09/2017 - 00:00
Recent developments in paediatric gastrointestinal surgery have focused on minimally invasive surgery, the accumulation of high-quality clinical evidence, and scientific research. The benefits of minimally invasive surgery for common disorders like appendicitis and hypertrophic pyloric stenosis are all supported by good clinical evidence. Although minimally invasive surgery has been extended to neonatal surgery, it is difficult to establish its role for neonatal disorders such as oesophageal atresia and biliary atresia through clinical trials because of the rarity of these disorders.

Low-oxygen dwarf galaxy shows us how the early universe looked

New Scientist - Ve, 08/09/2017 - 19:49
A star factory with the lowest oxygen level ever seen in such a galaxy could help us understand how the elements were distributed after the big bang

Gel-like ice is the lightest form of water ever discovered

New Scientist - Ve, 08/09/2017 - 18:59
A type of simulated water ice has a molecular structure so sparse it’s like frozen candy floss, making it the lightest type of ice we’ve ever seen

Hurricane Irma tears across Caribbean leaving chaos in its wake

New Scientist - Ve, 08/09/2017 - 15:15
The tropical storm has left a trail of devastation across the region, reducing islands to wreckage and leaving at least 14 people dead

Equifax data breach hits nearly half of US – and isn’t over yet

New Scientist - Ve, 08/09/2017 - 14:39
“Horrendous” hack of Equifax, a US firm responsible for millions of people’s credit ratings, is not the biggest in US history, but the data is the most sensitive

We seem to be getting stupider and population ageing may be why

New Scientist - Ve, 08/09/2017 - 14:29
Average IQ may be falling, a trend some think is due to smarter people having fewer children. Now evidence suggests longer lifespans may be to blame instead

Mexico on tsunami alert after biggest earthquake in 85 years

New Scientist - Ve, 08/09/2017 - 13:09
The US Geological Survey reported the earthquake's magnitude as 8.1, making it the biggest earthquake in Mexico since 1932

Box jellyfish will destroy future oceans by gobbling up the food

New Scientist - Ve, 08/09/2017 - 10:00
As the oceans become more acidic thanks to greenhouse gas emissions, box jellyfish will eat far more copepods – the foundations of marine food webs

Oral tetrahydrouridine and decitabine for non-cytotoxic epigenetic gene regulation in sickle cell disease: A randomized phase 1 study

PLoS Medicine - Gi, 07/09/2017 - 23:00

by Robert Molokie, Donald Lavelle, Michel Gowhari, Michael Pacini, Lani Krauz, Johara Hassan, Vinzon Ibanez, Maria A. Ruiz, Kwok Peng Ng, Philip Woost, Tomas Radivoyevitch, Daisy Pacelli, Sherry Fada, Matthew Rump, Matthew Hsieh, John F. Tisdale, James Jacobberger, Mitch Phelps, James Douglas Engel, Santhosh Saraf, Lewis L. Hsu, Victor Gordeuk, Joseph DeSimone, Yogen Saunthararajah

Background

Sickle cell disease (SCD), a congenital hemolytic anemia that exacts terrible global morbidity and mortality, is driven by polymerization of mutated sickle hemoglobin (HbS) in red blood cells (RBCs). Fetal hemoglobin (HbF) interferes with this polymerization, but HbF is epigenetically silenced from infancy onward by DNA methyltransferase 1 (DNMT1).

Methods and findings

To pharmacologically re-induce HbF by DNMT1 inhibition, this first-in-human clinical trial (NCT01685515) combined 2 small molecules—decitabine to deplete DNMT1 and tetrahydrouridine (THU) to inhibit cytidine deaminase (CDA), the enzyme that otherwise rapidly deaminates/inactivates decitabine, severely limiting its half-life, tissue distribution, and oral bioavailability. Oral decitabine doses, administered after oral THU 10 mg/kg, were escalated from a very low starting level (0.01, 0.02, 0.04, 0.08, or 0.16 mg/kg) to identify minimal doses active in depleting DNMT1 without cytotoxicity. Patients were SCD adults at risk of early death despite standard-of-care, randomized 3:2 to THU–decitabine versus placebo in 5 cohorts of 5 patients treated 2X/week for 8 weeks, with 4 weeks of follow-up. The primary endpoint was ≥ grade 3 non-hematologic toxicity. This endpoint was not triggered, and adverse events (AEs) were not significantly different in THU-decitabine—versus placebo-treated patients. At the decitabine 0.16 mg/kg dose, plasma concentrations peaked at approximately 50 nM (Cmax) and remained elevated for several hours. This dose decreased DNMT1 protein in peripheral blood mononuclear cells by >75% and repetitive element CpG methylation by approximately 10%, and increased HbF by 4%–9% (P < 0.001), doubling fetal hemoglobin-enriched red blood cells (F-cells) up to approximately 80% of total RBCs. Total hemoglobin increased by 1.2–1.9 g/dL (P = 0.01) as reticulocytes simultaneously decreased; that is, better quality and efficiency of HbF-enriched erythropoiesis elevated hemoglobin using fewer reticulocytes. Also indicating better RBC quality, biomarkers of hemolysis, thrombophilia, and inflammation (LDH, bilirubin, D-dimer, C-reactive protein [CRP]) improved. As expected with non-cytotoxic DNMT1-depletion, platelets increased and neutrophils concurrently decreased, but not to an extent requiring treatment holds. As an early phase study, limitations include small patient numbers at each dose level and narrow capacity to evaluate clinical benefits.

Conclusion

Administration of oral THU-decitabine to patients with SCD was safe in this study and, by targeting DNMT1, upregulated HbF in RBCs. Further studies should investigate clinical benefits and potential harms not identified to date.

Trial registration

ClinicalTrials.gov, NCT01685515

Bats crash into windows because of a glitch with their ‘sonar’

New Scientist - Gi, 07/09/2017 - 21:00
Until bats get very close, their echolocation makes them “see” smooth surfaces like windows as gaps rather than as a solid material – with impactful results

Worrying we are ill when we aren’t is not as bad as it seems

New Scientist - Gi, 07/09/2017 - 20:17
Extreme health anxiety can be crippling but a lot of today's internet-fuelled "cyberchondria" doesn't need formal psychological treatment, says Zara Aziz

Even a mask won’t hide you from the latest face recognition tech

New Scientist - Gi, 07/09/2017 - 19:52
A machine learning algorithm has been taught to see through basic disguises, and could identify protesters and criminals hiding their faces – and could render camouflage makeup obsolete
Condividi contenuti