Rationale and design of the multicentric, double-blind, double-placebo, randomized trial APrepitant versus HYdroxyzine in association with cytoreductive treatments for patients with myeloproliferative neoplasia suffering from Persistent Aquagenic Pruritus. Trial acronym: APHYPAP.

BACKGROUND: Aquagenic pruritus (AP), an intense sensation of scratching induced after water contact, is the most troublesome aspect of BCR-ABL1-negative myeloproliferative neoplasms (MPNs). Mostly described in polycythemia vera (PV, ~ 40%), it is also present in essential thrombocythemia (ET) and primary myelofibrosis (PMF) (10%). Even if this symptom can decrease or disappear under cytoreductive treatments, 30% of treated MPN patients still persist with a real impact on the quality of life (QoL). Because its pathophysiology is poorly understood, efficient symptomatic treatments of AP are missing. The neuropeptide substance P (SP) plays a crucial role in the induction of pruritus. Several studies showed the efficacy of aprepitant, an antagonist of SP receptor (NK-1R), in the treatment of chronic pruritus but never evaluated in AP. The objectives of APHYPAP are twofold: a clinical aim with the evaluation of the efficacy of two drugs in the treatment of a persistent AP for MPN patients and a biological aim to find clues to elucidate AP pathophysiology. METHODS/DESIGN: A multicentric, double-blind, double-placebo, randomized study will include 80 patients with MPN (PV or ET or PMF) treated since at least 6 months for their hemopathy but suffering from a persistent AP (VAS intensity ≥6/10). Patients will be randomized between aprepitant (80 mg daily) + placebo to match to hydroxyzine OR hydroxyzine (25 mg daily) + placebo to match to aprepitant for 14 days. At D0, baseline information will be collected and drugs dispense. Outcome measures will be assessed at D15, D30, D45, and D60. The primary study endpoint will be the reduction of pruritus intensity below (or equal) at 3/10 on VAS at D15. Secondary outcome measures will include the number of patients with a reduction or cessation of AP at D15 or D60; evaluation of QoL and AP characteristics at D0, D15, D30, D45, and D60 with MPN-SAF and AP questionnaires, respectively; modification of plasmatic concentrations of cytokines and neuropeptides at D0, D15, D30, and D60; and modification of epidermal innervation density and pruriceptor expression at D0 and D15. DISCUSSION: The APHYPAP trial will examine the efficacy of aprepitant vs hydroxyzine (reference treatment for AP) to treat persistent AP in MPN patients. The primary objective is to demonstrate the superiority of aprepitant vs hydroxyzine to treat persistent AP of MPN patients. The treatment received will be considered efficient if the AP intensity will be reduced at 3/10 or below on VAS after 14 days of treatment. The results of this study may provide a new treatment option for this troublesome symptom and also give us more insights in the pathophysiology understanding of AP. TRIAL REGISTRATION: APHYPAP. NCT03808805 , first posted: January 18, 2019; last update posted: June 10, 2021. EudraCT 2018-090426-66.

The contribution of personal audio system use and commuting by bus on daily noise dose.

BACKGROUND: For many young people, exposure to music from personal audio system use may represent a significant component of daily noise dose. Moreover, there is increasing concern for the hearing of those who listen at high volumes. The purpose of this study was to determine the noise levels experienced on commuter buses, and to investigate how these impact on the volume-setting behavior of young adult personal audio system users. METHODS: A questionnaire was used to probe transport use, personal audio system-listening behaviors and the extent of understanding about noise-induced hearing loss. The influence of bus noise on volume-setting behavior was determined by measuring, in a lab setting, the sound-level preferences of participants when listening to their favorite song, a generic song, or a podcast in the absence and presence of various levels of bus noise, simulated using output-adjusted recordings made of bus noise. Statistical analysis was conducted using analysis of variance. RESULTS: While the bus noise itself was below 85 dB Leq, as the sound level of the buses increased, so did the percentage of commuters who were found to exceed the equivalent of 8 hours of exposure at 85 dB Leq. IMPLICATIONS: Investment in buses with lower noise levels or the use of noise-canceling or noise-occluding headphones would help to reduce the likelihood of noise-induced hearing loss for bus commuters.

Relationship among oral health status, bolus formation and food comfortability during consumption of model cheeses in elderly.

The aim of this study was to investigate the impact of oral impairment on chewing behaviour, food bolus properties and food comfortability during elderly consumption of model cheeses. Seventy-two elderly persons (aged 66 to 88) was recruited and classified into two groups according to dental status (poor vs. satisfactory). They showed a wide range of salivary flow rates whatever their dental status (stimulated: 0.2-3.8 mL min-1, resting: 0.1-0.8 mL min-1). Standardized bites of four model cheeses with an identical composition but different textures (soft, hard, processed and whipped) were tested. The time and number of chewing cycles required to form a bolus were measured. The rheological properties of the bolus were studied, as was saliva moistening. Food comfortability was assessed by means of a questionnaire composed of 5 sections (1-oral comfort, 2-bolus formation, 3-pain, 4-texture and 5-flavour perception). The chewing parameters measured were not modified by the oral health. However, elderly with poor dentition formed harder boluses than elderly with satisfactory dentition. Moreover, for elderly with poor dentition, the quantity of saliva incorporated into the bolus was correlated with the stimulated salivary flow rate, which was not the case for elderly with satisfactory dentition. General oral comfort and its different attributes were poorly associated with the oral health of the elderly. A multifactorial analysis performed on an average cheese showed that food comfortability is independent of changes in the hardness and moistening of the bolus, regardless of dental status. In particular, poor dental status increases the hardness of the bolus without modifying its comfortability.

Bolus quality and food comfortability of model cheeses for the elderly as influenced by their texture.

The aim of this study was to examine the influence of the texture of dairy products on bolus properties and food comfortability as perceived by elderly persons. Four cheese models identical in terms of their nutritional composition but different by the type of texture (Soft, Hard, Processed and Whipped) were developed to resemble market cheese. Study was performed with a panel of 38 elderly persons without dental impairment but with variable rate of saliva flow. The time of chewing required to form the bolus was measured. The rheological properties of the bolus obtained were studied as well as the quantity of saliva incorporated. Food comfortability was assessed by means of a questionnaire asking about in-mouth comfort, bolus formation, pain, and perceived texture and flavor. Results showed that food comfortability was positively correlated to the ease of forming the bolus which depended on the food texture. Thus, the bolus formed with the Whipped product which required more saliva, was harder than the other three products and so judged the least comfortable. This product was characterized by a dry and sticky texture. On the other hand, the Soft and Processed products led to a softer food bolus that was more easily formed, and thus were judged as more comfortable. Their textures were perceived as soft, fatty and melting. This work highlights the importance of considering food bolus formation and related properties when looking for the link between food product characteristics and the enjoyment of eating in the case of the elderly population.

Li4Ti5O12/graphene nanoribbons composite as anodes for lithium ion batteries.

In this paper, we report the synthesis of a Li4Ti5O12/Graphene Nanoribbons (LTO/GNRs) composite using a solid-coating method. Electron microscope images of the LTO/GNRs composite have shown that LTO particles were wrapped around graphene nanoribbons. The introduction of GNRs was observed to have significantly improved the rate performance of LTO/GNTs. The specific capacities determined of the obtained composite at rates of 0.2, 0.5, 1, 2, and 5 C are 206.5, 200.9, 188, 178.1 and 142.3 mAh·g(-1), respectively. This is significantly higher than those of pure LTO (169.1, 160, 150, 106 and 71.1 mAh·g(-1), respectively) especially at high rate (2 and 5 C). The LTO/GNRs also shows better cycling stability at high rates. Enhanced conductivity of LTO/GNRs contributed from the GNR frameworks accelerated the kinetics of lithium intercalation/deintercalation in LIBs that also leads to excellent rate capacity of LTO/GNRs. This is attributed to its lower charge-transfer resistance (Rct = 23.38 Ω) compared with LTO (108.05 Ω), and higher exchange current density (j = 1.1 × 10(-3) mA cm(-2))-about 20 times than those of the LTO (j = 2.38 × 10(-4) mA cm(-2)).

Multispectral band selection and spatial characterization: Application to mitosis detection in breast cancer histopathology.

Breast cancer is the second most frequent cancer. The reference process for breast cancer prognosis is Nottingham grading system. According to this system, mitosis detection is one of the three important criteria required for grading process and quantifying the locality and prognosis of a tumor. Multispectral imaging, as relatively new to the field of histopathology, has the advantage, over traditional RGB imaging, to capture spectrally resolved information at specific frequencies, across the electromagnetic spectrum. This study aims at evaluating the accuracy of mitosis detection on histopathological multispectral images. The proposed framework includes: selection of spectral bands and focal planes, detection of candidate mitotic regions and computation of morphological and multispectral statistical features. A state-of-the-art of the methods for mitosis classification is also provided. This framework has been evaluated on MITOS multispectral dataset and achieved higher detection rate (67.35%) and F-Measure (63.74%) than the best MITOS contest results (Roux et al., 2013). Our results indicate that the selected multispectral bands have more discriminant information than a single spectral band or all spectral bands for mitotic figures, validating the interest of using multispectral images to improve the quality of the diagnostic in histopathology.

[Palatal fibromucosal graft to correct lower eyelid retraction]. / Greffe de fibromuqueuse palatine pour corriger la rétraction de la paupière inférieure.

INTRODUCTION: Retraction of the lower eyelids has multiple etiologies. Its surgical treatment is a vertical elongation of the tarsus. This can be obtained by using a graft. We describe a sampling and grafting technique using palatal fibromucosa intratarsal graft. TECHNICAL NOTE: The procedure is performed in two steps under general anesthesia. The graft is harvested on the lateral sides of the palatine vault to avoid neurovascular bundles. This area corresponds to the maxillary fibromucosa according to Delaire's classification. The graft is then inserted in the lower eyelid tarsus. DISCUSSION: Many "spacers" are available to extend the posterior lamella vertically; the palatal fibromucosa graft may be used directly and is easy to harvest. It has a similar stiffness to that of the tarsus and there is no need to harvest periosteum. Sparing the periosteum allows for a better healing of the donor site and decreases postoperative pain. The lateral harvesting area, away from the anterior palatine artery, seems more accessible than the median area, especially in ogival palates.

Paradiplozoon ichthyoxanthon n. sp. (Monogenea: Diplozoidae) from Labeobarbus aeneus (Cyprinidae) in the Vaal River, South Africa.

A new species, Paradiplozoon ichthyoxanthon (Monogenea: Diplozoidae) is described from the gills of Labeobarbus aeneus (Cyprinidae) in the Vaal Dam and Vaal River Barrage in the Vaal River, South Africa. This species is the first in this genus from southern Africa; Paradiplozoon aegtyptense and Paradiplozoon ghanense have been described from northern Africa. The new species differs from all other Paradiplozoon species on the basis of the combination of morphological characteristics, namely disk-like haptor, eggs without filaments, clamp and central hook morphology and size of specimens. The species description is accompanied by a description of the reproductive organs. The internal transcribed spacer of the ribosomal gene (ITS2) was studied and the South African individuals formed a distinct clade, supporting the establishment of a new species.

[Tubercular fibrosing conjunctivitis associated with facial cutaneous tuberculosis]. / Conjonctivite fibrosante tuberculeuse au cours d'une tuberculose cutanée faciale.

BACKGROUND: Tuberculous conjunctivitis has been described only rarely during the course of lupus vulgaris. We report a case of hemifacial cutaneous tuberculosis, diagnosed as atypical lupus vulgaris, associated with homolateral fibrosing tuberculous conjunctivitis. PATIENTS AND METHODS: An 83-year-old woman presented inflammatory conjunctivitis without bullous involvement in the left eye leading to corneal neovascularisation, symblepharons and ptosis. Erythematous and atrophic papules were seen on the left side of the face. Biopsy of the skin and conjunctiva revealed a tuberculoid granulomatous infiltrate. Bacterial culture and PCR were both positive for Mycobacterium tuberculosis. DISCUSSION: This case illustrates the need to consider tuberculosis when faced with an atypical facial eruption and ocular involvement.

[Acute blepharoptosis caused by fibrous dysplasia]. / Ptôsis aigu unilatéral révélant une dysplasie fibreuse.

We report a case of fibrous dysplasia revealed by acute ptosis in a 38-year-old patient. Ophthalmologic examination disclosed a moderate right ptosis. The rest of the results were strictly normal except for a known facial asymmetry. Visual acuity was 20/20 in both eyes, there was no extrinsic or intrinsic oculomotor disorder, and funduscopy was normal. Given this acute presentation, emergency cerebral imagery was carried out, providing a diagnosis of fibrous dysplasia with orbital and cavernous repercussions, with no sign of cerebral disorder or obvious vascular lesion. Progression was marked by a regression of the ptosis. Fibrous dysplasia is a rare pathology but presents varied clinical presentations. The authors present the broad characteristics of this pathology and the management of an acquired ptosis. They discuss the possible mechanisms involved in the drop of the right upper eyelid of this patient and the therapeutic solutions.

[Atrio-oesophageal fistula after radiofrequency ablation: predominant neurological symptoms]. / Fistule atrio-oesophagienne après radiofréquence: des signes neurologiques au premier plan.

A 58-year-old man was admitted to our hospital for septic shock and meningitis. He had undergone, three weeks earlier, a radiofrequency ablation for drug-refractory atrial fibrillation. A polymicrobian septicemy suggested a digestive etiology. A CT scan suggested an atrio-oesophageal fistula with cerebral and renal emboli. The patient deceased from brain death. The diagnosis of atrio-oesophageal fistula was confirmed by autopsy.

[Conjunctival melanoma at corneoscleral limbus on primary acquired melanosis. A case report]. / Mélanome conjonctival limbique développé sur mélanose acquise primitive.

A 51-year-old Caucasian man consulted for a visual loss in the left eye due to corneal extension of a conjunctival melanoma. This conjunctival melanoma arose from primary acquired melanosis with atypia at the temporal corneoscleral limbus. The patient was treated using a combination of surgical excision with physical treatment by ocular proton therapy. Progression remained under control 11 months after treatment: no local tumour recurrence or metastasis was observed. Primary acquired melanosis with atypia must be regarded as a premalignant melanocytic lesion. Based on this case report, the authors focus on primary acquired melanosis and its risk of transformation to a conjunctival malignant melanoma.

[Magnitude and strategies of cataract management in the world]. / Magnitude et strategies de prise en charge de la cataracte dans le monde.

Although cataracts cause 47% of global blindness, their epidemiologic impact in different countries is notoriously uneven and the world can be divided into two zones according to economic conditions. In advanced countries where care is good, cataracts account for only 5% of blindness while cataracts still account for 50% of blindness in developing countries. After a brief overview of historical, clinical and therapeutic aspects, this article updates epidemiological data on cataracts in the world. It also provides insight into political, socio-economic, and cultural factors adversely affecting care availability in developing countries thus making cataracts a major public health problem and an obstacle for development. Finally this article offers a few recommendations for reducing the backlog of cataracts in the world and for consolidating advances made over the last two decades thanks to experience gained in various National Blindness Prevention Programs (NBPP).

[Lacrimal adenocarcinoma and anophtalmos]. / Adénocarcinome lacrymal et orbite anophtalme.

INTRODUCTION: The classical symptoms of orbital tumors are modified in the event of an anophthalmic socket. CASE REPORT: We report a case of primary malignant neoplasm of the lacrimal gland in an enucleated 70-year-old women. DISCUSSION: Patients with an anophthalmic orbit often present postenucleation socket syndrome: problems of tolerance and rocking of the ocular prothesis, enophthalmos, ptosis, lower eyelid ectropion. Development of a malignant tumor of the lacrimal gland is however exceptional. An oversized lacrimal gland is suggestive of tumor development. Rigorous clinical and radiological follow-up (CT, MRI) is essential. We discuss diagnostic and therapeutic aspects including the type of exenteration, radiotherapy, and reconstruction technique.

[The organization and the activity of the Paramyxovirinae genome promoters are shaped by the «rule of six¼]. / Dans le génome des Paramyxovirinae, les promoteurs et leurs activités sont façonnés par la « règle de six ¼.

Paramyxoviruses form a virus family with a genome made of a single stranded RNA of negative polarity, tightly associated with multiple copies of the N protein in a nucleocapsid of helicoidal symmetry. For the Paramyxovirinae sub-family, genome replication depends on the obedience to the "rule of six", which infers that only the genomes whose total number of nucleotides is a multiple of 6 are replicated. This review will focus on the nucleotide sequence definition governing the viral ARN dependent RNA polymerase activity, in the context of the mechanism of application of the rule of six, as well as in the replication versus transcription regulation.

Characterisation of the pncA gene in Mycobacterium tuberculosis isolates from Gauteng, South Africa.

SETTING: The use of pyrazinamide (PZA) is important for the treatment of Mycobacterium tuberculosis as it is bactericidal to semi-dormant mycobacteria that are not affected by other drugs. The incidence of resistance to PZA and other drugs used in the treatment of M. tuberculosis is increasing in South Africa. OBJECTIVE: To characterise the pncA gene of M. tuberculosis isolates from Gauteng, South Africa, and to develop a rapid diagnostic method. DESIGN: The pncA gene and the putative regulatory gene were characterised by sequence analysis in a total of six PZA susceptible and 15 resistant isolates. The association with classical PZA susceptibility testing and PZase activity was determined. RESULTS: All PZA-resistant isolates were PZase negative as well as resistant to at least one other anti-tuberculosis drugs. Mutations were identified throughout the length of the pncA gene in 10/15 PZA-resistant isolates. Five lacked PZase activity, but the wild type pncA sequence was present. In all six PZase-positive strains, a PZA-susceptible pattern was obtained on BACTEC and the wild type pncA sequence was present. CONCLUSION: Sequencing is an effective means to identify mutations in the pncA gene in M. tuberculosis and therefore resistance to PZA. The fact that some PZA-resistant M. tuberculosis isolates lack mutations in the pncA gene suggests that alternative mechanisms for drug resistance exist. In PZase negative strains with no genetic changes which are resistant to 100 microg/ml and susceptible to 300 microg/ml, 300 microg/ml may be a more reliable breakpoint.

Effects of chronotropic incompetence and beta-blocker use on the exercise treadmill test in men.

OBJECTIVE: Our purpose was to assess the diagnostic characteristics of the exercise test in patients who fail to reach conventional target heart rates and in patients on beta-blockers. BACKGROUND: Exercise test results are often considered "inadequate" or "nondiagnostic" in patients taking beta-blockers and in patients who do not achieve 85% of their age-predicted maximal heart rate. METHODS: The results of exercise tests and coronary angiography performed to evaluate chest pain in 1282 male patients without a prior history of myocardial infarction, coronary revascularization, diagnostic Q wave on the baseline electrocardiogram, or previous cardiac catheterization were analyzed with respect to beta-blocker exposure and failure to reach 85% age-predicted maximal heart rate. Sensitivity, specificity, and predictive accuracy of exercise testing, as well as area under the curve for the receiver operating characteristic plots were calculated for these subgroups with use of coronary angiography as the reference. The angiographic criterion for significant coronary artery disease was 50% narrowing or greater in one or more major coronary arteries. RESULTS: The population was divided into 4 exclusive groups on the basis of whether they reached their target heart rates and whether they were receiving beta-blockers. Sixty to 40 percent of this clinical population failed to reach target heart rate, of which 24% (n = 303) were receiving beta-blockers and 40% (n = 518) were not. The group of patients who reached target heart rate and were not taking beta-blockers was taken as the reference group (n = 409). The group of patients supposedly beta-blocked but who reached the target heart rate (n = 52) had hemodynamic and test characteristics similar to those of the reference group and most likely were not taking their beta-blockers or were not adequately dosed. The prevalence of angiographic coronary disease was significantly higher in the 2 groups failing to reach target heart rate, both in the presence and absence of beta-blockers, compared with the reference group (68% and 64%, respectively, vs 49%, P <.01). Although the areas under the curve of the receiver operating characteristic curves for ST depression of the groups failing to reach target heart rate were not significantly different from the reference group, the predictive accuracy and sensitivity were significantly lower for 1 mm of ST depression in the beta-blocked group who did not reach target heart rate (predictive accuracy of 56% vs 67%, sensitivity of 44% vs 58%, P <.01). The only way to maintain sensitivity with the standard exercise test in the beta-blocker group who failed to reach target heart rate was to use a treadmill score or 0.5-mm ST depression as the criteria for abnormal. CONCLUSION: Sensitivity and predictive accuracy of standard ST criteria for exercise-induced ST depression are significantly decreased in male patients who are taking beta-blockers and do not reach target heart rate. In those who fail to reach target heart rate and are not beta-blocked, sensitivity and predictive accuracy are maintained.

"Rule of six": how does the Sendai virus RNA polymerase keep count?

The "rule of six" stipulates that the Paramyxovirus RNA polymerase efficiently replicates only viral genomes counting 6n + 0 nucleotides. Because the nucleocapsid proteins (N) interact with 6 nucleotides, an exact nucleotide-N match at the RNA 3'-OH end (3'-OH congruence) may be required for recognition of an active replication promoter. Alternatively, assuming that the six positions for the interaction of N with the nucleotides are not equivalent, the nucleotide position relative to N may be critical (N phase context). The replication abilities of various minireplicons, designed so that the 3'-OH congruence could be discriminated from the N phase context, were studied. The results strongly suggest that the application of the rule of six depends on the recognition of nucleotides positioned in the proper N phase context.