Challenging the Dogma: Stage migration or negative lymph nodes, which of them is the main player on gastric cancer prognosis?

Expanding loco-regional nodes harvesting is expected to increase survival. This improvement may be associated to stage migration (SM). However, the great bulk of harvested lymph nodes observed in large dissections is negative. M&M: 830 patients who received R0 gastrectomy for adenocarcinoma were included. pN+ patients with <26 nodes (n = 209) were included for a simulation to "offer 26 nodes" - SM (proportional and exponential based) was simulated and analysed through machine learning algorithms. Overall Survival (OS), in native and simulated stages, were compared. OS of extended lymphadenectomies (pN+, D ≥ 26, n = 273) was compared with the simulated curves. OS of patients in the following dissection intervals of negative nodes were compared: <16 (n = 233), 16-25 (n = 258), ≥26 (n = 339). RESULTS: After simulation to 26 nodes (pN+, D < 26 patients, n = 209), staging was recomputed. OS of native vs simulated early-stages (I-II) and advanced stages (III) were not different (p > 0.05). OS of patients with lymphadenectomy (≥26) was better than simulated for early and advanced stages (p = 0.008; p = 0.005). OS of patients included in distinct intervals of negative lymph nodes were different (p < 0.001). These intervals were an independent prognostic factor (multivariate analysis). CONCLUSIONS: The influence of Stage Migration was null in this set of simulations and Will Rogers phenomenon was not observed. Extended dissection performed better in OS. But the influence of the number of negative nodes, even in large dissections, was highlighted. By emphasizing the role of negative nodes, we aim to facilitate more informed decision-making in management of gastric cancer patients, ultimately leading to improved treatment outcomes and patient care.

Hepatocellular Carcinoma in Ceará: Epidemiology and Treatment in a Reference Liver Transplant Center in Northeast Brazil.

Hepatocellular carcinoma remains a significant worldwide malignancy and an important cause of cancer-related death. The incidence is increasing globally. In Latin America, there is no consistent data on the epidemiology of hepatocellular carcinoma. However, Brazil is considered a country with an intermediate incidence of this liver neoplasm. In the state of Ceará, situated in the northeast region of Brazil, there are no consistent clinical and epidemiologic data on the actual incidence and the treatment of hepatocellular carcinoma. The purpose of this article is to describe epidemiologic characteristics and treatment forms of patients with hepatocellular carcinoma who were treated in a Liver Transplant Center. A retrospective observational study was conducted using the database from the register of 299 patients with hepatocellular carcinoma between June 2004 and February 2022. Only patients born in Ceará were included. Therefore, most patients were eligible, based on the Milan Criteria, to undergo liver transplantation with a Model End Stage Liver Disease score of 12.48 ± 4.66 points, and the waiting list time was approximately 7 months with 8.7% hepatocellular carcinoma recurrence after liver transplant. A total of 38.5 % of cases were outside the Milan criteria at the time of cancer diagnosis, and transarterial chemoembolization was the main treatment choice. In conclusion, the diagnosis of hepatocellular carcinoma in Ceará mainly occurs in male patients with hepatitis C or alcoholism, with a mean age of 61.55 years and a previous diagnosis of liver disease. Liver transplantation was the best curative therapeutic form in patients with cirrhosis and hepatocellular carcinoma in Ceará, where a significant number of patients were diagnosed with intermediate and advanced-stage hepatocellular carcinoma, so public health policies are important for the screening and monitoring of liver disease.

Unresectable stage III non-small cell lung cancer: Insights from a Portuguese expert panel.

INTRODUCTION: The management of unresectable stage III non-small cell lung cancer (NSCLC) is clinically challenging and there is no current consensus on optimal strategies. Herein, a panel of Portuguese experts aims to present practical recommendations for the global management of unresectable stage III NSCLC patients. METHODS: A group of Portuguese lung cancer experts debated aspects related to the diagnosis, staging and treatment of unresectable stage III NSCLC in light of current evidence. Recent breakthroughs in immunotherapy as part of a standard therapeutic approach were also discussed. This review exposes the major conclusions obtained. RESULTS: Practical recommendations for the management of unresectable stage III NSCLC were proposed, aiming to improve the pathways of diagnosis and treatment in the Portuguese healthcare system. Clinical heterogeneity of patients with stage III NSCLC hinders the development of single standardised algorithm where all fit. CONCLUSIONS: A timely diagnosis and a proper staging contribute to the best management of each patient, optimizing treatment tolerance and effectiveness. The expert panel considered chemoradiotherapy as the preferable approach when surgery is not possible. Management of adverse events and immunotherapy as a consolidation therapy are also essential steps for a successful strategy.

Cardiovascular and metabolic comorbidities in patients with thyroid nodules: the impact of incidental diagnosis.

PURPOSE: The prevalence of thyroid nodules (TN) in the general population has increased as screening procedures are implemented and an association with metabolic and cardiovascular disorders has been reported. The aim of this study was to investigate the reason leading to the diagnosis of TN and to compare the clinical characteristics of patients diagnosed incidentally with those of patients diagnosed for thyroid-related reasons. METHODS: We designed a retrospective cross-sectional study including consecutive patients with TN from two high-volume hospital-based centers for thyroid diseases (Pavia and Messina) in Italy. Data regarding reason leading to TN diagnosis, age, sex, BMI, presence of cardio-metabolic comorbidities were collected. RESULTS: Among the 623 enrolled subjects, the US diagnosis of TN was prompted by thyroid-related reasons in 421 (67.6%, TD group) and incidental in 202 (32.4%, ID group) with a similar distribution in the two centers (p = 0.960). The ID group patients were more frequently males (38.6% vs 22.1%, p < 0.001) and significantly older (58.9 ± 13.7 vs 50.6 ± 15.5 years, p < 0.001) than the TD group ones, and had a higher rate of cardiovascular comorbidities (73.8% vs 47.5%, p < 0.001), despite having a similar BMI (27.9 ± 5.2 vs 27.8 ± 13.5, p = 0.893). CONCLUSIONS: Stratification of patients with TN according to the diagnostic procedure leading to diagnosis allows a better epidemiological characterization of this inhomogeneous and large population.

Modification of [18F]-FDG PET/CT imaging protocols in obese oncology patients: A nationwide survey.

INTRODUCTION: The use of medical imaging for diagnosis, staging and follow-up in Oncology context is incredibly important, being the use of [18F]-FDG PET/CT particularly advantageous in specific contexts like the case of obese patients. However, imaging the latter can be challenging sometimes, since their own body size may affect overall image quality and adds technical difficulties for the operator(s) performing the examination. METHODS: This research project was developed with the aim of analysing the current personal practices of Portuguese Nuclear Medicine Technologists (NMTs) in the adaptation of 18F-FDG PET/CT oncological protocols for obese patients and comparing the results with parameters referenced in literature. A non-experimental research study was conducted using a survey delivered online to NMTs through social media platforms (Facebook® and LinkedIn®) and by sending the link directly to contacts within the research team professional and personal networks. RESULTS: Answers from a total of 26 participants were obtained, with 88.5% of participants admitting modifying technical protocols in examinations for obese patients. Changes in PET protocols included an increase in the administered activity (60.9%), an increase in scan time per individual bed position (69.6%) and the use of Time-of-Flight (TOF) technology whenever available. Protocol changes in CT included increasing the mA (82.6%), raising the KVp (47.8%), the application of iterative reconstruction (69.6%) and the use of automatic exposure control (AEC) (52.2%). The remaining parameters (pitch, algorithm, slice thickness, display FOV, gantry rotation time and energy acceptance window) were claimed not to be modified by around 90% of professionals. CONCLUSION: Portuguese NMTs tend to change the [18F]-FDG PET/CT protocols for obese patients. However, while some of the parameters appear to be contradictory or redundant, others require further optimisation, especially in the CT component. IMPLICATIONS FOR PRACTICE: Efforts should be made to optimize acquisition protocols used in [18F]-FDG PET/CT scans for obese patients.

The effects of TiO2 nanotubes on bond strength and radiopacity of a self-adhesive resin cement in self-curing mode / Os efeitos de nanotubos de TiO2 na resistência de união e radiopacidade de um cimento resinoso auto-adesivo no modo auto-polimerizável

Objective: The aim of this in vitro study w as t o analyze the influence of the titanium dioxide nanotubes i n a self-cure mode polymerization of a dual resin luting agent through push out bond strength and radiopacity tests. Material and Methods: After mixed with a commercial du al self-adhesive resin cement, three concentrations o f tit anium dioxide nanotubes (0.3, 0.6, and 0.9% by weight) we re analyzed in self-curing mode. T he bond strength to bovine root dentin and fi berglass posts was assessed with the push out bond str ength t est and was evaluated in three thirds (cervical, middle and apical) (n=10), followed by failure mode analysis (SEM), and the ISO standard 9917-2 was followed for radiopacity test (n=10). Data were statistically analyzed by one-way ANOVA test, followed by Tukey's test (α=0.05). Results: Reinforced self-adhesive resin cement with 0.6% titanium dioxide nanotubes showed significant difference compared to the control gr oup for push out test (p=0.00158). The modified groups did not s how significant difference among thirds (p=0.782). Radiopacity sh owed higher value for group w ith 0.9% titanium dioxide nanotubes in comparison w ith control group (p<0.001). Conclusion: The addition of titanium dioxide nanotubes to a self-adhesive resin cement increased the bond strength to dentin and radiopacity values in the self-cure polymerization mode (AU)

Objetivo: O objetivo deste estudo in vitro foi analisar a influência de nanotubos de dióxido de titânio na polimerização química de um agente cimentante resinoso dual através de testes de resistência à união e radiopacidade. Material e Métodos: Após misturado com um cimento resinoso auto-adesivo comercial, três concentrações de nanotubos de dióxido de titânio (0,3, 0,6 e 0,9% em peso) foram analisadas. A resistência da união para a dentina da raiz bovina e os pinos de fibra de vidro foi avaliada pelo teste de push-out e avaliada em três terços (cervical, médio e apical) (n = 10), seguido pelo análise de modo de falha (MEV) e a norma ISO 9917-2 foi seguido para teste de radiopacidade (n = 10). Os dados foram analisados estatisticamente pelo teste ANOVA um fator seguido do teste de Tukey (α = 0,05). Resultados: O cimento resinoso auto-adesivo reforçado com nanotubos de dióxido de titânio a 0,6% mostrou diferença significativa em comparação com o grupo controle para teste de push-out (p=0,00158). Os grupos modificados não mostraram diferença significativa entre os terços (p=0,782). A radiopacidade mostrou maior valor para o grupo com nanotubos de dióxido de titânio 0,9% em comparação com o grupo controle (p<0,001). Conclusão: A adição de nanotubos de dióxido de titânio a um cimento resinoso auto-adesivo aumentou a os valores de resistência de união à dentina e radiopacidade no modo de polimerização química do agente cimentante (AU)

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.

Can a ToF-PET photon attenuation reconstruction test stopping-power estimations in proton therapy? A phantom study.

Objective. The aim of the phantom study was to validate and to improve the computed tomography (CT) images used for the dose computation in proton therapy. It was tested, if the joint reconstruction of activity and attenuation images of time-of-flight PET (ToF-PET) scans could improve the estimation of the proton stopping-power.Approach. The attenuation images, i.e. CT images with 511 keV gamma-rays (γCTs), were jointly reconstructed with activity maps from ToF-PET scans. Theß+activity was produced with FDG and in a separate experiment with proton-induced radioactivation. The phantoms contained slabs of tissue substitutes. The use of theγCTs for the prediction of the beam stopping in proton therapy was based on a linear relationship between theγ-ray attenuation, the electron density, and the stopping-power of fast protons.Main results. The FDG based experiment showed sufficient linearity to detect a bias of bony tissue in the heuristic look-up table, which maps between x-ray CT images and proton stopping-power.γCTs can be used for dose computation, if the electron density of one type of tissue is provided as a scaling factor. A possible limitation is imposed by the spatial resolution, which is inferior by a factor of 2.5 compared to the one of the x-ray CT.γCTs can also be derived from off-line, ToF-PET scans subsequent to the application of a proton field with a hypofractionated dose level.Significance. γCTs are a viable tool to support the estimation of proton stopping with radiotracer-based ToF-PET data from diagnosis or staging. This could be of higher potential relevance in MRI-guided proton therapy.γCTs could form an alternative approach to make use of in-beam or off-line PET scans of proton-inducedß+activity with possible clinical limitations due to the low number of coincidence counts.

Core outcome set for surgical trials in gastric cancer (GASTROS study): international patient and healthcare professional consensus.

BACKGROUND: Surgery is the primary treatment that can offer potential cure for gastric cancer, but is associated with significant risks. Identifying optimal surgical approaches should be based on comparing outcomes from well designed trials. Currently, trials report different outcomes, making synthesis of evidence difficult. To address this, the aim of this study was to develop a core outcome set (COS)-a standardized group of outcomes important to key international stakeholders-that should be reported by future trials in this field. METHODS: Stage 1 of the study involved identifying potentially important outcomes from previous trials and a series of patient interviews. Stage 2 involved patients and healthcare professionals prioritizing outcomes using a multilanguage international Delphi survey that informed an international consensus meeting at which the COS was finalized. RESULTS: Some 498 outcomes were identified from previously reported trials and patient interviews, and rationalized into 56 items presented in the Delphi survey. A total of 952 patients, surgeons, and nurses enrolled in round 1 of the survey, and 662 (70 per cent) completed round 2. Following the consensus meeting, eight outcomes were included in the COS: disease-free survival, disease-specific survival, surgery-related death, recurrence, completeness of tumour removal, overall quality of life, nutritional effects, and 'serious' adverse events. CONCLUSION: A COS for surgical trials in gastric cancer has been developed with international patients and healthcare professionals. This is a minimum set of outcomes that is recommended to be used in all future trials in this field to improve trial design and synthesis of evidence.

Developing and implementing a multi-modality imaging optimization study in paediatric radiology: Experience and recommendations from an IAEA coordinated research project.

Optimization of imaging examinations is a key requirement of both the International and European Basic Safety Standards, and the focus of much international activity. Although methodologies are well established in principle, there continues to be a variety of practical issues both in collecting and interpreting dose and image quality data and in making successful interventions to optimize exposures. A Coordinated Research Project, involving institutes from ten different countries, was established by the IAEA to assess the efficacy of recommended optimization methodologies in the field of paediatric radiology and to derive practical guidance on their implementation. The steps followed in this process were identification of the imaging process to be investigated (abdomen and chest x-rays, micturating cysto-urethrograms, and brain & thorax CT scans); collection of dose and image quality data; evaluation and comparison of the data between institutes and to standards; identification and implementation of interventions for optimization; and re-evaluation of dose and image quality parameters. The project succeeded both in achieving effective interventions for optimization of specific imaging tasks in individual institutes and in identifying key issues with potential to handicap this process. The main area in which problems were encountered was in the collation of reliable dose and image quality data. The reasons for this were explored and a series of recommendations have been made, summarized into 'ten practical tips' for optimization to assist institutes, particularly those in the early stages of addressing optimization issues.

Influence of different periods of pre-slaughter fasting on microbiological quality of bullfrog carcasses (Lithobates catesbeianus) / [Influência de diferentes períodos de jejum pré-abate na qualidade microbiológica de carcaças de rã-touro (Lithobates catesbeianus)]

The aim of this study was to evaluate the influence of different periods of pre-slaughter fasting (F1: 2 to 24 hours and F2: 48 to 72 hours) on the counts of hygiene indicator microorganisms and the presence of Salmonella spp. in carcasses of bullfrogs. Two different stages of the slaughter process were analyzed: after bleeding (A) and after the final carcasses cleaning (B). Samples from each fasting period were analyzed to count hygiene indicator microorganisms (n=30) and Salmonella spp. (n=140). For aerobic mesophilic microorganisms, the variation in fasting periods caused a reduction of 0.69 log10 CFU / g (P<0.05) in F2 when compared to F1 at point B of the slaughter. Coliforms at 35º C and Escherichia coli showed no differences (P >0.05) between the fasting analyzed periods. Considering the presence of E. coli, it was observed that F2 resulted in a reduction of 30% (P<0.05) positivity on point B. For Salmonella spp., the results showed that F2 contributed to an 11.5% reduction in the presence of this bacteria at point B. (P<0.05). Therefore, it is concluded that 48 to 72 hours of pre-slaughter fasting resulted in a positive impact on the microbiological quality of bullfrog carcasses.(AU)

O objetivo deste estudo foi avaliar a influência de diferentes períodos de jejum pré-abate (F1: duas a 24 horas e F2: 48 a 72 horas) nas contagens de micro-organismos indicadores de higiene e na presença de Salmonella spp. em carcaças de rãs-touro. Foram analisadas duas etapas do processo de abate: após a sangria (A) e após a toalete final da carcaça (B). As amostras de cada período de jejum foram utilizadas para contagem de indicadores de higiene (n = 30) e Salmonella spp. (n = 140). Para aeróbios mesófilos, a variação no tempo de jejum causou uma redução de 0,69 log10 UFC/g (P<0,05) em F2 quando comparado a F1 na etapa B do abate. Os coliformes a 35ºC e Escherichia coli não apresentaram diferenças (P>0,05) entre os dois períodos de jejum analisados. Considerando a presença de E. coli, F2 resultou em uma redução de 30% (P<0,05) de positividade na etapa B. Para Salmonella spp., os resultados mostraram que F2 contribuiu para uma redução de 11,5% na presença desse micro-organismo na etapa B. Portanto, conclui-se que 48 a 72 horas de jejum pré-abate tiveram um impacto positivo na qualidade microbiológica das carcaças de rã-touro.(AU)

[Validation of a new self-questionnaire to assess sexuality in patients operated on for urinary incontinence or genital prolapse (Pelvi-Perineal Surgery Sexuality Questionnaire - PPSSQ)]. / Validation d'un nouvel auto-questionnaire d'évaluation de la sexualité chez les patientes opérées d'une incontinence urinaire ou d'un prolapsus génital (Pelvi-Perineal Surgery Sexuality Questionnaire ­ PPSSQ).

INTRODUCTION: The main objective of this study was to validate a new questionnaire evaluating sexual health, in a population of sexually active women or not, who have surgery for stress urinary incontinence or pelvic organ prolapse with or without mesh reinforcement. MATERIAL AND METHODS: After the development of a first version of the questionnaire by members from the main French societies involved in the study of women's sexuality, a linguistic validation of the content of the questionnaire was carried out through semi-structured interviews. Then, a psychometric validation was carried out in a prospective multicenter cohort study. The questionnaire was evaluated in terms of acceptability, quality, dimensionality, internal consistency, temporal stability, sensitivity to changes and construction validity. RESULTS: Linguistic validation was carried out in 25 patients. Psychometric validation was carried out in 297 women (291 with available data) operated on for urinary incontinence by midurethral sling (n=79) or for pelvic organ prolapse by the vaginal route with mesh (n=105), without mesh (n=22) or by laparoscopic sacrocolpopexy (n=85) between January 18, 2013 and January 18, 2016. Within the 288/291 women who had filed the question No. 1 allowing to know their sexual "status", 159 (55%) women were sexually active and 129 (45%) women were not sexually active before surgery. Within the 288 women, 165 had completed the questionnaire preoperatively and at 12 months and 111 had completed the questionnaire at 12 months and 12 months+1 week. The questionnaire was well accepted by the women and of good quality. All the questions were kept, but a change in the order and numbering of the questions had to be made. Two clinically relevant dimensions were identified in this analysis: a "sexual health" dimension comprising 5 questions and a "discomfort and pain" dimension comprising 3 questions. The overall questionnaire and both dimensions had good reliability and moderate to excellent temporal stability. A statistically significant association was demonstrated between question 15 and the improvement reported by PGI-I and the anatomical success rate on POP-Q classification. A strong correlation was found between the "sexual health" score and the total FSFI score. CONCLUSION: The Pelvi-Perineal Surgery Sexuality Questionnaire (PPSSQ) is a 13-question self-questionnaire validated in a population of sexually active women or not, operated on for stress urinary incontinence or pelvic organ prolapse by laparoscopy or vaginal surgery, with or without mesh. LEVEL OF EVIDENCE: 4.

Iron triggers the early stages of cartilage degeneration in vitro: The role of articular chondrocytes.

Objective: Arthropathy is a major clinical problem in patients with hemochromatosis, the most common genetic disorder of iron overload. The pathological features of hemochromatosis arthropathy (HA) are heterogeneous and its specific nature remains unknown. One important drawback is the lack of proper in vitro models. The aim of the present study was to set up a model to investigate the biological response of cartilage to iron exposure. Design: Bovine articular cartilage explants were incubated with ferric citrate for up to 9 days. We evaluated chondrocyte viability, iron deposition, and biomarkers of cartilage degradation in the conditioned medium. Results: Iron accumulated within chondrocytes, which was associated with programmed cell death through chondroptosis. Iron treatment increased the release of sulfated glycosaminoglycans (sGAG), a component of the extracellular matrix, into the medium (p=0.0189). This was dependent on the presence of viable chondrocytes and was associated with increased activity of matrix-degrading metalloproteinases (MMP) (pro/active MMP-9, p=0.0317; pro MMP-2, p=0.0092; active MMP-2, p=0.0288). Co-treatment with the broad MMP/aggrecanase inhibitor prinomastat reduced iron-mediated sGAG release (0.02 â€‹µM, p=0.0425; 2 â€‹µM, p=0.0014), confirming that iron induces sGAG release via the activation of catabolic enzymes. Notably, iron-treated cartilage continued to release an increased amount of sGAG into the medium for 6 days after termination of the ferric citrate treatment (p=0.0259). Conclusions: Iron triggers the early stages of cartilage degeneration. Removal of iron exposure does not prevent further damage to the cartilage, thus providing a possible explanation why HA is not prevented after iron depletion by phlebotomy treatment.

DYNLT1 gene expression is downregulated in whole blood of patients at different Huntington's disease stages.

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG nucleotide expansion, which encodes the amino acid glutamine, in the huntingtin gene. HD is characterized by motor, cognitive, and psychiatric dysfunctions. In a previous study, we showed by qPCR that some genes altered in an HD mouse model were also altered in blood of HD patients. These alterations were mainly with respect to the dynein family. Therefore, this study aimed to investigate whether dynein light chain Tctex type 1 (DYNLT1) is altered in HD patients and if there is a correlation between DYNLT1 gene expression changes and disease progression. We assessed the DYNLT1 gene expression in the blood of 19 HD patients and 20 healthy age-matched controls. Also, in 6 of these patients, we analyzed the DYNLT1 expression at two time points, 3 years apart. The DYNLT1 gene expression in the whole blood of HD patients was significantly downregulated and this difference was widened in later stages. These data suggest that DYNLT1 could emerge as a peripheral prognostic indicator in HD and, also, might be a target for potential intervention in the 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.

Circulating microRNAs associated with liver fibrosis in chronic hepatitis C patients.

A major challenge in hepatitis C research is the detection of early potential for progressive liver disease. MicroRNAs (miRNAs) are small RNAs that regulate gene expression and can be biomarkers of pathological processes. In this study, we compared circulating miRNAs identified in hepatitis C virus (HCV)-infected patients presenting two extremes of liver disease: mild/moderate fibrosis and cirrhosis. The patients in the cirrhosis group subsequently developed hepatocellular carcinoma (HCC). We identified 163 mature miRNAs in the mild/moderate fibrosis group and 171 in the cirrhosis group, with 144 in common to both groups. Differential expression analysis revealed 5 upregulated miRNAs and 2 downregulated miRNAs in the cirrhosis group relative to the mild/moderate fibrosis group. Functional analyses of regulatory networks (target gene and miRNA) identified gene categories involved in cell cycle biological processes and metabolic pathways related to cell cycle, cancer, and apoptosis. These results suggest that the differentially expressed circulating miRNAs observed in this work (miR-215-5p, miR-483-5p, miR-193b-3p, miR-34a-5p, miR-885-5p, miR-26b-5p and miR -197-3p) may be candidates for biomarkers in the prognosis of liver disease.

Pathological Findings in Leatherback Sea Turtles (Dermochelys coriacea) During an Unusual Mortality Event in São Paulo, Brazil, in 2016.

The leatherback sea turtle (LST; Dermochelys coriacea) is highly migratory and is primarily distributed throughout tropical and subtropical regions. The LST populations found in Brazil are critically endangered. An unusual mortality event occurred between August and November 2016 with 23 LSTs stranded along a 100 km coastal segment in Iguape, Ilha Comprida and Ilha do Cardoso in southern São Paulo state. This study investigated the pathological findings and most likely causes of death of 10 LSTs. Male (n = 9) and adult (n = 9) animals predominated. All but one animal was in good body condition and all were found dead. The most prevalent gross findings were suggestive of bycatch, namely cutaneous erosions, abrasions and/or lacerations around the neck and flippers (n = 9), generalized congestion (n = 8) and pulmonary oedema (n = 6). Other prevalent gross findings were: cutaneous epibiosis by Stomatolepas elegans (n = 7); ileocecal diverticulitis (n = 7); distal oesophagitis (n = 5); and fibrinous coelomitis (n = 5). Microscopically, the most prevalent findings were: hepatic melanomacrophage centre hypertrophy or hyperplasia (n = 9); interstitial pneumonia (n = 8); multisystemic congestion (n = 6); pulmonary oedema with or without aspirated material (n = 5); adrenal coccidiosis (n = 5) with variable multiorgan involvement; and multiorgan bacterial disease (n = 5). Five animals had food ingesta (cnidarians, crustaceans) in the oesophagus or stomach; only one had evident plastic foreign bodies. Asphyxia due to entanglement in nets was the most frequently identified cause of death (n = 8); a cause of death was not identified in two animals. Our findings provide evidence of the severe negative impact of entanglement in fishing nets in LSTs, raising concerns for conservation. These findings also contribute to knowledge of the pathology of LSTs in South American populations.

Functionalizing nanoparticles with cancer-targeting antibodies: A comparison of strategies.

Standard cancer therapies sometimes fail to deliver chemotherapeutic drugs to tumor cells in a safe and effective manner. Nanotechnology takes the lead in providing new therapeutic options for cancer due to major potential for selective targeting and controlled drug release. Antibodies and antibody fragments are attracting much attention as a source of targeting ligands to bind specific receptors that are overexpressed on cancer cells. Therefore, researchers are devoting time and effort to develop targeting strategies based on nanoparticles functionalized with antibodies, which hold great promise to enhance therapeutic efficacy and circumvent severe side effects. Several methods have been described to immobilize antibodies on the surface of nanoparticles. However, selecting the most appropriate for each application is challenging but also imperative to preserve antigen binding ability and yield stable antibody-conjugated nanoparticles. From this perspective, we aim to provide considerable knowledge on the most widely used methods of functionalization that can be helpful for decision-making and design of conjugation protocols as well. This review summarizes adsorption, covalent conjugation (carbodiimide, maleimide and "click" chemistries) and biotin-avidin interaction, while discussing the advantages, limitations and relevant therapeutic approaches currently under investigation.