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Cardiac and hepatic functionality are intertwined in a multifaceted relationship. Pathologic processes involving one may affect the other through a variety of mechanisms, including hemodynamic and membrane transport effects.To better understand the effect of extrahepatic cholestasis on regulations of membrane transporters involving digoxin and its implication for digoxin clearance.Twelve adult rats were included in this study; baseline hepatic and renal laboratory values and digoxin pharmacokinetic (PK) studies were established before evenly dividing them into two groups to undergo bile duct ligation (BDL) or a sham procedure. After 7 d repeat digoxin PK studies were completed and tissue samples were taken to determine the expressions of cell membrane transport proteins by quantitative western blot and real-time polymerase chain reaction. Data were analyzed using SigmaStat 3.5. Means between pre-surgery and post-surgery in the same experimental group were compared by pairedDigoxin clearance was decreased and liver function, but not renal function, was impaired in BDL rats. BDL resulted in significant up-regulation of multidrug resistance 1 expression in the liver and kidney and its down-regulation in the small intestine. Organic anion transporting polypeptides (OATP)1A4 was up-regulated in the liver but down-regulated in intestine after BDL. OATP4C1 expression was markedly increased in the kidney following BDL.The results suggest that cell membrane transporters of digoxin are regulated during extrahepatic cholestasis. These regulations are favorable for increasing digoxin excretion in the kidney and decreasing its absorption from the intestine to compensate for reduced digoxin clearance due to cholestasis.

The pathophysiology of atopic dermatitis (AD) is complex, multifactorial, and not fully understood. Genes encoding collagens, the most abundant proteins in the extracellular matrix (ECM), may play a potential role in the pathogenesis of AD. Our study aimed to estimate the associations between Col3A1/rs1800255, Col6A5 /29rs12488457, and Col8A1/rs13081855 polymorphisms and the occurrence, course, and features of AD in the Polish population. Blood samples were collected from 157 patients with AD and 111 healthy volunteers. The genotype distribution of the investigated collagens genes did not differ significantly between the AD and control subjects (p > 0.05). The AA genotype of Col3A1/rs1800255 was significantly associated with the occurrence of mild SCORAD (OR = 0.16; 95% Cl: 0.03–0.78; p = 0.02) and mild pruritus (OR = 18.5; 95% Cl: 3.48–98.40; p = 0.0006), while the GG genotype was significantly associated with severe SCORAD (OR = 6.6; 95% Cl: 1.23–32.35; p = 0.03). Regarding Col6A5/29rs12488457 polymorphism, the average SCORAD score was significantly lower in the group of patients with genotype AA than in patients with the AC genotype (39.8 vs. 53.4; p = 0.04). Nevertheless, both average SCORAD scores were high, and represent the moderate and severe grades of the diseases, respectively. The single nucleotide polymorphisms (SNPs) of COL3A1/ rs1800255 and Col6A5/29rs12488457 seem to be associated with AD courses and symptoms, suggesting new disease biomarkers. The modulation of collagens, the major component of the ECM, may serve as a therapeutic target of AD in the future.

Recent studies have indicated a key role of the impaired suppressive capacity of regulatory T cells (Tregs) in psoriasis (PsO) pathogenesis. However, the genetic background of Treg dysfunctions remains unknown. The aim of this study was to evaluate the association of PsO development with selected single nucleotide polymorphisms (SNPs) of genes in which protein products play a significant role in the regulation of differentiation and function of Tregs. There were three study groups in our research and each consisted of different unrelated patients and controls: 192 PsO patients and 5605 healthy volunteers in the microarray genotyping group, 150 PsO patients and 173 controls in the ARMS–PCR method group, and 6 PsO patients and 6 healthy volunteers in the expression analysis group. The DNA microarrays analysis (283 SNPs of 57 genes) and ARMS–PCR method (8 SNPs in 7 genes) were used to determine the frequency of occurrence of SNPs in selected genes. The mRNA expression of selected genes was determined in skin samples. There were statistically significant differences in the allele frequencies of four SNPs in three genes (TNF, IL12RB2, and IL12B) between early-onset PsO patients and controls. The lowest p-value was observed for rs3093662 (TNF), and the G allele carriers had a 2.73 times higher risk of developing early-onset PsO. Moreover, the study revealed significant differences in the frequency of SNPs and their influence on PsO development between early- and late-onset PsO. Based on the ARMS–PCR method, the association between some polymorphisms of four genes (IL4, IL10, TGFB1, and STAT3) and the risk of developing PsO was noticed. Psoriatic lesions were characterized with a lower mRNA expression of FOXP3, CTLA4, and IL2, and a higher expression of TNF and IL1A in comparison with unaffected skin. In conclusion, the genetic background associated with properly functioning Tregs seems to play a significant role in PsO pathogenesis and could have diagnostic value.

Background: The frequency of tattoos varies from 10% to 30% across the population worldwide. The growing popularity of tattooing increases the number of cutaneous reactions connected with this procedure. As we have not found any previous studies in the literature concerning tattoo complications in Poland and other Eastern European countries, we believe this to be the first study of this kind. Objective: The primary objective of this study was to evaluate the clinical spectrum of complications associated with the procedure of permanent tattooing among patients from Northern Poland. Methods: Medical data of 53 patients who developed tattoo-related cutaneous conditions were analyzed. All of the patients were consulted in the Dermatology, Venereology and Allergology Clinic in Gdańsk in the years 2018–2021. Medical history, dermatological assessment, and photographic documentation of skin lesions were performed in each case. Dermoscopic examination was carried out in 16 cases and 20 skin biopsies of the tattoo reactions were performed. Results: Twenty-one patients (40%) presented tattoo ink hypersensitivity reactions, out of which 18 were triggered by the red ink. In 11 cases (21%), contact dermatitis has developed after tattooing, while 9 of the patients (17%) presented tattoo infectious complications, including local bacterial infections, common warts, molluscum contagiosum, and demodicosis. We collected 8 cases (15%) of papulonodular reactions in black tattoos, and in 6 of them, histology showed granuloma formation. In 2 cases (4%), symptoms of anaphylaxis were observed after the tattooing procedure, and in another 2 cases (4%), Koebner phenomenon in the tattoo was diagnosed. Dermoscopy was the clue to the diagnosis in 4 cases. Conclusions: This is the first report presenting multiple cases of tattoo complications from Eastern Europe. The results of the study are consistent with other researches, showing a similar distribution of tattoo complications and that across the different pigments used, the red ink is most frequently responsible for tattoo reactions. We emphasize the usefulness of dermoscopic examination in the diagnosis of tattoo-related infections and draw the reader’s attention to the rare, yet hazardous complications connected with peri-tattooing anaphylaxis.

We present the case of a 3‐year‐old female liver transplant recipient with a history of Caroli disease who presented with positive severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) reverse transcription polymerase chain reaction (RT‐PCR) test and was ultimately diagnosed with multisystem inflammatory syndrome in children (MIS‐C) complicated by portal vein thrombosis. To the best of our knowledge, this is the first case report of MIS‐C in a pediatric solid organ transplant (SOT) recipient. Based on our patient, MIS‐C could be a potential complication of Coronavirus disease 2019 (COVID‐19) in SOT recipients and may have a negative outcome on transplant graft function., The authors present the outcome of multisystem inflammatory syndrome in a pediatric solid organ transplant recipient with SARS‐CoV‐2.

Tumour microenvironment has an important effect on the progression of cutaneous T-cell lymphomas. Using PCR with sequence-specific primers, this study analysed single-nucleotide polymorphisms in the interleukin-17 genes of 150 patients with cutaneous T-cell lymphoma. GG homozygote rs8193036 A/G of interleukin-17A gene occurred less commonly in the cutaneous T-cell lymphoma group; however, patients with this single-nucleotide polymorphism experience significantly intense pruritus. Conversely, the rs2397084 AG heterozygote of interleukin-17F is more common in the lymphoma population. In addition, there were significant differences in the frequencies of interleukin-17 genotypes when comparing early (Ia to IIa) and advanced stages (IIb, III and IV) of this neoplasms. A similar result has been shown in comparison between Sézary syndrome and mycosis fungoides. The current data may serve as a possible explanation for the increased bacterial infection rates in the course of cutaneous T-cell lymphoma, especially caused by Staphylococcus aureus. In summary, specific single-nucleotide polymorphisms occur with different frequencies between cutaneous T-cell lymphoma and healthy patients. Moreover, genetic predisposition of several interleukin-17 single-nucleotide polymorphisms may be a factor causing impaired immune defence in cutaneous lymphomas.

Extreme climatic events (ECEs) and predator removal represent some of the most widespread stressors to ecosystems. Though species interactions can alter ecological effects of climate change (and vice versa), it is less understood whether, when and how predator removal can interact with ECEs to exacerbate their effects. Understanding the circumstances under which such interactions might occur is critical because predator loss is widespread and ECEs can generate rapid phase shifts in ecosystems which can ultimately lead to tropicalization. Our goal was to determine whether loss of predation risk may be an important mechanism governing ecosystem responses to extreme events, and whether the effects of such events, such as tropicalization, can occur even when species range shifts do not. Specifically, our goal was to experimentally simulate the loss of an apex predator, the tiger shark Galeocerdo cuvier effects on a recently damaged seagrass ecosystem of Shark Bay, Australia by applying documented changes to risk-sensitive grazing of dugong Dugong dugon herbivores. Using a 16-month-field experiment established in recently disturbed seagrass meadows, we used previous estimates of risk-sensitive dugong foraging behaviour to simulate altered risk-sensitive foraging densities and strategies of dugongs consistent with apex predator loss, and tracked seagrass responses to the simulated grazing. Grazing treatments targeted and removed tropical seagrasses, which declined. However, like in other mixed-bed habitats where dugongs forage, treatments also incidentally accelerated temperate seagrass losses, revealing that herbivore behavioural changes in response to predator loss can exacerbate ECE and promote tropicalization, even without range expansions or introductions of novel species. Our results suggest that changes to herbivore behaviours triggered by loss of predation risk can undermine ecological resilience to ECEs, particularly where long-lived herbivores are abundant. By implication, ongoing losses of apex predators may combine with increasingly frequent ECEs to amplify climate change impacts across diverse ecosystems and large spatial scales.

The term mastocytosis refers to a heterogeneous group of disorders characterised by accumulation of clonal mast cells in different organs, most commonly in the skin. Little is known about the role of dermoscopy in the diagnostics of mastocytosis. To date, no systematic review on the dermoscopic features of cutaneous mastocytosis has been performed. The aim of this study was to summarise the current knowledge in the field as well as to identify the knowledge gaps to show possible directions for further studies, based on a systematic search of PubMed, Scopus, and Web of Science databases and related references published before 3 January 2022. Dermoscopic features, type of dermoscope, polarisation mode, magnification, and number of cases were analysed. In total, 16 articles were included in this review (3 case series and 13 case reports), analysing 148 patients with different variants of cutaneous mastocytosis; all of the studies analysed had a low level of evidence (V). The main dermoscopic features of urticaria pigmentosa included brown structureless areas, brown lines arranged in a network, and linear vessels distributed in a reticular pattern, with this last finding also being typical of telangiectasia macularis eruptiva perstans. The presence of either circumscribed yellow structureless areas or diffuse yellowish background was a constant pattern of mastocytoma, while nodular, pseudoangiomatous xanthelasmoid, and plaque-type mastocytosis were typified by light-brown structureless areas and/or pigment network, though the first two variants also showed yellow/yellow-orange structureless areas. Finally, pigmented streaks of radial distribution surrounding hair follicles were described to be a pathognomonic dermoscopic feature of pseudoxanthomatous mastocytosis. Although this review shows that the various clinical forms of cutaneous mastocytosis may feature diagnostic dermoscopic clues, it also underlines the need for further investigation as several relevant data are missing, including evaluation of dermoscopic pattern according to anatomical locations or “lesion age”, studies on rare mastocytosis variants, evaluation of the prognostic role of dermoscopy in the context of systemic involvement, and comparative analyses with common clinical mimickers.

There is evidence that the concomitance of psoriasis and obesity may originate from the interplay between multiple genetic pathways and involve gene–gene interactions. The aim of this study was to compare the genetic background related to obesity among psoriatic patients versus healthy controls by means of a Genome-Wide Association Study (GWAS). A total of 972 psoriatic patients and a total of 5878 healthy donors were enrolled in this study. DNA samples were genotyped for over 500,000 single nucleotide polymorphisms (SNPs) using Infinium CoreExome BeadChips (Illumina, San Diego, CA, USA). Statistical analysis identified eleven signals (p < 1 × 10−5) associated with BMI across the study groups and revealed a varying effect size in each sub-cohort. Seven of the alternative alleles (rs1558902 in the FTO gene, rs696574 in the CALCRL gene, as well as rs10968110, rs4551082, rs4609724, rs9320269, and rs2338833,) are associated with increased BMI among all psoriatic patients and four (rs1556519 in the ITLN2 gene, rs12972098 in the AC003006.7 gene, rs12676670 in the PAG1 gene, and rs1321529) are associated with lower BMI. The results of our study may lead to further insights into the understanding of the pathogenesis of obesity among psoriatic patients.

Background: Little is known about the correlation between lesion- and patient-related variables and the dermoscopic features of blue nevi. The aim of the study was dermoscopic analysis of blue nevi in association with patient- and lesion-related variables, with a special interest in structures whose prevalence has not been previously reported. Methods: This was a double-center, retrospective study, which included the analysis of histopathologically confirmed blue nevi (n = 93). Results: There was no difference in the frequency of the observed dermoscopic features according to patients’ gender and age. Pink structureless areas were more common in patients with I/II Fitzpatrick skin phototypes as well as in the patients with photodamaged skin, while blue prominent skin markings over brownish/blue-gray background occurred exclusively in patients with phototype III. Structures of previously unreported prevalence in blue nevi were skin-colored circles (present in 32.3%), gray circles (2.2%), follicular ostia with no pigmentation (18.4%; present exclusively on the face), blue skin markings over brownish background (present in 18.2%; detected only on the limbs) and dark brown polygons (one lesion located on the lower extremity). Conclusion: Dermoscopic presentation of blue nevi may vary according to the patient’s phototype and lesion size/localization rather than gender and age.

Introduction: There is growing evidence of the potential uses of dermoscopy in diagnostics of demodicosis. No previous studies have analyzed dermoscopic features in patients with ocular demodicosis. Objectives: To evaluate the potential usefulness of videodermoscopy in diagnostics of ocular demodicosis. Methods: It was a single-center prospective observational study in which results of videodermoscopic examination of the eyelids were compared to the results of classic microscopic examination in patients with suspected ocular demodicosis and healthy volunteers. Results: Study group included 16 women and 15 men. In fifteen (48.4%) patients, microbiological examination of epilated eyelashes was positive. The results of forms filled by the patients concerning known subjective clinical symptoms of ocular demodicosis revealed no significant differences between the group with positive and negative results of microscopic examination. The presence of Demodex tails and madarosis observed during dermoscopic assessment correlated positively with positive results of microscopic examination. At least one Demodex tail was found in 86.7% (13/15) cases with positive results of microscopic examination. In the two remaining cases microscopic evaluation showed the presence of Demodex brevis. In 37.5% (6/16) of patients with negative results of microscopic examination, videodermoscopy showed the presence of Demodex tails. Conclusions: Videodermoscopy may facilitate the diagnostics of ocular demodicosis. Patients reporting clinical symptoms suggesting ocular demodicosis but negative results of videodermoscopic examination should be referred to classical microscopic examination to exclude the presence of Demodex brevis. In patients with negative microscopic examination results and symptoms suggesting ocular demodicosis, dermoscopy-guided microscopic re-evaluation could be considered.

The epidemiology of psoriasis has not been widely assessed in Polish population so far. This study aimed to investigate psoriasis epidemiological situation by evaluating disease course and severity, management, comorbidities, environmental factors, and knowledge about this disorder among psoriatic patients in Poland. A cross-sectional cohort population-based study enrolled 1080 psoriatic patients and 1200 controls. The mean age of psoriasis onset was 27.6 years; 78.24% had type I psoriasis. Positive family history of psoriasis was reported in 44.81% of patients, whereas itch was reported in vast majority of patients (83.33%). Based on PASI score moderate psoriasis was the most common in studied group (mean 12.63 ± 9.33, range 0–67.2). The DLQI score (12.01 ± 7.41, range 0–30.0) indicated a very large effect of psoriasis on the quality of life. Hypertension was the most prevalent comorbidity (33.80%), followed by obesity (16.85%) and dyslipidemia (11.85%). Stress was the foremost cause of disease exacerbation (66.20%); however, infections (44.07%) and seasonal changes (45.09%) had also an impact on the course of psoriasis. Psoriatic patients were more often smokers (37.59%) vs. general population (27.50%; p < 0.0001). In conclusion, epidemiological studies help clinicians in better disease and patient understanding, which may translate into better management and patient compliance.

Psoriasis comorbidities may emerge from pleiotropic mechanisms, including common proinflammatory pathways, cellular mediators or genetic predisposition. Obesity is considered to be an independent risk factor of psoriasis, which may influence the severity of the disease and its early onset, decrease patients’ quality of life, alter response to psoriasis therapies and affect morbidity by reduced life expectancy due to cardiovascular events. Although novel approaches, including genetic techniques, have provided a wide range of new research, there are still scarce studies elaborating on the common genetic background of psoriasis and obesity. The aim of this study was to present and evaluate a possible common genetic background of psoriasis and concomitant increased body mass based on the review of the available literature.

Patrycja Rogowska,1 Paula Walczak,2 Karolina Wrzosek-Dobrzyniecka,2 Roman J Nowicki,1 Aneta Szczerkowska-Dobosz1 1Department of Dermatology, Venereology and Allergology, Faculty of Medicine, Medical University of Gda&nacute;sk, Gda&nacute;sk, Poland; 2Faculty of Medicine, Medical University of Gda&nacute;sk, Gda&nacute;sk, PolandCorrespondence: Patrycja Rogowska, Department of Dermatology, Venereology and Allergology, Faculty of Medicine Medical University of Gda&nacute;sk, Smoluchowskiego 17 Street, Gda&nacute;sk, 80-214, Poland, Tel +48585844014, Fax +48585844020, Email patrycja.rogowska@gumed.edu.plPurpose: Among populations of Western countries, tattoos have become an accepted form of skin ornamenting. With tattoos growing in popularity, also patients suffering from chronic dermatoses may more often be willing to get tattooed. Psoriasis is not considered as a strict contraindication for tattooing; however, it is not advised to get a tattoo while undergoing immunosuppressive treatment and during an active stage of the disease. We attempted to assess the knowledge level of tattooed psoriatic patients about the potential risks connected with tattooing, as well as to explore their attitudes and tendencies towards this procedure. Moreover, we analyzed the frequency and type of tattoo complications in this study group.Patients and Methods: An anonymous, online questionnaire was performed among online communities dedicated to psoriasis. Data from 150 tattooed psoriatic patients have been scrutinized.Results: Eight percent of the surveyed psoriatic patients sought medical advice before getting a tattoo. While undergoing the tattooing procedure, 23 (15.3%) of the respondents received systemic psoriasis treatment: 8 (5.3%) being treated with methotrexate, 5 (3.3%) with cyclosporine A, one (0.7%) acitretin, and 9 (6%) patients were under biological treatment. Thirteen (8.7%) of the participants experienced complications associated with their tattoos, among which, the insurgence of the Koebner phenomenon on the tattoo, was the most frequent one (8 cases- 5.3%). Getting tattooed improved patients’ self-esteem in 76 (50.7%) of the cases.Conclusion: An increased level of education among patients, medical practitioners, and tattooists concerning general precautions of tattooing in psoriasis is advisable.Keywords: tattoo, psoriasis, psoriasis therapy, immunosuppression, Koebner phenomenon

In this study, novel biosorbents, based on chitosan and imidazolium ionic liquid, were prepared for the removal of fluoride from aqueous solutions. The adsorbents were characterized by FTIR, SEM-EDS and low-temperature nitrogen adsorption-desorption. To investigate the adsorption mechanism and behavior of chitosan adsorbents, batch experiments were conducted under different adsorbent dosages (2, 4, 10 g/L), pH (4, 7, 9) and initial concentration (0.5-25.0 mg/L). The influence of the method of synthesis of ionic liquid on the adsorption performance were also studied. Experimental data were evaluated by Freundlich, Langmuir and Sips models. The introduction of ionic liquid significantly improved the uptake of fluoride compared to pure chitosan. The adsorption was influenced by the experimental conditions, as well as the method of ionic liquid synthesis. The highest fluoride removal was observed at pH 4 and found to decrease with increasing pH. The removal efficiency and adsorption capacity values indicated that the dose of 4 g/L was the optimum adsorbent dosage. The equilibrium data fitted best with the Sips isotherm and the maximum adsorption capacity reached 8.068 mg/g for modified chitosan beads. The mechanism of fluoride adsorption onto ionic liquid-modified chitosan involves electrostatic attraction, ion exchange and ion pair interaction.

Purpose To assess the expression of selected cytokines in penile lichen sclerosus (PLS) and associate them with the occurrence of micro-incontinence (MI) in different stages of PLS. Methods The skin biopsies from 49 PLS affected, and 13 from nonlesional foreskins (healthy control adult males undergoing circumcision due to phimosis caused by short frenulum) were obtained. All specimens were used for RNA extraction and RT-qPCR. Quantitative assessment of the gene expression of interleukin 1-A (IL-1A), interleukin 1-B (IL-1B), interleukin 1 receptor antagonist (IL-1RN), interleukin 6 (IL-6), transforming growth factor β1 (TGF-β1), and interferon-gamma (INF-γ) was performed. To determinate the presence of MI, the patients were asked about voiding patterns, especially leaking tiny drops of urine from the urethral meatus after urination. Results IL-1A, IL-6, and INF-γ mRNA levels were approximately 150, 16, and 59 times higher in PLS than in control samples, respectively. The highest IL-1A mRNA levels were observed in early PLS (n = 13), INF-γ in moderate PLS (n = 32), while IL-6 in severe PLS (n = 4). MI was noted in 45 PLS patients vs. 0 in control (p Conclusion Occlusion and irritating urine effect are associated with the clinical progression of penile LS with increased mRNA expression of IL-1A, INF-γ, and IL-6 pro-inflammatory cytokines in the foreskin.

Background The clinical presentation of acute lymphoblastic lymphoma is highly varied. While prognosis is good, recurrence of disease can occur. Gastrointestinal relapse, including intussusception, is well-described but the absence of abdominal pain in this setting is rare. Case summary We report a 13-year-old male with B-cell precursor acute lymphoblastic leukemia in remission presenting with anemia and weight loss. Examination was significant for absence of abdominal pain, but a stool sample was positive for occult blood. Pan-endoscopy was performed with colonoscopy revealing a mass filling the colonic lumen. Biopsy of the mass confirmed recurrence of recurrent B-cell lymphoma. Computed tomography scan revealed ileocolic intussusception resulting from the tumor. This case is unusual in that the patient had no abdominal pain despite the presence of intussusception. Conclusion While intestinal involvement with lymphoma has been well described in the literature, presentation as painless intussusception has not been reported. This case report highlights the wide spectrum of clinical manifestations of recurrent B-cell lymphoma involving the gastrointestinal tract, in particular the near absence of symptoms despite the finding of intussusception.

Treatment of nail psoriasis, a condition that often accompanies cutaneous and arthropatic psoriasis, is a challenge. Symptoms characteristic for the clinical presentation of nail plate are: oil drops, subungual hyperkeratosis, splinter haemorrhages and onycholysis. The most common symptom - pitting - may be observed within the matrix. It is also accompanied by nail crumbling, leukonychia and red spots in the lunula. Pharmacotherapy is often chronic, associated with side effects, and non-effective in many cases. Non-pharmacological treatments involve local effects of UV, IPL or laser beam. The efficacy of these methods is documented. In most cases they are not associated with adverse events encountered in systemic therapies. Treatment efficacy may be assessed using the NAPSI score, which allows monitoring the resolution of lesions during and after conclusion of treatment.

There is increasing recognition of the importance of rapid adaptation in the dynamics of populations and communities. While the effects of rapid adaptation on the stability of populations h...

Background The features of Shwachman-Diamond syndrome (SDS) include exocrine pancreatic insufficiency, skeletal abnormalities and bone marrow dysfunction; an often overlooked feature is hepatic involvement. Case summary We report a child who initially presented with failure to thrive and mildly elevated transaminase levels and was determined to have pancreatic insufficiency due to SDS. During follow-up he had persistently elevated transaminase levels and developed hepatosplenomegaly. An investigation was performed to determine the etiology of ongoing liver injury, including a liver biopsy which revealed hepatic cirrhosis. Conclusion Cirrhosis has rarely been reported with SDS. While many of the hepatic disorders associated with SDS improve with age, there are rare exceptions with serious implications for long-term outcome.

Emerging treatments for moderate-to-severe atopic dermatitis (AD) may provide greater and faster improvement in AD signs and symptoms than current therapies.To examine JADE COMPARE (NCT03720470) data using stringent efficacy end points.Adults with moderate-to-severe AD were randomly assigned 2:2:2:1 to receive oral abrocitinib 200 or 100 mg once daily, subcutaneous dupilumab 300 mg every 2 weeks (600-mg loading dose), or placebo, with medicated topical therapy for 16 weeks. Stringent response thresholds were applied for Eczema Area and Severity Index (EASI), Investigator's Global Assessment, Dermatology Life Quality Index, Peak Pruritus Numerical Rating Scale, and Night Time Itch Scale severity.At week 16, 48.9%, 38.0%, and 38.8% of the abrocitinib 200-mg, 100-mg, and dupilumab groups, respectively, achieved greater than or equal to 90% improvement from baseline in EASI versus 11.3% placebo; 14.9%, 12.6%, and 6.5% achieved Investigator's Global Assessment 0 (clear) versus 4.8% placebo; 29.7%, 21.6%, and 24.0% achieved Dermatology Life Quality Index 0/1 (no/minimal impact on quality of life) versus 10.6% placebo; and 57.1%, 44.5%, and 46.1% achieved Night Time Itch Scale severity 0/1 (no/minimal night-time itch) versus 31.9% placebo. Kaplan-Meier median time to greater than or equal to 90% improvement from baseline in EASI was 59, 113, and 114 days in the abrocitinib 200-mg, 100-mg, and dupilumab groups, respectively, and was not evaluable for placebo; median time to Peak Pruritus Numerical Rating Scale 0/1 (no/very minimal itch) was 86 and 116 days for abrocitinib 200-mg and dupilumab groups, respectively, and was not evaluable for abrocitinib 100-mg and placebo groups.A greater proportion of patients treated with abrocitinib than placebo had almost complete control of AD signs and symptoms.

Psoriasis (PsO) is a chronic, immune-mediated, inflammatory skin disease associated in most cases with pruritus. Chemokines seem to play a significant role in PsO pathogenesis. The aim of the study was to analyse serum concentrations of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, CCL17/TARC, CCL18/PARC, CCL22/MDC and CXCL8/IL-8, and their correlation with PsO severity and pruritus intensity. The study included 60 PsO patients and 40 healthy volunteers. Serum concentrations of six (CCL2/MCP-1, CCL3/MIP-1α, CCL5/RANTES, CCL17/TARC, CCL18/PARC and CCL22/MDC) out of eight analysed chemokines were significantly elevated in PsO patients; however, they did not correlate with disease severity. The serum level of CCL5/RANTES was significantly higher in patients with the psoriasis area and severity index (PASI) ≥ 15 (p = 0.01). The serum concentration of CCL17/TARC correlated positively with pruritus assessed using the visual analogue scale (VAS) (R = 0.47; p = 0.05). The study indicated CCL17/TARC as a potential biomarker of pruritus intensity in PsO patients. Chemokines appear to be involved in the development of PsO systemic inflammation. Further detailed studies on the interactions between chemokines, proinflammatory cytokines and immune system cells in PsO are required to search for new targeted therapies.

Giant molluscum contagiosum (MC) is a peculiar variant of the disease with the presence of multiple or single lesions larger than 5 mm. In contrast to typical molluscum contagiosum, dermoscopic features of giant lesions have been poorly described, and none of the reports included multiple giant lesions in an immunocompromised patient. We present a patient with acquired immunodeficiency syndrome diagnosed with multiple giant molluscum contagiosum along with the dermoscopic features of this entity. We examined a 40-year-old patient who had been diagnosed with acquired immunodeficiency syndrome (AIDS) two months earlier. The disease defining AIDS was cerebral toxoplasmosis (initially presenting as a brain tumor several months earlier). Laboratory investigation showed a decreased CD4 cell count of 11 cells/mm3 and HIV viral load of 252 472 copies/mL. The patient was referred to the Department of Dermatology due to multiple flesh-colored, asymptomatic nodules with superficial telangiectasia that had been observed on the face for several weeks (Figure 1, a). Dermoscopy of larger (5 mm) skin lesions showed yellowish globules of different size and random distribution, separated by smaller, oval-shape white globules and polymorphic vessels (Figure 1, b-d). Dermoscopy of smaller skin lesions showed the presence of a central yellow globule and white structureless area with irregular linear vessels of radial arrangement at the periphery (Figure 1, e). Histopathological examination confirmed the diagnosis of molluscum contagiosum (MC); special staining showed the details of the lesion (Figure 2, a-c). Antiretroviral therapy with Triumeq® (dolutegravir + abacavir + lamivudine) was initiated. After discussing MC treatment options with the patient, we decided to delay the treatment and wait for the effect of antiretroviral therapy. Partial regression of MC lesions was observed after 5 months; laboratory investigations showed a CD4 cell count of 99 cells/mm3 and a HIV viral load of 56 copies/mL. Along with continuation of antiretroviral therapy, the patient received treatment with topical imiquimod (Aldara®) for 12 weeks. Subsequently, a few lesions resistant to previous treatment were treated with cryosurgery and the patient was instructed to apply imiquimod only to new-onset/regrowing lesions. Clinical evaluation after 2 months revealed a good clinical and aesthetic effect (Figure 3). MC is a viral disease caused by a DNA virus of the Poxviridae family (MCV-1 or MCV-2). The infection most commonly affects children and sexually active adults, and may be diagnosed based on physical examination in the majority of cases. Typical clinical presentation includes single to multiple, 2-5 mm, flesh-colored, asymptomatic nodules with central umbilication. Dermoscopy is a non-invasive diagnostic method that allows skin examination with magnification, therefore improving the accuracy of dermatological diagnosis. It was primarily developed to detect melanoma, but in recent years the role of this method in general dermatology has been constantly increasing. There have been several published reports that demonstrated the utility of dermoscopy in the diagnosis of MC. Most commonly observed structures include a central orifice and blood vessels arranged in punctiform, radial or mixed flower pattern (1). Giant molluscum contagiosum is an atypical variant of the disease, with the presence of multiple or single lesions larger than 5 mm (2). The diagnosis of giant MC usually indicates immunodeficiency and has been mainly described in HIV-positive patients, but also in coexistence with leukemia, sarcoidosis, Wiskott-Aldrich syndrome, selective immunoglobulin M deficiency, atopic dermatitis, and after splenectomy, bone marrow transplantation, and during immunosuppressive therapy (3). Giant MC may mimic other benign or malignant dermatoses, and the final diagnosis is usually based on histopathological examination. The list of differential diagnoses is long and includes basal cell carcinoma, keratoacanthoma, viral wart, varicella, intradermal nevi, pyogenic granuloma, lichen planus, atypical mycobacterial infection, pneumocystosis, cutaneous cryptococcosis, and histoplasmosis (3). In contrast to typical MC, dermoscopic features of giant MC have been poorly described, and none of the reports included multiple lesions in immunocompromised patient. Mun et al. described a pattern of multiple shiny white clods in giant MC observed in a 2-year-old girl in the perianal area (4). A different dermoscopic image - with prominent arborizing vessels and polylobular white structureless areas - was reported by Uzuncakmak et al., who described giant MC on the eyelid in a 25-year-old woman (2). Similar dermoscopic features of atypical MC (5 mm in size) were described by Zaballos et. al. (5). The course and treatment of MC differ in immunocompetent and in immunocompromised individuals. While the infection is usually mild and self-limiting in the former group, in the latter it may be extensive, symptomatic, and resistant to therapy. Treatment methods commonly applied in immunocompetent patients such as cryotherapy, curettage, and electrocautery are not generally recommended in patients with severe immunodeficiency as they pose a risk of secondary infection or autoinoculation (6). Additionally, such treatment of multiple lesions is connected with pain and higher risk of postinflammatory changes/scarring (7). According to the literature, treatment with local immunomodulators - including imiquimod cream, interferon-a (IFN-a) injections and cidofovir - appears to be effective (6). Topical 5% imiquimod was most commonly used, and although not licensed for this indication it was shown to be effective in HIV-positive individuals, including treatment of giant MC lesions (7). Regardless of the topical treatment, previous reports documented a correlation between immunity status and the extension of MC lesions. Therefore, effective antiretroviral therapy may itself lead to resolution of MC [8]. To sum up, the presented report introduced additional observations into the dermoscopic spectrum of giant MC. The observed dermoscopically large yellowish globules seem to correspond with the crypts and the surrounding white structures with the areas of lobulated, endophytic epidermal hyperplasia. The presence of vascular structures in dermoscopy corresponds with the blood vessels tightly surrounding inverted hyperplastic epidermal lobules (Figure 2, b). Dermoscopic features od giant MC are different than those observed in small lesions. Interestingly, the dermoscopic appearance of smaller lesions observed in our patient seemed to be similar to MC eruptions described in immunocompetent patients (1). In case of clinical suspicion giant MC coexisting with smaller lesions, dermoscopic assessment of the latter may serve as a clue to diagnosis.

Rapid and widespread declines in coral health and abundance have driven increased investments in coral reef restoration interventions to jumpstart population recovery. Microfragmentation, an asexual propagation technique, is used to produce large numbers of corals for research and restoration. As part of resilience-based restoration, coral microfragments of different genotypes and species are exposed to various stressors to identify candidates for propagation. Growth rate is one of several important fitness-related traits commonly used in candidate selection, and being able to rapidly and accurately quantify growth rates of different genotypes is ideal for high-throughput stress tests. Additionally, it is crucial, as coral restoration becomes more commonplace, to establish practical guidelines and standardized methods of data collection that can be used across independent groups. Herein, we developed a streamlined workflow for growth rate quantification of live microfragmented corals using a structured-light 3D scanner to assess surface area (SA) measurements of live tissue over time. We then compared novel 3D and traditional 2D approaches to quantifying microfragment growth rates and assessed factors such as accuracy and speed. Compared to a more conventional 2D approach based on photography and ImageJ analysis, the 3D approach had comparable reliability, greater accuracy regarding absolute SA quantification, high repeatability, and low variability between scans. However, the 2D approach accurately measured growth and proved to be faster and cheaper, factors not trivial when attempting to upscale for restoration efforts. Nevertheless, the 3D approach has greater capacity for standardization across dissimilar studies, making it a better tool for restoration practitioners striving for consistent and comparable data across users, as well as for those conducting networked experiments, meta-analyses, and syntheses. Furthermore, 3D scanning has the capacity to provide more accurate surface area (SA) measurements for rugose, mounding, or complex colony shapes. This is the first protocol developed for using structured-light 3D scanning as a tool to measure growth rates of live microfragments. While each method has its advantages and disadvantages, disadvantages to a 3D approach based on speed and cost may diminish with time as interest and usage increase. As a resource for coral restoration practitioners and researchers, we provide a detailed 3D scanning protocol herein and discuss its potential limitations, applications, and future directions.

Global decline of coral reefs has led to a widespread adoption of asexual propagation techniques for coral restoration, whereby coral colonies are fragmented and allowed to re-grow before being returned to the reef. While this approach has become increasingly popular and successful, many questions remain regarding best practices to maximize restoration speed, efficiency, and survival. Two variables that may influence growth and survival of asexually fragmented colonies include coral genet and growth substrate. Here, we evaluate the effects of genet and substrate (commercially available ceramic vs. in-house made cement) on the survival and growth of 221 microfragments of elkhorn coral Acropora palmata over 193 days. All corals survived the experimental period, and doubled their initial size in 45 days, with an average growth of 545% over the study duration. Growth was generally linear, though the growth of some corals more closely matched logistic, logarithmic, or exponential curves. Both genet and substrate had significant effects on coral growth, though the two factors did not interact. Genet had a stronger influence on coral growth than substrate, with the fastest genet growing at 216% the rate of the slowest genet. Corals on cement substrate grew at 111.9% the rate of those grown on ceramic. This represents both a significant cost savings and elimination of logistical challenges to restoration practitioners, as the cement substrate ingredients are cheap and globally available. Our work shows that both genet and substrate should be considered when undertaking asexual restoration of Acropora palmata to maximize restoration speed and efficiency.

Giant condyloma acuminatum, also known as Buschke-Lowenstein tumor (BLT), is a rare disease of the anogenital region. BLT is considered a locally aggressive tumor of benign histological appearance, but with the potential for destructive growth and high recurrence rates. BLT development is strongly associated with infection with low-risk human papillomaviruses (HPVs), mostly HPV-6 and -11. Immunity to HPVs plays a crucial role in the natural control of various HPV-induced lesions. Large condyloma acuminata are frequently reported in patients with primary (e.g., DOCK8 or SPINK5 deficiencies) and secondary (e.g., AIDS, solid organ transplantation) immune defects. Individuals with extensive anogenital warts, including BLT in particular, should therefore be tested for inherited or acquired immunodeficiency. Research into the genetic basis of unexplained cases is warranted. An understanding of the etiology of BLT would lead to improvements in its management. This review focuses on the role of underlying HPV infections, and human genetic and immunological determinants of BLT.

The aim of this study was to analyze the impact of severe plastic deformation on 1.4462 duplex stainless steel (UNS 2205) subjected to hydrostatic extrusion (HE) and subsequent heat treatment at selected temperatures. The tests were conducted on a material deformed with a total strain of e = 3.8 after annealing in the temperature range of 400–800 °C. The characterization was carried out using transmission electron microscopy (TEM), optical microscopy, Vickers hardness and tensile testing. The results showed that the strength of the steel was a function of strain aging, grain growth and phase transformation. The highest Ultimate Tensile Strength measured in the experiment was nearly 2.1 GPa compared with 1.7 GPa for the cold-deformed material. The changes in the austenite and ferrite phases after annealing were different, resulting in a peculiar microstructure with a mix of very small and fragmented γ and σ phases and recrystallized α grains. This resulted in an increase in its strength and a bimodal structure. Overall the research has described in detail the interactions that are present in high alloy steel during the heat treatment process.