Research Event

¹⁸F-PSMA-1007 is a novel prostate-specific membrane antigen (PSMA)–based radiopharmaceutical for imaging prostate cancer (PCa). The aim of this study was to compare the diagnostic accuracy of ¹⁸F-PSMA-1007 with ⁶⁸Ga-PSMA-11 PET/CT in the same patients presenting with newly diagnosed intermediate- or high-risk PCa. Methods: Sixteen patients with intermediate- or high-risk PCa underwent ¹⁸F-PSMA-1007 and ⁶⁸Ga-PSMA-11 PET/CT within 15 d. PET findings were compared between the 2 radiotracers and with reference-standard pathologic specimens obtained from radical prostatectomy. The Cohen -coefficient was used to assess the concordance between ¹⁸F-PSMA-1007 and ⁶⁸Ga-PSMA-11 for detection of intraprostatic lesions. The McNemar test was used to assess agreement between intraprostatic PET/CT findings and histopathologic findings. Sensitivity, specificity, positive predictive value, and negative predictive value were reported for each radiotracer. SUV_max was measured for all lesions, and tumor-to-background activity was calculated. Areas under receiver-operating-characteristic curves were calculated for discriminating diseased from nondiseased prostate segments, and optimal SUV cutoffs were calculated using the Youden index for each radiotracer. Results: PSMA-avid lesions in the prostate were identified in all 16 patients with an almost perfect concordance between the 2 tracers ( ranged from 0.871 to 1). Aside from the dominant intraprostatic lesion, similarly detected by both radiotracers, a second less intense positive focus was detected in 4 patients only with ¹⁸F-PSMA-1007. Three of these secondary foci were confirmed as Gleason grade 3 lesions, whereas the fourth was shown on pathologic examination to represent chronic prostatitis. Conclusion: This pilot study showed that both ¹⁸F-PSMA-1007 and ⁶⁸Ga-PSMA-11 identify all dominant prostatic lesions in patients with intermediate- or high-risk PCa at staging. ¹⁸F-PSMA-1007, however, may detect additional low-grade lesions of limited clinical relevance.

A joint Chatham House-RUSI project that focuses on strengthening common understanding across the Atlantic and develop new ideas for how the US and Europe can better engage with and respond to China’s rise.

More on Transatlantic Dialogue on China

3 March 2020

To the extent that perceptions of a crisis in liberal democracy in Europe can be confirmed, this paper investigates the nature of the problem and its causes, and asks what part, if any, digital technology plays in it.

Incorporation of ribonucleotides into DNA can severely diminish genome integrity. However, how ribonucleotides instigate DNA damage is poorly understood. In DNA, they can promote replication stress and genomic instability and have been implicated in several diseases. We report here the impact of the ribonucleotide rATP and of its naturally occurring damaged analog 1,N6-ethenoadenosine (1,N6-ϵrA) on translesion synthesis (TLS), mediated by human DNA polymerase η (hpol η), and on RNase H2–mediated incision. Mass spectral analysis revealed that 1,N6-ϵrA in DNA generates extensive frameshifts during TLS, which can lead to genomic instability. Moreover, steady-state kinetic analysis of the TLS process indicated that deoxypurines (i.e. dATP and dGTP) are inserted predominantly opposite 1,N6-ϵrA. We also show that hpol η acts as a reverse transcriptase in the presence of damaged ribonucleotide 1,N6-ϵrA but has poor RNA primer extension activities. Steady-state kinetic analysis of reverse transcription and RNA primer extension showed that hpol η favors the addition of dATP and dGTP opposite 1,N6-ϵrA. We also found that RNase H2 recognizes 1,N6-ϵrA but has limited incision activity across from this lesion, which can lead to the persistence of this detrimental DNA adduct. We conclude that the damaged and unrepaired ribonucleotide 1,N6-ϵrA in DNA exhibits mutagenic potential and can also alter the reading frame in an mRNA transcript because 1,N6-ϵrA is incompletely incised by RNase H2.

Vanessa J. Briscoe
Jul 1, 2006; 24:115-121
Feature Articles

Warren Clayton
Mar 1, 2009; 27:52-58
Features

Ideological differences in the Democratic Party over immigration that were once masked by unity against President Trump’s border wall and immigration agenda are now being exposed as Democratic presidential candidates seek to stand out in a crowded field and amid controversy over an emergency border spending bill. As the 2020 electoral calendar accelerates, how the party navigates the gulf between its most liberal and conservative wings will become a greater challenge for its leaders.

With a backlog of more than 1 million removal cases, the U.S. immigration court system is in crisis. Pressure from external forces, internal challenges, and lagging resources for the courts at a time of massive increases in spending on immigration enforcement have contributed to the backlog. This article explores how the system got to the breaking point, and what opportunities for reform exist.

Ian H. de Boer
Jan 1, 2014; 37:24-30
DCCT/EDIC 30th Anniversary Summary Findings

John M. Lachin
Jan 1, 2014; 37:39-43
DCCT/EDIC 30th Anniversary Summary Findings

Catherine L. Martin
Jan 1, 2014; 37:31-38
DCCT/EDIC 30th Anniversary Summary Findings

Tina Vilsbøll
Jun 1, 2007; 30:1608-1610
BR Emerging Treatments and Technologies

Gina Agiostratidou
Dec 1, 2017; 40:1622-1630
Continuous Glucose Monitoring and Risk of Hypoglycemia

Henry N Ginsberg
Sep 1, 1991; 14:839-855
Diet and Diabetes

William H. Polonsky
Oct 1, 2005; 28:2543-2545
BR Epidemiology/Health Services/Psychosocial Research

David M. Nathan
Jan 1, 2014; 37:9-16
DCCT/EDIC 30th Anniversary Summary Findings

Pearl G. Lee
Apr 1, 2017; 40:444-452
Emerging Science and Concepts for Management of Diabetes and Aging

David M. Nathan
Jan 1, 2014; 37:9-16
DCCT/EDIC 30th Anniversary Summary Findings

Guillermo E. Umpierrez
Aug 1, 2018; 41:1579-1589
Diabetes Care Symposium

Stony Brook School of Dental Medicine opened Dec. 5 its Center for Implant and Digital Technology, which will serve as a state-of-the-art space for digital dentistry-focused education, patient care and research.

The National Commission on Recognition of Dental Specialties and Certifying Boards announced March 4 it recognizes the American Dental Board of Anesthesiology as the national certifying board for dental anesthesiology.

You can find all of the same articles in a more visually appealing Blog.  From now on use www.schoolpsychologistfiles.com/blog.  Thanks!

Cleveland police say they have used DNA research to solve the 33-year-old strangling of a teenage girl, and arrest her killer.

Gujarat university, second MBBS examination, microbiology question papers, January 2015

Gujarat university, second MBBS examination, pathology question papers, January 2015

Gujarat university, second MBBS examination, pharmacology question papers (2010-2014)

Gujarat university, second MBBS examination, pharmacology question papers, January 2015

MD pharmacology examination, question papers, Gujarat university, April 2012

MD pharmacology examination, question papers, Gujarat university, October 2012

MD pharmacology examination, question papers, Gujarat university, April 2013

From the benefits of living a joyful life alongside sadness and tips to practice letting go of unhelpful ideals to how employers can better support workers during COVID-19 and the...

Cognitive-behavioral therapy improved both symptoms and markers of senescence in people with anxiety

-- Read more on ScientificAmerican.com

Hero worship alone doesn’t protect frontline clinicians from distress

-- Read more on ScientificAmerican.com

When freedom fighters in India inspired by Mahatma Gandhi turned violent in a clash with police in 1922, the nonviolent leader took personal responsibility, called off nationwide protests and starved himself for five days in a penitential fast. Gandhi was nearly alone in thinking an apology of such...

At the core of this fall's debate over Iraq lies one simple question: Can an increased number of U.S. troops subdue the Iraqi insurgency?

Americans like to live in diverse communities. At least, that's what they say.

Over the last several years it has become clear that higher order assemblies on membranes, exemplified by signalosomes, are a paradigm for the regulation of many membrane signaling processes. We have recently combined two-color direct stochastic optical reconstruction microscopy (dSTORM) with the (Clus-DoC) algorithm that combines cluster detection and colocalization analysis to observe the organization of 5-lipoxygenase (5-LO) and 5-lipoxygenase–activating protein (FLAP) into higher order assemblies on the nuclear envelope of mast cells; these assemblies were linked to leukotriene (LT) C4 production. In this study we investigated whether higher order assemblies of 5-LO and FLAP included cytosolic phospholipase A2 (cPLA2) and were linked to LTB4 production in murine neutrophils. Using two- and three-color dSTORM supported by fluorescence lifetime imaging microscopy we identified higher order assemblies containing 40 molecules (median) (IQR: 23, 87) of 5-LO, and 53 molecules (62, 156) of FLAP monomer. 98 (18, 154) molecules of cPLA2 were clustered with 5-LO, and 77 (33, 114) molecules of cPLA2 were associated with FLAP. These assemblies were tightly linked to LTB4 formation. The activation-dependent close associations of cPLA2, FLAP, and 5-LO in higher order assemblies on the nuclear envelope support a model in which arachidonic acid is generated by cPLA2 in apposition to FLAP, facilitating its transfer to 5-LO to initiate LT synthesis.

In Staphylococcus aureus–caused endocarditis, the pathogen secretes staphylocoagulase (SC), thereby activating human prothrombin (ProT) and evading immune clearance. A previous structural comparison of the SC(1–325) fragment bound to thrombin and its inactive precursor prethrombin 2 has indicated that SC activates ProT by inserting its N-terminal dipeptide Ile1-Val2 into the ProT Ile16 pocket, forming a salt bridge with ProT's Asp194, thereby stabilizing the active conformation. We hypothesized that these N-terminal SC residues modulate ProT binding and activation. Here, we generated labeled SC(1–246) as a probe for competitively defining the affinities of N-terminal SC(1–246) variants preselected by modeling. Using ProT(R155Q,R271Q,R284Q) (ProTQQQ), a variant refractory to prothrombinase- or thrombin-mediated cleavage, we observed variant affinities between ∼1 and 650 nm and activation potencies ranging from 1.8-fold that of WT SC(1–246) to complete loss of function. Substrate binding to ProTQQQ caused allosteric tightening of the affinity of most SC(1–246) variants, consistent with zymogen activation through occupation of the specificity pocket. Conservative changes at positions 1 and 2 were well-tolerated, with Val1-Val2, Ile1-Ala2, and Leu1-Val2 variants exhibiting ProTQQQ affinity and activation potency comparable with WT SC(1–246). Weaker binding variants typically had reduced activation rates, although at near-saturating ProTQQQ levels, several variants exhibited limiting rates similar to or higher than that of WT SC(1–246). The Ile16 pocket in ProTQQQ appears to favor nonpolar, nonaromatic residues at SC positions 1 and 2. Our results suggest that SC variants other than WT Ile1-Val2-Thr3 might emerge with similar ProT-activating efficiency.

Felipe Muñoz, Advisor to the President of Colombia for the Colombian-Venezuelan Border, discusses how Colombia is coping with the influx of Venezuelan migrants, plans for future policy decisions surrounding this migration, and developments in regional and international cooperation.

Tiger Woods says he was hurt by a racist slur from his former caddie Steve Williams, who referred to him as a "black arsehole".

If you’ve browsed your Twitter or Facebook page feeds in the last week, you have probably noticed that we changed…

Hey, it’s been quite some time without updates on this front, but our latest updates to our Android and iOS…

OBJECTIVE

We conducted an open-label, phase I study using autologous umbilical cord blood (UCB) infusion to ameliorate type 1 diabetes (T1D). Having previously reported on the first 15 patients reaching 1 year of follow-up, herein we report on the complete cohort after 2 years of follow-up.

Felipe Muñoz, Advisor to the President of Colombia for the Colombian-Venezuelan Border, discusses how Colombia is coping with the influx of Venezuelan migrants, plans for future policy decisions surrounding this migration, and developments in regional and international cooperation.

Steven B. Leichter
Jul 1, 2004; 22:129-131
The Business of Diabetes