Studies demonstrate that the investigational ⁶⁴Cu-DOTATATE radiopharmaceutical may provide diagnostic and logistical benefits over available imaging agents for patients with somatostatin receptor (SSTR)-positive neuroendocrine tumors (NETs). Accordingly, we aimed to prospectively determine the lowest dose of ⁶⁴Cu-DOTATATE that facilitates diagnostic quality scans and evaluated the diagnostic performance and safety in a phase III study of patients with SSTR-expressing NETs. Methods: A dose-ranging study was conducted in 12 patients divided into 3 dose groups (111 MBq [3.0 mCi], 148 MBq [4.0 mCi], and 185 MBq [5.0 mCi] ± 10%) to determine the lowest dose of ⁶⁴Cu-DOTATATE that produced diagnostic quality PET/CT images. Using the ⁶⁴Cu-DOTATATE dose identified in the dose-ranging study, 3 independent nuclear medicine physicians who were blinded to all clinical information read PET/CT scans from 21 healthy volunteers and 42 NET-positive patients to determine those with "Disease" and "No Disease," as well as "Localized" versus "Metastatic" status. Blinded-reader evaluations were compared to a patient-specific standard of truth (SOT), which was established by an independent oncologist who used all previously available pathology, clinical, and conventional imaging data. Diagnostic performance calculated for ⁶⁴Cu-DOTATATE included sensitivity, specificity, negative predictive value, positive predictive value, and accuracy. Inter- and intra-reader reliability, as well as ability to differentiate between localized and metastatic disease, was also determined. Adverse events (AEs) were recorded from ⁶⁴Cu-DOTATATE injection through 48 hours post-injection. Results: The dose-ranging study identified 148 MBq (4.0 mCi) as the optimal dose to obtain diagnostic quality PET/CT images. Following database lock, diagnostic performance from an initial majority read of the 3 independent readers showed a significant 90.9% sensitivity (P = 0.0042) and 96.6% specificity (P < 0.0001) for detecting NETs, which translated to a 100.0% sensitivity and 96.8% specificity after correcting for an initial SOT misread. Excellent inter- and intra-reader reliability, as well as ability to distinguish between localized and metastatic disease, was also noted. No AEs were related to ⁶⁴Cu-DOTATATE, and no serious AEs were observed. Conclusion: ⁶⁴Cu-DOTATATE PET/CT is a safe imaging technique that provides high-quality and accurate images at a dose of 148 MBq (4.0 mCi) for the detection of somatostatin-expressing NETs.

The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer (PCa). However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 biochemically recurrent PCa patients. Each subject served as his own control. [¹⁸F]DCFPyl PET/CT imaging sessions were performed 3 – 7 days apart, following oral administration of either 12.7 g of MSG or placebo. Data from the two sets of images were analyzed by placing regions of interest on lacrimal, parotid and submandibular glands, left ventricle, liver, spleen, kidneys, bowel, urinary bladder, gluteus muscle and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the ROI data. Results: A total of 142 pathological lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in maximal standardized uptake values corrected for lean body mass (SULmax) on images obtained following MSG administration in the parotids (24 ± 14%, P = 0.001), submandibular glands (35 ± 11%, P<0.001) and kidneys (23 ± 26%, P = 0.014). Significant decreases were also observed in lacrimal glands (49 ± 13%, P<0.001), liver (15 ± 6%, P<0.001), spleen (28 ± 13%, P = 0.001) and bowel (44 ± 13%, P<0.001). Mildly lower blood pool SULmean was observed after MSG administration (decrease of 11 ± 13%, P = 0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration compared to the placebo studies (SULmax median decrease 33%, range -1 to 75%, P<0.001). No significant adverse events occurred and vital signs were stable following placebo or MSG administration. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney and other normal organ PSMA radiotracer uptake in human subjects, using [¹⁸F]DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications.

We’ve heard this rhetoric in RnB jams: love is blind. So it’s nothing new. But Netflix decided to test its theory with a show, designed to prove whether or not love can be truly blind, in its literal sense. It’s not until watching the episodes that...

Allocation concealment - blinding which arm of a trial a patient is randomised to - is being questioned in an analysis published on thebmj.com. David Torgerson, director of the York Trials Unit at the university of York and colleagues have been looking at the way in which trials do this randomisation, and how they subsequently report it - and...

Welcome to the festive talk evidence, giving you a little EBM to take you into the new year. As always Duncan Jarvies is joined by Helen Macdonald (resting GP and editor at The BMJ) and Carl Heneghan (active GP, director of Oxford University’s CEBM and editor of BMJ Evidence)* This month: (1.20) Carl tells us about new research on treating...

OBJECTIVE

Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients.

Robert R. Henry
Mar 1, 2015; 38:412-419
Evolving Tactics With Inhibition of Sodium-Glucose Cotransporters

Hans-Ulrich Häring
Jun 1, 2014; 37:1650-1659
Emerging Technologies and Therapeutics

Khalid A. Jadoon
Oct 1, 2016; 39:1777-1786
Emerging Technologies and Therapeutics

OBJECTIVE

Topical oxygen has been used for the treatment of chronic wounds for more than 50 years. Its effectiveness remains disputed due to the limited number of robust high-quality investigations. The aim of this study was to assess the efficacy of multimodality cyclical pressure Topical Wound Oxygen (TWO2) home care therapy in healing refractory diabetic foot ulcers (DFUs) that had failed to heal with standard of care (SOC) alone.

OBJECTIVE

To confirm the presence of subclinical cardiovascular dysfunction in working-age adults with type 2 diabetes (T2D) and determine whether this is improved by a low-energy meal replacement diet (MRP) or exercise training.

London : D. Bogue, 1881.

Breslau : J.U. Kern, 1883.

Cassel : T. Fischer, 1878.

Wiesbaden : J.F. Bergmann, 1885.

Whether we categorize uneaten food as “lost” or “wasted” depends on where it goes out of the food supply chain. Imagine how everything we eat travels across a food supply chain, a complex journey that stretches from farm to table. Studies show that an astounding 1/3 of all the food we produce for human consumption never actually reaches our plates. Most [...]

Framed prints of Steven Camley's cartoons are available by calling 0141 302 6210.”

Omega-3 fatty acids (O3FA) are commonly used as complementary treatments in pediatric psychiatric disorders, including Tourette’s disorder (TD), and are well known to have anti-inflammatory properties. However, no studies to date have examined the effects of O3FA on pediatric TD.

This is the first double-blind, placebo-controlled clinical trial of O3FA in pediatric TD. The results indicate that O3FA supplementation may be beneficial in the reduction of tic-related impairment for some children and adolescents with TD, but not tics per se. (Read the full article)

Children with obstructive sleep apnea (OSA) are usually treated by surgical removal of their upper airway lymphadenoid tissue. Recently, medications were offered to patients with nonsevere OSA. Montelukast, for this indication, had never been studied in a randomized controlled manner.

Montelukast effectively reduced polysomnographic findings, symptoms, and the size of the adenoidal tissue in children with nonsevere OSA. The findings support the potential of a leukotriene modifier as a novel, safe, noninvasive alternative for children with mild to moderate OSA. (Read the full article)

Honey is recommended as a cough medication by the World Health Organization. To date, the efficacy of this treatment has been shown in 2 studies: one tested only buckwheat honey and the other study was not blinded.

In a randomized controlled trial, we compared 3 types of honey versus placebo as a treatment of upper respiratory tract infection–associated cough. These types of honey were superior to placebo in alleviating cough. (Read the full article)

Bronchiolitis, a leading cause of infant hospitalization, has few proven treatments. A few small studies have reported the beneficial effects of a mixture of 21% oxygen + 79% helium (Heliox). The 2010 Cochrane Review concluded that additional large randomized controlled trials were needed to determine the therapeutic role of Heliox in bronchiolitis.

The Bronchiolitis Randomized Controlled Trial Emergency-Assisted Therapy with Heliox—An Evaluation (BREATHE) trial is the largest multicenter randomized controlled trial to date to investigate the efficacy of Heliox in acute bronchiolitis. The delivery method for Heliox therapy was found to be crucial to its efficacy. (Read the full article)

Strictly-defined pediatric bipolar I disorder (BP-I) is a serious condition. Although lithium is a benchmark treatment and has shown effectiveness in adults for decades, no definitive efficacy or long-term safety studies had been performed in pediatric patients with BP-I.

This study provides evidence to support the efficacy of lithium in the acute treatment of youths with BP-I who are currently in a manic or mixed state. Lithium had an adverse effect profile that was acceptable for most patients. (Read the full article)

Contezolid (MRX-I), a new oxazolidinone, is an antibiotic in development for treating complicated skin and soft tissue infections (cSSTI) caused by resistant Gram-positive bacteria. This was a thorough QT study conducted in 52 healthy subjects who were administered oral contezolid at a therapeutic (800 mg) dose, a supratherapeutic (1600 mg) dose, placebo, and oral moxifloxacin 400 mg in 4 separate treatment periods. The pharmacokinetic profile of contezolid was also evaluated. Time-point analysis indicated that the upper bounds of the two-sided 90% confidence interval (CI) for placebo-corrected change-from-baseline QTc (QTc) were <10 ms for the contezolid therapeutic dose at each time point. The upper bound of the 90% CI for QTc were slightly more than 10 ms with the contezolid supratherapeutic dose at 3 and 4 hours postdose, and the prolongation effect on the QT/QTc interval was less than that of the positive control, moxifloxacin 400 mg. At 3 and 4 h after the moxifloxacin dose, the moxifloxacin group met the assay sensitivity criteria outlined in ICH Guidance E14 with having a lower confidence bound ≥5 ms. The results of a linear exposure-response model which were similar to that of a time point analysis demonstrated a slightly positive relationship between contezolid plasma levels and QTcF interval with a slope of 0.227 ms per mg/L (90% CI: 0.188 to 0.266). In summary, contezolid did not prolong the QT interval at a therapeutic dose and may have a slight effect on QT interval prolongation at a supratherapeutic dose.

JooYoung Seo, a doctoral candidate in the College of Education’s Learning, Design, and Technology program, has secured a highly competitive internship with RStudio that will allow him to help people just like himself — those with severe visual impairments.

The online window covering company introduces a program that refers prospects to people, not just a brand.

Celebrated wartime and celebrity photographer Tony Vaccaro, now 97, is getting over a bout with COVID-19. He attributes his longevity to 'blind luck, red wine' and grit

Whitepaper called Blind CreateRemoteThread Privilege Escalation.

This week the University of Nevada, Reno announced two discoveries in the Great Basin by the Nevada Bureau of Mines and Geology using a previously untried method for finding unknown, hidden geothermal resources.

Prague Daily Monitor

According to a story run in Deník N, a blind woman going out for a morning walk ran into a nightmare scenario on Monday in Prague's trendy Žižkov area.

read more

Title: Blind Cords Pose Danger to Toddlers, Doctors Warn
Category: Health News
Created: 4/30/2013 10:35:00 AM
Last Editorial Review: 4/30/2013 12:00:00 AM

Title: New Drug Could Help Stop Blindness From Thyroid Eye Disease
Category: Health News
Created: 1/22/2020 12:00:00 AM
Last Editorial Review: 1/23/2020 12:00:00 AM

Title: Transplanted Skin Stem Cells Help Blind Mice See Light
Category: Health News
Created: 4/21/2020 12:00:00 AM
Last Editorial Review: 4/22/2020 12:00:00 AM

Hypoxia is a hallmark of solid cancers, supporting proliferation, angiogenesis, and escape from apoptosis. There is still limited understanding of how cancer cells adapt to hypoxic conditions and survive. We analyzed transcriptome changes of human lung and breast cancer cells under chronic hypoxia. Hypoxia induced highly concordant changes in transcript abundance, but divergent splicing responses, underlining the cell type-specificity of alternative splicing programs. While RNA-binding proteins were predominantly reduced, hypoxia specifically induced muscleblind-like protein 2 (MBNL2). Strikingly, MBNL2 induction was critical for hypoxia adaptation by controlling the transcript abundance of hypoxia response genes, such as vascular endothelial growth factor A (VEGFA). MBNL2 depletion reduced the proliferation and migration of cancer cells, demonstrating an important role of MBNL2 as cancer driver. Hypoxia control is specific for MBNL2 and not shared by its paralog MBNL1. Thus, our study revealed MBNL2 as central mediator of cancer cell responses to hypoxia, regulating the expression and alternative splicing of hypoxia-induced genes.

Reactive immunization with a single-dose cholera vaccine that could rapidly (within days) protect immunologically naive individuals during virgin soil epidemics, when cholera reaches immunologically naive populations that have not experienced cholera for decades, would facilitate cholera control. One dose of attenuated Vibrio cholerae O1 classical Inaba vaccine CVD 103-HgR (Vaxchora) containing ≥2 x 10⁸ CFU induces vibriocidal antibody seroconversion (a correlate of protection) in >90% of U.S. adults. A previous CVD 103-HgR commercial formulation required ≥2 x 10⁹ CFU to elicit high levels of seroconversion in populations in developing countries. We compared the vibriocidal responses of Malians (individuals 18 to 45 years old) randomized to ingest a single ≥2 x 10⁸-CFU standard dose (n = 50) or a ≥2 x 10⁹-CFU high dose (n = 50) of PaxVax CVD 103-HgR with buffer or two doses (n = 50) of Shanchol inactivated cholera vaccine (the immunologic comparator). To maintain blinding, participants were dosed twice 2 weeks apart; CVD 103-HgR recipients ingested placebo 2 weeks before or after ingesting vaccine. Seroconversion (a ≥4-fold vibriocidal titer rise) between the baseline and 14 days after CVD 103-HgR ingestion and following the first and second doses of Shanchol were the main outcomes measured. By day 14 postvaccination, the rates of seroconversion after ingestion of a single standard dose and a high dose of CVD 103-HgR were 71.7% (33/46 participants) and 83.3% (40/48 participants), respectively. The rate of seroconversion following the first dose of Shanchol, 56.0% (28/50 participants), was significantly lower than that following the high dose of CVD 103-HgR (P = 0.003). The vibriocidal geometric mean titer (GMT) of the high dose of CVD 103-HgR exceeded the GMT of the standard dose at day 14 (214 versus 95, P = 0.045) and was ~2-fold higher than the GMT on day 7 and day 14 following the first Shanchol dose (P > 0.05). High-dose CVD 103-HgR is recommended for accelerated evaluation in developing countries to assess its efficacy and practicality in field situations. (This study has been registered at ClinicalTrials.gov under registration no. NCT02145377.)

Visual challenges remain before autonomous cars are ready for the masses.

A small Alberta town’s attempt to discourage geese from too getting comfortable there took flight about six weeks ago, but it’s getting mixed reviews and ruffling some feathers.

The 31-year-old is set to star in new Sky drama Gangs of London

Contestants have to keep their hands of one another lest the prize money goes down

'My agent had spent a load of time putting that together'

The casts of the company's top dramas could soon be isolating together

Harry, 32, a TV producer from London, meets Jayson, 25, a journalist from Hong Kong, in our latest virtual date

What were you hoping for?
A fun chat that didn’t involve a quiz.

The acclaimed Australian artist is painting black squares on a gallery wall with his eyes closed to protest against the values that led us to climate crisis.

We are on the precipice of spread COVID-19 from dialysis centers to nursing homes. But there is a safer way to administer this lifesaving care.

The Department has reached a settlement agreement with the Alameda County, Calif., Sheriff’s Office, under which it will provide sign language interpreters and other auxiliary aids and services to arrestees, detainees, suspects, victims, witnesses, complainants and visitors who are deaf, hard of hearing or deaf-blind at two jails.

The Justice Department announced today its participation in two related settlement agreements involving the accessibility of the Law School Admission Council’s online application service, which is used by law schools nationwide for their application processes.

The Justice Department announced today that it has reached a settlement with the Orange County Clerk of Courts in Florida to remedy violations of the Americans with Disabilities Act (ADA). The settlement resolves allegations that the Orange County Clerk of Courts failed to provide a blind attorney with electronic court documents in an accessible format readable by his screen reader technology, despite repeated requests. Indeed, a motion filed in one of his cases included over 20 exhibits, the majority of which were not provided in an accessible format for over four months