Utility of Prophylactic Percutaneous Gastrostomy in Patients With Head and Neck Cancer Receiving Concurrent Chemoradiotherapy: A Multicenter Analysis

Introduction: Patients with head and neck cancer (HNC) have an elevated incidence of cachexia and malnutrition due to the tumor's location interfering with oral feeding. Concurrent chemoradiation (CCRT) can have an emetic effect and cause dysphagia and oral mucositis. Adequate nutrition improves immunity, raises the response to therapy, reduces adverse effects, and improves survival. Numerous studies have suggested the utility of nutritional support from percutaneous endoscopic gastrostomy (PEG) in HNC patients. Although PEG is usually considered a safe procedure, it has a mortality rate of 0-2.2% and a risk of other procedure-related complications of 17-40%. Our work intends to evaluate the utility of PEG in patients with locally advanced HNC who underwent CCRT. Methods: We performed a cohort study at three institutions. We included patients with HNC who underwent definitive CCRT treatment from January 2013 to December 2022. The study consisted of an observational, descriptive, retrospective analysis of prespecified clinical data. Descriptive statistics were used to compare the data between the PEG group and the non-PEG group. Analysis of covariance (ANCOVA) was used for covariance analysis. Fisher's exact test was used to compare proportional data and Student's t-test was used to assess the differences in continuous data. Survival analysis was performed using the Kaplan-Meier estimator. P-values of <0.05 were considered to be indicative of statistical significance. The SPSS Statistics version 28.0 (Armonk, NY: IBM Corp.) was used to perform all statistical evaluations. Results: We identified 90 eligible patients diagnosed with local advanced HNC who had received definitive CCRT with three weekly cycles of cisplatin as follows: 44 with a prophylactic PEG tube and 46 without a prophylactic PEG tube. Most patients were male (84.4%) and 50% of patients were diagnosed with stage IVa HNC at the time of diagnosis. There wasn't an effect of PEG placement on BMI at the end of CCRT after controlling for the effect of baseline BMI (F {1.84}=0.065 {p=0.799}). In the study population, BMI was significantly lower after CCRT (21.30 kg/m2 vs. 23.97 kg/m2), t (86)=12.389, p<0.001. In the subgroup with baseline BMI <18.5 kg/m2 (15 patients), 90% of patients with prophylactic PEG were able to complete the three planned cycles of chemotherapy vs. 66.7% in the non-PEG group. Ten patients in the PEG group (22.7%) referred feeding tube dependency. Patients with dysphagia were 3.2 times more likely to have placed prophylactic PEG (p=0.007). The difference in overall survival and progression-free survival between the two groups was not statistically significant (p=0.57 and p=0.497, respectively). Conclusion: In this study using real-world data, we found a potentially protective effect of PEG in underweight patients with locally advanced HNC performing CCRT in order to complete three cycles of treatment.info:eu-repo/semantics/publishedVersio

Parallel RNA interference screens identify EGFR activation as an escape mechanism in FGFR3-mutant cancer.

Activation of fibroblast growth factor receptors (FGFR) is a common oncogenic event. Little is known about the determinants of sensitivity to FGFR inhibition and how these may vary between different oncogenic FGFRs. Using parallel RNA interference (RNAi) genetic screens, we show that the EGF receptor (EGFR) limits sensitivity to FGFR inhibition in FGFR3-mutant and -translocated cell lines, but not in other FGFR-driven cell lines. We also identify two distinct mechanisms through which EGFR limits sensitivity. In partially FGFR3-dependent lines, inhibition of FGFR3 results in transient downregulation of mitogen-activated protein kinase signaling that is rescued by rapid upregulation of EGFR signaling. In cell lines that are intrinsically resistant to FGFR inhibition, EGFR dominates signaling via repression of FGFR3, with EGFR inhibition rescued by delayed upregulation of FGFR3 expression. Importantly, combinations of FGFR and EGFR inhibitors overcome these resistance mechanisms in vitro and in vivo. Our results illustrate the power of parallel RNAi screens in identifying common resistance mechanisms to targeted therapies. SIGNIFICANCE: Our data identify a novel therapeutic approach to the treatment of FGFR3-mutant cancer, emphasizing the potential of combination approaches targeting both FGFR3 and EGFR. Our data extend the role of EGFR in mediating resistance to inhibitors targeting a mutant oncogene, showing that EGFR signaling can repress mutant FGFR3 to induce intrinsic resistance to FGFR targeting

Resistance and differential susceptibility of Bidens pilosa and B-subalternans biotypes to ALS-inhibiting herbicides

The frequent application of herbicides in agricultural areas may select resistant biotypes in weed populations, whose biological characteristics influence the speed and patterns of resistance. This research aims to charactere, simultaneously, resistance patterns and differential susceptibility of Bidens pilosa and B. subalternans biotypes to ALS-inhibiting herbicides of the imidazolinone and sulfonylurea chemical groups. Six hairy beggarticks biotypes, four suspected resistant and two known susceptible, were treated with eight rates of chlorimuron-ethyl or imazethapyr, in greenhouse conditions. Percent control and percent fresh weight of the plants were evaluated at 28 days after the application. B. subalternans is less susceptible to ALS-inhibiting herbicides than B. pilosa; B. subalternans biotypes were more resistant than B. pilosa biotypes; there are B. pilosa and B. subalternans biotypes with cross resistance to the ALS-inhibiting herbicides of the sulfonylurea and imidazolinone groups; there are different patterns of cross resistance to the diverse groups of ALS-inhibiting herbicides.63213914

Lead and Cadmium Levels and Balance and Vestibular Dysfunction among Adult Participants in the National Health and Nutrition Examination Survey (NHANES) 1999–2004

Background: Few studies have been conducted to identify risk factors for balance and vestibular dysfunction in general populations, but previous studies have reported evidence of adverse effects of lead and cadmium on balance control in high-risk groups

Mechanisms Involved in Alleviation of Intestinal Inflammation by Bifidobacterium Breve Soluble Factors

Objectives: Soluble factors released by Bifidobacterium breve C50 (Bb) alleviate the secretion of pro-inflammatory cytokines by immune cells, but their effect on intestinal epithelium remains elusive. To decipher the mechanisms accounting for the cross-talk between bacteria/soluble factors and intestinal epithelium, we measured the capacity of the bacteria, its conditioned medium (Bb-CM) and other Gram(+) commensal bacteria to dampen inflammatory chemokine secretion. Methods: TNFa-induced chemokine (CXCL8) secretion and alteration of NF-kB and AP-1 signalling pathways by Bb were studied by EMSA, confocal microscopy and western blotting. Anti-inflammatory capacity was also tested in vivo in a model of TNBS-induced colitis in mice. Results: Bb and Bb-CM, but not other commensal bacteria, induced a time and dose-dependent inhibition of CXCL8 secretion by epithelial cells driven by both AP-1 and NF-kB transcription pathways and implying decreased phosphorylation of p38-MAPK and IkB-a molecules. In TNBS-induced colitis in mice, Bb-CM decreased the colitis score and inflammatory cytokine expression, an effect reproduced by dendritic cell conditioning with Bb-CM. Conclusions: Bb and secreted soluble factors contribute positively to intestinal homeostasis by attenuating chemokine production. The results indicate that Bb down regulate inflammation at the epithelial level by inhibiting phosphorylation

High yielding synthesis of N-ethyl dehydroamino acids

Recently we reported the use of a sequence of alkylation and dehydration methodologies to obtain N-ethyl-α, β-dehydroamino acid derivatives. The application of this N-alkylation procedure to several methyl esters of β, β-dibromo and β--bromo, β-substituted dehydroamino acids protected with standard amine protecting groups was subsequently reported. The corresponding N-ethyl, β-bromo dehydroamino acid derivatives were obtained in fair to high yields and some were used as substrates in Suzuki cross coupling reactions to give N-ethyl, β, β-disubstituted dehydroalanine derivatives. Herein, we further explore N-ethylation of β-halo dehydroamino acid derivatives using triethyloxonium tetrafluoroborate as alkylating agent but substituting N,N-diisopropylethylamine for potassium tert-butoxide as auxiliary base. In these conditions, for all β-halo dehydroamino acid derivatives, reactions were complete and the N-ethylated derivative could be isolated in high yield. This method was also applied for N-ethylation of non-halogenated dehydroamino acids. Again, with all compounds the reactions were complete and the N-ethyl dehydroamino acid derivatives could be isolated in high yields. Some of these N-ethyl dehydroamino acid methyl ester derivatives were converted in high yields to their corresponding acids and coupled to an amino acid methyl ester to give N-ethyl dehydrodipeptide derivatives in good yields. Thus, this method constitutes a general procedure for high yielding synthesis of N-ethylated dehydroamino acids, which can be further applied in peptide synthesis.Foundation for Science and Technology (FCT)-Portugal and Fundo Europeu de Desenvolvimento Regional (FEDER) for financial support to Chemistry Centre of University of Minho. The NMR spectrometer Bruker Avance II+ 400 is part of the National NMR Network and was purchased in the framework of the National Program for Scientific Re-equipment; contract REDE/1517/RMN/2005, with funds from POCI 2010, FEDER and FCT

Pulmonary function testing in quadriplegic subjects

Study design: Cross-sectional study.Objective: Pulmonary functional capacity in 23 Brazilian quadriplegic subjects (ASIA A), aged 30 (9.5) years, weight 66 (10.75) kg, height 176 (7) cm, was investigated at 42 ( 64) months postinjury.Setting: University Hospital-UNICAMP, Campinas, Brazil.Method: Subjects performed forced vital capacity ( FVC) and maximal voluntary ventilation (MVV) tests while seated in their standard wheelchairs. Forced Expired Volume after 1 s (FEV1) and FVC/FEV1 ratio were calculated from these tests. Values obtained were compared to three prediction equations from the literature that are used specifically for spinal cord subjects and include different variables in their formulae, such as age, gender, height, postinjury time and injury level. Data are expressed as median (interquartile interval). Differences between values were demonstrated by median confidence interval with significance level set at a 0.05.Results: Obtained data were statistically different from prediction equation results, with FVC 3.11 ( 0.81), 4.46 (0.28), 4.16 (0.33), 4.26 (0.42); FEV1 2.77 (1.03), 3.67 (0.21), 3.66 (0.30), 3.45 (0.39) and MVV 92 (27), 154.2 (11.9), 156.6 (14),157.3 (16.8), where the first value is obtained experimentally and the second, third and fourth values correspond to predicted values. the results obtained from spirometry test in this study differed significantly from the results obtained when prediction equations were used.Conclusion: the use of prediction equations developed to estimate pulmonary function in wheelchair users significantly overestimates pulmonary function of quadriplegic individuals with complete lesions (ASIA group A), in comparison to measured values.Univ Estadual Campinas, Dept Orthopedia & Traumatol, FCM, BR-13083970 Campinas, SP, BrazilUniv Estadual Campinas, Fac Phys Educ, BR-13083970 Campinas, SP, BrazilUniversidade Federal de São Paulo, Santos, SP, BrazilUniv São Paulo, Fac Med, Dept Biomech Med & Rehabil Locomotor Syst, BR-14049 Ribeirao Preto, BrazilUniv São Paulo, Dept Elect Engn, Sao Carlos, SP, BrazilUniversidade Federal de São Paulo, Santos, SP, BrazilWeb of Scienc

Z boson production in Pb+Pb collisions at √Snn = 5.02 TeV measured by the ATLAS experiment

The production yield of Z bosons is measured in the electron and muon decay channels in Pb+Pb collisions at √S = 5.02 TeV with the ATLAS detector. Data from the 2015 LHC run corresponding to an integrated luminosity of 0.49 nb are used for the analysis. The Z boson yield, normalised by the total number of minimum-bias events and the mean nuclear thickness function, is measured as a function of dilepton rapidity and event centrality. The measurements in Pb+Pb collisions are compared with similar measurements made in proton-proton collisions at the same centre-of-mass energy. The nuclear modification factor is found to be consistent with unity for all centrality intervals. The results are compared with theoretical predictions obtained at next-to-leading order using nucleon and nuclear parton distribution functions. The normalised Z boson yields in Pb+Pb collisions lie 1-3σ above the predictions. The nuclear modification factor measured as a function of rapidity agrees with unity and is consistent with a next-to-leading-order QCD calculation including the isospin effect. nn -