International University of Catalonia

Objective Dementia with Lewy bodies (DLB) and Parkinson's disease (PD) share clinical, pathological, and genetic risk factors, including GBA1 and APOEε4 mutations. Biomarkers associated with the pathways of these mutations, such as glucocerebrosidase enzyme (GCase) activity and amyloid‐beta 42 (Aβ42) levels, may hold potential as predictive indicators, providing valuable insights into the likelihood of cognitive decline within these diagnoses. Our objective was to determine their association with cognitive decline in DLB and PD. Methods A total of 121 DLB patients from the European‐DLB Consortium and 117 PD patients from the Norwegian ParkWest Study were included in this study. The four most commonly associated variants of GBA1 mutations (E326K, T369M, N370S, L444P), APOEε4 status, and cerebrospinal fluid (CSF) Aβ42 levels and GCase activity were assessed, as well as global cognition using the Mini‐Mental State Examination. Linear mixed‐effects regression models were used to evaluate the association of CSF biomarkers with cognitive decline in each diagnostic group, adjusted for age, sex, education, and genetic mutation profile. Results Low CSF Aβ42 levels were associated with accelerated cognitive decline in DLB, whereas reduced CSF GCase activity predicted faster cognitive decline in PD. These associations were independent of GBA1 gene mutations or APOEε4 status. Interpretation Our study provides important evidence on the relationship between brain Aβ deposition and GCase activity in the Lewy body disease spectrum independent of their genetic mutation profile. This information could be relevant for designing future clinical trials targeting these pathways.

Conflicting results from randomized trials regarding the efficacy of remdesivir for COVID‐19 have been reported. We aimed to develop a neural network (NN) to identify COVID‐19 patients who would derive the greatest survival benefit from remdesivir. This multicenter observational study included adults hospitalized for COVID‐19 between February 2020 and February 2021. A derivation cohort from Hospital Clínic (Barcelona) was used to create the NN, which was split into 928/1160 (80%) for training and 232/1160 (20%) for internal validation. The model used three normalized input variables: Ct values from rRT‐PCR, lymphocyte count at diagnosis, and the duration of symptoms before testing. Effectiveness was assessed in an external validation cohort of 898 patients from Hospital Mútua Terrassa and Hospital Universitari La Fe, Valencia. In the derivation cohort (median age 66 years; IQR 55–78), symptom duration, Ct values, and lymphocyte count showed considerable variation. Overall, 60‐day mortality was 165/1160 (14.2%). In the training set, 385/928 (41.5%) patients were identified as benefiting from remdesivir, characterized by lower Ct values, reduced lymphocyte counts, and shorter symptom duration. Mortality in this subgroup was 93/385 (24.2%): 6/385 (7.2%) in patients receiving remdesivir versus 87/385 (28.8%) in those who did not ( p < 0.001). In the test set, 296/898 (33%) patients were identified as high‐benefit, with 60‐day mortality rates of 8/296 (11%) for those patients treated with remdesivir compared to 49/296 (22%) for those not treated ( p < 0.04). In conclusion, we successfully developed and validated a NN capable of identifying patients with distinct clinical phenotypes who are at higher risk of mortality without remdesivir.

Vertical analysis is an essential aspect of aesthetic facial diagnosis and planning [1, 2]. Classical cephalometric analyses have proposed a number of methods to vertically diagnose the face (Fig. 3.1) [3–6]. All of them are based either on numbers or on proportions between different thirds of the face. The most widely accepted norm, coming from the Renaissance masters, is that all three facial thirds should be equal [7].

Vertical evaluation of the face relies on perception rather than on measurements, since the “impression of short or long” is what matters. There are four components causing vertical problems: maxillary height, chin height, bite, and the transverse dimension of the face. Short faces need lengthening by means of clockwise maxillomandibular rotation and maxillary downgrafting, which are the typical movements associated with correction. Long faces, indeed, often do not need shortening but instead a redistribution of components. In the case of shortening of a long face, compensation should be achieved by anterior projection. Specifically, in relation to gummy smile, careful analysis is required to determine which of the three causes (vertical maxillary excess, lip hypermobility, and altered passive eruption) are implicated. Besides, the labiomental fold is often absent in long faces because of a lack of incisor torque and/or a receded chin.

The present article describes a specific protocol for maxillary segmentation in patients with a transverse skeletal maxillomandibular discrepancy, which can be resolved through orthopedic treatment with rapid palatal expansion. In grown patients, a surgical aid is usually required to allow reopening of the midpalatal suture, simultaneously releasing both the piriform and malar buttresses. The authors propose two techniques for maxillary expansion: segmentation and SARPE (surgically assisted rapid palatal expansion)/SAMARPE (surgically assisted miniscrew-assisted rapid palatal expansion). Segmentation is indicated in cases where maxillary surgery is needed for some reason (vertical and anteroposterior), and the transverse discrepancy is less than 7 mm. This technique involves a minimally invasive Le Fort I procedure and interdental and longitudinal osteotomies. The four fragments allow for maxillary expansion, which is carefully achieved by palatal subperiosteal elevation under the lateral segments. The four segments are then included in the splint and fixed with wire ligatures around the braces. SARPE/SAMARPE, on the other hand, is indicated in skeletally mature patients with an isolated transverse maxillary deficiency, and patients who will eventually sustain a regular orthognathic procedure but have a transverse discrepancy in excess of 6 mm, which cannot be solved through segmentation. SARPE involves the surgical release of the sites of resistance combined using orthopedic forces. The authors propose a surgical technique that entails the full release of all areas of resistance—midpalatal, piriform, zygomatic, and pterygoid—and which is performed under local anesthesia and sedation on an ambulatory basis.

Planning in orthognathic surgery has been and remains an open issue. We have evolved from two-dimensional (2D) classical cephalometric hard-tissue planning to 2D soft-tissue planning and finally to three-dimensional (3D) and hard- and soft-tissue evaluation. No current cephalometric analysis can be used as an absolute road map for facial planning, however. According to our personal “3D Facial Aesthetic Design,” a harmonious face should abide with two rules, which can be summarized as follows: symmetry and facial projection.

The mandible is operated first in most cases, except when custom patient-specific implants for the Le Fort I osteotomy are used. When sagittal osteotomy is carried out, a proper cortex cut reaching the bone marrow of the sagittal osteotomy including lingual cortex, mandibular ramus and lateral oblique ridge of the body, and buccal cortex including the inferior basal border avoids a bad-split fracture. When chiseling, the osteotomes should not be inserted more than 5 mm in order to avoid inferior alveolar nerve damage. Separation of both segments is carried out under direct visualization of proper separation of the two segments and inferior alveolar nerve preservation. Interferences between the distal and proximal bony segments should be checked for proper condyle settlement. Proper seating of the condyles into the uppermost anterior part of the fossa should be ensured with a bidirectional maneuver. Rigid internal fixation using a hybrid technique (a mini-plate fixed with four monocortical screws and a retromolar bicortical screw) is recommended, since it provides enough stability while allowing proper condyle accommodation to the glenoid fossa. Finally, suspension of the platysma of the upper aspect of the submandibular space to the uppermost mandibular periosteum can be performed to improve the jawline contour.

Full facial symmetry does not exist in humans, and the mandible is usually responsible for asymmetrical conditions. Maxillary asymmetry is usually a sequel of mandibular hypoplasia or hyperplasia. Facial asymmetry can be caused by a number of conditions such as trauma, tumors, congenital alterations, or simply developmental disorders of mandibular growth. Over the years, we have developed protocols to manage asymmetrical patients with an “as soon as possible” (ASAP) policy in relation to the onset of the problem. If diagnosed during infancy, and once the presence of a tumor process has been ruled out, we usually decide to “wait and see,” unless asymmetric mandibular growth causes compensatory malformations of the maxilla. If asymmetric growth proves to be active in young adults, our choice is to perform an early proportional condylectomy. This would be the case of condylar hyperplasia causing vertical asymmetric growth with the early onset of compensations in the maxilla. Hypoplastic conditions caused by trauma or rheumatoid arthritis should be managed early with orthopedics and eventually with surgery in order to avoid compensatory malformations in the rest of the facial skeleton.

Peroperative management of the patient, together with specific recommendations, improves the final outcomes and patient experience during the procedure. Preoperative assessment focuses on patient systemic health, the temporomandibular joint, and the evaluation of dental occlusion. Before surgery, professional dental cleaning is recommended, as well as strict dental hygiene during the entire peroperative period. A corticosteroid nasal spray every 8 h is prescribed 3 days before surgery. Intraoperative-controlled hypotension and proper medication, minimally invasive surgical techniques, and limiting the surgery time will improve the results and postoperative period. Intermaxillary elastic fixation is made to guide occlusion at the end of surgery, but at 1 week of follow-up, the patient is instructed in the “five-step procedure” for elastic removal, with mouth-opening exercises (10 times), eating a soft diet, observation of strict oral hygiene, and guiding elastics placement.

An appropriate chin position and proportion results in an adequate lip–chin relationship, contributes to normal vertical proportions, and gives support to the submandibular soft tissues. A minimally invasive technique preserving as much periosteum and muscle tissue as possible, and their final repositioning, is essential in order to minimize unpredictable soft-tissue changes. When an osteotomy is performed, it is mandatory to avoid dental roots and mental nerve damage. Moreover, the inclination of the saw will determine the direction of sliding and thus the final position of the distal segment. When a gap remains between bony segments, an interpositional autograft, bone block allograft, or off-the-shelf material block can be placed in between.

The classical and most frequent maxillary osteotomy is the Le Fort I technique. Years ago, we designed and published a minimally invasive Le Fort I osteotomy allowing mobilization of the maxilla, adopting a reduced approach and a special maneuver to provoke pterygomaxillary disjunction. Later, we designed an ancillary procedure to facilitate the technique through a transmucosal pterygomaxillary osteotomy using a piezoelectric saw. In our experience, this technique has proved useful for any type of clinical scenario, irrespective of the direction and amount of maxillary repositioning.

The Boston keratoprosthesis (BKPro) is a critical device for vision restoration in complex cases of corneal blindness, although its long-term retention is challenged by infection risks. This study aims to enhance the antimicrobial properties of the titanium (Ti) backplate of the BKPro by ion implanting silver and copper ions to achieve effective infection control while maintaining cytocompatibility. Research on antimicrobial modifications for BKPro is limited, and while metallic ions like Ag and Cu show promise for biomaterial improvement, their effects on human corneal keratocytes (HCKs) require further study. Ag and Cu were implanted onto rough Ti surfaces, as mono- and coimplantations. Cytotoxicity was assessed in HCKs, and antimicrobial efficacy was tested against Pseudomonas aeruginosa and Candida albicans. After 21 d, monoimplanted Ag samples released 300.4 ppb of Ag⁺, coimplanted samples released 427.5 ppb of Ag⁺ and 272.3 ppb of Cu ions, and monoimplanted Cu samples released 567.0 ppb of Cu ions. All ion-implanted surfaces supported HCK proliferation, exhibited no cytotoxicity, and showed strong antimicrobial activity. Ag-implanted surfaces provided antibacterial effects through membrane disruption and reactive oxygen species generation, while Cu-implanted surfaces exhibited antifungal effects via impaired enzymatic functions and reactive oxygen species. Coimplanted AgCu surfaces demonstrated synergistic antimicrobial effects, resulting from the synergy between the bactericidal actions of Ag and the oxidative stress contributions of Cu. Additionally, ion-implanted surfaces enhanced HCK adhesion under co-culture conditions. In conclusion, ion implantation effectively imparts antimicrobial properties to the Ti backplate of BKPro, reducing infection risks while preserving compatibility with corneal cells.

The human normal heart rhythm occurs when a person has a regular heartbeat originated by depolarization of the sinus node, which is normally transmitted through the atria to the AV node, and thereafter—in normal condition—through the His-Purkinje system to the myocytes of the ventricles. This normal heartbeat occurs at a rate which is appropriate to the clinical circumstances of the individual (e.g. faster during exercise than at rest) and is called sinus rhythm. The term arrhythmia comprises a group of heterogeneous conditions with abnormal electrical activity of the heart in origin, rate, or both which lead to an increased (tachyarrhythmias) or reduced (bradiarrhythmias) heart rate, compared to normal. This chapter summarizes the recommendations for diagnosis and pharmacological treatment of arrhythmias according to recent recommendations of major international scientific societies.

Objective The Joint SSRD, SEPES, and PROSEC Consensus Conference aimed to provide clinical statements and recommendations for the rehabilitation of worn dentition and to evaluate the necessity of an evaluation phase when increasing the occlusal vertical dimension (OVD) during full‐mouth rehabilitation. Materials and Methods Two systematic reviews were conducted before the conference. The findings of the reviews were analyzed, discussed in working group 2, and debated in plenary sessions until a consensus was reached. Consensus statements were formulated based on available evidence and expert opinion. Results Both direct and indirect minimally invasive approaches, utilizing materials such as composite resins and lithium disilicate ceramics, were deemed viable for managing worn dentitions. The choice of approach and material should depend on the extent of tooth substance loss and the treatment goals. Evidence on the necessity of an evaluation phase was inconclusive. However, an evaluation phase can aid in managing patient expectations, refining treatment sequencing, and supporting less experienced clinicians. Emphasis was placed on non‐invasive and minimally invasive techniques, adequate diagnostics, and the potential benefits of fixed interim restorations when evaluating increased OVD. Conclusions The consensus statements provide a framework for managing worn dentitions and decisions regarding OVD increases, emphasizing minimally invasive approaches and individualized treatment planning. However, gaps in evidence remain, particularly regarding the long‐term effectiveness of materials and the evaluation phase. Future research is required to address these uncertainties, focusing on long‐term outcomes, material comparisons, and patient‐reported outcomes.

In recent years, there has been a growing interest in the market targeting older adults, coinciding with the expansion of digitalization in the daily activities of people of all ages. Despite the abundant literature in the field of digitalization, little attention has been paid to applications designed for older individuals outside the health sector. Therefore, this article aims to provide a mapping of the market for applications tailored to older adults. To achieve this, all applications related to the target audience of older individuals available on the major app stores have been analysed. The study reveals that the predominant types of applications fall into categories such as Health, Entertainment, Interpersonal Communication, Social Networks, and Security. Additionally, the study identifies a need to improve the effectiveness of search results for apps related to this target audience, particularly through better use of keywords. These findings contribute to the literature by providing a starting point for further research on applications for older adults. Furthermore, they are relevant for managers and brands as the findings offer a detailed overview of the current market situation. As a result, this study identifies trends and opportunities in this market, serving as a guide for researchers, developers, and professionals in the industry who are interested in this growing niche.

We conducted an in-depth longitudinal study on an individual carrying the presenilin 2 p.Asn141Ile mutation, traditionally associated with dominantly inherited Alzheimer's disease (AD), who has remarkably remained asymptomatic past the expected age of clinical onset. This study combines genetic, neuroimaging and biomarker analyses to explore the underpinnings of this resilience. Unlike typical progression in dominantly inherited AD, tau pathology in this case was confined to the occipital region without evidence of spread, potentially explaining the preservation of cognitive functions. Genetic analysis revealed several variants that, although not previously associated with protection against AD, suggest new avenues for understanding disease resistance. Notably, environmental factors such as significant heat exposure and a unique proteomic profile rich in heat shock proteins might indicate adaptive mechanisms contributing to the observed phenotype. This case underscores the complexity of Alzheimer's pathology and suggests that blocking tau deposition could be a promising target for therapeutic intervention. The study highlights the need for further research to identify and validate the mechanisms that could inhibit or localize tau pathology as a strategy to mitigate or delay the onset of Alzheimer's dementia.

Background Attention-Deficit/Hyperactivity Disorder (ADHD) prevalence rates are around 5–10% of school-aged children. We test whether medication use for ADHD decreases the likelihood of risky behaviour (sexual behaviour, alcohol, tobacco, and drug consumption) and injuries amongst children aged 6–18. Methods We use a large administrative dataset for the whole population of Catalan children in Spain who were born between 1998 and 2012. We apply a scale that contains alternative definitions of ADHD so that over-diagnosis is also identified and estimate a count data model to explain the number of visits whilst accounting for confounding. Our identification strategy relies on instrumenting medication using an average indicator of the probability of prescribing medication for each most visited healthcare centre provider. Results Our results suggest that medication use significantly reduced the number of visits of children diagnosed with ADHD for injuries but not risky behaviour. This finding is robust irrespective of the considered span or the grace period after including ADHD-related comorbidities as controls. Conclusion In line with previous literature, medication use amongst children with ADHD reduces the prevalence of injuries but not risky behaviours.