Patient-centered Outcomes in Breast Cancer: Description of EQ-5D-5L and EORTC-QLQ-BR23 Measurements in Real-world Data and Their Association With Survival.

AIMS: In recent years, major improvements in breast cancer treatments have led to a significant increase in survival. Despite that, this population's quality of life (QoL) information is lacking, especially real-world data. MATERIALS AND METHODS: This was a prospective, multicentre, observational study of female breast cancer patients, without prior systemic treatment, treated between 2012 and 2019 in private health care in Brazil. QoL was assessed by two questionnaires, the EQ-5D-5L and the EORTC-QLQ-BR23. Additional data were retrospectively collected. RESULTS: The study comprised 1372 patients, most with early-stage disease (80.2% stages 0-II). At a median follow-up of 25.6 months, the estimated 3-year overall survival was 93.6%. Patients with locally advanced and metastatic breast cancer had the lowest visual analogue scale scores and the highest symptom burden in all dimensions of EQ-5D-5L, but with the most significant improvement after treatment. With the EORTC-QLQ-BR23 questionnaire, patients undergoing lumpectomy had a better perception of body image. Axillary dissection led to greater arm symptoms after 12 months, radiotherapy enhanced breast symptoms and patients treated with chemotherapy had significant worsening in the effects of systemic therapy compared with endocrine or HER2 therapy. Staging and immunohistochemical subtype correlated with survival and with several QoL parameters, but overall survival was not independently affected by patient-reported outcomes in this cohort. CONCLUSION: Our results show that early diagnosis and access to treatments with fewer side-effects, such as endocrine or targeted therapy, and less aggressive surgeries are the best strategies to achieve a better QoL for breast cancer patients.

Chronic nicotine attenuates behavioral and synaptic plasticity impairments in a streptozotocin model of Alzheimer's disease.

Brain glucose metabolism is altered in sporadic Alzheimer's disease (sAD), whose pathologies are reproduced in rodents by intracerebroventricular (icv) infusion of streptozotocin (STZ) in subdiabetogenic doses. The icv-STZ model also culminates in central cholinergic dysfunctions, which in turn are known to underlie both the sAD cognitive decline, and synaptic plasticity impairments. Considering the cognitive-enhancing potential of chronic nicotine (Nic), we investigated whether it attenuates icv-STZ-induced impairments in recognition memory and synaptic plasticity in a cognition-relevant substrate: the hippocampal CA1-medial prefrontal cortex (mPFC) pathway. Rats treated with icv-STZ were submitted to a chronic Nic regime, and were evaluated for recognition memory. We then examined long-term potentiation (LTP), paired-pulse facilitation (PPF) under urethane anesthesia, and brains were also evaluated for hippocampus-mPFC cell density. We found that Nic treatment prevents icv-STZ-induced disruptions in recognition memory and LTP. STZ did not precipitate neuronal death, while Nic alone was associated with higher neuronal density in CA1 when compared to vehicle-injected animals. Through combining behavioral, neurophysiological, and neuropathological observations into the Nic-STZ interplay, our study reinforces that cholinergic treatments are of clinical importance against early-stage Alzheimer's disease and mild cognitive impairments.

4% articaine buccal infiltration versus 2% lidocaine inferior alveolar nerve block for emergency root canal treatment in mandibular molars with irreversible pulpits: a randomized clinical study.

AIM: To compare the anaesthetic efficacy of inferior alveolar nerve blocks (IANB) with 1.8 mL of 2% lidocaine (LI) to a buccal infiltration (BI) with 1.8 mL of 4% articaine (AR), both with 1 : 100 000 epinephrine, in patients with symptomatic irreversible pulpits in a randomized controlled trial. METHODOLOGY: Volunteers presenting at the Emergency Centre (FOP-UNICAMP) were randomly divided into two groups (30 for AR and 20 for LI). Operator and patient were not blinded. Success was recorded when complete pain-free treatment was achieved after a single injection (IANB or BI) or when one supplemental injection was needed for emergency endodontic procedures. Success rate of supplemental injection was evaluated between and within groups using Fisher's exact test and chi-square test. RESULTS: A higher success rate (P = 0.03/Fisher's exact test) was observed with AR (40%) than with LI (10%). No significant difference was found when a single injection plus one supplemental injection was compared between groups (P = 1.0; AR = 70%; LI = 80%). However, supplemental injection increased the anaesthetic success rates (AR, P = 0.04; LI, P = 0.0001) within groups. CONCLUSIONS: Single anaesthesia techniques (IANB or BI) were not able to achieve pain-free emergency endodontic treatment. Supplemental anaesthetic techniques should be considered prior to treatment procedures in order to increase success rate (consort: registration number - NCT01912755/Fapesp: #2009/10834-4).

Assessment of antimutagenic and genotoxic potential of senna (Cassia angustifolia Vahl.) aqueous extract using in vitro assays.

Senna (Cassia angustifolia Vahl.) is widely used as a laxative, although potential side effects, such as toxicity and genotoxicity, have been reported. This study evaluated genotoxic and mutagenic effects of senna aqueous extract (SAE) by means of four experimental assays: inactivation of Escherichia coli cultures; bacterial growth inhibition; reverse mutation test (Mutoxitest) and DNA strand break analysis in plasmid DNA. Our results demonstrated that SAE produces single and double strand breaks in plasmid DNA in a cell free system. On the other hand, SAE was not cytotoxic or mutagenic to Escherichia coli strains tested. In effect, SAE was able to avoid H(2)O(2)-induced mutagenesis and toxicity in Escherichia coli IC203 (uvrA oxyR) and IC205 (uvrA mutM) strains, pointing to a new antioxidant/antimutagenic action of SAE.

Absence of mutagenic and citotoxic potentiality of senna (Cassia angustifolia Vahl.) evaluated by microbiological tests

Senna (Cassia angustifolia Vahl.) is widely used as laxative, but data from Ames test and animal and/or human studies with this agent have shown a mutagenic and carcinogenic potentiality. Using thee experimental models (bacterial inactivation test; bacterail mutagenisis assay-Mutoxitest; and growth Inhibition test, we investigated the toxicity of senna. Our data suggest an absence of mutagenic and citotoxic potentiality of senna.

Sena (Cassia angustifolia Vahl.) é uma espécie amplamente empregada como laxativa, mas dados mutagênicos realizados com teste de Ames e estudos animais e/ou em humanos com esse agente tem mostrado uma potencialidade mutagênica e carcinogênica. Usando três diferentes testes (inativação de bactérias; ensaio de mutagênese em bactérias - Mutoxitest; teste de inibição de crescimento), foi investigada a toxidade dessa planta. Nossos dados sugerem uma ausência da potencialidade mutagênica e citotoxicidade de sena.

[Serological markers of hepatitis B in users of services at an HIV Testing Center]. / Marcadores sorológicos da hepatite B em usuários de um Centro de Testagem para o HIV.

The objective of this investigation was to study the prevalence of serological markers of hepatitis B and possible risk factors for this disease in a sample of 404 people who attended a Testing and Couseling Center for HIV in the city of Ribeirão Preto, São Paulo State, Brazil. The overall prevalence of serologic hepatitis B markers was 14.6%, equal to that obtained for anti-HBc. HBsAg and anti-HBc IgM showed prevalences of 1%. After adjustment using logistic regression, hepatitis B markers showed association with the following variables: age, place of residence, use of injectable drugs and positivity to anti-HIV. The overall prevalence of human immunodeficiency virus infection was 6.9%. Hepatitis B markers were detected in 55.6% among intravenous drug users and in 42.9% among those who tested positive for HIV, confirming literature findings which indicates high levels of infection in these specific population groups.

Marcadores sorológicos da hepatite B em usuários de um Centro de Testagem para o HIV / Serological markers of hepatitis B in users of services at an HIV Testing Center

The objective of this investigation was to study the prevalence of serological markers of hepatitis B and possible risk factors for this disease in a sample of 404 people who attended a Testing and Couseling Center for HIV in the city of Ribeirão Preto, São Paulo State, Brazil. The overall prevalence of serologic hepatitis B markers was 14.6%, equal to that obtained for anti-HBc. HBsAg and anti-HBc IgM showed prevalences of 1%. After adjustment using logistic regression, hepatitis B markers showed association with the following variables: age, place of residence, use of injectable drugs and positivity to anti-HIV. The overall prevalence of human immunodeficiency virus infection was 6.9%. Hepatitis B markers were detected in 55.6% among intravenous drug users and in 42.9% among those who tested positive for HIV, confirming literature findings which indicates high levels of infection in these specific population groups.

Esta investigação objetivou estudar a prevalência de marcadores sorológicos de infecção pelo vírus da hepatite B e analisar possíveis fatores de risco em 404 usuários submetidos à sorologia anti-HIV no Centro de Testagem e Aconselhamento de Ribeirão Preto, SP, Brasil. A prevalência global dos marcadores para o vírus da hepatite B foi de 14,6%, idêntica à encontrada para o anti-HBc, com valores de 1% para o HBsAg e anti-HBc IgM. Após ajuste por regressão logística, os marcadores de infecção do vírus B mostraram associação com as variáveis: idade, local de residência, uso de drogas endovenosas e positividade para o HIV. A prevalência de infecção pelo vírus da imunodeficiência humana foi de 6,9%. Marcadores do vírus B foram detectados em 55,6% dos usuários de drogas endovenosas e em 42,9% dos positivos ao vírus da imunodeficiência humana, confirmando altos índices de infecção nestes grupos específicos.

Cytological alterations in dermal dendrocytes in vitro: evidence for transformation to a non-dendritic phenotype.

Dermal dendrocytes (DDs) are bone marrow-derived cells which are abundant in normal human and murine dermis, where they are closely associated with mast cells in the perivascular space. The biological role of DDs remains enigmatic. DDs express coagulation factor XIIIa and the recently described von Willebrand factor receptor, GPIb alpha, potentially indicating a function in tissue repair and haemostasis, although participation in antigen presentation is also speculated. In healing wounds and 'fibrohistiocytic' tumours, such as dermatofibromas, DDs are often associated with non-dendritic histiocytes, some of which also express factor XIIIa (FXIIIa). We have utilized human skin organ culture to examine the effects of various biological mediators on cytological characteristics of DDs. It was found that by 24 h in organ culture, immunoreactive DDs begin to lose their dendritic shape, assuming more rounded contours. This phenomenon was accentuated by mast cell degranulation; was independent of the nature of mast cell secretagogue; and could not be reproduced by recombinant tumour necrosis factor-alpha, a cytokine known to increase FXIIIa expression in DDs. Like their dendritic precursors, non-dendritic cells expressed variable FXIIIa, CD34 and CD68 and did not express CD1a or CD45. By ultrastructure, non-dendritic cells that develop in vitro resembled non-degenerating monocytes containing occasional primary lysosomes and lipid inclusions, and like DDs, expressed fibronexus-like plaques on the cell membrane. Transition of DDs from dendritic to non-dendritic cells as a consequence of specific microenvironmental influences may provide insight into the frequent concurrence of these two cytological types in fibrohistiocytic tissue reactions and neoplasia.

Mast cells and dendritic cells in basal cell carcinoma stroma.

BACKGROUND: The interaction of tumors with the surrounding stroma has become an important topic in tumor biology. Basal cell carcinoma (BCC) stroma has been characterized as hypervascular and rich in mast cells. The presence of dermal dendrocytes thought to have both antigen presenting and wound healing functions has recently been reported in BCC stroma. GP1b-alpha is a newly described vascular adhesion molecule with potential significance in tumor biology. OBJECTIVE: To further characterize the cellular phenotype of BCC stroma. METHODS: Eleven BCCs (8 nodular, 2 sclerosing, 1 adenoid-cystic) were examined using immunohistochemical techniques for the presence of antigens specific to vascular endothelium, mast cells, and dermal dendrocytes. RESULTS: The stroma of all BCCs demonstrated increased vascularity, increased numbers of mast cells, and increased numbers of dermal dendrocytes expressing both CD34 and GP1b-alpha adjacent to tumor nests. No differences in antigen expression were observed between histologic subtypes of BCC. CONCLUSION: The close proximity of stromal mast cells and dermal dendrocytes surrounding BCC nests suggests a biologically significant interaction. The pattern observed is similar to that observed in healing wounds.

Von Willebrand factor receptor GPIb alpha is expressed by human factor XIIIa-positive dermal dendrocytes and is upregulated by mast cell degranulation.

GPIb alpha, a glycoprotein component of the GPIb-IX-V complex, serves as a platelet membrane receptor that mediates adhesion to von Willebrand factor normally present in the vascular subendothelium. Recent data have demonstrated that GPIb alpha is not restricted to platelets, but is also expressed by endothelium in vitro. In this study, we describe the expression and distribution of GPIb alpha in normal adult and neonatal human skin. GPIb alpha is present, as detected by immunohistochemistry, on endothelial cells and on highly dendritic cells localized within the perivascular space, dermal-epidermal junction, and reticular dermis. By dual-labeling immunofluorescence and confocal microscopy, GPIb alpha-positive cells within the dermal interstitium are demonstrated to represent factor XIIIa-positive dermal dendrocytes. In organ cultures of neonatal human foreskin, mast cell degranulation induced by either substance P or compound 48/80 resulted in transiently increased GPIb alpha expression by dermal dendrocytes. Because the GPIb-IX-V complex plays a part in regulating hemostasis and may be important for cellular interactions with extracellular matrix molecules, these data provide additional insight into the potential function of FXIIIa-positive dermal dendrocytes in skin remodeling and repair.

Thrombin-like enzyme from Lachesis muta muta venom: isolation and topographical analysis of its active site structure by means of the binding of amidines and guanidines as competitive inhibitors.

A serine protease enzyme was purified from Lachesis muta muta venom, with 40% yield, by gel filtration on Sephadex G-100 and affinity chromatography on Sepharose-agmatin. Homogeneity of the enzyme preparation was demonstrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and the enzyme had a relative mol. wt of 45,000. The molar extinction coefficient at 280 nm was 62,127 (M x cm)-1. The enzyme hydrolysed Bz-Arg-Nan with Ks = 0.233 +/- 0.08 mM and kcat = 2.80 +/- 0.07 sec-1. All the amidines and guanidines tested for their inhibitory effect on thrombin-like enzyme behaved as competitive inhibitors of the enzyme with Ki values in the range 6.2 microM to 42.3 mM for amidines and 0.19 mM to 9.31 mM for guanidines. Dissociation constant values were analyzed in terms of the binding of the inhibitors with the subsite S1, the specificity pocket of the enzyme, Ki values were discussed in accordance with those for trypsin inhibition. beta-Naphthamidine was the strongest inhibitor, while guanidine was the weakest. The differences among the Ki values were interpreted in terms of the shape of the enzyme active site. For meta- and para-substituted benzamidinium ions a good correlation was found between log l/Ki and sigma Hammett values of the substituents. The substituent effects in the pi-electrons of the benzamidine ring were considered in the frame of Hückel molecular orbital theory. A model for the binding of p-benzamidine derivatives with the primary specificity S1 subsite of the enzyme active site was proposed.

Isolation of fungi from nature in the region of Botucatu, State of Sao Paulo, Brazil, an endemic area of Paracoccidioidomycosis

In an attempt to isolate Paracoccidioides brasiliensis from nature 887 samples of soil from Botucatu, SP, Brazil, were collected cultured in brain heart infusion agar supplement with dextrose, in potato dextrose agar and in yeast extract starch dextrose agar, all with antibiotics, at 25º and 37ºC. Five thermo-dependent dimorphic fungi morphologically resembling P. brasiliensis were isolated; two from armadillo holes; further studies of the biology, antigenicity and genetic features of the five dimorphic fungi are necessary to clarify their taxonomy and their possible relation to P.brasiliensis. In addition, 98 dematiaceous fungi and 581 different soecies of Aspergillus spp. were also isolated. Our findings emphasize that armadillos and their environment are associated with thermo-dimorphic fungi and confirm the ubiquity of pathogenic dematiaceous fungi and Aspergillus spp.

[Electrocardiographic symptom-signal correspondence in Holter records]. / Correspondência sintoma-sinal electrocardiográfico nos registos de Holter.

STUDY OBJECTIVE: To determine the correspondence symptom-sign in 24-hours ambulatory electrocardiography records. DESIGN: Retrospective study. SETTING: Pulido Valente Hospital (Lisbon). Serviço de Cardiologia. Department of Ambulatory Electrocardiography. PATIENTS: 80 patients, who made 24-hours ambulatory electrocardiography and wrote correctly the diary. Two observators analysed the correspondence symptom-sign of 269 symptomatic moments, 10 minutes before and after the symptom by reviewing the compressed print. RESULTS: We found correspondence symptom-sign in 50% of the symptomatic moments. The correspondence change with the symptom type (increased for palpitations and dyspnea), the presence of Cardiopathy (increased for chest pain and dyspnea in patients with cardiopathy) type of cardiopathy (increased in patients with Mitral Valve Prolapse and Valvular disease) and expression used by the patient.