Search

Objective: The mandibular advancement device (MAD) is currently suggested in patients with mild to moderate obstructive sleep apnea (OSA). This study investigated the effects of a new fully customizable MAD-type device called, "It Makes You Sleep" (IMYS), in patients with mild to moderate OSA., Methods: Sixteen patients (14 men and 2 women; mean age 62; SD ± 11 years) were retrospectively enrolled. Each patient received home sleep apnea testing (HSAT) at baseline (T0) and after three months (T1) of IMYS treatment. The Apnea-Hypopnea Index (AHI), the Oxygen Desaturation Index (ODI), the Minimum Oxygen Saturation (minSO2) and the Medium Oxygen Saturation (medSO2) were analyzed., Results: From T0 to T1, the IMYS treatment showed a significant reduction of AHI and ODI and a significant increase of minSO2 and medSO2., Conclusion: The IMYS appliance is an effective device for treating mild or moderate OSA.

Aim: This systematic review investigates the effectiveness of implant therapy in patients with and without a history of periodontitis in terms of implant loss, peri-implant marginal bone loss (MBL), and occurrence of peri-implant diseases., Methods: The protocol of the present meta-analysis was registered on PROSPERO (CRD42021264980). An electronic search was conducted up to April 2024. All prospective cohort studies reporting implant loss, MBL, and occurrence of peri-implant diseases in both patients with a history of periodontitis (HP) and patients with no history of periodontitis (NHP) after at least 36-month follow-up were included. The risk of bias was evaluated using the Newcastle-Ottawa Scale and the quality of the evidence was also assessed. A meta-analysis was performed on the selected outcomes at the available follow-up time points. Subgroup analyses were conducted based on follow-up time, rate of progression and severity of periodontitis, and implant surface characteristics. Publication bias was evaluated using the Funnel plot and Egger's test., Results: From 13 761 initial records, 14 studies (17 articles) were finally included. Eight studies had a low risk of bias level, and six had a medium risk of bias level. Meta-analysis showed that HP patients had a significantly greater risk for implant loss (HR: 1.75; 95% CI: 1.28-2.40; p = 0.0005; I 2  = 0%), MBL (MD: 0.41 mm; 95% CI 0.19, 0.63; p = 0.0002; I 2  = 54%), and peri-implantitis (3.24; 95% CI: 1.58-6.64; p = 0.001; I 2  = 57%) compared to NHP, whereas no significant intergroup difference for peri-implant mucositis was found. Subgroup analyses revealed a particularly greater risk for implant loss for HP patients over a ≥ 10-year follow-up (HR: 2.02; 95% CI: 1.06-3.85; p = 0.03; I 2  = 0%) and for patients with a history of grade C (formerly aggressive) periodontitis (HR: 6.16; 95% CI: 2.53-15.01; p < 0.0001; I 2  = 0%). A greater risk for implant loss for stages III-IV (severe) periodontitis, and implants with rough surfaces was also found., Conclusions: Within the limits of heterogeneous case definitions and methods of assessment, a history of periodontitis has been proved to significantly increase the risk for implant loss, particularly at long follow-up (≥ 10 years) and in case of rapidly progressive forms (grade C), and for MBL and peri-implantitis., (Journal of Periodontal Research© 2024 The Author(s). Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Background: The literature lacks a combined analysis of neurosurgical microvascular anastomosis training models. We performed a systematic literature search to provide an overview of the existing models and proposed a classification system based on the level of simulation and reproducibility of the microvascular anastomosis., Methods: The systematic literature search followed the PRISMA guidelines. We consulted MEDLINE, Web of Knowledge, and EMBASE independently for papers about bypass training models. Every training model was analyzed according to six tasks supposed to esteem their fidelity to the real operative setting by using a scoring system from zero to two. Finally, authors classified the models into five classes, from A to E, by summing the individual scores., Results: This study included 109 papers for analysis. Training models were grouped into synthetic tubes, ex vivo models (animal vessels, fresh human cadavers, human placentas) and in vivo simulators (live animals-rats, rabbits, pigs). By applying the proposed classification system, live animals and placentas obtained the highest scores, falling into class A (excellent simulators). Human cadavers and animal vessels (ex vivo) were categorized in class B (good simulators), followed by synthetic tubes (class C, reasonable simulators)., Conclusions: The proposed classification system helps the neurosurgeon to analyze the available training models for microvascular anastomosis critically, and to choose the most appropriate one according to the skills they need to improve.

Objective: Guidelines for the management of pediatric severe traumatic brain injury (TBI) recommend external ventricular drainage for CSF drainage as a first-tier treatment in the intracranial pressure (ICP) pathway. However, ventriculostomy in children can sometimes be challenging because of the small size of the lateral ventricles. External lumbar drainage (ELD) may be a useful alternative; therefore, the authors analyzed the outcome of a cohort of pediatric patients who underwent ELD to manage intracranial hypertension (ICH)., Methods: This study retrospectively enrolled pediatric patients with ICH following severe TBI who underwent ELD. Radiological and clinical severity scores (Marshall classification, Rotterdam score, Injury Severity Score, and Pediatric Trauma Score) were noted. ICP and cerebral perfusion pressure (CPP) curves were analyzed 12 hours before and after the procedure. Any change in medical therapy was recorded, as well as the total volume and duration of drainage. Cerebellar tonsillar position according to the McRae line was noted before and after ELD. Glasgow Outcome Scale-Extended score at follow-up was also noted., Results: Thirty patients were included, with a mean age of 8 ± 4.4 years, and a median admission Glasgow Coma Scale score of 7 ± 4 (range 3-13). ELD was performed after a median delay of 1 day (range 0-7 days), mean drainage volume/day was 296 ± 129 ml, and median duration of drainage was 7 ± 5 (range 2-12) days. Forty-three percent of the patients underwent ELD as a part of the first-tier therapy. ICP decreased after ELD (mean difference 13.4 ± 6.2 mm Hg, p < 0.001), whereas CPP increased (mean difference 10.6 ± 6.4 mm Hg, p < 0.001). Fifty-three percent of the cohort did not need any further second-tier therapy after ELD. The study found 1 case of drain revision and 3 cases of cerebellar tonsil herniation., Conclusions: These preliminary data suggest ELD is a valuable option to treat ICH in severely head-injured children, limiting the use of second-tier treatments. This pilot study should lay the foundation for a multicenter prospective trial.

Rat H9c2 cardiomyocytes overexpressing the abscisic acid (ABA) hormone receptors LANCL1 and LANCL2 have an increased mitochondrial proton gradient, respiration, and vitality after hypoxia/reoxygenation. Our aim was to investigate the role of the ABA/LANCL1-2 system in ROS turnover in H9c2 cells. H9c2 cells were retrovirally infected to induce the overexpression or silencing of LANCL1 and LANCL2, without or with the concomitant silencing of the transcription factor ERRα. Enzymes involved in radical production or scavenging were studied by qRT-PCR and Western blot. The mitochondrial proton gradient and ROS were measured with specific fluorescent probes. ROS-generating enzymes decreased, ROS-scavenging enzymes increased, and mitochondrial ROS were reduced in LANCL1/2-overexpressing vs. control cells infected with the empty vector, while the opposite occurred in LANCL1/2-silenced cells. The knockdown of ERRα abrogated all beneficial effects on ROS turnover in LANCL1/2 overexpressing cells. Taken together, these results indicate that the ABA/LANCL1-2 system controls ROS turnover in H9c2 via ERRα. The ABA/LANCL system emerges as a promising target to improve cardiomyocyte mitochondrial function and resilience to oxidative stress.

Aims: FGFR-fused central nervous system (CNS) tumours are rare and are usually within the glioneuronal and neuronal tumours or the paediatric-type diffuse low-grade glioma spectrum. Among this spectrum, FGFR2 fusion has been documented in tumours classified by DNA-methylation profiling as polymorphous low-grade neuroepithelial tumours of the young (PLNTY), a recently described tumour type. However, FGFR2 fusions have also been reported in glioneuronal tumours, highlighting the overlapping diagnostic criteria and challenges., Methods: We investigated the FGFR2 fusion landscape in a French national series of tumours sent to the RENOCLIP-LOC network. We comprehensively analysed histology, radiology and molecular data including DNA-methylation profiling for 16 FGFR2-fused glioneuronal tumours., Results: Most tumours were located in the temporal or parietal lobe with a median age at diagnosis of 7 years [1-44]. Epilepsy was the most frequent symptom. Five patients had tumour progression or recurrence with a median progression-free survival of 22.6 months. Histological phenotypes corresponding to PLNTY, GG, MVNT or unclassified tumours were recorded. Epigenetic profiling could not properly distinguish epigenetic clusters related to the GG and PLNTY methylation classes among FGFR2-fused glioneuronal tumours. However, a neuroradiological review identified strikingly distinct neuroradiological patterns., Conclusion: While delineating tumour types among the FGFR2-fused glioneuronal tumour spectrum, by histopathology or DNA-methylation profiling, remains challenging, neuroimaging data revealed two distinct patterns that could correlate to PLNTY and ganglioglioma. However, more series including extensive histo-radio-molecular data are needed to confirm this hypothesis., (© 2024 The Author(s). Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)

The coronavirus disease 2019 (COVID-19) pandemic rapidly boosted the introduction of certain changes in mental healthcare services, consequently driving up the adoption of remote care delivery options. We conducted an online Italian survey to evaluate telepsychology use, attitudes, acceptance, and training needs, as well as to understand patient-professional interactions in video-consultations, aiming to inform future mental healthcare practices and policies. The current study's survey responses were collected using an anonymous, self-reported questionnaire on the 'REDCap' platform from 25 October 2022 to 26 July 2023. In total, 128 mental health professionals and 113 patients completed the survey. In our sample, 69 % of patients and 79.7 % of mental health professionals reported having used telepsychology during COVID-19 pandemic; in particular, 84.6 % of patients and 95.1 % of professionals selected video-consultation modality. Data showed that participants expressed high satisfaction with this communication tool. The increase in satisfaction was directly proportional to increase in the quality of interactions and in relation to the quality of the experiences. The critical factors influencing the video-consultation experience include communication style, information completeness, patient-centredness, and the comfort underscoring the central role of the professional-patient relationship, which, substantially, remains a key element in the psychological treatment process. These findings reinforce the need for continued refinement and expansion of telepsychology services, thus highlighting the potential for integrating innovative technologies into mental health practise., Competing Interests: None., (© 2024 The Authors.)

Sudden cardiac death (SCD) prevention in cardiomyopathies such as hypertrophic (HCM), dilated (DCM), non-dilated left ventricular (NDLCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) remains a crucial but complex clinical challenge, especially among younger populations. Accurate risk stratification is hampered by the variability in phenotypic expression and genetic heterogeneity inherent in these conditions. This article explores the multifaceted strategies for preventing SCD across a spectrum of cardiomyopathies and emphasizes the integration of clinical evaluations, genetic insights, and advanced imaging techniques such as cardiac magnetic resonance (CMR) in assessing SCD risks. Advanced imaging, particularly CMR, not only enhances our understanding of myocardial architecture but also serves as a cornerstone for identifying at-risk patients. The integration of new research findings with current practices is essential for advancing patient care and improving survival rates among those at the highest risk of SCD. This review calls for ongoing research to refine risk stratification models and enhance the predictive accuracy of both clinical and imaging techniques in the management of cardiomyopathies.

A novel histomolecular tumor of the central nervous system (CNS), the "diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC)," has recently been identified, based on a distinct DNA methylation profile and has been added to the 2021 World Health Organization Classification of CNS Tumors. This glioneuronal tumor mainly affects the supratentorial area in children and recurrently presents with a monosomy of chromosome 14. Herein, we report the case of a DNA-methylation based diagnosis of DGONC having atypical features, such as pseudo-rosettes and the absence of a chromosome 14 monosomy, thus rendering its diagnosis very challenging. Because of the wide variety of morphologies harbored by DGONC, a large range of differential diagnoses may be hypothesized from benign to malignant. Interestingly, the current case, like one previously reported, exhibited a co-expression of OLIG2, synaptophysin and SOX10, without GFAP immunopositivity. This particular immunophenotype seems to be a good indicator for a DGONC diagnosis. The classification of DGONC amongst glioneuronal or embryonal tumors is still debated. The clinical (a pediatric supratentorial tumor), morphological (from a benign oligodendroglioma-like tumor with microcalcifications and possible neuropil-like islands to a malignant embryonal tumor with a possible spongioblastic pattern), and immunohistochemical (co-expression of OLIG2 and synaptophsyin) profiles resemble CNS, neuroblastoma, FOXR2-activated and may potentially bring them together in a future classification. Further comprehensive studies are needed to conclude the cellular origin of DGONC and its prognosis., (© 2024. The Author(s).)

Background: Prader-Willi syndrome (PWS) is a genetic disorder characterized by abnormalities in the 15q11-q13 region. Understanding the correlation between genotype and phenotype in PWS is crucial for improved genetic counseling and prognosis. In this study, we aimed to investigate the correlation between genotype and phenotype in 45 PWS patients who previously underwent methylation-sensitive high-resolution melting (MS-HRM) for diagnosis., Results: We employed methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and Sanger sequencing, along with collecting phenotypic data from the patients for comparison. Among the 45 patients, 29 (64%) exhibited a deletion of 15q11-q13, while the remaining 16 (36%) had uniparental disomy. No statistically significant differences were found in the main signs and symptoms of PWS. However, three clinical features showed significant differences between the groups. Deletion patients had a higher prevalence of myopia than those with uniparental disomy, as well as obstructive sleep apnea and an unusual skill with puzzles., Conclusions: The diagnostic tests (MS-HRM, MS-MLPA, and Sanger sequencing) yielded positive results, supporting their applicability in PWS diagnosis. The study's findings indicate a general similarity in the genotype-phenotype correlation across genetic subtypes of PWS., (© 2024. The Author(s).)

Up to 25% of pediatric cataract cases are inherited. There is sparse information in the literature regarding the cost of whole-exome sequencing (WES) for suspected hereditary pediatric cataracts. Molecular diagnosis of suspected hereditary pediatric cataracts is important for comprehensive genetic counseling. We performed a partial economic evaluation with a mixed costing analysis, using reimbursement data and microcosting approach with a bottom-up technique to estimate the cost of using WES for genetic diagnosis of suspected hereditary pediatric cataracts from the perspective of the Brazilian governmental health care system. One hundred and ten participants from twenty-nine families in Rio de Janeiro (RJ) were included. Costs of consumables, staff and equipment were calculated. Two scenarios were created: (1) The reference scenario included patients from RJ with suspected hereditary pediatric cataracts plus two family members. (2) The alternative scenario considered other genetic diseases, resulting in 5,280 exams per month. Sensitivity analysis was also performed. In the reference scenario, the total cost per exam was 700.09 United States dollars (USD), and in the alternative scenario, the total cost was 559.23 USD. The cost of WES alone was 527.85 USD in the reference scenario and 386.98 USD in the alternative scenario. Sensitivity analysis revealed that the largest costs were associated with consumables in both scenarios. Economic evaluations can help inform policy decisions, especially in middle-income countries such as Brazil., (© 2024. The Author(s).)

Background/Objectives: Although SARS-CoV-2 infection is a significant risk factor for venous thromboembolism (VTE), data on the impact of the use of non-invasive ventilation support (NIVS) to mitigate the risk of VTE during hospitalization are scarce. Methods: Data for 1471 SARS-CoV-2 patients, hospitalized in a single hub during the first pandemic wave, were collected from clinical records, including symptom duration and type, information on lung abnormalities on chest computed tomography (CT), laboratory parameters and the use of NIVS. Determining VTE occurrence during hospital stays was the main endpoint. Results: Patients with VTE (1.8%) had an increased prevalence of obesity (26% vs. 11%), diabetes (41% vs. 21%), higher CHA2DS2VASC score (4, IQR 2-5 vs. 3, IQR 1-4, age- and sex-adjusted, p = 0.021) and cough (65% vs. 44%) and experienced significantly higher rates of NIVS (44% vs. 8%). Using a stepwise multivariate logistic regression model, the prevalence of electrocardiogram abnormalities (odds ratio (OR) 2.722, 95% confidence interval (CI) 1.039-7.133, p = 0.042), cough (OR 3.019, 95% CI 1.265-7.202, p = 0.013), CHA2DS2-VASC score > 3 (OR 3.404, 95% CI 1.362-8.513, p = 0.009) and the use of NIVS (OR 15.530, 95% CI 6.244-38.627, p < 0.001) were independently associated with a risk of VTE during hospitalization. NIVS remained an independent risk factor for VTE even after adjustment for the period of admission within the pandemic wave. Conclusions: Our study suggests that NIVS is a risk factor for VTE during hospitalization in SARS-CoV-2 patients. Future studies should assess the optimal prophylactic strategy against VTE in patients with a SARS-CoV-2 infection candidate to non-invasive ventilatory support.

Digital complete dentures fabricated using a mucostatic impression, like intraoral scans, are desirable for their beneficial effect on long-term residual ridge stability but may have less retention than those fabricated with a mucocompressive impression. Border molding procedure may improve initial retention, thus favoring adaptation to new dentures, especially in cases where neuromuscular dysfunctions may diminish the patient's ability to cope with adapting to existing motor patterns or learn new ones. However, a mucocompressive impression may cause higher residual ridge resorption, thus resulting in a retention decrease over time. A desirable combination would be a digital denture with a mucostatic intaglio surface obtained from intraoral scans and functional borders. A cast-free digital workflow for that is demonstrated in this technical report., (© 2024 by the American College of Prosthodontists.)

Zika virus (ZIKV) infections during pregnancy can result in Congenital Zika Syndrome (CZS), a range of severe neurological outcomes in fetuses that primarily occur during early gestational stages possibly due to placental damage. Although some placentas can maintain ZIKV persistence for weeks or months after the initial infection and diagnosis, the impact of this viral persistence is still unknown. Here, we aimed to investigate the immunological repercussion of ZIKV persistence in term placentas. As such, term placentas from 64 pregnant women diagnosed with Zika in different gestational periods were analyzed by ZIKV RT-qPCR, examination of decidua and placental villous histopathology, and expression of inflammation-related genes and IFNL1-4 . Subsequently, we explored primary cultures of term decidual Extravillous Trophoblasts (EVTs) and Term Chorionic Villi (TCV) explants, as in vitro models to access the immunological consequences of placental ZIKV infection. Placenta from CZS cases presented low IFNL1-4 expression, evidencing the critical protective role of theses cytokines in the clinical outcome. Term placentas cleared for ZIKV showed increased levels of IFNL1 , 3 , and 4 , whether viral persistence was related with a proinflammatory profile. Conversely, upon ZIKV persistence placentas with decidual inflammation showed high IFNL1-4 levels. In vitro experiments showed that term EVTs are more permissive, and secreted higher levels of IFN-α2 and IFN-λ1 compared to TCV explants. The results suggest that, upon ZIKV persistence, the maternal-skewed decidua contributes to placental inflammatory and antiviral signature, through chronic deciduitis and IFNL upregulation. Although further studies are needed to elucidate the mechanisms underlying the decidual responses against ZIKV. Hence, this study presents unique insights and valuable in vitro models for evaluating the immunological landscape of placentas upon ZIKV persistence., Competing Interests: 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., (© 2024 The Authors.)

The orphan nuclear receptor ERRα is the most extensively researched member of the estrogen-related receptor family and holds a pivotal role in various functions associated with energy metabolism, especially in tissues characterized by high energy requirements, such as the heart, skeletal muscle, adipose tissue, kidney, and brain. Abscisic acid (ABA), traditionally acknowledged as a plant stress hormone, is detected and actively functions in organisms beyond the land plant kingdom, encompassing cyanobacteria, fungi, algae, protozoan parasites, lower Metazoa, and mammals. Its ancient, cross-kingdom role enables ABA and its signaling pathway to regulate cell responses to environmental stimuli in various organisms, such as marine sponges, higher plants, and humans. Recent advancements in understanding the physiological function of ABA and its mammalian receptors in governing energy metabolism and mitochondrial function in myocytes, adipocytes, and neuronal cells suggest potential therapeutic applications for ABA in pre-diabetes, diabetes, and cardio-/neuroprotection. The ABA/LANCL1-2 hormone/receptor system emerges as a novel regulator of ERRα expression levels and transcriptional activity, mediated through the AMPK/SIRT1/PGC-1α axis. There exists a reciprocal feed-forward transcriptional relationship between the LANCL proteins and transcriptional coactivators ERRα/PGC-1α, which may be leveraged using natural or synthetic LANCL agonists to enhance mitochondrial function across various clinical contexts.

The Zika virus (ZIKV) can be vertically transmitted, causing congenital Zika syndrome (CZS) in fetuses. ZIKV infection in early gestational trimesters increases the chances of developing CZS. This syndrome involves several pathologies with a complex diagnosis. In this work, we aim to identify biological processes and molecular pathways related to CZS and propose a series of putative protein and metabolite biomarkers for CZS prognosis in early pregnancy trimesters. We analyzed serum samples of healthy pregnant women and ZIKV-infected pregnant women bearing nonmicrocephalic and microcephalic fetuses. A total of 1090 proteins and 512 metabolites were identified by bottom-up proteomics and untargeted metabolomics, respectively. Univariate and multivariate statistical approaches were applied to find CZS differentially abundant proteins (DAP) and metabolites (DAM). Enrichment analysis (i.e., biological processes and molecular pathways) of the DAP and the DAM allowed us to identify the ECM organization and proteoglycans, amino acid metabolism, and arachidonic acid metabolism as CZS signatures. Five proteins and four metabolites were selected as CZS biomarker candidates. Serum multiomics analysis led us to propose nine putative biomarkers for CZS prognosis with high sensitivity and specificity.

Background and Objectives: When seizure onset affects a whole hemisphere, hemispheric disconnections are efficient and safe procedures. However, both lateral peri-insular hemispherotomy and vertical paramedian hemispherotomy approaches report a failure rate around 20%, which can be explained by residual connections giving rise to persistent seizures. In this study, we present the interhemispheric vertical hemispherotomy (IVH), a technical variation of the vertical paramedian hemispherotomy approach, that aims to increase seizure control avoiding residual connections while exposing the corpus callosum., Methods: This is a retrospective study of IVH in two centers, with analysis of clinical and MRI data and outcomes. A detailed description of the technique is provided with a video., Results: IVH was performed in 39 children. The mean age at surgery was 7.2 years, and etiologies were as follows: malformations of cortical development (n = 14), Rasmussen's encephalitis (n = 10), stroke (n = 10), post-traumatic (3), and Sturge-Weber Syndrome (2). Hemispheric disconnection was complete on postoperative MRI in 34 cases. There was no mortality, hydrocephalus occurred in one case, and subdural collection occurred in four cases. A second surgery was performed in four cases because of seizure relapse (n = 3) and/or incomplete disconnection on MRI (n = 4). With a mean follow-up of 3.2 years, International League Against Epilepsy class I epilepsy outcome was obtained for 37/39 patients., Conclusion: IVH is a safe and effective variation of the vertical approaches for hemispheric disconnection. It allows a good exposure and anatomic control of the corpus callosum, which is a frequent site of incomplete disconnection. IVH may be limited by the thalamic volume and the ventricular size, notably in hemimegalencephaly cases., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Statement of Problem: Comparative cost-analysis related to different manufacturing workflows for removable complete denture fabrication is seldom performed before the adoption of a new technology., Purpose: The purpose of this study was to compare the clinical and laboratory costs of removable complete dentures fabricated with a conventional (workflow C), a partial digital (workflow M), and a complete digital (workflow D) workflow and to calculate the break-even points for the implementation of digital technologies in complete denture fabrication., Material and Methods: Clinical and laboratory costs for each of the investigated workflows and the manufacturing options related to denture base and denture teeth fabrication were collected from 10 private Italian dental laboratories and clinics. The selected variables included the clinical and laboratory manufacturing time needed to complete each workflow (opportunity cost); costs for materials, labor, packaging, and shipping; and capital and fixed costs for software and hardware, including maintenance fees. The effect of manufacturing workflows and their options on the outcomes of interest was investigated by using generalized estimated equations models (α=.05). Cost minimization and sensitivity analysis were also performed, and break-even points were calculated for the equipment capital costs related to the implementation of workflows M and D., Results: From a laboratory standpoint, workflows M and D and related manufacturing options significantly (P<.001) reduced manufacturing time (5.90 to 6.95 hours and 6.30 to 7.35 hours, respectively), and therefore the opportunity cost of each denture compared with workflow C. Workflow M allowed variable costs savings between 81 and 169 USD, while workflow D allowed for an additional saving of 34 USD. The sensitivity analysis showed that the break-even point related to the capital investment for the equipment needed to implement workflows M and D could be reached, depending on the manufacturing options adopted, between 170 and 933 dentures for workflow M and between 73 and 534 dentures for workflow D. From a clinical standpoint, workflows C and M were almost identical. Conversely, workflow D, which included intraoral scanning, required 1 fewer appointment, saving 0.6 hours of chairside time and about 14 USD for materials compared with M., Conclusions: Digital workflows (partial and complete digital workflows) were more efficient and cost-effective than the conventional method of fabricating removable complete dentures, with workflow D showing the lowest opportunity and variable costs and break-even point. Savings increased when stock denture teeth were replaced with milled denture teeth and still further with the adoption of 3-dimensionally (3D) printed denture teeth. Milling equipment and materials for denture base fabrication were more expensive than those for 3D-printing. Milling monobloc dentures reduced opportunity and labor costs but increased material cost., (Copyright © 2022 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Among pro-inflammatory cytokines, Interleukin-1β is crucially involved in several inflammatory-based diseases and even cancer. Increased Interleukin-1β levels in oral fluids have been proposed as an early marker of periodontitis, a broadly diffused chronic inflammatory condition of periodontal-supporting tissues, leading eventually to tooth loss. We describe the development of a portable surface-plasmon-resonance-based optical fiber probe suitably coated with an anti-Interleukin-1β antibody monolayer. A pico-nanomolar linear range of determination was obtained in both buffer solution and saliva with a rapid (3 min) incubation and high selectivity in presence of interferents. Higher Interleukin-1β concentration in the saliva of a periodontitis patient compared to a healthy control was determined. These measurements were validated by an automated ELISA system. Our results sustain the potential applicability of the proposed SPR-POF as diagnostic point-of-care device for real-time monitoring of salivary Interleukin-1β, that can support early detection of oral inflammatory-based pathologies and rapid and timely therapeutic decisions., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

The analysis of salivary biomarkers as expression of periodontal health conditions has been proposed as a useful aid to conventional diagnostic approaches. In this study, we present a point-of-care test (POCT) exploiting a surface plasmon resonance (SPR)-based optical biosensor to detect salivary macrophage inflammatory protein (MIP)-1α, a promising marker of periodontitis. A plastic optical fiber (POF) was suitably modified and functionalized by an antibody self-assembled monolayer against MIP-1α for plasmonic detection. The proposed SPR-POF biosensor showed high selectivity and very low limit of detection for MIP-1α of 129 fM (1.0 pg/mL) in phosphate-buffered saline and 346 fM (2.7 pg/mL) in saliva. As a proof of concept, this POCT was also able to discriminate between a periodontitis patient and a healthy subject. The obtained results support the future application of this technology for an on-site detection and real-time monitoring of periodontal health conditions for diagnostic and therapeutic purposes., Competing Interests: The authors declare no competing interests with respect to the authorship and/or publication of this article., (© 2023 The Authors.)

Statement of Problem: Manufacturers of several intraoral scanners have recommended a 2-step strategy for scanning the edentulous mandible. The 2-step technique requires scanning one side first and then moving to the other side. However, whether inconsistency in stitching occurs that results in loss of accuracy or distortion is unclear., Purpose: The purpose of this clinical study was to measure the potential distortion of intraoral scans of edentulous mandibular arches made with a 2-step scanning strategy and to assess their differences with conventional impressions., Material and Methods: Twenty mandibular edentulous arches were scanned by 1 investigator with an intraoral scanner using a 2-step scanning strategy, and a corresponding polysulfide conventional impression was obtained. The conventional impression was then immediately scanned with the same intraoral scanner. The obtained standard tessellation language (STL) files were superimposed with a surface-matching software program. After a preliminary alignment, the STL meshes were trimmed and reoriented; then, the final alignment was carried out and meshes moved to a metrology software program where their mean distance was measured. In addition, a surface curve (SIOS) was traced on the intraoral scan from the right to left retromolar pad along the residual ridge and automatically projected onto to the conventional impression scan to obtain a new curve (SC). The mean distance between SIOS and SC was measured and recorded as an indicator of the distortion by considering the X-, Y-, and Z-axes and the overall 3-dimensional (3D) deviation. The analysis was performed for the full curve length and after dividing it into 6 regions of interest. Univariate and multivariate statistical analyses were used to investigate the significance of the extent of the mean 3D distance, as well as the effects of measurement positions (side and region) between and within patients on differences along the X-, Y-, and Z-axes (α=.05)., Results: The mean (-0.08 mm; standard error: 0.025) 3D distance between the intraoral scan and conventional impression was significantly different from zero (P=.003). No significant effect of the factor "side" was found by using generalized estimated equation models for the X-, Y-, and Z-axes, and global 3D deviations between SIOS and SC (P>.05), which appeared to exclude distortion. Conversely, a significant effect was found for the factor "region" (P<.05), with no significant differences (P>.05) between corresponding regions on the 2 sides., Conclusions: Intraoral scans of the edentulous mandibular arch made in a 2-step procedure did not exhibit significant distortion in comparison with conventional impressions., (Copyright © 2023 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to assess the relevance of using multi-positional MRI (mMRI) to identify cranio-vertebral junction (CVJ) instability in pediatric patients with CVJ anomalies while determining objective mMRI criteria to detect this condition., Material and Methods: Data from children with CVJ anomalies who underwent a mMRI between 2017 and 2021 were retrospectively reviewed. Mobility assessment using mMRI involved: (1) morphometric analysis using hierarchical clustering on principal component analysis (HCPCA) to identify clusters of patients by considering their mobility similarities, assessed through delta (Δ) values of occipito-cervical parameters measured on mMRI; and (2) morphological analysis based on dynamic geometric CVJ models and analysis of displacement vectors between flexion and extension. Receiver operating characteristics (ROC) curves were generated for occipito-cervical parameters to establish instability cut-off values. (3) Additionally, an anatomical qualitative analysis of the CVJ was performed to identify morphological criteria of instability., Results: Forty-seven patients with CVJ anomalies were included (26 females, 21 males; mean age: 10.2 years [3-18]). HCPCA identified 2 clusters: cluster №1 (stable patients, n = 39) and cluster №2 (unstable patients, n = 8). ΔpB-C2 (pB-C2 line delta) at ≥2.5 mm (AUC 0.98) and ΔBAI (Basion-axis Interval delta) ≥ 3 mm (AUC 0.97) predicted instability with 88% sensibility and 95% specificity and 88% sensitivity and 85% specificity, respectively. Geometric CVJ shape analysis differentiated patients along a continuum, from a low to a high CVJ motion that was characterized by a subluxation of C1 in the anterior direction. Qualitative analysis found correlations between instability and C2 anomalies, including fusions with C3 (body p = 0.032; posterior arch p = 0.045; inferior articular facets p = 0.012; lateral mass p = 0.029)., Conclusions: We identified a cluster of pediatric patients with CVJ instability among a cohort of CVJ anomalies that were characterized by morphometric parameters with corresponding cut-off values that could serve as objective mMRI criteria. These findings warrant further validation through prospective case-control studies.

Objective: The outcome of endoscopic third ventriculostomy (ETV) in children who had previously received shunts and who were experiencing shunt dysfunction is still discussed in terms of efficacy (success rate from 40% to 80%) and safety (0%-32.5% of complications). Reported predictive factors of secondary ETV failure are age, early onset of hydrocephalus, and prematurity. The best surgical strategy in the different subgroups of patients with shunt dysfunction is still debated. Therefore, the authors aimed to identify subgroups of patients in whom shunt treatment was associated with favorable outcome of ETV, to define the role of ETV in patients with global rostral midbrain dysfunction syndrome., Methods: This study was a monocentric retrospective case series and a meta-analysis of children who had previously received shunts and who underwent secondary ETV for shunt dysfunction between 2012 and 2022. Clinical and MRI features were examined, along with surgical outcome, etiology of hydrocephalus, and preoperative ETV Success Score. Univariate and multivariate analyses were performed to find predictors of outcome of secondary ETV. Youden's J index was calculated on age distribution to find an optimal age cutoff. Systematic review of the literature and a meta-analysis were performed according to the PRISMA statement., Results: Seventy consecutive patients were included. The overall success rate of secondary ETV was 63%. Primary obstructive hydrocephalus, age ≥ 36 months, and the presence of aqueductal obstruction were predictors of ETV success. Multivariate analysis found that age < 36 months, primary inflammatory hydrocephalus, and presence of fourth ventricular obstruction were associated with ETV failure. All patients with global rostral midbrain dysfunction syndrome experienced clinical and radiological improvement after ETV. The meta-analysis showed that postinflammatory etiology and age < 36 months were predictors of ETV failure., Conclusions: ETV is safe and effective for children with obstructive hydrocephalus experiencing shunt dysfunction, notably in cases of primary obstructive hydrocephalus with aqueductal stenosis, and among children whose age was ≥ 36 months who had postinflammatory hydrocephalus.

Background: Hydrocephalus frequently occurs with midline posterior fossa cystic collections. The classification of this heterogeneous group of developmental anomalies, including Dandy-Walker malformation, persisting Blake's pouch, retrocerebellar arachnoid cysts, and mega cisterna magna, is subject of debate. The absence of diagnostic criteria is confusing regarding the ideal management of PFCC-related hydrocephalus., Objective: To decipher the surgical strategy for the treatment of children with PFCC-related hydrocephalus through a retrospective analysis of the surgical outcome driven by their clinical and radiological presentation., Methods: This study enrolled patients operated of symptomatic PFCC-related hydrocephalus. Clinical and MRI features were examined, as well as the surgical outcome. Unbiased subgroup classification of the patients was performed with multiple component analysis as a function of imaging characteristics and hierarchical clustering on principal component. Outcome was assessed with binomial logistic regression and Kaplan-Meier analysis., Results: Fifty-four patients were included between 2007 and 2021. Multiple component analysis suggested that cerebellar and vermian hypoplasia, vermian rotation, basal-tentorial angle, and fastigial angle were strongly correlated. Hierarchical clustering and the distribution of the patients in the bidimensional plot showed the clear segregation of 3 major clusters, which correlated with the radiological diagnosis ( P < .01). Binomial logistic regression and survival analysis showed that endoscopic third ventriculostomy was an effective treatment for patients with persisting Blake's pouch, while failing to control hydrocephalus in most of patients with Dandy-Walker malformation., Conclusion: Preoperative MRI in patients with PFCC-related hydrocephalus is essential to better define the diagnosis. The choice of treatment strategy notably relies on correct radiological diagnosis., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

The cross-kingdom stress hormone abscisic acid (ABA) and its mammalian receptors LANCL1 and LANCL2 regulate the response of cardiomyocytes to hypoxia by activating NO generation. The overexpression of LANCL1/2 increases transcription, phosphorylation and the activity of eNOS and improves cell vitality after hypoxia/reoxygenation via the AMPK/PGC-1α axis. Here, we investigated whether the ABA/LANCL system also affects the mitochondrial oxidative metabolism and structural proteins. Mitochondrial function, cell cycle and the expression of cytoskeletal, contractile and ion channel proteins were studied in H9c2 rat cardiomyoblasts overexpressing or silenced by LANCL1 and LANCL2, with or without ABA. Overexpression of LANCL1/2 significantly increased, while silencing conversely reduced the mitochondrial number, OXPHOS complex I, proton gradient, glucose and palmitate-dependent respiration, transcription of uncoupling proteins, expression of proteins involved in cytoskeletal, contractile and electrical functions. These effects, and LANCL1/2-dependent NO generation, are mediated by transcription factor ERRα, upstream of the AMPK/PGC1-α axis and transcriptionally controlled by the LANCL1/2-ABA system. The ABA-LANCL1/2 hormone-receptor system controls fundamental aspects of cardiomyocyte physiology via an ERRα/AMPK/PGC-1α signaling axis and ABA-mediated targeting of this axis could improve cardiac function and resilience to hypoxic and dysmetabolic conditions.

Objective: The Mandibular Advancement Device (MAD) is actually recommended for the treatment of Obstructive Sleep Apnea (OSA) with mild or moderate severity. The present study evaluated the effects of a fully customizable MAD-type device (It Makes You Sleep, IMYS), in patients with moderate-to-severe OSA., Methods: Twenty-nine patients (15 men and 14 women; mean age 62, SD ±10 years) were retrospectively enrolled. Home Sleep Apnea Testing ;(HSAT) was performed for all patients at baseline (T0) and after three months (T1) of IMYS therapy. The analyzed respiratory parameters were: Apnea-Hypopnea Index (AHI), Oxygen Desaturation Index (ODI), Minimum Oxygen Saturation (minSO2) and Medium Oxygen Saturation (medSO2)., Results: From T0 to T1, a significant reduction of AHI and ODI was reported, as well as a significant increase of minSO2 and medSO2., Conclusion: The IMYS device could be an effective MAD appliance for treating moderate-to-severe OSA.

Background: The accuracy of surgical guides is a relevant factor in both surgical safety and prosthetic implications. The impact of widespread fabrication technologies (milling and 3D printing) was investigated., Methods: Surgical guides manufactured by means of two specific milling and 3D-printing systems were digitized and compared in a 3D analysis with the digital file of the designed guides. The surface mean 3D distance (at the surface where the teeth and mucosa made contact) and the axial and linear deviations of the sleeves' housings were measured by means of a metrological software program. Univariate and multivariate statistical analyses were used to investigate the effects of the fabrication technology, type of support, and arch type on the surgical guides' accuracy., Results: The median deviations of the intaglio surface in contact with the mucosa were significantly ( p < 0.001) lower for the milled surgical guides (0.05 mm) than for the 3D-printed guides (-0.07 mm), in comparison with the reference STL file. The generalized estimated equation models showed that the axial deviations of the sleeves' housings (a median of 0.82 degrees for the milling, and 1.37 degrees for the 3D printing) were significantly affected by the fabrication technology ( p = 0.011) (the milling exhibited better results), the type of support ( p < 0.001), and the combined effect of the fabrication technology and the sleeve-to-crest angle ( p = 0.003). The linear deviation (medians of 0.12 mm for the milling and 0.21 mm for the 3D printing) of their center points was significantly affected by the type of support ( p = 0.001), with the milling performing slightly better than the 3D printing., Conclusions: The magnitude of the difference might account for a limited clinical significance.

Objectives: The evaluation of salivary biomarkers has been proposed as a simple and non-invasive aid to the conventional periodontal diagnosis based on clinical-radiographic parameters. Matrix metalloproteinase-8 (MMP-8), especially in its active form, is considered one of the most reliable biomarkers of periodontitis, and point-of-care tests (POCTs) have been proposed for its clinical monitoring. In this proof-of-concept study, a novel highly sensitive POCT based on a plastic optical fiber (POF) biosensor exploiting surface plasmon resonance (SPR) to detect salivary MMP-8 is described., Methods: A SPR-POF biosensor was functionalized with a specific antibody to develop a surface-assembled monolayer (SAM) for the detection of total MMP-8. A white light source and a spectrometer connected to the biosensor were used to quantify MMP-8 level in both buffer and real matrix (saliva) by analysing the shift of the resonance wavelength determined by the specific antigen-antibody binding upon the SAM., Results: Dose-response curves by serial dilutions of human recombinant MMP-8 were realized, obtaining a limit of detection (LOD) of 40 pM (1.76 ng/ml) in buffer and 225 pM (9.9 ng/ml) in saliva and high selectivity compared to interferent analytes (MMP-2 and IL-6)., Conclusions: The proposed optical fiber-based POCT was able to detect and measure total MMP-8 with high selectivity and very low LOD in both buffer and saliva., Clinical Significance: The SPR-POF technology may be employed to create highly sensitive biosensors to monitor salivary MMP-8 levels. The possibility of specifically detecting its active, rather than total, form need to be further investigated. If confirmed and clinically validated, such a device may represent a promising tool to make an immediate, highly sensitive and reliable diagnosis of periodontitis, and to carry out a timely and targeted therapy, possibly helping to prevent the onset of local and systemic periodontitis-related complications., 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 © 2023. Published by Elsevier Ltd.)

Statement of Problem: Three-dimensional (3D) printing technologies commonly used for trial complete dentures use photopolymerizing resins. Although effective, some clinical, process-related, and practical issues associated with them are still unclear. The option of using alternative printing technologies may help in overcoming limitations., Purpose: The purpose of this in vitro study was to evaluate the trueness of trial dentures fabricated by using 3D-printing fused deposition modeling (FDM)., Material and Methods: Ten maxillary and 10 mandibular digital complete trial dentures designed from intraoral scans were fabricated from polylactic acid by using a FDM 3D-printer. Each denture was scanned, and the scans were compared with the digital file of the designed denture by means of a surface-matching software program. The mean distance (both signed and absolute) was measured and recorded for the intaglio surface, as well as for the entire denture surface. Statistical analysis was performed to investigate the significance of the extent of measured distances, as well as differences between intaglio and global deviations; subgroup analysis for arch type was also performed (α=.05)., Results: Mean values of the intaglio distance were not significantly different from zero (P=.223). The manufacturing accuracy of the intaglio surface was higher than that measured for the entire denture (P<.001), confirmed both by the averaged signed (0 mm and -0.028 mm, respectively) and the absolute mean deviations (0.06 mm and 0.08 mm, respectively). No significant differences were found between maxillary and mandibular trial dentures., Conclusions: 3D-printing may constitute a valid and practical option for accurate and affordable digital trial dentures., (Copyright © 2021 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyze, in vitro, the dimensional stability over time of 3D-printed surgical guides., Materials and Methods: Ten surgical guides, manufactured by digital light processing 3D-printing technology, were scanned immediately after post-processing and then after 5, 10, 15, and 20 days. The corresponding standard tessellation language (STL) files were used for comparison with the reference CAD project. Mean absolute deviation (MAD) of the intaglio surface, axial, and linear deviations of the sleeves' housings were measured. Generalized estimated equations models (α = 0.05) were used to investigate the effect of time., Results: MAD of the teeth intaglio surface showed less variation (minimum: 0.002, maximum: 0.014 mm) than that of the mucosa (minimum: 0.026, maximum: 0.074 mm). Axial variations of the sleeves' housings on the sagittal (minimum: -0.008°, maximum: -0.577°) and frontal plane (minimum: -0.193°, maximum: 0.525°) changed with similar patterns, but opposite trends (decreasing for the former). Linear deviations of center points of the sleeves' housings had a shifting (minimum: -0.074, maximum: 0.02 mm) pattern with a decreasing tendency. Time after processing had a significant effect, either alone or nested with guides volume, on all outcomes of interest, except for MAD of the mucosa intaglio surface (p < 0.001), which was significantly affected only by the time-volume nested effect (p = 0.012)., Conclusions: Within the limitations of the experimental design, postmanufacturing dimensional variations of surgical guides were statistically significant. Although limited, they are an additional source of variability affecting the overall accuracy of computer-guided surgery. As such, they should be addressed by further research., (© 2022 by the American College of Prosthodontists.)

Background: The role of interdental widths and palatal morphology on the development of obstructive sleep apnea (OSA) has not been well investigated in adult patients yet. The aim of this paper was to assess the morphology of maxilla and mandibular dental arches on three-dimensional (3D) casts and to correlate these measurements with the severity of OSA., Methods: Sixty-four patients (8 women and 56 men, mean age 52.4) with a diagnosis of mild-to-moderate OSA were retrospectively enrolled. On each patient, home sleep apnea test and 3D dental models were collected. Apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were recorded, as well as the dental measurements including inter-molar distance, anterior and posterior widths of maxillary and mandibular arches, upper and lower arch lengths, palatal height, and palatal surface area. The respiratory and dental variables were then correlated., Result: A statistically inverse correlation was found between ODI and anterior width of lower arch, maxillary arch length, palatal height, and palatal area. AHI showed a significant inverse correlation with anterior width of mandibular arch and maxillary length., Conclusion: A significant inverse correlation between maxillary and mandibular morphology and respiratory parameters was shown in the present paper., (© 2023. The Author(s).)

Point-of-Care tests based on biomarkers, useful to monitor acute and chronic inflammations, are required for advances in medicine. In this scope, a key role is played by pro-inflammatory cytokines, of which interleukin 6 (IL-6) is generally thought as one of the most relevant. To use IL-6 in real scenarios, detection in ultra-low concentration ranges is required. In this work, two IL-6 biosensors are obtained by exploiting the combination of the same antibody self-assembled monolayer with two different plasmonic probes. This approach has demonstrated, via experimental results, that two different IL-6 concentration ranges can be explored. More specifically, IL-6 in an atto-femto molar range can be detected via polymer-based nanoplasmonic chips. On the other hand, a pico-nano molar range is obtained by a surface plasmon resonance platform in plastic optical fibers. As a proof of concept, the detection of IL-6 at the femto molar range has been obtained in Saliva and Serum. The results show that the proposed sensing approach could be useful in developing Point-of-Care devices based on a general setup with the capability to exploit both the plasmonic biosensor chips to monitor the IL-6 in the concentration range of interest, to provide an important support for the diagnosis and monitoring of oral and systemic diseases., 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 © 2023 Elsevier B.V. All rights reserved.)

Objectives: The aim of the present randomized clinical trial (RCT) with a parallel arm design was to evaluate the clinical and microbiological efficacy of repeated ICG-aPDT as an adjunct to full-mouth subgingival debridement in the treatment of periodontitis., Materials and Methods: Twenty-four periodontitis patients were treated with full-mouth ultrasonic subgingival debridement (FMUD). Initial sites with probing depth (PD) > 4 mm were randomly assigned to receive the test (ICG-aPDT with an 810 nm diode laser) or the control treatment (off-mode aPDT) one and four weeks after FMUD. Clinical parameters were registered after 3 and 6 months. The presence of the main periodontal pathogens in subgingival samples was assessed with real-time PCR., Results: Both treatment modalities resulted in significant clinical improvements at 3 and 6 months. The only significant differences in favour of the test group were found at 6 months for a higher PD reduction in initial deep pockets (PD ≥ 6 mm) and a higher percentage of closed pockets (PD ≤ 4 mm/no bleeding on probing). Limited microbiological changes were observed in both groups after treatment with no inter-group difference, except for a more significant reduction in Aggregatibacter actinomycetemcomitans and Parvimonas micra levels in the test group at 3 months., Conclusion: The combination of repeated ICG-aPDT and FMUD provided no benefits except for selective clinical and microbiological improvements compared to FMUD alone., Clinical Relevance: Based on the obtained results, only limited adjunctive effects could be found for the combined use of ICG-aPDT and FMUD. Further, well-designed RCT with larger sample sizes are required to confirm these findings., Trial Registration: ClinicalTrials.gov NCT04671394., (© 2023. The Author(s).)

Zolpidem is a sedative drug that has been shown to induce a paradoxical effect, restoring brain function in wide range of neurological disorders. The underlying functional mechanism of the effect of zolpidem in the brain in clinical improvement is still poorly understood. Thus, we aimed to investigate rest brain function to study zolpidem-induced symptom improvement in a patient who developed postoperative pediatric cerebellar mutism syndrome, a postoperative complication characterized by delayed onset transient mutism/reduced speech that can occur after medulloblastoma resection. The patient experienced clinical recovery after a single dose of zolpidem. Brain function was investigated using arterial spin labeling MRI and resting-state functional MRI. Imaging was performed at three time-points: preoperative, postoperative during symptoms, and after zolpidem intake when the symptoms regressed. Whole brain rest cerebral blood flow (CBF) and resting state functional connectivity using Pearson coefficient correlations between pairs of regions of interest were investigated two-by-two at the different time points. A comparison between postoperative and preoperative images showed a significant decrease in rest CBF in the left supplementary motor area, Broca's area, and the left striatum and a decrease in functional connectivity within the dentato-thalamo-cortical and cortico-striato-pallido-thalamo-cortical loops. Post-zolpidem images showed increased CBF in the left striatum and increased functional connectivity within the disrupted loops relative to postoperative images. Thus, we observed functional changes within the broader speech network and thalamo-subcortical interactions associated with the paradoxical effect of zolpidem in promoting clinical recovery. This should encourage further functional investigations in the brain to better understand the mechanism of zolpidem in neurological recovery., 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 Boisgontier, Beccaria, Saitovitch, Blauwblomme, Guida, Fillon, Dufour, Grill, Lemaitre, Puget, Vinçon-Leite, Dangouloff-Ros, Charpy, Benichi, Levy, Roux, Grévent, Bourgeois, Saidoun, Gaillard, Zilbovicius and Boddaert.)

Purpose: Manufacturing-related inaccuracies of surgical guides for static computer-aided implant surgery may contribute to the overall potential error in the obtained implant position. Measuring such inaccuracies before surgery may provide quality control assessment and improve the safety and outcomes of guided implant surgery. This technical report demonstrates a workflow to measure the accuracy of a surgical guide (at the intaglio surface and sleeve housing) using a freeware metrology software program., Methods: The scan of a milled surgical guide was aligned to and compared with its reference computer-aided design model using a freeware metrology software program (GOM Inspect suite; GOM GmbH). The trueness of the internal surface of the surgical guide was measured as an indicator of adaptation to the supporting tissues. Additionally, some features were constructed to extract the plane at the sleeve entrance and sleeve axis and to set a local coordinate system on them. Linear and angular deviations between the planned and obtained sleeve axes were measured using this system. Such measurements, together with additional known data (sleeve offset and the planned implant length), allowed the estimation of linear errors in implant position at both the implant platform and apex by applying common geometric formulas, based on the assumption that all other sources of error in implant position could be effectively controlled during the surgical procedure., Conclusions: The proposed digital technique is a cost-effective approach for quality control of the inaccuracies of a surgical guide and predicts the related potential error in implant position.

Numerous pieces of evidence demonstrate that oxidative stress impairs biological functions, speeds up aging, and has a role in a variety of human diseases, including systemic and oral inflammatory disorders, and even cancer. Therefore, technologies providing accurate measures of oxidative stress indicators or biomarkers appear essential in the identification/prevention of such diseases, and in their management. Particularly advantageous is the employement of point-of-care tests based on affordable and small biochips since they can quickly process biological samples and deliver results near the point of care for a prompt therapeutic intervention. Malondialdehyde (MDA) is a key byproduct of oxidative reaction and has been identified as an effective marker of oxidative stress. Herein, we describe the detection of MDA in buffer and in a complex matrix such as saliva, using a plasmonic optical fiber device combined with a highly selective anti-MDA antibody. The experimental results highlight the excellent performance of the proposed biosensor, as well as its ability to provide a low-cost point-of-care test (PoC-T) to be used in real life situations. We demonstrated that a single saliva dilution step and a short incubation time are required for the accurate detection of low concentrations of total MDA (free and conjugated). As a proof-of-concept of future biomedical applications, the method has been tested to determine MDA concentration in saliva of a periodontitis patient compared to that of a healthy control. The obtained findings represent the basis for developing PoC-Ts to be employed in monitoring oral diseases like periodontitis, oral cancers or systemic oxidative-stress associated pathologies. Conclusively, our study puts the ground for an oxidative stress biosensor widely-applicable to different scenarios., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Epidural hematoma (EDH) has rarely been studied specifically in infants. The objective of this study was to investigate the outcomes of patients aged < 18 months (infants) with EDH., Methods: The authors conducted a single-center retrospective study of 48 infants aged less than 18 months who underwent an operation for a supratentorial EDH in the last decade. Clinical, radiological, and biological variables were used in a statistical analysis to identify factors predictive of radiological and clinical outcome., Results: Forty-seven patients were included in the final analysis. Seventeen children (36%) had cerebral ischemia on postoperative imaging, either due to stroke (cerebral herniation) or by local compression. Factors associated with ischemia after multivariate logistic regression were the presence of an initial neurological deficit (76% vs 27%, p = 0.03), low platelet count (mean 192 vs 267 per mm3, p = 0.01), low fibrinogen level (mean 1.4 vs 2.2 g/L, p = 0.04) and long intubation time (mean 65.7 vs 10.1 hours, p = 0.03). Cerebral ischemia on MRI was predictive of a poor clinical outcome., Conclusions: Infants with EDH have a low mortality rate but a high risk of cerebral ischemia, along with long-term neurological sequelae.

The abscisic acid (ABA)/LANC-like protein 1/2 (LANCL1/2) hormone/receptor system regulates glucose uptake and oxidation, mitochondrial respiration, and proton gradient dissipation in myocytes. Oral ABA increases glucose uptake and the transcription of adipocyte browning-related genes in rodent brown adipose tissue (BAT). The aim of this study was to investigate the role of the ABA/LANCL system in human white and brown adipocyte thermogenesis. Immortalized human white and brown preadipocytes, virally infected to overexpress or silence LANCL1/2, were differentiated in vitro with or without ABA, and transcriptional and metabolic targets critical for thermogenesis were explored. The overexpression of LANCL1/2 increases, and their combined silencing conversely reduces mitochondrial number, basal, and maximal respiration rates; proton gradient dissipation; and the transcription of uncoupling genes and of receptors for thyroid and adrenergic hormones, both in brown and in white adipocytes. The transcriptional enhancement of receptors for browning hormones also occurs in BAT from ABA-treated mice, lacking LANCL2 but overexpressing LANCL1. The signaling pathway downstream of the ABA/LANCL system includes AMPK, PGC-1α, Sirt1, and the transcription factor ERRα. The ABA/LANCL system controls human brown and "beige" adipocyte thermogenesis, acting upstream of a key signaling pathway regulating energy metabolism, mitochondrial function, and thermogenesis.

Digital workflows for removable partial dentures have enabled new machinable framework materials, including polyetheretherketone (PEEK). In addition, all denture components can be designed and manufactured digitally. Nonetheless, physical casts are still required for assembly of the components. The adoption of a cast-free fabrication procedure may enhance benefits, including a reduced number of procedures, faster processing, and reduced material waste. The purpose of this technical report was to demonstrate a workflow for the fabrication of a removable partial denture with a PEEK framework, milled teeth, and milled flanges, which uses intraoral scanning and no physical casts., (Copyright © 2021 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this multicenter parallel-group randomized controlled trial is to compare, in the same clinical scenario, 6 mm short with 11 mm long implants for the rehabilitation of completely edentulous non-atrophic mandibles., Materials and Methods: Thirty patients in three study centers received a fixed full-arch mandibular rehabilitation supported by five inter-foraminal implants, with no need for bone augmentation procedures. Patients were randomly allocated (1:1 ratio), at the time of surgery, to test (6 mm implants) or control group (11 mm implants). After 3 months, a screw-retained full-arch prosthesis was positioned (baseline). Peri-implant marginal bone level change (MBLc, primary outcome) together with implant and prosthesis survival rate, and biological/technical complications (secondary outcomes) were evaluated up to 5 years., Results: Twenty seven patients were controlled at 5 years (3 drop-outs). No implant or prosthesis loss occurred. No significant intergroup difference for biological/technical complications (p > .05, Fisher's exact test) and no significant intragroup and intergroup difference in the MBLc values were registered (test -0.03 ± 0.17 mm and control -0.13 ± 0.32 mm at 5-years; p > .025, one-sided Mann-Whitney U-test)., Conclusions: When used in comparable anatomic, surgical, and prosthetic conditions, no difference in the clinical and radiographic outcomes between 6-mm and 11-mm implants was observed at 5 years of follow-up. Short implants showed to be a reliable option for the rehabilitation of completely edentulous non-atrophic mandibles. There is growing clinical evidence supporting the use of short implants, even in the case of non-atrophic sites., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Abscisic acid (ABA), long known as a plant stress hormone, is present and functionally active in organisms other than those pertaining to the land plant kingdom, including cyanobacteria, fungi, algae, protozoan parasites, lower Metazoa, and mammals. The ancient, cross-kingdom role of this stress hormone allows ABA and its signaling pathway to control cell responses to environmental stimuli in diverse organisms such as marine sponges, higher plants, and humans. Recent advances in our knowledge about the physiological role of ABA and of its mammalian receptors in the control of energy metabolism and mitochondrial function in myocytes, adipocytes, and neuronal cells allow us to foresee therapeutic applications for ABA in the fields of pre-diabetes, diabetes, and cardio- and neuro-protection. Vegetal extracts titrated in their ABA content have shown both efficacy and tolerability in preliminary clinical studies. As the prevalence of glucose intolerance, diabetes, and cardiovascular and neurodegenerative diseases is steadily increasing in both industrialized and rapidly developing countries, new and cost-efficient therapeutics to combat these ailments are much needed to ensure disease-free aging for the current and future working generations.

Statement of Problem: Denture tooth displacement may have a significant impact on denture occlusion. This aspect has seldom been investigated, especially for digital denture processing techniques., Purpose: The purpose of this clinical study was to evaluate the accuracy of tooth position with milled digital dentures processed without physical casts., Material and Methods: Ten maxillary and 10 mandibular dentures designed from intraoral scans, milled, and processed without physical casts were investigated. The standard tessellation language (STL) files of the digitally designed dentures were compared with the scan of the dentures after processing (milling the denture base, milling teeth in a complete arch, and then bonding teeth into the base). The STL files were superimposed by using a surface-matching software program. After a preliminary alignment, the STL meshes were trimmed and reoriented; then, the final alignment was carried out by using the cameo surface. Six reference points (the mesiobuccal cusp on the most distal molar, the canine cusp, the middle of the incisal edge of the central incisor on both the left and the right side) were selected to measure tooth displacements along the X-, Y-, and Z-axes, corresponding (from the preliminary reorientation) to anteroposterior, mediolateral, and occlusal displacement, respectively. Tooth position accuracy was assessed by using median and interquartile range values. Univariate and multivariate statistical analyses were used to investigate the significance of the extent of displacements, as well as differences among displacement directions, reference teeth, side, and denture arch type (α=.05)., Results: Only the median (0.2 mm; interquartile range: 0.27 mm) occlusal displacement was significantly different from zero. A generalized estimated equation model addressing occlusal displacement as a dependent variable showed no significant effect of tooth type, side, or denture arch type, either alone or in combination., Conclusions: The tooth position of both maxillary and mandibular milled digital dentures processed without physical casts was accurate in the anteroposterior and mediolateral directions. Occlusal displacement seemed to be within the range of clinical acceptability; its consistency throughout the arch allowed optimization or compensation at the design or manufacturing step., (Copyright © 2021 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Statement of Problem: While the dimensional accuracy of the intaglio surface of a removable complete denture is key to its adaptation, comfort, and clinical performance, information on the ability of milling and 3D-printing workflows to accurately reproduce this surface is lacking., Purpose: The purpose of this clinical study was to compare the trueness of the intaglio surface of milled and 3D-printed removable complete digital dentures., Material and Methods: Intraoral scans were obtained from 14 participants for a total of 20 edentulous arches. Ten maxillary and 10 mandibular denture bases were then designed and fabricated with a completely digital workflow, both with milling and 3D-printing. Fabricated dentures were digitized with the same intraoral scanner used to obtain intraoral digital scans of the edentulous arches. Standard tessellation language (STL) files of the printed and milled denture bases were used for 3D analysis and comparisons with the STL file of the corresponding designed denture base. Specifically, a reverse engineering software program was used to trim and extract intaglio surfaces, align them, and measure their global mean 3D distance. In order to evaluate the homogeneity of production accuracy of each manufacturing process, the intaglio surfaces were also divided into several regions of interest and the corresponding 3D distances measured. Within- and between-group differences and maxillary and mandibular dentures differences were assessed with parametric and nonparametric tests (α=.05)., Results: Milling showed a global better trueness of the entire intaglio surface (-0.002 mm) than 3D-printing (0.018 mm), both for the whole data set (P<.001) and for maxillary (P=.032) or mandibular (P=.049) denture base subgroups. Within each fabrication technology, maxillary (P<.11) and mandibular dentures (P=.2) showed no significant difference in trueness. Measured deviations were significantly different from zero for the 3D-printed dentures (P<.001), but not for the milled dentures (P=.487). Additionally, for milled dentures, no significant difference in trueness was found among the 11 regions of interest identified for the maxillary dentures (P=.085) and the 13 regions of interest for the mandibular dentures (P=.211). Conversely, 3D-printing showed significant variations in trueness among the same zones of interest, both in maxillary (P<.001) and mandibular (P=.004) dentures., Conclusions: Within the limits of the manufacturing methodologies used for complete dentures, milling can provide a slightly better trueness of the intaglio surface than 3D-printing, with less variation across several zones of interest. However, given the magnitude of such differences, they may be reasonably considered to be of limited, if any, clinical significance., (Copyright © 2021 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

The purpose of the present study was to evaluate: (i) maxillary occlusal plane changes after clear aligners therapy with a 3D measurement technique; and (ii) as a secondary outcome, if such changes were correlated to the patient’s 1axilla-mandibular divergence. 3D maxillary models of 32 patients (7 males and 25 females; mean age 22.3 +/− 3.4 year) treated with clear aligners were analyzed. The angle (α) between a reference palatine plane and a maxillary occlusal plane was measured. Five angular cephalometric measurements (NSL/MP; PP-OP; OP-MP; PP-MP; PFH/AFH%) were performed and related to Δα. The subjects were further divided into three groups according to facial divergence. After aligner treatment, Δα increased in hyperdivergent patients and decreased in hypodivergent patients (p < 0.05). Δα showed a significant positive correlation with NSL/MP (rho = 0.44) and negative correlation with PFH/AFH% (rho = −0.53). Aligners treatment produced a counterlockwise rotation of the maxillary occlusal plane, even if this rotation occurs differently depending on divergence.

Objectives: To present a new short self-test, called the OSA wellness scale (OWS), for assessing the health-related quality of life (HRQoL) changes in obstructive apnea syndrome (OSA) patients treated with mandibular advancement device (MAD)., Methods: 51 OSA patients (8 women and 43 men, mean age 52.3) treated with a fully customizable MAD device (Protrusor) were retrospectively enrolled. Each patient received a home sleep apnea testing (HSAT) at baseline (T0) and after three months of MAD treatment (T1). Two self-test evaluations, the Epworth sleepiness scale (ESS), and OWS were also submitted at T0 and T1. The OWS was a short self-test of 8 questions for evaluating the daytime HRQoL. Patients gave an assessment from 0 to 3 for each question. At the end of the questionnaire, the patients had a score from 0 to 24, resulting from the sum of all 8 scores. The higher the score, the greater the patient's perceived state of discomfort., Results: At T1, a significant decrease in the oxygen desaturation index (ODI) and apnea-hypopnea index (AHI) was shown ( p < 0.0001), while no significant changes in body mass index (BMI) were found. Both the ESS and the OWS records showed a significant reduction in daytime sleepiness and HRQoL ( p < 0.0001)., Conclusion: The OWS could be a useful method to verify and numerically compare the perceived quality of life in OSA patients, before and after MAD therapy., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Domenico Ciavarella et al.)

Abscisic acid (ABA) regulates plant responses to stress, partly via NO. In mammals, ABA stimulates NO production by innate immune cells and keratinocytes, glucose uptake and mitochondrial respiration by skeletal myocytes and improves blood glucose homeostasis through its receptors LANCL1 and LANCL2. We hypothesized a role for the ABA-LANCL1/2 system in cardiomyocyte protection from hypoxia via NO. The effect of ABA and of the silencing or overexpression of LANCL1 and LANCL2 were investigated in H9c2 rat cardiomyoblasts under normoxia or hypoxia/reoxygenation. In H9c2, hypoxia induced ABA release, and ABA stimulated NO production. ABA increased the survival of H9c2 to hypoxia, and L-NAME, an inhibitor of NO synthase (NOS), abrogated this effect. ABA also increased glucose uptake and NADPH levels and increased phosphorylation of Akt, AMPK and eNOS. Overexpression or silencing of LANCL1/2 significantly increased or decreased, respectively, transcription, expression and phosphorylation of AMPK, Akt and eNOS; transcription of NAMPT, Sirt1 and the arginine transporter. The mitochondrial proton gradient and cell vitality increased in LANCL1/2-overexpressing vs. -silenced cells after hypoxia/reoxygenation, and L-NAME abrogated this difference. These results implicate the ABA-LANCL1/2 hormone-receptor system in NO-mediated cardiomyocyte protection against hypoxia.

ADP-ribosyl cyclases (ADPRCs) catalyze the synthesis of the Ca 2+ -active second messengers Cyclic ADP-ribose (cADPR) and ADP-ribose (ADPR) from NAD + as well as nicotinic acid adenine dinucleotide phosphate (NAADP + ) from NADP + . The best characterized ADPRC in mammals is CD38, a single-pass transmembrane protein with two opposite membrane orientations. The first identified form, type II CD38, is a glycosylated ectoenzyme, while type III CD38 has its active site in the cytosol. The ectoenzymatic nature of type II CD38 raised long ago the question of a topological paradox concerning the access of the intracellular NAD + substrate to the extracellular active site and of extracellular cADPR product to its intracellular receptors, ryanodine (RyR) channels. Two different transporters, equilibrative connexin 43 (Cx43) hemichannels for NAD + and concentrative nucleoside transporters (CNTs) for cADPR, proved to mediate cell-autonomous trafficking of both nucleotides. Here, we discussed how type II CD38, Cx43 and CNTs also play a role in mediating several paracrine processes where an ADPRC + cell supplies a neighboring CNT-and RyR-expressing cell with cADPR. Recently, type II CD38 was shown to start an ectoenzymatic sequence of reactions from NAD + /ADPR to the strong immunosuppressant adenosine; this paracrine effect represents a major mechanism of acquired resistance of several tumors to immune checkpoint therapy.

Purpose: Infantile hydrocephalus has various etiologies that may influence children's cognitive development and onset of neurological comorbidities such as epilepsy. However, few studies specifically analyzed etiologies encountered in this population. Here we report a 9-year retrospective analysis of the etiologies and short-term outcome of surgically treated patients in a major pediatric neurosurgical center in a high-income country., Methods: This was a single-center retrospective study for the period 2010 to 2018 using the database of the French medical classification for clinical procedures (CCAM) of the Necker Hospital, Paris. We included all the patients surgically treated for hydrocephalus before the age of 2 years and reviewed digital medical files and MRI., Results: Four hundred and sixty seven patients were included, with a mean age at diagnosis of 4.8 months and male predominance (M/F ratio=1/2). Etiologies comprised: intraventricular hemorrhage (27.8%), arachnoid cyst (13.9%), spinal dysraphism (12.4%), brain tumor (10.5%), associated brain malformation (8.6%), infection (7.5%), isolated aqueduct stenosis (5.1%), and other (14.1%). Epilepsy was more likely to occur in post-infection (40%) and post-hemorrhage (31%) hydrocephalus, and when brain malformation was associated (35%). Etiology, epileptic status and the number of dysfunctions influenced short-term school performance., Conclusion: This study identified various etiologies of infantile hydrocephalus, with different neurological outcomes. Specific follow-up is required according to these observations., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)