Unveiling the intricacies of BPA and BPS: comprehensive insights into its toxic effects using a cutting-edge microphysiological system.

Concerns over Bisphenol A (BPA) and its substitute, Bisphenol S (BPS), have led to innovative exploration due to potential adverse health effects. BPS, replacing BPA in some regions to avoid toxic impacts, remains insufficiently studied. Besides this, the organ-on-a-chip technology emerges as a transformative solution in drug discovery and chemiclas toxicity testing, minimizing costs and aligning with ethical standards by reducing reliance on animal models, by integrating diverse tissues and dynamic cell environments enhances precision in predicting organ function. Here, we employ a 3-organ-on-a-chip microfluidic device with skin, intestine, and liver cultures to assess the effects of BPA and BPS via topical and oral administration. Our evaluation focused on gene markers associated with carcinogenicity, systemic toxicity, and endocrine disruption. BPA exhibited expected absorption profiles, causing liver injury and genetic modulation in related pathways. BPS, a safer alternative, induced adverse effects on gene expression, particularly in topical absorption, with distinct absorption patterns. Our findings underscore the urgency of addressing BPA and BPS toxicity concerns, highlighting the crucial role of organ-on-a-chip technology in understanding associated health risks. The study promotes the organ-on-a-chip methodology as a valuable tool for safe drug development and disease treatments, offering a novel liver toxicity screening alternative to traditional animal tests. This contributes to advancing comprehension of the biological effects of these compounds, fostering improved safety assessments in human health.

Study of nitrogen heterocycles as DNA/HSA binder, topoisomerase inhibitors and toxicological safety.

Four new nitrogen-containing heterocyclic derivatives (acridine, quinoline, indole, pyridine) were synthesized and their biological properties were evaluated. The compounds showed affinity for DNA and HSA, with CAIC and CAAC displaying higher binding constants (Kb) of 9.54 × 104 and 1.06 × 106, respectively. The fluorescence quenching assay (Ksv) revealed suppression values ranging from 0.34 to 0.64 × 103 M-1 for ethidium bromide (EB) and 0.1 to 0.34 × 103 M-1 for acridine orange (AO). Molecular docking confirmed the competition of the derivatives with intercalation probes at the same binding site. At 10 µM concentrations, the derivatives inhibited topoisomerase IIα activity. In the antiproliferative assays, the compounds demonstrated activity against MCF-7 and T47-D tumor cells and nonhemolytic profile. Regarding toxicity, no acute effects were observed in the embryos. However, some compounds caused enzymatic and cardiac changes, particularly the CAIC, which increased SOD activity and altered heart rate compared to the control. These findings suggest potential antitumor action of the derivatives and indicate that substituting the acridine core with different cores does not interfere with their interaction and topoisomerase inhibition. Further investigations are required to assess possible toxicological effects, including reactive oxygen species generation.

Biochemical and teratogenic effects of a mixture of pyriproxyfen and glyphosate.

The mixture of agrochemicals can be made to improve pest control or accidentally. In this way, the effects on non-target organisms are a critical aspect of the environment and heath. Thus, this work aimed to show how a mixture of pyriproxyfen, and glyphosate can impair biochemical routes and embryonic development. Zebrafish embryos 0-72 hpf were exposed to 0.001-1 µg/mL of pyriproxyfen, glyphosate, and a mixture of both pesticides. The ADMETox was evaluated in silico. The FET-test was used to estimate teratogenic effects. The biochemical effects were estimated using AChE, SOD, and CAT as parameters. ROS generation was estimated using 30 µM H2DCF-DA and 5 µM DHE. The ADMETox reveals that intestinal absorption and P-glycoprotein are the main sites for PPx and Gly adsorption. The distribution parameters were diverse. PPx + Gly at 0.1 µg/mL leads to 50 % of lethality and at 1 µg/mL 100 % of lethality. PPx + Gly leads to a 22 % of lack of somite formation at 1 µg/mL. The heart rate was reduced by >10 % in all concentrations tested. The AChE has a decrease with IC20 19.6 µM and IC50 261.5 µM. SOD showed a reduction of 28 % to PPx and CAT was reduced by 58 % to PPx + Gly and Gly at 1 µg/mL. Glyphosate does not increase unspecific ROS generation. The superoxide generation was 2× higher in the PPx + Gly at 1 µg/mL. Summarily, was observed that the mixture of PPx + Gly potentiated the toxic effects. This finding suggests a possible synergism between the PPx and Gly even at lower concentrations.

Interaction study with DNA/HSA, anti-topoisomerase IIα, cytotoxicity and in vitro antiproliferative evaluations and molecular docking of indole-thiosemicarbazone compounds.

In this work we will discuss the antiproliferative evaluation and the possible mechanisms of action of indole-thiosemicarbazone compounds LTs with anti-inflammatory activity, previously described in the literature. In this perspective, some analyzes were carried out, such as the study of binding to human serum albumin (HSA) and to biological targets: DNA and human topoisomerase IIα (topo). Antiproliferative study was performed with DU-145, Jukart, MCF-7 and T-47D tumor lines and J774A.1, besides HepG2 macrophages and hemolytic activity. In the HSA interaction tests, the highest binding constant was 3.70 × 106 M-1, referring to LT89 and in the fluorescence, most compounds, except for LT76 and LT87, promoted fluorescent suppression with the largest Stern-Volmer constant for the LT88 3.55 × 104. In the antiproliferative assay with DU-145 and Jurkat strains, compounds LT76 (0.98 ± 0.10/1.23 ± 0.32 µM), LT77 (0.94 ± 0.05/1.18 ± 0.08 µM) and LT87 (0.94 ± 0.12/0.84 ± 0.09 µM) stood out, due to their IC50 values mentioned above. With the MCF-7 and T-47D cell lines, the lowest IC50 was presented by LT81 with values of 0.74 ± 0.12 µM and 0.68 ± 0.10 µM, respectively, followed by the compounds LT76 and LT87. As well as the positive control amsacrine, the compounds LT76, LT81 and LT87 were able to inhibit the enzymatic action of human Topoisomerase IIα.

A simple method for obtaining human albumin and its use for in vitro interaction assays with indole-thiazole and indole-thiazolidinone derivatives.

This work aimed to develop a simple and low-cost method to obtain human serum albumin (HSA) and its consequent application for in vitro drug interaction assays. The HSA was purified by classic principles of plasma precipitation and thermocoagulation, using a multiple-stage fractionation. The quality of the final product was assessed by electrophoresis, protein dosage by the Lowry method and the pharmacopeial thermal stability. At the end, an isotonic solution of HSA with a total protein concentration of 2.7 mg·mL-1 was obtained, which was visualized as a single band corresponding to the molecular weight of 66 kDa. After the thermal stability test, there was no indication of turbidity or color change of the solution. Finally, the HSA was useful for interaction assays with indole-thiazole and indole-thiazolidinone derivatives through UV-vis absorption and fluorescence spectroscopic studies, as well as by docking molecular analysis. Derivatives quenched the intrinsic fluorescence of HSA, disrupted the tryptophan residues microenvironment, and probably bind at Sudlow's site I. Therefore, the simplified methodology developed in this work proved to be effective in obtaining HSA that can be applied to research goals including drug interaction assays.

Hypertension is associated with a variant in the RARRES2 gene in populations of Ouro Preto, Minas Gerais, Brazil: a cross-sectional study.

BACKGROUND: Arterial hypertension (AH) is implicated in vascular health and contributes significantly to cardiovascular morbidity and mortality. In addition to the contribution of usual risk factors for AH, elucidating the influence of genetic factors is a promising area of investigation. Therefore, we evaluated the association between AH and cardiovascular risk factors (CVRFs) and genetic polymorphisms in communities in Southeast Brazil. METHODS: A total of 515 adults aged 18-91 years, who were cross-sectionally assessed between 2015-2016, were included. Demographic, clinical, behavioral, anthropometric characteristics, and laboratory parameters and 12 single nucleotide polymorphisms in seven candidate genes involved in cardiovascular risk (RARRES2, AGT, NOS3, GNB3, APOE, APOB, APOC3, LDLR, and PPARG) were evaluated, with AH as the outcome. Sex, age, and laboratory parameters were considered the main confounding factors. RESULTS: There was a significant association between age >60 years (odds ratio [OR] =6.74), alcohol dependence (OR=3.84), smoking (OR=1.74), overweight (OR=1.74), high plasma triglyceride (TG) levels (OR=1.98) and low high-density lipoprotein (HDL-c) (OR=6.22), diabetes (OR=3.68), and insulin resistance (OR=2.40) and AH. A significant association was observed between rs4721 in RARRES2 and AH. The T allele in homozygosis was a potent chance modifier for AH. The highest chance gradients for AH were characterized by the presence of the TT genotype and DMT2 (OR=9.70), high TG (OR=6.26), low HDL-c (OR=8.20), and age more than 60 years (OR=9.96). CONCLUSION: The interaction of the T allele of the rs4721 polymorphism in RARRES2 with CVRFs may predispose carriers to a higher cardiovascular risk.

Conducting Virtual Simulated Skills Multiple Mini-Interviews for General Surgery Residency Interviews.

OBJECTIVE: We describe the feasibility of transitioning simulated skills assessments during general surgery interviews from an in-person to virtual format. DESIGN/SETTING: Technical and nontechnical skill multiple mini-interviews (MMIs) were performed virtually and assessed for 109 applicants during virtual general surgery interviews over 2 days at a tertiary academic medical center. RESULTS: We demonstrate the feasibility of virtually assessing general surgery residency applicants' technical and non-technical skills. Using a virtual MMI format during general surgery interviews, we assessed communication, emotional intelligence, anatomical knowledge, interpretation of medical tests, knot tying, and suturing. Four tasks (communication, emotional intelligence , anatomical knowledge, and interpretation of tests) were assessed synchronously by trained general surgery interns. Applicants submitted a recording of themselves performing knot tying and suturing tasks, which were asynchronously assessed after the interview day. Applicants rated the MMI experience highly (4.3/5) via postinterview day survey and the majority of applicants felt that station objectives were met in the virtual format. CONCLUSIONS: We report a successful experience implementing technical and nontechnical virtual MMIs with capacity for 120 applicants during general surgery residency interviews. In the midst of a COVID-19 pandemic, the ability to assess surgical leaners virtually is essential. Virtual skills assessments may provide a more comprehensive picture of applicants and enable residency programs to better assess residents when gathering in person is not feasible.

Inspiring Young Learners Toward a Career in Healthcare Using Simulation.

STATEMENT: To inspire young learners toward a career in healthcare and provide them opportunities to learn lifesaving skills, a hospital-based simulation center collaborated with a local middle school to develop a 88-minute simulation-based educational activity. The activity consisted of eight 10-minute stations on lifesaving and basic medical skills. One hundred fifty students participated. Evaluation surveys showed students favored stations with extensive hands-on activities and valued the opportunity to interact with health professionals. Students also reported more interest in science careers after the visit. This collaborative effort is time-efficient and low-budget simulation-based learning experience that had an immediate impact on middle school students.

Clinical significance of SLN benign capsular nevi in patients with melanoma.

BACKGROUND: Benign capsular nevi (BCN) are not infrequent in sentinel lymph nodes (SLN) of patients with melanoma. Their prognostic significance is unknown and the literature is limited. This study evaluated the clinical significance of incidentally found BCN in these patients. METHODS: A multi-institutional retrospective review of patients undergoing SLN biopsy for cutaneous melanoma between 2000 and 2016. Patients were divided into the following groups: (a) negative SLN and no BCN, (b) negative SLN and presence of BCN, (c) positive SLN seen only on immunohistochemistry (IHC), and (d) positive SLN via hematoxylin and eosin (H&E). Outcomes measured were overall survival and any recurrence. RESULTS: A total of 1253 patients were identified (group 1 = 978, group 2 = 56, group 3 = 32, and group 4 = 187). Fifty-seven percent were male and the mean age was 59.3 years. BCN was identified in 77 patients (6.2%), of which the majority was in the node-negative group (72%). Multivariable analysis showed that BCN was associated with lower recurrence rates, though not statistically significant (hazard ratio [HR] = 0.5; P = .06). IHC- and H&E-positive SLNs were associated with a higher risk of recurrence (HR = 2.4; P = .02 and 2.0, P < .0001, respectively). CONCLUSION: Patients with BCN and negative SLN had lower recurrence rates than patients with negative SLN and no BCN. Our data suggest a possible protective effect against recurrence.

Brazilian Society of Surgical Oncology guidelines for surgical treatment of endometrial cancer in regions with limited resources.

BACKGROUND: Approximately 70% of cancer-related deaths occur in low- and middle-income countries. In addition to social and racial inequalities, treatment options in these countries are usually limited because of the lack of trained staff and equipment, limited patient access to health services, and a small number of clinical guidelines. OBJECTIVES: The Brazilian Society of Surgical Oncology developed this guideline to address these barriers and guide physicians treating patients with endometrial cancer (EC) in regions with limited resources and few specialized centers. METHODS: The guideline was prepared from 10 January to 25 October 20192019 by a multidisciplinary team of 56 experts to discuss the main obstacles faced by EC patients in Brazil. Thirteen questions considered critical to the surgical treatment of these patients were defined. The questions were assigned to groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments for presentations in meetings, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including staging, fertility spearing treatment, genetic testing, sentinel lymph node use, surgical treatment, and other clinical relevant questions, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSIONS: It is possible to provide adequate treatment for most EC patients in resource-limited areas, but the first option should be referral to specialized centers with more resources.

Citation Skew in Plastic Surgery Journals: Does the Journal Impact Factor Predict Individual Article Citation Rate?

BACKGROUND: Citation skew refers to the unequal distribution of citations to articles published in a particular journal. OBJECTIVES: We aimed to assess whether citation skew exists within plastic surgery journals and to determine whether the journal impact factor (JIF) is an accurate indicator of the citation rates of individual articles. METHODS: We used Journal Citation Reports to identify all journals within the field of plastic and reconstructive surgery. The number of citations in 2018 for all individual articles published in 2016 and 2017 was abstracted. RESULTS: Thirty-three plastic surgery journals were identified, publishing 9823 articles. The citation distribution showed right skew, with the majority of articles having either 0 or 1 citation (40% and 25%, respectively). A total of 3374 (34%) articles achieved citation rates similar to or higher than their journal's IF, whereas 66% of articles failed to achieve a citation rate equal to the JIF. Review articles achieved higher citation rates (median, 2) than original articles (median, 1) (P < 0.0001). Overall, 50% of articles contributed to 93.7% of citations and 12.6% of articles contributed to 50% of citations. A weak positive correlation was found between the number of citations and the JIF (r = 0.327, P < 0.0001). CONCLUSIONS: Citation skew exists within plastic surgery journals as in other fields of biomedical science. Most articles did not achieve citation rates equal to the JIF with a small percentage of articles having a disproportionate influence on citations and the JIF. Therefore, the JIF should not be used to assess the quality and impact of individual scientific work.

Laparoscopic Insertion of Various Shaped Trocars in a Porcine Model.

BACKGROUND AND OBJECTIVE: The number of laparoscopic procedures increases annually with an estimated 3% of complications, one third of them linked to Verres' needle or trocar insertion. The safety and efficacy of ports insertion during laparoscopic surgery may be related the technique but also to trocar design. This study aims to compare physical parameters of abdominal wall penetration for 5 different trocars. METHODS: Eleven pigs were studied. Five different commercially available trocars were randomically inserted at the midline. Real-time video recording of the insertions was achieved to measure the excursion of the abdominal wall and the time and distance the cutting surface of the bladed trocars was exposed inside the abdominal cavity. An especially designed hand sensor was developed and placed between the trocar and the hand of the surgeon to record force required for abdominal wall perforation. RESULTS: Greater deformations and forces occurred in nonbladed as compared to bladed trocars, and in conical trocars as compared to pyramidal pointed ones, except for peritoneum perforation. Greater distance and time of blade exposure occurred in pyramidal laminae as compared to conical. CONCLUSION: The bladed trocars have lower forces and deformations in their introduction, and should be those that cause less injury and are more suitable for first entry. Conical and pyramidal trocars with the same blade size showed similar force, deformation, time, and distance of exposed blade.

How Reliable Is CT Scan in Staging Right Colon Cancer?

BACKGROUND: The observation of inferior oncologic outcomes after surgery for proximal colon cancers has led to the investigation of alternative treatment strategies, including surgical procedures and neoadjuvant systemic chemotherapy in selected patients. OBJECTIVE: The purpose of this study was to determine the accuracy of CT staging in proximal colon cancer in detecting unfavorable pathologic features that may aid in the selection of ideal candidates alternative treatment strategies, including extended lymph node dissection and/or neoadjuvant chemotherapy. DESIGN: This was a retrospective consecutive series. SETTINGS: Trained abdominal radiologists from 2 centers performed a blinded review of CT scans obtained to locally stage proximal colon cancer according to previously defined prognostic groups, including T1/2, T3/4, N+, and extramural venous invasion. CT findings were compared with histopathologic results as a reference standard. Unfavorable pathologic findings included pT3/4, pN+, or extramural venous invasion. PATIENTS: Consecutive patients undergoing right colectomy in 2 institutions between 2011 and 2016 were retrospectively reviewed from a prospectively collected database. MAIN OUTCOME MEASURES: T status, nodal status, and extramural venous invasion status comparing CT with final histologic findings were measured. RESULTS: Of 150 CT scans reviewed, CT failed to identify primary cancer in 18%. Overall accuracy of CT to identify unfavorable pathologic features was 63% with sensitivity, specificity, positive predictive value, and negative predictive value of 63% (95% CI, 54%-71%), 63% (95% CI, 46%-81%), 87% (95% CI, 80%-94%) and 30% (95% CI, 18%-41%). Only cT3/4 (55% vs 45%; p = 0.001) and cN+ (42% vs 58%; p = 0.02) were significantly associated with correct identification of unfavorable features at final pathology. CT scans overstaged and understaged cT in 23.7% and 48.3% and cN in 28.7% and 53.0% of cases. LIMITATIONS: The study was limited by its retrospective design, relatively small sample size, and heterogeneity of CT images performed in different institutions with variable equipment and technical details. CONCLUSIONS: Accuracy of CT scan for identification of pT3/4, pN+, or extramural venous invasion was insufficient to allow for proper identification of patients at high risk for local recurrence and/or in whom to consider alternative treatment strategies. Locoregional overstaging and understaging resulted in inappropriate treatment strategies in <48%. See Video Abstract at http://links.lww.com/DCR/A935.

Prevalência de enterobactérias produtoras de Klebsiella pneumoniae carbapenemase em culturas de vigilância epidemiológica em unidade de terapia intensiva de um hospital de ensino de Minas Gerais / Prevalence of enterobacteria producers of Klebsiella pneumoniae carbapenemase in epidemiological surveillance cultures in intensive care unit of a teaching hospital in Minas Gerais, Brazil

O crescente aumento de bactérias multirresistentes no ambiente hospitalar e a falta de opções terapêuticas a curto e médio prazo tem se tornado um grande desafio para o controle das infecções relacionadas à assistência à saúde. As infecções por enterobactérias produtoras de Klebsiella pneumoniae carbapenemase (KPC), vem se destacando como a de maior risco para os pacientes debilitados que internam nas Unidades de Terapia Intensiva (UTIs). O objetivo do trabalho foi identificar a prevalência de KPC em culturas de vigilância epidemiológica de amostras de swab retal de pacientes internados nas UTI´s adulto, neonatal e pediátrica de um Hospital de Ensino de Minas Gerais, no período de janeiro a julho de 2014. Realizou-se um estudo transversal descritivo retrospectivo onde os dados foram analisados a partir dos registros dos livros do laboratório de microbiologia do hospital. Este estudo foi aprovado pelo Comitê de Ética e Pesquisa número do parecer 948.342. Foram analisadas 422 amostras de swab retal, sendo que 367 (86,9%) eram provenientes das UTIs adulto e 55 (13%) da UTI neonatal e pediátrica. Foram positivas para KPC 31 (7,3%) das quais 21 eram da UTI adulto e 10 da UTI neonatal e pediátrica. Das 31 culturas positivas para KPC uma (3%) foi em Escherichia coli, quatro (13%) em Enterobacter sp e 26 (84%) em Klebsiella pneumoniae. A detecção laboratorial de enterobactérias produtoras de KPC exprime a importância das culturas de vigilância epidemiológica na rotina como medida de prevenção e controle da disseminação desses microrganismos multirresistentes, principalmente nas UTIs.

The increasing number of multidrug-resistant bacteria in the hospital environment and the lack of treatment options in the short and medium term have become a major challenge for the control of infections related to health care. Infections caused by Enterobacteriaceae producing Klebsiella pneumoniae carbapenemase (KPC) have emerged as the highest risk for debilitated patients hospitalized in Intensive Care Units (ICUs). The aim of the study was to identify the prevalence of KPC in epidemiological surveillance cultures of samples of rectal swab of patients admitted to the adult, neonatal and pediatric ICUs, of a teaching hospital in Minas Gerais, Brazil in the period from January to July 2014. We conducted a retrospective descriptive cross-sectional study in which data were analyzed from the records of the hospital's microbiology lab books. This study was approved by the Research Ethics Committee, protocol number 948 342. 422 samples of rectal swab were analyzed, of which 367 (86.9%) were from the adult ICU's and 55 (13%) of neonatal and pediatric ICU. Thirty-one samples (7.3%) were positive for KPC, 21 in adult ICU and 10 in neonatal and pediatric ICU. Of the 31 positive cultures for KPC, one (3%) was for Escherichia coli, four (13%) for Enterobacter sp. and 26 (84%) for Klebsiella pneumoniae. Laboratory detection of KPC-producing Enterobacteriaceae expresses the importance of routine epidemiological surveillance cultures as a preventive and control measure for the spread of these multiresistant microorganisms, especially in ICUs.

Performance of crossbred heifers in different step-down waste milk-feeding strategies.

The aim of this study was to evaluate the consumption, performance, feed efficiency, glucose concentration, and the cost per kilogram of weight gain of crossbred Holstein-Gyr heifers (n = 33) subjected to one of the three waste milk step-down strategies: 6L-30d/4L-60d/2L-90d (T1), 6L-45d/4L-60d/2L-90d (T2), and 8L-30d/6L-60d/3L-90d (T3). Heifers were weaned at the age of 91 days. Water and starter were provided ad libitum. The average waste milk intake was higher in T3 than in T1 and T2 strategies until 30 days and between 60 and 90 days. The starter intake did not differ among the strategies until 45 days, but it was higher in strategy T1 than in strategy T3 between 60 and 90 days. The waste milk step-down strategy did not influence the total dry matter intake, average daily gain, body weight, and feed efficiency. Glucose concentrations in plasma varied within a range that could be considered normal and were similar among the treatments. The average cost per kilogram of weight gain was the lowest in strategy T1 (US$3.0) compared to that in the other strategies (T2, US$3.2, and T3, US$3.6). The 6L-30d/4L-60d/2L-90d waste milk step-down strategy was the most effective, since it increased the starter intake, led to normal glucose concentrations in plasma, and caused similar weight gain compared with the other strategies; however, it had a lower cost per kilogram.

Effect of temperature during embryonic development and first feeding of Trichogaster leeri larvae.

Temperature is an environmental factor that influences the development of fish, and when changed abruptly can lead to high mortality. Some species of fish are influenced by this factor, exhibiting a longer time for embryonic development and time to first feeding. This study aims to evaluate the effect of water temperature on embryonic and larval development up to first feeding, to describe the time in hours post fertilization (hpf) of the emergence of different structures and to determine the best hatching rate and survival of animals under different treatments. Five different egg incubation temperatures were used (24, 26, 28, 30 or 32°C, respectively). The eggs were observed at regular intervals of 30 min up to 24 h, every 2 h until 48 h and every 4 h until the display of first feeding in all treatments. Embryonic development was longer for eggs incubated at 24°C and the best results for hatching rate and survival of spawning efficiency were at 28°C. We recommend that incubation of Trichogaster leeri eggs is carried out at 28°C up to the first feeding of larvae.

Transanal Endoscopic Microsurgery (TEM) Following Neoadjuvant Chemoradiation for Rectal Cancer: Outcomes of Salvage Resection for Local Recurrence.

BACKGROUND: Transanal endoscopic microsurgery (TEM) has been considered an alternative for selected patients with rectal cancer following neoadjuvant chemoradiation (CRT). Immediate total mesorectal completion for all patients with unfavorable pathological features would result in unnecessary protectomies in a significant proportion of patients. Instead, salvage total mesorectal excision (TME) could be restricted for patients developing local recurrence. The aim of the present study is to determine oncological outcomes of salvage resection for local recurrences following CRT and TEM. METHODS: Consecutive patients undergoing TEM following neoadjuvant CRT for rectal cancer were reviewed. Patients with "near" complete response to CRT (≤3 cm; ycT1-2N0) were offered TEM. Salvage surgery was attempted in the event of a local recurrence. RESULTS: A total of 53 patients were managed by CRT followed by TEM. Unfavorable pathological features were present in 36 patients (68 %). None of the patients underwent immediate completion TME. There were 12 patients who developed local recurrence resulting in a 2-year local recurrence-free survival of 77 % (95 % CI, 53-100 %). Of these patients, 9 developed exclusively local recurrences, and all had at least 1 unfavorable pathological feature in the specimen after TEM (100 %). Eight patients (8 of 9) underwent salvage resection (abdominoperineal resection [APR] in 87 %) with CRM+ in 7 of 8 patients (87 %). Four patients developed local re-recurrence after a median 36 months of follow-up. The 2-year local re-recurrence free survival was 60 %. CONCLUSIONS: Salvage resection for local recurrence following CRT and TEM is associated with high rates of R1 resection (CRM+) and local re-recurrence. Immediate completion of TME should be considered for patients with unfavorable pathological features after TEM.

The Cerato-Platanin protein Epl-1 from Trichoderma harzianum is involved in mycoparasitism, plant resistance induction and self cell wall protection.

Trichoderma harzianum species are well known as biocontrol agents against important fungal phytopathogens. Mycoparasitism is one of the strategies used by this fungus in the biocontrol process. In this work, we analyzed the effect of Epl-1 protein, previously described as plant resistance elicitor, in expression modulation of T. harzianum genes involved in mycoparasitism process against phytopathogenic fungi; self cell wall protection and recognition; host hyphae coiling and triggering expression of defense-related genes in beans plants. The results indicated that the absence of Epl-1 protein affects the expression of all mycoparasitism genes analyzed in direct confrontation assays against phytopathogen Sclerotinia sclerotiorum as well as T. harzianum itself; the host mycoparasitic coiling process and expression modulation of plant defense genes showing different pattern compared with wild type strain. These data indicated the involvement T. harzianum Epl-1 in self and host interaction and also recognition of T. harzianum as a symbiotic fungus by the bean plants.