Objective Linguistic Markers Associated with Callous-Unemotional Traits in Early Childhood.

BACKGROUND: Callous-unemotional (CU) traits are associated with interpersonal difficulties and risk for severe conduct problems (CP). The ability to communicate thoughts and feelings is critical to social success, with language a promising treatment target. However, no prior studies have examined objective linguistic correlates of childhood CU traits in early childhood, which could give insight into underlying risk mechanisms and novel target treatments. METHODS: We computed lexical (positive emotion, sad, and anger words) and conversational (interruptions and speech rate) markers produced by 131 children aged 5-6 years (M = 5.98; SD = 0.54, 58.8% female) and their parents while narrating wordless storybooks during two online visits separated by 6-8 weeks (M = 6.56, SD = 1.11; two books, order counterbalanced). Audio recordings were diarized, time-aligned, and orthographically transcribed using WebTrans. Conversational markers were calculated using R and word frequencies were calculated using Linguistic Inquiry and Word Count (LIWC) software. We examined links between child CU traits and linguistic markers, and explored whether relationships were moderated by child sex. RESULTS: Higher CU traits were associated with fewer positive emotion words produced by parents and children. Higher CU traits were also associated with greater concordance in the degree of interruptions and expression of anger emotion words by parents and children. CONCLUSIONS: Results suggest that objective linguistic correlates of CU traits are detectable during early childhood, which could inform adjunctive treatment modules that improve outcomes by precisely tracking and targeting subtle communication patterns.

One Piece CAD/CAM Abutment for Screw-Retained Single-Tooth Restorations: A 5-Year Prospective Cohort Study.

BACKGROUND: The use of ceramic-coated patient-specific CAD/CAM titanium abutments represents a therapeutic option for the rehabilitation of single tooth. The utilization of highly customized abutments enables the accurate three-dimensional positioning of the prosthetic emergence. This study evaluates the clinical performance of implant-prosthetic rehabilitations carried out using ceramic-coated CAD/CAM titanium abutments. MATERIALS AND METHODS: Thirty implants were placed in thirty patients and rehabilitated with thirty single crowns attached to CAD/CAM titanium abutments. A conventional procedure was applied, with implant placement after post-extraction socket healing and prosthetic restoration after implant healing. Implants of lengths ranging from 6-15 mm and widths of 3.6, 4.2, and 4.8 mm were used in this study. At the time of prosthesis delivery (T0), after two years (T1), and after five years (T2), plaque (PI) and bleeding (BoP) indices, probing depths (PPD), marginal bone levels (MBL), and PES/WES were evaluated for each implant. RESULTS: No patient dropped out of the study during the follow-up period. All thirty implants were clinically successful at five years post-prosthesis delivery (survival rate: 100%) and showed no signs of peri-implant infection. Peri-implant soft tissues were in good health (BoP at T2: 0% in 73% of patients; 25% in 13% of patients; 50% in 10% of patients; and 75% in 3% of patients). The mean PPD was 2.05±0.56 mm at T0, 1.992±0.6 mm at T1, and 1.867±0.439 mm at T2. The mean MBL at T0 was 0.413±0.440 mm, at T1 was 0.306±0.388 mm, and at T2 was 0.263±0.368 mm. The mean PES, WES, and PES/WES indices, 7.43±1.04, 7.57±0.82, and 15.00±1.17, respectively, indicate good integration of soft tissues, satisfactory aesthetics, and an overall positive outcome. CONCLUSIONS: The success rates, maintenance of marginal bone levels, and periodontal and aesthetic indices suggest the validity of implant-prosthetic rehabilitations with CAD/CAM abutments in cases of single crowns.

Real-time active constraint generation and enforcement for surgical tools using 3D detection and localisation network.

Introduction: Collaborative robots, designed to work alongside humans for manipulating end-effectors, greatly benefit from the implementation of active constraints. This process comprises the definition of a boundary, followed by the enforcement of some control algorithm when the robot tooltip interacts with the generated boundary. Contact with the constraint boundary is communicated to the human operator through various potential forms of feedback. In fields like surgical robotics, where patient safety is paramount, implementing active constraints can prevent the robot from interacting with portions of the patient anatomy that shouldn't be operated on. Despite improvements in orthopaedic surgical robots, however, there exists a gap between bulky systems with haptic feedback capabilities and miniaturised systems that only allow for boundary control, where interaction with the active constraint boundary interrupts robot functions. Generally, active constraint generation relies on optical tracking systems and preoperative imaging techniques. Methods: This paper presents a refined version of the Signature Robot, a three degrees-of-freedom, hands-on collaborative system for orthopaedic surgery. Additionally, it presents a method for generating and enforcing active constraints "on-the-fly" using our previously introduced monocular, RGB, camera-based network, SimPS-Net. The network was deployed in real-time for the purpose of boundary definition. This boundary was subsequently used for constraint enforcement testing. The robot was utilised to test two different active constraints: a safe region and a restricted region. Results: The network success rate, defined as the ratio of correct over total object localisation results, was calculated to be 54.7% ± 5.2%. In the safe region case, haptic feedback resisted tooltip manipulation beyond the active constraint boundary, with a mean distance from the boundary of 2.70 mm ± 0.37 mm and a mean exit duration of 0.76 s ± 0.11 s. For the restricted-zone constraint, the operator was successfully prevented from penetrating the boundary in 100% of attempts. Discussion: This paper showcases the viability of the proposed robotic platform and presents promising results of a versatile constraint generation and enforcement pipeline.

From Hematopoietic Stem Cells to Platelets: Unifying Differentiation Pathways Identified by Lineage Tracing Mouse Models.

Platelets are the terminal progeny of megakaryocytes, primarily produced in the bone marrow, and play critical roles in blood homeostasis, clotting, and wound healing. Traditionally, megakaryocytes and platelets are thought to arise from multipotent hematopoietic stem cells (HSCs) via multiple discrete progenitor populations with successive, lineage-restricting differentiation steps. However, this view has recently been challenged by studies suggesting that (1) some HSC clones are biased and/or restricted to the platelet lineage, (2) not all platelet generation follows the "canonical" megakaryocytic differentiation path of hematopoiesis, and (3) platelet output is the default program of steady-state hematopoiesis. Here, we specifically investigate the evidence that in vivo lineage tracing studies provide for the route(s) of platelet generation and investigate the involvement of various intermediate progenitor cell populations. We further identify the challenges that need to be overcome that are required to determine the presence, role, and kinetics of these possible alternate pathways.

Lower Jaw Full-Arch Restoration: A Completely Digital Approach to Immediate Load.

The digital transformation has revolutionized various sectors, including dentistry. Dentistry has emerged as a pioneer in embracing digital technologies, leading to advancements in surgical and prosthetic oral healthcare. Immediate loading for full-arch edentulous dental implants, once debated, is now widely accepted. This case report describes a 74-year-old patient with dental mobility and significant bone loss who was rehabilitated using a Toronto Bridge protocol on four dental implants with immediate loading. Digital planning, surgical guides, 3D printing, and precision techniques were employed. The surgery involved implant placement and prosthetic procedures. The patient reported minimal post-operative discomfort, and after four months, the definitive prosthesis was successfully placed. This case demonstrates the efficacy of immediate loading in complex dental scenarios with digital innovation, resulting in improved patient outcomes. The full digital workflow, including 3D printing and the use of modern materials, enhances the efficiency and predictability of oral rehabilitation, marking a transformative era in dental care. The integration of digital technology in all phases of treatment, from diagnosis to finalization, makes this approach safer, reliable, and efficient, thereby benefiting both patients and clinicians.

Conometric Connection for Implant-Supported Crowns: A Prospective Clinical Cohort Study.

BACKGROUND: Traditional screw or cemented connections in dental implants present limitations, prompting the exploration of alternative methods. This study assesses the clinical outcomes of single crowns and fixed partial prostheses supported by conometric connections after one year of follow-up. METHODS: Twenty-two patients received 70 implants, supporting 33 rehabilitations. Biological responses and prosthodontic complications were evaluated at baseline, 6 months, and 12 months. RESULTS: All implants exhibited successful osseointegration, with no losses or peri-implant inflammation. Marginal bone levels showed minimal changes, well below pathological thresholds. The difference in marginal bone loss (MBL) was -0.27 ± 0.79 mm between T0 and T1, and -0.51 ± 0.93 mm between T0 and T2. No abutment screw loosening or crown chipping occurred. However, coupling stability loss was observed in nine cases. CONCLUSIONS: The conometric connection demonstrated successful integration and minimal complications after one year. This alternative shows promise, particularly in simplifying handling and improving marginal adaptation. Further research with larger sample sizes and longer follow-up is warranted for comprehensive validation.

Fully digital workflow for implant-supported fixed restorations consisting of a titanium primary structure and a zirconia secondary structure.

PURPOSE: To describe a fully digital workflow for an implant-supported fixed hybrid restoration that involves a double CAD/CAM structure and to highlight the benefits of this type of restoration. MATERIALS AND METHODS: Using a fully digital workflow, starting from intraoral scans, the necessary steps for producing the final hybrid prosthesis are described. The prosthesis consists of a titanium primary structure and a zirconia secondary structure that is cemented onto the primary structure in the laboratory. A clinical case is presented to illustrate the steps required for prosthetic rehabilitation. RESULTS: This technique enables the fabrication of clinically valid and passive prostheses using a fully digital workflow. CONCLUSION: In just three clinical sessions, a fully digital workflow makes it possible to produce robust implant-supported fixed hybrid prostheses, comprising a titanium primary structure and an outer secondary structure made of zirconia. This procedure can be applied to a wide range of cases from simple to extended, including full-arch restorations.

Especialización de enfermería en anestesiología y reanimación como necesidad formativa en Cuba / Nursing specialization in anesthesiology and resuscitation as a training need in Cuba

Introducción: Las especialidades de posgrado constituyen la formación académica que le proporciona al profesional la actualización, profundización, perfeccionamiento o ampliación de las competencias laborales para el desempeño asistencial que requiere. Objetivo: Explorar la percepción de los enfermeros certificados para la práctica de la anestesiología sobre la necesidad de la formación de enfermeros especialistas en anestesiología y reanimación. Métodos: Se realizó un estudio cualitativo, de tipo Investigación Convergente Asistencial en el Departamento de Docencia e Investigación del Hospital Provincial Pediátrico Universitario de Villa Clara, Cuba, entre los meses de enero y marzo del año 2022. El universo estuvo compuesto por 100 profesionales de enfermería certificados en anestesiología, y la muestra seleccionada a través de un muestreo teórico quedó constituida por 80. Se realizaron entrevistas informales y ocho grupos de discusión en el proceso investigativo. Resultados: Los participantes perciben como necesaria la formación de enfermeros especialistas en anestesiología, reanimación y alivio del dolor. Las estrategias para lograr esta formación deben estar dirigidas a su aprobación por parte de las instancias de posgrado del Ministerio de Salud Pública y el Ministerio de Educación Superior. Conclusiones: Perciben como perentorio la formación de enfermeros especialistas en anestesiología y reanimación, ya que permitirá garantizar la adecuada renovación de este recurso humano, contar con enfermeras capacitadas y capaces de brindar atención anestesiológica óptima, alcanzar un nivel profesional superior que los coloque paralelos a otras áreas del cuidado y formar recursos humanos más jóvenes que tengan un nivel de preparación superior en esta especialidad.

Introduction: Postgraduate specialties constitute the academic training that provides the professional with the updating, deepening, improvement or expansion of labor competencies for the care performance that is required. Objective: to explore the perception of certified nurses for the practice of anesthesiology on the need to train specialist nurses in anesthesiology and resuscitation. Methods: A qualitative study of the Convergent Care Research type was carried out in the Teaching and Research Department of The Provincial Pediatric University Hospital of Villa Clara, Cuba between the months of January and March of the year 2022. The universe was composed of 100 nursing professionals. certificates in anesthesiology and the sample selected through a proven theory was made up of 80. Informal interviews and discussion groups were conducted as instruments in the investigative process. Results: the participants will perceive as necessary the training of specialist nurses in anesthesiology, resuscitation and pain relief. The strategies to achieve this training must be directed to its approval by the postgraduate instances of the Ministry of Public Health and the Ministry of Higher Education. Conclusions: the training of nurses specialized in anesthesiology and resuscitation is imperative, as it will guarantee the adequate renewal of this human resource, have trained nurses capable of providing optimal anesthesiological care, reach a higher professional level than place them parallel to other areas. of care and train younger human resources that have a higher level of preparation in this specialty.

Towards a Procedure-Optimised Steerable Catheter for Deep-Seated Neurosurgery.

In recent years, steerable needles have attracted significant interest in relation to minimally invasive surgery (MIS). Specifically, the flexible, programmable bevel-tip needle (PBN) concept was successfully demonstrated in vivo in an evaluation of the feasibility of convection-enhanced delivery (CED) for chemotherapeutics within the ovine model with a 2.5 mm PBN prototype. However, further size reductions are necessary for other diagnostic and therapeutic procedures and drug delivery operations involving deep-seated tissue structures. Since PBNs have a complex cross-section geometry, standard production methods, such as extrusion, fail, as the outer diameter is reduced further. This paper presents our first attempt to demonstrate a new manufacturing method for PBNs that employs thermal drawing technology. Experimental characterisation tests were performed for the 2.5 mm PBN and the new 1.3 mm thermally drawn (TD) PBN prototype described here. The results show that thermal drawing presents a significant advantage in miniaturising complex needle structures. However, the steering behaviour was affected due to the choice of material in this first attempt, a limitation which will be addressed in future work.

One-Year Multicenter Randomised Controlled Trial Comparing OT Equator® and Locator Attachments to Retain an Early Loaded Implant Overdenture on Two Implants.

This investigation aimed to compare the effectiveness of the OT Equator® (Rhein, Bologna, Italy) and the Locator attachment systems used to retain early loaded implant-retained overdentures. This study was designed as a multicenter randomised controlled trial of parallel groups. After implant placement, the patients were randomised to receive OT Equator® attachments in the test group or Locator attachments in the control group. The outcome measures were implant and prosthetic success and survival rates, any biological and technical complication, marginal bone loss, patients' satisfaction, and periodontal parameters. Overall, 42 patients were consecutively enrolled and treated. One implant was lost in the control group, while no implants were lost in the test group. No prostheses failed in both groups. Only a few complications were experienced in both groups. The main was represented by loss of retention of the attachments (retentive caps). The OT Equator® attachment showed statistically lower periodontal parameters. In conclusion, both attachment systems were suitable for overdenture implant retention.

Spatio-temporal assessment of soil properties immediately and eight months after a high intensity-controlled burn in the south of Spain.

In recent years, the use of fire as a means by which to manage forest ecosystems has become more frequent in Europe. Fire has a significant impact on the soil, and it is therefore necessary to understand how controlled burns affect this invaluable resource. The purpose of this study was to evaluate the main alterations in the physical-chemical and biological properties of the soil because of a high intensity-controlled burn in "Los Boquerones" area (Villaviciosa de Córdoba, Spain). Additionally, we assessed the spatial heterogeneity of the alterations of different soil properties. A grid of 12 points was established on a hillside in Sierra Morena (Córdoba). Thermocouples were placed at each point, and soil samples were collected at two depths (0-2 cm and 2-5 cm) before burning, immediately after burning and eight months later. Soil pH, electrical conductivity, nutrient content and/or availability, among others, and their spatio-temporal variations were analysed. Soil pH, increased in the first centimetres of the soil (0-2 cm) immediately after burning up to >2 units, and the increase was maintained eight months following the burn. Additionally, the high-intensity burn had a positive short-term effect on some of the soil properties, such as nutrient availability for plants, which was considerably increased. The magnitude of the alterations in the soil indicators assessed was spatially explained by the behaviour of the fire during the controlled burning. The burn also had both direct and indirect effects on soil microorganisms. In conclusion, the possible immediate and short-term effects of burning on the soil resource should be considered for a more holistic management of fire in forest ecosystems, as its functionality and capacity to provide ecosystem services is largely altered by these events as a function of their intensity.

Morphological changes and Mitochondrial alterations on Cardiomyocytes exposed to Fluoride.

OBJECTIVE: To evaluate the morphological changes of cardiomyocytes exposed to different sodium fluoride (NaF) concentrations, as well as to evaluate the behavior of the mitochondria. METHODS: Rat H9c2 cardiomyocytes were exposed to NaF at concentrations of 0.5 to 5 mmol/L. The morphology and number of mitochondria in these cells were monitored, and the calcium ion (Ca2+) concentration was determined. RESULTS: Morphological changes were evident in the cells treated with different NaF concentrations, and both the number of mitochondria and the Ca2+ concentration decreased in a dose-dependent manner. CONCLUSION: Sodium fluoride induced morphological damage in cardiomyocytes, decreases the Ca2+ concentration and mitochondrial number.

Full-Arch Guided Restoration and Bone Regeneration: A Complete Digital Workflow Case Report.

OBJECTIVE: complex rehabilitations present multiple difficulties, regarding both the planification of the surgery and the design of the prothesis. A digital approach can support the workflow, as well as the degree of intraoperative precision, and improve the long-term prognosis. METHODS: A surgical guide was designed for implant placement. An extensive regeneration of the upper jaw was performed with contextual implant insertion, and a delayed load rehabilitation was chosen. After four months, a second surgery and a simultaneous soft tissue augmentation was performed, and a 3D-printed temporary restoration was placed. After another two months, new dental and facial scans, smile design, and facial bite registrations were obtained. Upper and lower dentures were built using an exclusively digital workflow. Both metal substructures were passivated and cemented in one session; in the following appointment, the aesthetic and occlusal checks were carried out. During the third visit, both prostheses were delivered. RESULTS: Careful case planning and the surgical guide made it possible to achieve primary stability and acceptable emergence profiles in an extremely reabsorbed upper jaw. Leukocyte-Platelet Rich Fibrin (L-PRF) made the extensive bone regeneration more approachable and lowered the post-operative pain and swelling, while speeding up the soft tissue healing process. During the re-entry surgery, the volumes of soft tissues were increased to improve aesthetics, and the amount of keratinized gingiva around the six implants was also increased. Smile design and facial scans have provided the means to create acceptable aesthetics and function in a few sessions with minimal patient discomfort. CONCLUSIONS: Computer-assisted implantology is a safe and precise method of performing dental implant surgery. Preliminary studies have a high degree of accuracy, but further studies are needed to arrive at a fully digital clinical protocol at all stages.

Long-term results of autologous periosteum-derived micro-grafts with poly(lactic-go-glycolic acid) in sinus lift augmentation surgeries: A 7-years follow-up observational study.

INTRODUCTION AND IMPORTANCE: The study aimed to present the long-term results of autologous and homologous micrografts for bone regeneration aimed at positioning dental implants after sinus lift augmentation surgeries, by combining autologous Rigenera® micrografts with poly(lactic-go-glycolic acid). CASE PRESENTATION: A total of 5 patients (2 males and 3 females) from 36 to 71 years were involved in the observational study. All the patients showed a good health status system (ASA1 and 2), according to their clinical history with neither system diseases, nor under medication able to interfere with osseointegration. CLINICAL DISCUSSION: The radiographic evaluations, after the implant placement and during the continuous follow-up upto 7 years, were carried out through periapical endoral x-rays. The survival and implant success rate was 100 %. Histological analyses were performed after 3 and 7 months after the surgical procedure. CONCLUSION: No adverse events have been observed that can be traced back to the use of autologous micrografts with poly(lactic-go-glycolic acid), showing safety and predictable results even in long term.

Dynamics of Chromatin Accessibility During Hematopoietic Stem Cell Differentiation Into Progressively Lineage-Committed Progeny.

Epigenetic mechanisms regulate the multilineage differentiation capacity of hematopoietic stem cells (HSCs) into a variety of blood and immune cells. Mapping the chromatin dynamics of functionally defined cell populations will shed mechanistic insight into 2 major, unanswered questions in stem cell biology: how does epigenetic identity contribute to a cell type's lineage potential, and how do cascades of chromatin remodeling dictate ensuing fate decisions? Our recent work revealed evidence of multilineage gene priming in HSCs, where open cis-regulatory elements (CREs) exclusively shared between HSCs and unipotent lineage cells were enriched for DNA binding motifs of known lineage-specific transcription factors. Oligopotent progenitor populations operating between the HSCs and unipotent cells play essential roles in effecting hematopoietic homeostasis. To test the hypothesis that selective HSC-primed lineage-specific CREs remain accessible throughout differentiation, we used ATAC-seq to map the temporal dynamics of chromatin remodeling during progenitor differentiation. We observed epigenetic-driven clustering of oligopotent and unipotent progenitors into distinct erythromyeloid and lymphoid branches, with multipotent HSCs and MPPs associating with the erythromyeloid lineage. We mapped the dynamics of lineage-primed CREs throughout hematopoiesis and identified both unique and shared CREs as potential lineage reinforcement mechanisms at fate branch points. Additionally, quantification of genome-wide peak count and size revealed overall greater chromatin accessibility in HSCs, allowing us to identify HSC-unique peaks as putative regulators of self-renewal and multilineage potential. Finally, CRISPRi-mediated targeting of ATACseq-identified putative CREs in HSCs allowed us to demonstrate the functional role of selective CREs in lineage-specific gene expression. These findings provide insight into the regulation of stem cell multipotency and lineage commitment throughout hematopoiesis and serve as a resource to test functional drivers of hematopoietic lineage fate.

3-D Path-Following Control for Steerable Needles With Fiber Bragg Gratings in Multi-Core Fibers.

Steerable needles have the potential for accurate needle tip placement even when the optimal path to a target tissue is curvilinear, thanks to their ability to steer, which is an essential function to avoid piercing through vital anatomical features. Autonomous path-following controllers for steerable needles have already been studied, however they remain challenging, especially because of the complexities associated to needle localization. In this context, the advent of fiber Bragg Grating (FBG)-inscribed multicore fibers (MCFs) holds promise to overcome these difficulties. OBJECTIVE: In this study, a closed-loop, 3-D path-following controller for steerable needles is presented. METHODS: The control loop is closed via the feedback from FBG-inscribed MCFs embedded within the needle. The nonlinear guidance law, which is a well-known approach for path-following control of aerial vehicles, is used as the basis for the guidance method. To handle needle-tissue interactions, we propose using Active Disturbance Rejection Control (ADRC) because of its robustness within hard-to-model environments. We investigate both linear and nonlinear ADRC, and validate the approach with a Programmable Bevel-tip Steerable Needle (PBN) in both phantom tissue and ex vivo brain, with some of the experiments involving moving targets. RESULTS: The mean, standard deviation, and maximum absolute position errors are observed to be 1.79 mm, 1.04 mm, and 5.84 mm, respectively, for 3-D, 120 mm deep, path-following experiments. CONCLUSION: MCFs with FBGs are a promising technology for autonomous steerable needle navigation, as demonstrated here on PBNs. SIGNIFICANCE: FBGs in MCFs can be used to provide effective feedback in path-following controllers for steerable needles.

Modular robotic platform for precision neurosurgery with a bio-inspired needle: System overview and first in-vivo deployment.

Over the past 10 years, minimally invasive surgery (MIS) has shown significant benefits compared to conventional surgical techniques, with reduced trauma, shorter hospital stays, and shorter patient recovery times. In neurosurgical MIS procedures, inserting a straight tool (e.g. catheter) is common practice in applications ranging from biopsy and laser ablation, to drug delivery and fluid evacuation. How to handle tissue deformation, target migration and access to deep-seated anatomical structures remain an open challenge, affecting both the preoperative planning phase and eventual surgical intervention. Here, we present the first neurosurgical platform in the literature, able to deliver an implantable steerable needle for a range of diagnostic and therapeutic applications, with a short-term focus on localised drug delivery. This work presents the system's architecture and first in vivo deployment with an optimised surgical workflow designed for pre-clinical trials with the ovine model, which demonstrate appropriate function and safe implantation.

Reconstruction of ovine axonal cytoarchitecture enables more accurate models of brain biomechanics.

There is an increased need and focus to understand how local brain microstructure affects the transport of drug molecules directly administered to the brain tissue, for example in convection-enhanced delivery procedures. This study reports a systematic attempt to characterize the cytoarchitecture of commissural, long association and projection fibres, namely the corpus callosum, the fornix and the corona radiata, with the specific aim to map different regions of the tissue and provide essential information for the development of accurate models of brain biomechanics. Ovine samples are imaged using scanning electron microscopy combined with focused ion beam milling to generate 3D volume reconstructions of the tissue at subcellular spatial resolution. Focus is placed on the characteristic cytological feature of the white matter: the axons and their alignment in the tissue. For each tract, a 3D reconstruction of relatively large volumes, including a significant number of axons, is performed and outer axonal ellipticity, outer axonal cross-sectional area and their relative perimeter are measured. The study of well-resolved microstructural features provides useful insight into the fibrous organization of the tissue, whose micromechanical behaviour is that of a composite material presenting elliptical tortuous tubular axonal structures embedded in the extra-cellular matrix. Drug flow can be captured through microstructurally-based models using 3D volumes, either reconstructed directly from images or generated in silico using parameters extracted from the database of images, leading to a workflow to enable physically-accurate simulations of drug delivery to the targeted tissue.

Stenocereus huastecorum-fruit juice concentrate protects against cisplatin-induced nephrotoxicity by nitric oxide pathway activity and antioxidant and antiapoptotic effects.

Cisplatin (CP) is an antineoplastic agent used to treat solid tumors, that has high nephrotoxicity caused by physiologic, hemodynamic, and biochemical alterations. Some studies have shown that naturally derived bioactive compounds in CP-induced nephrotoxicity reduce the side effects of this antineoplastic drug. Pitaya is an endemic fruit from Mexico with a high bioactive compound content, including betalains and phenolic compounds, with reports of antioxidant and anti-inflammatory properties. In this study, the aim was to establish the effect of a pitaya juice concentrate (PJC) on CP-induced nephrotoxicity in Wistar male rats through the identification of metabolites, determination of its chemical composition and antioxidant activity, and evaluation of the protective effect of a PJC on CP-induced nephrotoxicity in rats. The PJC showed a high content of betanins with antioxidant activity by an oxygen radical absorbance capacity assay (1299.6 ± 2.80 Trolox equivalents/g). PJC was administered daily (400 mg day-1, p. o.) for 3 days before CP administration until the end of the experiment. On day four, rats were administered a single injection of CP (6 mg kg, i.p.-1) and sacrificed 72 h later. We observed that CP provoked renal dysfunction (1.0 ± 0.1 vs. 0.4 ± 0.07 serum creatinine levels), oxidative stress, a decrease in nitrate and nitrite (NO2¯/NO3¯) levels (0.1 ± 0.08 vs. 0.4 ± 0.3) and activation of apoptosis and immune responses in kidney tissue. In addition, CP treatment induced tubular damage threefold. PJC administration prevented renal dysfunction (0.5 ± 0.06 vs. 1.0 ± 0.1), normalized degenerative structural damage prevented the increase in lipoperoxidation levels (0.04 ± 0.01 vs. 0.2 ± 0.1) and reduced the apoptosis index by 2.5 in kidney tissue. However, it did not modify the immune response caused by CP. Furthermore, PJC treatment increased nuclear factor erythroid two related factors two protein levels two times and NO2¯/NO3¯ levels 22 times in kidney tissue, which may play a role in the renoprotective effect. In conclusion, the renoprotective effect of PJC on CP-induced nephrotoxicity was associated with the attenuation of dysfunction, structural damage, apoptosis activation, and oxidative stress and was related to changes in the tumor necrosis factor-alpha and renal nitric oxide (NO) pathways. The changes in the NO pathway may be involved in renal hemodynamics. Pitaya could be used as a functional food and therapeutic coadjuvant during CP treatments due to its high bioactive levels and renoprotective compounds.

Excess Mortality among Physicians and Dentists during COVID-19 in Italy: A Cross-Sectional Study Related to a High-Risk Territory.

BACKGROUND: Many studies previously reported epidemiological data on mortality due to COVID-19 among health workers. All these studies included a partial sample of the population with a substantial selection bias. The present study evaluates the trend of mortality among physicians and dentists operating in an area considered to be at high risk during the COVID-19 pandemic. METHODS: Data relating to all physicians and dentists registered in the province of Pavia (Italy), a sample consisting of 5454 doctors in 2020 was analyzed. The mortality rates obtained were compared with those related to the 5-year period preceding the pandemic and with those related to the general population. RESULTS: In the area considered, a mortality rate of 0.83% (+69% compared to 2015-2019) was observed in the entire sample in 2020 and 0.43% (-11% compared to 2015-2019) in 2021; among physicians, there was a mortality rate of 0.76% (+53% compared to 2015-2019) in 2020 and 0.35% (-29% compared to 2015-2019) in 2021; for dentists, there was a mortality rate of 1.27% (+185% compared to 2015-2019) in 2020 and 1.01% (+127% compared to 2015-2019) in 2021. CONCLUSIONS: These data report the global impact of the SARS-CoV-2 pandemic on physicians and dentists in a high-risk territory. In 2020, a significant increase in the mortality rate compared to the previous 5 years was observed for both physicians and dentists; in 2021, a significant increase in the mortality rate was observed only for dentists. These data are also significant in evaluating the impact of vaccination on physicians and dentists and indicate that dentists were among the professions most at risk during the pandemic.