Brenna Cholerton
Nov 1, 2016; 29:210-219
From Research to Practice

Peggy Yarborough
Jan 1, 2003; 16:
Case Studies

The 2020 honours and awards selection and appointment of Justices of the Peace (JPs) exercise will be postponed, as well as the announcement of the list of honours and awards and JP appointments, the Government announced today.

It decided to defer the exercise to accord top priority to the ongoing anti-epidemic work and implementation of measures to retain employment, support businesses and ease people's livelihood in the face of challenges arising from the COVID-19 epidemic.

The Honours List and JP appointments will be announced on October 1 instead of July 1 as in previous years, the Government added.

(Lancaster University) Lancaster University's Dr Samuli Autti has been awarded a Young Scientist Prize 2020 by the International Union of Pure and Applied Physics. The prestigious prize, awarded only once every three years, was made by the Low Temperature Commission of the IUPAP.

(American Association for the Advancement of Science) A one-hour exercise designed to increase feelings of social belonging administered during the first year of college appears to significantly improve the lives and careers of black students up to 11 years later, psychologists report.

(American Geriatrics Society) The American Geriatrics Society (AGS) will this year honor past AGS President Todd Semla, PharmD, MS, AGSF, with the prestigious Nascher/Manning Award, given biannually at the AGS Annual Scientific Meeting (#AGS21, to be held next year May 13-15 in Chicago, Ill., following the cancellation of the AGS 2020 Annual Scientific Meeting due to COVID-19).

(Penn State) A new process to harness multiple disease models for outbreak management has been developed by an international team of researchers. The team will immediately implement the process to help inform policy decisions for the COVID-19 outbreak.

Chia-Feng Tsai
May 1, 2020; 19:828-838
Research

Numerous recent works highlight the limited utility of established tumor cell lines in recapitulating the heterogeneity of tumors in patients. More realistic preclinical cancer models are thought to be provided by transplantable, patient-derived tumor xenografts (PDX). Inter- and intra-tumor heterogeneity of PDX, however, present several challenges in developing optimal quantitative pipelines to assess response to therapy. The objective of this work was to develop and optimize image metrics of FDG-PET to assess response to combination docetaxel/carboplatin therapy in a co-clinical trial involving triple negative breast cancer (TNBC) PDX. We characterize the reproducibility of SUV metrics to assess response to therapy and optimize a preclinical PERCIST (µPERCIST) paradigm to complement clinical standards. Considerations in this effort included variability in tumor growth rate and tumor size; solid tumor vs. tumor heterogeneity and necrotic phenotype; and optimal selection of tumor slice versus whole tumor. A test-retest protocol was implemented to optimize the reproducibility of FDG-PET SUV thresholds, SUVpeak metrics, and µPERCIST parameters. In assessing response to therapy, FDG-PET imaging was performed at baseline and +4 days following therapy. The reproducibility, accuracy, variability, and performance of imaging metrics to assess response to therapy were determined. We defined an index—"Quantitative Response Assessment Score (QRAS)"—to integrate parameters of prediction and precision, and thus aid in selecting optimal image metrics of response to therapy. Our data suggests that a threshold value of 25% (SUV25) of SUVmax was highly reproducible (<9% variability). Concordance and reproducibility of µPERCIST were maximized at α=0.7 and β=2.8 and exhibited high correlation to SUV25 measures of tumor uptake. QRAS scores favor SUV25 followed by SUVP14 as optimal metrics of response to therapy. Additional studies are warranted to fully characterize the utility of SUV25 and µPERCIST SUVP14 as image metrics of response to therapy across a wide range of therapeutic regiments and PDX models.

Mass spectrometry (MS)-based proteomics has great potential for overcoming the limitations of antibody-based immunoassays for antibody-independent, comprehensive, and quantitative proteomic analysis of single cells. Indeed, recent advances in nanoscale sample preparation have enabled effective processing of single cells. In particular, the concept of using boosting/carrier channels in isobaric labeling to increase the sensitivity in MS detection has also been increasingly used for quantitative proteomic analysis of small-sized samples including single cells. However, the full potential of such boosting/carrier approaches has not been significantly explored, nor has the resulting quantitation quality been carefully evaluated. Herein, we have further evaluated and optimized our recent boosting to amplify signal with isobaric labeling (BASIL) approach, originally developed for quantifying phosphorylation in small number of cells, for highly effective analysis of proteins in single cells. This improved BASIL (iBASIL) approach enables reliable quantitative single-cell proteomics analysis with greater proteome coverage by carefully controlling the boosting-to-sample ratio (e.g. in general <100x) and optimizing MS automatic gain control (AGC) and ion injection time settings in MS/MS analysis (e.g. 5E5 and 300 ms, respectively, which is significantly higher than that used in typical bulk analysis). By coupling with a nanodroplet-based single cell preparation (nanoPOTS) platform, iBASIL enabled identification of ~2500 proteins and precise quantification of ~1500 proteins in the analysis of 104 FACS-isolated single cells, with the resulting protein profiles robustly clustering the cells from three different acute myeloid leukemia cell lines. This study highlights the importance of carefully evaluating and optimizing the boosting ratios and MS data acquisition conditions for achieving robust, comprehensive proteomic analysis of single cells.

Back with a bang as Computerworld editor Scott Carey leads the squad into the cauldron of convo. Christina Mercer explains why her beau Elon Musk took a car into space, Sean Bradley on that bursting Bitcoin bubble, and David Price to tell us all how Apple can charge even more for its stuff and keep on making record profit.

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Hepatic steatosis, the excess storage of intrahepatic lipids, is a rampant clinical problem associated with the obesity epidemic. Hepatic steatosis is linked to increased risk for insulin resistance, type 2 diabetes, and cardiovascular and advanced liver disease. Accumulating evidence shows that physical activity, exercise, and aerobic capacity have profound effects on regulating intrahepatic lipids and mediating susceptibility for hepatic steatosis. Moreover, exercise can effectively reduce hepatic steatosis independent of changes in body mass. In this perspective, we highlight 1) the relationship between obesity and metabolic pathways putatively driving hepatic steatosis compared with changes induced by exercise; 2) the impact of physical activity, exercise, and aerobic capacity compared with caloric restriction on regulating intrahepatic lipids and steatosis risk; 3) the effects of exercise training (modalities, volume, intensity) for treatment of hepatic steatosis, and 4) evidence for a sustained protection against steatosis induced by exercise. Overall, evidence clearly indicates that exercise powerfully regulates intrahepatic storage of fat and risk for steatosis.

Site-specific recombinases, such as Cre, are a widely used tool for genetic lineage tracing in the fields of developmental biology, neural science, stem cell biology, and regenerative medicine. However, nonspecific cell labeling by some genetic Cre tools remains a technical limitation of this recombination system, which has resulted in data misinterpretation and led to many controversies in the scientific community. In the past decade, to enhance the specificity and precision of genetic targeting, researchers have used two or more orthogonal recombinases simultaneously for labeling cell lineages. Here, we review the history of cell-tracing strategies and then elaborate on the working principle and application of a recently developed dual genetic lineage-tracing approach for cell fate studies. We place an emphasis on discussing the technical strengths and caveats of different methods, with the goal to develop more specific and efficient tracing technologies for cell fate mapping. Our review also provides several examples for how to use different types of DNA recombinase–mediated lineage-tracing strategies to improve the resolution of the cell fate mapping in order to probe and explore cell fate–related biological phenomena in the life sciences.

Errol B. Marliss
Feb 1, 2002; 51:S271-S283
Section 6: Pusatile and Phasic Insulin Release in Normal and Diabetic Men

24 January 2020

4 February 2020

Invitation Only Research Event

Portmore United captain Rosario Harriott says the Premier League Clubs Association shouldn’t rush to call off this season of the Red Stripe Premier League (RSPL) because of the COVID-19 pandemic. The league was stopped indefinitely in mid-March...

Philipe de Souto Barreto argues that, to reduce premature mortality, policies should focus on getting fully inactive people to do a little physical activity rather than strive for the entire population to meet current physical activity recommendations. Read the full analysis paper: http://www.bmj.com/content/350/bmj.h23

For decades research has shown that discrimination, harassment, and exclusion are pervasive experiences for staff from black and minority ethnic (BME) backgrounds in the National Health Service. In this podcast, the authors of a recent analysis article in The BMJ talk about the evidence for discrimination, what the NHS has done and is doing, and...

James Smoliga, from High Point University, North Carolina, and Ken Rundell, from The Commonwealth Medical College, Pennsylvania, join us to discuss how to test for, and manage, exercise induced bronchoconstriction, and particularly how to distinguish it from other respiratory conditions. Read the full review at...

It’s been called “the universal panacea” - exercise has a positive effect on almost all health measures, and governments are actively campaigning for us to do more. But at the opposite end of the scale, the realisation that some people may be addicted to exercise is gaining traction. In this podcast we're joined by Heather Hausenblas - professor...

Adoption of shared decision making into routine practice has been remarkably slow, despite 40 years of research and considerable policy support. In 2010, the Health Foundation in the UK commissioned the MAGIC (Making Good Decisions in Collaboration) programme to design, test, and identify the best ways to embed shared decision making into...

There's a crisis in old age care - not just in the UK, around the world, as population demographics shift, and the proportion of older people increase - there's a worry about who's going to look after them, and how much is it going to cost? However, a new analysis on bmj.com says this picture need not be so gloomy - they say that encouraging...

The Three Talk Model of shared decision is a framework to help clinicians to think about how to structure their consultation to ensure that shared decision making can most usefully take place. The model is based around 3 concepts - option talk, decision talk, and team talk - with active listening at the centre. Three Talk was first proposed in...

In this week's special episode of Sharp Scratch, we've got something a little different for you! Last week the panel talked microaggressions, so this week we're hearing from an expert guest who is leading the work the NHS is doing to combat inequality in healthcare. If you like this special edition, let us know on Facebook, Instagram or Twitter...

Reds manager David Bell has great corner outfield depth, but he doesn't have a regular center fielder. Determining who will get to play where and sorting out the log jam should be a challenge for Bell in his first season as a skipper in the big leagues.

THE EDITOR, Madam: On Wednesday at 8:30 a.m., while watching TVJ, I saw Get Moving home workout series. Very good, TVJ and the Ministry of Health, for bringing this workout programme into our homes. Minister Tufton was a participant; he truly...

A single bout of exercise enhances insulin action in the exercised muscle. However, not all human studies find that this translates into increased whole-body insulin action, suggesting that insulin action in rested muscle or other organs may be decreased by exercise. To investigate this, eight healthy men underwent a euglycemic-hyperinsulinemic clamp on 2 separate days: one day with prior one-legged knee-extensor exercise to local exhaustion (~2.5 h) and another day without exercise. Whole-body glucose disposal was ~18% lower on the exercise day as compared with the resting day due to decreased (~37%) insulin-stimulated glucose uptake in the nonexercised muscle. Insulin signaling at the level of Akt2 was impaired in the nonexercised muscle on the exercise day, suggesting that decreased insulin action in nonexercised muscle may reduce GLUT4 translocation in response to insulin. Thus, the effect of a single bout of exercise on whole-body insulin action depends on the balance between local effects increasing and systemic effects decreasing insulin action. Physiologically, this mechanism may serve to direct glucose into the muscles in need of glycogen replenishment. For insulin-treated patients, this complex relationship may explain the difficulties in predicting the adequate insulin dose for maintaining glucose homeostasis following physical activity.

As Greece's Aegean islands continue to grapple with migrants arriving on their shores, decisions regarding the needs of newcomers are negotiated in Brussels and Athens, far removed from the situation on the ground. Meanwhile, local communities have had successes in hosting migrants, as this article drawing on observations from the hospitality center and refugee camp on Lesvos explores.

Jordi Salas-Salvadó
May 1, 2019; 42:777-788
Continuing Evolution of Nutritional Therapy for Diabetes

While much attention has been given to the move by U.S. Citizenship and Immigration Services to raise its application fees—including an 83 percent hike to apply for U.S. citizenship—the policy changes embedded in the proposed rule have been less scrutinized. The changes, including the elimination of most fee waivers for lower-income applicants, would likely reduce the number and shift the profile of those getting a green card or other immigration status.

The question surfaces at the beginning of dental school, maybe even sooner, when the dream first takes hold. What kind of dentist do I want to be? Do I want to be a general dentist? An oral surgeon? A pediatric dentist? Every student’s path to becoming a dentist is unique. Choosing whether to specialize is no different.