Evaluation of interleukin-18 levels in patients affected by multiple myeloma and monoclonal gammopathy of undetermined significance: analysis and review of the literature.

OBJECTIVE: Monoclonal gammopathy of undetermined significance (MGUS) is a preneoplastic disease that often precedes multiple myeloma. The multistep evolutionary pattern of multiple myeloma is driven by genetic instability, a pro-inflammatory and immunosuppressive microenvironment, and tumor growth. Inflammation has long been recognized as a factor in both the onset and progression of cancer. PATIENTS AND METHODS: In this study, interleukin-18 plasma levels were compared in patients with multiple myeloma and monoclonal gammopathy of undetermined significance, as well as in a group of healthy controls. RESULTS: Our study shows that monoclonal gammopathy of undetermined significance patients have lower levels of interleukin-18 than healthy controls (521.657 ± 168.493 pg/ml vs. 1,266.481 ± 658.091 pg/ml for controls, p < 0.001). Thus, we discovered a significant difference in interleukin-18 levels between multiple myeloma patients and controls (418.177 ± 197.837 pg/ml; p = 0.001). CONCLUSIONS: In our work, we identified a reduction of interleukin-18 in monoclonal gammopathies. Furthermore, in this paper, we aimed to evaluate the existing literature on the potential mechanisms of action of this pro-inflammatory cytokine in the development of these diseases.

Optical scintillation in a maritime environment.

Free space optical propagation affects many application areas, including communication, LIDAR, and directed energy. Optical turbulence causes dynamic changes in the propagated beam that can impact these applications. A primary measure of these effects is the optical scintillation index. In this work, we report on a comparison of experimental measurements of optical scintillation, conducted on a 16 km range across the Chesapeake Bay over a period of three months, to model predictions. Models for turbulence parameters were based on NAVSLaM, a Monin Obhukov similarity theory, and used environmental measurements taken on the range simultaneously with the scintillation measurements. These parameters were then used in two different classes of optical scintillation models: Extended Rytov theory, and wave optic simulation. We show that wave optics simulation matched the data much better than Extended Rytov theory, and that prediction of scintillation using environmental parameters is possible. In addition, we show that optical scintillation over water has different characteristics in stable versus unstable conditions.

On the axial chirality of leucoindigo.

The diagonal components and the trace of two tensors which account for chiroptical response of the leucoindigo molecule C 16 H 12 N 2 O 2 that is, static anapole magnetizability, and dynamic electric dipole-magnetic dipole polarisability depending on the frequency of impinging light, are a function of the ϕ dihedral angle of torsion about the central CC bond, assumed to lie in the y direction of the coordinate system. They vanish for symmetry reasons at ϕ = 0 ∘ and ϕ = 180 ∘ , corresponding respectively to C 2 v and C 2 h point group symmetries, that is, cis and trans conformers characterized by the presence of molecular symmetry planes. Nonetheless, diagonal components and average value of static anapole polarizability and optical rotation tensors vanish at ϕ = 90 ∘ , where leucondigo is unquestionably chiral from the geometrical viewpoint. Vanishing values of the average chiroptical properties have been observed also in the proximity of other ϕ angles. Attempts have been made to explain the occurrence of accidental zeros of chiroptical properties in terms of transition frequencies and scalar products appearing in the numerator of their quantum mechanical definitions. Within the electric dipole approximation, the presence of anomalous vanishing values of tensor components of anapole magnetizability and electric-magnetic dipole polarizability is ascribed to physical achirality, arising from the lack of either toroidal or spiral electron flow along the x , y and z directions.

Continuous spatial self-cleaning in GRIN multimode fiber for self-referenced multiplex CARS imaging.

We demonstrate how spatial beam self-cleaning and supercontinuum generation in graded-index multimode optical fibers can be directly applied in multiplex coherent anti-Stokes Raman Scattering (M-CARS) spectroscopy. Although supercontinuum generation causes pump depletion mainly in the center of the beam, the partial recovery of the pump brightness due to self-cleaning may enable self-referenced M-CARS, with no additional delay lines to synchronize pump and Stokes waves. As a proof-of-principle, we report examples of imaging of single chemical compounds and polystyrene beads. The new scheme paves the way towards simpler M-CARS systems based on multimode fiber sources.

Thermalization of Orbital Angular Momentum Beams in Multimode Optical Fibers.

We report on the thermalization of light carrying orbital angular momentum in multimode optical fibers, induced by nonlinear intermodal interactions. A generalized Rayleigh-Jeans distribution of asymptotic mode composition is obtained, based on the conservation of the angular momentum. We confirm our predictions by numerical simulations and experiments based on holographic mode decomposition of multimode beams. Our work establishes new constraints for the achievement of spatial beam self-cleaning, giving previously unforeseen insights into the underlying physical mechanisms.

Statistical mechanics of beam self-cleaning in GRIN multimode optical fibers.

Since its first demonstration in graded-index multimode fibers, spatial beam self-cleaning has attracted a growing research interest. It allows for the propagation of beams with a bell-shaped spatial profile, thus enabling the use of multimode fibers for several applications, from biomedical imaging to high-power beam delivery. So far, beam self-cleaning has been experimentally studied under several different experimental conditions. Whereas it has been theoretically described as the irreversible energy transfer from high-order modes towards the fundamental mode, in analogy with a beam condensation mechanism. Here, we provide a comprehensive theoretical description of beam self-cleaning, by means of a semi-classical statistical mechanics model of wave thermalization. This approach is confirmed by an extensive experimental characterization, based on a holographic mode decomposition technique, employing laser pulses with temporal durations ranging from femtoseconds up to nanoseconds. An excellent agreement between theory and experiments is found, which demonstrates that beam self-cleaning can be fully described in terms of the basic conservation laws of statistical mechanics.

Helical plasma filaments from the self-channeling of intense femtosecond laser pulses in optical fibers: publisher's note.

This publisher's note contains a correction to Opt. Lett.47, 1 (2022)10.1364/OL.445321.

Helical plasma filaments from the self-channeling of intense femtosecond laser pulses in optical fibers.

We experimentally and numerically study the ignition of helical-shaped plasma filaments in standard optical fibers. Femtosecond pulses with megawatt peak power with proper off-axis and tilted coupling in the fiber core produce plasma skew rays. These last for distances as long as 1000 wavelengths thanks to a combination of linear waveguiding and the self-channeling effect. Peculiar is the case of graded-index multimode fibers; here the spatial self-imaging places constraints on the helix pitch. These results may find applications for fabricating fibers with helical-shaped core micro-structuration as well as for designing laser components and three-dimensional optical memories.

Rainbow Archimedean spiral emission from optical fibres.

We demonstrate a new practical approach for generating multicolour spiral-shaped beams. It makes use of a standard silica optical fibre, combined with a tilted input laser beam. The resulting breaking of the fibre axial symmetry leads to the propagation of a helical beam. The associated output far-field has a spiral shape, independently of the input laser power value. Whereas, with a high-power near-infrared femtosecond laser, a visible supercontinuum spiral emission is generated. With appropriate control of the input laser coupling conditions, the colours of the spiral spatially self-organize in a rainbow distribution. Our method is independent of the laser source wavelength and polarization. Therefore, standard optical fibres may be used for generating spiral beams in many applications, ranging from communications to optical tweezers and quantum optics.

Experimental observation of self-imaging in SMF-28 optical fibers.

Spatial self-imaging, consisting of the periodic replication of the optical transverse beam profile along the propagation direction, can be achieved in guided wave systems when all excited modes interfere in phase. We exploited material defects photoluminescence for directly visualizing self-imaging in a few-mode, nominal singlemode SMF-28 optical fiber. Visible luminescence was excited by intense femtosecond infrared pulses via multiphoton absorption processes. Our method permits us to determine the mode propagation constants and the cutoff wavelength of transverse fiber modes.

3D time-domain beam mapping for studying nonlinear dynamics in multimode optical fibers.

Characterization of the complex spatiotemporal dynamics of optical beam propagation in nonlinear multimode fibers requires the development of advanced measurement methods, capable of capturing the real-time evolution of beam images. We present a new space-time mapping technique, permitting the direct detection, with picosecond temporal resolution, of the intensity from repetitive laser pulses over a grid of spatial samples from a magnified image of the output beam. By using this time-resolved mapping, we provide, to the best of our knowledge, the first unambiguous experimental observation of instantaneous intrapulse nonlinear coupling processes among the modes of a graded index fiber.

Posterior dynamic neutralization and hybrid stabilization in degenerative spine diseases: long-term clinical and radiological outcomes.

Dynamic spinal stabilization aims to reduce some of the problems inherent with traditional fusion. The aim of our study is to analyse clinical and radiological outcomes and to identify the causes of clinical failure in patients who underwent posterior dynamic neutralization or posterior hybrid stabilization because of degenerative lumbar spine diseases. We retrospectively analysed 80 patients at 7.1 years mean follow-up (Range: 5.1 - 8.3 years): 50 were treated with Dynamic Stabilization System (Dynesys) (mean age 47 years old) and 30 with Dynamic Transition Option (mean age 48 years old). We performed clinical pre-and post-operative evaluation using Visual Analogue Scale (VAS), Oswestry Low Back Pain Scale (ODI) and X-rays study. Results: we reported an important reduction of VAS from 7 to 2 (p<.001) and minimal disability in 65% of the patients, moderate disability in 18.2%, severe disability in 12.5% and crippling back pain in 4.3%. X-ray analysis showed a significative decrease of 3.5° with respect to the preoperative values, exactly 2° in neutral position postop, 1.2° in flexion postop and 2.5° in extension postop. Data showed greater reduction of extension than flexion in postoperative period. Dynamic neutralization limits more the extension than flexion. The correct preoperative planning, the careful selection of patients and the meticulous surgical technique are mandatory to avoid clinical failures. It is very important to identify the correct screw positioning and to avoid excessive pre-tensioning of the implant. Posterior dynamic neutralization and hybrid stabilization are valid alternative to spinal fusion in degenerative spine disease.

Impaired activation of Notch-1 signaling hinders repair processes of bronchial epithelial cells exposed to cigarette smoke.

Notch-1 intervenes in the reparative processes of mucosa by controlling cell proliferation, differentiation and stem cell maintenance. Cigarette smoke alters airway epithelial homeostasis. The present study explored whether: Smokers showed altered Notch-1 expression; and whether in bronchial epithelial cells (16HBE): a) cigarette smoke extracts (CSE) altered the expression of Notch-1, of its ligand Jagged-1 (Jag-1) and the nuclear translocation of Notch-1; b) Notch-1 signaling activation as well as CSE modified Ki67, PCNA, p21, IL-33 expression, cell proliferation and repair processes. Notch-1 expression was assessed in the epithelium from large airway surgical samples from non-smoker and smoker subjects by immunohistochemistry.16HBE were cultured with/without CSE and Jag-1. A Notch-1 inhibitor (DAPT) was used as control. The expression of Notch-1, Jag-1, Ki67, PCNA, p21, IL-33 and cell proliferation (by CFSE) were all assessed by flow cytometry. Notch-1 nuclear expression was evaluated by immunofluorescence and western blot analysis. Repair processes were assessed by wound assay. Smokers had cytoplasmic but not nuclear Notch-1 expression. Although CSE increased Notch-1 expression, it counteracted Notch-1 signaling activation since it reduced Jag-1 expression and Notch-1 nuclear translocation. Notch-1 signaling activation by Jag-1 increased Ki67, PCNA and repair processes but reduced intracellular IL-33 and p21 expression without affecting cell proliferation. DAPT counteracted the effects of Notch-1 activation on PCNA and IL-33. CSE increased Ki67, PCNA, p21 and IL-33 expression but reduced cell proliferation and repair processes. In conclusion, cigarette smoke exposure, limiting Notch-1 signaling activation and hindering repair processes, amplifies injury processes in bronchial epithelial cells.

Cigarette smoke extract modulates E-Cadherin, Claudin-1 and miR-21 and promotes cancer invasiveness in human colorectal adenocarcinoma cells.

BACKGROUND: Cigarette smoke is considered a risk factor for lung and colorectal cancer. A convincing link between epithelial-to-mesenchymal transition (EMT) with colorectal cancer progression and therapeutic resistance has emerged. Deregulated expression of E-Cadherin and Claudin-1 and increased miR-21 expression and invasiveness represent hallmarks of EMT. The effects of cigarette smoke exposure on EMT in colorectal adenocarcinoma cells are largely unknown. AIM: The aim of the study is to evaluate the effect of cigarette smoke extract (CSE) on miR-21, Claudin-1 and E-Cadherin, molecules associated to EMT in colorectal cancer cells. METHODS: A human colorectal adenocarcinoma cell line (Caco-2) was treated with CSE at different concentration (5% and 10%) and for different time points (3 h and 24 h). Metabolic activity (by MTS assay), cell necrosis/cell apoptosis (evaluating Propidium Iodide/Annexin V expression by flow cytometry), miR-21, Claudin-1 and E-Cadherin gene expression were evaluated by Real time PCR. Cell permeability, actin polymerization and cancer cell migration was assessed by Trans-Epitelial Electrical Resistance (TEER), Phalloidin expression and matrigel system, respectively. RESULTS: CSE at all the tested concentrations and at all time points reduced cell necrosis. CSE at 10% increased miR-21 and reduced the metabolic activity, cell necrosis, Claudin-1 and E-cadherin mRNA at 3 h. Cell permeability, actin polymerization and cancer cell migration were all increased upon CSE exposure. CONCLUSION: These results showed that CSE increasing miR-21, Claudin-1 and E-Cadherin and enhancing the aggressiveness of cancer cells, may concur to colorectal cancer progression.

Comparação biomecânica de CRIF e placa de reconstrução na estabilização de fraturas distais de fêmur em cães / Biomechanical comparison of CRIF and reconstruction plate for stabilization of distal femur fractures in dogs

O presente estudo objetivou comparar, biomecanicamente, por meio do ensaio de compressão excêntrica, a resistência dos implantes Clamp and Rod Internal Fixation (CRIF) 5,0mm e placa de reconstrução 3,5mm na fixação de fraturas distais de fêmur de cão. Foram utilizados 22 fêmures de 11 cadáveres de cão entre 2 e 7 anos de idade e peso corporal entre 20 e 40kg e subdivididos em dois grupos, denominados grupo CRIF (GC - 11 fêmures) e grupo placa (GP - 11 fêmures). Para realização dos testes, foi simulada falha que mimetizasse uma fratura distal nos corpos de prova, por meio de uma osteotomia de até 0,5cm, realizada com auxílio de serra oscilatória, imediatamente proximal ao início da tróclea. Os implantes foram fixados segundo os padrões AOSIF, lateralmente ao fêmur, sendo utilizados três parafusos distais e cinco proximais ao foco de fratura. Foi empregado o programa de computador PMI para calcular o ponto máximo de resistência antes da falha e avaliaram-se as variáveis força máxima, deformação máxima real, rigidez, força intermediária e deformação intermediária real. Não foram encontradas diferenças estatisticamente significativas entre os GC e GP quanto às variáveis avaliadas, sugerindo que ambos os implantes são boas opções de fixações para tais fraturas.(AU)

This study aims to compare the biomechanical properties, through compression eccentric test, of the resistance of the 5.0mm Clamp and Rod Internal Fixation Implants (CRIF) and 3.5mm reconstruction plate in fixing dog femur distal fracture. It was used 22 femurs from 11 dog cadavers with age between 2 and 7 years old and body weight between 20 and 40kg, subdivided into two groups, called CRIF Group (CG - 11 femurs) and plate group (PG - 11 femurs). A distal fracture in the specimens with a gap of 0.5cm osteotomy, was simulated to perform the test, performed by the oscillating saw, just proximal to the beginning of the trochlea. The implants were fixed by the standards AO / SIF, laterally to the femur, using three distal screws and five proximal to the fracture site. PMI computer program was used to calculate the maximum point of resistance before failure and evaluated the variables maximum strength, real maximum deformation, stiffness, intermediate strength and real intermediate deformation. No statistically significant differences were found between the GC and GP as the variables evaluated, suggesting that both implants are good fixation options for such fractures.(AU)

Could Electronic Anapolar Interactions Drive Enantioselective Syntheses in Strongly Nonuniform Magnetic Fields? A Computational Study.

It is shown that the anapolar interaction of the electrons of a molecule with an external uniform magnetic field B and a uniform curl C = ∇ × B' determines different thermodynamic stabilization of the ground state for the enantiomers and diastereoisomers of a chiral molecule. A series of potential candidates for enantioselective syntheses have been investigated in a computational study via SCF-HF, B3LYP, and various coupled cluster approaches to determine the difference in energy between different enantiomers and diastereoisomers. The calculations show that these differences are very small for B and C presently available but approximately 3 orders of magnitude larger than those determined by parity violation effects. The chances that enantioselective synthesis may be attempted in the future are discussed. Recognition of anapolar interaction in chiral molecules via measurements of an induced magnetic dipole moment in the ordered phase may become possible in the presence of a nonuniform magnetic field with a strong gradient.

Budesonide, Aclidinium and Formoterol in combination limit inflammaging processes in bronchial epithelial cells exposed to cigarette smoke.

Inflammation and cellular senescence (also called inflammaging) are involved in the pathogenesis of premature lung aging, a key driver of chronic obstructive pulmonary disease (COPD). Downregulation of histone deacetylases and FoxO3 expression, activation of the ERK 1/2 pathway and IL-8 increase are hallmarks of lung inflammaging. The effects of Budesonide (BUD), Aclidinium (ACL) and Formoterol (FO) on lung inflammaging are unknown. This study was aimed to assess the effects of BUD, ACL and FO in bronchial epithelial cells exposed to cigarette smoke extract (CSE) by evaluating: a) Expression of TLR4 and survivin and LPS binding by flow cytometry; b) expression of HDAC2, HDAC3, SIRT1 and FoxO3 and activation of the ERK 1/2 pathway by western blot; c) IL-8 mRNA levels and release by Real Time-PCR and ELISA, respectively. Reported results show that CSE increased TLR4 and survivin, LPS binding, ERK 1/2 activation, IL-8 release and mRNA levels but decreased SIRT1, HDAC2, HDAC3 and FoxO3 nuclear expression. Combined therapy with BUD, ACL and FO counteracted the effects of CSE on LPS binding, FoxO3 nuclear expression, ERK 1/2 activation, survivin and IL-8 release and mRNA levels. These findings suggest a new role of combination therapy with BUD, ACL and FO in counteracting inflammaging processes induced by cigarette smoke exposure.

Measles immunity in an Italian teaching hospital.

BACKGROUND: Healthcare workers (HCWs) have an increased exposure risk to measles, which can put them, their patients and their relatives at risk of infection. In Italy, 4617 cases of measles were reported in 2017; 302 involving HCWs. According to the Italian National Immunization and Prevention Plan, all HCWs should have demonstrable evidence of immunity to measles. AIMS: To evaluate measles immunization status in HCWs at a large Italian teaching hospital. METHODS: We analysed clinical records and measles-specific IgG antibody titres of HCWs undergoing occupational health surveillance between 1 January and 31 August 2017. RESULTS: Among the 1532 HCWs (mean age 32.7 ± 10.4 years) included in the study, 87% (1328) had protective antibody titres. The proportion of protective titres was highest in those born before 1982. No significant gender differences in mean measles-specific IgG antibody titres were detected. CONCLUSIONS: Our study shows non-protective measles IgG antibody titres in a substantial percentage of HCWs, especially those born in the 1980s and 1990s. Due to the increased risk of measles transmission in the hospital environment, increased prevention strategies are required, including rigorous screening and prompt vaccination of non-immune workers.

Managing the risk of bacterial meningitis among healthcare workers.

BACKGROUND: Meningococcal disease is generally caused by A, B, C, W and Y subgroups of Neisseria meningitidis. In 2015, the Italian mass media focused on this disease due to the death of two nurses. This generated alarm in the general population, especially in healthcare workers (HCWs). The Occupational Medicine department of the Foundation PTV Polyclinic Tor Vergata (PTV) offered free MenACWY vaccine to HCWs and to students of the University of Rome Tor Vergata. AIMS: To analyse the prevalence of N. meningitidis in PTV, a large teaching hospital, and to evaluate preventive measures offered to individuals at risk (i.e. HCWs and students). METHODS: The Hospital Informatic Service provided data about patients admitted to PTV from January 2012 to December 2016. Hospital Discharge Registers were analysed and all cases of meningitis were selected. MenACWY vaccine administered to HCWs and students of PTV in 2017 was analysed. RESULTS: There was just one case of meningococcal disease in 2016. Of the 117 MenACWY vaccines administered, 42% were given to students, 32% to doctors, 8% to nurses, 2% to clerks and 16% to other healthcare professionals. CONCLUSIONS: International guidelines recommend MenACWY vaccine for microbiologists exposed to N. meningitidis isolates. The Italian Legislative Decree 81/2008, however, states that occupational physicians can adopt special protective measures such as vaccination programmes for HCWs. The response rate highlights how perceived risk may influence behaviour even in populations with a higher background knowledge than the general population.