Investigating the prognostic impact of NY-ESO-1 expression and HLA subtypes in metastatic synovial sarcoma.

BACKGROUND: To better understand the importance of the New York esophageal squamous cell carcinoma 1 (NY-ESO-1) and human leukocyte antigen (HLA) subtypes in treatment decision-making, further investigation of their prevalence and prognostic impact among patients with metastatic synovial sarcoma (mSS) is needed. PATIENTS AND METHODS: This was a retrospective clinico-biological cohort study of adults with mSS. Patient data were collected from the French Sarcoma Group NetSARC database and supplemented by electronic medical records. Primary tumor samples were collected and analyzed for NY-ESO-1 expression by immunohistochemistry (IHC) and HLA-A∗02 status by RNA sequencing (RNA-seq). The primary cohort included patients with available primary tumor samples; the impact of a larger sample size was explored by including patients who had either a primary or metastatic sample (termed the exploratory cohort). P values are provided for descriptive purposes. RESULTS: In 92 patients with primary tumor samples, ∼25% (n = 23) were positive for NY-ESO-1 and HLA-A∗02 expression (dual positive). Among 106 patients with IHC data, 61% (n = 65) were NY-ESO-1 positive, and among 94 patients with RNA-seq data, 45% (n = 42) were HLA-A∗02 positive. The median overall survival (OS) for positive versus negative NY-ESO-1 status was 35.3 and 21.7 months, respectively (unadjusted P = 0.0428). We observed no difference in median OS for HLA-A∗02-positive versus -negative and dual-positive patients versus others (both unadjusted P > 0.05). Multivariate analyses of OS showed no prognostic impact for NY-ESO-1 among primary tumor samples and in the exploratory cohort. However, in the latter we observed an association between NY-ESO-1 expression and OS in the first-line (P = 0.0041) but not in the second-line setting. CONCLUSIONS: The primary tumor cohort showed no association between NY-ESO-1 expression and OS (including stratification by HLA-A∗02 subtype and treatment line) when adjusting for important prognostic factors, possibly due to small sample sizes.

Electric Fields in Liquid Water Irradiated with Protons at Ultrahigh Dose Rates.

We study the effects of irradiating water with 3 MeV protons at high doses by observing the motion of charged polystyrene beads outside the proton beam. By single-particle tracking, we measure a radial velocity of the order of microns per second. Combining electrokinetic theory with simulations of the beam-generated reaction products and their outward diffusion, we find that the bead motion is due to electrophoresis in the electric field induced by the mobility contrast of cations and anions. This work sheds light on the perturbation of biological systems by high-dose radiations and paves the way for the manipulation of colloid or macromolecular dispersions by radiation-induced diffusiophoresis.

Post COVID-19 Vaccination-Associated Neurological Complications.

PURPOSE: Neurological sequelae after COVID-19 vaccination are rare. We investigated the possible pathogenesis behind the development of neurological complications within a short period after Saudi residents received a COVID-19 vaccine. PATIENTS AND METHODS: We evaluated 18 patients who recently received a COVID-19 vaccine (Comirnaty and Vaxzevria vaccines) and presented with neurological complications to the Saudi German Hospitals in Jeddah, Saudi Arabia. Neurologists assessed the patients' clinical presentation, radiological investigations, and laboratory findings. RESULTS: Three patients who received the first dose of the Vaxzevria vaccine experienced severe cerebral venous thrombosis, two of them were complicated by intracranial hemorrhage. Their laboratory investigations showed very high d-dimers and severe thrombocytopenia, which have been linked to higher mortality and poor outcome. Ischemic stroke occurred in eight cases (44.4%) with a predominance in older male patients. Three patients presented with seizures, two had optic neuritis. Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) occurred in two male patients following vaccination with Comirnaty. CONCLUSION: Neurological complications after COVID-19 vaccinations are very rare, and only a few cases have been reported worldwide. The shared pathophysiological basis between COVID-19 viral infection and COVID-19 vaccines stands behind the very rare neurological complications resulting from the hypercoagulable state triggered by the general inflammatory condition. We suspect some differences in the pathogenesis of ischemic stroke caused by COVID-19 infection and COVID-19 vaccines, which render COVID-19 vaccine-associated ischemic stroke more responsive to treatment. To date, no definitive association between the vaccine and GBS has been proven by any strong evidence, but it has recently been added as a very rare side effect of the Janssen COVID-19 vaccine. No possible links of Miller Fisher syndrome to COVID-19 vaccines have been reported before the one reported in this study.

Clinical and Laboratory Findings of COVID-19 in High-Altitude Inhabitants of Saudi Arabia.

Background: SARS-CoV-2, the causative agent of COVID-19, continues to cause a worldwide pandemic, with more than 147 million being affected globally as of this writing. People's responses to COVID-19 range from asymptomatic to severe, and the disease is sometimes fatal. Its severity is affected by different factors and comorbidities of the infected patients. Living at a high altitude could be another factor that affects the severity of the disease in infected patients. Methods: In the present study, we have analyzed the clinical, laboratory, and radiological findings of COVID-19-infected patients in Taif, a high-altitude region of Saudi Arabia. In addition, we compared matched diseased subjects to those living at sea level. We hypothesized that people living in high-altitude locations are prone to develop a more severe form of COVID-19 than those living at sea level. Results: Age and a high Charlson comorbidity score were associated with increased numbers of intensive care unit (ICU) admissions and mortality among COVID-19 patients. These ICU admissions and fatalities were found mainly in patients with comorbidities. Rates of leukocytosis, neutrophilia, higher D-dimer, ferritin, and highly sensitive C-reactive protein (CRP) were significantly higher in ICU patients. CRP was the most independent of the laboratory biomarkers found to be potential predictors of death. COVID-19 patients who live at higher altitude developed a less severe form of the disease and had a lower mortality rate, in comparison to matched subjects living at sea level. Conclusion: CRP and Charlson comorbidity scores can be considered predictive of disease severity. People living at higher altitudes developed less severe forms of COVID-19 disease than those living at sea level, due to a not-yet-known mechanism.

Assessing Taper Geometry, Head Size, Head Material, and Their Interactions in Taper Fretting Corrosion of Retrieved Total Hip Arthroplasty Implants.

BACKGROUND: Decreased fretting and corrosion damage at the taper interface of retrieved ceramic-on-polyethylene total hip arthroplasty (THA) implants has been consistently reported; however, resultant fretting corrosion as a function of femoral head size and taper geometry has not been definitively explained. METHODS: Eight cohorts were defined from 157 retrieved THA implants based on femoral head composition (n = 95, zirconia-toughened alumina, ZTA vs n = 62, cobalt-chromium alloy, CoCr), head size (n = 56, 32mm vs n = 101, 36mm), and taper geometry (n = 84, 12/14 vs n = 73, V40). THA implants were evaluated and graded for taper fretting and corrosion. Data were statistically analyzed, including via a 23 factorial modeling. RESULTS: Factorial-based analysis indicated the significant factors related to both resultant (summed) fretting and corrosion damage were head material and taper geometry; head material-taper geometry interaction was also a significant factor in resultant corrosion damage. Lower rates of moderate-to-severe fretting and corrosion damage were exhibited on ZTA heads (ZTA = 13%, CoCr = 38%), smaller heads (32mm = 18%, 36mm = 26%), and 12/14 tapers (12/14 = 13%, V40 = 35%). ZTA+32mm heads demonstrated the lowest rates of moderate-to-severe fretting and corrosion damage (12/14 = 2%, V40 = 7%), whereas CoCr heads with V40 tapers demonstrated the greatest rates of moderate-to-severe damage (32mm = 47%, 36mm = 59%). CONCLUSION: In this series, retrieved implants with ZTA, 32-mm heads paired with 12/14 tapers exhibited lower rates of moderate-to-severe damage. Factorial analysis showed head material, taper geometry, and their interactions were the most significant factors associated with resultant damage grades. Isolating implant features may provide additional information regarding factors leading to fretting and corrosion damage in THA. LEVEL OF EVIDENCE: IV (case series).

Monte Carlo study of patient and medical staff radiation exposures during interventional cardiology.

The aim of this study is to assess the radiation exposure of the patient and the medical staff during interventional cardiology procedures. Realistic exposure scenarios were developed using the adult reference anthropomorphic phantoms adopted by the International Commission on Radiological Protection (ICRP110Male and ICRP110Female), and the radiation transport code Geant4 (version 10.3). The calculated equivalent and effective doses were normalised by the simulated Kerma-Area Product (KAP), resulting in two conversion coefficients HT/KAP and E/KAP. To properly evaluate the risk of exposure, several dose-dependent parameters have been investigated, namely: radiological parameters (tube kilovoltage peak (kVp), type of projection, field size (FOV)), and operator positions. Four projections (AP,PA,LAO25° and RAO25°) were simulated for three X-ray energy spectra (80,100 and 120 kVp) with four different values of FOV (15×15 cm2,20×20 cm2,25×25 cm2 and 30×30 cm2). The results showed that the conversion coefficients values increase with increasing tube voltage as well as the FOV size. Recommended projection during the interventional cardiology procedures, whenever possible, should be the PA projection rather than AP projection. The most critical projection for the patient and the main operator is the RAO25° projection and the LAO25° projection respectively. The comparison of our results with the literature data showed good agreement allowing their use in the dosimetric characterization of interventional cardiology procedures.

Evaluation of Artificial Tactile Sense in Mass Detection in Silicone Phantom for the Diagnosis of Prostate Tumor.

We analyzed the kinetic and kinematic variables of artificial tactile and artificial vibrotactile sensing test for mass detection in silicon phantom to determine tactile intensity and speed to obtain the best result in detecting the type and location of the mass. This study has utilized Artificial Tactile Sensing Instrument for Mass Detection (ATSIMD) in cylindrical silicone phantoms. The masses embedded in these samples were inserted in axial and environmental, deep and surface positions. The loading velocity, probe location, and the frequency of the applied force were considered as the independent variables in this study. It was found that for superficial mases the accuracy of detection at low speed 5 mm/sec, although dependent on the probe, but was 50% higher than under other conditions. For deep masses, with increasing mass depth, the accuracy of detection at medium speed of 8 mm/sec was 30% higher than at low speed. Mass detection by ATSIMD used in this study showed maximum efficiency at medium loading velocity. At low and high loading velocities, the dependence of mass detection on the probe location is related to the interaction of the testing method, tissue, and viscoelastic properties of the tissue.

A simulation study of gold nanoparticles localisation effects on radiation enhancement at the mitochondrion scale.

This paper presents a Monte-Carlo study focusing on the effects of gold nanoparticles on the energy deposition patterns produced by incident photons in the close vicinity of the mitochondrial network modeled as a tube. Spherical shaped gold nanoparticles of 30 nm diameter were placed in a micrometric (10 × 10 × 10 µm3) water phantom containing a tube of 300 nm diameter and 5 µm length. The tube represented a mitochondrial fragment and nanoparticles were distributed in the water phantom outside the tube. Photons of 120 keV were simulated using the Geant4 Livermore processes and the Geant4-DNA electron processes to account for secondary electrons collisions. The Livermore processes took into account the Auger cascade inside the gold material. A data mining algorithm was then used to analyze the energy deposition clusters inside the water phantom and the tube. A comparison was made between the results obtained for a uniform distribution of nanoparticles and a vesicle distribution model. The results including energy deposition clusters are also compared to dose enhancement ratios.

Microdosimetry in 3D realistic mitochondria phantoms: Geant4 Monte Carlo tracking of 250keV photons in phantoms reconstructed from microscopic images.

Mitochondria are considered to be sensitive radiation targets since they control processes vital to the cell's functioning. These organelles are starting to get attention and some studies are investigating the radiation dose inside them. In previous studies, mitochondria are represented as simple ellipsoids inside the cell not taking into consideration the complexity of their shape. In this study, realistic phantoms are built based on deconvolved widefield fluorescent microscopic images of the mitochondrial networks of fibroblast cells. The phantoms are imported into Geant4 as tessellated volumes taking into account the geometrical complexity of these organelles. Irradiation with 250keV photons is performed and the lineal energy is calculated. The lineal energy distributions inside the produced phantoms are compared with those calculated inside simple volumes, a sphere and an ellipsoid, where the effect of the shape and volume is clearly seen on lineal energies.

Synthesis of some quinolinyl chalcone analogues and investigation of their anticancer and synergistic anticancer effect with doxorubicin.

Two derivatives of 2-(4-acetylanilino)quinolines (IIIa, b) were synthesized as scaffolds for synthesis of open chalcone analogues (Va-f) through Claisen-Schmidt condensation with a set of aromatic aldehydes (IVa-d). Derivatives (Va, b) were further manipulated into cyclic alpha,beta-unsaturated ketones by Michael-addition of acetylacetone and ethylacetoacetate affording derivatives (VI-VII). Deethoxycarboxylation of derivatives (VIIa, b) afforded cyclohexenons (VIIIa, b) allowing formation of a mini library of alpha,beta-unsaturated ketones for screening their anticancer and synergistic anticancer effect with doxorubicin using colon cancer cell line (Caco-2). Two open enones, (Vb) and (Ve), showed significant anticancer activity with IC50 of 5.0 and 2.5 microM respectively. Only one cyclic enone, (VIa) showed synergistic anticancer activity with doxorubicin at 10 microM.

[Current status of nosocomial infections in the Lebanese Hospital Center, Beirut]. / Aspects actuels des infections nosocomiales au Centre Hospitalier Libanais de Beyrouth.

Nosocomial infections are a significant problem and hospitals need to be aware of their nosocomial infection status. This retrospective study aimed to identify nosocomial bacterial infections in patients admitted to the Lebanese Hospital Center from January 2006 to January 2008 and determine the causative micro-organisms, the antibiotic sensitivity of the micro-organisms and evaluate the hospital treatment. In total 96 patients with nosocomial infection were included. Urinary infections were the commonest nosocomial infections (42%) followed by pulmonary infections (28%). Gram-negative bacteria were responsible for 89% of nosocomial infections and staphylococci for 7%, with Escherichia coli and Pseudomonas aeruginosa being the most common (46% and 26% respectively). The organisms were resistant to multiples antibiotics and 18% of the patients were treated with imipenem, 7% with vancomycin, 42% with third-generation cephalosporins and 24% with amikacin. Hospital hygiene measures and antibiotic prescription policies are required to fight nosocomial infections and reduce antibiotic resistance among organisms.

Drug-related problems identified by clinical pharmacist's students and pharmacist's interventions.

BACKGROUND: Drug-related problems constitute a major public health problem, because of their consequences on morbidity, mortality and cost. PATIENTS AND METHODS: A 6-month prospective study was conducted, including hospitalized patients in the internal medicine ward of the University Hospital of Beirut, in order to identify drug-related problems by clinical pharmacist's students participating in routine medical rounds, to assess the characteristics of patients presenting these drug-related problems and to analyze pharmacist's interventions. RESULTS: Ninety patients presenting drug-related problems were identified. Thirty-two percent were hydro-electrolytic problems and 24% gastrointestinal. Cardiovascular drugs were the most frequently implicated (44%), followed by anticoagulants (17%) and corticosteroids (14%). The most commonly identified drug-related problems were drug interactions (37%), overdosage (28%), non-conformity to guidelines or contra-indications (23%), underdosage (10%) and improper administration (2%). The clinical pharmacist's interventions consisted of dose adjustment (38%), addition drugs (31%), changes in drugs (29%) and optimization of administration (2%). DISCUSSION AND CONCLUSION: To decrease the risk of drug-related problems, drug treatment requires physicians to abide by prescribing recommendations, notably in elderly patients, as well as pharmacists' effective intervention at all levels. Routine participation of clinical pharmacists in clinical medical rounds facilitates the identification of drug-related problems and may prevent their occurrence.

Interpretation of the photoelectron spectra of superalkali species: Na3O and Na3O-.

Recently measured photoelectron spectra of the Na(3)O(-) anion have been interpreted with the aid of ab initio electron propagator calculations. As in the case of the Li(3)O(-), we propose that the photoionization of ground and excited neutral states, in a sequential two photon absorption mechanism, plays a role in the interpretation of the observed spectrum. The lowest vertical electron detachment energy of Na(3)O(-) corresponds to a Dyson orbital that is composed chiefly of diffuse Na s functions and connects a D(3h) singlet anion to an uncharged species with the same point group. Electron binding energies of isomers of the anion with different point groups or multiplicities have been considered. The relative magnitudes of the ionization energies of the neutral Li(3)O and Na(3)O species are also discussed. Whereas the most recent experimental data hold that Na(3)O has the higher ionization energy, this work asserts the opposite trend.

Interpretation of the photoelectron spectra of superalkali species: Li3O and Li3O-.

The present paper deals with the interpretation of the photoelectron spectrum of the Li(3)O(-). After several failed attempts to attribute all of the observed peaks in the experimental spectrum to anionic species, neutral species were considered assuming a sequential two-photon absorption mechanism. We find that only two of the six observed peaks can be attributed to photodetachments and that all other observed features can be assigned to ionizations from the ground and excited states of the neutral. Nuclear distributions other than three lithium atoms surrounding the oxygen are not likely to be stable. The interpretation of the experimental peak located at about 1.2 eV remains challenging. It can either be attributed to the second electron detachment (involving the HOMO -1 orbital) energy from the anion's triplet C(2v) state or to higher excited states (involving HOMO +10, 11, 12... orbitals) of the neutral species. Furthermore, we have examined the influence of vibrational displacements on the location of the observed peaks. We find that this effect is smaller than 0.05 eV and, therefore, must be considered as negligible.

A TD-DFT investigation of two-photon absorption of fluorene derivatives.

We report time-dependent density functional theory (TD-DFT) calculations on the two-photon absorption (TPA) properties of fluorene and derivatives. The influence of donor and acceptor groups and of dimerisation is investigated. Firstly the choice of a DFT functional and of the basis set is performed by comparison of experimental and calculated excitation energies and two-photon cross sections. Then, the calculations display an enhancement of the cross section with acceptor groups or with a combination of one donor and one acceptor groups (push-pull), at some positions on the cycles. Moreover, the largest cross section is obtained for bifluorene. The replacement of carbon atoms by nitrogen atoms, giving heterocycles, is not efficient. In chloroform as solvent, the excitation energy decreases and the two-photon cross section increases, mainly with a polar molecule. Finally, a rationalization of the results is given based on the three-level model by analysis of the transition moments and of the molecular orbitals.

Downregulation of male-specific cytochrome P450 by profenofos.

The health hazards of individual organophosphorus insecticides have been characterized by their acute toxicity, mainly by investigating their cholinesterase inhibition. However, the chronic effects of most of these toxicants on the drug-metabolizing enzymes have not been investigated. Profenofos (O-4-bromo-2-chlorophenyl O-ethyl S-propyl phosphorothioate) is an organophosphorus pesticide widely used in cotton cultivation. In the present study, we investigated the effect of profenofos on male-specific cytochrome P450 (CYP) enzymes in adult Wistar rats. We orally administered 17.8 mg/kg body weight, twice weekly for 65 days. Profenofos downregulated levels of hepatic and testicular CYP2C11 and CYP3A2 mRNA and protein expression. Testicular aromatase (CYP19A) mRNA was decreased in the profenofos-treated rats compared to controls. Overall, the present study suggests that profenofos acts as an endocrine disruptor of male-specific CYP enzymes and affects testosterone concentration, which implicates its deleterious effects on animal or human males chronically exposed to organophosphorus pesticide.

Protection by Nigella sativa against carbon tetrachloride-induced downregulation of hepatic cytochrome P450 isozymes in rats.

Nigella sativa (family Ranunculaceae) is an annual plant that has been traditionally used on the Indian subcontinent and in Middle Eastern countries. In this study, we investigated the effect of N. sativa oil on the drug-metabolizing cytochrome P450 (CYP) enzymes and whether it has a protective effect against the acute hepatotoxicity of CCl4. Intraperitoneal injection of rats with CCl4 drastically decreased CYP2E1, CYP2B, CYP3A2, CYP2C11, and CYP1A2 mRNA and protein expressions. Oral administration of 1 ml/kg N. sativa oil every day for one week prior to CCl4 injection alleviated CCl4-induced suppression of CYP2B, CYP3A2, CYP2C11, and CYP1A2. Moreover, CCl4 increased iNOS and TNFalpha mRNA, while N. sativa oil administration for one week prior to CCl4 injection downregulated the CCl4-induced iNOS mRNA and up-regulated IL-10 mRNA. These results indicate that N. sativa oil administration has a protective effect against the CCl4-mediated suppression of hepatic CYPs and that this protective effect is partly due to the downregulation of NO production and up-regulation of the anti-inflammatory IL-10.

What are the indications for plasma exchanges in autoimmune diseases?: The registry of the Société Française d'Hémaphérèse.

The use of plasma exchange (PE) in the autoimmune diseases is encouraged in France. Since 1990, the national registry of PE allows an analysis of the evolution of the coverage of these pathologies. The variation of the number of patients treated by PE is correlated in respect to the results of the therapeutic studies. After a decrease of PE activity in these indications during the 90s, one observes a new increase of the patients treated because of the validation of new indications. Autoimmune diseases represent the third cause of morbidity in developed countries, with a global prevalence of 5%, and concerns four groups of pathologies of organs or systems (neurology, haematology, nephrology and vasculitis). In 1976, Lockwood demonstrated the place of plasma exchanges (PE) in Goodpasture's syndrome [Lockwood CM, Rees AJ, Pearson TA, Evans DJ, Peters DK, Wilson CB. Immunosuppression and plasma exchange in the treatment of Goopasture's syndrome. Lancet 1976;1(7962):723-6. [1]], with a significant decrease of antibodies during large volume exchanges. In the 80s, several prospective studies began to estimate the efficiency of PE in other autoimmune diseases. The national registry of the Société Française d' Hémaphérèse, has collected the epidemiological and technical data of PE since 1985. This work analyses the evolution of the validated indications, between 1990 and 2005 in France.

Road safety engineering: an effective tool in the fight against whiplash injuries.

Road safety engineering can play an integral part in the prevention of whiplash injuries. While improvements to vehicle design can reduce the severity of whiplash injuries when a crash occurs, improvements to road safety can prevent whiplash-inducing crashes from occurring in the first place. Whiplash injuries are most commonly associated with rear end crashes. Unfortunately, rear end crashes are also the most common type of crash at urban signalized intersections, where the majority of crashes occur in British Columbia, Canada. The Insurance Corporation of British Columbia (ICBC), through the road improvement program, has been funding road improvements in order to reduce the frequency of collisions at high crash locations in British Columbia. Several road safety engineering countermeasures specifically targeted at rear end collisions have been researched and deployed. These countermeasures include simple and affordable solutions such as signal visibility enhancements, as well as complex and expensive solutions such as intersection geometric upgrades. When appropriately used, these countermeasures have proven to be extremely cost-effective in reducing the frequency of rear end collisions. Widespread application of signal visibility enhancements is now being pursued to further decrease the risk of rear end collisions and whiplash injuries. Costs are the direct cost of the ICBC portion of the investment and benefits are only those associated with reduced insurance claims over a 2-year period.

Three complement-type repeats of the low-density lipoprotein receptor-related protein define a common binding site for RAP, PAI-1, and lactoferrin.

The low-density lipoprotein receptor-related protein (LRP) is a 600-kD scavenger receptor that binds a number of protein ligands with high affinity. Although some ligands do not compete with each other, binding of all is uniformly blocked by the 39-kD receptor-associated protein (RAP). RAP is normally found in the endoplasmic reticulum and seems to function as a chaperone for LRP. To identify the binding sites for RAP, lactoferrin, and plasminogen activator inhibitor-1 (PAI-1), a bacterial expression system has been developed to produce soluble LRP fragments spanning residues 783-1399. These residues overlap most of the CNBr fragment containing the second cluster of complement-type repeats (C). Solid phase binding assays show that 125I-RAP binds to fragments containing three successive complement-type repeats: C5-C7. PAI-1 and lactoferrin bind to the same fragments. A fragment containing C5-C7 also blocks uptake and degradation of 125I-RAP by fibroblasts in a concentration-dependent manner. Binding competition experiments show that RAP, PAI-1, and lactoferrin each inhibit the binding of the others, suggesting that at this site in LRP, RAP acts as a competitive, rather than an allosteric, inhibitor of PAI-1 and lactoferrin binding.