Care of pharmaco-resistant absence seizures in childhood.

In childhood absence epilepsy, pharmaco-resistance occurs in 20-30% of patients. In that situation, glucose transporter type 1 deficiency has to be ruled out, especially if absences started before the age of four years and if neurological signs are present. If ethosuximide, valproate and lamotrigine have failed in monotherapy or in association, there are currently no valuable therapeutic options. The same rules apply for epilepsy with myoclonic absences. Importantly, arguments supporting that making the patient seizure-free will improve eventual associated cognitive deficits such as attention deficit are very weak. Therefore, limiting the cognitive side effects of the anti-epileptic drugs has always to be a priority when faced with typical refractory absences in childhood. In epilepsy with eyelid myoclonia, the majority of patients are pharmaco-resistant. However, absence seizures, if present, tend to be very brief, and seizures are limited in many patients to eyelid myoclonia that eventually do not affect their quality of life and are well attenuated by wearing blue lenses. Atypical absences occurring in the course a developmental and/or epileptic encephalopathy are often pharmaco-resistant. In that situation, characterizing the type of epilepsy syndrome and searching for a specific genetic or structural etiology are needed to offer the best therapeutic options to the patient.

Overexpression of the Small Ubiquitin-Like Modifier protease OTS1 gene enhances drought tolerance in sugarcane (Saccharum spp. hybrid).

Sugarcane is an economically important crop plant across the globe as it is the primary source of sugar and biofuel. Its growth and development are greatly influenced by water availability; therefore, in periods of water scarcity, yields are severely compromised. Small Ubiquitin-Like Modifier (SUMO) proteases play an important role in stress responses by regulating the SUMO-related post-translational modification of proteins. In an attempt to enhance drought tolerance in sugarcane, this crop was genetically transformed with a cysteine protease (OVERLY TOLERANT TO SALT-1; OTS1) from Arabidopsis thaliana using particle bombardment. Transgenic plants were analysed in terms of photosynthetic capacity, oxidative damage, antioxidant accumulation and the SUMO-enrich protein profile was assessed. Sugarcane transformed with the AtOTS1 gene displayed enhanced drought tolerance and delayed leaf senescence under water deficit compared to the untransformed wild type (WT). The AtOTS1 transgenic plants maintained a high relative moisture content and higher photosynthesis rate when compared to the WT. In addition, when the transgene was expressed at high levels, the transformed plants were able to maintain higher stomatal conductance and chlorophyl content under moderate stress compared to the WT. Under severe water deficit stress, the transgenic plants accumulated less malondialdehyde and maintained membrane integrity. SUMOylation of total protein and protease activity was lower in the AtOTS1 transformed plants compared to the WT, with several SUMO-enriched proteins exclusively expressed in the transgenics when exposed to water deficit stress. SUMOylation of proteins likely influenced various mechanisms contributing to enhanced drought tolerance in sugarcane.

Effect of methionine and trace minerals (zinc, copper and manganese) supplementation on growth performance of broilers subjected to Eimeria challenge.

Coccidiosis is a major intestinal challenge that causes economic loss to the broiler industry. Two battery cage studies were conducted to evaluate the effect of trace minerals, source and dose of methionine on growth performance and gut health of broilers subjected to Eimeria challenge. Experiment #1 consisted of 9 treatments of 2 × 2 × 2 factorial design + 1 arrangement with main factors of methionine (Met) sources (DL-Met vs. 2-hydroxy-4-(methylthio)-butanoic acid (HMTBa)), total sulfur amino acid (TSAA) levels (high vs. low; ±5% of recommended level), and sources of trace minerals (TM) Zn:Cu:Mn in the form Inorganic trace minerals (ITM) in sulfates (80:20:100ppm) vs. mineral methionine hydroxy-analogue bis-chelate (MMHAC, 40:10:50ppm), each with 8 pens of 10 birds. Experiment #2 consisted of 2 treatments--ITM [ZnSO4:tribasic copper chloride (TBCC):MnSO4 110:125:120ppm] and MMHAC (Zn:Cu:Mn, 40:30:40ppm), each with 36 pens of 10 birds. All birds except for treatment 9 in experiment #1 were orally gavaged with 1x, 4x and 16x recommended dose of coccidiosis vaccine on d0, d7 and d14, respectively. Data were subjected to one-way and/or three-way ANOVA, and means were separated by Fisher's protected LSD test with significance at p ≤ 0.05. In experiment #1, factorial analysis revealed the main effects of TSAA level and TM, but not Met source. High TSAA level improved body weight and cumulative feed intake at 14, 20, and 27d. MMHAC improved body weight at 14, and 27d; feed intake at 14, 20, and 27d; and cumulative FCR at 27d vs. sulfates. One-way ANOVA analysis showed that birds fed MMHAC and high levels of TSAA regardless of Met source had similar body weight as unchallenged birds on d27. In experiment #2, MMHAC improved body weight and cumulative FCR, and reduced jejunal IL-17A gene expression on d28. In summary, in broilers subjected to Eimeria challenge, supplementation of the reduced levels of bis-chelated trace minerals MMHAC improved growth performance compared to high levels of ITM (sulfates or TBCC), which might partially result from better immune response, high levels of TSAA improved growth performance, Met source had no effect. Supplementation of both bis-chelated trace minerals MMHAC and high levels of TSAA could overcome the growth performance challenge issue due to coccidiosis.

An expert curated global legume checklist improves the accuracy of occurrence, biodiversity and taxonomic data.

The Legume Phylogeny Working Group's Taxonomy Working Group was tasked to create a community endorsed global legume checklist that will serve as a primary source of taxa for biodiversity data platforms and legume-related research. The checklist was published in June 2021, recognising 772 genera and 22,360 species. It is disseminated through the new Legume Data Portal as part of the Global Biodiversity Information Facility (GBIF) hosted portal initiative. The process that was followed to publish and disseminate the checklist and its content is described here. The impact of the work by the Taxonomy Working Group are quantified by comparing the published checklist with the GBIF taxonomic backbone. A total of 44,157 names overlapped with the GBIF taxonomic backbone while 30,456 names were added, which enabled more accurate name matching of 61,235 legume occurrences. Continuous improvement to the World Checklist of Vascular Plants (WCVP): Fabaceae checklist will allow the GBIF taxonomic backbone and other checklist managers to converge to a consistent and comprehensive list of legume taxa globally over time.

[Enoxaparin and tinzaparin in pediatrics: Impact of recommendation on prescription quality and anti-Xa levels]. / Énoxaparine et tinzaparine en pédiatrie : impact de recommandations sur la qualité des prescriptions et l'activité anti-Xa.

OBJECTIVES: A protocol has been written and distributed in May 2017 to all prescribers in a pediatric hospital to standardize and to secure the prescriptions of enoxaparin and tinzaparin considered as two high risk medications. The aim of this study is to evaluate the impact of the protocol on those prescriptions in a pediatric population. METHODS: This is a monocentric retrospective study comparing prescriptions of this two low-molecular-weight heparins for patients under 18 years old in 2016 and 2018, thus before and after the protocol redaction. RESULTS: In 2016, 2246 prescriptions of enoxaparin and tinzaparin were analyzed for 627 patients. Among them, 142 (22.6%) patients have had at least one anti-Xa level dosed. On the other hand, in 2018, 2061 prescriptions were written for 628 patients including 96 (15.3%) who have had at least one anti-Xa level dosed. The conformity rate of the first dose in IU/kg/administration of the first enoxaparin prescription goes from 36.3% before protocol to 52.1% after (P=0.03*). Concerning tinzaparin, the conformity rate goes from 69.2% to 83.3%. (P=0.19). The rate of first anti-Xa level in the range 0.4 to 1.2 IU/ml increase between 2016 and 2018 from 27.7% to 43.8% (P<0.001*). CONCLUSION: This protocol enabled to improve the quality of prescriptions in terms of: dosage written in IU/kg/administration, frequency of administration, dilution conformity, and result of the first anti-Xa level. Some efforts must be made in writing the dose in IU not in mg or ml.

Safety and immunogenicity of the epicutaneous reactivation of pertussis toxin immunity in healthy adults: a phase I, randomized, double-blind, placebo-controlled trial.

OBJECTIVES: Protection induced by acellular vaccines can be short, requiring novel immunization strategies. Objectives of this study were to evaluate safety and capacity of a recombinant pertussis toxin (PTgen) -coated Viaskin® epicutaneous patch to recall memory responses in healthy adults. METHODS: This double-blind, placebo-controlled randomized trial (Phase I) assessed the safety and immunogenicity of PTgen administered on days 0 and 14 to healthy adults using Viaskin® patches applied directly or after epidermal laser-based skin preparation. Patch administration was followed by Boostrix®dTpa on day 42. Antibodies were assessed at days 0, 14, 28, 42 and 70. RESULTS: Among 102 volunteers enrolled, 80 received Viaskin-PT (Viaskin-PT 25 µg (n = 25), Viaskin-PT 50 µg (n = 25), laser + Viaskin-PT 25 µg (n = 5), laser + Viaskin-PT 50 µg (n = 25)), Viaskin-placebo (n = 10) or laser + Viaskin-placebo (n = 2). Incidence of adverse events was similar across groups (any local event: 21/25 (84.0%), 24/25 (96.0%), 4/5 (80.0%), 24/25 (96.0%), 8/10 (80.0%), 10/12 (83.0%), respectively). Direct application induced no detectable response. On day 42, PT-IgG geometric mean concentrations were significantly higher following laser + Viaskin-PT 25 µg and 50 µg (139.87 (95% CI 87.30-224.10) and 121.76 (95% CI 95.04-156.00), respectively), than laser + Viaskin-placebo (59.49, 95% CI 39.37-89.90). Seroresponse rates were higher following laser + Viaskin-PT 25 µg (4/5 (80.0%), 95% CI 28.4-99.5) and 50 µg (22/25 (88.0%), 95% CI 68.8-97.5) than laser + Viaskin-placebo (0/12 (0.0%), 95% CI 0.0-26.5). CONCLUSIONS: Viaskin-PT applied after laser-based epidermal skin preparation showed encouraging safety and immunogenicity results: anti-PT booster responses were not inferior to those elicited by Boostrix®dTpa. This study is registered at ClinicalTrials.gov (NCT03035370) and was funded by DBV Technologies.

Radiotherapy is safe in patients with implantable cardiac devices. Analysis of a systematic interrogation follow-up.

INTRODUCTION: The number of patients who have a cardiac implantable electronic device (CIEDs) that undergo a course of radiotherapy is increasing due to the ageing population. The majority of clinical studies only evaluate any CIED malfunction at the end of a course of irradiation or in a case of there being symptoms of possible malfunction. As a result, little data has been collected on CIED status acquired during an active course of irradiation. MATERIAL AND METHODS: We aimed to evaluate the correct functioning of a CIED during a course of radiotherapy. So, a retrospective analysis was made of all patients having CIEDS in a single institution during their course of radiotherapy. All CIEDs were systematically checked before and during the course of radiotherapy according to the risk of device failure and patient dependence. RESULTS: Data was analysed from 56 patients (43 men, 13 women) with a mean age of 78.2 years, of whom 87.5% of the patients carried a pacemaker (PM), the 39% of the patients were PM dependent, and the remaining patients carried an implantable cardioverter-defibrillator (ICD). An observable dose of irradiation was evident in only 10 cases. 69.1% of the CIEDs were checked daily and the remainder were checked weekly. During the radiotherapy course, 82% of the patients did not complain of any cardiological event. The CIED of five patients experienced an increase in the threshold and, in another case, a sudden reduction in the duration of the battery was reported. Another patient with a CIED experienced a cardiac insufficiency episode triggered by a ventricular tachycardia. CONCLUSION: In conclusions, although adverse clinical events from exposure of a CIED to irradiation are rare, they can appear in any group of risk. No dose-dependency was observed on the malfunction of the CIED.

Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients.

INTRODUCTION: No therapy has yet proven effective in COVID-19. Tocilizumab (TCZ) in patients with severe COVID-19 could be an effective treatment. METHOD: We conducted a retrospective case-control study in the Nord Franche-Comté Hospital, France. We compared the outcome of patients treated with TCZ and patients without TCZ considering a combined primary endpoint: death and/or ICU admissions. RESULTS: Patients with TCZ (n=20) had a higher Charlson comorbidity index (5.3 [±2.4] vs 3.4 [±2.6], P=0.014), presented with more severe forms (higher level of oxygen therapy at 13L/min vs 6L/min, P<0.001), and had poorer biological findings (severe lymphopenia: 676/mm3 vs 914/mm3, P=0.037 and higher CRP level: 158mg/L vs 105mg/L, P=0.017) than patients without TCZ (n=25). However, death and/or ICU admissions were higher in patients without TCZ than in the TCZ group (72% vs 25%, P=0.002). CONCLUSION: Despite the small sample size and retrospective nature of the work, this result strongly suggests that TCZ may reduce the number of ICU admissions and/or mortality in patients with severe SARS-CoV-2 pneumonia.

Tips & tricks for transoral approach for submandibular lithiasis (TASL).

INTRODUCTION: Sialolithiases mainly affect the submandibular gland. More often, the lithiasis is large and located at the junction of the middle and the posterior third of the duct, in the hilum region. In such situation, transoral approach is recommended to avoid sialadenectomy because of its lower morbidity. TIPS AND TRICKS: Because of our experience, with over 300 cases operated with this transoral approach, we have decided to describe the tips and tricks that can help the surgeon who operates large stones impacted in the hilum of the submandibulary gland. DISCUSSION: The benefits of these tips and tricks are exposed. CONCLUSION: These keypoints can help to overcome intraoperative issues and save time.

A review of the ethnobotany, contemporary uses, chemistry and pharmacology of the genus Thesium (Santalaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Many plant species representing the hemi-parasitic genus Thesium play important roles in communities around the globe as evidenced by the numerous ethnobotanical and contemporary uses, and pharmacological activities. However, no attempt has been made to amalgamate and analyze all of the available information. A comprehensive survey is needed to highlight knowledge gaps, as well as to determine the economic importance and commercial potential of the genus. AIMS OF THIS REVIEW: To provide a comprehensive report on the species diversity, geographical distribution, ethnobotany, contemporary uses, chemistry, pharmacology and toxicology of the genus Thesium, as well as to give insights into possible future research opportunities. MATERIALS AND METHODS: Literature on the ethnobotany, contemporary uses, chemistry and pharmacology of Thesium was gathered from standard search engines (Google, Google Scholar, PubMed, SciFinder and Scopus) using the phrase Thesium, as well as generic synonyms. Additional information came from relevant books, theses, patents and label information from herbarium specimens in the National Herbarium in Pretoria, South Africa. Information on geographical distributions was compiled from regional floras, regional revisions, original species descriptions and databases (GBIF, IPNI, Plants of the World online and The Plant List). Scientific names and synonyms were validated through www.plantsoftheworldonline.org. RESULTS: A total of 23 Thesium species, 17 from Africa and six from Asia, were found to have traditional and contemporary uses. Despite the near cosmopolitan distribution of the genus, no uses were recorded for Europe, Australia and North America. Thesium plants are most commonly used as medicines (18 species), functional foods and beverages (seven species), charms (six species) and crafts (three species), but also have several other minor uses. Charm uses were restricted to southern and East Africa, while several contemporary uses such as functional feeds and fodders, growth mediums and fertilizers and veterinary medicine were unique to Asia. Thesium chinense is by far the most utilized and versatile species with a total of 173 uses in nine use categories, followed by T. longifolium with 39 uses in six use categories. No specific trends were observed in the plant parts used. As a medicine Thesium is used to treat 137 ailments, predominantly reproductive and breast (22), respiratory tract (18), degenerative (11), digestive (11) and urinary (10) ailments. Chemical analyses are available for only eight species, with flavonoids, fatty acids and alkaloids as the main compounds. The potential influence of the host plants on the chemistry and pharmacology remains unexplored. The pharmacological activities of two species, T. chinense and T. viride, have been studied, while three other species are reported to be poisonous. Thesium chinense has analgesic, anti-inflammatory, anti-oxidation, chemopreventive, cytotoxic and other general therapeutic properties, and T. viride anti-bacterial activity. CONCLUSION: This study has highlighted the ethnobotanical, contemporary and pharmacological importance of Thesium and informed possible future research opportunities. While ample information is available on the traditional uses of the richly diverse African Thesium species, the few Asian species dominate the literature on contemporary uses and pharmacology, while relevant literature on species in the rest of the world is altogether lacking. In light of the popularity of Asian species as ingredients in contemporary medicines and products, further research is needed into African species and their uses, including potential commercial uses. As an important medicinal hemi-parasite in both Africa and Asia, the identities of ethnobotanically relevant species and their phytochemistry, pharmacology and toxicology remain underexplored and require more research attention.

Simultaneous Biofortification of Wheat with Zinc, Iodine, Selenium, and Iron through Foliar Treatment of a Micronutrient Cocktail in Six Countries.

Field experiments were conducted on wheat to study the effects of foliar-applied iodine(I) alone, Zn (zinc) alone, and a micronutrient cocktail solution containing I, Zn, Se (selenium), and Fe (iron) on grain yield and grain concentrations of micronutrients. Plants were grown over 2 years in China, India, Mexico, Pakistan, South Africa, and Turkey. Grain-Zn was increased from 28.6 mg kg-1 to 46.0 mg-1 kg with Zn-spray and 47.1 mg-1 kg with micronutrient cocktail spray. Foliar-applied I and micronutrient cocktail increased grain I from 24 µg kg-1 to 361 µg kg-1 and 249 µg kg-1, respectively. Micronutrient cocktail also increased grain-Se from 90 µg kg-1 to 338 µg kg-1 in all countries. Average increase in grain-Fe by micronutrient cocktail solution was about 12%. The results obtained demonstrated that foliar application of a cocktail micronutrient solution represents an effective strategy to biofortify wheat simultaneously with Zn, I, Se and partly with Fe without yield trade-off in wheat.

Botulinum toxin for ductal stenosis and fistulas of the main salivary glands.

This study was performed to present the authors' experience with botulinum toxin therapy for salivary stenosis and salivary fistula in terms of the procedure, dosage, effectiveness, and complications. A retrospective study of all patients treated in the maxillofacial surgery department for salivary stenosis or fistula from January 2014 to September 2018 was performed. Intraglandular injections of incobotulinumtoxinA (Xeomin) were utilized. The frequency of relapse and the pain recorded before injection and at 3 months after each injection or fistula resolution were assessed. Swallowing dysfunction or any diffusion of toxin into the facial muscles was recorded. This study included 22 patients (mean age 53 years). Botulinum therapy was indicated for parotid duct stenosis in 14 patients, submandibular duct stenosis in four patients, and parotid fistula in four patients. The frequency of relapse (P = 0.0001) and pain level (P = 0.0001) decreased after botulinum therapy. The average duration of the botulinum effect was 4.50±2.00 months after the first injection. No complication was observed. Botulinum therapy with 100 IU of Xeomin proved effective at resolving salivary fistula. Botulinum therapy is an effective treatment for symptoms of salivary duct stenosis in patients for whom minimally invasive procedures have failed. Botulinum therapy can also be used for the treatment of salivary fistulas.

Mucoceles of the anterior ventral surface of the tongue and the glands of Blandin-Nuhn: 5 cases.

INTRODUCTION: Mucoceles are cystic diseases of the oral mucosa. The most common are ranula and mococeles of the lower lip. Blandin and Nuhn mucoceles, which develop at the ventral side of the tongue, are rare benign lesions. They are often misdiagnosed and sometimes confused with ranula. The recommended treatment is a complete surgical excision of the gland. PATIENTS AND METHODS: We describe 5 clinical cases managed in service between 2009 and 2016. Clinical cases are presented in order to detail their clinical history, paraclinical and treatment. RESULTS: The clinical appearance is a longitudinal swelling of the ventral surface of the tongue, parallel to the frenulum. The volume of the swelling is variable; it is normally around 30 × 10 mm. The paraclinical (ultrasound, CT, MRI, or ponction) could be performed. CT showed an cyst located on the ventral surface of the tongue, with liquid density. Blandin and Nunh mucocele were strictly anechogenic. MRI confirms the liquid content of this cyst (low T1signal, high T2signal and no post-contrast-enhanced). The resection of Blandin and Nuhn glands should respect the sublingual gland, the lingual nerve and the lingual veins in the mouth floor. CONCLUSION: This study demonstrates that Blandin and Nuhn mucoceles must be understood and recognised to propose complete excision of the Blandin and Nuhn gland and avoid recurrence.

The Stensen's duct line: A landmark in parotid duct and gland injury and surgery. A prospective anatomical, clinical and radiological study.

INTRODUCTION: The parotid duct (PD) is often involved in parotid gland diseases. A skin landmark could help the surgeon to locate its position. The parotid duct line (PDL) joins the tragus-antitragus point to the middle of the half upper lip. The aim of this study was to assess and scientifically validate this landmark. METHODS: A monocentric prospective anatomical, clinical and radiological study was conducted. Six fresh cadavers' PD were dissected. A subcutaneous flap was performed and the PD's position spotted by needle checking through the skin. 10 subjects with parotid obstructive symptoms were included for sialendoscopy, which light through the skin revealed the PDL's position. MRI was conducted on 20 PDs. The radiologist virtually drew the PDL and did a 3D reconstruction of the PD. The distance from the PDL to the PD was measured. RESULTS: Anatomical study: 2 PDs were on the PDL, 2 under and 2 over. Sialendoscopic study: 6 PDs were on the PDL (60%), 3 under and 1 over. MRI study: 13 over 20 PDs crossed the PDL (65%). Maximum mean distance from the PD was 10.44 mm [5.01-15.87] and minimum mean distance from the PD was 2.42 mm [0-5.75]. DISCUSSION: This study sought to assess the relevance of the PDL, which is not parallel to the PD that runs a «S-Shape¼ curve when crossing the PDL. It could be used when evaluating a potential ductal injury in trauma management and when locating proximal parotid lithiasis during sialendoscopy.

Hooliganism and maxillofacial trauma: The surgeon should be warned.

INTRODUCTION: With more than 270 million spectators, football - or soccer - is the most popular sport in the world. International football events generate many risky situations, including hooliganism and are an opportunity to analyze the incidence and the particularities of associated trauma. We sought to underline the potential rapid and brutal increase in maxillofacial trauma during a world-class competition. MATERIAL AND METHODS: A retrospective multicenter study of the epidemiology of maxillofacial traumas during the UEFA 2016 Cup was conducted. All the medical data from each UEFA 2016 World Cup matches from 10 June 2016 to 10 July 2016 were collected. Only the maxillofacial traumas requiring a surgery under general anesthesia and a hospitalization were included. RESULTS: 11 patients from 3 different cities were included. The main etiology was interpersonal violence (7/11), followed by road accidents (3/11). Open reduction with internal fixation of a mandibular fracture was the most performed surgery (9/11). Patients were 18 to 50 year-old, with an average age of 30.6 years. DISCUSSION: This study underlines the violence of riots between "ultra" supporters during the 2016 UEFA cup. We noticed an upsurge of maxillofacial trauma severe enough to require a surgery under general anesthesia. Hooligan behaviors should be known by every practitioner dealing with trauma care, and may requires transitional adjustment of public health policy.