Robotic-assisted versus laparoscopic incisional hernia repair: a systematic review and meta-analysis.

PURPOSE: This study aimed to perform a systematic review and meta-analysis comparing the efficacy and safety outcomes of robotic-assisted and laparoscopic techniques for incisional hernia repair. METHODS: PubMed, Embase, Scopus, Cochrane databases, and conference abstracts were systematically searched for studies that directly compared robot-assisted versus laparoscopy for incisional hernia repair and reported safety or efficacy outcomes in a follow-up of ≥ 1 month. The primary endpoints of interest were postoperative complications and the length of hospital stay. RESULTS: The search strategy yielded 2104 results, of which four studies met the inclusion criteria. The studies included 1293 patients with incisional hernia repairs, 440 (34%) of whom underwent robot-assisted repair. Study follow-up ranged from 1 to 24 months. There was no significant difference between groups in the incidence of postoperative complications (OR 0.65; 95% CI 0.35-1.21; p = 0.17). The recurrence rate of incisional hernias (OR 0.34; 95% CI 0.05-2.29; p = 0.27) was also similar between robotic and laparoscopic surgeries. Hospital length of stay (MD - 1.05 days; 95% CI - 2.06, - 0.04; p = 0.04) was significantly reduced in the robotic-assisted repair. However, the robot-assisted repair had a significantly longer operative time (MD 69.6 min; 95% CI 59.0-80.1; p < 0.001). CONCLUSION: The robotic approach for incisional hernia repair was associated with a significant difference between the two groups in complications and recurrence rates, a longer operative time than laparoscopic repair, but with a shorter length of stay.

Microfluidic-based skin-on-chip systems for safety assessment of nanomaterials.

The skin is the body's largest organ, continuously exposed to and affected by natural and anthropogenic nanomaterials (materials with external and internal dimensions in the nanoscale range). This broad spectrum of insults gives rise to irreversible health effects (from skin corrosion to cancer). Organ-on-chip systems can recapitulate skin physiology with high fidelity and potentially revolutionize the safety assessment of nanomaterials. Here, we review current advances in skin-on-chip models and their potential to elucidate biological mechanisms. Further, strategies are discussed to recapitulate skin physiology on-chip, improving control over nanomaterials exposure and transport across cells. Finally, we highlight future opportunities and challenges from design and fabrication to acceptance by regulatory bodies and industry.

Association of Lower Age and Cardiorespiratory Events during Intra-Arterial Chemotherapy for Retinoblastoma: A Prospective Observational Study.

BACKGROUND AND PURPOSE: Retinoblastoma is the most common primary intraocular tumor in childhood. Intra-arterial chemotherapy is becoming the standard of care for both first-line and rescue therapy, thus improving survival rates and decreasing the adverse effects of retinoblastoma treatment. Cardiorespiratory adverse events during general anesthesia for intra-arterial chemotherapy, including decreased lung compliance and bradycardia, have been described, but data regarding associated factors are still lacking. We aimed to assess the characteristics of patients and procedures associated with cardiorespiratory events during intra-arterial chemotherapy. MATERIALS AND METHODS: We performed a prospective monocenter observational study in children diagnosed with retinoblastoma undergoing intra-arterial chemotherapy under general anesthesia. The occurrence of cardiorespiratory events was registered. We also assessed clinical and procedural characteristics potentially associated with these events. RESULTS: A cardiorespiratory event was observed in 22 (12.5%) procedures, predominantly a decrease in tidal volume observed in 16 (9%) procedures. The median age was lower in the procedures with a cardiorespiratory event (20.43 [SD, 11.76] months versus 30.11 [SD, 24.17] months) (P < .05). Other variables such as bilateral disease or a previous intra-arterial chemotherapy treatment were not associated with the occurrence of a cardiorespiratory event. CONCLUSIONS: In children undergoing intra-arterial chemotherapy for retinoblastoma treatment, cardiorespiratory events were observed in 12.5% of procedures. Lower age was associated with this complication. Although predominantly mild, these events should have prompt diagnosis and treatment to prevent further deterioration and worse outcomes.

From transabdominal to totally extra-peritoneal robotic ventral hernia repair: observations and outcomes.

PURPOSE: While robotic-assisted hernia repair has increased the popularity of minimally invasive hernia surgery, selecting between the types of approaches is a challenge for both experts and novices alike. In this study, we compared a single surgeon's early experience transitioning from transabdominal hernia repair with sublay mesh in either the pre-peritoneal or retrorectus space (TA-SM) and enhanced-view totally extra-peritoneal (eTEP) ventral hernia repair in the peri-operative and long-term post-operative time periods. METHODS: We conducted a retrospective review of 50 eTEP and 108 TA-SM procedures to collect demographics, intraoperative details, and 30-day and 1-year post-operative outcomes. Statistical analysis was performed utilizing Chi-square analysis, Fisher's test, and two sample t-tests with equal variances. RESULTS: There were no significant differences in patient demographics or comorbidities. eTEP patients had larger defects (109.1 cm2 vs. 31.8 cm2, p = 0.043) and mesh used (432.8 cm2 vs. 137.9 cm2, p = 0.001). Operative times were equivalent (158.3 ± 90.6 min eTEP and 155.8 ± 65.2 min TA-SM, p = 0.84), but conversion to alternate procedure type was higher for the transabdominal approach (4% eTEP vs. 22% TA-SM, p < 0.05). Hospital stay was less in the eTEP cohort (1.3 days vs. 2.2 days, p < 0.05). Within 30 days, there were no significant differences in emergency visits or hospital readmissions. There was a greater propensity for eTEP patients to develop seromas (12.0% vs. 1.9%, p < 0.05). At 1 year, there was no statistically significant difference in recurrence rate (4.56% eTEP vs. 12.2% TA-SM, p = 0.28) respective to average time to recurrence (9.17 months eTEP vs. 11.05 months TA-SM). CONCLUSION: The eTEP approach can be adopted safely and efficiently, and may have superior peri-operative outcomes including fewer conversions and reduced hospital stay.

Upregulated MYC expression and p53 mutations may contribute to the oncogenesis of canine Meibomian gland carcinomas.

Sebaceous carcinomas of the human ocular adnexa commonly exhibit pagetoid spread, mutations in tumor-suppressor genes, and protooncogene copy number gain. Sebaceous carcinomas are rarely reported in other species, and while the Meibomian gland (MG) represents the most common ocular adnexal structure of the canine eyelid to develop neoplasia, most are clinically and histologically benign. The objective of this study was to compare molecular features of canine MG carcinomas and adenomas. Two retrospectively identified MG carcinomas were subject to immunohistochemistry and qPCR. When compared with normal glands, MYC was upregulated in benign and malignant MG neoplasms. Aberrant p53 expression was restricted to the nuclei of intraepithelial neoplastic cells in MG carcinomas. Adipophilin expression was diminished in MG neoplasms compared with the normal MG. Our findings, if confirmed in a larger cohort of cases, could suggest that MG oncogenesis in a dog may exhibit similar molecular features as their human counterparts.

Validation of the online PREDICT tool in a cohort of early breast cancer in Brazil.

PREDICT is a tool designed to estimate the benefits of adjuvant therapy and the overall survival of women with early breast cancer. The model uses clinical, histological, and immunohistochemical variables. This study aimed to evaluate the model's performance in a Brazilian population. We assessed the discrimination and calibration of the PREDICT model to estimate overall survival (OS) in five and ten years of follow-up in a cohort of 873 women with early breast cancer diagnosed from January 2001 to December 2016. A total of 743 patients had estrogen receptor (ER)-positive and 130 had ER-negative tumors. The area under the receiver operating characteristic (ROC) curve (AUC) for discrimination was 0.72 (95%CI: 0.66-0.78) at five years and 0.67 (95%CI: 0.61-0.72) at ten years for women with ER-positive tumors. The AUC was 0.72 (95%CI: 0.62-0.81) at five years and 0.67 (95%CI: 0.54-0.77) at ten years for women with ER-negative tumors. The predicted survival in ER-positive tumors was 91.0% (95%CI: 90.2-91.6%) at five years and 79.3% (95%CI: 77.7-81.0%) at ten years, and the observed survival 90.7% (95%CI: 88.6-92.9%) and 77.2% (95%CI: 73.4-81.4%), respectively. The predicted survival in ER-negative tumors was 84.5% (95%CI: 82.5-86.6%) at five years and 75.0% (95%CI: 71.6-78.5%) at ten years, and the observed survival 76.3% (95%CI: 69.1-84.3%) and 67.9% (95%CI: 58.6-78.6%), respectively. In conclusion, PREDICT was accurate to estimate OS in women with ER-positive tumors and overestimated the OS in women with ER-negative tumors.

Lung cancer in never smokers: Tumor immunology and challenges for immunotherapy.

Lung cancer is the second most common and the most lethal malignancy worldwide. It is estimated that lung cancer in never smokers (LCINS) accounts for 10-25% of cases, and its incidence is increasing according to recent data, although the reasons remain unclear. If considered alone, LCINS is the 7th most common cause of cancer death. These tumors occur more commonly in younger patients and females. LCINS tend to have a better prognosis, possibly due to a higher chance of bearing an actionable driver mutation, making them amenable to targeted therapy. Notwithstanding, these tumors respond poorly to immune checkpoint inhibitors (ICI). There are several putative explanations for the poor response to immunotherapy: low immunogenicity due to low tumor mutation burden and hence low MANA (mutation-associated neo-antigen) load, constitutive PD-L1 expression in response to driver mutated protein signaling, high expression of immunosuppressive factors by tumors cells (like CD39 and TGF-beta), non-permissive immune TME (tumor microenvironment), abnormal metabolism of amino acids and glucose, and impaired TLS (Tertiary Lymphoid Structures) organization. Finally, there is an increasing concern of offering ICI as first line therapy to these patients owing to several reports of severe toxicity when TKIs (tyrosine kinase inhibitors) are administered sequentially after ICI. Understanding the biology behind the immune response against these tumors is crucial to the development of better therapeutic strategies.

Antimicrobial resistance, biofilm production and invasion of mammary epithelial cells by Enterococcus faecalis and Enterococcus mundtii strains isolated from bovine subclinical mastitis in Brazil.

Members of the genus Enterococcus are among the most relevant etiologic agents of bovine clinical and subclinical mastitis, a major problem for the dairy industry. In Brazil, clonal diversity, and multidrug resistance profiles related to bovine infections need further investigation. In this study, 11 bacterial strains recovered from mastitis subclinical cases detected in different farms of São Paulo, Brazil, were identified as Enterococcus faecalis (n = 8) and Enterococcus mundtii (n = 3) by biochemical testing and MALDI-TOF mass spectrometry. Pulsed-field gel electrophoresis categorized the enterococcal isolates into two main clusters (A and B) with similarity ranging from 85 to 100%. The isolates were shown to be resistant tetracycline (73%), erythromycin (73%), quinupristin-dalphopristin (64%), norfloxacin (9%), fosfomycin (9%) and linezolid (9%). Moreover, seven strains (64%) were considered multidrug-resistant. All the isolates were able to produce biofilms when grown in milk for 24 h: 54·54% were classified as moderate producers and 45·45% were weak producers. Interestingly, only two strains (Ef17 and Em42) remained as moderate biofilm producers after 48 h incubation. Moreover, all isolates showed no ability to form biofilm in tryptic soy broth (TSB) after 24 and 48 h incubation. In addition, cytoskeleton components were partially involved in E. faecalis and E. mundtii entry to epithelial cells as demonstrated by induction of actin stress fibre. In conclusion, enterococci isolates recovered from bovine subclinical mastitis were resistant to several classes of antibiotics, showing the ability to form biofilms in milk and invade mammary epithelial cells, suggesting an advantageous feature in mammary gland colonization during mastitis development. In addition, they can spread along the food chain by different routes and eventually constitute a possible threat for public health, including E. mundtii specie.

Validation of the online PREDICT tool in a cohort of early breast cancer in Brazil

PREDICT is a tool designed to estimate the benefits of adjuvant therapy and the overall survival of women with early breast cancer. The model uses clinical, histological, and immunohistochemical variables. This study aimed to evaluate the model's performance in a Brazilian population. We assessed the discrimination and calibration of the PREDICT model to estimate overall survival (OS) in five and ten years of follow-up in a cohort of 873 women with early breast cancer diagnosed from January 2001 to December 2016. A total of 743 patients had estrogen receptor (ER)-positive and 130 had ER-negative tumors. The area under the receiver operating characteristic (ROC) curve (AUC) for discrimination was 0.72 (95%CI: 0.66-0.78) at five years and 0.67 (95%CI: 0.61-0.72) at ten years for women with ER-positive tumors. The AUC was 0.72 (95%CI: 0.62-0.81) at five years and 0.67 (95%CI: 0.54-0.77) at ten years for women with ER-negative tumors. The predicted survival in ER-positive tumors was 91.0% (95%CI: 90.2-91.6%) at five years and 79.3% (95%CI: 77.7-81.0%) at ten years, and the observed survival 90.7% (95%CI: 88.6-92.9%) and 77.2% (95%CI: 73.4-81.4%), respectively. The predicted survival in ER-negative tumors was 84.5% (95%CI: 82.5-86.6%) at five years and 75.0% (95%CI: 71.6-78.5%) at ten years, and the observed survival 76.3% (95%CI: 69.1-84.3%) and 67.9% (95%CI: 58.6-78.6%), respectively. In conclusion, PREDICT was accurate to estimate OS in women with ER-positive tumors and overestimated the OS in women with ER-negative tumors.

Safety of assisted reproductive techniques in young women harboring germline pathogenic variants in BRCA1/2 with a pregnancy after prior history of breast cancer.

BACKGROUND: Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants. PATIENTS AND METHODS: This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy. RESULTS: Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group. CONCLUSION: This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing.

Dietary nucleotide supplementation as an alternative to in-feed antibiotics in weaned piglets.

Nucleotides are important to cell growth and division and are crucial to the rapid proliferation of such cells as the intestinal mucosa and immune cells. Accordingly, the nucleotide requirements of animals are high during periods of rapid growth and periods of stress like post-weaning period. Thus, nucleotide supplementation may be a possible alternative to in-feed antibiotics as growth promoter in this phase. The study aimed to evaluate dietary nucleotide supplementation as an alternative to in-feed antibiotics on performance and gut health of weaned piglets. Ninety-six 21-day-old piglets, weighing 7.44 ±â€¯0.65 kg, were allocated into 1 of 3 treatments (8 pens per treatment; 4 pigs per pen) in a 14-day trial. Dietary treatments consisted of control: corn-soybean meal-based diet; nucleotides: control +2 g/kg of a nutritional additive with purified nucleotides; and antibiotic: control +0.8 g/kg of antibiotic growth promoter based on colistin and tylosin. Performance variables and fecal score were not affected (P > 0.05) by supplementing nucleotide or antibiotic. Nucleotides treatment had similar effect to antibiotic and superior to control (P < 0.05) on enhancing duodenum villus height, jejunum crypt depth, and reduction of Paneth cellular area. Duodenum and ileum of animals supplemented with nucleotides or antibiotics had higher (P < 0.05) number of proliferating cells than did those of control animals, whereas the jejunum of animals that received antibiotic diets presented more (P < 0.05) proliferating cells than either the nucleotides or control animals. Jejunum of nucleotide-treated piglets showed a greater number of apoptotic cells than those fed antibiotic or control diets (P < 0.05). Nucleotides and antibiotic treatments decreased the B lymphocyte counts in duodenum and ileum (P < 0.05) but increased in the jejunum (P < 0.05), when compared to the control treatment. Relative abundance of mitogen-activated protein kinases-6, haptoglobin, and tumor necrosis factor-α mRNA was not influenced (P > 0.05) by treatments. In the ileal, antibiotic supplementation reduced total bacteria quantification compared to nucleotide supplementation or the control (P < 0.05), whereas nucleotides supplementation increased enterobacteria proliferation compared to the antibiotic or control diets (P < 0.05). However, nucleotides and antibiotic reduced (P < 0.05) colon total bacteria quantification when compared to control. These results suggest that the nucleotides source used to weaned piglets improved gut health by modulating the local immune response and modulating intestinal mucosa development, and, therefore, nucleotides may be an alternative to antibiotics as growth promoters.

3D alveolar in vitro model based on epithelialized biomimetically curved culture membranes.

There is increasing evidence that surface curvature at a near-cell-scale influences cell behaviour. Epithelial or endothelial cells lining small acinar or tubular body lumens, as those of the alveoli or blood vessels, experience such highly curved surfaces. In contrast, the most commonly used culture substrates for in vitro modelling of these human tissue barriers, ion track-etched membranes, offer only flat surfaces. Here, we propose a more realistic culture environment for alveolar cells based on biomimetically curved track-etched membranes, preserving the mainly spherical geometry of the cells' native microenvironment. The curved membranes were created by a combination of three-dimensional (3D) micro film (thermo)forming and ion track technology. We could successfully demonstrate the formation, the growth and a first characterization of confluent layers of lung epithelial cell lines and primary alveolar epithelial cells on membranes shaped into an array of hemispherical microwells. Besides their application in submerged culture, we could also demonstrate the compatibility of the bioinspired membranes for air-exposed culture. We observed a distinct cellular response to membrane curvature. Cells (or cell layers) on the curved membranes reveal significant differences compared to cells on flat membranes concerning membrane epithelialization, areal cell density of the formed epithelial layers, their cross-sectional morphology, and proliferation and apoptosis rates, and the same tight barrier function as on the flat membranes. The presented 3D membrane technology might pave the way for more predictive barrier in vitro models in future.

Associations of plasma lipids, lipoproteins, and cardiovascular outcomes with climatic variations in a large Brazilian population of Campinas, São Paulo state: an eight-year study

In this eight-year retrospective study, we evaluated the associations between climatic variations and the biological rhythms in plasma lipids and lipoproteins in a large population of Campinas, São Paulo state, Brazil, as well as temporal changes of outcomes of cardiovascular hospitalizations. Climatic variables were obtained at the Center for Meteorological and Climatic Research Applied to Agriculture (University of Campinas - Unicamp, Brazil). The plasma lipid databases surveyed were from 27,543 individuals who had their lipid profiles assessed at the state university referral hospital in Campinas (Unicamp). The frequency of hospitalizations was obtained from the Brazilian Public Health database (DATASUS). Temporal statistical analyses were performed using the methods Cosinor or Friedman (ARIMA) and the temporal series were compared by cross-correlation functions. In normolipidemic cases (n=11,892), significantly different rhythmicity was observed in low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol (C) both higher in winter and lower in summer. Dyslipidemia (n=15,651) increased the number and amplitude of lipid rhythms: LDL-C and HDL-C were higher in winter and lower in summer, and the opposite occurred with triglycerides. The number of hospitalizations showed maximum and minimum frequencies in winter and in summer, respectively. A coincident rhythmicity was observed of lower temperature and humidity rates with higher plasma LDL-C, and their temporal series were inversely cross-correlated. This study shows for the first time that variations of temperature, humidity, and daylight length were strongly associated with LDL-C and HDL-C seasonality, but moderately to lowly associated with rhythmicity of atherosclerotic outcomes. It also indicates unfavorable cardiovascular-related changes during wintertime.

Outcome of radiotherapy for invasive bladder cancer in older patients - not candidates for or decline cystectomy.

PURPOSE: Retrospective study to assess the role of radiotherapy (RT) in bladder cancer (BC) in patients who decline cystectomy or for whom it was contraindicated, regarding BC related events. MATERIALS AND METHODS: A cross-sectional study, of patients with BC treated with RT, with or without chemotherapy was carried out, during the period March 2005 to March 2017, excluding patients who performed cystectomy. BC-related events were defined as haematuria, episodes requiring intravesical irrigations or transurethral resection or admission in Urology Department caused by symptoms related to BC. RESULTS: Fifty-eight patients were included, 44 men and 14 women, whose median age at diagnosis was 78.3 years. Nine patients were treated with a RT dose below 50Gy (20-45Gy), in relation with non-resectable disease, nodal involvement, presence of metastasis or poor performance status. Forty-nine patients were treated with a RT dose above 50Gy (maximum 60.4Gy). The median follow-up time was 24 months, with BC-specific survival at 1/5 years of 87.5%/0.0% and 83.1%/33.9% in the group treated with RT dose below 50Gy and above 50Gy, respectively. Results revealed that the number of events decreased significantly after RT for both groups. For the two groups, the median of events before RT was 2.0, decreasing for 1.0 after RT (RT dose<50Gy: P=0.011; RT dose≥50Gy: P=0.026). CONCLUSION: This therapeutic approach can have an important role in older patients with bladder cancer, in terms of reducing disease related events. Symptom control was significantly achieved in both therapeutic groups.

Effect of Rolipram on in vitro maturation, gene expression and embryonic development in bovines / Efeito de rolipram na maturação in vitro, expressão gênica e desenvolvimento embrionário em bovinos

The aim of this work was to evaluate the effect of the Rolipram during the maturation of bovine oocytes and gene expression of embryos produced in vitro. Bovine ovaries were collected in slaughterhouse. The COCs were selected and divided into 5 groups: Control 0 time; Control: IVM for 24 hours; Rolipram treatments with IVM blocking for 24 hours in maturation medium containing (100, 150 and 200µM). After 24 hours all groups were reseated in IVM for another 24 hours. Subsequently COCs were subjected to the same IVM system and fertilized, being checked for cleavage post fertilization and for blastocyst. In addition, performed expression of the following genes: Mater, BMP15 and Bax. No difference was found in gene expression. Of oocytes evaluated shortly after follicular aspiration, 79.00% were in GV, GVBD, MI, while 13.40%, were in MII and 7.60%, D/NI. Significant difference was observed in different concentrations (T100, T200 and T150µM) in oocytes that have reached the MII phase compared to control treatments (P= 0.003). Differences were observed in cleavage rate (P< 0.05) between T150 and T200 when compared to the C/24 Group. A high difference was observed on blastocyst rate (P< 0.001) among treatments compared to the control group.(AU)

O objetivo deste trabalho foi avaliar o efeito do rolipram durante a maturação de oócitos bovinos, expressão gênica e embriões produzidos in vitro. Os ovários bovinos foram coletados no matadouro. Os COCs foram selecionados e divididos em cinco grupos: controle 0 tempo; controle: MIV por 24 horas; tratamentos rolipram com bloqueio MIV por 24 horas em meio de maturação contendo 100, 150 e 200µM. Após 24 horas, todos os grupos foram recolocados em MIV por mais 24 horas. Subsequentemente COCs foram submetidos ao mesmo sistema MIV e fertilizados, sendo avaliada a taxa de clivagem e de blastocisto, além da expressão dos seguintes genes: Mater, BMP15 e Bax. Nenhuma diferença foi observada na expressão gênica. Dos oócitos avaliados logo após a aspiração folicular, 79,0% estavam em GV, GVBD, MI, enquanto 13,40% estavam em MII, e 7,60% em D/NI. A diferença significativa foi observada em diferentes concentrações (T100, T200 e T150µM) em oócitos que atingiram a fase MII em comparação aos tratamentos de controle (P=0,3). Diferenças foram observadas nas taxas de clivagem (P<0,5) entre T150 e T200 quando comparadas com as taxas do grupo C/24. Uma grande diferença foi observada na taxa de blastocisto (P<0,1) entre os tratamentos em relação ao grupo controle.(AU)

Colorectal tumor-on-a-chip system: A 3D tool for precision onco-nanomedicine.

Awareness that traditional two-dimensional (2D) in vitro and nonrepresentative animal models may not completely emulate the 3D hierarchical complexity of tissues and organs is on the rise. Therefore, posterior translation into successful clinical application is compromised. To address this dearth, on-chip biomimetic microenvironments powered by microfluidic technologies are being developed to better capture the complexity of in vivo pathophysiology. Here, we describe a "tumor-on-a-chip" model for assessment of precision nanomedicine delivery on which we validate the efficacy of drug-loaded nanoparticles in a gradient fashion. The model validation was performed by viability studies integrated with live imaging to confirm the dose-response effect of cells exposed to the CMCht/PAMAM nanoparticle gradient. This platform also enables the analysis at the gene expression level, where a down-regulation of all the studied genes (MMP-1, Caspase-3, and Ki-67) was observed. This tumor-on-chip model represents an important development in the use of precision nanomedicine toward personalized treatment.

Avaliação psicométrica em português do indicador de dor crônica de Helsinki em cães com sinais crônicos de osteoartrite / Psychometric testing in Portuguese of Helsinki's chronic pain index for dogs with chronic signs of osteoarthritis

Objetivou-se determinar a validade, a confiabilidade e a sensibilidade do indicador de dor crônica de Helsinki (IDCH) em português, além de estabelecer correlação entre a plataforma de pressão em cães com displasia coxofemoral (DCF). O questionário foi preenchido por tutores de 40 animais com DCF e por 16 tutores de cães saudáveis. Os animais com DCF foram tratados com carprofeno 4,4mg/kg (GT= 21) ou placebo (GP= 19), administrados uma vez ao dia, durante quatro semanas. A avaliação consistiu no preenchimento do questionário (IDCH), na escala analógica visual de dor (EAVdor) e na escala analógica visual de locomoção (EAVloc) com duas semanas (A1) e imediatamente antes do tratamento (A2), duas (S2) e quatro (S4) semanas de tratamento e após duas semanas do término do tratamento (S6). A consistência interna dos dados foi considerada excelente (alfa de Cronbach = 0,89). Houve correlação moderada entre o IDCH e a EAVdor e boa entre o IDCH e a EAVloc, porém não houve diferença entre o grupo tratado com carprofeno e placebo no IDCH. Não houve correlação entre os dados da plataforma de pressão e o IDCH. O questionário apresentou validade de constructo, critério e fidedignidade e pode-se empregá-lo em países de língua portuguesa em cães com osteoartrite.(AU)

We aimed to determine validity, reliability, and sensitivity of Helsinki's chronic pain index (HCPI) and stablish a correlation between HCPI in dogs with hip dysplasia (HD) using pressure sensitive walkway. Forty-owners of dogs with HD and 16 owners of health dogs filled a questionnaire. Dogs with HD were treated with carprofen 4.4mg/kg (GT n= 21) or with placebo (GP n= 19), both were administered once a day for 4 weeks. Evaluation was performed by the owners using the questionnaire (HCPI), the Visual Analogue Scale for pain (VASpain) and the VAS for locomotion (VASloc). The evaluation was performed 2 weeks before the treatment began (A1), immediately after treatment (A2), two (S2), four (S4) and two weeks after the end of treatment (S6) and the lameness was evaluated by pressure sensitive walkway. The internal consistency of the data was considered excellent (Cronbach´α coefficient= 0.89). There was a moderate correlation between the HCPI and VASpain. For VASloc the correlation was good. However, there was no difference between treatments, indicating low sensibility. No correlation was observed between pressure sensitive walkway and HCPI. We concluded that the questionnaire has construct and criterion validity, reliability and can be applied in dogs with osteoarthritis in Portuguese-speaking countries.(AU)

Peripheral perfusion index does not accurately reflect hypoperfusion in healthy dogs undergoing elective ovariohysterectomy.

This study evaluated the variability of the peripheral perfusion index (PI) in 22 anaesthetised female dogs undergoing elective ovariohysterectomy and examined the relationship between peripheral PI and heart rate, blood pressure, blood pH, end tidal CO2 (EtCO2), O2 saturation (SpO2), core-peripheral temperature gradient (ΔTc-p), partial pressure of CO2 (PCO2), and concentrations of glucose, cortisol, lactate and bicarbonate (HCO3-). Blood pH, lactate and glucose concentrations were determined 15, 30, 45min into the ovariohysterectomy procedure and after extubation. Cortisol concentrations were assessed before anaesthesia and after extubation. Other variables were recorded at every 5min throughout the ovariohysterectomy procedure. Hyperglycaemia was observed in 59% of bitches during surgery, but serum cortisol concentrations remained unchanged. Most measures of perfusion (ΔTc-p, pH, PCO2, EtCO2, SpO2) and heart rate remained unchanged throughout anaesthesia and did not correlate with peripheral PI. Mean arterial pressure increased during the ovariohysterectomy procedure, while peripheral PI decreased, resulting in negative correlations between these variables at 30 and 45min. Lactate concentrations decreased from baseline to the time of measurement post-extubation. Peripheral PI gradually decreased during the ovariohysterectomy procedure, probably reflecting vasoconstriction induced by nociceptive stimuli. Using lactate concentrations as the reference standard for peripheral perfusion, low peripheral PI in healthy bitches undergoing ovariohysterectomy might not represent peripheral hypoperfusion.

Tumor metabolism assessed by FDG-PET/CT and tumor proliferation assessed by genomic grade index to predict response to neoadjuvant chemotherapy in triple negative breast cancer.

PURPOSE: Survival is increased when pathological complete response (pCR) is reached after neoadjuvant chemotherapy (NAC), especially in triple-negative breast cancer (TNBC) patients. Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG) and the genomic grade index (GGI), each separately, showed good potential to predict pCR. Our study was designed to evaluate the predictive value for the therapeutic response of a combination of parameters based on FDG-PET, histoclinical features and molecular markers of proliferation. METHODS: Molecular parameters were measured on pre-treatment biopsy. Tumor metabolic activity was measured using two PET/CT scans, one before and one after 2 cycles of NAC. The pCR was determined on specimen after NAC. Event-free survival (EFS) was estimated using the Kaplan Meier method. RESULTS: Of 55 TNBC patients, 19 (35%) reached pCR after NAC. Tumor grade and Ki67 were not associated with pCR whereas GGI (P = 0.04) and its component KPNA2 (P = 0.04) showed a predictive value. The change of FDG uptake between PET1 and PET2 (ΔSUVmax) was highly associated with pCR (P = 0.0001) but the absolute value of baseline SUVmax was not (P = 0.11). However, the AUC of pCR prediction increased from 0.63 to 0.76 when baseline SUVmax was combined with the GGI (P = 0.016). The only two parameters associated with EFS were ΔSUVmax (P = 0.048) and pathological response (P = 0.014). CONCLUSIONS: The early tumor metabolic change during NAC is a powerful parameter to predict pCR and outcome in TNBC patients. The GGI, determined on pretreatment biopsy, is also predictive of pCR and the combination GGI and baseline SUVmax improves the prediction.