Matrix Metalloproteinase-9 Expression Is Associated with the Absence of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients.

Triple-negative breast cancer (TNBC) is particularly challenging due to the weak or absent response to therapeutics and its poor prognosis. The effectiveness of neoadjuvant chemotherapy (NAC) response is strongly influenced by changes in elements of the tumor microenvironment (TME). This work aimed to characterize the residual TME composition in 96 TNBC patients using immunohistochemistry and in situ hybridization techniques and evaluate its prognostic implications for partial responders vs. non-responders. Compared with non-responders, partial responders containing higher levels of CD83+ mature dendritic cells, FOXP3+ regulatory T cells, and IL-15 expression but lower CD138+ cell concentration exhibited better OS and RFS. However, along with tumor diameter and positive nodal status at diagnosis, matrix metalloproteinase-9 (MMP-9) expression in the residual TME was identified as an independent factor associated with the impaired response to NAC. This study yields new insights into the key components of the residual tumor bed, such as MMP-9, which is strictly associated with the lack of a pathological response to NAC. This knowledge might help early identification of TNBC patients less likely to respond to NAC and allow the establishment of new therapeutic targets.

Modulation of hNav by Tst1, a ß-toxin purified from the scorpion Tityus stigmurus.

Scorpion venoms are known as a rich mixture of components, including peptides that can interact with different ion channels, particularly voltage-gated potassium channels (Kv), calcium channels (Cav) and sodium channels (Nav), essential membrane proteins for various physiological functions in organisms. The present work aimed to characterize the modulation of hNa+-channels by Tst1, a peptide purified from the venom of Tityus stigmurus, using whole-cell patch clamp. Tst1 at 100 nM provoked current inhibition in Nav 1.3 (85.23%), Nav 1.2 (67.26%) and Nav 1.4 (63.43%), while Nav 1.1, 1.5, 1.6, and 1.7 were not significantly affected. Tst1 also shifted the voltage of activation and steady-state inactivation to more hyperpolarized states and altered the recovery from inactivation of the channels, reducing repetitive firing of cells, which was more effective in Nav 1.3. Tst1 also demonstrated that the effect on Nav 1.3 is dose-dependent, with an IC50 of 8.79 nM. Taken together, these results confirmed that Tst1, the first Tityus stigmurus NaScTx assayed in relation to Nav channels, is a ß-toxin, as was previously suggested due to its amino acid sequence. KEY CONTRIBUTION: First ß-toxin purified from the venom of Tityus stigmurus scorpion broadly characterized in hNa+-channels.

CD68 and CD83 immune populations in non-metastatic axillary lymph nodes are of prognostic value for the survival and relapse of breast cancer patients.

BACKGROUND: The foremost cause of death of breast cancer (BC) patients is metastasis, and the first site to which BC predominantly metastasizes is the axillary lymph node (ALN). Thus, ALN status is a key prognostic indicator at diagnosis. The immune system has an essential role in cancer progression and dissemination, so its evaluation in ALNs could have significant applications. In the present study we aimed to investigate the association of clinical-pathological and immune variables in the primary tumour and non-metastatic ALNs (ALNs-) of a cohort of luminal A and triple-negative BC (TNBC) patients with cancer-specific survival (CSS) and time to progression (TTP). METHODS: We analysed the differences in the variables between patients with different outcomes, created univariate and multivariate Cox regression models, validated them by bootstrapping and multiple imputation of missing data techniques, and used Kaplan-Meier survival curves for a 10-years follow-up. RESULTS: We found some clinical-pathological variables at diagnosis (tumour diameter, TNBC molecular profile and presence of ALN metastasis), and the levels of several immune markers in the two studied sites, to be associated with worse CSS and TTP. Nevertheless, only CD68 and CD83 in ALNs- were confirmed as independent prognostic factors for TTP. CONCLUSIONS: The study identified the importance of macrophage and dendritic cell markers as prognostic factors of relapse for BC. We highlight the importance of studying the immune response in ALNs-, which could be relevant to the prediction of BC patients' outcome.

Osteosarcoma of the Trapezium.

Osteogenic sarcoma is a malignant tumor that rarely affects the hand. When it does, it most often involves the phalanges or metacarpal heads. We present the case of a 51-year-old woman with a low-grade osteosarcoma affecting the trapezium bone of her left hand. A total trapeziectomy with partial removal of the first metatarsal, scaphoid, trapezoid, and capitate bones was performed, and no adjuvant therapy was administered. Six years after the intervention, the patient is disease-free, with excellent functionality and yearly imaging tests showing no signs of recurrence.

Congenital Supravalvar Mitral Ring - A Case Report.

Congenital mitral valve stenosis is a rare and severe disease, usually associated with other heart defects. The appropriate intervention depends on the site and mechanism of valvular obstruction and the aim is to avoid or delay valve replacement since it is associated with significant morbidity and mortality. Early single-stage complete repair is associated with better prognosis. We report the case of a 20-month-old child with a supravalvar mitral ring combined with a ventricular septal defect; pulmonary arterial systolic pressure before the surgery was 79 mmHg. The patient underwent a successful surgical repair with good clinical resolution.

[Extraovarian granulosa cell tumor with FOXL2 mutation. Morphological and immunohistochemical differential diagnosis]. / Tumor de células de la granulosa extraovárico con mutación FOXL2. Diagnóstico diferencial morfológico e inmunohistoquímico.

Extraovarian granulosa cell tumor is a very uncommon tumor and the identification of a recurrent mutation in FOXL2 may be used as another diagnostic tool along with the classical morphological and immunohistochemical findings. Here, we report a new case of extraovarian granulosa cell tumor in a 57 years old female patient presented with a sub-hepatic mass and abdominal pain. Histopathological examination of the excised mass showed features of adult-type granulosa cell tumor with α-inhibin, calretinin, WT1, S100, CD99 and progesterone receptor immunoreactivity. A FOXL2 mutation was detected on molecular biology study. A final diagnosis was an extraovarian adult-type granulosa cell tumor. We discuss the histopathological and immunohistochemical differential diagnosis.

Congenital supravalvar mitral ring - a case report

Abstract Congenital mitral valve stenosis is a rare and severe disease, usually associated with other heart defects. The appropriate intervention depends on the site and mechanism of valvular obstruction and the aim is to avoid or delay valve replacement since it is associated with significant morbidity and mortality. Early single-stage complete repair is associated with better prognosis. We report the case of a 20-month-old child with a supravalvar mitral ring combined with a ventricular septal defect; pulmonary arterial systolic pressure before the surgery was 79 mmHg. The patient underwent a successful surgical repair with good clinical resolution.

[Health record linkage: Andalusian health population database]. / Conexión de registros sanitarios: base poblacional de salud de Andalucía.

OBJECTIVE: To describe the development of an information system that connects data from multiple health records to improve assistance to patients, health services administration, management, evaluation, and inspection, as well as public health and research. METHOD: Deterministic connection of pseudonymized data from a population of 8.5 million inhabitants provided by: a users database, DIRAYA electronic medical records, minimum basic data sets (inpatients, outpatient mayor surgery, hospital emergencies and medical day hospital), mental health information systems, analytical and image tests, vaccines, renal patients, and pharmacy. An automatic coder was used to code clinical diagnoses and 80 chronic pathologies were identified to follow-up. The architecture of the information system consisted of three layers: data (Oracle Database 11g), applications (MicroStrategy BI) and presentation (MicroStrategy Web, JavaScript libraries, HTML 5 and CSS style sheets). Measures for the governance of the system were implemented. RESULTS: Data from 12.5 million health system users between 2001 and 2017 were gathered, including 435.5 million diagnoses, 88.7% of which were generated by the automatic coder. Data can be accessed through predefined reports or dynamic queries, both exportable to CSV files for processing outside the system. Expert analysts can directly access the databases and perform queries using SQL or directly treat the data with external tools. CONCLUSION: The work has shown that the connection of health records opens new possibilities for data analysis.

Cardiac metastasizing leiomyoma: A case report.

INTRODUCTION: Cardiac intracavitary growth of metastasizing tumour is unusual. Benign Metastasizing Leiomyoma (BML) from the uterus to the heart is extremely rare. It affects premenopausal women with a history of uterine leiomyoma. PRESENTATION OF CASE: We report a case of a 42-year-old woman who presented three tumours in the right side of the heart, two years after a hysterectomy due to leiomyomatosis. The cardiac tumours were resected and the diagnosis was uterine leiomyoma. DISCUSSION: The patient developed cardiac failure due to three masses at the right side of the heart. Cardiac involvement in BML is usually asymptomatic and rare. The heart masses were surgically removed and a peri ovarian mass was detected and also removed. Although histologically benign, BML exhibits metastatic qualities. CONCLUSION: It suggests that BML should be included as a differential diagnosis when a female patient presents an intra cardiac mass and a history of hysterectomy.

Localization of nickel in tissues of Streptanthus polygaloides Gray (Cruciferae) and endemic nickel hyperaccumulators from California.

The genus Streptanthus Nutt. is one of the most important indicators of ultramafic floras in western North America. This genus contains taxa that are endemic or tolerant of ultramafic soils. Streptanthus polygaloides is an annual nickel hyperaccumulator strictly confined to ultramafic soils throughout the Californian Sierra Nevada foothills. Nickel concentration in S. polygaloides populations was evaluated by elemental microanalysis using inductively coupled plasma mass spectrometry (ICP-MS). Representative samples of S. polygaloides roots, stems, leaves, flowers, and fruits were studied by scanning electron microscopy (SEM) coupled to an energy-dispersive X-ray probe (SEM-EDX). Results show Ni accumulation values between 0.09 and 1.18 %, and a distribution pattern similar to that observed in other Ni hyperaccumulator taxa, with the leaf epidermis accumulating the largest concentrations.

Entrada capacitativa de calcio: un mecanismo nuevo de entrada de calcio en células cardiacas / Capacitative calcium entry: a new mechanism for calcium entry in cardiac cells

Las células cardiacas requieren de una apropiada regulación del calcio intracelular para cumplir su función contráctil. Los mecanismos que regulan la entrada de calcio al interior celular, descritos hasta ahora, incluyen canales voltaje dependientes, bombas e intercambiadores. Este trabajo presenta evidencias de la presencia de un mecanismo adicional de entrada de calcio que es activado por el vaciamiento de los depósitos intracelulares de calcio. Se utilizaron células ventriculares aisladas enzimaticamente, del corazón de ratas, y cargadas con el indicador de calcio Fura-2. El vaciamiento del retículo sarcoplasmático (RS) se obtuvo activando los canales de liberación de calcio con Clorocresol (CmC), un agonista de los receptores de ryanodina. O inhibiendo la Ca2+ -ATPasa del RS con Tapsigagina. El vaciamiento del RS indujo un aumento del calcio intracelular al colocar las células en un medio externo con calcio. Este mecanismo de entrada de calcio es permeable al manganeso y muestra una inhibición > 80 por ciento en presencia de SKF-96365. Estas evidencias indican que en miocitos ventriculares de rata existe una mecanismo de entrada de calcio similar a la denominada corriente capacitativa. La velocidad de activación de este mecanismo depende del tiempo transcurrido desde que se vació el RS, sugiriendo un acoplamiento indirecto entre los canales capacitativos y el RS.

Cardiac cells need to regulate the intracellular calcium level to function as a pump. Calcium entry at the plasmalemma is regulated by proteins that functions as channels, pumps or exchangers. This work has evidence that in cardiac cells there is a new mechanism for calcium entry. The mechanism is activated after the intracellular stores are depleted. We used rat enzimatically isolated ventricular cells loaded with Fura-2. The sarcoplasmic reticulum (SR) calcium stores were depleted by activating the calcium release channels with Chlorocresol, a ryanodine receptor agonist. Or by decreasing the calcium uptake with Thapsigargin. After store depletion was completed, expousing the cells to extracellular calcium induced a raise in [Ca2+]i. This calcium entry mechanism is permeable to Manganese and is inhibited by a capacitative calcium entry blocker (SKF-96365). These evidences support the presence of a capacitative calcium entry mechanism.Our results also show that gating of this mechanism depends on the time elapsed after store depletion, being faster at longer time after depletion. This result may suggest an indirect coupling between the calcium entry mechanism and RS.

Programa computarizado para análisis de razón de mortalidad proporcional. Una versión para Venezuela / Computed program for the analysis of proportional mortality ratio: A version to Venezuela

El análisis de mortalidad proporcional es un método epidemiológico útil, rápido y de bajo costo, para generar hipótesis y llevar a cabo programas de vigilancia de mortalidad. Los cálculos de razón de mortalidad proporcional (RMPs) frecuentemente requieren conocimiento especial de lenguajes de programación. Estos requisitos limitan el uso de ésta metodología. Para superar dicho obstáculo se preparó un programa interactivo BASIC, el cual permite calcular razones de mortalidad en microcomputadoras compatible IBM. Dicho programa genera un cuadro de muertes observadas y esperadas, la razón de mortalidad, y su intervalo de confianza (95 por ciento) una prueba estadística de chi cuadrado, para 60 causas de mortalidad, basadas en la distribución de edad, sexo y año de defunción del grupo bajo estudio y las mortalidades proporcionales de Venezuela de 1970 hasta 1989. Cuadros por edad y años de defunción de causas individuales pueden ser seleccionadas. El programa se usa eficientemente con programas de bases de datos u hojas de trabajo para manejar y seleccionar subgrupos de análisis y ocupa menos de 1 Mb en un diskette flexible funcionando con menos de 128Kb de memoria RAM