Changes in insulin and insulin signaling in Alzheimer\u27s disease: Cause or consequence?

Individuals with type 2 diabetes have an increased risk for developing Alzheimer’s disease (AD), although the causal relationship remains poorly understood. Alterations in insulin signaling (IS) are reported in the AD brain. Moreover, oligomers/fibrils of amyloid-β (Aβ) can lead to neuronal insulin resistance and intranasal insulin is being explored as a potential therapy for AD. Conversely, elevated insulin levels (ins) are found in AD patients and high insulin has been reported to increase Aβ levels and tau phosphorylation, which could exacerbate AD pathology. Herein, we explore whether changes in ins and IS are a cause or consequence of AD

CRLF2 rearrangement in Ph-like acute lymphoblastic leukemia predicts relative glucocorticoid resistance that is overcome with MEK or Akt inhibition.

Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) is a genetically heterogeneous subtype of B-cell ALL characterized by chromosomal rearrangements and mutations that result in aberrant cytokine receptor and kinase signaling. In particular, chromosomal rearrangements resulting in the overexpression of cytokine receptor-like factor 2 (CRLF2) occur in 50% of Ph-like ALL cases. CRLF2 overexpression is associated with particularly poor clinical outcomes, though the molecular basis for this is currently unknown. Glucocorticoids (GCs) are integral to the treatment of ALL and GC resistance at diagnosis is an important negative prognostic factor. Given the importance of GCs in ALL therapy and the poor outcomes for patients with CRLF2 overexpression, we hypothesized that the aberrant signal transduction associated with CRLF2 overexpression might mediate intrinsic GC insensitivity. To test this hypothesis, we exposed Ph-like ALL cells from patient-derived xenografts to GCs and found that CRLF2 rearranged (CRLF2R) leukemias uniformly demonstrated reduced GC sensitivity in vitro. Furthermore, targeted inhibition of signal transduction with the MEK inhibitor trametinib and the Akt inhibitor MK2206, but not the JAK inhibitor ruxolitinib, was sufficient to augment GC sensitivity. These data suggest that suboptimal GC responses may in part underlie the poor clinical outcomes for patients with CRLF2 overexpression and provide rationale for combination therapy involving GCs and signal transduction inhibitors as a means of enhancing GC efficacy

Understanding Patient Trust in the Athletic Setting through Interviews

Trust is a vital component of the patient-clinician relationship yet little is known about trust in the athletic training (AT) profession. Purpose: The purpose of this qualitative study was to define and understand trust in an athletic training setting. Methods: Interviews with Division I student-athlete patients (n=9) and athletic trainers (n=3) were conducted to collect data about participant views and definitions of trust. Data were analyzed using classical and constant comparison techniques; the trustworthiness of findings were assessed via peer debriefing, member checks, and reflexive journaling. Results: The analyses yielded 21 codes and four themes described to promote trust: (1) athletic trainers’ attributes, (2) interactions between athletic trainers and athletes, (3) the quality of this relationship and (4) the overall experience. Conclusion: A working definition of trust in the athletic training setting was developed via this work; furthermore, athletic trainers and patients agreed that trust is a complex construct but is vital to developing a productive therapeutic relationship

White-tailed Deer (\u3ci\u3eOdocoileus virginianus\u3c/i\u3e) Subsidize Gray Wolves (\u3ci\u3eCanis lupus\u3c/i\u3e) During a Moose (\u3ci\u3eAlces americanus\u3c/i\u3e) Decline: A Case of Apparent Competition?

Moose (Alces americanus) in northeastern Minnesota have declined by 55% since 2006. Although the cause is unresolved, some studies have suggested that Gray Wolves (Canis lupus) contributed to the decline. After the Moose decline, wolves could either decline or switch prey. To determine which occurred in our study area, we compared winter wolf counts and summer diet before and after the Moose decline. While wolf numbers in our study area nearly doubled from 23 in winter 2002 to an average of 41 during winters 2011–2013, calf:cow ratios (the number of calves per cow observed during winter surveys) in the wider Moose range more than halved from 0.93 in 2002 to an average of 0.31 during 2011–2013. Compared to summer 2002, wolves in summers 2011–2013 consumed fewer Moose and more White-tailed Deer (Odocoileus virginianus). While deer densities were similar during each period, average vulnerability, as reflected by winter severity, was greater during 2011–2013 than 2002, probably explaining the wolf increase. During the wolf increase Moose calves remained a summer food item. These findings suggest that in part of the Moose range, deer subsidized wolf numbers while wolves also preyed on Moose calves. This contributed to a Moose decline and is a possible case of apparent competition and inverse-density-dependent predation

Evaluation of a Formula that Categorizes Female Gray Wolf Breeding Status by Nipple Size

The proportion by age class of wild Canis lupus (Gray Wolf) females that reproduce in any given year remains unclear; thus, we evaluated the applicability to our long-term (1972–2013) data set of the Mech et al. (1993) formula that categorizes female Gray Wolf breeding status by nipple size and time of year. We used the formula to classify Gray Wolves from 68 capture events into 4 categories (yearling, adult non-breeder, former breeder, current breeder). To address issues with small sample size and variance, we created an ambiguity index to allow some Gray Wolves to be classed into 2 categories. We classified 20 nipple measurements ambiguously: 16 current or former breeder, 3 former or adult non-breeder, and 1 yearling or adult non-breeder. The formula unambiguously classified 48 (71%) of the nipple measurements; based on supplemental field evidence, at least 5 (10%) of these were incorrect. When used in conjunction with an ambiguity index we developed and with corrections made for classifications involving very large nipples, and supplemented with available field evidence, the Mech et al. (1993) formula provided reasonably reliable classification of breeding status in wild female Gray Wolves

Yellowstone wolf (\u3ci\u3eCanis lupus\u3c/i\u3e) density predicted by elk (\u3ci\u3eCervus elaphus\u3c/i\u3e) biomass

The Northern Range (NR) of Yellowstone National Park (YNP) hosts a higher prey biomass density in the form of elk (Cervus elaphus L., 1758) than any other system of gray wolves (Canis lupus L., 1758) and prey reported. Therefore, it is important to determine whether that wolf–prey system fits a long-standing model relating wolf density to prey biomass. Using data from 2005 to 2012 after elk population fluctuations dampened 10 years subsequent to wolf reintroduction, we found that NR prey biomass predicted wolf density. This finding and the trajectory of the regression extend the validity of the model to prey densities 19% higher than previous data and suggest that the model would apply to wolf–prey systems of even higher prey biomass. Le domaine nord (Northern Range; NR) du parc national de Yellowstone (YNP) contient une biomasse de proies de plus grande densité, représentée par les wapitis (Cervus elaphus L., 1758), que tout autre système de loups gris (Canis lupus L., 1758) et proies connu. Il importe donc de déterminer si le système loups–proies concorde avec un modèle établi de longue date qui relie la densité des loups a` la biomasse des proies. En nous servant de données de 2005 a` 2012 après l’atténuation sur une période de 10 ans des fluctuations de la population de wapitis a` la suite de la réintroduction des loups, nous avons constaté que la biomasse des proies du NR prédisait la densité des loups. Cette constatation et la trajectoire de la régression élargissent la validité du modèle a` des densités de proies de 19 % supérieures aux données antérieures et donnent a` penser que le modèle s’appliquerait a` des systèmes loups–proies de biomasse de proies encore plus grande

Gray Wolf (\u3ci\u3eCanis lupus\u3c/i\u3e) Dyad Monthly Association Rates by Demographic Group

Preliminary data from GPS-collared wolves (Canis lupus) in the Superior National Forest of northeastern Minnesota indicated wolves had low association rates with packmates during summer. However, aerial-telemetry locations of very high frequency (VHF)-radioed wolves in this same area showed high associations among packmates during winter. We analyzed aerial-telemetry-location data from VHF-collared wolves in several packs (n=18 dyads) in this same area from 1994-2012 by month, and found lowest association rates occurred during June. While other studies have found low association among wolf packmates during summer, information on differences in association patterns depending on the wolf associates’ demographics is sparse. During May-July, association rates were greatest for breeding pairs, followed by sibling dyads, and lowest for parent–offspring dyads. Our findings improve our understanding of how individual wolf relationships affect monthly association rates. We highlight some important remaining questions regarding wolf packmate associations

Cannabis Content in Athletic Training and Physical Therapy Curriculums in the United States

Background: Cannabis is the most commonly used illicit drug in the U.S. and its use is becoming more popular with the legalization of medical marijuana. Currently, 36/50 states and the District of Columbia have legalized marijuana for medical purposes. These changes have allowed for more cannabis-related research to be conducted. It is unknown how health professional education programs such as physical therapy and athletic training have integrated cannabis-related curriculum into their students’ training. This study aimed to identify how physical therapy and athletic training education programs are approaching teaching students about cannabis-related topics. Methods: There were 111 individuals from 40 states who responded to the survey (Males=53; Female=58), including 88 athletic training and 23 physical therapy faculty. Methods: An email was sent to all program directors of athletic training and physical therapy programs in the US with a Qualtrics survey link for faculty to complete. The 23-item questionnaire included closed-ended questions on demographics, where they sought cannabis-related information, and whether program curriculum includes cannabis-related topics. Frequencies were computed for sources of cannabis-related information and whether program curriculum includes cannabis-related topics. Results: Sixty (53.5%) participants stated they have not received information or completed any training related to cannabis. Of those receiving information or completing training (n=51), the most common sources of information were live lectures (n=23), peer-reviewed manuscripts (n=24), and social media/news (n=21). Also, 43 (38%) participants noted teaching cannabis-related topics in their curriculum. However, 33 participants reported either not completing training related to cannabis or being self-educated through the current literature. Conclusions: These results suggest program faculty may benefit from formal cannabis education in an effort to adequately integrate the content into curriculums

Very long baseline astrometry of PSR J1012+5307 and its implications on alternative theories of gravity

PSR J1012+5307, a millisecond pulsar in orbit with a helium white dwarf (WD), has been timed with high precision for about 25 years. One of the main objectives of this long-term timing is to use the large asymmetry in gravitational binding energy between the neutron star and the WD to test gravitational theories. Such tests, however, will be eventually limited by the accuracy of the distance to the pulsar. Here, we present VLBI (very long baseline interferometry) astrometry results spanning approximately 2.5 years for PSR J1012+5307, obtained with the Very Long Baseline Array as part of the MSPSRPI project. These provide the first proper motion and absolute position for PSR J1012+5307 measured in a quasi-inertial reference frame. From the VLBI results, we measure a distance of $0.83^{+0.06}_{-0.02}$kpc (all the estimates presented in the abstract are at 68% confidence) for PSR J1012+5307, which is the most precise obtained to date. Using the new distance, we improve the uncertainty of measurements of the unmodeled contributions to orbital period decay, which, combined with three other pulsars, places new constraints on the coupling constant for dipole gravitational radiation $\kappa_D=(-1.7\pm1.7)\times 10^{-4}$ and the fractional time derivative of Newton's gravitational constant $\dot{G}/G = -1.8^{\,+5.6}_{\,-4.7}\times 10^{-13}\,{\rm yr^{-1}}$ in the local universe. As the uncertainties of the observed decays of orbital period for the four leading pulsar-WD systems become negligible in $\approx10$ years, the uncertainties for $\dot{G}/G$ and $\kappa_D$ will be improved to $\leq1.5\times10^{-13}\,{\rm yr^{-1}}$ and $\leq1.0\times10^{-4}$, respectively, predominantly limited by the distance uncertainties.Comment: published in ApJ (2020ApJ...896...85D

Effects of Combined Opioids on Pain and Mood in Mammals

The authors review the opioid literature for evidence of increased analgesia and reduced adverse side effects by combining mu-opioid-receptor (MOR) agonists, kappa-opioid-receptor (KOR) agonists, and nonselective low-dose-opioid antagonists (LD-Ant). We tested fentanyl (MOR agonist) and spiradoline (KOR agonist), singly and combined, against somatic and visceral pain models. Combined agonists induced additive analgesia in somatic pain and synergistic analgesia in visceral pain. Other investigators report similar effects and reduced tolerance and dependence with combined MOR agonist and KOR agonist. LD-Ant added to either a MOR agonist or KOR agonist markedly enhanced analgesia of either agonist. In accordance with other place-conditioning (PC) studies, our PC investigations showed fentanyl-induced place preference (CPP) and spiradoline-induced place aversion (CPA). We reduced fentanyl CPP with a low dose of spiradoline and reduced spiradoline CPA with a low dose of fentanyl. We propose combined MOR agonist, KOR agonist, and LD-Ant to produce superior analgesia with reduced adverse side effects, particularly for visceral pain