Search

Polymer materials containing filler particles are widely used in automotive components, construction materials, packaging materials, medical devices and supplies, and much more. The fillers strongly modulate the properties of the composite. In some applications, one is interested in smart features of those composites, meaning one can post-synthetically and reversibly change the characteristics as a response to an easy-to-apply trigger. For example, if the excision of an implant material may become necessary, then the polymer-filler hybrid changing from mechanically robust to soft(er) would be very beneficial. Here, we present a proof-of-concept study that shows that stimuli-responsive polymer-filler composites can be achieved by functional organosilica nanoparticles. The nanoparticles comprise a superparamagnetic core surrounded by a mesoporous organosilica shell. The polymer matrix is attached to the filler via Diels-Alder coupling to maleimide groups present at the surface of the organosilica. Exposure to an alternating magnetic field generates local heat in the organosilica particles. Utilizing fluorescence probes bound to the polymer backbone's side chains, we could prove that detachment occurs via a retro-Diels-Alder reaction within minutes.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects several organs, causing significant morbidity and increased mortality. It's more frequent in young, fertile women and can appear in all ethnic groups. The worldwide prevalence report indicates that there are at least 5 million patients with SLE. Although this disease can be found in every geographic region, certain races are more affected, such as Afro-American, Hispanic, and Asian populations. Furthermore, most of the epidemiologic information comes from Europe or the USA. In Latin America, only a few countries have reported data, like Argentina, Colombia, or Mexico, and even in these countries, the numbers vary., Competing Interests: Declaration of competing interest The authors have no conflict of interests to declare., (Copyright © 2024 Sociedad Española de Reumatología (SER), Colegio Mexicano de Reumatología (CMR) and Elsevier España, S.L.U. All rights reserved.)

Background: Subdural hematoma is a rare manifestation of hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease. Here, the authors present a patient with HHT and a large chronic subdural hematoma, for whom nonsurgical management was pursued., Observations: A 49-year-old right-handed male with a history of hypertension and familial HHT presented with complaints of mild confusion and left hemiparesis over several days. Noncontrast head computed tomography images demonstrated a large chronic right hemisphere subdural hematoma compressing the right cerebral hemisphere and causing a 1.3-cm midline shift. Due to concerns about surgical complications arising from hemorrhages of cryptic telangiectasias, the patient was treated conservatively with middle meningeal artery embolization and adjuvant tranexamic acid. There was clinical and radiological resolution several months later., Lessons: This case highlights the rarity of a subdural hematoma as a manifestation of HHT and the nonsurgical treatment strategy as a mechanism to avoid hemorrhagic complications of surgical evacuation. https://thejns.org/doi/10.3171/CASE24483.

Objective: The objective of this study was to know the prevalence and clinical-epidemiological characteristics of patients with chronic infection due to hepatitis D virus (HDV)., Patients and Methods: A retrospective descriptive study was carried out on patients with HDV infection under follow-up in a hospital in 2023. All patients carrying HBsAg were tested for antibodies against HDV. HDV RNA detection was performed in all antibody-positive samples. The medical records were reviewed., Results: Of the 340 patients carrying HBsAg, 24 (7.1%) had anti-HDV antibodies, and 6 (25%) had detectable HDV RNA (chronic infection). The prevalence of chronic hepatitis in HBsAg carriers was 1.8%. All patients had a genotype 1 infection. Half of the patients were of African origin and 29.2% were Spanish. Of the 6 patients with chronic infection, 5 (83.3%) had cirrhosis and 2 (33.3%) had hepatocellular carcinoma. Half of the patients had some exacerbation of the disease during follow-up. Of the 18 patients without viremia, 2 (11.1%) presented cirrhosis (one recently diagnosed). The mean follow-up time of patients without viremia was 13.5 years., Conclusions: The prevalence of chronic HDV hepatitis in our area is low and in all cases it presents as an advanced disease, with exacerbations during follow-up. Patients without viremia have probably resolved the infection, as viremia was not detected in any moment., (Copyright © 2024 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

The growing population in Yucatan has led to the expansion of construction in the Mayan jungle for tourist spaces, residential areas, and agriculture. Recently, rabies cases in cats ( Felis catus ) have increased in the state. This study aimed to perform antigenic and genetic characterization of the rabies viruses in felines and to present the spatial distribution and environmental features of the areas where these cases were reported. The ArcGIS software and R were employed to generate maps depicting the geographic locations of rabies cases in cats. A total of nine feline rabies cases occurred during the period 2003-2022. Three antigenic variants were detected: dog-related RVV1 ( n = 1); vampire bat variant RVV3 ( n = 1); and the canine-originated atypical variant ( n = 7). Cases reported in Merida ( n = 4) and Muna ( n = 4) were localized to urban areas, while Cuncunul ( n = 1) was rural. This study highlights the concerning resurgence of rabies infections in cats, emphasizing the looming threat of its reintroduction in dogs should vaccination rates diminish. The genetic affinity between the atypical variant and the canine virus underscores the urgent need for vigilance in maintaining high vaccination coverage across all susceptible species.

Objective: This study aimed to investigate the current status and performance of machine learning (ML) approaches in providing reproducible treatment response predictions., Methods: This systematic review was conducted in accordance with the PRISMA statement and the CHARMS checklist. We searched PubMed, Cochrane Library, Web of Science, Scopus, and EBSCO databases for cohort studies that derived and/or validated ML models focused on predicting rheumatoid arthritis (RA) treatment response. We extracted data and critically appraised studies based on the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) and Prediction Model Risk of Bias Assessment Tool (PROBAST) guidelines., Results: From 210 unduplicated records identified by the literature search, we retained 29 eligible studies. Of these studies, 10 developed a predictive model and reported a mean adherence to the TRIPOD guidelines of 45.6 % (95 % CI: 38.3-52.8 %). The remaining 19 studies not only developed a predictive model but also validated it externally, with a mean adherence of 42.9 % (95 % CI: 39.1-46.6 %). Most of the articles had an unclear risk of bias (41.4 %), followed by a high risk of bias, which was present in 37.9 %., Conclusions: In recent years, ML methods have been increasingly used to predict treatment response in RA. Our critical appraisal revealed unclear and high risk of bias in most of the identified models, suggesting that researchers can do more to address the risk of bias and increase transparency, including the use of calibration measures and reporting methods for handling missing data., Funding: None., Competing Interests: Declaration of competing interest The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Our aim was to analyse the relation between serial values of the indocyanine green plasma disappearance rate (ICG-PDR) with hospital mortality in the first 48 hours of ICU admission in patients with septic shock., Methods: A prospective observational study was carried out over 12 months of patients admitted to the ICU with septic shock. Each patient underwent noninvasive determination of ICG-PDR at 24 and 48 hours with the LiMON® module. Follow-up was performed until hospital discharge or exitus., Results: 63 patients. Age 61.1±12.3 years. 60.3% men. SOFA score on admission 8.7±3.3, APACHE II score was 27.9±10.7 points. A total of 44.4% of patients died. The ICG-PDR values in the first 24 hours of ICU admission were lower in nonsurvivors: 10.5 (5.7-13.0)%/min vs. 15.9 (11.4-28.0)%/min, p <0.001. Furthermore, in nonsurvivors, there was no improvement in ICG-PDR between 24 h and 48 h, while in survivors, there was an increase of 25%: 15.9 (11.4-28.0)%/min and 20.9 (18.0-27.0)%/min, p=0.020. The silhouette measure of ICG-PDR cohesion and separation for the clusters analysed (nonsurvivors and survivors) was satisfactory (0.6). ICG-PDR<11.7%/min was related to in-hospital mortality, ICG-PDR> 18%/min to survival, and the interval between 11.7% and 18%/min covered a range of uncertainty. In the two-stage cluster, ICG-PDR, SOFA and APACHE II present satisfactory predictive scores 24 hours after patient admission., Conclusions: ICG-PDR in our setting is a useful clinical prognostic tool and could optimise the decision tree in patients with septic shock., (©The Author 2024. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

1,2,3,4-Tetrahydroquinolines (THQs) are essential structural cores in many natural products and pharmaceutical drugs. Especially relevant are those presenting substitutions at position 2, yet practical methods for their one-step assembly from acyclic precursors are very scarce. Herein, we present a straightforward approach to assembling these skeletons from ortho -methylanilines using a palladium-catalyzed C(sp 3 )-H activation/formal cycloaddition sequence. Key for the success of the approach is the use of dienes as partners, since they lead to stable π-allyl palladium intermediates that prevent β-hydride elimination processes and allow installation of versatile alkenyl handles at position 2. Moreover, installing a perfluorobenzenesulfonyl substituent at the amine not only facilitates the C-H activation but also allows for an easy recovery of the free amine.

Knowledge is scarce to what extent environmental drivers and native symbiotic fungi in soil induce abrupt (short-term), systemic (multiple traits), or specific (a subset of traits) shifts in C 3 plants' ecophysiological/mycorrhizal responses. We cultivated an emblematic native C 3 species (Capsicum annuum var. glabriusculum, "Chiltepín") to look at how the extreme heat of the Sonoran desert, sunlight regimes (low = 2, intermediate = 15, high = 46 mol m 2 d -1 ) and density of native arbuscular mycorrhizal fungi in soil (low AMF = 1% v/v, high AMF = 100% v/v), drive shifts on mycorrhizal responses through multiple functional traits (106 traits). The warming thresholds were relentlessly harsh even under intensive shade (e.g. superheat maximum thresholds reached ranged between 47-63°C), and several pivotal traits were synergistically driven by AMF (e.g. photosynthetic capacity, biomass gain/allometry, and mycorrhizal colonization traits); whereas concurrently, sunlight regimes promoted most (76%) alterations in functional acclimation traits in the short-term and opposite directions (e.g. survival, phenology, photosynthetic, carbon/nitrogen economy). Multidimensional reduction analysis suggests that the AMF promotes a synergistic impact on plants' phenotypic integration and functional plasticity in response to sunlight regimes; however, complex relationships among traits suggest that phenotypic variation determines the robustness degree of ecophysiological/mycorrhizal phenotypes between/within environments. Photosynthetic canopy surface expansion, Rubisco activity, photosynthetic nitrogen allocation, carbon gain, and differential colonization traits could be central to plants' overall ecophysiological/mycorrhizal fitness strengthening. In conclusion, we found evidence that a strong combined effect among environmental factors in which AMF are key effectors could drive important trade-offs on plants' ecophysiological/mycorrhizal fitness in the short term., (© 2024 Scandinavian Plant Physiology Society.)

Introduction: Renal cell neoplasms are known to be associated with paraneoplastic syndromes, and the association with Castleman-like regional lymphadenopathy has been rarely reported. We aim to characterize the association between renal neoplasms and Castleman-like lymphadenopathy., Methods: A search for renal neoplasms with concurrent Castleman-like lymphadenopathy in one single medical institution from 2000 to 2023 resulted in 4 specimens. A literature search for "Castleman" and "renal neoplasm" resulted in 8 reports. Patients' demographics, clinical presentation, gross and histologic features, results of ancillary studies, treatment, and follow-up were evaluated., Results: Our patients included 3 men and 1 woman, with a mean age of 60 years. Four different subtypes of renal neoplasms were diagnosed, including clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, and mucinous cystadenoma of the renal pelvis. For Castleman-like regional lymphadenopathy, 2 were plasma-cell predominant, and 2 were hyaline-vascular. After a median follow-up of 84 months, all patients were alive with no recurrence or progression of Castleman-like features following nephrectomies., Conclusion: Castleman-like regional lymphadenopathy should be considered in patients with renal tumors and lymphadenopathy. Although more prevalent in clear cell RCC, it can be also associated with other renal neoplasms. The concurrent lymphadenopathy was remitted following the renal tumor resections., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The study examines the reflections of various experts in risk management when asked about uncertainty generated by a health threat and the response to such a threat: what criteria should guide action when potential harm is anticipated, but not known with certainty? The objective of the research is to obtain a holistic perspective of ethical conflicts in risk management, based on experts' accounts within the Spanish territory. A qualitative study was conducted through semi-structured interviews with 27 experts from various fields related to health risk management and its ethical implications, following the grounded theory method. The method includes theory generation through an inductive approach, based on the identified categories. The 27 narratives obtained revealed a variety of fundamental issues grouped into 8 subcategories and subsequently grouped into three main categories. The first category focuses on human vulnerability in health matters. The second category explores the agents and instruments for decision-making that arise from uncertain or traumatic social events. The third category refers to the need for common ethical paradigms for all humanity that implement justice over universal values. A main theory was suggested on the concept of responsibility in a global common good. There is an urgent need to assume this integrative responsibility as an inherent strategy in decision-making. To achieve this, the involved actors must acquire specific humanistic training, conceptualizing fundamental ethical principles, and emphasizing skills more related to humanistic virtues than technical knowledge., (© 2024 The Author(s). Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)

Identification of Aedes aegypti breeding hotspots is essential for the implementation of targeted vector control strategies and thus the prevention of several mosquito-borne diseases worldwide. Training computer vision models on satellite and street view imagery in the municipality of Rio de Janeiro, we analyzed the correlation between the density of common breeding grounds and Aedes aegypti infestation measured by ovitraps on a monthly basis between 2019 and 2022. Our findings emphasized the significance (p ≤ 0.05) of micro-habitat proxies generated through object detection, allowing to explain high spatial variance in urban abundance of Aedes aegypti immatures. Water tanks, non-mounted car tires, plastic bags, potted plants, and storm drains positively correlated with Aedes aegypti egg and larva counts considering a 1000 m mosquito flight range buffer around 2700 ovitrap locations, while dumpsters, small trash bins, and large trash bins exhibited a negative association. This complementary application of satellite and street view imagery opens the pathway for high-resolution interpolation of entomological surveillance data and has the potential to optimize vector control strategies. Consequently it supports the mitigation of emerging infectious diseases transmitted by Aedes aegypti, such as dengue, chikungunya, and Zika, which cause thousands of deaths each year., (© 2024. The Author(s).)

Hedonic hotspots are brain subregions that causally amplify the hedonic impact of palatable tastes, measured as increases in affective orofacial 'liking' reactions to sweetness. Previously, two cortical hedonic hotspots in orbitofrontal cortex and insula were identified by neurochemical stimulation using opioid or orexin microinjections. Here we used optogenetic stimulation in rats as an independent neurobiological technique for activating cortical hedonic hotspots to identify hedonic functions and map boundaries. We report that channelrhodopsin stimulations within rostral orbitofrontal and caudal insula hotspots doubled the number of hedonic 'liking' reactions elicited by sucrose taste. This independently confirms their robust functional identity as causal amplifiers of hedonic 'liking' and confirms their anatomical boundaries. Additionally, we confirmed an intervening suppressive hedonic coldstrip, to stretching from caudal orbitofrontal cortex to rostral insula. By contrast to localized hedonic hotspots for 'liking' enhancement, motivational 'wanting' for reward, measured as laser self-stimulation, was mediated by more widely distributed anatomical sites.

Objective: To investigate the risk of DM and evaluate the impact of SLE therapies on the risk of developing DM in patients with SLE., Methods: Electronic database searches of PubMed, Embase, Cochrane Library and Web of Science were performed from inception to February 2023. Cohort and cross-sectional studies that analysed the risk of DM in patients with SLE were included. The associations between diabetes and antirheumatic agents, such as antimalarials and glucocorticoids, were analysed in cohort studies. Data were pooled using fixed- or random-effects meta-analysis to estimate pooled odd ratios (OR), relative risks (RR) and 95% confidence intervals (CIs). This study was registered with PROSPERO (CRD42023402774)., Results: A total of 37 studies (23 cross-sectional and 14 cohort studies) involving 266 537 patients with SLE were included. The pooled analyses from cross-sectional studies and cohort studies did not show an increased risk of DM in SLE patients (OR = 1.05, 95% CI 0.87-1.27; P = 0.63 and RR = 1.32, 95% CI 0.93-1.87; P = 0.12, respectively). However, several cohort studies consistently demonstrated a reduced risk of diabetes with antimalarials, while glucocorticoid use has been associated with an increased risk of developing diabetes. Age, sex, hypertension and immunosuppressants have not been identified as risk factors for DM in SLE patients., Conclusion: Although there was no increased risk of DM in patients with SLE compared with controls, HCQ users or adherents had a decreased risk, whereas glucocorticoid users had an increased risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

A female patient with a history of ductal carcinoma in situ in the left breast, status-post bilateral mastectomy with deep inferior epigastric perforator artery flap reconstructive surgery, presented with a right breast asymmetry concerning for fat necrosis. Histological analysis revealed the presence of benign glands and associated stroma within fibroadipose tissue, confirmed as endometriosis by immunohistochemical analysis. Further investigation revealed that the patient had a previous diagnosis of endometriosis associated with a cesarean section scar that likely seeded the ectopic endometrial glands into a tertiary site by utilizing abdominal tissue that may have harbored endometriosis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

One of the reasons to suggest olive oil consumption for a healthy life is its potential to induce robust lipidomic remodeling through membrane modification by dietary lipids. This remodeling might, in turn, modulate essential lipid-protein interactions while maintaining accurate transmembrane protein/domain orientation. Oleic acid, the primary compound in olive oil, has been suggested as a modulator of ion channel function. In this study, we explored whether this lipid could rescue the trafficking of mutated transmembrane proteins. In our initial approach, we supplemented the cell culture medium of HEK-293 cells expressing cyclic nucleotide channels tagged using green fluorescent protein (CNG-GFP) with olive oil or oleic acid. In addition to wild-type channels, we also expressed R272Q and R278W mutant channels, two non-functional intracellularly retained channels related to retinopathies. We used fluorescence microscopy and patch-clamp in the inside-out configuration to assess changes in the cell localization and function of the tested channels. Our results demonstrated that olive oil and oleic acid facilitated the transport of cyclic nucleotide-gated R272Q mutant channels towards the plasma membrane, rendering them electrophysiologically functional. Thus, our findings reveal a novel property of olive oil as a membrane protein traffic inductor., 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 © 2024 Avalos-Hernandez, Juarez-Navarro, Ruiz-Baca, Meneses-Morales, Espino-Saldaña, Martinez-Torres and Lopez-Rodriguez.)

Background: Follicular helper T cells (Tfh) are pivotal in B cell responses. Activation of the purinergic receptor P2X7 on Tfh cells regulates their activity. We investigated the ATP-P2X7R axis in circulating Tfh (cTfh) cells during Respiratory Syncytial Virus (RSV) infection., Methods: We analyzed two cohorts: children with RSV infection (moderate, n=30; severe, n=21) and healthy children (n=23). We utilized ELISA to quantify the levels of PreF RSV protein-specific IgG antibodies, IL-21 cytokine, and soluble P2X7R (sP2X7R) in both plasma and nasopharyngeal aspirates (NPA). Additionally, luminometry was employed to determine ATP levels in plasma, NPA and supernatant culture. The frequency of cTfh cells, P2X7R expression, and plasmablasts were assessed by flow cytometry. To evaluate apoptosis, proliferation, and IL-21 production by cTfh cells, we cultured PBMCs in the presence of Bz-ATP and/or P2X7R antagonist (KN-62) and a flow cytometry analysis was performed., Results: In children with severe RSV disease, we observed diminished titers of neutralizing anti-PreF IgG antibodies. Additionally, severe infections, compared to moderate cases, were associated with fewer cTfh cells and reduced plasma levels of IL-21. Our investigation revealed dysregulation in the ATP-P2X7R pathway during RSV infection. This was characterized by elevated ATP levels in both plasma and NPA samples, increased expression of P2X7R on cTfh cells, lower levels of sP2X7R, and heightened ATP release from PBMCs upon stimulation, particularly evident in severe cases. Importantly, ATP exposure decreased cTfh proliferative response and IL-21 production, while promoting their apoptosis. The P2X7R antagonist KN-62 mitigated these effects. Furthermore, disease severity positively correlated with ATP levels in plasma and NPA samples and inversely correlated with cTfh frequency., Conclusion: Our findings indicate that activation of the ATP-P2X7R pathway during RSV infection may contribute to limiting the cTfh cell compartment by promoting cell death and dysfunction, ultimately leading to increased disease severity., 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 © 2024 Russo, Raiden, Algieri, Bruera, De Carli, Sarli, Cairoli, De Lillo, Morales, Seery, Otero, Sananez, Simaz, Alfiero, Rubino, Moya, Aedo Portela, Herrero, Blanco, Salcedo Pereira, Ferrero, Geffner and Arruvito.)

Multiple sclerosis (MS) is a chronic neurological disease frequently associated with significant fatigue, anxiety, depression, and stress. These symptoms are difficult to treat, and prominently contribute to the decreases in quality of life observed with MS. The underlying mechanisms of these "silent" symptoms are not well understood and include not just the psychological responses to a chronic disease, but also biological contributions from bidirectional psycho-neuro-immune (dys)regulation of systemic inflammatory biology. To address these issues, we conducted a prospective, observational pilot study to investigate the psychological, biological, and neuroarchitecture changes associated with a mindfulness-based stress reduction (MBSR) program in MS. The overarching hypothesis was that MBSR modulates systemic and central nervous system inflammation via top-down neurocognitive control over forebrain limbic areas responsible for the neurobiological stress response. 23 patients were enrolled in MBSR and assessed pre/post-program with structural 3 T MRI, behavioral measures, hair cortisol, and blood measures of peripheral inflammation, as indexed by the Conserved Transcriptional Response to Adversity (CTRA) profile. MBSR was associated with improvements across a variety of behavioral outcomes, as well as on-study enlargement of the head of the right hippocampus. The CTRA analyses revealed that greater inflammatory gene expression was related to worse patient-reported anxiety, depression, stress, and loneliness, in addition to lower eudaimonic well-being. Hair cortisol did not significantly change from pre- to post-MBSR. These results support the use of MBSR in MS and elucidate inflammatory mechanisms related to key patient-reported outcomes in this population., (© 2024. The Author(s).)

The aim of this study was to analyze the immunogenic response elicited in swine by two synthetic peptides derived from GP5 to understand the role of lineal B epitopes in the humoral and B-cell-mediated response against the porcine reproductive and respiratory syndrome virus (PRRSV). For inoculation, twenty-one-day-old pigs were allocated into six groups: control, vehicle, vaccinated (Ingelvac-PRRSV, MLV ® ), non-vaccinated and naturally infected, GP5-B and GP5-B3. At 2 days post-immunization (dpi), the GP5-B3 peptide increased the serum concentrations of cytokines associated with activate adaptive cellular immunity, IL-1β (1.15 ± 1.15 to 10.17 ± 0.94 pg/mL) and IL-12 (323.8 ± 23.3 to 778.5 ± 58.11 pg/mL), compared to the control group. The concentration of IgGs anti-GP5-B increased in both cases at 21 and 42 dpi compared to that at 0 days (128.3 ± 8.34 ng/mL to 231.9 ± 17.82 and 331 ± 14.86 ng/mL), while IgGs anti-GP5-B3 increased at 21 dpi (105.1 ± 19.06 to 178 ± 15.09 ng/mL) and remained at the same level until 42 dpi. Also, antibody-forming/Plasma B cells (CD2+/CD21-) increased in both cases (9.85 ± 0.7% to 13.67 ± 0.44 for GP5-B and 15.72 ± 1.27% for GP5-B3). Furthermore, primed B cells (CD2-/CD21+) from immunized pigs showed an increase in both cases (9.62 ± 1.5% to 24.51 ± 1.3 for GP5-B and 34 ± 2.39% for GP5-B3) at 42 dpi. Conversely the naïve B cells from immunized pigs decreased compared with the control group (8.84 ± 0.63% to 6.25 ± 0.66 for GP5-B and 5.78 ± 0.48% for GP5-B3). Importantly, both GP5-B and GP5-B3 peptides exhibited immunoreactivity against serum antibodies from the vaccinated group, as well as the non-vaccinated and naturally infected group. In conclusion, GP5-B and GP5-B3 peptides elicited immunogenicity mediated by antigen-specific IgGs and B cell activation.

Objective: Mood disorders in patients with epilepsy are common, with depression being the most prevalent. However, this comorbidity is often underdiagnosed. The systematic use of scales such as NDDI-E and QOLIE-10 in prolonged video-EEG monitoring units could be a useful tool for the detection of this comorbidity., Methods: Descriptive cross-sectional study of a series of patients with epilepsy evaluated in a prolonged video-EEG monitoring unit., Results: Three hundred forty-nine patients were included. The mean age was 49.1 years, and 49.3% were female. 66.2% had focal epilepsy. 20.4% had pharmacoresistant epilepsy. 38.7% of patients had NDDI-E > 13. 43% of patients with focal epilepsy had NDDI-E > 13 versus 21.8% of patients with idiopathic generalized epilepsy (p = .015). Patients with focal temporal epilepsy had the highest rate of NDDI-E > 13 (48.5%). Significant association was found between patient-perceived mood and NDDI-E score (p < .001). However, in the group of patients with NDDI-E > 13, 37.6% had reported feeling "very good" or "good" in mood. Likewise, in the group that had reported feeling "very good" or "good" 21.6% had NDDI-E > 13. In 50.5% of patients with NDDI-E > 13 some kind of therapeutic intervention aimed at this comorbidity was performed. Perceived quality of life as measured by the QOLIE-10 scale was lower in patients with NDDI-E > 13 (p < .001)., Significance: The use of scales such as the NDDI-E and QOLIE-10 at the time of admission in video-EEG monitoring units allows screening for major depressive disorders in patients with epilepsy, which subsequently needs to be confirmed by formal assessment by a psychiatrist. Their systematic use in these units prevents some patients from going undiagnosed. Detection of these disorders allows targeted therapeutic intervention., (© 2024 International League Against Epilepsy.)

Objectives: Status epilepticus (SE) is a serious event associated with high mortality. This study aims to validate the recently developed ADAN (Abnormal speech, ocular Deviation, Automatisms, and Number of motor epileptic seizures) scale for detecting high risk for SE., Material and Methods: Prospective, multicenter, observational study in adults with suspected epileptic seizures. Consecutive recruitment took place over a 27-month period in 4 hospital emergency departments (EDs). The main endpoint was the proportion of patients with criteria for SE based on the collection and analysis of clinical characteristics and the ADAN scale criteria on arrival at the ED., Results: Of the 527 patients recruited, 203 (38.5%) fulfilled the criteria that predicted SE. Multiple regression analysis demonstrated that the 4 ADAN criteria were the only variables independently associated with a final diagnosis of SE (P .001). The predictive power of the scale was 90.9% (95% CI, 88.4%-93.4%) for a final SE diagnosis. We established 3 risk groups based on ADAN scores: low (score, 0-1: 8.7%), moderate (2, 46.6%), and high (> 2, 92.6%). A cut point of more than 1 had a sensitivity of 88.2% for predicting SE, specificity of 77.8%, positive predictive value of 71.3%, and negative predictive value of 91.3%., Conclusion: The ADAN scale is a prospectively validated, simple clinical tool for identifying patients in the ED who are at high risk for SE.

The recombinant human interferon alpha-2b (IFN-α2b) nasal drop formulation (Nasalferon) was studied as prophylaxis for SARS-CoV-2. Healthy volunteers between 19 and 80 years of age received 0.5 million international units of IFN in one drop (0.05 mL ) in each nostril, twice a day, for 10 consecutive days. The nondetection of SARS-CoV-2 by real-time polymerase chain reaction was the primary outcome variable. Several IFN-α biomarkers, including intranasal gene expression and innate immune effector activity, were increased in participants who received intranasal IFN-α2b. The study included 2,930 international travelers and 5,728 persons who were their close contacts. The subjects were treated with Nasalferon in January 2021, and 9,162 untreated travelers were included as controls. COVID-19 rate in treated subjects was significantly lower than in untreated subjects (0.05% vs. 4.84%). The proportion of travelers with COVID-19 decreased from 60.9% to 2.2% between December 2020 and February 2021. Furthermore, 1,719 tourism workers also received Nasalferon, and no cases of SARS-CoV-2 infection were detected, whereas 39 COVID-19 cases (10.6%) were reported in 367 untreated subjects. The main adverse events associated with the use of intranasal IFN-α2b were nasal congestion, headache, and rhinorrhea. Our prophylactic health interventions study demonstrates that the daily administration of Nasalferon for 10 days decreases the risk of developing COVID-19 in healthy volunteers. [Figure: see text].

Objective: Neighborhoods provide essential resources (eg, education, safe housing, green space) that influence neurodevelopment and mental health. However, we need a clearer understanding of the mechanisms mediating these relationships. Limited access to neighborhood resources may hinder youths from achieving their goals and, over time, shape their behavioral and neurobiological response to negatively biased environments blocking goals and rewards., Method: To test this hypothesis, 211 youths (aged ∼13.0 years, 48% boys, 62% identifying as White, 75% with a psychiatric disorder diagnosis) performed a task during functional magnetic resonance imaging. Initially, rewards depended on performance (unbiased condition); but later, rewards were randomly withheld under the pretense that youths did not perform adequately (negatively biased condition), a manipulation that elicits frustration, sadness, and a broad response in neural networks. We investigated associations between the Childhood Opportunity Index (COI), which quantifies access to youth-relevant neighborhood features in 1 metric, and the multimodal response to the negatively biased condition, controlling for age, sex, medication, and psychopathology., Results: Youths from less-resourced neighborhoods responded with less anger (p < .001, marginal R 2  = 0.42) and more sadness (p < .001, marginal R 2  = 0.46) to the negatively biased condition than youths from well-resourced neighborhoods. On the neurobiological level, lower COI scores were associated with a more localized processing mode (p = .039, marginal R 2  = 0.076), reduced connectivity between the somatic-motor-salience and the control network (p = .041, marginal R 2  = 0.040), and fewer provincial hubs in the somatic-motor-salience, control, and default mode networks (all p FWE  < .05)., Conclusion: The present study adds to a growing literature documenting how inequity may affect the brain and emotions in youths. Future work should test whether findings generalize to more diverse samples and should explore effects on neurodevelopmental trajectories and emerging mood disorders during adolescence., Diversity & Inclusion Statement: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Millions of people are exposed to harmful emissions of gases, vapors, and other inorganic particles during and after volcanic eruptions. These gases have potential short- and long-term effects on human health, particularly on respiratory, ophtalmic, mental systems, as well as on the skin, among others. It has also been described that volcanic eruptions can increase the mortality risk. In 2023, the Popocatepetl volcano has registered recent intense activity, putting the area on high alert. Understanding local volcanic phenomena is essential to assist health personnel in providing informed and timely care. It is clear that health surveillance systems are required to monitor and help control the possible adverse health effects of volcanic eruptions. This review summarizes the most relevant evidence assessing the human health effects of emissions generated after volcanic eruptions and options for their control., (Licencia CC 4.0 (BY-NC-ND) © 2024 Revista Médica del Instituto Mexicano del Seguro Social.)

Background: This study aimed to assess COVID-19 vaccine confidence among healthcare personnel in the safety net sector of the United States and Puerto Rico. This study aimed to examine the extent to which increased knowledge and positive attitudes toward COVID-19 vaccine safety and efficacy were associated with healthcare workers' COVID-19 vaccination status and their recommendation of the vaccine to all patients., Methods: Online survey data were collected from health care workers working in Free and Charitable Clinics across the United States and Federally Qualified Health Centers in Puerto Rico. The survey consisted of 62 questions covering various demographic measures and constructs related to healthcare workers' vaccination status, beliefs, and recommendations for COVID-19 vaccination. Statistical analyses, including multivariate analysis, were conducted to identify the factors associated with the COVID-19 vaccine status and recommendations among healthcare personnel., Results: Among the 2273 respondents, 93% reported being vaccinated against COVID-19. The analysis revealed that respondents who believed that COVID-19 vaccines were efficacious and safe were three times more likely to be vaccinated and twice as likely to recommend them to all their patients. Respondents who believed they had received adequate information about COVID-19 vaccination were 10 times more likely to be vaccinated and four times more likely to recommend it to all their patients., Conclusions: The study results indicate that healthcare workers' confidence in COVID-19 vaccines is closely tied to their level of knowledge, positive beliefs, and attitudes about vaccine safety and efficacy. The study emphasizes the significance of healthcare workers feeling well informed and confident in their knowledge to recommend the vaccine to their patients. These findings have important implications for the development of strategies to boost COVID-19 vaccine confidence among healthcare workers and increase vaccine uptake among patients., (© 2024. The Author(s).)

Inhibitory control is central to many theories of cognitive and brain development, and impairments in inhibitory control are posited to underlie developmental psychopathology. In this study, we tested the possibility of shared versus unique associations between inhibitory control and three common symptom dimensions in youth psychopathology: attention-deficit/hyperactivity disorder (ADHD), anxiety, and irritability. We quantified inhibitory control using four different experimental tasks to estimate a latent variable in 246 youth (8-18 years old) with varying symptom types and levels. Participants were recruited from the Washington, D.C., metro region. Results of structural equation modeling integrating a bifactor model of psychopathology revealed that inhibitory control predicted a shared or general psychopathology dimension, but not ADHD-specific, anxiety-specific, or irritability-specific dimensions. Inhibitory control also showed a significant, selective association with global efficiency in a frontoparietal control network delineated during resting-state functional magnetic resonance imaging. These results support performance-based inhibitory control linked to resting-state brain function as an important predictor of comorbidity in youth psychopathology.

Objective: Most patients with Dravet syndrome (DS) have unremarkable neuroimaging studies. However, a small number of patients exhibit focal abnormalities that may modify the epilepsy phenotype. We report a case series of DS patients carrying SCN1A variants concurrent with additional focal brain lesions, aiming to provide details regarding their clinical course, electrographic findings, and imaging features., Methods: We reviewed the electronic medical records of patients with developmental and epileptic encephalopathies in our center, from January 2000 to December 2022, identifying 90 patients with DS resulting from SCN1A variants. Of these, patients displaying focal brain lesions were eligible., Results: Five patients (4 males and 1 female), with median age of 26 years, were included. All exhibited clinical and electroencephalographic features consistent with the DS spectrum. Sequencing analysis of the SCN1A gene identified pathogenic variants. Magnetic resonance imaging (MRI) revealed focal cortical dysplasia (FCD) in two patients, while the remaining three had cystic lesions. Three patients had previously undergone resective epilepsy surgery in other centers, with no improvement in seizure frequency. Neuropathology studies revealed the presence of FCD type IIA, intracranial teratomas, and dysembryoplastic neuroepithelial tumor (DNET)., Significance: When an individual with an established diagnosis of genetic epilepsy and a focal lesion on MRI is undergoing preoperative evaluation, it is crucial to conduct a comprehensive analysis to understand the relevance of the focal finding for the patient's phenotype and thus anticipate potential surgical outcomes. In instances where epilepsy in DS patients is influenced by a specific focal structural lesion, resective surgery should be carefully considered after precise pharmacological treatment, acknowledging the persistent influence of an SCN1A variant on expected outcomes., (© 2023 International League Against Epilepsy.)

Oligomeric assemblies of the amyloid β peptide (Aβ) have been investigated for over two decades as possible neurotoxic agents in Alzheimer's disease. However, due to their heterogeneous and transient nature, it is not yet fully established which of the structural features of these oligomers may generate cellular damage. Here, we study distinct oligomer species formed by Aβ40 (the 40-residue form of Aβ) in the presence of four different metal ions (Al 3+ , Cu 2+ , Fe 2+ , and Zn 2+ ) and show that they differ in their structure and toxicity in human neuroblastoma cells. We then describe a correlation between the size of the oligomers and their neurotoxic activity, which provides a type of structure-toxicity relationship for these Aβ40 oligomer species. These results provide insight into the possible role of metal ions in Alzheimer's disease by the stabilization of Aβ oligomers.

We developed a mobile application to promote healthy lifestyles and collect non-communicable disease (NCD) data in Mexico. Its theoretical foundations are supported by a framework-guided literature review. With design sprints, Scrum, Model-View-Controller, and Representational State Transfer architecture, we operationalized evidence-based nutrition/physical activity information into a crowdsourcing- and gamification-based application. The application was piloted for three months to monitor the response of 520 adults. Potential improvements were characterized, considering benchmarking, expert guidance, and standards. Salud Activa (English: Active Health) has two crowdsourcing modules: Nutritional scanner, scanning products' bar codes, providing nutritional data, and allowing new product registry feeding our databases; Surveys, comprising gradually-released NCD questions. Three intervention modules were generated: Drinks diary, a beverage assessment component to receive hydration recommendations; Step counter, monitoring users' steps via Google Fit/Health-iOS; Metabolic Avatar, interconnecting modules and changing as a function of beverage and step records. The 3-month median of Salud Activa use was seven days (IQR = 3-12), up to 35% of participants completed a Survey section, and 157 food products were registered through Nutritional scanner. Better customization might benefit usability and user engagement. Quantitative and qualitative data will enhance Salud Activa's design, user uptake, and efficacy in interventions delivered through this platform., (© 2024. The Author(s).)

Butyrate is a promising candidate for an antitumoral drug, as it promotes cancer cell apoptosis and reduces hormone receptor activity, while promoting differentiation and proliferation in normal cells. However, the effects of low-dose butyrate on breast cancer cell cultures are unclear. We explored the impact of sub-therapeutic doses of butyrate on estrogen receptor alpha (ERα) transcriptional activity in MCF-7 cells, using RT-qPCR, Western blot, wound-healing assays, and chromatin immunoprecipitation. Our results showed that sub-therapeutic doses of sodium butyrate (0.1 - 0.2 mM) increased the transcription of ESR1, TFF1, and CSTD genes, but did not affect ERα protein levels. Moreover, we observed an increase in cell migration in wound-healing assays. ChIP assays revealed that treatment with 0.1 mM of sodium butyrate resulted in estrogen-independent recruitment of ERα at the pS2 promoter and loss of NCoR. Appropriate therapeutic dosage of butyrate is essential to avoid potential adverse effects on patients' health, especially in the case of estrogen receptor-positive breast tumors. Sub-therapeutic doses of butyrate may induce undesirable cell processes, such as migration due to low-dose butyrate-mediated ERα activation. These findings shed light on the complex effects of butyrate in breast cancer and provide insights for research in the development of antitumoral drugs.

Antiphospholipid antibody syndrome (usually named antiphospholipid syndrome, APS) is an autoimmune disorder seen mainly in young people. Clinically, APS is described by pregnancy complications and/or a hypercoagulable state, including the venous or arterial vasculature, and strongly related to antiphospholipid antibodies. Although several cardiac manifestations have been involved with APS, and accelerated atherosclerosis is present in this condition, little is known about cardiovascular (CV) risk and the relation between APS. Several studies have used imaging markers to associate them with the main clinical features of patients with APS and the probability of having subclinical atherosclerosis. However, it has not yet been established which markers are most related to the risk of developing CV diseases (CVD) in these patients. In this narrative review, we focus on non-invasive imaging markers that can predict CVD, including carotid intima-media thickness and carotid plaques assessed by carotid ultrasonography or coronary artery calcium score, which usually by computed tomography. We also examine the evidence about vascular function markers used in APS, such as arterial flow-mediated brachial dilation and artery stiffness measured by the velocity of the pulse wave. We present the current status of non-invasive imaging markers, which suggest the existence of subclinical atherosclerosis in patients with APS. However, new prospective research is required to identify the predictive value of these findings and their modification by current treatments for APS., Competing Interests: Declaration of Competing Interest All authors have nothing to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Rationale: Hodgkin lymphoma, a lymphatic system cancer, is treated by chemotherapy, radiation therapy, and hematopoietic stem cell transplantation. Posterior reversible encephalopathy syndrome (PRES) is a rare neurotoxic effect associated with several drugs and systemic conditions. This case study emphasizes the potential risks of intensive chemotherapy regimens and postulates the impact of the circle of Willis variants on the heterogeneity of hemispheric lesions in PRES., Patient Concerns: A 42-year-old woman diagnosed with stage IIA nodular sclerosing Hodgkin lymphoma and chronic thrombocytopenia presented after 6 years of initial diagnosis and 4 years post-haploidentical transplant. She underwent planned chemotherapy with ifosfamide, carboplatin, and etoposide., Diagnoses: She developed an alteration in her mental status. A computerized tomography scan and angiogram of the head and neck revealed findings consistent with PRES and a left fetal-type posterior cerebral artery with an aplastic A1 segment of the left anterior cerebral artery. One hour later she was found comatose with clinical sequelae of an uncal herniation., Interventions: Subsequent events led to emergent intubation, and administration of 23.4% hypertonic saline. A repeat computerized tomography scan showed a right intraparenchymal hemorrhage with fluid-fluid levels measuring up to 4.7 cm, bilateral subarachnoid hemorrhage, right uncal herniation, and 15 mm of leftward midline shift. She emergently underwent a right decompressive hemi-craniectomy., Outcomes: An magnetic resonance imaging of the brain demonstrated bilateral cytotoxic edema involving the parieto-occipital lobes. Despite interventions, the patient's neurological condition deteriorated, leading to a declaration of brain death on the 8th day., Lessons: This case underscores the importance of recognizing the severe neurological complications, including PRES, associated with chemotherapeutic treatments in Hodgkin lymphoma. PRES may also be exacerbated by coagulopathies such as thrombocytopenia in this case. The circle of Willis variants may influence cerebral blood flow, autoregulation, and other factors of hemodynamics, leading to increased susceptibility to both radiographic lesion burden and the worst clinical outcomes., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Here the synthesis of magnetic aerogels from iron platinum and cobalt platinum nanoparticles is presented. The use of hydrazine monohydrate as destabilizing agent triggers the gelation directly from organic solution, and therefore a phase transfer to aqueous media prior to the gelation is not necessary. The aerogels were characterized through Transmission Electron Microscopy, Scanning Electron Microscopy, Powder X-Ray Diffraction Analysis and Argon Physisorption measurements to prove the formation of a porous network and define their compositions. Additionally, magnetization measurements in terms of hysteresis cycles at 5 K and 300 K (M-H-curves) as well as zero field cooled-field cooled measurements (ZFC-FC measurements) of the dried colloids and the respective xero- and aerogels were performed, in order to analyze the influence of the gelation process and the network structure on the magnetic properties.

This study uses methods recently developed to study the complex evolution of atmospheric phenomena which have some similarities with the dynamics of the human brain. In both cases, it is possible to record the activity of particular centers (geographic regions or brain nuclei) but not to make an experimental modification of their state. The study of "causality", which is necessary to understand the dynamics of these complex systems and to develop robust models that can predict their evolution, is hampered by the experimental restrictions imposed by the nature of both systems. The study was performed with data obtained in the thalamus and basal ganglia of awake humans executing different tasks. This work studies the linear, non-linear and more complex relationships of these thalamic centers with the cortex and main BG nuclei, using three complementary techniques: the partial correlation regression method, the Gaussian process regression/distance correlation and a model-free method based on nearest-neighbor that computes the conditional mutual information. These causality methods indicated that the basal ganglia present a different functional relationship with the anterior-ventral (motor), intralaminar and medio-dorsal thalamic centers, and that more than 60% of these thalamus-basal ganglia relationships present a non-linear dynamic (35 of the 57 relationships found). These functional interactions were observed for basal ganglia nuclei with direct structural connections with the thalamus (primary somatosensory and motor cortex, striatum, internal globus pallidum and substantia nigra pars reticulata), but also for basal ganglia without structural connections with the thalamus (external globus pallidum and subthalamic nucleus). The motor tasks induced rapid modifications of the thalamus-basal ganglia interactions. These findings provide new perspectives of the thalamus - BG interactions, many of which may be supported by indirect functional relationships and not by direct excitatory/inhibitory interactions., (© 2023. The Author(s).)

Background: Epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS) is a rare syndrome associated with cognitive and behavioural regression. On the basis of mostly small observational and retrospective studies, corticosteroids and clobazam are often considered the most effective treatments for this syndrome. We aimed to compare cognitive outcomes of children with EE-SWAS 6 months after starting treatment with either corticosteroids or clobazam., Methods: We did a multicentre, randomised controlled trial at eight tertiary referral centres for rare epilepsies in seven European countries. Children were eligible to participate if they were aged 2-12 years, were diagnosed with EE-SWAS within 6 months before inclusion, and had not been treated with corticosteroids or clobazam previously. Participants were randomly assigned (1:1) to treatment with corticosteroids (either continuous treatment with 1-2 mg/kg per day of prednisolone orally or pulse treatment with 20 mg/kg per day of methylprednisolone intravenously for 3 days every 4 weeks) or clobazam (0·5-1·2 mg/kg per day orally). The primary outcome was cognitive functioning after 6 months of treatment, which was assessed by either the intelligence quotient (IQ) responder rate (defined as improvement of ≥11·25 IQ points) or the cognitive sum score responder rate (defined as improvement of ≥0·75 points). Safety was assessed by number of adverse events and serious adverse events. Data were analysed in the intention-to-treat population, which included all children as randomised who had primary outcome data available at 6 months. The trial is registered with the Dutch Trial Register, Toetsingonline, NL43510.041.13, and the ISRCTN registry, ISRCTN42686094. The trial was terminated prematurely because enrolment of the predefined number of 130 participants was deemed not feasible., Findings: Between July 22, 2014, and Sept 3, 2022, 45 children were randomly assigned to either corticosteroids (n=22) or clobazam (n=23); two children assigned clobazam dropped out before 6 months and were excluded from the intention-to-treat analysis. At the 6-month assessment, an improvement of 11·25 IQ points or greater was reported for five (25%) of 20 children assigned corticosteroids versus zero (0%) of 18 assigned clobazam (risk ratio [RR] 10·0, 95% CI 1·2-1310·4; p=0·025). An improvement of 0·75 points or more in the cognitive sum score was recorded for one (5%) of 22 children assigned corticosteroids versus one (5%) of 21 children assigned clobazam (RR 1·0, 95% CI 0·1-11·7, p=0·97). Adverse events occurred in ten (45%) of 22 children who received corticosteroids, most frequently weight gain, and in 11 (52%) of 21 children who received clobazam, most often fatigue and behavioural disturbances. Occurrence of adverse events did not differ between groups (RR 0·8, 95% CI 0·4-1·4; p=0·65). Serious adverse events occurred in one child in the corticosteroid group (hospitalisation due to laryngitis) and in two children in the clobazam group (hospitalisation due to seizure aggravation, and respiratory tract infection). No deaths were reported., Interpretation: The trial was terminated prematurely, and the target sample size was not met, so our findings must be interpreted with caution. Our data indicated an improvement in IQ outcomes with corticosteroids compared with clobazam treatment, but no difference was seen in cognitive sum score. Our findings strengthen those from previous uncontrolled studies that support the early use of corticosteroids for children with EE-SWAS., Funding: EpilepsieNL, WKZ fund, European Clinical Research Infrastructure Network, and Ming fund., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To assess efficacy and tolerability of stiripentol (STP) as adjunctive treatment in Dravet syndrome and non-Dravet refractory developmental and epileptic encephalopathies (DREEs)., Methods: Retrospective observational study of all children and adults with DREE and prescribed adjunctive STP at Hospital Ruber Internacional from January 2000 to February 2023. Outcomes were retention rate, responder rate (proportion of patients with ≥50% reduction in total seizure frequency relative to baseline), seizure freedom rate, responder rate for status epilepticus, rate of adverse event and individual adverse events, reported at 3, 6, and 12 months and at final visit. Seizure outcomes are reported overall, and for Dravet and non-Dravet subgroups., Results: A total of 82 patients (55 Dravet syndrome and 27 non-Dravet DREE) were included. Median age was 5 years (range 1-59 years), and median age of epilepsy onset was younger in the Dravet group (4.9 [3.6-6] months) than non-Dravet (17.9 [6-42.3], P < 0.001). Median follow-up time STP was 24.1 months (2 years; range 0.3-164 months) and was longer in the Dravet group (35.9 months; range 0.8-164) than non-Dravet (17 months range 0.3-62.3, P < 0.001). At 12 months, retention rate, responder rate and seizure free rate was 68.3% (56/82), 65% [48-77%] and 18% [5.7-29%], respectively. There were no statistically significant differences between groups on these seizure outcomes. Adverse events were reported in 46.3% of patients (38/82), without differences between groups., Significance: In this population of patients with epileptic and developmental encephalopathies, outcomes with adjunctive STP were similar in patients with non-Dravet DREE to patients with Dravet syndrome., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Engineered antibody formats, such as antibody fragments and bispecifics, have the potential to offer improved therapeutic efficacy compared to traditional full-length monoclonal antibodies (mAbs). However, the translation of these non-natural molecules into successful therapeutics can be hampered by developability challenges. Here, we systematically analyzed 64 different antibody constructs targeting Tumor Necrosis Factor (TNF) which cover 8 distinct molecular format families, encompassing full-length antibodies, various types of single chain variable fragments, and bispecifics. We measured 15 biophysical properties related to activity, manufacturing, and stability, scoring variants with a flag-based risk approach and a recent in silico developability profiler. Our comparative assessment revealed that overall developability is higher for the natural full-length antibody format. Bispecific antibodies, antibodies with scFv fragments at the C-terminus of the light chain, and single-chain Fv antibody fragments (scFvs) have intermediate developability properties, while more complicated formats, such as scFv- scFv, bispecific mAbs with one Fab exchanged with a scFv, and diabody formats are collectively more challenging. In particular, our study highlights the propensity for fragmentation and aggregation, both in bulk and at interfaces, for many current engineered formats.

Let S be either a free group or the fundamental group of a closed hyperbolic surface. We show that if G is a finitely generated residually- p group with the same pro- p completion as S , then two-generated subgroups of G are free. This generalises (and gives a new proof of) the analogous result of Baumslag for parafree groups. Our argument relies on the following new ingredient: if G is a residually-(torsion-free nilpotent) group and H ≤ G is a virtually polycyclic subgroup, then H is nilpotent and the pro- p topology of G induces on H its full pro- p topology. Then we study applications to profinite rigidity. Remeslennikov conjectured that a finitely generated residually finite G with profinite completion G ^ ≅ S ^ is necessarily G ≅ S . We confirm this when G belongs to a class of groups H ab that has a finite abelian hierarchy starting with finitely generated residually free groups. This strengthens a previous result of Wilton that relies on the hyperbolicity assumption. Lastly, we prove that the group S × Z n is profinitely rigid within finitely generated residually free groups., (© The Author(s) 2024.)

Objective: To describe the results from the Global Burden Disease (GBD) study 2019 on the burden of other musculoskeletal (MSK) disorders in Latin America and the Caribbean (LAC)., Methods: In this cross-sectional study, we analyzed data from all LAC region in the GBD study from 1990 to 2019. Other MSK (other than rheumatoid arthritis, osteoarthritis, gout, low back pain, and neck pain) burden was measured as prevalence, mortality, years lived with disability (YLD), and disability-adjusted life (DALY), by year, sex, and country. We show the counts, rates, and 95% uncertainty intervals (95% UI). Joinpoint regression analysis was used to estimate the average annual percentage change (AAPC) from 1990 to 2019. A correlational analysis between the burden parameters and sociodemographic index (SDI) was performed., Results: In 2019, there were 52.0 million (95% UI, 44.8-60.1 million) individuals with other MSK disorders in LAC. The age-standardized mortality rate in 2019 was 1.2 (95% UI, 0.8-1.6) per 100,000 inhabitants. The AAPC was estimated as 0.1% (95% confidence interval [CI], 0.1-0.2) and 0.2% (95% CI, 0.1-0.3) for prevalence and mortality rates, respectively. The age-standardized DALY rate was 685.4 (95% UI, 483.6-483.6) per 100,000 inhabitants, representing an AAPC of 0.2% (95% CI, 0.1-0.3). The burden was larger in women and the elderly. The SDI was positively correlated with the prevalence of YLD in 2019., Conclusions: LAC region has experienced a significant burden of other MSK disorders over the last three decades. To challenge this growing burden, population-based strategies designed to reduce the burden of other MSK and strengthen health systems to contribute effective and cost-efficient care are necessary., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study aimed to describe the disease burden and trends of musculoskeletal (MSK) disorders in Mexico from 1990 to 2019., Method: A cross-sectional study using systematic analysis from the Global Burden of Disease Study 2019 (GBD study 2019) was performed to analyze data on MSK disorders and estimate crude and age-standardized rates per 100,000 population concerning disease prevalence, incidence, mortality, disability-adjusted life-years (DALY), and years lived with disability (YLD). The average annual percentage change (AAPC) was calculated using the joinpoint regression., Results: In 2019, there were 4.8 million (95% UI 4.3, 5.4) new cases and 3,312 (95% UI 2201, 4,790) deaths attributable to MSK disorders. In 2019, MSK disorders ranked first, increasing from 1990 (second rank) for the YLD in Mexico. Subnational variations were identified, with the state of Oaxaca having the highest age-standardized incidence rate (ASIR) per 100,000 population in 2019. Joinpoint analysis revealed a significant increase in prevalence in Mexico from 1990 to 2019 (AAPC: 0.14%; 95%CI 0.09-0.19), incidence (AAPC: 0.05%; 95%CI 0.03-0.07), DALY (AAPC: 0.13%; 95%CI 0.04-0.22), and YLD (AAPC: 0.13%; 95%CI 0.02-0.24). Among the risk factors, occupational ergonomic factors and high body mass index (BMI) had the largest influence on MSK disorders., Conclusions: In Mexico, we observed an increase the national burden of MSK disorders from 1990 to 2019. Specific determinants, such as occupational ergonomic factors and high BMI, contribute to the MSK disorder burden. The burden of MSK disorders requires an improved and prompt assessment to plan valuable diagnostic and management approaches. Key Points • In Mexico, the burden of musculoskeletal (MSK) disorders increased from 1990 to 2019. • Specific risk factors, such as occupational ergonomic factors and high body mass index, contribute to the MSK disorder burden., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

We analyzed the T-cell responses induced by lineal epitopes of glycoprotein 5 (GP5) from PRRSV to explore the role of this protein in the immunological protection mediated by T-cells. The GP5 peptides were conjugated with a carrier protein for primary immunization and booster doses. Twenty-one-day-old pigs were allocated into four groups (seven pigs per group): control (PBS), vehicle (carrier), PTC1, and PTC2. Cytokine levels were measured at 2 days post-immunization (DPI) from serum samples. Cytotoxic T-lymphocytes (CTLs, CD8+) from peripheral blood were quantified via flow cytometry at 42 DPI. The cytotoxicity was evaluated by co-culturing primed lymphocytes with PRRSV derived from an infectious clone. The PTC2 peptide increased the serum concentrations of pro-inflammatory cytokines (i.e., TNF-α, IL-1β, IL-8) and cytokines that activate the adaptive cellular immunity associated with T-lymphocytes (i.e., IL-4, IL-6, IL-10, and IL-12). The concentration of CTLs (CD8+) was significantly higher in groups immunized with the peptides, which suggests a proliferative response in this cell population. Primed CTLs from immunized pigs showed cytolytic activity in PRRSV-infected cells in vitro. PTC1 and PTC2 peptides induced a protective T-cell-mediated response in pigs immunized against PRRSV, due to the presence of T epitopes in their sequences.

Aortic arch surgery is a surgical challenge due to its technical complexity and brain and body protection requirements., Aim: To describe the surgical protocol and the short and long-term results of aortic arch replacement surgery in a center in the metropolitan region of Santiago, Chile., Methods: Retrospective descriptive study from April 2015 to August 2022. Elective, urgent, and emergency patients were included, with diagnoses of arch aneurysm and acute or chronic type I and II DeBakey aortic dissection., Technique: Arterial cannulation at the brachiocephalic trunk, right axillary artery, or directly into the true lumen of the aortic dissection with Seldinger technique, guided by epiaortic and transesophagic ultrasound. Deep hypothermia at 24°C. Uni or bilateral antegrade cerebral perfusion according to runoff. Four devices were used: a straight tube, a tube with 3 or 4 branches, and a frozen elephant trunk., Results: 37 patients were operated on; 24 of them were men. The average age was 57 years old. In seven patients, a straight tube with anastomosis was used with anastomosis on the island; in six patients, a tube with 3 branches; in ten patients, a tube with four branches; and in fourteen patients, a frozen elephant trunk. There were twenty-one patients (57%) with associated morbidity: prolonged mechanical ventilation 14 the most frequent, paralysis chordae in 7 patients; there were six neurological morbidities, one of them permanent, renal dysfunction in 5 patients, pneumonia associated with mechanical ventilation in 4 patients, reoperation due to bleeding in 4. There was no associated cardiac morbidity. Operative and global mortality at 30 days was 13.5%. Follow-up was closed in October 2022 and is complete in the 30 survivors; the average was 20 months. Two patients died in the follow-up at five years; the survival in the follow-up was 90%., Conclusion: The management protocol has good results regarding morbidity and mortality, similar to the international series.

The introduction of iron ionic sites by metal exchange of defective homometallic nickel pyrazolate frameworks generates non-precious, Earth-abundant, first-row heterometallic Fe/Ni-pyrazolate frameworks. The Fe incorporation at the Ni nodes of the framework allows to control the hydrogen peroxide activation, minimizing its decomposition and O 2 liberation, occurring at the homometallic Ni nodes. The generation of Fe-OH reactive oxygen species at the heterometallic Fe/Ni nodes is demonstrated by the higher activity in the proof-of-concept oxidation of 1-phenylethanol to acetophenone in an aqueous medium., (© 2023 The Authors. ChemPlusChem published by Wiley-VCH GmbH.)

Rhagovelia Mayr, 1865 (Hemiptera, Heteroptera, Veliidae) is a diverse genus of small to medium-sized true bugs that live on the surface of the water, preferentially in lotic environments with moderate to strong current. The Rhagovelia angustipes species complex is particularly speciose in Colombia, and has recently been the subject of a revision. Nonetheless, new species of the complex are still being discovered in the country. We present here the description of Rhagovelia andradei sp. nov., collected on the eastern Colombian Andes, new records for three other species, R. calceola, R. gastrotricha and R. molanoi, an updated key, and a summary of the distribution of the complex in the country.