Fast Clinical Response of Bimekizumab in Nail Psoriasis: A Retrospective Multicenter 36-Week Real-Life Study.

(1) Background/Objectives: Nail psoriasis (NP) is a chronic and difficult-to-treat disease, which causes significant social stigma and impairs the patients' quality of life. Moreover, nail psoriasis is a true therapeutic challenge for clinicians. The presence of nail psoriasis can be part of a severe form of psoriasis and can have predictive value for the development of psoriatic arthritis. Our real-world-evidence multicenter study aims to evaluate the efficacy of bimekizumab in nail psoriasis. (2) Methods: A retrospective analysis of a multicenter observational study included 834 patients affected by moderate-to-severe psoriasis, in 33 Dermatologic Units in Italy, treated with bimekizumab from December 2022 to September 2023. Clinimetric assessments were based on Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Physician's Global Assessment of Fingernail Psoriasis (PGA-F) for the severity of nail psoriasis at 0, 12, 24, and 36 weeks. (3) Results: Psoriatic nail involvement was present in 27.95% of patients. The percentage of patients who achieved a complete clearance of NP in terms of PGA-F 0 was 31.7%, 57%, and 88.5% at week 4, 16, and 36, respectively. PASI 100 was achieved by 32.03% of patients at week 4, by 61.8% at week 16, and by 78.92% of patients at week 36. The mean baseline PASI was 16.24. The mean DLQI values for the entire group of patients at baseline, at week 4, at week 16, and at week 36 were 14.62, 3.02, 0.83, and 0.5, respectively. (4) Conclusions: Therapies that promote the healing of both the skin and nails in a short time can also ensure a lower risk of subsequently developing arthritis which is disabling over time. Bimekizumab proved to be particularly effective to treat NP, with a fast response in terms of complete clearance, with over 88.5% of patients free from NP after 36 weeks. The findings of our real-world study showed that patients with moderate-to-severe PsO and concomitant NP had significantly faster and more substantial improvements in NP up to 36 weeks with respect to previous research findings. Considering the rapid healing of the nail, the dual inhibition of IL17 A and F might have a great value in re-establishing the dysregulation of keratin 17 at the nail level.

Evaluation of the Climate Impact and Nutritional Quality of Menus in an Italian Long-Term Care Facility.

Global warming poses a significant threat to our planet, with the food sector contributing up to 37% of total greenhouse gas emissions. This study aimed to assess the climate change impact and healthiness of menus in a long-term care facility in Italy. We analyzed two 28-day cyclical menus using the carbon footprint (CF) and the Modified EAT-Lancet Diet Score (MELDS) to evaluate adherence to the Planetary Health Diet (PHD). Monte Carlo simulations were employed to explore 20,000 daily menu permutations. Results showed that the mean GHGEs of spring/summer and autumn/winter daily menus were 2.64 and 2.82 kg of CO2eq, respectively, with 99% of menus exceeding the 2.03 kg of CO2eq benchmark. Only 22% of menus were adherent to the PHD, with MELDSs ranging from 12 to 29. A strong inverse association between the CF and adherence to the PHD was observed. These findings suggest significant potential for reducing the CFs of meals served in nursing homes while promoting adherence to a planetary diet, presenting an opportunity to set new standards in caregiving and environmental sustainability.

Stoichiometric reconstruction of the Al2O3(0001) surface.

Macroscopic properties of materials stem from fundamental atomic-scale details, yet for insulators, resolving surface structures remains a challenge. We imaged the basal (0001) plane of α-aluminum oxide (α-Al2O3) using noncontact atomic force microscopy with an atomically defined tip apex. The surface formed a complex ([Formula: see text] × [Formula: see text])R±9° reconstruction. The lateral positions of the individual oxygen and aluminum surface atoms come directly from experiment; we determined with computational modeling how these connect to the underlying crystal bulk. Before the restructuring, the surface Al atoms assume an unfavorable, threefold planar coordination; the reconstruction allows a rehybridization with subsurface O that leads to a substantial energy gain. The reconstructed surface remains stoichiometric, Al2O3.

Second Victims in Industries beyond Healthcare: A Scoping Review.

The second victim phenomenon (SVP) refers to workers negatively impacted by involvement in unanticipated adverse events or errors. While this phenomenon has been extensively studied in healthcare since its acknowledgment over 20 years ago, its presence and management in other high-risk industries have remained unclear. We conducted a scoping review aiming to map the SVP in non-healthcare industries, as well as to explore the available interventions or support programs addressed to help second victims (SVs). A total of 5818 unique records were identified and, after the screening process, 18 studies from eight sectors were included. All industries acknowledged the existence of the SVP, though many did not use a specific term for defining the SV. Similarities in psychological and emotional consequences were found across sectors. Support strategies varied, with the aviation sector implementing the most comprehensive programs. Self-care and peer support were the most reported interventions, while structured clinical support was not mentioned in any industry. Our review highlighted a lack of standardized terminology and industry-specific, evidence-based support interventions for the SVP outside of healthcare. Healthcare appears to be at the forefront of formally recognizing and addressing the SVP, despite traditionally learning from other high-reliability industries in safety practices. This presents opportunities for reciprocal learning and knowledge transfer between healthcare and other high-risk sectors.

Beneficial effects of a combined lifestyle intervention for older people in a long-term-care facility on redox balance and endothelial function.

Objective: It has recently been highlighted how a short healthy life-style program (LSP) can improve the functional outcomes of older people admitted to a Long-Term Care (LTC) facility. Although it is known that life-style medicine-based interventions can exert anti-aging effects through the modulation of oxidative stress and mitochondrial function, the mechanisms underlying the aforementioned effects have not been clarified, yet. For this reason, in this study, the outcomes were focused on the investigation of the possible mechanisms underlying the benefits of a short LSP in older people. This was achieved by examining circulating markers of oxidative stress and immunosenescence, such as Tymosin ß (Tß4), before and after LSP and the effects of plasma of older people undergone or not LSP on endothelial cells. Methods: Fifty-four older people were divided into two groups (n = 27 each): subjects undergoing LSP and subjects not undergoing LSP (control). The LSP consisted of a combination of caloric restriction, physical activity, and psychological intervention and lasted 3 months. Plasma samples were taken before (T0) and after LSP (T1) and were used to measure thiobarbituric acid reactive substances (TBARS), 8-hydroxy-2-deoxyguanosine (8OHdG), 8-Isoprostanes (IsoP), glutathione (GSH), superoxide dismutase (SOD) activity and Tß4. In addition, plasma was used to stimulate human vascular endothelial cells (HUVEC), which were examined for cell viability, mitochondrial membrane potential, reactive oxygen species (ROS) and mitochondrial ROS (MitoROS) release. Results: At T1, in LSP group we did not detect the increase of plasma TBARS and IsoP, which was observed in control. Also, plasma levels of 8OHdG were lower in LSP group vs control. In addition, LSP group only showed an increase of plasma GSH and SOD activity. Moreover, plasma levels of Tß4 were more preserved in LSP group. Finally, at T1, in HUVEC treated with plasma from LSP group only we found an increase of the mitochondrial membrane potential and a reduction of ROS and MitoROS release in comparison with T0. Conclusions: The results of this study showed that a short LSP in older persons exerts antiaging effects by modulating oxidative stress also at cellular levels. Implications of those findings could be related to both prognostic and therapeutic strategies, which could be pursued as antiaging methods.

Impact of Human Milk Oligosaccharides and Probiotics on Gut Microbiome and Mood in Autism: A Case Report.

Recent evidence has highlighted the role of the gut-brain axis in the progression of autism spectrum disorder (ASD), with significant changes in the gut microbiome of individuals with this condition. This report investigates the effects of probiotics and human milk oligosaccharide (HMO) supplements on the gut microbiome, inflammatory cytokine profile, and clinical outcomes in an ASD adolescent with chronic gastrointestinal dysfunction and cognitive impairment. Following treatment, we observed a decrease in proinflammatory cytokines' concentration alongside Sutterella relative abundance, a bacterium reported to be linked with gastrointestinal diseases. Also, we reported a notable increase in mood stability. The study aims to evaluate the use of gut microbiome-based therapy in selected ASD patients, highlighting its potential to improve related clinical symptoms.

Next-generation sequencing reveals additional HLA class I and class II alleles associated with type 1 diabetes and age at onset.

Introduction: Type 1 diabetes is an autoimmune disease with an significant genetic component, played mainly by the HLA class II genes. Although evidence on the role of HLA class I genes in developing type 1 diabetes and its onset have emerged, current HLA screening is limited to determining DR3 and DR4 haplotypes. This study aimed to investigate the role of HLA genes on type 1 diabetes risk and age of onset by extensive typing. Methods: This study included 115 children and young adults with type 1 diabetes for whom typing of HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1 and -DPB1 genes was conducted using Next Generation Sequencing. Results: We observed that 13% of type 1 diabetes subjects had non-classical HLA haplotypes that predispose to diabetes. We also found that compared to type 1 diabetes subjects with classical HLA haplotypes, non-classical HLA subjects had a significantly higher frequency of HLA-B*39:06:02 (p-value=0.01) and HLA-C*07:02:01 (p-value=0.03) alleles, known to be involved in activating the immune response. Non-classical HLA subjects also presented peculiar clinical features compared to classical HLA subjects, such as multiple diabetic antibodies and the absence of other autoimmune diseases (i.e., coeliac disease and thyroiditis). We also observed that subjects with early onset had a higher frequency of DQ2/DQ8 genotype than late-onset individuals. Moreover, subjects with late-onset had a higher frequency of alleles HLA-B*27 (p-value=0.003), HLA-C*01:02:01 (p-value=0.027) and C*02:02:02 (p-value=0.01), known to be associated with increased protection against viral infections. Discussion: This study reveals a broader involvement of the HLA locus in the development and onset of type 1 diabetes, providing insights into new possible disease prevention and management strategies.

The Role of Family or Community Nurse in Dealing with Frail and Chronic Patients in Italy: A Scoping Review.

Even though Family and Community Nurses (FCNs) were introduced into the Italian healthcare system in 2000, to date, there is a substantial knowledge gap regarding the implementation of these professional figures within the Primary Care (PC) system. This scoping review aims to provide a comprehensive picture of the role of FCNs in managing older adults and the elderly with chronic conditions within the Italian PC system. A search on Medline, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Embase, and Scopus was conducted including studies published until 7 April 2023. Among 141 potential articles, only 4 met our inclusion criteria. Each of these studies attributed their findings to the presence of FCNs. They reported a significant decrease in the prevalence of several behaviours among patients diagnosed with hypertension, a reduction in metabolic complications among frail patients receiving home enteral nutrition, a decline in hospital readmissions or emergency services utilization among patients >65 years of ages with at least one chronic disease, and, notably, a high level of effectiveness in detecting major cardiovascular events in patients with cardiac implantable electronic devices. Despite the effectiveness of interventions managed by FCNs, comprehensive information and research on the integration of this role within the PC setting are still lacking in the Italian healthcare system.

The Deep Proteomics Approach Identified Extracellular Vesicular Proteins Correlated to Extracellular Matrix in Type One and Two Endometrial Cancer.

Among gynecological cancers, endometrial cancer is the most common in developed countries. Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles that contain proteins involved in immune response and apoptosis. A deep proteomic approach can help to identify dysregulated extracellular matrix (ECM) proteins in EVs correlated to key pathways for tumor development. In this study, we used a proteomics approach correlating the two acquisitions-data-dependent acquisition (DDA) and data-independent acquisition (DIA)-on EVs from the conditioned medium of four cell lines identifying 428 ECM proteins. After protein quantification and statistical analysis, we found significant changes in the abundance (p < 0.05) of 67 proteins. Our bioinformatic analysis identified 26 pathways associated with the ECM. Western blotting analysis on 13 patients with type 1 and type 2 EC and 13 endometrial samples confirmed an altered abundance of MMP2. Our proteomics analysis identified the dysregulated ECM proteins involved in cancer growth. Our data can open the path to other studies for understanding the interaction among cancer cells and the rearrangement of the ECM.

NH3 adsorption and competition with H2O on a hydroxylated aluminosilicate surface.

The interaction between ammonia (NH3) and (alumino)silicates is of fundamental and applied importance, yet the specifics of NH3 adsorption on silicate surfaces remain largely unexplored, mainly because of experimental challenges related to their electrically insulating nature. An example of this knowledge gap is evident in the context of ice nucleation on silicate dust, wherein the role of NH3 for ice nucleation remains debated. This study explores the fundamentals of the interaction between NH3 and microcline feldspar (KAlSi3O8), a common aluminosilicate with outstanding ice nucleation abilities. Atomically resolved non-contact atomic force microscopy, x-ray photoelectron spectroscopy, and density functional theory-based calculations elucidate the adsorption geometry of NH3 on the lowest-energy surface of microcline, the (001) facet, and its interplay with surface hydroxyls and molecular water. NH3 and H2O are found to adsorb molecularly in the same adsorption sites, creating H-bonds with the proximate surface silanol (Si-OH) and aluminol (Al-OH) groups. Despite the closely matched adsorption energies of the two molecules, NH3 readily yields to replacement by H2O, challenging the notion that ice nucleation on microcline proceeds via the creation of an ordered H2O layer atop pre-adsorbed NH3 molecules.

Effectiveness of a combined lifestyle intervention for older people in long-term care: A randomized controlled trial.

PURPOSE: Lifestyle medicine interventions combining physical, nutritional, and psychological components have been found effective in general older population. However, evidence from the long-term care (LTC) is scarce. METHODS: We conducted a pragmatic, two-arm, parallel group, superiority randomized controlled trial. Residents living in a LTC facility for one or more years, able to discern and to express informed consent, and requiring nursing care were considered eligible. The three-months intervention combined bi-weekly physical exercise groups, a healthy diet, and weekly psychological wellbeing sessions. Patients of the control group were subjected to routine care. At the end of the study participants were assessed using Barthel Index, Katz Activities of Daily Living, and Tinetti scales. RESULTS: A total of 54 patients with a mean age of 84 years took part to the study. Physical exercise and psychological wellbeing sessions were mostly attended by all the subjects of the intervention group. Both groups took less calories than planned in the diets; in addition, the intervention group showed a lower energy and carbohydrates intake than the control group. At the end of the study, the intervention group showed a significant improvement in the total scores of all the scales. CONCLUSIONS: This intervention was effective in improving functionality in older people living in the LTC setting. Results were achieved in a short timeframe, likely due to synergistic interactions between components. However, a further exploration of underlying factors is needed, to better understand the barriers that hampered a complete intervention delivery in this context.

Traditional Lecture Versus Procedural Video Randomized Trial: Comparative Analysis of Instructional Methods for Teaching Baclofen Pump Management.

OBJECTIVE: This study compared the effectiveness of traditional lectures and microvideos in teaching baclofen pump programming and refilling to physicians who have completed less than 10 refills for the previous 2 yrs. DESIGN: A mixed-method approach was used with 60 participating physicians specializing in physical medicine and rehabilitation or pain management. Preintervention and postintervention assessments were conducted using a rubric, and the participants' perceptions and preferences were gathered through focus group sessions. RESULTS: Two thirds of the participants specialized in physical medicine and rehabilitation. No significant differences in the preintervention, postintervention, or knowledge retention scores were found between the traditional lecture and microvideo groups. Both methods demonstrated comparable effectiveness in improving the baclofen pump refilling and programming skills. Qualitatively, participants perceived both approaches as equally helpful, but those in the microvideo group raised concerns because of instructors' unavailability and online platform navigation. Nevertheless, they preferred the convenience, accessibility, and time efficiency of the microvideos. CONCLUSIONS: The study concluded that microvideos are an effective alternative to traditional lectures for acquiring knowledge on baclofen pump programming and refilling. Further research should consider learners' characteristics and investigate the benefits of blended learning in medical education.

Multi-failure psoriasis patients: characterization of the patients and response to biological therapy in a multicenter Italian cohort.

INTRODUCTION: Patients with psoriasis who have failed multiple biologic drugs have been defined as "multi-failure," although there are no clear data on the characteristics, comorbidities, and best treatment strategies for this population. Nowadays, given the next generation and the number of biologics available, patients are considered multi-failure when ≥4 biologics fail to achieve a good response. METHODS: Demographic characteristics and efficacy of anti-interleukin drugs in multi-failure patients were compared to a cohort of general psoriatic patients treated with IL-23 or IL-17 inhibitors. RESULTS: In total 97 multi-failure patients (≥4 lines of biologics) were compared with 1,057 patients in the general cohort. The current drugs in the multi-failure group were risankizumab (34), ixekizumab (23), guselkumab (21), brodalumab (7), tildrakizumab (5), ustekinumab (4), secukinumab (2), and certolizumab pegol (1). A significant difference was found in the multi-failure cohort for age of psoriasis onset (mean 29.7 vs. 35.1, P < 0.001), concurrent psoriatic arthritis (45.4 vs. 26.9%, P < 0.001), diabetes mellitus (30.9 vs. 10.9%, P < 0.001), and cardiovascular comorbidity (54.6 vs. 39.8%, P = 0.005). In multi-failure patients, current biological therapy showed a good initial response (PASI 90 and 100 of 41.24 and 27.84%, respectively, at 16 weeks); the response tended to decline after 40 weeks. Anti-IL-17 agents showed clinical superiority over IL-23 agents in terms of achieving PASI90 at 28 weeks (P < 0.001) and 40 weeks (P = 0.007), after which they reached a plateau. In contrast, IL-23 agents showed a slower but progressive improvement that was maintained for up to 52 weeks. A similar trend was also seen for PASI100 (28 weeks P = 0.032; 40 weeks P = 0.121). CONCLUSIONS: The multi-failure patient is characterized by many comorbidities and longstanding inflammatory disease that frequently precedes the introduction of systemic biologic therapy. Further studies are needed to identify more specific criteria that could be applied as a guideline by clinicians.

How Water Binds to Microcline Feldspar (001).

Microcline feldspar (KAlSi3O8) is a common mineral with important roles in Earth's ecological balance. It participates in carbon, potassium, and water cycles, contributing to CO2 sequestration, soil formation, and atmospheric ice nucleation. To understand the fundamentals of these processes, it is essential to establish microcline's surface atomic structure and its interaction with the omnipresent water molecules. This work presents atomic-scale results on microcline's lowest-energy surface and its interaction with water, combining ultrahigh vacuum investigations by noncontact atomic force microscopy and X-ray photoelectron spectroscopy with density functional theory calculations. An ordered array of hydroxyls bonded to silicon or aluminum readily forms on the cleaved surface at room temperature. The distinct proton affinities of these hydroxyls influence the arrangement and orientation of the first water molecules binding to the surface, holding potential implications for the subsequent condensation of water.

Long-Term Drug Survival and Effectiveness of Secukinumab in Patients with Moderate to Severe Chronic Plaque Psoriasis: 42-Month Results from the SUPREME 2.0 Study.

Purpose: SUPREME, a phase IIIb study conducted in Italy, demonstrated safety and high efficacy of secukinumab for up to 72 weeks in patients with moderate-to-severe plaque-type psoriasis. SUPREME 2.0 study aimed to provide real-world data on the long-term drug survival and effectiveness of secukinumab beyond 72 weeks. Patients and Methods: SUPREME 2.0 is a retrospective observational chart review study conducted in patients previously enrolled in SUPREME study. After the end of the SUPREME study, eligible patients continued treatment as per clinical practice, and their effectiveness and drug survival data were retrieved from medical charts. Results: Of the 415 patients enrolled in the SUPREME study, 297 were included in SUPREME 2.0; of which, 210 (70.7%) continued secukinumab treatment throughout the 42-month observation period. Patients in the biologic-naïve cohort had higher drug survival than those in the biologic-experienced cohort (74.9% vs 61.7%), while HLA-Cw6-positive and HLA-Cw6-negative patients showed similar drug survival (69.3% and 71.9%). After 42 months, Psoriasis Area and Severity Index (PASI) 90 was achieved by 79.6% of patients overall; with a similar proportion of biologic-naïve and biologic-experienced patients achieving PASI90 (79.8% and 79.1%). The mean absolute PASI score reduced from 21.94 to 1.38 in the overall population, 21.90 to 1.24 in biologic-naïve and 22.03 to 1.77 in biologic-experienced patients after 42 months. The decrease in the absolute PASI score was comparable between HLA-Cw6-positive and HLA-Cw6-negative patients. The baseline Dermatology Life Quality Index scores also decreased in the overall patients (10.5 to 2.32) and across all study sub-groups after 42 months. Safety was consistent with the known profile of secukinumab, with no new findings. Conclusion: In this real-world cohort study, secukinumab showed consistently high long-term drug survival and effectiveness with a favourable safety profile.

Diagnosis of prostate cancer with magnetic resonance imaging in men treated with 5-alpha-reductase inhibitors.

PURPOSE: The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2). METHODS: This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients. RESULTS: 705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1-2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively. CONCLUSIONS: Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions. TRIAL REGISTRATION: The present study was registered at ClinicalTrials.gov number: NCT05078359.

Reduced Graphene Oxide Electrolyte-Gated Transistor Immunosensor with Highly Selective Multiparametric Detection of Anti-Drug Antibodies.

The advent of immunotherapies with biological drugs has revolutionized the treatment of cancers and auto-immune diseases. However, in some patients, the production of anti-drug antibodies (ADAs) hampers the drug efficacy. The concentration of ADAs is typically in the range of 1-10 pm; hence their immunodetection is challenging. ADAs toward Infliximab (IFX), a drug used to treat rheumatoid arthritis and other auto-immune diseases, are focussed. An ambipolar electrolyte-gated transistor (EGT) immunosensor is reported based on a reduced graphene oxide (rGO) channel and IFX bound to the gate electrode as the specific probe. The rGO-EGTs are easy to fabricate and exhibit low voltage operations (≤ 0.3 V), a robust response within 15 min, and ultra-high sensitivity (10 am limit of detection). A multiparametric analysis of the whole rGO-EGT transfer curves based on the type-I generalized extreme value distribution is proposed. It is demonstrated that it allows to selectively quantify ADAs also in the co-presence of its antagonist tumor necrosis factor alpha (TNF-α), the natural circulating target of IFX.