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Previous published studies have shown an improvement of penile hemodynamic parameters after low-intensity extracorporeal shockwave therapy (Li-ESWT). However, the clinical significance of these findings remains unclear, and definitive selection criteria for Li-ESWT based on preexisting comorbidities have yet to be established. This was an observational study of 113 patients with ED, evaluated between January 2019 and December 2021 in Andrology Unit at the Department of Urology and Renal Transplantation, University of Foggia (Foggia, Italy). Penile dynamic Doppler was performed to evaluate vascular parameters and 5-item version of the International Index of Erectile Dysfunction (IIEF-5) questionnaire was administered to assess the severity of ED. This was repeated 1 month after treatment. Patients with a peak systolic velocity (PSV) 30 cm s−1 at posttherapeutic penile dynamic Doppler. A clinically significant IIEF-5 score improvement was observed in 7 patients, 21 patients, and 2 patients with mild-to-moderate, moderate, and severe pretreatment ED, respectively. No different outcomes were assessed based on smoking habits, previous pelvic surgery, or use of oral phosphodiesterase-5 inhibitor (PDE5i). On the other side, only 1 (6.7%) in 15 patients with diabetes mellitus showed an IIEF-5 score improvement after Li-ESWT. Shockwave treatment determined a significant increase in PSV and correlated IIEF-5 improvement in ED patients. This advantage seemed particularly evident for moderate ED and was not affected by smoking habits, previous pelvic surgery, and use of PDE5i. Conversely, diabetic patients did not benefit from the treatment.

Oxidative stress is one of the main mechanisms responsible for male infertility. Various conditions such as varicocele, obesity, advanced age, and lifestyle can lead to an increase in reactive oxygen species, causing an oxidative imbalance in the reproductive environment. Spermatozoa are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizing the egg. Excessive reactive oxygen species can affect sperm metabolism, leading to immobility, impaired acrosome reaction, and cell death, thereby impairing reproductive success. This double-blind randomized study evaluated the effect of supplementation with L-carnitine, acetyl-L-carnitine, vitamins, and other nutrients on semen quality in 104 infertile patients with or without varicocele, while also investigating the impact of factors such as obesity and advanced age on treatment. Sperm concentration significantly increased in the supplemented group compared to the placebo group (P = 0.0186). Total sperm count also significantly increased in the supplemented group (P = 0.0117), as did sperm motility (P = 0.0120). The treatment had a positive effect on patients up to 35 years of age in terms of sperm concentration (P = 0.0352), while a body mass index (BMI) above 25 kg m−2 had a negative effect on sperm concentration (P = 0.0110). Results were not showing a net benefit in stratifying patients in accordance with their BMI since sperm quality increase was not affected by this parameter. In conclusion, antioxidant supplementation may be beneficial for infertile patients and has a more positive effect on younger patients with a normal weight.

Non-Hodgkin lymphomas (NHLs) encompass a diverse group of malignancies arising from B cells, T cells, and natural killer (NK) cells at various stages of differentiation. Conversely, classical Hodgkin lymphomas (cHLs) primarily feature Reed-Sternberg cells (RSCs) amid a background of reactive immune cells. Immunomodulatory pathways, notably the PD-1/PD-L1 axis, play pivotal roles in tumor immune evasion across both NHLs and cHLs. Elevated expression of PD-1 and PD-L1 is observed in a spectrum of lymphomas, influencing prognosis and treatment response. Therapeutically, immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have revolutionized lymphoma management, particularly in relapsed/refractory cases. Nivolumab and pembrolizumab, among others, have demonstrated efficacy in various B-cell lymphomas, with promising outcomes in cHL. Combination strategies incorporating ICIs with conventional chemotherapy or targeted agents show enhanced efficacy and are being explored extensively. In this review we discuss the most important features of the tumor microenvironment of NHLs and cHLs, address the therapeutic approaches with ICIs and try to outline future perspectives.

Blended learning usually refers to the combination of online/offline instructional methods. In this paper, we describe a university course in "E-learning Psychology" designed to blend not only modes of teaching, tools, and media, but also learning contexts; specifically, academic and professional contexts. To achieve an effective blend of learning contexts, students were monitored by academic and company tutors through an instant messaging app (WhatsApp). The unique contribution of the company tutor to the blending of academic and professional contexts is explored. By qualitatively analyzing (i) process data (four WhatsApp log chats) and (ii) self-report data (interviews with six company tutors), we found that the company tutor contributed to both the traditional blended dimension (mixing online and offline) and to the blend of the academic and professional contexts. When company tutors participated in the chat, students moved from an organizational dynamic, featuring chats monitored by only the academic tutor, toward a more collaborative and reflective dynamic. The company tutors considered the opportunity to blend academic and professional contexts as the best aspect of the course for both themselves as educators/company representatives, and for the students. This paper offers insights into the ongoing discussion about what blended is--or should be--and the role of company tutors in blending educational contexts.

BACKGROUND: There is limited evidence on the efficacy of peroral endoscopic myotomy (POEM) in patients with esophageal diverticula. AIMS: This meta-analysis aimed to assess the efficacy and safety profile of POEM in patients with Zenker (ZD) and epiphrenic diverticula. METHODS: With a literature search through August 2020, we identified 12 studies (300 patients) assessing POEM in patients with esophageal diverticula. The primary outcome was treatment success. Results were expressed as pooled rates and 95% confidence intervals. RESULTS: Pooled rate of technical success was 95.9% (93.4%-98.3%) in ZD patients and 95.1% (88.8%-100%) in patients with epiphrenic diverticula. Pooled rate of treatment success was similar for ZD (90.6%, 87.1%-94.1%) and epiphrenic diverticula (94.2%, 87.3%-100%). Rates of treatment success were maintained at 1 year (90%, 86.4%-97.4%) and 2 years (89.6%, 82.2%-96.9%) in ZD patients. Pooled rate of symptom recurrence was 2.6% (0.9%-4.4%) in ZD patients and 0% in patients with epiphrenic diverticula. Pooled rates of adverse events and severe adverse events were 10.6% (4.6%-16.6%) and 3.5% (0%-7.4%) in ZD and 8.4% (0%-16.8%) and 8.4% (0%-16.8%) in epiphrenic diverticula, respectively. CONCLUSION: POEM represents an effective and safe therapy for the treatment of esophageal diverticula.

Abstract Urban regeneration is aimed at improving settlement contexts, and indirectly at solving the housing issue. In Italy there is no national regulation on urban regeneration, but many policies from 2000 up to now have resorted to it with the aim of intervening and containing the housing problem. The work examines the city of Foggia, in southern Italy, an area in a demographic contraction, but equally characterized by “high housing tension”, indeed there are numerous eviction proceedings, in the private and public sector of the house, and, as a consequence, phenomena of illegal occupation housing, abandoned buildings, informal settlements. The research will look at how in the last 20 years various national public funding (among these, the last PNRR—Piano Nazionale di Ripresa e Resilienza derived from the Next Generation EU) and regional ones have resorted to urban regeneration strategies to address the problem, reporting failures, gaps and relevant issues.

Abstract We have developed a state-of-the-art apparatus for laser-based spin- and angle-resolved photoemission spectroscopy with micrometer spatial resolution (µ-SARPES). This equipment is realized by the combination of a high-resolution photoelectron spectrometer, a 6 eV laser with high photon flux that is focused down to a few micrometers, a high-precision sample stage control system, and a double very-low-energy-electron-diffraction spin detector. The setup achieves an energy resolution of 1.5 (5.5) meV without (with) the spin detection mode, compatible with a spatial resolution better than 10 µm. This enables us to probe both spatially-resolved electronic structures and vector information of spin polarization in three dimensions. The performance of µ-SARPES apparatus is demonstrated by presenting ARPES and SARPES results from topological insulators and Au photolithography patterns on a Si (001) substrate.

The increasing importance of treatment of lower urinary tract symptoms (LUTS), while avoiding side effects and maintaining sexual function, has allowed for the development of minimally invasive surgical therapies (MISTs). Recently, the European Association of Urology guidelines reported a paradigm shift from the management of benign prostatic hyperplasia (BPH) to the management of nonneurogenic male LUTS. The aim of the present review was to evaluate the efficacy and safety of the most commonly used MISTs: ablative techniques such as aquablation, prostatic artery embolization, water vapor energy, and transperineal prostate laser ablation, and nonablative techniques such as prostatic urethral lift and temporarily implanted nitinol device (iTIND). MISTs are becoming a new promise, even if clinical trials with longer follow-up are still lacking. Most of them are still under investigation and, to date, only a few options have been given as a recommendation for use. They cannot be considered as standard of care and are not suitable for all patients. Advantages and disadvantages should be underlined, without forgetting our objective: treatment of LUTS and re-treatment avoidance.

Abstract Edible electronics leverages the electronic properties of food‐derived materials to deliver safer technologies that can be degraded (or digested) in the environment (or body) at the end‐of‐life. Sensors will be central to future smart edible robots, and edible strain sensors are particularly interesting as they can transduce deformation, providing real time feedback of the movement. Yet, to date edible strain sensors have been limited to the use of ionic conductive hydrogels, resulting in sensors not directly suitable for direct current operation and therefore not compatible with existing edible batteries. Here, the first edible strain sensor based on electronic conduction made of a novel conductive ink sprayed over an edible substrate is presented. The ink formulation consists of activated carbon (conductor), Haribo gummy bears (binder), and water−ethanol mixture (dispersant). The ink, deposited on multiple substrates by spray deposition, produces edible electrically conductive composite coatings with resistivity of ≈50 Ω cm. The coatings were used as a piezoresistive layer to fabricate strain sensors with gauge factors of 19−92 suitable for direct current operation. As a proof‐of‐concept of future edible systems, the sensor is validated by integrating it within a gelatin actuator to produce a sensorized gripper powered by an edible battery.

Meningioma represents the most frequent tumor of the central nervous system (CNS). Correlations between the presence of mast cells (MCs) and grade or other histological features of meningioma are still debated. Our study aimed to better understand the relationship between mast cells and meningiomas and to compare our results based on specific histological subtypes and novel 2021 CNS WHO grading system. We observed some differences as regards the number of MCs and meningioma grade. In low-grade (grade 1) meningiomas, MCs were observed in 7/22 cases, while they were consistently present in all eight high-grade cases (grade 2 and grade 3). Among the grade 1 meningiomas, we observed two “low-positive”, two “intermediate-positive”, and three “high-positive” cases. Among the group of high-grade meningiomas, the six cases grade 2 were considered as “low-positive”, while the two grade 3 cases showed a higher number of MCs and were included in the “intermediate-positive” group. Even though with no statistical significance, due to the low number of cases, our results seem to confirm a sort of relationship between meningioma grading and the number of MCs, as demonstrated by the higher percentage of high-grade meningiomas showing MCs infiltrates, compared to low-grade meningiomas.

Zenker’s Diverticulum (ZD) is the most common hypopharyngeal diverticulum; however, it is often underdiagnosed. It results from the herniation of the mucosa and submucosa through Killian’s Triangle. Dysphagia is the primary symptom, occurring in 80–90% of cases. The primary goal of treatment is to transect the cricopharyngeal muscle (CM) and connect the ZD cavity to the esophageal lumen. Traditional treatments include surgical open transcervical diverticulectomy and CM septomyotomy, using rigid or flexible endoscopes. However, surgery is burdened by technical difficulties and not negligible rates of adverse events (AEs). For this reason, endoscopic techniques for ZD treatment have gained traction in recent years. Flexible endoscopic septum division (FESD), introduced nearly 20 years ago, involves a full-thickness incision of the diverticular septum. The advent of third-space endoscopy has led to the application of these techniques to ZD treatment as well. Zenker-POEM (Z-POEM) and, subsequently, Per Oral Endoscopic Septomyotomy (POES) have been developed. Hybrid techniques, such as Peroral Endoscopic Diverticulotomy (POED) and tunneling-free methods, represent additional ZD treatment options. This review outlines the armamentarium of ZD endoscopic management, summarizing the characteristics of these techniques, their benefits and limitations, and highlighting future research directions.

Introduction: Urinary incontinence is a prevalent condition, especially in elderly men, with stress urinary incontinence (SUI) being a common cause after radical prostatectomy. The artificial urinary sphincter (AUS), particularly the AMS 800™ device, has been the gold-standard treatment for moderate-severe male SUI for decades. Despite some technical advancements and alternative devices like ZSI-375, Victo, and BR-SL-AS 904 being introduced, there is limited literature comparing their effectiveness to the AMS 800™. Methods: This literature review compares the AMS 800™ to the newer technologies in the management of SUI. We reviewed the current literature on urinary sphincter implant in male stress incontinence, including AMS 800™, ZSI-375, Victo, and BR-SL-AS 904. Findings: The AMS 800™ is a sophisticated system consisting of an inflatable cuff, a pressure-regulating balloon, and a control pump. Studies show continence rates ranging from 61% to 100% with AMS 800™ implants, with low infection rates and significant improvement in patients’ quality of life. The ZSI-375 sphincter is a unique single-piece cuff without an abdominal reservoir, simplifying implantation. Preliminary data show a social continence rate of 73% at six months, with lower complication rates than the AMS 800™. The VICTO® device offers adjustable pressure and a stress relief mechanism, providing conditional occlusion of the urethra. Early studies report a satisfaction rate of up to 94.2% and a complication rate of 17.6%. BR-SL-AS 904 is a newly proposed urinary sphincter, but due to the limited number of cases and a single study, its efficacy and complication rates remain uncertain. Conclusions: Overall, AMS 800™ remains the gold-standard treatment for SUI after radical prostatectomy. Alternative devices like ZSI-375 and VICTO® show promising results, but longer studies and more data are needed to establish their effectiveness and safety compared with the AMS 800™. Further research and ongoing monitoring are essential to address mechanical issues associated with AUS implants.

Background: A growing body of evidence underscores the beneficial impact of therapeutic drug monitoring (TDM) on the efficacy and cost-effectiveness of anti-tumour necrosis factor (TNF) therapy in patients with inflammatory bowel disease (IBD). Objectives: We surveyed clinician attitudes, perceptions and barriers related to TDM in IBD in the Middle East. Design: A 15-question survey was distributed through national gastroenterological societies in five Middle Eastern countries (UAE, Saudi Arabia, Kuwait, Lebanon and Egypt). Methods: Data on clinician characteristics, demographics, utilization patterns and obstacles related to the adoption of TDM with anti-TNFs were gathered. Logistic regression analysis was used to predict factors influencing the utilization of TDM. Results: Among 211 respondents (82% male), 82% were consultants, 8% were physicians with an interest in gastroenterology (GI), and 6% were GI trainees. Of these, 152 met inclusion criteria, treating >5 IBD patients per month and ⩾1 with an anti-TNF per month. TDM was used in clinical practice by 78% (95% CI: 71–85) of respondents. TDM was utilized following the loss of response (LOR) in 93%, for primary non-response (PNR) in 40% and before restarting anti-TNF therapy after a drug holiday in 33% of respondents, while 34% used TDM proactively. No specific factors were associated with the use of TDM. Barriers to TDM use included cost (85%), time lag to results (71%) and lack of insurance reimbursement (65%). Overall knowledge of TDM (70%), interpretation and actioning of results (76%) or awareness of clinical guidelines (57%) were not perceived as barriers. If barriers were removed, 95% would use TDM more frequently; 93% for LOR, 60% for PNR, 50% when restarting after a drug holiday, and 54% would use TDM proactively. Conclusion: Most gastroenterologists use TDM for LOR, with cost, time lag and insurance reimbursement being significant barriers. Addressing these barriers would increase the judicious use of reactive and proactive TDM to optimize anti-TNF therapy in IBD.

BackgroundSeveral interventions with variable efficacy are available as first-line therapy for patients with achalasia. We assessed the comparative efficacy of different strategies for management of achalasia, through a network meta-analysis combining direct and indirect treatment comparisons.MethodsWe identified six randomized controlled trials in adults with achalasia that compared the efficacy of pneumatic dilation (PD; n = 260), laparoscopic Heller myotomy (LHM; n = 309), and peroral endoscopic myotomy (POEM; n = 176). Primary efficacy outcome was 1-year treatment success (patient-reported improvement in symptoms based on validated scores); secondary efficacy outcomes were 2-year treatment success and physiologic improvement; safety outcomes were risk of gastroesophageal reflux disease (GERD), severe erosive esophagitis, and procedure-related serious adverse events. We performed pairwise and network meta-analysis for all treatments, and used GRADE criteria to appraise quality of evidence.ResultsLow-quality evidence, based primarily on direct evidence, supports the use of POEM (RR [risk ratio], 1.29; 95% confidence intervals [CI], 0.99-1.69), and LHM (RR, 1.18 [0.96-1.44]) over PD for treatment success at 1 year; no significant difference was observed between LHM and POEM (RR 1.09 [0.86-1.39]). The incidence of severe esophagitis after POEM, LHM, and PD was 5.3%, 3.7%, and 1.5%, respectively. Procedure-related serious adverse event rate after POEM, LHM, and PD was 1.4%, 6.7%, and 4.2%, respectively.ConclusionsPOEM and LHM have comparable efficacy, and may increase treatment success as compared to PD with low confidence in estimates. POEM may have lower rate of serious adverse events compared to LHM and PD, but higher rate of GERD.

IgA Nephropathy (IgAN) is the most common form of primary glomerulonephritis and is one of the most common causes of end-stage kidney disease (ESKD) worldwide. The immunopathogenic mechanism underlying IgAN is poorly identified. Currently, the mainstay treatment of IgAN is centered on the optimization of blood pressure and a reduction in proteinuria, using an angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARBs). According to KDIGO, patients who persistently remain at a high risk of progressive ESKD, despite maximal supportive care, are candidates for glucocorticoid therapy. Recent discoveries regarding the pathogenesis of this disease have led to the testing of new therapeutic drugs targeting, in particular, the excessive mucosal immune reaction and the resulting systemic response as well as the complement activation and the following kidney damage and fibrosis. In this review, we examine the various therapeutic approaches to this intriguing disease.

Abstract Background Lymphatic complications are common in patients with Fontan circulation. Three-dimensional balanced steady-state free precession (3D bSSFP) angiography by cardiovascular magnetic resonance (CMR) is widely used for cardiovascular anatomical assessment. We sought to determine the frequency of thoracic duct (TD) visualization using 3D bSSFP images and assess whether TD characteristics are associated with clinical outcomes. Methods This was a retrospective, single-center study of patients with Fontan circulation who underwent CMR. Frequency matching of age at CMR was used to construct a comparison group of patients with repaired tetralogy of Fallot (rTOF). TD characteristics included maximum diameter and a qualitative assessment of tortuosity. Clinical outcomes included protein-losing enteropathy (PLE), plastic bronchitis, listing for heart transplantation, and death. A composite outcome was defined as presence of any of these events. Results The study included 189 Fontan patients (median age 16.1 years, IQR 11.0–23.2 years) and 36 rTOF patients (median age 15.7 years, IQR 11.1–23.7 years). The TD diameter was larger (median 2.50 vs. 1.95 mm, p = 0.002) and more often well visualized (65% vs. 22%, p

This paper aims to investigate how empathy and assertiveness are expressed linguistically in two corpora (MUJERES y HOMBRES) of fifteen TED talks each, with a view to identifying whether the women in the sample adopt a more empathetic communicative style than men. The frequency and use of deictics, and a number of intensifiers and hedges will be analyzed starting from the comparison of key POS lists in the two corpora. The results of the study suggest a marked preference of the women in the sample for the use of affiliative, empathetic mechanisms, since they employ first person narratives associated with affective vocabulary, inclusive nosotros, question tags and verbs in the second person plural more often (although for the same purposes) than men.

Abstract Edible electronics and robotics are emerging areas intimately bridging food science and engineering to deliver technology using food‐derived materials. Edible devices offer unprecedented opportunities thanks to features such as bioresorbability, nutritional value, associated taste, minimal toxicity, and sustainability. However, several challenges need to be addressed to bring edible devices closer to reality. Although prototypal edible sensors are available, rotation sensors—an essential component for orientation perception—are still missing. Integrating sensors, actuators, and structural components into an edible system also remains a challenge due to the lack of processes and standardization. Here the first edible tilt sensor is presented. Starting from a commercial nonedible bistable tilt sensor, each material is replaced with edible equivalents using simple and straightforward fabrication approaches. Its functionality is validated in the first implementation of an autonomous and partly edible rolling robot, which has a nutritional value of 807.5 kcal and integrates gelatin actuators, an array of tilt sensors, and an edible wheeled frame. The robot works in closed loop, perceiving its orientation and input for actuation from the sensors. These findings may pave the way to novel edible technologies, from drug delivery for wild animals to health applications.

Three different mechanisms of neovascularization have been described in tumor growth, including sprouting angiogenesis, intussusceptive microvascular growth and glomeruloid vascular proliferation. Tumors can also grow by means of alternative mechanisms including vascular co-option, vasculogenic mimicry, angiotropism, and recruitment of endothelial precursor cells. Vascular co-option occurs in tumors independently of sprouting angiogenesis and the non-angiogenic cancer cells are described as exploiting pre-existing vessels. Vascular co-option is more frequently observed in tumors of densely vascularized organs, including the brain, lung and liver, and vascular co-option represents one of the main mechanisms involved in metastasis, as occurs in liver and lung, and resistance to anti-angiogenic therapy. The aim of this review article is to analyze the role of vascular co-option as mechanism through which tumors develop resistance to anti-angiogenic conventional therapeutic approaches and how blocking co-option can suppress tumor growth.

Summary: Decades of research have not yet fully explained the mechanisms of epithelial self-organization and 3D packing. Single-cell analysis of large 3D epithelial libraries is crucial for understanding the assembly and function of whole tissues. Combining 3D epithelial imaging with advanced deep-learning segmentation methods is essential for enabling this high-content analysis. We introduce CartoCell, a deep-learning-based pipeline that uses small datasets to generate accurate labels for hundreds of whole 3D epithelial cysts. Our method detects the realistic morphology of epithelial cells and their contacts in the 3D structure of the tissue. CartoCell enables the quantification of geometric and packing features at the cellular level. Our single-cell cartography approach then maps the distribution of these features on 2D plots and 3D surface maps, revealing cell morphology patterns in epithelial cysts. Additionally, we show that CartoCell can be adapted to other types of epithelial tissues. Motivation: A major bottleneck in developing neural networks for cell segmentation is the need for labor-intensive manual curation to develop a training dataset. The present work addresses this limitation by developing an automated image-analysis pipeline that utilizes small datasets to generate accurate labels of cells in complex 3D epithelial contexts. The overall goal is to provide an automatic and feasible method to achieve high-quality epithelial reconstructions and to enable high-content analysis of morphological features, which can improve our understanding of how these tissues self-organize.

We report neuropsychological and neuropathological findings for a patient (A.B.), who developed memory impairment after a cardiac arrest at age 39. A.B. was a clinical psychologist who, although unable to return to work, was an active participant in our neuropsychological studies for 24 y. He exhibited a moderately severe and circumscribed impairment in the formation of long-term, declarative memory (anterograde amnesia), together with temporally graded retrograde amnesia covering ∼5 y prior to the cardiac arrest. More remote memory for both facts and autobiographical events was intact. His neuropathology was extensive and involved the medial temporal lobe, the diencephalon, cerebral cortex, basal ganglia, and cerebellum. In the hippocampal formation, there was substantial cell loss in the CA1 and CA3 fields, the hilus of the dentate gyrus (with sparing of granule cells), and the entorhinal cortex. There was also cell loss in the CA2 field, but some remnants remained. The amygdala demonstrated substantial neuronal loss, particularly in its deep nuclei. In the thalamus, there was damage and atrophy of the anterior nuclear complex, the mediodorsal nucleus, and the pulvinar. There was also loss of cells in the medial and lateral mammillary nuclei in the hypothalamus. We suggest that the neuropathology resulted from two separate factors: the initial cardiac arrest (and respiratory distress) and the recurrent seizures that followed, which led to additional damage characteristic of temporal lobe epilepsy.

Background: Urine cytology is useful to diagnose urinary neoplasms, whereas its role in the study of microhematuria is debatable. Usually, standard urinalysis (dipstick test and sediment examination with bright field microscope) detects the presence of microhematuria, but only urinalysis with phase-contrast microscopy (PCM) (dipstick test and sediment examination with PCM) allows the observation of red blood cell (RBC) morphology and identify their source. Usually glomerular diseases show RBCs with morphological alterations in high percentages, whereas on urologic bleeding, RBCs are rather homogeneous without morphological alterations. Aims: We compare, for the first time, RBC morphology observed in urine cytology and in urinalysis with PCM, to verify whether urinary cytology allows the recognition of the source of bleeding. Methods and Material: A total of 60 patients who had performed both urine cytology and urinalysis with PCM for microhematuria, detected with standard urinalysis, were investigated. Urine cytology showed RBCs and were negative for neoplastic cells or for inflammatory events. Urine samples were processed with the automated method ThinPrep®. RBCs with abnormal and variable shapes were defined as deformed. RBCs of the same spherical shape were defined as non-deformed. Results: Fifty-six urine cytology with RBCs deformed were confirmed in 55 urinalysis with PCM. One case showed RBCs non deformed in urine cytology and in urine sediment. Overall, agreement, between RBC morphology in urine cytology and urinalysis with PCM, was found in 56/60 cases (93%). Conclusions: Therefore, since sediment examination with PCM is available in only few laboratories, we propose that cytopathologist always reports, in urine cytology, any morphological abnormalities of RBCs in order to provide information of the hematuria origin and correctly refer the patient to a nephrologist rather than a urologist.

Conclusions: The results of this study provide an overview of the variations in microbiota diversity present in Saudi IBD patients compared to healthy controls. Results: The key finding was three negative bacterial biomarkers, Paraprevotellaceae, the Muribaculaceae families of Bacteroidetes phylum, and the Leuconostocaceae family of Firmicutes phylum, which had a higher relative abundance in healthy individuals compared to IBD patients. It was also found that primary microbiota signatures at certain genera and species levels, including Prevotella copri, Bifidobacterium adolescentis, Ruminococcus callidus, Coprococcus sp., Ruminococcus gnavus, Dorea formicigenerans, Leuconostoc, Dialister, Catenibacterium, Eubacterium biforme, and Lactobacillus mucosae, were absent in almost all IBD patients, while Veillonella dispar was absent in all healthy individuals. Methods: After obtaining an informed consent, fecal samples were collected from 11 participants with IBD (patients) and 10 healthy individuals (controls). The bacterial components of the microbial population were identified by next-generation sequencing of partial 16S rRNA. Statistically significant dissimilarities were observed between samples for all metrics. Background: Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory condition attributed to a complex interaction between imbalances in the gut microbiome, environmental conditions, and a deregulated immune response. The aim of the study was to investigate the composition of the gut microbiome of Saudi patients with IBD.

Background & Aims: DNA methylation alterations may provide important insights into gene-environment interaction in cancer, aging, and complex diseases, such as inflammatory bowel disease (IBD). We aim first to determine whether the circulating DNA methylome in patients requiring surgery may predict Crohn’s disease (CD) recurrence following intestinal resection; and second to compare the circulating methylome seen in patients with established CD with that we had reported in a series of inception cohorts. Methods: TOPPIC was a placebo-controlled, randomized controlled trial of 6-mercaptopurine at 29 UK centers in patients with CD undergoing ileocolic resection between 2008 and 2012. Genomic DNA was extracted from whole blood samples from 229 of the 240 patients taken before intestinal surgery and analyzed using 450KHumanMethylation and Infinium Omni Express Exome arrays (Illumina, San Diego, CA). Coprimary objectives were to determine whether methylation alterations may predict clinical disease recurrence; and to assess whether the epigenetic alterations previously reported in newly diagnosed IBD were present in the patients with CD recruited into the TOPPIC study. Differential methylation and variance analysis was performed comparing patients with and without clinical evidence of recurrence. Secondary analyses included investigation of methylation associations with smoking, genotype (MeQTLs), and chronologic age. Validation of our previously published case-control observation of the methylome was performed using historical control data (CD, n = 123; Control, n = 198). Results: CD recurrence in patients following surgery is associated with 5 differentially methylated positions (Holm P < .05), including probes mapping to WHSC1 (P = 4.1 × 10-9, Holm P = .002) and EFNA3 (P = 4.9 × 10-8, Holm P = .02). Five differentially variable positions are demonstrated in the group of patients with evidence of disease recurrence including a probe mapping to MAD1L1 (P = 6.4 × 10-5). DNA methylation clock analyses demonstrated significant age acceleration in CD compared with control subjects (GrimAge + 2 years; 95% confidence interval, 1.2–2.7 years), with some evidence for accelerated aging in patients with CD with disease recurrence following surgery (GrimAge +1.04 years; 95% confidence interval, -0.04 to 2.22). Significant methylation differences between CD cases and control subjects were seen by comparing this cohort in conjunction with previously published control data, including validation of our previously described differentially methylated positions (RPS6KA2 P = 1.2 × 10-19, SBNO2 = 1.2 × 10-11) and regions (TXK [false discovery rate, P = 3.6 × 10-14], WRAP73 [false discovery rate, P = 1.9 × 10-9], VMP1 [false discovery rate, P = 1.7 × 10-7], and ITGB2 [false discovery rate, P = 1.4 × 10-7]). Conclusions: We demonstrate differential methylation and differentially variable methylation in patients developing clinical recurrence within 3 years of surgery. Moreover, we report replication of the CD-associated methylome, previously characterized only in adult and pediatric inception cohorts, in patients with medically refractory disease needing surgery.

The autophagy process recycles dysfunctional cellular components and protein aggregates by sequestering them in autophagosomes directed to lysosomes for enzymatic degradation. A basal level of autophagy is essential for skeletal muscle maintenance. Increased autophagy occurs in several forms of muscular dystrophy and in the merosin-deficient congenital muscular dystrophy 1A mouse model (dy3k/dy3k) lacking the laminin-α2 chain. This pilot study aimed to compare autophagy marker expression and autophagosomes presence using light and electron microscopes and western blotting in diagnostic muscle biopsies from newborns affected by different congenital muscular myopathies and dystrophies. Morphological examination showed dystrophic muscle features, predominance of type 2A myofibers, accumulation of autophagosomes in the subsarcolemmal areas, increased number of autophagosomes overexpressing LC3b, Beclin-1 and ATG5, in the merosin-deficient newborn suggesting an increased autophagy. In Duchenne muscular dystrophy, nemaline myopathy, and spinal muscular atrophy the predominant accumulation of p62+ puncta rather suggests an autophagy impairment.

IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage kidney disease (ESKD). Presently, the primary strategy for managing IgAN revolves around optimizing blood pressure and mitigating proteinuria. This is achieved through the utilization of renin–angiotensin system (RAS) inhibitors, namely, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As outlined by the KDIGO guidelines, individuals who continue to show a persistent high risk of progressive ESKD, even with comprehensive supportive care, are candidates for glucocorticoid therapy. Despite these therapies, some patients have a disease refractory to treatment, defined as individuals that present a 24 h urinary protein persistently >1 g after at least two rounds of regular steroids (methylprednisolone or prednisone) and/or immunosuppressant therapy (e.g., mycophenolate mofetil), or who do not tolerate regular steroids and/or immunosuppressant therapy. The aim of this Systematic Review is to revise the current literature, using the biomedical database PubMed, to investigate possible therapeutic strategies, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, fecal microbiota transplantation, as well as blockade of complement components.

The Noi Techpark project in Bolzano has substantially transformed a portion of the Bolzano surroundings, localizing university and management functions in an area characterized by the presence of a dismissed industrial settlement built between the two World Wars by the Montecatini group. The project was pursued through the creation of a technology park, renovating the structures of the old factory which was in a state of abandon and then acquired by the Autonomous Province of Bolzano. This allowed the establishment of a pole of new public- private structures for technology transfer. The present paper intends to retrace the history of this intervention, describing its main characteristics in terms of urban form, functions and presence of public spaces in relation to the achievement of the objective of re- evaluating an entire urban area. including the relevant residential zone. But at the same time the ambition of the essay lies in the attempt to represent how, in the assessment of the complexity of local policies of territorial development, a significant role is played by the ability to contribute to economic growth in terms of birth of new businesses, improvement of competitiveness of existing ones, enhancement of financial resources, human and material present in the area and, finally, the ability to attract new productive factors in the area. In this sense, the Noi Techpark project is emblematic. Il Progetto Noi Techpark a Bolzano ha trasformato in maniera sostanziale una porzione consistente della periferia di Bolzano, localizzando funzioni universitarie e direzionali in un’area caratterizzata dalla presenza di un insediamento industriale dismesso realizzato, negli anni tra le due guerre mondiali, dal gruppo Montecatini. L’intervento è stato perseguito mediante la realizzazione di un parco tecnologico che, attraverso il risanamento delle strutture del vecchio opificio – acquisito al patrimonio della Provincia autonoma di Bolzano dopo il suo abbandono – ha permesso l’istituzione di un polo di nuove strutture pubblico-private destinate al trasferimento tecnologico. Il presente contributo intende ripercorrere la storia di questo intervento, soffermandosi nel descriverne le principali caratteristiche in termini di forma urbana, funzioni e presenza di spazi pubblici in relazione al raggiungimento dell’obiettivo di rivalutare un’intera area urbana. Ivi compreso quella occupata dal tessuto residenziale di pertinenza. Ma allo stesso tempo l’ambizione del saggio risiede nel tentativo di rappresentare come, nella valutazione della complessità delle politi- che di sviluppo locale di un territorio, un ruolo rilevante sia ricoperto dalla capacità di contribuire alla crescita economica nei termini di nascita di nuove imprese, di miglioramento della competitività di quelle esistenti, di valorizzazione delle risorse finanziarie, umane e materiali presenti in loco e, infine, dalla capacità di attrarre nuovi fattori produttivi sul territorio. Proprio in questo senso Il progetto del parco tecnologico Noi Techpark sembra emblematico. Nell’aver perseguito, oltre al risanamento di un’area industriale di smessa, l’obiettivo della creazione e della diffusione dell’innovazione per mezzo di un brand territoriale. In questo modo, al vantaggio di arginare la perdita di valore del contesto edilizio dell’intera area, si aggiunge il risultato prestigioso di aver messo in contatto i laboratori di ricerca, da un lato, e il tessuto imprenditoriale, dell’altro. L’intera operazione restituisce, dunque, un contesto entro cui è stato possibile sviluppare la capacità di trasferire know-how, di diffondere informazioni tecnologiche sul territorio, di creare un network di relazioni che stanno alla base della diffusione e della creazione della conoscenza e dello sviluppo di un ambito territoriale. Tutti elementi, non immediatamente quantificabili in termini economici nel breve periodo, ma che ci sembra debbano essere presi in considerazione nelle valutazioni complessive del vantaggio dell’opportunità di portare a termine questo tipo di iniziative.

Abstract Background In myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), several areas of demyelination are detectable in mouse cerebral cortex, where neuroinflammation events are associated with scarce inflammatory infiltrates and blood–brain barrier (BBB) impairment. In this condition, the administration of mesenchymal stem cells (MSCs) controls neuroinflammation, attenuating astrogliosis and promoting the acquisition of stem cell traits by astrocytes. To contribute to the understanding of the mechanisms involved in the pathogenesis of EAE in gray matter and in the reverting effects of MSC treatment, the neocortex of EAE-affected mice was investigated by analyzing the cellular source(s) of chemokine CCL2, a molecule involved in immune cell recruitment and BBB-microvessel leakage. Methods The study was carried out by immunohistochemistry (IHC) and dual RNAscope IHC/in situ hybridization methods, using astrocyte, NG2-glia, macrophage/microglia, and microglia elective markers combined with CCL2. Results The results showed that in EAE-affected mice, hypertrophic microglia are the primary source of CCL2, surround the cortex neurons and the damaged BBB microvessels. In EAE-affected mice treated with MSCs, microgliosis appeared diminished very soon (6 h) after treatment, an observation that was long-lasting (tested after 10 days). This was associated with a reduced CCL2 expression and with apparently preserved/restored BBB features. In conclusion, the hallmark of EAE in the mouse neocortex is a condition of microgliosis characterized by high levels of CCL2 expression. Conclusions This finding supports relevant pathogenetic and clinical aspects of the human disease, while the demonstrated early control of neuroinflammation and BBB permeability exerted by treatment with MSCs may have important therapeutic implications.

Ulcerative colitis and Crohn’s disease are traditionally defined as the two main subtypes of inflammatory bowel disease. However, a more recent view considers IBD as a spectrum of heterogeneous phenotypes with consistent differences in clinical presentation and behaviors, likely explained by differences in underlying pathogenetic mechanisms. The etiology is still elusive, and the suggested pathogenesis is a complex interplay among genetic predisposition and abnormal immune response at the mucosal intestinal level, activated by only partially identified environmental triggers leading to altered intestinal permeability and impaired handling of gut microbiota. The undeniable continuous progress of medical therapy with more frequent shifts from traditional to more advanced modalities also underlines the actual unmet needs. We are using medications with completely different mechanisms of action, with a lack of predictive factors of outcomes and response and still an unsatisfactory rate of success. In addition, we are missing still valuable and accurate markers to predict disease progression and severity in order to avoid under- or over-treatment. In such a complex scenario, it is undoubtful that the application of artificial intelligence and machine learning algorithms may improve the management and pave the way for precision and eventually personalized medicine in these patients; however, there are still several challenges that will be the focus of this review.

This study offers valuable insights into the precipitation behavior of 13Ni maraging steels, emphasizing the role of molybdenum content in their microstructure, strengthening, and precipitate evolution. Precipitate morphology and crystallography were examined using a combination of high-resolution transmission electron microscopy and selected area electron diffraction. Strengthening mechanisms were assessed through Vickers hardness measurements. All the examined samples exhibited a lath martensite microstructure and displayed an increasing hardness over the aging time. The molybdenum content not only influenced the presence of retained austenite in the initial microstructure but also affected the type of precipitates formed during the early aging stages. Initially, Ni3Mo precipitates were formed, succeeded by the formation of more stable Fe2(Mo,Ti) Laves precipitates. The ultra-high strength of 13Ni maraging steels arises from the combination of the precipitate type and size distribution. The base composition of 13Ni maraging steels achieved a peak hardness of 798 HV1 through the precipitation of Laves Fe2(Mo,Ti) phases ranging from 3 to 14 nm in diameter.