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Juan Manuel Reséndiz-Hernández,1 Enrique Ambrocio-Ortiz,1 Gloria Pérez-Rubio,1 Luis Alberto López-Flores,1 Edgar Abarca-Rojano,2 Gandhi Fernando Pavón-Romero,3 Fernando Flores-Trujillo,4 Rafael de Jesús Hernández-Zenteno,4 Ángel Camarena,1 Martha Pérez-Rodríguez,5 Ana María Salazar,6 Alejandra Ramírez-Venegas,4 Ramcés Falfán-Valencia1 1HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico; 2Research and Graduate Studies Section, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico; 3Department of Allergy and Clinical Immunology, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico; 4Tobacco Smoking and COPD Research Department, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico; 5Unit of Medical Research in Immunology, CMN S-XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico; 6Department of Genomic Medicine and Environmental Toxicology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico Background: Smoking and smoke from biomass burning (BB) are the main environmental risk factors for COPD. Clinical differences have been described between COPD related to smoking and related to wood smoke, but no studies have shown genetic differences between patients exposed to these two risk factors. Methods: To investigate a possible association of tumor necrosis factor (TNF) promoter polymorphisms, we conducted a case–control study. A total of 1,322 subjects were included in four groups: patients with a diagnosis of COPD secondary to smoking (COPD-S, n=384), patients with COPD secondary to biomass burning (COPD-BB, n=168), smokers without COPD (SWOC, n=674), and biomass burning-exposed subjects (BBES n=96). Additionally, a group of 950 Mexican mestizos (MMs) was included as a population control. Three single nucleotide polymorphisms (SNPs) were selected in the TNF gene (rs1800629, rs361525, and rs1800750) and one SNP in the lymphotoxin alpha gene (rs909253). Results: Statistically significant differences were found with genotype GA of the rs1800629: COPD-S vs SWOC, (p

Andrew N de la Torre,1,2 Sohail Contractor,3 Ismael Castaneda,1 Charles S Cathcart,4 Dolly Razdan,5 David Klyde,3 Piotr Kisza,3 Sharon F Gonzales,3 Andres M Salazar6 1Department of Surgery, St Joseph’s Regional Medical Center, Paterson, 2Department of Surgery, Rutgers New Jersey Medical School-University Hospital, 3Department of Interventional Radiology, Rutgers New Jersey Medical School-University Hospital, 4Department of Radiation Oncology, Beth Israel Medical Center, Newark, 5Department of Radiation Oncology, Clara Maas Hospital, Belleville, NJ, 6Oncovir, Washington, DC, USA Purpose: To determine the safety of an approach to immunologically enhance local treatment of hepatocellular cancer (HCC) by combining nonlethal radiation, local regional therapy with intratumoral injection, and systemic administration of a potent Toll-like receptor (TLR) immune adjuvant. Methods: Patients with HCC not eligible for liver transplant or surgery were subject to: 1) 3 fractions of 2-Gy focal nonlethal radiation to increase tumor antigen expression, 2) intra-/peri-tumoral (IT) injection of the TLR3 agonist, polyinosinic-polycytidylic acid polylysine carboxymethylcellulose (poly-ICLC), to induce an immunologic “danger” response in the tumor microenvironment with local regional therapy, and 3) systemic boosting of immunity with intramuscular poly-ICLC. Primary end points were safety and tolerability; secondary end points were progression-free survival (PFS) and overall survival (OS) at 6 months, 1 year, and 2 years. Results: Eighteen patients with HCC not eligible for surgery or liver transplant were treated. Aside from 1 embolization-related severe adverse event, all events were ≤grade II. PFS was 66% at 6 months, 39% at 12 months, and 28% at 24 months. Overall 1-year survival was 69%, and 2-year survival 38%. In patients 60 years (P

OBJECTIVE: To ascertain the value of relatively simple quantitative radiologic measurements after head injury. Despite major advances in neuroradiology, analysis and reporting of imaging studies is based primarily on individual subjective and local experience, rather than on reproducible, standardized parameters; reliance on newer technologies can improve care, but also raises diagnostic costs. DESIGN: Blinded, retrospective, quantitative assessment of computerized tomography studies done some 14 years post-injury. OUTCOME MEASURES: Frontal horn width (FHW); septum-caudate distance (SCD); temporal horn width (THW); interuncal distance (IUD); third ventricle width (3VW); ventricular score (VS); sulcal width (SW); gray-white matter discriminability (GWMD) and subjective assessment of atrophy (SAOA). RESULTS: Diffuse and frontal damage was noted in both closed (CHI) and penetrating (PHI) head injury groups. Enlargement of frontal lobe parameters (septum caudate distance and frontal horn width suggest frontal injury in both closed and penetrating traumatic brain injury (TBI). Temporal horn width and inter-uncal distance were related to VS, 3VW and FHW in closed, but not in penetrating head injury. CONCLUSIONS: Simple linear CSF space measurements are correlated with volumetric and parenchymal measures, and can represent valuable and reliable low-cost quantitative measures of long term brain damage after TBI. [ABSTRACT FROM AUTHOR]

Context: Traumatic brain injury (TBI) is a principal cause of death and disability in young adults. Rehabilitation for TBI has not received the same level of scientific scrutiny for efficacy and cost-efficiency that is expected in other medical fields.Objective: To evaluate the efficacy of inpatient cognitive rehabilitation for patients with TBI.Design and Setting: Single-center, parallel-group, randomized trial conducted from January 1992 through February 1997 at a US military medical referral center.Patients: One hundred twenty active-duty military personnel who had sustained a moderate-to-severe closed head injury, manifested by a Glasgow Coma Scale score of 13 or less, or posttraumatic amnesia lasting at least 24 hours, or focal cerebral contusion or hemorrhage on computed tomography or magnetic resonance imaging.Interventions: Patients were randomly assigned to an intensive, standardized, 8-week, in-hospital cognitive rehabilitation program (n=67) or a limited home rehabilitation program with weekly telephone support from a psychiatric nurse (n=53).Main Outcome Measures: Return to gainful employment and fitness for military duty at 1-year follow-up, compared by intervention group.Results: At 1-year follow-up, there was no significant difference between patients who had received the intensive in-hospital cognitive rehabilitation program vs the limited home rehabilitation program in return to employment (90% vs 94%, respectively; P=.51; difference, 4% [95% confidence interval ¿CI¿, -5% to 14%]) or fitness for duty (73% vs 66%, respectively; P=. 43; difference, 7% [95% CI, -10% to 24%]). There also were no significant differences in cognitive, behavioral, or quality-of-life measures. In a post-hoc subset analysis of patients who were unconscious for more than 1 hour (n = 75) following TBI, the in-hospital group had a greater return-to-duty rate (80% vs 58%; P=. 05).Conclusions: In this study, the overall benefit of in-hospital cognitive rehabilitation for patients with moderate-to-severe TBI was similar to that of home rehabilitation. These findings emphasize the importance of conducting randomized trials to evaluate TBI rehabilitation interventions. JAMA. 2000;283:3075-3081 [ABSTRACT FROM AUTHOR]

The Automated Neuropsychological Assessment Metrics (ANAM) is a computerized measure of processing speed, cognitive efficiency, and memory. This study describes performance and psychometric properties of ANAM in an active duty, healthy military sample (N = 2,371) composed primarily of young (18-46 years) adult males. Rarely have neuropsychological reference values for use with individuals in the military been derived from a large, active duty military population, and this is the first computerized neuropsychological test battery with military-specific reference values. Although these results do not provide demographically corrected, formal normative data, they provide reference points for neuropsychologists and other health care providers who are using ANAM data in research or clinical settings, with patients of comparable demographics to the present sample. [ABSTRACT FROM AUTHOR]

CD4 + T cells can either enhance or inhibit tumour immunity. Although regulatory T cells have long been known to impede antitumour responses 1-5 , other CD4 + T cells have recently been implicated in inhibiting this response 6,7 . Yet, the nature and function of the latter remain unclear. Here, using vaccines containing MHC class I (MHC-I) neoantigens (neoAgs) and different doses of tumour-derived MHC-II neoAgs, we discovered that whereas the inclusion of vaccines with low doses of MHC-II-restricted peptides (LDVax) promoted tumour rejection, vaccines containing high doses of the same MHC-II neoAgs (HDVax) inhibited rejection. Characterization of the inhibitory cells induced by HDVax identified them as type 1 regulatory T (Tr1) cells expressing IL-10, granzyme B, perforin, CCL5 and LILRB4. Tumour-specific Tr1 cells suppressed tumour rejection induced by anti-PD1, LDVax or adoptively transferred tumour-specific effector T cells. Mechanistically, HDVax-induced Tr1 cells selectively killed MHC-II tumour antigen-presenting type 1 conventional dendritic cells (cDC1s), leading to low numbers of cDC1s in tumours. We then documented modalities to overcome this inhibition, specifically via anti-LILRB4 blockade, using a CD8-directed IL-2 mutein, or targeted loss of cDC2/monocytes. Collectively, these data show that cytotoxic Tr1 cells, which maintain peripheral tolerance, also inhibit antitumour responses and thereby function to impede immune control of cancer., (© 2024. The Author(s).)

Neural circuits governing all motor behaviors in vertebrates rely on the proper development of motor neurons and their precise targeting of limb muscles. Transcription factors are essential for motor neuron development, regulating their specification, migration, and axonal targeting. While transcriptional regulation of the early stages of motor neuron specification is well-established, much less is known about the role of transcription factors in the later stages of maturation and terminal arborization. Defining the molecular mechanisms of these later stages is critical for elucidating how motor circuits are constructed. Here, we demonstrate that the transcription factor Nuclear Factor-IA (NFIA) is required for motor neuron positioning, axonal branching, and neuromuscular junction formation. Moreover, we find that NFIA is required for proper mitochondrial function and ATP production, providing a new and important link between transcription factors and metabolism during motor neuron development. Together, these findings underscore the critical role of NFIA in instructing the assembly of spinal circuits for movement.

Malaria caused byPlasmodium vivaxis a pressing public health problem in tropical and subtropical areas.However, little progress has been made toward developing a P. vivaxvaccine, with only three candidates being tested in clinical studies. We previously reported that one chimeric recombinant protein (PvCSP-All epitopes) containing the conserved C-terminus of the P. vivax Circumsporozoite Protein (PvCSP), the three variant repeat domains, and aToll-like receptor-3 agonist,Poly(I:C), as an adjuvant (polyinosinic-polycytidylic acid, a dsRNA analog mimicking viral RNA), elicits strong antibody-mediated immune responses in mice to each of the three allelic forms of PvCSP. In the present study, a pre-clinical safety evaluation was performed to identify potential local and systemic toxic effects of the PvCSP-All epitopes combined with the Poly-ICLC (Poly I:C plus poly-L-lysine, Hiltonol®) or Poly-ICLC when subcutaneously injected into C57BL/6 mice and New Zealand White Rabbits followed by a 21-day recovery period. Overall, all observations were considered non-adverse and were consistent with the expected inflammatory response and immune stimulation following vaccine administration. High levels of vaccine-induced specific antibodies were detected both in mice and rabbits. Furthermore, mice that received the vaccine formulation were protected after the challenge with Plasmodium berghei sporozoites expressing CSP repeats from P. vivax sporozoites (Pb/Pv-VK210). In conclusion, in these non-clinical models, repeated dose administrations of the PvCSP-All epitopes vaccine adjuvanted with a Poly-ICLC were immunogenic, safe, and well tolerated., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: R.F.M., A.M.G., and I.S.S. are co-inventors of the potential P. vivax vaccine evaluated in this study. The patent is under evaluation process, application number BR102022005915-2. A.M.S is President and CEO of Oncovir, Inc., which is developing poly-ICLC (Hiltonol) for clinical trials. O.C. and A.S work for Orygen® which licensed Hiltonol from Oncovir for Latin America., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Pulmonary hypertension (PH) is a known chronic condition that can lead to increased morbidity and mortality. Patients who develop PH due to thromboembolic disease are catalogued as chronic thromboembolic pulmonary hypertension (CTEPH). Anticoagulation remains a topic of interest in these patients. PUBMED, EMBASE and COCHRANE databases were searched by two investigators until December 2023. Information was analyzed for all-cause mortality, venous thromboembolism and major bleeding. We included a total of 10 studies in this meta-analysis. Our pooled analysis demonstrated that DOACs were non-inferior in all-cause mortality [OR 0.88, 95 % CI (0.48, 1.61)], venous thromboembolism [OR 1.00, 95 % CI (0.50, 1.98)] and major bleeding [OR 0.78, 95 % CI (0.43, 1.40)] when compared to VKAs. In conclusion, our meta-analysis supports the use of DOACs in patients with CTEPH. Further randomized trials are still needed to confirm our results in terms of safety and mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Central nervous system (CNS) WHO grade 2 low-grade glioma (LGG) patients are at high risk for recurrence and with unfavorable long-term prognosis due to the treatment resistance and malignant transformation to high-grade glioma. Considering the relatively intact systemic immunity and slow-growing nature, immunotherapy may offer an effective treatment option for LGG patients., Methods: We conducted a prospective, randomized pilot study to evaluate the safety and immunological response of the multipeptide IMA950 vaccine with agonistic anti-CD27 antibody, varlilumab, in CNS WHO grade 2 LGG patients. Patients were randomized to receive combination therapy with IMA950 + poly-ICLC and varlilumab (Arm 1) or IMA950 + poly-ICLC (Arm 2) before surgery, followed by adjuvant vaccines., Results: A total of 14 eligible patients were enrolled in the study. Four patients received pre-surgery vaccines but were excluded from postsurgery vaccines due to the high-grade diagnosis of the resected tumor. No regimen-limiting toxicity was observed. All patients demonstrated a significant increase of anti-IMA950 CD8+ T-cell response postvaccine in the peripheral blood, but no IMA950-reactive CD8+ T cells were detected in the resected tumor. Mass cytometry analyses revealed that adding varlilumab promoted T helper type 1 effector memory CD4+ and effector memory CD8+ T-cell differentiation in the PBMC but not in the tumor microenvironment., Conclusion: The combinational immunotherapy, including varlilumab, was well-tolerated and induced vaccine-reactive T-cell expansion in the peripheral blood but without a detectable response in the tumor. Further developments of strategies to overcome the blood-tumor barrier are warranted to improve the efficacy of immunotherapy for LGG patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aging is a risk factor for disease via increased susceptibility to infection, decreased ability to maintain homeostasis, inefficiency in combating stress, and decreased regenerative capacity. Multiple diseases, including urinary tract infection (UTI), are more prevalent with age; however, the mechanisms underlying the impact of aging on the urinary tract mucosa and the correlation between aging and disease remain poorly understood. Here, we show that, relative to young (8-12 weeks) mice, the urothelium of aged (18-24 months) female mice accumulates large lysosomes with reduced acid phosphatase activity and decreased overall autophagic flux in the aged urothelium, indicative of compromised cellular homeostasis. Aged bladders also exhibit basal accumulation of reactive oxygen species (ROS) and a dampened redox response, implying heightened oxidative stress. Furthermore, we identify a canonical senescence-associated secretory phenotype (SASP) in the aged urothelium, along with continuous NLRP3-inflammasome- and Gasdermin-D-dependent pyroptotic cell death. Consequently, aged mice chronically exfoliate urothelial cells, further exacerbating age-related urothelial dysfunction. Upon infection with uropathogenic E. coli, aged mice harbor increased bacterial reservoirs and are more prone to spontaneous recurrent UTI. Finally, we discover that treatment with D-mannose, a natural bioactive monosaccharide, rescues autophagy flux, reverses the SASP, and mitigates ROS and NLRP3/Gasdermin/interleukin (IL)-1β-driven pyroptotic epithelial cell shedding in aged mice. Collectively, our results demonstrate that normal aging affects bladder physiology, with aging alone increasing baseline cellular stress and susceptibility to infection, and suggest that mannose supplementation could serve as a senotherapeutic to counter age-associated urothelial dysfunction., Competing Interests: Declaration of interests I.U.M. serves on the scientific advisory board of Luca Biologics., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Tricuspid valve infective endocarditis (TVIE), often associated with vegetation in people who inject drugs, has introduced a less invasive option for vegetation removal: transcatheter vacuum-assisted mass extraction (TVME). This technique is emerging as an alternative to standard surgical debridement (SD) and valve repair. However, the comparative effectiveness of TVME versus SD in treating TVIE has yet to be investigated. A comprehensive systematic literature search was performed on PubMed, Embase, and Cochrane to identify all relevant studies comparing TVME with SD in patients with TVIE. The search covered studies from inception up to August 15, 2023. For data analysis, Review Manager (RevMan) 5.4 software was employed, using a random-effects model to calculate risk ratios (RRs), mean differences, and 95% confidence intervals (CIs). Five studies included a total of 431 patients (244 in the TVME arm and 187 in the SD arm). In-hospital mortality (p = 0.72), procedural mortality (p = 0.77), 30-day mortality (p = 0.25), and 1-year mortality (p = 0.44) insignificantly favored SD over TVME. Overall mortality across the 5 studies insignificantly favored TVME over SD (RR = 0.66, 95% CI 0.31 to 1.39, p = 0.27, I 2  = 57%). When addressing heterogeneity by excluding 1 study, no statistical significance in the difference between the 2 arms regarding overall mortality was observed (RR 0.99, 95% CI 0.60 to 1.63, p = 0.97, I 2  = 0%). This meta-analysis of the 5 observational studies found no significant difference in overall mortality between TVME and SD for the treatment of TVIE. However, prospective randomized controlled trials are necessary to further understand and compare the outcomes of these 2 approaches., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Current evidence shows higher production of cytokines and antibodies against severe acute respiratory coronavirus 2 (SARS-CoV-2) in severe and critical cases of Coronavirus Disease 2019 (COVID-19) in comparison with patients with moderate or mild disease. A recent hypothesis proposes an important role of genotoxicity and cytotoxicity in the induction of the cytokine storm observed in some patients at later stages of the disease. Interestingly, in this study, we report significantly higher levels of interleukin (IL)-1 β , IL-6, MCP-1, and IL-4 cytokines in mild COVID-19 patients versus severe cases, as well as a high frequency of karyorrhexis (median [Me] = 364 vs. 20 cells) and karyolysis (Me = 266 vs. 52 cells) in the mucosal epithelial cells of both groups of patients compared with uninfected individuals. Although we observed higher levels of anti-SARS-CoV-2 IgM and IgG antibodies in COVID-19 patients, IgM antibodies were significantly higher only in mild cases, for the N and the S viral antigens. High levels of IgG antibodies were observed in both mild and severe cases. Our results showed elevated concentrations of proinflammatory and anti-inflammatory cytokines in mild cases, which may reflect an active innate immune response and could be related to the higher IgM and IgG antibody levels found in those patients. In addition, we found that SARS-CoV-2 infection induces cytotoxic damage in the oral mucosa, highlighting the importance of studying the genotoxic and cytotoxic events induced by infection and its role in the pathophysiology of COVID-19.

Pulmonary hypertension (PH) is a progressive disease with a high morbidity and mortality. The treatment is based on the type of PH. Prognosis still remains poor despite the use of different medications. Pulmonary artery denervation (PADN) has been studied as a novel therapeutic option in these patients. PUBMED, EMBASE and COCHRANE databases were searched by 2 investigators until January 2023. Information was analyzed for the following outcomes: 6-minute walk distance (6MWD), mean pulmonary artery pressure, pulmonary vascular resistance and cardiac output. Subgroup analysis comparing pre and post PADN in different PH groups was done. Statistical analysis was performed with the Review Manager version 5.4. This meta- analysis included 6 controlled trials and 6 single-arm prospective studies with a total of 616 patients. Our pooled analysis showed a significant reduction in mean pulmonary artery pressure [WMD -6.51, 95% CI (-9.87, -3.15), p = 0.0001], pulmonary vascular resistance [WMD -3.69, 95% CI (-6.74, -0.64), p = 0.02] and increased cardiac output [WMD -0.37, 95% CI (0.08, 0.65), p = 0.01]. Subgroup analysis pre and post PADN demonstrated a significant improvement in 6MWD in the WHO group 1 [WMD 99.53, 95% CI (19.60, 179.47), p = 0.01], group 2 [WMD: 69.96, 95% CI (36.40, 103.51), p = < 0.0001] and group 4 [WMD: 99.54, 95% CI (21.80, 177.28), p = 0.01]. This meta-analysis supports PADN as a therapeutic option for patients with PH, regardless of group class. Further randomized trials are still needed to evaluate safety and efficacy., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Arsenic is associated with the development of breast cancer. However, the molecular mechanisms of arsenic induction of breast cancer are not fully defined. Interaction with zinc finger (ZnF) motifs in proteins is one of the proposed mechanisms of arsenic toxicity. GATA3 is a transcription factor that regulates the transcription of genes associated with cell proliferation, cell differentiation and the epithelial-mesenchymal transition (EMT) in mammary luminal cells. Given that GATA3 possesses two ZnF motifs essential for the function of this protein and that arsenic could alter the function of GATA3 through interaction with these structural motifs, we evaluated the effect of sodium arsenite (NaAsO 2 ) on GATA3 function and its relevance in the development of arsenic-induced breast cancer. Breast cell lines derived from normal mammary epithelium (MCF-10A), hormone receptor-positive and hormone receptor negative breast cancer cells (T-47D and MDA-MB-453, respectively) were used. We observed a reduction on GATA3 protein levels at non-cytotoxic concentrations of NaAsO 2 in MCF-10A and T-47D, but not in MDA-MB-453 cells. This reduction was associated with an increase in cell proliferation and cell migration in MCF-10A, but not in T-47D or MDA-MB-453 cells. The evaluation of cell proliferation and EMT markers indicate that the reduction on GATA3 protein levels by arsenic, disrupts the function of this transcription factor. Our data indicate that GATA3 is a tumor suppressor in the normal mammary epithelium and that arsenic could act as an initiator of breast cancer by disrupting the function of GATA3., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Recent studies have revealed that a combination of zero-valent iron (ZVI) and pyrite (FeS 2 ) can effectively remove (Cr(VI)) from water, but the reasons behind this synergistic effect are still unclear. Our batch experiments showed that dissolved oxygen (DO) is a critical factor in the improved removal of Cr(VI) by ZVI and pyrite. When 0.08 g/L pyrite was combined with 0.5 g/L ZVI in the presence of DO, total Cr was reduced from 10 mg/L to 0.02 mg/L within 6 h. Conversely, in the absence of DO, total Cr was only reduced to 5.6 mg/L. DO oxidation of pyrite produced protons that promote ZVI corrosion, and mixing pyrite with water creates dissolved sulfide, which also contributes to the improved removal of Cr(VI). Electron microscopy images and X-ray absorption near edge structure analyses revealed that the presence of dissolved sulfide led to the formation of ferrous sulfide precipitates on the ZVI surface, preventing the formation of a passivating layer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Plant microbiomes are pivotal for healthy plant physiological development. Microbes live in complex co-association with plant hosts, and interactions within these microbial communities vary with plant genotype, plant compartment, phenological stage, and soil properties, among others. Plant microbiomes also harbor a substantial and diverse pool of mobile genes encoded on plasmids. Several plasmid functions attributed to plant-associated bacteria are relatively poorly understood. Additionally, the role of plasmids in disseminating genetic traits within plant compartments is not well known. Here, we present the current knowledge on the occurrence, diversity, function, and transfer of plasmids in plant microbiomes, emphasizing the factors that could modulate gene transfer in-planta. We also describe the role of the plant microbiome as a plasmid reservoir and the dissemination of its genetic material. We include a brief discussion on the current methodological limitations in studying plasmid transfer within plant microbiomes. This information could be useful to elucidate the dynamics of the bacterial gene pools, the adaptations different organisms have made, and variations in bacterial populations that might have never been described before, particularly in complex microbial communities associated with plants in natural and anthropogenic impacted environments., Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Immunization with the Amastigote Surface Protein-2 (ASP-2) and Trans-sialidase (TS) antigens either in the form of recombinant protein, encoded in plasmids or human adenovirus 5 (hAd5) confers robust protection against various lineages of Trypanosoma cruzi. Herein we generated a chimeric protein containing the most immunogenic regions for T and B cells from TS and ASP-2 (TRASP) and evaluated its immunogenicity in comparison with our standard protocol of heterologous prime-boost using plasmids and hAd5. Mice immunized with TRASP protein associated to Poly-ICLC (Hiltonol) were highly resistant to challenge with T. cruzi, showing a large decrease in tissue parasitism, parasitemia and no lethality. This protection lasted for at least 3 months after the last boost of immunization, being equivalent to the protection induced by DNA/hAd5 protocol. TRASP induced high levels of T. cruzi-specific antibodies and IFNγ-producing T cells and protection was primarily mediated by CD8 + T cells and IFN-γ. We also evaluated the toxicity, immunogenicity, and efficacy of TRASP and DNA/hAd5 formulations in dogs. Mild collateral effects were detected at the site of vaccine inoculation. While the chimeric protein associated with Poly-ICLC induced high levels of antibodies and CD4 + T cell responses, the DNA/hAd5 induced no antibodies, but a strong CD8 + T cell response. Immunization with either vaccine protected dogs against challenge with T. cruzi. Despite the similar efficacy, we conclude that moving ahead with TRASP together with Hiltonol is advantageous over the DNA/hAd5 vaccine due to pre-existing immunity to the adenovirus vector, as well as the cost-benefit for development and large-scale production., (© 2023. The Author(s).)

Bisphenol A (BPA) is a ubiquitous synthetic compound used as a monomer in the production of polycarbonate plastics and epoxy resins. Even at low doses, BPA has been associated with the molecular progression of diseases such as obesity, metabolic syndrome, and hormone-regulated cancers due to its activity as an endocrine-disrupting chemical (EDC). Consequently, the use of BPA has been regulated worldwide by different health agencies. BPA structural analogs such as bisphenol S and bisphenol F (BPS and BPF) have emerged as industrial alternatives, but their biological activity in the molecular progression of cancer remains unclear. Prostate cancer (PCa) is a hormone-dependent cancer, and the role of BPA structural analogs in PCa progression is still undescribed. In this work, we use an in vitro model to characterize the transcriptomic effect of low-concentration exposure to bisphenol A, S, or F in the two main stages of the disease: androgen dependency (LNCaP) and resistance (PC-3). Our findings demonstrated that the low concentration exposure to each bisphenol induced a differential effect over PCa cell lines, which marks the relevance of studying the effect of EDC compounds through all the stages of the disease.

Introduction: Insulin resistance in muscle can originate from a sedentary lifestyle, hypercaloric diets, or exposure to endocrine-disrupting pollutants such as arsenic. In skeletal muscle, insulin stimulates glucose uptake by translocating GLUT4 to the sarcolemma. This study aimed to evaluate the alterations induced by sucrose and arsenic exposure in vivo on the pathways involved in insulinstimulated GLUT4 translocation in the quadriceps and gastrocnemius muscles., Methods: Male Wistar rats were treated with 20% sucrose (S), 50 ppm sodium arsenite (A), or both (A+S) in drinking water for 8 weeks. We conducted an intraperitoneal insulin tolerance (ITT) test on the seventh week of treatment. The quadriceps and gastrocnemius muscles were obtained after overnight fasting or 30 min after intraperitoneal insulin injection. We assessed changes in GLUT4 translocation to the sarcolemma by cell fractionation and abundance of the proteins involved in GLUT4 translocation by Western blot., Results: Male rats consuming S and A+S gained more weight than control and Atreated animals. Rats consuming S, A, and A+S developed insulin resistance assessed through ITT. Neither treatments nor insulin stimulation in the quadriceps produced changes in GLUT4 levels in the sarcolemma and Akt phosphorylation. Conversely, A and A+S decreased protein expression of Tether containing UBX domain for GLUT4 (TUG), and A alone increased calpain-10 expression. All treatments reduced this muscle's protein levels of VAMP2. Conversely, S and A treatment increased basal GLUT4 levels in the sarcolemma of the gastrocnemius, while all treatments inhibited insulin-induced GLUT4 translocation. These effects correlated with lower basal levels of TUG and impaired insulin-stimulated TUG proteolysis. Moreover, animals treated with S had reduced calpain-10 protein levels in this muscle, while A and A+S inhibited insulin-induced Akt phosphorylation., Conclusion: Arsenic and sucrose induce systemic insulin resistance due to defects in GLUT4 translocation induced by insulin. These defects depend on which muscle is being analyzed, in the quadriceps there were defects in GLUT4 retention and docking while in the gastrocnemius the Akt pathway was impacted by arsenic and the proteolytic pathway was impaired by arsenic and sucrose., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pánico, Velasco, Salazar, Ostrosky-Wegman and Hiriart.)

A major challenge in the biology of aging is to understand how specific age-onset pathologies relate to the overall health of the organism. The integrity of the intestinal epithelium is essential for the wellbeing of the organism throughout life. In recent years, intestinal barrier dysfunction has emerged as an evolutionarily conserved feature of aged organisms, as reported in worms, flies, fish, rodents and primates. Moreover, age-onset intestinal barrier dysfunction has been linked to microbial alterations, elevated immune responses, metabolic alterations, systemic health decline and mortality. Here, we provide an overview of these findings. We discuss early work in the Drosophila model that sets the stage for examining the relationship between intestinal barrier integrity and systemic aging, then delve into research in other organisms. An emerging concept, supported by studies in both Drosophila and mice, is that directly targeting intestinal barrier integrity is sufficient to promote longevity. A better understanding of the causes and consequences of age-onset intestinal barrier dysfunction has significant relevance to the development of interventions to promote healthy aging., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Objective: The objective of this study was to determine the difference in tolerance for sodium glucose cotransporter 2 inhibitors between patients with heart failure classified as frail according to the FRAIL questionnaire, compared to those with heart failure without frailty., Methods: A prospective cohort study was performed between 2021 and 2022 that included patients with heart failure at a heart failure unit in Bogotá who were being treated with a sodium glucose cotransporter 2 inhibitor. Clinical and laboratory data were collected during an initial visit and 12-48 weeks after that. The FRAIL questionnaire was applied to all participants through a phone call or during the follow-up visit. The primary outcome was the adverse effect rate and as a secondary outcome we compared the estimated glomerular filtration rate change between frail and non-frail patients., Results: One hundred and twelve patients were included in the final analysis. Frail patients had a more than twice increased risk of having adverse effects (95% confidence interval 1.5-3.9). Age was also a risk factor for the appearance of these.  The estimated glomerular filtration rate decrease was inversely correlated with the age, left ventricular ejection fraction, and renal function before the use of sodium glucose cotransporter 2 inhibitors., Conclusions: When prescribing in heart failure, it is important to remember that frail patients are more likely to have adverse effects with the use of sodium glucose cotransporter 2 inhibitors, of which the most common are those related to osmotic diuresis. Nonetheless, these do not appear to increase the risk of discontinuation or abandonment of therapy in this population., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

A global increase in older individuals creates an increasing demand to understand numerous healthcare challenges related to aging. This population is subject to changes in tissue physiology and the immune response network. Older individuals are particularly susceptible to infectious diseases, with one of the most common being urinary tract infections (UTIs). Postmenopausal and older women have the highest risk of recurrent UTIs (rUTIs); however, why rUTIs become more frequent after menopause and during old age is incompletely understood. This increased susceptibility and severity among older individuals may involve functional changes to the immune system with age. Aging also has substantial effects on the epithelium and the immune system that led to impaired protection against pathogens, yet heightened and prolonged inflammation. How the immune system and its responses to infection changes within the bladder mucosa during aging has largely remained poorly understood. In this review, we highlight our understanding of bladder innate and adaptive immunity and the impact of aging and hormones and hormone therapy on bladder epithelial homeostasis and immunity. In particular, we elaborate on how the cellular and molecular immune landscape within the bladder can be altered during aging as aged mice develop bladder tertiary lymphoid tissues (bTLT), which are absent in young mice leading to profound age-associated change to the immune landscape in bladders that might drive the significant increase in UTI susceptibility. Knowledge of host factors that prevent or promote infection can lead to targeted treatment and prevention regimens. This review also identifies unique host factors to consider in the older, female host for improving rUTI treatment and prevention by dissecting the age-associated alteration of the bladder mucosal immune system., Competing Interests: Declaration of competing interest IUM serves on the scientific advisory board of Luca Biologics., (Copyright © 2022. Published by Elsevier Inc.)

LGTBQ+ youth in foster care need unique support and acceptance; however, few case workers and caregivers receive specialized training. To address this, the Connecting: Sexual Orientation and Gender Identity Expression (SOGIE) eLearning was developed. This evaluation assesses whether attitudes and behavioral intentions regarding LGBTQ+ youth improved as a result of this training. Caregivers and child welfare professionals showed growth in many areas, including how important they felt it was to learn strategies and skills to support LGBTQ+ youth, as well as their confidence to care for LGBTQ+ youth. The Connecting: SOGIE eLearning is a promising tool for child welfare systems., Competing Interests: Declaration of Interest: The authors have no conflicts of interest to report.

Purpose: Astrocytomas are a type of malignant brain tumor with an unfavorable clinical course. The impact of AGT and MGMT somatic variants in the prognosis of astrocytoma is unknown, and it is controversial for TP53. Moreover, there is a lack of knowledge regarding the molecular characteristics of astrocytomas in Mexican patients., Methods: We studied 48 Mexican patients, men and women, with astrocytoma (discovery cohort). We performed DNA deep sequencing in tumor samples, targeting AGT, MGMT and TP53, and we studied MGMT gene promoter methylation status. Then we compared our findings to a cohort which included data from patients with astrocytoma from The Cancer Genome Atlas (validation cohort)., Results: In the discovery cohort, we found a higher number of somatic variants in AGT and MGMT than in the validation cohort (10.4% vs < 1%, p < 0.001), and, in both cohorts, we observed only women carried variants AGT variants. We also found that the presence of either MGMT variant or promoter methylation was associated to better survival and response to chemotherapy, and, in conjunction with TP53 variants, to progression-free survival., Conclusions: The occurrence of AGT variants only in women expands our knowledge about the molecular differences in astrocytoma between men and women. The increased prevalence of AGT and MGMT variants in the discovery cohort also points towards possible distinctions in the molecular landscape of astrocytoma among populations. Our findings warrant further study., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Metabolic syndrome (MS) and obesity have become a worldwide epidemic with an alarming prevalence in women of reproductive age. Maternal metabolic condition is considered a risk factor for adverse birth outcomes and long-term MS. In this study, we developed a rabbit model of maternal overnutrition via the chronic intake of a high-fat and carbohydrate diet (HFCD), and we determined the effects of this diet on maternal metabolism and offspring metabolic set points and temporal metabolic regulation in adult life. Before and during pregnancy, the female rabbits that consumed the HFCD exhibited significant changes in body weight, serum levels of analytes associated with carbohydrate and lipid metabolism, levels of liver and kidney damage markers, and liver histology. Our data suggest that rabbits are a valuable model for studying the development of MS associated with the chronic intake of unbalanced diets and fetal metabolic programming. Furthermore, the offspring of overnourished dams exhibited considerable changes in 24-h serum metabolite profiles in adulthood, with notable sexual dimorphism. These data suggest that maternal nutritional conditions due to the chronic intake of an HFCD adversely impact key elements related to the development of circadian rhythmicity in offspring. NEW & NOTEWORTHY Maternal overnutrition previous and during pregnancy leads to long-term changes in the 24-h regulation and setpoint of metabolic profiles of the offspring.

Objectives: This study: 1) measures the effect of sample thickness and high irradiance on the depth-dependent time delay before photopolymerization reaction onset; 2) determines if exposure reciprocity exists; 3) measures the conversion rate at four irradiance levels; 4) determines the time, t 0 , at which the maximum DC rate is reached for two bulk-fill and one conventional posterior resin-based composites (RBCs)., Methods: Tetric PowerFill IVA shade (Ivoclar Vivadent) and Aura bulk-fill ultra universal restorative (SDI), and one conventional posterior resin-based composite (RBC), Heliomolar A3 (Ivoclar Vivadent), that were either 0.2 mm, 2 mm, or 4 mm thick were photocured using a modified Bluephase G4 (Ivoclar Vivadent) light-curing unit (LCU) that delivered a single emission band (wavelength centered at 449 nm). The same radiant exposure of 24 J/cm 2 was delivered at irradiances ranging from 0.5 to 3 W/cm 2 by adjusting the exposure time. PowerFill was also photocured for 3 s or 6 s using a Bluephase PowerCure LCU (Ivoclar Vivadent) on the 3 s mode setting. The degree of conversion (DC) was measured in real-time at a high temporal resolution at 30 °C using Attenuated Total Reflection (ATR) FTIR spectroscopy with a sampling rate of 13 DC data points per second. The DC data were analyzed using a phenomenological autocatalytic model. The RBC viscosity was measured at 21 °C and 30 °C. Light transmission through the RBC samples at 22 °C was monitored with time to calculate the extinction coefficients of the RBCs., Results: The time delay before photopolymerization started increased as the RBC thickness increased and the irradiance decreased. An autocatalytic model described the DC data. The time t 0 was less than 77 ms for the 0.2 mm thick samples of PowerFill irradiated using the highest irradiance of 3 W/cm 2 . Among the three RBCs for each sample thickness and irradiance level, the PowerFill had the smallest time t 0 . There was a time delay of 0.59 s and 1.25 s before the DC started to increase at the bottom of 4 mm thick samples for the PowerFill and Aura, respectively, when an irradiance of 1 W/cm 2 was delivered. The time delay increased to 3.65 s for the Aura when an irradiance of 0.5 W/cm 2 was delivered. The extinction coefficients near 449 nm were 0.78 mm -1 , 0.76 mm -1 , and 1.55 mm -1 during the first 2 s after the start of photocuring of PowerFill, Aura, and Heliomolar, respectively. Only PowerFill followed exposure reciprocity. At T = 30 °C, the viscosity was 3400, 17000, and 5200 Paˑs for PowerFill, Aura, and Heliomolar, respectively., Significance: The time delay between when photopolymerization starts at the top and bottom of 2- or 4-mm thick RBC restorations may affect the structural integrity of the bond between the tooth and the bottom of the restoration. Only PowerFill followed exposure reciprocity between irradiance levels of 0.5 to 3 W/cm 2 . Exposure reciprocity did not occur for Aura or Heliomolar, neither of which are optimized for short light exposure or high irradiance conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Transcatheter mitral valve-in-valve (MViV) replacement has emerged as an alternative to redo surgical mitral valve replacement (redo-SMVR) in patients with failed mitral bioprostheses deemed to be at a high surgical risk. The aim of this analysis was to compare the outcomes of MViV replacement with those of redo-SMVR in patients with a failed bioprosthetic mitral valve., Methods: We performed a study-level meta-analysis that compared MViV replacement with redo-SMVR in patients with failed mitral bioprostheses. Seven observational studies, with a total of 5083 patients, were included (1138 patients [22.4%] in the MViV replacement arm). The primary focus was all-cause mortality. Additional outcomes included major bleeding, stroke, vascular complications, and mean mitral valve gradient at follow-up., Results: The in-hospital mortality was lower in patients who underwent MViV replacement than in those who underwent redo-SMVR (odds ratio [OR], 0.64; 95% CI, 0.53-0.78; P = .0023). The short-term mortality (<1 year) was numerically lower in the MViV replacement group (OR, 0.45; 95% CI, 0.18-1.13; P  = .069). At 1 year, the risk of mortality was similar in the 2 groups (OR, 0.99; 95% CI, 0.69-1.40; P = .906), and at midterm follow-up (≥1 year), there was a numerically higher risk of mortality in the MViV replacement group (OR, 1.51; 95% CI, 1.00-2.29; P = .051). The risk of major bleeding was significantly lower in the MViV replacement group (OR, 0.23; 95% CI, 0.10-0.56; P = .01). Additionally, stroke and vascular complications were similar between the 2 groups., Conclusions: The in-hospital mortality was lower in the MViV replacement group than in the redo-SMVR group. There were no differences in mortality at short-term (<1 year), 1-year, or midterm (≥1 year) follow-ups., (© 2022 The Authors.)

The COVID-19 pandemic impacted people's lives all over the world, requiring health and safety measures intended to stop the virus from spreading. This study explores whether an unintended consequence of these measures is a new form of ageism. We explore, using qualitative methods, the experiences of older adults living through the pandemic in the United Kingdom and Colombia. Although there were some small differences between countries, for the most part, the experiences were similar. We found that older adults reported that they were seen as a homogenous group and experienced both benevolent and hostile ageism and a loss of autonomy as a consequence of COVID-19 protection measures. Participants from both countries expressed anger and frustration, and increased anxiety, and felt that their individuality was ignored. We recommend that policy-makers, the media, and wider society consider the impact of such health and safety measures on older adults in preparing for future pandemics and health challenges., Competing Interests: The authors declare that there are no conflicts of interest within this work., (© 2022 The Authors. Journal of Social Issues published by Wiley Periodicals LLC on behalf of Society for the Psychological Study of Social Issues.)

The gut microbiome is a critical modulator of systemic physiology, including infectious disease susceptibility. Although this niche is a reservoir for uropathogenic Escherichia coli, knowledge of its role in urinary tract infections (UTIs) is limited. We discuss two recent studies, Thänert et al. (2022) and Worby et al. (2022), that interrogate the roles of the gut-bladder axis in UTIs., Competing Interests: Declaration of interests I.U.M. serves on the scientific advisory board of Luca Biologics., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The recommendations of the current guidelines are based on low quality evidence. Periodic updating is required, taking recent evidence into consideration., Objective: To synthesise the best available clinical evidence on the efficacy and safety of second-generation antidepressants and antipsychotics in patients with anorexia nervosa., Methods: Systematic review (CRD42020150577). We searched PubMed, SCOPUS, Ovid(Cochrane), EMBASE and LILACS for randomised clinical trials performed in patients with anorexia nervosa that evaluated the use of second-generation antipsychotics or oral antidepressants, at any dose and for any length of time, in outpatient and/or hospital treatment, taking weight (body mass index), psychopathological entities and safety as results., Results: Five studies were included, with four assessed as having a high risk of bias. The evidence indicates that patients receiving treatment with olanzapine or fluoxetine tend to stay in treatment programmes for longer. Olanzapine showed favourable results (one study) in terms of weight gain, but did not show the same results in psychopathology, where the evidence is contradictory., Conclusions: In accordance with previous reviews, our work allows us to conclude that there is contradictory information on the efficacy of psychotropic drugs in the treatment of anorexia nervosa. Future work should focus on developing clinical trials of high methodological quality., (Copyright © 2021 Asociación Colombiana de Psiquiatría. Published by Elsevier España, S.L.U. All rights reserved.)

Exposure to arsenic in drinking water is a worldwide health problem. This pollutant is associated with increased risk of developing chronic diseases, including metabolic diseases. Metabolic syndrome (MS) is a complex pathology that results from the interaction between environmental and genetic factors. This condition increases the risk of developing type 2 diabetes, cardiovascular diseases, and cancer. The MS includes at least three of the following signs, central obesity, impaired fasting glucose, insulin resistance, dyslipidemias, and hypertension. Here, we summarize the existing evidence of the multiple mechanisms triggered by arsenic to developing the cardinal signs of MS, showing that this pollutant could contribute to the multifactorial origin of this pathology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pánico, Velasco, Salazar, Picones, Ortiz-Huidobro, Guerrero-Palomo, Salgado-Bernabé, Ostrosky-Wegman and Hiriart.)

Calpain-10 (CAPN10) belongs to the calpain superfamily. Genetic polymorphisms of the CAPN10 gene are associated with susceptibility to develop type 2 diabetes mellitus. Although the role of CAPN10 in the pathophysiology of diabetes has been extensively investigated, its biochemical properties are largely unknown. In this report, we made the surprising discovery that CAPN10 cDNA transcripts are subject to cryptic splicing and unexpected protein products were expressed. The same set of splicing products was reproducibly detected in four types of cultured cells including the primary culture of mouse myoblast. At least, one of the products was identical to a natural splicing variant. Sequence analysis of the splicing potential of CAPN10 cDNA, together with mutagenesis studies, resulted in the identification of a powerful splicing acceptor site at the junction of the sequences encoded by exons 9 and 10. We successfully extended the analysis to create expression construct resistant to splicing for both human and mouse CAPN10. The construct allowed us to analyze two major CAPN10 isoforms and reveal their difference in substrate proteolysis and potential cell functions. These results demonstrate that proteins produced from cDNA do not necessarily reflect the original nucleotide sequence. We provide insight into the property of recombinantly expressed CAPN10 proteins in cultured cells circumventing unexpected protein products., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

BACKGROUNDLong-term prognosis of WHO grade II low-grade gliomas (LGGs) is poor, with a high risk of recurrence and malignant transformation into high-grade gliomas. Given the relatively intact immune system of patients with LGGs and the slow tumor growth rate, vaccines are an attractive treatment strategy.METHODSWe conducted a pilot study to evaluate the safety and immunological effects of vaccination with GBM6-AD, lysate of an allogeneic glioblastoma stem cell line, with poly-ICLC in patients with LGGs. Patients were randomized to receive the vaccines before surgery (arm 1) or not (arm 2) and all patients received adjuvant vaccines. Coprimary outcomes were to evaluate safety and immune response in the tumor.RESULTSA total of 17 eligible patients were enrolled - 9 in arm 1 and 8 in arm 2. This regimen was well tolerated with no regimen-limiting toxicity. Neoadjuvant vaccination induced upregulation of type-1 cytokines and chemokines and increased activated CD8+ T cells in peripheral blood. Single-cell RNA/T cell receptor sequencing detected CD8+ T cell clones that expanded with effector phenotype and migrated into the tumor microenvironment (TME) in response to neoadjuvant vaccination. Mass cytometric analyses detected increased tissue resident-like CD8+ T cells with effector memory phenotype in the TME after the neoadjuvant vaccination.CONCLUSIONThe regimen induced effector CD8+ T cell response in peripheral blood and enabled vaccine-reactive CD8+ T cells to migrate into the TME. Further refinements of the regimen may have to be integrated into future strategies.TRIAL REGISTRATIONClinicalTrials.gov NCT02549833.FUNDINGNIH (1R35NS105068, 1R21CA233856), Dabbiere Foundation, Parker Institute for Cancer Immunotherapy, and Daiichi Sankyo Foundation of Life Science.

Distal radial artery access (DRA) is recommended as the preferred approach over the traditional proximal radial artery access (TRA) for coronary procedures; however, there are limited randomized controlled trials (RCTs) that compared the 2. We conducted an updated meta-analysis of all RCTs from inception to July 26, 2021, that compared DRA versus TRA in patients who underwent coronary procedures. The statistical analysis was performed using a random effect model to calculate risk ratios (RRs) with 95% confidence intervals (CIs). A total of 5 RCTs were included with a total of 1,005 patients. A pooled analysis of the data showed that the rate of successful cannulation was similar between the 2 arms (RR 0.85, 95% CI 0.68 to 1.07, p = 0.16, I 2  = 94%). The rate of radial artery spasm significantly favored the DRA arm as compared with TRA (RR 0.51, 95% CI 0.34 to 0.75, p = 0.0007, I 2  = 0%). Significantly more patients from the DRA arm required alternative arterial access. Moreover, the DRA group had an insignificantly decreased rates of radial artery occlusion (RR 0.24, 95% CI 0.05 to 1.20, p = 0.08, I 2  = 46%) and early discharge after transradial stenting of coronary arteries access-site hematomas (RR 0.52, 95% CI 0.18 to 1.149, p = 0.22, I 2  = 0%). The mean time for hemostasis was significantly shorter in the DRA arm (mean difference -6.64, 95% CI -10.37 to -2.90, p = 0.0005, I 2  = 88%). In conclusion, DRA should be considered as a viable, effective, and safe arterial access method for patients who underwent coronary procedures., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)