Effects of technological running shoes versus barefoot running on the intrinsic foot muscles, ankle mobility, and dynamic control: a novel cross-sectional research.

BACKGROUND: Technological running shoes have become increasingly popular, leading to improvements in performance. However, their long-term effects on foot musculature and joint mobility have not been thoroughly studied. OBJECTIVE: To compare the activation of the intrinsic foot muscles between runners wearing technological footwear and barefoot runners. Secondary objectives included assessing ankle dorsiflexion (DF) range of motion (ROM) and dynamic postural control in both groups. METHODS: A cross-sectional study was conducted involving 22 technological footwear runners and 22 barefoot runners. Ultrasonography was used to measure the thickness of the plantar fascia (PF) and the quadratus plantae (QP), abductor digiti minimus (ADM), abductor hallucis (AH), and flexor hallucis longus (FHL) muscles. Ankle mobility and dynamic postural control were also recorded. RESULTS: Ultrasonography measurements showed statistically significant differences for PF thickness (mean difference [MD]: -0.10 cm; 95% CI: -0.13, -0.05 cm), QP cross-sectional area (CSA) (MD: -0.45 cm2; 95% CI: -0.77, -0.12 cm2), ADM CSA (MD: -0.49 cm2; 95% CI: -0.70, -0.17 cm2), and FHL thickness (MD: 0.82 cm; 95% CI: 0.53, 1.09 cm), with all measurements being lower in the group wearing technological footwear compared to the barefoot runners. Ankle DF ROM was also significantly greater for the barefoot runners (MD: -5.1°; 95% CI: -8.6, -1.7°). CONCLUSIONS: These findings suggest potential implications for the foot musculature and ankle mobility in runners using technological footwear.

Nickel-catalysed enantioselective alkene dicarbofunctionalization enabled by photochemical aliphatic C-H bond activation.

The development of novel strategies to rapidly construct complex chiral molecules from readily available feedstocks is a long-term pursuit in the chemistry community. Radical-mediated alkene difunctionalizations represent an excellent platform towards this goal. However, asymmetric versions remain highly challenging, and more importantly, examples featuring simple hydrocarbons as reaction partners are elusive. Here we report an asymmetric three-component alkene dicarbofunctionalization capitalizing on the direct activation of C(sp 3)-H bonds through the combination of photocatalysed hydrogen atom transfer and nickel catalysis. This protocol provides an efficient platform for installing two vicinal carbon-carbon bonds across alkenes in an atom-economic fashion, providing a wide array of high-value chiral α-aryl/alkenyl carbonyls and phosphonates, as well as 1,1-diarylalkanes from ubiquitous alkane, ether and alcohol feedstocks. This method exhibits operational simplicity, broad substrate scope and excellent regioselectivity, chemoselectivity and enantioselectivity. The compatibility with bioactive motifs and expedient synthesis of pharmaceutically relevant molecules highlight the synthetic potential of this protocol.

Extracellular ATP/P2X7 receptor, a regulatory axis of migration in ovarian carcinoma-derived cells.

ATP is actively maintained at high concentrations in cancerous tissues, where it promotes a malignant phenotype through P2 receptors. In this study, we first evaluated the effect of extracellular ATP depletion with apyrase in SKOV-3, a cell line derived from metastatic ovarian carcinoma. We observed a decrease in cell migration and an increase in transepithelial electrical resistance and cell markers, suggesting a role in maintaining a mesenchymal phenotype. To identify the P2 receptor that mediated the effects of ATP, we compared the transcript levels of some P2 receptors and found that P2RX7 is three-fold higher in SKOV-3 cells than in a healthy cell line, namely HOSE6-3 (from human ovarian surface epithelium). Through bioinformatic analysis, we identified a higher expression of the P2RX7 transcript in metastatic tissues than in primary tumors; thus, P2X7 seems to be a promising effector for the malignant phenotype. Subsequently, we demonstrated the presence and functionality of the P2X7 receptor in SKOV-3 cells and showed through pharmacological approaches that its activity promotes cell migration and contributes to maintaining a mesenchymal phenotype. P2X7 activation using BzATP increased cell migration and abolished E-cadherin expression. On the other hand, a series of P2X7 receptor antagonists (A438079, BBG and OxATP) decreased cell migration. We used a CRISPR-based knock-out system directed to P2RX7. According to the results of our wound-healing assay, SKOV3-P2X7KO cells lacked receptor-mediated calcium mobilization and decreased migration. Altogether, these data let us propose that P2X7 receptor is a regulator for cancer cell migration and thus a potential drug target.

The molecular immune modulator adenosine deaminase-1 enhances HIV specific humoral and cellular responses to a native-like HIV envelope trimer DNA vaccine.

There is currently no prophylactic vaccine available for human immunodeficiency virus (HIV). Research efforts have resulted in improved immunogens that mimic the native envelope (Env) glycoprotein structure. Recently, a novel triple tandem trimer (TTT) platform has been used to generate a plasmid encoding Env immunogen (pBG505-TTT) that expresses only as trimers, making it more suitable for nucleic acid vaccines. We have previously demonstrated that adenosine deaminase-1 (ADA-1) is critical to the T follicular helper (TFH) function and improves vaccine immune responses in vivo. In this study, we demonstrate that co-delivery of plasmid-encoded adenosine deaminase 1 (pADA) with pBG505-TTT enhances the magnitude, durability, isotype switching and functionality of HIV-specific antibodies in a dose-sparing manner. Co-delivery of the molecular immune modulator ADA-1 also enhances HIV-specific T cell polyfunctionality, activation, and degranulation as well as memory B cell responses. These data demonstrate that pADA enhances HIV-specific cellular and humoral immunity, making ADA-1 a promising immune modulator for HIV-targeting vaccines.

A comparison of the upper anterior teeth movements with optimized and conventional attachment.

Background: Invisalign® attachments are divided into two main groups: the conventional group and the optimized group, which is also known as the SmartForce™. The aim of this study is to compare the movements produced by an optimized crescent-shaped attachment in superior incisor teeth with the movements produced by a conventional rectangular attachment (vertical and horizontal) in the same teeth. Material and Methods: This retrospective study examined the movement table of the initial ClinCheck® and the first refinement of 95 patients (mean age 44.18 ± 4.125, 40 males and 55 females). It represented 147 upper incisors divided into two groups: 87 with rectangular attachment and 60 with optimized attachment. Applying Kravitz's accuracy formula for each movement and each tooth of interest (with attachments of interest), we underlined the effectiveness of each attachment. Mann-Whitney U test, Kruskal-Wallis test, and Pearson and Spearman correlation coefficients were used for statistical analysis. Results: The accuracies of rotation, mesio-distal angulation and vestibulo-lingual inclination are highly significantly related to the type of attachment used on the upper lateral incisor. The optimized attachment presented greater accuracy in the rotation of the lateral incisors than the conventional attachment. However, conventional vertical attachment showed a higher accuracy (p<.01) in the mesio-distal angulation and horizontal attachments showed a higher accuracy (p<.01) in the vestibulo-lingual inclination in the same group of teeth. Conclusions: Optimized attachments rotate better lateral incisors; conventional vertical attachments are more efficient to improve mesio-distal angulation; and horizontal attachments serve best for torque movements. Key words:Orthodontics, clear aligners, orthodontic tooth movements, attachments.

Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines.

Recombinant native-like HIV-1 envelope glycoprotein (Env) trimers are used in candidate vaccines aimed at inducing broadly neutralizing antibodies. While state-of-the-art SOSIP or single-chain Env designs can be expressed as native-like trimers, undesired monomers, dimers and malformed trimers that elicit non-neutralizing antibodies are also formed, implying that these designs could benefit from further modifications for gene-based vaccination approaches. Here, we describe the triple tandem trimer (TTT) design, in which three Env protomers are genetically linked in a single open reading frame and express as native-like trimers. Viral vectored Env TTT induced similar neutralization titers but with a higher proportion of trimer-specific responses. The TTT design was also applied to generate influenza hemagglutinin (HA) trimers without the need for trimerization domains. Additionally, we used TTT to generate well-folded chimeric Env and HA trimers that harbor protomers from three different strains. In summary, the TTT design is a useful platform for the design of HIV-1 Env and influenza HA immunogens for a multitude of vaccination strategies.

Emergency appointments and psychological distress during COVID-19 lockdown among orthodontic patients in Spain.

Background: COVID-19 created an unexpected situation for dental patients. However, the impact of the lockdown on orthodontic patients is still unknown. Hence, this study was conducted to analyse the number and type of emergencies, distress and fear of getting infected among brackets and aligners orthodontic patients during the COVID-19 lockdown. Material and Methods: A total of 324 questionnaires about emergency appointments during the lockdown and Kessler Psychological Distress Scale-K10 were distributed between March and December 2022 among patients who were on active orthodontic treatment during lockdown at the Master of Orthodontics at the University Alfonso X el Sabio during February and December 2022. Chi-square was used to compare groups. Results: Emergency appointment was needed by 37.78% of patients during lockdown: 73.5% among those with aligners and 45.9% with brackets (p<.01). Loose bracket was the most prevalent emergency for bracket patients and lack of aligners among invisible orthodontic patients. Of those, 36.95% in need of orthodontic emergency appointments didn´t attend the clinic for fear of being infected; 21% of patients had high or very high anxiety levels. Conclusions: Orthodontic patients had moderate levels of anxiety and fear of being infected during lockdown. Of these, 31.78% needed an emergency appointment. Key words:Orthodontics, COVID-19, dental healthcare, dentistry, emergency.

Discovery and Characterization of Active CBP/EP300 Degraders Targeting the HAT Domain.

Proteolysis Targeting Chimeras (PROTACs) are bifunctional molecules that simultaneously bind an E3 ligase and a protein of interest, inducing degradation of the latter via the ubiquitin-proteasome system. Here we present the development of degraders targeting CREB-binding protein (CBP) and E1A-associated protein (EP300)-two homologous multidomain enzymes crucial for enhancer-mediated transcription. Our PROTAC campaign focused on CPI-1612, a reported inhibitor of the histone acetyltransferase (HAT) domain of these two proteins. A novel asymmetric synthesis of this ligand was devised, while PROTAC-SAR was explored by measuring degradation, target engagement, and ternary complex formation in cellulo. Our study demonstrates that engagement of Cereblon (CRBN) and a sufficiently long linker between the E3 and CBP/EP300 binders (≥21 atoms) are required for PROTAC-mediated degradation using CPI-1612 resulting in a new active PROTAC dCE-1. Lessons learned from this campaign, particularly the importance of cell-based assays to understand the reasons underlying PROTAC performance, are likely applicable to other targets to assist the development of degraders.

Effects of non-nutritive sucking habits on malocclusions: a systematic review.

The development of the craniomandibular system is guided by genetic interactions and environmental factors, including specific habits such as breastfeeding, bottle feeding, thumb sucking and the use of pacifiers. These habits can have a considerable impact on the growth of the developing jaws and can lead to malocclusion in children. This review aims to investigate potential associations between non-nutritive sucking habits (NNSHs) and malocclusions compared to the presence of nutritive sucking habits (NSHs). To carry out this systematic review, we followed the PRISMA protocol and performed a bibliographic search of the existing literature until April 2023 in the following electronic databases: Medline, PubMed, The Cochrane Library and Embase. Out of a total of 153 records, we included 21 studies. We found that the chances of diagnosing a malocclusion were higher for children with bottle nutrition when compared to breast-fed children. Breastfeeding provides protection against malocclusions. In the same manner, persistent NNSH habits appeared to be associated with increased chances of having malocclusions. The longer the child was breastfed, the shorter the duration of the pacifier habit and the lower the risk of developing moderate/severe malocclusions. The duration of the habits has a positive influence on the appearance of occlusion defects.

Case report: Prosthetic aortic valve endocarditis due to Staphylococcus epidermidis with acquired resistance in the walK gene.

We report the case of a patient with infective endocarditis on a prosthetic aortic valve due to Staphylococcus epidermidis, not a candidate for prosthetic replacement surgery. After three months of supressive treatment with dalbavancin, fever reappears, with growth of S. epidermidis. Susceptibility testing showed new-onset resistance to dalbavancin, with a mutation in walK gene.

Rapid antigen test for adenovirus in children: Age and onset of symptoms are important / Antígeno de adenovirus en niños: la edad y la aparición de los síntomas son importantes

Introduction: Respiratory infection is the most common human adenovirus (HAdV) disease accounting for 7–8% of viral respiratory diseases in children less than 5 years. Differentiation of bacterial infections and viral infections is a common clinical problem. Material and methods: One hundred oropharyngeal swabs obtained from October 2019 to November 2020 from patients attending the paediatric emergency room with suspicion of upper respiratory tract infection and negative results in influenza and RSV tests were included. Oropharyngeal swabs specimens were rapidly processed with STANDARD™ F Adeno Respi Ag FIA and the results were confirmed by RealStar® Adenovirus PCR Kit 1.0 (Altona diagnostics). Results: STANDARD™ F Adeno Respi Ag FIA had sensitivity and specificity values of 71.93% and 100% respectively. The performance of the test was higher in samples from children younger than 24 months and taken less than 72h since the beginning of symptoms. In this subgroup the test had 88.8% sensitivity and 100% specificity. Conclusion: STANDARD™ F Adeno Respi Ag FIA may improve the management of respiratory diseases in children younger than 24 months and less than 72h since the beginning of symptoms in paediatric emergency rooms.(AU)

Introducción: Las infecciones respiratorias son la enfermedad más común asociada a los adenovirus humanos (AdvH)y causan del 7 al 8% de las enfermedades respiratorias víricas en niños menores de 5 años. La distinción entre las infecciones bacterianas y las víricas constituye un problema clínico frecuente. Materiales y métodos: El estudio incluyó 100 hisopos orofaríngeos obtenidos entre octubre de 2019 y noviembre de 2020 de pacientes que habían acudido a los servicios de urgencias pediátricas con sospecha de infección de las vías respiratorias superiores y resultados negativos en las pruebas de gripe y VRS. Las muestras de los hisopos orofaríngeos se procesaron rápidamente con Standard™ F Adeno Respi Ag FIA y los resultados se confirmaron mediante RealStar® Adenovirus PCR Kit 1.0 (altona Diagnostics). Resultados: Standard™ F Adeno Respi Ag FIA tenía unos valores de sensibilidad y especificidad del 71,93% y el 100%, respectivamente. El rendimiento de la prueba fue superior en muestras de niños menores de 24 meses y tomadas menos de 72 horas después del inicio de los síntomas. En este subgrupo, la prueba tuvo una sensibilidad del 88,8% y una especificidad del 100%. Conclusión: Standard™ F Adeno Respi Ag FIA puede mejorar la gestión de las enfermedades respiratorias en niños menores de 24 meses con menos de 72 desde el inicio de los síntomas en servicios de urgencias pediátricas.(AU)

Considerations on the implementation of the Clinical Microbiology and Parasitology training program in Spanish hospitals: A national survey.

INTRODUCTION: The specialty of Microbiology and Parasitology is a four-year multidisciplinary training with a central role in the diagnosis and epidemiological surveillance of infectious diseases. The aim of this study is to analyze the degree of implementation of the official program and the degree of satisfaction of residents with their training. METHODS: We conducted an online survey distributed in eight sections to which active residents of the Specialty of Clinical Microbiology and Parasitology had access. RESULTS: A total of 69 responses were received, with a predominance of residents from the regions of Madrid (43.5%) and of FIR admission route (55%). The areas in which the residents feel best prepared correspond to systematic bacteriology, antimicrobials and clinical aspects of microbiology. The areas with the worst preparation, on the other hand, are mycology, parasitology and microbiological emergencies. There are significant differences between the clinical rotation time for residents with MIR access pathway with respect to residents with other degrees. Respondents perceive a high degree of responsibility and a medium agreement with the quality of teaching. Attendance at clinical sessions and external rotations is frequent. Research activity is perceived as complicated, both at the level of doctoral studies and with respect to entering research lines and the publication of scientific results. CONCLUSION: Some points of improvement of the training itinerary have been identified that need to be reinforced. Likewise, it would be interesting to seek a better balance between care, teaching and research activities.

Prevalence of Tooth Transposition among Orthodontic Patients in Spain.

Objectives: The aim of this retrospective study was to analyze the prevalence of tooth transposition within an orthodontic population and explore its correlation with facial biotype, skeletal class and sex. Material and methods: This study examined a sample of 2,500 initial orthodontic records from consecutive orthodontic patients who received treatment at the Master Universitario de Orthodontia (Madrid, Spain) between 2014 and 2023. Patients exhibiting incomplete or poor-quality medical records were excluded from the study. The chi-square test was used to assess variations in distribution based on facial biotype, skeletal class and sex. A p-value of < 0.05 was considered statistically significant. Results: The study findings revealed a tooth transposition prevalence rate of 0.28%. No significant differences in prevalence were observed based on sex or facial biotype, but the prevalence of transposition was found to be higher among class I patients (p < 0.05). Conclusion: The prevalence of tooth transposition among orthodontic patients is relatively low (0.28%). However, it is more commonly observed among patients with skeletal class I malocclusion.

Sulfonate-Based Triazine Multiple-Electron Anolyte for Aqueous Organic Flow Batteries.

A new highly soluble triazine derivative (SPr)34TpyTz showing three reversible redox processes with fast kinetics and high diffusion coefficients has been synthesized using an efficient, low-cost, and straightforward synthetic route. Concentrated single cell tests and DFT studies reveal a tendency of the reduced triazine species to form aggregates which could be avoided by tuning the supporting electrolyte concentration. Under the right conditions, (SPr)34TpyTz shows no capacity decay and good Coulombic, voltage, and energy efficiencies for the storage of two electrons. The storage of further electrons leads to a higher capacity decay and an increase of the electrolyte pH, suggesting the irreversible protonation of the generated species. So, a plausible mechanism has been proposed. A higher concentration of (SPr)34TpyTz shows slightly higher capacity decay and lower efficiencies due to the aggregate formation.

Festivals following the easing of COVID-19 restrictions: Prevalence of new psychoactive substances and illicit drugs.

The market for illicit drugs and new psychoactive substances (NPS) has grown significantly and people attending festivals have been identified as being at high risk (high extent and frequency of substance use). Traditional public health surveillance data sources have limitations (high costs, long implementation times, and ethical issues) and wastewater-based epidemiology (WBE) can cost-effectively support surveillance efforts. Influent wastewater samples were analyzed for NPS and illicit drug consumption collected during New Year period (from 29-Dec-2021 to 4-Jan-2022) and a summer Festival (from 29-June-2022 to 12-July-2022) in a large city in Spain. Samples were analyzed for phenethylamines, cathinones, opioids, benzodiazepines, plant-based NPS, dissociatives, and the illicit drugs methamphetamine, MDA, MDMA, ketamine, heroin, cocaine, and pseudoephedrine by liquid chromatography mass spectrometry. High consumption rates of specific NPS and established illicit drugs were identified at the peak of each event. Furthermore, a dynamic change in NPS use (presence and absence of substances) was detected over a period of six months. Eleven NPS, including synthetic cathinones, benzodiazepines, plant-based NPS and dissociatives, and seven illicit drugs were found across both the New Year and summer Festival. Statistically significant differences (p < 0.05) were seen for 3-MMC (New Year vs summer Festival), eutylone (New Year vs summer Festival), cocaine (summer Festival vs normal week and summer Festival vs New Year), MDMA (New Year vs normal week and summer Festival vs normal week), heroin (summer Festival vs New Year) and pseudoephedrine (summer Festival vs New Year). This WBE study assessed the prevalence of NPS and illicit drugs at festivals following the reduction of the COVID-19 pandemic restrictions highlighting the high use of specific substances at the peak of each event. This approach identified in a cost-effective and timely manner without any ethical issues the most used drugs and changes in use patterns and, thus, can complement public health information.

Dual Nickel/Photoredox-Catalyzed Asymmetric Carbosulfonylation of Alkenes.

An asymmetric three-component carbosulfonylation of alkenes is presented here. The reaction, involving the simultaneous formation of a C-C and a C-S bond across the π-system, uses a dual nickel/photoredox catalytic system to produce both ß-aryl and ß-alkenyl sulfones in high yields and with excellent levels of stereocontrol (up to 99:1 er). This protocol exhibits a broad substrate scope and excellent functional group tolerance and its synthetic potential has been demonstrated by successful applications toward pharmacologically relevant molecules. A broad array of control experiments supports the involvement of a secondary alkyl radical intermediate generated through radical addition of a sulfonyl radical to the double bond. Moreover, stoichiometric and cross-over experiments further suggest an underlying Ni(0)/Ni(I)/Ni(III) pathway operative in these transformations.

Influence of social media on the esthetic perception of the lip profile of orthodontic patients.

Objective: To identify the use of social media as an influencing factor of the orthodontic patient's preferences regarding the lip profile protrusion. Methods: A two-part cross-sectional questionnaire was distributed to orthodontic patients in Spain and The Netherlands. The first part collected general data and frequency of use of different social media. The second part consisted of a series of modified female and male silhouettes presenting different lip profile positions. Each participant was required to choose both the (male and female) most attractive silhouette and the least attractive one.Student t-test, one-way ANOVA and Chi-square test were performed. Effect sizes were calculated to express the magnitude of differences between samples. Results: The Spanish sample resulted in a moderate higher tendency (R2 = 0.060) to choose protrusive lips as the most attractive lip profile for females, on subjects with more frequent use of social media. A medium tendency (R2=0,26) was observed as result of low users of social media choosing and ideal lip profile for men.The Dutch sample showed that high users of social media tended to choose as attractive a more protrusive female lip profile versus low users (p < .01). This was also observed (p < .05) on male attractive lip profiles. Conclusions: Results suggest that frequent users of social media platforms tend to prefer more protruded lips than their less frequent counterparts. This information is valuable to be considered when formulating a treatment plan to satisfy the patient's expectations.

Germline-targeting HIV-1 Env vaccination induces VRC01-class antibodies with rare insertions.

Targeting germline (gl-) precursors of broadly neutralizing antibodies (bNAbs) is acknowledged as an important strategy for HIV-1 vaccines. The VRC01-class of bNAbs is attractive because of its distinct genetic signature. However, VRC01-class bNAbs often require extensive somatic hypermutation, including rare insertions and deletions. We describe a BG505 SOSIP trimer, termed GT1.2, to optimize binding to gl-CH31, the unmutated common precursor of the CH30-34 bNAb lineage that acquired a large CDRH1 insertion. The GT1.2 trimer activates gl-CH31 naive B cells in knock-in mice, and B cell responses could be matured by selected boosting immunogens to generate cross-reactive Ab responses. Next-generation B cell sequencing reveals selection for VRC01-class mutations, including insertions in CDRH1 and FWR3 at positions identical to VRC01-class bNAbs, as well as CDRL1 deletions and/or glycine substitutions to accommodate the N276 glycan. These results provide proof of concept for vaccine-induced affinity maturation of B cell lineages that require rare insertions and deletions.

Rapid antigen test for adenovirus in children: Age and onset of symptoms are important.

INTRODUCTION: Respiratory infection is the most common human adenovirus (HAdV) disease accounting for 7-8% of viral respiratory diseases in children less than 5 years. Differentiation of bacterial infections and viral infections is a common clinical problem. MATERIAL AND METHODS: One hundred oropharyngeal swabs obtained from October 2019 to November 2020 from patients attending the paediatric emergency room with suspicion of upper respiratory tract infection and negative results in influenza and RSV tests were included. Oropharyngeal swabs specimens were rapidly processed with STANDARD™ F Adeno Respi Ag FIA and the results were confirmed by RealStar® Adenovirus PCR Kit 1.0 (Altona diagnostics). RESULTS: STANDARD™ F Adeno Respi Ag FIA had sensitivity and specificity values of 71.93% and 100% respectively. The performance of the test was higher in samples from children younger than 24 months and taken less than 72h since the beginning of symptoms. In this subgroup the test had 88.8% sensitivity and 100% specificity. CONCLUSION: STANDARD™ F Adeno Respi Ag FIA may improve the management of respiratory diseases in children younger than 24 months and less than 72h since the beginning of symptoms in paediatric emergency rooms.