Neratinib could be effective as monotherapy or in combination with trastuzumab in HER2-low breast cancer cells and organoid models.

BACKGROUND: Previous studies have suggested that patients with HER2-low breast cancers do not benefit from trastuzumab treatment although the reasons remain unclear. METHODS: We investigated the effect of trastuzumab monotherapy and its combination with different HER2 targeting treatments in a panel of breast cancer cell lines and patient-derived organoids (PDOs) using biochemical methods and cell viability assays. RESULTS: Compared to sensitive HER2 over-expressing (IHC3 + ) breast cancer cells, increasing doses of trastuzumab could not achieve IC50 in MDA-MB-361 (IHC 2 + FISH + ) and MDA-MB-453 (IHC 2 + FISH-) cells which showed an intermediate response to trastuzumab. Trastuzumab treatment induced upregulation of HER ligand release, resulting in the activation of HER receptors in these cells, which could account for their trastuzumab insensitivity. Adding a dual ADAM10/17 inhibitor to inhibit the shedding of HER ligands in combination with trastuzumab only showed a modest decrease in the cell viability of HER2-low breast cancer cells and PDOs. However, the panHER inhibitor neratinib was an effective monotherapy in HER2-low breast cancer cells and PDOs, and showed additive effects when combined with trastuzumab. CONCLUSION: This study demonstrates that neratinib in combination with trastuzumab may be effective in a subset of HER2-low breast cancers although further validation is required in a larger panel of PDOs and in future clinical studies.

Self-assembled monolayer-based blue perovskite LEDs.

Blue perovskite light-emitting diodes (LEDs) have shown external quantum efficiencies (EQEs) of more than 10%; however, devices that emit in the true blue-those that accord with the emission wavelength required for Rec. 2100 primary blue-have so far been limited to EQEs of ~6%. We focused here on true blue emitting CsPbBr3 colloidal nanocrystals (c-NCs), finding in early studies that they suffer from a high charge injection barrier, a problem exacerbated in films containing multiple layers of nanocrystals. We introduce a self-assembled monolayer (SAM) active layer that improves charge injection. We identified a bifunctional capping ligand that simultaneously enables the self-assembly of CsPbBr3 c-NCs while passivating surface traps. We report, as a result, SAM-based LEDs exhibit a champion EQE of ~12% [CIE of (0.132, 0.069) at 4.0 V with a luminance of 11 cd/m2], and 10-fold-enhanced operating stability relative to the best previously reported Rec. 2100-blue perovskite LEDs.

Lower Limb Muscles' Activation during Ascending and Descending a Single Step-Up Movement: Comparison between In water and On land Exercise at Different Step Cadences in Young Injury-Free Adults.

(1) Background: Forward step-up (FSU) simulates the stance phase in stair ascension. With the benefits of physical properties of water, aquatic FSU exercise may be more suitable for patients with lower limb weakness or pain. The purpose of this study is to investigate the effect of progressive steps per min on the surface electromyography (sEMG) of gluteus maximus (GM), biceps femoris (BF), rectus femoris (RF), and gastrocnemius (GA), when performing FSU exercise with different steps per min in water and on land. (2) Methods: Participants (N = 20) were instructed to perform FSU exercises at different steps per min (35, 60, and 95 bpm) in water and on land. The sEMG of the tested muscles were collected. The percentage maximum voluntary isometric contraction (%MVIC) of GM, RF, GA and BF at different environments and steps per min was compared. (3) Result: There was a statistically significant difference of %MVIC of RF at all steps per min comparisons regardless of the movement phases and environments (p < 0.01, except for descending phases of 35 bpm vs. 60 bpm). All tested muscles showed a statistically significant lower muscle activation in water (p < 0.05) (4) Conclusion: This study found that the %MVIC of the tested muscle in both investigated environments increase as steps per minute increases. It is also found that the movement pattern of FSU exercise activates RF the most among all the tested muscles. Muscle activation of all tested muscles is also found to be smaller in water due to buoyancy property of water. Aquatic FSU exercise might be applicable to patients with lower limb weakness or knee osteoarthritis to improve their lower limb strength.

Psychological well-being and coping strategies of healthcare students during the prolonged COVID-19 pandemic.

Background: This study aimed to investigate the psychological well-being, and stress coping strategies, as well as their relationships, among healthcare students during prolonged COVID-19 pandemic. Methods: An online questionnaire was used to assess psychological well-being (the Ryff Scale) and coping strategies (the brief Coping Orientation to Problems Experienced Inventory [COPE] Scale). COPE scores were categorized to identify the primary coping strategies: "approach" indicates more active coping strategies; "avoidant" indicates more dysfunctional and maladaptive mechanisms. Results: A total of 202 valid questionnaire were collected. Those with lower academic confidence and lower self-rated peer and family relationship scores during the COVID-19 pandemic had lower Ryff scores, indicating poorer psychological well-being. Nursing students reported the lowest psychological well-being and the highest levels of adopting avoidant coping strategies (26.4%). Conclusion: The study's findings may help educators identify the healthcare students most vulnerable to stress and develop interventions to empower students to adopt problem-focused stress coping strategies.

Life Functioning in Chinese Survivors of Childhood Cancer in Hong Kong.

Background: Evidence on self-care ability and occupational outcomes in Chinese survivors of childhood cancer is clearly lacking. This study aims to identify clinical and behavioral factors associated with poor life functioning in this population. Methods: This was a cross-sectional study conducted at an ambulatory clinic of a public hospital in Hong Kong. Licensed occupational therapists administered the Life Functioning Assessment Inventory on survivors diagnosed with cancer <19 years old and ≥5 years post-diagnosis. Survivors' career development self-efficacy, subjective happiness, and motivation were evaluated using structured questionnaires. Clinical information was obtained from medical records. Multivariable linear regression was used to evaluate factors associated with life functioning outcomes, adjusting for clinically relevant variables. Results: Eighty survivors were recruited (58.7% male; age at diagnosis: 6.7 [standard deviation (SD) = 4.8] years; age at evaluation: 24.4 [SD = 6.5] years). Compared to survivors of leukemia, survivors of brain tumor performed worse in social functioning (ß = -0.79, standard error [SE] = 0.36; p = 0.034). Survivors who had been treated with cranial radiation also had lower worker life functioning than those who had not (ß = -0.91, SE = 0.031; p = 0.021). Higher activity motivation was significantly associated with better leisure functioning (ß = 0.086, SE = 0.03; p = 0.008), social functioning (ß = 0.036, SE = 0.02; p = 0.036), and career development self-efficacy (ß = 1.04, SE = 0.26; p < 0.0001). Conclusion: Survivors of brain tumors and survivors who were treated with radiation have poorer life functioning, particularly in social and work domains. Future work includes validating the study findings in a larger cohort of survivors in Hong Kong. Addressing modifiable behavioral factors include motivating survivors to engage in meaningful activities that contribute to self-care and participation in society, as well as providing at-risk survivors with ongoing support from community vocational services.

Characteristics and effectiveness of cognitive behavioral therapy for older adults living in residential care: a systematic review.

OBJECTIVES: Cognitive behavioral therapy (CBT) for depression and anxiety for older adults living in residential aged care facilities (RACFs) needs to accommodate the care needs of residents and the circumstances of RACFs. This systematic review examines the delivery and content characteristics of these interventions, in relation to participant satisfaction, staff appraisal, uptake rate, attrition rate, and treatment effectiveness. Such a review could provide important information for the development of future CBT-based interventions. METHOD: Studies that examined the application of CBT for depression or anxiety in RACFs were identified by systematically searching a number of relevant databases. Reference lists of all included studies were examined, and citation searches on the Web of Science were conducted. Two independent reviewers were involved in screening articles and in extracting data and assessing methodological quality of the selected studies. RESULTS: Across the 18 studies included in this review, the most common therapeutic strategy was pleasant activities scheduling. Studies varied on treatment duration (2-24 weeks), number of sessions (6-24), and length of sessions (10-120 min). Residents and staff members were satisfied with the CBT interventions. The average uptake rate was 72.9%. The average attrition rate was 19.9%. Statistically significant results were reported in 8 of the 12 randomized controlled trials (RCTs). In these eight RCTs, CBT was characterized by psychoeducation, behavioral activation, and problem-solving techniques; further, the therapists in six of these studies had training in psychology. CONCLUSION: CBT interventions for depression and anxiety are acceptable to RACF residents and judged positively by staff members. Effective studies differed from non-effective studies on content and training characteristics, but not on other delivery features.

Keystone predators govern the pathway and pace of climate impacts in a subarctic marine ecosystem.

Predator loss and climate change are hallmarks of the Anthropocene yet their interactive effects are largely unknown. Here, we show that massive calcareous reefs, built slowly by the alga Clathromorphum nereostratum over centuries to millennia, are now declining because of the emerging interplay between these two processes. Such reefs, the structural base of Aleutian kelp forests, are rapidly eroding because of overgrazing by herbivores. Historical reconstructions and experiments reveal that overgrazing was initiated by the loss of sea otters, Enhydra lutris (which gave rise to herbivores capable of causing bioerosion), and then accelerated with ocean warming and acidification (which increased per capita lethal grazing by 34 to 60% compared with preindustrial times). Thus, keystone predators can mediate the ways in which climate effects emerge in nature and the pace with which they alter ecosystems.

Characteristics of Cognitive Behavioral Therapy for Older Adults Living in Residential Care: Protocol for a Systematic Review.

BACKGROUND: The prevalence rates of depressive and anxiety disorders are high in residential aged care settings. Older adults in such settings might be prone to these disorders because of losses associated with transitioning to residential care, uncertainty about the future, as well as a decline in personal autonomy, health, and cognition. Cognitive behavioral therapy (CBT) is efficacious in treating late-life depression and anxiety. However, there remains a dearth of studies examining CBT in residential settings compared with community settings. Typically, older adults living in residential settings have higher care needs than those living in the community. To date, no systematic reviews have been conducted on the content and the delivery characteristics of CBT for older adults living in residential aged care settings. OBJECTIVE: The objective of this paper is to describe the systematic review protocol on the characteristics of CBT for depression and/or anxiety for older adults living in residential aged care settings. METHODS: This protocol was developed in compliance with the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Studies that fulfill the inclusion criteria will be identified by systematically searching relevant electronic databases, reference lists, and citation indexes. In addition, the PRISMA flowchart will be used to record the selection process. A pilot-tested data collection form will be used to extract and record data from the included studies. Two reviewers will be involved in screening the titles and abstracts of retrieved records, screening the full text of potentially relevant reports, and extracting data. Then, the delivery and content characteristics of different CBT programs of the included studies, where available, will be summarized in a table. Furthermore, the Downs and Black checklist will be used to assess the methodological quality of the included studies. RESULTS: Systematic searches will commence in May 2018, and data extraction is expected to commence in July 2018. Data analyses and writing will happen in October 2018. CONCLUSIONS: In this section, the limitations of the systematic review will be outlined. Clinical implications for treating late-life depression and/or anxiety, and implications for residential care facilities will be discussed. TRIAL REGISTRATION: PROSPERO 42017080113; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=80113 (Archived by WebCite at http://www.webcitation.org/70dV4Qf54). REGISTERED REPORT IDENTIFIER: RR1-10.2196/9902.

Implementation of an interprofessional team-based learning program involving seven undergraduate health and social care programs from two universities, and students' evaluation of their readiness for interprofessional learning.

BACKGROUND: Interprofessional learning is gaining momentum in revolutionizing healthcare education. During the academic year 2015/16, seven undergraduate-entry health and social care programs from two universities in Hong Kong took part in an interprofessional education program. Based on considerations such as the large number of students involved and the need to incorporate adult learning principles, team-based learning was adopted as the pedagogy for the program, which was therefore called the interprofessional team-based learning program (IPTBL). The authors describe the development and implementation of the IPTBL program and evaluate the effectiveness of the program implementation. METHODS: Eight hundred and one students, who are predominantly Chinese, participated in the IPTBL. The quantitative design (a pretest-posttest experimental design) was utilized to examine the students' gains on their readiness to engage in interprofessional education (IPE). RESULTS: Three instructional units (IUs) were implemented, each around a clinical area which could engage students from complementary health and social care disciplines. Each IU followed a team-based learning (TBL) process: pre-class study, individual readiness assurance test, team readiness assurance test, appeal, feedback, and application exercise. An electronic platform was developed and was progressively introduced in the three IUs. The students' self-perceived attainment of the IPE learning outcomes was high. Across all four subscales of RIPLS, there was significant improvement in student's readiness to engage in interprofessional learning after the IPTBL. A number of challenges were identified: significant time involvement of the teachers, difficulty in matching students from different programs, difficulty in making IPTBL count towards a summative assessment score, difficulty in developing the LAMS platform, logistics difficulty in managing paper TBL, and inappropriateness of the venue. CONCLUSIONS: Despite some challenges in developing and implementing the IPTBL program, our experience showed that TBL is a viable pedagogy to be used in interprofessional education involving hundreds of students. The significant improvement in all four subscales of RIPLS showed the effects of the IPTBL program in preparing students for collaborative practice. Factors that contributed to the success of the use of TBL for IPE are discussed.

Effect of plasmapheresis on serum levels of clobazam, levetiracetam and topiramate.

A 27-year-old man with a diagnosis of new onset refractory status epilepticus (NORSE) was treated with five anti-seizure drugs (ASDs) including clobazam, levetiracetam and topiramate. He received plasma exchange (PE) for presumed autoimmune etiology. Serum ASD levels were serially monitored in two sessions. Levels of clobazam, levetiracetam and topiramate were significant reduced by PE. Serum clobazam level dropped down to at least 85% and 75% of the baseline during and after the procedure respectively; levetiracetam dropped down to 83% and 83%; and topiramate dropped to 86% and 79%. The results may imply a theoretical risk of breakthrough seizure during PE due to low ASD levels.

Automatic measurement of pennation angle and fascicle length of gastrocnemius muscles using real-time ultrasound imaging.

Muscle imaging is a promising field of research to understand the biological and bioelectrical characteristics of muscles through the observation of muscle architectural change. Sonomyography (SMG) is a technique which can quantify the real-time architectural change of muscles under different contractions and motions with ultrasound imaging. The pennation angle and fascicle length are two crucial SMG parameters to understand the contraction mechanics at muscle level, but they have to be manually detected on ultrasound images frame by frame. In this study, we proposed an automatic method to quantitatively identify pennation angle and fascicle length of gastrocnemius (GM) muscle based on multi-resolution analysis and line feature extraction, which could overcome the limitations of tedious and time-consuming manual measurement. The method started with convolving Gabor wavelet specially designed for enhancing the line-like structure detection in GM ultrasound image. The resulting image was then used to detect the fascicles and aponeuroses for calculating the pennation angle and fascicle length with the consideration of their distribution in ultrasound image. The performance of this method was tested on computer simulated images and experimental images in vivo obtained from normal subjects. Tests on synthetic images showed that the method could identify the fascicle orientation with an average error less than 0.1°. The result of in vivo experiment showed a good agreement between the results obtained by the automatic and the manual measurements (r=0.94±0.03; p<0.001, and r=0.95±0.02, p<0.001). Furthermore, a significant correlation between the ankle angle and pennation angle (r=0.89±0.05; p<0.001) and fascicle length (r=-0.90±0.04; p<0.001) was found for the ankle plantar flexion. This study demonstrated that the proposed method was able to automatically measure the pennation angle and fascicle length of GM ultrasound images, which made it feasible to investigate muscle-level mechanics more comprehensively in vivo.

Development of a chitosan-based nanoparticle formulation for delivery of a hydrophilic hexapeptide, dalargin.

Nanoparticle based delivery systems can offer opportunities for targeting, controlled release, and enhanced stability of their drug, protein, or gene therapy payload. This study investigated the use of chitosan in combination with the ionic additives sulfobutyl-ether-7-beta-cyclodextrin (SB-CD) or SB-CD/dextran sulfate (SB-CD/DS) mixture in comparison with chitosan: DS in the formulation of nanoparticles incorporating the hexapeptide dalargin. The physical characteristics (particle size, zeta potential), entrapment and loading efficiency, and release of dalargin were quantified. It was demonstrated that anionic cyclodextrin, SB-CD, can be used in complex coacervation with chitosan, with and without the presence of DS, to form nanoparticles. The presence of SB-CD or DS in the nanoparticle formulation and the weight ratio of chitosan to anionic additive(s) influenced the physical properties of the nanoparticles and their ability to carry dalargin. In addition, the particle size of nanoparticles was also affected by the molecular weight of chitosan and DS. The use of either DS or SB-CD/DS mixture produced chitosan nanoparticles with small particle size, high dalargin entrapment efficiency, enhanced peptide stability, and sustained release characteristics.

Construction of Multi-dimensional Arterial Health Status Map based on Molecular and Clinical Measurements, Fuzzy System and Data Cubes.

Atherosclerosis results from inflammatory processes involving biomarkers, such as lipid profile, haemoglobin A1C, oxidative stress, coronary artery calcium score and flow-mediated endothelial response through nitric oxide. This paper proposes a health status coefficient, which comprehends molecular and clinical measurements concerning atherosclerosis to provide a measure of arterial health. An arterial health status map is produced to map the multi-dimensional measurements to the health status coefficient. The mapping is modeled by a fuzzy system embedded with the health domain expert knowledge. The measurements obtained from the pilot study are used to tune the fuzzy system. The inferred arterial health coefficients are stored into the data cubes of a multi-dimensional database. Due to this adaptability and transparency of fuzzy system, the health status map can be easily updated when the refinement of fuzzy rule base is needed or new measurements are obtained.

Reliability and validity of the Test of Visual-Perceptual Skills (Non-Motor)--Revised for Chinese preschoolers.

OBJECTIVE: The reliability and validity of the Test of Visual-Perceptual Skills (Non-Motor)-Revised (TVPS-R) were examined for its usefulness on Hong Kong Chinese preschoolers. METHOD: Content validity was evaluated by six experts. Test-retest reliability, construct validity, and criterion validity were examined on 66 typically developing preschoolers while concurrent validity was examined on these preschoolers plus 52 preschoolers with visual-perception difficulties. RESULTS: Test-retest reliability was high for the total score (intraclass correlation coefficient [ICC] =.88), but not for all subtests (ICC ranged .38 to .77) or for individual items (mean kappa = 0.32). The standard error of measurement (SEM; 1.53) and internal consistency (Cronbach's alpha = .90) were satisfactory. Evidence supporting the test's validity included a significant developmental trend (F = 4.99, p < .001), a lack of gender bias (F = .04, p = .84), and positive known-group differentiation (Wilks's lambda = 52.42, p < .001). The correlation between the Motor-Free Visual-Perceptual Test-Revised composite score and the TVPS-R composite was moderate at r = .60. CONCLUSIONS: When based on the total scores, the TVPS-R was reliable and valid. The use of subtest scores and item scores for decision making or treatment planning is not recommended.