Treatment of HER2+ metastatic salivary ductal carcinoma in a pregnant woman: a case report

Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with a high mortality and poor response to treatment in the advanced setting. Human epidermal growth factor 2 (HER2) can be amplified in a fraction of SDC. We describe the case of HER2+ metastatic SDC of the submandibular gland in a young pregnant woman treated by multimodal treatment (chemotherapy, radiotherapy and targeted therapy). During pregnancy, a 27-year-old woman developed SDC of the left submandibular gland with lung and bone metastases. Given the HER2 overexpression, she was treated with trastuzumab, paclitaxel and cisplatin. Since the tumor had arisen during pregnancy, triptorelin was administered after delivery. A complete remission was observed, and after eight cycles of chemotherapy, radiotherapy was started in association with trastuzumab and triptorelin. A prolonged disease control and complete visceral remission were observed. Multimodal therapy based on patient's tumor characteristics showed good clinical efficacy in the treatment of metastatic SDC

Nod2 Deficiency in mice is Associated with Microbiota Variation Favouring the Expansion of mucosal CD4+ LAP+ Regulatory Cells

Nucleotide-binding Oligomerization Domain-2 (NOD2) mutations are associated with an increased risk to develop Crohn's Disease. In previous studies, we have shown that Nod2-/- mice manifest increased proportion of Lamina Propria (LP) CD4+ LAP+ Foxp3- regulatory cells, when compared with Nod2+/+ mice, while CD4+ Foxp3 + regulatory cells were not affected. Here, we investigated the Nod2 gut microbiota, by 16S rRNA pyrosequencing, at steady state and after TNBS-colitis induction in mice reared separately or in cohousing, correlating the microbial profiles with LP regulatory T cells proportion and tissue cytokines content. We found that enrichment of Rikenella and Alistipes (Rikenellaceae) in Nod2-/- mice at 8 weeks of age reared separately was associated with increased proportion of CD4+ LAP+ Foxp3- cells and less severe TNBS-colitis. In co-housed mice the acquisition of Rickenellaceae by Nod2+/+ mice was associated with increased CD4+ LAP+ Foxp3- proportion and less severe colitis. Severe colitis was associated with enrichment of gram-negative pathobionts (Escherichia and Enterococcus), while less severe colitis with protective bacteria (Barnesiella, Odoribacter and Clostridium IV). Environmental factors acting on genetic background with different outcomes according to their impact on microbiota, predispose in different ways to inflammation. These results open a new scenario for therapeutic attempt to re-establish eubiosis in Inflammatory Bowel Disease patients with NOD2 polymorphisms

Nonsequential Double Ionization with Polarization-gated Pulses

We investigate laser-induced nonsequential double ionization by a polarization-gated laser pulse, constructed employing two counter-rotating circularly polarized few cycle pulses with a time delay $T_{d}$. We address the problem within a classical framework, and mimic the behavior of the quantum-mechanical electronic wave packet by means of an ensemble of classical electron trajectories. These trajectories are initially weighted with the quasi-static tunneling rate, and with suitably chosen distributions for the momentum components parallel and perpendicular to the laser-field polarization, in the temporal region for which it is nearly linearly polarized. We show that, if the time delay $T_{d}$ is of the order of the pulse length, the electron-momentum distributions, as functions of the parallel momentum components, are highly asymmetric and dependent on the carrier-envelope (CE) phase. As this delay is decreased, this asymmetry gradually vanishes. We explain this behavior in terms of the available phase space, the quasi-static tunneling rate and the recollision rate for the first electron, for different sets of trajectories. Our results show that polarization-gating technique may provide an efficient way to study the NSDI dynamics in the single-cycle limit, without employing few-cycle pulses.Comment: 17 pages, 6 figure

Transition to chaos in a reduced-order model of a shear layer

The present work studies the non-linear dynamics of a shear layer, driven by a body force and confined between parallel walls, a simplified setting to study transitional and turbulent shear layers. It was introduced by Nogueira \& Cavalieri (J. Fluid Mech. 907, A32, 2021), and is here studied using a reduced-order model based on a Galerkin projection of the Navier-Stokes system. By considering a confined shear layer with free-slip boundary conditions on the walls, periodic boundary conditions in streamwise and spanwise directions may be used, simplifying the system and enabling the use of methods of dynamical systems theory. A basis of eight modes is used in the Galerkin projection, representing the mean flow, Kelvin-Helmholtz vortices, rolls, streaks and oblique waves, structures observed in the cited work, and also present in shear layers and jets. A dynamical system is obtained, and its transition to chaos is studied. Increasing Reynolds number $Re$ leads to pitchfork and Hopf bifurcations, and the latter leads to a limit cycle with amplitude modulation of vortices, as in the DNS by Nogueira \& Cavalieri. Further increase of $Re$ leads to the appearance of a chaotic saddle, followed by the emergence of quasi-periodic and chaotic attractors. The chaotic attractors suffer a merging crisis for higher $Re$, leading to chaotic dynamics with amplitude modulation and phase jumps of vortices. This is reminiscent of observations of coherent structures in turbulent jets, suggesting that the model represents dynamics consistent with features of shear layers and jets.Comment: 28 pages, 18 figure

Adaptive Dispersion Compensation for Remote Fiber Delivery of NIR Femtosecond Pulses

We report on remote delivery of 25 pJ broadband near-infrared femtosecond light pulses from a Ti:sapphire laser through 150 meters of single-mode optical fiber. Pulse distortion due to dispersion is overcome with pre-compensation using adaptive pulse shaping techniques, while nonlinearities are mitigated using an SF10 rod for the final stage of pulse compression. Near transform limited pulse duration of 130 fs is measured after the final compression.Comment: 3 pages, 4 figure

Why small particle fixed dose triple therapy? An excursus from COPD pathology to pharmacological treatment evolution

Although bronchodilators are the cornerstone in chronic obstructive pulmonary disease (COPD) therapy, the treatment with a single-agent bronchodilator may not provide adequate symptoms control in COPD. The combination of drugs with different mechanisms of action may be more effective in inducing bronchodilation and preventing exacerbations, with a lower risk of side-effects in comparison with the increase of the dose of a single molecule. Several studies comparing the triple therapy with the association of long-acting ß2 agonist (LABA)/inhaled corticosteroid (ICS) or long-acting muscarinic antagonist (LAMA)/LABA reported improvement of lung function and quality of life. A significant reduction in moderate/severe exacerbations has been observed with a fixed triple combination of beclometasone dipropionate (BDP), formoterol fumarate (FF) and glycopyrronium (G) in a single inhaler. The TRILOGY, TRINITY and TRIBUTE studies have provided confirming evidence for a clinical benefit of triple therapy over ICS/LABA combination treatment, LAMA monotherapy and LABA/LAMA combination, with prevention of exacerbations being a key finding. A pooled post hoc analysis of the published clinical studies involving BDP/FF/G fixed combination demonstrated a reduction in fatal events in patients treated with ICS-containing medications, with a trend of statistical significance [hazard ratio = 0.72, 95% confidence interval (CI) 0.50–1.02, p = 0.066], that becomes significant if we consider reduction in fatal events for non-respiratory reasons (hazard ratio = 0.65, 95% CI 0.43–0.97, p = 0.037). In conclusion, a fixed combination of more drugs in a single inhaler can improve long-term adherence to the therapy, reducing the risk of exacerbations and hospital resources utilization. The twice a day administration may provide a better coverage of night, particularly in COPD patients who are highly symptomatic. The inhaled extrafine formulation that allows drug deposition in both large and small – peripheral – airways, is the value added

Yeast as a model to investigate the mitochondrial role in adaptation to dietary fat and calorie surplus

Several research strategies are focused towards understanding the genetic basis and molecular mechanisms that regulate uptake, synthesis, deposition, and mobilization of lipids, in the context of energy homeostasis. Because of the complexity of the problem, major input comes from the use of model systems. The aim of this work was to test the feasibility of using yeast as a model organism for studies related to dietary challenges due to high fat diet and investigate the correlation between FA metabolism and oxidative metabolism. In particular, we ask to what extent the utilization of oleic acid is dependent on mitochondrial function. We studied growth on oleic acid as a sole carbon source, and oleate stress (growth in 2 and 5% oleate) in both laboratory (BY4741 wild-type and Δsco1, Δsco2, Δtgl3, Δtgl4 mutants) and natural strains, comparing the growth phenotypes with the respiratory behaviour for each strain. We confirmed that respiratory competence is fundamental for growth on oleic acid, since the respiratory deficient mutant Δsco1 was unable to grow on oleic acid. In order to understand if the ability to use oleate as carbon source and adapt to high oleate concentrations is a general trait for the Saccharomyces cerevisiae genus, we also studied some natural strains, both diploid and haploid, identifying two meiotic derivatives of SGU90 as unable to grow in oleic acid as a sole carbon source. We investigate some aspects of mitochondrial metabolism in order to gain insights on this new finding

Attosecond streaking of correlated two-electron transitions in helium

We present fully ab initio simulations of attosecond streaking for ionization of helium accompanied by shake-up of the second electron. This process represents a prototypical case for strongly correlated electron dynamics on the attosecond timescale. We show that streaking spectroscopy can provide detailed information on the Eisenbud-Wigner-Smith time delay as well as on the infrared field dressing of both bound and continuum states. We find a novel contribution to the streaking delay that stems from the interplay of electron-electron and infrared-field interactions in the exit channel. We quantify all the contributions with attosecond precision and provide a benchmark for future experiments.Comment: 5 pages, 4 figure