Unraveling the clinicopathological and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-low and HER2-0 breast cancer.

BACKGROUND: The characterization and comparison of gene expression and intrinsic subtype (IS) changes induced by neoadjuvant chemotherapy (NACT) and endocrine therapy in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-low versus HR+/HER2-0 breast cancer (BC) has not been conducted so far. Most evidence on the association of HER2 status with pathologic responses and prognosis in HR+/HER2-negative BC is controversial and restricted to NACT-treated disease. Similarly, a temporal heterogeneity in HER2 status has been described only with NACT. METHODS: We retrospectively recruited a consecutive cohort of 186 patients with stage I-IIIB HR+/HER2-negative BC treated with neoadjuvant therapy (NAT). Available diagnostic biopsies and surgical samples were characterized for main pathological features, PAM50 IS and ROR-P score, and gene expression. Associations with pathologic complete response, residual cancer burden-0/I, event-free survival (EFS) and overall survival (OS) based on HER2 status were assessed. Pre/post pathologic/molecular changes were analyzed in matched samples. RESULTS: The HER2-low (62.9%) and HER2-0 (37.1%) cohorts did not differ significantly in main baseline features, treatments administered, breast-conserving surgery, pathologic complete response and residual cancer burden-0/I rates, EFS, and OS. NAT induced, regardless of HER2 status, a significant reduction of estrogen receptor/progesterone receptor and Ki67 levels, a down-regulation of PAM50 proliferation- and luminal-related genes/signatures, an up-regulation of selected immune genes, and a shift towards less aggressive IS and lower ROR-P. Moreover, 25% of HER2-0 changed to HER2-low and 34% HER2-low became HER2-0. HER2 shifts were significant after NACT (P < 0.001), not neoadjuvant endocrine therapy (P = 0.063), with consistent ERBB2 mRNA level dynamics. HER2 changes were not associated with EFS/OS. CONCLUSIONS: HER2-low and HER2-0 status change after NAT in ∼30% of cases, mostly after NACT. Targeted adjuvant strategies should be investigated accordingly. Molecular downstaging with current chemo/endocrine agents and immunotherapy should not rely on HER2 immunohistochemical levels in HR+/HER2-negative BC. Instead, HER2-low-targeted approaches should be explored to pursue more effective and/or less toxic dimensional downstaging.

Neurologic outcomes of carotid and other emergent interventions for ischemic stroke over 6 years with dataset enhanced by machine learning.

BACKGROUND: The current mainstays of ischemic stroke treatment include the use of thrombolysis (tissue plasminogen activator [tPA]), urgent carotid endarterectomy (uCEA) or urgent carotid artery stenting (uCAS), and mechanical endovascular reperfusion/thrombectomy (MER). Scarce data describe the presenting stroke severity and neurologic outcomes for these acute ischemic stroke interventions, alone or in combination. The authors hypothesize that patients undergoing carotid interventions experience better functional neurologic outcomes than other stroke interventions. METHODS: A comprehensive stroke center dataset was combined with data for stroke-related procedures, comorbidities, complications, and physician documentation collected from electronic medical record data. A total of 10,975 patient encounter records from January 1, 2015, through July 31, 2021, were retrieved. The presenting stroke severity was determined by vascular/stroke neurologists using the National Institutes of Health Stroke Scale (NIHSS). Functional neurologic outcomes were reported using the modified Rankin scale (mRS) score, which quantifies the degree of neurologic disability. Because mRS values were only available for 3627 encounters in the original dataset, the authors developed a machine learning algorithm to analyze physician documentation and assign an mRS value. After the exclusion and machine learning analysis, a total of 5170 patient encounters were included for statistical analysis. Statistical analyses included the χ2 test, one-way analysis of variance and logistic regression on 30-day complications, stroke severity, and neurologic outcomes. RESULTS: Patients were divided into five cohorts: (1) uCEA or uCAS (n = 189), (2) tPA alone (n = 1053), (3) MER alone (n = 418), (4) tPA + MER (n = 199), and (5) no intervention (n = 3311). Patients undergoing uCEA/uCAS were significantly more likely to be male, smokers, and have a history of peripheral arterial disease compared with other stroke cohorts. The length of stay was shortest for patients who only received tPA or no intervention (6 days), followed by uCEA/uCAS (7.2 days), MER (10.2 days), and tPA + MER (8.8 days) cohorts (P < .001). The 30-day mortality was highest in the MER cohort (12.2%) and lowest in the uCEA/uCAS cohort (2.6%). The uCEA/uCAS cohort compared with other cohorts had the lowest presenting stroke severity (NIHSS 4.9 vs NIHSS 6.9-16.0), and best neurologic outcomes (mRS 1.7 vs mRS 1.8-2.6). CONCLUSIONS: After an ischemic stroke, patients undergoing urgent carotid interventions had the lowest presenting stroke severity (NIHSS) and highest rate of independent neurologic outcomes (mRS) compared with other stroke interventions. Incoming stroke severity correlates with functional neurologic outcomes, and patients who present with an NIHSS of 10 or less who undergo uCEA/uCAS have a high likelihood of independent neurologic functional outcome (mRS of ≤2).

Tatuaje de amalgama: Pigmentación exógena más común de la cavidad oral / Amalgam tattoo: Most common exogenous pigmentation of the oral cavity

Resumen El propósito de este estudio es analizar las características clínicas de la pigmentación de amalgama en la cavidad oral, comúnmente, denominada también tatuaje de amalgama, el objetivo es aumentar el conocimiento de esta entidad patológica y diferenciarla de otras lesiones de mayor importancia clínica.

Abstract The purpose of this study is to analyze the clinical characteristics of amalgam pigmentation in the oral cavity, commonly known as amalgam tattoo, in order to increase the knowledge of this pathological entity and to differentiate it from other important lesions.

Caracterización de la población con obstrucción de poros faciales a quienes se les aplico laserterapia en la Unidad de Dermatología UNIMEL / Characterization of the population with facial pore obstruction to whom laser therapy was applied at the UNIMEL Dermatology Unit / Caracterização da população com obstrução dos poros faciais a quem foi aplicada terapia a laser no Serviço de Dermatologia da UNIMEL

INTRODUCCIÓN: el poro es un orificio de excreción que se encuentra en la epidermis de la piel, en donde pueden producirse problemas de eliminación deficiente del sebo en personas que presentan exceso de grasas. OBJETIVO: analizar las características y tratamiento laser aplicado a la población con obstrucción de poros faciales que acuden a la consulta de la Unidad de Dermatología UNIMEL. MATERIALES Y MÉTODOS: estudio descriptivo, de campo, prospectivo y transversal, la población fue de 653 pacientes de ambos sexos que acudieron a la consulta de dermatología y recibieron laserterapia por presentar obstrucción de poros faciales. Se aplicó estadística descriptiva para la representación de datos. El instrumento utilizado fue una lista de registro. RESULTADOS: los pacientes presentaron una edad promedio de 37 años, se aplicaron diferentes tratamientos según los criterios diagnósticos, se les realizó el procedimiento de fotona Black peel en un 0,15%, Vela de Nova en un 5,05% y Qs Quimioespectra a un 94,79% que representan un total de 619 personas. CONCLUSIÓN: el mayor grupo de pacientes que asistió a tratamiento se ubicó entre los 31 a 40 años de edad, un alto porcentaje mujeres afectadas por secuelas de daño facial producido por obstrucción de los poros y acumulación de sebo, un grupo importante 48,8% presenta acné posterior a los 18 años de edad.

INTRODUCTION: the pore is an excretion hole found in the epidermis of the skin, where problems of poor sebum removal can occur in people with excess fat; irregular synthesis occurs in the production of sebum increases its production with occlusion of the pores by dead cells. OBJECTIVE: to analyze the characteristics and laser treatment applied to the population with facial pore obstruction that come to the UNIMEL Dermatology Unit consultation. METHODS: a descriptive, field, prospective and cross-sectional study, the study population was 653 patients of both sexes who attended the dermatology consultation and received laser therapy for presenting facial pore obstruction. Descriptive statistics were applied for data representation. The instrument used was a registration list. RESULTS: the patients had an average age of 37 years, different treatments were applied according to the diagnostic criteria, and the photone Black peel procedure was performed in 0.15%, Nova candle in 5.05% and Qs Chemospectra at 94.79% representing a total of 619 people. CONCLUSION: the largest group of patients who attended treatment was between 31 to 40 years of age, a high percentage of women affected by sequelae of facial damage caused by pore obstruction and sebum accumulation, an important group 48.8% you have acne after 18 years of age.

INTRODUÇÃO: o poro é um orifício de excreção que se encontra na epiderme da pele, onde podem ocorrer problemas com a má remoção de sebo em pessoas com excesso de gordura. OBJETIVO: analisar as características e o tratamento a laser aplicado à população com obstrução de poro facial que frequenta a consulta do Serviço de Dermatologia da UNIMEL MATERIAIS E MÉTODOS: estudo descritivo, de campo, prospectivo e transversal, a população foi de 653 pacientes de ambos os sexos que compareceu à consulta de dermatologia e recebeu terapia a laser devido à obstrução dos poros faciais. Estatísticas descritivas foram aplicadas para representar os dados. O instrumento utilizado foi uma lista de registro. RESULTADOS: os pacientes tinham idade média de 37 anos, diferentes tratamentos foram aplicados de acordo com os critérios diagnósticos, o procedimento de fotone Black peel foi realizado em 0,15%, Vela de Nova em 5,05% e Qs Chemospectra em 94,79% representando um total de 619 pessoas. CONCLUSÃO: o maior grupo de pacientes que frequentou o tratamento teve entre 31 e 40 anos de idade, elevado percentual de mulheres acometidas por sequelas de lesões faciais causadas por obstrução de poros e acúmulo de sebo, importante grupo 48,8% tem acne após 18 anos de idade.

Cardiovascular images: constrictive pericarditis and tricavitary effusion in a dog with pericardial mesothelioma.

This report describes the transthoracic echocardiographic findings and computed tomography features of a 12-year-old West Highland white terrier with constrictive pericarditis (CP) secondary to pericardial mesothelioma. Although pericardial mesothelioma is well described in dogs, its association with CP in the canine population is not as widely reported. In this clinical case, a multidisciplinary imaging approach was helpful to identify anatomical and hemodynamic abnormalities that allowed for a diagnosis of CP.

Uso de enzimas como tratamiento dermatológico regenerador de las líneas de expresión / Use of enzymes as a regenerative dermatological treatment of expression lines / Uso de enzimas como tratamento dermatológico regenerativo de linhas de expressão

INTRODUCCIÓN: el tratamiento con enzimas es una alternativa estética mínimamente invasiva para mejorar la apariencia facial y disminuir las líneas de expresión. OBJETIVO: Determinar el uso de las enzimas hialuronidasa, colagenasa y lipasa como tratamiento enzimático dermatológico para las líneas de expresión facial. MATERIALES Y MÉTODO: estudio de campo, prospectivo, población 457 pacientes que acudieron a la consulta dermatológica entre los años 2013 y 2018 para tratamiento con enzimas. El instrumento de recolección de datos fue la hoja de registro y la fuente documental las historias clínicas. El método estadístico fue descriptivo, la información se presenta en tablas y gráficos. RESULTADOS: la edad promedio de los pacientes fue de 45,2 ± 10,1 años, 40,9% recibió 2 kits de enzimas con los 3 componentes básicos de colagenasa, hialuronidasas y lipasas. Se encontró diferencia significativa en la relación de atención entre hombres y mujeres, de 1:14, es decir las mujeres acudieron más a la consulta solicitando la colocación de este tratamiento. CONCLUSIÓN: el tratamiento con enzimas aporta beneficios al incrementar la permeabilidad dérmica, aumenta el flujo sanguíneo y el drenaje linfático, disminuye los tabiques fibrosos de la celulitis, la flacidez, adiposidades, y rejuvenece el aspecto general. Por lo que se plantea como un tratamiento efectivo para disminuir las líneas de expresión.

INTRODUCTION: enzyme treatment represents a minimally invasive aesthetic alternative to improve facial appearance and decrease expression lines. OBJECTIVE: to determine the use of the enzymes hyaluronidase, collagenase and lipase as a dermatological enzyme treatment as a regenerative treatment for expression lines. METHODS: a prospective field study was conducted of a population made up of 457 patients who attended the UNIMEL dermatological consultation between 2013 and 2018 to be treated with enzymes. The data collection instrument was the record sheet and the documentary source was the medical records. The statistical method was descriptive, the information is presented in tables and graphs. RESULTS: the average age was 45.2 ± 10.1 years of age, to whom a majority of 40.9% were applied 2 kits of enzymes with the 3 basic components of collagenase, hyaluronidases and lipases to act synergistically each other enhancing functions and revitalizing the cells of the face. A significant difference was found in the care ratio between men and women, 1:14, that is, the women attended the consultation more requesting the placement of this treatment. CONCLUSION: the use of enzymes provides great benefits to increase skin permeability, increases lymphatic drainage, reduces fibrous septa of cellulite, sagging and fat, increases blood flow and rejuvenates the general appearance. So, it is proposed as an effective treatment to reduce expression lines

INTRODUÇÃO: o tratamento enzimático é uma alternativa estética minimamente invasiva para melhorar a aparência facial e diminuir as linhas de expressão. OBJETIVO: determinar o uso das enzimas hialuronidase, colagenase e lipase como tratamento enzimático dermatológico para linhas de expressão facial. MATERIAIS E MÉTODOS: estudo de campo em perspectiva, população de 457 pacientes que compareceram à consulta dermatológica entre 2013 e 2018 para tratamento enzimático. O instrumento de coleta de dados foi a folha de registros e a fonte documental foram os registros médicos. O método estatístico foi descritivo, as informações são apresentadas em tabelas e gráficos. RESULTADOS: a idade média dos pacientes foi de 45,2 ± 10,1 anos, 40,9% receberam 2 kits de enzimas com os 3 componentes básicos de colagenase, hialuronidases e lipases. Foi encontrada diferença significativa de 1:14 na relação de atenção entre homens e mulheres, ou seja, as mulheres compareceram mais frequentemente as consultas para a colocação desse tratamento do que aos homes. CONCLUSÃO: o tratamento enzimático oferece benefícios ao aumentar a permeabilidade dérmica, aumenta o fluxo sanguíneo e a drenagem linfática, reduz os septos fibrosos da celulite, flacidez, adiposidade e rejuvenesce a aparência geral. Por isso, é proposto como um tratamento eficaz para diminuir as linhas de expressão.

A novel approach to childhood obesity: circulating chemokines and growth factors as biomarkers of insulin resistance.

BACKGROUND: Insulin resistance (IR) in children with obesity constitutes a risk factor that should be precisely diagnosed to prevent further comorbidities. OBJECTIVE: Chemokines were evaluated to identify novel predictors of IR with clinical application. METHODS: We analysed the levels of cytokines (tumour necrosis factor [TNF] α and interleukins [ILs] 1ß, 4, 6 and 10), chemokines (stromal cell derived factor 1α, monocyte chemoattract protein [MCP] 1, eotaxin and fractalkine) and growth factors (brain-derived neurotrophic factor, pro-fibrotic platelet-derived growth factor [PDGF-BB] and insulin-like growth factor 1) in serum of prepubertal children with obesity (61 girls/59 boys, 50% IR and 50% non-IR) and 32 controls. Factor analysis, correlation, binary logistic regression and receiver operating characteristic analysis of combined biomarkers were used to validate their capability for preventive interventions of IR. RESULTS: Changes in MCP1, eotaxin, IL1ß and PDGF-BB were observed in IR children with obesity. Bivariate correlation between stromal cell derived factor 1α, MCP1, eotaxin, TNFα, brain-derived neurotrophic factor and/or PDGF-BB explained the high variance (65.9%) defined by three components related to inflammation and growth that contribute towards IR. The combination of leptin, triglyceride/high-density lipoprotein, insulin-like growth factor 1, TNFα, MCP1 and PDGF-BB showed a sensitivity and specificity of 93.2% for the identification of IR. The percentage of correct predictions was 89.6. CONCLUSIONS: Combined set of cytokines, adipokines and chemokines constitutes a model that predicts IR, suggesting a potential application in clinical practice as biomarkers to identify children with obesity and hyperinsulinaemia.

Low intensity sonosynthesis of iron carbide@iron oxide core-shell nanoparticles.

Here we demonstrate a simple method for the organic sonosynthesis of stable Iron Carbide@Iron Oxide core-shell nanoparticles (ICIONPs) stabilized by oleic acid surface modification. This robust synthesis route is based on the sonochemistry reaction of organometallic precursor like Fe(CO)5 in octanol using low intensity ultrasonic bath. As obtained, nanoparticles diameter sizes were measured around 6.38 nm ±â€¯1.34 with a hydrodynamic diameter around 25 nm and an estimated polydispersity of 0.27. Core-Shell structure of nanoparticles was confirmed using HR-TEM and XPS characterization tools in which a core made up of iron carbide (Fe3C) and a shell of magnetite (γ-Fe2O3) was found. The overall nanoparticle presented ferromagnetic behavior at 4 K by SQUID. With these characteristics, the ICIONPs can be potentially used in various applications such as theranostic agent due to their properties obtained from the iron oxides and iron carbide phases.

Cooperative role of the glucagon-like peptide-1 receptor and ß3-adrenergic-mediated signalling on fat mass reduction through the downregulation of PKA/AKT/AMPK signalling in the adipose tissue and muscle of rats.

AIM: To explore the cooperation of GLP-1 receptor and ß3-adrenergic receptor (ß3-AR)-mediated signalling in the control of fat mass/feeding behaviour by studying the effects of a combined therapy composed of the GLP-1R agonist liraglutide and the ß3-AR agonist CL316243. METHODS: The study included the analysis of key mechanisms regulating lipid/cholesterol metabolism, and thermogenesis in brown (BAT) and epididymal white (eWAT) adipose tissues, abdominal muscle and liver of male rats. RESULTS: CL316243 (1 mg kg-1 ) and liraglutide (100 µg kg-1 ) co-administration over 6 days potentiated an overall negative energy balance (reduction in food intake, body weight gain, fat/non-fat mass ratio, liver fat content, and circulating levels of non-essential fatty acids, triglycerides, very low-density lipoprotein-cholesterol and leptin). These effects were accompanied by increased plasma levels of insulin and IL6. We also observed increased gene expression of uncoupling proteins regulating thermogenesis in BAT/eWAT (Ucp1) and muscle (Ucp2/3). Expression of transcription factor and enzymes involved either in de novo lipogenesis (Chrebp, Acaca, Fasn, Scd1, Insig1, Srebp1) or in fatty acid ß-oxidation (Cpt1b) was enhanced in eWAT and/or muscle but decreased in BAT. Pparα and Pparγ, essentials in lipid flux/storage, were decreased in BAT/eWAT but increased in the muscle and liver. Cholesterol synthesis regulators (Insig2, Srebp2, Hmgcr) were particularly over-expressed in muscle. These GLP-1R/ß3-AR-induced metabolic effects were associated with the downregulation of cAMP-dependent signalling pathways (PKA/AKT/AMPK). CONCLUSION: Combined activation of GLP-1 and ß3-ARs potentiate changes in peripheral pathways regulating lipid/cholesterol metabolism in a tissue-specific manner that favours a switch in energy availability/expenditure and may be useful for obesity treatment.

Ivabradina en el manejo de la falla cardiaca aguda por miocarditis / Ivabradine in acute heart failure due to myocarditis

Resumen Presentamos el caso de una paciente de 47 años de edad, remitida a nuestra institución por cuadro de la falla cardiaca aguda secundaria a la miocarditis viral, en quien se utilizó la ivabradina como terapia coadyuvante para el control de la frecuencia cardiaca en el contexto del choque cardiogénico.

Abstract The case of a 47 year-old female patient is presented. She was referred to our institution due to acute heart failure secondary to viral myocarditis, where ivabradine was used as an adjuvant therapy for controlling the heart rate in the context of a cardiogenic shock.

Detection and classification of the breast abnormalities in digital mammograms via regional Convolutional Neural Network.

Automatic detection and classification of the masses in mammograms are still a big challenge and play a crucial role to assist radiologists for accurate diagnosis. In this paper, we propose a novel computer-aided diagnose (CAD) system based on one of the regional deep learning techniques: a ROI-based Convolutional Neural Network (CNN) which is called You Only Look Once (YOLO). Our proposed YOLO-based CAD system contains four main stages: mammograms preprocessing, feature extraction utilizing multi convolutional deep layers, mass detection with confidence model, and finally mass classification using fully connected neural network (FC-NN). A set of training mammograms with the information of ROI masses and their types are used to train YOLO. The trained YOLO-based CAD system detects the masses and classifies their types into benign or malignant. Our results show that the proposed YOLO-based CAD system detects the mass location with an overall accuracy of 96.33%. The system also distinguishes between benign and malignant lesions with an overall accuracy of 85.52%. Our proposed system seems to be feasible as a CAD system capable of detection and classification at the same time. It also overcomes some challenging breast cancer cases such as the mass existing in the pectoral muscles or dense regions.

Patients' preference of trastuzumab administration (subcutaneous versus intravenous) in HER2-positive metastatic breast cancer: Results of the randomised MetaspHer study.

HannaH (NCT00950300) and PrefHer (NCT01401166) studies validated the subcutaneous (H-s.c.) formulation of trastuzumab as effective and safe as intravenous (H-i.v.) and highly preferred by patients in early breast cancer. The present randomised MetaspHer trial (NCT01810393) is the first study assessing patient's preference in metastatic setting. METHODS: Patients with HER2-positive metastatic breast cancer who completed a first line chemotherapy with trastuzumab and achieved a long-term response lasting more than 3 years were randomised to receive 3 cycles of 600-mg fixed-dose adjuvant H-s.c., followed by 3 cycles of standard H-i.v., or the reverse sequence. Primary end-point was overall preference for H-s.c. or H-i.v. at cycle six, assessed by Patient Preference Questionnaire (PPQ). Secondary end-points included healthcare professional (HCP) satisfaction; safety and tolerability; quality of life. RESULTS: Hundred and thirteen patients were randomised and treated. H-s.c. was preferred by 79/92 evaluable intent-to-treat patients (85.9%, 95% confidence interval [CI; 78.8-93.0]; p < 0.001), 13/92 preferred H-i.v. (14.1%, 95% CI [7.0-21.3]). HCPs were most satisfied with H-s.c. (56/88 available data, 63.6%, [53.6-73.7]). On the safety population, adverse events occurred in 73 (67.6%) and 49 (44.1%) patients during the H-s.c. and H-i.v. periods, respectively; 7 (6.5%) and 4 (3.6%) were grade ≥ III, 3 (2.8%) and 2 (1.8%) were serious. CONCLUSION: The safety was consistent with the known H-i.v. and H-s.c. profiles without safety concern raised. Definitively, patients preferred H-s.c. as reported in early stage by PrefHer study.

Diagnosis of acute follicular conjunctivitis: A 5-year retrospective analysis in a referral center.

OBJECTIVE AND METHODS: A retrospective analysis was performed using the medical records in a referral center in Mexico over a period of 5 years, in order to determine the frequency of acute follicular conjunctivitis. RESULTS AND CONCLUSIONS: A total of 859,986 ophthalmology consultations were given, from which 8,930 were diagnosed with acute follicular conjunctivitis (1.03% of the total). The number of patients diagnosed range between 100 and 200 in the majority of months. In August 2012 an increase was observed with 308 cases, and then decreasing after two months. This study did not demonstrate a highest frequency by month, with exception of year 2012 that showed a peak incidence in the third trimester.

The P7C3 class of neuroprotective compounds exerts antidepressant efficacy in mice by increasing hippocampal neurogenesis.

Augmenting hippocampal neurogenesis represents a potential new strategy for treating depression. Here we test this possibility by comparing hippocampal neurogenesis in depression-prone ghrelin receptor (Ghsr)-null mice to that in wild-type littermates and by determining the antidepressant efficacy of the P7C3 class of neuroprotective compounds. Exposure of Ghsr-null mice to chronic social defeat stress (CSDS) elicits more severe depressive-like behavior than in CSDS-exposed wild-type littermates, and exposure of Ghsr-null mice to 60% caloric restriction fails to elicit antidepressant-like behavior. CSDS resulted in more severely reduced cell proliferation and survival in the ventral dentate gyrus (DG) subgranular zone of Ghsr-null mice than in that of wild-type littermates. Also, caloric restriction increased apoptosis of DG subgranular zone cells in Ghsr-null mice, although it had the opposite effect in wild-type littermates. Systemic treatment with P7C3 during CSDS increased survival of proliferating DG cells, which ultimately developed into mature (NeuN+) neurons. Notably, P7C3 exerted a potent antidepressant-like effect in Ghsr-null mice exposed to either CSDS or caloric restriction, while the more highly active analog P7C3-A20 also exerted an antidepressant-like effect in wild-type littermates. Focal ablation of hippocampal stem cells with radiation eliminated this antidepressant effect, further attributing the P7C3 class antidepressant effect to its neuroprotective properties and resultant augmentation of hippocampal neurogenesis. Finally, P7C3-A20 demonstrated greater proneurogenic efficacy than a wide spectrum of currently marketed antidepressant drugs. Taken together, our data confirm the role of aberrant hippocampal neurogenesis in the etiology of depression and suggest that the neuroprotective P7C3-compounds represent a novel strategy for treating patients with this disease.

A dose-finding study with a novel water-soluble formulation of paclitaxel for the treatment of malignant high-grade solid tumours in dogs.

A new formulation of water-soluble paclitaxel (Paccal® Vet) has been developed for canine cancer patients, without the need for pre-medication (traditionally required in non-water-soluble paclitaxel formulations). The objective of the study was to determine a clinically safe and efficacious dose of Paccal Vet and to estimate progression-free and overall survival and to evaluate single-dose pharmacokinetics in tumour-bearing dogs. A positive risk:benefit ratio was established for Paccal Vet administered at 150 mg m(-2) intravenous (IV) for three or more treatment cycles. Preliminary efficacy was demonstrated by best objective response rate (86%), median time to response (14 days) and median progression-free survival (131 days). Paccal Vet was associated with expected adverse events (AE) (e.g. myelosuppression), however the majority were transient, clinically silent and manageable. This is the first clinical report of a water-soluble formulation of paclitaxel suggesting successful administration and being safely used without pre-medication in dogs.

Clinical efficacy and safety of a water-soluble micellar paclitaxel (Paccal Vet) in canine mastocytomas.

OBJECTIVE: To determine the clinical efficacy and safety of a cremophor-free formulation of paclitaxel (Paccal Vet, Oasmia Pharmaceuticals) in dogs with mast cell tumours. METHODS: Paccal Vet was administered at a median dose of 145 (range, 135 to 150) mg/m(2) intravenously once every 21 days for three cycles to 29 dogs with macroscopic grade 2 or 3 mast cell tumour. Efficacy was assessed by tumour response (Response Evaluation Criteria in Solid Tumours version 1.0) and performance status score. Progression-free survival, quality of life and safety/adverse events were also evaluated. Clinical safety was assessed by clinicopathological analyses and recording of adverse events. RESULTS: Complete or partial response was observed in 59% of dogs. Performance status score remained constant or improved for 20 dogs and decreased by one grade for 9 dogs. Median time to progression was 247 (range, 42 to 268) days. Expected, transient frequently subclinical adverse events (primarily grade 3/4 neutropenia and grade 1/2 leukopenia) were observed in the majority of dogs. Nine dogs were euthanased and one dog died due to disease progression. CLINICAL SIGNIFICANCE: Paccal Vet appears to be a clinically safe and effective treatment for canine mast cell tumours. Further controlled confirmatory investigation is warranted.

Molecular biological aspects on canine and human mammary tumors.

The high incidence of mammary tumor disease reported in certain canine breeds suggests a significant genetic component, as has already been described in human familial breast cancer-in BRCA1- and BRCA2-associated breast cancer in particular. The identification of genetic risk factors is critical to improvements in the prevention, diagnosis, and treatment of these tumors. In recent years, there has been significant progress in developing the tools and reagents necessary to analyze the canine genome. This work has culminated in a high-quality draft genome sequence, as well as a single-nucleotide polymorphism map and single-nucleotide polymorphism arrays for genomewide association analysis. These tools provide an unprecedented opportunity to characterize the genetic influences in canine diseases such as cancer, eventually allowing for exploration of more effective therapies. Given the high homology between the canine genome sequence and its human counterpart--as well as the many similarities regarding the morphology, biological behavior, and clinical course of mammary tumors in both species--the dog has proven to be an excellent comparative model. This review highlights the comparative aspects regarding certain areas within molecular biology, and it discusses future perspectives. The findings in larger genomewide association analyses and cDNA expression arrays are described, and the BRCA1/BRCA2 complex is compared in detail between the 2 species.

[Partial jejunal volvulus due to a mesenteric cystic lymphangioma]. / Vólvulo yeyunal incompleto por linfangioma quístico mesentérico.

Mesenteric cysts are unusual benign tumours that include lymphangioma. Their clinical presentation is variable and acute symptoms can be produced due to complications. This tumour appears especially in childhood, and its prognosis after surgical removal is excellent. We present the case of a 15 year old female patient with symptoms of postprandial abdominal pain and palpation of smooth mass in hypogastrium. Radiological studies showed a big polilobular mass of cystic substance that included a portion of jejune with incomplete volvulus. The treatment was the removal of the cyst and a jejunal portion and the pathological diagnosis was mesenteric cyst lymphangioma. The patient is asymptomatic more than three years after the intervention.

Valoración de las pruebas diagnósticas para tuberculosis bovina en un rebaño bovino ubicado en zona de alta incidencia del estado Zulia Venezuela / Valuation of diagnostic tests for bovine tuberculosis in cattle herd located in a high incidence area of Zulia state Venezuela

Las pruebas de tuberculina son las de uso generalizado para el diagnóstico y el control de la tuberculosis (TBC) en el hombre y en los animales. Se caracteriza por una compleja mezcla de antígenos de mycobacterias capaces de inducir reacciones de hipersensibilidad en animales infectados, incluso con mycobacterias diferentes al Mycobacterium bovis, por efectos de reactividad cruzada. La preparación del derivado protéico purificado (PPD), es similar a la de la tuberculina, a diferencia de la concentración de proteínas, las cuales se separan por precipitación con agentes químicos y no por calor, aumentando su especificidad. Los primeros resultados obtenidos con las pruebas serológicas para el diagnóstico de tuberculosis bovina muestran que existe una gran reactividad antigénica cruzada entre las especies de mycobacterias, por lo que se requiere de antígenos más específicos. Se implementó un ELISA-TBC para la detección de anticuerpos anti M. bovis. El ensayo inmunoenzimático para el IFN-y bovino cuando se utilizó conjuntamente con el sistema de cultivo de sangre completa resultó en un ensayo in vitro rápido y sensible para detectar la reactividad de la inmunidad mediada por células al M. bovis en el ganado infectado. A partir de estas pruebas se compararon los resultados obtenidos para establecer la sensibilidad y especificidad utilizando como prueba oro, los datos obtenidos en el cultivo bacteriológico y la reacción en cadena de la polimerasa (PCR). Los animales reaccionantes a la tuberculina incluyeron animales positivos a PPD-B y PPD-A, así como animales negativos a cultivo bacteriológico y PCR. Los PPD-B positivos, no son en su totalidad, los mismos reaccionantes al IFN-y o al ELISA-TBC. Aún cuando su sensibilidad es baja, muestra mayor especificidad y concordancia que el resto de las pruebas utilizadas.

The tuberculin tests are widely used for diagnosis and control of tuberculosis (TB) in humans and animals. It is characterized by a complex mixture of mycobacteria antigens able to induce hypersensitivity reactions even in animals infected with mycobacteria other than M. bovis, for purposes of cross-reactivity. The preparation of purified protein derivative (PPD) is similar to the tuberculin, unlike the concentration of proteins which are separated by precipitation with chemical agents and not by increasing its specific heat. The first results obtained with the serological tests for diagnosis of bovine tuberculosis show that there is a great antigenic cross-reactivity between mycobacterias species so it requires more specific antigens. It implemented a cattle IFN-g test and ELISA-TBC to detect anti M. bovis activity. The immunoassay test for IFN-g used in conjunction with the cropping system of whole blood resulted in an essay in vitro rapid and sensitive to detect the reactivity of the cell-mediated immunity to M. bovis in livestock infected. Comparative test of the tuberculina, test of Gamma Interferon (INF-y) and a test ELISA-TBC, soon was taken to slaughter house to take linfoides weave samples and nodules, to which the test of chain reaction of Polimerasa was applied to them, to bacteriological culture and (PCR), for the identification from the pathogen. From these tests the patterns of immune response settled down and the obtained results of the different tests were compared to establish sensitivity and specificity using with t gold standard, the data collected in culture and PCR. The results were analyzed using the statistical method of analysis of variance for nonparametric tests. The PPD B-positive, are not the same reacting to IFN-y or at ELISA-TBC. Although its sensitivity is low, it shows greater specificity and consistency as the rest of the tests used.