Genetic improvement of tomato by targeted control of fruit softening

Controlling the rate of softening to extend shelf life was a key target for researchers engineering genetically modified (GM) tomatoes in the 1990s, but only modest improvements were achieved. Hybrids grown nowadays contain 'non-ripening mutations' that slow ripening and improve shelf life, but adversely affect flavor and color. We report substantial, targeted control of tomato softening, without affecting other aspects of ripening, by silencing a gene encoding a pectate lyase

Survival impact of bowel resection at the time of interval cytoreductive surgery for advanced ovarian cancer.

ObjectivesTo evaluate the impact of bowel resection at the time of interval cytoreductive surgery on survival.MethodsWe identified patients with advanced ovarian cancer who underwent neoadjuvant chemotherapy and interval cytoreductive surgery between 2008 and 2018 from a single-institution tumor registry. Kaplan-Meier survival analysis and Cox proportional hazards models were performed comparing patients who underwent bowel resection to those who did not.ResultsOf 158 patients, 43 (27%) underwent bowel resection. Rates of optimal (95%) and sub-optimal (5%) resection did not differ with bowel resection. Patients that required bowel resection had worse three-year survival (43% vs. 63%), even after adjusting for confounding variables of age, stage, number of neoadjuvant cycles, R0 resection, and ASA score (HR 2.27, p < 0.01). Adjusted progression-free survival did not differ between groups (HR 0.92, p = 0.72). Patients who underwent bowel resection were more likely to require blood transfusion (p < 0.01), and have a longer hospital stay (5 days vs 7.5 days, p < 0.01).ConclusionsBowel resection at the time of interval cytoreduction confers a greater than 2-fold increased risk of mortality and does not impact progression-free survival. Long-term sequelae of the peri-operative morbidity of bowel resection may contribute to increased mortality, and bowel resection may be a surrogate for disease biology with poor prognosis

Survival impact of bowel resection at the time of interval cytoreductive surgery for advanced ovarian cancer.

ObjectivesTo evaluate the impact of bowel resection at the time of interval cytoreductive surgery on survival.MethodsWe identified patients with advanced ovarian cancer who underwent neoadjuvant chemotherapy and interval cytoreductive surgery between 2008 and 2018 from a single-institution tumor registry. Kaplan-Meier survival analysis and Cox proportional hazards models were performed comparing patients who underwent bowel resection to those who did not.ResultsOf 158 patients, 43 (27%) underwent bowel resection. Rates of optimal (95%) and sub-optimal (5%) resection did not differ with bowel resection. Patients that required bowel resection had worse three-year survival (43% vs. 63%), even after adjusting for confounding variables of age, stage, number of neoadjuvant cycles, R0 resection, and ASA score (HR 2.27, p < 0.01). Adjusted progression-free survival did not differ between groups (HR 0.92, p = 0.72). Patients who underwent bowel resection were more likely to require blood transfusion (p < 0.01), and have a longer hospital stay (5 days vs 7.5 days, p < 0.01).ConclusionsBowel resection at the time of interval cytoreduction confers a greater than 2-fold increased risk of mortality and does not impact progression-free survival. Long-term sequelae of the peri-operative morbidity of bowel resection may contribute to increased mortality, and bowel resection may be a surrogate for disease biology with poor prognosis

The past, present, and future of opioid prescribing: Perioperative opioid use in gynecologic oncology patients after laparotomy at a single institution from 2012 to 2021

Objective: To describe the evolution of perioperative opioid management in gynecologic oncology patients after open surgeries and determine current opioid over-prescription rates. Methods: Part one of this two-part study was a retrospective chart review of adult patients who underwent laparotomy by a gynecologic oncologist from July 1, 2012 to June 30, 2021, comparing changes in clinical characteristics, pain management and discharge opioid prescription sizes between fiscal year 2012 (FY2012) and 2020 (FY2020). In part two, we prospectively surveyed patients after laparotomy in 2021 to determine opioid use after hospital discharge. Results: 1187 patients were included in the chart review. Demographic and surgical characteristics remained stable from FY2012 to FY2020 with differences notable for increased rates of interval cytoreductive surgeries for advanced ovarian cancer and decreased rates of full lymph node dissection. Median inpatient opioid use decreased by 62 % from FY2012 to FY2020. Median discharge opioid prescription size was 675 oral morphine equivalents (OME) per patient in FY2012 and decreased by 77.7 % to 150 OME in FY2020. Of 95 surveyed patients in 2021, median self-reported opioid use after discharge was 22.5 OME. Patients had an excess of opioids equivalent to 1331 doses of 5-milligram oxycodone tablets per 100 patients. Conclusion: Inpatient opioid use in our gynecologic oncology open surgical patients and post-discharge opioid prescription size significantly decreased over the last decade. Despite this progress, our current prescribing patterns continue to significantly overestimate patients’ actual opioid use after hospital discharge. Individualized point of care tools are needed to determine an appropriate opioid prescription size

Validation of Anticorrelated TGFβ Signaling and Alternative End-Joining DNA Repair Signatures that Predict Response to Genotoxic Cancer Therapy.

PurposeLoss of TGFβ signaling increases error-prone alternative end-joining (alt-EJ) DNA repair. We previously translated this mechanistic relationship as TGFβ and alt-EJ gene expression signatures, which we showed are anticorrelated across cancer types. A score representing anticorrelation, βAlt, predicts patient outcome in response to genotoxic therapy. Here we sought to verify this biology in live specimens and additional datasets.Experimental designHuman head and neck squamous carcinoma (HNSC) explants were treated in vitro to test whether the signatures report TGFβ signaling, indicated by SMAD2 phosphorylation, and unrepaired DNA damage, indicated by persistent 53BP1 foci after irradiation or olaparib. A custom NanoString assay was implemented to analyze the signatures' expression in explants. Each signature gene was then weighted by its association with functional responses to define a modified score, βAltw, that was retested for association with response to genotoxic therapies in independent datasets.ResultsMost genes in each signature were positively correlated with the expected biological response in tumor explants. Anticorrelation of TGFβ and alt-EJ signatures measured by NanoString was confirmed in explants. βAltw was significantly (P < 0.001) better than βAlt in predicting overall survival in response to genotoxic therapy in The Cancer Genome Atlas (TCGA) pancancer patients and in independent HNSC and ovarian cancer patient datasets.ConclusionsAssociation of the TGFβ and alt-EJ signatures with their biological response validates TGFβ competency as a key mediator of DNA repair that can be readily assayed by gene expression. The predictive value of βAltw supports its development to assist in clinical decision making

A habilidade de atenção auditiva sustentada em crianças com fissura labiopalatina e transtorno fonológico Sustained auditory attention ability in children with cleft lip and palate and phonological disorders

OBJETIVO: Verificar a habilidade de atenção auditiva sustentada em crianças com fissura labiopalatina e transtorno fonológico, comparando o desempenho com crianças com fissura labiopalatina e ausência de transtorno fonológico. MÉTODOS: Dezessete crianças com idade entre 6 e 11 anos, com fissura labiopalatina transforame unilateral operada e ausência de queixa e/ou alteração auditiva, separadas em dois grupos: GI (com transtorno fonológico) e GII (com au&#349;encia de transtorno fonológico). Para detecção de alteração auditiva foram realizadas audiometria e timpanometria. Para avaliação fonológica foram utilizados os seguintes instrumentos: Teste de Linguagem Infantil e Consciência Fonológica: Instrumento de Avaliação Sequencial. Para avaliar a habilidade de atenção auditiva foi aplicado o Teste da Habilidade de Atenção Auditiva Sustentada. RESULTADOS: Das sete crianças com transtorno fonológico (41%), duas (29%) apresentaram alteração nos resultados do Teste da Habilidade de Atenção Auditiva Sustentada. Não houve diferença entre as crianças com fissura labiopalatina e transtorno fonológico e as crianças com fissura labiopalatina e ausência de transtorno fonológico quanto aos resultados do Teste de Habilidade de Atenção Auditiva Sustentada. CONCLUSÃO: A habilidade de atenção auditiva sustentada nas crianças com fissura labiopalatina e transtorno fonológico não difere da habilidade de atenção auditiva sustentada de crianças com fissura labiopalatina sem transtorno fonológico.<br>PURPOSE: To verify the ability of sustained auditory attention in children with cleft lip and palate and phonological disorder, in comparison with the performance of children with cleft lip and palate and absence of phonological disorder. METHODS: Seventeen children with ages between 6 and 11 years, with repaired unilateral complete cleft lip and palate and absence of auditory complaints or hearing problems, were divided into two groups: GI (with phonological disorder) and GII (absence of phonological disorder). Audiometry and tympanometry were carried out to detect hearing problems. To diagnose phonological disorder, the following instruments were used: Child Language Test, and Phonological Awareness: Instrument of Sequential Assessment. The ability of auditory attention was assessed using the Test of Sustained Auditory Attention Ability. RESULTS: From seven children with phonological disorder (41%), two (29%) had altered results in the Test of Sustained Auditory Attention Ability. There was no difference between children with cleft lip and palate and phonological disorder and children with cleft lip and palate and absence of phonological disorder regarding the results of the Test of Sustained Auditory Attention Ability. CONCLUSION: The sustained auditory attention ability in children with cleft lip and palate and phonological disorder do not differ from the sustained auditory attention ability of children with cleft lip and palate without phonological disorder