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Second-harmonic generation microscopy represents an important tool to evaluate extracellular matrix collagen structure, which undergoes changes during cancer progression. Thus, it is potentially relevant to assess breast cancer development. We propose the use of second-harmonic generation images of tumor stroma selected on hematoxylin and eosin-stained slides to evaluate the prognostic value of collagen fibers analyses in peri and intratumoral areas in patients diagnosed with invasive ductal breast carcinoma. Quantitative analyses of collagen parameters were performed using ImageJ software. These parameters presented significantly higher values in peri than in intratumoral areas. Higher intratumoral collagen uniformity was associated with high pathological stages and with the presence of axillary lymph node metastasis. In patients with immunohistochemistry-based luminal subtype, higher intratumoral collagen uniformity and quantity were independently associated with poorer relapse-free and overall survival, respectively. A multivariate response recursive partitioning model determined 12.857 and 11.894 as the best cut-offs for intratumoral collagen quantity and uniformity, respectively. These values have shown high sensitivity and specificity to differentiate distinct outcomes. Values of intratumoral collagen quantity and uniformity exceeding the cut-offs were strongly associated with poorer relapse-free and overall survival. Our findings support a promising prognostic value of quantitative evaluation of intratumoral collagen by second-harmonic generation imaging mainly in the luminal subtype breast cancer.

Background: Several factors are associated with the presence of chronic low back pain; one of them is the flexibility of the hamstring muscles that influences the posture of the pelvic spine., Objective: Investigate the influence of two different time periods of passive static stretching on the flexibility of the hamstring., Methods: Forty-six physiotherapy students were divided into two groups performing stretching exercises: 30 s and 60 s duration. The collections consisted of: (1) pre-test: evaluation of the flexibility of the hip and knee, using a manual goniometer by means of the following tests: Straight Leg Raise Test (SLR), Passive Hip Flexion Test (PHFT) and Modified Knee Extension Test (MKET), (2) intervention: stretching with different runtimes, (3) post-test: reappraisal of flexibility, conducted immediately after the intervention., Results: Significant difference was observed intra groups, group that did stretching exercises lasting 30 seconds (G30) (SLR p = 0.000. PHFT p = 0.003 and MKET p = 0.000) and group that did stretching exercises lasting 60 seconds (G60) (SLR p = 0.000. PHFT p = 0.001 and MKET p = 0.002). Comparing the groups, no significant difference was found (SLR p = 0.307; PHFT p = 0.904; MKET p = 0.132)., Conclusion: Thus it can be inferred that 30 seconds are sufficient for increased flexibility of young women. Therefore the time-treatment sessions can be optimized. Only the acute effect of stretching was observed; further investigation of the long-term effect is required.

This study aimed to evaluate whether XPC A2920C, XPF T30028C, TP53 Arg72Pro, and GSTP1 Ile105Val polymorphisms alter outcomes of cutaneous melanoma (CM) patients. DNA from 237 CM patients seen at the University of Campinas Teaching Hospital from April 2000 to February 2014 was analyzed by polymerase chain reaction and restriction fragment length polymorphism assays. The prognostic impact of genotypes of polymorphisms on progression-free survival (PFS) and overall survival (OS) of CM patients were examined using the Kaplan-Meier probability estimates and univariate and multivariate Cox regression analyses. At 60 months of follow-up, shorter PFS and OS were seen in patients with XPF CC genotype (48.9 vs. 66.7 %, P = 0.002; 77.9 vs. 83.5 %, P = 0.006, respectively) and XPF CC + TP53 ArgArg (43.6 vs. 65.9 %, P = 0.007; 71.6 vs. 84.8 %, P = 0.006, respectively) compared with those with remaining genotypes (Kaplan-Meier estimates). Patients with XPF CC (hazard ratio (HR) 2.45, P = 0.002; HR 3.77, P = 0.005) and XPF CC + TP53 ArgArg (HR 2.67, P = 0.009; HR 4.04, P = 0.03) genotypes had more chance to present tumor progression in univariate and multivariate analyses, whereas patients with XPF CC (HR 2.78, P = 0.009) and XPF CC + TP53 ArgArg (HR 3.84, P = 0.01) genotypes were under greater risk of progressing to death in univariate analysis, compared with those with the remaining genotypes. The data suggest, for the first time, that inherited abnormalities in DNA repair pathway related to XPF 30028C and TP53 Arg72Pro polymorphisms act as prognostic factors for PFS and OS of CM patients.

This is a methodological study and technological production that aims to describe the development of a computerized system of nursing care quality indicators for the Intensive Care Unit. The study population consisted of a systems analyst and fifteen critical care nurses. For the development of the system we adopted some of the best practices of the Unified Process methodology using the Unified Modeling Language and the programming language Java Enterprise Edition 7. The system consists of an access menu with the following functions: Home (presents general information), New Record (records the indicator), Record (record search), Census (add information and indicators of the patient), Report (generates report of the indicators) and Annex (accesses the Braden Scale). This information system allows for measurement of the quality of nursing care and to evaluate patient safety in intensive care unit by monitoring quality indicators in nursing.

We examined the influence of the CYP1A1 A4889G and T6235C, GSTM1 and GSTT1 polymorphisms, involved in carcinogen metabolism, on the head and neck (HN) squamous cell carcinoma (SCC) risk. DNA from 142 HNSCC patients and 142 controls was analysed by polymerase chain reaction (PCR)-restriction fragment length polymorphism or multiplex-PCR for the polymorphisms analyses. Excesses of the CYP1A1 4889AG+GG and 4889AG+GG plus GSTT1 null genotype were seen in patients with heavy tobacco habit compared with controls (41.9% versus 26.8%, P = 0.03; 26.2% versus 10.3%, P = 0.04, respectively). Carriers of the referred genotypes and heavy tobacco consumption were under a 2.0-fold and 2.8-fold increased risks for HNSCC than others, respectively. The CYP1A1 6235TC+CC plus GSTM1 and GSTT1 null genotypes were more common in pharyngeal SCC patients than in controls (5.3% versus 0.7%, P = 0.04). Carriers of the combined genotype had 16.0-fold increased risk for the disease than others. The frequency of one null genotype of the GSTM1 or GSTT1 gene was higher in patients with pharyngeal SCC and heavy smoking status than in controls (76.3% versus 57.7%, P = 0.04). Carriers of the referred genotype and heavy tobacco status had a 2.4-fold increased risk for pharyngeal SCC than others. In contrast, the CYP1A1 6235TC+CC genotype was more common in controls than in laryngeal SCC patients (35.9% versus 21.6%, P = 0.01). Carriers of the genotype had a 0.2-fold decreased risk for the disease than others. Our data present preliminary evidence that inherited combined CYP1A1 A4889G and T6235C abnormalities and GSTM1 and GSTT1 pathways are important determinants of HNSCC, particularly pharyngeal SCC in heavy smoking individuals from south-eastern Brazil.

This pilot study has compared the polymorphic genotype frequencies of methylenetetrahydrofolate reductase (MTHFR A1298C and C677T), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), and thymidylate synthase (TS 2R/3R) in 113 patients with sporadic colorectal adenocarcinoma (SCA) and 188 healthy blood donors, used as matched controls. The aim was to assess the role of these genotypes in the increased risk of SCA among the southeastern Brazilian population. Carriers of genotype MTRR 66GG, or the combined variants MTHFR 1298AC + CC plus 677CT + TT, or MTHFR 677CT + TT plus MTR 2756AG + GG, or MTHFR 1298AC + CC plus 677CT + TT plus MTR 2756AG + GG, or yet, MTHFR 1298AC + CC plus 677CT + TT plus MTRR 66AG + GG, respectively, showed an increased risk of the order of 1.99-, 3.26-, 2.22-, 10.92-, and 14.88-fold of developing SCA when compared with carriers of the other studied polymorphic genotypes, whether in isolation or in combination. In addition, individuals with the MTHFR 677CT + TT or the MTR 2756AG + GG genotypes had a 2.12- and a 1.42-fold increased risks of SCA onset before 50 years of age. African-Brazilians with the MTRR 66GG genotype had a 1.98-fold increased risk of SCA while individuals with the MTR 2756AG + GG and the MTHFR 677CT + TT genotypes showed a 2.11- and a 1.62-fold increased risk of undifferentiated and advanced tumors at diagnosis, respectively. Carriers of genotype MTHFR 1298AC + CC or MTHFR 1298AC + CC plus MTRR 66AG + GG had a 1.42- and a 3.07-fold increased risk of rectal tumor, respectively. Additionally, carriers of MTHFR 677CT + TT or MTHFR 677CT + TT plus TS 2R/3R + 3R/3R had a 1.55- and a 5.39-fold increased risk for colon tumor, respectively, in comparison with carriers of the wild genotypes. These data suggest that all polymorphisms coding for folate and methionine-dependent enzymes, particularly when present in combination with other polymorphisms, have consistent roles in the increased risk of SCA among the southeastern population of Brazil.

Analysis of blood and lymphatic vessel in colorectal cancer is controversial in the literature, possibly due to variations in the methods of analysis. In this study, it was aimed to search for a reliable approach in the quantification of angio- and lymphangiovascular density and area as a prognostic factor and to compare such vessel counts in normal mucosa, adenomas and cancer. A retrospective study was performed on 60 sporadic colorectal cancer, 30 colorectal adenomas, and 10 colorectal non-neoplastic lesions. Archival tissues were submitted to immunohistochemical evaluation using antibodies to CD31, CD34, CD105, VEGF-A, VEGF-C, and D2-40. Microvessel density and total vascular area were determined by computer image analysis and values were compared in the three groups of lesions; the prognostic value of these parameters was evaluated in the group of colorectal cancer. Most markers showed progressive vessel counts from non-neoplastic tissue to carcinoma, both for microvessel density and total vascular area. Only microvessel density determined by CD34 in the central areas of the cancer correlated with recurrence/metastasis (p = 0.04) and survival (p = 0.02). Different methods of quantification (microvessel counting versus estimation of total vascular area), immunohistochemical markers (pan-endothelial marker versus neovessels and lymphatic markers), and areas of analysis (periphery versus inner portions of the lesion) were assessed using image analysis. The results corroborate the increase in vascularization of carcinoma and suggest that microvessel density determined by immunostaining for CD34 in the inner portion of the tumor might represent a prognostically relevant parameter in colorectal cancer.

The wild and the variant alleles of the C936T and G634C vascular endothelial grow factor (VEGF) polymorphisms seem to be linked to higher angiogenic phenotype than the remaining alleles and may act on breast cancer (BC) origin. We investigated the influence of the VEGF C936T and G634C polymorphisms on the occurrence and clinicopathologic characteristics of sporadic breast cancer (SBC) in 235 patients and 235 controls. Peripheral blood samples of all individuals were analysed by the polymerase chain reaction for identification of genotypes and by enzyme-linked immunosorbent assay (ELISA) for quantification of serum VEGF levels. The variant 634CC genotype isolated (16.2% versus 10.7%, P  = 0.01) and in combination with the wild 936CC genotype (10.6% versus 5.5%, P  = 0.01) were more common in patients than in controls. The carriers of the respective genotypes were under a 2.20-fold and a 3.08-fold increased risks for the disease. Additionally, the frequency of the wild 936CC genotype was higher in patients with tumours of histological grade III compared to those with tumours of I+II histological grades (84.0% versus 64.7%, P  = 0.004) and in patients with positive oestrogen receptor tumours compared to those with tumours lacking oestrogen receptor expression (84.7% versus 73.9%, P  = 0.02). Similar serum values of VEGF were seen in patients and controls with the distinct genotypes of the VEGF. The data suggest that the VEGF wild 936CC and the variant 634CC genotypes constitute inherited determinants of SBC and SBC aggressiveness in Brazil, but are not significant predictors of circulating VEGF levels.

It is well established that hypoxic microenvironment contributes to breast cancer progression by activation of transcriptional genes that promote angiogenesis. By promoting the antioxidant activity of glutathione, glutathione S-transferases (GSTs) are likely to facilitate the hypoxia-inducible factor-1α (HIF-1α) activity, therefore stimulating the angiogenesis. We investigated herein the influence of the GSTM1 and GSTT1 polymorphisms in the intratumoral angiogenesis of 87 patients with sporadic breast cancer. The intratumoral microvessel density (IMVD) of formalin-fixed paraffin-embedded tissues samples from all patients was determined by immunohistochemistry. The high IMVD was defined as a median microvessel counting higher than 18.7 after the analysis of histogram with all the results. The high IMVD was more common in patients with the GSTT1 wild genotype than in those with the GSTT1 null genotype (P = 0.04). Our results suggest, for the first time, that the GSTT1 polymorphism constitutes an inherited determinant of intratumoral angiogenesis in sporadic breast cancer.