Factors related to swallowing oral phase

Introduction: Efficacy of swallowing oral phase is often impaired in dysphagic patients and may impact on pharyngeal stage, meal consumption, nutritional status and quality of life. However, factors related to oral phase of swallowing have been little studied. Matherial & Methods: Thirty-nine adult patients with dysphagia of different etiology were enrolled. FEES and the Test of Mastication and Swallowing Solids (TOMASS) were performed. The Penetration-Aspiration scale, the Yale Pharyngeal Residue Severity Rating Scale and the Dysphagia Outcome and Severity Scale (DOSS) were used to assess the FEES. Tongue strength was assessed using the Iowa Oral Performance Instrument. Patients completed the Eating Assessment Tool-10. The time the patients needed to consume a meal, the Functional Oral Intake Scale score and the body mass index (BMI) were recorded. Correlations between the TOMASS and other variables were studied using Spearman\u2019s correlation coefficient. TOMASS scores were compared between patients with complete denture and those with partial edentulism through Mann-Whitney test. Results: The number of discrete bites correlated only with the BMI (r=-0.38; p=0.01). Statistically significant correlations were found between the number of masticatory cycles and tongue strength (r=-0.47; p<0.01), pharyngeal residue (r=0.42; p<0.01), DOSS (r=-0.38; p=0.01). The total time of the TOMASS correlated with tongue strength (r=-0.45; p<0.01), pharyngeal residue (r=0.48; p<0.01), time needed to consume a meal (r=0.41; p=0.01) and DOSS (r=-0.36; p=0.02). A significant difference was found between patients with complete denture and patients with partial edentulism for the number of masticatory cycles (p=0.02) and total time (p=0.03). Conclusions: Swallowing oral phase seems to correlate with tongue strength, denture, pharyngeal residue, overall dysphagia severity, duration of meals and BMI. Further studies involving a larger sample size are necessary to confirm present data

A Theoretical and Experimental Analysis of a Self-contained R-290 Refrigeration Unit Applied to a Glass Door Reach-in Supermarket Display Case

This paper presents a theoretical and experimental analysis of a self-contained variable speed R290 refrigeration unit applied to a typical 1.25m long two-glass-door reach-in supermarket display case, originally designed to run on an integrated R404a single speed refrigeration unit. A semi-empirical mathematical model was put forward to predict system energy consumption and cabinet psychometrics as a function of environmental conditions (ambient temperature and relative humidity), compressor model (single-speed, variable-speed and compressor displacement), refrigerant fluid (R290 and R404a) and geometry (heat exchangers overall heat transfer coefficient). One energy consumption test was performed at 32°C ambient temperature and used to calibrate components overall heat transfer coefficients. The model validation was then performed by using the calibrated model to predict the system energy consumption at 27°C ambient temperature. A good agreement between experimental and numerical results was found with errors lower than 1% and 3% on energy consumption and compressor running time ratio respectively. Finally, the model was applied to predict annual energy consumption for two units (R290 self-contained and R404a integrated) as a function of the monthly average ambient temperatures for Joinville, Santa Catarina, Brazil. The simulation results indicate an annual energy consumption saving up to 30% when a self-contained R290 variable speed hermetic refrigeration unit is applied to a cabinet originally designed for an integrated R404a single speed compressor refrigeration unit

<b><i>Topoisomerase 1</i></b> Promoter Variants and Benefit from Irinotecan in Metastatic Colorectal Cancer Patients

Objective: Topoisomerase 1 (topo-1) is an important target for the treatment of metastatic colorectal cancer (CRC). The aim of the present study was to evaluate the correlation between topo-1 single-nucleotide polymorphisms (SNPs) and clinical outcome in metastatic CRC (mCRC) patients. Methods: With the use of specific software (PROMO 3.0), we performed an in silico analysis of topo-1 promoter SNPs; the rs6072249 and rs34282819 SNPs were included in the study. DNA was extracted from 105 mCRC patients treated with FOLFIRI ± bevacizumab in the first line. SNP genotyping was performed by real-time PCR. Genotypes were correlated with clinical parameters (objective response rate, progression-free survival, and overall survival). Results: No single genotype was significantly associated with clinical variables. The G allelic variant of rs6072249 topo-1 SNP is responsible for GC factor and X-box-binding protein transcription factor binding. The same allelic variant showed a nonsignificant trend toward a shorter progression-free survival (GG, 7.5 months; other genotypes, 9.3 months; HR 1.823, 95% CI 0.8904-3.734; p = 0.1). Conclusion: Further analyses are needed to confirm that the topo-1 SNP rs6072249 and transcription factor interaction could be a part of tools to predict clinical outcome in mCRC patients treated with irinotecan-based regimens

Primary tumor sidedness and benefit from FOLFOXIRI plus bevacizumab as initial therapy for metastatic colorectal cancer. Retrospective analysis of the TRIBE trial by GONO

Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status

The molecular species responsible for α1-antitrypsin deficiency are suppressed by a small molecule chaperone

The formation of ordered Z (Glu342Lys) α1-antitrypsin polymers in hepatocytes is central to liver disease in α1-antitrypsin deficiency. In&nbsp;vitro experiments have identified an intermediate conformational state (M*) that precedes polymer formation, but this has yet to be identified in&nbsp;vivo. Moreover, the mechanism of polymer formation and their fate in cells have been incompletely characterised. We have used cell models of disease in conjunction with conformation-selective monoclonal antibodies and a small molecule inhibitor of polymerisation to define the dynamics of polymer formation, accumulation and secretion. Pulse-chase experiments demonstrate that Z α1-antitrypsin accumulates as short-chain polymers that partition with soluble cellular components and are partially secreted by cells. These precede the formation of larger, insoluble polymers with a longer half-life (10.9&nbsp;±&nbsp;1.7&nbsp;h and 20.9&nbsp;±&nbsp;7.4&nbsp;h for soluble and insoluble polymers, respectively). The M* intermediate (or a by-product thereof) was identified in the cells by a conformation-specific monoclonal antibody. This was completely abrogated by treatment with the small molecule, which also blocked the formation of intracellular polymers. These data allow us to conclude that the M* conformation is central to polymerisation of Z α1-antitrypsin in&nbsp;vivo; preventing its accumulation represents a tractable approach for pharmacological treatment of this condition; polymers are partially secreted; and polymers exist as two distinct populations in cells whose different dynamics have likely consequences for the aetiology of the disease

k cl co transport plays an important role in normal and β thalassemic erythropoiesis

Background and Objectives Cell volume changes are hallmarks of both cell maturation and apoptosis, and are paralleled by modulation of membrane ion transport pathways. We evaluated the possible role of K-Cl co-transport (KCC) in both normal and β-thalassemic erythropoiesis in vitro . Design and Methods We studied the effects of the KCC inhibitor, DIOA, on cell proliferation and differentiation, on expression of KCC mRNA and polypeptides, and on expression of cell cycle and apoptosis genes in in vitro liquid-cultures of CD34+ cells from normal and β-thalassemic subjects. Results β-thalassemic erythroid precursors showed increased abundance of KCC1-3 mRNA and of KCC polypeptides in late erythropoiesis. DIOA markedly modified the composition of normal erythroid precursors, promoting differentiation and arrest at the polychromatic erythroblast stage and resulting in a precursor distribution profile similar to that of untreated β-thalassemic cells. DIOA up-regulated cyclin-D mRNA levels in late erythropoiesis in both cell models, paralleling changes in the percentage of S-phase-cells. Caspase-3 activity in late erythropoiesis declined to similar degrees in both cell models. DIOA did not modify caspase-3 or -8 mRNA levels. Interpretation and Conclusions Ineffective erythropoiesis of in vitro cultured β-thalassemic cells is likely related to impaired cell maturation. KCC activity appears to contribute to erythroid cell growth during late erythropoiesis

Folfoxiri with or Without Bevacizumab (Bev) As First-Line Treatment of Metastatic Colorectal Cancer (Mcrc): a Propensity Score-Based Analysis

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Prevalence and Determinants of Liver Disease in Relatives of Italian Patients With Advanced MASLD

Background & Aims: Metabolic dysfunction associated steatotic liver disease (MASLD) has a strong genetic component. The aim of this study was to examine noninvasively the prevalence of MASLD and of advanced fibrosis in relatives of patients with advanced MASLD and the risk factors for liver involvement, with a focus on the contribution of common genetic risk variants. Methods: We prospectively enrolled 98 consecutive probands with advanced fibrosis and/or hepatocellular carcinoma caused by MASLD and 160 nontwin first-degree relatives noninvasively screened for MASLD and advanced fibrosis at 4 Italian centers. We evaluated common genetic determinants and polygenic risk scores of liver disease. Results: Among relatives, prevalence of MASLD was 56.8% overall, whereas advanced fibrosis was observed in 14.4%. At multivariable analysis in relatives, MASLD was associated with body mass index (odds ratio [OR], 1.31 [1.18–1.46]) and tended to be associated with diabetes (OR, 5.21 [0.97–28.10]), alcohol intake (OR, 1.32 [0.98–1.78]), and with female sex (OR, 0.54 [0.23–1.15]), whereas advanced fibrosis was associated with diabetes (OR, 3.13 [1.16–8.45]) and nearly with body mass index (OR, 1.09 [1.00–1.19]). Despite that the PNPLA3 risk variant was enriched in probands (P =.003) and overtransmitted to relatives with MASLD (P =.045), evaluation of genetic risk variants and polygenic risk scores was not useful to guide noninvasive screening of advanced fibrosis in relatives. Conclusions: We confirmed that about 1 in 7 relatives of patients with advanced MASLD has advanced fibrosis, supporting clinical recommendations to perform family screening in this setting. Genetic risk variants contributed to liver disease within families but did not meaningfully improve fibrosis risk stratification

development of a new clinical nomogram including velocity rate of disease progression to predict outcome in metastatic colorectal cancer patients treated with bevacizumab beyond progression a subanalysis from tribe trial

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Randomized phase II trial of avelumab alone or in combination with cetuximab for patients with previously treated, locally advanced, or metastatic squamous cell anal carcinoma: The CARACAS study

Background No standard therapies beyond first line are established for advanced squamous cell anal carcinoma (aSCAC). Earlier preliminary data suggest activity of epidermal growth factor receptor (EGFR) inhibition and programmed cell death ligand (PD-(L))1 blockade in patients with previously treated disease. Aim of this study was to explore activity and safety of avelumab with/without cetuximab in patients with aSCAC. Methods In this open-label, non-comparative, € pick the winner', multicenter randomized phase II trial (NCT03944252), patients with aSCAC progressing after one or more lines of treatment were randomized 1:1 to the anti-PD-L1 agent avelumab alone (arm A) or combined with cetuximab (arm B). Overall response rate (ORR) was the primary endpoint. With one-sided α error set at 0.05 and power of 80%, at least 4 responses out of 27 patients per arm had to be observed to declare the study positive. Secondary endpoints were progression free survival (PFS), overall survival (OS), and safety. Results Thirty patients per arm were enrolled. Three patients in arm A and five in arm B achieved partial response: primary endpoint was reached in combination arm. ORR was 10% (95% CI 2.1 to 26.5) and 17% (95% CI 5.6 to 34.7) in arms A and B; disease control rate was 50% (95% CI 31.3 to 68.7) in arm A and 57 (95% CI 37.4-74.5) in arm B. At a median follow-up of 26.7 months (IQR 26.5-26.9), median PFS was 2.0 months (95% CI 1.8 to 4.0) in arm A and 3.9 (95% CI 2.1 to 5.6) in arm B. Median OS was 13.9 months (95% CI 7.7 to 19.4) in arm A and 7.8 (95% CI 6.2 to 11.2) in arm B. Acceptable safety profile was observed in both arms. Conclusions CARACAS study met its primary endpoint in arm B, documenting promising activity of dual EGFR and PD-L1 blockade in aSCAC