Mechanical and Functional Responses in Astrocytes under Alternating Deformation Modes Using Magneto-Active Substrates.

This work introduces NeoMag, a system designed to enhance cell mechanics assays in substrate deformation studies. NeoMag uses multidomain magneto-active materials to mechanically actuate the substrate, transmitting reversible mechanical cues to cells. The system boasts full flexibility in alternating loading substrate deformation modes, seamlessly adapting to both upright and inverted microscopes. The multidomain substrates facilitate mechanobiology assays on 2D and 3D cultures. The integration of the system with nanoindenters allows for precise evaluation of cellular mechanical properties under varying substrate deformation modes. The system is used to study the impact of substrate deformation on astrocytes, simulating mechanical conditions akin to traumatic brain injury and ischemic stroke. The results reveal local heterogeneous changes in astrocyte stiffness, influenced by the orientation of subcellular regions relative to substrate strain. These stiffness variations, exceeding 50% in stiffening and softening, and local deformations significantly alter calcium dynamics. Furthermore, sustained deformations induce actin network reorganization and activate Piezo1 channels, leading to an initial increase followed by a long-term inhibition of calcium events. Conversely, fast and dynamic deformations transiently activate Piezo1 channels and disrupt the actin network, causing long-term cell softening. These findings unveil mechanical and functional alterations in astrocytes during substrate deformation, illustrating the multiple opportunities this technology offers.

Tumor proliferation and invasion are intrinsically coupled and unraveled through tunable spheroid and physics-based models.

Proliferation and invasion are two key drivers of tumor growth that are traditionally considered independent multicellular processes. However, these processes are intrinsically coupled through a maximum carrying capacity, i.e., the maximum spatial cell concentration supported by the tumor volume, total cell count, nutrient access, and mechanical properties of the tissue stroma. We explored this coupling of proliferation and invasion through in vitro and in silico methods where we modulated the mechanical properties of the tumor and the surrounding extracellular matrix. E-cadherin expression and stromal collagen concentration were manipulated in a tunable breast cancer spheroid to determine the overall impacts of these tumor variables on net tumor proliferation and continuum invasion. We integrated these results into a mixed-constitutive formulation to computationally delineate the influences of cellular and extracellular adhesion, stiffness, and mechanical properties of the extracellular matrix on net proliferation and continuum invasion. This framework integrates biological in vitro data into concise computational models of invasion and proliferation to provide more detailed physical insights into the coupling of these key tumor processes and tumor growth. STATEMENT OF SIGNIFICANCE: Tumor growth involves expansion into the collagen-rich stroma through intrinsic coupling of proliferation and invasion within the tumor continuum. These processes are regulated by a maximum carrying capacity that is determined by the total cell count, tumor volume, nutrient access, and mechanical properties of the surrounding stroma. The influences of biomechanical parameters (i.e., stiffness, cell elongation, net proliferation rate and cell-ECM friction) on tumor proliferation or invasion cannot be unraveled using experimental methods alone. By pairing a tunable spheroid system with computational modeling, we delineated the interdependencies of each system parameter on tumor proliferation and continuum invasion, and established a concise computational framework for studying tumor mechanobiology.

Unusual biclonal IgA plasma cell myeloma with aberrant expression of high-risk immunophenotypes: first report of a new diagnostic and clinical challenge.

IgA plasma cell myeloma (PCM) has been linked to molecular abnormalities that confer a higher risk for adverse patient outcomes. However, since IgA PCM only accounts for approximately 20% of all PCM, there are very few reports on high-risk IgA PCM. Moreover, no such reports are found on the more infrequent biclonal IgA PCM. Hence, we present a 65-year-old Puerto Rican female with acute abdominal pain, concomitant hypercalcemia, and acute renal failure. Protein electrophoresis with immunofixation found high IgA levels and detected a biclonal IgA gammopathy with kappa specificity. Histomorphologically, bone marrow showed numerous abnormal plasma cells (32%) replacing over 50% of the marrow stroma. Immunophenotyping analysis detected CD45-negative plasma cells aberrantly expressing CD33, CD43, OCT-2, and c-MYC. Chromosomal analysis revealed multiple abnormalities including the gain of chromosome 1q. Thus, we report on an unusual biclonal IgA PCM and the importance of timely diagnosing aggressive plasma cell neoplasms.

Single Plane Illumination Microscopy for Microfluidic Device Imaging.

Three-dimensional imaging of live processes at a cellular level is a challenging task. It requires high-speed acquisition capabilities, low phototoxicity, and low mechanical disturbances. Three-dimensional imaging in microfluidic devices poses additional challenges as a deep penetration of the light source is required, along with a stationary setting, so the flows are not perturbed. Different types of fluorescence microscopy techniques have been used to address these limitations; particularly, confocal microscopy and light sheet fluorescence microscopy (LSFM). This manuscript proposes a novel architecture of a type of LSFM, single-plane illumination microscopy (SPIM). This custom-made microscope includes two mirror galvanometers to scan the sample vertically and reduce shadowing artifacts while avoiding unnecessary movement. In addition, two electro-tunable lenses fine-tune the focus position and reduce the scattering caused by the microfluidic devices. The microscope has been fully set up and characterized, achieving a resolution of 1.50 µm in the x-y plane and 7.93 µm in the z-direction. The proposed architecture has risen to the challenges posed when imaging microfluidic devices and live processes, as it can successfully acquire 3D volumetric images together with time-lapse recordings, and it is thus a suitable microscopic technique for live tracking miniaturized tissue and disease models.

Memantine-Derived Schiff Bases as Transdermal Prodrug Candidates.

Condensation reactions of salicylaldehyde, 2-pyridinecarboxaldehyde, and pyridoxaldehyde with memantine (Me) produced novel memantine-derived Schiff bases (1-3). Speciation predictions and calculations of Log P, Log D, and of the percentage (%) of neutral species for (1-3) were carried out. In comparison with Me, the Schiff bases presented increased log P and log D in all cases and pH values, suggesting higher hydrophobicity. The determined solubilities in n-octanol were 34.7 mg/mL for memantine hydrochloride and 67.3 mg/mL for (3). According to the molecular weights and calculated logP, compounds (1-3) are suitable for transdermal administration, especially compound (3). In addition, hydrolysis of 3 with the release of pyridoxal, a daily cofactor in human metabolism, was observed. The results suggested that 3 is the most promising compound and that formation of the pyridoxal Schiff base with Me might be an effective strategy to obtain a prodrug candidate with increased lipophilicity, which would be able to passively cross biological barriers during transdermal delivery and might have applications in the treatment of Alzheimer's disease and other neurological disorders.

Princípios orientadores da docência em enfermagem nos estágios da educação de nível médio / Guiding principles of nursing teaching in the stages of secondary education

A prática docente na formação do enfermeiro requer o desenvolvimento de competências específicas e pedagógicas, que se articula em atividades planejadas nos diversos ambientes de aprendizagem. Compreende-se que os princípios orientadores da prática docente são aqueles que sustentam o desenvolvimento das competências dos alunos, assim pressupõe-se que a falta de compreensão destes princípios pelo professor no planejamento e execução dos estágios e atividades teórico-práticas poderá significar a reprodução dos mesmos de forma desarticulada e mecanizada pelo aluno, comprometendo a formação profissional na enfermagem. Objetiva-se com esse estudo identificar e descrever os princípios orientadores da docência em enfermagem nos estágios da educação de nível médio a partir da ótica docente. Trata-se de um estudo descritivo-exploratório de caráter qualitativo. O estudo foi realizado em uma instituição de educação profissional técnica de nível médio localizada em um município de médio porte no interior do estado de São Paulo, com os docentes que orientavam estágios e ou atividades teórico práticas. Com o desenvolvimento do estudo, foram identificados como princípios que orientam a prática docente; organização dos estágios e atividades teórico práticas; planejamento das atividades; importância do plano de cuidado; prática de enfermagem pautada em respeito, ética e postura profissional; e estímulo ao desenvolvimento de saberes. Dessa forma, com a realização desse estudo, foi possível compreender quais princípios orientam o docente em sua prática, porém a discussão acerca dessa temática não está saturada e pode subsidiar estudos futuros

The teaching practice in the training of nurses requires the development of specific and pedagogical skills, which is articulated in activities planned in the different learning environments. It is understood that the guiding principles of teaching practice are those that support the development of students' skills, so it is assumed that the lack of understanding of these principles by the teacher in the planning and execution of internships and theoretical-practical activities may mean the reproduction of students. disarticulated and mechanized by the student, compromising professional training in nursing. The objective of this study is to identify and describe the guiding principles of teaching in nursing in the stages of high school education from the teaching perspective. This is a qualitative descriptive-exploratory study. The study was carried out in a medium-level technical professional education institution located in a medium-sized municipality in the interior of the state of São Paulo, with teachers who guided internships and or theoretical practical activities. With the development of the study, they were identified as principles that guide the teaching practice; organization of internships and practical theoretical activities; planning of activities; importance of the care plan; nursing practice based on respect, ethics and professional attitude; and encouraging the development of knowledge. Thus, with the completion of this study, it was possible to understand which principles guide the teacher in his practice, but the discussion on this topic is not saturated and can support future studies

Development of an Inverted Epifluorescence Microscope for Long-Term Monitoring of Bacteria in Multiplexed Microfluidic Devices.

Developing more efficient methods for antibiotic susceptibility testing is a pressing issue in novel drug development as bacterial resistance to antibiotics becomes increasingly common. Microfluidic devices have been demonstrated to be powerful platforms that allow researchers to perform multiplexed antibiotic testing. However, the level of multiplexing within microdevices is limited, evidencing the need of creating simple, low-cost and high-resolution imaging systems that can be integrated in antibiotic development pipelines. This paper describes the design and development of an epifluorescence inverted microscope that enables long-term monitoring of bacteria inside multiplexed microfluidic devices. The goal of this work is to provide a simple microscope powerful enough to allow single-cell analysis of bacteria at a reduced cost. This facilitates increasing the number of microscopes that are simultaneously used for antibiotic testing. We prove that the designed system is able to accurately detect fluorescent beads of 100 nm, demonstrating comparable features to high-end commercial microscopes and effectively achieving the resolution required for single-cell analysis of bacteria. The proposed microscope could thus increase the efficiency in antibiotic testing while reducing cost, size, weight, and power requirements, contributing to the successful development of new antibiotic drugs.

Reafirmación profesional en los estudiantes: desafío para los docentes de la educación superior / Professional reaffirmation in students: challenge for higher education professors

RESUMEN Fundamento: la reafirmación profesional se fortalece a través de influencias educativas, necesarias para que el estudiante se identifique con la profesión escogida. Objetivo: elaborar un sistema de acciones para la reafirmación profesional de los estudiantes de la carrera de Licenciatura en Educación Prescolar en su formación continua. Métodos: se realizó una investigación de desarrollo en la Facultad de Educación Infantil de la sede "Félix Varela Morales" en el período septiembre 2017-julio 2018. Se utilizaron métodos teóricos: ascenso de lo abstracto a lo concreto, análisis-síntesis, inducción-deducción, sistémico-estructural y el histórico-lógico; empíricos: encuesta en forma de cuestionario, entrevista biográfico-narrativa y la técnica de los diez deseos; y matemático-estadísticos para los valores absolutos y relativos. Resultados: los resultados obtenidos reflejaron predominio de los niveles Medio y Bajo, respecto a la satisfacción con la profesión escogida y una marcada incidencia de motivos extrínsecos; los análisis efectuados demostraron la necesidad de elaborar un sistema de acciones que contribuya a la reafirmación profesional. Conclusiones: fue valorado por criterios de especialistas como adecuado, y al aplicarlo se modificaron las carencias diagnosticadas en sentido positivo: los estudiantes comprendieran el significado que tiene la profesión, se enriqueció la motivación, se ampliaron sus expectativas y se creó un vínculo afectivo adecuado para el desempeño profesional.

ABSTRACT Background: the professional reaffirmation is strengthened through educational influences, necessary for the student to identify with the chosen profession. Objective: to elaborate a system of actions for the professional reaffirmation of the students of the Degree in Preschool Education in their continuing education. Methods: a development research was carried out in the Faculty of Early Childhood Education of the "Félix Varela Morales" University center in the period from September 2017 to July 2018. Theoretical methods were used: ascent from the abstract to the concrete, analysis-synthesis, induction- deduction, systemic-structural and historical-logical; empirical ones: survey in the form of questionnaire, biographical-narrative interview and the technique of the ten wishes; and mathematical-statistics for absolute and relative values. Results: the results obtained showed a predominance of the medium and low levels, with respect to satisfaction with the chosen profession and a marked incidence of extrinsic motives; the analyzes carried out demonstrated the need to elaborate a system of actions that contribute to professional reaffirmation. Conclusions: it was assessed by criteria of specialists as adequate, and in applying it, the diagnosed deficiencies were modified in a positive sense: the students understood the meaning of the profession, motivation was enriched, their expectations were broadened and an adequate affective bond was created to professional performance.

Collaborative study on the effect of grinding on the detection of bones from processed animal proteins in feed by light microscopy.

Bone fragments are essential structures for the detection of processed animal proteins (PAPs) in feed by light microscopy for official controls according to Annex VI of European Union Regulation EC/152/2009. The preparation of samples submitted for analysis requires a grinding step to make them suitable for microscopic slide preparation and observation. However, there are no technical guidelines set down for this step despite the fact that it can lead to an increase in bone numbers due to fragmentation. This was demonstrated by an in-house study carried out by the Irish National Reference Laboratory (NRL) for animal protein detection. The present collaborative study investigated the possible effects of three different grinding conditions on the final result for a feed adulterated with 0.05 and 0.01% (w/w) of PAP. The microscopic analysis either combined or not with an Alizarin Red staining was carried out by 10 different laboratories. The results demonstrated that although a large variation in the numbers of bone fragments was noted, five of the six different grinding/staining combinations applied at two levels of PAP adulteration did not significantly (at p = 0.05) differ from one another. The only exception occurred when grinding the feed containing 0.05% of PAP with a rotor mill equipped with a 0.5-mm sieve and combined with a staining which resulted in a greater number of bone fragments by forced fragmentation. Overall, the impact of the grinding/staining combinations on the final results was shown to be negligible when considering the regulatory limit of detection (LOD) requirement for the method and the current rules of implementation of the light microscopic method. From a total of 180 analyses carried out on the feed matrix containing 0.05% of PAP no false-negative result was observed, and at a level of 0.01% PAP only 10 false-negative results occurred.

Prevalence of obesity in panama: some risk factors and associated diseases.

BACKGROUND: To estimate the prevalence of obesity in Panama and determine some risk factors and associated diseases in adults aged 18 years and older. METHODS: A cross-sectional descriptive study was conducted in the provinces of Panama and Colon where 60.4 % of all Panamanians 18 years or older reside, by administering a survey regarding the consumption of protective and predisposing foods and assessing the development of obesity by measuring the weight, height, and waist circumference of 3590 people. A single-stage, probabilistic, and randomized sampling strategy employing multivariate stratification was used. Individuals with a body mass index ≥ 30 kg/m(2) (men and women) were considered obese. Prevalence and descriptive analysis were conducted according to sex using Odds Ratio, with statistical significance set at a p value ≤ 0.05. RESULTS: The general prevalence of obesity was 27.1 % (30.9 % women and 18.3 % men). In women, obesity was associated with living in urban areas, being 40-59 years of age, being Afro-Panamanian, consuming beverages / foods rich in sugar, being physically inactive and having a family history of obesity. In men, obesity was associated with living in urban areas, consuming beverages/foods rich in sugar, and having a family history of obesity. Almost the totality of obese women (97.9 %), and 80.0 % of men with obesity had abdominal obesity according to the WHO classification. In both sexes, obesity was a risk factor associated to type 2 Diabetes Mellitus, hypertension, LDL values ≥ 100 mg/dL, and low HDL values (<50 mg/dL for women and < 40 mg/dL for men), Odds Ratio > 1.0; P < 0.05. CONCLUSIONS: Obesity represents a very serious threat to Panamanian public health. Our study confirms a direct association in Panama between excess weight, hypertension, type 2 Diabetes Mellitus, LDL values ≥ 100 mg/dL and low HDL values for women and men (<50 mg/dL and < 40 mg/dL, respectively). Intervention / treatment programs should be targeted, specially, to Afro-Panamanian women, whom are 40-59 years old, living in urban areas, and those having a family history of obesity.

Improving the pathologic evaluation of lung cancer resection specimens.

Accurate post-operative prognostication and management heavily depend on pathologic nodal stage. Patients with nodal metastasis benefit from post-operative adjuvant chemotherapy, those with mediastinal nodal involvement may also benefit from adjuvant radiation therapy. However, the quality of pathologic nodal staging varies significantly, with major survival implications in large populations of patients. We describe the quality gap in pathologic nodal staging, and provide evidence of its potential reversibility by targeted corrective interventions. One intervention, designed to improve the surgical lymphadenectomy, specimen labeling, and secure transfer between the operating theatre and the pathology laboratory, involves use of pre-labeled specimen collection kits. Another intervention involves application of an improved method of gross dissection of lung resection specimens, to reduce the inadvertent loss of intrapulmonary lymph nodes to histologic examination for metastasis. These corrective interventions are the subject of a regional dissemination and implementation project in diverse healthcare systems in a tri-state region of the United States with some of the highest lung cancer incidence and mortality rates. We discuss the potential of these interventions to significantly improve the accuracy of pathologic nodal staging, risk stratification, and the quality of specimens available for development of stage-independent prognostic markers in lung cancer.

Many M©B(n) boron wheels are local, but not global minima.

Twenty-six planar boron wheels with a central hypercoordinate atom (M©B(n), M is a 2nd or 3rd period element) were designed following the Schleyer-Boldyrev concept of geometric and electronic fit whereby in-plane σ- as well as π-aromaticity contribute to the chemical bonding. Global minimum searches using an efficient newly implemented method reveal that most of these boron wheels are only local, rather than global minima. However, the Be©B(8) triplet planar wheel global minimum is a new member of the planar hypercoordinate M©B(n) family. Six categories classify the structures of the other global minima: planar wheels, planar non-wheel forms, quasi-two-center-wheels, as well as leaf-like, pyramid-like, and umbrella-like geometries.

Identification of a probable new adrenergic agonist by nuclear magnetic resonance and mass spectrometry.

In animal production, it is consolidated the synthesis and the illegal use of growth promoters of new generation, able to skip routine screening and confirmatory analysis. In this work it is reported the nuclear magnetic resonance (NMR) and the mass spectrometry identification of a probable new adrenergic drug found in a feed premix. The substance was selectively purified on alpha 1 acid glycoprotein affinity columns; then its structure was first achieved by recording the 13C NMR spectrum that gave the total number of carbons of the molecule, successively sorted by DEPT experiments into quaternary, CH, CH2, and CH3 groups. However, the complete assignments of all resonances were derived from the bi-dimensional analysis and the crucial indications from the 1H-13C reverse experiments. Further characterisation was performed by atmospheric pressure chemical ionisation both in positive and negative ion mode, matching the molecular ion and the fragmentation pattern with those of most recently described new adrenergic agonists. After the loss of a ter-butylic group, the structure shows an internal symmetry along with the presence of Chlorine clusters. The proposed formula of the compound, the 8,8'-diamino-9,9'-dichloro-1-terbutyl-1,1',4,4-tetrahydro-5H,5'H-2,2'-bi-1-benzazepine-5,5'-dione, partially resembles that of Zilpaterol for the presence of a heterocyclic ring; Further work is in progress to characterise the structure-activity relationship.

Food poisoning by clenbuterol in Portugal.

This paper describes the occurrence of four cases of acute food poisoning, involving a total of 50 people, due to the ingestion of lamb and bovine meat containing residues of clenbuterol. Symptoms shown by the intoxicated people may be generally described as gross tremors of the extremities, tachycardia, nausea, headaches and dizziness. Analytical methodology developed for the determination of clenbuterol in meat, liver and blood samples is described. Procedures are described which should be followed when the described symptoms are evident in a group of people who have ingested contaminated meat, and particularly liver of ruminants.

Aspectos clínico-epidemiológicos de 60 casos de cólera atendidos en el Hospital Central Militar de 1991 a 1995 / Clinical and epidemiological aspects in 60 cases of cholera who were treated in the Military

La reciente epidemia de cólera se extendió en la mayor parte del país lo que motivó a proporcionar al personal médico y paramédico una capacitación y actualización en los conocimientos que se tenían de la enfermedad. En epidemias pasadas no se tiene conocimiento de casos atendidos en el HCM, fue en noviembre de 1991 cuando se presentó el primer caso de los pacientes que se atendieron hasta junio de 1995. A través de un estudio observacional, descriptivo y retrospectivo se llevó a cabo la revisión de los casos diagnosticados como cólera, la información se recabó de los expedientes en el archivo clínico de la institución. Se encontraron 38 pacientes del sexo masculino y 22 del sexo femenino. El 100 por ciento de los casos ingresó a la unidad hospitalaria con diversos grados de deshidratación y del total de pacientes el 12 por ciento tenía antecedente de diabetes mellitus. El 67 por ciento habían consumido alimentos en la vía pública. Todos recibieron solución de Ringer lactado, el medicamento utilizado fue trimetropim-sulfametoxazol; el 100 por ciento respondió favorablemente al tratamiento en un periodo de 3 a 5 días. El tratamiento oportuno disminuye la letalidad

Esofagocoloplastia retroesternal extrapleural en el niño / Retrosternal extrapleural esophagocoloplasty in children

Se estudian las historias clínicas de 30 pacientes operados en el Hospital Pediátrico Docente "Centro Habana", entre los meses de julio de 1973 y julio de 1988, a quienes se les realizó esofagocoloplastia retroesternal extrapleural. El grupo de edad que prevaleció en esta variedad de sustitución esofáfica fue el comprendido entre los 5 primeros años de vida, con predominio del sexo masculino. La enfermedad básica que motivó la sustitución esofágica fue la estenosis esofágica por cástico (80%) y atresia esofágica (20%). Fue utilizado el colon derecho con mayor frecuencia como segmento de trasplante (80,4%); ocurrieron complicaciones en 21 pacientes y no hubo fallecidos en esta serie

Esofagocoloplastia retroesternal extrapleural en el niño / Retrosternal extrapleural esophagocoloplasty in children

Se estudian las historias clínicas de 30 pacientes operados en el Hospital Pediátrico Docente "Centro Habana", entre los meses de julio de 1973 y julio de 1988, a quienes se les realizó esofagocoloplastia retroesternal extrapleural. El grupo de edad que prevaleció en esta variedad de sustitución esofáfica fue el comprendido entre los 5 primeros años de vida, con predominio del sexo masculino. La enfermedad básica que motivó la sustitución esofágica fue la estenosis esofágica por cástico (80

) y atresia esofágica (20

). Fue utilizado el colon derecho con mayor frecuencia como segmento de trasplante (80,4

); ocurrieron complicaciones en 21 pacientes y no hubo fallecidos en esta serie