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Abstract: Cytomegalovirus (CMV) reactivation is a major complication among seropositive allogeneic hematopoietic cell transplantation recipients; however, data on CMV reactivation after chimeric antigen receptor (CAR) T-cell therapy are limited. We report the incidence and outcomes of 95 adult CMV-seropositive patients who received CAR T-cell therapy between February 2018 and February 2023. CMV outcomes were CMV reactivation (any viremia) and clinically significant CMV infection (cs-CMV). Thirty-one patients (33%) had evidence of CMV reactivation (any viremia), and 10 patients (11%) had cs-CMV. The median time from CAR T-cell infusion to CMV reactivation was 19 days (interquartile range [IQR], 9-31). The cumulative incidence of CMV (any viremia) was significantly higher among patients with grade 3 to 4 cytokine release syndrome (67 vs 28%; P = .01), and those who received corticosteroids (39 vs 21%; P = .03), anakinra (56 vs 28%; P = .02), or ≥2 immunosuppressants (41 vs 21%; P = .02). Receipt of corticosteroids (18 vs 0%; P = .004), tocilizumab (14 vs 0%; P = .04), anakinra (33 vs 7%; P = .008), and ≥2 immunosuppressants (20 vs 0%; P = .001) were all associated with cs-CMV. Receiving ≥2 immunosuppressants was associated with a twofold increase in CMV reactivation in multivariate analyses (adjusted odds ratio [aOR], 2.27; 95% confidence interval, 1.1-4.8; P = .03). Overall, the 1-year mortality was significantly higher in those with CMV reactivation (57% vs 23%; P = .001). Immunosuppression, particularly with corticosteroids, for the management of CAR T-cell toxicities, is a major risk factor for CMV reactivation., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Introduction: Inappropriate sinus tachycardia (IST) is a common condition with frequently not tolerated beta-blockers or ivabradine and a high rate of complication in ablation strategy; we describe an alternative anatomical approach of sinus node (SN) modulation., Methods: This retrospective study describes a case series of 6 patients from two centers diagnosed with symptomatic IST undergoing SN ablation., Results: The mean age was 40.6 ± 13.9 years; five of the six patients were female, 100% of patients reported heart palpitations, and 66% reported dizziness, the average heart rate (HR) on a 24-h Holter was 93.2 ± 7.9 bpm. HR during the first stage of a stress test using a standard Bruce protocol was 150 ± 70 bpm, The average HR on 24-h Holter postablation was 75 ± 5.6 bpm, the sinus rate HR during stage 1 of a Bruce protocol exercise stress test was 120 ± 10 bpm., Conclusion: This is the first case series reporting the acute and long-term results of a novel anatomical approach for SN modulation to treat IST targeting the arcuate ridge (AR) under intracardiac echography (ICE) guidance. The novel anatomic ICE-guided catheter ablation approach aimed to identify the earliest activation at the AR with an extension of RF lesions toward its septal region seems effective and safe to modulate the SN in symptomatic patients with IST refractory to medical treatment., (© 2024 Wiley Periodicals LLC.)

Stillbirth is a fundamental component of childhood mortality, but its causes are still insufficiently understood. This study aims to explore stillbirth risk factors by using a multidisciplinary approach to stimulate public policies and protocols to prevent stillbirth, improve maternal care and support bereaved families. METHODS AND ANALYSIS: In this case-control study with stillbirths and live births in 14 public hospitals in São Paulo, mothers are interviewed at hospitals after delivery, and hospital records and prenatal care registries are reviewed. Maternal and umbilical cord blood samples and placentas are collected to analyse angiogenesis and infection biomarkers, and the placenta's anatomopathological exam. Air pollutant exposure is estimated through the participant's residence and work addresses. Traditional and non-invasive autopsies by image-guided histopathology are conducted in a subset of stillbirths. Subsample mothers of cases are interviewed at home 2 months after delivery on how they were dealing with grief. Information contained in the official prenatal care registries of cases and controls is being compiled. Hospital managers are interviewed about the care offered to stillbirth mothers. Data analysis will identify the main risk factors for stillbirth, investigate their interrelations, and evaluate health services care and support for bereaved families. We hope this project will contribute to the understanding of stillbirth's risk factors and related health services in Brazil, providing new knowledge about this central public health problem, contributing to the improvement of public policies and prenatal and puerperal care, helping to prevent stillbirths and improve the healthcare and support for bereaved families. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of the Municipal Health Secretary (process no 16509319.0.3012.5551) and of the Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (process no 16509319.0.0000.0068). Results will be communicated to the study participants, policy-makers and the scientific community., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Nasal allergen challenge (NAC) is used to investigate the effects of allergen exposure and assess treatment efficacy in allergic rhinitis (AR). This study aims to establish dose-responses to NAC using licensed silver birch (SB) pollen and house dust mite (HDM) sublingual tablets as sources of the allergen extracts in participants with AR., Methods: Sixteen volunteers with HDM-induced perennial AR and 15 volunteers with SB pollen-induced seasonal rhinitis underwent a graded up-dosing NAC with extracts derived from HDM allergen (Acarizax®) and SB (Itulazax®) tablets, respectively. Total nasal symptom score (TNSS, range 0-12) and peak nasal inspiratory flow (PNIF) were recorded before, at 10 min and at the end of the NAC. The dose of each allergen that provoked a TNSS of at least 7 ("provoking dose 7") in most allergic participants was identified. NACs using the "provoking dose 7" were performed on 5 non-allergic individuals to test for irritant effects. The "provoking dose 7" of HDM extract was used in a subgroup of two SB allergic, non-HDM allergic, volunteers, and vice versa for SB extract, to test for allergen specificity of the responses., Results: Most patients experienced a TNSS of at least 7/12 at a median concentration of 1500 AU/mL for both SB pollen and HDM. The average decline in PNIF at this dose was 63.15% for SB and 63.99% for HDM. NACs using the 1500 AU/mL concentrations were performed on 5 non-allergic individuals with no symptomatic or PNIF response. 1500 AU/mL of HDM extract produced no symptoms in SB allergics nor 1500 AU/mL SB extract in HDM allergics., Conclusion: For both SB and HDM extracts, the optimal allergen dose for NAC to cause a moderate-severity response ("provoking dose 7/12") was 1500 AU/mL. Licensed sublingual allergen tablets provide a readily available and inexpensive source of SB and HDM extracts for use in future interventional studies in AR., (© 2024 The Author(s). Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Background: The shape and microstructure of the human crystalline lens alter with ageing, and this has an effect on the optical properties of the eye. The aim of this study was to characterise the age-related differences in the morphology and transparency of the eye lenses of healthy subjects through the optical signal discontinuity (OSD) zones in optical coherence tomography (OCT) images. We also investigated the association of those changes with the optical quality of the eye and visual function., Methods: OCT images of the anterior segment of 49 eyes of subjects (9-78 years) were acquired, and the OSD zones (nucleus, C1-C4 cortical zones) were identified. Central thickness, curvature and optical density were measured. The eye's optical quality was evaluated by the objective scatter index (OSI). Contrast sensitivity and visual acuity tests were performed. The correlation between extracted parameters and age was assessed., Results: The increase in lens thickness with age was dominated by the thickening of the cortical zone C3 (0.0146 mm/year). The curvature radii of the anterior lens surface and both anterior and posterior nucleo-cortical interfaces decreased with age (- 0.053 mm/year, - 0.013 mm/year and - 0.006 mm/year, respectively), and no change was observed for the posterior lens radius. OCT-based densitometry revealed significant correlations with age for all zones except for C1β, and the highest increase in density was in the C2-C4 zones (R = 0.45, 0.74, 0.56, respectively, P < 0.001). Increase in OSI was associated with the degradation of visual function., Conclusions: OCT enables the identification of OSD zones of the crystalline lens. The most significant age-related changes occur in the C3 zone as it thickens with age at a faster rate and becomes more opaque than other OSD zones. The changes are associated with optical quality deterioration and reduction of visual performance. These findings contribute to a better understanding of the structure-function relationship of the ageing lens and offer insights into both pathological and aging alterations., (© 2023. The Author(s).)

Sporting events were cancelled, and sports training was banned to prevent the spread of COVID-19. These changes during the COVID-19 pandemic decreased the physical activity levels, increased sedentary time, and also impaired the mental health of elite and sub-elite athletes. The impact on body composition and physical performance is not clear, however, especially considering a systematic review with meta-analysis. Thus, our objective was to conduct a review in accordance with the PRISMA Statement studies published in scientific journals (PubMed, Web of Science, or Scopus databases) that investigated the effect that social distancing during the COVID-19 pandemic had on the physical performance (muscle power, cardiorespiratory capacity, and sprint) or body composition (body weight, percentage of fat, fat mass, and fat-free mass) of athletes. Data from 24 studies indicate that, throughout the global lockdown, the athletes maintained muscle power, cardiorespiratory capacity, and sprint, and prevented significant changes in fat mass and fat-free mass. However, the total body weight (meta-analysis with 18 studies), showed a significant increase ( p = 0.006), with a small ES = 0.12; 95% CI = 0.04 to 0.21. Furthermore, the time of follow-up, level of training, and the age of the athletes were possible moderators of these effects. The data reinforce the importance of general strength and endurance exercises sessions to maintain physical fitness during non-competitive periods or due to the mandatory lockdown.

The epithelium covering the surfaces of the cerebral ventricular system is known as the ependyma, and is essential for maintaining the physical and functional integrity of the central nervous system. Additionally, the ependyma plays an essential role in neurogenesis, neuroinflammatory modulation and neurodegenerative diseases. Ependyma barrier is severely affected by perinatal hemorrhages and infections that cross the blood brain barrier. The recovery and regeneration of ependyma after damage are key to stabilizing neuroinflammatory and neurodegenerative processes that are critical during early postnatal ages. Unfortunately, there are no effective therapies to regenerate this tissue in human patients. Here, the roles of the ependymal barrier in the context of neurogenesis and homeostasis are reviewed, and future research lines for development of actual therapeutic strategies are discussed., 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 Paez-Gonzalez, Sebastian, Ceron-Funez, Jimenez and Rodríguez-Perez.)

Clinical evidence based on real-world data (RWD) is accumulating exponentially providing larger sample sizes available, which demand novel methods to deal with the enhanced heterogeneity of the data. Here, we used RWD to assess the prediction of cognitive decline in a large heterogeneous sample of participants being enrolled with cognitive stimulation, a phenomenon that is of great interest to clinicians but that is riddled with difficulties and limitations. More precisely, from a multitude of neuropsychological Training Materials (TMs), we asked whether was possible to accurately predict an individual's cognitive decline one year after being tested. In particular, we performed longitudinal modelling of the scores obtained from 215 different tests, grouped into 29 cognitive domains, a total of 124,610 instances from 7902 participants (40% male, 46% female, 14% not indicated), each performing an average of 16 tests. Employing a machine learning approach based on ROC analysis and cross-validation techniques to overcome overfitting, we show that different TMs belonging to several cognitive domains can accurately predict cognitive decline, while other domains perform poorly, suggesting that the ability to predict decline one year later is not specific to any particular domain, but is rather widely distributed across domains. Moreover, when addressing the same problem between individuals with a common diagnosed label, we found that some domains had more accurate classification for conditions such as Parkinson's disease and Down syndrome, whereas they are less accurate for Alzheimer's disease or multiple sclerosis. Future research should combine similar approaches to ours with standard neuropsychological measurements to enhance interpretability and the possibility of generalizing across different cohorts., (© 2023 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

The left ventricular summit is a site of origin for idiopathic ventricular arrhythmias. With advancements in mapping and ablation techniques, sites previously considered inaccessible can now be approached. Anatomical knowledge of the 3-dimensional landmarks of this space is important, as critical structures reside within its boundaries and are potentially liable to collateral injury during ablation. This article reviews reported complications from ablation of ventricular arrhythmias arising from the left ventricular summit and its vicinity and discusses the pros and cons of different ablation technique and the role of an individualized anatomical approach to reduce procedural related complications and improve outcomes., Competing Interests: Disclosures Neither author reports conflicts of interest pertaining to the writing of this article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Gay, bisexual, and other men who have sex with men (GBMSM) continue to be overrepresented in human immunodeficiency virus (HIV) infection in the United States. HIV prevention and care interventions that are tailored to an individual's serostatus have the potential to lower the rate of new infections among GBMSM. Mobile technology is a critical tool for disseminating targeted messaging and increasing uptake of basic prevention services including HIV testing, sexually transmitted infection (STI) testing, and pre-exposure prophylaxis (PrEP). Mobile Messaging for Men (M-Cubed) is a mobile health HIV prevention intervention designed to deliver video- and text-based prevention messages, provide STI and HIV information, and link GBMSM to prevention and healthcare resources. The current report describes an iterative process of identifying and selecting publicly available videos to be used as part of the M-Cubed intervention. We also conducted interviews with GBMSM to assess the acceptability, comprehension, and potential audience reach of the selected video messages., Methods: The selection of videos included balancing of specific criteria [e.g., accuracy of scientific information, video length, prevention domains: HIV/STI testing, antiretroviral therapy (ART), PrEP, engagement in care, and condom use] to ensure that they were intended for our GBMSM audiences: HIV-negative men who engage in condomless anal sex, HIV-negative men who do not engage in condomless anal sex, and men living with HIV. This formative study included in-person interviews with 26 GBMSM from three U.S. cities heavily impacted by the HIV epidemic-New York City, Detroit, and Atlanta., Results: Following a qualitative content analysis, the study team identified five themes across the interviews: participant reactions to the video messages, message comprehension, PrEP concerns, targeting of video messaging, and prompted action., Conclusions: Study results informed a final selection of 12 video messages for inclusion in a randomized controlled trial of M-Cubed. Findings may serve as a guide for researchers who plan to develop HIV prevention interventions that utilize publicly available videos to promote behavioral change. Further, the findings presented here suggest the importance of developing videos with broad age and gender diversity for use in interventions such as M-Cubed, and in other health promotion settings., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://mhealth.amegroups.com/article/view/10.21037/mhealth-21-53/coif). PSS reports that his funding from CDC and NIH are payments made to his institution for other research projects, and they are not related to the present work. ISY has been a full-time employee of Mattel Global Consumer Insights since 2021, but received no support related to this publication. The other authors have no conflicts of interest to declare., (2023 mHealth. All rights reserved.)

In this study, chitosan-coated biogenic silver nanoparticles (AgNP-CH) were obtained through green chemistry by recycling wheat crop leaf residues. The nanoparticles were characterized by UV-VIS spectroscopy, and total reflectance-Fourier transform infrared spectroscopy confirmed the nanoparticle formation, and the incorporation of chitosan surrounding silver nanoparticles. The size and morphology of nanoparticles were evaluated by microscopy techniques, showing a size range of 2-10 nm, with spherical shape and narrow distribution. The antifungal assay indicated a higher antimicrobial activity showing values of minimum inhibitory concentrations of 41.7 μg/mL against Fusarium oxysporum, and 208.37 μg/mL for Aspergillus niger, A. versicolor and A. brasiliensis. Finally, non-phytotoxic effects were observed in germination assays at early plant stage of development, and an increase in chlorophyll levels were observed at the doses tested with AgNP-CH. Thus, the use of AgNP-CH could be a potential alternative for the prevention of fungal infections in cereals in the early stages of wheat crop development., 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 B.V. All rights reserved.)

Heparanase (HPSE) is an endo-β-glucuronidase involved in extracellular matrix remodeling in rapidly healing tissues, most cancers and inflammation, and viral infection. Its importance as a therapeutic target warrants further study, but such is hampered by a lack of research tools. To expand the toolkits for probing HPSE enzymatic activity, we report the design of a substrate scaffold for HPSE comprised of a disaccharide substrate appended with a linker, capable of carrying cargo until being cleaved by HPSE. Here exemplified as a fluorogenic, coumarin-based imaging probe, this scaffold can potentially expand the availability of HPSE-responsive imaging or drug delivery tools using a variety of imaging moieties or other cargo. We show that electronic tuning of the scaffold provides a robust response to HPSE while simplifying the structural requirements of the attached cargo. Molecular docking and modeling suggest a productive probe/HPSE binding mode. These results further support the hypothesis that the reactivity of these HPSE-responsive probes is predominantly influenced by the electron density of the aglycone. This universal HPSE-activatable scaffold will greatly facilitate future development of HPSE-responsive probes and drugs.

Carotenoids are C40 isoprenoids with well-established roles in photosynthesis, pollination, photoprotection, and hormone biosynthesis. The enzymatic or ROS-induced cleavage of carotenoids generates a group of compounds named apocarotenoids, with an increasing interest by virtue of their metabolic, physiological, and ecological activities. Both classes are used industrially in a variety of fields as colorants, supplements, and bio-actives. Crocins and picrocrocin, two saffron apocarotenoids, are examples of high-value pigments utilized in the food, feed, and pharmaceutical industries. In this study, a unique construct was achieved, namely O6, which contains CsCCD2L , UGT74AD1 , and UGT709G1 genes responsible for the biosynthesis of saffron apocarotenoids driven by a patatin promoter for the generation of potato tubers producing crocins and picrocrocin. Different tuber potatoes accumulated crocins and picrocrocin ranging from 19.41-360 to 105-800 μg/g DW, respectively, with crocetin, crocin 1 [(crocetin-(β-D-glucosyl)-ester)] and crocin 2 [(crocetin)-(β-D-glucosyl)-(β-D-glucosyl)-ester)] being the main compounds detected. The pattern of carotenoids and apocarotenoids were distinct between wild type and transgenic tubers and were related to changes in the expression of the pathway genes, especially from PSY2 , CCD1 , and CCD4 . In addition, the engineered tubers showed higher antioxidant capacity, up to almost 4-fold more than the wild type, which is a promising sign for the potential health advantages of these lines. In order to better investigate these aspects, different cooking methods were applied, and each process displayed a significant impact on the retention of apocarotenoids. More in detail, the in vitro bioaccessibility of these metabolites was found to be higher in boiled potatoes (97.23%) compared to raw, baked, and fried ones (80.97, 78.96, and 76.18%, respectively). Overall, this work shows that potatoes can be engineered to accumulate saffron apocarotenoids that, when consumed, can potentially offer better health benefits. Moreover, the high bioaccessibility of these compounds revealed that potato is an excellent way to deliver crocins and picrocrocin, while also helping to improve its nutritional value., 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 Gómez Gómez, Morote, Frusciante, Rambla, Diretto, Niza, López-Jimenez, Mondejar, Rubio-Moraga, Argandoña, Presa, Martín-Belmonte, Luján, Granell and Ahrazem.)

The aim of this study was to investigate the metabolic and inflammatory fluctuations in two seasonal phases of badminton training, and the ability of youth badminton athletes to respond to an inflammatory challenge given by acute exercise on these markers. Thirteen youth badminton athletes who participated in national and international competitions were recruited. Metabolic and cytokine profile were measured at rest and in response to a maximal exercise intermittent test, in the pre- and final phases of a badminton annual season. At rest, glucose (-7.58 mg/dL; p = 0.045) and HDL-cholesterol (HDL-c) (-26.87 mg/dL; p &lt; 0.0001) decreased at final-season. The variation of HDL-c in response to a maximal exercise test increased at final-season in comparison to pre-season (+ 10.20 mg/dL p = 0.042). Similarly, delta changes of IL-10 (+ 3.41 pg/ml; p = 0.047) and IL-1Ra (+ 141.3 pg/ml; p = 0.031) were greater at final-season. In addition, a significantly greater variation of the anti-inflammatory IL-10/IL-17 ratio was observed at final-season (+ 0.37; p = 0.010). In conclusion, our results showed a major responsivity of IL-10 and IL-1Ra to a maximal exercise even at the end of an entire season. The major responsivity of these cytokines at this time point suggests a more effective acute inflammatory response in youth badminton athletes. Therefore, the results of this study may be applied by coaches, trainers and sport nutritionist for proper training management., (© 2022. The Author(s).)

Recent literature has shown how the HIV architecture, including community systems, has been critical for fighting COVID-19 in many countries, while sustaining the HIV response. Innovative initiatives suggest that fostering the integration of health services would help address the colliding pandemics. However, there are few documented real-life examples of community mobilisation strategies responding to COVID-19 and HIV. The African Union and Africa Centres for Disease Control and Prevention (Africa CDC) launched the Partnership to Accelerate COVID-19 Testing (PACT) in June 2020 with the goal of training and deploying one million community health workers across the continent. UNAIDS partnered with Africa CDC to implement the PACT initiative in seven countries, i.e. Algeria, Côte d'Ivoire, Gabon, Ghana, Madagascar, Malawi and Namibia. The initiative engaged networks of people living with HIV and community-led organisations to support two of its pillars, test and trace, and the sensitisation to protective measures against COVID-19 for the most vulnerable populations. It later expanded to improve access to COVID-19 vaccines. Based on the assessment of country projects, this article explains how PACT activities implemented by communities contributed to mitigating COVID-19 and HIV among vulnerable and marginalised groups. This article contributes to a better understanding of the impact of a community-based approach in responding effectively to emerging health threats and provides lessons from integrated COVID-19 and HIV community-led responses.

In 2020 the Global Fund for AIDS, Tuberculosis and Malaria initiated a new funding modality, the COVID-19 Response Mechanism, to mitigate the pandemic's effects on HIV, TB and malaria programmes and health systems in implementer countries. In 2021 UNAIDS introduced an innovative technical virtual support mechanism for COVID-19 Response Mechanism proposal development to help countries quickly implement COVID-19 interventions while at the same time adapting HIV and related services to the pandemic's circumstances and mitigate its impact while maintaining hard-won gains. It also intended to ensure more attention was paid to communities, human rights and gender considerations in proposal development, resulting in successful proposals to mitigate COVID-19's impact, bring human rights-based and people-centred HIV programmes back on track and even expand their reach through using new delivery platforms. In 2021, applications from 18 sub-Saharan African and Asian countries received in-depth remote peer reviews. We discuss the reviews' key findings and recommendations to improve proposal quality and identify future opportunities for virtual technical support. The model was successful and contributed to better quality funding applications, but also highlighted challenges in pandemic mitigation, adaptations and innovations of HIV programmes. Countries still fell short on comprehensive community, human rights and gender interventions, as well as innovations in HIV service delivery, especially in prevention and gender-based violence. Several other weaknesses meant that some countries would have to refine their programme design and implementation model in the final version of their funding application. There are implications for future assistance to countries trying to mitigate the impact of COVID-19 on their health programmes and innovative ways to deliver technical support using new technologies and local expertise.

The current status of controversy regarding the use of certain preservatives in cosmetic products makes it necessary to seek new ecological alternatives that are free of adverse effects on users. In our study, two different natural terpenes Carvacrol and Eugenol were encapsulated in chitosan nanoparticles in different ratios of Chitosan:terpene. The nanoparticles were characterized by DLS and TEM showing a maximum particle size of 100 nm. The chemical structure, thermal properties, and release profile of terpenes were evaluated showing a successful protection of terpene in Chitosan matrix. Two different release profile were observed showing a faster release profile in the case of Eugenol. Antimicrobial properties of nanoparticles were evaluated against typical microbial contaminants found in cosmetic products, showing higher antimicrobial properties with chitosan encapsulation of terpenes. Furthermore, natural moisturizing cream inoculated with beforementioned microorganisms was formulated with Carvacrol-chitosan nanoparticles and Eugenol-chitosan nanoparticles to evaluate the preservative efficiency, indicating a highest preservative efficiency with the use of Eugenol-chitosan nanoparticles., (Copyright © 2022 Elsevier B.V. All rights reserved.)

During cytokinesis, the intercellular bridge (ICB) connecting the daughter cells experiences pulling forces, which delay abscission by preventing the assembly of the ESCRT scission machinery. Abscission is thus triggered by tension release, but how ICB tension is controlled is unknown. Here, we report that caveolae, which are known to regulate membrane tension upon mechanical stress in interphase cells, are located at the midbody, at the abscission site, and at the ICB/cell interface in dividing cells. Functionally, the loss of caveolae delays ESCRT-III recruitment during cytokinesis and impairs abscission. This is the consequence of a twofold increase of ICB tension measured by laser ablation, associated with a local increase in myosin II activity at the ICB/cell interface. We thus propose that caveolae buffer membrane tension and limit contractibility at the ICB to promote ESCRT-III assembly and cytokinetic abscission. Together, this work reveals an unexpected connection between caveolae and the ESCRT machinery and the first role of caveolae in cell division.

In this study, garlic essential oil (GEO) has been encapsulated in chitosan nanoparticles (NPCH) with sodium tripolyphosphate (TPP). Fourier transform infrared (FT-IR) spectroscopy, UV-vis spectrophotometry, thermogravimetric analysis (TGA) and X-ray diffraction (XRD) techniques were applied to characterize GEO-NPCH. The obtained nanoparticles exhibited a regular distribution and spherical shape with size range of 200-400 nm as revealed by scanning electron microscopy (SEM). The maximum encapsulation efficiency (EE) and loading capacity (LC) of GEO-loaded chitosan nanoparticles were about 32.8% and 19.8% respectively. Nanoparticle formulations of GEO were found to have antifungal activity against Aspergillus versicolor, A. niger and Fusarium oxysporum. In addition, they showed growth promoting effects by increasing emergence, shoot and root fresh weight on wheat, oat and barley., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To describe electrocardiographic vector patterns during early VF transition (Wiggers stage 1)., Methods: In 100 electrophysiology studies with VF induction, the first 3 beats of VF were analyzed in lead I for left/right axis (LA/RA), V1 for left/right bundle (LB/RB), and aVF for superior/inferior axis (SA/IA). Correlation with demographic/clinical factors was performed using regression analyses and mixed effect modeling., Results: VF initiated more likely with LA than RA (P < 0.001) and LB than RB (P = 0.04) suggesting original wavebreak in the right ventricle. The 3-dimensional morphology changed in 69% of VF during the first 3 beats, with predominant increase in RB, suggesting a transition of QRS-originating vector to septum/left ventricle. Conservation of morphology (31%) was favored by initial RB (P = 0.002) and LA morphology (P = 0.01). Initiation of VF with LA vs RA was more likely in African-Americans (P = 0.016) and increasing age (P = 0.032). Ischemic cardiomyopathy favored VF initiation with RB 6.7-fold (P = 0.025), possibly linking LV myocardial scar to initial VF wavebreak location. Male gender and ischemic cardiomyopathy prolonged time-to-loss of predominant vector by 119% (P = 0.002) and 71% (P = 0.017), respectively, suggesting more preserved anatomic/functional reentry., Conclusion: The predominant QRS vectors during early Wiggers stage 1 VF are not random and suggest an initial wavebreak more commonly in the right ventricle, followed by a transitional shift to the septum/left ventricle. Ethnicity, male gender, age, and co-morbidities result in directional preservation of initiating VF vectors possibly due to myocardial mass/fibrosis. Findings may allow new treatment/ablation approaches., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Badminton is a racket sport, with fast and explosive movements and mental skills employed to anticipate the opponent's movements. The COVID-19 pandemic, led to social restriction in Brazil and sport event cancellations, subsequently, sports training was banned. Thus, the objective of this study was to compare the impact of long-period detraining due to COVID-19 social restriction (8 months and 1-year) on cardiorespiratory fitness, body composition, nutritional behavior, and profile of mood states in badminton athletes and to verify if the athletes who returned to their regular training 4 months earlier than athletes who stopped their daily training routine during 1-year would improve these variables., Methods: Twenty-three young badminton athletes were analyzed: retrained group (14 athletes who stopped their daily training routine for 8 months due to the COVID-19 pandemic plus 4 months of retraining), and detrained group (9 athletes who stopped their daily training routine during 1 year of the COVID-19 pandemic but performed home-based training). We evaluated body composition, cardiorespiratory fitness, nutritional behavior, and mood states profiles., Results: Retrained athletes showed lower body fat (- 24.1% vs. + 20.8%, p  < 0.001) and higher fat-free mass (+ 6.0% vs. - 0.2%, p  = 0.007) after 1 year compared with the detrained group. For cardiorespiratory fitness [retrained: baseline = 55.5 ± 5.3 (47.1, 63.9) and after 1 year = 58.1 ± 2.4 (54.2, 61.9), ES = 0.65 vs. detrained: baseline = 53.4 ± 6.7 (47.2, 59.5) and after 1 year = 53.1 ± 5.6 (48.0, 58.3), ES = - 0.03] and nutritional behavior, including sauces and spices [retrained: baseline = 8.9 ± 7.0 (4.5, 13.4), and after 1 year = 3.4 ± 2.9 (1.8, 5.5), ES = - 1.11 vs. detrained: baseline = 6.8 ± 6.7 (1.6, 11.9) and after 1 year = 6.3 ± 5.5 (2.1, 10.6), ES = - 0.08], the ESs were medium and large, respectively, for Retrained but trivial for detrained group. For depression, ES was trivial in the retrained [baseline = 2.7 ± 3.3 (0.7, 4.7) and after 1 year = 2.6 ± 2.9 (0.8, 4.4), ES = 0.03] and moderate for detrained [baseline = 1.0 ± 1.5 (- 0.1, 2.1) and after 1 year = 1.8 ± 2.7 (- 0.3, 3.8), ES = 0.50]., Conclusions: Young badminton athletes who returned to their regular daily training 4 months earlier than athletes who stopped their daily training routine during 1-year due to COVID-19 social restriction decreased fat mass and increased fat-free mass. There were no significant differences between groups for cardiorespiratory fitness, nutritional behavior, and profile of mood state response., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer-Verlag Italia S.r.l., part of Springer Nature 2022.)

Introduction: The use of traditional birth attendants (TBAs) in low- and middle-income countries remains controversial. The aim of this secondary analysis was to observe factors associated with visiting a TBA in addition to a skilled nurse for antepartum care and how this additional care was associated with birth characteristics and outcomes., Methods: The study included a convenience sample of women living in Southwestern Guatemala enrolled in a community nursing program between October 1, 2018, and December 3, 2019. This analysis describes the sociodemographic characteristics, antepartum care, birth outcomes, and postpartum behaviors of women who received antepartum care with skilled nurses only compared with women who received antepartum care with skilled nurses and a TBA., Results: Of the 316 enrollees, 259 had given birth and completed their postpartum visit at the time of analysis. Three women were excluded because of missing data. The majority of women in the study sample reported visiting a TBA over the course of their pregnancies (80.9%). Women who saw a TBA in addition to the nurse were similar to the comparator sample except that they were almost 3 times more likely to have 8 or more prenatal contacts with the nurse. In separate multivariable logistic regression models adjusted for number of prenatal visits, women who saw a TBA in addition to nurses had a reduced likelihood of cesarean birth, increased likelihood of birth with a TBA, and increased likelihood of breastfeeding within one hour of birth compared with women who only received antenatal care from nurses. Patient-reported adverse outcomes were not included in the analysis because of low prevalence and concern about data quality and missing data., Discussion: Among a convenience sample of women in the Trifinio community in rural Guatemala, a large proportion of women continued to seek the care of a TBA in pregnancy while using a skilled nursing program for antenatal care. Intentionally integrating the TBA into the maternity care workforce may be beneficial for improving pregnancy care quality measures., (© 2022 by the American College of Nurse-Midwives.)

Crocetin is an apocarotenoid formed from the oxidative cleavage of zeaxanthin, by the carotenoid cleavage enzymes CCD2 (in Crocus species) and specific CCD4 enzymes in Buddleja davidii and Gardenia jasminoides. Crocetin accumulates in the stigma of saffron in the form of glucosides and crocins, which contain one to five glucose molecules. Crocetin glycosylation was hypothesized to involve at least two enzymes from superfamily 1 UDP-sugar dependent glycosyltransferases. One of them, UGT74AD1, produces crocins with one and two glucose molecules, which are substrates for a second UGT, which could belong to the UGT79, 91, or 94 families. An in silico search of Crocus transcriptomes revealed six candidate UGT genes from family 91. The transcript profiles of one of them, UGT91P3, matched the metabolite profile of crocin accumulation, and were co-expressed with UGT74AD1. In addition, both UGTs interact in a two-hybrid assay. Recombinant UGT91P3 produced mostly crocins with four and five glucose molecules in vitro, and in a combined transient expression assay with CCD2 and UGT74AD1 enzymes in Nicotiana benthamiana. These results suggest a role of UGT91P3 in the biosynthesis of highly glucosylated crocins in saffron, and that it represents the last missing gene in crocins biosynthesis.

This article reviews the basis for image integration of intracardiac echocardiography (ICE) with three-dimensional electroanatomic mapping systems and preprocedural cardiac imaging modalities to enhance anatomic understanding and improve guidance for atrial and ventricular ablation procedures. It discusses the technical aspects of ICE-based integration and the clinical evidence for its use. In addition, it presents the current technical limitations and future directions for this technology. This article also includes figures and videos of clinical representative arrhythmia cases where the use of ICE is key to a safe and successful outcome., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Tetanus toxin blocks the release of the inhibitory neurotransmitters in the central nervous system and causes tetanus and its main form of prevention is through vaccination. The vaccine is produced by inactivation of tetanus toxin with formaldehyde, which may cause side effects. An alternative way is the use of ionizing radiation for inactivation of the toxin and also to improve the potential immunogenic response and to reduce the post-vaccination side effects. Therefore, the aim of this study was to characterize the tetanus toxin structure after different doses of ionizing radiation of 60 Co., Methods: Irradiated and native tetanus toxin was characterized by SDS PAGE in reducing and non-reducing conditions and MALD-TOF. Enzymatic activity was measured by FRET substrate. Also, antigenic properties were assessed by ELISA and Western Blot data., Results: Characterization analysis revealed gradual modification on the tetanus toxin structure according to doses increase. Also, fragmentation and possible aggregations of the protein fragments were observed in higher doses. In the analysis of peptide preservation by enzymatic digestion and mass spectrometry, there was a slight modification in the identification up to the dose of 4 kGy. At subsequent doses, peptide identification was minimal. The analysis of the enzymatic activity by fluorescence showed 35 % attenuation in the activity even at higher doses. In the antigenic evaluation, anti-tetanus toxin antibodies were detected against the irradiated toxins at the different doses, with a gradual decrease as the dose increased, but remaining at satisfactory levels., Conclusion: Ionizing radiation promoted structural changes in the tetanus toxin such as fragmentation and/or aggregation and attenuation of enzymatic activity as the dose increased, but antigenic recognition of the toxin remained at good levels indicating its possible use as an immunogen. However, studies of enzymatic activity of tetanus toxin irradiated with doses above 8 kGy should be further analyzed., Competing Interests: Competing interests: The authors declare that they have no competing interests.

A 33-year-old woman presented with sustained monomorphic ventricular tachycardia (VT). The 12-lead electrocardiogram, 3-dimensional (3D) picture of chest electrodes, and cardiac magnetic resonance were used to create a noninvasive 3D electrocardiographic imaging map to identify the most likely site of VT origin. This map was integrated with a 3D mapping system to aid in VT ablation. ( Level of Difficulty: Advanced. )., Competing Interests: Catheter Precision (Ledgewood, New Jersey) provided technical support for their VIVO system, and Biosense Webster (Irvine, California) provided technical support for their CARTO system. Dr. Jeudy has reported unpaid consulting for Catheter Precision. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 Published by Elsevier on behalf of the American College of Cardiology Foundation.)

The centrosome is the main organizer of microtubules and as such, its position is a key determinant of polarized cell functions. As the name says, the default position of the centrosome is considered to be the cell geometrical center. However, the mechanism regulating centrosome positioning is still unclear and often confused with the mechanism regulating the position of the nucleus to which it is linked. Here, we used enucleated cells plated on adhesive micropatterns to impose regular and precise geometrical conditions to centrosome-microtubule networks. Although frequently observed there, the equilibrium position of the centrosome is not systematically at the cell geometrical center and can be close to cell edge. Centrosome positioning appears to respond accurately to the architecture and anisotropy of the actin network, which constitutes, rather than cell shape, the actual spatial boundary conditions the microtubule network is sensitive to. We found that the contraction of the actin network defines a peripheral margin in which microtubules appear bent by compressive forces. The progressive disassembly of the actin network at distance from the cell edges defines an inner zone where actin bundles were absent, where microtubules were more radially organized and where dynein concentration was higher. We further showed that the production of dynein-based forces on microtubules places the centrosome at the center of this zone. In conclusion, the spatial distribution of cell adhesion and the production of contractile forces define the architecture of the actin network with respect to which the centrosome-microtubule network is centered., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In many animal models, primordial germ cell (PGC) development depends on maternally deposited germ plasm, which prevents somatic cell fate. Here, we show that PGCs respond to regulatory information from the germ plasm in two distinct phases using two distinct mechanisms in zebrafish. We demonstrate that PGCs commence zygotic genome activation together with the somatic blastocysts with no demonstrable differences in transcriptional and chromatin opening. Unexpectedly, both PGC and somatic blastocysts activate germ-cell-specific genes, which are only stabilized in PGCs by cytoplasmic germ plasm determinants. Disaggregated perinuclear relocalization of germ plasm during PGC migration is regulated by the germ plasm determinant Tdrd7 and is coupled to dramatic divergence between PGC and somatic transcriptomes. This transcriptional divergence relies on PGC-specific cis-regulatory elements characterized by promoter-proximal distribution. We show that Tdrd7-dependent reconfiguration of chromatin accessibility is required for elaboration of PGC fate but not for PGC migration., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Pulmonary toxoplasmosis is rare in immunocompetent patients. Herein, a Toxoplasma gondii strain isolated in Brazil from an immunocompetent patient who had severe pulmonary involvement was biologically and molecularly characterized for the first time. The TgHumIMTBr1 isolate was bioassayed in mice showing a virulent phenotype. Restriction fragment length polymorphism (RFLP) genotyping using 11 markers [SAG1, SAG2 (5´3´SAG2 and alt. SAG2), SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, Apico and CS3] revealed a new non-archetypal genotype assigned as #312. Genotyping using ROP18/ROP5 markers exhibited the virulent combination of alleles 4 and 1. Microsatellite analysis using 15 markers (TUB2, W35, TgM-A, B18, B17, M33, IV.1, X1.1, N60, N82, AA, N61, N83, M48 and M102) revealed an atypical genotype with three unique alleles and a rare combination of alleles 246 (W35) and 203 (TgM-A) that is typical of the Amazon region. Non-archetypal genotypes with unique alleles may function in the occurrence of severe toxoplasmosis in immunocompetent patients in Brazil. Attempts to isolate or molecularly detect T. gondii for further genotyping studies would contribute to the understanding of causes related to the severity of toxoplasmosis in immunocompetent patients.

African Americans have disproportionate rates of post-cessation weight gain compared to non-Hispanic whites, but few studies have examined this weight gain in a multiracial sample of smokers receiving evidence-based treatment in a community setting. We examined race differences in short-term weight gain during an intervention to foster smoking cessation plus weight management. Data were drawn from the Best Quit Study, a randomized controlled trial conducted via telephone quitlines across the U.S. from 2013 to 2017. The trial tested the effects on cessation and weight gain prevention of adding a weight control intervention either simultaneously with or sequentially after smoking cessation treatment. African Americans (n = 665) and whites (n = 1723) self-reported smoking status and weight during ten intervention calls. Random effects longitudinal modeling was used to examine predictors of weight change over the intervention period (average 16 weeks). There was a significant race × treatment effect; in the simultaneous group, weight increased for African Americans at a faster rate compared to whites (b = 0.302, SE = 0.129, p  < 0.05), independent of smoking status, age, baseline obesity, and education. After stratifying the sample, the effect of treatment group differed by race. Education level attenuated the rate of weight gain for African Americans in the simultaneous group, but not for whites. African Americans receiving smoking and weight content simultaneously gained weight faster than whites in the same group; however, the weight gain was slower for African Americans with higher educational attainment. Future studies are needed to understand social factors associated with treatment receptivity that may influence weight among African American smokers., Competing Interests: The authors at Alere Wellbeing (TB, AJT, and KW) declare that they are employed by Alere Wellbeing (a subsidiary of Optum) which provides tobacco cessation and weight management services to states and commercial clients. They have no other competing interests. MT, JCL, HJ, and BS have no conflicts to disclose. No financial disclosures were reported by the authors of this paper., (© 2020 The Authors.)

Background: COVID-19 is one of the biggest pandemics in human history, along with other disease pandemics, such as the H1N1 influenza A, bubonic plague, and smallpox pandemics. This study is a small contribution that tries to find contrasted formulas to alleviate global suffering and guarantee a more manageable future., Objective: In this study, a statistical approach was proposed to study the correlation between the incidence of COVID-19 in Spain and search data provided by Google Trends., Methods: We assessed the linear correlation between Google Trends search data and the data provided by the National Center of Epidemiology in Spain-which is dependent on the Instituto de Salud Carlos III-regarding the number of COVID-19 cases reported with a certain time lag. These data enabled the identification of anticipatory patterns., Results: In response to the ongoing outbreak, our results demonstrate that by using our correlation test, the evolution of the COVID-19 pandemic can be predicted in Spain up to 11 days in advance., Conclusions: During the epidemic, Google Trends offers the possibility to preempt health care decisions in real time by tracking people's concerns through their search patterns. This can be of great help given the critical, if not dramatic need for complementary monitoring approaches that work on a population level and inform public health decisions in real time. This study of Google search patterns, which was motivated by the fears of individuals in the face of a pandemic, can be useful in anticipating the development of the pandemic., (©Alberto Jimenez Jimenez, Rosa M Estevez-Reboredo, Miguel A Santed, Victoria Ramos. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 18.12.2020.)

Objectives: COVID-19 is a public health emergency of international concern whose detection in recovered asymptomatic patients is dependent on accurate diagnosis as it enables the estimation of the susceptibility of the population to the infection. This demand has resulted in the development of several commercial assays employing recombinant proteins, but the results of these assays are not reliable as they do not involve comparison with natural viral antigens. We independently used the SARS-CoV-2 whole viral antigen (WVA) and recombinant nucleocapsid protein (rNP) to develop in-house ELISAs for IgG detection; the results of these ELISAs were then compared to obtain reliable results., Methods: WVA and rNP ELISAs were performed on COVID-19 negative sera from patients before the pandemic in Brazil, and on RT-qPCR-positive or SARS-CoV-2-IgG against rNP and IgG against WVA-positive samples from recently infected patients in Sao Paulo, Brazil., Results: Both ELISAs detected a large fraction of infected patients but exhibited certain drawbacks. Higher signals and lower numbers of false-negatives were observed in rNP ELISA; however, a higher fraction of false-positives was observed in control groups. A high number of false-negatives was observed with WVA ELISA. Correlating the results of rNP and WVA ELISAs resulted in improved performance for COVID-19 diagnosis., Conclusion: The choice of antigen is an important aspect in optimizing the laboratory diagnosis of COVID-19. The use of rNP ELISA for the detection of anti-SARS-CoV-2 IgG antibodies seems promising, but comparison of the results with those of WVA ELISA is crucial for accurate test development prior to commercialization. IgG serology using several assays, and with the spectral patterns of SARS-CoV-2, resulted in confusing information that must be clarified before the establishment of diagnostic serology criteria.

Accessing the epicardial space without a sternotomy or a surgical pericardial window to treat ventricular arrhythmias in Chagas disease became a medical necessity in South America. Since the introduction of the dry percutaneous epicardial access approach, epicardial access has been standard procedure for management of ventricular arrhythmias in ischemic and nonischemic cardiomyopathies and atrioventricular accessory pathways after failed conventional endocardial ablation. Understanding the epicardial space and neighboring structures has become an important subject of teachings in electrophysiology. The evolution of complex ablation procedures to treat atrial and ventricular arrhythmias and device interventions to prevent cardioembolic stroke requires thorough understanding of pericardial anatomy., Competing Interests: Disclosure A.J. Restrepo—no disclosures; T.M. Dickfeld—Biosense Webster (Research Support), Catheter Precision (Research Support)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: This analysis describes the interpregnancy interval (time from livebirth to subsequent conception) in a convenience sample of women living in Southwest Guatemala and the association of antepartum characteristics and postpartum outcomes with a short interpregnancy interval (< 24 months)., Methods: This is an observational study of a convenience sample of women enrolled in the Madres Sanas community antenatal/postnatal nursing program supported by the Center for Human Development in Southwest Trifinio, Guatemala, between October 1, 2018 and October 1, 2019. We observed the distribution of interpregnancy intervals among the population of women with a reported date of last live birth, and used bivariate comparisons to compare women with a short interpregnancy interval (< 24 months) to those with an optimal interval ([Formula: see text] 24 months) by antepartum, obstetric and delivery, and postpartum outcomes., Results: 171 parous women enrolled in the Madres Sanas program between October 1, 2018 and October 1, 2019, and reported the date of their last live birth. One hundred-forty-one (82.5%) women delivered and 130 of those women (92.2%) were seen for their 40-day postpartum visit. The mean interval was 37.1 months with a 22.1-month standard deviation. The median interval was 33.7 months with an interquartile range of 19.6-49.5 months. Among these women, 113 (66.1%) the interpregnancy interval was at least 24 months. The only covariate of all sociodemographic, obstetric and antepartum, delivery, and postpartum characteristics that differed between women who achieved an interval ([Formula: see text] 24 months) compared to those that did not (< 24 months), was age (median 22.9, interquartile range (IQR) [19.1,27.0] vs median 24.8, IQR [21.6,27.9], respectively, p = 0.006). A regression model found that with each increasing year of age, the interpregnancy interval increases by 1.08 months, p = 0.025., Conclusion: Among parous women, two-thirds of women space pregnancies at least 24 months. Older women were more likely to have a longer interval between live births.

Purpose: Purpose: Protein irradiation causes aggregation, chain breakage, and oxidation, enhancing its uptake by antigen-presenting cells. To evaluate if irradiated proteins participate on the protection, we studied the immune response induced in mice immunized with irradiated soluble extracts of T. gondii tachyzoites (STag) or irradiated intact T. gondii RH tachyzoites (RH 0.25 kGy ). Material and Methods: Soluble extracts of Toxoplasma gondii tachyzoites (STag) were irradiated at different dose by Cobalt-60 source. By polyacrylamide gel electrophoresis (SDS-Page) we evaluated the effects on primary structures of protein STags induced by irradiation. By Enzyme-linked Immunosorbent Assay (ELISA) we evaluated the difference between humoral immune response induced by irradiated STag or RH tachyzoites in immunized mice from the detection of specific immunoglobulin G (IgG) antibodies in the serum of immunized mice. From challenge with viable RH strain of T. gondii we evaluated the protection induced in the immunized animals. By cytometry we performed the phenotyping of T and B lymphocytes in the peripheral blood of the immunized animals. Results: Irradiation dose of 1.5 kGy induced minimal changes in most proteins, without affecting their antigenicity or immunogenicity. Immunization showed saturation at the dose of 10 µg/mice, with worst response at higher doses. STag irradiated at 1.5  kGy (STag 1.5 kGy ) induced higher survival and protection similar to T. gondii RH strain irradiated at 0.25 kGy (RH 0.25 kGy ), with higher serum levels of high affinity IgG compared to STag native. Blood immune memory cells of mice immunized with STag 1.5 kGy had higher proportions of CD19 + (cluster of differentiation 19) and CD4 + (cluster of differentiation 14) cells, whereas mice RH 0.25 kGy had high proportion of memory CD8 + (cluster of differentiation 8) cells. Conclusions: Our data suggest that major histocompatibility complex type I (MHCI) pathway, appears seem to be used by RH 0.25 kGy to generate cytotoxic cells while STag1.5 kGy uses a major histocompatibility complex type II (MHCII) pathway for B-cell memory, but both induce sufficient immune response for protection in mice without any adjuvant. Irradiation of soluble protein extracts enhances their immune response, allowing similar protection against T. gondii in mice as compared to irradiated intact parasites.

Accidents by freshwater stingrays are common in northern Brazil, there is no specific therapy for high morbidity and local tissue destruction. The irradiation of venoms and toxins by ionizing radiation has been used to produce appropriate immunogens for the production of antisera. We planned to study the efficacy of stinging mucus irradiation in the production of antisera, with serum neutralization assays of edematogenic activity and quantification of cytokines performed in animal models of immunization with native and irradiated mucus of Paratrygon aiereba, a large freshwater stingray. Antiserum potency and its cross-reactivity with mucus from other freshwater stingrays were detected by ELISA. Immunization models demonstrated the ability to stimulate a strong humoral response with elevated levels of serum IgG detectable by ELISA, and both native and irradiated mucus were immunogenic and capable of recognizing mucus proteins from other freshwater neotropical stingrays. Mucus P. aiereba causes cellular and humoral adaptive immune responses in cells of immunized mice producing antibodies and cytokines such as TNF-α, IL-6 and IL-17. Rabbit antisera immunized with mucus from P. aiereba irradiated at 2 kGy showed a significant reduction of mucus-induced edematogenic activity in mice. Our data suggest that the use of antisera against freshwater stingray mucus show the possibility of specific therapy for these accidents., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Microtubules are part of the dynamic cytoskeleton network and composed of tubulin dimers. They are the main tracks used in cells to organize organelle positioning and trafficking of cargos. In this Review, we compile recent findings on the involvement of microtubules in anterograde protein transport. First, we highlight the importance of microtubules in organelle positioning. Second, we discuss the involvement of microtubules within different trafficking steps, in particular between the endoplasmic reticulum and the Golgi complex, traffic through the Golgi complex itself and in post-Golgi processes. A large number of studies have assessed the involvement of microtubules in transport of cargo from the Golgi complex to the cell surface. We focus here on the role of kinesin motor proteins and protein interactions in post-Golgi transport, as well as the impact of tubulin post-translational modifications. Last, in light of recent findings, we highlight the role microtubules have in exocytosis, the final step of secretory protein transport, occurring close to focal adhesions., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Liposomes containing phosphatidylserine (PS) has been used for the delivery of drugs into the intramacrophage milieu. Leishmania (L.) infantum parasites live inside macrophages and cause a fatal and neglected viscerotropic disease, with a toxic treatment. Sertraline was studied as a free formulation (SERT) and also entrapped into phosphatidylserine liposomes (LP-SERT) against intracellular amastigotes and in a murine model of visceral leishmaniasis. LP-SERT showed a potent activity against intracellular amastigotes with an EC 50 value of 2.5 μM. The in vivo efficacy of SERT demonstrated a therapeutic failure. However, when entrapped into negatively charged liposomes (-58 mV) of 125 nm, it significantly reduced the parasite burden in the mice liver by 89% at 1 mg/kg, reducing the serum levels of the cytokine IL-6 and upregulating the levels of the chemokine MCP-1. Histopathological studies demonstrated the presence of an inflammatory infiltrate with the development of granulomas in the liver, suggesting the resolution of the infection in the treated group. Delivery studies showed fluorescent-labeled LP-SERT in the liver and spleen of mice even after 48 h of administration. This study demonstrates the efficacy of PS liposomes containing sertraline in experimental VL. Considering the urgent need for VL treatments, the repurposing approach of SERT could be a promising alternative., (Copyright © 2019 Romanelli, da Costa-Silva, Cunha-Junior, Dias Ferreira, Guerra, Galisteo, Pinto, Barbosa, Torres-Santos and Tempone.)

The retention using selective hooks (RUSH) system allows to retain a target protein fused to green fluorescent protein (GFP) and a streptavidin-binding peptide (SBP) due to the interaction with a molar excess of streptavidin molecules ("hooks") targeted to selected subcellular compartments. Supplementation of biotin competitively disrupts the interaction between the SBP moiety and streptavidin, liberating the chimeric target protein from its hooks, while addition of avidin causes the removal of biotin from the system and reestablishes the interaction. Based on this principle, we engineered two chimeric proteins involved in autophagy, namely microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B, best known as LC3) and sequestosome-1 (SQSTM1, best known as p62) to move them as SBP-GFP-LC3 and p62-SBP-GFP at will between the cytosol and two different organelles, the endoplasmic reticulum (ER) and the Golgi apparatus. Although both proteins were functional in thus far that SBP-GFP-LC3 and p62-SBP-GFP could recruit their endogenous binding partners, p62 and LC3, respectively, their enforced relocation to the ER or Golgi failed to induce organelle-specific autophagy. Hence, artificial tethering of LC3 or p62 to the surface of the ER and the Golgi is not sufficient to trigger autophagy.

LC3 is a protein that can associate with autophagosomes, autolysosomes, and phagosomes. Here, we show that LC3 can also redistribute toward the damaged Golgi apparatus where it clusters with SQSTM1/p62 and lysosomes. This organelle-specific relocation, which did not involve the generation of double-membraned autophagosomes, could be observed after Golgi damage was induced by various strategies, namely (i) laser-induced localized cellular damage, (ii) local expression of peroxidase and exposure to peroxide and diaminobenzidine, (iii) treatment with the Golgi-tropic photosensitizer redaporfin and light, (iv) or exposure to the Golgi-tropic anticancer peptidomimetic LTX-401. Mechanistic exploration led to the conclusion that both reactive oxygen species-dependent and -independent Golgi damage induces a similar phenotype that depended on ATG5 yet did not depend on phosphatidylinositol-3-kinase catalytic subunit type 3 and Beclin-1. Interestingly, knockout of ATG5 sensitized cells to Golgi damage-induced cell death, suggesting that the pathway culminating in the relocation of LC3 to the damaged Golgi may have a cytoprotective function.