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Samuel Romano-Feinholz,1,* Alelí Salazar-Ramiro,2,* Emilio Muñoz-Sandoval,3 Roxana Magaña-Maldonado,2 Norma Hernández Pedro,4 Edgar Rangel López,5 Alberto González Aguilar,1 Aurora Sánchez García,6 Julio Sotelo,2 Verónica Pérez de la Cruz,7 Benjamín Pineda2 1Division of Neurosurgery, 2Neuroimmunology and Neuro-oncology Unit, National Institute of Neurology and Neurosurgery (NINN), Mexico City, 3Division of Advanced Materials, IPICYT, San Luis Potosí, 4Experimental Oncology Laboratory, National Cancer Institute of Mexico, 5Excitatory Aminoacids Laboratory, 6Pathology Laboratory, 7Neurochemistry Unit, National Institute of Neurology and Neurosurgery (NINN), Mexico City, Mexico *These authors contributed equally to this work Abstract: Despite multiple advances in the diagnosis of brain tumors, there is no effective treatment for glioblastoma. Multiwalled carbon nanotubes (MWCNTs), which were previously used as a diagnostic and drug delivery tool, have now been explored as a possible therapy against neoplasms. However, although the toxicity profile of nanotubes is dependent on the physicochemical characteristics of specific particles, there are no studies exploring how the effectivity of the carbon nanotubes (CNTs) is affected by different methods of production. In this study, we characterize the structure and biocompatibility of four different types of MWCNTs in rat astrocytes and in RG2 glioma cells as well as the induction of cell lysis and possible additive effect of the combination of MWCNTs with temozolomide. We used undoped MWCNTs (labeled simply as MWCNTs) and nitrogen-doped MWCNTs (labeled as N-MWCNTs). The average diameter of both pristine MWCNTs and pristine N-MWCNTs was ~22 and ~35 nm, respectively. In vitro and in vivo results suggested that these CNTs can be used as adjuvant therapy along with the standard treatment to increase the survival of rats implanted with malignant glioma. Keywords: carbon nanotubes, glioblastoma therapy, temozolomide, malignant glioma

Este artículo muestra cómo se aplicó la estrategia didáctica denominada Praccis, a través de una cartilla didáctica titulada "El Zooplancton de la Ciénaga de Ayapel y su papel en la Ecología de este Ecosistema", como producto de la investigación denominada "Dinámica espacial y temporal del Zooplancton asociado a las macrófitas en el complejo cenagoso de Ayapel, Córdoba, Colombia". La aplicación de dicha estrategia se llevó a cabo como una prueba piloto y se recolectó la información a través de diferentes textos, a saber: dos diarios de campo, cinco cartillas diligenciadas, 52 encuestas tramitadas por la comunidad no científica y una conversación con la coordinadora del taller. Estos textos se leyeron desde una perspectiva hermenéutica: a partir de los prejuicios, se reflexionó, analizó, comparó, comprendió e interpretó las concurrencias y las ocurrencias de los participantes en el evento para encontrar unidades de significación con el fin de establecer la unidad de sentido, es decir, avalar la estrategia didáctica para facilitar la circulación del conocimiento científico en comunidades no científicas y ser capaz de generar cultura, en este caso, alrededor del objeto agua.

The identity of the natural landscape is subordinate to the natural elements; whereas the cultural identity is constructed from the human action on original means. The work has its main objetive in analyze the paper that plays the landscape and the cultural identity in the promotion of the tourist image of Isla Margarita (Venezuela). The results indicate that the efforts have concentrated in the advantage of the product Sun and Beach; nevertheless the visitors emphasize the natural physical attributes, the activities associated to those attributes and the social component. However, the patrimonial resources are not valued, because they are not recognized like part of the landscape, which demonstrates a deficient policy of promotion of these attributes.

Background: Tenuous blood supply carries a risk of wound-healing problems and subsequent infection following total knee arthroplasty (TKA). This risk may be increased by the presence of previous incisions. Performing a sham incision procedure allows for detection of wound-healing problems prior to performing TKA. The purpose of this retrospective case series is to describe the indications for and technique of a sham incision procedure in patients with previous knee incisions who underwent TKA following this procedure and to report the clinical outcomes observed in these patients following further surgery., Methods: Patients who had prior knee incisions, had undergone a sham incision prior to TKA, and had a minimum follow-up of 2 years were identified, and their cases were retrospectively reviewed. The identified cases typically adhered to the surgeon's standard protocol, which consisted of making a midline incision adventitious to TKA, dissecting down to deep fascia, and closing the wound with suture. Incisions were then observed for at least 4 weeks to determine the viability of the skin flaps before TKA was performed via the same incision., Results: A total of 47 knees in 47 patients were included in the study cohort. TKA was performed at an average of 21.1 weeks (range, 4 to 163 weeks) following the sham incision. There were no cases of skin necrosis or periprosthetic joint infection at an average follow-up of 4.6 years (range, 2 to 12 years) after sham incision. A total of 11 patients (23.4%) required manipulation under anesthesia for stiffness., Conclusions: In our series, no patients developed skin necrosis or periprosthetic joint infection following TKA subsequent to a sham incision procedure, suggesting that healed sham incisions are safe to use for TKA and may be considered prior to TKA in cases in which local previous incisions increase the risk of wound-healing problems., Level of Evidence: Prognostic Level IV . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: No external funding was received for this work. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/I212 )., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Functional near-infrared spectroscopy (fNIRS) stands poised to revolutionize our understanding of auditory detection, speech perception, and language development in infants. In this study, we conducted a meticulous integrative review across Medline, Scopus, and LILACS databases, targeting investigations utilizing fNIRS to explore language-related features and cortical activation during auditory stimuli in typical infants. We included studies that used the NIRS technique to study language and cortical activation in response to auditory stimuli in typical infants between 0 and 3 years old. We used the ROBINS-I tool to assess the quality and the risk of bias in the studies. Our analysis, encompassing 66 manuscripts, is presented in standardized tables for streamlined data extraction. We meticulously correlated findings with children's developmental stages, delineating crucial insights into brain development and its intricate interplay with language outcomes. Although most studies have a high risk for overall bias, especially due to the high loss of data in NIRS studies, the low risk in the other domains is predominant and homogeneous among the studies. Highlighted are the unique advantages of fNIRS for pediatric studies, underscored by its innate suitability for use in children. This review accentuates fNIRS' capacity to elucidate the neural correlates of language processing and the sequential steps of language acquisition. From birth, infants exhibit abilities that lay the foundation for language development. The progression from diffuse to specific neural activation patterns is extremely influenced by exposure to languages, social interaction, and prosodic features and, reflects the maturation of brain networks involved in language processing. In conclusion, fNIRS emerges as an indispensable functional imaging modality, providing insights into the temporal dynamics of language acquisition and associated developmental milestones. This synthesis presents the pivotal role of fNIRS in advancing our comprehension of early language development and paves the way for future research endeavors in this domain., (© 2024 International Society for Developmental Neuroscience.)

Persistent human papillomavirus infection is associated with the development of premalignant lesions that can eventually lead to cervical cancer. In this study, we evaluated the expression of activating (NKG2D, DNAM-1) and inhibitory immune checkpoints receptors (PD-1, TIGIT, and Tim-3) in peripheral blood NKT-like (CD3 + CD56 + ) lymphocytes from patients with cervical carcinoma (CC, n = 19), high-grade lesions (HG, n = 8), low-grade lesions (LG, n = 19) and healthy donors (HD, n = 17) using multiparametric flow cytometry. Dimensional data analysis showed four clusters within the CD3 + CD56 + cells with different patterns of receptor expression. We observed upregulation of CD16 in CC and HG patients in one of the clusters. In another, TIGIT was upregulated, while DNAM-1 was downregulated. Throughout manual gating, we observed that NKT-like cells expressing activating receptors also co-express inhibitory receptors (PD-1 and TIGIT), which can affect the activation of these cells. A deeper characterization of the functional state of the cells may help to clarify their role in cervical cancer, as will the characterization of the NKT-like cells as cytotoxic CD8 + T cells or members of type I or type II NKT cells., Competing Interests: Declaration of competing interest The authors state no commercial or financial conflicts of interest., (Copyright © 2024 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

CMTM6 is a membrane protein that acts as a regulator of PD-L1, maintaining its expression on the cell surface, and can prevent its lysosome-mediated degradation. It is unknown if CMTM6 is present in the plasma of patients with cervical cancer, and if it has non-canonical subcellular localizations in cell lines derived from cervical cancer. Our objective was to determine whether CMTM6 is found in plasma derived from cervical cancer patients and its subcellular localization in cell lines. Patient plasma was separated into exosome-enriched, exosome-free, and total plasma fractions. The levels of CMTM6 in each fraction were determined using ELISA and Western blot. Finally, for the cellular model, HeLa, SiHa, CaSki, and HaCaT were used; the subcellular locations of CMTM6 were determined using immunofluorescence and flow cytometry. Soluble CMTM6 was found to be elevated in plasma from patients with cervical cancer, with a nearly three-fold increase in patients (966.27 pg/mL in patients vs. 363.54 pg/mL in controls). CMTM6 was preferentially, but not exclusively, found in the exosome-enriched plasma fraction, and was positively correlated with exosomal PD-L1; CMTM6 was identified in the membrane, intracellular compartments, and culture supernatant of the cell lines. These results highlight that CMTM6, in its various presentations, may play an important role in the biology of tumor cells and in immune system evasion.

Objective: The objective of this study is to outline the training of peer coaches in the Moving Well intervention, which was designed to reduce anxiety, depression, and pain catastrophizing in patients before and after total knee replacement (TKR)., Methods: Selected peer coaches had a history of knee osteoarthritis (KOA), a TKR of 12 months or more before training, and were 60 or older. Training was primarily conducted virtually, with a later addition of one in-person session. Training centered on developing skills in motivational interviewing (MoI), encompassing techniques like open-ended questions, affirmations, reflective listening, and summarization. It also covered the MoI processes of engagement, focus, evocation, and planning. Coaches were required to discuss at least 90% of session-specific topics, which were monitored using checklists for each certification, and to complete individual MoI training, which was not graded. The evaluation of peer coach training involved surveys and a focus group., Results: Three women and two men, averaging 75 years in age, completed the peer coach training for the Moving Well intervention. An in-person training session was added to address technology and MoI skill concerns, greatly enhancing their grasp of MoI skills and their ability to guide others through the program effectively. Peer coaches stressed the importance of live feedback, in-person training, and incorporating personal experiences into the program content during their training., Conclusion: To effectively train older adults as peer coaches for the Moving Well intervention, flexibility in learning formats, personalized guidance, peer support, and regular evaluations were essential in building the necessary MoI competencies to guide research participants in the program., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Towards improving the knowledge of possible paleo-microorganisms interaction with trace metals (micro-nutrients and toxicants), we studied adsorption of Mn, Zn, Sr, Cd, and Pb onto modern Chloroflexus aurantiacus, thermophilic anoxygenic phototrophic bacterium which could be highly abundant in the Precambiran aquatic environments. Acid-base surface titrations allowed quantifying the number of proton-active surface groups, whereas non-electrostatic linear programming method (LPM) was used to assess the surface site concentrations and adsorption reaction constants between divalent cations (Zn, Mb, Sr, Cd, Pb) and bacterial surface, based on results of pH-dependent adsorption edge and constant-pH 'langmuirian' adsorption experiments. The total proton/hydroxyl binding site number of Chl. aurantiacus surfaces was sizably lower than that of other phototrophic anaerobic bacteria studied previously using similar experimental and modeling approach. Divalent metals exhibited a decreasing order of adsorption affinity (Pb > Cd ≥ Zn ≥ Mn > Sr), which reflected the order of cation hydrolysis and was similar to adsorption order on other phototrophic bacteria. At the same time, adsorption of Zn increased with increasing of temperature, from 4 °C to 60 °C and was stronger under light compared to the darkness. This suggested some active metabolic control involved in this metal interaction with bacterial surfaces. Overall, Chl. aurantiacus exhibited trace metal adsorption parameters (site number and binding constants) which were lower compared to other anoxygenic phototrophic bacteria (Rhodopseudomonas palustris; Rhodobacter blasticus) and cyanobacteria. This may reflect different bioavailability of trace metals in the paleo-ocean, given that thermophilic Chl. aurantiacus are among the oldest phototrophs on the planet., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Telomerase is a specialized reverse transcriptase that uses an intrinsic RNA subunit as the template for telomeric DNA synthesis. Biogenesis of human telomerase requires its RNA subunit (hTR) to fold into a multi-domain architecture that includes the template-containing pseudoknot (t/PK) and the three-way junction (CR4/5). These two hTR domains bind the telomerase reverse transcriptase (hTERT) protein and are thus essential for telomerase catalytic activity. Here, we probe the structure of hTR in living cells using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) and ensemble deconvolution analysis. Unexpectedly, approximately 15% of the steady state population of hTR has a CR4/5 conformation lacking features thought to be required for hTERT binding. The proportion of hTR CR4/5 that is folded into the primary functional conformation does not require hTERT expression and the fraction of hTR that assumes a misfolded CR4/5 domain is not refolded by overexpression of its hTERT binding partner. This result suggests a functional role for an RNA folding cofactor other than hTERT during telomerase biogenesis. Mutagenesis demonstrates that stabilization of the alternative CR4/5 conformation is detrimental to telomerase assembly and activity. Moreover, the alternative CR4/5 conformation is not found in telomerase RNP complexes purified from cells via an epitope tag on hTERT, supporting the hypothesis that only the major CR4/5 conformer is active. We propose that this misfolded portion of the cellular hTR pool is either slowly refolded or degraded. Thus, kinetic traps for RNA folding that have been so well-studied in vitro may also present barriers for assembly of ribonucleoprotein complexes in vivo., Competing Interests: Competing Interests T.R.C. is a scientific advisor for Eikon Therapeutics, Storm Therapeutics, lincSwitch Therapeutics, and Somalogic, Inc. The other authors declare no competing interests.

Heterometallic hydride complexes are of growing interest due to their potential to contribute to highly active insertion-based catalysis; however, methods to modulate electron density within this class of molecules are underexplored. Addition of ancillary ligands to heterotrimetallic NiAl 2 H 2 species (1) results in the formation of heterobimetallic NiAl-hydride complexes with varying phosphine donors (2-(L)2). Incorporation of sigma donating ancillary ligands of increasing strength led to contractions of the Ni-Al distances correlated to a strengthening of a back donation interaction to the Al-H sigma antibonding orbital, most prominently present in 2-(PMe3)2. Demethylation of the aryl ether from 2-(PMe3)2 provides access to a novel anionic nickel-aluminum complex (3) with a maintained bridged hydride moiety between Ni and Al. Increased negative charge in complex 3 results in an elongation of the Ni-Al interaction. Combined crystallographic, spectroscopic, and computational studies support a 3-center interaction within the Al-H-Ni subunits and were used to map the degree of Ni-H character of the series within the Al-H-Ni bonding continuum.

Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of diversity (including geographical, socioeconomic, sociodemographic, sex and neurodegeneration) on the brain-age gap is unknown. We analyzed datasets from 5,306 participants across 15 countries (7 Latin American and Caribbean countries (LAC) and 8 non-LAC countries). Based on higher-order interactions, we developed a brain-age gap deep learning architecture for functional magnetic resonance imaging (2,953) and electroencephalography (2,353). The datasets comprised healthy controls and individuals with mild cognitive impairment, Alzheimer disease and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (functional magnetic resonance imaging: mean directional error = 5.60, root mean square error (r.m.s.e.) = 11.91; electroencephalography: mean directional error = 5.34, r.m.s.e. = 9.82) associated with frontoposterior networks compared with non-LAC models. Structural socioeconomic inequality, pollution and health disparities were influential predictors of increased brain-age gaps, especially in LAC (R² = 0.37, F² = 0.59, r.m.s.e. = 6.9). An ascending brain-age gap from healthy controls to mild cognitive impairment to Alzheimer disease was found. In LAC, we observed larger brain-age gaps in females in control and Alzheimer disease groups compared with the respective males. The results were not explained by variations in signal quality, demographics or acquisition methods. These findings provide a quantitative framework capturing the diversity of accelerated brain aging., (© 2024. The Author(s).)

Background: Accurate breast density evaluation allows for more precise risk estimation but suffers from high inter-observer variability., Purpose: To evaluate the feasibility of reducing inter-observer variability of breast density assessment through artificial intelligence (AI) assisted interpretation., Study Type: Retrospective., Population: Six hundred and twenty-one patients without breast prosthesis or reconstructions were randomly divided into training (N = 377), validation (N = 98), and independent test (N = 146) datasets., Field Strength/sequence: 1.5 T and 3.0 T; T1-weighted spectral attenuated inversion recovery., Assessment: Five radiologists independently assessed each scan in the independent test set to establish the inter-observer variability baseline and to reach a reference standard. Deep learning and three radiomics models were developed for three classification tasks: (i) four Breast Imaging-Reporting and Data System (BI-RADS) breast composition categories (A-D), (ii) dense (categories C, D) vs. non-dense (categories A, B), and (iii) extremely dense (category D) vs. moderately dense (categories A-C). The models were tested against the reference standard on the independent test set. AI-assisted interpretation was performed by majority voting between the models and each radiologist's assessment., Statistical Tests: Inter-observer variability was assessed using linear-weighted kappa (κ) statistics. Kappa statistics, accuracy, and area under the receiver operating characteristic curve (AUC) were used to assess models against reference standard., Results: In the independent test set, five readers showed an overall substantial agreement on tasks (i) and (ii), but moderate agreement for task (iii). The best-performing model showed substantial agreement with reference standard for tasks (i) and (ii), but moderate agreement for task (iii). With the assistance of the AI models, almost perfect inter-observer variability was obtained for tasks (i) (mean κ = 0.86), (ii) (mean κ = 0.94), and (iii) (mean κ = 0.94)., Data Conclusion: Deep learning and radiomics models have the potential to help reduce inter-observer variability of breast density assessment., Level of Evidence: 3 TECHNICAL EFFICACY: Stage 1., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: Our prospective international survey evaluated the impact of the early phase of the COVID-19 pandemic on the management gynaecological malignancies from the multidisciplinary physicians' perspective with particular focus on clinical infrastructures and trial participation., Methods: Our survey consisted of 53 COVID-related questions. It was sent to healthcare professionals in gynaecological oncology centres across Europe and Pan-Arabian region via the study groups and gynaecological societies from April 2020 to October 2020. All healthcare professionals treating gynaecological cancers were able to participate in our survey., Results: A total of 255 answers were collected from 30 countries. The majority (73%) of participants were gynaecological oncologists from university hospitals (71%) with at least an Intensive Care Unit with cardiopulmonary support available at their institutions. Most institutions continued to perform elective surgeries only for oncological cases (98%). Patients had to wait on average 2 weeks longer for their surgery appointments compared to previous years (range 0-12 weeks). Most cases that were prioritised for surgical intervention across all gynaecological tumours were early-stage disease (74%), primary situation (61%) and good ECOG status (63%). The radicality of surgery did not change in the majority of cases (78%) across all tumour types. During the pandemic, only 38% of clinicians stated they would start a new clinical trial. Almost half of the participants stated the pandemic negatively impacted the financial structure and support for clinical trials. Approximately 20% of clinicians did not feel well-informed regarding clinical algorithm for COVID-19 patients throughout the pandemic. Thirty percent stated that they are currently having trouble in providing adequate medical care due to staff shortage., Conclusion: Despite well-established guidelines, pandemic clearly affected clinical research and patientcare. Our survey underlines the necessity for building robust emergency algorithms tailored to gynaecological oncology to minimise negative impact in crises and to preserve access to clinical trials., (© 2024. The Author(s).)

Frailty is a clinical state reflecting a decrease in physiological reserve capacities, known to affect numerous biological pathways and is associated with health issues, including neurodegenerative diseases. However, how global protein expression is affected in the central nervous system in frail subject remains underexplored. In this post hoc cross-sectional biomarker analysis, we included 90 adults (52-85 years) suspected of normal pressure hydrocephalus (NPH) and presenting with markers of neurodegenerative diseases. We investigated the human proteomic profile of cerebrospinal fluid associated with frailty defined by an established cumulated frailty index (FI, average = 0.32), not enriched for neurology clinical features. Using a label-free quantitative proteomic approach, we identified and quantified 999 proteins of which 13 were positively associated with frailty. Pathway analysis with the top positively frailty-associated proteins revealed enrichment for proteins related to inflammation and immune response. Among the 60 proteins negatively associated with frailty, functional pathways enriched included neurogenesis, synaptogenesis and neuronal guidance. We constructed a frailty prediction model using ridge regression with 932 standardized proteins. Our results showed that the "proteomic model" could become an equivalent predictor of FI in order to study chronological age. This study represents the first comprehensive exploration of the proteomic profile of frailty within cerebrospinal fluid. It sheds light on the physiopathology of frailty, particularly highlighting processes of neuroinflammation and inhibition of neurogenesis. Our findings unveil a range of biological mechanisms that are dysregulated in frailty, in NPH subjects at risk of neurodegenerative impairment, offering new perspectives on frailty phenotyping and prediction., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of multimodal diversity (geographical, socioeconomic, sociodemographic, sex, neurodegeneration) on the brain age gap (BAG) is unknown. Here, we analyzed datasets from 5,306 participants across 15 countries (7 Latin American countries -LAC, 8 non-LAC). Based on higher-order interactions in brain signals, we developed a BAG deep learning architecture for functional magnetic resonance imaging (fMRI=2,953) and electroencephalography (EEG=2,353). The datasets comprised healthy controls, and individuals with mild cognitive impairment, Alzheimer's disease, and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (fMRI: MDE=5.60, RMSE=11.91; EEG: MDE=5.34, RMSE=9.82) compared to non-LAC, associated with frontoposterior networks. Structural socioeconomic inequality and other disparity-related factors (pollution, health disparities) were influential predictors of increased brain age gaps, especially in LAC (R 2 =0.37, F 2 =0.59, RMSE=6.9). A gradient of increasing BAG from controls to mild cognitive impairment to Alzheimer's disease was found. In LAC, we observed larger BAGs in females in control and Alzheimer's disease groups compared to respective males. Results were not explained by variations in signal quality, demographics, or acquisition methods. Findings provide a quantitative framework capturing the multimodal diversity of accelerated brain aging., Competing Interests: Additional Declarations: There is NO Competing Interest. Competing Interest Statement None of the authors have competing financial or non-financial interests as defined by Nature Portfolio.

Objective: To describe and analyze auditory and academic complaints of students and employees of a federal public university., Methods: The study was carried out using a non-probabilistic. The EAPAC Scale with adaptations was used to fulfill the research objectives. It has 14 questions about complaints related to listening skills and 12 questions related to the academic environment. Descriptive data analysis was performed through the frequency distribution of categorical variables and Pearson's chi-square test was used for association analyses., Results: 646 individuals aged between 17 and 67 years old participated in the research. The most prevalent complaints were academic difficulty related to memory, concentration, and planning, hearing and understanding speech in noise, and memorization of tasks that were only heard. There was an association with bidirectional statistical significance between academic and auditory complaints., Conclusion: It was possible to observe that there is an association between auditory and academic complaints in adults, marked by the relationship between cognitive and auditory aspects. It is relevant that these factors are considered when performing assessments of Central Auditory Processing when intervening in patients with auditory complaints, and in student life.

Background: LV geometry with shape index (SI) and eccentricity index (EI) measured by myocardial perfusion positron emission tomography/computed tomography (PET/CT) may allow the evaluation of left ventricular (LV) adverse remodeling. This first study aims to explore the relationship of SI and EI values acquired by Nitrogen-13 ammonia PET/CT in patients with normal perfusion, ischemia, and myocardial infarction. And evaluate the correlations between the variables of LV geometry, and with the variables of LV function., Methods and Results: One hundred and forty patients who underwent an electrocardiogram (ECG)-gated PET/CT were selected and classified into 4 groups according to ischemia or infarction burden (normal perfusion, mild ischemia, moderate-severe ischemia, and infarction). The variables were automatically retrieved using dedicated software (QPS/QGS; Cedars-Sinai, Los Angeles, CA, USA). On multicomparison analysis (one-way ANOVA and Dunnett's Test), subjects in the infarction group had significant higher values of SI end-diastolic rest (P < 0.001), and stress (P = 0.003), SI end-systolic rest (P = 0.002) and stress (P < 0.001) as well as statistically significant lower values of EI rest (P < 0.001) and stress (P < 0.001) when compared with all other groups. Regarding Pearson correlation, in the infarcted group all the variables of SI and EI were significantly correlated (P < 0.001) with strong correlation coefficients (>0.60). SI end-systolic correlated significantly with the variables of LV function independently of the group of patients (P < 0.05)., Conclusions: Shape and eccentricity indices differ in patients with myocardial infarction as compared to patients with ischemia or normal perfusion. This encourage further research in their potential for detecting LV adverse remodeling., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Recently, lifestyle medicine (LSM) application has shown feasibility for musculoskeletal pain patients with co-existing lifestyle-related chronic diseases. This study describes early results of a LSM program for musculoskeletal patients with goals to optimize health prior to orthopedic surgery. Fifty-four patients (age: 61 ± 11 years; 39 [72%] females) completed the program from 3/8/22-12/1/23. Data included patient goals, utilization, goal attainment, and patient outcomes. Most patients (41/54 [76%]) enrolled with established surgical dates. Mean BMI was 43.2 ± 5.3 kg/m 2 , and 89% had ≥2 lifestyle-related chronic diseases. The majority reported impaired sleep (79%) and zero cumulative minutes of physical activity/week (57%). Mean program duration was 13 ± 8 weeks involving 5 ± 4 visits with members of the interprofessional team. Fifty-two (96%) patients successfully attained pre-program goals, and 49/54 (91%) met their surgical goal. Of the patients enrolled without surgical dates, 11/13 (85%) optimized their health and proceeded to surgery. Forty-two (78%) patients reported decreases in weight and BMI, averaging 11 ± 7 lbs and 1.8 ± 1.3 kg/m 2 , respectively. Rates of improvement in pain, PROMIS-10 physical and mental health, and PHQ-4 were 52%, 37%, 45%, and 47%, respectively. These data demonstrate the feasibility and effectiveness of a LSM program to address whole-person health optimization and enable orthopedic patients to improve lifestyle behaviors and proceed to orthopedic surgery., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 The Author(s).)

Background: Patients who have spinal stiffness and deformity are at the highest risk for dislocation after total hip arthroplasty (THA). Previous reports of this cohort are limited to antero-lateral and postero-lateral (PL) approaches. We investigated the dislocation rate after direct anterior (DA) and PL approach THA with a contemporary high-risk protocol to optimize stability., Methods: We investigated patients undergoing THA who had preoperative biplanar imaging from January-December 2019. Patients were identified using radiographic criteria of spinal-stiffness (<10-degree change in sacral slope from standing to seated) and deformity (flatback deformity with >10-degree difference in pelvic incidence and lumbar lordosis). There were 367 patients identified (181 DA, 186 PL). The primary outcome was dislocation rate at 2-years postoperatively. Risk-factors for dislocation were evaluated using logistic regressions (significance level of 0.05)., Results: There were 6 (1.6%) dislocations in the entire cohort, with low dislocation rates for both DA (0.6%) and PL-THA (2.7%). We observed increased utilization of dual mobility with larger outer head bearings (>38 mm) with PL-THA (34.4 versus 5.0%, P < .01) and conversely increased utilization of 32-mm femoral-heads with DA-THA (39.4 versus 7.0%, P < .001). Surgical approach (PL) was not a significant risk-factor for dislocation (odds ratio: 5.03, P = .15). Patients who had a history of lumbar-fusion had 8-times higher odds for dislocation (OR: 8.20, P = .020)., Conclusions: To the best of our knowledge, this is the largest series to date evaluating DA and PL-THA in the hip-spine 2B-group. Our results demonstrate lower dislocation rate than expected with either surgical approach using a high-risk protocol., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Due to their vectorial capacity, mosquitoes (Diptera: Culicidae) receive special attention from health authorities and entomologists. These cosmopolitan insects are responsible for the transmission of many viral diseases, such as dengue and yellow fever, causing huge impacts on human health and justifying the intensification of research focused on mosquito-borne diseases. In this context, the study of the virome of mosquitoes can contribute to anticipate the emergence and/or the reemergence of infectious diseases. The assessment of mosquito viromes also contributes to the surveillance of a wide variety of viruses found in these insects, allowing the early detection of pathogens with public health importance. However, the study of mosquito viromes can be challenging due to the number and complexities of steps involved in this type of research. Therefore, this article aims to describe, in a straightforward and simplified way, the steps necessary for obtention and assessment of mosquito viromes. In brief, this article explores: the capture and preservation of specimens; sampling strategies; treatment of samples before DNA/RNA extraction; extraction methodologies; enrichment and purification processes; sequencing choices; and bioinformatics analysis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Age-related macular degeneration (AMD), a leading cause of vision loss, primarily arises from the degeneration of retinal pigment epithelium (RPE) and photoreceptors. Current therapeutic options for dry AMD are limited. Encouragingly, cultured RPE cells on parylene-based biomimetic Bruch's membrane demonstrate characteristics akin to the native RPE layer. In this study, we cultivated human embryonic stem cell-derived polarized RPE (hESC-PRPE) cells on parylene membranes at both small- and large-scale settings, collecting conditioned supernatant, denoted as PRPE-SF. We conducted a comprehensive analysis of the morphology of the cultured hESC-RPE cells and the secreted growth factors in PRPE-SF. To evaluate the in vivo efficacy of these products, the product was administered via intravitreal injections of PRPE-SF in immunodeficient Royal College of Surgeons (iRCS) rats, a model for retinal degeneration. Our study not only demonstrated the scalability of PRPE-SF production while maintaining RPE cell phenotype but also showed consistent protein concentrations between small- and large-scale batches. We consistently identified 10 key factors in PRPE-SF, including BMP-7, IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-6, MANF, PEDF, PDGF-AA, TGFβ1, and VEGF. Following intravitreal administration of PRPE-SF, we observed a significant increase in the thickness of the outer nuclear layer (ONL) and photoreceptor preservation in iRCS rats. Furthermore, correlation analysis revealed that IGFBP-3, IGFBP-4, MANF, PEDF, and TGFβ1 displayed positive associations with in vivo bioactivity, while GDF-15 exhibited a negative correlation. Overall, this study highlights the feasibility of scaling up PRPE-SF production on parylene membranes without compromising its essential constituents. The outcomes of PRPE-SF administration in an animal model of retinal degeneration present substantial potential for photoreceptor preservation. Moreover, the identification of candidate surrogate potency markers, showing strong positive associations with in vivo bioactivity, lays a solid foundation for the development of a promising therapeutic intervention for retinal degenerative diseases., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Lipid-based nanoparticles (LNPs) are advanced materials (AdMa), particularly relevant for drug delivery of poorly water-soluble compounds, while also providing protection, stabilization, and controlled release of the drugs/active substances. The toxicological data available often focus on the specific applications of the LNPs-drug tested, with indication of low toxicity. However, the ecotoxicological effects of LNPs are currently unknown. In the present study, we investigated the ecotoxicity of a formulation of Lipid Surfactant Submicron Particles (LSSPs) loaded with melatonin at 1 mg/mL. The LSSPs formulation has been developed to be fully compliant with regulatory for its potential use in the market and all components are food additives. The same formulation without the thickening agent xanthan gum (stabilizer in water phase) designated as LSSP-xg, was also tested. Two soil model invertebrate species were tested in LUFA 2.2 soil: Enchytraeus crypticus (Oligochaeta) and Folsomia candida (Collembola). Effects were assessed based on the OECD standard guideline (28 days) and its extension, the longer-term exposure (56 days). Assessed endpoints were survival, reproduction, and size. LSSPs and LSSP-xg were toxic to E. crypticus and F. candida reducing their survival and reproduction in a dose-dependent way: e.g., 28-day exposure: E. crypticus: LC/EC50 = 30/15 mg LSSPs/kg soil and F. candida LC/EC50 = 55/44 mg LSSPs/kg soil, with similar values for LSSP-xg. Size was also reduced for F. candida but was the least sensitive endpoint. There were no indications that toxicity increased with longer term exposure. The results provide relevant information on ecotoxicity of a AdMa and highlights the need for awareness of the potential risks, even on products and additives usually used in food or cosmetic industry. Further information on single components and on their specific assembly is necessary for the interpretation of results, as it is not fully clear what causes the toxicity in this specific AdMa. This represents a typical challenge for AdMa hazard assessment scenario., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

High altitude (alpine) lakes are efficient sentinels of environmental processes, including local pollution and long-range atmospheric transfer, because these lakes are highly vulnerable to ongoing climate changes and increasing anthropogenic pressure. Towards improving the knowledge of trace element geochemistry in the water column of alpine lakes, we assessed 64 physico-chemical parameters, including macro- and micronutrients, major and trace element concentrations in the water column of 18 lakes in the Pyrenees, located along the border between France and Spain. Lake depth, morphology, retention time and watershed rock lithology did not exhibit sizable impact on major and trace element concentrations in the water column. However, acidic (pH = 4.7 ± 0.2) lakes were distinctly different from circumneutral lakes (pH = 6.8 ± 0.5) as they exhibited >10 times higher concentrations of SO 4 2- and trace metals (Fe, Mn, Zn, Cd, Pb, Co, Ni, Be, Al, Ga and REEs). While some of these elements clearly mark the presence of sulphide-rich minerals within the watershed (Fe, Zn, Cd and Pb), the increased mobility of lithogenic elements (Be, Al, Ga and REEs) in acidic lakes may reflect the leaching of these elements from silicate dust derived from atmospheric deposits or surrounding granites. At the same time, compared to circumneutral lakes, acidic lake water displayed lower concentrations of dissolved oxyanions (As, Mo, V, B and W) and elevated SO 4 2- concentrations. The latter could lead to efficient Ba removal from the water column. The exploitation of metal ores within the watershed of three lakes clearly impacted high Zn and Cd concentrations observed in their water column, despite two of these lakes not being acidic. We conclude that local impacts have a greater effect on the water column than long-range atmospheric inputs and that dissolved trace element concentration measurements can be used for revealing sulphide-rich minerals or acid mine drainage within the lakes' watershed., 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.)

Background: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants., Methods: Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV&#95;1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV&#95;2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years., Results: Two hundred one infants were vaccinated (RSV&#95;1D: 65; RSV&#95;2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2., Conclusions: ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906., Competing Interests: Potential conflicts of interest. V. N., Y. Z., W. P., D. F., I. D., A. G. L., R. M., S. K. S., and N. V. are or were employees of GSK during the conduct of the study. I. D., W. P., and S. K. S. hold GSK shares/stocks. R. M. and S. K. S. hold stock/stock options in Moderna. B. T., E. J. A., B. S. C., E. C. D., H. S., J. D. C., J. M. M. A., K. L., M. M. M.-P., M. R., S. N. F., F. B.-A., and T. P. report grants and/or other support from GSK for the conduct of the study. J. M. L. reports grants from GSK paid to her institution for the conduct of the study and holds the CIHR-GSK Chair in Pediatric Vaccinology at Dalhousie University. B. T. reports grants from GSK, Merck, and Pfizer for other trials. C. e. reports support for scientific meetings from GSK and ViiV and advisory consultancy fees from GSK. E. J. A. has consulted for Pfizer, Sanofi Pasteur, GSK, Janssen, Moderna, and Medscape, and his institution receives funds to conduct clinical research unrelated to this manuscript from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Novavax, Sanofi Pasteur, Janssen, and Micron; he serves on a safety monitoring board for Kentucky BioProcessing and Sanofi Pasteur; serves on a data adjudication board for WCG and ACI Clinical; and his institution has also received funding from the National Institutes of Health to conduct clinical trials of COVID-19 vaccines. B. S. C. reports grants for other vaccine trials from GSK and MSD paid to his institution. E. C. D. performs contract work for the Eskisehir Osmangazi University funded by GSK, Sanofi Pasteur, and Pfizer. E. K. reports honoraria for lectures from GSK, MSD, AstraZeneca, Sanofi, and Pfizer. E. L.-M. reports grants from Centro de Estudios en Infectología Pediátrica. F. M.-T. reports grants from Janssen, MSD, and AstraZeneca; personal fees from Ablynx, GSK, Pfizer, MSD, Sanofi Pasteur, Novavax, Seqirus, and Biofabri; nonfinancial support from GSK, Pfizer, MSD, and Seqirus; and trial fees paid to his institution from these different companies (except Biofabri). H. S. reports personal fees and trial fees paid to his institution from MSD, Seqirus, Pfizer, Janssen, and Sanofi Pasteur. I. S. C. has received payment to his institution from GSK for the conduct of the study, by contract approved by the corresponding ethical committees and health authorities, and for trials of other vaccine manufacturers, and has received grants and/or honoraria as a consultant/advisor/speaker or for attending conferences and practical courses from GSK and other vaccine manufacturers. J. D. C. is a member of the Committee on Infectious Diseases of the American Academy of Pediatrics and reports funds paid to his university to study RSV vaccines. J. D.-D. reports grants from GSK, MSD, and Sanofi Pasteur paid to his institution. J. M. M. A. reports fees for medical meetings from GSK and Pfizer. K. L. reports grants from ReViral and Shionogi. M. M.-P. reports grants from MSD, Roche, GSK, Janssen, Takeda, and Syneos. M. R. reports grants for other vaccine trials from GSK and other vaccine manufacturers paid to his institution. S. N. F. reports fees paid to his institution for attending meetings, advisory boards, and/or grants for clinical trials from AstraZeneca/Medimmune, GSK, J&J, Pfizer, Sanofi, Seqirus, Sandoz, Valneva, Novavax, and Merck. X. S.-L. reports grants from Cevaxin Vaccine Research Center. F. B.-A. reports consultancy fees from GSK, Pfizer, and MSD and grants from MSD. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: The use of imageless navigation in total hip arthroplasty (THA) is frequently associated with prolonged surgical times, predominantly during the learning period. The purpose of the present study was to characterize the learning period of a novel imageless navigation system, specifically as it related to surgical time and acetabular navigation accuracy., Materials and Methods: This was a retrospective observational study of a consecutive group of 158 patients who underwent primary unilateral THA for osteoarthritis by a team headed by a single surgeon. All procedures used an imageless navigation system to measure acetabular cup inclination and anteversion angles, referencing a generic sagittal and frontal plane. Navigation accuracy was determined by assessing differences between intraoperative inclination and anteversion values and those obtained from standardized 6-week follow-up radiographs. Operative time and navigation accuracy were assessed by plotting moving averages of 7 consecutive cases. The learning period was defined using Mann-Kendall trend analyses, student t -tests and nonlinear regression modeling based on surgical time and navigation accuracy. Alpha error was 0.05., Results: The average surgical time was 67.3 min (SD:9.2) (range 45-95). The average navigation accuracy for inclination was 0.01° (SD:4.2) (range - 10 to 10), and that for anteversion was - 4.9° (SD:3.8) (range - 14 to 5). Average surgical time and navigation accuracy were similar between the first and final cases in the series with no learning period detected., Conclusions: There was no discernible learning period effect on surgical time or system measurement accuracy during the early phases of adoption for this imageless navigation system., Competing Interests: Conflict of interestAuthor A.G.D.V. is a paid consultant for, and owns stock or stock options in Naviswiss., (© Indian Orthopaedics Association 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: The live-attenuated influenza virus vector-based intranasal SARS-CoV-2 vaccine (dNS1-RBD, Pneucolin; Beijing Wantai Biological Pharmacy Enterprise, Beijing, China) confers long-lasting and broad protection in animal models and is, to our knowledge, the first COVID-19 mucosal vaccine to enter into human trials, but its efficacy is still unknown. We aimed to assess the safety and efficacy (but not the immunogenicity) of dNS1-RBD against COVID-19., Methods: We did a multicentre, randomised, double-blind, placebo-controlled, adaptive design, phase 3 trial at 33 centres (private or public hospitals, clinical research centres, or Centre for Disease Control and Prevention) in four countries (Colombia, Philippines, South Africa, and Viet Nam). Men and non-pregnant women (aged ≥18 years) were eligible if they had never been infected with SARS-CoV-2, and if they did not have a SARS-CoV-2 vaccination history at screening or if they had received at least one dose of other SARS-CoV-2 vaccines 6 months or longer before enrolment. Eligible adults were randomly assigned (1:1) to receive two intranasal doses of dNS1-RBD or placebo administered 14 days apart (0·2 mL per dose; 0·1 mL per nasal cavity), with block randomisation via an interactive web-response system, stratified by centre, age group (18-59 years or ≥60 years), and SARS-CoV-2 vaccination history. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary outcomes were safety of dNS1-RBD in the safety population (ie, those who had received at least one dose of dNS1-RBD or placebo) and efficacy against symptomatic SARS-CoV-2 infection confirmed by RT-PCR occurring 15 days or longer after the second dose in the per-protocol population (ie, those who received two doses, were followed up for 15 days or longer after the second dose, and had no major protocol deviations). The success criterion was predefined as vaccine efficacy of more than 30%. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2100051391) and is completed., Findings: Between Dec 16, 2021, and May 31, 2022, 41 620 participants were screened for eligibility and 31 038 participants were enrolled and randomly assigned (15 517 in the vaccine group and 15 521 in the placebo group). 30 990 participants who received at least one dose (15 496 vaccine and 15 494 placebo) were included in the safety analysis. The results showed a favourable safety profile, with the most common local adverse reaction being rhinorrhoea (578 [3·7%] of 15 500 vaccine recipients and 546 [3·5%] of 15 490 placebo recipients) and the most common systemic reaction being headache (829 [5·3%] vaccine recipients and 797 [5·1%] placebo recipients). We found no differences in the incidences of adverse reactions between participants in the vaccine and placebo groups. No vaccination-related serious adverse events or deaths were observed. Among 30 290 participants who received two doses, 25 742 were included in the per-protocol efficacy analysis (12 840 vaccine and 12 902 placebo). The incidence of confirmed symptomatic SARS-CoV-2 infection caused by omicron variants regardless of immunisation history was 1·6% in the vaccine group and 2·3% in the placebo group, resulting in an overall vaccine efficacy of 28·2% (95% CI 3·4-46·6), with a median follow-up duration of 161 days., Interpretation: Although this trial did not meet the predefined efficacy criteria for success, dNS1-RBD was well tolerated and protective against omicron variants, both as a primary immunisation and as a heterologous booster., Funding: Beijing Wantai Biological Pharmacy Enterprise, National Science and Technology Major Project, National Natural Science Foundation of China, Fujian Provincial Science and Technology Plan Project, Natural Science Foundation of Fujian Province, Xiamen Science and Technology Plan Special Project, Bill & Melinda Gates Foundation, the Ministry of Education of China, Xiamen University, and Fieldwork Funds of Xiamen University., Competing Interests: Declaration of interests JT, JJ, and XC were employees of Beijing Wantai Biological Pharmacy Enterprise during the conduct of the study. JH and XY are employees of and have stock options in Beijing Wantai Biological Pharmacy Enterprise. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Transthyretin amyloidosis (ATTR amyloidosis) is a progressive, multisystemic, life-threatening disease resulting from the deposition of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in various tissues and organs., Methods: Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal, observational study of patients with ATTR amyloidosis, including both hereditary and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This analysis describes the baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2022), providing a consolidated overview of 15-year data from the THAOS registry., Results: This analysis included 4428 symptomatic patients and 1707 asymptomatic gene carriers. The majority of symptomatic patients were male (70.8%) with a mean (standard deviation [SD]) age at symptom onset of 56.6 (17.9) years. Compared with the 14-year analysis, V30M remained the most prevalent genotype in Europe (62.2%), South America (78.6%), and Japan (74.2%) and ATTRwt remained most common in North America (56.2%). Relative to the 14-year analysis, there was an increase of mixed phenotype (from 16.6 to 24.5%) and a reduction of predominantly cardiac phenotype (from 40.7 to 31.9%). The proportion of patients with predominantly neurologic phenotype remained stable (from 40.1 to 38.7%). Asymptomatic gene carriers were 58.5% female with a mean age at enrollment of 41.9 years (SD 15.5)., Conclusions: This overview of > 6000 patients enrolled over 15 years in THAOS represents the largest registry analysis of ATTR amyloidosis to date and continues to emphasize the genotypic and phenotypic heterogeneity of the disease. Nearly a quarter of the symptomatic population within THAOS was mixed phenotype, underscoring the need for multidisciplinary management of ATTR amyloidosis., Trial Registration: ClinicalTrials.gov Identifier: NCT00628745., (© 2023. The Author(s).)

Background: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications., Methods: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125., Findings: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22)., Interpretation: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea., Funding: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong., Competing Interests: Declaration of interests DC received research grants from the Canadian Institutes of Health Research (CIHR), speaker fees from Servier outside of the current study, and advisory board fees from Roche Diagnostics and Trimedics outside of the current study. EP is funded by a research contract (SLT017/20/000089) supported by the Department of Health of the Generalitat de Catalunya, Spain. DIS serves on advisory boards and has equity interests in Calorint, TransQtronics, the Health Data Analytics Institute, Medasense, and Perceptive Medical. DIS is the chair of the Department of Outcomes Research at the Cleveland Clinic. WFM received speaker fees from Bayer, Servier, and Eli Lilly, and consulting fees from AtriCure and Trimedics, all outside the current study. SSJ received grant support from Boston Scientific, and speaker fees from Pendopharm and Penumbra. JSH received research grants and speaker fees from Boston Scientific, BMS/Pfizer, and Medtronic. PJD is a member of a research group with a policy of not accepting honorariums or other payments from industry for own personal financial gain. They do accept honorariums or payments from industry to support research endeavours and costs to participate in meetings. Based on study questions that PJD originated and grants he has written, he has received grants from Abbott Diagnostics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cloud DX, Coviden, Octapharma, Philips Healthcare, Roche Diagnostics, Siemens, and Stryker. He has also participated in an advisory board meeting for GlaxoSmithKline and an expert panel meeting with AstraZeneca, Boehringer Ingelheim, and Roche. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The integration of digital health technologies in geriatric oncology has the potential to enhance patient care and self-management. This review article discusses the applications of these technologies, including teleassessment, telemonitoring, and teleintervention, within geriatric oncology, and evaluates their potential to improve cancer care and patient outcomes. We also review challenges to the implementation of digital health technologies among populations of older patients with cancer. The article provides a perspective for clinicians, researchers, policymakers, and patients on the integration and utilisation of digital health technologies in current geriatric oncology practice., Competing Interests: Declaration of Competing Interest Colm Mac Eochagain: None. Nicolás María González Senac: None. Mukul Roy: None. Andrea Ciccone: None. Beatriz Contreras: None. Rogelio Velasco: None. Melody Schiaffino: None. Giuseppe Dario Testa: None. Joana Marinho: None. Adolfo Gonzales Serrano: None. Mercedes Cavanagh: None. Fabio Gomes: Dr. Gomes reports grants from Pfizer, personal fees from Roche, personal fees from BMS, personal fees from AstraZeneca, personal fees from Takeda, outside the submitted work., (Copyright © 2023. Published by Elsevier Ltd.)

Public concerns over environmental protection have increased after Fukushima accident. The soil-plant transfer factor (Fv) is a critical parameter for environmental risk assessment. 137 Cs Fv values determined in acid Brazilian soils could be two orders of magnitude higher than Fv values measured in soils affected by the Chernobyl accident. This paper studied the behaviour of 90 Sr in Brazilian soils where very few 90 Sr Fv data is available. All classes of studied soils (Ferralsol, Acrisol and Nitisol) showed that more than 80% of total 90 Sr in soils remains potentially mobile, mainly at the bioavailable phase, more than 2 years after soil contamination in an experiment conducted in lysimeters. Higher 90 Sr Fv for maize and cabbage was observed in the acid soils with low content of exchangeable Ca, lower Fv values occurred at Nitisol, the subtropical soil type. It seems that the behaviour of 90 Sr in these soils are mainly controlled by ionic competition mechanisms occurring for root uptake and sorption sites, with stable Sr and major nutrients (Ca, Mg and K). The mineralogy also seems to play a relevant role, since goethite rich clay soil presented 90 Sr Fv values higher one or two orders of magnitude than 90 Sr Fv values observed at clayed soil goethite rich with trace of vermiculite, for all studied crops. The high rate of 90 Sr migration down the soil profiles observed for the studied soils during the 2 first years after contamination suggests a high rate of transfer to groundwater, even transfer to leafy crop group can be also a relevant pathway. In the present study, maize, among other plant species, presented the lowest Fv values, even when compared with maize cultivated in temperate soil. Our results suggest that stable Sr may not be a very good analogue of 90 Sr for determining plant Fv values: geometric mean of stable Sr Fv for maize was Fv maize  = 6.3E-1 ± 2.1E0 (n = 8) and for 90 Sr was Fv maize  = 1.8E-2 ± 2.5E0 (n = 16), geometric mean of stable Sr Fv for cabbage was Fv cabbage  = 1.4E0 ± 3.9E0 (n = 17) and for 90 Sr was Fv cabbage  = 7.9E-1 ± 4.4E0 (n = 18)., 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.)

Introduction: In June 2020 when elective total knee arthroplasty (TKA) resumed after the initial COVID-19 surge, we adapted our TKA pathway focusing on a shorter hospitalization, increased home discharge, and use of post-discharge telemedicine and telerehabilitation. The purpose of this study was to evaluate if changes in postoperative care affected early TKA outcomes., Materials and Methods: Five hundred and fifty-four patients who underwent elective primary unilateral TKA for primary osteoarthritis between June and August 2020 (study group) were matched 1:1 for age, sex, body mass index, and Charlson comorbidity index with control patients who underwent surgery between August and November 2019. Study patients were discharged 25 h earlier on average compared to controls, more frequently on the same-day or postoperative day-1 (24.9% vs. 16.1%; p = 0.001), and more frequently home (97.3% vs. 83.8%; p < 0.001). Study patients used telemedicine (11.7% vs. 0%; p < 0.001) and telerehabilitation (19.7% vs. 2.5%; p < 0.001) at higher rates than controls. Generalized estimating equations, Mann-Whitney U, and Chi-Square tests were used to compare outcomes between groups including unscheduled office visits, ER visits, readmissions, Center for Medicare and Medicaid Services (CMS) complications, manipulation under anesthesia (MUA), and patient-reported outcomes measures (PROMs)., Results: Rates of emergency room visits, readmissions, CMS complications, MUA, and improvements in PROMs were similar between cohorts. Study patients experienced higher rates of unscheduled outpatient visits (9.2% vs. 4.9%; p = 0.004), predominantly due to wound complications., Conclusions: A protocol implemented during the COVID-19 pandemic that leveraged a shortened hospitalization, higher rates of home discharge, and increased use of telemedicine and telerehabilitation was safe and effective., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Lumbar spine pathology frequently coexists in patients who have hip arthrosis. There is controversy on whether lumbar or hip pathology should be first addressed. The purpose of this study was to evaluate the outcomes of sequential lumbar spine (LSP) or hip arthroplasty (THA)., Methods: Using a large national database from 2010 to 2020, we reviewed the records of 241,279 patients who had concurrent hip arthritis and lumbar spine disease defined as spinal stenosis, lumbar radiculopathy, or degenerative disc disease. During the study period, 6,458 (2.7%) patients with concurrent hip/spine disease underwent sequential operative treatment of either the hip joint or lumbar spine within 2 years. The rates of subsequent surgery in either the hip or the spine, opioid requirements, and rates of hip dislocation were determined and analyzed using compared Chi-squared analyses., Results: Patients undergoing THA first had lower risk of subsequent spinal procedure compared to patients who had spinal procedures first (5.7 versus 23.7%, P < .001). This disparity was maintained up to 5 years (P < .001). Opioid requirements at 1 year were highest in patients who underwent spinal procedures only (836 pills/patient) compared to any other group THA only (566 pills/patient), LSP and then THA (564 pills/patient), THA and LSP (586 pills/patient). Also, THA following LSP was associated with significantly higher rates of dislocation compared to patients undergoing THA first (3.2 versus 1.9%, P < .001)., Conclusion: Total hip arthroplasty first in patients who have concurrent spine disease was associated with lower risk of subsequent surgery, opioid requirement, and risk of postoperative instability compared to patients having lumbar procedure first., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Point-of-care testing provides a representation of the patient's coagulability status during effective postpartum hemorrhage management. Baseline values of rotational thromboelastometry (ROTEM) have not yet been reported in a heterogeneous obstetric population. This study aimed to establish a baseline for a diverse population representative of the United States. The secondary aim was to evaluate the association of these hematologic parameters with comorbidities, race, and socioeconomic factors., Methods: The study was a retrospective review of collected ROTEM values of women undergoing vaginal or cesarean delivery with a history of or at risk for postpartum hemorrhage. Patients were divided into healthy and comorbid groups. Exclusion criteria for both groups included active or recent bleeding, receipt of blood products or clot-enhancing factors, and liver disease. Mean values of ROTEM by race and comorbidities were included. Median values were reported for intrinsic pathway thromboelastometry (INTEM), extrinsic pathway thromboelastometry (EXTEM), and fibrin polymerization thromboelastometry (FIBTEM) amplitude at 10 minutes (A10) and 20 minutes (A20), coagulation time, clot formation time, and maximum clot firmness., Results: A total of 681 records were reviewed; 485 met inclusion criteria, and 267 met healthy criteria. The mean (standard deviation) demographics for maternal age (years), body mass index (kg/m 2 ), and gestational age (weeks) were 32.2 (5.7), 34 (7.3), and 35.4 (5), respectively. The median INTEM, EXTEM, and FIBTEM A10 were 63, 65, and 23 mm. The mean for INTEM, EXTEM, and FIBTEM A10 was increased for those who were Black or obese, whereas a decreased FIBTEM and EXTEM A10 was noted in those who were Asian or those who had the hemolysis, elevated liver enzymes, low platelet syndrome., Conclusions: Our heterogeneous population presents ROTEM values within the interquartile range of those previously reported in European studies. Black race, obesity, and preeclampsia were associated with hypercoagulable profiles., Competing Interests: The authors report no funding or conflicts of interest., (Copyright © 2023 Baylor University Medical Center.)

Glass fiber-reinforced polymer (GFRP) of high performance, as a relatively ideal partial or complete substitute for steel, could increase the possibility of adapting structures to changes in harsh weather environments. While GFRP is combined with concrete in the form of bars, the mechanical characteristics of GFRP cause the bonding behavior to differ significantly from that of steel-reinforced members. In this paper, a central pull-out test was applied, according to ACI440.3R-04, to analyze the influence of the deformation characteristics of GFRP bars on bonding failure. The bond-slip curves of the GFRP bars with different deformation coefficients exhibited distinct four-stage processes. Increasing the deformation coefficient of the GFRP bars is able to significantly improve the bond strength between the GFRP bars and the concrete. However, while both the deformation coefficient and concrete strength of the GFRP bars were increased, the bond failure mode of the composite member was more likely to be changed from ductile to brittle. The results show members with larger deformation coefficients and moderate concrete grades, which generally have excellent mechanical and engineering properties. By comparing with the existing bond and slip constitutive models, it was found that the proposed curve prediction model was able to well match the engineering performance of GFRP bars with different deformation coefficients. Meanwhile, due to its high practicality, a four-fold model characterizing representative stress for the bond-slip behavior was recommended in order to predict the performance of the GFRP bars.