Search

The ubiquitous clathrin heavy chain (CHC), the main component of clathrin-coated vesicles, is well characterized for its role in intracellular membrane traffic and endocytosis from the plasma membrane (PM). Here, we demonstrate that in skeletal muscle CHC

Introduction: In recent times, there has been a growing emphasis on the significance of fostering intergenerational learning and interaction. This involves individuals from diverse age groups engaging in purposeful and mutually beneficial activities aimed at enhancing their knowledge, skills, and values. Objectives: This systematic review was undertaken to explore the psychosocial consequences of intergenerational learning experiences among primary school-age children and older adults. Methods: In accordance with the PRISMA guidelines, a comprehensive review of both quantitative and qualitative data was conducted. Electronic databases such as PubMed, Scopus, and ERIC were meticulously searched up to July 26, 2022, using the following Population (P) - Exposure (E) - Outcome (O) criteria: primary school-age children and older adults (P), participation in intergenerational learning (E), and psychosocial effects (O). Additionally, we extensively scrutinized the reference lists of included datasets and pertinent review articles (Figure 1). To evaluate the quality of the eligible studies, we employed the Mixed Methods Appraisal Tool (MMAT). Data analysis was structured around a narrative synthesis approach. Results: A total of seventeen studies were deemed eligible for inclusion in this review. The findings regarding the psychosocial consequences of engaging in intergenerational activities for both children and older adults predominantly underscored positive improvements in their attitudes, well-being, happiness, and various other aspects of their social and psychological well-being, although certain methodological limitations were identified (Figure 2). Image: Image 2: Conclusions: Promoting intergenerational interactions and learning experiences holds promise as a means to enhance the overall quality of life and well-being for both younger and older members of our communities. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Objectives To compare the clinical efficacy of two formulations (alcohol and alcohol free) of 0.2% chlorhexidine ( CHX) rinses on plaque, gingivitis and discoloration of teeth. Methods This double-blind crossover study consisted of one group of 10 volunteer dental students that followed two 21-day experimental gingivitis test periods. During these periods, the subjects abstained from oral hygiene except for the oral rinse provided. The study started after an initial two-week preparation programme that included a professional prophylaxis and repeated oral hygiene instructions. This was repeated for the 14-day washout period between the two rinses, including prophylaxis as per the first stage of the study. A calibrated examiner performed the clinical measurements at the beginning (baseline) and end of each study stage. The presence and amount of plaque were recorded using the Silness and Löe plaque index ( PI) and gingival inflammation by the gingival index ( GI) while the discoloration index (DI) was recorded on the buccal and lingual surfaces of the six anterior teeth of both the mandible and maxilla. Results Mean PI increased similarly for both solutions; however, the differences between initial and final values were statistically significant only for CHLOREL®. Similarly, the mean values for the GI showed small increases over the course of the study periods, but not statistically significant for either solution. The mean DI increased significantly for both solutions. Regarding the comparison of the initial and final values between the solutions, per index, no statistically significant differences were observed. Conclusion The non-alcoholic chlorhexidine rinse had comparable levels of action as the generally recognized gold standard alcoholic rinse. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between ED overcrowding and outcomes for critically ill patients. Design and Setting: We included medical and surgical pts that all of them were intubated promptly to ED of 2 general hospitals of Athens GR, for 12 months. Pts survived > 24hours were divided into 2 groups: ED boarding < 6 hrs (group A) and ED boarding = 6 hrs (group B). In the ED, 196 critically ill patients with a mean age 59.6±20.9 yrs and APACHE II score 24.6±12.7 were intubated.Results: Group A = 76 pts (mean time ED boarding, LOS, mortality): 28 pts were admitted to CCU (30.7±20.4, 7.7±9.3, 42.9%), 32 to ICU (231.25±103.1, 11.9±7.8, 37.5%) and 16 to intermediate unit (191.3±33.5, 7.8±5.7, 0%). Group B = 120 pts (mean time ED boarding, LOS, mortality): 28 pts were admitted to ICU (559.28±101.6, 15.6±10.3, 58.7%) and 92 to intermediate unit (3094.4±3273.4, 19.1±14.5, 78.3%). Hospital LOS was 19.2±20.4 days for group A vs 41.5±62.7 days for group B (P<0.001), and mortality 26.8% vs 45.7% respectively (P<0.001). Delayed admission, higher Apache II, age > 61 yrs, female gender and direct admission to ICU were associated with lower hospital survival (odds ratio 0.815; 95% 0.612-0.976).Conclusions: Boarding time of critically ill from ED to ICUs is very important because it is strongly related to the hospital LOS and mortality rate. [ABSTRACT FROM AUTHOR]

Background: Patients with inflammatory bowel disease (IBD) are at increased risk of infection. The aim of this study was to assess the cumulative incidence and risk of infection in patients with IBD treated with interleukin (IL)-targeting agents., Methods: We searched PubMed, EMBASE, and Web of Science for randomized controlled trials including patients with IBD receiving IL-targeting agents compared with patients receiving placebo or treatment that only differed from the intervention arm in the absence of an IL-targeting agent. The primary outcome of interest was the relative risk (RR) of any-grade and severe infection during the induction phase., Results: There was no difference in risk of any-grade (RR, 0.98; 95% confidence interval [CI], 0.89-1.09) or severe (RR, 0.64; 95% CI, 0.38-1.10) infection in patients receiving any IL-targeting agent compared with the control group. During the maintenance period, the cumulative incidence of any-grade infection in patients receiving IL-12/23p40-targeting agents (mean follow-up 29 weeks) was 34.82% (95% CI, 26.78%-43.32%), while the cumulative incidence of severe infection was 3.07% (95% CI, 0.93%-6.21%). The cumulative incidence of any-grade infection in patients receiving IL-23p19-targeting agents (mean follow-up 40.9 weeks) was 32.16% (95% CI, 20.63%-44.88%), while the cumulative incidence of severe infection was 1.75% (95% CI, 0.60%-3.36%). During the maintenance phase of the included studies, the incidence of infection was 30.66% (95% CI, 22.12%-39.90%) for any-grade and 1.59% (95% CI, 0.76%-2.63%) for severe infection in patients in the control group., Conclusions: There was no difference in risk of infection between patients with IBD who received IL-targeting agents compared with the control group. Case registries and randomized controlled trials reporting the safety of IL inhibitors should provide detailed information about the risk of specific infectious complications in patients with IBD receiving IL-targeting agents., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Source Citation: Taylor K, Eastwood S, Walker V, et al. Incidence of diabetes after SARS-CoV-2 infection in England and the implications of COVID-19 vaccination: a retrospective cohort study of 16 million people. Lancet Diabetes Endocrinol. 2024;12:558-568. 39054034., Competing Interests: Disclosures: Disclosure forms are available with the article online.

The hallmark of non-selective autophagy is the formation of cup-shaped phagophores that capture bulk cytoplasm. The process is accompanied by the conjugation of LC3B to phagophores by an E3 ligase complex comprising ATG12-ATG5 and ATG16L1. Here we combined two complementary reconstitution approaches to reveal the function of LC3B and its ligase complex during phagophore expansion. We found that LC3B forms together with ATG12-ATG5-ATG16L1 a membrane coat that remodels flat membranes into cups that closely resemble phagophores. Mechanistically, we revealed that cup formation strictly depends on a close collaboration between LC3B and ATG16L1. Moreover, only LC3B, but no other member of the ATG8 protein family, promotes cup formation. ATG16L1 truncates that lacked the C-terminal membrane binding domain catalyzed LC3B lipidation but failed to assemble coats, did not promote cup formation and inhibited the biogenesis of non-selective autophagosomes. Our results thus demonstrate that ATG16L1 and LC3B induce and stabilize the characteristic cup-like shape of phagophores., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Clathrin-mediated endocytosis has characteristic features in neuronal dendrites and presynapses, but how membrane proteins are internalized along the axon shaft remains unclear. We focused on clathrin-coated structures and endocytosis along the axon initial segment (AIS) and their relationship to the periodic actin-spectrin scaffold that lines the axonal plasma membrane. A combination of super-resolution microscopy and platinum-replica electron microscopy on cultured neurons revealed that AIS clathrin-coated pits form within "clearings", circular areas devoid of actin-spectrin mesh. Actin-spectrin scaffold disorganization increased clathrin-coated pit formation. Cargo uptake and live-cell imaging showed that AIS clathrin-coated pits are particularly stable. Neuronal plasticity-inducing stimulation triggered internalization of the clathrin-coated pits through polymerization of branched actin around them. Thus, spectrin and actin regulate clathrin-coated pit formation and scission to control endocytosis at the AIS.

Background: Early in the pandemic, extensive attention was cast on limited inclusion of historically underrepresented patient populations in COVID-19 clinical trials. How diverse representation improved following these initial reports remains unclear., Methods: PubMed, Embase and the Cochrane Library were searched (through April 2024) for US-based COVID-19 trials. Utilizing random-effects, we compared expected proportions of trial participants from racial and ethnic groups and of female sex between trials enrolling primarily in 2020 versus primarily 2021-2022. Meta-regression was performed to assess associations between trial characteristics and group representation., Results: We retrieved 157 studies comprising 198,012 participants. White (2020: 63.1% [95% CI, 60.8%-67.3%]; 2021-2022: 73.8% [95% CI, 71.5%-76.0%]) and female representation (2020: 46.1% [95% CI, 44.7%-47.4%)]; 2021-2022: 51.1% [95% CI, 49.3%-52.8%) increased across enrollment periods. Industry-sponsored trials were associated with higher White (coefficient, 0.10 [95% CI, 0.03-0.18]) and Hispanic or Latinx representation (coefficient, 0.16 [95% CI, 0.08-0.25]) and lower Asian (coefficient, -0.03 [95% CI, -0.06- -0.003]) and female representation (coefficient, -0.03 [95% CI, -0.07- -0.002]). Outpatient trials were associated with higher White (coefficient, 0.20 [95% CI, 0.13-0.26]) and female representation (coefficient, 0.16 [95% CI, 0.13-0.18]), and lower Black representation (coefficient, -0.10 [95% CI, -0.10- -0.08])., Conclusions: Despite improved female representation in COVID-19 trials over time, there was no clear increase in non-White representation. Trial characteristics such as primary sponsor, clinical setting, and intervention type correlate with representation of specific demographic groups and should be considered in future efforts to improve participant diversity., 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 Elsevier Inc. All rights reserved.)

Patients with rheumatoid arthritis (RA) who receive immunosuppressive medications have a heightened risk of infection. The goal of our study was to calculate the pooled cumulative incidence and risk of infection in patients with RA treated with Janus kinase inhibitors (JAKi). The PubMed and EMBASE databases were queried for randomized controlled trials comparing patients with RA treated with JAKi (upadacitinib, baricitinib, tofacitinib, peficitinib, or filgotinib), defined as the treatment group, compared with control subjects, defined as participants receiving placebo or treatment regimen that was similar to that of participants in the treatment group, with the exception of JAKi. The primary study endpoint was the relative risk (RR) of any-grade and severe infection. The secondary endpoints were RR and cumulative incidence of opportunistic infections, herpes zoster, and pneumonia. The Stata v17 software was used for all data analysis. Results showed that treatment with baricitinib was associated with an increased risk of any-grade (RR 1.34; 95% CI: 1.19-1.52) and opportunistic (RR 2.69; 95% CI: 1.22-5.94) infection, whereas treatment with filgotinib (RR 1.21; 95% CI: 1.05-1.39), peficitinib (RR 1.40; 95% CI: 1.05-1.86) and upadacitinib (RR 1.30; 95% CI: 1.09-1.56) was associated with increased risk of any-grade infection only. Analysis based on type of infection showed a pooled cumulative incidence of 32.44% for any-grade infections, 2.02% for severe infections, 1.74% for opportunistic infections, 1.56% for herpes zoster, and 0.49% for pneumonia in patients treated with any JAKi during the follow-up period. Treatment with specific JAKi in patients with RA is associated with an increased risk of any-grade and opportunistic infections but not severe infection. Close clinical monitoring of patients with RA treated with JAKi is required to establish the long-term infection risk profile of these agents., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ouranos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Following the Delphi consensus process, the term steatotic liver disease (SLD) was introduced to replace fatty liver disease, while the term metabolic dysfunction-associated steatotic liver disease (MASLD) emerged as the successor to the term nonalcoholic fatty liver disease (NAFLD). 1 This revised nomenclature aims to enhance precision and mitigate negative connotations and potential stigmatization, while refining comprehension and disease categorization. Concurrently, a novel category was introduced to capture individuals whose alcohol consumption exceeded the previously defined thresholds of NAFLD but remained unclassified within the existing system. This category, termed MetALD, now delineates a spectrum of conditions and is defined as a daily intake of 20 to 50 g of alcohol (or weekly 140-350 g) for females and 30 to 60 g daily for males (or weekly 210-420 g). 1 Within the MetALD spectrum, some individuals might predominantly exhibit MASLD characteristics, whereas others might be more inclined toward alcoholic liver disease (ALD). 1 In the present study, we used a US nationally representative data set to calculate the prevalence of SLD and its subcategories in the United States., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Clathrin assembles into honeycomb-like lattices at the plasma membrane but also on internal membranes, such as at the Golgi and tubular endosomes. Clathrin assemblies primarily regulate the intracellular trafficking of different cargoes, but clathrin also has non-endocytic functions in cell adhesion through interactions with specific integrins, contributes to intraluminal vesicle formation by forming flat bilayered coats on endosomes and even assembles on kinetochore k-fibers during mitosis. In this Cell Science at a Glance article and the accompanying poster, we review our current knowledge on the different types of canonical and non-canonical membrane-associated clathrin assemblies in mammalian cells, as observed by thin-section or platinum replica electron microscopy in various cell types, and discuss how the structural plasticity of clathrin contributes to its functional diversity., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Aim: The purpose of this study was to present the use of computer-assisted periodontal surgery utilizing a novel surgical guide for cases with severe gingival enlargement through a clinical application in a patient with hereditary gingival fibromatosis., Materials and Methods: The treatment plan included nonsurgical periodontal therapy, surgical periodontal treatment, and regular periodontal maintenance before the initiation of orthodontic treatment. Due to the increased soft tissue thickness, a surgical guide with a novel design was fabricated to facilitate the periodontal surgery since most of the patient's teeth were malpositioned and underexposed due to fibromatosis. For this purpose, the patient's intraoral scan was merged with a CBCT image in order to plan surgical excisions based on the anatomy of the teeth and the bone contour., Results: The customized surgical guide facilitated the gingivectomy by controlling not only the shape of the initial incisions but also their orientation toward the level of the cementoenamel junction, improving the efficiency of the clinical time compared with freehand surgery and assisting in the verification of the final soft tissue shape, based on the treatment plan., Conclusion: Digital technology through the superimposition of multiple data sets can assist in the diagnosis and multidisciplinary management of cases with gingival fibromatosis. The proposed design of the surgical guide can facilitate soft tissue surgery based on the digital treatment plan, leading to more predictable management of the soft tissue, especially in patients with severe gingival enlargement, as in cases with hereditary gingival fibromatosis or drug-induced gingival overgrowth.

Large transcellular pores elicited by bacterial mono-ADP-ribosyltransferase (mART) exotoxins inhibiting the small RhoA GTPase compromise the endothelial barrier. Recent advances in biophysical modeling point toward membrane tension and bending rigidity as the minimal set of mechanical parameters determining the nucleation and maximal size of transendothelial cell macroaperture (TEM) tunnels induced by bacterial RhoA-targeting mART exotoxins. We report that cellular depletion of caveolin-1, the membrane-embedded building block of caveolae, and depletion of cavin-1, the master regulator of caveolae invaginations, increase the number of TEMs per cell. The enhanced occurrence of TEM nucleation events correlates with a reduction in cell height due to the increase in cell spreading and decrease in cell volume, which, together with the disruption of RhoA-driven F-actin meshwork, favor membrane apposition for TEM nucleation. Strikingly, caveolin-1 specifically controls the opening speed of TEMs, leading to their dramatic 5.4-fold larger widening. Consistent with the increase in TEM density and width in siCAV1 cells, we record a higher lethality in CAV1 KO mice subjected to a catalytically active mART exotoxin targeting RhoA during staphylococcal bloodstream infection. Combined theoretical modeling with independent biophysical measurements of plasma membrane bending rigidity points toward a specific contribution of caveolin-1 to membrane stiffening in addition to the role of cavin-1/caveolin-1-dependent caveolae in the control of membrane tension homeostasis., Competing Interests: CM, EL, FT, TO, NS, MM, AS, MA, CS, YB, FV, CL, SV, MP, DG, CL, EL No competing interests declared, PB Reviewing editor, eLife, (© 2023, Morel et al.)

Background: The prevalence of steatotic liver disease (SLD) among patients with rheumatoid arthritis (RA) remains largely unknown., Aims: To investigate the prevalence of SLD and liver fibrosis among patients with RA., Methods: We utilized data from the United States (US)-based National Health and Nutrition Examination Survey (NHANES) 2017-2020 cycle. After applying established sample weights, we estimated the age-adjusted prevalence of SLD and its subclassifications (CAP ≥ 285 dB/m), high-risk NASH (FAST score) and liver fibrosis (LSM) among participants with self-reported RA. Multivariable logistic regression was performed to identify independent risk factors for metabolic dysfunction associated SLD (MASLD), high-risk NASH and fibrosis, respectively, among participants with RA. We present adjusted odds ratios (aORs) and 95% confidence intervals (CIs)., Results: Age-adjusted prevalence of MASLD among US adults with RA was 34.91% (95% CI: 24.02-47.65%). We also found that the age-adjusted prevalence of high-risk NASH (FAST score > 0.35) and significant fibrosis (LSM > 8.6 kPa) was 12.97% (95% CI: 6.89-23.07%) and 10.35% (95% CI: 5.55-18.48%), respectively. BMI ≥ 30 kg/m 2 , (aOR 6.23; 95% CI: 1.95-19.88), diabetes (aOR 5.90; 95% CI: 1.94-17.94), and dyslipidemia (aOR 2.83; 95% CI: 1.12-7.11) were independently associated with higher odds of MASLD among participants with RA. Diabetes (aOR 19.34; 95% CI: 4.69-79.70) was also independently associated with high-risk NASH., Conclusions: The prevalence of MASLD, high-risk NASH, and liver fibrosis among patients with RA is equal or higher than the general population. Future studies of large cohorts are needed to substantiate the role of systemic inflammation in the pathophysiology of MASLD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hidradenitis suppurativa (HS) is a painful skin condition that significantly affects patients' quality of life. Biologic agents, including anti-TNF agents and IL-17 inhibitors, have shown promise as treatment options for HS. However, there is concern about the increased risk of infections associated with these therapies. We conducted a systematic review and meta-analysis following PRISMA and MOOSE guidelines. We searched PubMed and Embase until February 1, 2023. The primary outcome of interest was the incidence of any infectious complications. Secondary outcomes included serious and opportunistic infections in HS patients treated with biologics or other immunomodulators. Twenty-four studies met our inclusion criteria, comprising 1,696 patients. The pooled incidence rate for any infection was 24.2%, primarily consisting of mild respiratory and skin infections. Subgroup analysis based on the mechanism of action (MOA) showed a pooled incidence of 7.77% for anti-IL1, 14.24% for anti-PDE4, and 21.96% for anti-TNF. Notably, patients receiving anti-IL17 had the highest incidence rate of infection at 33.6%, but the relative risk compared to placebo was not significantly elevated (0.99, 95% CI: 0.86-1.14). Serious infections were rare, with pooled incidences of 0.39% for anti-IL17 and 0.03% for anti-TNF. Opportunistic infections were infrequent, with 10 reported cases, including eight oral candidiasis, one cryptosporidiosis, and one Blastocystis hominis infection. The use of biologic therapies in HS patients does not significantly increase the risk of infectious complications. Additionally, the occurrence of serious or opportunistic infections in HS patients treated with biologics appears to be minimal., (© 2023 the International Society of Dermatology.)

Influenza infection is associated with cardiovascular complications that range significantly in presentation and severity. The cumulative incidence of cardiovascular complications due to laboratory-confirmed influenza, however, is not reported in the literature. We conducted a systematic review and random-effects meta-analysis to evaluate the cumulative incidence and mortality rate of influenza virus-related cardiovascular complications in hospitalized patients. We searched the PubMed and EMBASE databases for studies reporting acute myocardial infarction (AMI), heart failure (HF), arrhythmia of any kind, stroke or transient ischemic attack (TIA), and myocarditis in hospitalized patients with laboratory-confirmed influenza virus infection. Prospective studies, retrospective cohort studies, and randomized controlled trials (RCTs) were included in the analysis. We followed the PRISMA checklist and used 95% confidence intervals (CIs) to report meta-analysis outcomes. This study was registered on PROSPERO (CRD42023427849). After retrieving 2803 studies, we identified 19 studies (18 observational and 1 RCT) with relevant data, and we included 6936 patients in our analysis, of whom 690 (9.9%) developed a cardiovascular outcome of interest. The cumulative incidence of HF was 17.47% (95% CI: 5.06%-34.54%), arrhythmia of any kind 6.12% (95% CI: 0.00%-21.92%), myocarditis 2.56% (95% CI: 0.66%-5.38%), AMI 2.19% (95% CI: 1.03%-3.72%), and stroke or TIA 1.14% (95% CI: 0.00%-4.05%). The in-hospital mortality rate from cardiovascular events was 1.38% (95% CI: 0.00%-4.80%). Cardiovascular complications occur in patients with influenza virus infection, with the cumulative incidence of specific cardiac manifestations varying considerably (1.51%-17.47%). Preventive strategies and close clinical monitoring after infection remain a priority., (© 2023 John Wiley & Sons Ltd.)

The impact of COVID-19 and the associated lockdown measures on people's physical and mental wellbeing, as well as their daily lives and functioning, has been extensively studied. This study takes the approach of investigating the consequences of COVID-19 on a national scale, considering sociodemographic factors. The main objective is to make a contribution to ongoing research by specifically examining how age, gender, and marital status influence the overall impact of COVID-19 and wellbeing indicators during the second lockdown period that was implemented in response to the COVID-19 pandemic in the Greek population. The study involved a sample of 16,906 individuals of all age groups in Greece who completed an online questionnaire encompassing measurements related to personal wellbeing, the presence and search for meaning in life, positive relationships, as well as symptoms of depression, anxiety, and stress. Additionally, to gauge the levels of the perceived COVID-19-related impact, a valid and reliable scale was developed. The results reveal that a higher perception of COVID-19 consequences is positively associated with psychological symptoms and the search for meaning in life, while being negatively correlated with personal wellbeing and the sense of meaning in life. In terms of individual differences, the findings indicate that unmarried individuals, young adults, and females tend to report higher levels of psychological symptoms, a greater search for meaning in life, and a heightened perception of COVID-19-related impact. These findings are analyzed in depth, and suggestions for potential directions for future research are put forth.

Invadosomes and caveolae are mechanosensitive structures that are implicated in metastasis. Here, we describe a unique juxtaposition of caveola clusters and matrix degradative invadosomes at contact sites between the plasma membrane of cancer cells and constricting fibrils both in 2D and 3D type I collagen matrix environments. Preferential association between caveolae and straight segments of the fibrils, and between invadosomes and bent segments of the fibrils, was observed along with matrix remodelling. Caveola recruitment precedes and is required for invadosome formation and activity. Reciprocally, invadosome disruption results in the accumulation of fibril-associated caveolae. Moreover, caveolae and the collagen receptor β1 integrin co-localize at contact sites with the fibrils, and integrins control caveola recruitment to fibrils. In turn, caveolae mediate the clearance of β1 integrin and collagen uptake in an invadosome-dependent and collagen-cleavage-dependent mechanism. Our data reveal a reciprocal interplay between caveolae and invadosomes that coordinates adhesion to and proteolytic remodelling of confining fibrils to support tumour cell dissemination., (© 2023. The Author(s).)

Background/objectives: The aim of this trial was to investigate the effect of mastic mouthwash on halitosis using as a proxy the levels of the Volatile Sulfur Compounds (VSCs), and the effect on plaque and gingival indices in adolescents undergoing orthodontic treatment with fixed conventional labial appliances., Subjects/methods: The study was a double-blinded, placebo-controlled, parallel-group, randomized clinical trial. Thirty patients with fixed orthodontic appliances were randomly allocated at a 1:1 ratio, to either the mastic-mouthwash or the placebo-mouthwash group. Eligibility criteria included ages between 13 and 18, active orthodontic treatment with fixed appliances, good general health, and total initial VSCs levels above 150 ppb. The primary outcome was the objective hydrogen sulfide (H2S) level, measured with the Oral ChromaTM device. The secondary outcomes were (1.) the methyl-mercaptan (CH3SH) and (2.) dimethyl sulfide [(CH3)2S] levels, measured with the same device, (3.) the subjective perception of the own malodour via questionnaires, and (4.) the oral hygiene assessed with the use of the Modified Silness and Löe Plaque Index (PI-M) and the Silness and Löe Gingival Index (GI) at baseline (T0) and after 2 weeks (T1). Stratified randomization by gender was used, and allocation was concealed with opaque numbered sealed envelopes., Results: H2S level dropped from 221.00 ppb (T0) to 125.00 ppb (T1), and the difference between treatment groups was statistically significant in favour of the mastic group (coef: 72.34, 95% CI: 8.48, 136.27, P = 0.03). The levels of the other VSCs, the subjective measurements of oral malodour, and the oral hygiene indices did not differ between treatment arms., Limitations: The objective organoleptic assessment by a calibrated examiner was not performed., Conclusions/implications: Mastic mouthwashes could be an alternative treatment for adolescent patients suffering from halitosis during orthodontic treatment with fixed appliances., Registration: The trial was registered at ClinicalTrials.gov (identifier: NCT05647369)., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Sarcomeres are the basic contractile units within cardiac myocytes, and the collective shortening of sarcomeres aligned along myofibrils generates the force driving the heartbeat. The alignment of the individual sarcomeres is important for proper force generation, and misaligned sarcomeres are associated with diseases, including cardiomyopathies and COVID-19. The actin bundling protein, α-actinin-2, localizes to the 'Z-Bodies" of sarcomere precursors and the 'Z-Lines' of sarcomeres, and has been used previously to assess sarcomere assembly and maintenance. Previous measurements of α-actinin-2 organization have been largely accomplished manually, which is time-consuming and has hampered research progress. Here, we introduce sarcApp, an image analysis tool that quantifies several components of the cardiac sarcomere and their alignment in muscle cells and tissue. We first developed sarcApp to utilize deep learning-based segmentation and real space quantification to measure α-actinin-2 structures and determine the organization of both precursors and sarcomeres/myofibrils. We then expanded sarcApp to analyze 'M-Lines' using the localization of myomesin and a protein that connects the Z-Lines to the M-Line (titin). sarcApp produces 33 distinct measurements per cell and 24 per myofibril that allow for precise quantification of changes in sarcomeres, myofibrils, and their precursors. We validated this system with perturbations to sarcomere assembly. We found perturbations that affected Z-Lines and M-Lines differently, suggesting that they may be regulated independently during sarcomere assembly., Competing Interests: AN, JH, ZS, NT, AF, SM, SV, DB No competing interests declared, (© 2023, Neininger-Castro et al.)

Background: Nonalcoholic fatty liver disease (NAFLD) is a growing public health concern worldwide. Early detection and management of modifiable risk factors are critical to mitigating its impact. This study aimed to investigate the prevalence and risk factors of NAFLD, nonalcoholic steatohepatitis (NASH), and fibrosis among lean adults in the United States (US), using the latest National Health and Nutrition Examination Survey (NHANES) dataset from 2017-2020., Methods: Using controlled attenuation parameter scores of ≥285 dB/m, we assessed the age-adjusted prevalence of lean NAFLD. To determine the age-adjusted prevalence of high-risk NASH and significant fibrosis, we used the FibroScan-aspartate aminotransferase (FAST) score (cutoffs 0.35 and 0.67) and vibration-controlled transient elastography (liver stiffness measurement ≥8 kPa). Multivariate logistic regression was used to identify potential risk factors., Results: We found the age-adjusted prevalence of lean NAFLD to be 6.30%. Among lean US adults, the age-adjusted prevalence of high-risk NASH and significant fibrosis was 1.29% and 4.35%, respectively. Older age and metabolic comorbidities, such as hypertension, diabetes, and dyslipidemia were associated with NAFLD and its complications., Conclusion: These findings suggest that the prevalence of NAFLD is of concern among lean individuals, particularly those aged 40 and older with metabolic comorbidities, while a targeted approach to screening and risk stratification for hepatic fibrosis upon lean NAFLD diagnosis is warranted., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Aim: To describe a digital workflow utilizing 3D printing technology to guide esthetic crown lengthening and control tooth preparation., Clinical Considerations: After the initial intraoral and face scans, an esthetic treatment plan was performed digitally based on the patient's personality and face type using artificial intelligence-based 3D smile design software. A 3D-printed tray relined with silicone over a 3D-printed model was used for the mock-up. A 3D-printed guide was implemented to assist esthetic crown lengthening by incorporating, simultaneously, information about the desired free gingival line and the alveolar bone level. Based on the initial planning, a set of reduction guides was 3D printed to check and correct the tooth preparation. Prior to the start of construction of the final monolithic restorations, their design was verified using 3D-printed prototypes. A stabilization splint was digitally designed and 3D printed to protect and maintain the final result., Conclusions: Technologic advances can improve the predictability of an interdisciplinary esthetic approach. Digital planning can be transferred to clinical reality using a digital workflow, utilizing a set of appropriate 3D-printed guides, which can help to control clinical procedures based on the initial planning., Clinical Significance: By following the proposed step-by-step workflow, clinicians can achieve predictable results through an interdisciplinary approach, guiding both the periodontal plastic surgery and the restorative treatment after an individualized CAD/CAD procedure for 3D-printed guides.

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. The association between prior hepatitis B virus (HBV), hepatitis A virus (HAV), hepatitis E virus (HEV) infection and NAFLD remains unclear. We utilized the 2017-2020 National Health and Nutrition Examination Survey (NHANES) and performed multivariable logistic regression analyses to examine the association of prior HBV, HAV and HEV infection with NAFLD, as well as high risk non-alcoholic steatohepatitis (NASH) and liver fibrosis. Our analysis included 2565 participants with available anti-HBc serology results, 1480 unvaccinated participants with anti-HAV results, and 2561 participants with anti-HEV results. Among participants with NAFLD, the age-adjusted prevalence of prior HBV, HAV and HEV infection was 3.48%, 32.08% and 7.45%, respectively. Prior infection with HBV, HAV and HEV was not associated with NAFLD (cut-off 285 dB/m) [aOR: 0.99 (95% CI, 0.77-1.29), 1.29 (95% CI, 0.95-1.75), and 0.94 (95% CI, 0.70-1.27), respectively] or high-risk NASH [aOR 0.72 (95% CI, 0.45-1.17), 0.92 (95% CI, 0.55-1.52), and 0.89 (95% CI, 0.41-1.94), respectively]. Participants with anti-HBc and anti-HAV seropositivity were more likely to have significant fibrosis [aOR: 1.53 (95% CI, 1.05-2.23) and 1.69 (95% CI, 1.16-2.47), respectively]. The odds of significant fibrosis are 53%, and 69% greater for participants with prior history of HBV and HAV infection. Healthcare providers should prioritize vaccination efforts and employ a tailored approach to NAFLD in patients with prior viral hepatitis and especially HBV or HAV infection to limit disease-related outcomes., (© 2023 John Wiley & Sons Ltd.)

Objective: The aim of the present randomized controlled trial (RCT) was to evaluate the efficacy of different alveolar ridge preservation (ARP) techniques on dimensional alterations after tooth extraction, based on clinical measurements., Background: Alveolar ridge preservation (ARP) is a common procedure in every day clinical practice, when dental implants are involved in treatment planning. In ARP procedures, a bone grafting material is combined with a socket sealing (SS) material in order to compensate the alveolar ridge dimensional alterations after tooth extraction. Xenograft and allograft are the most frequently used bone grafts in ARP, while free gingival graft (FGG), collagen membrane, and collagen sponge (CS) usually applied as SS materials. The evidence comparing xenograft and allograft directly in ARP procedure is scarce. In addition, FGG is usually combined with xenograft as SS material, while the evidence combing allograft with FGG is absent. Moreover, CS could probably be an alternative choice in ARP as SS material, since it has been used in previous studies but more clinical trials are required to evaluate its effectiveness., Materials and Methods: Forty-one patients were randomly assigned in four treatment groups: (A) freeze-dried bone allograft (FDBA) covered with collagen sponge (CS), (B) FDBA covered with free gingival graft (FGG), (C) demineralized bovine bone mineral xenograft (DBBM) covered with FGG, and (D) FGG alone. Clinical measurements were performed immediately after tooth extraction and 4 months later. The related outcomes pertained to both vertical and horizontal assessment of bone loss., Results: Overall, groups A, B, and C presented significantly less vertical and horizontal bone resorption compared to group D. No statistically significant difference was observed between allograft and xenograft, except for the vertical bone resorption at the buccal central site, where xenograft showed marginally statistically significantly reduced bone loss compared to allograft (group C vs group B: adjusted β coef: 1.07 mm; 95%CI: 0.01, 2.10; p = 0.05). No significant differences were observed in hard tissue dimensions when CS and FGG were applied over FDBA., Conclusions: No differences between FDBA and DBBM could practically be confirmed. In addition, CS and FGG were equally effective socket sealing materials when combined with FDBA, regarding bone resorption. More RCTs are needed to compare the histological differences between FDBA and DBBM and the effect of CS and FGG on soft tissue dimensional changes., Clinical Relevance: Xenograft and allograft were equally efficient in ARP 4 months after tooth extraction in horizontal level. Xenograft maintained the mid-buccal site of the socket marginally better than the allograft, in vertical level. FGG and CS were equally efficient as SS materials regarding the hard tissue dimensional alterations., Trial Registration: Clinical trial registration Number: NCT04934813 (clinicaltrials.gov)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Purpose: CAV3 gene mutations, mostly inherited as an autosomal dominant trait, cause various skeletal muscle diseases. Clinical presentations encompass proximal myopathy, distal myopathy, or isolated persistent high creatine kinase (CK) with a major overlapping phenotype., Methods: Twenty-three patients with CAV3 symptomatic mutations, from 16 different families, were included in a retrospective cohort. Mean follow-up duration was 24.2 ± 15.0 years. Clinical and functional data were collected during the follow-up. The results of muscle imaging, electroneuromyography, muscle histopathology, immunohistochemistry, and caveolin-3 Western blot analysis were also compiled., Results: Exercise intolerance was the most common phenotype (52%). Eighty percent of patients had calf hypertrophy, and only 65% of patients presented rippling. One patient presented initially with camptocormia. A walking aid was required in only two patients. Electroneuromyography was mostly normal. CK level was elevated in all patients. No patient had cardiac or respiratory impairment. Muscle imaging showed fatty involvement of semimembranosus, semitendinosus, rectus femoris, biceps brachialis, and spinal muscles. Almost all (87%) of the biopsies were abnormal but without any specific pattern. Whereas a quarter of patients had normal caveolin-3 immunohistochemistry results, Western blots disclosed a reduced amount of the protein. We report nine mutations, including four not previously described. No phenotype-genotype correlation was evidenced., Conclusions: Caveolinopathy has diverse clinical, muscle imaging, and histological presentations but often has limited functional impact. Mild forms of the disease, an atypical phenotype, and normal caveolin-3 immunostaining are pitfalls leading to misdiagnosis., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Aims: Liver disease remains a leading cause of morbidity and mortality among people living with HIV (PLWH). Emerging data suggest that PLWH are at high risk for developing nonalcoholic fatty liver disease (NAFLD). The aim of this review is to examine the current literature and provide an accurate estimate of the prevalence of NAFLD, nonalcoholic steatohepatitis (NASH), and fibrosis, and identify potential risk factors for NAFLD in PLWH., Methods: We searched PubMed and Embase databases to identify studies reporting the prevalence of NAFLD and/or fibrosis in PLWH monoinfection. We performed a random effects meta-analysis of proportions to estimate the pooled prevalence of NAFLD, NASH, and fibrosis among PLWH monoinfection. We also examined potential risk factors for NAFLD by comparing characteristics of PLWH monoinfection with and without NAFLD., Results: A total of 43 studies, reporting data for 8230 patients, met our eligibility criteria and were included in the meta-analysis. Based on imaging studies the overall pooled prevalence of NAFLD and moderate liver fibrosis (METAVIR ≥ F2) among PLWH monoinfection was 33.9% (95% confidence interval [CI], 29.67%-38.39%), and 12.00% (95% CI, 10.02%-14.12%), respectively. Based on biopsy studies, prevalence of NASH and significant liver fibrosis (stage ≥F2 on histology) was 48.77% (95% CI, 34.30%-63.34%) and 23.34% (95% CI, 14.98%-32.75%), respectively. Traditional metabolic syndrome and HIV-related factors were associated with NAFLD in PLWH., Conclusions: Our study confirms that the burden of NAFLD, NASH, and fibrosis is high among PLWH monoinfection. Prospective longitudinal studies are needed to delineate NAFLD, NASH, and fibrosis risk factors, and identify early interventions and new therapies for NAFLD in this population., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Excitation-contraction coupling requires a highly specialized membrane structure, the triad, composed of a plasma membrane invagination, the T-tubule, surrounded by two sarcoplasmic reticulum terminal cisternae. Although the precise mechanisms governing T-tubule biogenesis and triad formation remain largely unknown, studies have shown that caveolae participate in T-tubule formation and mutations of several of their constituents induce muscle weakness and myopathies. Here, we demonstrate that, at the plasma membrane, Bin1 and caveolae composed of caveolin-3 assemble into ring-like structures from which emerge tubes enriched in the dihydropyridine receptor. Bin1 expression lead to the formation of both rings and tubes and we show that Bin1 forms scaffolds on which caveolae accumulate to form the initial T-tubule. Cav3 deficiency caused by either gene silencing or pathogenic mutations results in defective ring formation and perturbed Bin1-mediated tubulation that may explain defective T-tubule organization in mature muscles. Our results uncover new pathophysiological mechanisms that may prove relevant to myopathies caused by Cav3 or Bin1 dysfunction., Competing Interests: EL, JL, MB, GM, AB, CL, AM, AC, PA, JV, NR, MB, VM, IM, BC, LP, SV No competing interests declared, (© 2023, Lemerle et al.)

Introduction: Rituximab and azathioprine are used to induce or maintain remission in patients with ANCA-associated vasculitis (AAV). We evaluated the incidence of serious infections and infection-related deaths in patients with AAV treated with rituximab and azathioprine, during the maintenance of remission period., Methods: We searched PubMed and EMBASE for randomized clinical trials (RCTs) and observational studies evaluating immunosuppressive agents in patients with AAV. We defined serious or severe infections according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The study was registered on PROSPERO (CRD42022366269)., Results: From 1,265 abstracts, we identified 21 studies (7 RCTs and 14 observational), with relevant data. We included data from 1,284 and 2,938 individuals for assessment in our primary and secondary outcomes, respectively. The overall cumulative incidence of serious infections was 15.99% (CI 95%: 6.95-27.53%) during the total follow-up period (induction and maintenance) and 7.62% (CI 95%: 4.43-11.43%) during the maintenance period. Additionally, we found a 0.49% overall case fatality rate (CI 95%: 0.02-1.37%) and a 0.09% infection-related mortality rate (CI 95%: 0.00-0.51%) during maintenance treatment. Notably, we found a 14.61% (CI 95%: 10.19-19.61%) cumulative incidence of serious infections among patients who received rituximab and a 5.93% (CI 95%: 1.19-13.26%) cumulative incidence of serious infections among patients who received azathioprine during maintenance. Moreover, the cumulative incidence of serious infections during the total follow-up period (induction and maintenance) was 20.81% (CI 95%:4.56-43.70%) for the combination of cyclophosphamide and azathioprine and 14.12% (CI 95%: 5.20-26.00%) for rituximab., Discussion: The cumulative incidence of serious infections during total follow-up and maintenance was within expected limits, while fatal infections during maintenance treatment were uncommon. Additionally, treatment with rituximab for both induction and maintenance did not exceed the anticipated by previous studies incidence of serious infections. Clinical practice and long-term follow up data are needed to corroborate these findings., Systematic Review Registration: Identifier: PROSPERO (CRD42022366269)., 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 Vassilopoulos, Vassilopoulos, Kalligeros, Shehadeh and Mylonakis.)

Aim: To assess any differences (1) in the prevalence of periodontitis and necrotizing periodontal diseases, specifically necrotizing gingivitis (NG) and necrotizing periodontitis (NP) between HIV patients receiving antiretroviral therapy (HAART) and those not receiving the therapy and (2) in the severity of periodontitis based on probing depths (PDs) and clinical attachment loss (CAL) between the two groups., Materials and Methods: Systematic electronic search on five databases (PubMed, Google Scholar, Scopus, Web of Science and Scielo) was conducted to identify cross-sectional and longitudinal studies reporting on prevalence of NG, NP and periodontitis among HIV patients who either receive or do not receive HAART treatment. The differences in clinical parameters of PDs and CAL among these patients were assessed., Results: Eighteen articles were considered. The meta-analysis for NG showed that the overall assessment for the relative frequency ratio in the two groups was 0.45 (n = 7; 95% confidence interval [CI]: [0.21, 0.97]; p < .042). Regarding NP, the overall assessment for the relative frequency ratio in both groups was 0.60 (n = 5; 95% CI [0.22, 1.64]; p = .321). With regard to periodontitis, the overall assessment for the relative frequency ratio in the two groups was 1.17 (n = 9; 95% CI [0.90, 1.52]; p = .248). No significant differences in PD and CAL were found between the two groups 0.00 (n = 3; 95% CI [-0.52, -0.53]; p = .985) and 0.32 (n = 3; 95% CI [-0.19, 0.82]; p = .22), respectively., Conclusions: The prevalence of NG appeared to be significantly reduced in patients receiving antiretroviral therapy. No statistical significant difference was found in the prevalence of NP or periodontitis between the two groups., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Patients with multiple myeloma are at higher risk for infections due to disease pathogenesis and administered therapies. The purpose of this study was to estimate the risk for any grade and severe infections associated with the use of anti-CD38 monoclonal antibodies in patients with multiple myeloma., Methods: We searched PubMed and EMBASE for randomized controlled trials (RCTs) that included patients with multiple myeloma who received CD38-targeting monoclonal antibody regimens and reported outcomes of infection and performed a random-effects meta-analysis to estimate the relative risk for infections., Results: After screening 673 citations, we retrieved 17 studies providing data on 11 RCTs. Overall, the included reports evaluated 5316 patients (2797 in the intervention arm and 2519 in the control arm). The relative risk (RR) for both any grade or severe infections was 1.27 (95% CI, 1.17-1.37 and 1.14-1.41, respectively). The cumulative incidence of any grade infections for patients who received anti-CD38 agents was 77% (95% CI, 68%-86%), while for severe infections it was 28% (95% CI, 23%-34%). Patients treated with anti-CD38 agents had a 39% higher risk for any grade pneumonia (RR, 1.39; 95% CI, 1.12-1.72) and a 38% higher risk for severe pneumonia (RR, 1.38; 95% CI, 1.09-1.75). For upper respiratory tract infections, the relative risk was 1.51 and 1.71 for any grade and severe infections, respectively. Regarding varicella-zoster virus (VZV) reactivation, we found no evidence of increased risk (RR, 3.86; 95% CI, 0.66-22.50)., Conclusions: Patients with multiple myeloma treated with regimens that included an anti-CD38 monoclonal antibody were at higher risk for any grade or severe infections without an associated higher mortality rate during the follow-up period of the retrieved studies. No evidence of increased risk for VZV reactivation was noted, but there was a significant association between CD38-targeting treatment and pneumonia risk. Increased surveillance for infections, development of effective prophylactic strategies, and studies with long follow-up are needed for patients with multiple myeloma treated with anti-CD38-based regimens., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are prone to infections. Aims: Provide a pooled estimate of the cumulative incidence for infections that fulfilled the criteria associated with severe infectious adverse events for grade 3 or higher (including pneumonia, febrile neutropenia and sepsis) in patients who receive targeted therapies. Methods: We searched PubMed and EMBASE for randomized controlled trials (RCT) that included patients with CLL/SLL who received targeted therapies and performed a random-effects meta-analysis to estimate the cumulative incidence of infections. Results: Of 2,914 studies screened, we retrieved 31 which evaluated 11,660 patients. The pooled cumulative incidence of infections for patients who received treatment regimens based on a BTK inhibitors was 19.86%. For patients who received treatment based on rituximab and second generation anti-CD20 monoclonal antibodies, the pooled cumulative incidence of infections was 19.85 and 13.46%, respectively. Regarding PI3K inhibitor-based regimens the cumulative incidence of severe infections was 30.89%. BCL-2 inhibitors had a cumulative incidence of infections of 17.49% while lenalidomide and alemtuzumab had an incidence of 13.33 and 45.09%, respectively. The cumulative incidence of pneumonia ranged from 3.01 to 8.45% while febrile neutropenia ranged from 2.68 to 10.80%. Regarding sepsis, the cumulative incidence ranged from 0.9 to 4.48%. Conclusion: Patients with CLL/SLL who receive targeted therapies may develop severe infections at significant rates that, in addition to disease stage and other complications, depend on the mechanism of action of the used drug. Surveillance for infections and development of effective prophylactic strategies are critical for patients with CLL/SLL who receive targeted therapies. Systematic Review Registration: [https://systematicreview.gov/], identifier [registration number]., 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 © 2022 Vassilopoulos, Shehadeh, Kalligeros, Tran, Schiffman and Mylonakis.)