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The stiffening of the extracellular matrix (ECM) with age hinders muscle regeneration by causing intrinsic muscle stem cell (MuSC) dysfunction through a poorly understood mechanism. Here, the study aims to study those age-related molecular changes in the differentiation of MuSCs due to age and/or stiffness. Hence, young and aged MuSCs are seeded onto substrates engineered to mimic a soft and stiff ECM microenvironment to study those molecular changes using single-cell RNA sequencing (scRNA). The trajectory of scRNA data of the MuSCs under four different conditions undergoing differentiation is analyzed as well as the active molecular pathways and transcription factors driving those differentiation fates. Data revealed the presence of a branching point within the trajectory leading to the emergence of an age-related fibroblastic population characterized by activation of the TNF-related apoptosis-inducing ligand (TRAIL) pathway, which is significantly activated in aged cells cultured on stiff substrates. Next, using the collagen cross-linking inhibitor β-aminopropionitrile (BAPN) in vivo, the study elucidates stiffness changes on TRAIL downstream apoptotic targets (caspase 8 and caspase 3) using immunostaining. TRAIL activity is significantly inhibited by BAPN in aged animals, indicating a complex mechanism of age-related declines in muscle function through inflammatory and apoptotic mediators., (© 2024 The Author(s). Advanced Biology published by Wiley‐VCH GmbH.)

The oxidation free energies of DNA nucleobases in aqueous solution are still matter of extensive discussion because of the contrasting results reported so far. With the aim of settling a longstanding debate about the oxidation potentials of DNA constituents, herein we report the results of state-of-the-art DFT-based molecular dynamics simulations, in which the whole solvent environment is modeled at the atomistic level, by using DFT supercell calculations, with periodic boundary conditions. Calculated vertical ionization energies are very close to those observed by photoelectron spectroscopy both in the gas phase and in solution. One-electron oxidation free energies in aqueous solution agree well with the results of differential pulse voltammetry measurements and with those inferred by photoelectron spectroscopy with the aid of theoretical computations to estimate vibrational relaxation.

Objectives: Can the type of implant rehabilitation influence peri-implant bone loss in case of full-arch mandibular prosthesis? The purpose of the study was to assess, using orthopantomograms (OPGs), the bone loss around implants in different types of implant-supported prosthetic rehabilitations and identify potential risk factors, associated with the number and location of implants, that may have an association with bone defects., Methods: A radiographic study was conducted on 22,317 OPGs from 2010 to 2024. All OPGs with implant-supported prosthetic mandibular rehabilitations were included in the study., Results: A total of 155 OPGs were evaluated, with peri-implant bone loss identified in 64 (41.3%). Distal implants (furthest from the center) across various positioning patterns were most susceptible to bone loss, with positions 3.6 and 4.6 demonstrating the most frequent occurrence (25 and 26 cases, respectively). The χ 2 test revealed significant associations between both the implant positioning pattern ( p < 0.001) and number of implants ( p < 0.001) with peri-implant bone loss. Also, by updating the sample of OPGs, increased susceptibility to bone resorption was found for implants placed distal to the mental foramen compared to mesial ones in full-arch-implant-supported fixed prostheses., Conclusions: Prospective clinical studies will therefore be useful in investigating this finding further.

Background and Aims: Adaptive immunity is gaining a significant role in progression of metabolic dysfunction-associated steatotic liver disease (MASLD). B-cell activity can be assessed by serum-free light chains (sFLCs) k and λ levels. The objective of the present investigation is to examine the utility of sFLCs as non-invasive biomarkers for the stratification of MASLD., Methods: We enrolled a consecutive cohort from an outpatient liver unit. Diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) was made with liver biopsy according to current guidelines. Compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH) were defined according to Baveno VII criteria. sFLCs were measured by turbidimetry using an immunoassay., Results: We evaluated 254 patients, 162/254 (63.8%) were male. Median age was 54 years old, and the median body mass index was 28.4 kg/m 2 . A total of 157/254 (61.8%) subjects underwent liver biopsy: 88 had histological diagnosis of MASH, 89 were considered as simple metabolic dysfunction-associated steatotic liver (MASL) and 77/254 (30.3%) patients with compensated metabolic dysfunction-associated cirrhosis. By using Baveno VII criteria, 101/254 (39.7%) patients had cACLD; among them, 45/101 (44.5%) had CSPH. Patients with cACLD showed higher sFLC levels compared with patients without cACLD (p < .01), and patients with CSPH showed higher sFLC levels than patients without CSPH (p < .01). At multivariable analysis, sFLCs were associated with cACLD (p < .05) independently from γ-globulins and other known dysmetabolic risk factors. κFLC was associated with CSPH (p < .05) independently from γ-globulins and other known dysmetabolic risk factors., Conclusion: sFLCs could be a simple biomarker for stratification of cACLD in MASLD patients., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Hypothesis: Investigating solid-liquid interactions to determine advancing and receding contact angles, and consequently contact angle hysteresis, is crucial for understanding material wetting properties. A reliable, automated, and possibly open-source tool is desirable, to standardize and automatize the measurement and make it user-independent., Experiments: This study introduces an open-source software, DropenVideo, as an extension of Dropen. DropenVideo automates frame-by-frame video analysis for the advancing and receding contact angle determination, by considering needle presence, contrast tuning, and compensating for missing drop edge data. Contact angles are calculated using convolution mask, circle, and polynomial fittings. An innovative feature in DropenVideo is the automatic protocol for identifying advancing and receding contact angles: (i) the advancing contact angle is determined as the average value during drop inflation; and (ii) the receding contact angle is determined from the frame of incipient motion during drop deflation., Findings: Exploring the application of DropenVideo across a range of complex surfaces as representative test cases, we highlight existing challenges in interpreting wetting measurements by addressing different wetting scenarios. Our study demonstrates that employing frame-by-frame automatic analysis of contact angle measurement videos using DropenVideo significantly mitigates the potential risks of subjective bias associated with manual interpretation and enhances the precision of identified wetting characteristics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Glioblastoma (GBM) stands as the most prevalent and aggressive form of adult gliomas. Despite the implementation of intensive therapeutic approaches involving surgery, radiation, and chemotherapy, Glioblastoma Stem Cells contribute to tumor recurrence and poor prognosis. The induction of Glioblastoma Stem Cells differentiation by manipulating the transcriptional machinery has emerged as a promising strategy for GBM treatment. Here, we explored an innovative approach by investigating the role of the depolarized resting membrane potential (RMP) observed in patient-derived GBM sphereforming cell (GSCs), which allows them to maintain a stemness profile when they reside in the G0 phase of the cell cycle., Methods: We conducted molecular biology and electrophysiological experiments, both in vitro and in vivo, to examine the functional expression of the voltage-gated sodium channel (Na v ) in GSCs, particularly focusing on its cell cycle-dependent functional expression. Na v activity was pharmacologically manipulated, and its effects on GSCs behavior were assessed by live imaging cell cycle analysis, self-renewal assays, and chemosensitivity assays. Mechanistic insights into the role of Na v in regulating GBM stemness were investigated through pathway analysis in vitro and through tumor proliferation assay in vivo., Results: We demonstrated that Na v is functionally expressed by GSCs mainly during the G0 phase of the cell cycle, suggesting its pivotal role in modulating the RMP. The pharmacological blockade of Na v made GBM cells more susceptible to temozolomide (TMZ), a standard drug for this type of tumor, by inducing cell cycle re-entry from G0 phase to G1/S transition. Additionally, inhibition of Na v substantially influenced the self-renewal and multipotency features of GSCs, concomitantly enhancing their degree of differentiation. Finally, our data suggested that Na v positively regulates GBM stemness by depolarizing the RMP and suppressing the ERK signaling pathway. Of note, in vivo proliferation assessment confirmed the increased susceptibility to TMZ following pharmacological blockade of Na v ., Conclusions: This insight positions Na v as a promising prognostic biomarker and therapeutic target for GBM patients, particularly in conjunction with temozolomide treatment., (© 2024. The Author(s).)

Introduction: One of the leading causes of morbidity and mortality worldwide is out-of-hospital cardiac arrest. Early defibrillation and high-quality cardiopulmonary resuscitation (CPR) have improved survival. The main goal of CPR is to achieve return of spontaneous circulation (ROSC), which is assessed by looking for a pulse, analyzing the heart rhythm, and assessing carbon dioxide levels. The use of cartography during CPR to confirm the correct position of the endotracheal tube during intubation or to assess the effectiveness of chest compressions has increased significantly in the last years. The aim of this review was to identify correlations between end-tidal carbon dioxide levels and the likelihood of ROSC in patients with out-of-hospital cardiac arrest., Methods: A literature search was performed in MEDLINE (via Pubmed), Scopus, Web of Science, and Google Scholar databases from September to November 2022. Keywords combined with the Boolean operators (AND/OR) were used in both free text and Medical Subject Headings. Studies on adult patients published between 01/01/2016 and 28/09/2022 were searched, with no geographical restrictions., Results: At the end of the selection process, 14 studies were included that investigated capnography in out-of-hospital CPR and reported at least 1 outcome between end-tidal carbon dioxide and ROSC or survival., Discussion: Capnography is an advantageous tool due to its noninvasive characteristics, ease of use, and immediacy of data. In out-of-hospital cardiac arrest, the use of the end-tidal carbon dioxide appears to be an appropriate complementary tool to support clinical decisions, such as correct positioning of the endotracheal tube, optimizing ventilation in CPR, and as a predictor of ROSC., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article.

Intraarticular knee injuries and subsequent posttraumatic arthritis (PTOA) are common in athletes. Unfortunately, PTOA may significantly affect performance and overall function, but this condition remains difficult to characterize. In this review, we provide an overview of imaging modalities used to evaluate PTOA among athletes and physically active individuals following knee injury, with the goal to discuss the strengths and limitations of their application in this population. A literature search was performed to identify clinical studies focusing of knee injuries in athletes and athletic persons, specifically using imaging for diagnosis or monitoring disease progression. A total of 81 articles were identified, and 23 were included for review. Studies on plain radiographs (n = 8) and magnetic resonance imaging (MRI) assessed arthritic burden (n = 13), with MRI able to depict the earliest cartilage changes. Few studies (n = 2) leveraged ultrasound. Challenges persist, particularly regarding standardization and reliability across different radiographic grading systems. Additionally, further research is needed to establish the clinical significance of techniques to assess cartilage composition on MRI, including ultrashort echo-time enhanced T2*, T1rho and T2 imaging. Addressing these challenges through standardized protocols and intensified research efforts will enhance the diagnostic utility of imaging modalities in musculoskeletal medicine and enable high-quality prospective studies., (© 2024 The Author(s). PM&R published by Wiley Periodicals LLC on behalf of American Academy of Physical Medicine and Rehabilitation.)

Skeletal muscle wasting is the hallmark pathophysiological adaptation to unloading or disuse that demonstrates the dependency on frequent mechanical stimulation (e.g. muscle activation and subsequent loading) for homeostasis of normally load-bearing muscles. In the absence of mitigation strategies, no mammalian organism is resistant to muscle atrophy driven by unloading. Given the profound impact of unloading-induced muscle wasting on physical capacity, metabolic health and immune function; mitigation strategies during unloading and/or augmentation approaches during recovery have broad healthcare implications in settings of bed-bound hospitalization, cast immobilization and spaceflight. This topical review aims to: (1) provide a succinct, state-of-the-field summary of seminal and recent findings regarding the mechanisms of unloading-induced skeletal muscle wasting; (2) discuss unsuccessful vs. promising mitigation and recovery augmentation strategies; and (3) identify knowledge gaps ripe for future research. We focus on the rapid muscle atrophy driven by relatively short-term mechanical unloading/disuse, which is in many ways mechanistically distinct from both hypermetabolic muscle wasting and denervation-induced muscle atrophy. By restricting this discussion to mechanical unloading during which all components of the nervous system remain intact (e.g. without denervation models), mechanical loading requiring motor and sensory neural circuits in muscle remain viable targets for both mitigation and recovery augmentation. We emphasize findings in humans with comparative discussions of studies in rodents which enable elaboration of key mechanisms. We also discuss what is currently known about the effects of age and sex as biological factors, and both are highlighted as knowledge gaps and novel future directions due to limited research., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

The novel 2D quasi-hexagonal phase of covalently bonded fullerene molecules (qHP C 60 ), the so-called graphullerene, has displayed far superior electron mobilities, if compared to the parent van der Waals three-dimensional crystal (vdW C 60 ). Herein, we present a comparative study of the electronic properties of vdW and qHP C 60 using state-of-the-art electronic-structure calculations and a full quantum-mechanical treatment of electron transfer. We show that both materials entail polaronic localization of electrons with similar binding energies (≈0.1 eV) and, therefore, they share the same charge transport via polaron hopping. In fact, we quantitatively reproduce the sizable increment of the electron mobility measured for qHP C 60 and identify its origin in the increased electronic coupling between C 60 units.

The COVID-19 pandemic has put a lot of pressure on all the world's health systems and public health leaders who have often found themselves unprepared to handle an emergency of this magnitude. This study aims to bring together published evidence on the qualities required to leaders to deal with a public health issue like the COVID-19 pandemic. This scoping literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. A search of relevant articles was performed in the PubMed, Scopus and Web of Science databases. A total of 2499 records were screened, and 45 articles were included, from which 93 characteristics of effective leadership were extrapolated and grouped into 6 clusters. The qualities most frequently reported in the articles were human traits and emotional intelligence (46.7%) and communication skills such as transparency and reliability (48.9%). Responsiveness and preparedness (40%), management skills (33.3%) and team working (35.6%) are considered by a significant percentage of the articles as necessary for the construction of rapid and effective measures in response to the emergency. A considerable proportion of articles also highlighted the need for leaders capable of making evidence-based decisions and driving innovation (31.1%). Although identifying leaders who possess all the skills described in this study appears complex, determining the key characteristics of effective public health leadership in a crisis, such as the COVID-19 pandemic, is useful not only in selecting future leaders but also in implementing training and education programmes for the public health workforce., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Resistance training confers numerous health benefits that are mediated in part by circulating factors. Toward an enhanced molecular understanding, there is growing interest in a class of signaling biomarkers called extracellular vesicles (EV). EVs support physiological adaptations to exercise by transporting their cargo (e.g., microRNA (miRNA)) to target cells. Previous studies of changes in EV cargo have focused on aerobic exercise, with limited data examining the effects of resistance exercise. We examined the effect of acute resistance exercise on circulating EV miRNAs and their predicted target pathways., Methods: Ten participants (5 men; age, 26.9 ± 5.5 yr; height, 173.4 ± 10.5 cm; body mass, 74.0 ± 11.1 kg; body fat, 25.7% ± 11.6%) completed an acute heavy resistance exercise test (AHRET) consisting of six sets of 10 repetitions of back squats using 75% one-repetition maximum. Pre-/post-AHRET, EVs were isolated from plasma using size exclusion chromatography, and RNA sequencing was performed. Differentially expressed miRNAs between pre- and post-AHRET EVs were analyzed using Ingenuity Pathway Analysis to predict target messenger RNAs and their target biological pathways., Results: Overall, 34 miRNAs were altered by AHRET ( P < 0.05), targeting 4895 mRNAs, with enrichment of 175 canonical pathways ( P < 0.01), including 12 related to growth/metabolism (p53, IGF-I, STAT3, PPAR, JAK/STAT, growth hormone, WNT/β-catenin, ERK/MAPK, AMPK, mTOR, and PI3K/AKT) and 8 to inflammation signaling (TGF-β, IL-8, IL-7, IL-3, IL-6, IL-2, IL-17, IL-10)., Conclusions: Acute resistance exercise alters EV miRNAs targeting pathways involved in growth, metabolism, and immune function. Circulating EVs may serve as significant adaptive signaling molecules influenced by exercise training., (Copyright © 2024 by the American College of Sports Medicine.)

Understanding the microbiological profiles of peri-implant conditions is crucial for developing effective preventive and therapeutic strategies. This narrative review analyzes the microbial profiles associated with healthy peri-implant sites, peri-implant mucositis, and peri-implantitis, along with related microbiological sampling and analyses. Healthy peri-implant sites are predominantly colonized by Streptococcus , Rothia , Neisseria , and Corynebacterium species, in addition to Gram-positive cocci and facultatively anaerobic rods, forming a stable community that prevents pathogenic colonization and maintains microbial balance. In contrast, peri-implant mucositis shows increased microbial diversity, including both health-associated and pathogenic bacteria such as red and orange complex bacteria, contributing to early tissue inflammation. Peri-implantitis is characterized by even greater microbial diversity and a complex pathogenic biofilm. Predominant pathogens include Porphyromonas gingivalis , Tannerella forsythia , Treponema denticola , Fusobacterium nucleatum , and unique species like Filifactor alocis and Fretibacterium fastidiosum . Additionally, less common species such as Staphylococcus and Enterobacteriaceae , contributing to disease progression through biofilm formation and increased inflammatory response, along with EBV and human cytomegalovirus with a still not defined role, and Candida albicans contribute to disease progression through biofilm formation, immune modulation, and synergistic inter-kingdom interactions. Future research should standardize diagnostic criteria, employ advanced molecular techniques, integrate microbial data with clinical factors, and highlight inter-kingdom interactions.

Concurrent resistance and endurance exercise training (CET) has well-studied benefits; however, inherent hormonal and genetic differences alter adaptive responses to exercise between sexes. Extracellular vesicles (EVs) are factors that contribute to adaptive signaling. Our purpose was to test if EV characteristics differ between men and women following CET. 18 young healthy participants underwent 12-weeks of CET. Prior to and following CET, subjects performed an acute bout of heavy resistance exercise (AHRET) consisting of 6 × 10 back squats at 75% 1RM. At rest and following AHRET, EVs were isolated from plasma and characteristics and miRNA contents were analyzed. AHRET elevated EV abundance in trained men only (+51%) and AHRET-induced changes were observed for muscle-derived EVs and microvesicles. There were considerable sex-specific effects of CET on EV miRNAs, highlighted by larger variation following the 12-week program in men compared to women at rest. Pathway analysis based on differentially expressed EV miRNAs predicted that AHRET and 12 weeks of CET in men positively regulates hypertrophy and growth pathways more so than in women. This report highlights sex-based differences in the EV response to resistance and concurrent exercise training and suggests that EVs may be important adaptive signaling factors altered by exercise training., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Introduction: Falls are a major worldwide health problem in older people. Several physical rehabilitation programs with home-based technologies, such as the online DigiRehab platform, have been successfully delivered. The PRECISE project combines personalized training delivered through the application with an artificial intelligence-based predictive model (AI-DSS platform) for fall risk assessment. This new system, called DigiRehab, will enable early identification of significant risk factors for falling and propose an individualized physical training plan to attend to these critical areas., Methods: The study will test the usability of the DigiRehab platform in generating personalized physical rehabilitation programs at home. Fifty older adults participants will be involved, 20 of them testing the beta version prototype, and 30 participants testing the updated version afterwards. The inclusion criteria will be age ≥65, independent ambulation, fall risk (Tinetti test), Mini Mental State Examination ≥24, home residents, familiarity with web applications, ability and willingness to sign informed consent. Exclusion criteria will be unstable clinical condition, severe visual and/or hearing impairment, severe impairment in Activities of Daily Living and absence of primary caregiver., Discussion: The first part of the screening consists in a structured questionnaire of 10 questions regarding the user's limitations, including the risk of falling, while the second consists in 10 physical tests to assess the functional status. Based on the results, the program will help define the user's individual profile upon which the DSS platform will rate the risk of falling and design the personalized exercise program to be carried out at home. All measures from the initial screening will be repeated and the results will be used to optimize the predictive algorithms in order to prepare the tool in its final version. For the usability assessment, the System Usability Scale will be administered. The follow-up will take place after the 12-week intervention at home. A semi-structured satisfaction questionnaire will also be administered to verify whether the project will meet the needs of older adults and their family caregiver., Conclusion: We expect that personalized training prescribed by DigiRehab platform could help to reduce the need for care in older adults subjects and the care burden. Clinical trial registration : [https://clinicaltrials.gov/], identifier [NCT05846776]., Competing Interests: MH and NH were employed by DigiRehab A/S. AR is employed by DigiRehab Benelux, B.V. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 D’Ambrosio, Harbo, Contiero, Bonfigli, Cicconi, Heuer, Roos, Fischer Pedersen, Fabbietti and Gagliardi.)

We investigated transmission dynamics of a large human immunodeficiency virus (HIV) outbreak among persons who inject drugs (PWID) in KY and OH during 2017-20 by using detailed phylogenetic, network, recombination, and cluster dating analyses. Using polymerase ( pol ) sequences from 193 people associated with the investigation, we document high HIV-1 diversity, including Subtype B (44.6 per cent); numerous circulating recombinant forms (CRFs) including CRF02&#95;AG (2.5 per cent) and CRF02&#95;AG-like (21.8 per cent); and many unique recombinant forms composed of CRFs with major subtypes and sub-subtypes [CRF02&#95;AG/B (24.3 per cent), B/CRF02&#95;AG/B (0.5 per cent), and A6/D/B (6.4 per cent)]. Cluster analysis of sequences using a 1.5 per cent genetic distance identified thirteen clusters, including a seventy-five-member cluster composed of CRF02&#95;AG-like and CRF02&#95;AG/B, an eighteen-member CRF02&#95;AG/B cluster, Subtype B clusters of sizes ranging from two to twenty-three, and a nine-member A6/D and A6/D/B cluster. Recombination and phylogenetic analyses identified CRF02&#95;AG/B variants with ten unique breakpoints likely originating from Subtype B and CRF02&#95;AG-like viruses in the largest clusters. The addition of contact tracing results from OH to the genetic networks identified linkage between persons with Subtype B, CRF02&#95;AG, and CRF02&#95;AG/B sequences in the clusters supporting de novo recombinant generation. Superinfection prevalence was 13.3 per cent (8/60) in persons with multiple specimens and included infection with B and CRF02&#95;AG; B and CRF02&#95;AG/B; or B and A6/D/B. In addition to the presence of multiple, distinct molecular clusters associated with this outbreak, cluster dating inferred transmission associated with the largest molecular cluster occurred as early as 2006, with high transmission rates during 2017-8 in certain other molecular clusters. This outbreak among PWID in KY and OH was likely driven by rapid transmission of multiple HIV-1 variants including de novo viral recombinants from circulating viruses within the community. Our findings documenting the high HIV-1 transmission rate and clustering through partner services and molecular clusters emphasize the importance of leveraging multiple different data sources and analyses, including those from disease intervention specialist investigations, to better understand outbreak dynamics and interrupt HIV spread., Competing Interests: None declared., (Published by Oxford University Press 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Inflammatory cytokines released by synovium after trauma disturb the gene regulatory network and have been implicated in the pathophysiology of osteoarthritis. A mechanistic understanding of how aging perturbs this process can help identify novel interventions. Here, we introduced network paradigms to simulate cytokine-mediated pathological communication between the synovium and cartilage. Cartilage-specific network analysis of injured young and aged murine knees revealed aberrant matrix remodeling as a transcriptomic response unique to aged knees displaying accelerated cartilage degradation. Next, network-based cytokine inference with pharmacological manipulation uncovered IL6 family member, Oncostatin M (OSM), as a driver of the aberrant matrix remodeling. By implementing a phenotypic drug discovery approach, we identified that the activation of OSM recapitulated an "inflammatory" phenotype of knee osteoarthritis and highlighted high-value targets for drug development and repurposing. These findings offer translational opportunities targeting the inflammation-driven osteoarthritis phenotype., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Injuries to skeletal muscle are among the most common injuries in civilian and military populations, accounting for nearly 60% of extremity injuries. The standard of care for severe extremity injury has been focused upon limb salvage procedures and the utilization of tissue grafts or orthotics in conjunction with rehabilitation to avoid amputation. Nonetheless, many patients have persistent strength and functional deficits that permanently impact their quality of life. Preclinical and clinical studies have shown that partial restoration of functional skeletal muscle tissue following injury can be achieved by the implantation of a biologic scaffold composed of extracellular matrix (ECM). These favorable outcomes are mediated, at least in part, through local immunomodulation. The mechanisms underlying this immunomodulatory effect, however, are poorly understood. The present study investigates a potential mechanistic driver of the immunomodulatory effects; specifically, the effect of selected ECM components upon inflammation resolution and repair. Results show that the host response to skeletal muscle injury is profoundly altered and functional recovery decreased in il33 -/- mice compared to age- and sex-matched wildtype counterparts by 14 days post-injury. Results also show that IL-33, contained within matrix-bound nanovesicles (MBV), supports skeletal muscle regeneration by regulating local macrophage activation toward a pro-remodeling phenotype via canonical and non-canonical pathways to improve functional recovery from injury compared to untreated il33 -/- counterparts. Taken together, these data suggest that MBV and their associated IL-33 cargo represent a novel homeostatic signaling mechanism that contributes to skeletal muscle repair., (© 2024. The Author(s).)

Background: Consolidative thoracic radiotherapy (TRT) has been commonly used in the management of extensive-stage small cell lung cancer (ES-SCLC). Nevertheless, phase III trials exploring first-line chemoimmunotherapy have excluded this treatment approach. However, there is a strong biological rationale to support the use of radiotherapy (RT) as a boost to sustain anti-tumor immune responses. Currently, the benefit of TRT after chemoimmunotherapy remains unclear. The present report describes the real-world experiences of 120 patients with ES-SCLC treated with different chemoimmunotherapy combinations. Preclinical data supporting the hypothesis of anti-tumor immune responses induced by RT are also presented., Methods: A total of 120 ES-SCLC patients treated with chemoimmunotherapy since 2019 in the South of Italy were retrospectively analyzed. None of the patients included in the analysis experienced disease progression after undergoing first-line chemoimmunotherapy. Of these, 59 patients underwent TRT after a multidisciplinary decision by the treatment team. Patient characteristics, chemoimmunotherapy schedule, and timing of TRT onset were assessed. Safety served as the primary endpoint, while efficacy measured in terms of overall survival (OS) and progression-free survival (PFS) was used as the secondary endpoint. Immune pathway activation induced by RT in SCLC cells was explored to investigate the biological rationale for combining RT and immunotherapy., Results: Preclinical data supported the activation of innate immune pathways, including the STimulator of INterferon pathway (STING), gamma-interferon-inducible protein (IFI-16), and mitochondrial antiviral-signaling protein (MAVS) related to DNA and RNA release. Clinical data showed that TRT was associated with a good safety profile. Of the 59 patients treated with TRT, only 10% experienced radiation toxicity, while no ≥ G3 radiation-induced adverse events occurred. The median time for TRT onset after cycles of chemoimmunotherapy was 62 days. Total radiation dose and fraction dose of TRT include from 30 Gy in 10 fractions, up to definitive dose in selected patients. Consolidative TRT was associated with a significantly longer PFS than systemic therapy alone (one-year PFS of 61% vs. 31%, p<0.001), with a trend toward improved OS (one-year OS of 80% vs. 61%, p=0.027)., Conclusion: Multi-center data from establishments in the South of Italy provide a general confidence in using TRT as a consolidative strategy after chemoimmunotherapy. Considering the limits of a restrospective analysis, these preliminary results support the feasibility of the approach and encourage a prospective evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Longo, Della Corte, Russo, Spinnato, Ambrosio, Ronga, Marchese, Del Giudice, Sergi, Casaluce, Gilli, Montrone, Gristina, Sforza, Reale, Di Liello, Servetto, Lipari, Longhitano, Vizzini, Manzo, Cristofano, Paolelli, Nardone, De Summa, Perrone, Bisceglia, Derosa, Nardone, Viscardi, Galetta and Vitiello.)

Objective Dental caries in Mexico continues to be a public health problem, indicated by it is high prevalence and incidence in children. This disease is associated with pain in preschool and school children, with large-scale consequences for the individual, society, and health systems. The objective of the present study was to determine the experience (mean of caries indices), prevalence, and severity of caries in children 2-12 years of age who sought dental care at a dental school in Mexico. Material and methods A cross-sectional study was carried out on 826 clinical records of patients ages 2-12 years. The dependent variable was caries, in terms of experience (mean primary teeth (dmft) and permanent teeth (DMFT) indices), prevalence (dmft and DMFT greater than 0), and severity (cutoffs of caries indices at various levels). The independent variables were age and sex. The data were analyzed in Stata 14 (StataCorp LLC, College Station, Texas). Results The average age was 7.2±2.3; 52.4% were boys. In the primary dentition, the caries experience (mean dmft) was 3.01±3.30, the prevalence of caries was 65.8%, and the severity dmft>3=37.3% and dmft>6=15.6%. In the permanent dentition, the caries experience (mean DMFT) was 0.99±1.88, the prevalence of caries was 31.5%, and the severity DMFT>3=12.5% ​​and DMFT>6=1.6%. The percentage of caries-free children in both dentitions was 26.1% (n=216/826). The experience, prevalence, and severity of caries were statistically different by age (p<0.001). Only in the severity of dmft>3 were differences observed across sex (p<0.05). Among children with mixed dentition, primary teeth were more affected than permanent teeth (2.46±2.87 vs 0.88±1.61; p<0.0001). Conclusions About seven out of 10 children were affected by cavities in either or both dentitions. It was observed that age was positively associated with dental caries, equally affecting girls and boys. In this sample, the primary dentition was impacted more than the permanent dentition. Despite being preventable, dental caries continues to be a health problem in children., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Vera-Virrueta et al.)

Accumulated fat in skeletal muscle (i.e. myosteatosis), common in sedentary older individuals, compromises skeletal muscle health and function. A mechanistic understanding of how physical activity levels dictate fat accumulation represents a critical step towards establishment of therapies that promote healthy ageing. Using a network medicine paradigm that characterized the transcriptomic response of aged muscle to exercise versus immobilization protocols, this study explored the shared molecular cascade that regulates the fate of fibro-adipogenic progenitors (FAPs), the cell population primarily responsible for fat accumulation. Specifically, gene set enrichment analyses with network propagation revealed Pgc-1α as a functional hub of a large gene regulatory network underlying the regulation of FAPs by physical activity in aged muscle, but not in young counterparts. Integrated in silico and in situ approaches to induce Pgc-1α overexpression in aged muscle promoted mitochondrial fatty acid oxidation and inhibited FAP adipogenesis. These findings suggest that the Pgc-1α-mitochondrial fatty acid oxidation axis is a shared mechanism by which physical activity regulates age-related myosteatosis. The network medicine paradigm introduced provides mechanistic insight into exercise adaptation in elderly skeletal muscle and offers translational opportunities to advance exercise prescription for older populations. KEY POINTS: Fat accumulation is a quintessential feature of aged skeletal muscle. While increasing physical activity levels has been proposed as an effective strategy to reduce the fat in skeletal muscle (i.e. myosteatosis), the molecular cascade underlying these benefits has been poorly defined. This study implemented a series of network medicine approaches and uncovered Pgc-1α as a mechanistic driver of the regulation of fibro-adipogenic progenitors (FAPs) by physical activity. Integrated in silico and in situ approaches to induce Pgc-1α overexpression promoted mitochondrial fatty acid oxidation and inhibited FAP adipogenesis. Together, the findings of the current study suggest a novel hypothesis that physical activity reduces myosteatosis via upregulation of Pgc-1α-mediated mitochondrial fatty acid oxidation and subsequent inhibition of FAP adipogenesis., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

For many pathologies associated with aging, female patients present with higher morbidity and more frequent adverse events from treatments compared to male patients. While preclinical models are the foundation of our mechanistic understanding of age-related diseases, the most common models fail to recapitulate archetypical female aging trajectories. For example, while over 70% of the top age-related diseases are influenced by the systemic effects of reproductive senescence, we found that preclinical studies that include menopausal phenotypes modeling those seen in humans make up <1% of published aging biology research. The long-term impacts of pregnancy, birthing and breastfeeding are also typically omitted from preclinical work. In this Perspective, we summarize limitations in the most commonly used aging models, and we provide recommendations for better incorporating menopause, pregnancy and other considerations of sex in vivo and in vitro. Lastly, we outline action items for aging biology researchers, journals, funding agencies and animal providers to address this gap., (© 2023. Springer Nature America, Inc.)

The nature of alpha-D-mannose-natural aldohexose sugar, C-2 glucose epimer, whose intended use is for preventing urinary tract infections-in the interaction with E. coli is addressed in order to drive the issue of its regulatory classification as a medicinal product or medical device. PRISMA systematic review approach was applied; Delphi Panel method was used to target consensus on statements retrieved from evidence. Based on regulatory definitions and research evidence, the mechanism of D-mannose does not involve a metabolic or immunological action while there is uncertainty regarding the pharmacological action. Specific interaction between the product and the bacteria within the body occurs, but its nature is inert: it does not induce a direct response activating or inhibiting body processes. Moreover, the action of D-mannose takes place, even if inside the bladder, outside the epithelium on bacteria that have not yet invaded the urothelial tissue. Therefore, its mechanism of action is not directed to host structures but to structures (bacteria) external to the host's tissues. On the basis of current regulation, the uncertainty as regard a pharmacological action of alpha-D-mannose makes possible its medical device classification: new regulations and legal judgments can add further considerations. From a pharmacological perspective, research is driven versus synthetic mannosides: no further considerations are expected on alpha-D-mannose., (© 2023. The Author(s).)

Novel foods, including edible insects, are emerging because of their nutritional characteristics and low environmental impacts and could represent a valid alternative source of food in a more sustainable way. Edible insects have been shown to have beneficial effects on human health. Insect-derived bioactive peptides exert antihypertensive, antioxidant, anti-inflammatory, and antimicrobial properties and have protective effects against common metabolic conditions. In this review, the roles of edible insects in human health are reported, and the possible applications of these peptides in clinical practice are discussed. A special mention is given to the role of antimicrobial peptides and their potential applications in controlling infections in orthodontic procedures. In this context, insects' antimicrobial peptides might represent a potential tool to face the onset of infective endocarditis, with a low chance to develop resistances, and could be manipulated and optimized to replace common antibiotics used in clinical practice so far. Although some safety concerns must be taken into consideration, and the isolation and production of insect-derived proteins are far from easy, edible insects represent an interesting source of peptides, with beneficial effects that may be, in the future, integrated into clinical and orthodontic practice., Competing Interests: The authors declare no conflict of interest.

Skeletal muscle regeneration relies on the tightly temporally regulated lineage progression of muscle stem/progenitor cells (MPCs) from activation to proliferation and, finally, differentiation. However, with aging, MPC lineage progression is disrupted and delayed, ultimately causing impaired muscle regeneration. Extracellular vesicles (EVs) have attracted broad attention as next-generation therapeutics for promoting tissue regeneration. As a next step toward clinical translation, strategies to manipulate EV effects on downstream cellular targets are needed. Here, we developed an engineering strategy to tune the therapeutic potential of EVs using nanotopographical cues. We found that EVs released by young MPCs cultured on flat substrates (fEVs) promoted the proliferation of aged MPCs while EVs released by MPCs cultured on nanogratings (nEVs) promoted myogenic differentiation. We then employed a bioengineered 3D muscle aging model to optimize the administration protocol and test the therapeutic potential of fEVs and nEVs in a high-throughput manner. We found that the sequential administration first of fEVs during the phase of MPC proliferative expansion (i.e., 1 day after injury) followed by nEV administration at the stage of MPC differentiation (i.e., 3 days after injury) enhanced aged muscle regeneration to a significantly greater extent than fEVs and nEVs delivered either in isolation or mixed. The beneficial effects of the sequential EV treatment strategy were further validated in vivo , as evidenced by increased myofiber size and improved functional recovery. Collectively, our study demonstrates the ability of topographical cues to tune EV therapeutic potential and highlights the importance of optimizing the EV administration strategy to accelerate aged skeletal muscle regeneration.

Chronic exposure to environmental arsenic is a public health crisis affecting hundreds of millions of individuals worldwide. Though arsenic is known to contribute to many pathologies and diseases, including cancers, cardiovascular and pulmonary diseases, and neurological impairment, the mechanisms for arsenic-promoted disease remain unresolved. This is especially true for arsenic impacts on skeletal muscle function and metabolism, despite the crucial role that skeletal muscle health plays in maintaining cardiovascular health, systemic homeostasis, and cognition. A barrier to researching this area is the challenge of interrogating muscle cell-specific effects in biologically relevant models. Ex vivo studies investigating mechanisms for muscle-specific responses to arsenic or other environmental contaminants primarily utilize traditional 2-dimensional culture models that cannot elucidate effects on muscle physiology or function. Therefore, we developed a contractile 3-dimensional muscle construct model-composed of primary mouse muscle progenitor cells differentiated in a hydrogel matrix-to study arsenic exposure impacts on skeletal muscle regeneration. Muscle constructs exposed to low-dose (50 nM) arsenic exhibited reduced strength and myofiber diameter following recovery from muscle injury. These effects were attributable to dysfunctional paracrine signaling mediated by extracellular vesicles (EVs) released from muscle cells. Specifically, we found that EVs collected from arsenic-exposed muscle constructs recapitulated the inhibitory effects of direct arsenic exposure on myofiber regeneration. In addition, muscle constructs treated with EVs isolated from muscles of arsenic-exposed mice displayed significantly decreased strength. Our findings highlight a novel model for muscle toxicity research and uncover a mechanism of arsenic-induced muscle dysfunction by the disruption of EV-mediated intercellular communication., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The prevalence of overweight and obesity is continuously increasing, both in the adult and pediatric populations, posing a substantial challenge to public health. Understanding the epidemiological burden of metabolic syndrome (MetS) among children, particularly regarding its complications and long-term effects in adulthood, is crucial for identifying effective preventive measures and enhancing the clinical care of obese children. Therefore, by searching two databases, a systematic review was conducted in order to evaluate studies that specifically addressed the epidemiological MetS impact among overweight/obese European children and adolescents. Overall, 15 studies were considered. The epidemiological data concerning the MetS impact were contingent on the diagnostic criteria used and varied across countries, resulting in a prevalence range of 1.44% to 55.8%. Spanish studies were the most numerous (34%), revealing a country prevalence rate ranging from 2.5% to 19.6%. Males (prevalence range: 1.4-55.8%) and subjects with overweight/obesity (prevalence range: 12.9-55.8%) were mainly affected. Obesity emerged as the main risk factor in the MetS development and the consequent onset of cardiovascular complications and diabetes. Knowing the MetS burden and its risk factors could improve their prevention, detection, and treatment, and guide the development of targeted public health interventions to appropriately address the health needs of younger patients.

Objective: Mechanisms of neurocognitive injury as post-operative sequelae of coronary artery bypass grafting (CABG) are not understood. The systemic inflammatory response to surgical stress causes skeletal muscle impairment, and this is also worsened by immobility. Since evidence supports a link between muscle vitality and neuroprotection, there is a need to understand the mechanisms by which promotion of muscle activity counteracts the deleterious effects of surgery on long-term cognition., Methods: We performed a clinical trial to test the hypothesis that adding neuromuscular electrical stimulation (NMES) to standard rehabilitation care in post-CABG patients promotes the maintenance of skeletal muscle strength and the expression of circulating neuroprotective myokines., Results: We did not find higher serum levels of neuroprotective myokines, except for interleukin-6, nor better long-term cognitive performance in our intervention group. However, a greater increase in functional connectivity at brain magnetic resonance was seen between seed regions within the default mode, frontoparietal, salience, and sensorimotor networks in the NMES group. Regardless of the treatment protocol, patients with a Klotho increase 3 months after hospital discharge compared to baseline Klotho values showed better scores in delayed memory tests., Significance: We confirm the potential neuroprotective effect of Klotho in a clinical setting and for the first time post-CABG., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lo Re, Russelli, Lo Gerfo, Alduino, Bulati, Iannolo, Terzo, Martucci, Anzani, Panarello, Sparacia, Parla, Avorio, Raffa, Pilato, Speciale, Agnese, Mamone, Tuzzolino, Vizzini, Conaldi and Ambrosio.)

Background: Mandibular flexion (MF) is a complex biomechanical phenomenon, which involves a deformation of the mandible, due mainly to the contraction of the masticatory muscles, and it can have numerous clinical effects. The deformation of the lower jaw caused by mandibular flexion is generally very small, and it is often overlooked and considered irrelevant from a clinical point of view by many authors; however, it should be important to remember that median mandibular flexure (MMF) has a multifactorial aetiology. The main aim of the current systematic review is to highlight the different factors that can increase MF in order to help clinicians identify patients to whom they should pay more attention. As a secondary outcome, we wanted to analyse the preventive measures and suitable techniques to be adopted to minimise the negative effects of this phenomenon on oral fixed rehabilitations., Methods: The review, which was carried out in accordance with the "Preferred Reporting Items for Systematic reviews and Meta-Analyses" (PRISMA) flowchart, was recorded in the "International Prospective Register of Systematic Reviews" (PROSPERO). As research questions, "Patient/Population, Intervention, Comparison and Outcomes" (PICO) questions were employed. Using the ROBINS-I technique, the risk of bias in non-randomised clinical studies was evaluated., Results: The initial electronic search identified over 1300 potential articles, of which 54 studies were included in this systematic review. Information regarding the relationship between MF and individual factors, mandibular movements, impression taking, and fixed rehabilitations were obtained., Conclusions: The studies included in this systematic review showed that MF is greater during protrusive movements, in the posterior areas of the lower jaw, and in patients with brachial facial type, greater jaw length; small gonial angle; and less density, length, and bone surface of the symphysis. The biomechanical effects of mandibular flexion on fixed restorations are debated. Prospective clinical and radiological observational studies should be conducted to evaluate the potential short-, medium-, and long-term consequences of MF.

We have previously demonstrated that circulating extracellular vesicles (EVs) are essential to the beneficial effect of young serum on the skeletal muscle regenerative cascade. Here, we show that infusions of young serum significantly improve age-associated memory deficits, and that these effects are abolished after serum depletion of EVs. RNA-seq analysis of the choroid plexus demonstrates EV-mediated effects on genes involved in barrier function and trans-barrier transport. Comparing the differentially expressed genes to recently published chronological aging clock genes reveals a reversal of transcriptomic aging in the choroid plexus. Following young serum treatment, the hippocampal transcriptome demonstrates significant upregulation of the anti-aging gene Klotho, along with an abrogated effect after EV depletion. Transcriptomic profiling of Klotho knockout and heterozygous mice shows the downregulation of genes associated with transport, exocytosis, and lipid transport, while upregulated genes are associated with activated microglia. The results of our study indicate the significance of EVs as vehicles to deliver signals from the periphery to the brain and the importance of Klotho in maintaining brain homeostasis.

We have adopted an open bioinformatics ecosystem to address the challenges of bioinformatics implementation in public health laboratories (PHLs). Bioinformatics implementation for public health requires practitioners to undertake standardized bioinformatic analyses and generate reproducible, validated and auditable results. It is essential that data storage and analysis are scalable, portable and secure, and that implementation of bioinformatics fits within the operational constraints of the laboratory. We address these requirements using Terra, a web-based data analysis platform with a graphical user interface connecting users to bioinformatics analyses without the use of code. We have developed bioinformatics workflows for use with Terra that specifically meet the needs of public health practitioners. These Theiagen workflows perform genome assembly, quality control, and characterization, as well as construction of phylogeny for insights into genomic epidemiology. Additonally, these workflows use open-source containerized software and the WDL workflow language to ensure standardization and interoperability with other bioinformatics solutions, whilst being adaptable by the user. They are all open source and publicly available in Dockstore with the version-controlled code available in public GitHub repositories. They have been written to generate outputs in standardized file formats to allow for further downstream analysis and visualization with separate genomic epidemiology software. Testament to this solution meeting the requirements for bioinformatic implementation in public health, Theiagen workflows have collectively been used for over 5 million sample analyses in the last 2 years by over 90 public health laboratories in at least 40 different countries. Continued adoption of technological innovations and development of further workflows will ensure that this ecosystem continues to benefit PHLs.

Objectives:  The study aims to report the perception of dental practices and assess the individual's psychological stress level and related temporomandibular disorders (TMD) symptoms by evaluating the changes that occurred during the year following the first lockdown (May 2020)., Materials and Methods:  An online questionnaire was submitted to the Italian population between 20 March and 20 April 2021. It was sent via online platforms and included 14 questions., Statistical Analysis:  The data were analyzed using a chi-squared test and a comparison of the current data with the May 2020 survey data was performed using independent samples t -tests. The level of significance was set at p  < 0.05., Results:  Forty-three percent of subjects (872) considered the dental practice to be a place with a high risk of infection. Temporomandibular pain and joint sounds were reported by 35.7% (724) of the population; of these more frequently were women (71.8%, 520/724, p  < 0.001). About 31% of the participants had moderate/severe psychological distress and, among them, it was found that 46.4% (294/634) reported TMD pain ( p  < 0.001) and 34.9% (221/634) complained of temporomandibular joint sounds ( p  < 0.001)., Conclusions:  Most participants did not consider dental practices as a place with a higher risk of coronavirus disease 2019 transmission and, in contrast to the data from a previous study, people were less afraid to go to dental practices. After the first year of the pandemic, the level of stress and depression increased and the prevalence of TMD pain and joint sounds increased, in association with gender, age, and level of distress., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Objective: Despite the increased use of platelet-rich plasma in the treatment of osteoarthritis, whether and how age of the platelet-rich plasma donor affects therapeutic efficacy is unclear., Design: In vitro, male osteoarthritic human chondrocytes were treated with platelet-rich plasma from young (18-35 yrs) or old (≥65 yrs) donors, and the chondrogenic profile was evaluated using immunofluorescent staining for two markers of chondrogenicity, type II collagen and SOX-9. In vivo, we used a within-subjects design to compare Osteoarthritis Research Society International scores in aged mouse knee joints injected with platelet-rich plasma from young or old individuals., Results: In vitro experiments revealed that platelet-rich plasma from young donors induced a more youthful chondrocyte phenotype, as evidenced by increased type II collagen ( P = 0.033) and SOX-9 expression ( P = 0.022). This benefit, however, was significantly blunted when cells were cultured with platelet-rich plasma from aged donors. Accordingly, in vivo studies revealed that animals treated with platelet-rich plasma from young donors displayed a significantly improved cartilage integrity when compared with knees injected with platelet-rich plasma from aged donors ( P = 0.019)., Conclusions: Injection of platelet-rich plasma from a young individual induced a regenerative effect in aged cells and mice, whereas platelet-rich plasma from aged individuals showed no improvement in chondrocyte health or cartilage integrity., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Klotho is a protein associated with protection from aging-related diseases and health conditions. Obesity is associated with lower Klotho concentrations. Thus, this secondary analysis of adults with obesity examined 1) the change in serum Klotho concentration in response to a behavioral weight loss intervention by the magnitude of weight loss achieved; and 2) the association among serum Klotho concentration and weight, body composition, and cardiorespiratory fitness. Methods: Participants were randomized to either diet alone (DIET), diet plus 150 min of physical activity per week (DIET + PA150), or diet plus 250 min of physical activity per week (DIET + PA250). Participants [ n = 152; age: 45.0 ± 7.9 years; body mass index (BMI): 32.4 ± 3.8 kg/m 2 ] included in this secondary analysis provided blood samples at baseline, 6-, and 12 months, and were classified by weight loss response (Responder: achieved ≥10% weight loss at 6 or 12 months; Non-responder: achieved <5% weight loss at both 6 and 12 months). Serum Klotho was measured using a solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). Analyses of covariance (ANCOVA's) were used to examine changes in weight, body composition, cardiorespiratory fitness, and Klotho concentration by weight loss response across the 12-month weight loss intervention. Results: Responders had a greater reduction in measures of weight and body composition, and a greater increase in cardiorespiratory fitness, compared to Non-Responders ( p < 0.05). Change in Klotho concentration differed between Responders and Non-Responders ( p < 0.05), with the increase in Klotho concentration from baseline to 6 months for Responders being statistically significant. The 6-month change in Klotho concentration was inversely associated with the 6-month change in weight ( r s = -0.195), BMI ( r s = -0.196), fat mass ( r s = -0.184), and waist circumference ( r s = -0.218) ( p -values <0.05). Discussion: Findings provide evidence within the context of a behavioral intervention, with and without exercise, that change in Klotho concentration is significantly different between adults with weight loss ≥10% compared to <5% across 12 months. These findings suggest that weight loss and reduction in fat mass may be favorably associated with the change in Klotho concentration. This may reduce the risk of negative health consequences associated with accelerated aging in middle-aged adults., Competing Interests: JJ currently receives compensation for serving on the Scientific Advisory Board for Wondr Health, Inc., is the Principal Investigator on a research contract awarded to the University of Kansas Medical Center by Epitomee Medical Inc., and previously received compensation for serving on the Scientific Advisory Board for WW International, Inc. and as a consultant for Educational Initiatives, Inc., has received remuneration for professional presentations, and serves as a volunteer in a professional leadership role to the American College of Sports Medicine. RR is a consultant and instructor for Wondr Health, Inc., has received remuneration for professional presentations, and serves as a volunteer in a professional leadership role to the American College of Sports Medicine. ES serves on the Scientific Advisory Board for Hay Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Collins, Ambrosio, Rogers, Lang, Schelbert, Davis and Jakicic.)

Exercise promotes healthy aging of skeletal muscle. This benefit may be mediated by youthful factors in the circulation released in response to an exercise protocol. While numerous studies to date have explored soluble proteins as systemic mediators of rejuvenating effect of exercise on tissue function, here we showed that the beneficial effect of skeletal muscle contractile activity on aged muscle function is mediated, at least in part, by regenerative properties of circulating extracellular vesicles (EVs). Muscle contractile activity elicited by neuromuscular electrical stimulation (NMES) decreased intensity of expression of the tetraspanin surface marker, CD63, on circulating EVs. Moreover, NMES shifted the biochemical Raman fingerprint of circulating EVs in aged animals with significant changes in lipid and sugar content in response to NMES when compared to controls. As a demonstration of the physiological relevance of these EV changes, we showed that intramuscular administration of EVs derived from aged animals subjected to NMES enhanced aged skeletal muscle healing after injury. These studies suggest that repetitive muscle contractile activity enhances the regenerative properties of circulating EVs in aged animals., Competing Interests: Competing interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of this umbrella review is to evaluate what are the most common medications and systemic diseases that can affect bone-implant integration, the success rate and survival rate of dental implants, peri-implant tissue health, and implant loss. Systematic reviews, with meta-analysis or not, about how systemic diseases and medications influence dental implant osseointegration, survival rate, success rate, and peri-implant diseases, published only in the English language, are electronically searched across the most important scientific databases. The present umbrella review includes eight systematic reviews, and osteoporosis and diabetes are the most investigated pathologies. Systemic diseases, such as neurologic disorders, HIV, hypothyroidism, cardiovascular diseases, and drugs, such as beta blockers, anti-hypertensives, or diuretics do not show a decreased rate of implant osseointegration. It seems that drugs, such as proton-pump inhibitors (PPIs) or serotonin reuptake inhibitors (SSRIs), negatively affect implant osseointegration. Few studies compare the effects of drugs and systemic diseases on the parameters considered in this overview. It is important to underline how the results of this review need to be validated with subsequent and more reviews.

Antibiotics have undoubtedly revolutionized medicine and the health and survival of patients with life-threatening infections, being nonetheless free from potential adverse effects, and the risk of intestinal dysbiosis, antimicrobial resistance, and the resulting consequences for the patient's health and the public purse. The present study narratively reviewed the epidemiological data on worldwide antibiotic consumption and administration in dental practice, patients' adherence to prescriptions, the antimicrobial resistance phenomenon in dentistry, and the evidence supporting and recommending appropriate antibiotic use in dental care. Eligible systematic reviews and original studies in humans published in the English language from January 2000 to 26 January 2023 were considered. A total of 78 studies, 47 on the epidemiology of antibiotic use and prescription in dentistry, 6 on antibiotic therapy in dentistry, 12 on antibiotic prophylaxis in dentistry, 0 on adherence of dental patients to antibiotic prescription, and 13 on antimicrobial resistance in dentistry, were presently considered. Retrieved evidence revealed that antibiotics are frequently overused and misused in dental practice, dental patients frequently do not adhere to prescriptions, and antimicrobial resistance in dentistry is a still rising phenomenon also secondary to improper oral antiseptics use. The present findings highlighted the need to establish more evidence-based and accurate antibiotic prescriptions to sensitize dentists and dental patients to minimize and rationalize the use of antibiotics only when it is indicated and necessary, improve patients' adherence, and enhance knowledge and awareness of the antimicrobial resistance in dentistry.

Given the need to improve patient knowledge about HPV-related oral lesions, awareness of HPV infection prevention measures, and compliance with vaccination, as well as patient demand for free and easy access to well-tailored and time-saving health information, the present cross-sectional study examined the accuracy of relevant YouTube videos and their suitability for mass-reach health communication and HPV vaccination promotion. A video search was performed, using keywords obtained from the Google Trends website, until 9 January 2023. Video selection and data collection were performed by independent, pre-calibrated examiners. Descriptive statistics were performed on videos' general characteristics, source reliability, popularity, information and quality, content topics, vaccination-encouraging/discouraging messages, and educational value. Pearson's correlation was calculated between educational value and all parameters. Mann-Whitney U test compared very low/low vs. medium/good/excellent educational value and HPV vaccination-encouraging vs. -discouraging videos. Most of the 97 YouTube videos analyzed were moderately accurate and reliable, 53% had moderate/good/excellent educational value, and 80% encouraged HPV vaccination, making them suitable for mass-reach communication. The limited role of oral healthcare providers in uploading relevant content, with the poor dissemination of information about HPV-related benign and malignant oral lesions, may be expanded by purposefully using YouTube and other mass media to improve patient knowledge of HPV-related oral lesions and promote HPV vaccination, which also underscores its potential beneficial oral effects.

COVID-19 is a major global health threat, with millions of confirmed cases and deaths worldwide. Containment and mitigation strategies, including vaccination, have been implemented to reduce transmission and protect the population. We conducted two systematic reviews to collect nonrandomized studies investigating the effects of vaccination on COVID-19-related complications and deaths in the Italian population. We considered studies conducted in Italian settings and written in English that contained data on the effects of vaccination on COVID-19-related mortality and complications. We excluded studies that pertained to the pediatric population. In total, we included 10 unique studies in our two systematic reviews. The results showed that fully vaccinated individuals had a lower risk of death, severe symptoms, and hospitalization compared to unvaccinated individuals. The review also looked at the impact of vaccination on post-COVID-19 syndrome, the effectiveness of booster doses in older individuals, and nationwide adverse events. Our work highlights the crucial role that vaccination campaigns have played in reducing the burden of COVID-19 disease in the Italian adult population, positively impacting the pandemic trajectory in Italy.

The present umbrella review of four systematic reviews with meta-analysis aimed to assess whether clear aligners are associated with better periodontal conditions compared with fixed appliances in patients undergoing orthodontic treatment. The present study protocol was developed in accordance with the PRISMA statement before the literature search, data extraction, and analysis and was registered on PROSPERO (CRD42023401808). The question formulation, search, and study selection strategies were developed according to the PICO model. Systematic reviews with a meta-analysis published in English without date restriction were electronically searched across the Cochrane Library, Web of Science (Core Collection), Scopus, EMBASE, and MEDLINE/PubMed databases until 10 February 2023. An assessment of study quality was performed using the AMSTAR 2 tool. Differences in the PI, GI, and BOP in the short- and medium-term follow-ups, in the PPD in long-term follow-up, and the gingival recessions in the short-term follow-up were found between subjects with clear aligners and fixed appliances, revealing a slight tendency for clear aligners to be associated with healthier periodontal conditions. However, even if statistically significant, such differences would be negligible in a clinical environment. Therefore, the impact of orthodontic treatment with clear aligners and fixed appliances on periodontal health status should be considered comparable.