HIGH RESOLUTION THZ AND FIR SPECTROSCOPY OF SOCl2_2

Author Institution: Laboratoire de Physico-Chimie de l'Atmosphere, EA 4493, Universite du Littoral Cote d'Opale, 59140 Dunkerque, France; Institut des Sciences Moleculaires d'Orsay, CNRS, UMR 8214, Universite Paris XI, bat. 210, 91405 Orsay Cedex, France; SOLEIL Synchrotron, AILES beamline, L'orme des Merisiers, Saint-Aubin, 91192 Gif-Sur-Yvette, FranceThionyl chloride (SOCl$_2$) is an extremely powerful oxidant widely used in industrial processes and playing a role in the chemistry of the atmosphere, \textit{J. Phys. Chem. A} 107, 6183 (2003)}. In addition, it has a molecular configuration similar to that of phosgene (COCl$_2$), and is therefore of particular interest for security and defense applications. Low resolution vibrational spectra of gas phase SOCl$_2$ 22,1193 (1954)} as well as high resolution pure rotational transitions up to 25 GHz 90, 3473 (1994)} have previously been investigated. To date no high resolution data are reported at frequencies higher than 25 GHz. \vspace{1em} We have investigated the THz absorption spectrum of SOCl$_2$ in the spectral region 70--650 GHz using a frequency multiplier chain coupled to a 1 m long single path cell containing a pressure of about 15 $\mu$bar. At the time of the writing, about 8000 pure rotational transitions of SO$^{35}$Cl$_2$ with highest $J$ and $K_a$ values of 110 and 50 respectively have been assigned on the spectrum. We have also recorded the high resolution FIR spectra of SOCl$_2$ in the spectral range 50--700 \wn~using synchrotron radiation at the AILES beamline of SOLEIL facility. A White-type cell aligned with an absorption path length of 150 m has been used to record, at a resolution of 0.001 \wn,~two spectra at pressures of 5 and 56 $\mu$bar of SOCl$_2$. On these spectra all FIR modes of SOCl$_2$ are observed ($\nu_2$ to $\nu_6$) and present a resolved rotational structure. Their analysis is in progress

TERAHERTZ ROTATIONAL SPECTROSCOPY OF THE SO RADICAL

Author Institution: Laboratoire de Physico-Chimie de l'Atmosphere, EA 4493, Universite du Littoral Cote d'Opale, 59140 Dunkerque, France; Institut des Sciences Moleculaires d'Orsay, CNRS, UMR 8214, Universite Paris XI, bat. 210, 91405 Orsay Cedex, France; SOLEIL Synchrotron, AILES beamline, L'orme des Merisiers, Saint-Aubin, 91192 Gif-Sur-Yvette, FranceSulfur monoxide SO (X$^3\Sigma^-$) is a well-known interstellar radical identified in a wide variety of astrophysical environments 184, L59 (1973)} which is particularly abundant in star forming regions, \textit{Astrophys. J.} 315, 621 (1987)}. Due to its high reactivity and its role in chemical reactions involving O and S atoms, SO is also a reaction intermediate in combustion processes and chemistry of the Earth atmosphere, \textit{J. Mol. Spectrosc.} 124, 379 (1987)}. %The pure rotational spectrum of SO has been extensively studied in the laboratory from sub-millimeter to THz wavelength, \textit{J. Mol. Speectrosc.} 182, 85 (1997)}. However no far infrared (FIR) broadband investigation on this radical has been reported up to date, and several rotational transitions belonging to the spectral windows of the HIFI instrument (on board of the Herschel satellite) require accurate laboratory measurements. %\vspace{1em} We have recorded pure rotational transitions of SO in the THz spectral range using synchrotron-based Fourier-Transform (FT) FIR and continous wave (CW) THz techniques. A FT-FIR spectrum of SO has been recorded at the AILES beamline of SOLEIL synchrotron in the spectral range 44--93 \wn~using a resolution of 0.001~\wn~allowing an accuracy on line position of 0.00007~\wn~($\sim$ 2 MHz). A multipass absorption discharge cell aligned to an absorption path length of 24 m has been used, \textit{Rev. Sci. Instrum.} 82, 113106 (2011)}. A continuous electrical discharge (1~A / 980~V) in a flowing mixture of H$_2$S, He, H$_2$ and air (respectively at pressure of 0.01, 1.15, 0.14 and 0.06~mbar) was used to produce SO. On this spectrum, 102 transitions of SO have been identified with $N=31$ to $65$. Among the observed lines, 99 are detected for the first time (22 new transitions belong to the HIFI spectral windows). Due to our limited instrumental resolution, transitions involving $N$ ranging from $31$ to $43$ show unresolved fine structure triplets. Recently, in order to observe all fine structure components in the HIFI spectral windows, we have recorded a high resolution CW-THz spectrum of SO, \textit{J. Mol. Struct.} 1006, 13 (2011)}. At the time of the writing, this spectrum was under analysis

Mevalonate kinase deficiencies: from mevalonic aciduria to hyperimmunoglobulinemia D syndrome

Mevalonic aciduria (MVA) and hyperimmunoglobulinemia D syndrome (HIDS) represent the two ends of a clinical spectrum of disease caused by deficiency of mevalonate kinase (MVK), the first committed enzyme of cholesterol biosynthesis. At least 30 patients with MVA and 180 patients with HIDS have been reported worldwide. MVA is characterized by psychomotor retardation, failure to thrive, progressive cerebellar ataxia, dysmorphic features, progressive visual impairment and recurrent febrile crises. The febrile episodes are commonly accompanied by hepatosplenomegaly, lymphadenopathy, abdominal symptoms, arthralgia and skin rashes. Life expectancy is often compromised. In HIDS, only febrile attacks are present, but a subgroup of patients may also develop neurological abnormalities of varying degree such as mental retardation, ataxia, ocular symptoms and epilepsy. A reduced activity of MVK and pathogenic mutations in the MVK gene have been demonstrated as the common genetic basis in both disorders. In MVA, the diagnosis is established by detection of highly elevated levels of mevalonic acid excreted in urine. Increased levels of immunoglobulin D (IgD) and, in most patients of immunoglobulin A (IgA), in combination with enhanced excretion of mevalonic acid provide strong evidence for HIDS. The diagnosis is confirmed by low activity of mevalonate kinase or by demonstration of disease-causing mutations. Genetic counseling should be offered to families at risk. There is no established successful treatment for MVA. Simvastatin, an inhibitor of HMG-CoA reductase, and anakinra have been shown to have beneficial effect in HIDS

Creatine and guanidinoacetate reference values in a French population

Creatine and guanidinoacetate are biomarkers of creatine metabolism. Their assays in body fluids may be used for detecting patients with primary creatine deficiency disorders (PCDD), a class of inherited diseases. Their laboratory values in blood and urine may vary with age, requiring that reference normal values are given within the age range. Despite the long known role of creatine for muscle physiology, muscle signs are not necessarily the major complaint expressed by PCDD patients. These disorders drastically affect brain function inducing, in patients, intellectual disability, autistic behavior and other neurological signs (delays in speech and language, epilepsy, ataxia, dystonia and choreoathetosis), being a common feature the drop in brain creatine content. For this reason, screening of PCDD patients has been repeatedly carried out in populations with neurological signs. This report is aimed at providing reference laboratory values and related age ranges found for a large scale population of patients with neurological signs (more than 6 thousand patients) previously serving as a background population for screening French patients with PCDD. These reference laboratory values and age ranges compare rather favorably with literature values for healthy populations. Some differences are also observed, and female participants are discriminated from male participants as regards to urine but not blood values including creatine on creatinine ratio and guanidinoacetate on creatinine ratio values. Such gender differences were previously observed in healthy populations; they might be explained by literature differential effects of testosterone and estrogen in adolescents and adults, and by estrogen effects in prepubertal age on SLC6A8 function. Finally, though they were acquired on a population with neurological signs, the present data might reasonably serve as reference laboratory values in any future medical study exploring abnormalities of creatine metabolism and transport

Stenosis and Aneurysm of Coronary Arteries in A Patient with Behcet’s Disease

Coronary artery disease is extremely rare in patients with Behçet’s disease. We report the case of a patient with a history of Behçet’s disease who was admitted in our hospital with instable angina pectoris. The patient’s electrocardiogram was normal. Coronary angiography revealed aneurysm of the distal right coronary artery with a tight stenosis of the proximal part of the posterolateral branch. These two conditions were initially treated with immunosuppressive treatment. Three years later coronary angiography showed a total occlusion of the right coronary artery treated with medical therapy. More than fourteen cases of coronary involvement were reported in the literature but the etiopathogeny and the treatment are yet unknow

International Expert Consensus on Switching Platelet P2Y(12) Receptor-Inhibiting Therapies

Dual antiplatelet therapy with aspirin and a P2Y(12) inhibitor is the treatment of choice for the prevention of atherothrombotic events in patients with acute coronary syndromes and for those undergoing percutaneous coronary interventions. The availability of different oral P2Y(12) inhibitors (clopidogrel, prasugrel, ticagrelor) has enabled physicians to contemplate switching among therapies because of specific clinical scenarios. The recent introduction of an intravenous P2Y(12) inhibitor (cangrelor) further adds to the multitude of modalities and settings in which switching therapies may occur. In clinical practice, it is not uncommon to switch P2Y(12) inhibitor, and switching may be attributed to a variety of factors. However, concerns about the safety of switching between these agents have emerged. Practice guidelines have not fully elaborated on how to switch therapies, leaving clinicians with limited guidance on when and how to switch therapies when needed. This prompted the development of this expert consensus document by key leaders from North America and Europe with expertise in basic, translational, and clinical sciences in the field of antiplatelet therapy. This expert consensus provides an overview of the pharmacology of P2Y(12) inhibitors, different modalities and definitions of switching, and available literature and recommendations for switching between P2Y(12) inhibitors

Usefulness of Routine Fractional Flow Reserve for Clinical Management of Coronary Artery Disease in Patients With Diabetes

Importance: Approximately one-third of patients considered for coronary revascularization have diabetes, which is a major determinant of clinical outcomes, often influencing the choice of the revascularization strategy. The usefulness of fractional flow reserve (FFR) to guide treatment in this population is understudied and has been questioned. Objective: To evaluate the usefulness and rate of major adverse cardiovascular events (MACE) of integrating FFR in management decisions for patients with diabetes who undergo coronary angiography. Design, setting, and participants: This cross-sectional study used data from the PRIME-FFR study derived from the merger of the POST-IT study (Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease [March 2012-November 2013]) and R3F study (French Study of FFR Integrated Multicenter Registries Implementation of FFR in Routine Practice [October 2008-June 2010]), 2 prospective multicenter registries that shared a common design. A population of all-comers for whom angiography disclosed ambiguous lesions was analyzed for rates, patterns, and outcomes associated with management reclassification, including revascularization deferral, in patients with vs without diabetes. Data analysis was performed from June to August 2018. Main outcomes and measures: Death from any cause, myocardial infarction, or unplanned revascularization (MACE) at 1 year. Results: Among 1983 patients (1503 [77%] male; mean [SD] age, 65 [10] years), 701 had diabetes, and FFR was performed for 1.4 lesions per patient (58.2% of lesions in the left anterior descending artery; mean [SD] stenosis, 56% [11%]; mean [SD] FFR, 0.81 [0.01]). Reclassification by FFR was high and similar in patients with and without diabetes (41.2% vs 37.5%, P = .13), but reclassification from medical treatment to revascularization was more frequent in the former (142 of 342 [41.5%] vs 230 of 730 [31.5%], P = .001). There was no statistical difference between the 1-year rates of MACE in reclassified (9.7%) and nonreclassified patients (12.0%) (P = .37). Among patients with diabetes, FFR-based deferral identified patients with a lower risk of MACE at 12 months (25 of 296 [8.4%]) compared with those undergoing revascularization (47 of 257 [13.1%]) (P = .04), and the rate was of the same magnitude of the observed rate among deferred patients without diabetes (7.9%, P = .87). Status of insulin treatment had no association with outcomes. Patients (6.6% of the population) in whom FFR was disregarded had the highest MACE rates regardless of diabetes status. Conclusions and relevance: Routine integration of FFR for the management of coronary artery disease in patients with diabetes may be associated with a high rate of treatment reclassification. Management strategies guided by FFR, including revascularization deferral, may be useful for patients with diabetes.info:eu-repo/semantics/publishedVersio

Idebenone reduces respiratory complications in patients with Duchenne muscular dystrophy

In Duchenne muscular dystrophy (DMD), progressive loss of respiratory function leads to restrictive pulmonary disease and places patients at significant risk for severe respiratory complications. Of particular concern are ineffective cough, secretion retention and recurrent respiratory tract infections. In a Phase 3 randomized controlled study (DMD Long-term Idebenone Study, DELOS) in DMD patients 10–18 years of age and not taking concomitant glucocorticoid steroids, idebenone (900 mg/day) reduced significantly the loss of respiratory function over a 1-year study period. In a post-hoc analysis of DELOS we found that more patients in the placebo group compared to the idebenone group experienced bronchopulmonary adverse events (BAEs): placebo: 17 of 33 patients, 28 events; idebenone: 6 of 31 patients, 7 events. The hazard ratios (HR) calculated “by patient” (HR 0.33, p = 0.0187) and for “all BAEs” (HR 0.28, p = 0.0026) indicated a clear idebenone treatment effect. The overall duration of BAEs was 222 days (placebo) vs. 82 days (idebenone). In addition, there was also a difference in the use of systemic antibiotics utilized for the treatment of BAEs. In the placebo group, 13 patients (39.4%) reported 17 episodes of antibiotic use compared to 7 patients (22.6%) reporting 8 episodes of antibiotic use in the idebenone group. Furthermore, patients in the placebo group used systemic antibiotics for longer (105 days) compared to patients in the idebenone group (65 days). This post-hoc analysis of DELOS indicates that the protective effect of idebenone on respiratory function is associated with a reduced risk of bronchopulmonary complications and a reduced need for systemic antibiotics