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As an integral part of the concept of lifelong learning, non formal learning enables adults to acquire the necessary skills to adapt more easily to the ever-changing social life. Concerned with these values, through the lens of the ODD, with reference to Health and well-being, which indicates "ensuring a healthy life and promoting well-being for all ages", we wanted to investigate a group of teachers who followed a training program aimed at the healthy lifestyle of the educable. Healthy lifestyle education can play a significant role in changing health behaviors and attitudes towards our own health, as well as those we educate. Teachers become not only mentors for children, but also role models. Starting from this concept, we want to find out if the learners are able to include health-promoting behaviors in their daily routine and if they implement strategies that promote health, well-being, for themselves, including the learners. A number of N=63 teaching staff from Ia?i county, located in the north-eastern part of Romania, participated in this study. Of these, a number of N=35 respondents teach at the preschool education level and a number of N=28 at the primary education level. All respondents are female, of whom N=49 teach in urban areas, and N=14 in rural areas. The research tools were applied in electronic version, using Google forms. The obtained data were statistically analyzed using IBM SPSS software. Findings indicate significant effects of the training program on all target variables. The results of this research will be used to add to our knowledge of behavioral change and learning in adulthood.

Metastatic (m) colorectal cancer (CRC) is an incurable disease with a poor prognosis and thus remains an unmet clinical need. Immune checkpoint blockade (ICB)-based immunotherapy is effective for mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) mCRC patients, but it does not benefit the majority of mCRC patients. NK cells are innate lymphoid cells with potent effector responses against a variety of tumor cells but are frequently dysfunctional in cancer patients. Memory-like (ML) NK cells differentiated after IL-12/IL-15/IL-18 activation overcome many challenges to effective NK cell anti-tumor responses, exhibiting enhanced recognition, function, and in vivo persistence. We hypothesized that ML differentiation enhances the NK cell responses to CRC. Compared to conventional (c) NK cells, ML NK cells displayed increased IFN-γ production against both CRC cell lines and primary patient-derived CRC spheroids. ML NK cells also exhibited improved killing of CRC target cells in vitro in short-term and sustained cytotoxicity assays, as well as in vivo in NSG mice. Mechanistically, enhanced ML NK cell responses were dependent on the activating receptor NKG2D as its blockade significantly decreased ML NK cell functions. Compared to cNK cells, ML NK cells exhibited greater antibody-dependent cytotoxicity when targeted against CRC by cetuximab. ML NK cells from healthy donors and mCRC patients exhibited increased anti-CRC responses. Collectively, our findings demonstrate that ML NK cells exhibit enhanced responses against CRC targets, warranting further investigation in clinical trials for mCRC patients, including those who have failed ICB.

Andrea Ciorba, Chiara Bianchini, Stefano Pelucchi, Antonio PastoreENT and Audiology Department, University Hospital of Ferrara, Ferrara, ItalyAbstract: Hearing loss is the most common sensory deficit in the elderly, and it is becoming a severe social and health problem. Especially in the elderly, hearing loss can impair the exchange of information, thus significantly impacting everyday life, causing loneliness, isolation, dependence, and frustration, as well as communication disorders. Due to the aging of the population in the developed world, presbycusis is a growing problem that has been reported to reduce quality of life (QoL). Progression of presbycusis cannot be remediated; therefore, optimal management of this condition not only requires early recognition and rehabilitation, but it also should include an evaluation of QoL status and its assessment.Keywords: hearing loss, presbycusis, quality of life, elderly

Despite the spread of novel-generation cochlear-implant (CI) magnetic systems, access to magnetic resonance imaging (MRI) for CI recipients is still limited due to safety concerns. The aim of this study is to assess and record the experiences of Hires Ultra 3D (Advanced Bionics) recipients who underwent an MRI examination. A multicentric European survey about this topic was conducted focusing on safety issues, and the results were compared with the current literature. We collected a total of 65 MRI scans performed in 9 otologic referral centers for a total of 47 Hires Ultra 3D recipients, including, for the first time, 2 children and 3 teenagers. Preventive measures were represented by scanning time and sedation for children. Head wrapping was used in eight cases, and six of the eight cases received local anesthesia, even if both measures were not needed. Only three patients complained of pain (3/65 examinations, 4.6%) due to the tight head bandage, and one of the three cases required MRI scan interruption. No other adverse events were reported. We believe that these results should encourage MRI execution in accordance with manufacturer recommendations for Ultra 3D recipients.

Data-driven computational analysis is becoming increasingly important in biomedical research, as the amount of data being generated continues to grow. However, the lack of practices of sharing research outputs, such as data, source code and methods, affects transparency and reproducibility of studies, which are critical to the advancement of science. Many published studies are not reproducible due to insufficient documentation, code, and data being shared. We conducted a comprehensive analysis of 453 manuscripts published between 2016–2021 and found that 50.1% of them fail to share the analytical code. Even among those that did disclose their code, a vast majority failed to offer additional research outputs, such as data. Furthermore, only one in ten articles organized their code in a structured and reproducible manner. We discovered a significant association between the presence of code availability statements and increased code availability. Additionally, a greater proportion of studies conducting secondary analyses were inclined to share their code compared to those conducting primary analyses. In light of our findings, we propose raising awareness of code sharing practices and taking immediate steps to enhance code availability to improve reproducibility in biomedical research. By increasing transparency and reproducibility, we can promote scientific rigor, encourage collaboration, and accelerate scientific discoveries. We must prioritize open science practices, including sharing code, data, and other research products, to ensure that biomedical research can be replicated and built upon by others in the scientific community.

Background and Study Aim. Elite handball goalkeepers undergo intensive training for reflexes and advanced techniques. They develop mental toughness to handle the pressure and responsibility at key moments of the game. Thus, they protect the goal of the team. This study aims to investigate and highlight the specific training characteristics of elite handball players specialized in the goalkeeper position. Material and Methods. The best 4 goalkeepers specialized in elite handball in Romania, aged between 22 and 33 years, were selected. Specific motor tests were used: Test 1 - Jumps 15 seconds; Test 2 – Reaction speed to visual stimulus; Test 3 – Execution speed. Technical tests were used: Test specific to goalkeeper, Triangle moving, The Ten Jump, Ball throwing, Standing long jump, Passes to a fixed point; The Cooper test. To improve specific training, there were applied strategies for training optimization which include stretching for mobility, segmental muscle strength, goalkeeping specific exercises and plyometrics. The nonparametric Spearman’s correlation coefficient was used to evaluate the relationship between technical training and motor skills parameters. The statistical significance level was set at p

Children with single-sided deafness (SSD) may experience delays in language and speech development. Reduced speech discrimination and poor sound localization abilities in young SSD patients may result in greater cognitive efforts required to focus and process auditory information, as well as increased listening-related fatigue. Consequently, these children can have a higher risk of academic failure and are often in need of extra help at school. Recently, cochlear implants (CIs) have been introduced as a rehabilitative option for these children, but their effectiveness is still a topic of debate. A literature review was performed according to PRISMA guidelines, searching the Medline database from inception to October 2023. The research identified nine papers that met the inclusion criteria. Data extracted from the selected studies included 311 children affected by SSD and cochlear implants. The reported audiological outcomes were further analyzed. Overall, a high level of satisfaction was described by parents of children with SSD and CI, and those who received a CI under the age of 3 presented better results. However, a proportion of patients did not use the device daily. Our review highlights the possible, and still controversial, role of CI for the hearing rehabilitation of children with unilateral deafness, underlining the need for further research in this field. To date, careful and comprehensive counseling with the child and the family is necessary before considering this option.

Background and Aims: The dual sugar absorption test as a classic measure of human intestinal permeability has limited clinical utility due to lengthy and cumbersome urine collection, assay variability, and long turnaround. We aimed to determine if the orally administered fluorophore MB-102 (relmapirazin) (molecular weight [MW] = 372) compares to lactulose (L) (MW = 342) and rhamnose (R) (MW = 164)-based dual sugar absorption test as a measure of gut permeability in people with a spectrum of permeability including those with Crohn’s disease (CD). Methods: We performed a single-center, randomized, open-label, crossover study comparing orally administered MB-102 (1.5 or 3.0 mg/kg) to L (1000 mg) and R (200 mg). Adults with active small bowel CD on magnetic resonance enterography (cases) and healthy adults (controls) were randomized to receive either MB-102 or L and R on study day 1, and the other tracer 3 to 7 days later. Urine was collected at baseline and 1, 2, 4, 6, 8, 10, and 12 hours after tracer ingestion to calculate the cumulative urinary percent excretion of MB-102 and L and R. Results: Nine cases and 10 controls completed the study without serious adverse events. Urinary recovery of administered MB-102 correlated with recovery of lactulose (r-squared = 0.83) for all participants. MB-102 urine recovery was also tracked with the L:R ratio urine recovery (r-squared = 0.57). In controls, the percentages of L and MB-102 recovered were similar within a narrow range, unlike in CD patients. Conclusion: This first-in-human study of an orally administered fluorophore to quantify gastrointestinal permeability in adults with CD demonstrates that MB-102 is well tolerated, and its recovery in urine mirrors that of percent L and the L:R ratio.

Abstract Background Sudden sensorineural hearing loss (SSNHL) is an abrupt loss of hearing, still idiopathic in most of cases. Several mechanisms have been proposed including genetic and epigenetic interrelationships also considering iron homeostasis genes, ferroptosis and cellular stressors such as iron excess and dysfunctional mitochondrial superoxide dismutase activity. Results We investigated 206 SSNHL patients and 420 healthy controls for the following genetic variants in the iron pathway: SLC40A1 − 8CG (ferroportin; FPN1), HAMP − 582AG (hepcidin; HEPC), HFE C282Y and H63D (homeostatic iron regulator), TF P570S (transferrin) and SOD2 A16V in the mitochondrial superoxide dismutase-2 gene. Among patients, SLC40A1 − 8GG homozygotes were overrepresented (8.25% vs 2.62%; P = 0.0015) as well SOD2 16VV genotype (32.0% vs 24.3%; P = 0.037) accounting for increased SSNHL risk (OR = 3.34; 1.54–7.29 and OR = 1.47; 1.02–2.12, respectively). Moreover, LINE-1 methylation was inversely related (r 2 = 0.042; P = 0.001) with hearing loss score assessed as pure tone average (PTA, dB HL), and the trend was maintained after SLC40A1 − 8CG and HAMP − 582AG genotype stratification (Δ SLC40A1 = + 8.99 dB HL and Δ HAMP = − 6.07 dB HL). In multivariate investigations, principal component analysis (PCA) yielded PC1 (PTA, age, LINE-1, HAMP, SLC40A1) and PC2 (sex, HFE C282Y , SOD2, HAMP) among the five generated PCs, and logistic regression analysis ascribed to PC1 an inverse association with moderate/severe/profound HL (OR = 0.60; 0.42–0.86; P = 0.0006) and with severe/profound HL (OR = 0.52; 0.35–0.76; P = 0.001). Conclusion Recognizing genetic and epigenetic biomarkers and their mutual interactions in SSNHL is of great value and can help pharmacy science to design by pharmacogenomic data classical or advanced molecules, such as epidrugs, to target new pathways for a better prognosis and treatment of SSNHL.

Introduction Innate lymphoid cells (ILCs) are a group of immune cells that exhibit lymphoid characteristics yet lack antigen-specific receptors found on T and B cells (1). Group 3 ILCs (ILC3s) [...], Group 3 innate lymphoid cells (ILC3s) are key players in intestinal homeostasis. ER stress is linked to inflammatory bowel disease (IBD). Here, we used cell culture, mouse models, and human specimens to determine whether ER stress in ILC3s affects IBD pathophysiology. We show that mouse intestinal ILC3s exhibited a 24-hour rhythmic expression pattern of the master ER stress response regulator inositol-requiring kinase 1[alpha]/X-box-binding protein 1 (IRE1[alpha]/XBP1). Proinflammatory cytokine IL-23 selectively stimulated IRE1[alpha]/XBP1 in mouse ILC3s through mitochondrial ROS (mtROS). IRE1[alpha]/XBP1 was activated in ILC3s from mice exposed to experimental colitis and in inflamed human IBD specimens. Mice with Ire1[alpha] deletion in ILC3s ([Ire1[alpha].sup.[DELTA]Rorc]) showed reduced expression of the ER stress response and cytokine genes including Il22 in ILC3s and were highly vulnerable to infections and colitis. Administration of IL-22 counteracted their colitis susceptibility. In human ILC3s, IRE1 inhibitors suppressed cytokine production, which was upregulated by an IRE1 activator. Moreover, the frequencies of intestinal [XBP1s.sup.+] ILC3s in patients with Crohn's disease before administration of ustekinumab, an anti-IL-12/IL- 23 antibody, positively correlated with the response to treatment. We demonstrate that a noncanonical mtROS-IRE1[alpha]/XBP1 pathway augmented cytokine production by ILC3s and identify [XBP1s.sup.+] ILC3s as a potential biomarker for predicting the response to anti-IL-23 therapies in IBD.

Processing sustainability and the concept of zero waste discharge are of great interest for many industries. Every year, fruit and vegetable processing industries generate huge amounts of by-products, which are often intended for animal feed or discarded as waste, posing a problem to both environmental and economic points of view. However, to minimize the waste burden, the valorization of these residues received increased interest. In fact, fruit and vegetable by-products are an excellent source of valuable compounds, such as proteins, dietary fibers, lipids, minerals, vitamins, phenolic acids, flavonoids, anthocyanins, carotenoids, and pigments, which can be recovered and reused, creating new business prospects from a circular economy perspective. Understanding the chemical characteristics of these materials is a key concern for their valorization and the identification of their most appropriate intended use. In this study, the phytochemical and functional properties of fruit and vegetable processing by-products (peel and pomace) were investigated. Samples of different plants (i.e., apple, black and orange carrot, cucumber, kumquat, mango, parsnip, peach, black plum) were analyzed using chemical analytical methods and characterized using Fourier Transform Mid-Infrared spectroscopy (FT-MIR). The results highlighted their high nutritional composition in terms of protein, lipids, fiber, and ash, as well as bioactive and antioxidant profiles. These characteristics make these residues suitable as natural ingredients for the development of high-added-value products in food, cosmetic, and pharmaceutical industries.

ABSTRACT Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, much effort has been dedicated to identifying effective antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A number of calpain inhibitors show excellent antiviral activities against SARS-CoV-2 by targeting the viral main protease (Mpro), which plays an essential role in processing viral polyproteins. In this study, we found that calpain inhibitors potently inhibited the infection of a chimeric vesicular stomatitis virus (VSV) encoding the SARS-CoV-2 spike protein but not Mpro. In contrast, calpain inhibitors did not exhibit antiviral activities toward the wild-type VSV with its native glycoprotein. Genetic knockout of calpain-2 by CRISPR/Cas9 conferred resistance of the host cells to the chimeric VSV-SARS-CoV-2 virus and a clinical isolate of wild-type SARS-CoV-2. Mechanistically, calpain-2 facilitates SARS-CoV-2 spike protein-mediated cell attachment by positively regulating the cell surface levels of ACE2. These results highlight an Mpro-independent pathway targeted by calpain inhibitors for efficient viral inhibition. We also identify calpain-2 as a novel host factor and a potential therapeutic target responsible for SARS-CoV-2 infection at the entry step.IMPORTANCEMany efforts in small-molecule screens have been made to counter SARS-CoV-2 infection by targeting the viral main protease, the major element that processes viral proteins after translation. Here, we discovered that calpain inhibitors further block SARS-CoV-2 infection in a main protease-independent manner. We identified the host cysteine protease calpain-2 as an important positive regulator of the cell surface levels of SARS-CoV-2 cellular receptor ACE2 and, thus, a facilitator of viral infection. By either pharmacological inhibition or genetic knockout of calpain-2, the SARS-CoV-2 binding to host cells is blocked and viral infection is decreased. Our findings highlight a novel mechanism of ACE2 regulation, which presents a potential new therapeutic target. Since calpain inhibitors also potently interfere with the viral main protease, our data also provide a mechanistic understanding of the potential use of calpain inhibitors as dual inhibitors (entry and replication) in the clinical setting of COVID-19 diseases. Our findings bring mechanistic insights into the cellular process of SARS-CoV-2 entry and offer a novel explanation to the mechanism of activities of calpain inhibitors.

BackgroundPatients with chronic inflammatory disease (CID) treated with immunosuppressive medications have increased risk for severe COVID-19. Although mRNA-based SARS-CoV-2 vaccination provides protection in immunocompetent persons, immunogenicity in immunosuppressed patients with CID is unclear.ObjectiveTo determine the immunogenicity of mRNA-based SARS-CoV-2 vaccines in patients with CID.DesignProspective observational cohort study.SettingTwo U.S. CID referral centers.ParticipantsVolunteer sample of adults with confirmed CID eligible for early COVID-19 vaccination, including hospital employees of any age and patients older than 65 years. Immunocompetent participants were recruited separately from hospital employees. All participants received 2 doses of mRNA vaccine against SARS-CoV-2 between 10 December 2020 and 20 March 2021. Participants were assessed within 2 weeks before vaccination and 20 days after final vaccination.MeasurementsAnti-SARS-CoV-2 spike (S) IgG+ binding in all participants, and neutralizing antibody titers and circulating S-specific plasmablasts in a subset to assess humoral response after vaccination.ResultsMost of the 133 participants with CID (88.7%) and all 53 immunocompetent participants developed antibodies in response to mRNA-based SARS-CoV-2 vaccination, although some with CID developed numerically lower titers of anti-S IgG. Anti-S IgG antibody titers after vaccination were lower in participants with CID receiving glucocorticoids (n = 17) than in those not receiving them; the geometric mean of anti-S IgG antibodies was 357 (95% CI, 96 to 1324) for participants receiving prednisone versus 2190 (CI, 1598 to 3002) for those not receiving it. Anti-S IgG antibody titers were also lower in those receiving B-cell depletion therapy (BCDT) (n = 10). Measures of immunogenicity differed numerically between those who were and those who were not receiving antimetabolites (n = 48), tumor necrosis factor inhibitors (n = 39), and Janus kinase inhibitors (n = 11); however, 95% CIs were wide and overlapped. Neutralization titers seemed generally consistent with anti-S IgG results. Results were not adjusted for differences in baseline clinical factors, including other immunosuppressant therapies.LimitationsSmall sample that lacked demographic diversity, and residual confounding.ConclusionCompared with nonusers, patients with CID treated with glucocorticoids and BCDT seem to have lower SARS-CoV-2 vaccine-induced antibody responses. These preliminary findings require confirmation in a larger study.Primary funding sourceThe Leona M. and Harry B. Helmsley Charitable Trust, Marcus Program in Precision Medicine Innovation, National Center for Advancing Translational Sciences, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.