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Background and objectives: Evaluation of patients included in the registry of biological/targeted therapy BIOREP in the Czech Republic. Methods: A retrospective evaluation of patients to date 31 December 2023 enrolled in the BIOREP registry was performed. The aim of our study was to evaluate patients on biological/targeted treatment in the given period in individual categories and to analyze the population of patients with psoriasis, hidradenitis suppurativa and atopic dermatitis. In the case of categorical variables, the results were expressed using number and percentage. Continuous variables were described using count, mean, standard deviation, median, minimum, and maximum Results: As of 31 December 2023, a total of 6,676 patients were registered in the BIOREP registry: 4,763 (71.3%) patients with psoriasis, 538 (8.1%) with hidradenitis, 1,346 (20.2%) with atopic dermatitis and 29 (0.4%) were treated off label with targeted treatment. Of the psoriasis group, 62.5% of patients were men. The average patient age at the end of 2023 was 52.3 years, the mean age at the time of diagnosis was 25.6 years, and the age at first biological/targeted treatment was 46.4 years. In 2023, the average time from diagnosis to the introduction of targeted treatment was 20.8 years, the average duration of biological/targeted treatment was 5.2 years. The comorbidities occurred in 70.6% of patients. The most common disorder were metabolic/endocrine diseases (39.2%) and cardiovascular diseases (37.8%). From the individual comorbidities, hypertension (35.2%), dyslipidemia (26.5%) and diabetes mellitus (12.5%) were the most common. A total of 76.1% of patients were overweight or obese and 33% of patients were smokers. Psoriatic arthritis was observed in 30.8% of patients. At the start of treatment and at the last visit, the mean PASI was 18.6 and 1.8, respectively, the mean BSA 29% and 2.5%, respectively and DLQI 16.1 and 1.6, respectively. After 12 months of treatment, a total of 91.8%; 82.6%; 64.7% and 40.8% of patients achieved PASI50, PASI75, PASI90 and PASI100, respectively. In 2023, a total of 645 patients newly started treatment and at the end of year 2023, a total of 4.120 patients were treated, the most patients used Skyrizi (15.7%), Humira (12.1%) and Cosentyx (12%). As of 31 December 2023, there were a total of 538 patients with hidradenitis suppurativa in the registry of mean age 44.5 years and 55.4% were men. The mean age at the time of diagnosis was 32.7 years and the age at first biological treatment was 41,7 years. The average time from diagnosis to the start of the biological treatment was 9 years and patients were treated for an average of 2.7 years. In 2023, a total of 85 patients started the biological treatment. At the end of 2023, a total of 422 patients were treated and the average duration of treatment was 2.4 years, the most common medication was Humira (67.8%). At the end of 2023, there were a total of 1,346 patients with atopic dermatitis in the registry of mean age 36.2 years, 51% were men. The mean age at the time of diagnosis was 5.2 years and the age at first targeted treatment was 34.9 years. The average time from diagnosis to the start of the targeted treatment was 29.8 years and patients were treated for an average of 1.7 years. A total of 60.1% of patients had concomitant allergic rhinitis, 54.8% food allergy and 42.1% allergic asthma. Ocular comorbidities occurred in 23.6% of patients, the most common were atopic conjunctivitis (12.2%). At the start of treatment and at the last visit, the mean EASI was 30.8 and 4.1, respectively, mean BSA was 56% and 8%, respectively, and mean DLQI 18.2 and 3.7 respectively. In 2023, a total of 496 patients started the biological treatment. At the end of 2023, a total of 1,239 patients were treated and the average duration of treatment was 1.6 years, the most common medication was Dupixent (81%). Conclusion: The analysis confirmed the high activity of diseases according to objective evaluation and the significant negative impact on the quality of life before initiation of targeted treatment, with a decrease in the evaluated scores during treatment. At the same time, it demonstrates a high prevalence of comorbidities and risk factors and a long diseases duration before the introduction of targeted treatment. [ABSTRACT FROM AUTHOR]

Copyright of Czecho-Slovak Dermatology / Cesko-Slovenska Dermatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Czecho-Slovak Dermatology / Cesko-Slovenska Dermatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Czecho-Slovak Dermatology / Cesko-Slovenska Dermatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and objectives: The evaluation of patients with atopic dermatitis in the BIOREP registry in the Czech Republic. Methods: A retrospective evaluation of patients with atopic dermatitis treated with dupilumab enrolled in the BIOREP registry was performed to date 21st May 2021. Results: A total of 219 patients with atopic dermatitis were registered in the BIOREP registry, 53.9% were men and 46.1% were women. The average patient age was 39.5 years and 38.4 years at the start of biological treatment. The mean time from diagnosis to the initiation of biological treatment was 33.8 years. The most common comorbidities were allergic rhinitis in 67.1% of patients, food allergies in 56.6% and allergic asthma in 53.0% of patients. Eye involvement was observed in 29.2% of patients. From the other evaluated comorbidities, at least one occurred in more than half of the analyzed patients (53.4%), the most common disorders were metabolic/endocrine (19.6%), cardiovascular (15.1%), and psychiatric diseases (6.8%). At the start of treatment, the mean EASI was 33.2 and DLQI was 19.2. Patients are treated with dupilumab for an average of 10.3 months. The 50% improvement in EASI was achieved by 95.7% of patients after 3 months of treatment, 98.3% after 6 months and 100% after 12 and 18 months of treatment. At the same time, the 75% improvement in EASI was achieved by 68.3%; 93.4%; 93.8% and 97.0% of patients, respectively. During the treatment there was a significant improvement in the quality of life of patients, after 3 months of treatment the DLQI value decreased from the original 19.2 to 4.9. After 6 and 18 months of treatment, the value further decreased to 3.5 and 1.9 respectively. Conclusion: BIOREP, as one of the oldest registries for biological/targeted therapy in dermatology, included patients with atopic dermatitis (BIOREP-AD) in 2020. The presented data complete the lacking information from real clinical practice and confirm the long duration of atopic dermatitis with the negative impact on a quality of life, the frequent association with comorbidities, the long period of previous insufficient treatment and the successful use of dupilumab. [ABSTRACT FROM AUTHOR]

Objective: Evaluation of the effectiveness of biological treatment of psoriasis according to the achievement of PASI 75, 90 and 100 in each group of biologics. Methods: A retrospective evaluation of patients diagnosed with plaque psoriasis from the BIOREP registry, who were treated with anti-TNF, anti-IL-12/23, anti-IL-17, or anti-IL-23 drugs during the registry follow-up period was performed. Results: The total study population of 2,873 patients included 1,832 males (63.8%) and 1,041 females (36.2%). The mean age at the time of diagnosis was 24.8 ± 13.5 years, the mean age at the time of initiation of the first biologic was 46.0 ± 13.0 years. The average time from the diagnosis of psoriasis to the first biological therapy was 21.2 ± 12.1 years. Psoriatic arthritis was diagnosed in 1,008 (35.1%) patients, 70.7% of patients had at least one comorbidity and 72.9% of patients with overweight or obese. A total of 4,938 treatment series were recorded in the evaluated patients; anti-TNF (2,961 series, 60.0%), anti-IL-12/23 (626 series, 12.7%), anti-IL-17 (1,008 series, 20.4%) and anti-IL-23 (343 series, 6.9%). After 3–4 months of treatment, PASI 75 was achieved in 64.9% of cases, PASI 90 in 42.5% of cases and PASI 100 in 23.4% of cases with a further increase at 6 months (PASI 75, 90 and 100 in 76,9%, 55.6% and 32.7%, respectively) and maintaining response until 24 months of treatment. The higher achievement of PASI75/90/100 was in the group treated with anti-IL-17 and anti-IL-23 even with a faster response rate compared to anti-TNF and anti IL-12/23. A higher achievement of PASI75/90/100 was observed in naive patients (with no previous biological treatment). Conclusion: The analysis of the BIOREP registry confirmed data from registries of other countries as well as meta-analyzes of clinical studies. Although anti-TNF drugs have made significant advances in the treatment of psoriasis and adalimumab is still the most widely used drug, newer molecules provide higher efficacy. Our analysis demonstrates a significant response in all PASI categories as well as a faster response to anti-IL-23 and anti-IL-17 drugs compared to older groups of biologics. Early and effective treatment of severe plaque psoriasis is important not only to improve quality of life and to reduce the risk of comorbidities, but also to achieve the highest response and the consequent long-term persistence on the treatment. [ABSTRACT FROM AUTHOR]

Background and objectives: Evaluation of patients included in the registry of biological/targeted therapy BIOREP in the Czech Republic in 2020. Methods: A retrospective evaluation of patients enrolled in the BIOREP registry to date 31 December 2020 was performed. The objects of our study were patients on biological/targeted treatment in the given period in each category and the evaluation of the population of patients with psoriasis and hidradenitis. Results: As of 31 December 2020, a total of 3121 patients were registered in the BIOREP registry: 2870 (92.0%) patients with psoriasis, 243 (7.8%) with hidradenitis and 8 (0.3%) treated with off label treatment. In the psoriasis group, 63.6% of patients were men. The average age of patients at the end of 2020 was 51.8 years, the mean age at the time of diagnosis was 24.8 years, and the age at the time of first biological/targeted treatment was 46.1 years. In 2020, the average time from diagnosis to the introduction of biological treatment was 21.4 years, the average duration of biological/targeted treatment was 5.4 years. Comorbidities occurred in 72.2% of patients, mostly metabolic/endocrine diseases (53.8%) and cardiovascular diseases (53.2%), more specifically hypertension (50.6%), dyslipidemia (38.6%) and diabetes mellitus (13.3%) were the most common. More than 75% of patients were overweight or obese and 31.6% of patients were smokers. Psoriatic arthritis was observed in 35.1% of patients. At the start of the treatment and at the last visit, the mean PASI was 18.8 and 3.0, respectively and DLQI 16.4 and 2.4 respectively. In 2020, a total of 366 patients newly started treatment. As of 31 December 2020, there were 243 patients with hidradenitis suppurativa in the registry, 52.3% were men and the mean age was 45 years. The mean age at the time of diagnosis was 34.2 years and the age at the time of the initiation of the first biological treatment was 43.2 years. The average time from diagnosis to the start of the biological treatment was 9.0 years and patients were treated for an average of 2.1 years. In 2020, a total of 52 patients started the biological treatment. At the end of 2020, a total of 206 patients were treated and the average duration of treatment with one medication was 2.2 years. Conclusion: BIOREP is the first registry of patients for biological treatment of psoriasis in Central and Eastern Europe. The results, when compared to European registries, show a comparable or higher prevalence of co-morbidities and risk factors and a long period of inadequate treatment before initiating biologic therapy. [ABSTRACT FROM AUTHOR]

Copyright of Czecho-Slovak Dermatology / Cesko-Slovenska Dermatologie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The aim of the study was to establish and compare the model of the biodegradability and ecotoxicological properties of oil samples in aqueous environment.The unused new mineral oil Turbinol and used (after 1 year of usage) recovered oil Turbinol purified by the electrostatical method were the tested samples. For the determination of the ecotoxicological properties, the test organisms used were seeds of Sinapis alba L. and the small aquatic crustaceans Daphnia magna. Preliminary tests were positive and determined the acute toxicity with the values of IC50 and EC50. Biodegradability was determined by the manometric method, in tests which lasted 28 days. Tests of toxicity were positive, and the samples were found to be hard to biodegrade. Determination of the oil composition by gas chromatography with mass detection (GC - MS); found that the composition of the electrostatically cleaned oil is comparable to the new oil, which is confirmed by the results obtained with the response inhibition in selected tests. Regeneration extends the oil life, reducing the cost of disposal of waste oils, saving fossil raw materials, thus belonging to the environmentally friendly techniques. [ABSTRACT FROM AUTHOR]

Nowadays, many countries worldwide have accepted laws to ban smoking in enclosed public places and workplaces, to protect no-smokes from the risk of passive smoking. These restrictions cannot protect children, the most vulnerable population, from their exposure at homes and private motor vehicles. The health risk for children is not only inhalation of the secondhand smoke, but also contacts with persisting thirdhand smoke and risks of domestic accidents (fires, burns, poisoning). Close relatives are also models to be imitated. The widespread movements invited smokers voluntary create smoke free homes and smoke-free cars were impulses to seek conditions for such approach in our society. Methods: The managers of two primary schools and one kindergarten were interested for the project Smoke-Free homes realization. Two informative brochures, leaflets for parents and stories for children, sticks for the determination of smoke-free rules were prepared as well as the oral presentation for parents. The anonymous questionnaire about children knowledge, attitudes and exposure to relatives´ smoking were filled in face-to-face discussion with trained medical students. Another questionnaire for parent included some similar questions. Results: Together 128 children aged 5-8 years (34 from kindergarten and 94 from the 2nd class of primary schools), and their parents were invited for the participation. Half of all children had smokers in their close relatives. Although the majority of children declared that smoking is not allowed in their homes, 25% of children are directly exposed to their relatives smoking. More than 95% of children do not like smoking, mainly due to the bad smell and irritation. They have appropriate knowledge about health risks of active and passive smoking. While almost 83% of children declare, they will not smoke in future, 17% are thinking about it; more of them live in smoking families. The responsive rate from parents was 60%; they were good educated (high schools/university). Almost 30% of them were smokers and 20% had smoking partners. Majority (82%) of parents claimed the rules for smoke-free environment at homes, including also smoking visitors. Despite of the good education, 20% did not admit the contribution of smoking to cancers (other than of lung), and 30% of parents do not understand the role of the bad model of smokers for their children. Nevertheless, they refused the discussion about these topics. Conclusion: The Czech society is not fully prepared to accept comprehensive approach to protect children against their exposure to passive smoking. It is necessary to state this topic as a politic priority. [ABSTRACT FROM AUTHOR]

The authors identify two nonstandard cases of medical staff, who were injured by contaminated, sharp objects. These cases are interesting in that neither staff member didn't have proof of vaccination against viral hepatitis B (VHB) or proof of positive serum antibodies against HBsAg (anti HBs). The authors deal with the concrete outcome of these two cases in relation to the epidemiology of viral hepatitis B. They are based on current legislation relating to occupational services, to system of epidemiological vigilance for selected infections, to vaccination against infectious diseases and public health and on guidelines for general practitioner in the Czech Republic. [ABSTRACT FROM AUTHOR]

Three cases of patients with severe chronic plaque psoriasis in whom classical systemic therapy failed or was discontinued due to side effects are described. After three months of ustekinumab administration more than a year-long remission was achieved in all cases. The therapy is tolerated well, followed laboratory tests are within normal range. Authors draw attention to the new biological agent in the treatment of severe plaque psoriasis. [ABSTRACT FROM AUTHOR]

Olfactory self-inspection has been observed in various mammals, including humans. This behaviour can help individuals to monitor own state, including health and hygiene. This study's aim was to explore the frequency of sniffing particular body parts and investigate possible gender differences. Further, we tested a possible function of this behaviour, namely monitoring health and hygiene, by investigating associations between the frequency of self-sniffing and health, hygiene, and disgust sensitivity. Respondents completed an online survey on self-sniffing behaviour, health status, hygiene habits, and disgust sensitivity. Self-sniffing behaviour was investigated using a purpose-built inventory which explored the incidence and frequency of sniffing different parts of own body. Principal Component Analysis identified three main axes of self-sniffing behaviour: Social acceptability self-inspection, Intimate self-inspection, and Cosmetic self-inspection. Our results further show that respondents with lower standards of hygienic habits engage significantly more in intimate self-inspection (sniffing body parts such as genitals, anus, or navel). Interestingly, individuals who reported more frequent health issues sniff more frequently areas such as the armpits, feet, or own breath (Social acceptability self-inspection), probably to check for possible changes in smell due to illness. Our results indicate that olfactory self-inspection probably has several functions depending on the location from which the smell originates., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Psoriasis is a chronic, immune-mediated inflammatory skin disease. Despite the availability of several therapies, many patients affected by this disease remain untreated, do not have adequate response, or suffer from treatment-related toxic effects. It has been shown that the interleukin (IL)-17 pathway plays a key role in the immunopathogenesis of psoriasis. Brodalumab, the first human monoclonal IgG2 antibody that selectively binds to subunit A of the human IL-17 receptor, blocking interactions with a number of cytokines of the IL-17 family, has confirmed fast onset of action, high complete clearance rates, and sustained efficacy. Nevertheless, there is only a limited amount of published real-world evidence (RWE) data., Methods: This was an open-label, multicenter, real-world, prospective, non-interventional, non-controlled (single-arm) observational study (LIBERO-CZ) assessing the management of moderate to severe psoriasis with brodalumab in daily practice for up to 52 weeks of treatment., Results: Fifty-four patients (70.4% male, mean age 46.9 ± 13.4 years, weight 95.6 ± 22.7 kg, disease duration 18.6 ± 12.7 years) were enrolled and included in the final analysis. Forty-nine of the patients completed the study and five discontinued prematurely; 51.8% of all the enrolled patients were biologic-naïve. At baseline, 28% patients were classified as severe (psoriasis area severity index (PASI) ≥ 20). Overall, the mean PASI decreased by 15.6 from 16.1 (± 5.0) at baseline to 0.5 (± 1.2) at the last visit. The primary endpoint of an absolute PASI ≤ 3 at week 12 (as observed analysis) was achieved by 95.9% of patients. The static Physician's Global Assessment (sPGA) success (defined as clear = 0 and almost clear = 1) at week 52 was achieved by 92.1% of patients. PASI 75, PASI 90, and PASI 100 were achieved by 98.0%, 87.8%, and 75.5% of patients, respectively, after approximately 52 weeks of treatment. The study also recorded very positive results concerning patient-reported outcomes., Conclusions: LIBERO-CZ confirms the fast onset and high clearance rates of brodalumab in real life in both biologic-naïve and biologic-experienced patients., (© 2023. The Author(s).)

Several previous studies have shown that in mammals, the health status of conspecifics can be assessed based on perceptual cues. Olfactory, visual, or acoustic cues may lead to avoidant behavior, thus reducing the risk of contagion by close contact with infected individuals. We tested whether immune system activation after immunization leads to perceptible changes in body odor and facial and vocal attractiveness in humans. We have experimentally activated the immune system of male participants using vaccination against hepatitis A/B and meningococcus. Their body odor, facial photographs, and vocal recordings were collected before and 14 days after vaccination. Subsequently, the body odor samples, facial photographs, and vocal recordings were assessed by female raters for their attractiveness and healthiness. We have also measured skin coloration (from facial photographs and in vivo using a spectrophotometer), vocal parameters, and C-reactive protein (CRP) levels as a marker of inflammation. We found an increase in perceived body odor attractiveness, a decrease in facial attractiveness and healthiness, and no change in vocal attractiveness 14 days after vaccination compared to the prevaccination condition. Moreover, there was no change in facial coloration or vocal parameters between the prevaccination and postvaccination conditions. Prevaccination CRP levels were negatively associated with body odor and facial attractiveness and positively associated with body odor intensity. Overall, our results suggest that perceived body odor as well as facial but not vocal attractiveness may provide cues to activation of the immune response and that each modality may carry specific information about the individual's condition., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The behavioral immune system, with disgust as its motivational part, serves as the first line of defense in organisms' protection against pathogens. Laboratory studies indicate that disgust sensitivity adaptively adjusts to simulated environmental threat, but whether disgust levels similarly change in response to real-life threats, such as a pandemic, remains largely unknown. In a preregistered within-subject study, we tested whether the threat posed by the Covid-19 pandemic would lead to increased perceived disgust. The perception of threat was induced by testing during two phases of the Covid-19 pandemic (periods of high vs. low pathogen threat). We found heightened levels of moral disgust during a "wave" of the pandemic, but the effect was not observed in the domain of pathogen or sexual disgust. Moreover, the age of respondents and levels of trait anxiety were positively associated with pathogen and moral disgust, suggesting that variation in disgust sensitivity may be based chiefly on stable characteristics., (© 2023. The Author(s).)

Most cancer-related deaths among patients with solid tumors are caused by metastases. Migrastatic strategies represent a unique therapeutic approach to prevent all forms of cancer cell migration and invasion. Because the migration machinery has been shown to promote metastatic dissemination, successful migrastatic therapy may reduce the need for high-dose cytotoxic therapies that are currently used to prevent the risk of metastatic dissemination. In this review we focus on anti-invasive and antimetastatic strategies that hold promise for the treatment of solid tumors. The best targets for migrastatic therapy would be those that are required by all forms of motility, such as ATP availability, mitochondrial metabolism, and cytoskeletal dynamics and cell contractility., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous research has indicated that facial attractiveness may provide cues to the functioning of the immune system. Mating with individuals who have a more effective immune system could lead to a higher reproductive success. Our main aim was to test a possible association between immunoreactivity (stimulated by vaccination) and perceived facial attractiveness and healthiness. We experimentally activated the immune system of healthy men using vaccination against hepatitis A/B and meningococcus and measured levels of specific antibodies (markers of immune system reactivity) before and 30 days after the vaccination. Further, 1 day before the vaccination, we collected their facial photographs that were judged by females for attractiveness, healthiness, and facial skin patches for healthiness. In view of its proposed connection with the functioning of the immune system, we also measured skin colouration (both from the facial photographs and in vivo using a spectrophotometer) and we assessed its role in attractiveness and healthiness judgements. Moreover, we measured the levels of steroid hormones (testosterone and cortisol) and the percentage of adipose tissue, because both are known to have immunomodulatory properties and are related to perceived facial attractiveness and healthiness. We found no significant associations between antibody levels induced by vaccination and perceived facial attractiveness, facial healthiness, or skin healthiness. We also found no significant connections between steroid hormone levels, the amount of adipose tissue, rated characteristics, and antibody levels, except for a small negative effect of cortisol levels on perceived facial healthiness. Higher forehead redness was perceived as less attractive and less healthy and higher cheek patch redness was perceived as less healthy, but no significant association was found between antibody levels and facial colouration. Overall, our results suggest that perceived facial attractiveness, healthiness, and skin patch healthiness provide limited cues to immunoreactivity, and perceived characteristics seem to be related only to cortisol levels and facial colouration., (© 2022. The Author(s).)

Recent work has demonstrated that human body odour alters with changing emotional state and that emotionally laden odours can affect the physiology and behaviour of people exposed to them. Here we review these discoveries, which we believe add to a growing recognition that the human sense of smell and its potential role in social interactions have been underappreciated. However, we also critically evaluate the current evidence, with a particular focus on methodology and the interpretation of emotional odour studies. We argue that while the evidence convincingly indicates that humans retain a capacity for olfactory communication of emotion, the extent to which this occurs in ordinary social interaction remains an open question. Future studies should place fewer restrictions on participant selection and lifestyle and adopt more realistic experimental designs. We also need to devote more consideration to underlying mechanisms and to recognise the constraints that these may place on effective communication. Finally, we outline some promising approaches to address these issues, and raise some broader theoretical questions that such approaches may help us to answer., Competing Interests: Conflicts of Interest: SCR, JTF, AS, BL, PS, VT and JH declare none., (© The Author(s) 2022.)

Objectives: The aim of the study was to assess the effectiveness and safety of dupilumab therapy in patients with moderate-to-severe atopic dermatitis (AD) in a real-life Czech bicentric cohort., Methods: We retrospectively analysed 50 patients with moderate-to-severe AD treated with dupilumab in two centres in the Czech Republic. Baseline characteristics, the Eczema Area and Severity Index (EASI) score and Dermatology Life Quality Index (DLQI) were collected at baseline and each 3 following months. The proportion of patients achieving EASI50, EASI75, EASI90 and EASI100 were analysed. Levels of immunoglobulin E (IgE) were collected before and after 6 and 12 months of therapy. Adverse events were recorded as well., Results: Thirty-two men and 18 women with mean body mass index (BMI) of 25.7 were enrolled in our analysis. The mean age of the patients was 37.6 years and the mean time from diagnosis until the initiation of dupilumab therapy was 35.0 years. After 4 months, EASI75 was achieved by 75.7%, out of which 40.5% achieved EASI90 and 10.8% achieved complete clearance. Improvement continued with time, and the proportion of patients with EASI90 increased to 71.4% at the 6th month and at the 12th month of therapy the EASI90 was 65.2%. EASI100 was achieved by 14.3% and 13.0% at the 6th and 12th month, respectively. A marked reduction was observed in the DLQI and also in IgE levels. EASI responses were independent of BMI. No new safety issues were identified. Adverse events were experienced by 44% (22/50) of the patients and they were all mild in intensity. Conjunctivitis and herpes simplex virus infection were the most common adverse events., Conclusion: Our results confirmed the effectiveness and safety of dupilumab in a real-life setting in adult patients with moderate-to-severe AD in the Czech Republic. Dupilumab was well-tolerated and resulted in a significant clinical improvement in combination with improvement of quality of life.

Septins, a family of GTP-binding proteins that assemble into higher order structures, interface with the membrane, actin filaments and microtubules, and are thus important regulators of cytoarchitecture. Septin 9 (SEPT9), which is frequently overexpressed in tumors and mutated in hereditary neuralgic amyotrophy (HNA), mediates the binding of septins to microtubules, but the molecular determinants of this interaction remained uncertain. We demonstrate that a short microtubule-associated protein (MAP)-like motif unique to SEPT9 isoform 1 (SEPT9_i1) drives septin octamer-microtubule interaction in cells and in vitro reconstitutions. Septin-microtubule association requires polymerizable septin octamers harboring SEPT9_i1. Although outside of the MAP-like motif, HNA mutations abrogate this association, identifying a putative regulatory domain. Removal of this domain from SEPT9_i1 sequesters septins on microtubules, promotes microtubule stability and alters actomyosin fiber distribution and tension. Thus, we identify key molecular determinants and potential regulatory roles of septin-microtubule interaction, paving the way to deciphering the mechanisms underlying septin-associated pathologies. This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Previous studies have shown that women perceive male faces with a more reactive immune system as more attractive, but whether body odor might likewise provide cues to immune function has not been investigated yet. These two studies tested a possible relationship between body odor quality and immunoreactivity (Study 1) and immune system function (Study 2). In Study 1, we collected body odor samples from 21 men just before and two weeks after vaccination against hepatitis A/B and meningococcus. We determined the levels of specific antibodies (selected as markers of immune system's reactivity), testosterone, and cortisol. Subsequently, 88 female raters assessed the odor samples for their attractiveness, intensity, and healthiness. In Study 2, we collected body odor and blood samples from 35 men and women. We assessed key parameters of their innate and adaptive immunity, such as complement activity or total lymphocyte T and B counts and asked 95 raters to assess the odor samples for their attractiveness, intensity, and healthiness. In Study 1, we found no significant association between antibody levels induced by vaccination and perceived body odor attractiveness, intensity, and healthiness. We also found no significant relationship between antibody levels and steroid hormones (testosterone and cortisol). In Study 2, we likewise found no association between basal key parameters (innate and adaptive) of the immune system and body odor quality. Our results indicate that body odor may not serve as a cue to the reactivity of the immune system., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Pathogenic variants in the low density lipoprotein receptor gene are associated with familial hypercholesterolemia. Some of these variants can result in incorrect folding of the LDLR protein, which is then accumulated inside the cell and cannot fulfill its function to internalize LDL particles. We analyzed the functional impact of 10 LDLR variants localized in the beta-propeller of epidermal growth factor precursor homology domain. The experimental part of the work was complemented by a structural analysis on the basis of 3D LDLR protein structure. Methods: T-Rex Chinese hamster ovary cells transfected with the human LDLR gene were used for live cell imaging microscopy, flow cytometry, and qRT-PCR analysis. Results: Our results showed that the analyzed LDLR protein variants can be divided into three groups. (1) The variants buried inside the 3D protein structure expressing proteins accumulated in the endoplasmic reticulum (ER) with no or reduced plasma membrane localization and LDL particle internalization, and associated with an increased gene expression of ER-resident chaperones. (2) The variants localized on the surface of 3D protein structure with slightly reduced LDLR plasma membrane localization and LDL particle internalization, and associated with no increased mRNA level of ER-resident chaperones. (3) The variants localized on the surface of the 3D protein structure but expressing proteins with cell responses similar to the group 1. Conclusion: All analyzed LDLR variants have been evaluated as pathogenic but with different effects on protein localization and function, and expression of genes associated with ER stress., (Copyright © 2020 Dušková, Nohelová, Loja, Fialová, Zapletalová, Réblová, Tichý, Freiberger and Fajkusová.)

Dominance hierarchy is often established via repeated agonistic encounters where consistent winners are considered dominant. Human body odour contains cues to psychological dominance and competition, but it is not known whether competition outcome (a marker of a change in dominance hierarchy) affects the hedonic quality of human axillary odour. Therefore, we investigated the effect of winning and losing on odour quality. We collected odour samples from Mixed Martial Arts fighters approximately 1 h before and immediately after a match. Raters then assessed samples for pleasantness, attractiveness, masculinity and intensity. We also obtained data on donors' affective state and cortisol and testosterone levels, since these are known to be associated with competition and body odour quality. Perceived body odour pleasantness, attractiveness and intensity significantly decreased while masculinity increased after a match irrespective of the outcome. Nonetheless, losing a match affected the pleasantness of body odour more profoundly, though bordering formal level of significance. Moreover, a path analysis revealed that match loss led to a decrease in odour attractiveness, which was mediated by participants' negative affective states. Our study suggests that physical competition and to some extent also its outcome affect the perceived quality of human body odour in specific real-life settings, thus providing cues to dominance-related characteristics. This article is part of the Theo Murphy meeting issue 'Olfactory communication in humans'.

Mixed Martial Arts (MMA) is a multielement combat sport where fighters need to quickly react to an opponent's movements under fatigued conditions. Research indicates that fast reaction time is important in many sports, but the effect of fatigue has shown negative, null, or even positive influences on reaction time. However, few studies have been conducted in a controlled setting, especially using MMA figthers, whose matches are frequently resolved in a split-second. Therefore, this study investigated whether acute neuromuscular fatigue affects reaction and movement times, and their consistency in MMA fighters (N = 45). Before and after an upper-body Wingate test, a simple visual reaction time task was completed. Results showed a significant negative effect of fatigue on the reaction times and their consistency, with longer reactions (1.5% change) and lower consistency (14.7% change) after the Wingate test. Further, greater amounts of fatigue during the Wingate test seemed to negatively affect the consistency of post-Wingate movement time. Due to cumulative fatigue and the dynamic nature of MMA, our data indicate that not only the decrements in aerobic and anaerobic power likely affect a fighter's performance, but their reaction time and motor time may also be compromised during a fight., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.