Comparative evaluation of two cetylpyridinium chloride-based mouthwashes on the mechanical properties and strength loss of elastomeric chains used in dentistry: An vitro study.

Objectives: Evaluate the strength degradation of polymeric ligature chains after their immersion in cetylpyridinium chloride-based mouthwashes. Methods: 240 elastomeric samples from four different manufacturers (Rocky Mountain®, Ormco®, Morelli® and Dentaurum®) in two types of configurations (with and without intermodular links) and divided in 3 groups (distilled water, Vitis CPC Protect® and PERIO·AID® 0.05%) at 5 follow-up periods (0-24 h, 7-14 -21 days) were immersed twice a day for 60 s, following the manufacturers' protocols. A universal traction machine was used to perform the measurements and a post hoc multiple comparisons were based on the Bonferroni test and extended to a 3-way ANOVA test (α = 0.05). Results: There was a drop in strength up to 35.9% at 24 h. After a week, the short chains (52%) degraded less than the long ones (57.3%) with significant differences (p < 0.001) and the same pattern was observed until 21 days (p < 0.001). At 24 h, the degradation of the chains exposed in distilled water was 25.8%, in VITIS CPC Protect® 28.6% and in PERIO· AID® 0.05%, 27% with significant differences (p < 0.001). At 21 days, the VITIS CPC Protect® group obtained a much greater loss of strength, being this drop statistically significant (p < 0.001). The chains from Ormco® and RMO® experienced the least loss of force when immersed in the control group or PERIO AID® 0 0.05% (48% and 51%), while Dentaurum's in VITIS CPC Protect® lost more than 75%. Conclusions: The orthodontic elastomeric chains suffer a sharp drop in strength during the first days of treatment. When comparing the mouthwashes, there were statistically significant differences in terms of strength degradation. Clinical significance: Based on the results, some types of chains, such as the ones without intermodular links from Ormco® showed better properties throughout the study. When immersed in PERIO·AID®0.05%, all showed significantly better results over time. Thus, PERIO·AID®0.05% can be recommended as a complementary oral hygiene element in dental treatments when elastomeric chains are used.

RALDH1 Inhibition Shows Immunotherapeutic Efficacy in Hepatocellular Carcinoma.

Globally, hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers and a leading cause of cancer-related death. We previously identified an immune evasion pathway whereby tumor cells produce retinoic acid (RA) to promote differentiation of intratumoral monocytes into protumor macrophages. Retinaldehyde dehydrogenase 1 (RALDH1), RALDH2, and RALDH3 are the three isozymes that catalyze RA biosynthesis. In this study, we have identified RALDH1 as the key driver of RA production in HCC and demonstrated the efficacy of RALDH1-selective inhibitors (Raldh1-INH) in suppressing RA production by HCC cells. Raldh1-INH restrained tumor growth in multiple mouse models of HCC by reducing the number and tumor-supporting functions of intratumoral macrophages as well as increasing T-cell infiltration and activation within tumors. Raldh1-INH also displayed favorable pharmacokinetic, pharmacodynamic, and toxicity profiles in mice thereby establishing them as promising new drug candidates for HCC immunotherapy.

Análisis del uso de la contención mecánica en una unidad de geriatría de agudos: estudio observacional / Analysis of the use of mechanical restraint in an acute geriatric unit: observational study

Objetivos: Analizar el perfil del paciente geriátrico hospitalizado en una unidad de geriatría de agudos que requiere contención mecánica, así como medir la prevalencia del uso de la contención mecánica y determinar si el aumento de la comorbilidad, la fragilidad y el acompañamiento están relacionados con el uso de la contención mecánica. Asimismo, evaluar si presentar antecedentes de delirium, demencia o deterioro cognitivo se asocia a mayor uso de contención mecánica en este perfil de pacientes. Metodología: Estudio observacional, prospectivo, descriptivo y analítico, realizado en un hospital de segundo nivel durante diciembre de 2022 y enero de 2023. Se analizaron las características demográficas y clínicas de los pacientes geriátricos. Se obtuvo el dictamen favorable del comité ético de referencia y se realizó el análisis estadístico mediante RStudio. Resultados: Se incluyó una muestra de 107 pacientes de la unidad de geriatría de agudos, de los cuales el 10,28% fueron sometidos a contención mecánica, siendo los hombres el grupo más afectado (72,72%), y la contención abdominal la más usada (72,73%). No se encontró una asociación significativa entre el uso de contención mecánica y la comorbilidad, fragilidad, antecedentes neurológicos, delirium o deterioro cognitivo. Se observó una asociación estadísticamente significativa entre la contención mecánica y el tiempo que el paciente estuvo acompañado (p = 0,019). Conclusiones: se destaca la importancia de una atención personalizada para reducir la necesidad de contención mecánica y mejorar la calidad asistencial.(AU)

Objectives: To analyze the profile of hospitalized geriatric patients in an acute geriatric unit requiring mechanical restraint, measure the prevalence of mechanical restraint use, and determine if increased comorbidity, frailty, and patient accompaniment are associated with mechanical restraint use. Additionally, to evaluate if a history of delirium, dementia, or cognitive impairment is associated with increased use of mechanical restraint in this patient profile. Methodology: An observational, descriptive, prospective, descriptive, and analytical study was conducted in a secondary-level hospital during December 2022 and January 2023. Demographic and clinical characteristics of geriatric patients were analyzed. Ethical approval was obtained, and statistical analysis was performed using RStudio. Results: A sample of 107 patients from the acute geriatric unit was included, with 10.28% undergoing mechanical restraint. Men were the most affected group (72.72%), and abdominal restraint was the most used commonly (72.73%). No significant association was found between mechanical restraint use and comorbidity, frailty, neurological history, delirium, or cognitive impairment. A statistically significant association was observed between mechanical restraint use and patient accompaniment time (p = 0.019). Conclusions: The importance of personalized care is emphasized to reduce the need for mechanical restraint and improve the quality of healthcare provided.(AU)

Vigilancia activa en cáncer de próstata en un grupo de pacientes asistidos en el Centro Docente Asociado de Oncología Médica Rivera: Cooperativa Médica de Rivera (COMERI) / Active surveillance in prostate cancer in a group of patients assisted at the Rivera Associated Teaching Center for Medical Oncology: Rivera Medical Cooperative (COMERI) / Vigilância ativa do câncer de próstata em um grupo de pacientes atendidos no Rivera Associated Teaching Center for Medical Oncology: Rivera Medical Cooperative (COMERI)

Introducción: En Uruguay el cáncer de próstata ocupa el primer lugar en incidencia y el tercer lugar en mortalidad en el hombre. La mayoría de estos cánceres se diagnostican en estadios precoces. Hoy en día, para pacientes con adenocarcinoma de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, la vigilancia activa es una opción adecuada. Objetivos: Describir una población de pacientes con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, en vigilancia activa en COMERI. Material y métodos: Estudio descriptivo, observacional, retrospectivo. Se incluyeron pacientes con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, tratados entre 2010 y 2018 en COMERI. Se recopilaron datos en el sistema de registro clínico electrónico. Resultados: Se incluyeron 33 pacientes, la mediana de edad al diagnóstico fue de 74 años. Todos los pacientes fueron sometidos a controles clínicos y determinación de PSA cada 3 meses. El tacto rectal se realizó en forma anual. El tiempo mediano de vigilancia activa fue de 33 meses. Durante el seguimiento, se observaron pocas variaciones en los valores de PSA. El 21% de los pacientes fue sometido a una nueva biopsia durante el seguimiento activo, y en todos los casos, el Gleason se mantuvo incambiado. Ningún paciente abandonó la modalidad de vigilancia activa. Conclusión: En nuestro entorno, la vigilancia activa se considera una opción terapéutica válida para pacientes altamente seleccionados con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, y es bien aceptada por ellos.

Introduction: In Uruguay, prostate cancer ranks first in incidence and third in mortality among men. The majority of these cancers are diagnosed at early stages. Nowadays, active surveillance is an appropriate option for patients with adenocarcinoma of very low risk, low risk, or favorable intermediate risk. Objectives: To describe a population of patients with prostate cancer of very low risk, low risk, or favorable intermediate risk under active surveillance at COMERI. Materials and Methods: Descriptive, observational, retrospective study. Patients with prostate cancer of very low risk, low risk, or favorable intermediate risk treated between 2010 and 2018 at COMERI were included. Data were collected from the electronic clinical registry system. Results: Thirty-three patients were included, with a median age at diagnosis of 74 years. All patients underwent clinical monitoring and PSA determination every 3 months. Digital rectal examination was performed annually. The median time of active surveillance was 33 months. During follow-up, there were few variations in PSA values. 21% of patients underwent a repeat biopsy during active surveillance, and in all cases, the Gleason score remained unchanged. No patient discontinued active surveillance. Conclusion: In our setting, active surveillance is considered a valid therapeutic option for highly selected patients with prostate cancer of very low risk, low risk, or favorable intermediate risk, and it is well accepted by them.

Introdução: No Uruguai, o câncer de próstata ocupa o primeiro lugar em incidência e o terceiro lugar em mortalidade entre os homens. A maioria desses cânceres é diagnosticada em estágios precoces. Atualmente, para pacientes com adenocarcinoma de risco muito baixo, baixo risco ou risco intermediário favorável, a vigilância ativa é uma opção adequada. Objetivos: Descrever uma população de pacientes com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável sob vigilância ativa em COMERI. Material e métodos: Estudo descritivo, observacional, retrospectivo. Foram incluídos pacientes com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável, tratados entre 2010 e 2018 em COMERI. Os dados foram coletados no sistema de registro clínico eletrônico. Resultados: Foram incluídos 33 pacientes, com mediana de idade no diagnóstico de 74 anos. Todos os pacientes foram submetidos a controles clínicos e determinação de PSA a cada 3 meses. O toque retal foi realizado anualmente. O tempo médio de vigilância ativa foi de 33 meses. Durante o acompanhamento, houve poucas variações nos valores de PSA. 21% dos pacientes foram submetidos a uma nova biópsia durante a vigilância ativa, e em todos os casos, o Gleason permaneceu inalterado. Nenhum paciente abandonou a modalidade de vigilância ativa. Conclusão: Em nosso ambiente, a vigilância ativa é considerada uma opção terapêutica válida para pacientes altamente selecionados com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável, e é bem aceita por eles.

Traditional, complementary and integrative healthcare: global stakeholder perspective on WHO's current and future strategy.

As the 'WHO Traditional Medicine Strategy: 2014-2023' is entering its final phase, reflection is warranted on progress and the focus for a new strategy. We used WHO documentation to analyse progress across the objectives of the current strategy, adding the role of traditional, complementary and integrative healthcare (TCIH) to address specific diseases as a dimension absent in the current strategy. Our analysis concludes on five areas. First, TCIH research is increasing but is not commensurate with TCIH use. TCIH research needs prioritisation and increased funding in national research policies and programmes. Second, WHO guidance for training and practice provides useful minimum standards but regulation of TCIH practitioners also need to reflect the different nature of formal and informal practices. Third, there has been progress in the regulation of herbal medicines but TCIH products of other origin still need addressing. A risk-based regulatory approach for the full-range of TCIH products seems appropriate and WHO should provide guidance in this regard. Fourth, the potential of TCIH to help address specific diseases is often overlooked. The development of disease strategies would benefit from considering the evidence and inclusion of TCIH practices, as appropriate. Fifth, inclusion of TCIH in national health policies differs between countries, with some integrating TCIH practices and others seeking to restrict them. We encourage a positive framework in all countries that enshrines the role of TCIH in the achievement of universal health coverage. Finally, we encourage seeking the input of stakeholders in the development of the new WHO Traditional Medicine Strategy.

Three-dimensional quantification of mandibular asymmetries in Caucasian adult patients with different sagittal and vertical skeletal patterns. A cone beam study using 3D segmentation and mirroring procedures.

INTRODUCTION: An accurate identification of mandibular asymmetries is required by modern orthodontics and orthognathic surgery to improve diagnosis and treatment planning of such deformities. Although craniofacial deformities are very frequent pathologies, some types of asymmetries can be very difficult to assess without the proper diagnostic tools. The purpose of this study was to implement the usage of three-dimensional (3D) segmentation procedures to identify asymmetries at the mandibular level in adult patients with different vertical and sagittal patterns where the asymmetries could go unnoticed at the observational level. METHODS: The study sample comprised 60 adult patients (33 women and 27 men, aged between 18 and 60 years). Subjects were divided into 3 sagittal and vertical skeletal groups. CBCT images were segmented, mirrored and voxel-based registered with reference landmarks using ITK-SNAP® and 3DSlicer® software's. 3D surface models were constructed to evaluate the degree of asymmetry at different anatomical levels. RESULTS: There was a degree of asymmetry, with the left hemimandible tending to contain the right one (0.123 ± 0.270 mm (CI95% 0.036-0.222; p < 0.001). Although the subjects under study did not present significant differences between mandibular asymmetries and their sagittal or vertical skeletal pattern (p = 0.809 and p = 0.453, respectively), a statistically significant difference has been found depending on the anatomical region (p < 0.001; CI95%=1.020-1.021), being higher in the condyle, followed by the ramus and the corpus. CONCLUSIONS: Although mandibular asymmetries cannot be correlated with vertical and sagittal skeletal patterns in symmetric patients, knowledge about 3D segmentation procedures and color maps can provide valuable information to identify mandibular asymmetries.

Post-thaw application of ROCK-inhibitors increases cryopreserved T-cell yield.

Emerging cell-based therapies such as CAR-T (Chimeric Antigen Receptor T) cells require cryopreservation to store and deliver intact and viable cells. Conventional cryopreservation formulations use DMSO to mitigate cold-induced damage, but do not address all the biochemical damage mechanisms induced by cold stress, such as programmed cell death (apoptosis). Rho-associated protein kinases (ROCK) are a key component of apoptosis, and their activation contributes to apoptotic blebbing. Here we demonstrate that the ROCK inhibitor fasudil hydrochloride, when supplemented into the thawing medium of T-cells increases the overall yield of healthy cells. Cell yield was highest using 5 or 10% DMSO cryopreservation solutions, with lower DMSO concentrations (2.5%) leading to significant physical damage to the cells. After optimisation, the post-thaw yield of T-cells increased by approximately 20% using this inhibitor, a significant increase in the context of a therapy. Flow cytometry analysis did not show a significant reduction in the relative percentage of cell populations undergoing apoptosis, but there was a small reduction in the 8 hours following thawing. Fasudil also led to a reduction in reactive oxygen species. Addition of fasudil into the cryopreservation solution, followed by dilution (rather than washing) upon thaw also gave a 20% increase in cell yield, demonstrating how this could be deployed in a cell-therapy context, without needing to change clinical thawing routines. Overall, this shows that modulation of post-thaw biochemical pathways which lead to apoptosis (or other degradative pathways) can be effectively targeted as a strategy to increase T-cell yield and function post-thaw.

Inverse Cubic and Hexagonal Mesophase Evolution within Ionizable Lipid Nanoparticles Correlates with mRNA Transfection in Macrophages.

mRNA lipid nanoparticle (LNP) technology presents enormous opportunities to prevent and treat various diseases. Here, we developed a novel series of LNPs containing ionizable amino-lipids showing a remarkable array of tunable and pH-sensitive lyotropic liquid crystalline mesophases including the inverse bicontinuous cubic and hexagonal phases characterized by high-throughput synchrotron radiation X-ray scattering. Furthermore, with an interest in developing mRNA therapeutics for lung macrophage targeting, we discovered that there is a strong correlation between the mesophase transition of the LNPs during acidification and the macrophage association/transfection efficiency of mRNAs. The slight molecular structural differences between the SM-102 and ALC-0315 ionizable lipids are linked to the LNP's ability to transform their internal structures from an amorphous state to the inverse micellar, hexagonal, and finally cubic structures during endosomal maturation. SM-102 LNPs showed exceptionally improved transfection efficiency due to their ability to form a cubic structure at a lower pH than the ALC-0315 analogues, which remained within the hexagonal structure, previously attributed to promoting endosomal escape of the ionizable LNPs. Overall, the new knowledge draws our attention to the important role of mesophase transition in endosomal escape, and the novel LNP libraries reported herein have broad prospects for advancing mRNA therapeutics.

A ternary eutectic solvent for cellulose nanocrystal production: exploring the recyclability and pre-pilot scale-up.

Deep eutectic solvents (DES) formed using choline chloride (ChCl), p-toluenesulfonic acid (pTSA) of stoichiometry ChCl: pTSA (1:1) and (1:2), and its ternary eutectic mixtures with phosphoric acid (PA) 85% as an additive (ChCl: pTSA: PA) were evaluated for cellulose nanocrystal (CNC) isolation. Initially, the hydrolytic efficiency to produce CNC of each DES was compared before and after adding phosphoric acid by Hammett acidity parameters and the Gutmann acceptor number. Moreover, different DES molar ratios and reaction time were studied at 80°C for CNC optimization. The nanomaterial characteristics were analyzed by field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). The ternary eutectic mixture ChCl: pTSA: PA molar ratio (1:1:1.35) was chosen as a suitable recyclable ternary system at the laboratory scale. A CNC yield of about 80% was obtained from the hydrolysis of commercial cellulose in five cycles of recovery, but it dropped to 35% in pre-pilot scaling. However, no variation in the average size of the resulting CNC was observed (132 ± 50 nm x 23 ± 4 nm), which presented high thermal stability (Tmax 362°C) and high crystallinity of about 80% after 3 h of reaction time.

Effect of mouthwashes on the force decay of polymeric ligature chains used for dental purposes: a systematic review and meta-analysis.

BACKGROUND: External factors such as the daily use of antimicrobial mouthwashes to maintain oral hygiene and to reduce the microbial activity can contribute to alter the mechanical properties of the elastomeric chains used during orthodontic treatments, causing loss of effectiveness. This systematic review and a meta-analysis assessed the rate of force decay and degradation of the polymeric chains depending on the type of mouthwash. METHODS: A systematic search of the literature were there was an exposure of orthodontic elastomeric chains to certain mouthwashes was conducted in the electronic databases of PubMed, Cochrane Library (CENTRAL), Scopus, EMBASE and Web of Science, as well as grey literature (Opengrey). No limit was placed on publication year and research was done up to June 2022. Based on inclusion/ exclusion criteria, data were extracted by two independent reviewers. For the quantitative analysis, studies were analysed with a mixed-effect (random effect) meta-regression model, with beta coefficients and R [2] values. I [2] index and Q and Egger tests were used to find heterogeneity among studies. RESULTS: A total of 178 potentially eligible studies were identified, of which 14 were eventually included in the qualitative analysis and 14 in the quantitative meta-analysis. The meta-analysis showed that all the mouthwashes were associated with a greater force decay than the control groups. After 7 days (p = 0.005) significant differences were found among the different mouthwashes, with those containing alcohol having significantly higher impact on the force decay than those containing chlorhexidine 0.2%, sodium fluoride or Persica. However, at 24 h (p = 0.200), 14 days (p = 0.076), 21 days (p = 0.120) and 28 days (p = 0.778) no statistically significant differences among the different mouthwashes were found, although those containing alcohol presented a strong tendency. CONCLUSION: Although mouthwashes tend to increase the speed of force decay of elastomeric chains, especially those containing alcohol, clorhexidine 0.2% can be a good alternative due to its low impact on the force decay and its ability to maintain low microbial activity. More in vitro and in vivo studies comparing different manufacturers and other agents should be performed.

Role of (F-18) Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Prediction of Response to Neoadjuvant Therapy in Esophageal Cancer: Correlation with Pathological Response and Survival.

Purpose: The purpose of this study is to assess the correlation between metabolic response with fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and pathological response in patients with locally advanced esophageal cancer treated with neoadjuvant chemoradiotherapy and to study FDG-PET parameters for the prediction of pathological response and outcome. Methods: Twenty-five patients with locally advanced esophageal cancer underwent two FDG-PET/CT scans for initial staging and after neoadjuvant chemoradiotherapy. FDG uptake in the primary tumor was calculated in both scans (SUVmax, SULpeak, and TLG). Metabolic response was assessed according to the reduction of PET parameters: complete response (mCR = 100%), partial response (mPR ≥50%), and no response (mNR ≤50%). Pathological response was also classified as complete (pCR), partial (pPR), or no response (pNR). Patients were followed up (range, 8-99 months) determining free-disease interval (FDI) and overall survival (OS). Results: Two patients were excluded due to exitus for nonesophageal-related causes. The metabolic response was observed in 18/23 remaining patients (3mCR, 15 mPR), of which 12/18 patients showed a pathological response (3 pCR, 9 pPR). A major discrepancy was observed in 2 mNR patients who achieved pPR. FDI and OS were longer in patients with metabolic response than nonresponders, but no statistical difference was found. No significant correlation was found between PET parameters and pathological response, FDI, and OS. Conclusions: FDG-PET/CT is a useful technique to assess response to neoadjuvant chemoradiotherapy in esophageal cancer. Although in this preliminary study, no correlation between metabolic and pathologic response was found and no statistical differences between responders and nonresponders were observed, a tendency of longer FDI and OS was apparently found in responders patients.

Cost-effectiveness analysis of spontaneous vaginal delivery vs elective cesarean delivery for maternal outcomes in Colombia.

BACKGROUND: In worldwide literature, it has been found that cesarean deliveries represent higher costs and are associated with maternal morbidity and other complications. OBJECTIVE: This study aimed to estimate the cost-effectiveness of elective cesarean delivery compared with spontaneous vaginal delivery in short-term maternal outcomes for low-risk obstetrical population in Colombia. STUDY DESIGN: A cost-effectiveness study using a healthcare-system perspective was performed in 2019 in Colombia. The reference population were women with full-term and low-risk pregnancy, either by spontaneous vaginal delivery or elective cesarean delivery under medical or nonmedical indications. An analytical decision model (decision tree) was designed for maternal outcomes. The time horizon was 42 days postpartum, and the health effects were measured by Quality Adjusted Life Years. A review of the literature and a validation process by a national expert committee were conducted to determine the maternal outcomes and estimate their probabilities. Costs were estimated with a top-down analysis, an incremental cost-effectiveness ratio was calculated, and finally, a sensitivity analysis was performed. RESULTS: Within a 42-day time horizon, it was found that spontaneous vaginal delivery is the less-expensive and more-effective mode of delivery, it showed a reduction in costs (324 USD) and a gain in Quality Adjusted Life Years (0.03) compared with elective cesarean delivery. Our analysis suggests that spontaneous vaginal delivery is the dominant alternative compared with elective cesarean delivery. CONCLUSION: Spontaneous vaginal delivery showed to be the cost-effective mode of delivery for low-risk obstetrical population in Columbia. These results are useful not only for obstetricians but for decision makers, who should encourage nationwide health policies in favor of spontaneous vaginal delivery.

Real-world discontinuations due to neuropsychiatric symptoms in people living with HIV treated with second-generation integrase inhibitors: a systematic review.

INTRODUCTION: Second-generation integrase strand transfer inhibitors such as bictegravir (BIC) and dolutegravir (DTG) are the standard of care for starting therapy in people living with HIV (PLHIV). However, their use has been associated with neuropsychiatric symptoms (NPSs) that may lead to treatment discontinuation. We aim to describe and synthesize information on safety and discontinuation rates and to summarize potential risk factors associated with the development of NPSs in PLHIV treated with these regimens. AREAS COVERED: A systematic review of the literature was carried out in the international databases PubMed/Medline, Web of Science (WoS), Scopus, Embase, and Cochrane Library from 2013 to June 2022. Ninety observational studies reporting data on treatment discontinuation due to drug-related adverse events and NPSs were identified. EXPERT OPINION: Discontinuation rates due to NPSs increase with treatment time and, in light of the reviewed studies, are higher in PLHIV treated with DTG-based regimens compared with those treated with BIC/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF). This information could be useful for clinicians during treatment decision-making, reducing discontinuation rates and thereby promoting treatment success and durability. Additionally, the identification of potential risk factors in PLHIV prior to starting therapy could also help make the best therapy choices based on the characteristics of each individual.

PKD phosphorylation and COP9/Signalosome modulate intracellular Spry2 protein stability.

Spry2 is a molecular modulator of tyrosine kinase receptor signaling pathways that has cancer-type-specific effects. Mammalian Spry2 protein undergoes tyrosine and serine phosphorylation in response to growth factor stimulation. Spry2 expression is distinctly altered in various cancer types. Inhibition of the proteasome functionality results in reduced intracellular Spry2 degradation. Using in vitro and in vivo assays, we show that protein kinase D (PKD) phosphorylates Spry2 at serine 112 and interacts in vivo with the C-terminal half of this protein. Importantly, missense mutation of Ser112 decreases the rate of Spry2 intracellular protein degradation. Either knocking down the expression of all three mammalian PKD isoforms or blocking their kinase activity with a specific inhibitor contributes to the stabilization of Spry2 wild-type protein. Downregulation of CSN3, a component of the COP9/Signalosome that binds PKD, significantly increases the half-life of Spry2 wild-type protein but does not affect the stability of a Spry2 after mutating Ser112 to the non-phosphorylatable residue alanine. Our data demonstrate that both PKD and the COP9/Signalosome play a significant role in control of Spry2 intracellular stability and support the consideration of the PKD/COP9 complex as a potential therapeutic target in tumors where Spry2 expression is reduced.

Características clínico-patológicas de los pacientes asistidos en el Centro Docente Asociado de Oncología Médica en el Hospital Departamental de Soriano durante su primer año de funcionamiento / Clinical-pathological characteristics of patients assisted at the Associated Teaching Center of Medical Oncology at Soriano Departmental Hospital during its first year of operation / Características clínico-patológicas dos pacientes atendidos no Centro Docente Associado de Oncologia Médica no Hospital Departamental de Soriano durante seu primeiro ano de funcionamento

Introducción: Según el Ministerio de Salud las muertes por cáncer constituyen un cuarto del total de las defunciones registradas en Uruguay cada año. Objetivo: Conocer el perfíl epidemiológico de los pacientes diagnosticados de cáncer asistidos en el Hospital Departamental de Soriano. Material y métodos: Estudio observacional, retrospectivo y descriptivo que incluyó a los pacientes diagnosticados de cáncer asistidos en el Hospital Departamental de Soriano durante el 2022. Se mantuvo el anonimato de los pacientes en el análisis estadístico y se contó con la aprobación del Comité de Ética del Hospital de Clínicas. Resultados: Se incluyeron 113 pacientes nuevos; 53.1% fueron hombres, siendo la mediana de edad al diagnóstico de 69 años. Los 4 tumores más frecuentes para ambos sexos reunidos fueron: mama, próstata, pulmón y colo-recto; la distribución por estadio fue la siguiente: E IV 48.6% pacientes; EIII 22.5%; EII 26.5%; y EI 2.6%. En el 79.6% de las pacientes se contaba con la confirmación del diagnóstico mediante anatomía patológica. El tiempo entre el diagnóstico y el primer tratamiento oncológico fue ≤ 3 meses para el 88.2% de los pacientes. El total de los pacientes con EIV fueron contactados con la Unidad de Cuidados Paliativos. Únicamente el 15% de los casos fueron discutidos en Comité de Tumores. Conclusiones: Los datos analizados permitieron caracterizar el perfil epidemiológico del cáncer de los pacientes procedente de Soriano asistidos en el ámbito público y pueden contribuir a la implementación de políticas públicas orientadas a la prevención y por ende a la mejora en la asistencia pacientes asistidos.

Introduction: According to the Ministry of Health, cancer deaths constitute a quarter of the total deaths registered in Uruguay each year. Objective: To identify the epidemiological profile of patients diagnosed with cancer treated at the Departmental Hospital of Soriano. Materials and Methods: An observational, retrospective and descriptive study that included patients diagnosed with cancer attended at the Departmental Hospital of Soriano during 2022. The anonymity of the patients was maintained in the statistical analysis and approval was obtained from the Ethics Committee of the Hospital de Clínicas. Results: A total of 113 new patients were included; 53.1% were men, with a median age at diagnosis of 69 years old. The four most frequent tumors for both sexes were: breast, prostate, lung and colorectal; the distribution by stage was as follows: Stage IV 48.6% patients; Stage III 22.5%; Stage II 26.5%; and Stage I 2.6%. In 79.6% of the patients the diagnosis was confirmed by pathological anatomy. The time between diagnosis and first oncological treatment was ≤ 3 months for 88.2% of patients. The total number of patients with Stage IV were contacted by the Palliative Care Unit. Only 15% of the cases were discussed in the Tumor Committee. Conclusions: The data analyzed made it possible to characterize the epidemiological profile of cancer in patients from Soriano assisted in the public sector and may contribute to the implementation of public policies aimed at prevention and, therefore, at improving patient care.

Introdução: Segundo o Ministério da Saúde, as mortes por câncer constituem um quarto de todas as mortes registradas no Uruguai a cada ano. Objetivos: Conhecer o perfil epidemiológico dos pacientes diagnosticados com câncer atendidos no Hospital Departamental de Soriano. Material e Métodos: Estudo observacional, retrospectivo e descritivo que incluiu pacientes diagnosticados com câncer atendidos no Hospital Departamental de Soriano durante o ano de 2022. O anonimato dos pacientes foi mantido na análise estatística e foi aprovado pelo Comitê de Ética do Hospital de Clínicas. Resultados: foram incluídos 113 novos pacientes; 53,1% eram homens, com mediana de idade ao diagnóstico de 69 anos. Os 4 tumores mais frequentes para ambos os sexos combinados foram: mama, próstata, pulmão e colorretal; a distribuição por estágio foi a seguinte: E IV 48,6% pacientes; EIII 22,5%; EII 26,5%; EI 2,6%. Em 79,6% dos pacientes houve confirmação do diagnóstico pela patologia. O tempo entre o diagnóstico e o primeiro tratamento oncológico foi ≤ 3 meses para 88,2% dos pacientes. Todos os doentes com DIV foram contactados com a Unidade de Cuidados Paliativos. Apenas 15% dos casos foram discutidos no Comitê de Tumores. Conclusões: Os dados analisados ​​permitiram caracterizar o perfil epidemiológico do câncer em pacientes de Soriano atendidos na esfera pública e podem contribuir para a implementação de políticas públicas voltadas para a prevenção e, consequentemente, para a melhoria na assistência aos pacientes atendidos.

Synthesis of Poly(2-(methylsulfinyl)ethyl methacrylate) via Oxidation of Poly(2-(methylthio)ethyl methacrylate): Evaluation of the Sulfoxide Side Chain on Cryopreservation.

Conventional cryopreservation solutions rely on the addition of organic solvents such as DMSO or glycerol, but these do not give full recovery for all cell types, and innovative cryoprotectants may address damage pathways which these solvents do not protect against. Macromolecular cryoprotectants are emerging, but there is a need to understand their structure-property relationships and mechanisms of action. Here we synthesized and investigated the cryoprotective behavior of sulfoxide (i.e., "DMSO-like") side-chain polymers, which have been reported to be cryoprotective using poly(ethylene glycol)-based polymers. We also wanted to determine if the polarized sulfoxide bond (S+O- character) introduces cryoprotective effects, as this has been seen for mixed-charge cryoprotective polyampholytes, whose mechanism of action is not yet understood. Poly(2-(methylsulfinyl)ethyl methacrylate) was synthesized by RAFT polymerization of 2-(methylthio)ethyl methacrylate and subsequent oxidation to sulfoxide. A corresponding N-oxide polymer was also prepared and characterized: (poly(2-(dimethylamineoxide)ethyl methacrylate). Ice recrystallization inhibition assays and differential scanning calorimetry analysis show that the sulfoxide side chains do not modulate the frozen components during cryopreservation. In cytotoxicity assays, it was found that long-term (24 h) exposure of the polymers was not tolerated by cells, but shorter (30 min) incubation times, which are relevant for cryopreservation, were tolerated. It was also observed that overoxidation to the sulfone significantly increased the cytotoxicity, and hence, these materials require a precision oxidation step to be deployed. In suspension cell cryopreservation investigations, the polysulfoxides did not increase cell recovery 24 h post-thaw. These results show that unlike hydrophilic backboned polysulfides, which can aid cryopreservation, the installation of the sulfoxide group onto a polymer does not necessarily bring cryoprotective properties, highlighting the challenges of developing and discovering macromolecular cryoprotectants.

What can be improved in learning to care for people with autism? A qualitative study based on clinical nursing simulation.

AIM/OBJECTIVE: The aim of this study was to identify the main patterns of errors that 4th year nursing students made in simulated clinical practice with scenarios of care for people with Autism Spectrum Disorder (ASD). BACKGROUND: Clinical simulation currently plays a major role in the training of nursing students and provides the participants with the opportunity to practice and develop their clinical sills with a pediatric patient diagnosed with ASD. DESIGN: A retrospective longitudinal qualitative study was performed. METHODS: Content analysis of the existing debriefing records from a period of 7 academic years (2016-2022) was carried out. The scenario was simulated by a standardized patient diagnosed with ASD, with 23 groups of nursing students. RESULTS: The results showed different patterns of errors. These patterns were grouped into 1 main category (weaknesses) and 5 major subcategories: clinical, communication, knowledge about ASD, emotions, and behavior towards parents. The most repeated errors were excessive use of verbal communication, abundant stimuli, low demand for information from primary caregivers, low demand for information about the child's emotions and interests, and a lack of knowledge of the profile of the child with ASD. CONCLUSION: From the findings of this study, we can highlight the lack of training that students received on the practical approach for providing care to these individuals. It has also been inferred in this study that clinical simulation is a tool that favors reflection and experiential learning for students when they are faced with caring for people with ASD.

Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance.

Human papillomavirus (HPV)-associated cervical cancer is a leading cause of cancer deaths in women. Here we present an integrated multi-omic analysis of 643 cervical squamous cell carcinomas (CSCC, the most common histological variant of cervical cancer), representing patient populations from the USA, Europe and Sub-Saharan Africa and identify two CSCC subtypes (C1 and C2) with differing prognosis. C1 and C2 tumours can be driven by either of the two most common HPV types in cervical cancer (16 and 18) and while HPV16 and HPV18 are overrepresented among C1 and C2 tumours respectively, the prognostic difference between groups is not due to HPV type. C2 tumours, which comprise approximately 20% of CSCCs across these cohorts, display distinct genomic alterations, including loss or mutation of the STK11 tumour suppressor gene, increased expression of several immune checkpoint genes and differences in the tumour immune microenvironment that may explain the shorter survival associated with this group. In conclusion, we identify two therapy-relevant CSCC subtypes that share the same defining characteristics across three geographically diverse cohorts.