Identifying predictors of adverse outcomes after termination of seclusion in psychiatric intensive care units.

BACKGROUND: Seclusion is a restrictive practice that many healthcare services are trying to reduce. Previous studies have sought to identify predictors of seclusion initiation, but few have investigated factors associated with adverse outcomes after seclusion termination. AIMS: To assess the factors that predict an adverse outcome within 24 h of seclusion termination. METHOD: In a cohort study of individuals secluded in psychiatric intensive care units, we investigated factors associated with any of the following outcomes: actual violence, attempted violence, or reinitiation of seclusion within 24 h of seclusion termination. Among the seclusion episodes that were initiated between 29 March 2018 and 4 March 2019, we investigated the exposures of medication cooperation, seclusion duration, termination out of working hours, involvement of medical staff in the final seclusion review, lack of insight, and agitation or irritability. In a mixed-effects logistic regression model, associations between each exposure and the outcome were calculated. Odds ratios were calculated unadjusted and adjusted for demographic and clinical variables. RESULTS: We identified 254 seclusion episodes from 122 individuals (40 female, 82 male), of which 106 (41.7%) had an adverse outcome within 24 h of seclusion termination. Agitation or irritability was associated with an adverse outcome, odds ratio 1.92 (95% CI 1.03 to 3.56, P = 0.04), but there was no statistically significant association with any of the other exposures, although confidence intervals were broad. CONCLUSIONS: Agitation or irritability in the hours preceding termination of seclusion may predict an adverse outcome. The study was not powered to detect other potentially clinically significant factors.

Prognostic Value of Histone Acetyl Transferase 1 (HAT-1) and Inflammatory Signatures in Pancreatic Cancer.

Pancreatic cancer is a type of gastrointestinal tumor with a growing incidence and mortality worldwide. Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of cases, and late-stage diagnosis is common, leading to a 5-year survival rate of less than 10% in high-income countries. The use of biomarkers has different proven translational applications, facilitating early diagnosis, accurate prognosis and identification of potential therapeutic targets. Several studies have shown a correlation between the tissue expression levels of various molecules, measured through immunohistochemistry (IHC), and survival rates in PDAC. Following the hallmarks of cancer, epigenetic and metabolic reprogramming, together with immune evasion and tumor-promoted inflammation, plays a critical role in cancer initiation and development. In this study, we aim to explore via IHC and Kaplan-Meier analyses the prognostic value of various epigenetic-related markers (histones 3 and 4 (H3/H4), histone acetyl transferase 1 (HAT-1), Anti-Silencing Function 1 protein (ASF1), Nuclear Autoantigenic Sperm Protein (NASP), Retinol Binding Protein 7 (RBBP7), importin 4 (IPO4) and IPO5), metabolic regulators (Phosphoglycerate mutase (PGAM)) and inflammatory mediators (allograft inflammatory factor 1 (AIF-1), interleukin 10 (IL-10), IL-12A and IL-18) in patients with PDAC. Also, through a correlation analysis, we have explored the possible interconnections in the expression levels of these molecules. Our results show that higher expression levels of these molecules are directly associated with poorer survival rates in PDAC patients, except in the case of IL-10, which shows an inverse association with mortality. HAT1 was the molecule more clearly associated with mortality, with a hazard risk of 21.74. The correlogram demonstrates an important correlation between almost all molecules studied (except in the case of IL-18), highlighting potential interactions between these molecules. Overall, our study demonstrates the relevance of including different markers from IHC techniques in order to identify unexplored molecules to develop more accurate prognosis methods and possible targeted therapies. Additionally, our correlation analysis reveals potential interactions among these markers, offering insights into PDAC's pathogenesis and paving the way for targeted therapies tailored to individual patient profiles. Future studies should be conducted to confirm the prognostic value of these components in PDAC in a broader sample size, as well as to evaluate the possible biological networks connecting them.

Conformational Defects in the Limbs of Menorca Purebred Horses and Their Relationship to Functionality.

Limb-conformation defects significantly influence equine performance and welfare, necessitating thorough investigation for effective management. This study examines the prevalence and genetic parameters of 14 limb-conformation defects in Menorca Purebred horses using data from 1120 records (509 animals with an average age of 101.87 ± 1.74 months) collected between 2015 and 2023. Defects were evaluated using a three-class scale by three appraisers, and a Bayesian approach via Gibbs sampling was employed to estimate genetic parameters including gender, birth period, stud selection criteria, evaluation age and appraiser as fixed effects. Splay-footed forelimb and closed hocks were the most prevalent defects (67.20% and 62.53%, respectively). Horses with any of the defects analyzed have been observed to obtain significantly lower scores for both walk and trot. Heritability estimates range from 0.12 (s.d.: 0.025) for closed hock to 0.30 (s.d.: 0.054) for base narrow, confirming the genetic influences on the expression of limb conformation defects. The divergent defect in hind limbs showed the highest genetic correlations with forelimb defects (camped under, -0.69; s.d: 0.32 and camped out, 0.70; s.d: 0.27). The significant genetic correlations between defects highlight the complexity of the relationships, which requires careful consideration.

Double blocking of carbon metabolism causes a large increase of Calvin-Benson cycle compounds in cyanobacteria.

Carbon-flow-regulator A (CfrA) adapts carbon flux to nitrogen conditions in non-diazotrophic cyanobacteria. Under nitrogen deficiency, CfrA leads to the storage of excess carbon, which cannot combine with nitrogen, mainly as glycogen. cfrA overexpression from the arsenite-inducible, nitrogen-independent ParsB promoter allows analysis of the metabolic effects of CfrA accumulation. Considering that the main consequence of cfrA overexpression is glycogen accumulation, we examined carbon distribution in response to cfrA expression in Synechocystis sp. PCC 6803 strains impaired in synthesizing this polymer. We carried out a comparative phenotypic analysis to evaluate cfrA overexpression in the wild-type strain and in a mutant of ADP-glucose pyrophosphorylase (ΔglgC), which is unable to synthesize glycogen. The accumulation of CfrA in the wild-type background caused a photosynthetic readjustment although growth was not affected. However, in a ΔglgC strain, growth decreased depending on CfrA accumulation and photosynthesis was severely affected. An elemental analysis of the H, C, and N content of cells revealed that cfrA expression in the wildtype caused an increase in the C/N ratio, due to decreased nitrogen assimilation. Metabolomic study indicated that these cells store sucrose and glycosylglycerol, in addition to the previously described glycogen accumulation. However, cells deficient in glycogen synthesis accumulated large amounts of Calvin-Benson cycle intermediates as cfrA was expressed. These cells also showed increased levels of some amino acids, mainly alanine, serine, valine, isoleucine and leucine. The findings suggest that by controlling cfrA expression, in different conditions and strains, we could change the distribution of fixed carbon, with potential biotechnological benefits.

Immune response to vaccination in people with psychotic disorders relative to healthy controls: prospective study of SARS-CoV-2 vaccination.

This prospective study examines the immune response to SARS-CoV-2 vaccination in patients with psychotic disorders compared with healthy volunteers. Participants were recruited naturalistically as part of the UK's COVID-19 vaccination programme. Prior to receiving their first COVID-19 vaccine, blood samples were provided by participants to examine anti-SARS-CoV-2 immunoglobulins (IgG) at baseline, followed by a repeat assay 1 month after receiving their first vaccine to assess vaccine response. The increase of IgG levels from baseline to 1 month post-vaccination was significantly lower in patients compared with controls, supporting evidence of impaired vaccine response in people with psychotic disorders. When excluding patients treated with clozapine from the analysis, this difference was no longer significant, suggesting that effects may be particularly marked in people taking clozapine.

Rheumatology Patients' Experiences of a Mandatory Nationwide Transition to an Adalimumab Biosimilar.

OBJECTIVE: Transitions to biosimilars are common to reduce the cost burden of biologics. While brand changes can be daunting for patients, few studies have explored patients' experiences with the transitioning process. This study examined rheumatology patients' experiences with a mandatory nationwide brand change to an adalimumab biosimilar. METHODS: People with rheumatic diseases involved in the adalimumab transition in Aotearoa New Zealand completed a nationwide online survey. Participants (n = 117, 48% with rheumatoid arthritis) reported their satisfaction with the biosimilar, logistics and supply, information and communication, and availability of support. They also reported what did and did not go well during the transition and provided recommendations for future transitions. RESULTS: The mean [SD] satisfaction score with the transition was 6.2 [3.2] on a 0-10 scale, with 10 indicating high satisfaction. Participants were the least satisfied with the support and information from patient support organizations, and training for the device during the transition. Participants were most satisfied with the biosimilar supply, support from pharmacists, and how early they were informed before the transition occurred. After the transition, participants were less satisfied with the device quality, patient support program, biosimilar safety and efficacy, and the provision of alcohol wipes and sharps bins (p < 0.05 for all). Satisfaction with training for the biosimilar device (B = .25, p = .036) predicted overall satisfaction. Participants appreciated less injection pain and the ease of the biosimilar device. The lack of alcohol wipes and loss of the bio-originator support program were viewed negatively. CONCLUSION: Future biosimilar transitions should ensure the availability of alcohol wipes, sharps bins, and a comparable patient support program. Patient support organizations could be involved in providing information to patients about the change.

Shear Bond Strength of Simulated Single-Retainer Resin-Bonded Bridges Made of Four CAD/CAM Materials for Maxillary Lateral Incisor Agenesis Rehabilitation.

OBJECTIVES: Maxillary lateral incisor agenesis (MLIA), treated orthodontically by space opening, requires complimentary aesthetic rehabilitation. Resin-bonded bridges (RBBs) can be equated as interim rehabilitation until skeletal maturity is achieved to place an implant-supported crown or as definitive rehabilitation in case of financial restrictions or implant contraindications. Scientific evidence of the best material must be confirmed in specific clinical situations. Computer-aided design and computer-aided manufacturing (CAD/CAM) materials are promising versatile restorative options. This study aimed to identify a straightforward material to deliver interim or definitive RBBs for nonprepared tooth replacement in MLIA. MATERIALS AND METHODS: Single-retainer RBB made from CAD/CAM ceramic blocks (Vita Enamic [ENA], Suprinity [SUP], and zirconia [Y-ZPT]) and a three-dimensional (3D) printed material (acrylonitrile butadiene styrene [ABS]) were evaluated by shear bond strength (SBS) and mode of failure, after adherence to an artificial tooth with RelyX Ultimate used in a three-step adhesive strategy. STATISTICAL ANALYSIS: The load to fracture (N) was recorded, and the mean shear stress (MPa) was calculated with standard deviations (SD) for each group and compared between materials using boxplot graphics. One-way analysis of variance (ANOVA) followed by the Tukey-Kramer post hoc test was used to compare the differences (α = 0.05). A meta-analysis focusing on CAD/CAM materials evaluated the magnitude of the difference between groups based on differences in means and effect sizes (α = 0.05; 95% confidence interval [CI]; Z-value = 1.96). Failure mode was determined by microscopic observation and correlated with the maximum load to fracture of the specimen. RESULTS: The mean ± SD SBS values were ENA (24.24 ± 9.05 MPa) < ABS (24.01 ± 1.94 MPa) < SUP (29.17 ± 4.78 MPa) < Y-ZPT (37.43 ± 12.20 MPa). The failure modes were mainly adhesive for Y-ZPT, cohesive for SUP and ENA, and cohesive with plastic deformation for ABS. CONCLUSION: Vita Enamic, Suprinity, Y-ZPT zirconia, and 3D-printed ABS RBBs are optional materials for rehabilitating MLIA. The option for each material is conditioned to estimate the time of use and necessity of removal for orthodontic or surgical techniques.

Orthopedic Diseases in the Pura Raza Española Horse: The Prevalence and Genetic Parameters of Angular Hoof Deviations.

Abnormalities in hoof shape are usually connected with limb conformation defects. The role of angular hoof deviations is important for longevity in sports competitions and is increasingly recognized as a factor associated with lameness in performance horses. In this paper, we measured the prevalence of four defects related to the angulation of the hoof in the Pura Raza Española horse (PRE): splay-footed forelimb (SFF), pigeon-toed forelimb (PTF), splay-footed rear limb (SFR), and pigeon-toed rear limb (PTR). A total of 51,134 animals were studied, of which only 15.75% did not have any of the four angular hoof defects investigated, while 26.61%, 23.76%, 79.53%, and 3.86% presented SFF, PTF, SFR, and PTR, respectively. Angular defects were evaluated using two different models; model A was a linear scale composed of three categories, where 0 corresponded to the absence of defects, 1 to a minor presence of the defect and 2 to the highest degree of the defect. Model B was composed of two categories, where 0 corresponded to the absence of defects and 1 to the presence of defects, joining classes 1 and 2. We measured the factors influencing the appearance of these defects: age, inbreeding coefficient, sex, and birth stud size. The heritability of each defect was also estimated using a multivariate animal model, using the Gibbsf90+ software from the BLUPF90 family, resulting in heritability estimates of 0.18 (s.d. = 0.009), 0.20 (s.d. = 0.010), 0.11 (s.d. = 0.009), and 0.31 (s.d. = 0.010) for SFF, PTF, SFR, and PTR defects, respectively, for model A, and 0.17 (s.d. = 0.008), 0.19 (s.d. = 0.009), 0.11 (s.d. = 0.009), and 0.29 (s.d. = 0.009) for SFF, PTF, SFR, and PTR defects, respectively, for model B. Finally, the genetic correlation between the diameter of the superficial digital flexor tendon (SDFT) and the proportionality index (PI) in relation to the higher or lower prevalence of the defects was analyzed. We concluded that diameter of SDFT development is strongly correlated with inward toe conditions (PTF, PTR; P≠0 ≥ 0.95), while PI is associated with outward toe defects (SFF, SFR; P≠0 ≥ 0.95).

Health Care Providers' Experiences of a Mandatory Nationwide Transition to an Adalimumab Biosimilar.

OBJECTIVE: Transitioning patients to biosimilars has become common to reduce costs and improve access. However, it is unclear how the transition process impacts health care providers at the frontline of the brand change. This study explores health care providers' experiences of a mandatory brand change to an adalimumab biosimilar. METHODS: A cross-sectional study was conducted in Aotearoa New Zealand with 164 providers involved in the nationwide adalimumab brand change. Rheumatologists (n = 39), rheumatology nurses (n = 16), and pharmacists (n = 109) completed a survey that assessed their satisfaction with logistics and supply, information and education, support, and administrative workload and reported what did and did not go well during the transition. RESULTS: The mean satisfaction score (0-10) with the transition was 5.7 (SD = 2.6). Providers were the least satisfied with training for the biosimilar device, information from government agencies, and administrative workload during the transition. Satisfaction with adalimumab safety, efficacy and device quality, and the availability of sharps bins, alcohol wipes, and patient support was lower following the transition. Satisfaction with administrative workload (B = 0.37, P < 0.001) and training for the device (B = 0.20, P = 0.020) predicted overall satisfaction. Providers reported that a poorly implemented initial authorization process, loss of a patient support program, and insufficient communication between providers complicated the transition. The citrate-free preservative and longer authorization duration after the transition were viewed positively. CONCLUSION: Providers experienced an increased workload and reported less satisfaction with the biosimilar following the transition. Experiences may be improved by ensuring training for the device, a high-quality patient support program, and functioning authorization processes throughout the transition.

Is Insulin Receptor Substrate4 (IRS4) a Platform Involved in the Activation of Several Oncogenes?

The IRS (insulin receptor substrate) family of scaffold proteins includes insulin receptor substrate-4 (IRS4), which is expressed only in a few cell lines, including human kidney, brain, liver, and thymus and some cell lines. Its N-terminus carries a phosphotyrosine-binding (PTB) domain and a pleckstrin homology domain (PH), which distinguishes it as a member of this family. In this paper, we collected data about the molecular mechanisms that explain the relevance of IRS4 in the development of cancer and identify IRS4 differences that distinguish it from IRS1 and IRS2. Search engines and different databases, such as PubMed, UniProt, ENSEMBL and SCANSITE 4.0, were used. We used the name of the protein that it encodes "(IRS-4 or IRS4)", or the combination of these terms with the word "(cancer)" or "(human)", for searches. Terms related to specific tumor pathologies ("breast", "ovary", "colon", "lung", "lymphoma", etc.) were also used. Despite the lack of knowledge on IRS4, it has been reported that some cancers and benign tumors are characterized by high levels of IRS-4 expression. Specifically, the role of IRS-4 in different types of digestive tract neoplasms, gynecological tumors, lung cancers, melanomas, hematological tumors, and other less common types of cancers has been shown. IRS4 differs from IRS1 and IRS2 in that can activate several oncogenes that regulate the PI3K/Akt cascade, such as BRK and FER, which are characterized by tyrosine kinase-like activity without regulation via extracellular ligands. In addition, IRS4 can activate the CRKL oncogene, which is an adapter protein that regulates the MAP kinase cascade. Knowledge of the role played by IRS4 in cancers at the molecular level, specifically as a platform for oncogenes, may enable the identification and validation of new therapeutic targets.

Corrigendum: Exploring genetic variability of Giardia duodenalis and Enterocytozoon bieneusi in raw vegetables and fruits: implications for food safety and public health in Mozambique.

[This corrects the article DOI: 10.3389/fmicb.2023.1223151.].

A luminescence-based method to assess antigen presentation and antigen-specific T cell responses for in vitro screening of immunomodulatory checkpoints and therapeutics.

Investigations into the strength of antigen-specific responses in vitro is becoming increasingly relevant for decision making in early-phase research of novel immunotherapeutic approaches, including adoptive cell but also immune checkpoint inhibitor (ICI)-based therapies. In the latter, antigen-specific rapid and high throughput tools to investigate MHC/antigen-specific T cell receptor (TCR) activation haven't been implemented yet. Here, we present a simple and rapid luminescence-based approach using the human papillomavirus 16 (HPV16) E711-20 peptide as model antigen and E7-TCR transgenic Jurkat.NFAT-luciferase reporter cells. Upon E7 peptide pulsing of HLA-A2+ cell lines and macrophages, an effector to target ratio dependent increase in luminescence compared to non-pulsed cells was observed after co-incubation with E7-TCR expressing Jurkat, but not with parental cells. Analogous experiments with cells expressing full-length HPV16 identified that E7-specific activation of Jurkat cells enabled detection of endogenous antigen processing and MHC-I presentation. As proof of concept, overexpression of established checkpoints/inhibitory molecules (e.g., PD-L1 or HLA-G) significantly reduced the E7-specific TCR-induced luminescence, an effect that could be restored after treatment with corresponding targeting antagonistic antibodies. Altogether, the luminescence-based method described here represents an alternative approach for the rapid evaluation of MHC-dependent antigen-specific T cell responses in vitro. It can be used as a rapid tool to evaluate the impact of the immunosuppressive tumor microenvironment or novel ICI in triggering effective T cell responses, as well as speeding up the development of novel therapeutics within the immune-oncology field.

Exploring genetic variability of Giardia duodenalis and Enterocytozoon bieneusi in raw vegetables and fruits: implications for food safety and public health in Mozambique.

Giardia duodenalis and Enterocytozoon bieneusi are etiological agents of enteric diseases characterized by diarrhea that can progress to chronicity in humans, especially in children and in immunocompromised patients. This study aims to assess the genetic pattern of G. duodenalis and E. bieneusi detected in vegetables and fruits commercialized in Maputo markets, Mozambique and determine their public health importance. Eight study points were sampled: a farmer zone, a wholesale, four retail markets, and two supermarkets in Maputo city, where eight types of horticultural products were purchased. Using nested-PCR methods, 2.8% (9/321) and 1.3% (4/321) of samples monitored were positive for G. duodenalis and E. bieneusi, respectively. Based on the analysis of the ß-giardin and ITS rRNA sequences of G. duodenalis and E. bieneusi detected, respectively, four different sequences of G. duodenalis (three novel sequences: BgMZ1, BgMZ2, and BgMZ3, and one known sequence) all from assemblage B and three genotypes of E. bieneusi (two novel sequences: EbMZ4 and EbMZ5, and one known sequence: KIN-1) from group 1. These microorganisms were found and characterized for the first time in horticultural products in Maputo markets. All identified G. duodenalis and E. bieneusi display high genetic similarity within their ß-giardin and ITS rRNA sequences, respectively, having been clustered into assemblages and genotypes with high zoonotic transmission potential. Our study may represent a relevant step in the understanding of these intestinal pathogens in association with fresh vegetables and fruits for human consumption, for a better and broader "One Health" approach.

Perfil das internações por diabetes mellitus e hipertensão arterial sistêmica: um estudo descritivo / Profile of hospitalizations for diabetes mellitus and systemic arterial hypertension: a descriptive study

Objetivo: analisar o perfil as internações por Diabetes Mellitus (DM) e Hipertensão Arterial Sistêmica (HAS) no estado de Pernambuco no período de 2018 a 2022. Metodologia: estudo epidemiológico descritivo, documental, com abordagem quantitativa sobre as internações médicas em consequência de DM e HAS no estado de Pernambuco, presentes no Sistema de Informações Hospitalares. Resultados: Houve 36.605 internações médicas, sendo 27.721 (75,73%) relacionadas a DM e 8.884 (24,27%) a HAS, com um gasto total de R$33 milhões. Houve maior prevalência de internações nas mulheres (51,29% e 58,62%), idosos (54,11% e 58,62,0%), pardos (81,41% e 63,92%) e oriundos emergência (91,29% e 95,57%). Em relação a morbimortalidade hospitalar, as maiores taxas foram encontradas nas mulheres (54,91% e 57,01%) e em idosos (72,84% e 83,76%). Conclusão: foi evidenciado que a DM e HAS é importante causa de internação no estado de Pernambuco, gerando uma alta pressão sobre os serviços de saúde.(AU)

Objective: To analyze the profile of hospitalizations for Diabetes Mellitus (DM) and Systemic Arterial Hypertension (SAH) in the state of Pernambuco from 2018 to 2022. Methodology: This is a descriptive epidemiological study with a quantitative approach on medical admissions due to DM and SAH in the state of Pernambuco, which are included in the Hospital Information System. Results: There were 36,605 medical admissions, of which 27,721 (75.73%) were related to DM and 8,884 (24.27%) to SAH, with a total cost of R$33 million. There was a higher prevalence of hospitalizations among women (51.29% and 58.62%), the elderly (54.11% and 58.62.0%), brown people (81.41% and 63.92%) and people coming from emergencies (91.29% and 95.57%). With regard to hospital morbidity and mortality, the highest rates were found among women (54.91% and 57.01%) and the elderly (72.84% and 83.76%). Conclusion: DM and SAH were found to be important causes of hospitalization in the state of Pernambuco, generating a high level of pressure on health services.(AU)

Objetivo: Analizar el perfil de los ingresos hospitalarios por Diabetes Mellitus (DM) e Hipertensión Arterial Sistémica (HAS) en el estado de Pernambuco entre 2018 y 2022. Metodología: Se trata de un estudio epidemiológico descriptivo con enfoque cuantitativo sobre los ingresos médicos por DM e HSA en el estado de Pernambuco, registrados en el Sistema de Información Hospitalaria. Resultados: Hubo 36.605 internaciones médicas, de las cuales 27.721 (75,73%) se relacionaron con DM y 8.884 (24,27%) con HSA, con un costo total de 33 millones de reales. Hubo mayor prevalencia de hospitalizaciones en mujeres (51,29% y 58,62%), ancianos (54,11% y 58,62%), morenos (81,41% y 63,92%) y personas procedentes de urgencias (91,29% y 95,57%). En cuanto a la morbimortalidad hospitalaria, las tasas más elevadas se encontraron entre las mujeres (54,91% y 57,01%) y los ancianos (72,84% y 83,76%). Conclusión: La DM y la HSA fueron encontradas como una de las principales causas de hospitalización en el estado de Pernambuco, generando un alto nivel de presión sobre los servicios de salud.(AU)

The Relevance of the Expected Value of the Proportion of Arabian Genes in Genetic Evaluations for Eventing Competitions.

The Arabian horse is a generally reliable sport horse, and continues to be a remarkable endurance horse, so the relevance of the expected value of the proportion of Arabian genes (EV%AG) in horses participating in eventing could be a relevant factor. A total of 1089 horses participating in eventing (8866 records) were used. A GLM revealed that the EV%AG was significant in dressage, show jumping and cross-country. A BLUP genetic evaluation was computed with five genetic models (without the EV%AG (0) using as a covariate (A), as a fixed effect (B), with variance heterogeneity, and in genetic groups without (C) and with (D)). Dressage heritability ranged from 0.103 to 0.210, show jumping ranged from 0.117 to 0.203 and cross-country ranged from 0.070 to 0.099. The lowest DIC value was used as a criterion of fitness. The best fits (those which included variance heterogeneity) showed fewer than two points of difference in DIC values. The highest average estimated breeding value in dressage, show jumping and cross-country was found for horses with an expected value of the proportion of Arabian genes of 0%, ≥1% to <25%, and 100%, respectively. Therefore, the best way to model the EV%AG effect seems to be by considering the variance heterogeneity.

Chronic Venous Disease during Pregnancy Is Related to Inflammation of the Umbilical Cord: Role of Allograft Inflammatory Factor 1 (AIF-1) and Interleukins 10 (IL-10), IL-12 and IL-18.

Chronic venous disease (CVD) is a common condition that affects the veins in the lower limbs, resulting in a variety of symptoms, such as swelling, pain, and varicose veins (VVs). The plenty hormonal, hemodynamic and mechanical changes occurred in pregnancy make women especially vulnerable to suffer from this condition in this period. Previous works have identified that CVD is associated with an increased inflammatory milieu and significant damage in maternofetal tissues, such as the umbilical cord. However, the inflammatory status of this structure in these patients has not been studied yet. Thus, the aim of the present study was to examine gene and protein expression of a set of inflammatory markers-Allograft inflammatory factor 1 (AIF-1), the proinflammatory cytokines interleukin 12A (IL-12A) and IL-18 and the anti-inflammatory product IL-10-in the umbilical cord of women with CVD during pregnancy (N = 62) and healthy pregnant women (HC; N = 52) by the use of real time qPCR and immunohistochemistry (IHC). Our results demonstrate that the umbilical cord tissue from CVD women exhibit an increased expression of AIF-1, IL-12A and IL-18 along with a decrease in IL-10. Therefore, our study suggests an inflammatory status of this structure related to CVD. Further studies should be conducted to evaluate the expression of other inflammatory markers, as well as to analyze the maternofetal impact of these findings.

Esthetic Perception of Different Clinical Situations of Maxillary Lateral Incisor Agenesis According to Populations with Dental and Non-Dental Backgrounds: A Systematic Review and Meta-Analysis.

Treatment of unilateral or bilateral maxillary lateral incisor agenesis is challenging, time-consuming, expensive, and requires careful treatment planning, predictability, and esthetics. This review aimed to identify differences in esthetic perception among orthodontists, general dentists, differentiated dentists, and laypersons, which may interfere with treatment options. EBSCO, PubMed, ScienceDirect, Cochrane Library databases, and Google Scholar were searched using keyword pairing and a Boolean expression, "(congenitally missing OR agenesis OR hypodontia) AND (maxillary lateral incisors) AND (esthetic perception OR smile) AND (laypersons OR dental professional OR general dentist OR orthodontists)." Reviews and case studies were excluded. A total of 13 studies were selected for qualitative analysis (adapted ROBINS-I) and 11 were selected for meta-analysis (p < 0.05) after being sub-grouped into "Opening vs. Closure" and "No remodeling vs. Dental remodeling vs. Dental and gingival remodeling" groups. A meta-analysis evaluated the magnitude of the difference between groups based on differences in means and effect sizes (α = 0.05; 95% CI; Z-value 1.96), revealing that the esthetic perception of maxillary lateral incisor agenesis treatment remains controversial even among professionals. Gingival remodeling was not valued compared to isolated dental remodeling. Studies lack rigorously comparable methodologies. Discussion with the patient is pertinent in doubtful situations, as the best treatment option remains unclear, and overtreatment should be avoided.

Effectiveness of Self-Adhesive Resin Luting Cement in CAD-CAM Blocks-A Systematic Review and Meta-Analysis.

Self-adhesive resin cements (SARCs) are used because of their mechanical properties, ease of cementation protocols, and lack of requirements for acid conditioning or adhesive systems. SARCs are generally dual-cured, photoactivated, and self-cured, with a slight increase in acidic pH, allowing self-adhesiveness and increasing resistance to hydrolysis. This systematic review assessed the adhesive strength of SARC systems luted to different substrates and computer-aided design and manufacturing (CAD/CAM) ceramic blocks. The PubMed/MedLine and Science Direct databases were searched using the Boolean formula [((dental or tooth) AND (self-adhesive) AND (luting or cement) AND CAD-CAM) NOT (endodontics or implants)]. Of the 199 articles obtained, 31 were selected for the quality assessment. Lava Ultimate (resin matrix filled with nanoceramic) and Vita Enamic (polymer-infiltrated ceramic) blocks were the most tested. Rely X Unicem 2 was the most tested resin cement, followed by Rely X Unicem > Ultimate > U200, and µTBS was the test most used. The meta-analysis confirmed the substrate-dependent adhesive strength of SARCs, with significant differences between them and between SARCs and conventional resin-based adhesive cement (α < 0.05). SARCs are promising. However, one must be aware of the differences in the adhesive strengths. An appropriate combination of materials must be considered to improve the durability and stability of restorations.

Understanding HAT1: A Comprehensive Review of Noncanonical Roles and Connection with Disease.

Histone acetylation plays a vital role in organizing chromatin, regulating gene expression and controlling the cell cycle. The first histone acetyltransferase to be identified was histone acetyltransferase 1 (HAT1), but it remains one of the least understood acetyltransferases. HAT1 catalyzes the acetylation of newly synthesized H4 and, to a lesser extent, H2A in the cytoplasm. However, 20 min after assembly, histones lose acetylation marks. Moreover, new noncanonical functions have been described for HAT1, revealing its complexity and complicating the understanding of its functions. Recently discovered roles include facilitating the translocation of the H3H4 dimer into the nucleus, increasing the stability of the DNA replication fork, replication-coupled chromatin assembly, coordination of histone production, DNA damage repair, telomeric silencing, epigenetic regulation of nuclear lamina-associated heterochromatin, regulation of the NF-κB response, succinyl transferase activity and mitochondrial protein acetylation. In addition, the functions and expression levels of HAT1 have been linked to many diseases, such as many types of cancer, viral infections (hepatitis B virus, human immunodeficiency virus and viperin synthesis) and inflammatory diseases (chronic obstructive pulmonary disease, atherosclerosis and ischemic stroke). The collective data reveal that HAT1 is a promising therapeutic target, and novel therapeutic approaches, such as RNA interference and the use of aptamers, bisubstrate inhibitors and small-molecule inhibitors, are being evaluated at the preclinical level.