Implementing Standard Diagnosis and Treatment for Locally Advanced Breast Cancer Through Global Research in Latin America: Results From a Multicountry Pragmatic Trial.

PURPOSE: Breast cancer mortality rates in Latin America (LA) are higher than those in the United States, possibly because of advanced disease presentation, health care disparities, or unfavorable molecular subtypes. The Latin American Cancer Research Network was established to address these challenges and to promote collaborative clinical research. The Molecular Profiling of Breast Cancer Study (MPBCS) aimed to evaluate the clinical characteristics and treatment outcomes of LA participants with locally advanced breast cancer (LABC). PATIENTS AND METHODS: The MPBCS enrolled 1,449 participants from Argentina, Brazil, Chile, Mexico, and Uruguay. Through harmonized procedures and quality assurance measures, this study evaluated clinicopathologic characteristics, neoadjuvant chemotherapy response, and survival outcomes according to residual cancer burden (RCB) and the type of surgery. RESULTS: Overall, 711 and 480 participants in the primary surgery and neoadjuvant arms, respectively, completed the 5-year follow-up period. Overall survival was independently associated with RCB (worse survival for RCBIII-adjusted hazard ratio, 8.19, P < .001, and RCBII [adjusted hazard ratio, 3.69, P < .008] compared with RCB0 [pathologic complete response or pCR]) and type of surgery (worse survival in mastectomy than in breast-conserving surgery [BCS], adjusted hazard ratio, 2.97, P = .001). The hormone receptor-negative-human epidermal growth factor receptor 2-positive group had the highest proportion of pCR (48.9%). The analysis of the ASCO Quality Oncology Practice Initiative breast module revealed high compliance with pathologic standards but lower adherence to treatment administration standards. Notably, compliance with trastuzumab administration varied widely among countries (33.3%-88.7%). CONCLUSION: In LABC, we demonstrated the survival benefit of BCS and the prognostic effect of the response to available neoadjuvant treatments despite an important variability in access to key treatments. The MPBCS represents a significant step forward in understanding the real-world implementation of oncologic procedures in LA.

Cochlear dysfunction as an early biomarker of cognitive decline in normal hearing and mild hearing loss.

INTRODUCTION: Age-related hearing loss is an important risk factor for cognitive decline. However, audiogram thresholds are not good estimators of dementia risk in subjects with normal hearing or mild hearing loss. Here we propose to use distortion product otoacoustic emissions (DPOAEs) as an objective and sensitive tool to estimate the risk of cognitive decline in older adults with normal hearing or mild hearing loss. METHODS: We assessed neuropsychological, brain magnetic resonance imaging, and auditory analyses on 94 subjects > 64 years of age. RESULTS: We found that cochlear dysfunction, measured by DPOAEs-and not by conventional audiometry-was associated with Clinical Dementia Rating Sum of Boxes (CDR-SoB) classification and brain atrophy in the group with mild hearing loss (25 to 40 dB) and normal hearing (<25 dB). DISCUSSION: Our findings suggest that DPOAEs may be a non-invasive tool for detecting neurodegeneration and cognitive decline in the older adults, potentially allowing for early intervention.

Psychological factors are associated with pain extent in patients with carpal tunnel syndrome.

INTRODUCTION: Widespread pain may be related to psychosocial aspects in several musculoskeletal conditions, but the literature on carpal tunnel syndrome (CTS) is scarce. OBJECTIVE: To determine the relationship between pain extent and psychological factors (catastrophizing, kinesiophobia, anxiety symptoms, and depression) in people with CTS. METHODS: A cross-sectional study was conducted. The independent variables were: pain intensity, disability (QuickDASH), duration of symptoms, anxiety and depressive symptoms, catastrophizing, and kinesiophobia. The main outcome was: pain extent (% of total area and categories "pain within the median nerve-innervated territory" versus "extra-median nerve pain"). Correlation analysis was performed using Spearman's correlation coefficient. A linear regression model and binary logistic regression (both with forward selection) were performed to determine the main predictors of pain extent. RESULTS: Forty-eight participants were included. A moderate positive correlation was found between catastrophizing (r = 0.455; p = 0.024) and disability (r = 0.448; p = 0.024) with total pain extent area. Regression models indicated that catastrophizing explained 22% of the variance in the pain extent (ß = 0.003; 95% CI: 0.002-0.005), while kinesiophobia was the variable that best explained the distribution of pain in the extra-median territory (R2 Nagelkerke = 0.182). Null or weak correlations were found for the rest of the associations. CONCLUSION: Catastrophizing and kinesiophobia were the main indicators of pain extent in people with CTS. Clinicians are advised to use specific questionnaires to check for the presence of catastrophizing or kinesiophobia in people with CTS and wider pain extension.

Assessing subjective cognitive decline in older adults attending primary health care centers: what question should be asked?

INTRODUCTION: Subjective Cognitive Decline (SCD) refers to a self-perceived experience of decreased cognitive function without objective signs of cognitive impairment in neuropsychological tests or daily living activities. Despite the abundance of instruments addressing SCD, there is no consensus on the methods to be used. Our study is founded on 11 questions selected due to their recurrence in most instruments. The objective was to determine which one of these questions could be used as a simple screening tool. METHODS: 189 participants aged 65 and over selected from Primary Care centers in Santiago de Chile responded to these 11 questions and were evaluated with the MiniMental State Examination (MMSE), the Free and Cued Selective Reminding Test (FCSRT), the Pfeffer functional scale, and the Geriatric Depression Scale (GDS). An Item ResponseTheory (IRT) method was performed to assess the contribution of each of the 11 questions to the SCD latent trait and its discrimination ability. RESULTS: Based on the results of the exploratory factor analysis showing very high/low saturation of several questions on the factors, and the high residual correlation between some questions, the IRT methods led to select one question ("Do you feel like your memory has become worse?") which revealed to be the most contributive and discriminant. Participants who answered yes had a higher GDS score. There was no association with MMSE, FCSRT, and Pfeffer scores. CONCLUSION: The question "Do you feel like your memory has become worse?" may be a good proxy of SCD and could be included in routine medical checkups.

VolumePeeler: a novel FIJI plugin for geometric tissue peeling to improve visualization and quantification of 3D image stacks.

MOTIVATION: Quantitative descriptions of multi-cellular structures from optical microscopy imaging are prime to understand the variety of three-dimensional (3D) shapes in living organisms. Experimental models of vertebrates, invertebrates and plants, such as zebrafish, killifish, Drosophila or Marchantia, mainly comprise multilayer tissues, and even if microscopes can reach the needed depth, their geometry hinders the selection and subsequent analysis of the optical volumes of interest. Computational tools to "peel" tissues by removing specific layers and reducing 3D volume into planar images, can critically improve visualization and analysis. RESULTS: We developed VolumePeeler, a versatile FIJI plugin for virtual 3D "peeling" of image stacks. The plugin implements spherical and spline surface projections. We applied VolumePeeler to perform peeling in 3D images of spherical embryos, as well as non-spherical tissue layers. The produced images improve the 3D volume visualization and enable analysis and quantification of geometrically challenging microscopy datasets. AVAILABILITY: ImageJ/FIJI software, source code, examples, and tutorials are openly available in https://cimt.uchile.cl/mcerda.

Protocol for extracting live blastoderm cells from embryos of annual killifish.

The implementation of in vitro approaches using undifferentiated embryonic cells from annual killifish to complement existing in vivo developmental studies has been hindered by a lack of efficient isolation techniques. Here, we present a protocol to isolate annual killifish blastoderm cells, at the epiboly and early dispersion phase, from embryos. We describe steps for hair removal, embryo cleaning, dechorionation, and cell purification. This protocol may also be used to develop strategies to isolate cells from embryos presenting similar challenges.

The "when" matters: Evidence from memory markers in the clinical continuum of Alzheimer's disease.

OBJECTIVE: Cognitive assessment able to detect impairments in the early neuropathological stages of Alzheimer's disease (AD) is urgently needed. The visual short-term memory binding task (VSTMBT) and the Free and Cued Selective Reminding Test (FCSRT) have been recommended by the neurodegenerative disease working group as promising tests to aid in the early detection of AD. In this study, we investigated their complementary value across the clinical stages of the AD continuum. METHOD: One hundred and seventeen older adults with subjective cognitive complaint (SCC), 79 with mild cognitive impairment (MCI), 31 patients with AD dementia (ADD), and 37 cognitively unimpaired (CU) subjects, underwent assessment with the VSTMBT and the picture version of the Spanish FCSRT. RESULTS: After controlling for multiple comparisons, significant differences were found across groups. The VSTMBT was the only test that "marginally" differentiated between CU and SCC (d = 0.47, p = .052). Moreover, whereas the FCSRT showed a gradient (CU = SCC) > MCI > ADD, the VSTMBT gradient was CU > SCC > (MCI = ADD) suggesting that conjunctive binding deficits assessed by the latter may be sensitive to the very early stages of the disease. CONCLUSIONS: Our results suggest that the VSTMBT and the FCSRT are sensitive to the clinical continuum of AD. Whereas the former detects changes in the early prodromal stages, the latter is more sensitive to the advanced prodromal stages of AD. These novel tests can aid in the early detection, monitor disease progression and response to treatment, and thus support drug development programs. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A computational framework for testing hypotheses of the minimal mechanical requirements for cell aggregation using early annual killifish embryogenesis as a model.

Introduction: Deciphering the biological and physical requirements for the outset of multicellularity is limited to few experimental models. The early embryonic development of annual killifish represents an almost unique opportunity to investigate de novo cellular aggregation in a vertebrate model. As an adaptation to seasonal drought, annual killifish employs a unique developmental pattern in which embryogenesis occurs only after undifferentiated embryonic cells have completed epiboly and dispersed in low density on the egg surface. Therefore, the first stage of embryogenesis requires the congregation of embryonic cells at one pole of the egg to form a single aggregate that later gives rise to the embryo proper. This unique process presents an opportunity to dissect the self-organizing principles involved in early organization of embryonic stem cells. Indeed, the physical and biological processes required to form the aggregate of embryonic cells are currently unknown. Methods: Here, we developed an in silico, agent-based biophysical model that allows testing how cell-specific and environmental properties could determine the aggregation dynamics of early Killifish embryogenesis. In a forward engineering approach, we then proceeded to test two hypotheses for cell aggregation (cell-autonomous and a simple taxis model) as a proof of concept of modeling feasibility. In a first approach (cell autonomous system), we considered how intrinsic biophysical properties of the cells such as motility, polarity, density, and the interplay between cell adhesion and contact inhibition of locomotion drive cell aggregation into self-organized clusters. Second, we included guidance of cell migration through a simple taxis mechanism to resemble the activity of an organizing center found in several developmental models. Results: Our numerical simulations showed that random migration combined with low cell-cell adhesion is sufficient to maintain cells in dispersion and that aggregation can indeed arise spontaneously under a limited set of conditions, but, without environmental guidance, the dynamics and resulting structures do not recapitulate in vivo observations. Discussion: Thus, an environmental guidance cue seems to be required for correct execution of early aggregation in early killifish development. However, the nature of this cue (e.g., chemical or mechanical) can only be determined experimentally. Our model provides a predictive tool that could be used to better characterize the process and, importantly, to design informed experimental strategies.

The limitations and challenges in the assessment of executive dysfunction associated with real-world functioning: The opportunity of serious games.

Nowadays, there is a broad range of methods for detecting and evaluating executive dysfunction ranging from clinical interview to neuropsychological evaluation. Nevertheless, a critical issue of these assessments is the lack of correspondence of the neuropsychological test's results with real-world functioning. This paper proposes serious games as a new framework to improve the neuropsychological assessment of real-world functioning. We briefly discuss the contribution and limitations of current methods of evaluation of executive dysfunction (paper-and-pencil tests, naturalistic observation methods, and Information and Communications Technologies) to inform on daily life functioning. Then, we analyze what are the limitations of these methods to predict real-world performance: (1) A lack of appropriate instruments to investigate the complexity of real-world functioning, (2) the vast majority of neuropsychological tests assess well-structured tasks, and (3) measurement of behaviors are based on simplistic data collection and statistical analysis. This work shows how serious games offer an opportunity to develop more efficient tools to detect executive dysfunction in everyday life contexts. Serious games provide meaningful narrative stories and virtual or real environments that immerse the user in natural and social environments with social interactions. In those highly interactive game environments, the player needs to adapt his/her behavioral performance to novel and ill-structured tasks which are suited for collecting user interaction evidence. Serious games offer a novel opportunity to develop better tools to improve diagnosis of the executive dysfunction in everyday life contexts. However, more research is still needed to implement serious games in everyday clinical practice.

Detection of intermuscular coordination based on the causality of empirical mode decomposition.

Considering the stochastic nature of electromyographic (EMG) signals, nonlinear methods may be a more accurate approach to study intermuscular coordination than the linear approach. The aims of this study were to assess the coordination between two ankle plantar flexors using EMG by applying the causal decomposition approach and assessing whether the intermuscular coordination is affected by the slope of the treadmill. The medial gastrocnemius (MG) and soleus muscles (SOL) were analyzed during the treadmill walking at inclinations of 0°, 5°, and 10°. The coordination was evaluated using ensemble empirical mode decomposition, and the causal interaction was encoded by the instantaneous phase dependence of time series bi-directional causality. To estimate the mutual predictability between MG and SOL, the cross-approximate entropy (XApEn) was assessed. The maximal causal interaction was observed between 40 and 75 Hz independent of inclination. XApEn showed a significant decrease between 0° and 5° (p = 0.028), between 5° and 10° (p = 0.038), and between 0° and 10° (p = 0.014), indicating an increase in coordination. Thus, causal decomposition is an appropriate methodology to study intermuscular coordination. These results indicate that the variation of loading through the change in treadmill inclination increases the interaction of the shared input between MG and SOL, suggesting increased intermuscular coordination.

Diversification of habenular organization and asymmetries in teleosts: Insights from the Atlantic salmon and European eel.

Habenulae asymmetries are widespread across vertebrates and analyses in zebrafish, the reference model organism for this process, have provided insight into their molecular nature, their mechanisms of formation and their important roles in the integration of environmental and internal cues with a variety of organismal adaptive responses. However, the generality of the characteristics identified in this species remains an open question, even on a relatively short evolutionary scale, in teleosts. To address this question, we have characterized the broad organization of habenulae in the Atlantic salmon and quantified the asymmetries in each of the identified subdomains. Our results show that a highly conserved partitioning into a dorsal and a ventral component is retained in the Atlantic salmon and that asymmetries are mainly observed in the former as in zebrafish. A remarkable difference is that a prominent left-restricted pax6 positive nucleus is observed in the Atlantic salmon, but undetectable in zebrafish. This nucleus is not observed outside teleosts, and harbors a complex presence/absence pattern in this group, retaining its location and cytoarchitectonic organization in an elopomorph, the European eel. These findings suggest an ancient origin and high evolvability of this trait in the taxon. Taken together, our data raise novel questions about the variability of asymmetries across teleosts and their biological significance depending on ecological contexts.

Palmitic acid control of ciliogenesis modulates insulin signaling in hypothalamic neurons through an autophagy-dependent mechanism.

Palmitic acid (PA) is significantly increased in the hypothalamus of mice, when fed chronically with a high-fat diet (HFD). PA impairs insulin signaling in hypothalamic neurons, by a mechanism dependent on autophagy, a process of lysosomal-mediated degradation of cytoplasmic material. In addition, previous work shows a crosstalk between autophagy and the primary cilium (hereafter cilium), an antenna-like structure on the cell surface that acts as a signaling platform for the cell. Ciliopathies, human diseases characterized by cilia dysfunction, manifest, type 2 diabetes, among other features, suggesting a role of the cilium in insulin signaling. Cilium depletion in hypothalamic pro-opiomelanocortin (POMC) neurons triggers obesity and insulin resistance in mice, the same phenotype as mice deficient in autophagy in POMC neurons. Here we investigated the effect of chronic consumption of HFD on cilia; and our results indicate that chronic feeding with HFD reduces the percentage of cilia in hypothalamic POMC neurons. This effect may be due to an increased amount of PA, as treatment with this saturated fatty acid in vitro reduces the percentage of ciliated cells and cilia length in hypothalamic neurons. Importantly, the same effect of cilia depletion was obtained following chemical and genetic inhibition of autophagy, indicating autophagy is required for ciliogenesis. We further demonstrate a role for the cilium in insulin sensitivity, as cilium loss in hypothalamic neuronal cells disrupts insulin signaling and insulin-dependent glucose uptake, an effect that correlates with the ciliary localization of the insulin receptor (IR). Consistently, increased percentage of ciliated hypothalamic neuronal cells promotes insulin signaling, even when cells are exposed to PA. Altogether, our results indicate that, in hypothalamic neurons, impairment of autophagy, either by PA exposure, chemical or genetic manipulation, cause cilia loss that impairs insulin sensitivity.

Automatic language analysis identifies and predicts schizophrenia in first-episode of psychosis.

Automated language analysis of speech has been shown to distinguish healthy control (HC) vs chronic schizophrenia (SZ) groups, yet the predictive power on first-episode psychosis patients (FEP) and the generalization to non-English speakers remain unclear. We performed a cross-sectional and longitudinal (18 months) automated language analysis in 133 Spanish-speaking subjects from three groups: healthy control or HC (n = 49), FEP (n = 40), and chronic SZ (n = 44). Interviews were manually transcribed, and the analysis included 30 language features (4 verbal fluency; 20 verbal productivity; 6 semantic coherence). Our cross-sectional analysis showed that using the top ten ranked and decorrelated language features, an automated HC vs SZ classification achieved 85.9% accuracy. In our longitudinal analysis, 28 FEP patients were diagnosed with SZ at the end of the study. Here, combining demographics, PANSS, and language information, the prediction accuracy reached 77.5% mainly driven by semantic coherence information. Overall, we showed that language features from Spanish-speaking clinical interviews can distinguish HC vs chronic SZ, and predict SZ diagnosis in FEP patients.

Socioeconomic, Clinical, and Molecular Features of Breast Cancer Influence Overall Survival of Latin American Women.

Molecular profile of breast cancer in Latin-American women was studied in five countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Data about socioeconomic characteristics, risk factors, prognostic factors, and molecular subtypes were described, and the 60-month overall cumulative survival probabilities (OS) were estimated. From 2011 to 2013, 1,300 eligible Latin-American women 18 years or older, with a diagnosis of breast cancer in clinical stage II or III, and performance status ≦̸1 were invited to participate in a prospective cohort study. Face-to-face interviews were conducted, and clinical and outcome data, including death, were extracted from medical records. Unadjusted associations were evaluated by Chi-squared and Fisher's exact tests and the OS by Kaplan-Meier method. Log-rank test was used to determine differences between cumulative probability curves. Multivariable adjustment was carried out by entering potential confounders in the Cox regression model. The OS at 60 months was 83.9%. Multivariable-adjusted death hazard differences were found for women living in Argentina (2.27), Chile (1.95), and Uruguay (2.42) compared with Mexican women, for older (≥60 years) (1.84) compared with younger (≤40 years) women, for basal-like subtype (5.8), luminal B (2.43), and HER2-enriched (2.52) compared with luminal A subtype, and for tumor clinical stages IIB (1.91), IIIA (3.54), and IIIB (3.94) compared with stage IIA women. OS was associated with country of residence, PAM50 intrinsic subtype, age, and tumor stage at diagnosis. While the latter is known to be influenced by access to care, including cancer screening, timely diagnosis and treatment, including access to more effective treatment protocols, it may also influence epigenetic changes that, potentially, impact molecular subtypes. Data derived from heretofore understudied populations with unique geographic ancestry and sociocultural experiences are critical to furthering our understanding of this complexity.

The Transcriptomic Portrait of Locally Advanced Breast Cancer and Its Prognostic Value in a Multi-Country Cohort of Latin American Patients.

Purposes: Most molecular-based published studies on breast cancer do not adequately represent the unique and diverse genetic admixture of the Latin American population. Searching for similarities and differences in molecular pathways associated with these tumors and evaluating its impact on prognosis may help to select better therapeutic approaches. Patients and Methods: We collected clinical, pathological, and transcriptomic data of a multi-country Latin American cohort of 1,071 stage II-III breast cancer patients of the Molecular Profile of Breast Cancer Study (MPBCS) cohort. The 5-year prognostic ability of intrinsic (transcriptomic-based) PAM50 and immunohistochemical classifications, both at the cancer-specific (OSC) and disease-free survival (DFS) stages, was compared. Pathway analyses (GSEA, GSVA and MetaCore) were performed to explore differences among intrinsic subtypes. Results: PAM50 classification of the MPBCS cohort defined 42·6% of tumors as LumA, 21·3% as LumB, 13·3% as HER2E and 16·6% as Basal. Both OSC and DFS for LumA tumors were significantly better than for other subtypes, while Basal tumors had the worst prognosis. While the prognostic power of traditional subtypes calculated with hormone receptors (HR), HER2 and Ki67 determinations showed an acceptable performance, PAM50-derived risk of recurrence best discriminated low, intermediate and high-risk groups. Transcriptomic pathway analysis showed high proliferation (i.e. cell cycle control and DNA damage repair) associated with LumB, HER2E and Basal tumors, and a strong dependency on the estrogen pathway for LumA. Terms related to both innate and adaptive immune responses were seen predominantly upregulated in Basal tumors, and, to a lesser extent, in HER2E, with respect to LumA and B tumors. Conclusions: This is the first study that assesses molecular features at the transcriptomic level in a multicountry Latin American breast cancer patient cohort. Hormone-related and proliferation pathways that predominate in PAM50 and other breast cancer molecular classifications are also the main tumor-driving mechanisms in this cohort and have prognostic power. The immune-related features seen in the most aggressive subtypes may pave the way for therapeutic approaches not yet disseminated in Latin America. Clinical Trial Registration: ClinicalTrials.gov (Identifier: NCT02326857).

Altered neural control of gait and its association with pain and joint impairment in adults with haemophilic arthropathy: Clinical and methodological implications.

INTRODUCTION: It is unknown whether altered neural control is associated with clinical outcomes in people with haemophilic arthropathy (PWHA). The dynamic motor control index during walking (Walk-DMC) is a summary metric of neural control. AIMS: The primary aim of this study was to apply the Walk-DMC to assess if people diagnosed with haemophilic arthropathy have impaired neural control of gait and investigate the association of Walk-DMC with pain and joint impairment. METHOD: The Walk-DMC was assessed using surface electromyography in 11 leg muscles. Twenty-two PWHA and 15 healthy subjects walked on a 30-m walkway at 1 m/s. In addition, pain (visual analogue scale), knee flexion contracture (degrees) and joint impairment (Haemophilia Joint Health Score, HJHS) were assessed. The clinical outcomes were correlated with the Walk-DMC. Multiple regression analysis was performed to predict the Walk-DMC using the clinical outcomes. RESULTS: In 13 PWHA the Walk-DMC was beyond the normal range (80-120 pts). PWHA with an altered Walk-DMC showed more years with arthropathy, more pain, higher knee flexion contracture and a higher HJHS score (P < .05, effect size > .8). Significant negative moderate associations between Walk-DMC and pain, knee flexion contracture and HJHS were found (P < .05). The model that best predicted the Walk-DMC was the pain with knee flexion contracture (R2  = .44; P = .004). CONCLUSIONS: PWHA with abnormal neural control of gait also has more years with arthropathy, more pain, and more impaired joints. Our results indicate an association between the Walk-DMC index and joint damage, specifically with pain in combination with knee flexion contracture.

The dendritic ERGIC: Microtubule and actin cytoskeletons participate in stop-and-go movement of mobile carriers between stable structures.

The endoplasmic reticulum (ER)-to-Golgi intermediate compartment (ERGIC) is a membranous organelle that mediates protein transport between the ER and the Golgi apparatus. In neurons, clusters of these vesiculotubular structures are situated throughout the cell in proximity to the ER, passing cargo to the cis-Golgi cisternae, located mainly in the perinuclear region. Although ERGIC markers have been identified in neurons, the distribution and dynamics of neuronal ERGIC structures have not been characterized yet. Here, we show that long-distance ERGIC transport occurs via an intermittent mechanism in dendrites, with mobile elements moving between stationary structures. Slow and fast live-cell imaging have captured stable ERGIC structures remaining in place over long periods of time, as well as mobile ERGIC structures advancing very short distances along dendrites. These short distances have been consistent with the lengths between the stationary ERGIC structures. Kymography revealed ERGIC elements that moved intermittently, emerging from and fusing with stationary ERGIC structures. Interestingly, this movement apparently depends not only on the integrity of the microtubule cytoskeleton, as previously reported, but on the actin cytoskeleton as well. Our results indicate that the dendritic ERGIC has a dual nature, with both stationary and mobile structures. The neural ERGIC network transports proteins via a stop-and-go movement in which both the microtubule and the actin cytoskeletons participate.

Geometrical characterization of active contraction pulses in epithelial cells using the two-dimensional vertex model.

Several models have been proposed to describe the dynamics of epithelial tissues undergoing morphogenetic changes driven by apical constriction pulses, which differ in where the constriction is applied, either at the perimeter or in the medial regions. To help discriminate between these models, we analyse the impact of where constriction is applied on the final geometry of the active contracted cell, using the two-dimensional vertex model. We find that medial activity, characterized by a reduction in the reference area, generates anisotropic cell shapes, whereas isotropic cell shapes are produced when the reference perimeter is reduced. When plasticity is included, sufficiently slow processes of medial contractile activity, compared with the characteristic times of elasticity and plasticity, cells can achieve less elongated shapes. Similarly, for perimeter activity, the highest level of contraction is achieved. Finally, we apply the model to describe the apical contractile pulses observed within the epithelial enveloping cell layer during the pre-epiboly of the annual killifish Austrolebias nigripinnis. The analysis of the cell shape changes allowed a global fit of all parameters of the vertex model, with the pulses being quantitatively captured using perimeter activity and area plasticity.

Adaptación de una metodología de especificaciones en la calificación y retroalimentación en la enseñanza de cursos de ciencias básicas en una carrera de la salud para mejorar los aprendizajes y la motivación / Adaptation of a specifications gradings and feedback methodology for basic sciences courses teaching in a health science career to improving learning and motivation

Introducción: la enseñanza de cursos de ciencias básicas en carreras de la salud es un desafío por no estar directa e inmediatamente rela-cionada con el ámbito profesional. Por otra parte, las condiciones de estrés que ha impuesto el trabajo a distancia requiere de metodologías motivantes, y, que a su vez permitan una evaluación significativa. Objetivos: reportar las adaptaciones metodológicas y los resultados de una adaptación local de la metodología de especificaciones de las calificaciones y retroalimentación del trabajo. Métodos: se aplica una metodología de formación basada en la retroalimentación en el curso de Física para estudiantes de Tecnología Médica (N=106) durante un semestre. Las calificaciones promedio de los estudiantes fueron comparadas con las obtenidas en años anteriores. Para evaluar el desempeño docente se realizaron 2 encuestas a los estudiantes. El cumplimiento de los logros de aprendizaje se midió mediante auto-evaluación (escala likert 1 a 5) al inicio y término de cada uno de los cuatro capítulos. Resultados: las reprobaciones y eliminaciones de estudiantes en el curso fueron menores a años anteriores, siendo las notas significativamente mayores subiendo desde 4,89 a 6,29 (escala de 1 a 7, p<0,001). Los estudiantes se mostraron en un 95% satisfechos con el desempeño docente y finalmente, la auto-evaluación de logros de aprendizaje mostró un aumento promedio de 1 punto. Conclusiones: la metodología de evaluación basada en especificaciones adaptada a dos entregas y con evaluaciones en una escala no-binaria mejoró el rendimiento, los logros de los aprendizajes esperados y la motivación de los estudiantes.

Background: Teaching basic science courses in health careers is a challenge because these courses are not directly linked to professional practice. On the other hand, the stressful conditions imposed by distance work require motivating methodologies and a meaningful evaluation. Objectives: To report the methodological adaptations and the results of a local adaptation of the specifications grading and feedback methodology. Methods: A training methodology based on feedback is applied in the Physics course for Medical Technology students (N = 106) during one semester. We compared the students' average grades to those obtained in previous years with the same topics. To evaluate the teaching performance, we conducted two student surveys. We measure compliance with learning achievements by self-assessment (Likert scale 1 to 5) at the beginning and end of each of the four chapters. Results: Failures and eliminations of students in the course were lower than previous years, with significantly higher grades from 4.89 to 6.29 (p <0.001). The students were 95% satisfied with the teaching performance, and finally, the self-evaluation of learning achievements showed an average increase of 1 point. Conclusion: The evaluation methodology based on specifications adapted to two deliveries and evaluations on a non-binary scale improved the performance, expected learning achievements, and students' motivation.

Qualitative ultrasonography scale of the intensity of local twitch response during dry needling and its association with modified joint range of motion: a cross-sectional study.

BACKGROUND: The relevance of local twitch response (LTR) during dry needling technique (DNT) is controversial, and it is questioned whether LTR is necessary for successful outcomes. Furthermore, because the LTR during the deep DNT may be evoked with different intensities, it is unknown whether the magnitude of LTR intensity is associated with optimal clinical results, especially concerning to the effects of joint maximal range of motion (ROM). This study aimed to (i) determine whether visual inspections can quantify the LTR intensity during the DNT through a qualitative ultrasonography scale of LTR intensity (US-LTR scale), and (ii) assess the differences of US-LTR scale associated with changes in the maximal joint ROM. METHODS: Using a cross-sectional design, seven asymptomatic individuals were treated with DNT in the latent myofascial trigger point in both medial gastrocnemius muscles. During DNT, three consecutive LTRs were collected. The US-LTR scale was used to classify the LTRs into strong, medium, and weak intensities. The categories of US-LTR were differentiated by the velocity of LTRs using the optical flow algorithm. ROM changes in ankle dorsiflexion and knee extension were assessed before and immediately after DNT. RESULTS: The US-LTR scale showed the third LTR was significantly smaller than the first one (p < 0.05). A significant difference in velocity was observed between US-LTR categories (p < 0.001). A significant difference in the ROM was observed between the strong and weak-medium intensity (p < 0.05). CONCLUSIONS: The present findings suggest that the LTR intensity can be assessed using a qualitative US-LTR scale, and the effects of DNT on joint maximal ROM is maximized with higher LTR intensity. This study reports a novel qualitative method for LTR analysis with potential applications in research and clinical settings. However, further research is needed to achieve a broader application.