Early improvement of global longitudinal strain after iron deficiency correction in heart failure with reduced ejection fraction.

BACKGROUND: Iron deficiency correction with ferric carboxymaltose improves symptoms and reduces rehospitalization in patients with reduced left ventricular ejection fraction. The mechanisms underlying these improvements are poorly understood. This study aimed to determine changes in left ventricular contractility after iron treatment as reflected in global longitudinal strain. METHODS: Prospective single-center study including 43 adults with reduced ejection fraction, non-anemic iron deficiency, and functional class II-III heart failure despite optimal medical treatment. Global longitudinal strain through speckle-tracking echocardiography was measured at baseline and 4 weeks after ferric carboxymaltose. RESULTS: A significant improvement in global longitudinal strain was detected (from -12.3% ± 4.0% at baseline to -15.6% ± 4.1%, p < .001); ferritin and transferrin saturation index had increased, but ejection fraction presented no significant changes (baseline 35.7% ± 4.6%, follow-up 37.2% ± 6.6%, p = .073). CONCLUSIONS: In patients with heart failure and reduced ejection fraction, the correction of iron deficiency with ferric carboxymaltose is associated with an early improvement in global longitudinal strain, possibly suggesting a direct effect of iron correction on myocardial contractility.

[Clinical and periodontal predictive factors of severity in gingival recession (GR)]. / Parámetros clínicos y periodontales predictores de la severidad de la recesión gingival (RG).

INTRODUCTION: Gingival recession is an unsightly condition due to root exposure. It can lead to dental hypersensitivity, root caries, and tooth loss. OBJECTIVE: To determine the influence of different clinical and periodontal parameters on the severity of gingival recession evaluated at four periods: initial, 6, 12, and 18 months of follow-up. MATERIAL AND METHODS: Forty patients with gingival recession were included in the study. Sociodemographic data, systemic diseases, harmful habits, dental hygiene habits, parafunctional habits, and orthodontic treatment were collected. Periodontal status (plaque index, gingival bleeding index, attached gingiva loss, pocket probing depth, and attachment loss) was also measured. RESULTS: None of the clinical parameters studied influenced the number of teeth with gingival recession. Smokers showed a higher number of teeth with attached gingiva loss (p=0.03). A direct relationship between the severity of gingival recession and plaque index (p=0.02) or 4-6 mm attachment loss (p=0.04) was observed. At six months of follow-up, gingival index was the only parameter that influenced the severity of gingival recession (p=0.01).

Upscale energy transfer in three-dimensional rapidly rotating turbulent convection.

Rotating Rayleigh-Bénard convection exhibits, in the limit of rapid rotation, a turbulent state known as geostrophic turbulence. This state is present for sufficiently large Rayleigh numbers representing the thermal forcing of the system, and is characterized by a leading order balance between the Coriolis force and pressure gradient. This turbulent state is itself unstable to the generation of depth-independent or barotropic vortex structures of ever larger scale through a process known as spectral condensation. This process involves an inverse cascade mechanism with a positive feedback loop whereby large-scale barotropic vortices organize small scale convective eddies. In turn, these eddies provide a dynamically evolving energy source for the large-scale barotropic component. Kinetic energy spectra for the barotropic dynamics are consistent with a k-3 downscale enstrophy cascade and an upscale cascade that steepens to k-3 as the box-scale condensate forms. At the same time the flow maintains a baroclinic convective component with an inertial range consistent with a k-5/3 spectrum. The condensation process resembles a similar process in two dimensions but is fully three-dimensional.

Optical phased-array ladar.

We demonstrate a ladar with 0.5 m class range resolution obtained by integrating a continuous-wave optical phased-array transmitter with a Geiger-mode avalanche photodiode receiver array. In contrast with conventional ladar systems, an array of continuous-wave sources is used to effectively pulse illuminate a target by electro-optically steering far-field fringes. From the reference frame of a point in the far field, a steered fringe appears as a pulse. Range information is thus obtained by measuring the arrival time of a pulse return from a target to a receiver pixel. This ladar system offers a number of benefits, including broad spectral coverage, high efficiency, small size, power scalability, and versatility.

Assessing the Hands-on Usability of the Healthy Jeart App Specifically Tailored to Young Users.

BACKGROUND: The widespread adoption of mobile devices by adolescents underscores the potential to harness these tools to instill healthy habits into their daily lives. An exemplary manifestation of this initiative is the Healthy Jeart app, crafted with the explicit goal of fostering well-being. METHODOLOGY: This study, framed within an applied investigation, adopts an exploratory and descriptive approach, specifically delving into the realm of user experience analysis. The focus of this research is a preliminary examination aimed at understanding users' perceived usability of the application. To glean insights, a comprehensive questionnaire was administered to 101 teenagers, seeking their evaluations on various usability attributes. The study took place during 2022. RESULTS: The findings reveal a considerable consensus among users regarding the evaluated usability aspects. However, the areas for improvement predominantly revolve around managing the information density, particularly for a subset of end users grappling with overwhelming content. Additionally, recommendations are put forth to streamline the confirmation process for user suggestions and comments. CONCLUSION: This analysis illuminates both the strengths of the app and areas ripe for refinement, paving the way for a more user-centric and efficacious Healthy Jeart application.

Impact of the use of plaque modification techniques on coronary microcirculation using an angiography-derived index of microcirculatory resistance.

Many lesions in patients undergoing percutaneous coronary intervention (PCI) exhibit significant calcification. Several techniques have been developed to improve outcomes in this setting. However, their impact on coronary microcirculation remains unknown. The aim of this study is to evaluate the influence of plaque modification techniques on coronary microcirculation across patients with severely calcified coronary artery disease. In this multicenter retrospective study, consecutive patients undergoing PCI with either Rotablation (RA) or Shockwave-intravascular-lithotripsy (IVL) were included. Primary endpoint was the impairment of coronary microvascular resistances assessed by Δ angiography-derived index of microvascular resistance (ΔIMRangio) which was defined as the difference in IMRangio value post- and pre-PCI. Secondary endpoints included the development of peri procedural PCI complications (flow-limiting coronary dissection, slow-flow/no reflow during PCI, coronary perforation, branch occlusion, failed PCI, stroke and shock developed during PCI) and 12-month follow-up adverse events. 162 patients were included in the analysis. Almost 80% of patients were male and the left descending anterior artery was the most common treated vessel. Both RA and IVL led to an increase in ΔIMRangio (22.3 and 10.3; p = 0.038, respectively). A significantly higher rate of PCI complications was observed in patients with ΔIMRangio above the median of the cohort (21.0% vs. 6.2%; p = 0.006). PCI with RA was independently associated with higher ΔIMRangio values (OR 2.01, 95% CI: 1.01-4.03; p = 0.048). Plaque modification with IVL and RA during PCI increases microvascular resistance. Evaluating the microcirculatory status in this setting might help to predict clinical and procedural outcomes and to optimize clinical results.

Repair of Aortic Regurgitation in Young Adults: Sooner Rather Than Later.

Background Establishing surgical criteria for aortic valve replacement (AVR) in severe aortic regurgitation in young adults is challenging due to the lack of evidence-based recommendations. We studied indications for AVR in young adults with severe aortic regurgitation and their outcomes, as well as the relationship between presurgical echocardiographic parameters and postoperative left ventricular (LV) size, function, clinical events, and valve-related complications. Methods and Results Data were collected retrospectively on 172 consecutive adult patients who underwent AVR or repair for severe aortic regurgitation between 2005 and 2019 in a tertiary cardiac center (age at surgery 29 [22-41] years, 81% male). One-third underwent surgery before meeting guideline indications. Postsurgery, 65% achieved LV size and function normalization. LV ejection fraction showed no significant change from baseline. A higher presurgical LV end-systolic diameter correlated with a lack of LV normalization (odds ratio per 1-cm increase 2.81, P<0.01). The baseline LV end-systolic diameter cut-off for predicting lack of LV normalization was 43 mm. Pre- and postoperative LV dimensions and postoperative LV ejection fraction predicted clinical events during follow-up. Prosthetic valve-related complications occurred in 20.3% during an average 5.6-year follow-up. Freedom from aortic reintervention was 98%, 96.5%, and 85.4% at 1, 5, and 10 years, respectively. Conclusions Young adult patients with increased baseline LV end-systolic diameter or prior cardiac surgery are less likely to achieve LV normalization after AVR. Clinicians should carefully balance the long-term benefits of AVR against procedural risks and future interventions, especially in younger patients. Evidence-based criteria for AVR in severe aortic regurgitation in young adults are crucial to improve outcomes.

The upper and lower respiratory tract microbiome in severe aspiration pneumonia.

Uncertainty persists whether anaerobic bacteria represent important pathogens in aspiration pneumonia. In a nested case-control study of mechanically ventilated patients classified as macro-aspiration pneumonia (MAsP, n = 56), non-macro-aspiration pneumonia (NonMAsP, n = 91), and uninfected controls (n = 11), we profiled upper (URT) and lower respiratory tract (LRT) microbiota with bacterial 16S rRNA gene sequencing, measured plasma host-response biomarkers, analyzed bacterial communities by diversity and oxygen requirements, and performed unsupervised clustering with Dirichlet Multinomial Models (DMM). MAsP and NonMAsP patients had indistinguishable microbiota profiles by alpha diversity and oxygen requirements with similar host-response profiles and 60-day survival. Unsupervised DMM clusters revealed distinct bacterial clusters in the URT and LRT, with low-diversity clusters enriched for facultative anaerobes and typical pathogens, associated with higher plasma levels of SPD and sCD14 and worse 60-day survival. The predictive inter-patient variability in these bacterial profiles highlights the importance of microbiome study in patient sub-phenotyping and precision medicine approaches for severe pneumonia.

High speed, high power one-dimensional beam steering from a 6-element optical phased array.

Beam steering at high speed and high power is demonstrated from a 6-element optical phased array using coherent beam combining (CBC) techniques. The steering speed, defined as the inverse of the time to required to sweep the beam across the steering range, is 40 MHz and the total power is 396 mW. The measured central lobe FWHM width is 565 µrad. High on-axis intensity is maintained periodically by phase-locking the array via a stochastic-parallel-gradient-descent (SPGD) algorithm. A master-oscillator-power-amplifier (MOPA) configuration is used where the amplifier array elements are semiconductor slab-coupled-optical-waveguide-amplifiers (SCOWAs). The beam steering is achieved by LiNbO(3) phase modulators; the phase-locking occurs by current adjustment of the SCOWAs. The system can be readily scaled to GHz steering speed and multiwatt-class output.

High efficiency coherent beam combining of semiconductor optical amplifiers.

We demonstrate 40 W coherently combined output power in a single diffraction-limited beam from a one-dimensional 47-element array of angled-facet slab-coupled optical waveguide amplifiers at 1064 nm. The output from each emitter was collimated and overlapped onto a diffractive optical element combiner using a common transform lens. Phase locking was achieved via active feedback on each amplifier's drive current to maximize the power in the combined beam. The combining efficiency at all current levels was nearly constant at 87%.

Heat transport in low-Rossby-number Rayleigh-Bénard convection.

We demonstrate, via simulations of asymptotically reduced equations describing rotationally constrained Rayleigh-Bénard convection, that the efficiency of turbulent motion in the fluid bulk limits overall heat transport and determines the scaling of the nondimensional Nusselt number Nu with the Rayleigh number Ra, the Ekman number E, and the Prandtl number σ. For E << 1 inviscid scaling theory predicts and simulations confirm the large Ra scaling law Nu-1 ≈ C(1)σ(-1/2)Ra(3/2)E(2), where C(1) is a constant, estimated as C(1) ≈ 0.04 ± 0.0025. In contrast, the corresponding result for nonrotating convection, Nu-1 ≈ C(2)Ra(α), is determined by the efficiency of the thermal boundary layers (laminar: 0.28 ≤ α ≤ 0.31, turbulent: α ~ 0.38). The 3/2 scaling law breaks down at Rayleigh numbers at which the thermal boundary layer loses rotational constraint, i.e., when the local Rossby number ≈ 1. The breakdown takes place while the bulk Rossby number is still small and results in a gradual transition to the nonrotating scaling law. For low Ekman numbers the location of this transition is independent of the mechanical boundary conditions.

External cavity beam combining of 21 semiconductor lasers using SPGD.

Active coherent beam combining of laser oscillators is an attractive way to achieve high output power in a diffraction limited beam. Here we describe an active beam combining system used to coherently combine 21 semiconductor laser elements with an 81% beam combining efficiency in an external cavity configuration compared with an upper limit of 90% efficiency in the particular configuration of the experiment. Our beam combining system utilizes a stochastic parallel gradient descent (SPGD) algorithm for active phase control. This work demonstrates that active beam combining is not subject to the scaling limits imposed on passive-phasing systems.

Surfactant Protein D Influences Mortality During Abdominal Sepsis by Facilitating Escherichia coli Colonization in the Gut.

Determine the role of surfactant protein D (SPD) in sepsis. DESIGN: Murine in vivo study. SETTING: Research laboratory at an academic medical center. PATIENTS: SPD knockout (SPD-/-) and wild-type (SPD+/+) mice. INTERVENTIONS: SPD-/- and SPD+/+ mice were subjected to cecal ligation and puncture (CLP). After CLP, Escherichia coli bacteremia was assessed in both groups. Cecal contents from both groups were cultured to assess for colonization by E. coli. To control for parental effects on the microbiome, SPD-/- and SPD+/+ mice were bred from heterozygous parents, and levels of E. coli in their ceca were measured. Gut segments were harvested from mice, and SPD protein expression was measured by Western blot. SPD-/- mice were gavaged with green fluorescent protein, expressing E. coli and recombinant SPD (rSPD). MEASUREMENTS AND MAIN RESULTS: SPD-/- mice had decreased mortality and decreased E. coli bacteremia compared with SPD+/+ mice following CLP. At baseline, SPD-/- mice had decreased E. coli in their cecal flora. When SPD-/- and SPD+/+ mice were bred from heterozygous parents and then separated after weaning, less E. coli was cultured from the ceca of SPD-/- mice. E. coli gut colonization was increased by gavage of rSPD in SPD-/- mice. The source of enteric SPD in SPD+/+ mice was the gallbladder. CONCLUSIONS: Enteral SPD exacerbates mortality after CLP by facilitating colonization of the mouse gut with E. coli.

Active coherent beam combining of diode lasers.

We have demonstrated active coherent beam combination (CBC) of up to 218 semiconductor amplifiers with 38.5 W cw output using up to eleven one-dimensional 21-element individually addressable diode amplifier arrays operating at 960 nm. The amplifier array elements are slab-coupled-optical-waveguide semiconductor amplifiers (SCOWAs) set up in a master-oscillator-power-amplifier configuration. Diffractive optical elements divide the master-oscillator beam to seed multiple arrays of SCOWAs. A SCOWA was phase actuated by adjusting the drive current to each element and controlled using a stochastic-parallel-gradient-descent (SPGD) algorithm for the active CBC. The SPGD is a hill-climbing algorithm that maximizes on-axis intensity in the far field, providing phase locking without needing a reference beam.

mTORC1 is a mechanosensor that regulates surfactant function and lung compliance during ventilator-induced lung injury.

The acute respiratory distress syndrome (ARDS) is a highly lethal condition that impairs lung function and causes respiratory failure. Mechanical ventilation (MV) maintains gas exchange in patients with ARDS but exposes lung cells to physical forces that exacerbate injury. Our data demonstrate that mTOR complex 1 (mTORC1) is a mechanosensor in lung epithelial cells and that activation of this pathway during MV impairs lung function. We found that mTORC1 is activated in lung epithelial cells following volutrauma and atelectrauma in mice and humanized in vitro models of the lung microenvironment. mTORC1 is also activated in lung tissue of mechanically ventilated patients with ARDS. Deletion of Tsc2, a negative regulator of mTORC1, in epithelial cells impairs lung compliance during MV. Conversely, treatment with rapamycin at the time MV is initiated improves lung compliance without altering lung inflammation or barrier permeability. mTORC1 inhibition mitigates physiologic lung injury by preventing surfactant dysfunction during MV. Our data demonstrate that, in contrast to canonical mTORC1 activation under favorable growth conditions, activation of mTORC1 during MV exacerbates lung injury and inhibition of this pathway may be a novel therapeutic target to mitigate ventilator-induced lung injury during ARDS.

Notch1 upregulates LPS-induced macrophage activation by increasing NF-kappaB activity.

Macrophages present different Notch receptors and ligands on their surface. Following macrophage activation by LPS or other TLR ligands, Notch1 expression is upregulated. We report here that Notch signaling increases both basal and LPS-induced NF-kappaB activation, favoring the expression of genes implicated in the inflammatory response, such as the cytokines TNF-alpha and IL-6, or enzymes, such as iNOS. Delta4 seems to be the most effective ligand to induce Notch activation and increasing NF-kappaB transcriptional activity in macrophages. We show that Notch1 signaling promotes NF-kappaB translocation to the nucleus and DNA binding by increasing both phosphorylation of the IkappaB kinase alpha/beta complex and the expression of some NF-kappaB family members. Treatment of macrophages with the gamma-secretase inhibitor DAPT, which prevents the cleavage and activation of Notch receptors, inhibits all these processes, diminishing NF-kappaB activity following LPS stimulation. Additionally, we show that the active intracellular Notch fragment can directly interact with TNF-alpha and iNOS promoters. Our results suggest that Notch signaling results in an amplification of the macrophage-dependent inflammatory response by enhancing NF-kappaB signaling.

Post-sepsis immunosuppression depends on NKT cell regulation of mTOR/IFN-γ in NK cells.

As treatment of the early, inflammatory phase of sepsis improves, post-sepsis immunosuppression and secondary infection have increased in importance. How early inflammation drives immunosuppression remains unclear. Although IFN-γ typically helps microbial clearance, we found that increased plasma IFN-γ in early clinical sepsis was associated with the later development of secondary Candida infection. Consistent with this observation, we found that exogenous IFN-γ suppressed macrophage phagocytosis of zymosan in vivo, and antibody blockade of IFN-γ after endotoxemia improved survival of secondary candidemia. Transcriptomic analysis of innate lymphocytes during endotoxemia suggested that NKT cells drove IFN-γ production by NK cells via mTORC1. Activation of invariant NKT (iNKT) cells with glycolipid antigen drove immunosuppression. Deletion of iNKT cells in Cd1d-/- mice or inhibition of mTOR by rapamycin reduced immunosuppression and susceptibility to secondary Candida infection. Thus, although rapamycin is typically an immunosuppressive medication, in the context of sepsis, rapamycin has the opposite effect. These results implicated an NKT cell/mTOR/IFN-γ axis in immunosuppression following endotoxemia or sepsis. In summary, in vivo iNKT cells activated mTORC1 in NK cells to produce IFN-γ, which worsened macrophage phagocytosis, clearance of secondary Candida infection, and mortality.

1450-nm high-brightness wavelength-beam combined diode laser array.

We have demonstrated wavelength beam combining of a 1450-nm diode laser array with a novel smile compensation method. We have achieved 20-W cw from a 25-element single bar with an M(2) of 1.9 (fast axis) x 10 (wavelength-beam-combined dimension).

Randomized phase II study of cisplatin and 5-FU continuous infusion (PF) versus cisplatin, UFT and vinorelbine (UFTVP) as induction chemotherapy in locally advanced squamous cell head and neck cancer (LA-SCHNC).

OBJECTIVES: We conducted a multicentric randomized phase II trial comparing 5-FU continuous infusion (PF) and cisplatin, UFT and vinorelbine (UFTVP) as induction chemotherapy (IC) in locally advanced squamous cell head and neck cancer (LA-SCHNC). Primary objective was complete response (CR) to IC and overall survival (OS) was a secondary objective. MATERIALS AND METHODS: PF: cisplatin 100 mg/m(2) i.v. Day 1 (D1) and 5-FU 1,000 mg/m(2) per day i.v. continous infusion D1-D5, every 21 days. UFTVP: cisplatin 100 mg/m(2) i.v. D1; UFT 200 mg/m(2) per day p.o. D1-D21 and vinorelbine 25 mg/m(2) i.v. D1 and D8, every 21 days. Four IC courses were planned in both arms. RESULTS: A total of 206 patients (pts) were included (PF/UFTVP: 99/107): oral cavity: 8%/10%, oropharynx: 20%/25%, hypopharynx: 17%/14%, larynx: 54%/50%. Stage (TNM, 2002): III: 41%/35%, IVA: 23%/27%, IVB: 35%/38%. Complete response to IC: PF:36%/UFTVP:31% (P: no significative (NS)). G 3-4 toxicity (PF/UFTVP): neutropenia: 52%/72%; febrile neutropenia: 3%/20% (P < 0.001); anaemia:1%/14% (P < 0.001); trombocytopenia: 5%/0% (P = 0.02); mucositis: 15%/7% (P < 0.001). Deaths during IC: 2(2%)/3(3%). IC with UFTVP was associated with a favourable OS in the Cox analysis (actuarial 5 year OS: 49% vs. 34%; HR: 0.67, 95% CI: 0.47-0.95, P: 0.03). CONCLUSIONS: Although clinical response is equal in both arms, overall survival (Cox) is better in the UFTVP arm. Febrile neutropenia and anaemia were more frequent with UFTVP while mucositis and trombocytopenia were more severe with PF.