The Combination of Dupilumab with Other Monoclonal Antibodies

Introduction: Dupilumab is an interleukin-4 (IL-4) receptor alpha antagonist indicated for the treatment of moderate-to-severe atopic dermatitis (AD), which could be associated with atopic and non-atopic comorbidities for which concomitant administration of targeted pharmacotherapy including monoclonal antibodies could be required. However, the safety of combining dupilumab with other monoclonal antibodies for different therapeutic indication may be debated. Methods: We conducted an extensive search in MEDLINE via PubMed for original articles published from January 1, 2017 to October 22, 2022, reporting clinical cases in whic

Overview of Atopic Dermatitis in Different Ethnic Groups

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with a high prevalence worldwide, including countries from Asia, Africa, and Latin America, and in different ethnic groups. In recent years, more attention has been placed on the heterogeneity of AD associated with multiple factors, including a patient’s ethnic background, resulting in an increasing body of clinical, genetic, epidemiologic, and immune-phenotypic evidence that delineates differences in AD among racial groups. Filaggrin (FLG) mutations, the strongest genetic risk factor for the development of AD, are detected in up to 50% of European and 27% of Asian AD patients, but very rarely in Africans. Th2 hyperactivation is a common attribute of all ethnic groups, though the Asian endotype of AD is also characterized by an increased Th17-mediated signal, whereas African Americans show a strong Th2/Th22 signature and an absence of Th1/Th17 skewing. In addition, the ethnic heterogeneity of AD may hold important therapeutic implications as a patient’s genetic predisposition may affect treatment response and, thereby, a tailored strategy that better targets the dominant immunologic pathways in each ethnic subgroup may be envisaged. Nevertheless, white patients with AD represent the largest ethnicity enrolled and tested in clinical trials and the most treated in a real-world setting, limiting investigations about safety and efficacy across different ethnicities. The purpose of this review is to describe the heterogeneity in the pathophysiology of AD across ethnicities and its potential therapeutic implications

Advanced Glycation End Products are Increased in the Skin and Blood of Patients with Severe Psoriasis

Psoriasis is frequently associated with metabolic comorbidities. Advanced glycation end products (AGEs) are highly oxidant, biologically active compounds that accumulate in tissues in association with hyperglycaemia, hyperlipidaemia and oxidative stress. This is a cross-sectional case-control study involving 80 patients with mild/severe psoriasis and 80 controls matched for age, sex and body mass index (40 with severe eczema, 40 healthy individuals). Patients and healthy individuals with a smoking habit, diabetes, dyslipidaemia, hypercholesterolaemia, hypertension or who were under systemic treatment were excluded from the study. Skin AGEs were measured in normal-appearing skin by a standard fluorescence technique, and blood AGEs (total AGEs, pentosidine and AGEs receptor) by enzyme-linked immunosorbent assay. Levels of cutaneous AGEs (p < 0.04), serum AGEs (p < 0.03) and pentosidine (p < 0.05) were higher in patients with severe psoriasis. Cutaneous AGEs correlated well with serum AGEs (r = 0.93, p < 0.0001) and with Psoriasis Area and Severity Index score (r = 0.91, p < 0.0001). Receptor levels were lower (p < 0.001) in severe psoriasis, and inversely correlated with disease severity (r = –0.71, p < 0.0002). Patients with severe psoriasis have accumulation of skin and serum AGEs, independent of associated metabolic disorders

Easy preparation of liposome@pda microspheres for fast and highly efficient removal of methylene blue from water

Mussel-inspired chemistry was usefully exploited here with the aim of developing a high-efficiency, environmentally friendly material for water remediation. A micro-structured material based on polydopamine (PDA) was obtained by using liposomes as templating agents and was used for the first time as an adsorbent material for the removal of methylene blue (MB) dye from aqueous solutions. Phospholipid liposomes were made by extrusion and coated with PDA by self-polymerization of dopamine under simple and mild conditions. The obtained Liposome@PDA microspheres were characterized by DLS and Zeta potential analysis, TEM microscopy, and FTIR spectroscopy. The effects of pH, temperature, MB concentration, amount of Liposome@PDA, and contact time on the adsorption process were investigated. Results showed that the highest adsorption capacity was obtained in weakly alkaline conditions (pH = 8.0) and that it could reach up to 395.4 mg g−1 at 298 K. In addition, adsorption kinetics showed that the adsorption behavior fits a pseudo-second-order kinetic model well. The equilibrium adsorption data, instead, were well described by Langmuir isotherm. Thermodynamic analysis demonstrated that the adsorption process was endothermic and spontaneous (∆G0 = −12.55 kJ mol−1, ∆H0 = 13.37 kJ mol−1 ) in the investigated experimental conditions. Finally, the applicability of Liposome@PDA microspheres to model wastewater and the excellent reusability after regeneration by removing MB were demonstrated

Buccal mucosa is a promising graft in Peyronie's disease surgery. Our experience and a brief literature review on autologous grafting materials

AIM: Peyronie's Disease (PD) is an under reported acquired benign condition that, at the moment, is not curable with medical therapy. Surgery represent the gold standard of treatment. Surgical approaches are several and they consist in "plication techniques" or plaque incision/excision with grafting of resulting albuginea defect. Among grafting procedures, albuginea defect substitution with autologous materials demonstrated over the years not inferior results respect to heterologous grafts. Buccal mucosa graft (BMG) is not usually emphasized in many review articles and clinical series are yet limited. METHODS: We present our experience with seventeen plaque incision procedures and BMG in surgical correction of complex penile curvatures due to PD performed in a period of 30 months. Our analyses was focused on buccal mucosa graft characteristics as major determinant of the surgical success. We also conducted a brief literature review on autologous grafting materials used in reconstructive penile surgery for PD. RESULTS: Our cosmetics and functional results consists in a 100% of functional penile straightening with no relapses and 5,8% of de novo erectile dysfunction. Mean age was 56.4 years, mean follow-up of 22.5 (6-36) months. No complications graft related were observed. Operative time was 115.3 minutes in mean. Over 94% of patients referred they were "really much better" and "much better" satisfied based on PGI-I questionnaire administrated at the last follow- up visit. CONCLUSION: BMG is revealing as an optimal choice for reconstructive surgery in PD. Anatomical characteristics consisting in the great elasticity, the quick integration time and the easy harvesting technique lead to high cosmetics and functional success rate, without omitting economical and invasiveness aspects

Valorization of chestnut shells for hydrogen production by Clostridium butyricum fermentation

Chestnut shell s (CS) is an agronomic waste generated from the peeling process of the chestnut fruit. It is well-known that the extract of CS contains high amounts of tannins, which are polyphenolic antioxidants1, but this agronomic residue also contains about 36% sugars in form of polysaccharides, and no utilization of chestnut shells as potential source of fermentable sugars has been considered so far. As consequence, this waste represents an interesting exploitable source for monosaccharides production, and in this study we evaluated the potential of biohydrogen production from CS hydrolyzate

Calibration and performance tests of the Very-Front-End electronics for the CMS electromagnetic calorimeter

The Very-Front-End electronics processing signals from photodetectors of the CMS electromagnetic calorimeter have been put through an extensive test programme to guarantee functionality and reliability. The final characteristics of the VFE boards designed for the calorimeter barrel and endcaps are presented. The results, which have been also verified during test beam at CERN, confirm the high quality of the boards production and show that the CMS detector specifications are reached

Expression and Function of Neurotrophins and Their Receptors in Cultured Human Keratinocytes

Whereas nerve growth factor has been extensively studied in human keratinocytes, little is known on the role of other members of the neurotrophin family. We investigated the expression and function of neurotrophins and neurotrophin receptors in cultured human keratinocytes. We demonstrated by reverse transcription–polymerase chain reaction that keratinocytes synthesize neurotrophin-3, brain-derived neurotrophic factor, and neurotrophin-4/5. These cells also express tyrosinase kinase A and C, the nerve growth factor and neuro-trophin-3 high-affinity receptors, respectively. On the other hand, only the truncated extracellular isoform of tyrosinase kinase B, the high-affinity brain-derived neurotrophic factor and neurotrophin-4/5 receptor, is detected in keratinocytes. Moreover, neurotrophin-3, brain-derived neurotrophic factor, and neurotrophin-4/5 proteins are secreted by human keratinocytes at low levels. Keratinocyte stem cells synthesize the highest amounts of nerve growth factor, while they secrete higher levels of nerve growth factor as compared with transit amplifying cells. Neurotrophin-3 stimulates keratinocyte proliferation, where brain-derived neurotrophic factor or neurotrophin-4/5 does not exert any effect on keratinocyte proliferation. Addition of neurotrophin-3 slightly upregulates the secretion of nerve growth factor, whereas nerve growth factor strongly augments neurotrophin-3 release. Ultraviolet B irradiation downregulates nerve growth factor, whereas it augments neurotrophin-3 and neurotrophin-4/5 protein levels. Ultraviolet A irradiation increases the level of neurotrophin-3, whereas it does not exert any effect on the other neurotrophins. Finally, neurotrophins other than nerve growth factor fail to protect human keratinocytes from ultraviolet B-induced apoptosis. This work delineates a functional neurotrophin network, which may contribute to epidermal homeostasis

Early MicroRNA expression profile as a prognostic biomarker for the development of pelvic inflammatory disease in a mouse model of chlamydial genital infection

It is not currently possible to predict the probability of whether a woman with a chlamydial genital infection will develop pelvic inflammatory disease (PID). To determine if specific biomarkers may be associated with distinct chlamydial pathotypes, we utilized two Chlamydia muridarum variants (C. muridarum Var001 [CmVar001] and CmVar004) that differ in their abilities to elicit upper genital tract pathology in a mouse model. CmVar004 has a lower growth rate in vitro and induces pathology in only 20% of C57BL/6 mouse oviducts versus 83.3% of oviducts in CmVar001-infected mice. To determine if chemokine and cytokine production within 24 h of infection is associated with the outcome of pathology, levels of 15 chemokines and cytokines were measured. CmVar004 infection induced significantly lower levels of CXCL1, CXCL2, tumor necrosis factor alpha (TNF-α), and CCL2 in comparison to CmVar001 infection with similar rRNA (rs16) levels for Chlamydiae. A combination of microRNA (miRNA) sequencing and quantitative real-time PCR (qRT-PCR) analysis of 134 inflammation-related miRNAs was performed 24 h postinfection to determine if the chemokine/cytokine responses would also be reflected in miRNA expression profiles. Interestingly, 12 miRNAs (miR-135a-5p, miR298-5p, miR142-3p, miR223-3p, miR299a-3p, miR147-3p, miR105, miR325-3p, miR132-3p, miR142-5p, miR155-5p, and miR-410-3p) were overexpressed during CmVar004 infection compared to CmVar001 infection, inversely correlating with the respective chemokine/cytokine responses. To our knowledge, this is the first report demonstrating that early biomarkers elicited in the host can differentiate between two pathological variants of chlamydiae and be predictive of upper tract disease. © 2014 Yeruva et al