Allogenic bone marrow-derived mesenchymal stromal cell-based therapy for patients with chronic low back pain: a prospective, multicentre, randomised placebo controlled trial (RESPINE study).

OBJECTIVES: To assess the efficacy of a single intradiscal injection of allogeneic bone marrow mesenchymal stromal cells (BM-MSCs) versus a sham placebo in patients with chronic low back pain (LBP). METHODS: Participants were randomised in a prospective, double-blind, controlled study to receive either sham injection or intradiscal injection of 20 million allogeneic BM-MSC, between April 2018 and December 2022. The first co-primary endpoint was the rate of responders defined by improvement of the Visual Analogue Scale (VAS) for pain of at least 20% and 20 mm, or improvement of the Oswestry Disability Index (ODI) of 20% between baseline and month 12. The secondary structural co-primary endpoint was assessed by the disc fluid content measured by quantitative MRI T2, between baseline and month 12. Secondary endpoints included pain VAS, ODI, the Short Form (SF)-36 and the minimal clinically important difference in all timepoints (1, 3, 6, 12 and 24 months). We determined the immune response associated with allogeneic cell injection between baseline and 6 months. Serious adverse events (SAEs) were recorded. RESULTS: 114 patients were randomised (n=58, BM-MSC group; n=56, sham placebo group). At 12 months, the primary outcome was not reached (74% in the BM-MSC group vs 69% in the placebo group; p=0.77). The groups did not differ in all secondary outcomes. No SAE related to the intervention occurred. CONCLUSIONS: While our study did not conclusively demonstrate the efficacy of allogeneic BM-MSCs for LBP, the procedure was safe. Long-term outcomes of MSC therapy for LBP are still being studied. TRIAL REGISTRATION NUMBER: EudraCT 2017-002092-25/ClinicalTrials.gov: NCT03737461.

National Study of Fournier Gangrene in Spain (2016-2021): Gender/Sex Differences in Mortality and Risks.

Background and Objective: The aim of this study was to analyze sex differences in risk factors associated with hospital mortality in patients with Fournier gangrene (FG). Materials and Methods: A retrospective population-based study (2016-2021) included FG hospitalizations in Spain. To identify the risk factors, we used multivariable logistic regression and reported adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results: There were 3644 admissions for FG during the study period (82.5% men and 17.5% women). The mean hospitalization rate per 1000 admissions/year was 0.23 for men and 0.05 for women, and the mean hospitalization rate per 100,000 inhabitants/year was 2.7 for men and 0.4 in women. The most common comorbidities were hypertension (44.9%) and diabetes mellitus (35.6%). The main complications were sepsis (22.1%), 29.8% were admitted to the intensive care unit and 16.1% died. Mortality was higher in women (aOR 1.32, 95% CI 1.07-1.63). The main independent risk factors for mortality in the entire sample were older age, neoplasms, chronic kidney disease, heart failure, sepsis, acute kidney injury, and admission to the intensive care unit. In women, they were older age, leukemia, sepsis, acute kidney injury, and admission to the intensive care unit. Conclusions: The overall FG mortality rate was slightly higher in women than in men, people aged >64 years, people with chronic kidney disease, sepsis, and acute kidney injury, and admission to the intensive care unit. The independent factors associated with mortality in women were similar in both sexes.

[The relevant role of caregivers of patients using opioid analgesics]. / El relevante papel de los cuidadores de pacientes usuarios de analgésicos opioides.

Aging is a global reality that is accompanied by an increase in polypharmacy. In this vital stage, caregivers emerge as relevant actors since their intervention impacts on the safety of the medication use process and on the quality of life of the patient they assist. As the knowledge about the treatments that caregivers supervise for the patient under their care conditions the health outcomes of the medications, the main objective of this study is to characterize the caregivers of patients who use opioid analgesics and to identify factors that increase the risk of the appearance of Medication Related Problems (DRP).The results reveal that the caregiver profile affects the health outcomes of this therapeutic group in both the prevalence and type of DRP. Of the 63 patients using opioid analgesics under pharmacotherapeutic follow-up during this study, 17 (27%) had caregivers. The caregiver in this study was predominantly female (61.1%).Considering DRP and kinship, a higher prevalence of DRP was observed when the caregivers were children or external personnel.Analyzing the pharmacotherapy of these caregivers, 4.8% have started antidepressant treatment, 3.2% hypnotic treatment after becoming caregivers of these patients. The Zarit Test reveals that 29.4% of the caregivers of these patients manifest overload.We conclude that Pharmaceutical Care should consider the opportunity and relevance of designing and implementing intervention and education protocols focused on caregivers.

Thermally and Photoinduced Spin-Crossover Behavior in Iron(II)-Silver(I) Cyanido-Bridged Coordination Polymers Bearing Acetylpyridine Ligands.

We report two new cyanido-bridged Fe(II)-Ag(I) coordination polymers using different acetylpyridine isomers, {Fe(4acpy)2[Ag(CN)2]2} 1 and {Fe(3acpy)[Ag(CN)2]2} 2 (4acpy = 4-acetylpyridine; 3acpy = 3-acetylpyridine) displaying thermally and photoinduced spin crossover (SCO). In both cases, the acetylpyridine ligand directs the coordination polymer structure and the SCO of the materials. Using 4-acetylpyridine, a two-dimensional (2D) structure is observed in 1 made of layers stacked on each other by silver-ketone interactions leading to a complete SCO and reversible thermally and photoswitching of the magnetic and optical properties. Changing the acetyl group to a 3-position, a completely different structure is obtained for 2. The unexpected coordination of the carbonyl group to the Fe(II) centers induces a three-dimensional (3D) structure, leading to statistical disorder around the Fe(II) with three different coordination spheres, [N6], [N4O2], and [N5O]. This disorder gives rise to an incomplete thermally induced SCO with a poor photoswitchability. These results demonstrate that the choice of the acetyl position on the pyridine dictates the structural characteristics of the compounds with a direct impact on the SCO behavior. Remarkably, this work opens interesting perspectives for the future design of Fe-Ag cyanido coordination polymers with judiciously substituted pyridine ligands to tune the thermally and photoinduced SCO properties.

Iron-Reduced Graphene Oxide Core-Shell Micromotors Designed for Magnetic Guidance and Photothermal Therapy under Second Near-Infrared Light.

Core-shell micro/nanomotors have garnered significant interest in biomedicine owing to their versatile task-performing capabilities. However, their effectiveness for photothermal therapy (PTT) still faces challenges because of their poor tumor accumulation, lower light-to-heat conversion, and due to the limited penetration of near-infrared (NIR) light. In this study, we present a novel core-shell micromotor that combines magnetic and photothermal properties. It is synthesized via the template-assisted electrodeposition of iron (Fe) and reduced graphene oxide (rGO) on a microtubular pore-shaped membrane. The resulting Fe-rGO micromotor consists of a core of oval-shaped zero-valent iron nanoparticles with large magnetization. At the same time, the outer layer has a uniform reduced graphene oxide (rGO) topography. Combined, these Fe-rGO core-shell micromotors respond to magnetic forces and near-infrared (NIR) light (1064 nm), achieving a remarkable photothermal conversion efficiency of 78% at a concentration of 434 µg mL-1. They can also carry doxorubicin (DOX) and rapidly release it upon NIR irradiation. Additionally, preliminary results regarding the biocompatibility of these micromotors through in vitro tests on a 3D breast cancer model demonstrate low cytotoxicity and strong accumulation. These promising results suggest that such Fe-rGO core-shell micromotors could hold great potential for combined photothermal therapy.

Assessment of Untargeted Metabolomics by Hydrophilic Interaction Liquid Chromatography-Mass Spectrometry to Define Breast Cancer Liquid Biopsy-Based Biomarkers in Plasma Samples.

An early diagnosis of cancer is fundamental not only in regard to reducing its mortality rate but also in terms of counteracting the progression of the tumor in the initial stages. Breast cancer (BC) is the most common tumor pathology in women and the second deathliest cancer worldwide, although its survival rate is increasing thanks to improvements in screening programs. However, the most common techniques to detect a breast tumor tend to be time-consuming, unspecific or invasive. Herein, the use of untargeted hydrophilic interaction liquid chromatography-mass spectrometry analysis appears as an analytical technique with potential use for the early detection of biomarkers in liquid biopsies from BC patients. In this research, plasma samples from 134 BC patients were compared with 136 from healthy controls (HC), and multivariate statistical analyses showed a clear separation between four BC phenotypes (LA, LB, HER2, and TN) and the HC group. As a result, we identified two candidate biomarkers that discriminated between the groups under study with a VIP > 1 and an AUC of 0.958. Thus, targeting the specific aberrant metabolic pathways in future studies may allow for better molecular stratification or early detection of the disease.

Pitahaya (Hylocereus ocamponis)-Peel and -Flesh Flour Obtained from Fruit Co-Products-Assessment of Chemical, Techno-Functional and In Vitro Antioxidant Properties.

The aim of this work was to assess the chemical composition and physico-chemical, techno-functional, and in vitro antioxidant properties of flours obtained from the peel and flesh of pitahaya (Hylocereus ocamponis) to determine their potential for use as ingredients for food enrichment. The chemical composition, including total betalains, mineral content, and polyphenolic profile, was determined. The techno-functional properties (water holding, oil holding, and swelling capacities) were also evaluated. For the antioxidant capacity, four different methodologies, namely ferrous ion-chelating ability assay, ferric-reducing antioxidant power assay; 1,1-Diphenyl-2-picrylhydrazyl radical scavenging ability assay, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical assay, were used. Pitahaya-peel flour had higher values for protein (6.72 g/100 g), ash (11.63 g/100 g), and dietary fiber 56.56 g/100 g) than pitahaya-flesh flour, with values of 6.06, 3.63, and 8.22 g/100 g for protein, ash, and dietary fiber, respectively. In the same way, pitahaya peel showed a higher content of minerals, betalains, and polyphenolic compounds than pitahaya-flesh flour, with potassium (4.43 g/100 g), catechin (25.85 mg/g), quercetin-3-rhamnoside (11.66 mg/g) and myricetrin (12.10 mg/g) as principal compounds found in the peel. Again, pitahaya-peel flour showed better techno-functional and antioxidant properties than pitahaya-flesh flour. The results obtained suggest that the flours obtained from the peel and pulp of pitahaya (H. ocamponis) constitute a potential material to be utilized as an ingredient in the food industry due to the high content of bioactive compounds such as betalains, phenolic acids, and flavonoids, with notable antioxidant capacity.

Multi-lineage heart-chip models drug cardiotoxicity and enhances maturation of human stem cell-derived cardiovascular cells.

Cardiovascular toxicity causes adverse drug reactions and may lead to drug removal from the pharmaceutical market. Cancer therapies can induce life-threatening cardiovascular side effects such as arrhythmias, muscle cell death, or vascular dysfunction. New technologies have enabled cardiotoxic compounds to be identified earlier in drug development. Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) and vascular endothelial cells (ECs) can screen for drug-induced alterations in cardiovascular cell function and survival. However, most existing hiPSC models for cardiovascular drug toxicity utilize two-dimensional, immature cells grown in static culture. Improved in vitro models to mechanistically interrogate cardiotoxicity would utilize more adult-like, mature hiPSC-derived cells in an integrated system whereby toxic drugs and protective agents can flow between hiPSC-ECs that represent systemic vasculature and hiPSC-CMs that represent heart muscle (myocardium). Such models would be useful for testing the multi-lineage cardiotoxicities of chemotherapeutic drugs such as VEGFR2/PDGFR-inhibiting tyrosine kinase inhibitors (VPTKIs). Here, we develop a multi-lineage, fully-integrated, cardiovascular organ-chip that can enhance hiPSC-EC and hiPSC-CM functional and genetic maturity, model endothelial barrier permeability, and demonstrate long-term functional stability. This microfluidic organ-chip harbors hiPSC-CMs and hiPSC-ECs on separate channels that can be subjected to active fluid flow and rhythmic biomechanical stretch. We demonstrate the utility of this cardiovascular organ-chip as a predictive platform for evaluating multi-lineage VPTKI toxicity. This study may lead to the development of new modalities for the evaluation and prevention of cancer therapy-induced cardiotoxicity.

Antimicrobial Effect of Cannabidiol on Intracellular Mycobacterium tuberculosis.

Introduction: Mycobacterium tuberculosis, the etiologic agent of tuberculosis (TB), has killed nearly one billion people during the last two centuries. Nowadays, TB remains a major global health problem ranked among the top 10 causes of death worldwide. One of the main challenges in developing new strategies to fight TB is focused on reducing the duration and complexity of drug regimens. Cannabidiol (CBD) is the main nonpsychoactive ingredient extracted from the Cannabis sativa L. plant, which has been shown to be biologically active against bacteria. The purpose of this work was to investigate the antimicrobial effect of CBD on M. tuberculosis intracellular infection. Materials and Methods: To assess the minimum inhibitory concentration (MIC) of CBD on mycobacterial strains, the MTT assay was performed on Mycobacterium smegmatis, and the Colony-Forming Unit (CFU) assay was conducted on MtbH37Rv. Additionally, the cytotoxic effect of CBD on THP-1 cells was assessed by MTT assay. Moreover, macrophages derived from the THP-1 cell were infected with MtbH37Rv (multiplicity of infection 1:10) to evaluate the intracellular activity of CBD by determining the CFU/mL. Results: Antimicrobial activity against M. smegmatis (MIC=100 µM) and MtbH37Rv (MIC=25 µM) cultures was exhibited by CBD. Furthermore, the effect of CBD was also evaluated on MtbH37Rv infected macrophage cells. Interestingly, a reduction in viable intracellular MtbH37Rv bacteria was observed after 24 h of treatment. Moreover, CBD exhibited a safe profile toward human THP-1 cells, since it showed no toxicity (CC50=1075 µM) at a concentration of antibacterial effect (selectivity index 43). Conclusion: These results extend the knowledge regarding the antimicrobial activity of CBD and demonstrate its ability to kill the human intracellular pathogen M. tuberculosis.

Reposicionamiento Labial. Caso Clínico

El reposicionamiento labial es un procedimiento quirúrgico mínimamente invasivo que se utiliza para tratar una sonrisa gingival, la cual, es una afección en la que una cantidad significativa de la encía queda expuesta cuando una persona sonríe y puede deberse a una variedad de factores, como un exceso de tejido gingival, un labio superior corto o músculos hiperactivos del labio superior, entre otros. El alargamiento clínico de la corona, por otro lado, consiste en eliminar el exceso de tejido gingival y, si es necesario, el tejido óseo para exponer una mayor parte de la corona natural del diente. Se reporta un caso clínico de paciente femenino de 31 años que presentó una sonrisa gingival provocada por hipermovilidad de labio superior y un exceso de tejido gingival localizado. El plan de tratamiento involucró una combinación de reposicionamiento labial y alargamiento de corona. Los resultados estéticos fueron significativos, con la sonrisa del paciente más equilibrada y proporcionada. Se redujo la cantidad de tejido gingival expuesto cuando la paciente sonreía y la longitud de los dientes fue más visible, lo que dio como resultado una sonrisa de aspecto más natural, además de aumentar su aceptación al sonreír.

SUMMARY: Lip repositioning is a minimally invasive surgical procedure used to treat a gummy smile, which is a condition in which a significant amount of the gum is exposed when a person smiles and may be due to a variety of factors, such as excess gum tissue, a short upper lip or overactive muscles of the upper lip, among others. Clinical crown lengthening, on the other hand, involves removing excess gingival tissue and, if necessary, bone tissue to expose more of the natural crown of the tooth. Clinical case: A clinical case of a 31-year-old female patient who presented a gummy smile caused by hypermobility of the upper lip and an excess of localized gingival tissue is reported. The treatment plan involved a combination of lip repositioning and crown lengthening. The aesthetic results were significant, with the patient's smile more balanced and displayed. The amount of the patient's exposed gum tissue when smiled was reduced and the length of the teeth was more visible, resulting in a more natural-looking smile, as well as increasing their acceptance of smiling.

Intravitreal allogeneic mesenchymal stem cells: a non-randomized phase II clinical trial for acute non-arteritic optic neuropathy.

BACKGROUND: An effective treatment for acute non-arteritic ischemic optic neuropathy (NA-AION) has not been known or proven yet. Previous studies have suggested a neuroprotective effect of allogeneic bone marrow-derived mesenchymal stem cells. This study aims to report the results of a clinical trial on patients with acute non-arteritic optic neuropathy (NA-AION) treated with an intravitreal injection of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) (MSV®). METHODS: We conducted a prospective, non-randomized, clinical phase-II study (Eudra CT number 2016-003029-40; ClinicalTrials.gov Registry NCT03173638) that included 5 patients with acute unilateral NA-AION diagnosed within 2 weeks after symptom onset and who received an intravitreal injection of allogeneic BM-MSCs (0.05 ml; cell concentration: 1.5 × 106cells/mL). The patients underwent regular ophthalmological examinations and were followed for one year. RESULTS: In this trial, allogeneic BM-MSCs appeared to be safe as no patients developed signs of acute nor chronic intraocular inflammation or a significant change in intraocular pressure, although an epiretinal membrane was developed in one patient. A retrolental aggregate formed shortly after the injection spontaneously disappeared within a few weeks in another phakic patient, leaving a subcapsular cataract. Visual improvement was noted in 4 patients, and amplitudes of P100 on the visually evoked potentials recordings increased in three patients. The retinal nerve fiber layer and macular ganglion cell layer thicknesses significantly decreased during the follow-up. CONCLUSIONS: Besides the development of an epiretinal membrane in one patient, the intravitreal application of allogeneic BM-MSCs appeared to be intraocularly well tolerated. Consequently, not only NA-AION but also BM-MSCs deserve more clinical investigational resources and a larger randomized multicenter trial that would provide stronger evidence both about safety and the potential therapeutic efficacy of intravitreally injected allogeneic BM-MSCs in acute NA-AION. TRIAL REGISTRATION: Safety Assessment of Intravitreal Mesenchymal Stem Cells for Acute Non-Arteritic Anterior Ischemic Optic Neuropathy (NEUROSTEM). NCT03173638. Registered June 02, 2017 https://clinicaltrials.gov/ct2/show/NCT03173638 .

Incongruence between transcriptional and vascular pathophysiological cell states.

The Notch pathway is a major regulator of endothelial transcriptional specification. Targeting the Notch receptors or Delta-like ligand 4 (Dll4) dysregulates angiogenesis. Here, by analyzing single and compound genetic mutants for all Notch signaling members, we find significant differences in the way ligands and receptors regulate liver vascular homeostasis. Loss of Notch receptors caused endothelial hypermitogenic cell-cycle arrest and senescence. Conversely, Dll4 loss triggered a strong Myc-driven transcriptional switch inducing endothelial proliferation and the tip-cell state. Myc loss suppressed the induction of angiogenesis in the absence of Dll4, without preventing the vascular enlargement and organ pathology. Similarly, inhibition of other pro-angiogenic pathways, including MAPK/ERK and mTOR, had no effect on the vascular expansion induced by Dll4 loss; however, anti-VEGFA treatment prevented it without fully suppressing the transcriptional and metabolic programs. This study shows incongruence between single-cell transcriptional states, vascular phenotypes and related pathophysiology. Our findings also suggest that the vascular structure abnormalization, rather than neoplasms, causes the reported anti-Dll4 antibody toxicity.

The Thoracic Inlet Length as a Reference Point to Radiographically Assess Cardiac Enlargement in Dogs with Myxomatous Mitral Valve Disease.

The diagnostic value of the vertebral heart size (VHS) in dogs with mitral valve degeneration (MVD) is compromised when middle thoracic vertebral anomalies are present. The objective of this study was to assess the use of the thoracic inlet heart score (TIHS) to identify left heart enlargement (LHE) secondary to MVD. The cardiac silhouette of 50 clinically healthy dogs and 106 MVD dogs in different stages was assessed on a right lateral chest radiograph. The TIHS and VHS value were calculated for each patient and compared. The TIHS was significantly different between the control dogs and the dogs with MMVD, increasing with disease stage, control 2.91 ± 0.23, Stage B1 2.98 ± 0.36, B2 3.25 ± 0.34, and C 3.53 ± 0.36, p < 0.05. A THIS ≥3.3 showed 69% sensitivity and 81% specificity to identify LHE. The TIHS showed moderate correlation with the VHS, LA/Ao, and LVIDDN 0.59, 0.42, and 0.62, respectively. The intraobserver and interobserver agreement were almost perfect, 0.96, and substantial, 0.73. The TIHS method can be used to identify LHE secondary to MMVD on dogs' thoracic radiographs.

Role of Artificial Intelligence in Colonoscopy Detection of Advanced Neoplasias : A Randomized Trial.

BACKGROUND: The role of computer-aided detection in identifying advanced colorectal neoplasia is unknown. OBJECTIVE: To evaluate the contribution of computer-aided detection to colonoscopic detection of advanced colorectal neoplasias as well as adenomas, serrated polyps, and nonpolypoid and right-sided lesions. DESIGN: Multicenter, parallel, randomized controlled trial. (ClinicalTrials.gov: NCT04673136). SETTING: Spanish colorectal cancer screening program. PARTICIPANTS: 3213 persons with a positive fecal immunochemical test. INTERVENTION: Enrollees were randomly assigned to colonoscopy with or without computer-aided detection. MEASUREMENTS: Advanced colorectal neoplasia was defined as advanced adenoma and/or advanced serrated polyp. RESULTS: The 2 comparison groups showed no significant difference in advanced colorectal neoplasia detection rate (34.8% with intervention vs. 34.6% for controls; adjusted risk ratio [aRR], 1.01 [95% CI, 0.92 to 1.10]) or the mean number of advanced colorectal neoplasias detected per colonoscopy (0.54 [SD, 0.95] with intervention vs. 0.52 [SD, 0.95] for controls; adjusted rate ratio, 1.04 [99.9% CI, 0.88 to 1.22]). Adenoma detection rate also did not differ (64.2% with intervention vs. 62.0% for controls; aRR, 1.06 [99.9% CI, 0.91 to 1.23]). Computer-aided detection increased the mean number of nonpolypoid lesions (0.56 [SD, 1.25] vs. 0.47 [SD, 1.18] for controls; adjusted rate ratio, 1.19 [99.9% CI, 1.01 to 1.41]), proximal adenomas (0.94 [SD, 1.62] vs. 0.81 [SD, 1.52] for controls; adjusted rate ratio, 1.17 [99.9% CI, 1.03 to 1.33]), and lesions of 5 mm or smaller (polyps in general and adenomas and serrated lesions in particular) detected per colonoscopy. LIMITATIONS: The high adenoma detection rate in the control group may limit the generalizability of the findings to endoscopists with low detection rates. CONCLUSION: Computer-aided detection did not improve colonoscopic identification of advanced colorectal neoplasias. PRIMARY FUNDING SOURCE: Medtronic.

The Role of Anesthetic Drugs and Statins in Prostate Cancer Recurrence: Starting at the Actual Knowledge and Walking through a New Paradigm.

Prostate cancer has become a major health problem in men. Its incidence is increasing as the average age of the affected population tends to be higher. Of all the possible treatments, surgery is the gold standard in its treatment. Surgery produces a deregulation in the immune system that can favour the development of distant metastases. Different anesthetic techniques have raised the hypothesis that different anesthetic drugs influence tumor recurrence and prognosis. Some mechanisms are beginning to be understood by which halogenated agents in cancer patients and the use of opioids may negatively affect patients. In this document, we group together all the available evidence on how the different anesthetic drugs affect tumor recurrence in prostate cancer.

Human iPSC-derived neural progenitor cells secreting GDNF provide protection in rodent models of ALS and retinal degeneration.

Human induced pluripotent stem cells (iPSCs) are a renewable cell source that can be differentiated into neural progenitor cells (iNPCs) and transduced with glial cell line-derived neurotrophic factor (iNPC-GDNFs). The goal of the current study is to characterize iNPC-GDNFs and test their therapeutic potential and safety. Single-nuclei RNA-seq show iNPC-GDNFs express NPC markers. iNPC-GDNFs delivered into the subretinal space of the Royal College of Surgeons rodent model of retinal degeneration preserve photoreceptors and visual function. Additionally, iNPC-GDNF transplants in the spinal cord of SOD1G93A amyotrophic lateral sclerosis (ALS) rats preserve motor neurons. Finally, iNPC-GDNF transplants in the spinal cord of athymic nude rats survive and produce GDNF for 9 months, with no signs of tumor formation or continual cell proliferation. iNPC-GDNFs survive long-term, are safe, and provide neuroprotection in models of both retinal degeneration and ALS, indicating their potential as a combined cell and gene therapy for various neurodegenerative diseases.

A Remote Diet and Exercise Intervention for Surgical Patients With Prefrailty and Frailty During the COVID-19 Pandemic.

Objectives: To facilitate the success of surgical patients with prefrailty and frailty in meeting diet and exercise goals in the context of the COVID-19 pandemic, and to encourage patient satisfaction with remote care. Methods: In the setting of the COVID-19 pandemic, surgical patients with prefrailty and frailty were offered remote visits with a geriatrician and a remote diet and exercise coaching program. Results: The coaching participants set a mean of 37 (±15) individualized dietary goals and 17 (±11) individualized exercise goals. 75% of the coaching participants met at least 65% of their dietary goals and 75% met at least 50% of their exercise goals. All patients met at least one diet goal and at least one exercise goal. Patients endorsed high levels of satisfaction with the program. Discussion: Diet and exercise interventions for surgical patients with prefrailty and frailty have potential for adaptation to remote formats. Such interventions may facilitate patients' meeting of individualized diet and exercise goals and may also encourage patient satisfaction.

Maternal hepatocytes heterogeneously and dynamically exhibit developmental phenotypes partially via yes-associated protein 1 during pregnancy.

Pregnancy induces reprogramming of maternal physiology to support fetal development and growth. Maternal hepatocytes undergo hypertrophy and hyperplasia to drive maternal liver growth and alter their gene expression profiles simultaneously. This study aimed to further understand maternal hepatocyte adaptation to pregnancy. Timed pregnancies were generated in mice. In a nonpregnant state, most hepatocytes expressed Cd133, α-fetal protein (Afp) and epithelial cell adhesion molecule (Epcam) mRNAs, whereas overall, at the protein level, they exhibited a CD133-/AFP- phenotype; however, pericentral hepatocytes were EpCAM+. As pregnancy advanced, although most maternal hepatocytes retained Cd133, Afp, and Epcam mRNA expression, they generally displayed a phenotype of CD133+/AFP+, and EpCAM protein expression was switched from pericentral to periportal maternal hepatocytes. In addition, we found that the Hippo/yes-associated protein (YAP) pathway does not respond to pregnancy. Yap1 gene deletion specifically in maternal hepatocytes did not affect maternal liver growth or metabolic zonation. However, the absence of Yap1 gene eliminated CD133 protein expression without interfering with Cd133 transcript expression in maternal livers. We demonstrated that maternal hepatocytes acquire heterogeneous and dynamic developmental phenotypes, resembling fetal hepatocytes, partially via YAP1 through a posttranscriptional mechanism. Moreover, maternal liver is a new source of AFP. In addition, maternal liver grows and maintains its metabolic zonation independent of the Hippo/YAP1 pathway. Our findings revealed a novel and gestation-dependent phenotypic plasticity in adult hepatocytes.NEW & NOTEWORTHY We found that maternal hepatocytes exhibit developmental phenotypes in a temporal and spatial manner, similarly to fetal hepatocytes. They acquire this new property partially via yes-associated protein 1.

Fijadores externos para tratar fractura mandibular causada por herida de arma de fuego. Reporte de caso / External fxators as treatment for mandibular fracture caused by gunshot wound. Case report

Introducción: las heridas por proyectil de arma de fuego en la región craneofacial provocan daños funcionales devastadoras y deformidades estéticas, que se suman al trauma psicológico al momento del regreso a la vida cotidiana de un paciente. Por esta razón, la reconstrucción adecuada es esencial para una rehabilitación integral. La fijación externa es un método de reducción cerrada de fracturas que implica el uso de tornillos para manipular segmentos sueltos de hueso, que luego se fijan mediante conexiones externas. Es importante recalcar que las fracturas mandibulares causadas por proyectil de arma de fuego son un reto para este tipo de tratamiento. Objetivo: presentar el caso de un paciente con fractura mandibular por proyectil de arma de fuego tratado con fijadores externos y revisión de la literatura sobre este tipo de tratamiento. Caso clínico: paciente masculino de 19 años que presentó fractura de rama mandibular izquierda causado por proyectil de arma de fuego; la fractura se manejó mediante la colocación de fijación intermaxilar con arcos barra tipo Erich y fijación externa durante 3 meses. Como parte del resultado, el paciente presentó una correcta oclusión dentaria y mantiene sus movimientos mandibulares sin ninguna limitación. Esto demuestra que la reducción cerrada y fijación externa debe mantenerse en el arsenal terapéutico debido a sus adecuados resultados comprobados en la literatura y en este caso. Ahora bien, aunque la reducción abierta y fijación interna con material de osteosíntesis hace parte del manejo idóneo para todo tipo de fractura, todos los casos requieren ser individualizados.

Background: wounds from a frearm projectile in the craniofacial region cause devastating functional damage and aesthetic deformities, along with psychological trauma when returning to daily life. This is why proper reconstruction is essential for comprehensive rehabilitation. External fxation is a method of closed fracture reduction that involves the use of screws to manipulate loose segments of bone that are then fxed using external connections. Objective: to present the case of a patient with a mandibular fracture caused by a frearm projectile treated with external fixators and review the literature. Clinical case: a 19-year-old male patient who presented a fracture of the left mandibular ramus caused by a frearm projectile, the fracture was managed by placing intermaxillary fxation with Erich-type bar arches and external fixation for 3 months. The patient presented a correct dental occlusion and maintains his mandibular movements without any limitation. Conclusion: mandibular fractures caused by frearm projectiles are a challenge for treatment. Open reduction and internal fixation with osteosynthesis material is the ideal management for all types of fractures, however, all cases must be individualized, and it must be considered that closed reduction and external fxation must remain in our therapeutic arsenal due to their adequate results verifed in the literature and in our case.