Predicting residual neoplasia after a non-curative gastric ESD: validation and modification of the eCura system in the Western setting: the W-eCura score.

OBJECTIVE: To evaluate the risk factors for lymph node metastasis (LNM) after a non-curative (NC) gastric endoscopic submucosal dissection (ESD) and to validate and eventually refine the eCura scoring system in the Western setting. Also, to assess the rate and risk factors for parietal residual disease. DESIGN: Retrospective multicentre multinational study of prospectively collected registries from 19 Western centres. Patients who had been submitted to surgery or had at least one follow-up endoscopy were included. The eCura system was applied to assess its accuracy in the Western setting, and a modified version was created according to the results (W-eCura score). The discriminative capacities of the eCura and W-eCura scores to predict LNM were assessed and compared. RESULTS: A total of 314 NC gastric ESDs were analysed (72% high-risk resection (HRR); 28% local-risk resection). Among HRR patients submitted to surgery, 25% had parietal disease and 15% had LNM in the surgical specimen. The risk of LNM was significantly different across the eCura groups (areas under the receiver operating characteristic curve (AUC-ROC) of 0.900 (95% CI 0.852 to 0.949)). The AUC-ROC of the W-eCura for LNM (0.916, 95% CI 0.870 to 0.961; p=0.012) was significantly higher compared with the original eCura. Positive vertical margin, lymphatic invasion and younger age were associated with a higher risk of parietal residual lesion in the surgical specimen. CONCLUSION: The eCura scoring system may be applied in Western countries to stratify the risk of LNM after a gastric HRR. A new score is proposed that may further decrease the number of unnecessary surgeries.

Endoscopic submucosal dissection of appendicular lesions is feasible and safe: a retrospective multicenter study (with video).

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is challenging for appendicular lesions. We report the outcomes of ESD in this context. METHODS: We collected data of ESD procedures for appendiceal neoplasia in a multicenter prospective registry. Main study endpoints were R0, en-bloc, and curative resection rates and adverse event rate. RESULTS: One hundred twelve patients were included, 47 (42%) with previous appendectomy. Fifty-six (50%) were Toyonaga type 3 lesions (15 [13.4%] postappendectomy). En-bloc and R0 resection rates were 86.6% and 80.4%, respectively, with no significant difference associated with different grades of appendiceal invasion (P = .9 and P = .4, respectively) or previous appendectomy (P = .3 for both). The curative resection rate was 78.6%. Additional surgery was performed in 16 cases (14.3%), including 10 (62.5%) Toyonaga type 3 lesions (P = .04). This included the treatment of 5 cases (4.5%) of delayed perforation and 1 acute appendicitis. CONCLUSIONS: ESD for appendicular lesions is a potentially safer and effective alternative to surgery for a significant proportion of patients.

Immunonutrients and intestinal microbiota: a gap in the literature.

The human intestinal microbiota is composed of a wide variety of microorganisms that play an important role in intestinal permeability, digestion, and especially, in the maturation of host's immune system. At the same time, effectiveness of immunomodulatory nutrients is known, especially in situations of stress and in strengthening body's defenses. However, the influence of the use of immunonutrients on microbiota's composition and variability is still poorly investigated. Studies indicate that the use of immunomodulators such as omega 3, glutamine, and arginine, can play a role in its modulation, through the immunological enhancement of the hosts. Therefore, this article sought to concentrate the latest evidence on the influence of the use of the main immunonutrients used in clinical practice on human gut microbiota, and their potential benefits.

Comparison of genotyping methods and toxin gene profiles of Staphylococcus aureus isolates from clinical specimens.

Staphylococcus aureus is a frequent cause of infections worldwide. Methicillin-resistant S. aureus (MRSA) is one of the main causes of Gram-positive infections, and methicillin-susceptible strains (MSSA) primarily colonize and infect community hosts. Multiple virulence factors are involved, with toxins playing a significant role in several diseases. In this study, we assess the prevalence of toxin genes in 89 S. aureus clinical isolates (31 MRSA and 58 MSSA). We evaluated the discriminatory power of the association of internal transcribed spacer-PCR (ITS-PCR) and 3'- end coa gene ( coa-PCR) when compared with other more commonly used and costly techniques. The isolates showed a high level of genetic diversity, and toxins were found in all the isolates. While most toxin classes displayed no statistically significant correlations and were equally distributed in isolates regardless of their resistance status, classic enterotoxins ( sea-see) showed a positive correlation with MSSA isolates. The combination of coa-PCR with ITS-PCR showed a discriminatory index of 0.84, discriminating 22 genotypes that agree with previously determined data by PFGE and MLST. This association between the two PCR-based methods suggests that they can be useful for an initial molecular epidemiological investigation of S. aureus in hospitals, providing significant information while requiring fewer resources.

Efficient synthesis and antitumor evaluation of 4-aminomethyl-N-arylpyrazoles: Discovery of potent and selective agents for ovarian cancer.

A new one-pot two-step sequential methodology for synthesis of novel 3-carboxyethyl 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives is reported. One-pot transformation of ß-enamino diketones and arylhydrazines generated 4-iminium-N-arylpyrazole salt intermediates in situ, which were easily transformed into 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives by NaBH3CN. The products could be isolated in the free or hydrochloride salt forms. Also, it was possible to obtain the products in the zwitterionic form by ester group hydrolysis. Furthermore, all synthesised compounds were evaluated in vitro against a panel of eight human tumor cell lines. The 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives were much more powerful than the hydrochloride and zwitterionic forms. Moreover, the results suggest that the N-aryl group at the pyrazole ring is vital for modulating antiproliferative activity. The 3-carboxyethyl 4-[(tert-butylamino)methyl]-N-phenylpyrazoles 3a-g exhibited higher inhibitory activities against OVCAR-3, with GI50 values of 0.013-8.78 µM, and lower inhibitory activities against normal human cell lines. Molecular docking was performed to evaluate the probable binding mode of 3a into active site of CDK2.

Amino acid restriction alters survival mechanisms in pancreatic beta cells: possible role of the PI3K/Akt pathway.

BACKGROUND AND AIMS: Malnutrition in the early stages of life may lead to changes in the glycemic metabolism during adulthood, such as pancreatic beta cells dysfunction and failure. Therefore, this study aimed to evaluate the effects of an in vitro amino acid restriction model on the function and viability of pancreatic beta cells. METHODS: Insulin-producing cells (INS-1E) were maintained in control or amino acid restricted culture medium containing 1 × or 0.25 × of amino acids, respectively, for 48 h. RESULTS: Amino acid restricted group showed lower insulin secretion and insulin gene expression, reduced mitochondrial oxygen consumption rate and reactive oxygen species production. Besides, amino acid restricted group also showed higher levels of endoplasmic reticulum stress and apoptosis markers and enhanced Akt phosphorylation. However, even with higher levels of apoptosis markers, amino acid restricted group did not show higher levels of cell death unless the PI3K/Akt pathway was inhibited. CONCLUSION: Amino acid restricted beta cell viability seems to be dependent on the PI3K/Akt pathway.

Maternal soy protein isolate diet during lactation programmes to higher metabolic risk in adult male offspring.

Soy consumption and its components, including its protein, are related to the beneficial effects of the lipid profile, decreased insulin resistance and glycaemia. However, the safety of the consumption of products containing phytoestrogens in critical stages of development has been questioned, since they may be associated with endocrine-metabolic dysfunctions in adult life. The purpose is to evaluate the effects of maternal dietary soy protein isolate (SPI) during lactation on the breast milk composition, body composition, lipid and glycaemic profiles, and thyroid hormones of dams and offspring at weaning (21 days) and in adulthood (150 days). Lactating rats were divided into casein control (C) and SPI diet groups. At 150 days, the SPI offspring presented lower body protein mass and total mineral content, higher serum FT4, insulin, TC and TG. Maternal consumption of SPI during lactation programmes the progeny to higher metabolic risk profile.

Amino acid restriction increases ß-cell death under challenging conditions.

Malnutrition programs metabolism, favor dysfunction of ß cells. We aimed to establish an in vitro protocol of malnutrition, assessing the effect of amino acid restriction upon the ß cells. Insulin-producing cells INS-1E and pancreatic islets were maintained in RPMI 1640 medium containing 1× (Ctl) or 0.25× (AaR) of amino acids. We evaluated several markers of ß-cell function and viability. AaR Insulin secretion was reduced, whereas cell viability was unaltered. Calcium oscillations in response to glucose increased in AaR. AaR showed lower Ins1 RNAm, snap 25, and PKC (protein kinase C) protein content, whereas phospho-eIF2α was increased. AaR cells exposed to nutrient or chemical challenges displayed higher apoptosis rates. We showed that amino acid restriction programmed ß cell and induced functional changes. This model might be useful for the study of molecular mechanisms involved with ß-cell programming helping to establish novel therapeutic targets to prevent harmful outcomes of malnutrition.

Holocene history of a lake filling and vegetation dynamics of the Serra Sul dos Carajás, southeast Amazonia.

Down-core changes in sedimentary facies, elemental geochemistry, pollen, spore, δ13C, δ15N and radiocarbon records from a filled lake, named R4, of the Serra Sul dos Carajás were used to study the relationship between the paleomorphological and paleoecological processes and their significance for Holocene paleoclimatology of the southeast Amazonia. The sediment deposition of the R4 lake started around 9500 cal yr BP. Increase of detrital components from 9500 to 7000 cal yr BP suggests high weathering of surrounding catchment rocks and soils, and deposition into the lake basin under mudflows. At that time, montane savanna and forest formation were already established suggesting predominance of wet climate. However, from 7000 to 3000 cal yr BP, a decline of detrital input occurred. Also, forest formation and pteridophytes were declined, while palms and macrophytes were remained relatively stable, indicating that water levels of the lake is likely dropped allowing the development of plants adapted to subaerial condition under drier climate conditions. After 3000 cal yr BP, eutrophication and low accommodation space lead to high lake productivity and the final stage of the lake filling respectively, and forest formation may has acquired its current structure, which suggests return of wetter climate conditions.

Structural Characterization and Biological Evaluation of 18-Nor-ent-labdane Diterpenoids from Grazielia gaudichaudeana.

The phytochemical investigation of Grazielia gaudichaudeana aerial parts yielded 15 compounds, including diterpenes, triterpenes, sterols and flavonoids. With exception to ent-kaurenoic acid diterpenes, the compounds isolated are being described for the first time in this species. Some unusual 1 H-NMR chemical shifts of 18-nor-ent-labdane (7-9) led us carry out a conformational analysis by theoretical calculations in order to support the experimental data. Moreover, due to the limitation of studies focused on pharmacological potential of Grazielia gaudichaudeana, the present study was carried out to investigate the antioxidant, antiproliferative, antiviral, antileishmanial and antimicrobial activities from the extract, fractions and isolated compounds obtained from this species. Ethyl acetate fraction showed significant activity in the antiproliferative assay, with GI50 range of 3.9 to 27.2 µg mL-1 . Dichloromethane fraction, rich in diterpenoids, inhibited all human tumor cell lines tested, and the nor-labdane 7 showed potent cytotoxic activity against glioma and ovary cancer cell lines.

Cranberry (Vaccinium macrocarpon) extract treatment improves triglyceridemia, liver cholesterol, liver steatosis, oxidative damage and corticosteronemia in rats rendered obese by high fat diet.

PURPOSE: Obese individuals have higher production of reactive oxygen species, which leads to oxidative damage. We hypothesize that cranberry extract (CE) can improve this dysfunction in HFD-induced obesity in rats since it has an important antioxidant activity. Here, we evaluated the effects of CE in food intake, adiposity, biochemical and hormonal parameters, lipogenic and adipogenic factors, hepatic morphology and oxidative balance in a HFD model. METHODS: At postnatal day 120 (PN120), male Wistar rats were assigned into two groups: (1) SD (n = 36) fed with a standard diet and (2) HFD (n = 36), fed with a diet containing 44.5% (35.2% from lard) energy from fat. At PN150, 12 animals from SD and HFD groups were killed while the others were subdivided into four groups (n = 12/group): animals that received 200 mg/kg cranberry extract (SD CE, HFD CE) gavage/daily/30 days or water (SD, HFD). At PN180, animals were killed. RESULTS: HFD group showed higher body mass and visceral fat, hypercorticosteronemia, higher liver glucocorticoid sensitivity, cholesterol and triglyceride contents and microsteatosis. Also, HFD group had higher lipid peroxidation (plasma and tissues) and higher protein carbonylation (liver and adipose tissue) compared to SD group. HFD CE group showed lower body mass gain, hypotrygliceridemia, hypocorticosteronemia, and lower hepatic cholesterol and fatty acid synthase contents. HFD CE group displayed lower lipid peroxidation, protein carbonylation (liver and adipose tissue) and accumulation of liver fat compared to HFD group. CONCLUSION: Although adiposity was not completely reversed, cranberry extract improved the metabolic profile and reduced oxidative damage and steatosis in HFD-fed rats, which suggests that it can help manage obesity-related disorders.

Factors associated with molar-incisor hypomineralisation in schoolchildren aged 8-10 years: a case-control study.

BACKGROUND: The aetiology of molar-incisor hypomineralisation (MIH) is multifactorial and may involve genetic and environmental factors. AIM: To verify the factors associated with MIH in schoolchildren from 8 to 10 years of age. DESIGN: This is a case-control study with a sample consisting of children aged 8 to 10 years, paired by gender and school type, in a ratio of 1:3. The case group included 186 children with MIH and the control included 558 children without MIH. Data were collected through a semi-structured questionnaire and clinical examination. Chi-square, linear-by-linear, Mann-Whitney, and logistic regression tests were conducted. A value of P < 0.05 was considered significant. RESULTS: The prevalence of mild MIH was 19.5%, moderate MIH 2.2% and severe MIH 3.2%. An association was observed between MIH with treatment need and a higher mean DMF-T and decayed and missing teeth (P < 0.05). According to the aetiological factors studied, mothers who presented a fever during pregnancy had a 2.54 times greater chance of having children with severe MIH than mothers who did not present a fever (P = 0.045). CONCLUSION: The presence of fever during pregnancy and the need for treatment were associated with MIH.

[Improving the complementarity of patient education proposals: Experience feedback and recommendations]. / Améliorer la complémentarité des offres d'éducation thérapeutique du patient : retour d'expérience et recommandations.

INTRODUCTION: Implementing patient education (PE) in a defined geographic area, based on a population-based approach, implies using community resources according to a logic of complementarity, in order to mitigate the risk of rupture in patient care. METHODS: The PE Resource Centre for the Ile-de-France Region convened a multidisciplinary and multi-setting meeting attended by 45 participants in order to define the ways to improve the complementarity of all available PE resources, while taking into account the diversity of patients' needs. Three working groups successively explored three dimensions: structure, processes and outcomes, in order to assess this complementarity. RESULTS: Each group worked on three aspects: PE resources; patient's health trajectory in a defined geographic area, and a multidisciplinary team approach.Participants identified various deficits: clustering and lack of visibility for PE resources, programme framing constraints and difficulties of access for patients. Nevertheless, they highlighted several positive elements emerging from their shared experience. They recommend: 1) sharing of the available resources by developing communication and multidisciplinary training and more flexible programme formats; 2) building links between stakeholders, by promoting local PE programmes, and by encouraging coordination and practice analysis; 3) using and articulating a diversity of evaluation approaches, while reinforcing the multidimensional nature of PE contributions, not only for patients but also for professionals and the healthcare system. DISCUSSION: PE Resource Centres may facilitate implementation of these recommendations by supporting a collective and dynamic approach, contributing to a reduction of social inequalities in PE access.