Sex-differences in relation to the association between patterns of physical activity and sedentary behavior with frailty.

Objective: To investigate the sex-difference in relation to the association between moderate-vigorous physical activity (MVPA) and sedentary time (ST) patterns with frailty.

Method: Accelerometry from ≥50 year olds from the National Health and Nutrition Examination Survey (2003-04/2005-06 cycles) were included. Bouted and sporadic MVPA were defined as MVPA in ≥10 min or <10 min durations, respectively.

mTORC1 activity is essential for erythropoiesis and B cell lineage commitment.

Mechanistic target of rapamycin (mTOR) is a serine/threonine protein kinase that mediates phosphoinositide-3-kinase (PI3K)/AKT signalling. This pathway is involved in a plethora of cellular functions including protein and lipid synthesis, cell migration, cell proliferation and apoptosis. In this study, we proposed to delineate the role of mTORC1 in haemopoietic lineage commitment using knock out (KO) mouse and cell line models.

A Case History in Cooperative Biological Research: Compendium of Studies and Program Analyses in Kazakhstan.

Kazakhstan and the United States have partnered since 2003 to counter the proliferation of weapons of mass destruction. The US Department of Defense (US DoD) has funded threat reduction programs to eliminate biological weapons, secure material in repositories that could be targeted for theft, and enhance surveillance systems to monitor infectious disease outbreaks that would affect national security. The cooperative biological research (CBR) program of the US DoD's Biological Threat Reduction Program has provided financing, mentorship, infrastructure, and biologic research support to Kazakhstani scientists and research institutes since 2005.

Subcellular Fractionation of Primary Chronic Lymphocytic Leukemia Cells to Monitor Nuclear/Cytoplasmic Protein Trafficking.

Nuclear export of macromolecules is often deregulated in cancer cells. Tumor suppressor proteins, such as p53, can be rendered inactive due to aberrant cellular localization disrupting their mechanism of action. The survival of chronic lymphocytic leukaemia (CLL) cells, among other cancer cells, is assisted by the deregulation of nuclear to cytoplasmic shuttling, at least in part through deregulation of the transport receptor XPO1 and the constitutive activation of PI3K-mediated signaling pathways.

A Quasi-Experimental Study Examining the Impact and Challenges of Implementing a Fitness-Based Health Risk Assessment and a Physical Activity Counseling Intervention in the Workplace Setting.

Objectives: Few adults participate in enough physical activity for health benefits. The workplace provides a unique environment to deliver heath interventions and can be beneficial to the employee and the employer. The purpose of the study was to explore the use of a physical activity counseling (PAC) program and a fitness-based health risk assessment (fHRA) in the hospital workplace.

Regarding the Yin and Yang of Precision Cancer- Screening and Treatment: Are We Creating a Neglected Majority?

In this commentary, we submit that the current emphasis of precision cancer screening and treatment (PCST) has been to provide and interpret the implications of "positive" screening results for those deemed to be at greatest risk for cancer or most likely to benefit from targeted treatments. This is an important, but proportionately small target group, regardless of the cancer context. Overlooked by this focus is the larger majority of those screened who receive "negative" results.

Lack of Detection of the Analgesic Properties of PF-05089771, a Selective Na 1.7 Inhibitor, Using a Battery of Pain Models in Healthy Subjects.

Sodium channel blockers are used for the treatment of pain, but this is limited by the lack of selectivity for different sodium channel subtypes, which can result in central nervous system and cardiovascular side effects. As such, there is special interest in the Na 1.7 subtype, which is expressed predominantly in nociceptive and sympathetic neurons.

The grant is dead, long live the data - migration as a pragmatic exit strategy for research data preservation.

Open research, data sharing and data re-use have become a priority for publicly- and charity-funded research. Efficient data management naturally requires computational resources that assist in data description, preservation and discovery. While it is possible to fund development of data management systems, currently it is more difficult to sustain data resources beyond the original grants.

Prehabilitation: The Right Medicine for Older Frail Adults Anticipating Transcatheter Aortic Valve Replacement, Coronary Artery Bypass Graft, and Other Cardiovascular Care.

The wait before elective cardiac intervention or surgery presents an opportunity to prevent further physiologic decline preoperatively in older patients. Implementation of prehabilitation programs decreases length of hospital stay postoperatively, decreases time spent in the intensive care unit, decreases postoperative complications, and improves self-reported quality of life postsurgery. Prehabilitation programs should adopt multimodal approaches including nutrition, exercise, and worry reduction to improve patient resilience in the preoperative period.

Presenilin-1 Established ER-Ca Leak: a Follow Up on Its Importance for the Initial Insulin Secretion in Pancreatic Islets and β-Cells upon Elevated Glucose.

Background/aims: In our recent work, the importance of GSK3β-mediated phosphorylation of presenilin-1 as crucial process to establish a Ca leak in the endoplasmic reticulum and, subsequently, the pre-activation of resting mitochondrial activity in β-cells was demonstrated. The present work is a follow-up and reveals the importance of GSK3β-phosphorylated presenilin-1 for responsiveness of pancreatic islets and β-cells to elevated glucose in terms of cytosolic Ca spiking and insulin secretion.

Methods: Freshly isolated pancreatic islets and the two pancreatic β-cell lines INS-1 and MIN-6 were used.

Feasibility and acceptability of using an IVRS to assess decision making about sun protection.

Objective: We developed an interactive voice response system (IVRS), an automated telephone survey technology, to assess real-time decision making about sun protection. We examined the feasibility and acceptability of IVRS in this electronic health (eHealth) context.

Methods: Melanoma patients who underwent surgery referred their first-degree relatives (FDRs) for participation.

Using NCI-Designated Cancer Center Catchment-Area Data to Understand an Ignored but High-Need Constituent: People Uncertain or Avoidant about Their Cancer Risk.

In 2016, the NCI provided supplemental funding to 15 NCI-designated cancer centers to enhance cancer centers' capacity to collect critical catchment-area data across behavioral and psychosocial domains [March 2019 issue of ()-]. In response, we highlight opportunities for cancer risk perception research when collecting and utilizing catchment-area data given the remarkably high proportions of individuals who report they are at average cancer risk, high levels of cancer risk information avoidance, and extremely negative ("death") associations with cancer. First, we advocate for enhanced measurement specificity regarding whether some participants may be uncertain regarding their cancer risk.

Variation in a New Mexico Population.

Background: The Melanocortin 1 Receptor () contributes to pigmentation, an important risk factor for developing melanoma. Evaluating SNPs in and association with race/ethnicity, skin type, and perceived cancer risk in a New Mexico (NM) population will elucidate the role of in a multicultural population.

Methods: We genotyped in 191 NMs attending a primary care clinic in Albuquerque.

Psychosocial and Cultural Determinants of Interest and Uptake of Skin Cancer Genetic Testing in Diverse Primary Care.

Background: Translational research in genomics has limited reach and requires efforts to broaden access and utility in diverse populations. Skin cancer is common and rates are rising, including among Hispanics. Germline variants in the melanocortin-1 receptor (MC1R) gene are common in the population and confer moderate risk for melanoma and basal cell cancers across skin types.

Characterising antibody kinetics from multiple influenza infection and vaccination events in ferrets.

The strength and breadth of an individual's antibody repertoire is an important predictor of their response to influenza infection or vaccination. Although progress has been made in understanding qualitatively how repeated exposures shape the antibody mediated immune response, quantitative understanding remains limited. We developed a set of mathematical models describing short-term antibody kinetics following influenza infection or vaccination and fit them to haemagglutination inhibition (HI) titres from 5 groups of ferrets which were exposed to different combinations of trivalent inactivated influenza vaccine (TIV with or without adjuvant), A/H3N2 priming inoculation and post-vaccination A/H1N1 inoculation.

Collaboration of MYC and RUNX2 in lymphoma simulates T-cell receptor signaling and attenuates p53 pathway activity.

MYC and RUNX oncogenes each trigger p53-mediated failsafe responses when overexpressed in vitro and collaborate with p53 deficiency in vivo. However, together they drive rapid onset lymphoma without mutational loss of p53. This phenomenon was investigated further by transcriptomic analysis of premalignant thymus from RUNX2/MYC transgenic mice.

Mapping non-native pitch contours to meaning: Perceptual and experiential factors.

Infants show interesting patterns of flexibility and constraint early in word learning. Here, we explore perceptual and experiential factors that drive associative learning of labels that differ in pitch contour. Contrary to the salience hypothesis proposed in Experiment 1, English-learning 14-month-olds failed to map acoustically distinctive level and dipping labels to novel referents, even though they discriminated the labels when no potential referents were present.

Live cell imaging of signaling and metabolic activities.

The interplay of metabolic and signaling processes is prerequisite for the functionality of cells. Any disturbances may have severe consequences, resulting in the development of diseases. However, the complex coordination of metabolism and signaling events makes it difficult to decipher the link between molecular irregularities and pathogenesis.

Now Is the Time for Transparency in Value-Based Healthcare Decision Modeling.

In contrast to many other countries, during the 20 years since the founding of Value in Health, the United States has moved further away from using value-based healthcare decision modeling (VHDM) for drugs and other medical care choices. US public and private health plans can be typically characterized as using "budget impact" decision making rather than VHDM, with drugs having low per-member per-month spending likely to be covered and reimbursed regardless of value. Orphan drugs and specialty drugs with relatively few patients (eg, end-stage cancer drugs) are often covered, whether cost-effective or not, because health plans want to avoid negative publicity.

Lay beliefs about risk: relation to risk behaviors and to probabilistic risk perceptions.

Lay illness risk beliefs are commonly held philosophies about how risk works. These include beliefs that one's personal illness risk is unknowable and beliefs that thinking about one's risk can actually increase that risk. Beliefs about risk may impact risk behaviors and thereby subsequent health status.

Analgesic potential of PF-06372865, an α2/α3/α5 subtype-selective GABA partial agonist, in humans.

Background: This study investigated the analgesic effects of two doses (15 and 65 mg) of PF-06372865, a novel α2/α3/α5 gamma-aminobutyric acid A (GABA) subunit selective partial positive allosteric modulator (PAM), compared with placebo and pregabalin (300 mg) as a positive control.

Methods: We performed a randomised placebo-controlled crossover study (NCT02238717) in 20 healthy subjects, using a battery of pain tasks (electrical, pressure, heat, cold and inflammatory pain, including a paradigm of conditioned pain modulation). Pharmacodynamic measurements were performed at baseline and up to 10 h after dose.

The EMA Review of Mylotarg (Gemtuzumab Ozogamicin) for the Treatment of Acute Myeloid Leukemia.

On February 22, 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product gemtuzumab ozogamicin (Mylotarg; Pfizer, New York City, NY), intended for the treatment of acute myeloid leukemia. Mylotarg was designated as an orphan medicinal product on October 18, 2000. The applicant for this medicinal product was Pfizer Limited (marketing authorization now held by Pfizer Europe MA EEIG).