A survey of the treatment and management of patients with severe chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is characterized by the recurrent appearance of weals, angio‐oedema or both, occurring at least twice weekly for longer than 6 weeks.1 It is often managed with antihistamines, but occasionally requires other systemic agents in recalcitrant cases. A cross‐sectional survey was conducted by means of an internet‐based survey tool (Typeform; https://www.typeform.com). Participating consultants with a specialist interest in urticaria were identified through the specialist registers of the British Society of Allergy and Clinical Immunology (BSACI), the Improving Quality in Allergy Services (IQAS) Group and the British Association of Dermatologists (BAD), and invited to take part. The survey content was based on current CSU treatment guidelines from EAACI/GA2LEN/EDF/WAO1 and the British Society for Allergy and Clinical Immunology (BSACI).2 The EAACI/GA2LEN/EDF/WAO guidelines are a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA2LEN) (a European Union‐funded network of excellence), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO). To standardize responses, all participants were presented with a case of recalcitrant CSU (failed on maximum dose of nonsedating antihistamines and montelukast), requiring alternative systemic treatment. Questions covered usage of systemic treatments, routine disease severity assessments, adherence to treatment guidelines and perceived barriers to prescribing. Responses (Table 1) were received from 19 UK consultants (26 surveys sent; completion rate 73%), 15 of whom had > 10 years’ experience in the treatment of CSU. The majority were allergy (58%) and dermatology consultants (37%). Of the 19 consultants, 56% provide a dedicated urticaria service, 37% treat both adult and paediatric patients, and the majority (79%) use systemic medications other than antihistamines and montelukast. Omalizumab and ciclosporin were the most commonly used first‐line agents (47% and 27% respectively) (Fig. 1). The majority (84%) of consultants use validated measures to assess disease severity, including the weekly Urticaria Activity Score (UAS‐7, 63%), the Physician Global Assessment (63%), the Patient Global Assessment (44%) and the Dermatology Quality of Life Index (DLQI) (38%). Guidelines are used by 89% to direct their management of CSU, with 50% using the EAACI/GA2LEN/EDF/WAO guideline,1 compared with 31% primarily using the BSACI guideline.2 The main perceived barriers to prescribing systemic medications were potential adverse effects (AEs) (32% strongly agreed), potential long‐term toxicity (26% strongly agreed), cost of treatment (42% strongly agreed), and views expressed by the patient and their family (37% agreed)

Hypothalamic control of food intake in cats and monkeys

The role of the central nervous system in regulating food intake was probably suggested first by the discovery that either obesity or emaciation may occur in patients with nervous diseases. For a while these observations were not properly evaluated, because emphasis was laid upon the obesity as such, or the leanness, rather than upon the changed eating habits responsible for the clinical picture. Interest was focused on the hypothalamic region by the experimental studies of many workers (Hetherington, 1941; Hetherington & Ranson, 1940, 1942 a, b; Brobeck, Tepperman & Long, 1943; Kennedy, 1950; Ranson, Fisher & Ingram, 1938) who showed that bilateral lesions in the medial hypothalamus, especially lesions in or ventro-lateral to the ventromedial nucleus, resulted in obesity. The confusion introduced by the notion that pituitary disturbances caused obesity was also clarified by Hetherington (1943), who showed that the hypophysis is in no way directly concerned with the pathogenesis of obesity following injury to the base of brain. Brobeck et al. (1943) demonstrated that this hypothalamic obesity was due to increased food intake (hypothalamic hyperphagia) rather than to disturbances in the fat, carbohydrate or intermediary metabolism. From the time of its discovery this hyperphagia was assumed to be a release phenomenon brought about through the destruction of an inhibitory mechanism.The existence of another mechanism in the lateral hypothalamus of the rat, which controls the 'instinct' or the 'urge' to eat, was demonstrated by Anand & Brobeck (1951 a, b). They showed that bilateral destruction of a well localized area in the lateral hypothalamus, at the same rostro-caudal level as the ventro-medial nucleus, produces complete aphagia and death due to starvation, in spite of the availability of food. It was also observed that of the two mechanisms the lateral one exerts the more basic type of control over food intake and the medial one (inhibitory) produces its effects only when the lateral is intact. The lateral mechanism is designated a 'feeding centre', or even an 'appetite centre', while the medial one is called a 'satiety centre'. Joliffe named the two, together, the 'appestat'. The present study was undertaken to determine, whether similar mechanisms exist in the hypothalamic regions of higher mammals, cats and monkeys, and also whether they are modified by the more highly evolved higher nervous centres

Influence of annealing conditions on the optical and structural properties of spin-coated As_2S_3 chalcogenide glass thin films

Spin-coating of chalcogenide glass is a low-cost, scalable method to create optical grade thin films, which are ideal for visible and infrared applications. In this paper, we study the influence of annealing on optical parameters of As_2S_3 films by examining UV-visible and infrared spectroscopy and correlating the results to changes in the physical properties associated with solvent removal. Evaporation of excess solvent results in a more highly coordinated, denser glass network with higher index and lower absorption. Depending on the annealing temperature and time, index values ranging from n = 2.1 to the bulk value (n = 2.4) can be obtained, enabling a pathway to materials optimization

Efektivitas Penggunaan Aplikasi Wordwall dalam Pembelajaran IPS Secara Daring (Online) di Kelas Tinggi Sekolah Dasar

Situasi pandemi Covid-19 mengubah pembelajaran tatap muka di kelas menjadi pembelajaran daring (online). Media pembelajaran online yang menjamin keutuhan kegiatan pembelajaran serta mengangkat motivasi dan fokus peserta didik adalah aplikasi Wordwall. Masalah penelitian adalah ‘Bagaimana efektivitas penggunaan media wordwall pada kegiatan pembelajaran IPS secara daring di kelas tinggi SD?”, Penelitian bertujuan melihat efektivitas penggunaan media wordwall pada kegiatan pembelajaran IPS secara daring di kelas tinggi SD. Penelitian ini adalah jenis Mixed Method. Analisis data menggunakan analisis kuantitatif pada angket dan tes, analisis kualitatif pada wawancara. Subjek penelitian adalah peserta didik  kelas tinggi SDK Canosa. Hasil penelitian menunjukan rata-rata kelas hasil belajar IPS peserta didik  kelas tinggi adalah sebesar  79.99. Ditinjau dari KKM 70, maka diketahui 55 dari 58 (94.83%) orang peserta didik  tuntas, 3 orang (5.20%) tidak tuntas. Angket menunjukkan tingkat capaian responden (peserta didik ) sebesar 91.90% atau sangat efektif, hasil wawancara kepala sekolah dan guru mengindikasikan peserta didik  terlibat secara aktif dalam pembelajaran dan antusias mengerjakan kuis-kuis, menggabungkan kata, menemukan kata, dan melakukan game

Comparison of hierarchical temporal memories and artificial neural networks under noisy data

The ability of two different machine learning approaches to map non-linear problems from experimental data is evaluated under controlled experiments. A well-known machine learning algorithm (Artificial Neural Network) is compared against a new computing paradigm (Hierarchical Temporal Memory) under a controlled scenario. The chosen scenario is the detection of impacts in a cantilever beam under vibration instrumented with fiber Bragg gratings. The main characteristics of both of the machine learning approaches are analyzed while varying environmental parameters such as the number of sensing points and their location. From the achieved results some clues can be extracted regarding dealing with noisy or partial data using different machine learning approaches

Comparative transcriptional profiling of the limbal epithelial crypt demonstrates its putative stem cell niche characteristics

<p>Abstract</p> <p>Background</p> <p>The Limbal epithelial crypt (LEC) is a solid cord of cells, approximately 120 microns long. It arises from the undersurface of interpalisade rete ridges of the limbal palisades of Vogt and extends deeper into the limbal stroma parallel or perpendicular to the palisade. There are up to 6 or 7 such LEC, variably distributed along the limbus in each human eye.</p> <p>Morphological and immunohistochemical studies on the limbal epithelial crypt (LEC) have demonstrated the presence of limbal stem cells in this region. The purpose of this microarray study was to characterise the transcriptional profile of the LEC and compare with other ocular surface epithelial regions to support our hypothesis that LEC preferentially harbours stem cells (SC).</p> <p>Results</p> <p>LEC was found to be enriched for SC related Gene Ontology (GO) terms including those identified in quiescent adult SC, however similar to cornea, limbus had significant GO terms related to proliferating SC, transient amplifying cells (TAC) and differentiated cells (DC). LEC and limbus were metabolically dormant with low protein synthesis and downregulated cell cycling. Cornea had upregulated genes for cell cycling and self renewal such as <it>FZD7, BTG1, CCNG</it>, and <it>STAT3 </it>which were identified from other SC populations. Upregulated gene expression for growth factors, cytokines, WNT, Notch, TGF-Beta pathways involved in cell proliferation and differentiation were noted in cornea. LEC had highest number of expressed sequence tags (ESTs), downregulated and unknown genes, compared to other regions. Genes expressed in LEC such as <it>CDH1, SERPINF1, LEF1, FRZB1</it>, <it>KRT19, SOD2, EGR1 </it>are known to be involved in SC maintenance. Genes of interest, in LEC belonging to the category of cell adhesion molecules, WNT and Notch signalling pathway were validated with real-time PCR and immunofluorescence.</p> <p>Conclusions</p> <p>Our transcriptional profiling study identifies the LEC as a preferential site for limbal SC with some characteristics suggesting that it could function as a 'SC niche' supporting quiescent SC. It also strengthens the evidence for the presence of "transient cells" in the corneal epithelium. These cells are immediate progeny of SC with self-renewal capacity and could be responsible for maintaining epithelial turn over in normal healthy conditions of the ocular surface (OS). The limbus has mixed population of differentiated and undifferentiated cells.</p

Non-Markovian polymer reaction kinetics

Describing the kinetics of polymer reactions, such as the formation of loops and hairpins in nucleic acids or polypeptides, is complicated by the structural dynamics of their chains. Although both intramolecular reactions, such as cyclization, and intermolecular reactions have been studied extensively, both experimentally and theoretically, there is to date no exact explicit analytical treatment of transport-limited polymer reaction kinetics, even in the case of the simplest (Rouse) model of monomers connected by linear springs. We introduce a new analytical approach to calculate the mean reaction time of polymer reactions that encompasses the non-Markovian dynamics of monomer motion. This requires that the conformational statistics of the polymer at the very instant of reaction be determined, which provides, as a by-product, new information on the reaction path. We show that the typical reactive conformation of the polymer is more extended than the equilibrium conformation, which leads to reaction times significantly shorter than predicted by the existing classical Markovian theory.Comment: Main text (7 pages, 5 figures) + Supplemantary Information (13 pages, 2 figures

"Practical Knowledge" and Perceptions of Antibiotics and Antibiotic Resistance Among Drugsellers in Tanzanian Private Drugstores.

Studies indicate that antibiotics are sold against regulation and without prescription in private drugstores in rural Tanzania. The objective of the study was to explore and describe antibiotics sale and dispensing practices and link it to drugseller knowledge and perceptions of antibiotics and antibiotic resistance. Exit customers of private drugstores in eight districts were interviewed about the drugstore encounter and drugs bought. Drugsellers filled in a questionnaire with closed- and open-ended questions about antibiotics and resistance. Data were analyzed using mixed quantitative and qualitative methods. Of 350 interviewed exit customers, 24% had bought antibiotics. Thirty percent had seen a health worker before coming and almost all of these had a prescription. Antibiotics were dispensed mainly for cough, stomachache, genital complaints and diarrhea but not for malaria or headache. Dispensed drugs were assessed as relevant for the symptoms or disease presented in 83% of all cases and 51% for antibiotics specifically. Non-prescribed drugs were assessed as more relevant than the prescribed. The knowledge level of the drugseller was ranked as high or very high by 75% of the respondents. Seventy-five drugsellers from three districts participated. Seventy-nine percent stated that diseases caused by bacteria can be treated with antibiotics but 24% of these also said that antibiotics can be used for treating viral disease. Most (85%) said that STI can be treated with antibiotics while 1% said the same about headache, 4% general weakness and 3% 'all diseases'. Seventy-two percent had heard of antibiotic resistance. When describing what an antibiotic is, the respondents used six different kinds of keywords. Descriptions of what antibiotic resistance is and how it occurs were quite rational from a biomedical point of view with some exceptions. They gave rise to five categories and one theme: Perceiving antibiotic resistance based on practical experience. The drugsellers have considerable "practical knowledge" of antibiotics and a perception of antibiotic resistance based on practical experience. In the process of upgrading private drugstores and formalizing the sale of antibiotics from these outlets in resource-constrained settings, their "practical knowledge" as well as their perceptions must be taken into account in order to attain rational dispensing practices

Three dimensional porous scaffolds derived from collagen, elastin and fibrin proteins orchestrate adipose tissue regeneration

Current gold standard to treat soft tissue injuries caused by trauma and pathological condition are autografts and off the shelf fillers, but they have inherent weaknesses like donor site morbidity, immuno-compatibility and graft failure. To overcome these limitations, tissue-engineered polymers are seeded with stem cells to improve the potential to restore tissue function. However, their interaction with native tissue is poorly understood so far. To study these interactions and improve outcomes, we have fabricated scaffolds from natural polymers (collagen, fibrin and elastin) by custom-designed processes and their material properties such as surface morphology, swelling, wettability and chemical cross-linking ability were characterised. By using 3D scaffolds, we comprehensive assessed survival, proliferation and phenotype of adipose-derived stem cells in vitro. In vivo, scaffolds were seeded with adipose-derived stem cells and implanted in a rodent model, with X-ray microtomography, histology and immunohistochemistry as read-outs. Collagen-based materials showed higher cell adhesion and proliferation in vitro as well as higher adipogenic properties in vivo. In contrast, fibrin demonstrated poor cellular and adipogenesis properties but higher angiogenesis. Elastin formed the most porous scaffold, with cells displaying a non-aggregated morphology in vitro while in vivo elastin was the most degraded scaffold. These findings of how polymers present in the natural polymers mimicking ECM and seeded with stem cells affect adipogenesis in vitro and in vivo can open avenues to design 3D grafts for soft tissue repair