Anatomy-based prediction method for determining ipsilateral lung doses in postoperative breast radiation therapy assisted by diagnostic computed tomography images

BackgroundThis study aimed to investigate whether ipsilateral lung doses (ILDs) could be predicted by anatomical indexes measured using diagnostic computed tomography (CT) prior to the planning stage of breast radiation therapy (RT).Materials and methodsThe thoracic diameters and the length of lines drawn manually were measured on diagnostic CT images. The parameters of interest were the skin maximum lung distance (sMLD), central lung distance (CLD), Haller index (HI), and body mass index (BMI). Lung dose-volume histograms were created with conformal planning, and the lung volumes receiving 5–40 Gy (V5–V40) were calculated. Linear regression models were used to investigate the correlations between the anatomical indexes and dose differences and to estimate the slope and 95% confidence intervals (CIs).ResultsA total of 160 patients who had undergone three-dimensional conformal RT after breast-conserving surgery were included. Univariable analysis revealed that the sMLD (p < 0.001), CLD (p < 0.001), HI (p = 0.002), and BMI (p < 0.001) were significantly correlated with the V20. However, multivariable analysis revealed that only the sMLD (slope: 0.147, p = 0.001, 95% CI: 0.162–0.306) and CLD (0.157, p = 0.005, 0.048–0.266) were strongly correlated with the V20. The p-value for the sMLD was the lowest among the p-values for all indexes, thereby indicating that the sMLD had the best predictive power for ILD.ConclusionssMLD and CLD are anatomical markers that can be used to predict ILD in whole breast RT. An sMLD > 20.5 mm or a CLD > 24.3 mm positively correlated with a high ILD.     

A rapid and sensitive method for the identification and quantitation of sub-picomolar amounts of neurohypophysial peptides

A simple, rapid and sensitive method, using isocratic reversed-phase HPLC, is described for the concomitant identification and quantitation of low levels of the various neurohypophysial peptides in biological tissues and fluids. The method requires little or no sample preparation and utilises UV peak detection at 215 nm with a serial signal amplification system to achieve a usable maximum sensitivity of less than 200 fmol of peptide.     

Association of short-term memory with a variant within DYX1C1 in developmental dyslexia

A substantial genetic contribution in the etiology of developmental dyslexia (DD) has been well documented with independent groups reporting a susceptibility locus on chromosome 15q. After the identification of the DYX1C1 gene as a potential candidate for DD, several independent association studies reported controversial results. We performed a family-based association study to determine whether the DYX1C1 single nucleotide polymorphisms (SNPs) that have been associated with DD before, that is SNPs '-3GA' and '1249GT', influence a broader phenotypic definition of DD. A significant linkage disequilibrium was observed with 'Single Letter Backward Span' (SLBS) in both single-marker and haplotype analyses. These results provide further support to the association between DD and DYX1C1 and it suggests that the linkage disequilibrium with DYX1C1 is more saliently explained in Italian dyslexics by short-term memory, as measured by 'SLBS', than by the categorical diagnosis of DD or other related phenotypes.     

Activation of the Na-K(NH4)-2Cl-cotransporter from rat submandibular glands in response to VIP

A cellular suspension from rat submandibular glands was prepared with collagenase. The intracellular pH (pH_i) was estimated with 2′,7′-bis-(2-carboxy-ethyl)-5(6)-carboxyfluorescein (BCECF). After exposure to NH₄Cl, the pH_i transiently increased (diffusion of NH₃) and then dropped (influx of NH₄⁺). Isoproterenol increased 2.5-fold the rate of NH₄⁺ influx; bumetanide, an inhibitor of the Na⁺-K⁺-2Cl⁻-cotransporter blocked the response to isoproterenol, confirming that the beta-adrenergic agonist stimulated the cotransporter. Forskolin (1 μmol/L) mimicked the response to isoproterenol. VIP (1 nmol/L-1 μmol/L) also increased the activity of the cotransporter. Cyclic AMP rather than calcium was the mediator of this activation since 1) carbachol which increased the [Ca²⁺]_i fivefold increased the uptake of NH₄⁺ by only 50%; 2) only high concentrations of VIP significantly increased the [Ca²⁺]_i; 3) incubation in the presence of EGTA had no effect on the response to VIP; 4) low concentrations (nmol/L) of the neuropeptide increased the intracellular level of cAMP; and 5) the stimulation of the cotransporter by VIP, forskolin, and isoproterenol was inhibited by H8, an inhibitor of cAMP-dependent protein kinase. It is concluded that the Na⁺-K⁺-2Cl⁻-cotransporter of rat submandibular glands is activated by isoproterenol, forskolin, and neuropeptides of the VIP family by a mechanism involving cAMP-dependent processes. The activation of the cotransporter by VIP could partly explain the potentiating effect of VIP on the response to sialagogues like substance P or muscarinic agonists.¹     

Rab17 Regulates Membrane Trafficking through Apical Recycling Endosomes in Polarized Epithelial Cells

A key feature of polarized epithelial cells is the ability to maintain the specific biochemical composition of the apical and basolateral plasma membrane domains while selectively allowing transport of proteins and lipids from one pole to the opposite by transcytosis. The small GTPase, rab17, a member of the rab family of regulators of intracellular transport, is specifically induced during cell polarization in the developing kidney. We here examined its intracellular distribution and function in both nonpolarized and polarized cells. By confocal immunofluorescence microscopy, rab17 colocalized with internalized transferrin in the perinuclear recycling endosome of BHK-21 cells. In polarized Eph4 cells, rab17 associated with the apical recycling endosome that has been implicated in recycling and transcytosis. The localization of rab17, therefore, strengthens the proposed homology between this compartment and the recycling endosome of nonpolarized cells. Basolateral to apical transport of two membrane-bound markers, the transferrin receptor and the FcLR 5-27 chimeric receptor, was specifically increased in Eph4 cells expressing rab17 mutants defective in either GTP binding or hydrolysis. Furthermore, the mutant proteins stimulated apical recycling of FcLR 5-27. These results support a role for rab17 in regulating traffic through the apical recycling endosome, suggesting a function in polarized sorting in epithelial cells.     

Purification, Characterization, and Functional Role of a Novel Extracellular Protease from Pleurotus ostreatus

A new extracellular protease (PoSl; Pleurotus ostreatus subtilisin-like protease) from P. ostreatus culture broth has been purified and characterized. PoSl is a monomeric glycoprotein with a molecular mass of 75 kDa, a pI of 4.5, and an optimum pH in the alkaline range. The inhibitory profile indicates that PoSl is a serine protease. The N-terminal and three tryptic peptide sequences of PoSl have been determined. The homology of one internal peptide with conserved sequence around the Asp residue of the catalytic triad in the subtilase family suggests that PoSl is a subtilisin-like protease. This hypothesis is further supported by the finding that PoSl hydrolysis sites of the insulin B chain match those of subtilisin. PoSl activity is positively affected by calcium. A 10-fold decrease in the K_m value in the presence of calcium ions can reflect an induced structural change in the substrate recognition site region. Furthermore, Ca²⁺ binding slows PoSl autolysis, triggering the protein to form a more compact structure. These effects have already been observed for subtilisin and other serine proteases. Moreover, PoSl protease seems to play a key role in the regulation of P. ostreatus laccase activity by degrading and/or activating different isoenzymes.     

Effect of the catechol-O-methyltransferase val(158)met genotype on children's early phases of facial stimuli processing

The ability to process and identify human faces matures early in life, is universal and is mediated by a distributed neural system. The temporal dynamics of this cognitive-emotional task can be studied by cerebral visual event-related potentials (ERPs) that are stable from midchildhood onwards. We hypothesized that part of individual variability in the parameters of the N170, a waveform that specifically marks the early, precategorical phases of human face processing, could be associated with genetic variation at the functional polymorphism of the catechol-O-methyltransferase (val(158)met) gene, which influences information processing, cognitive control tasks and patterns of brain activation during passive processing of human facial stimuli. Forty-nine third and fourth graders underwent a task of implicit processing of other children's facial expressions of emotions while ERPs were recorded. The N170 parameters (latency and amplitude) were insensitive to the type of expression, stimulus repetition, gender or school grade. Although limited by the absence of met- homozygotes among boys, data showed shorter N170 latency associated with the presence of 1-2 met158 alleles, and family-based association tests (as implemented in the PBAT version 2.6 software package) confirmed the association. These data were independent of the serotonin transporter promoter polymorphism and the N400 waveform investigated in the same group of children in a previous study. Some electrophysiological features of face processing may be stable from midchildhood onwards. Different waveforms generated by face processing may have at least partially independent genetic architectures and yield different implications toward the understanding of individual differences in cognition and emotions.     

Optimal control of the spatial allocation of COVID-19 vaccines: Italy as a case study

While campaigns of vaccination against SARS-CoV-2 are underway across the world, communities face the challenge of a fair and effective distribution of a limited supply of doses. Current vaccine allocation strategies are based on criteria such as age or risk. In the light of strong spatial heterogeneities in disease history and transmission, we explore spatial allocation strategies as a complement to existing approaches. Given the practical constraints and complex epidemiological dynamics, designing effective vaccination strategies at a country scale is an intricate task. We propose a novel optimal control framework to derive the best possible vaccine allocation for given disease transmission projections and constraints on vaccine supply and distribution logistics. As a proof-of-concept, we couple our framework with an existing spatially explicit compartmental COVID-19 model tailored to the Italian geographic and epidemiological context. We optimize the vaccine allocation on scenarios of unfolding disease transmission across the 107 provinces of Italy, from January to April 2021. For each scenario, the optimal solution significantly outperforms alternative strategies that prioritize provinces based on incidence, population distribution, or prevalence of susceptibles. Our results suggest that the complex interplay between the mobility network and the spatial heterogeneities implies highly non-trivial prioritization strategies for effective vaccination campaigns. Our work demonstrates the potential of optimal control for complex and heterogeneous epidemiological landscapes at country, and possibly global, scales.     

The influence of ethylene on in vitro rooting of GF 677 (Prunus persica × Prunus amygdalus) hybrid peach rootstock

Summary Treatments differing from each other for the type of tube closure (i.e., cotton plug for free gas exchange, airtight rubber cap, and rubber cap with ethysorb) and/or rooting culture medium (i.e., enriched or not by 25 to 100 μM acetylsalicylic acid) were compared for their effects on gaseous composition of the culture atmosphere and microcutting rooting of the GF 677 (Prunus persica × Prunus amygdalus) hybrid. Rubber capping, which leads to rapid ethylene accumulation inside tubes, strongly reduced rooting time and in some cases enhanced final rooting percentage over that of cotton plugs. Ethysorb almost completely absorbed ethylene produced by shoots, which showed lower rooting percentages within 9 d than microcuttings cultured in the absence of ethysorb. In contrast, no significant difference in rooting was found between the two treatments after 14 d. Carbon dioxide concentration was similar in all treatments within 5 to 9 d and seemed to be ineffective for rooting. The influence of acetylsalicylic acid on rooting was unclear. Root number and length were not significantly influenced by the treatments. These results demonstrate that the use of airtight closures, leading to rapid ethylene accumulation, can reduce time of rooting expression for GF 677 microcuttings. However, free gas exchange towards the end of the rooting period (from Day 9 to Day 14) is advisable to prevent leaf yellowing. No significant difference in plantlet survival and growth after transfer ex vitro was found among treatments.