Longitudinal performance of senescence accelerated mouse prone-strain 8 (SAMP8) mice in an olfactory-visual water maze challenge

© 2018 Lam, Takechi, Albrecht, D’Alonzo, Graneri, Hackett, Coulson, Fimognari, Nesbit and Mamo. Morris water maze (MWM) is widely used to assess cognitive deficits in pre-clinical rodent models. Latency time to reach escape platform is frequently reported, but may be confounded by deficits in visual acuity, or differences in locomotor activity. This study compared performance of Senescence Accelerated Mouse Prone-Strain 8 (SAMP8) and control Senescence Accelerated Mouse Resistant-Strain 1 (SAMR1) mice in classical MWM, relative to performance in a newly developed olfactory-visual maze testing protocol. Performance indicated as the escape time to rescue platform for classical MWM testing showed that SAMP8 mice as young as 6 weeks of age did poorly relative to age-matched SAMR1 mice. The olfactory-visual maze challenge described better discriminated SAMP8 vs. SAMR1 mice than classical MWM testing, based on latency time measures. Consideration of the distance traveled rather than latency time in the classical MWM found no treatment effects between SAMP8 and SAMR1 at 40 weeks of age and the olfactory-visual measures of performance confirmed the classical MWM findings. Longitudinal (repeat) assessment of SAMP8 and SAMR1 performance at 6, 20, 30, and 40 weeks of age in the olfactory-visual testing protocol showed no age-associated deficits in SAMP8 mice to the last age end-point indicated. Collectively, the results from this study suggest the olfactory-visual testing protocol may be advantageous compared to classical MWM as it avoids potential confounders of visual impairment in some strains of mice and indeed, may offer insight into cognitive and behavioral deficits that develop with advanced age in the widely used SAMP8 murine model

Comparisons between group- and individual-based interventions to support recovery from stroke and ischaemic heart disease in the community: a scoping review

Purpose To map and summarise available literature on the effectiveness or other benefits of group- and individual-based interventions provided for adults living with stroke or ischaemic heart disease (IHD) in the community. Material and Methods The review was conducted based on JBI methodology and reported using Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. Articles were retrieved from: Medline, PsychInfo, Embase, Scopus, and CINAHL from 2002–2022. Extracted data from eligible studies included type of health outcomes (e.g., impairments), retention and adherence, social connectedness, and the costs associated with group- and individual-based interventions. Results After screening, five articles (representing 4 unique studies) comparing a group- and individual-based intervention were included (total sample size n = 87). Three types of interventions were assessed: exercise (3/5), communication (1/5), and occupational therapy (1/5). Effectiveness of group- and individual-based interventions at improving health outcomes (i.e. physical ability, communication, motivation, and quality of life) is unclear. Currently there is insufficient evidence to guide clinical practice. Conclusions There is limited evidence comparing interventions delivered in a group and individual modality for adults living with stroke or IHD. Adequately powered studies are needed to determine if mode of delivery is equivalent or more cost effective. IMPLICATIONS FOR REHABILITATION Rehabilitation interventions can be offered individually or in group settings with clinicians choosing the most appropriate modality. Both group- and individual-based interventions have advantages and disadvantages, with clinical, practical, and economic factors as important considerations when deciding between the two modalities. Based on this scoping review, the authors conclude that there is currently insufficient evidence to guide clinical practice in deciding which mode of delivery (group or individual) is optimal. There is insufficient research evidence to guide clinicians in their choice between offering rehabilitation interventions for stroke or IHD in groups or individually

Hypomethylating agent decitabine sensitizes diffuse large B-cell lymphoma to venetoclax

Despite recent advances in the therapy of diffuse large B-cell lymphoma (DLBCL), many patients are still not cured. Therefore, new therapeutic strategies are needed. The anti-apoptotic B-cell lymphoma 2 (BCL2) gene is commonly dysregulated in DLBCL due to various mechanisms such as chromosomal translocation t(14;18)(q32;q21) and copy number alterations; however, targeting BCL-2 with the selective inhibitor, venetoclax, led to response in only a minority of patients. Thus, we sought to identify a rational combination partner of venetoclax to improve its activity against DLBCL cells. Utilizing a functional assay, dynamic BH3 profiling, we found that the DNA hypomethylating agent decitabine increased mitochondrial apoptotic priming and BCL-2 dependence in DLBCL cells. RNA-sequencing analysis revealed that decitabine suppressed the pro-survival PI3K-AKT pathway and altered the mitochondria membrane composition in DLBCL cell lines. Additionally, it induced a DNA damage response and increased BAX and BAK activities. The combination of decitabine and venetoclax synergistically suppressed proliferation of DLBCL cells both in vitro and in vivo in a DLBCL cell line-derived xenograft mouse model. Our study suggests that decitabine plus venetoclax is a promising combination to explore clinically in DLBCL

A Four-Way Comparison of Cardiac Function with Normobaric Normoxia, Normobaric Hypoxia, Hypobaric Hypoxia and Genuine High Altitude.

There has been considerable debate as to whether different modalities of simulated hypoxia induce similar cardiac responses.This was a prospective observational study of 14 healthy subjects aged 22-35 years. Echocardiography was performed at rest and at 15 and 120 minutes following two hours exercise under normobaric normoxia (NN) and under similar PiO2 following genuine high altitude (GHA) at 3,375m, normobaric hypoxia (NH) and hypobaric hypoxia (HH) to simulate the equivalent hypoxic stimulus to GHA.All 14 subjects completed the experiment at GHA, 11 at NN, 12 under NH, and 6 under HH. The four groups were similar in age, sex and baseline demographics. At baseline rest right ventricular (RV) systolic pressure (RVSP, p = 0.0002), pulmonary vascular resistance (p = 0.0002) and acute mountain sickness (AMS) scores were higher and the SpO2 lower (p<0.0001) among all three hypoxic groups (GHA, NH and HH) compared with NN. At both 15 minutes and 120 minutes post exercise, AMS scores, Cardiac output, septal S', lateral S', tricuspid S' and A' velocities and RVSP were higher and SpO2 lower with all forms of hypoxia compared with NN. On post-test analysis, among the three hypoxia groups, SpO2 was lower at baseline and 15 minutes post exercise with GHA (89.3±3.4% and 89.3±2.2%) and HH (89.0±3.1 and (89.8±5.0) compared with NH (92.9±1.7 and 93.6±2.5%). The RV Myocardial Performance (Tei) Index and RVSP were significantly higher with HH than NH at 15 and 120 minutes post exercise respectively and tricuspid A' was higher with GHA compared with NH at 15 minutes post exercise.GHA, NH and HH produce similar cardiac adaptations over short duration rest despite lower SpO2 levels with GHA and HH compared with NH. Notable differences emerge following exercise in SpO2, RVSP and RV cardiac function

Statistical analysis plan for the Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke randomised controlled clinical trial

Background: Unplanned hospital presentations may occur post-stroke due to inadequate preparation for transitioning from hospital to home. The Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke (ReCAPS) trial was designed to test the effectiveness of receiving a 12-week, self-management intervention, comprising personalised goal setting with a clinician and aligned educational/motivational electronic messages. Primary outcome is as follows: self-reported unplanned hospital presentations (emergency department/admission) within 90-day post-randomisation. We present the statistical analysis plan for this trial. Methods/design: Participants are randomised 1:1 in variable block sizes, with stratification balancing by age and level of baseline disability. The sample size was 890 participants, calculated to detect a 10% absolute reduction in the proportion of participants reporting unplanned hospital presentations/admissions, with 80% power and 5% significance level (two sided). Recruitment will end in December 2023 when funding is expended, and the sample size achieved will be used. Logistic regression, adjusted for the stratification variables, will be used to determine the effectiveness of the intervention on the primary outcome. Secondary outcomes will be evaluated using appropriate regression models. The primary outcome analysis will be based on intention to treat. A p-value ≤ 0.05 will indicate statistical significance. An independent Data Safety and Monitoring Committee has routinely reviewed the progress and safety of the trial. Conclusions: This statistical analysis plan ensures transparency in reporting the trial outcomes. ReCAPS trial will provide novel evidence on the effectiveness of a digital health support package post-stroke. Trial registration: ClinicalTrials.gov ACTRN12618001468213. Registered on August 31, 2018. SAP version 1.13 (October 12 2023) Protocol version 1.12 (October 12, 2022) SAP revisions Ni

Experiences of adolescent witnesses to peer victimization: The bystander effect

Many anti-bullying programs now emphasize the role of bystanders - youth who witness peer victimization. Using a large sample of adolescents (aged 12-18) from the United Kingdom who completed an online survey, the present study examined the types of bystander interventions, their outcomes, and reasons for intervening and not intervening. No significant group differences by any demographic group were found in intervening or not. Results showed that those who had a negative affective reaction when they witnessed bullying were more likely to intervene. Two intervening behaviors (telling the bully to stop and telling an adult) were the strongest predictors of positive results. The most frequently selected reason for not intervening was not knowing what to do, and for intervening, having prosocial and altruistic motives was most common. These and other results are discussed for theoretical and practical implications.24 month embargo; available online 19 May 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Alternative Management of the Capsule in the Bristow-Latarjet Procedure

The Bristow-Latarjet procedure is considered the current gold standard for the management of anterior glenohumeral joint instability in which significant glenoid bone loss is present, and numerous techniques have been proposed for capsular management after the bony augmentation component of the procedure. These techniques for capsular management include excision of the capsule and labrum, 2-flap elevation, T-capsulotomy, or an L-shaped incision into the capsule. Capsular management during open shoulder procedures may vary among surgeons and may or may not include capsulolabral repair after the Bristow-Latarjet procedure. The purpose of this Technical Note was to illustrate an alternative approach to capsular management, focusing on the elevation of the capsulolabral complex as a sleeve along with augmentation using the coracoacromial ligament during the Bristow-Latarjet procedure in patients with anterior glenohumeral instability. The proposed technique provides the benefit of improvement in visualization to more reliably identify the ideal location for bone block placement and allows for the surgeon to perform a large inferior-to-superior capsular shift to prevent inferior subluxation or instability

Longitudinal advocacy training for medical students: a virtual workshop series

Implication StatementAdvocacy curricula in Canadian medical schools vary significantly. Expert-led, interactive workshops can effectively teach students how to address social determinants of health and advocate for patients. The Longitudinal Advocacy Training Series (LATS) is a free-of-charge, virtual program providing advocacy training created for Canadian medical students by students. The program was straightforward to implement and had high participation rates with 1140 participants representing 9.7% of enrolled Canadian medical students. As well, the program had high satisfaction reported by 87.6% of participants. The LATS toolkit enables health professional programs to develop similar programs for empowering effective health advocates.Énoncé des implications de la rechercheAu Canada, les programmes de formation en matière de promotion et de défense des droits varient considérablement d'une faculté de médecine à l'autre. Les ateliers interactifs dirigés par des experts constituent un outil efficace pour enseigner aux étudiants la façon aborder les déterminants sociaux de la santé afin de défendre les droits des patients. La Longitudinal Advocacy Training Series (LATS) est un programme virtuel gratuit de formation à la défense des droits, créé par des étudiants pour les étudiants. Le programme, facile à mettre en œuvre, a connu un taux de participation élevé, à savoir 1140 participants représentant 9,7 % des étudiants en médecine au Canada. En outre, 87,6 % des participants se sont dits très satisfaits du programme. La trousse à outils LATS permet aux programmes de formation des professions de la santé de mettre sur pied des modules similaires pour donner aux étudiants les moyens de devenir des défenseurs de la santé efficaces

Formation longitudinale à la promotion et à la défense des droits pour les étudiants en médecine : une série d’ateliers virtuels

Implication Statement Advocacy curricula in Canadian medical schools vary significantly. Expert-led, interactive workshops can effectively teach students how to address social determinants of health and advocate for patients. The Longitudinal Advocacy Training Series (LATS) is a free-of-charge, virtual program providing advocacy training created for Canadian medical students by students. The program was straightforward to implement and had high participation rates with 1140 participants representing 9.7% of enrolled Canadian medical students. As well, the program had high satisfaction reported by 87.6% of participants. The LATS toolkit enables health professional programs to develop similar programs for empowering effective health advocates.Énoncé des implications de la recherche Au Canada, les programmes de formation en matière de promotion et de défense des droits varient considérablement d'une faculté de médecine à l'autre. Les ateliers interactifs dirigés par des experts constituent un outil efficace pour enseigner aux étudiants la façon aborder les déterminants sociaux de la santé afin de défendre les droits des patients. La Longitudinal Advocacy Training Series (LATS) est un programme virtuel gratuit de formation à la défense des droits, créé par des étudiants pour les étudiants. Le programme, facile à mettre en œuvre, a connu un taux de participation élevé, à savoir 1140 participants représentant 9,7 % des étudiants en médecine au Canada. En outre, 87,6 % des participants se sont dits très satisfaits du programme. La trousse à outils LATS permet aux programmes de formation des professions de la santé de mettre sur pied des modules similaires pour donner aux étudiants les moyens de devenir des défenseurs de la santé efficaces