Search

Este estudio cuasi-experimental con grupo control y metodología mixta evalúa los efectos de un programa de arteterapia y musicoterapia en pacientes adultos oncológicos hospitalizados. Tras tres sesiones de intervención, el grupo experimental experimentó mejoras significativas en dolor, ansiedad, depresión y distrés emocional en comparación con el grupo control, que recibió tratamiento médico estándar. Las reducciones significativas incluyeron el dolor (-4.72; p < 0.001), la ansiedad (-4.78; p < 0.001), la depresión (-4.06; p < 0.001) y el distrés (-5.28; p < 0.001), medidas a través de las escalas EVA, HADS, PHQ-9, y DME/TD. Además, se observaron mejoras fisiológicas notables, como la reducción de la presión arterial sistólica (-25.34 mmHg) y diastólica (-11.92 mmHg), así como de la frecuencia cardíaca. Aunque los cambios en la autonomía funcional evaluada con el índice BABVD no alcanzaron significancia estadística, se observó una tendencia positiva. Las entrevistas semiestructuradas revelaron mejoras en el bienestar emocional, la motivación y las relaciones interpersonales. Estos hallazgos subrayan el valor de integrar terapias creativas como complemento en la atención oncológica, contribuyendo a mejorar el bienestar físico y emocional de los pacientes hospitalizados.

Abstract This study aimed to identify the factors associated with health-related quality of life (HRQOL) among community-dwelling older adults. Physical and mental HRQOL were measured by the 12-item Short Form Health Survey (SF-12) at baseline and follow-up. Linear regression models were used to evaluate associations between socio-demographic, health, and lifestyle factors and HRQOL. The sample included 661 participants (mean age = 77.4 years). Frailty was negatively associated with physical HRQOL (B = − 5.56; P

Eighteen mongrel dogs of unknown age and naturally infected with Leishmania (Leishmania) chagasi, were obtained from the City Hall of Belo Horizonte, Brazil. Four dogs were used as control. Lung samples were obtained and immediately fixed in formalin. The histopathological picture of all lung tissue sections was a chronic and diffuse interstitial pneumonitis. The thickened inter-alveolar septa were characterized by the cellular exudate (mostly macrophages, lymphocytes and plasmocytes) associated with collagen deposition. Morphometric analysis showed greater septal thickness in the infected animals than in controls. In fact, the morphometric study of collagen stained with ammoniac silver confirmed a larger deposition of collagen in the infected animals. The parasitologic method was carried out during the study of the lesions on the slides. However, we did not observe any correlation between the histopathologic and morphometric data and the clinical status of the animals. We conclude that the pulmonary lesions observed in all naturally infected dogs were correlated with the disease and that the morphometric method used was satisfactory for the analysis of septal thickness and of increased collagen deposition, confirming the presence of fibrosis.

This systematic review aimed to identify, evaluate, and summarize the results of relevant studies on radicular prominence and its relationship with gingival recessions. This review was conducted according to the PRISMA (Preferred Reporting Reviews and Meta-Analysis) guidelines, and the focused PICO question was “In teeth with vestibular site-specific root or alveolar bone prominence, what are the chances that this will lead to gingival recession or difficulty in root coverage procedures, compared to teeth correctly positioned in the alveolar bone or without anatomical root prominence?”. A search was carried out on three databases: Embase, PubMed/MedLine, and Wiley Library. This initial search was complemented with manual research. It included any clinical study, such as a randomized clinical trial, controlled clinical trial, prospective/retrospective clinical study, case series, or case report, published in English from January 2012 to December 2023, which reported any involvement of the root/bone prominence approach. The exclusion criteria were clinical studies without report results/details of the case(s), studies based on questionnaires, editorial letters, any review, in vitro/in silica and animal studies, and interviews. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement was applied for quality assessment. A total of 163 articles were found, but only three articles were included (k = 0.98). The included studies observed negative correlations when comparing the variables root prominence with linear root coverage, root surface area covered, and linear tissue thickness gain. It suggested a significant reduction in root coverage for prominences greater than 1 mm; therefore, relevant keratinized tissue gains can be achieved in gingival recession treatment after the application of the odontoplasty. The STROBE checklist evaluated 22 items, and all the included studies had a high-quality assessment (greater than 75%) with values greater than 85%. Then, it was not possible to draw conclusions due to the number of articles included, even though they had high-quality assessments. Otherwise, it is possible to suggest that the root prominence may impact gingival recession. Therefore, new and well-designed studies must be developed to establish a significant conclusion about this condition.

Abstract More than half a century after their discovery in the Ionian Sea near Riace Marina (Italy, 1972 CE), the Riace Bronzes continue to fascinate and interest. They are a pair of statues most likely sculpted in Greece in the mid-5th century and are considered masterpieces of Classical Greek sculpture. Many studies have been conducted, yet there are no morphometric studies that delve into their facial features. The aim of this study is to determine dentofacial characteristics and the presence of golden ratios in the so-called “young-man” warrior statue, equipped with a silver foil to represent the upper teeth. The interpupillar, interalar, intercanthal distances and mesio-distal diameter of the upper central incisors were subjected to virtual photogrammetry (GIMP-GNU Image Manipulation Programme). The presence of vertical and horizontal golden ratios between different landmarks (intercanthal distance: centre of the nose; centre of pupils: base of nose: base of upper incisors; centre of pupil-base of nose: base of upper incisors-base of chin; centre of pupils- base of upper incisors: base of the chin) were analysed using a dedicated software (PhiMatrix). The face and teeth satisfy most of golden canons, as also corroborated by the one-way ANOVA-statistic test (p

Abstract Inactivating TP53 mutations leads to a loss of function of p53, but can also often result in oncogenic gain-of-function (GOF) of mutant p53 (mutp53) proteins which promotes tumor development and progression. The GOF activities of TP53 mutations are well documented, but the mechanisms involved remain poorly understood. Here, we study the mutp53 interactome and find that by targeting minichromosome maintenance complex components (MCMs), GOF mutp53 predisposes cells to replication stress and chromosomal instability (CIN), leading to a tumor cell-autonomous and cyclic GMP–AMP synthase (cGAS)-stimulator of interferon genes (STING)-dependent cytosolic DNA response that activates downstream non-canonical nuclear factor kappa light chain enhancer of activated B cell (NC-NF-κB) signaling. Consequently, GOF mutp53-MCMs-CIN-cytosolic DNA-cGAS-STING-NC-NF-κB signaling promotes tumor cell metastasis and an immunosuppressive tumor microenvironment through antagonizing interferon signaling and regulating genes associated with pro-tumorigenic inflammation. Our findings have important implications for understanding not only the GOF activities of TP53 mutations but also the genome-guardian role of p53 and its inactivation during tumor development and progression.

Along with the creation of medical profiles of patients, Electronic Health Records have several secondary missions, such as health economy and research. The recent, increasing adoption of a common standard, i.e., the Fast Healthcare Interoperability Resources (FHIR), makes it easier to exchange medical data among the several parties involved, for example, in an epidemiological research activity. However, this exchange process is hindered by regulatory frameworks due to privacy issues related to the presence of personal information, which allows patients to be identified directly (or indirectly) from their medical data. When properly used, de-identification techniques can provide crucial support in overcoming these problems. FHIR-DIET aims to bring flexibility and concreteness to the implementation of de-identification of health data, supporting many customised data-processing behaviours that can be easily configured and tailored to match specific use case requirements. Our solution enables faster and easier cooperation between legal and IT professionals to establish and implement de-identification rules. The performance evaluation demonstrates the viability of processing hundreds of FHIR patient information data per second using standard hardware. We believe FHIR-DIET can be a valuable tool to satisfy the current regulation requirements and help to create added-value for the secondary use of healthcare data.

Brown spot of pear (BSP), caused by Stemphylium vesicarium, is one of the most dangerous pear fungal diseases, being responsible for huge losses in production. Currently, in order to increase its containment, chemical control is implemented in conjunction with agronomic techniques able to reduce BSP inoculum sources (e.g., orchard grass sanitation, litter removal or application of biocontrol agents). Regardless, despite the introduction of agronomic practices, the complete control of the disease is still rarely possible, which suggests that other sources of S. vesicarium inoculum that are currently neglected may be involved. The aim of this study is to investigate the possible wintering forms of Pleospora allii/S. vesicarium on pear wood and whether any spore-forming productions (conidial or ascosporic) might infect the green tissues of the plant in the following spring. Symptomatic fragments of woody tissue from a commercial pear orchard (in Ferrara, Emilia-Romagna, Italy) with a high BSP pressure (~40% incidence) were analysed. The results prove that pseudothecia and the maturation of ascospores of P. allii also develop on one-year-old branch cankers of pear trees, thus representing an additional source of inoculum. In conclusion, the pruning of affected branches and removal of relative residues should be preventatively performed in order to improve BSP management and control.

Background/Objectives: Cranioplasty (CP) is the main surgical procedure aiming to repair a morphological defect in the skull. It has been shown that early CP is useful for patients with traumatic brain injury (TBI) to achieve functional recovery, whereas few studies have investigated the clinical effects of ultra-late CP on TBI outcomes. Methods: Here, we describe the clinical course over 2 years of a TBI patient who underwent CP 19 months after fronto-parietal decompressive craniectomy (DC) of a limited size. Results: We found that after ultra-late CP, a meaningful functional recovery (cognitive and motor), with emergence from a minimally conscious state and recovery of functional communication, was revealed. Conclusions: Our preliminary findings contribute to the actual debate on the timing of CP for this neurosurgical procedure’s therapeutic success, as early CP has already been shown.

Marek’s disease is caused by Mardivirus gallidalpha2, commonly known as Marek’s disease virus (MDV). This pathogen infects various bird species resulting in a range of clinical manifestations. The meq gene, which is crucial for oncogenesis, has been extensively studied, but molecular investigations of MDV in noncommercial South American birds are limited. This study detected MDV in backyard and ornamental birds from Brazil and Peru and characterized the meq gene. MDV was confirmed in all seven outbreaks examined. Three isoforms of meq (S-meq, meq, and L-meq) and two to seven proline repeat regions (PRRs) were detected among the sequenced strains. At the amino acid level, genetic profiles with low and high virulence potential were identified. Phylogenetic analysis grouped the sequences into three distinct clusters. Selection pressure analysis revealed 18 and 15 codons under positive and negative selection, respectively. The results demonstrate significant MDV diversity in the studied birds, with both high and low virulence potentials. This study highlights the importance of monitoring and characterizing circulating MDV in backyard and ornamental birds, as they can act as reservoirs for future epidemiological outbreaks.

Patients with chronic kidney disease (CKD) often experience mild cognitive impairment and other neurocognitive disorders. Studies have shown that erythropoietin (EPO) and its receptor have neuroprotective effects in cell and animal models of nervous system disorders. Recombinant human EPO (rHuEPO), commonly used to treat anemia in CKD patients, could be a neuroprotective agent. In this systematic review, we aimed to assess the published studies investigating the cognitive benefits of rHuEPO treatment in individuals with reduced kidney function. We comprehensively searched Pubmed, Cochrane Library, Scopus, and Web of Science databases from 1990 to 2023. After selection, 24 studies were analyzed, considering study design, sample size, participant characteristics, intervention, and main findings. The collective results of these studies in CKD patients indicated that rHuEPO enhances brain function, improves performance on neuropsychological tests, and positively affects electroencephalography measurements. These findings suggest that rHuEPO could be a promising neuroprotective agent for managing CKD-related cognitive impairment.

The use of integrative taxonomy has confirmed the existence of a new distinct crab species, cryptic, within the group of the former genus Liocarcinus, now Polybius, closely related to P. holsatus, P. vernalis and P. marmoreus. Previous reports have considered it to be the Atlantic form of P. vernalis, or as a species “affinis” or “comparable to” P. holsatus. Diagnostic morphological characters are presented for identification and the morphological variability in these species, mainly within P. vernalis (the most related) is analysed. Furthermore, based on molecular and other previous data, a new combination (genus change) is proposed. This new species, Polybius dioscurus sp. nov., lives on infralittoral sandy bottoms, coexisting with the other species mentioned, in the temperate and subtropical zone of the North Atlantic Ocean, including the Alboran Sea (westernmost Mediterranean).

IntroductionShigella is the etiologic agent of a bacillary dysentery known as shigellosis, which causes millions of infections and thousands of deaths worldwide each year due to Shigella’s unique lifestyle within intestinal epithelial cells. Cell adhesion/invasion assays have been extensively used not only to identify targets mediating host-pathogen interaction, but also to evaluate the ability of Shigella-specific antibodies to reduce virulence. However, these assays are time-consuming and labor-intensive and fail to assess differences at the single-cell level.Objectives and methodsHere, we developed a simple, fast and high-content method named visual Adhesion/Invasion Inhibition Assay (vAIA) to measure the ability of anti-Shigellaantibodies to inhibit bacterial adhesion to and invasion of epithelial cells by using the confocal microscope Opera Phenix.ResultsWe showed that vAIA performed well with a pooled human serum from subjects challenged with S. sonnei and that a specific anti-IpaD monoclonal antibody effectively reduced bacterial virulence in a dose-dependent manner.DiscussionvAIA can therefore inform on the functionality of polyclonal and monoclonal responses thereby supporting the discovery of pathogenicity mechanisms and the development of candidate vaccines and immunotherapies. Lastly, this assay is very versatile and may be easily applied to other Shigella species or serotypes and to different pathogens.

Steven M Falowski,1,&ast; Louis J Raso,2 Vipul Mangal,3 Ali Nairizi,4 Denis G Patterson,5 Michael D Danko,6 Rafael Justiz,7 Rainer S Vogel,8 Sebastian Koga,9 Yousseff Josephson,10 Jason E Pope,11,&ast; Oluwatodimu Richard Raji12 1Argires-Marotti Neurosurgical Associates of Lancaster, Lancaster, PA, USA; 2Jupiter Medical Center, Jupiter, FL, USA; 3National Spine and Pain Centers, Oxon Hill, MD, USA; 4Reno Tahoe Pain Associates, Reno, NV, USA; 5Nevada Pain Specialists, Reno, NV, USA; 6Premier Pain Treatment Institute, Loveland, OH, USA; 7Oklahoma Pain Physicians, Oklahoma City, OK, USA; 8Comprehensive and Interventional Pain Management, Henderson, NV, USA; 9Koga Neurosurgery, Covington, LA, USA; 10National Spine and Pain Centers, Voorhees, NJ, USA; 11Evolve Restorative Center, Santa Rosa, CA, USA; 12Medical Device Development, San Francisco, CA, USA&ast;These authors contributed equally to this workCorrespondence: Oluwatodimu Richard Raji, Medical Device Development, 2390 Mission Street, Suite 8, San Francisco, CA, 94110, USA, Tel +15105707741, Email richardraji@mdevdev.comPurpose: Lumbar interlaminar decompression with interspinous fixation is an established safe and effective treatment for spinal stenosis. Early maintenance of improvements in pain intensity and function are critical for durability of symptom relief. The purpose of this study was to investigate the efficacy of minimally invasive treatments for low back pain during the early period after treatment and their utility in setting the course for longer term success.Patients and Methods: This study utilized patient evaluations at 3- and 6-months following treatment and is part of an actively enrolling, institutional review board (IRB) approved, single-arm, multicenter, prospective, open-label 12-month study. Clinical efficacy was assessed primarily using the change from baseline in Oswestry Disability Index (ODI), Visual Analog Scale (VAS) of the back and leg pain during walking and standing, and Zurich Claudication Questionnaire (ZCQ), and secondarily using the Patient Global Impression of Change (PGIC) and Patient-Reported Outcomes Measurement Information System (PROMIS) 29 v2.1. The safety endpoints were the adverse events and reoperations or revisions at the index level(s).Results: At 6-month post-op, 76%, 62%– 64%, and 64% of patients demonstrated clinical meaningful, and statistically significant improvement in their pain as defined by ZCQ, VAS (back and leg), and ODI, respectively. In addition, 78% of patients noted improvement in PGIC. Two procedure-related adverse events were noted which fully resolved without surgical intervention.Conclusion: This 6-month interim analysis at 42% enrollment of patients was conducted to determine prolonged safety and efficacy of the interspinous fusion device. Our analysis showed a sustained improvement in clinical efficacy, and safety endpoints, when compared to the 3-months evaluations, across both interventional pain and neurosurgery specialties.Keywords: interspinous fixation, degenerative disc disease, neurogenic claudication, spinal stenosis

Abstract DNA replication and repair defects or genotoxic treatments trigger interferon (IFN)-mediated inflammatory responses. However, whether and how IFN signaling in turn impacts the DNA replication process has remained elusive. Here we show that basal levels of the IFN-stimulated gene 15, ISG15, and its conjugation (ISGylation) are essential to protect nascent DNA from degradation. Moreover, IFNβ treatment restores replication fork stability in BRCA1/2-deficient cells, which strictly depends on topoisomerase-1, and rescues lethality of BRCA2-deficient mouse embryonic stem cells. Although IFNβ activates hundreds of genes, these effects are specifically mediated by ISG15 and ISGylation, as their inactivation suppresses the impact of IFNβ on DNA replication. ISG15 depletion significantly reduces cell proliferation rates in human BRCA1-mutated triple-negative, whereas its upregulation results in increased resistance to the chemotherapeutic drug cisplatin in mouse BRCA2-deficient breast cancer cells, respectively. Accordingly, cells carrying BRCA1/2 defects consistently show increased ISG15 levels, which we propose as an in-built mechanism of drug resistance linked to BRCAness.

Among the non-communicable neurological diseases, epilepsy is characterized by abnormal brain activity with several peripheral implications. The role of peripheral inflammation in the relationship between seizure development and nonalcoholic fatty liver disease based on sex difference remains still overlooked. Severe early-life infections lead to increased inflammation that can aggravate epilepsy and hepatic damage progression, both related to increased odds of hospitalization for epileptic patients with liver diseases. Here, we induced a post-natal-day 3 (PND3) infection by LPS (1 mg/kg, i.p.) to determine the hepatic damage in a genetic model of young epileptic WAG/Rij rats (PND45). We evaluated intra- and inter-gender differences in systemic and liver inflammation, hepatic lipid dysmetabolism, and oxidative damage related to mitochondrial functional impairment. First, epileptic rats exposed to LPS, regardless of gender, displayed increased serum hepatic enzymes and altered lipid profile. Endotoxin challenge triggered a more severe inflammatory and immune response in male epileptic rats, compared to females in both serum and liver, increasing pro-inflammatory cytokines and hepatic immune cell recruitment. Conversely, LPS-treated female rats showed significant alterations in systemic and hepatic lipid profiles and reduced mitochondrial fatty acid oxidation. The two different sex-dependent mechanisms of LPS-induced liver injury converge in increased ROS production and related mitochondrial oxidative damage in both sexes. Notably, a compensatory increase in antioxidant defense was evidenced only in female rats. Our study with a translational potential demonstrates, for the first time, that early post-natal infections in epileptic rats induced or worsened hepatic disorders in a sex-dependent manner, amplifying inflammation, lipid dysmetabolism, and mitochondrial impairment.

Little is known of the geospatial architecture of individual cell populations in lung adenocarcinoma (LUAD) evolution. Here, we perform single-cell RNA sequencing of 186,916 cells from five early-stage LUADs and 14 multiregion normal lung tissues of defined spatial proximities from the tumors. We show that cellular lineages, states, and transcriptomic features geospatially evolve across normal regions to LUADs. LUADs also exhibit pronounced intratumor cell heterogeneity within single sites and transcriptional lineage-plasticity programs. T regulatory cell phenotypes are increased in normal tissues with proximity to LUAD, in contrast to diminished signatures and fractions of cytotoxic CD8+ T cells, antigen-presenting macrophages, and inflammatory dendritic cells. We further find that the LUAD ligand-receptor interactome harbors increased expression of epithelial CD24, which mediates protumor phenotypes. These data provide a spatial atlas of LUAD evolution, and a resource for identification of targets for its treatment. SIGNIFICANCE: The geospatial ecosystem of the peripheral lung and early-stage LUAD is not known. Our multiregion single-cell sequencing analyses unravel cell populations, states, and phenotypes in the spatial and ecologic evolution of LUAD from the lung that comprise high-potential targets for early interception.This article is highlighted in the In This Issue feature, p. 2355.

Abstract Shigellosis is a leading cause of diarrheal disease in low-middle-income countries (LMICs). Effective vaccines will help to reduce the disease burden, exacerbated by increasing antibiotic resistance, in the most susceptible population represented by young children. A challenge for a broadly protective vaccine against shigellosis is to cover the most epidemiologically relevant serotypes among >50 Shigella serotypes circulating worldwide. The GMMA platform has been proposed as an innovative delivery system for Shigella O-antigens, and we have developed a 4-component vaccine against S. sonnei, S. flexneri 1b, 2a and 3a identified among the most prevalent Shigella serotypes in LMICs. Driven by the immunogenicity results obtained in clinic with a first-generation mono-component vaccine, a new S. sonnei GMMA construct was generated and combined with three S. flexneri GMMA in a 4-component Alhydrogel formulation (altSonflex1-2-3). This formulation was highly immunogenic, with no evidence of negative antigenic interference in mice and rabbits. The vaccine induced bactericidal antibodies also against heterologous Shigella strains carrying O-antigens different from those included in the vaccine. The Monocyte Activation Test used to evaluate the potential reactogenicity of the vaccine formulation revealed no differences compared to the S. sonnei mono-component vaccine, shown to be safe in several clinical trials in adults. A GLP toxicology study in rabbits confirmed that the vaccine was well tolerated. The preclinical study results support the clinical evaluation of altSonflex1-2-3 in healthy populations, and a phase 1–2 clinical trial is currently ongoing.

Abstract TROP2 antibody drug conjugates (ADCs) are under active development. We seek to determine whether we can enhance activity of TROP2 ADCs by increasing TROP2 expression. In metaplastic breast cancers (MpBC), there is limited expression of TROP2, and downregulating transcription factor ZEB1 upregulates E-cad and TROP2, thus sensitizing cancers to TROP2 ADC sacituzumab govitecan (SG). Demethylating agent decitabine decreases DNA methyltransferase expression and TROP2 promoter methylation and subsequently increases TROP2 expression. Decitabine treatment as well as overexpression of TROP2 significantly enhance SG antitumor activity. Decitabine also increases SLFN11, a biomarker of topoisomerase 1 inhibitor (TOP1) sensitivity and is synergistic with SG which has a TOP1 payload, in TROP2-expressing SLFN11-low BC cells. In conclusion, TROP2 and SLFN11 expression can be epigenetically modulated and the combination of demethylating agent decitabine with TROP2 ADCs may represent a novel therapeutic approach for tumors with low TROP2 or SLFN11 expression.

Objective: to estimate the prevalence of medication-induced delirium and drug-related problems (DRP) in older people hospitalized in intensive care unit (ICU). Methods: A systematic review were conducted in PubMed, EMBASE, LILACS, Ageline, Web of Science, and Cochrane databases (until March 2023). Clinical trials and observational studies that investigated the contribution of medication in the occurrence of delirium and compared with critically ill older patients (aged≥65 years old) without the syndrome were included. We excluded emergency departments, medical wards, primary and secondary healthcare levels, patients with delirium tremens; metabolic encephalopathy; dementia; palliative care; and brain metastasis. The references were entered into Rayyan QCRI. Two pairs of reviewers selected the articles, extracted data, and assessed the risk of bias (ROBINS-I). Results: Of 12,492 studies retrieved, after de-duplication exclusion (n=6,025), title/abstract (n=6,467) and full reading (n=286), two met the inclusion criteria. Both were observational (cohort), developed in high-income countries, with high level of risk of bias (overall). The frequency of delirium and subsyndromal delirium was 15.8% to 33.9%. Independent risk factors were the exposure of opioids and use of corticosteroids. Delirium increased the length of hospital stay in ICU, and the mechanical ventilation. Conclusion: Further studies are necessary to understand the DRP and characteristics of pharmacotherapy associated with delirium in critically ill older people. Adverse drug reactions and deliriogenic load seem to contribute to the occurrence of syndrome.

Abstract is missing (Short communication)