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Ion channels are integral membrane protein complexes critical for regulation of membrane potential, cell volume, and other signaling events. As complex molecular assemblies with many interacting partners, ion channels have multiple structural and functional domains. While channel sequence and functional data are readily available across multiple online resources, there is an unmet need for functional annotation directly relating primary sequence information, 2D interactions, and three-dimensional protein structure. To this end, we present ChanFAD (Channel Functional Annotation Database), to provide the research community with a centralized resource for ion channel structure and functional data. ChanFAD provides functional annotation of PDB structures built on the National Center for Biotechnology Information’s iCn3D structure viewing tool while providing additional information such as primary sequence, organism, and relevant links to other databases. Here we provide a brief tour of ChanFAD functionality while showing example use cases involving drug-channel interactions and structural changes based on mutation. ChanFAD is freely available and can be accessed at https://www.chanfad.org/.

Introduction Ventriculoperitoneal shunt insertion, a common procedure for hydrocephalus, has a revision rate of approximately 20–30% within the first year, and continues to increase with each consecutive year. In Leeds, the average work-up cost for suspected shunt malfunctions was £765/patient. Additionally, patients with malfunctioning shunts present with vague symptoms potentially contributing to delayed presentation, especially important in Low-Middle Income Countries (LMICs) where neurosurgical expertise is less accessible. To reduce investigative costs and delayed presentations, we sought to design an epidermal shunt reservoir sensor to detect shunt malfunction by measuring the reservoir pressure. Method Literature searches were conducted to identify a proof of concept and suitable materials to engineer a concept device based on a Failure Modes and Effects Analysis (FMEA) table with design specifications to assess relative clinical risks. Using the IDEAL-D Framework, we designed our low-fidelity prototype using Solidworks® software. Results Literature revealed several devices aimed to detect shunt malfunctions. For our concept device, our focus was an accurate sensor and reliable connectivity. Our prototype uses gold nanowires to achieve high sensitivity to pressure change, as small as 15mPa. Near-field communication (NFC) for connectivity has less power requirement and has rapid connectivity compared to Bluetooth. Estimated cost of the device is £500. Conclusions Our device, in Stage 0 of the IDEAL-D Framework, identified potential sensors and connectivity methods. We could utilise magnets to adhere to the reservoir with overlying hair. However, magnetic fields and atmospheric pressure could cause interference. Power source options still require exploring before benchtop testing for accuracy, interference, and feasibility.

Zonza Christian Barthélémy. Écrire la mort d’Henri III au XVIIe siècle : de la Providence de Dieu au hasard de la Fortune. In: Albineana, Cahiers d'Aubigné, 31, 2019. Paradoxes d’historiens : les enjeux de l’écriture de l’histoire en France (1560-1630) pp. 89-108.

Objective A decreased sensitivity to 6-n-propylthiouracil (PROP) has been shown to be associated with increased energy intake and therefore an increased body mass index, although other studies have not confirmed this association, suggesting the involvement of other factors. We investigated whether the endocannabinoid system, which also modulates hunger/satiety and energy balance, plays a role in modulating eating behavior influenced by a sensitivity to PROP. Methods The plasma profile of the endocannabinoids 2-arachidonoylglycerol (2-AG), anandamide (AEA), and congeners of AEA, palmitoylethanolamide and oleylethanolamide (OEA), was determined in normal-weight PROP supertasters (STs) and PROP non-tasters (NTs). A cognitive eating behavior disorder was assessed by the Three-Factor Eating Questionnaire, which estimates dietary restraint, disinhibition, and perceived hunger. Results The disinhibition score of NTs was higher than those of STs ( P = 0.02). Moreover, in NTs, OEA was inversely correlated to the perceived hunger score ( r = −0.7, P = 0.002), and AEA was positively correlated to the restraint score ( r = 0.5, P = 0.04) and negatively to the perceived hunger score, although the latter correlation was at the limit of statistical significance ( r = −0.47, P = 0.05). In addition, we found lower concentrations of AEA and 2-AG in the plasma of NT compared with ST subjects (AEA, P = 0.034; 2-AG, P = 0.003). Conclusions Our data suggest that a higher disinhibition behavior in NTs may be compensated in part, in normal-weight subjects, by the decrease of peripheral endocannabinoids to downregulate the hunger–energy intake circuitry.

The PROP taste phenotype varies greatly among individuals, influencing eating behavior and therefore may play a role in body composition. This variation is associated with polymorphisms in the bitter receptor gene TAS2R38 and the taste-bud trophic factor gustin gene. The aim of this study was to examine the relationship between TAS2R38 haplotypes and the gustin gene polymorphism rs2274333 in modulating PROP taste phenotype. PROP phenotype was determined in seventy-six volunteers (29 males, 47 females, age 25±3 y) by scaling methods and threshold measurements. TAS2R38 and gustin gene genotyping was performed using PCR techniques. The lowest responsiveness in PROP nontasters is strongly associated with the AVI nontasting TAS2R38 variant and the highest responsiveness in supertasters is strongly associated to allele A and genotype AA of the gustin gene. These data support the hypothesis that the greater sensitivity of supertasters could be mediated by a greater taste-bud density. Polymorphisms in TAS2R38 and gustin gene, together, accounted for up to 60% of the phenotypic variance in PROP bitterness and to 40% in threshold values. These data, suggest that other unidentified factors may be more relevant for detecting low concentrations of PROP. Moreover, the presence of the PAV variant receptor may be important for detecting high concentrations of PROP, whereas the presence of allele A in gustin polymorphism may be relevant for perceiving low concentrations. These data show how the combination of the TAS2R38 and gustin gene genotypes modulate PROP phenotype, providing an additional tool for the evaluation of human eating behavior and nutritional status.

De nombreux romans dans la premiere moitie du XVIIe siecle cherchent a divertir le lecteur en multipliant les aventures. Cela est possible grâce a leur longueur, au nombre de personnages, a la diversite des lieux ou l’action se deroule. L’apparition de nouvelles historiques au milieu du siecle a signifie de ce fait la reduction du nombre de pages, de lieux, de personnages et une exigence de vraisemblance. Le principal defi pour ces auteurs de nouvelles consiste a conserver tout l’interet du lecteur avec des moyens limites. Comment s’y prennent-ils donc pour combiner plaisir des aventures d’une part, brievete et vraisemblance d’autre part ?

La Vita de Jacques-Auguste de Thou, parue en 1621, est ecrite a la troisieme personne et attribuee a un narrateur pretendument proche de l’historien dont il aurait lu un journal, donne comme principale source du recit. Desireux de rehabiliter au regard de la posterite l’Historia sui temporis de De Thou, qui avait fait l’objet de violentes critiques, le biographe fictif se montre plein de compassion pour celui qu’il presente comme une victime incomprise, mais egalement comme un temoin et un acteur de l’histoire, une âme genereuse et un esprit humaniste. La Vita apparait donc comme un plaidoyer en faveur de Jacques-Auguste de Thou et de sa grande œuvre historiographique.

Zonza Christian. Le discours politique dans les tragédies de Claude Billard. In: Albineana, Cahiers d'Aubigné, 22, 2010. « Une volée de poètes » : D’Aubigné et la génération poétique des années 1570-1610, sous la direction de Julien Goeury, Pierre Martin et Marie-Hélène Servet. pp. 101-123.

Zonza Christian Barthélémy. Les mots et les choses dans l'Histoire comique de Francion. In: Littératures classiques, n°41, hiver 2001. Charles Sorel, Histoire comique de Francion pp. 155-166.

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Hashimoto's encephalopathy and Creutzfeldt-Jakob disease (CJD) often have similar clinical features and may be confused, especially at onset. A 61-year-old woman developed rapidly progressive ataxia, myoclonus and dementia, with abnormalities seen on electroencephalography (EEG). Serum analysis disclosed high titers of antithyroid autoantibodies. Both clinical course and autopsy led to a definitive diagnosis of CJD. This case and a literature review of previous cases confirm that CJD may be confused with Hashimoto's encephalopathy. EEG, clinical and laboratory findings (including the positivity of 14.3.3 protein in the cerebrospinal fluid) are not conclusive for a differential diagnosis, especially at early stages. Only the results of genetic exams can allow a definitive diagnosis in a small percentage of cases while patients are still alive. In patients with unclear symptomatology and rapid onset of myoclonus, dementia and ataxia, the presence of antithyroid antibodies should be examined. If their levels are abnormal, corticosteroid therapy remains mandatory.

PROP sensitivity varies greatly among individuals and can strongly influence food choice and satiety. It is associated with the bitter receptor gene (TAS2R38) and with differences in the salivary proteins involved in taste function. Among them, the enzyme Zn dependent gustin, a trophic factor of taste buds. We investigated the possible association of PROP taste phenotype with TAS2R38 haplotypes, gustin gene polymorphism rs2274333 (A/G), salivary Zn2+concentration and BMI. BMI were determined in 76 volunteers (29 males, 47 females, age 25 ± 3 y). PROP phenotype was determined by scaling methods and threshold measurements. The salivary Zn2+ concentration was determined and molecular analysis of TAS2R38 and gustin gene polymorphisms were performed using PCR techniques. PROP threshold determination can discriminate tasters from nontasters, while scaling methods distinguish also medium tasters from supertasters. Salivary Zn2+ and BMI were greater in nontasters than in supertasters. Molecular analysis of gustin DNA showed that allele A were more frequent in supertasters, while allele G were more frequent in nontasters. The lowest responsiveness in nontasters is strongly associated to AVI nontasting variant of TAS2R38, while the highest responsiveness in supertasters is strongly associated to allele A of gustin gene. The two genes account for up to 60% of phenotypic variance in PROP bitterness and to 40% in threshold values. These data demonstrated that sensitivity to PROP is inversely related to BMI and salivary Zn2+ and directly associated with the dimorphism rs2274333 in gustin gene that is hypothesized to affect its function. In addition, showed how the combination of TAS2R38 and gustin gene genotypes modulate PROP phenotype providing an additional tool for the evaluation of human eating behaviour and nutritional status.

Cet article est un compte-rendu du livre : Narratologie : « Problèmes du roman historique », 7, 2008, sous la direction de Aude Déruelle & Alain Tassel, 414 p., EAN 9782296050365.

The ability to perceive the bitter taste of 6-n-propylthiouracil (PROP) is a variable phenotype that has been associated with body mass index (in kg/m(2)) and linked to food choice and satiety. PROP-sensitive and -nonsensitive individuals are defined as tasters and nontasters, respectively. Sensitivity to PROP is a heritable trait based on the TAS2R38 gene on chromosome 7q34. In a recent study we demonstrated an association between PROP sensitivity and the single-nucleotide polymorphism (SNP) rs2274333 (+292A/G) within a coding sequence of the gustin/carbonic anhydrase VI gene. The purpose of this study was to develop a rapid and inexpensive screening method for identification of the rs2274333 SNP in individuals with varying sensitivity to PROP. Our results show that the methodology employed allows distinguishing A/G alleles perfectly, with a simple DNA digestion of a polymerase chain reaction fragment covering the SNP site of interest. So, the polymerase chain reaction followed by restriction fragment length polymorphism assay described in this article can be used as an alternative to sequencing in bitter taster status research, and could be employed as a survey tool in nutrigenomic studies.

Il sangue da sempre e stato considerato nella cultura dell’uomo come fonte inesauribile di energia vitale. Diventava importante acquisire, attraverso l’assunzione del sangue, l’energia vitale del nemico sconfitto, sia che si trattasse di un uomo, di un eroe nemico per esempio, che di una fiera. La storia dell’uomo ha metabolizzato questa immagine archetipica, primaria, e ha continuato a riproporla nei diversi momenti della sua storia, segnando una specie di contrappunto simbolico della nostra mutata sensibilita.

Postpartum depression (PPD) is a non-psychotic depressive disease with varying severity, from moderate to severe, which according to the DSM IV originates after the 4th to 6th week from giving birt...

Method: We analyzed fertilization of 1692 oocytes previously microinjected and cultured in EMBRYOSCOPE from April to December 2011. Out of these 1692, 1269 underwent normal fertilization (75%), 48 were uni-pronucleated (2.8%) and 63 were tri-pronucleated (3.7%). The remaining 312 oocytes suffered degeneration or had no pronuclei. The EMBRYOSCOPE is a time-lapse incubator that allows us to view, like in a film, the embryo development from the moment of ICSI until transfer by taking pictures of the embryos every 20 minutes in seven different depth fields. Thanks to the EMBRYOVIEWER, we are able to know the time after ICSI of many events that we consider to be important for the embryo evaluation, such as pronuclei appearance and disappearance, cell cleavage, etc. In addition, it allows us to measure certain parameters, such as pronuclei area and different lengths. We also registered the number of good quality embryos in day +3, considering these to be the A and B category embryos, according to the ASEBIR scale. After the ovarian puncture the oocytes are injected and cultured in EMBRYOSCOPE with GLOBAL culture media (LifeGlobal, IVFOnline) until day 3. Statistical analysis was performed with G-STAT. Differences were considered statistically significant at P< 0.05.

Acute diffuse peritonitis is still an unpredictable occurrence that hinders patient's survival and is a severe challenge for the surgeon regarding diagnosis and management. The Authors report their experience on 94 cases of acute diffuse peritonitis due to different causes observed during a period of 10 years. Surgical treatment was mainly based on severity of clinica data and general conditions of the patients. Overall mortality was 6.3%. Modern diagnostic techniques, proper usage of antibiotics and accurate timing of surgical procedure constitute the main factors for un update management of peritonitis.

The general surgeon has sometimes to face problems arising from an acute abdomen due to gynecologic causes. Such conditions are mainly found in women in reproductive age; the most frequent pathologies are due to complications of ovarian cysts, perlvic inflammatory disease and extrauterine pregnancy. Some short clinical commentaries are herein presented on two cases of gynecologic acute abdomen: the first case reported is related to an intraperitoneal rupture of a large uterine sarcoma and the second an ovarian neoplasm associated with a diffuse peritonitis from perforation of tubo-ovarian abscess.

Large colonic villous adenomas are benign neoplasms capable of malignant transformation with a higher frequency than other adenomas. Such transformation often requires surgical therapy after endoscopic resection. The aim of the present study was to establish the indications for surgery in a series of 13 cases of large colonic villous adenomas initially submitted to endoscopic resection. The patients (8 males and 5 females; mean age; 62 years) were observed over the period 1993-2000. All endoscopic resections were performed using the piecemeal technique. In 7 cases there were 2 endoscopic sessions and in one case 3; a single case of post-endoscopic bleeding was treated conservatively. In 5 cases, endoscopic resection was deemed not to be radical and these patients were submitted to surgical resection. Histology on the surgical specimens revealed 2 cases of carcinoma (T1 and T2, respectively), confirmation of colonic villous adenoma in 2 cases and the presence of inflammatory tissue in 1 case. Among the patients treated with endoscopic resection alone one death occurred at two years due to lung and systemic metastases probably due to the malignant adenoma. After a review of the literature and on the basis of their own experience, the authors stress the importance of a combined pathological and endoscopic approach to establish when surgery is required.

The Authors report a case of small bowel venous ischaemia due to a peculiar form of vasculitis called Mesenteric Inflammatory Veno-Occlusive Disease. Such disease represents a new anatomopathological entity, with exclusive thrombotic and inflammatory infiltration of the mesenteric veins, with no arterial flogistic involvement. Clinical manifestation of the diseases is that of the venous mesenteric thrombosis in patients in whom the more common forms of systemic vasculitis are not recognizable.

Method: We analyzed fertilization of 1692 oocytes previously microinjected and cultured in EMBRYOSCOPE from April to December 2011. Out of these 1692, 1269 underwent normal fertilization (75%), 48 were uni-pronucleated (2.8%) and 63 were tri-pronucleated (3.7%). The remaining 312 oocytes suffered degeneration or had no pronuclei. The EMBRYOSCOPE is a time-lapse incubator that allows us to view, like in a film, the embryo development from the moment of ICSI until transfer by taking pictures of the embryos every 20 minutes in seven different depth fields. Thanks to the EMBRYOVIEWER, we are able to know the time after ICSI of many events that we consider to be important for the embryo evaluation, such as pronuclei appearance and disappearance, cell cleavage, etc. In addition, it allows us to measure certain parameters, such as pronuclei area and different lengths. We also registered the number of good quality embryos in day +3, considering these to be the A and B category embryos, according to the ASEBIR scale. After the ovarian puncture the oocytes are injected and cultured in EMBRYOSCOPE with GLOBAL culture media (LifeGlobal, IVFOnline) until day 3. Statistical analysis was performed with G-STAT. Differences were considered statistically significant at P< 0.05.

Apres avoir ete utilise comme figure politique, soit tyran, soit pacificateur, Jules Cesar devient dans la France apaisee des annees 1660 une incarnation de valeurs galantes portees par les femmes. Mlle de Scudery, Mme de Villedieu, Anne de la Roche-Guilhen, Louis de Mailly, Pierre de Lesconvel ou Jean de La Chapelle, loin d’en faire le vil seducteur modele par Suetone, l’erigent en modele de l’amour parfait. Les femmes mises en scene sont aimees pour leur intelligence et leur conversation, elles sont considerees comme des actrices de l’histoire tandis que le Cesar historique est parfois reduit a n’etre qu’un personnage de roman. Doue pour la conversation et pour l’ecriture, goutant les raffinements de la vie en societe, il fait de l’amour un sentiment a la mesure de sa grandeur morale et heroique qui explique l’identification entre le roi de France et le general romain. Apres avoir porte des valeurs politiques, le personnage finit par vehiculer des valeurs culturelles et sociales propres a la seconde moitie du XVIIe siecle et caracterise fort bien ce melange de l’amour et de la politique propre a la cour et aux nouveaux genres romanesques naissants.

Resume Les auteurs rapportent un nouveau cas de septicemie a Pasteurella multocida , consecutif a une morsure profonde chez un homme de 26 ans, en parfaite sante, malgre une antibiotherapie prophylactique appropriee. L'evolution ne fut favorable qu'apres excision d'un abces et antibiotherapie a forte dose.

In the evolution of ALS, involvement of bulbar structures is an obligatory stage, with typical difficulties in swallowing and speech.