Frizzled-7 is required for Wnt signaling in gastric tumours with and without Apc mutations

A subset of patients with gastric cancer have mutations in genes that participate in or regulate Wnt signaling at the level of ligand (Wnt) receptor (Fzd) binding. Moreover, increased Fzd expression is associated with poor clinical outcome. Despite these findings, there are no in vivo studies investigating the potential of targeting Wnt receptors for treating gastric cancer, and the specific Wnt receptor transmitting oncogenic Wnt signaling in gastric cancer is unknown. Here, we use inhibitors of Wnt/Fzd (OMP-18R5/vantictumab) and conditional gene deletion to test the therapeutic potential of targeting Wnt signaling in preclinical models of intestinal-type gastric cancer and ex vivo organoid cultures. Pharmacologic targeting of Fzd inhibited the growth of gastric adenomas in vivo. We identified Fzd7 to be the predominant Wnt receptor responsible for transmitting Wnt signaling in human gastric cancer cells and mouse models of gastric cancer, whereby Fzd7-deficient cells were retained in gastric adenomas but were unable to respond to Wnt signals and consequently failed to proliferate. Genetic deletion of Fzd7 or treatment with vantictumab was sufficient to inhibit the growth of gastric adenomas with or without mutations to Apc. Vantictumab is currently in phase Ib clinical trials for advanced pancreatic, lung, and breast cancer. Our data extend the scope of patients that may benefit from this therapeutic approach as we demonstrate that this drug will be effective in treating patients with gastric cancer regardless of APC mutation status

Stroke Caregiver Outcomes from the Telephone Assessment and Skill-Building Kit (TASK)

Purpose: Stroke caregivers often express the need for information about stroke and assistance with stroke-related care in the early discharge period. The Telephone Assessment and Skill-Building Kit (TASK) is an 8-week program that addresses caregiver needs. This study explored the efficacy of the TASK program in improving stroke caregiver outcomes. Method: Guided by a conceptual model, 6 outcomes (optimism, task difficulty, threat appraisal, depressive symptoms, life changes, general health perceptions) were measured in 40 caregivers randomized to the TASK (n = 21) or an attention control group (n = 19). Data were analyzed using analysis of covariance (ANCOVA), controlling for baseline scores and minutes spent with the nurse. Results: Significant increases in optimism at 4 weeks, 8 weeks, and 12 weeks were found, with medium effect sizes for the TASK group relative to the control group (p < .05). Significant improvements in task difficulty at 4 weeks, and threat appraisal at both 8 weeks and 12 weeks were also found (p < .05). Conclusion: Caregivers receiving the TASK intervention improved in optimism, task difficulty, and threat appraisal. Further testing of an enhanced version of the TASK program is warranted, with attention directed toward more distal stroke caregiver outcomes

Content Validity and Satisfaction With a Stroke Caregiver Intervention Program

Background and Purpose Establishing evidence of content validity and satisfaction is an integral part of intervention research. The purpose of this article is to describe content validity and satisfaction relative to the Telephone Assessment and Skill-Building Kit (TASK), an 8-week follow-up program based on individualized assessment of stroke caregiver needs. Design and Methods The TASK intervention enables caregivers to develop skills based on assessment of their own needs. During the development of the TASK program, 10 experts rated the validity of the TASK intervention components for accuracy, feasibility, acceptability, and problem relevance. After incorporating feedback from the experts, a randomized controlled clinical trial was instituted using a convenience sample of 40 stroke caregivers to determine satisfaction (usefulness, case of use, and acceptability) with the TASK intervention (n=21) compared with an attention control group (n=19). Data collection occurred between March 2005 and June 2006. Data were analyzed using descriptive statistics, independent sample t tests, and content analysis. Findings Expert ratings on a 1 to 5 scale, with 5 being strongly agree, provided evidence of content validity (accuracy 4.71, feasibility 4.46, acceptability 4.40, problem relevance 4.67). Caregivers in the TASK group scored significantly higher than the attention control group on all satisfaction measures (usefulness p=.02; ease of use p=.02; acceptability p=.05). Qualitative comments from caregivers provided further evidence of satisfaction. Conclusions Evidence of content validity and user satisfaction for the TASK intervention relative to an attention control group was found. Clinical Relevance The TASK program may be a viable telephone-based program that can be implemented by nurses to support family caregivers during the first few months after stroke survivors are discharged home

Maternal high-fat feeding in pregnancy programmes atherosclerotic lesion size in the ApoE*3 Leiden mouse

Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high fat diet in utero, programmed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28d postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (p<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol, however transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared to wild-type controls (p=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R2=0.563, p<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol 2-fold higher than in chow fed mothers, p=0.011). The data strongly suggest that maternal hypercholesterolaemia programmes later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models

Maternal high-fat feeding in pregnancy programmes atherosclerotic lesion size in the ApoE*3 Leiden mouse

Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high fat diet in utero, programmed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28d postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (p<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol, however transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared to wild-type controls (p=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R2=0.563, p<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol 2-fold higher than in chow fed mothers, p=0.011). The data strongly suggest that maternal hypercholesterolaemia programmes later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models

Recovery Strategies in Endurance Athletes

In order to achieve optimal performance, endurance athletes, whether at the professional or recreational level, need to implement a variety of recovery strategies that are specific to their individual training and competition. Recovery is a multidimensional process involving physiological, psychological, emotional, social, and behavioral aspects. PURPOSE: The purpose of the current study is to examine current implementation, beliefs, and sources of information associated with recovery strategies in endurance athletes. METHODS: Participants included 240 self-identified endurance athletes (m=112, f=126, non-binary=1, and preferred not to answer=1) across different sports (cycling=57, running=100, triathlon = 61, other=22; pro=13, current/former collegiate athlete=67, recreational=160). The participants ranged in age from 18 to 79 years old (40.7±13.73) and were primarily white (n=213). Participants completed an online survey through Qualtrics on demographics, recovery strategies used in practice and competition, perceived benefit of the strategy, and their sources of information regarding recovery strategies. RESULTS: Hydration was the most frequently reported recovery strategy in both training (91.3%, n = 219) and competition r (80.4%, n = 193). Nutrition followed in training (78.8%, n = 189) and competition (78.3%, n = 188). Sleep was the third most utilized strategy in training (77.9%, n = 187) and competition (76.7%, n = 184). The least used recovery strategy was ultrasound in training (1.3%, n = 3) and competition (1.7% n = 4). Chi-squared analyses showed no significant differences between training and competition for the use of the recovery strategies. Hydration was reported as a beneficial recovery strategy after practice (96.5%, n = 223) and competition (94.7%, n = 200) by the greatest percentage of participants, with sleep the second most frequently considered beneficial (91.4%, n = 213; 92.5%, n = 199), followed by nutrition (91.3%, n = 211; 92.5%, n = 198). The participants were most likely to get their information about recovery strategies from a fellow athlete (46.3%, n = 111), a coach (42.5%, n = 102), or a website (30.4%, n = 74). CONCLUSION: Hydration is the most common recovery strategy and found to be beneficial in both training and competition settings. These athletes are relying on the people around them and websites for information and recommendations. Endurance athletes should be educated on other strategies to address the multidimensionality of recovery. These findings will be useful for healthcare professionals, practitioners, and coaches in understanding recovery strategies in endurance athletes

Expressing one’s feelings and listening to others increases emotional intelligence: a pilot study of Asian medical students

&lt;p&gt;Background: There has been considerable interest in Emotional Intelligence (EI) in undergraduate medical education, with respect to student selection and admissions, health and well-being and academic performance. EI is a significant component of the physician-patient relationship. The emotional well-being of the physician is, therefore, a significant component in patient care. The aim is to examine the measurement of TEIQue-SF in Asian medical students and to explore how the practice of listening to the feelings of others and expressing one’s own feelings influences an individual’s EI, set in the context of the emotional well-being of a medical practitioner.&lt;/p&gt; &lt;p&gt;Methods: A group of 183 international undergraduate medical students attended a half-day workshop (WS) about mental-health and well-being. They completed a self-reported measure of EI on three occasions, pre- and post-workshop, and a 1-year follow-up.&lt;/p&gt; &lt;p&gt;Result: The reliability of TEIQue-SF was high and the reliabilities of its four factors were acceptable. There were strong correlations between the TEIQue-SF and personality traits. A paired t-test indicated significant positive changes after the WS for all students (n=181, p= .014), male students (n=78, p= .015) and non-Japanese students (n=112, p= .007), but a repeated measures analysis showed that one year post-workshop there were significant positive changes for all students (n=55, p= .034), female students (n=31, p= .007), especially Japanese female students (n=13, p= .023). Moreover, 80% of the students reported that they were more attentive listeners, and 60% agreed that they were more confident in dealing with emotional issues, both within themselves and in others, as a result of the workshop.&lt;/p&gt; &lt;p&gt;Conclusion: This study found the measurement of TEIQue-SF is appropriate and reliable to use for Asian medical students. The mental health workshop was helpful to develop medical students’ EI but showed different results for gender and nationality. The immediate impact on the emotional awareness of individuals was particularly significant for male students and the non-Japanese group. The impact over the long term was notable for the significant increase in EI for females and Japanese. Japanese female students were more conscious about emotionality. Emotion-driven communication exercises might strongly influence the development of students’ EI over a year.&lt;/p&gt

New record in the Hawaiian Islands of Orasema minutissima (Hymenoptera: Eucharitidae), an ant-parasitic wasp and a potential biocontrol agent against the Little Fire Ant, Wasmannia auropunctata (Hymenoptera: Formicidae)

Orasema minutissima Howard (Hymenoptera: Eucharitidae) is recorded fromthe Hawaiian Islands for the first time. It has been established on the island of Hawai?isince at least 2019. The wasp is a parasitoid of the immature stages of Pheidole andWasmannia (Formicidae: Myrmicinae), both of which are significant pests on several ofthe Hawaiian Islands. Already found in substantial numbers, the wasp is a potential biological control agent for Wasmannia auropunctata, the Little Fire Ant.Fil: Heraty, John Michael. University of California; Estados UnidosFil: Rogers, Valle D.. University of California; Estados UnidosFil: Johnson, M. Tracy. Institute of Pacific Islands Forestry; Estados UnidosFil: Perreira, Williams D.. No especifíca;Fil: Baker, Austin J.. University of California; Estados UnidosFil: Bitume, Ellyn. Institute of Pacific Islands Forestry; Estados UnidosFil: Murray, Elizabeth. Washington State University; Estados UnidosFil: Varone, Laura. Fundación para el Estudio de Especies Invasivas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin