SQ HDM sublingual immunotherapy tablet for the treatment of HDM allergic rhinitis and asthma improves subjective sleepiness and insomnia: an exploratory analysis of the real-life CARIOCA study.

BACKGROUND AND OBJECTIVE: There are still gaps in the knowledge regarding the effectiveness of house dust mite (HDM) sublingual immunotherapy (SLIT) on allergic rhinitis (AR) and asthma (AA)-associated sleep disorders. A non-interventional study was conducted to assess the effect of the Standardized quality (SQ) HDM SLIT-tablet on safety and symptoms in adults with HDM respiratory allergies. The aim was to describe the status of insomnia and daytime sleepiness in AR and/or AA patients treated with the SQ HDM SLIT-tablet. METHODS: This was a 12-month multicenter, longitudinal and prospective study. Participants started the SQ HDM SLIT-tablet for moderate-to-severe HDM AR, persistent despite the use of symptom-relieving medication; or HDM AA not well controlled by inhaled corticosteroids and associated with mild-to-severe HDM AR. Sleep symptoms were measured using the Insomnia Severity Index (ISI) questionnaire and the Epworth Sleepiness Scale (ESS). RESULTS: A total of 1,526 adult patients were enrolled and 1,483 were included in the analysis. At baseline, 41.5% of patients reported sleep disorders: 77.0% of them had insomnia and 28.9% suffered from excessive daytime sleepiness. Insomnia was significantly more frequent among patients with uncontrolled AR (83.1%) than those with controlled AR (52.6%) (p<0.0001). Over time, 48.3% and 59.7% of patients reported an improvement greater than the minimal clinically important difference on the ISI and ESS scales respectively. CONCLUSION: In patients with HDM AR and/or asthma associated sleep disorders, an improvement in subjective insomnia and sleepiness was observed after one year of treatment with the SQ HDM SLIT-tablet in a real-life setting.

Night-Time Ionospheric Localized Enhancements (NILE) Observed in North America Following Geomagnetic Disturbances.

The Ionospheric Data Assimilation Four-Dimensional (IDA4D) technique has been coupled to Sami3, which is another model of the ionosphere (SAMI3). In this application, ground-based and space-based GPS total electron content (TEC) data have been assimilated into SAMI3, while in-situ electron densities, autoscaled ionosonde NmF2, and reference GPS stations have been used for validation. IDA4D/SAMI3 shows that night-time ionospheric localized enhancements (NILE) are formed following geomagnetic storms in November 2003 and August 2018. The NILE phenomenon appears as a moderate, longitudinally extended enhancement of NmF2 at 30°-40°N MLAT, occurring in the late evening (20-24 LT) following much larger enhancements of the equatorial anomaly crests in the main phase of the storms. The NILE appears to be caused by upward and northward plasma transport around the dusk terminator, which is consistent with eastward polarization electric fields. Independent validation confirms the presence of the NILE, and indicates that IDA4D is effective in correcting random errors and systematic biases in SAMI3. In all cases, biases and root-mean-square errors are reduced by the data assimilation, typically by a factor of 2 or more. During the most severe part of the November 2003 storm, the uncorrected ionospheric error on a GPS 3D position at 1LSU (Louisiana) is estimated to exceed 34 m. The IDA4D/SAMI3 specification is effective in correcting this down to 10 m.

Costs of perennial allergic rhinitis and allergic asthma increase with severity and poor disease control.

BACKGROUND: Perennial allergic rhinitis (PAR) represents a global and public health problem, due to its prevalence, morbidity, and impact on the quality of life. PAR is frequently associated with allergic asthma (AA). Costs of PAR with or without AA are poorly documented. OBJECTIVE: Our study aimed to detail medical resource utilization (MRU) and related direct cost for PAR, with or without concomitant AA, in France. METHODS: Using Electronic Health Records (EHRs), we identified in 2010 two cohorts of PAR patients, based on General Practitioners' diagnoses and prescribing data, with and without concomitant AA. For each patient, the EHRs were linked to corresponding claims data with MRU and costs during years 2011 to 2013. Predefined subgroup analyses were performed according to severity of PAR and level of AA control. RESULTS: The median annual cost reimbursed by social security system for a patient with PAR, and no AA was 159€ in 2013. This varied from 111€ to 188€ depending on PAR severity. For patients with PAR and concomitant AA, the median annual cost varied between 266€ and 375€, and drug treatment accounted for 42-55% of the costs, depending on asthma control. CONCLUSION: This study linking diagnoses from EHRs to claims data collected valid information on PAR management, with or without concomitant AA, and on related costs. There was a clear increase in costs with severity of PAR and control of AA.

[An excessive diagnosis of constipation in children complaining of abdominal pain in a pediatric emergency department: an example of practice patterns]. / Une prévalence excessive du diagnostic de constipation chez les enfants consultant pour douleurs abdominales aux urgences: un exemple d'évaluation des pratiques.

UNLABELLED: Prescriptions of abdominal x-ray and diagnosis of constipation seemed too frequent in children evaluated for abdominal pain (AP) in a paediatric emergency unit. OBJECTIVE: To evaluate the prevalence of constipation in children with AP, to determine clinical and radiological signs related to this diagnosis, and to compare frequencies of clinical criteria of functional chronic constipation (FCC) in children with AP with those of controls (children with mild traumatisms without AP). METHODS: This prospective observational study included children older than 4 years of age consulting for AP. RESULTS: Among 196 patients with AP, 53% had a diagnosis of constipation on discharge (28% isolated and 25% associated with an other diagnosis), and 88% had a plain abdominal x-ray. A faecal retention was considered by emergency practitioners in 92% of children with the diagnosis of constipation vs 22% with other diagnosis (OR=38; CI 95%: 15-101). Clinical criteria of FCC were associated with the diagnosis of constipation (OR=2.7; CI 95%: 1.4-5.2). A FCC was as prevalent in the control population as in AP population (32 vs 34%). CONCLUSION: An excessive prevalence of diagnosis of constipation was mainly associated with contestable x-ray diagnosis of faecal retention secondary to inappropriate indications of abdominal x-ray.

Smac/DIABLO and colon cancer.

Apoptosis is a genetically programmed process of controlled and orderly cell suicide, which is critical for multicellular organisms during development and tissue homeostasis. In cancer, the ratio of apoptosis to cell division is altered, resulting in a net gain of malignant tissue. Tumor cells may acquire resistance to apoptosis by the expression of anti-apoptotic proteins, or by the down-regulation or mutation of pro-apoptotic mediators. In the classic pathway of apoptosis, this process is primarily coordinated by activation of caspases. Decreased expression of caspases inversely correlates with the aggressiveness of cancer. Increased activity of caspases renders cancer cells susceptible to chemoradiotherapeutic modalities. Thus, caspase activity is pivotal in carcinogenesis. The functions of activated caspases are inhibited by the binding of inhibitors of apoptosis (IAPs). The function of IAPs is regulated by pro-apoptotic protein Second Mitochondria-Derived Activator of Caspases (Smac) or Direct IAP Binding Protein with low isoelectric point, pI (DIABLO). Induction of apoptosis leads to increased mitochondrial permeability to Smac/DIABLO, which adheres to IAPs inhibiting their caspase-binding activity. The role of Smac/DIABLO, therefore, may have significant diagnostic and therapeutic features in carcinogenesis. The role of Smac/DIABLO in colorectal carcinogenesis is ill defined. Data continues to accumulate to suggest that decreased levels of Smac/DIABLO may be important in chemoradiation-resistance to apoptosis in advanced colon cancer. The aim of this review is to provide the available evidence of the role of Smac/DIABLO in colon carcinogenesis.

6-tioguanine monitoring in steroid-dependent patients with inflammatory bowel diseases receiving azathioprine.

BACKGROUND: 6-Thioguanine (6-tioguanine) nucleotides are the active metabolites of azathioprine. AIM: The aim of the study was to evaluate the rate of clinical remission without steroids in steroid-dependent Crohn's disease and ulcerative colitis patients receiving azathioprine, the medium- and long-term efficacy and the predictive factors of clinical response when monitoring 6-tioguanine. METHODS: Steroid-dependent Crohn's disease and ulcerative colitis patients receiving either azathioprine or not (treated later with a daily dose of 2.5 mg/kg) were prospectively included. 6-tioguanine was monitored at 1 and 2 months and every 3 months thereafter for 1 year. The azathioprine dose was adapted to reach a 6-tioguanine level of >250 pmol/8 x 10(8) red blood cells. Thiopurine methyltransferase genotype/phenotype was evaluated in some patients. RESULTS: A total of 106 patients were prospectively included (70 Crohn's disease, 36 ulcerative colitis). The clinical remission rate without steroids in patients receiving azathioprine, in intention-to-treat analysis, was 72% and 59% at 6 and 12 months, respectively. The remission rate was significantly higher in patients with 6-tioguanine >250 pmol/8 x 10(8) RBC (86% and 69% at 6 and 12 months, respectively; P < 0.01). No significant difference was observed between Crohn's disease and ulcerative colitis patients whether treated by azathioprine or not on inclusion. In the univariate analysis, the absence of Crohn's disease stenosis, a 6-tioguanine level >250 pmol/8 x 10(8) RBC, and an increase of erythrocyte mean corpuscular volume were the factors predictive of a favourable clinical response. In the multivariate analysis, only a 6-tioguanine level of >250 pmol/8 x 10(8) red blood cells was a predictive factor of favourable clinical remission. CONCLUSIONS: Clinical remission without steroids is significantly more likely when monitoring 6-tioguanine so as to reach a level of >250 pmol/8 x 10(8) red blood cells in steroid-dependent Crohn's disease and ulcerative colitis patients receiving azathioprine (86% and 69% at 6 and 12 months, respectively).

Molecular dynamic simulation of disorder induced amorphization in pyrochlore.

The defect accumulation mechanism of amorphization has been studied for the La2Zr2O7 pyrochlore by means of classical molecular dynamic simulations. Present calculations show that the accumulation of cation Frenkel pairs is the main driving parameter for the amorphization process, while the oxygen atoms simply rearrange around cations. Under Frenkel pair accumulation, the structure follows the pyrochlore-fluorite-amorphous sequence. Present results consequently provide atomic-level interpretation to previous experimental irradiation observations of the two-step phase transition.

[Cow's milk protein allergy after neonatal intestinal surgery]. / Allergie aux protéines du lait de vache après chirurgie digestive néonatale.

UNLABELLED: Cases of cow's milk protein allergy have been occasionally reported after neonatal intestinal surgery. AIM OF THE STUDY: To measure the prevalence of cow's milk protein allergy (CMPA) following neonatal intestinal surgery. PATIENTS AND METHODS: The files of all children who underwent intestinal surgery in the neonatal period over a four-year-period were reviewed. The diagnosis of CMPA was made on the association of one or several symptoms suggesting food allergy after the introduction of cow's milk protein in the diet, the disappearance of the symptoms after exclusion of cow's milk protein from the diet and their reappearance after reintroduction of cow's milk protein. RESULTS: During the study period, 251 neonates underwent an intestinal surgery. Among them, 11 babies (4.3%) developed CMPA. None of them had a medical history of family atopy. Moreover, while 5 children were fed with a diet containing cow's milk protein before surgery: none of them presented initially with symptoms suggesting CMPA before intestinal surgery. Small intestine suffering was observed during operation in seven of 11 patients. No specific neonatal digestive disease or malformation was associated with CMPA. The signs revealing CMPA were primarily digestive : diarrhoea (N =3), vomiting (N =4), abdominal distension (N =2), colic or anorexia (N =2). Casein specific immunoglobulin E were present in nine of ten cases, alpha lactalbumin and/or beta lactoglobulin specific immunoglobulin E were present in six of ten cases. Prick test were performed in three children and were positive. CONCLUSION: The high prevalence of CMPA among these patients with no risk factors of allergy raises the question of the role of neonatal intestinal surgery in developing food allergy. These data should be confirmed by prospective case-control studies. They underline the interest to evoke the diagnosis of CMPA when digestive symptoms occur after milk protein introduction in children undergoing neonatal intestinal surgery. Breast feeding or milk protein hydrolysate formula should be used for refeeding these patients.

[Hypertrophic pulmonary osteo-arthropathy revealed by a pulmonary epithelioid hemangioendothelioma in a 15-year-old girl]. / Ostéo-arthropathie hypertrophiante pneumique et hémangio-endothéliome épithélioïde pulmonaire chez une adolescente de 15 ans.

UNLABELLED: Pulmonary epithelioid hemangioendothelioma is a rare vascular tumor of the lung, that may be revealed by hypertrophic pulmonary osteo-arthropathy. CASE REPORT: A 15-year-old patient was admitted because of a 1-month history of pneumonia associated with clubbing. A hypertrophic pulmonary osteo-arthropathy due to a paraneoplastic syndrome associated with lung epithelioid hemangioendothelioma was diagnosed. Despite surgical resection and chemotherapy, the patient died 6 months later. COMMENTS: Hypertrophic pulmonary osteo-arthropathy is a rare syndrome in childhood, and is frequently associated with chronic respiratory failure. Diagnosis is confirmed by long bones proliferative periostitis on standard X-ray examination. Pulmonary epithelioid hemangioendothelioma is a rare vascular malignant tumor, that spreads from the vascular pulmonary or hepatic tissues. The prognosis is variable, depending on the malignancy of the tumor. In the absence of a chronic cardiorespiratory disease, the diagnosis of a pulmonary hypertrophic osteo-arthropathy in childhood should prompt the search for a tumoral cause.

[Effectiveness of a short-stay observation unit in a pediatric emergency department]. / Utilité d'une unité d'hospitalisation de courte durée aux urgences pédiatriques.

UNLABELLED: Short-Stay Observation Units (SSOUs) in paediatric emergency departments are effective in reducing inpatient admissions but can also generate excessive short-stay hospitalisations. The aim of the study was to evaluate both these consequences and the different missions of SSOUs. METHODS: This prospective study included all children admitted in a 10-bed-medico-surgical SSOU of a tertiary-care paediatric emergency department from September 4, to October 31, 2001. At the time of SSOU admission, the physician indicated the purpose of the admission and which decision he would have made in the absence of a SSOU. RESULTS: Five hundred and nine children (median age = 4 years, chronic disease: 26%, trauma: 34%) were included, accounting for 15% of admissions. The mean length of stay was 14 +/- 8h. The decision in the absence of a SSOU would have been: inpatient hospitalization (77%), transfer to another hospital in the absence of inpatient room vacancy (7%), discharge home (10%), prolonged waiting in the emergency ward (4%), do not know or not indicated (2%). The SSOU admission was deemed appropriate in 81%: discharge home within 24h was likely in 65% and the final orientation of the child was uncertain in 16%. The admission was debatable in 13% and inappropriate in 6%. Sixty six per cent of children were discharged home. CONCLUSION: The SSOU reduced inpatient hospitalisations, generated few inappropriate short stay hospitalisations, and seemed particularly efficient for paediatric diseases. Proposed indicators should allow inter-hospital comparisons.

Undergraduate student experience in dental service delivery in rural South Australia: an analysis of costs and benefits.

BACKGROUND: Rural experience for dental students can provide valuable clinical education, change attitudes to rural practice, and make a valuable contribution to clinical service provision. The aim of this paper is to assess the costs and benefits of service delivery by students through rural training programmes. METHODS: Groups of two students worked in the public dental clinics in adjacent rural centres where there had been long-term difficulties in recruiting staff. The costs and benefits of the programme were assessed by the impact on waiting lists, the total cost per patient of a course of care and by the marginal cost of adding service provision by students to existing arrangements. RESULTS: The total costs of emergency and complete treatment provided by students were greater than the costs of treatment provided by public-sector dentists but less than the costs of private providers treating public patients. However, the value of services were greater when care was provided by students or private providers and the marginal cost of students providing services was 50-70 per cent of the cost of care provided by public dentists. CONCLUSION: This assessment suggests that the service benefits achieved compliment the primary objective of influencing the attitude of students to rural practice.

[Chiari type I malformation in children: presentation in 34 cases]. / Malformation de Chiari de type I de l'enfant: modes de révélation de 34 observations.

UNLABELLED: Incidental diagnoses of Chiari I malformation are more and more frequent in pauci or asymptomatic children. The value of neurophysiological investigations for surgical indications is discussed. OBJECTIVE: To determine clinical presentations of Chiari I malformation and relative frequencies of severe and incidental forms, and to evaluate the usefulness of neurophysiological investigations for surgical indications. METHODS: This retrospective study included 34 patients admitted from 1984 to 2000, with Chiari I malformation diagnosis in different pediatric (intensive care, neurology and neurosurgery) units of a university hospital. RESULTS: The clinical presentation was severe (two children died) in four cases (12%). Signs of brain stem compression were found in 41% of cases, scoliosis in 21%, and incidental diagnosis in 26%. The polysomnography, performed in 12 cases, showed sleep-apneas in six cases. One child with an incidental diagnosis of Chiari I malformation had many sleep-apneas which required a surgical treatment. A surgical decompression was performed in 69% of cases, with clinical improvement in 77%. CONCLUSION: The high incidence (12%) of severe forms revealing Chiari I malformations justifies systematic neurophysiological investigations for the initial evaluation and the follow-up of Chiari 1 malformations, including the less symptomatic forms.

Cerivastatin, an inhibitor of HMG-CoA reductase, inhibits urokinase/urokinase-receptor expression and MMP-9 secretion by peripheral blood monocytes--a possible protective mechanism against atherothrombosis.

It is now recognised that acute myocardial infarction results from the rupture of atherosclerotic plaques. Lymphocytes and macrophages, which infiltrate rupture sites, contribute to plaque degradation by expressing urokinase (u-PA) bound to cell membrane by urokinase receptor (u-PAR) and by secreting metalloproteinase MMP-9. We have previously demonstrated that the uptake of oxidised LDL (ox-LDL) by monocytes induces an increase of u-PA and u-PAR expression. The present study shows that the expression of u-PA and u-PAR induced by ox-LDL on monocyte surface is suppressed by cerivastatin (a synthetic inhibitor of HMG-CoA reductase, Bayer) from 2 nM. This leads to reduced plasmin generation and monocyte adhesion to vitronectin. Furthermore, higher concentrations of cerivastatin (50-100 nM) reduce the expression of u-PA and u-PAR on unstimulated monocytes. It also inhibits MMP-9 secretion but has no effect on TIMP-1 secretion, suggesting that the decrease in MMP-9 has a real protective effect on plaque stabilisation. The inhibitory effect of cerivastatin on u-PA expression and MMP-9 secretion can be explained by the inhibition of NF-kappa B translocation into the nucleus, as shown by immunofluorescence. As farnesyl-pyrophosphate reverses the effect of cerivastatin, it is postulated that these effects could also be due to the inhibition of Ras prenylation. This was confirmed by confocal microscopy, which shows the Ras delocalisation from the monocyte membrane. The cerivastatin-induced effects on monocyte functions could explain, at least in part, the protective effect of this drug against atherothrombotic events.

Accuracy comparison of absolute optical frequency measurement between harmonic-generation synthesis and a frequency-division femtosecond comb

Using an iodine-stabilized He-Ne laser as a transfer oscillator, we compare absolute measurements of the optical frequency from a traditional frequency synthesis chain based on harmonic generation and from the frequency division technique of an ultrawide bandwidth femtosecond frequency comb. The agreement between these two measurements, both linked to the Cs standard, is 220+/-770 Hz, yielding a measurement accuracy of 1.6x10(-12). We report 473 612 353 604.8+/-1.2 kHz as a preliminary updated value of the absolute frequency of the " f" component for the He-Ne laser international standard at 633 nm.

A Drosophila RNA helicase gene, pitchoune, is required for cell growth and proliferation and is a potential target of d-Myc.

This article describes the characterization of a new Drosophila gene that we have called pitchoune (pit) (meaning small in Provence) because mutations in this gene produce larvae that cannot grow beyond the first instar larval stage although they can live as long as 7-10 days. All the tissues are equally affected and the perfectly shaped larvae are indistinguishable from first instar wild-type animals. Analysis of mutant somatic clones suggests a function in cell growth and proliferation, which is supported by the fact that cell proliferation is promoted by pit overexpression. Tagged-Pit, when transfected in S2 cells, localizes mainly to the nucleolus, pointing towards a possible role in ribosome biogenesis and, consequently, in protein biosynthesis. pit encodes a DEAD-box RNA helicase, a family of proteins involved in the control of RNA structure in many cellular processes and its closest homologue is a human DEAD-box RNA helicase, MrDb, whose corresponding gene transcription is directly activated by Myc-Max heterodimers (Grandori, C., Mac, J., Siëbelt, F., Ayer, D. E. and Eisenman, R. N. (1996) EMBO J. 15, 4344-4357). The patterns of expression of d-myc and pit are superimposable. Ectopic expression of myc in the nervous system drives an ectopic expression of pit in this tissue indicating that in Drosophila as well, pit is a potential target of d-Myc. These results suggest that myc might promote cell proliferation by activating genes that are required in protein biosynthesis, thus linking cell growth and cell proliferation.

Diffraction effects in single- and two-laser photothermal lens spectroscopy.

A simple method for calculating the effects of optical geometry on photothermal lens signals is shown. This method is based on calculating cumulative electric-field phase shifts produced by a series of Gaussian refractive-index perturbations produced by the photothermal effect. Theoretical results are found for both pulsed-laser and continuous Gaussian laser excitation sources and both single- and two-laser apparatuses commonly employed in photothermal lens spectroscopy. The effects of apparatus geometry on the resulting signal are shown. Analytical time-dependent signal results are found for small signals. Analytical pump-probe focus geometry results allow direct optimization for certain conditions. The calculations indicate that the photothermal lens signal is, in general, optimized for near-field detection-plane geometries.

Accurate measurements of organic dye solutions by use of pulsed laser photothermal deflection spectroscopy.

Organic dye molecules having a finite triplet quantum yield are shown to yield anomalous photothermal signals magnitudes when pulsed laser excitation is used. These anomalous signals can be due to optical bleaching of the electronic singlet states with subsequent optical absorption within the triplet spin state manifold. A model based on excitation and excited state relaxation rate expressions is derived and applied to the analysis of excitation laser irradiance-dependent photothermal signal magnitude data. The model is found to fit the experimental results very precisely. It is subsequently used to correct the photothermal signal at high irradiances and to deduce photodynamic parameters from the studied molecule. Regression of the model to the excitation irradiance-dependent data allows determination of the T2-->T1 relaxation rate constant and the triplet state cross absorption section. Model regression is applied to the analyses of erythrosin in water and ethanol solvent and of eosin and 1,1'-diethyl-2,2'-cyanine iodide dyes in ethanol solutions. A method for quantitative determination of analyte concentration is developed.

[What is the place of conventional radiology in the exploration of esophageal dyskinesia and hiatal hernia?]. / Que reste-t-il de la radiologie conventionnelle dans l'exploration des dyskinésies oesophagiennes et des hernies hiatales?

Esophageal dyskinesias are due to various aetiologies and sometimes present with marked clinical symptoms. The barium swallow remains the preferred first-line examination. Upper GI endoscopy and manometry are useful to confirm the functional nature and eliminate any concomitant or secondary mucosal lesions of these motor disorders. The clinical signs of hiatus hernia are essentially due to complications related to gastro-esophageal reflux. They can be asymptomatic or may present in the form of atypical, sometimes extra-gastrointestinal, symptoms. Although conventional radiology allows the diagnosis of hiatus hernia by specifying the type, the morphology and the anatomical relations, it may fail to detect the consequences of gastro-esophageal reflux, especially ulcerated lesions. Upper gastrointestinal endoscopy appears to be the first-line examination of choice for the diagnosis of hiatus hernia. Barium swallow is useful in cases of failure of endoscopy and in the context of preoperative assessment, as these two investigations are often complementary.