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Abstract Background Microglial cell iron load and inflammatory activation are significant hallmarks of late-stage Alzheimer’s disease (AD). In vitro, microglia preferentially upregulate the iron importer, divalent metal transporter 1 (DMT1, gene name Slc11a2) in response to inflammatory stimuli, and excess iron can augment cellular inflammation, suggesting a feed-forward loop between iron import mechanisms and inflammatory signaling. However, it is not understood whether microglial iron import mechanisms directly contribute to inflammatory signaling and chronic disease in vivo. These studies determined the effects of microglial-specific knockdown of Slc11a2 on AD-related cognitive decline and microglial transcriptional phenotype. Methods In vitro experiments and RT-qPCR were used to assess a role for DMT1 in amyloid-β-associated inflammation. To determine the effects of microglial Slc11a2 knockdown on AD-related phenotypes in vivo, triple-transgenic Cx3cr1 Cre−ERT2 ;Slc11a2 flfl ;APP/PS1 +or – mice were generated and administered corn oil or tamoxifen to induce knockdown at 5–6 months of age. Both sexes underwent behavioral analyses to assess cognition and memory (12–15 months of age). Hippocampal CD11b+ microglia were magnetically isolated from female mice (15–17 months) and bulk RNA-sequencing analysis was conducted. Results DMT1 inhibition in vitro robustly decreased Aβ-induced inflammatory gene expression and cellular iron levels in conditions of excess iron. In vivo, Slc11a2 KD APP/PS1 female, but not male, mice displayed a significant worsening of memory function in Morris water maze and a fear conditioning assay, along with significant hyperactivity compared to control WT and APP/PS1 mice. Hippocampal microglia from Slc11a2 KD APP/PS1 females displayed significant increases in Enpp2, Ttr, and the iron-export gene, Slc40a1, compared to control APP/PS1 cells. Slc11a2 KD cells from APP/PS1 females also exhibited decreased expression of markers associated with subsets of disease-associated microglia (DAMs), such as Apoe, Ctsb, Ly9, Csf1, and Hif1α. Conclusions This work suggests a sex-specific role for microglial iron import gene Slc11a2 in propagating behavioral and cognitive phenotypes in the APP/PS1 model of AD. These data also highlight an association between loss of a DAM-like phenotype in microglia and cognitive deficits in Slc11a2 KD APP/PS1 female mice. Overall, this work illuminates an iron-related pathway in microglia that may serve a protective role during disease and offers insight into mechanisms behind disease-related sex differences.

The U.S. population has suffered worse health consequences owing to COVID-19 than comparable wealthy nations. COVID-19 had caused more than 1.1 million deaths in the U.S. as of May 2023 and contributed to a 3-year decline in life expectancy. A coalition of public health workers and community activists launched an external review of the Centers for Disease Control and Prevention's pandemic management from January 2021 to May 2023. The authors used a modified Delphi process to identify core pandemic management areas, which formed the basis for a survey and literature review. Their analysis yields 3 overarching shortcomings of the Centers for Disease Control and Prevention's pandemic management: (1) Centers for Disease Control and Prevention leadership downplays the serious impacts and aerosol transmission risks of COVID-19, (2) Centers for Disease Control and Prevention leadership has aligned public guidance with commercial and political interests over scientific evidence, and (3) Centers for Disease Control and Prevention guidance focuses on individual choice rather than emphasizing prevention and equity. Instead, the agency must partner with communities most impacted by the pandemic and encourage people to protect one another using layered protections to decrease COVID-19 transmission. Because emerging variants can already evade existing vaccines and treatments and Long COVID can be disabling and lacks definitive treatment, multifaceted, sustainable approaches to the COVID-19 pandemic are essential to protect people, the economy, and future generations.

Introduction The COVID-19 outbreak had significant implications worldwide, including mental health. Consultations in the Emergency Service of the Hospital Clínic of Barcelona varied in terms of reasons for consultations, psychopathology, and other aspects, before and during the pandemic. Objectives This study aims to assess differences in the profile of patients admitted within the last three years to the Psychiatric Emergency Service of a third-level hospital, in order to analyze variations in the number of patients visited, diagnoses and admissions throughout the different seasons. Methods All adults admitted from 2019 to 2021 to the Psychiatric Emergency Service of Hospital Clínic of Barcelona, Spain, were retrospectively included for analysis and divided into three groups depending on the year they attended the Emergency Service. SPSS v25.0 and R statistics were used in order to compare differences between groups. Results A total of 13677 adult individuals who attended the psychiatric emergency service of Hospital Clínic of Barcelona between 2019 and 2021 were included in the analysis. 4814 patients were visited in 2019, 4007 in 2020 and 4856 in 2021. The majority of patients were male (50.1%), with a mean age of 40.47 years (SD 15.83). In terms of acute admission rates, 24.6% of the total sample were hospitalized in an acute psychiatric unit, whereas in the spring of 2020, 34.3% of patients attending the Emergency Service were hospitalized. This revealed significant differences when compared with spring of 2019 and 2021 and with the rest of seasons (p

Abstract  Goal of this study was to investigate whether appropriately applied spa therapy in several indications could be associated with a subsequent fall in the need for costly health services and missed working days due to sick-leave. The Naiade project was a multicenter observational, longitudinal, questionnaire-based study comparing an “entry” inquiry addressed to patients before an entry thermal cycle, and a “return” inquiry after 1 year. Routine statistical methods were used for comparisons. The study was carried out in 297 of the 340 certified Italian spa centers. Inquiries were managed by the spa doctor(s), with the collaboration of family doctors, and when necessary, hospitals, other health services, labour offices and employers. After exclusion of regular customers and of patients with acute disease phases or severe health conditions, 39,943 patients divided into eight diseases subgroups (rheumatic, respiratory, dermatologic, gynaecologic, otorhynologic, urinary, vascular and gastroenteric) underwent entry inquiry and appropriate spa treatment. Patients who returned for treatment after 1 year (“index year”) were 23,680 (59.2%) and received return inquiry. Outcomes considered were: frequency and duration of hospitalisation periods; missed working days; regular use of disease-specific drugs; and resort to “non-spa” rehabilitation therapies. The data collected at return inquiry were compared with those of entry inquiry. All the considered outcomes appeared to be significantly reduced in the index year in seven of the eight disease subgroups in comparison with the previous year. In conclusion, disease-appropriate spa treatments were followed by a reduction in the need of subsequent health interventions in most disease subgroups. The health promoting value of spa treatments should therefore undergo more rigorous assessment with randomised controlled studies. [ABSTRACT FROM AUTHOR]

Introduction: Guselkumab, a human monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23), has shown efficacy in psoriasis and psoriatic arthritis. However, long-term real-world data on its effectiveness in patients with inadequate response to ustekinumab are limited. This study investigates guselkumab's long-term effectiveness and safety in patients with psoriasis with partial response to ustekinumab., Methods: We performed a retrospective multicentric study analyzing data of patients with psoriasis from seven Italian hospitals between January 2021 and May 2024. The study included 169 patients who switched from ustekinumab to guselkumab. Primary endpoints were Psoriasis Area and Severity Index (PASI) 75, PASI 90, PASI 100, and absolute PASI ≤ 2. Site-specific Physician Global Assessment (PGA) scores were also collected for difficult-to-treat areas., Results: The study included 169 patients. After 3 years of treatment, PASI 75, PASI 90 and PASI 100 were achieved by 88.4%, 55.8%, and 32.6% of patients, respectively. Site-specific PGA showed significant improvements, especially in the scalp and genital areas. After 3 years of treatment, no significant impact of higher body mass index (BMI) or cardiometabolic comorbidities on guselkumab effectiveness was detected. No severe adverse events were reported during the study period., Conclusions: In our study, guselkumab provided significant long-term effectiveness and safety in patients partially responsive to ustekinumab, improving both PASI score and site-specific PGA and confirming its potential use for patients with psoriasis switching from ustekinumab., Competing Interests: Declarations Conflict of Interest Mario Valenti has been a consultant and/or speaker for Sanofi, Leo Pharma, Eli Lilly, Novartis, Janssen, UCB-Pharma, Difa-Cooper, Almirall, AbbVie and Boehringer Ingelheim. Luciano Ibba has been a consultant for Almirall. Piergiorgio Malagoli has been a speaker for AbbVie, Lilly, Novartis, Janssen-Cilag, Celgene, Leopharma, and Almirall. Andrea Carugno has been speaker and/or consultant for Almirall, Amgen, Abbvie, Boehringer-Ingelheim, Eli-Lilly, Leopharma, Jansse-Cilag, Novartis, UCB Pharma. Francesca M. Gaiani acted as a speaker or consultant for Novartis, Abbvie, Eli Lilly, Celgene, LeoPharma, and Almirall. Carlo G. Carrera has served as a board participant or speaker for Abbvie, Lilly, Janssen, Novartis, Celgene, Almirall, and Leopharma. Angelo V. Marzano reports consultancy/advisory boards disease-relevant honoraria from AbbVie, Boehringer-Ingelheim, Novartis, Pfizer, Sanofi and UCB. Antonio Costanzo has been a consultant and/or speaker for Abb-Vie, Almirall, Amgen, Janssen, Leo Pharma, Eli Lilly, Galderma, Boehringer, Novartis, Pfizer, Sandoz, and UCB. Alessandra Narcisi has served on advisory boards, received honoraria for lectures and research grants from Almirall, Abbvie, Leo Pharma, Celgene, Eli Lilly, Janssen, Novartis, Sanofi‐Genzyme, Amgen and Boehringer Ingelheim. Davide Strippoli has been a consultant and/or speaker for Abbvie, Celgene, Janssen, Eli Lilly, Novartis, Pfizer. Marco Campoli, Nicola Zerbinati, Ruggero Cascio Ingurgio and Federica Mola, have nothing to declare. Ethical Approval Institutional review board approval was exempted as the study protocol did not deviate from standard clinical practice. All patients received ixekizumab as part of routine clinical practice in accordance with European guidelines. All included patients had provided written consent for retrospective study of data collected during routine clinical practice (demographics, clinical scores). The study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments. Data collection and handling complied with applicable laws, regulations, and guidance regarding patient protection, including patient privacy., (© 2024. The Author(s).)

Background: Tirbanibulin 1% ointment is approved for the field treatment of Olsen grade I actinic keratoses (AKs) of the face and scalp., Methods: We performed a multicenter retrospective study involving 15 dermatologic units in Italy to investigate the efficacy and tolerability of tirbanibulin in a real-life setting. 250 patients were enrolled. Tirbanibulin, 1% ointment, was applied daily for five consecutive days. The efficacy of treatment was measured with modifications of the Actinic Keratosis Area and Severity Index (AKASI). A satisfactory response was defined by complete (100% reduction in the number of lesions) or partial clearance (75-99%) of treated AKs., Results: Overall, the AKASI score was significantly reduced in the studied population (mean, from 4.1 ± 2.7 to 1.4 ± 1.5; P < 0.001). A satisfactory response was observed in 222 (88.8%) cases. The proportion of satisfactory responses was higher when follow-up was performed after 8 weeks (34/35, 97.1%). The reduction in AKASI was significant in patients with Olsen grade II or III lesions (from 5.3 ± 2.8 to 1.6 ± 1.6; P < 0.001). A satisfactory response was observed in 91/104 (87.5%) cases. AKASI reduction was also significant in patients with trunk or limb AKs (from 7.0 ± 1.3 to 2.0 ± 1.6; P = 0.018) since a satisfactory response was observed in 7/8 (87.5%) cases. Tirbanibulin was well tolerated; all adverse events (AEs) included transient local reactions at the site of treatment. Overall, 231 patients had at least one AE. Only 7 (2.8%) grade 4 AEs were recorded., Conclusion: Our retrospective study confirmed that tirbanibulin 1% ointment is effective and well tolerated in a real-life setting and is also promising for Olsen grade II and grade III AKs and AKs localized on difficult-to-treat areas., (© 2024 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

The definition of paradoxical psoriasis (PP) encompasses 2 main scenarios, namely, (i) new-onset psoriasis in patients treated for a different disease and (ii) worsening as well as phenotypical change of pre-existing psoriasis. Originally restricted to the appearance of an untoward psoriasiform reaction under TNF inhibitors, the term has gained new meaning, with the progressive observation of psoriasis-like eruptions also with other medications. Although the conceptual framework of PP has expanded, a molecular and clinicotherapeutic classification is still lacking. In addition, a certain degree of confusion surrounds the correct terminology to indicate these eruptions. In this paper, evidence on the epidemiology, clinical features, pathogenesis, and treatment of PP is reviewed, providing a perspective on possible pathogenesis-driven therapeutic approaches., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In recent years, the capabilities of Large Language Models (LLMs), such as ChatGPT, to imitate human behavioral patterns have been attracting growing interest from experimental psychology. Although ChatGPT can successfully generate accurate theoretical and inferential information in several fields, its ability to exhibit a Theory of Mind (ToM) is a topic of debate and interest in literature. Impairments in ToM are considered responsible for social difficulties in many clinical conditions, such as Autism Spectrum Disorder (ASD). Some studies showed that ChatGPT can successfully pass classical ToM tasks, however, the response style used by LLMs to solve advanced ToM tasks, comparing their abilities with those of typical development (TD) individuals and clinical populations, has not been explored. In this preliminary study, we administered the Advanced ToM Test and the Emotion Attribution Task to ChatGPT 3.5 and ChatGPT-4 and compared their responses with those of an ASD and TD group. Our results showed that the two LLMs had higher accuracy in understanding mental states, although ChatGPT-3.5 failed with more complex mental states. In understanding emotional states, ChatGPT-3.5 performed significantly worse than TDs but did not differ from ASDs, showing difficulty with negative emotions. ChatGPT-4 achieved higher accuracy, but difficulties with recognizing sadness and anger persisted. The style adopted by both LLMs appeared verbose, and repetitive, tending to violate Grice's maxims. This conversational style seems similar to that adopted by high-functioning ASDs. Clinical implications and potential applications are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Attanasio, Mazza, Le Donne, Masedu, Greco and Valenti.)

Background: Melanoma is currently the most prevalent malignant neoplasm among adults and represents the second most common cancer in both sexes among individuals aged 0 to 39 years. This retrospective multicenter study delves into the distinctive clinical, anamnestic, histopathologic, and prognostic attributes of melanoma in Adolescent and Young Adults (AYA), defined as patients diagnosed at ≤40 years, across four Italian centers. Methods: Through a computer-based review of clinical records from 1 January 2010 to 30 September 2023, AYA melanomas were contrasted with non-AYA melanomas (>40 years) among 1452 patients. Data on demographics, melanoma localization, histological type, Breslow thickness, ulceration, and sentinel lymph node (SLN) biopsy status were meticulously collected and analyzed. Results: Our analysis revealed a female predominance in the AYA group and a male predominance in the non-AYA group, with significant differences in anatomical localization and histological types between the two. AYA melanomas showed nearly equal trunk and limb involvement, contrasting with the trunk predominance in non-AYA melanomas. While Breslow thickness was similar across both groups, the presence of ulceration and total number of nevi showed no significant difference. Survival analysis indicated a marginally higher Disease-Free Survival (DFS) in AYA patients compared to non-AYA patients, without a significant difference in Overall Survival (OS). Conclusions: This study highlights demographic and clinical distinctions between AYA and non-AYA melanoma patients, underscoring the need for tailored follow-up and treatment strategies. Despite these insights, the heterogeneity of melanoma among young adults calls for further research, including genetic analyses, to fully understand this unique melanoma subgroup. Indeed, AYA melanoma patients could represent a different and specific target for both follow-up and treatments.

Background/Objectives : The purposes of the present study were to assess gait by using a novel approach that plots two adjacent joint angles and the postural control in individuals with autism (ASD) and individuals with typical neurodevelopmental (TD). Methods : The surface electromyography (sEMG) activity was measured synchronously with the other variables. Twenty young adult men, 10 with TD and 10 with a diagnosis of ASD, took part in this study. Results: There was a significant difference between ASD and TD groups in the area described by the knee-ankle diagram ( p < 0.05). The sEMG activity recorded from the lateral gastrocnemius (LG) during the contact phase of gait was significantly lower in the ASD group compared with the TD group ( p < 0.05). The sEMG activity recorded in the different postural conditions showed differences in LG and tibialis anterior (TA) between the ASD and TD groups ( p < 0.05). Conclusions : The knee-ankle diagram provided a sensitive and specific movement descriptor to differentiate individuals with ASD from individuals with TD. The reduced LG activation is responsible for the reduced area in the knee-ankle diagram and 'toe-walking' in individuals with ASD and represents the common denominator of an altered ankle strategy during locomotion and postural control.

Introduction/aims: Laboratory and clinical data suggest a link between neurologically mediated inflammation and psoriasis, but the risk and features of peripheral neuropathy in psoriasis or psoriatic arthritis remain unknown. The aim of this exploratory study was to evaluate the risk and to describe the features of peripheral neuropathy in patients with psoriasis and psoriatic arthritis., Methods: One hundred patients with psoriasis and/or psoriatic arthritis and 100 control subjects were consecutively enrolled. Diagnostic confirmation included electrophysiological examination, skin biopsy, and nerve ultrasound for confirmed polyneuropathy., Results: Nine patients were diagnosed with confirmed polyneuropathy, while none of the control subjects had the condition (relative risk [RR] = 19.00, 95% confidence interval [CI] = 1.12-322.11). Specific relative risks for polyneuropathy were 22.09 (95% CI = 1.17-416.43) in psoriasis patients and 18.75 (95% CI = 1.07-327.62) in psoriatic arthritis patients. The observed polyneuropathy in all nine patients was length-dependent, symmetrical, and predominantly sensory, with minimal or no disability. Comorbidities and exposure to therapies known to increase the risk of polyneuropathy were more frequent in psoriasis and/or psoriatic arthritis patients compared to controls (42% vs. 4%, p = .0001). Analyzing data after excluding possible contributory causes, the risk of polyneuropathy in patients with psoriasis and/or psoriatic arthritis was not significant., Discussion: Psoriasis and psoriatic arthritis appear to be associated with an increased risk of polyneuropathy. This increased risk seems to be linked to the higher prevalence of contributing factors for polyneuropathy, rather than a direct increase in neuropathy risk specifically related to psoriasis and psoriatic arthritis., (© 2024 Wiley Periodicals LLC.)

Background: Psoriasis is a chronic skin disease driven by immune system dysfunction and associated with increased cardiovascular risk and metabolic disorders. Risankizumab is an anti-interleukin-23 humanized monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis., Objective: We conducted a 3-year retrospective study to evaluate the effectiveness and the safety of risankizumab in patients with moderate-to-severe psoriasis, comparing those with and without the presence of at least one cardiometabolic comorbidity (CMD)., Results: Our study included 333 patients treated with risankizumab for at least one year. One hundred and sixty-two patients had at least one CMD. After one year of treatment, a reduction of at least 90% and 100% in Psoriasis Area and Severity Index (PASI) score compared with baseline (PASI90 and PASI100, respectively) was observed in 80.3% and 63% of patients with CMDs compared to 83% and 63.2% of patients without CMDs. No statistically significant differences were observed between the two cohorts of patients in terms of effectiveness and rates of adverse events. No significant safety findings were observed throughout the study period. Our study supports data from clinical trials and real-world studies, even in patients with concomitant cardiometabolic comorbidities.

Anorectal melanoma (ARM) is a rare malignancy often associated with a poor prognosis due to its late diagnosis and aggressive biological behavior. This review aims to comprehensively investigate ARM's diagnosis, management, and treatment, emphasizing its clinical characteristics, laboratory findings, and implications for patient prognosis. A systematic literature search was conducted in PubMed, Embase, and Cochrane CENTRAL databases from inception to 1 July 2024. This review synthesizes existing literature to provide a comprehensive understanding of this rare primary malignancy. A total of 110 articles reporting on 166 patients were included. Gender data were available for 131 cases, comprising 67 females (51.1%) and 64 males (48.9%). The median age was 66 years. The overall median time to diagnosis was 4 months for anal melanoma, 3 months for rectal melanoma, and 4 months for anorectal junction melanoma. The clinical presentation was nodular in 98.2% of cases. Pre-diagnosis symptoms included bleeding in 84.9% of cases, mucous elimination (6%), pain (68.7%), tenesmus (16.9%), and changes in bowel movements (28.5%). Overall survival (OS) was reported in 82 cases, with a median OS of 11 months: 11 months for anal melanoma, 7 months for rectal melanoma, and 12 months for anorectal junction melanoma. ARM is a rare and aggressive melanoma subtype often diagnosed at an advanced stage, leading to a poor prognosis. A female predominance was observed, consistent with other mucosal melanomas. Anal melanoma exhibited better progression-free survival, and OS compared to rectal and anorectal junction melanoma., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

In this study we investigate the compositional changes in dissolved organic matter (DOM) fractions across diverse water sources and treatment processes in three Drinking Water Treatment Plants (DWTPs). High-Performance Size Exclusion Chromatography coupled with Diode Array Detection and Organic Carbon Detection (HPSEC-DAD-OCD) was employed to characterize DOM fractions, offering insights into treatment optimization. We examine bulk water parameters, DOM distributions, and the efficiency of treatment trains in reducing DOM fractions. Results reveal distinct DOM composition profiles in river-sourced versus reservoir-sourced waters, with implications for treatment processes. Coagulation, Granular Activated Carbon (GAC) adsorption, Electrodialysis Reversal (EDR), and Ion Exchange (IEX) were evaluated for their efficacy in removing DOM fractions. The analysis highlights the effectiveness of coagulation in reducing high molecular weight (MW) fractions, while GAC filtration targets lower MW fractions. EDR shows significant removal of anions and aromatics, while IEX demonstrates high removal efficiencies for removing humic substances (HS) fractions. Spectroscopic analysis further elucidates changes HS sub-fractions and their role in disinfection by-products (DBP) formation. To quantitatively assess the relationship between HS sub-fractions and trihalomethane formation potentials (THMFP), Pearson correlation analysis were conducted, unveiling robust associations between HS sub-fractions and THM-FP that can be predicted by surrogate parameters such as A 254 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Genital involvement in atopic dermatitis(AD) can have a significant impact on the patient's quality of life. However, inspection of genital areas is not usually conducted during routine examination and patients may be reluctant to inform the clinician or show this area., Objective: to evaluate the efficacy of tralokinumab in AD patients with genital involvement., Methods: Adult patients with moderate/severe AD and genital involvement receiving tralokinumab have been analyzed. Primary endpoints were EASI, DLQI, PP-NRS, genital-IGA (g-IGA) and genital itching (GI) at week 16., Results: out of 48 patients with moderate/severe AD under treatment with tralokinumab, 12 patients (25%) showed a genital involvement. Seven patients reported itching in the genital area (58%), while none reported a positive history of genital infections. Median scores at T0 were EASI 17.5, PP-NRS 8 and DLQI 14. After 16 weeks of treatment, we observed a median EASI of 3, a median PP-NRS of 1 and a median DLQI of 1. Finally, concerning the genital response, after 16 weeks of treatment, we observed a statistically significant decrease in mean GI and g-IGA scores., Conclusion: despite the small size of our sample, tralokinumab can be considered as a valid treatment option for AD with genital involvement.

Purpose: Tildrakizumab is a selective inhibitor of IL-23 approved for the treatment of moderate-to-severe plaque psoriasis in two dosages. We conducted a 16-week multicenter retrospective study to compare the effectiveness and safety of tildrakizumab 200 mg versus tildrakizumab 100 mg in patients with a high disease burden or high body weight., Materials and Methods: Our retrospective study included 134 patients treated with tildrakizumab 200 mg and 364 patients treated with tildrakizumab 100 mg from 28 Italian Dermatology Units affected by moderate-to-severe plaque psoriasis. The patients had a body weight above 90 kg or a high disease burden (Psoriasis Area and Severity Index [PASI] ≥ 16 or the involvement of difficult-to-treat areas). We evaluated the effectiveness of tildrakizumab at the week-16 visit in terms of PASI90, PASI100 and absolute PASI ≤ 2., Results: After 16 weeks of treatment with tildrakizumab 200 mg, PASI90 was reached by 57.5% of patients and PASI100 by 39.6% of patients. At the same time point, 34.3% and 24.2% of patients treated with tildrakizumab 100 mg achieved PASI90 and PASI100, respectively., Conclusions: Our data suggest that tildrakizumab 200 mg has better effectiveness than tildrakizumab 100 mg in patients with a body weight ≥ 90 kg and a high disease burden.

Background: Guselkumab is a monoclonal antibody approved for treating moderate-to-severe plaque psoriasis. Long-term data on the effectiveness and safety of guselkumab in a real-world setting are still limited., Materials and Methods: We conducted a 104-week monocentric retrospective study on 102 psoriasis patients, all treated with guselkumab for at least 16 weeks. At each visit, we used the Psoriasis Area and Severity Index (PASI): effectiveness endpoints were the percentages of patients achieving 75%/90%/100% (PASI 75/90/100) improvement in PASI compared with baseline. The Kaplan-Meier curve was used to assess the drug survival., Results: At week 16, PASI 90 and PASI 100 were achieved by 49.02% and 32.35% of patients. At week 52, PASI 90 and PASI 100 were achieved by 71.58% and 55.79% of patients. After 2 years, PASI 90 and PASI 100 were achieved by 79.63% and 61.11% of patients. Obese and overweight patients had comparable PASI 90 and PASI 100 responses throughout the study. At week 104, no significant differences were observed between bio-na&iuml;ve and bio-experienced patients regarding all effectiveness endpoints. No significant safety signals were reported in our study. After 24 months, 91.57% of our cohort was still on treatment with guselkumab., Conclusion: Our findings, although limited by the study's retrospective nature, confirm that guselkumab is a safe and effective therapeutic option for a "real-life" cohort of patients with psoriasis. J Drugs Dermatol. 2024;23(8):632-639.&nbsp; doi:10.36849/JDD.7486R1.

Background and Objectives : Amelanotic/hypomelanotic melanomas (AHMs) account for 2-8% of all cutaneous melanomas. Due to their clinical appearance and the lack of specific dermoscopic indicators, AHMs are challenging to diagnose, particularly in thinner cutaneous lesions. The aim of our study was to evaluate the clinicopathological and dermoscopic features of thin AHMs. Identifying the baseline clinical-pathological features and dermoscopic aspects of thin AHMs is crucial to better understand this entity. Materials and Methods : We divided the AHM cohort into two groups based on Breslow thickness: thin (≤1.00 mm) and thick (>1.00 mm). This stratification helped identify any significant clinicopathological differences between the groups. For dermoscopic analysis, we employed the "pattern analysis" approach, which involves a simultaneous and subjective assessment of different criteria. Results : Out of the 2.800 melanomas analyzed for Breslow thickness, 153 were identified as AHMs. Among these, 65 patients presented with thin AHMs and 88 with thick AHMs. Red hair color and phototype II were more prevalent in patients with thin AHMs. The trunk was the most common anatomic site for thin AHMs. Patients with thin AHMs showed a higher number of multiple melanomas. Dermoscopic analysis revealed no significant difference between thin AHMs and thick AHMs, except for a more frequent occurrence of residual reticulum in thin AHMs. Conclusions : Thin AHMs typically affect individuals with lower phototypes and red hair color. These aspects can be related to the higher presence of pheomelanin, which provides limited protection against sun damage. This also correlates with the fact that the trunk, a site commonly exposed to intermittent sun exposure, is the primary anatomical location for thin AHMs. Multiple primary melanomas are more common in patients with thin AHMs, likely due to an intrinsic predisposition as well as greater periodic dermatologic follow-ups in this class of patients. Apart from the presence of residual reticulum, no other significant dermoscopic differences were observed, complicating the differential diagnosis between thin and thick AHMs based on dermoscopy alone.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent and painful nodules and abscesses in intertriginous skin areas, which can progress to sinus tract formation, tissue destruction, and scarring. HS is highly debilitating and severely impairs the psychological well-being and quality of life of patients. The therapeutic approach to HS is based on medical therapy and surgery. First-line medical therapy includes topical antibiotics, systemic antibiotics, and biologics. Main surgical procedures include deroofing, local excision, and wide local excision. Despite the availability of multiple therapeutic options, the rates of disease recurrence and progression continue to be high. In recent years, the possibility of combining biologic therapy and surgery has raised considerable interest. In a clinical trial, the perioperative use of adalimumab has been associated with greater response rates and improved inflammatory load and pain, with no increased risk of postoperative infectious complications. However, several practical aspects of combined biologic therapy and surgery are poorly defined. In June 2022, nine Italian HS experts convened to address issues related to the integration of biologic therapy and surgery in clinical practice. To this purpose, the experts identified 10 areas of interest based on published evidence and personal experience: (1) patient profiling (diagnostic criteria, disease severity classification, assessment of response to treatment, patient-reported outcomes, comorbidities); (2) tailoring surgery to HS characteristics; (3) wide local excision; (4) presurgery biologic treatment; (5) concomitant biologic and surgical treatments; (6) pre- and postsurgery management; (7) antibiotic systemic therapy; (8) biologic therapy after radical surgery; (9) management of adverse events to biologics; and (10) management of postoperative infectious complications. Consensus between experts was reached using the Estimate-Talk-Estimate method (Delphi Method). The statements were subsequently presented to a panel of 27 HS experts from across Italy, and their agreement was assessed using the UCLA Appropriateness Method. This article presents and discusses the consensus statements., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Chronic pelvic pain (CPP) is a multifactorial syndrome that can substantially affect a patient's quality of life. Endometriosis is one cause of CPP, and alterations of the immune and microbiome profiles have been observed in patients with endometriosis. The objective of this pilot study was to investigate differences in the vaginal and gastrointestinal microbiomes and cervicovaginal immune microenvironment in patients with CPP and endometriosis diagnosis compared to those with CPP without endometriosis and no CPP., Methods: Vaginal swabs, rectal swabs, and cervicovaginal lavages (CVL) were collected among individuals undergoing gynecologic laparoscopy. Participants were grouped based on patients seeking care for chronic pain and/or pathology results: CPP and endometriosis (CPP-Endo) (n = 35), CPP without endometriosis (n = 23), or patients without CPP or endometriosis (controls) (n = 15). Sensitivity analyses were performed on CPP with endometriosis location, stage, and co-occurring gynecologic conditions (abnormal uterine bleeding, fibroids). 16S rRNA sequencing was performed to profile the microbiome, and a panel of soluble immune mediators was quantified using a multiplex assay. Statistical analysis was conducted with SAS, R, MicrobiomeAnalyst, MetaboAnalyst, and QIIME 2., Results: Significant differences were observed between participants with CPP alone, CPP-Endo, and surgical controls for body mass index, ethnicity, diagnosis of ovarian cysts, and diagnosis of fibroids. In rectal microbiome analysis, both CPP alone and CPP-Endo exhibited lower alpha diversity than controls, and both CPP groups revealed enrichment of irritable bowel syndrome-associated bacteria. CPP-Endo exhibited an increased abundance of vaginal Streptococcus anginosus and rectal Ruminococcus. Patients with CPP and endometrioma (s) demonstrated increased vaginal Streptococcus, Lactobacillus, and Prevotella compared to other endometriosis sites. Further, abnormal uterine bleeding was associated with an increased abundance of bacterial vaginosis-associated bacteria. Immunoproteomic profiles were distinctly clustered by CPP alone and CPP-Endo compared to controls. CPP-Endo was enriched in TNF⍺, MDC, and IL-1⍺., Conclusions: Vaginal and rectal microbiomes were observed to differ between patients with CPP alone and CPP with endometriosis, which may be useful in personalized treatment for individuals with CPP and endometriosis from those with other causes of CPP. Further investigation is warranted in patients with additional co-occurring conditions, such as AUB/fibroids, which add additional complexity to these conditions and reveal the enrichment of distinct pathogenic bacteria in both mucosal sites. This study provides foundational microbiome-immunoproteomic knowledge related to chronic pelvic pain, endometriosis, and co-occurring gynecologic conditions that can help improve the treatment of patients seeking care for pain., (© 2024. The Author(s).)

Introduction: Folliculitis decalvans (FD) is a rare scarring alopecia mainly affecting middle-aged men, characterized by recurring episodes of follicular pustules, crusts, erythema, tufted hairs, and scars., Objectives: This study investigates the effectiveness of reflectance confocal microscopy (RCM) compared to trichoscopy for diagnosing and monitoring FD., Methods: The study involved 24 Caucasian patients diagnosed with FD. Patients were examined using trichoscopy and RCM, with a focus on specific features like erythema and inflammatory cell distribution. A subgroup of 16 patients was followed up after 3 months of therapy. The reproducibility of RCM and trichoscopy was assessed using Cohen Kappa Test., Results: RCM and trichoscopy consistently detected features such as tufted hairs, pustules, and perifollicular fibrosis. However, RCM provided more detailed insights into inflammatory activity and types of fibrosis, often overlooked by trichoscopy. It showed a reduction in vessels and inflammatory cells, which trichoscopy failed to detect. The concordance between RCM evaluations was excellent, indicating high reproducibility., Conclusions: RCM is effective in diagnosing and monitoring FD, offering detailed insights into inflammation and fibrosis. It complements trichoscopy, especially in aspects where trichoscopy is limited, such as precise measurement of inflammation. The study suggests that combining RCM with trichoscopy could enhance the accuracy of diagnosis and monitoring of FD, leading to tailored therapeutic approaches. Further studies with larger sample sizes and longitudinal designs are recommended to confirm these findings.

Objective: We aimed to evaluate the clinical usefulness of the systemic score in the prediction of life-threatening evolution in Still disease. We also aimed to assess the clinical relevance of each component of the systemic score in predicting life-threatening evolution and to derive patient subsets accordingly., Methods: A multicenter, observational, prospective study was designed including patients included in the Gruppo Italiano Di Ricerca in Reumatologia Clinica e Sperimentale Adult-Onset Still Disease Study Group and the Autoinflammatory Disease Alliance Network Still Disease Registry. Patients were assessed to see if the variables to derive the systemic score were available. The life-threatening evolution was defined as mortality, whatever the clinical course, and/or macrophage activation syndrome, a secondary hemophagocytic lymphohistiocytosis associated with a poor prognosis., Results: A total of 597 patients with Still disease were assessed (mean ± SD age 36.6 ± 17.3 years; male 44.4%). The systemic score, assessed as a continuous variable, significantly predicted the life-threatening evolution (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.07-1.42; P = 0.004). A systemic score ≥7 also significantly predicted the likelihood of a patient experiencing life-threatening evolution (OR 3.36; 95% CI 1.81-6.25; P < 0.001). Assessing the clinical relevance of each component of the systemic score, liver involvement (OR 1.68; 95% CI 1.48-2.67; P = 0.031) and lung disease (OR 2.12; 95% CI 1.14-4.49; P = 0.042) both significantly predicted life-threatening evolution. The clinical characteristics of patients with liver involvement and lung disease were derived, highlighting their relevance in multiorgan disease manifestations., Conclusion: The clinical utility of the systemic score was shown in identifying Still disease at a higher risk of life-threatening evolution in a large cohort. Furthermore, the clinical relevance of liver involvement and lung disease was highlighted., (© 2024 American College of Rheumatology.)

Actinic keratosis (AK) is a frequent precancerous skin lesion that mostly affects chronically sun-exposed areas. Chronic sun damage leads to various mutations in onco-suppressor and oncogenic genes which cause an uncontrolled proliferation of atypical keratinocytes. Untreated AKs may evolve in cutaneous squamous cell carcinoma (cSCC), with the consequent need for dermato-surgical excision or even for systemic immunotherapy in case of invasive/metastatic cSCCs. Epidemiology data on AK prevalence are various, however, the literature unanimously reports an increasing prevalence due to the aging of the population. Clinically AKs appear as a scaly, erythematous macule or papule or hyperkeratotic plaque. Management of AKs and the field of cancerization is important to avoid the natural evolution into squamous cell carcinomas (SCCs). Both physical and topical treatments are approved for managing AKs. Patient compliance with topical regimens is usually low due to the length of the posology and frequent skin adverse events. A recently approved tirbanibulin-based ointment, showed potential for inhibiting cell proliferation and blocking SRC-kinases, implicated in the progression of AKs in SCCs. The advantage of this new treatment is the practical posology, with a daily application for 5 consecutive days on AKs of the face-scalp area. Local skin reactions are usually mild and do not require treatment discontinuation. The short course of this new therapy and its excellent tolerance massively increased patient compliance. This article reviews what is currently known about this new therapy from its mechanism of action to clinical trial outcomes regarding safety, effectiveness, and patient adherence to the treatment.

Biological drugs have dramatically changed the approach to treating moderate-to-severe plaque psoriasis, achieving excellent skin clearance and safety outcomes. However, the management of difficult-to-treat areas (e.g., scalp, palms/soles, nails, and genitalia) still represents a challenge in psoriasis treatment. Data in the literature on difficult-to-treat sites are limited and, frequently, no specific analysis is performed during clinical trials. We conducted a 52-week, retrospective study to evaluate the effectiveness of ixekizumab in 120 patients with moderate-to-severe plaque psoriasis of at least one difficult-to-treat area (scalp, palmoplantar surfaces, nails, and genitalia). Ninety-nine patients had scalp psoriasis, 35 had involvement of the palms or soles, 27 were affected by genital psoriasis, and 22 patients reported involvement of the nails. After 1 year of treatment, 96% of patients with scalp involvement, 95.6% of patients with palmoplantar psoriasis, 95.2% of patients with genital psoriasis, and 85% of patients with nail involvement achieved a site-specific Physician's Global Assessment of 0 or 1 (clear or almost clear). No serious adverse events were observed during the study. Our study supports the effectiveness of ixekizumab in plaque psoriasis involving difficult-to-treat sites., (© 2024 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Introduction: The introduction of biological therapies has revolutionized the treatment of moderate-to-severe plaque psoriasis. In particular, ixekizumab, an inhibitor of interleukin-17A, has shown great results in terms of efficacy and safety in both clinical trials and real-world experiences. However, there is a lack of long-term real-world data available for ixekizumab., Methods: We conducted a multicenter real-life study to evaluate the effectiveness and safety of ixekizumab in patients with moderate-to-severe plaque psoriasis. Psoriasis Area and Severity Index score (PASI) was collected at baseline and after 1, 2, 3, 4, and 5 years. The occurrence of any adverse events was recorded at each time point., Results: We enrolled 1096 patients treated with ixekizumab for at least 1 year. At week 52, the percentages of PASI 90 and PASI 100 were 85.04% and 69.07%, respectively. After 5 years of treatment with ixekizumab, out of 145 patients, a PASI 90 response was achieved by 86.90% of patients, while complete skin clearance was reached by 68.28% of patients. We did not observe any new significant safety findings throughout the study period., Conclusion: This study supports the long-term effectiveness and safety of ixekizumab in a real-world setting., (© 2024. The Author(s).)

Introduction: Functional connectivity (FC) is defined in terms of temporal correlations between physiological signals, which mainly depend upon structural (axonal) connectivity; it is commonly studied using functional magnetic resonance imaging (fMRI). Interhemispheric FC appears mostly supported by the corpus callosum (CC), although several studies investigating this aspect have not provided conclusive evidence. In this context, patients in whom the CC was resected for therapeutic reasons (split-brain patients) provide a unique opportunity for research into this issue. The present study was aimed at investigating with resting-state fMRI the interhemispheric FC in six epileptic patients who have undergone surgical resection of the CC., Methods: The analysis was performed using fMRI of the Brain Software Library; the evaluation of interhemispheric FC and the recognition of the resting-state networks (RSNs) were performed using probabilistic independent component analysis., Results: Generally, bilateral brain activation was often observed in primary sensory RSNs, while in the associative areas, such as those composing the default mode and fronto-parietal networks, the activation was often unilateral., Discussion: These results suggest that even in the absence of the CC, some interhemispheric communication is still present. This residual FC might be supported through extra-callosal pathways that are likely subcortical, making it possible for some interhemispheric integration. Further studies are needed to confirm these conclusions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Marcantoni, Piccolantonio, Ghoushi, Valenti, Reversi, Mariotti, Foschi, Lattanzi, Burattini, Fabri and Polonara.)

Purpose: The multi-kinase inhibitor (mKi) regorafenib has demonstrated efficacy in chemorefractory patients with metastatic colorectal cancer (mCRC). However, lack of predictive biomarkers and concerns over significant toxicities hamper the use of regorafenib in clinical practice., Experimental Design: Serial liquid biopsies were obtained at baseline and monthly until disease progression in chemorefractory patients with mCRC treated with regorafenib in a phase II clinical trial (PROSPECT-R n = 40; NCT03010722) and in a multicentric validation cohort (n = 241). Tissue biopsies collected at baseline, after 2 months and at progression in the PROSPECT-R trial were used to establish patient-derived organoids (PDO) and for molecular analyses. MicroRNA profiling was performed on baseline bloods using the NanoString nCounter platform and results were validated by digital-droplet PCR and/or ISH in paired liquid and tissue biopsies. PDOs co-cultures and PDO-xenotransplants were generated for functional analyses., Results: Large-scale microRNA expression analysis in longitudinal matched liquid and tissue biopsies from the PROSPECT-R trial identified MIR652-3p as a biomarker of clinical benefit to regorafenib. These findings were confirmed in an independent validation cohort and in a "control" group of 100 patients treated with lonsurf. Using ex vivo co-culture assays paired with single-cell RNA-sequencing of PDO established pre- and post-treatment, we modeled regorafenib response observed in vivo and in patients, and showed that MIR652-3p controls resistance to regorafenib by impairing regorafenib-induced lethal autophagy and by orchestrating the switch from neo-angiogenesis to vessel co-option., Conclusions: Our results identify MIR652-3p as a potential biomarker and as a driver of cell and non-cell-autonomous mechanisms of resistance to regorafenib., (©2024 American Association for Cancer Research.)

Statement of Problem: Data on the clinical performance of monolithic Zirconia screw-retained crowns on external hexagon implants fabricated from digital scans through a cast-free, fully digital workflow is lacking and needs to be included., Purpose: This retrospective multicentric study aimed to evaluate the real-life clinical results of monolithic Zirconia screw-retained crowns without the interposition of a Ti-base on external hexagon implants fabricated from intraoral scans and a cast-free approach in private practices., Materials and Methods: Single external hex implant fixtures were restored with monolithic zirconia crowns without the interposition of a Tibase. The crowns were directly screwed on external hexagonal implant connections with a castfree, fully digital workflow. Data were analyzed using descriptive statistics and the Kaplan- Meier test. Between September 2022 and March 2023, the California Dental Association modified criteria were adopted for clinical evaluation after recalling all patients., Results: A total of 304 single tooth restorations in the maxillary and mandibular posterior regions fabricated between July 2014 and July 2022 in 252 patients (120 males and 132 females, mean age 53.6 years, SD 23.3). Seven crowns were excluded because of patient dropout. The most common minor technical complications were screw loosening (3 crowns) and loss of the screw-access hole filling (3 crowns). Four failures included two implant failures with mobility and two fractured crowns. No screw or implant fractures were recorded. The overall cumulative survival rate was 98.6% and the average success rate (crowns experiencing no failures or complications) was 96.0%. The mean overall survival time was 101.3 months (standard error, 0.847; 95% confidence interval for the mean, 99.67-102.99). The overall survival probability was 87.9% up to 97 months., Conclusions: With careful case selection and comprehensive periodontal maintenance program, single crowns directly screwed onto an external hexagon platform have shown to have excellent survival and success (complication-free) rates, comparable to available data regarding single crowns with a metal implant- prosthetic interface.

Objective: Anti-Müllerian hormone is a reliable measure of ovarian reserve associated with menopause timing and fertility. Previous studies have observed that individuals with endometriosis have lower anti-Müllerian hormone levels than those without. However, sample sizes have been small and information is limited regarding the long-term influence of endometriosis on anti-Müllerian hormone levels among the general population, which may have important implications for menopause timing and chronic disease risk., Methods: Among 1961 premenopausal women in the Nurses' Health Study II who provided a blood sample and had not been pregnant in the last 6 months, we used generalized linear models to determine the association between laparoscopically-confirmed endometriosis and log-transformed plasma anti-Müllerian hormone level, adjusted for age (continuous and squared) and other potential confounding variables., Results: Participants were on average 40 years old (interquartile range 37-42 years) at blood draw. Women with endometriosis diagnosed prior to blood draw (n = 119) had a lower mean anti-Müllerian hormone level (1.6 ng/mL [SD = 2.3]) than women without known endometriosis (n = 1842) (2.8 ng/mL [SD = 3.0]). In multivariable adjusted models, women with endometriosis had 29.6 % lower anti-Müllerian hormone levels (95 % CI: -45.4, -9.2 %) than women without. This association was greater among women with a body mass index of 25 kg/m 2 or more (percent difference: -44.0 % (-63.7, -13.8)), compared to those with a body mass index of under 25 kg/m 2 (percent difference: -19.8 % (-41.7, 10.4)), but did not vary by parity or infertility history., Conclusions: Lower anti-Müllerian hormone levels in women with endometriosis may be one mechanism through which endometriosis influences risk of infertility, younger age at menopause, and cardiovascular disease., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Individuals with Autism Spectrum Disorder (ASD) present atypical sensory processing in the perception of moving stimuli and biological motion. The present study aims to explore the performance of young adults with ASD in a time to contact (TTC) estimation task involving social and non-social stimuli. TTC estimation involves extrapolating the trajectory of a moving target concealed by an occluder, based on the visible portion of its path, to predict the target's arrival time at a specific position. Sixteen participants with a diagnosis of level-1 ASD (M = 19.2 years, SE = 0.54 years; 3 F, 13 M) and sixteen participants with TD (M = 22.3 years, SE = 0.44 years; 3 F, 13 M) took part in the study and underwent a TTC estimation task. The task presented two object types (a car and a point-light walker), different object speeds, occluder lengths, motion directions and motion congruency. For the car object, a larger overestimation of TTC emerged for ASDs than for TDs, whereas no difference between ASDs and TDs emerged for the point-light walker. ASDs exhibited a larger TTC overestimation for the car object than for the point-light walker, whereas no difference between object types emerged for TDs. Our results indicated an atypical TTC estimation process in young adults with ASD. Given its importance in daily life, future studies should further explore this skill. Significant effects that emerged from the analysis are discussed., (© 2024. The Author(s).)

Purpose: Studies involving minimally invasive hysterectomy and robotic sacrocolpopexy have demonstrated safety and feasibility of same-day discharge. There are limited data, however, on same-day discharge outcomes for vaginal hysterectomy and pelvic reconstruction. This study aimed to compare 30 and 90-day surgical outcomes between same-day discharge versus overnight stay following vaginal hysterectomy and apical suspension., Patients and Methods: This retrospective study evaluated surgeries performed over two time periods. Overnight stay was standard between December 2018 and February 2020. Same-day discharge was standard from December 2020 to February 2022. All patients who underwent vaginal hysterectomy with apical suspension were included. The primary outcome was to determine if there was an increase in 30-day readmission rates. Secondary outcomes included emergency department visits and reoperations within 30 days, the previous variables at 90 days, and the rate for successful same-day discharge., Results: A total of 324 patients were analyzed over the 30 months: 149 (46%) in the overnight stay group and 175 (54%) in the same-day discharge group. At 30 days, no difference was found between groups for readmissions (2.7% vs 4.0%, p = 0.56), emergency department visits (14.8% vs 14.9%, p = 1.0), or reoperations (2.0% vs.1.7%, p = 1.0). At 90 days, outcomes were also similar. Same-day discharge as standard practice was successful in 80% of patients., Conclusion: In this retrospective two cohort study, the safety of same-day discharge following vaginal hysterectomy with apical suspension was demonstrated with no increased risk of 30 or 90-day readmissions, emergency visits, or reoperation rates. The majority (80%) of patients were discharged on the day of surgery, suggesting feasibility of this model., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Ray et al.)

Evidence continues to accumulate on the influence of the menstrual phase on several biobehavioral outcomes (e.g., substance misuse). Expansion of this knowledge is limited due to the burdensomeness of accurate menstrual phase assessment. Thus, we sought to create and validate a questionnaire that can be used as a stand-alone item within low-resource settings and numerous study designs (e.g., cross-sectional) to accurately identify both the follicular phase (FP) and the luteal phase (LP). Participants completed the self-administered four-item Menstrual Phase Identification Questionnaire (MPIQ) in two recently completed clinical trials. We assessed the accuracy of two MPIQ scoring criteria (less restrictive and more restrictive), as compared to self-report of onset of menses alone, with progesterone confirmation via dried blood spots. Participants ( n = 59) were, on average, 33.7 (standard deviation [ SD ]: ± 4.3) years old and provided a total of 83 responses. Assessing FP and LP using the self-reported onset of menses alone classified 65.1% of the responses with an overall phase identification accuracy of 60.2%. While the more restrictive MPIQ scoring classified 100% of the responses, it yielded a similar accuracy (68.4%). In contrast, the less restrictive MPIQ scoring classified 100% of the responses and also significantly improved phase identification accuracy to 92.1% ( p < .001). The MPIQ, as a stand-alone item, allows all cross-sectional responses to be classified with a high level of accuracy. This low-burden questionnaire can be used alone to identify FP and LP in studies that may be otherwise limited by study design, finances, and/or participant burden. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Purpose: Literature supports the use of technological tools such as augmented reality, 3 D avatars and mobile devices to improve individuals with autism spectrum disorder skills. Possibilities of including these technological tools in intervention and the critical issues related to intervention design are essential research questions. The aim of the current work is to present an interdisciplinary research study on the design of an autism intervention considering these technologies., Materials and Methods: This study used qualitative evidence and thematic analysis to identify the main design guidelines. A semi-structured interview was administered to a total of twenty participants representing four stakeholder categories: ASD, clinicians, therapists and caregivers. Interviews focussed on three dimensions related to user, technology and environment since they represent a complex system within which the individual using technology is situated., Results: Thematic analysis of the interviews identified a total of 10 themes considered central to the design of the technological intervention., Conclusions: Since the application of technology in autism intervention is a relatively new area, the guidelines related to the potential incentives and barriers of the proposed technology are helpful to inform future treatment studies.Implications for RehabilitationThis study highlights the strengths and barriers associated with the use of smartphones and augmented reality in autism spectrum disorder interventions considering the dimensions within which the user using assistive technology is located.Strengths and major concerns that emerged are key points to consider during the development of the technological intervention.Considering these points can foster the use of technology within the intervention and promote its effectiveness.

Upadacitinib is a selective Janus kinase inhibitor approved for the treatment of severe atopic dermatitis (AD). This systematic review aims to summarize the most recent data in terms of effectiveness and safety of upadacitinib in the treatment of severe AD in a real-world setting. The review included a comprehensive search of databases, including PubMed, Google Scholar and Web of Science, according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The literature search initially identified 242 studies. Of these, 214 were excluded after reviewing their titles and abstracts. We then conducted a full-text review of 25 studies, of which 17 met our inclusion criteria and were therefore included in our systematic review. The analysis of real-world studies showed high effectiveness of upadacitinib, in terms of both clinical signs and subjective symptoms, in different patient populations, including those resistant to other treatments. No new significant safety concerns have emerged as compared to randomized clinical trials., Competing Interests: L. Gargiulo has been a consultant for Almirall. L. Ibba has been a consultant for Almirall. A. Costanzo has served as an advisory board member, consultant and has received fees and speaker’s honoraria or has participated in clinical trials for AbbVie, Almirall, Biogen, LEO Pharma, Lilly, Janssen, Novartis, Pfizer, Sanofi Genzyme, and UCB-Pharma. A. Narcisi has served on advisory boards, received honoraria for lectures and research grants from Almirall, AbbVie, Leo Pharma, Celgene, Eli Lilly, Janssen, Novartis, Sanofi‐Genzyme, Amgen and Boehringer Ingelheim. M Valenti reports personal fees from AbbVie, personal fees from Eli-Lilly, personal fees from Almirall, personal fees from Novartis, personal fees from UCB, personal fees from Leopharma, personal fees from Boehringer-Ingelheim, personal fees from Sanofi, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2024 Ibba et al.)

Severe acute undernutrition (SAU) is still a crucial global health issue in the 0-59 months population, increasing the risk of mortality as well as of long-term consequences. In Sudan, 3.3 million children suffered from acute malnutrition between 2018 and 2019. This study was planned to evaluate, in the area of Port Sudan, the prevalence of acute undernutrition after the COVID-19 pandemic and to identify the most important factors favoring the development of acute undernutrition. The available clinical records of all the under-five children ( n = 1012) admitted to the Port Sudan Emergency Pediatric Hospital from 1 February 2021 to 31 January 2022 were analyzed. The presence of wasting and kwashiorkor was assessed and children were categorized according to age, gender, place of residence, main reason for hospitalization, and underlying comorbidities. Acute undernutrition was evidenced in 493 (48.7%) children. Of them, only 16 (3.2%) were diagnosed with kwashiorkor. Children with SAU had a higher prevalence of acute gastroenteritis ( p < 0.05) and parasitosis ( p < 0.05). Infants aged 0-6 months were those with the lowest risk of undernutrition, whereas those aged 7-12 months were those with the greater risk. In these patients, multivariate analysis revealed that SAU and MAU were 2.5 times (OR 2.51; 95% CI, 1.79-3.55) and 5.5 times (OR 5.56; 95% CI, 2.59-18.7) higher. This study shows that the area of Port Sudan is still suffering from an alarming prevalence of severe wasting and the risk of developing acute undernutrition seems strictly related to the introduction of complementary feeding and tends to reduce with increasing age. Measures already in place to prevent acute malnutrition should be reinforced with improvement of mother education on child feeding.

Awareness of the importance of assessing social cognition skills under conditions showing atypical social behaviours has increased over the years. However, the evaluation of the psychometric properties of the measures and the availability of normative values for the clinical context are still limited. This study aims to revise, provide normative values, and evaluate the clinical validity of the Italian version of three social cognition measures: Advanced Theory of Mind (A-ToM) task, the Emotion Attribution Task (EAT), and the Social Situation Task (SST). Measures were administered to 580 adolescents and adult healthy controls (age range 14-50). We performed differential item functioning and Rasch analysis to revise each task, so normative data of the revised measures were calculated. Moreover, the revised measures were administered to 38 individuals with autism spectrum disorder (ASD) and 35 individuals with schizophrenia spectrum disorders (SSD): ASD and SSD were matched by age, gender, and IQ with a control sample to evaluate clinical validity. ROC analysis showed that the SST is the best measure differentiating between healthy and clinical groups, compared to the A-ToM (AUC ASD  = 0.70; AUC SSD  = 0.65) and EAT (AUC ASD  = 0.67; AUC SSD  = 0.50), which showed poorer performance. For SSD diagnosis, two SST subscales (Violation and Gravity score) indicated the best accuracy (AUCs of 0.88 and 0.84, respectively); for the ASD diagnosis, we propose a combined score between the SST subscale and A-ToM (AUC = 0.86). The results suggest that the proposed measures can be used to support the diagnostic process and clinical practice., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Psoriasis can have a significant impact on quality of life and productivity, especially with increased severity. However, there is limited evidence on biologics' efficacy in highly severe cases compared to moderate-to-severe ones. This study aimed to evaluate the effectiveness and safety of novel biological therapies in very severe psoriasis. We conducted a retrospective analysis on patients ≥ 18 years old affected by very severe psoriasis who had received a biological agent for at least 16 weeks. We used PASI to assess disease severity and effectiveness at weeks 16, 52, 104, and 156. Safety was evaluated by tracking treatment discontinuation rates and adverse events. This study included 29 males and 11 females, with a mean age of 55.80 years (SD 13.82). Cardiometabolic diseases were the most common comorbidities (25.00%). Twenty-eight (70.00%) patients had psoriasis involvement in at least one difficult-to-treat area. All patients completed 16 weeks of treatment. The mean PASI was 31.60 (SD 2.57) at baseline, 3.48 (SD 4.13) at week 16, 0.58 (SD 1.70) at week 52, 0.77 (SD 1.66) at week 104, and 1.29 (SD 2.12) at week 156. PASI90 and 100 were achieved by 52.50% and 30.00% of patients at week 16, by 96.15% and 80.77% at week 52, by 93.33% and 66.67% at week 104, and by 85.71% and 42.86% at week 156. PASIs ≤ 2 were achieved by 50.00% of patients at week 16, 88.46% at week 52, 86.67% at week 104, and 85.71% at week 156. Only two patients discontinued biologics due to complete remission, and mild AEs were reported by four patients. Our findings show that biologics are effective and well tolerated for treating very severe psoriasis, maintaining long-term effectiveness.

Early diagnosis is crucial for Autism spectrum disorder (ASD) and is achieved through a screening of developmental indicators to recognise children who are at risk of autism. One of the most widely used instruments in clinical practice for assessing child development is the Griffiths Mental Development Scale (GMDS). We sought (a) to assess longitudinally whether children diagnosed with ASD, with a mean age of 33.50 months (SD 7.69 months), show a developmental delay of abilities measured by the GMDS over time and (b) to analyse which skills of the GMDS could be associate to the symptomatologic severity of ASD. Our results showed lower scores of General Quotient and all sub-quotients of GMDS from first (T0) to second assessment (T1), except for the Performance sub-quotient. Three sub-quotients (Personal-Social, Hearing and Language and Practical Reasoning) also associate symptom severity at the time when the diagnosis of ASD is made., (© 2022. The Author(s).)