Dialectical Interrelation Between: Problematic Situation, Real Problem, Scientific Problem, Object and Field, in the Investigation Design: A Necessary Reflection

All research responds to the need of solutions to a problem that directly or indirectly affects society. The development of the same largely certifies and determines the constant search for solutions. The main objective of the present study was to arrive at a clear conceptualization, as complete as possible, of some the most important terms that come up during an investigation design: Problematic Situation, Real Problem, Scientific Problem, and Object and Field, given the visible shortcomings observed in pre- and post-graduate theses when the research work is being developed and defended. The methodology consisted of basically developing a reflection around these terms (the vision that different authors have in this regard was very helpful), as well as the presentation of varied examples contributed to see the meaning of these important concepts more clearly. The study shows in a scientifically grounded way the achievement of the above. The way in which the presentation of the different concepts was handled removes any possibility of mistakes. Keywords: methodology scientific investigation, problem, object, field. Resumen Toda investigación parte del apremio en dar una respuesta a la solución de un problema que afecta de una manera directa o indirecta a la Sociedad. En gran medida, el propio desarrollo de la misma compulsa y determina esa constante búsqueda de soluciones. El objetivo principal del presente estudio fue llegar a una conceptualización clara, y lo más acabada posible, de algunos de los más importantes términos que se manejan durante el diseño de una investigación: Situación Problémica, Problema Real, Problema Científico, Objeto y Campo, dada las visibles falencias que se observan en tesistas de pre y postgrado a la hora de desarrollar y defender sus trabajos de investigación. La metodología consistió, básicamente, en desarrollar una reflexión en torno a estos términos; para lo cual resultó de gran ayuda la visión que tienen diferentes autores al respecto; así como, la exposición de variados ejemplos contribuyó a ver más definidamente el significado de estos importantes conceptos. El estudio muestra de forma científicamente fundamentada el logro de lo anterior. La forma en que se maneja la presentación de los diferentes conceptos aleja toda posibilidad de equívocos. Palabras clave: metodología investigación científica, problema, objeto, campo

Kinetics of antibodies in sera, saliva, and urine samples from adult patients with primary or secondary dengue 3 virus infections

SummaryObjectivesThe kinetics of three serological markers (IgM, IgA, and IgG) in serum, saliva, and urine samples from adult patients with primary or secondary dengue infection were studied.DesignSerum, saliva, and urine samples were collected from 22 patients with clinical and confirmed dengue 3 virus infection during the outbreak in Havana City in 2001. They were tested by capture IgM (MAC-ELISA), IgA (AAC-ELISA), and IgE (EAC-ELISA) and IgG ELISA inhibition method (EIM) to detect specific dengue antibodies.ResultsSimilar kinetics were observed in IgM, IgA, and IgG antibodies in saliva and IgA and IgG in urine samples from secondary cases compared with kinetics in serum samples, although the values were lower. No IgG antibody was detected in saliva and urine samples in primary cases and IgM antibody was not detected in urine samples from either primary or secondary infection. All secondary cases were positive for IgG in saliva and urine samples at day 7. The kinetics of specific IgE antibodies in primary and secondary cases were different.ConclusionsThe kinetics of three serological markers (IgM, IgA, and IgG) in serum, saliva, and urine samples from adult patients with primary or secondary dengue 3 virus infection were studied for the first time, showing its behavior and usefulness in dengue virus diagnosis. The specific IgE could play a role as a serological marker in secondary infections

A Pictorial Exploration of Mammary Paget Disease: Insights and Perspectives

Mammary Paget disease (MPD) is a rare condition primarily affecting adult women, characterized by unilateral skin changes in the nipple–areolar complex (NAC) and frequently associated with underlying breast carcinoma. Histologically, MPD is identified by large intraepidermal epithelial cells (Paget cells) with distinct characteristics. Immunohistochemical profiles aid in distinguishing MPD from other skin conditions. Clinical evaluation and imaging techniques, including magnetic resonance imaging (MRI), are recommended if MPD is suspected, although definitive diagnosis always requires histological examination. This review delves into the historical context, epidemiology, pathogenesis, clinical manifestations, and diagnosis of MPD, emphasizing the need for early detection. The classification of MPD based on pathogenesis is explored, shedding light on its varied presentations. Treatment options, including mastectomy and breast-conserving surgery, are discussed with clear guidelines for different scenarios. Adjuvant therapies are considered, particularly in cases with underlying breast cancer. Prognostic factors are outlined, underlining the importance of early intervention. Looking to the future, emerging techniques, like liquid biopsy, new immunohistochemical and molecular markers, and artificial intelligence-based image analysis, hold the potential to transform MPD diagnosis and treatment. These innovations offer hope for early detection and improved patient care, though validation through large-scale clinical trials is needed

Characterization and Comparison of 2 Distinct Epidemic Community-Associated Methicillin-Resistant Staphylococcus aureus Clones of ST59 Lineage.

Sequence type (ST) 59 is an epidemic lineage of community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates. Taiwanese CA-MRSA isolates belong to ST59 and can be grouped into 2 distinct clones, a virulent Taiwan clone and a commensal Asian-Pacific clone. The Taiwan clone carries the Panton-Valentine leukocidin (PVL) genes and the staphylococcal chromosomal cassette mec (SCCmec) VT, and is frequently isolated from patients with severe disease. The Asian-Pacific clone is PVL-negative, carries SCCmec IV, and a frequent colonizer of healthy children. Isolates of both clones were characterized by their ability to adhere to respiratory A549 cells, cytotoxicity to human neutrophils, and nasal colonization of a murine and murine sepsis models. Genome variation was determined by polymerase chain reaction of selected virulence factors and by multi-strain whole genome microarray. Additionally, the expression of selected factors was compared between the 2 clones. The Taiwan clone showed a much higher cytotoxicity to the human neutrophils and caused more severe septic infections with a high mortality rate in the murine model. The clones were indistinguishable in their adhesion to A549 cells and persistence of murine nasal colonization. The microarray data revealed that the Taiwan clone had lost the ø3-prophage that integrates into the β-hemolysin gene and includes staphylokinase- and enterotoxin P-encoding genes, but had retained the genes for human immune evasion, scn and chps. Production of the virulence factors did not differ significantly in the 2 clonal groups, although more α-toxin was expressed in Taiwan clone isolates from pneumonia patients. In conclusion, the Taiwan CA-MRSA clone was distinguished by enhanced virulence in both humans and an animal infection model. The evolutionary acquisition of PVL, the higher expression of α-toxin, and possibly the loss of a large portion of the β-hemolysin-converting prophage likely contribute to its higher pathogenic potential than the Asian-Pacific clone

UNATI/FOSJC/UNESP: Promobiendo la ciudadania y la salud de las personas de la tercera edad

Objetivou-se avaliar a autopercepção dos idosos pertencentes à UNATI/FOSJC/UNESP quanto as condições da saúde bucal, por meio da entrevista semidiretiva e da aplicação do Índice de Gohai. O resultado obtido mostra uma condição bucal considerada de “regular” para “boa”. Esse resultado deriva da autopercepção que os entrevistados têm da própria boca, gengivas e dentes, e que justificam pelo fato de 59,26% não usarem próteses totais, apenas 20,40% portarem próteses parciais e 55,56% manterem, por seus critérios, boas condições das gengivas. Quando se relaciona a condição bucal à classe social a qual o idoso pertence, reafirma-se que ela é satisfatória, assim como relatam os diferentes estudos revisados. Apenas 5,26% dos pertencentes à classe média se auto-avaliam como “excelente”, enquanto 34,22% dessa classe e 10,53% dos pertencentes à chamada classe trabalhadora se auto-avaliam com “boa” condição bucal. Quanto ao perfil do entrevistado, 16,67% pertencem ao gênero masculino e 83,33% ao feminino e 51,85% são casados. Com relação à UNATI, 40,74% dos idosos a reconhecem como um centro de convivência, como espaço de atualização do conhecimento e rede de auxílio para novas amizades. Concluiu-se que: (1) o conhecimento sobre a autopercepção dos idosos da UNATI se revela pelo Índice de Gohai como “satisfatória”, segundo os critérios subjetivos, e pela ausência de qualquer incômodo nos últimos meses, devido a bons hábitos bucais, higienização e escolha do creme e da escova dental; (2) é necessário o conhecimento dos fatores epidemiológicos, por meio de exames clínicos, para colaborar na compreensão da auto-avaliação e também para identificar qualquer discrepância entre os critérios subjetivos e os técnicos e, assim, facilitar a elaboração de um programa e de ações educativas direcionando ao autodiagnóstico e autocuidado.The objective was to evaluate the self-perception of the elderly pertaining ones tothe UNATI/FOSJC/UNESP regarding buccal health, by means of the half-directiveinterview and of the application of the Index of Gohai. The result is that the oralhealth was considered as between "regular" and "good". This result comes fromthe self-perception that the interviewed ones have of their own mouths, gingivasand teeth and justified by the fact that 59,26% do not to use complete denture, only20.40% to carry partial dentures; 55,56% to keep, at their discretion, goodcondition of gingiva. Regarding to oral health to the social classroom which theelderly belongs, it is reaffirmed that it is satisfactory, as well as tell the differentrevised studies. But 5.26% of the pertaining ones to the middle classes if selfassessmentas being "excellent", while 34.22% in these classrooms and 10.53% ofpertaining to the calls the diligent classrooms if auto-assessment as having "good"oral health. As of the profile of the interviewed ones, 16.67% are from male genderand 83.33% to the female, and 51.85% are married. With relation to UNATI,40.74% of elder consider it as a aging center, as space of update of theirknowledge and network for new friendships. One concluded that: (1) theknowledge on the self-perception of the aged ones of the UNATI is considered"satisfactory" according to the Index of Gohai, subjective criteria, and for theabsence of any bother in the last months, for the factors as good buccal habits, forthe hygienic cleaning and the choice of the dental cream and the dental brush; (2)the epidemiologistic factors knowledge by means of clinical examinations isnecessary to help understanding of the self-assessment, as well to identify anydiscrepancies between subjective and technician criteria, thus to facilitate theelaboration of a program and educative actions directing to the self-diagnosis andself-care.El objetivo es evaluar la autopercepción de las personas de la tercera edad, pertenecientes a UNATI/FOSJC/UNESP, en relación a las condiciones de la salud bucal, realizado por médio de una entrevista semidirecta y de la aplicación del Índice de Gohai. El resultado obtenido muestra una condición bucal considerada de "regular" para "buena". Ese resultado deriba de la autopercepción que los entrevistados tienen de la propia boca, encias y dientes, y justifican por el hecho de que 59.26% no usaron prótesis total, apenas 20.4% usaron prótesis parcial y 55.56% mantubieron, por sus propios criterios buenas condiciones de las encias. Cuando se relaciona la condición bucal a la clase social a la cual el idoso pertenece, se afirma que ella es satisfactoria, como describen los diferentes estudios analisados. Apenas 5.26% de los pertenecientes a la clase media se autoevaluan como "excelentes", en cuanto que 34.22% de esa clase y 10.53% delos pertenecientes a la llamada clase trabajadora se autoevaluan como condición bucal "buena". En relación al perfil del entrevistado, 16.67% pertenecen al género masculino y 83.33% al femenino y 51.85% son casados. En relación al UNATI, 40,74% de los de la tercera edad lo reconocen como un centro de convivência, como espacio de actualización del conocimiento y red de auxilio para nuevas amistades. Concluimos que: (1) el conocimiento sobre la autopercepción de los dela tercera edad de la UNATI se rebela por el índice de Gohai como "satisfactoria", según los criterios subjetivos, y por la ausencia de cualquier incómodo en los últimos meses, debido a buenos hábitos bucales, higiene y elección de la crema dental y cepillo de dientes; (2) es necesario el conocimiento de los factores epidemiológicos por medio de exames clínicos, para colaborar en la comprensiónde la auto-avaliación y tambien para identificar cualquier conflicto entre los criterios subjetivos y los técnicos y, facilitar la colaboración de un programa y de acciones educativas direccionadas al autodiagnóstico y autocuidado

UNATI/FOSJC/UNESP: Promobiendo la ciudadania y la salud de las personas de la tercera edad

Objetivou-se avaliar a autopercepção dos idosos pertencentes à UNATI/FOSJC/UNESP quanto as condições da saúde bucal, por meio da entrevista semidiretiva e da aplicação do Índice de Gohai. O resultado obtido mostra uma condição bucal considerada de “regular” para “boa”. Esse resultado deriva da autopercepção que os entrevistados têm da própria boca, gengivas e dentes, e que justificam pelo fato de 59,26% não usarem próteses totais, apenas 20,40% portarem próteses parciais e 55,56% manterem, por seus critérios, boas condições das gengivas. Quando se relaciona a condição bucal à classe social a qual o idoso pertence, reafirma-se que ela é satisfatória, assim como relatam os diferentes estudos revisados. Apenas 5,26% dos pertencentes à classe média se auto-avaliam como “excelente”, enquanto 34,22% dessa classe e 10,53% dos pertencentes à chamada classe trabalhadora se auto-avaliam com “boa” condição bucal. Quanto ao perfil do entrevistado, 16,67% pertencem ao gênero masculino e 83,33% ao feminino e 51,85% são casados. Com relação à UNATI, 40,74% dos idosos a reconhecem como um centro de convivência, como espaço de atualização do conhecimento e rede de auxílio para novas amizades. Concluiu-se que: (1) o conhecimento sobre a autopercepção dos idosos da UNATI se revela pelo Índice de Gohai como “satisfatória”, segundo os critérios subjetivos, e pela ausência de qualquer incômodo nos últimos meses, devido a bons hábitos bucais, higienização e escolha do creme e da escova dental; (2) é necessário o conhecimento dos fatores epidemiológicos, por meio de exames clínicos, para colaborar na compreensão da auto-avaliação e também para identificar qualquer discrepância entre os critérios subjetivos e os técnicos e, assim, facilitar a elaboração de um programa e de ações educativas direcionando ao autodiagnóstico e autocuidado.The objective was to evaluate the self-perception of the elderly pertaining ones tothe UNATI/FOSJC/UNESP regarding buccal health, by means of the half-directiveinterview and of the application of the Index of Gohai. The result is that the oralhealth was considered as between "regular" and "good". This result comes fromthe self-perception that the interviewed ones have of their own mouths, gingivasand teeth and justified by the fact that 59,26% do not to use complete denture, only20.40% to carry partial dentures; 55,56% to keep, at their discretion, goodcondition of gingiva. Regarding to oral health to the social classroom which theelderly belongs, it is reaffirmed that it is satisfactory, as well as tell the differentrevised studies. But 5.26% of the pertaining ones to the middle classes if selfassessmentas being "excellent", while 34.22% in these classrooms and 10.53% ofpertaining to the calls the diligent classrooms if auto-assessment as having "good"oral health. As of the profile of the interviewed ones, 16.67% are from male genderand 83.33% to the female, and 51.85% are married. With relation to UNATI,40.74% of elder consider it as a aging center, as space of update of theirknowledge and network for new friendships. One concluded that: (1) theknowledge on the self-perception of the aged ones of the UNATI is considered"satisfactory" according to the Index of Gohai, subjective criteria, and for theabsence of any bother in the last months, for the factors as good buccal habits, forthe hygienic cleaning and the choice of the dental cream and the dental brush; (2)the epidemiologistic factors knowledge by means of clinical examinations isnecessary to help understanding of the self-assessment, as well to identify anydiscrepancies between subjective and technician criteria, thus to facilitate theelaboration of a program and educative actions directing to the self-diagnosis andself-care.El objetivo es evaluar la autopercepción de las personas de la tercera edad, pertenecientes a UNATI/FOSJC/UNESP, en relación a las condiciones de la salud bucal, realizado por médio de una entrevista semidirecta y de la aplicación del Índice de Gohai. El resultado obtenido muestra una condición bucal considerada de "regular" para "buena". Ese resultado deriba de la autopercepción que los entrevistados tienen de la propia boca, encias y dientes, y justifican por el hecho de que 59.26% no usaron prótesis total, apenas 20.4% usaron prótesis parcial y 55.56% mantubieron, por sus propios criterios buenas condiciones de las encias. Cuando se relaciona la condición bucal a la clase social a la cual el idoso pertenece, se afirma que ella es satisfactoria, como describen los diferentes estudios analisados. Apenas 5.26% de los pertenecientes a la clase media se autoevaluan como "excelentes", en cuanto que 34.22% de esa clase y 10.53% delos pertenecientes a la llamada clase trabajadora se autoevaluan como condición bucal "buena". En relación al perfil del entrevistado, 16.67% pertenecen al género masculino y 83.33% al femenino y 51.85% son casados. En relación al UNATI, 40,74% de los de la tercera edad lo reconocen como un centro de convivência, como espacio de actualización del conocimiento y red de auxilio para nuevas amistades. Concluimos que: (1) el conocimiento sobre la autopercepción de los dela tercera edad de la UNATI se rebela por el índice de Gohai como "satisfactoria", según los criterios subjetivos, y por la ausencia de cualquier incómodo en los últimos meses, debido a buenos hábitos bucales, higiene y elección de la crema dental y cepillo de dientes; (2) es necesario el conocimiento de los factores epidemiológicos por medio de exames clínicos, para colaborar en la comprensiónde la auto-avaliación y tambien para identificar cualquier conflicto entre los criterios subjetivos y los técnicos y, facilitar la colaboración de un programa y de acciones educativas direccionadas al autodiagnóstico y autocuidado

High USP6NL levels in breast cancer sustain chronic AKT phosphorylation and GLUT1 stability fueling aerobic glycolysis

USP6NL, also named RN-tre, is a GTPase activating protein (GAP) involved in control of endocytosis and signal transduction. Here we report that USP6NL is overexpressed in breast cancer (BC), mainly of the basal-like/integrative cluster 10 subtype. Increased USP6NL levels were accompanied by gene amplification and were associated with worse prognosis in the METABRIC dataset, retaining prognostic value in multivariable analysis. High levels of USP6NL in BC cells delayed endocytosis and degradation of the epidermal growth factor receptor (EGFR), causing chronic AKT activation. In turn, AKT stabilized the glucose transporter GLUT1 at the plasma membrane, increasing aerobic glycolysis. In agreement, elevated USP6NL sensitized BC cells to glucose deprivation, indicating that their glycolytic capacity relies on this protein. Depletion of USP6NL accelerated EGFR/AKT downregulation and GLUT1 degradation, impairing cell proliferation exclusively in BC cells that harbored increased levels of USP6NL. Overall, these findings argue that USP6NL overexpression generates a metabolic rewiring that is essential to foster the glycolytic demand of BC cells and promote their proliferation

Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites

The centrosome is the master orchestrator of mitotic spindle formation and chromosome segregation in animal cells. Centrosome abnormalities are frequently observed in cancer, but little is known of their origin and about pathways affecting centrosome homeostasis. Here we show that autophagy preserves centrosome organization and stability through selective turnover of centriolar satellite components, a process we termed doryphagy. Autophagy targets the satellite organizer PCM1 by interacting with GABARAPs via a C-terminal LIR motif. Accordingly, autophagy deficiency results in accumulation of large abnormal centriolar satellites and a resultant dysregulation of centrosome composition. These alterations have critical impact on centrosome stability and lead to mitotic centrosome fragmentation and unbalanced chromosome segregation. Our findings identify doryphagy as an important centrosome-regulating pathway and bring mechanistic insights to the link between autophagy dysfunction and chromosomal instability. In addition, we highlight the vital role of centriolar satellites in maintaining centrosome integrity