Transthyretin mutagenesis: impact on amyloidogenesis and disease.

Transthyretin (TTR), a homotetrameric protein found in plasma, cerebrospinal fluid, and the eye, plays a pivotal role in the onset of several amyloid diseases with high morbidity and mortality. Protein aggregation and fibril formation by wild-type TTR and its natural more amyloidogenic variants are hallmarks of ATTRwt and ATTRv amyloidosis, respectively. The formation of soluble amyloid aggregates and the accumulation of insoluble amyloid fibrils and deposits in multiple tissues can lead to organ dysfunction and cell death. The most frequent manifestations of ATTR are polyneuropathies and cardiomyopathies. However, clinical manifestations such as carpal tunnel syndrome, leptomeningeal, and ocular amyloidosis, among several others may also occur. This review provides an up-to-date listing of all single amino-acid mutations in TTR known to date. Of approximately 220 single-point mutations, 93% are considered pathogenic. Aspartic acid is the residue mutated with the highest frequency, whereas tryptophan is highly conserved. "Hot spot" mutation regions are mainly assigned to ß-strands B, C, and D. This manuscript also reviews the protein aggregation models that have been proposed for TTR amyloid fibril formation and the transient conformational states that convert native TTR into aggregation-prone molecular species. Finally, it compiles the various in vitro TTR aggregation protocols currently in use for research and drug development purposes. In short, this article reviews and discusses TTR mutagenesis and amyloidogenesis, and their implications in disease onset.

The Midfoot Joint Complex (Foot Arch) Contributes to the Upper Body Position in Bipedal Walking and Coordinates With the Lower Limb Joints.

This study estimated the contribution of the midfoot joint complex (MJC) kinematics to the pelvis anterior-posterior positions during the stance phase of walking and investigated whether the MJC is functionally coordinated with the lower limb joints to maintain similar pelvic positions across steps. Hip, knee, ankle, and MJC sagittal angles were measured in 11 nondisabled participants during walking. The joints' contributions to pelvic positions were computed through equations derived from a link-segment model. Functional coordination across steps was identified when the MJC contribution to pelvic position varied and the summed contributions of other joints varied in the opposite direction (strong negative covariations [r ≤ -.7] in stance phase instants). We observed that the MJC plantarflexion (arch raising) during the midstance and late stance leads the pelvis backward, avoiding excessive forward displacement. The MJC was the second joint that contributed most to the pelvis positions (around 18% of all joints' contributions), after the ankle joint. The MJC and ankle were the joints that were most frequently coordinated with the other joints (≅70% of the stance phase duration). The findings suggest that the MJC is part of the kinematic chain that determines pelvis positions during walking and is functionally coordinated with the lower limb joints.

Nutrient-efficient catfish-based aquaponics for producing lamb's lettuce at two light intensities.

BACKGROUND: Aquaponic systems are sustainable processes of managing water and nutrients for food production. An innovate nutrient-efficient catfish-based (Clarias gariepinus) aquaponics system was implemented for producing two cultivars of two leafy vegetables largely consumed worldwide: lamb's lettuce (Valerianella locusta var. Favor and Valerianella locusta var. de Hollande) and arugula (Eruca vesicaria var. sativa and Eruca sativa). Different growing treatments (4 × 2 factorial design) were applied to plants of each cultivar, grown at two light intensities (120 and 400 µmol m-2 s-1). During growth, several morphological characteristics (root length, plant height, leaf number, foliage diameter and biggest leaf length) were measured. At harvest, plants were weighed and examined qualitatively in terms of greenness and health status. Additionally, leaf extracts were obtained and used to determine total phenolic contents, antioxidant capacities, and levels of cytotoxicity to Caco-2 intestinal model cells. RESULTS: After a 5-week growth period, both lamb's lettuce cultivars presented high levels of greenness and health status, at both light intensities, particularly the var. de Hollande that also showed higher average performance in terms of plant morphology. In turn, arugula cultivars showed lower levels of greenness and health status, especially the cultivar E. vesicaria var. sativa submitted to direct sunlight during growth. In addition, plant specimens submitted to higher levels of light intensity showed higher contents in antioxidants/polyphenols. Cultivars with a higher content in antioxidants/polyphenols led to higher Caco-2 cell viability. CONCLUSION: For successful industrial implementation of the aquaponics technology, different and optimized acclimatizing conditions must be applied to different plant species and cultivars. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Nutritive Value and Bioactivities of a Halophyte Edible Plant: Crithmum maritimum L. (Sea Fennel).

Crithmum maritimum L. (sea fennel), an edible xerophyte of coastal habitats, is considered an emerging cash crop for biosaline agriculture due to its salt-tolerance ability and potential applications in the agri-food sector. Here, the nutritional value and bioactive properties of sea fennel are described. Sea fennel leaves, flowers, and schizocarps are composed of carbohydrates (>65%) followed by ash, proteins, and lipids. Sea fennel's salty, succulent leaves are a source of omega-6 and omega-3 polyunsaturated fatty acids, especially linoleic acid. Extracts obtained from flowers and fruits/schizocarps are rich in antioxidants and polyphenols and show antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermis, Candida albicans, and Candida parapsilosis. Plant material is particularly rich in sodium (Na) but also in other nutritionally relevant minerals, such as calcium (Ca), chlorine (Cl), potassium (K), phosphorus (P), and sulfur (S), beyond presenting a potential prebiotic effect on Lactobacillus bulgaricus and being nontoxic to human intestinal epithelial Caco-2 model cells, up to 1.0% (w/v). Hence, the rational use of sea fennel can bring nutrients, aroma, and flavor to culinary dishes while balancing microbiomes and contributing to expanding the shelf life of food products.

Lessons on protein structure from interleukin-4: All disulfides are not created equal.

Interleukin-4 (IL-4) is a hematopoietic cytokine composed by a four-helix bundle stabilized by an antiparallel beta-sheet and three disulfide bonds: Cys3-Cys127, Cys24-Cys65, and Cys46-Cys99. IL-4 is involved in several immune responses associated to infection, allergy, autoimmunity, and cancer. Besides its physiological relevance, IL-4 is often used as a "model" for protein design and engineering. Hence, to understand the role of each disulfide in the structure and dynamics of IL-4, we carried out several spectroscopic analyses (circular dichroism [CD], fluorescence, nuclear magnetic resonance [NMR]), and molecular dynamics (MD) simulations on wild-type IL-4 and four IL-4 disulfide mutants. All disulfide mutants showed loss of structure, altered interhelical angles, and looser core packings, showing that all disulfides are relevant for maintaining the overall fold and stability of the four-helix bundle motif, even at very low pH. In the absence of the disulfide connecting both protein termini Cys3-Cys127, C3T-IL4 showed a less packed protein core, loss of secondary structure (~9%) and fast motions on the sub-nanosecond time scale (lower S2 order parameters and larger τc correlation time), especially at the two protein termini, loops, beginning of helix A and end of helix D. In the absence of Cys24-Cys65, C24T-IL4 presented shorter alpha-helices (14% loss in helical content), altered interhelical angles, less propensity to form the small anti-parallel beta-sheet and increased dynamics. Simultaneously deprived of two disulfides (Cys3-Cys127 and Cys24-Cys65), IL-4 formed a partially folded "molten globule" with high 8-anilino-1-naphtalenesulphonic acid-binding affinity and considerable loss of secondary structure (~50%decrease), as shown by the far UV-CD, NMR, and MD data.

Affordance-based practice: An ecological-enactive approach to chronic musculoskeletal pain management.

BACKGROUND: The biomedical understanding of chronic musculoskeletal pain endorses a linear relationship between noxious stimuli and pain, and is often dualist or reductionist. Although the biopsychosocial approach is an important advancement, it has a limited theoretical foundation. As such, it tends to be misinterpreted in manners that lead to artificial boundaries between the biological, psychological, and social, with fragmented and polarized clinical applications. OBJECTIVE: We present an ecological-enactive approach to complement the biopsychosocial model. In this approach, the disabling aspect of chronic pain is characterized as an embodied, embedded, and enactive process of experiencing a closed-off field of affordances (i.e., shutting down of action possibilities). Pain is considered as a multi-dimensional, multicausal, and dynamic process, not locatable in any of the biopsychosocial component domains. Based on a person-centered reasoning approach and a dispositional view of causation, we present tools to reason about complex clinical problems in face of uncertainty and the absence of 'root causes' for pain. Interventions to open up the field of affordances include building ability and confidence, encouraging movement variability, carefully controlling contextual factors, and changing perceptions through action according to each patient's self-identified goals. A clinical case illustrates how reasoning based on an ecological-enactive approach leads to an expanded, multi-pronged, affordance-based intervention. CONCLUSIONS: The ecological-enactive perspective can provide an overarching conceptual and practical framework for clinical practice, guiding and constraining clinicians to choose, combine, and integrate tools that are consistent with each other and with a true biopsychosocial approach.

Breast Cancer Brain Metastases: Implementation and Characterization of a Mouse Model Relying on Malignant Cells Inoculation in the Carotid Artery.

Breast cancer (BC) brain metastases (BCBM) is a severe condition frequently occurring in the triple-negative subtype. The study of BCBM pathogenesis and treatment has been hampered by the difficulty in establishing a reliable animal model that faithfully recapitulates the preferential formation of brain metastases. The injection of BC cells in the carotid artery of mice has been proposed but the procedure is challenging, with the metastatic pattern being scarcely characterized. In this work, we thoroughly describe an improved procedure, highlighting the tricks and challenges of the process, and providing a characterization of the brain and peripheral metastatic pattern at the cellular and molecular level. Triple-negative BC (4T1) cells were inoculated in the common carotid artery of BALB/c mice. Brains and peripheral organs were harvested at 7-14 days for the histological characterization of the metastases' pattern and the immunofluorescence analysis of specific markers. With our surgical procedure, both mouse death and procedure-associated weight loss were negligible. Brain metastases mostly occurred in the hippocampus, while sparse peripheral lesions were only detected in the lungs. Brain-colonizing BC cells presented proliferative (Ki-67) and epithelial (pan-cytokeratin and tomato lectin) features, which account for metastases' establishment. The presented surgical approach constitutes an important and reliable tool for BCBM studies.

Conceptions of disability among physiotherapists: an exploratory qualitative study.

INTRODUCTION: Physiotherapists' (PTs) assumptions about disability, for the most part unrecognized and unquestioned, may or may not be aligned with the vision of the International Classification of Functioning, Disability, and Health (ICF). They can influence a wide range of PT practices and impact the lives of patients. OBJECTIVE: To investigate whether PTs at different stages of their training rely on medical, social, or biopsychosocial conceptions of disability in line with the International Classification of Functioning, Disability and Health (ICF). METHODS: A qualitative study with three focus groups: 1) PT students at the beginning; and 2) at the end of their training; and 3) PTs active in several different clinical fields. Content analysis was used identify definitions, causes, judgments, and solutions to disability. RESULTS: Some clinicians and senior students expressed views of functioning and disability as interactive, situational, continuous, and ubiquitous features of the human condition. However, in all groups there was a strong predominance of medical definitions and causal attributions for disability, some fitting the tripartite linear causal logic from impairment to subnormal performance to social disadvantage. Most of moral judgments were negative and associated disability with a 'diminished state,' personal loss, and suffering. Surprisingly, most solutions to disability-related problems were of a social or interactionist character, including vigilance against ableism. CONCLUSIONS: Results revealed paradoxical conceptions and point to challenges of ensuring a deeper understanding of non-medical framings, to avoid an uncritical adoption of the ICF that may neutralize its potential to challenge culturally entrenched medical conceptions of disability.

Narrowing the physiotherapy knowledge-practice gap: faculty training beyond the health sciences.

Physiotherapists seek to improve client movement and promote function within an individual's unique environmental and social realities. Despite this intention, there is a well-noted knowledge-practice gap, that is, therapists generally lack sufficient foundational preparation to effectively navigate societal challenges impacting contemporary healthcare. As one step toward addressing the issue, we propose an educational solution targeting current and future physiotherapy faculty, whose responsibilities for entry-level course development and curriculum design substantially impact student readiness for clinical practice. We propose that physiotherapy faculty trained via postprofessional education in a non-biomedical field (e.g. psychology, education, and philosophy) will be uniquely prepared to provide students with tools for dealing with complex social issues facing their clients; critical analysis skills; statistical and technological training; and a deeper theoretical and philosophical understanding of practice. Taken together, such interdisciplinary tools could help address the knowledge-practice gap for physiotherapists and promote the ongoing evolution of the profession in concert with contemporary healthcare. Physiotherapists who pursue interdisciplinary studies may more deeply understand the challenges faced by clinicians and may be well-positioned to leverage knowledge and methods in another scientific discipline to expand and transform the scope of solutions to these challenges.

Measuring subjective aspects of participation in adults with disabilities: A systematic review of the coverage, content validity and internal structure of standardised instruments.

OBJECTIVE: To systematically review evidence on the coverage, content validity and internal structure of self-report measures capturing subjective aspects of participation for adults with disabilities. DATA SOURCES: EMBASE, MEDLINE and reference lists were searched until July 10th, 2022 for articles on measurement properties of instruments measuring participation as defined in the International Classification of Functioning, Disability and Health, from a subjective perspective. METHOD: Each instrument was assessed for its coverage of subjective aspects of participation. The Consensus-based Standards for the Selection of Health Measurement Instruments were used to assess the quality of each study. Content validity and internal structure (structural validity, internal consistency and cross-cultural validity) were rated against published standards and qualified by the adapted Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Thirty-eight studies regarding 10 instruments were analysed. Most instruments mix activity and participation items. Only the Measure of Experiential Aspects of Participation (with high-quality evidence of sufficient structural validity and generally sufficient internal consistency), the Participation Enfranchisement and the Community Integration Measure showed adequate coverage. For all instruments, evidence of content validity is of low- to very low quality. There is high-quality evidence that the Participation Scale is not unidimensional. CONCLUSION: In general, the coverage and the evidence for content validity and internal structure of measures capturing experiential aspects of participation are limited. The Measure of Experiential Aspects of Participation has the best level of evidence in support of its use. The score of the Participation Scale cannot be considered an adequate reflection of participation.

Effects of Age and Attentional Focus on the Performance and Coordination of the Sit-to-Stand Task.

This study investigated whether age and attentional focus affect synergy organization of sit-to-stand (STS). Young and older adults performed STS while holding a cup under internal (IF) and external focus (EF) instructions. Uncontrolled manifold analysis was used to decompose trial-to-trial variability in joint kinematics into variability that preserves (VUCM) and interferes (VORT) with the horizontal and vertical positions of the center of mass (CoM) and cup. VUCM was significantly higher than VORT for all variables in both age groups and focus conditions. Older adults demonstrated higher VUCM for all variables and higher VORT for all variables except the vertical position of the cup. IF instructions benefited older adults, leading to decreased VORT of the vertical position of CoM and horizontal and vertical positions of the cup.

Edible flowers of Helichrysum italicum: Composition, nutritive value, and bioactivities.

Helichrysum italicum (H. italicum) is a halophyte shrub with bright yellow flowers with a strong curry-like aroma. The essential oils of H. italicum have been used in the production of cosmetics and pharmaceuticals, due to their antiallergic and anti-inflammatory properties. In the agri-food sector, H. italicum flowers can be used for seasoning and flavoring food, and as natural food preservatives. Here, we report on the composition, bioactive compounds, and nutritive value of H. italicum flowers. Flowers were mainly composed of carbohydrates (>80 % dry weight), followed by minerals (6.31 ± 0.95 % dw), protein (5.44 ± 0.35 % dw), and lipids (3.59 % ± 0.53 % dw). High percentages of Fe, Zn, Ca, and K were found in the flower material, along with a high content in antioxidants, polyphenols, and carotenoids, as corroborated by the nuclear magnetic resonance (NMR) data. Flowers were mainly composed of saturated fatty acids (SFAs) (54.50 ± 0.95 % of total FA), followed by polyunsaturated fatty acids (PUFAs) (37.73 ± 1.25 % of total FA) and monounsaturated fatty acids (MUFAs) (7.77 ± 0.34 %), as detected by gas chromatography mass spectrometry (GC-MS). The omega-6 PUFA linoleic acid (22.55 ± 0.76 % of total FA) was the most abundant fatty acid found. Flower extracts showed antimicrobial activity against Saccharomyces cerevisiae and Komagataella phaffii, as well as against Gram-negative (Klebsiella pneumoniae) and Gram-positive (Staphylococcus aureus) bacteria. H. italicum flower material was nontoxic to human intestinal Caco-2 model cells at concentrations up to 1.0 % w/v.

Por que as ocupações "femininas pagam menos? Um estudo longitudinal / Why do "female" occupations pay less? A longitudinal study / ¿Por qué las ocupaciones «femeninas¼ tienen salarios más bajos? Un estudio longitudinal

Resumo Nas últimas décadas, a taxa de participação feminina na força de trabalho cresceu de maneira expressiva no Brasil, passando de 18,5% em 1970 para 48,9% em 2010. Apesar disso, a segregação ocupacional por sexo persiste e pode ser um fator determinante para explicar a diferença salarial em desfavor das mulheres no país. Nesse sentido, o objetivo do presente trabalho é compreender porque as ocupações femininas pagam menos. A fim de testar a teoria sociológica da desvalorização do trabalho feminino, avalia-se o impacto da transição entre ocupações distintas quanto à composição por sexo no rendimento dos trabalhadores. Para isso, são utilizados os microdados longitudinais de divulgação trimestral das edições de 2012 a 2019 da PNAD Contínua (IBGE) em um modelo de painel de efeitos fixos. A tipologia de integração ocupacional proposta por Oliveira (2001) é adotada para classificar as ocupações em predominantemente femininas, predominantemente masculinas ou integradas. Os resultados mostram que o trabalhador experimenta queda no rendimento quando transita para uma ocupação feminina, de modo que a hipótese da desvalorização é suportada. Observa-se, ainda, que os maiores rendimentos são recebidos nas ocupações integradas, indicando que a relação entre a composição ocupacional por sexo e os rendimentos é não linear.

Abstract During the last decades, female participation in the labor force has increased significantly in Brazil, going from 18.5% in 1970 to 48.9% in 2010. Despite this, occupational gender segregation persists and may be determinant to explain the gender pay gap. This study aims to understand why female occupations have lower pay. In order to test the sociological theory of female work devaluation we evaluate the impact of the transition between different occupations regarding the sex composition on the salary of workers in the Brazilian labor market. To that end, we use a model with fixed effects with microdata from the 2012-2019 editions of the PNAD Contínua (IBGE). The typology of occupational integration proposed by Oliveira (2001) is adopted to classify occupations as predominantly female, predominantly male, or integrated. Results show that workers experience a decrease in wages when moving to a female occupation, hence supporting the devaluation theory. Also, the highest salaries are observed in integrated occupations, indicating that the relationship between occupational sex composition and pay is a non-linear one.

Resumen En las últimas décadas, la tasa de participación femenina en la fuerza de trabajo creció significativamente en Brasil, del 18,5 % en 1970 al 48,9 % en 2010. A pesar de esto, la segregación ocupacional por sexo persiste y puede ser un factor determinante para explicar la brecha salarial que desfavorece a las mujeres en el país. En este sentido, el objetivo de este trabajo es comprender por qué las ocupaciones femeninas tienen salarios más bajos. Con el fin de probar la teoría sociológica de la desvalorización del trabajo femenino, se evalúa el impacto de la transición entre distintas ocupaciones en cuanto a la composición por sexo sobre los salarios de los trabajadores. Para eso, se utilizan microdatos longitudinales de divulgación trimestral de las ediciones entre 2012 y 2019 de la PNAD continua (IBGE) en un modelo de panel de efectos fijos. Se adopta la tipología de integración ocupacional propuesta por Oliveira (2001) para clasificar las ocupaciones en predominantemente femeninas, predominantemente masculinas o integradas. Los resultados muestran que el trabajador sufre la caída de su salario cuando pasa a una ocupación femenina, lo que sustenta la hipótesis de la devaluación. También se observa que los salarios más altos se reciben en ocupaciones integradas, lo que indica que la relación entre la composición ocupacional por sexo y los salarios no es lineal.

Family-Centered practice in a Brazilian rehabilitation network service.

BACKGROUND: Family-centered practice (FCP) is widely accepted as a best practice in pediatric rehabilitation. However, its implementation in Brazil is incipient, and systematic documentation of the extent to which it has been achieved is not available. OBJECTIVES: To determine parents' and service providers' perceptions of family-centeredness and specific areas in need of improvement in four rehabilitation hospitals. METHODS: A total of 107 caregivers and 89 service providers responded to the Measure of Processes of Care-20 (MPOC-20) and the Measure of Processes of Care for Service providers (MPOC-SP), respectively. The MPOC questionnaires evaluate FCP from the point of view of parents and rehabilitation professionals. Domain scores within each questionnaire were compared with Kruskal-Wallis and Mann-Whitney tests. MPOC items with low scores (from 1-4 out of 7 by 33% or more of respondents) were considered to indicate weaknesses in service delivery. RESULTS: Median MPOC-20 scores varied from 5.2 (4.7, 5.8) (Providing General Information) to 7.0 (6.0, 7.0) (Enabling and Partnership). The Providing General Information scores were significantly lower than those of other domains (p <  0.003). The MPOC-SP scores varied from 4.8 (4.0, 5.8) (Providing General Information) to 6.1 (5.8, 6.6) (Treating People Respectfully). Scores for Treating People Respectfully were significantly higher (p <  0.0001) and Providing General Information scores significantly lower (p <  0.0001) than those of the other domains. Most items with high percentages of low scores were from the domain Providing General Information. CONCLUSION: Except for Providing General Information, the results indicated that services implement FCP "to a fairly great extent," comparing favorably to international data. Provision of information can be improved.

Testing a new active learning approach to advance motor learning knowledge and self-efficacy in physical therapy undergraduate education.

BACKGROUND: Motor learning (ML) science is foundational for physical therapy. However, multiple sources of evidence have indicated a science-practice gap. Clinicians report low self-efficacy with ML concepts and indicate that the lack of access to systematic training is a barrier for practical implementation. The general goal of this preliminary study was to describe the effects of a new educational intervention on physical therapy student's ML self-efficacy and knowledge. METHODS: Self-efficacy was assessed with the Physical Therapists' Perceptions of Motor Learning questionnaire. Data was acquired from third-semester students before their participation in the ML educational intervention. Reference self-efficacy data was also acquired from physical therapy professionals and first and last-semester students. The educational intervention for third-semester students was designed around an established framework to apply ML principles to rehabilitation. A direct experience, the "Learning by Doing" approach, in which students had to choose a motor skill to acquire over 10 weeks, provided the opportunity to apply ML theory to practice in a personally meaningful way. After the intervention self-efficacy was re-tested. ML knowledge was tested with an objective final exam. Content analysis of coursework material was used to determine how students comprehended ML theory and related it to their practical experience. The Kruskal-Wallis and Mann-Whitney U tests were used to compare self-efficacy scores between the four groups. Changes in self-efficacy after the educational intervention were analyzed with the Wilcoxon test. Spearman rank correlation analysis was used to test the association between self-efficacy and final exam grades. RESULTS: By the end of the intervention, students' self-efficacy had significantly increased (p < 0.03), was higher than that of senior students (p < 0.00) and experienced professionals (p < 0.00) and correlated with performance on an objective knowledge test (p < 0.03). Content analysis revealed that students learned to apply the elements of ML-based interventions present in the scientific literature to a real-life, structured ML program tailored to personal objectives. CONCLUSIONS: Positive improvements were observed after the intervention. These results need confirmation with a controlled study. Because self-efficacy mediates the clinical application of knowledge and skills, systematic, active training in ML may help reduce the science-practice gap.

Corema album spp: Edible wild crowberries with a high content in minerals and organic acids.

Edible wild plants are part of the ethnobotanical and gastronomic heritage of different geographical areas. Corema album (L.) D. Don is an endemic species of the dune systems of the Atlantic coast of the Iberian Peninsula. The aerial parts of Corema album are a source of nutrients and antioxidants. The Corema album white berry (Portuguese crowberry) is rich in calcium, iron, and zinc. The plant also shows high phenolic content and antioxidant capacity associated with the leaves, fruit, and flowers. The presence of organic acids, namely phenolic acids, such as hydroxycinnamic acids, and long chain polyunsaturated fatty acids (PUFAs) omega-3 and omega-6 has also been confirmed. Toxicity studies evaluated by cell viability tests with human intestinal epithelium model cells (Caco-2) have shown that, at low concentrations, plant extracts may present beneficial effects.

Attention Focus Does Not Influence Performance of Sit-to-Stand in Young and Older Adults.

An external focus of attention can improve performance, but there is little research on effects for the elderly in every day, well-learned mobility tasks. 57 older and 59 young adults performed the sit-to-stand and stand-to-sit while holding a cup, at three difficulty levels (cup empty or full, at normal or fast speed). Half were instructed to focus internally (on their movements) and half externally (on the cup). The effects of focus, age, and difficulty level were tested for movement time, mean inclination of the cup, inclination variability, and smoothness with 2 × 2 × 3 ANOVAs. Significant effects of difficulty were consistent across variables (p < 0.05). An effect of focus was present only for the inclination variability of the stand-to-sit (p < 0.03), favoring an internal focus (less variability). The age × focus interaction was significant for mean cup inclination, but post hoc tests failed to reveal any significant differences. The results of this study, together with the literature, suggest that an external focus may not benefit the performance of young or older adults in general mobility activities of daily living. The prevalent assumption that an external focus is always beneficial for performance needs further empirical testing.

Oligomerization Profile of Human Transthyretin Variants with Distinct Amyloidogenicity.

One of the molecular hallmarks of amyloidoses is ordered protein aggregation involving the initial formation of soluble protein oligomers that eventually grow into insoluble fibrils. The identification and characterization of molecular species critical for amyloid fibril formation and disease development have been the focus of intense analysis in the literature. Here, using photo-induced cross-linking of unmodified proteins (PICUP), we studied the early stages of oligomerization of human transthyretin (TTR), a plasma protein involved in amyloid diseases (ATTR amyloidosis) with multiple clinical manifestations. Upon comparison, the oligomerization processes of wild-type TTR (TTRwt) and several TTR variants (TTRV30M, TTRL55P, and TTRT119M) clearly show distinct oligomerization kinetics for the amyloidogenic variants but a similar oligomerization mechanism. The oligomerization kinetics of the TTR amyloidogenic variants under analysis showed a good correlation with their amyloidogenic potential, with the most amyloidogenic variants aggregating faster (TTRL55P > TTRV30M > TTRwt). Moreover, the early stage oligomerization mechanism for these variants involves stepwise addition of monomeric units to the growing oligomer. A completely different behavior was observed for the nonamyloidogenic TTRT119M variant, which does not form oligomers in the same acidic conditions and even for longer incubation times. Thorough characterization of the initial steps of TTR oligomerization is critical for better understanding the origin of ATTR cytotoxicity and developing novel therapeutic strategies for the treatment of ATTR amyloidosis.

Stress, anxiety, self-efficacy, and the meanings that physical therapy students attribute to their experience with an objective structured clinical examination.

BACKGROUND: Excessive stress and anxiety can impair learning. The objective structured clinical examination (OSCE) is a valuable tool to assess and promote the acquisition of clinical skills. However, significant OSCE-related stress and anxiety are frequently reported. The aim of this study was to investigate the relationships between physiological stress, self-reported levels of anxiety due to an OSCE, self-efficacy, and the meanings that physical therapy students attribute to their experience with the exam. DESIGN: Concurrent mixed methods study. METHODS: A total of 32 students took part in this study. All were enrolled in the third semester of a 10-semester Physical Therapy Bachelor Program. Salivary cortisol levels, self-reported anxiety (State-Trait Anxiety Inventory, STAI) were measured before the OSCE. Exam scores and self-efficacy ratings were also recorded. Correlations between variables were tested with the Pearson correlation, with ɑ at 0.05. Semi-structured interviews were used to explore the personal perspectives of students. Thematic analysis was used to investigate emergent themes. RESULTS: Trait anxiety scores were significantly higher than normative values (p < 0.001). A high proportion of students showed high (STAI> 49) state anxiety (37.5%) and trait anxiety (65.6%). Salivary cortisol was not associated anxiety (p > 0.05). Neither stress nor anxiety correlated with OSCE scores. A moderate and significant direct correlation was found for self-efficacy scores and OSCE scores (r = 0.475, p = 0.007). Students reported that confidence had a calming effect and led to better self-perceived performance. They also reported that the OSCE can provide meaningful learning experiences despite being stressful. CONCLUSIONS: A high proportion of our students reported a stable/lingering negative affect. However, neither stress nor anxiety related to OSCE scores. Students' confidence in their capabilities was correlated with their performance. Their subjective reports suggest that self-confidence may have protected them from the negative effects of stress and anxiety on academic performance.