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Most of the foundation liquids in the market need makeup removers for cleaning, while the excessive use of makeup removers might lead to skin barrier damage, which would further lead to many kinds of dermatosis, such as skin sensitivity, facial telangiectasia, rosacea, acne, as well as various cosmetic contact dermatitis. Inspired by the protective effect of fiber-rich diet on the intestinal mucosal mechanical barrier, a novel hemp/cellulose nanocrystals (CNCs)-based foundation liquid featuring easy-wiping property has been constructed, which will effectively solve the post-makeup skin cleaning problems. In this experiment, the formula of the foundation liquid can be obtained through hemp/CNCs instead of mineral oil and titanium oxide, which are considered to have undesirable local tolerance, sensitizing potential, and are environmental pollutants, to create a moisture barrier. Industrial hemp is a hot issue in cosmetic research, and a great quantity of discarded industrial hemp stalk is available to be used to produce hemp/CNCs through grinding and acidification. The graft technique is adapted to obtain hemp/CNCs-g-polylactic acid (PLA). By replacing the hydroxyl group on the side of hemp/CNCs, hemp/CNCs-g-PLA reduces the intermolecular hydrogen bonding, resulting in a higher dispersion in the oil phase. The hemp/CNCs-g-PLA has excellent performance in terms of biological compatibility, water resistance, and non-penetration into the skin. With basic features of a foundation liquid to alleviate discoloration, age spots, and skin roughness, the foundation liquid based on hemp/CNCs-g-PLA provides a novel characteristic of easy-wiping, which helps to avoid the damage to the skin barrier caused by excessive cleansing.

Point-of-interest (POI) recommendation has great significance in helping users find favorite places from a large number of candidate venues. One challenging in POI recommendation is to effectively exploit geographical information since users usually care about the physical distance to the recommended POIs. Though spatial relevance has been widely considered in recent recommendation methods, it is modeled only from the POI perspective, failing to capture user personalized preference to spatial distance. Moreover, these methods suffer from a diversity-deficiency problem since they are often based on collaborative filtering which always favors popular POIs. To overcome these problems, we propose in this article a personalized geographical influence modeling method called PGIM, which jointly learns users’ geographical preference and diversity preference for POI recommendation. Specifically, we model geographical preference from three aspects: user global tolerance, user local tolerance, and spatial distance. We also extract user diversity preference from interactions among users for diversity-promoting recommendation. Experimental results on three real-world datasets demonstrate the superiority of PGIM.

Dura mater defects are a common problem following neurosurgery. Dural grafts are used to repair these defects; among them are biodegradable polymeric synthetic grafts. ArtiFascia is a novel synthetic and fibrous Dural graft, composed of poly(l-lactic-co-caprolactone acid) (PLCL) and poly(d-lactic-co-caprolactone acid). In this study, the biodegradability and local tolerance of ArtiFascia was evaluated in rabbits and compared with a bovine collagen matrix as a reference control. ArtiFascia implantation resulted in the formation of neo-dura at the site of implantation and recovery of the dural damage and the calvaria bone above. The implanted graft was completely absorbed after 12 months and the remaining macrophages were morphologically consistent with the anti-inflammatory M2-like phenotype, which contributes to tissue healing and are not pro-inflammatory. The site of the drilled skull bone had a continuous smooth surface, without exuberant tissue or inflammation and a newly formed trabecular bone formation indicated the healing process of the bone. These results support the local tolerability and biodegradability of ArtiFascia when used as a dural graft in rabbits. This study suggests that PLCL-based grafts including ArtiFascia are safe and effective to repair Rabbit Dura.

Continuous subcutaneous (s.c.) apomorphine infusion is an effective therapy for Parkinson’s disease (PD), but a limitation is the formation of troublesome s.c. nodules. Various chemically non-identical apomorphine formulations are available. Anecdotal experiences have suggested that shifting from one of these (Apo-Go PumpFill®; apoGPF) to another (Apomorphine PharmSwed®; apoPS) may influence the occurrence and severity of s.c. nodules. We, therefore, followed 15 people with advanced PD (median PD-duration, 15 years; median “off”-phase Hoehn and Yahr, IV) on apoGPF and with troublesome s.c. nodules who were switched to apoPS. Data were collected at baseline, at the time of switching, and at a median of 1, 2.5, and 7.3 months post-switch. Total nodule numbers (P P P P = 0.058), and pain (P ≤ 0.032) improved over the observation period. PD severity and dyskinesias tended to improve and increase, respectively. Apomorphine doses were stable, but levodopa doses increased by 100 mg/day. Patient-reported apomorphine efficacy tended to increase and all participants remained on apoPS throughout the observation period; with the main patient-reported reason being improved nodules. These observations suggest that patients with s.c. nodules caused by apoGPF may benefit from switching to apoPS in terms of s.c. nodule occurrence and severity. Alternatively, observed benefits may have been due to the switch itself. As nodule formation is a limiting factor in apomorphine treatment, a controlled prospective study comparing local tolerance with different formulations is warranted.

إن الإسلام دين سليم كامل موافق لعقول الإنسان, يغير حضارة الشعوب على سلوكها وأخلاقها وعقيدتها. وكان انتشاره ناجحا بفضل العلوم الإسلامية منها علم التصوف لأنه يقف موقف التسامح للحضارة المحلية, ومن أهم آثارها مخطوطات ثمينة القيم. في هذه المناسبة اخترت احدى المخطوطات لدراستها, تحت عنوان " نصيحة المسلمين وتذكرة المؤمنين"فيها بيان عن الجهاد في سبيل الله و فضائله, وينقسم البحث إلى وصف المخطوطة, وتقديم حياة مؤلف المخطوطة, وتحقيق النص والأفكار الهامة التى وردت في النص, و ترجمة النص إلى اللغة الإندونيسية وأما الغرض من هذا البحث فهو:تقديم النص ليسهل القراءة في فهمه وبيان مقاصده حتى تعم الفائدة بعد دراسة المخطوطة.والجدير بالذكر هنا فأنا كالباحثة أقوم بتخريج الأحاديث فيها وهذه النسخة تشتمل على المخطوطتين فحققتهما بعمل دراسة مقارنة لإختيار النسخة الجيدة واعتمدت بمنهج ستاندار الذي صحيحا وهو الإعتماد على النسخة التى تعيد أكثرها صحيحا ومع الإشارة إلى الأخطاء الواردة في النص التى وضعتها في الهامش. للمخطوطة أهمية بليغة و ثمينة وآثار كبيرة, خاصة في تنمية فكرة عن حالة الثقافة الإسلامية وتقدمها, كما أنها تحفظ على التراث القديم في العالم وتؤدي دراسة المخطوطات إلى تواصل الأجيال وترابط الأمم وازدهار الحضارات, لأن فيها معلومة كثيرة يلزم للطلاب الجامعة معرفتها. --- Abstract Islam is a religion full sound OK to human minds, alters the civilization of peoples on the behavior and morals and faith. It was successful thanks to the spread of Islamic Sciences them aware of mysticism because it stand the local tolerance of civilization, and the most important effects of precious manuscripts values.On this occasion, I chose one of the manuscripts for study, titled "Advice Muslims and ticket believers," the statement from the Jihad for the sake of God and the virtues, is divided Find a description of the manuscript, and make the life of the author of the manuscript, and the achievement of important text contained in the text, and translate text to and ideas Indonesian language and the purpose of this research is: to provide the text for easy reading in his understanding and statement purposes until the benefit after studying Almkhtooth.walagdir mentioning here I Kalpagesh I graduated conversations in this version include Almkhtoottin Vhakguethma doing a comparative study to choose the good version and adopted the approach Standard that right It is relying on the version that will restore the most correct and with reference to the errors contained in the text drawn up by the margin The manuscript importance eloquent and precious and great effects, especially in the development of the idea on the status of Islamic culture and progress, as it kept the ancient heritage of the world and lead the study of manuscripts to the continuity of generations and the interdependence of nations and civilizations flourished, because the many information necessary for university students know

Introduction Androgenic alopecia (AGA) is a common and chronic condition. It may impact self-esteem, self-image and quality of life. Benefit, tolerability, cosmetic acceptance and patient satisfaction are key to ensuring good treatment outcome. Aim Assessment of hair loss improvement and hair quality with AC5 in subjects with mild AGA in real life settings. Materials and methods Open-label, observational, international real-life study in 527 adult subjects with mild AGA who received AC5 (2,4-Diamino-Pyrimidine-N-Oxyde, arginine, 6-O glucose linoleate (SP94), piroctone olamine and Vichy mineralizing water) once daily for 3 months. After 3 months, investigators evaluated the impact of AC5 on hair loss and product satisfaction, and asked subjects about local tolerance; subjects assessed hair growth and quality, as well as satisfaction. Results Data from 357 subjects were evaluable for the benefit analysis; 59.9% of subjects were female; the mean age was 33.6±8.7 years. Duration of hair loss was 1.62±2.24 years. 71.3% of women had a Ludwig score of 1 and 40.8% of men had a Hamilton Norwood score of 2. At the end of study, hair loss was reduced in 89.0% of subjects; it was slightly higher in women (92.5%) than in men (83.8%). Subject satisfaction on a scale from 0 (not satisfied at all) to 10 (completely satisfied) was 7.9±1.7. Tolerance was rated good to very good by 98.6% of all subjects. Conclusion AC5 reduces mild AGA in both men and women and has a pleasant texture. AC5 was well tolerated and highly appreciated. This article is protected by copyright. All rights reserved.

Background High-intensity focused ultrasound (HIFU) operating at 20 MHz is new and applicable to skin. Details of use and instrumentation are not documented. Materials and methods A GLP compliant 12-week study of Gottingen minipigs (n = 3) was undertaken. Effects of HIFU treatment at different focal depths, energy levels and field size (single shot vs 5 × 5 multiple shots) were studied. Clinical scoring and histology of treated sites were made. Results High-intensity focused ultrasound showed instant and initial effects with wheal and flare responses followed by delayed inflammatory reactions associated with outer skin necrosis, depending on energy dose. HIFU treatment was tunable in the range 0.3-1.5 J, ablative at higher energy level. Transducers with deeper focal points gave more profound effects, while epidermal effects were comparable. Multiple doses of 5 × 5 shots produced stronger reactions than single dose indicating that nearby applied shots were synergistic. Recovery from single doses was faster than in multidose areas. Clinical scarring at the end point was not seen despite occasional fibrous change of dermis. Findings illustrated intended therapeutic use; no special safety issues of concern were raised. Conclusion The new 20 MHz HIFU was reproducible, tunable and produced targeted effects in the outer skin, for example instant wheal and flare followed by inflammation and possibly necrosis depending on energy setting. Reactions recovered during the study with only minor findings at study end. No special safety concerns were raised. The method can be controlled and modulated, and it is ready for clinical testing of dermatological disease indications including conditions presently treated with lasers.

Purpose A PET/CT scan of a uniformly filled 68Ga phantom resulted in an unexpectedly low SUVmean of 0.88. A potential contributing cause of underestimation of 68Ga SUV is overestimation of 68Ga activity in the Radionuclide Calibrator associated with the PET/CT scanner. To investigate this, a Radionuclide Calibrator cross-calibration exercise was performed. Methods A source of 68Ga was measured in 5 Capintec CRC-55tR calibrators using the pre-set 68Ga calibrator factor of 416, and a Veenstra VDC-505 calibrator using a factor recommended by the manufacturer. The source was then measured in an externally located Fidelis Secondary Standard Radionuclide Calibrator. Manual adjustments were made to the Capintec calibrator factors to match the decay corrected Fidelis measurement, followed by a repeat PET/CT scan of a uniform 68Ga phantom. Results The cross-calibration results showed that the 5 Capintec calibrators systematically overestimated 68Ga activity by 7.8–9.4% (mean 8.5%) compared to the Fidelis. The calibrator factors were adjusted to 456–464 to match the Fidelis measurement, and the repeat phantom scan resulted in a SUVmean of 0.97, within the local tolerance of 1.00 ± 5%. The result for the Veenstra calibrator was within the tolerance of ±5%. Conclusions Underestimation of 68Ga SUV was primarily caused by overestimation of 68Ga activity using the pre-set calibrator factor setting on a Capintec CRC-55tR. Improvement in quantification accuracy was achieved by adjusting the 68Ga calibrator factor based upon a cross-calibration exercise. We recommend SUV checks using a uniform phantom and regular calibrator cross-calibration exercises for all isotopes used for quantitative PET/CT imaging.

Introduction The number of dermatological or cosmetic procedures carried out has continuously increased over the last decades. Almost all may cause transient local skin reactions such as erythema, blistering, crusts, scaling, hypo- or hyperpigmentation, or hemorrhagic lesions. One issue of dermatological procedures is the downtime, during which patients need to hide their skin, due to these local reactions. Aim To provide dermatologists with easy-to-follow recommendations for the right timing of use of corrective makeup for patients who have undergone or who plan to undergo dermatological procedures, according to the invasiveness of the dermatological procedure chosen. Methodology A group of experts in dermatological procedures met in 2019 and at the beginning of 2020 to discuss the different procedures, their local reactions and downtime, and the opportunities to use specific corrective makeup in order to hide these transient reactions. Results As a result of the discussions, the experts proposed a tabulated algorithm of use based on a classification of the different dermatological procedures according to their invasiveness and recommended timing of the first post-procedure corrective makeup application. Conclusion Corrective makeup may be considered as a complement to certain dermatological procedures in order to minimize downtime. However, its use is conditioned by the correct understanding of skin barrier alteration and recovery time. The proposed algorithm of use of corrective makeup after procedures may help the practitioner to indicate his patient the right moment for applying corrective makeup in order to avoid local tolerance issues and post-procedure complications.

Purpose To analyze results from three years of in vivo transit EPID dosimetry of abdominal and pelvic stereotactic radiotherapy and to establish tolerance levels for routine clinical use. Material 80 stereotactic VMAT treatments (152 fractions) targeting the abdomen or pelvis were analyzed. In vivo 3D doses were reconstructed with an EPID commercial algorithm. Gamma Agreement Index (GAI) and DVH differences in Planning Target Volume (PTV) and Clinical Target Volume (CTV) were evaluated. Initial tolerance level was set to GAI > 85% in PTV. Fractions Over Tolerance Level (OTL) were deemed to be due to set-up errors, incorrect use of immobilization devices, 4D errors, transit EPID algorithm errors and unknown/unidentified errors. Statistical Process Control (SPC) was applied to determine local tolerance levels. Results Average GAI were (82.7 ± 20.9) % in PTV and (72.9 ± 29.7) % in CTV. 37.8% of fractions resulted OTL and were classified as: set-up errors (3.3%), incorrect use of immobilization devices (2.1%), 4D errors (2.1%), EPID transit algorithm errors (17.1%). OTL causes for the remaining 13.2% of fractions were not identified. The differences between PTV and CTV measured in vivo and calculated mean dose (average difference ± standard deviation) were (−3.3% ± 3.2%) and (−2.3% ± 3.0%). When tolerance levels based on SPC to PTV mean dose differences were applied, the percentage of OTL decreased to 7% and no EPID algorithm error occurred. One error was not identified. Conclusions The application of local tolerance levels to EPID in vivo dosimetry proved to be useful for detecting extra-lung SBRT treatment errors.

The objective: to evaluate the effectiveness of the therapeutic effect, the overall and local tolerance of ValeVita Rinogel Spray and ValeVita Nazo-Vit in treatment of children with acute postvirus rhinosinusitis (APRS). Materials and methods. The clinical study included 30 children (17 boys and 13 girls) who were on an outpatient treatment in ENT department of the city’s Children’s Clinical Hospital №1 in Kyiv. The age of patients ranged from 8 to 15 years old (mean age 11.5±0.5 years old). The main group of children (n=15) used ValeVita Rinogel Spray and ValeVita Nazo-Vit; the control group (n=15) used nasal decongestants (xylometazoline) and sodium chloride 0.9%. In children of both observed groups there were evaluated clinical symptoms of APRS, microbiological and cytomorphological studies of the nasal mucosa before and after the treatment. Results. According to the analysis of rhinoscopic and endoscopic examination there was a more rapid regress of clinical symptoms of APRS in children of the main group compared with the control group. Cytomorphological study in the main group noted a significant decrease of inflammatory cells (eosinophils, neutrophil granulocytes, lymphocytes) in nasal mucosa of children with APRS during treatment period compared with children of the control group. Combined use of ValeVita Rinogel Spray and ValeVita Nazo-Vit in the main group promoted normalization of immune clearance of nasal mucous lining as manifested by decrease of pathogenic organisms compared with the control group. During observation time no complications, side effects associated with the use of ValeVita Rinogel Spray and ValeVita Nazo-Vit were noted in patients. Conclusion. Combination of ValeVita Rinogel Spray and ValeVita Nazo-Vit is effective and safe in the treatment of acute postvirus rhinosinusitis in children 8-15 years old, does not cause local and general pathological changes, as evidenced by performed clinical and laboratory examination of patients.

Objective: The objective of this randomized clinical study was to assess the onset time of the whitening effect of a combined use of a nonabrasive, activator-containing toothpaste and a light emitting diode (LED) device, compared to that of the toothpaste alone. Materials and Methods: A nonabrasive, activator-containing toothpaste was used twice daily alone or combined with an LED device for 15 days. The onset of the tooth whitening effect was evaluated through tooth color (a* b*, CIELAB) and tooth whiteness (WIO) by image analysis of standardized images. Local tolerance was assessed at days 1, 8, and 15. Results: On day 8, a significant (P = 0.003) tooth whitening effect compared to day 1 was observed with the toothpaste and the LED device, sustaining until the end of the study. Whitening using the toothpaste alone was significant compared to day 1 after 15 days, only. One subject reported mild redness, itching, and burning on day 1 on the gum of the lower jaw that was possibly related to with the toothpaste. The subject withdrew from the study. No adverse event was reported in the group using the LED device. Conclusion: Both tooth whitening methods had a significant whitening effect after 15 days of use. However, the onset of whitening was significantly faster when using the nonabrasive, activator-containing toothpaste combined with an LED device. The toothpaste and LED device were both safe.

The use of minipigs has been increasing in the areas of pharmacology researches and drug development. The microminipig developed by Fuji Micra Inc. (Shizuoka, Japan) inherits characteristics of other pig strains showing several similarities to humans in anatomy, physiology, omnivorousness and diurnal, but at the same time has several advantages over other pig strains because of its small size which allows easy keeping, handling and dosing, and saving of test substances. The microminipig weighs about 10 kg at the age of 6 months. Canine cages can be used to keep the animal. Swine leukocyte antigens (SLA) are defined in each individual animal which is useful for testing immunological reactions. As there are many similarities in metabolic enzymes and transporters to those in humans, the microminipig is a powerful animal model for toxicokinetic studies. Unfortunately as in other minipigs the microminipig is not appropriate for embryo-fetal development studies of antibody drugs due to its poor placental transfer, but can be used for other reproductive and developmental studies. Repeat dose toxicity, safety pharmacology, immunotoxicity and local tolerance studies should be also other arenas of this animal model.

Background:Adalimumab (ADL) is typically self-administered every 2 weeks (W) as a subcutaneous (s.c.) injection by patients (pts) for diverse indications, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and psoriasis (PsO). Conflicting evaluations of local tolerance to formulations containing citrate buffer have created insecurities among health care professionals and pts.1,2Objectives:To evaluate local tolerance of SDZ-ADL (GP2017), a biosimilar ADL with low citrate concentration (1.2 mM),3 in 466 healthy volunteers (HV) and 408 pts (RA: 177 and PsO: 231 including PsA: 52) from four phase I pharmacokinetic (PK) and two phase III confirmatory studies.Methods:HV evaluated their injection site pain (ISP) using a Visual Analogue Scale (VAS) of 0–100 mm. HV received a single 40 mg/0.8 mL s.c. injection and pts received SDZ-ADL every 2W during 48–51W duration of study. Injection site reactions (ISR) as well as adverse events (AEs) were assessed by investigators during the clinical studies. Details of study designs have been reported previously.4–7Results:Overall, 456 (97.9%) HV experienced no ISR. Ten HV experienced ISR. These were mostly of mild intensity; only 1 (0.2%) had an ISR of moderate intensity. 96.6% of HV experienced no pain (VAS score 0–4 mm)8 at 1-hour post-dose (Figure 1). In the phase III studies, a low number of ISR/ISP events were observed, which decreased during the course of study. Detailed results are provided in Table 1. No ISR/ISP led to treatment or study discontinuation in any study.Conclusion:The proportion of HV and pts experiencing ISR and ISP after administration of SDZ-ADL was low, with no events leading to treatment or study discontinuation. These results call into question the clinical impact of citrate and its concentration in ADL formulations on the incidence and intensity of ISP.References:[1]Nash et al. Rheumatol Ther. 2016;3:257–70.[2]NHS. Regional medicines optimisation committee briefing, best value biologicals: adalimumab update 6. July 2019. https://www.sps.nhs.uk/wp-content/uploads/2019/07/Adalimumab-RMOC-Briefing-6.pdf.[3]https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761071lbl.pdf.[4]Blauvelt A, et al. Br J Dermatol. 2018;179:623–31.[5]Wiland P, et al. BioDrugs 2020;34:809–23.[6]Richter OV, et al. Expert Opin Biol Ther. 2019;19:1057–64.[7]Richter OV, et al. Expert Opin Biol Ther. 2019;19:1075–83.[8]Hawker GA, et al. Arthritis Care Res. 2011;63:240–52.Figure 1.Proportion of HV with ISP in phase I PK studiesTable 1.ISP and ISR results from phase I PK and phase III confirmatory studiesPhase I PK studiesStudy101(N=73)102(N=108)103(N=178)104(N=107)Pooled studies (N=466)VAS scores (mm) at 1-hour post-doseMean (SD)0.89 (2.07)0.07 (0.52)1.03 (1.71)1.03 (2.49)0.79 (1.84)Median00100ISR scores at 1-hour post-dose, n (%)None73 (100)106 (98.2)178 (100)99 (92.5)456 (97.9)Mild0 (0)1 (0.9)0 (0)8 (7.5)9 (1.9)Moderate0 (0)1 (0.9)0 (0)0 (0)1 (0.2)Phase III confirmatory studiesADACCESS5* (PsO and PsA pts)ADMYRA6* (RA pts)W0–17 (N=231)W0–51 (N=168; including pts re-randomised to continue SDZ-ADL after W17)W0–24 (N=177)W0–48 (N=177; all pts continued SDZ-ADL after W24)DosageInduction 80 mg W0, then 40 mg EoW s.c.40 mg EoW s.c.40 mg EoW s.c.40 mg EoW s.c.Study duration, W17512448AEs - ISR, n (%), events15 (6.5), 349 (5.4), 267 (4.0), 117 (4.0), 12Mild14 (6.1), 309 (5.4), 267 (4.0), 117 (4.0), 12Moderate1 (0.4), 4000AEs - ISP (reported as ISR), n (%)3 (1.3)1 (0.6)2 (1.1)2 (1.1)*ADACCESS and ADMYRA were switch studies, therefore, only pts exposed to SDZ-ADL throughout the study period are included here. EoW, every other week, N, number of HV or ptsDisclosure of Interests:Piotr Wiland Speakers bureau: Celltrion, Celgene, Eli Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, Consultant of: Celltrion, Celgene, Eli Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, Andrew Blauvelt Speakers bureau: AbbVie, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Leo, Novartis, Pfizer, Rapt, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma., Consultant of: AbbVie, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Leo, Novartis, Pfizer, Rapt, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma., Lena Lemke Employee of: Hexal AG, Oliver von Richter Employee of: Hexal AG, Alison Balfour Employee of: Hexal AG, Fabricio Furlan Employee of: Hexal AG, Norman Gaylis: None declared

International audience; Hand hygiene plays a key role in nosocomial infection prevention. To achieve users' adherence, products' dermal tolerance is essential. We aimed at making a comparative assessment of skin irritation and phototoxicity of the 3 alcohols commonly used in alcohol-based hand rubs (Ethanol, Propan-2-ol, Propan-1-ol) at 60, 70, 80 or 85% w/w in water or with co-formulates (hydrating, emollient and skin protective agents). In vitro validated OECD methods 439 and 432 were used. For irritation, EpiSkin™ Small Model was the chosen Reconstructed Human Epidermis (RhE). For phototoxicity, co-formulates alone or in mixture with and without alcohol were tested using BALB/c 3T3 cell cultures. Whilst Ethanol and Propan-2-ol could not be differentiated and displayed good skin tolerance profiles, Propan-1-ol based products lead to significant viability impairments of RhE at 60, 70 or 80% and at 60% in the presence of co-formulates. However, these results could not be reproduced in another RhE model. Taking also into account bibliographic data on Propan-1-ol, this suggests that our results are probably related to a lack of specificity of the used RhE. Therefore, it can be relevant in case of significant results to use two different RhE models before performing any classification and/or performing any complementary tests.

Introduction Acne in adult women is an increasing reason for dermatological consultations. Objective The aim of this study was to assess in adult women with mild acne the efficacy and tolerance of a daily adjunctive application of a skincare (Normaderm®, Laboratoires Vichy, France) to a fixed combination of adapalene/benzoyl peroxide daily or every other evening and a standard emollient. Methods Subjects were randomised to receive the fixed combination applied either every evening or every other evening and a daily application of the standard emollient and the test care or a once daily application of the fixed combination and the standard emollient alone. Clinical evaluations at Day 0, Day 45 and Day 90 included the count of acne lesions, assessment of clinical improvement and local tolerance. The quantitative lipid profile of the stratum corneum of the forehead was also determined. Results After 90 days of application, acne had improved in all 299 subjects with a statistically significant difference in favour of the test care regimens (p

Objective To evaluate the safety and tolerability of repeated intratympanic administration of the gel-formulated NMDA receptor antagonist AM-101 in acute patients with inner ear tinnitus. Study Design Prospective, double-blind, randomized, placebo-controlled study. Setting Sixty-nine secondary and tertiary sites in North America, Europe, and Asia. Subjects and Methods In total, 343 subjects with persistent acute tinnitus after traumatic cochlear injury or otitis media were randomized to receive 3 intratympanic doses of either AM-101 0.87 mg/mL or placebo over 3 to 5 days. They were followed for 84 days. The primary safety end point was the incidence of a clinically meaningful hearing deterioration from baseline to study day 35. Further safety assessments included tympanic membrane closure rates, analysis of adverse events, hematology, blood chemistry, and vital signs. In addition, data were collected on applied anesthetics and injection techniques. Results The treatment was well tolerated, with no intervention-related serious adverse events. The incidence of clinically meaningful hearing deterioration was low, comparable between treatment groups ( P = .82 for the primary safety end point) and not different between treated and untreated ears in unilaterally treated subjects. The rate of treatment and procedure-related adverse events was similar among treatment groups. The tympanic membrane was closed in 92% of subjects within 1 week and in all subjects by study day 84. Blood values and vital signs were inconspicuous. Conclusion Repeated intratympanic injections of AM-101 over a 3- to 5-day period appear to be safe and well tolerated, demonstrating the ability to potentially use this delivery approach over longer time periods.

This article deals with the long-term preclinical validation of WIMAGINE® (Wireless Implantable Multi-channel Acquisition system for Generic Interface with Neurons), a 64-channel wireless implantable recorder that measures the electrical activity at the cortical surface (electrocorticography, ECoG). The WIMAGINE® implant was designed for chronic wireless neuronal signal acquisition, to be used e.g., as an intracranial Brain-Computer Interface (BCI) for severely motor-impaired patients. Due to the size and shape of WIMAGINE®, sheep appeared to be the best animal model on which to carry out long-term in vivo validation. The devices were implanted in two sheep for a follow-up period of 10 months, including idle state cortical recordings and Somato-Sensory Evoked Potential (SSEP) sessions. ECoG and SSEP demonstrated relatively stable behavior during the 10-month observation period. Information recorded from the SensoriMotor Cortex (SMC) showed an SSEP phase reversal, indicating the cortical site of the sensorimotor activity was retained after 10 months of contact. Based on weekly recordings of raw ECoG signals, the effective bandwidth was in the range of 230 Hz for both animals and remarkably stable over time, meaning preservation of the high frequency bands valuable for decoding of the brain activity using BCIs. The power spectral density (in dB/Hz), on a log scale, was of the order of 2.2, -4.5 and -18 for the frequency bands (10-40), (40-100), and (100-200) Hz, respectively. The outcome of this preclinical work is the first long-term in vivo validation of the WIMAGINE® implant, highlighting its ability to record the brain electrical activity through the dura mater and to send wireless digitized data to the external base station. Apart from local adhesion of the dura to the skull, the neurosurgeon did not face any difficulty in the implantation of the WIMAGINE® device and post-mortem analysis of the brain revealed no side effect related to the implantation. We also report on the reliability of the system; including the implantable device, the antennas module and the external base station.

PQ Grass represents an allergen-specific immunotherapy for pre-seasonal treatment of patients with seasonal allergic rhinitis (or rhinoconjunctivitis) with or without mild-to-moderate bronchial asthma. It consists of a native pollen extract for 13 grass species, chemically modified with glutaraldehyde, and adsorbed to l-tyrosine in a microcrystalline form with addition of the adjuvant Monophosphoryl Lipid A (MPL® ). Previous non-clinical safety testing, including rat repeat dose toxicity in adult and juvenile animals, rat reproductive toxicity and rabbit local tolerance studies showed no safety findings of concern. A new Good Laboratory Practice compliant rat subcutaneous repeat dose toxicity study to evaluate a higher clinical dose and modified posology (once every 2 weeks for 13 weeks) showed no signs of toxicity. As seen in previous studies, relatively minor, immunostimulatory effects were seen such as reversible increased white cell count (notably neutrophils), increased globulin level (resulting in decreased A/G ratio) and increased fibrinogen as well as minor dose site reaction in the form of inflammatory cell infiltrate. These findings are likely due to the immunostimulatory nature of MPL and/or the presence of l-tyrosine within the adjuvanted vaccine. This new toxicity study with PQ Grass therefore supports longer posology with higher dose levels.

Human-elephant conflict (HEC) poses a serious problem in Africa for both local livelihoods and elephant conservation. Elephant damage is the price local people pay for coexisting with this species, and is assumed to reduce tolerance for elephants. However, conservation-related projects, through the benefits they offer may enhance local tolerance toward elephants. This study aimed to examine how crop damage by elephants and the benefits gained from conservation activities affect local people’s tolerance toward elephants around Moukalaba-Doudou National Park in southwest Gabon based on long-term ethnographic research and interview surveys in two periods (2010 and 2019). Based on the results, crop damage by elephants had a significant negative impact on the local social economy, leading to a decrease in human population in the area and making local people highly resentful of elephants. However, in one of the villages where employment from research and conservation activities was concentrated, many acknowledged the benefits associated with wildlife and expressed high tolerance for elephants. These findings suggest that benefits from conservation activities can increase tolerance toward elephants, which is negatively affected by the crop damage they cause. However, it should also be noted that externally generated projects have limitations and drawbacks. It is important to establish a system in which the benefits of conservation are shared widely and distributed appropriately, and wherein income resources are diversified. Multisectoral interventions focusing on local socio-ecological vulnerability are needed to mitigate human-elephant conflict and advance the conservation of African elephants.