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Abstract The COVIVAX study assessed the association between COVID-19 vaccination and the risk of common neurological disorders in a multicenter case-control design. Vaccination exposure was compared between individuals with a first diagnosis of a neurological disorder (cases) and age- and sex-matched controls. A total of 624 participants were enrolled, and after random 1:1 matching 265 cases and 265 matched controls (total 530 participants) were included in the analyses. The most frequent neurological diagnosis in cases were stroke (60.4%), multiple sclerosis (11.3%) and seizures (6.4%). The proportion of vaccinated participants was 72.1% among cases and 79.6% among controls. A protective role of vaccination on the risk of developing a new neurological disorder was detected in the unadjusted analysis (OR 0.50; 95% CI 0.29–0.86; p = 0.0114). After adjustment for confounders, the number of vaccination doses received was associated with a reduced risk of developing new neurological disorders for participants aged over 60 years ( p = 0.0472; OR 0.14, 95% CI 0.03–0.68), with pre-existing comorbidities (p = 0.0122; OR 0.04, 95% CI 0.01–0.99) and for stroke (p = 0.0232; OR 0.04, 95% CI 0.02–0.97). The COVIVAX study provided no warning sign regarding an increase in the risk of developing new neurological disorders following COVID-19 vaccination of any type or doses. A potentially protective effect of multiple doses of COVID-19 vaccines against the risk of stroke in people aged over 60 needs to be confirmed by further studies.

Abstract Background Facioscapulohumeral dystrophy (FSHD) is a myopathy characterized by the loss of repressive epigenetic features affecting the D4Z4 locus (4q35). The assessment of DNA methylation at two regions (DUX4-PAS and DR1) of D4Z4 locus proved to be an effective method to detect epigenetic signatures compatible with FSHD. The present study aims at validating the employment of this method into clinical practice and improving the protocol by refining the classification thresholds of 4qA/4qA patients. To this purpose, 218 subjects with clinical suspicion of FSHD collected in 2022–2023 were analyzed. Each participant underwent in parallel the traditional FSHD molecular testing (D4Z4 sizing) and the proposed methylation assay. The results provided by both analyses were compared to evaluate the concordance and calculate the performance metrics of the methylation test. Results Among the 218 subjects, the 4q variant type distribution was 54% 4qA/4qA, 43% 4qA/4qB and 3% 4qB/4qB. The methylation analysis was performed only on carriers of at least one 4qA allele. After refining the classification threshold, the test reached the following performance metrics: sensitivity = 0.90, specificity = 1.00 and accuracy = 0.93. These results confirmed the effectiveness of the methylation assay in identifying patients with genetic signature compatible with FSHD1 and FSHD2 based on their DUX4-PAS and DR1 profile, respectively. The methylation data were also evaluated with respect to the clinical information. Conclusions The study confirmed the ability of the method to accurately identify methylation profiles compatible with FSHD genetic signatures considering the 4q genotype. Moreover, the test allows the detection of hypomethylated profiles in asymptomatic patients, suggesting its potential application in identifying preclinical conditions in patients with positive family history and FSHD genetic signatures. Furthermore, the present work emphasizes the importance of interpreting methylation profiles considering the patients’ clinical data.

Although the implementation of area-wide inoculum reduction and Asian citrus psyllid control are decisive in controlling Huanglongbing (HLB) epidemics, growers continue looking for enhanced nutritional and/or resistance inducer (ENRI) treatments to mitigate yield damage in HLB-affected trees. Therefore, an experiment was set up in an 8-year-old sweet orange orchard to evaluate the effects of the foliar application of nutrients, phosphite, and salicylate sprayed four to five times per year during flushing periods. The trial had eight treatments in four randomized blocks. HLB incidence and yield were assessed from December 2010 to January 2017. HLB-symptomatic trees with less than 5% HLB severity were selected from each plot in the first (Group 1), second (Group 2), and third years (Group 3) after the beginning of treatments to assess the frequency of trees with different HLB symptoms and micronutrient deficiencies, HLB severity, and fruit yield until January 2017. Twenty asymptomatic trees from each plot were also harvested for comparison each year. ENRI treatments did not reduce the progress of HLB incidence in the plots or the HLB severity progress or frequency of HLB symptoms in the selected trees. ENRI treatments did not improve the yield of symptomatic trees compared with asymptomatic trees. Hence, in a scenario without HLB-symptomatic tree removal in mature orchards, disease severity progress and yield reduction in HLB-affected trees remained regardless of ENRI treatment. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Background The use of intravenous fluid therapy in patients with major trauma in prehospital settings is still controversial. We conducted an umbrella review to evaluate which is the best volume expansion in the resuscitation of a hemorrhagic shock to support the development of major trauma guideline recommendations. Methods We searched PubMed, Embase, and CENTRAL up to September 2022 for systematic reviews (SRs) investigating the use of volume expansion fluid on mortality and/or survival. Quality assessment was performed using AMSTAR 2 and the Certainty of the evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results We included 14 SRs investigating the effects on mortality with the comparisons: use of crystalloids, blood components, and whole blood. Most SRs were judged as critically low with slight overlapping of primary studies and high consistency of results. For crystalloids, inconsistent evidence of effectiveness in 28- to 30-day survival (primary endpoint) was found for the hypertonic saline/dextran group compared with isotonic fluid solutions with moderate certainty of evidence. Pre-hospital blood component infusion seems to reduce mortality, however, as the certainty of evidence ranges from very low to moderate, we are unable to provide evidence to support or reject its use. The blood component ratio was in favor of higher ratios among all comparisons considered with moderate to very low certainty of evidence. Results about the effects of whole blood are very uncertain due to limited and heterogeneous interventions in studies included in SRs. Conclusion Hypertonic crystalloid use did not result in superior 28- to 30-day survival. Increasing evidence supports the scientific rationale for early use of high-ratio blood components, but their use requires careful consideration. Preliminary evidence is very uncertain about the effects of whole blood and further high-quality studies are required.

Abstract Gut microbiota is an emerging editable cardiovascular risk factor. We aim to investigate gut and coronary plaque microbiota, using fecal samples and angioplasty balloons from patients with acute coronary syndrome (ACS), chronic coronary syndrome (CCS) and control subjects. We examined bacterial communities in gut and coronary plaques by 16S rRNA sequencing and we performed droplet digital PCR analysis to investigate the gut relative abundance of the bacterial genes CutC/CntA involved in trimethylamine N-oxide synthesis. Linear discriminant analysis effect size (LEfSe) at the genus and species levels displayed gut enrichment in Streptococcus, Granulicatella and P. distasonis in ACS compared with CCS and controls; Roseburia, C. aerofaciens and F. prausnitzii were more abundant in controls than in patients. Principal component analysis (PCA) of 41 differentially abundant gut taxa showed a clustering of the three groups. In coronary plaque, LEfSe at the genus level revealed an enrichment of Staphylococcus and Streptococcus in ACS, and Paracoccus in CCS, whereas PCA of 15 differentially abundant plaque taxa exhibited clustering of ACS and CCS patients. CutC and CntA genes were more abundant in ACS and CCS than in controls while no significant difference emerged between ACS and CCS. Our results indicate that ACS and CCS exhibit a different gut and plaque microbial signature, suggesting a possible role of these microbiotas in coronary plaque instability.

Abstract Background The development of e-health technologies for teleconsultation and exchange of knowledge is one of the core purposes of European Reference Networks (ERNs), including the ERN EURO-NMD for rare neuromuscular diseases. Within ERNs, the Clinical Patient Management System (CPMS) is a web-based platform that seeks to boost active collaboration within and across the network, implementing data sharing. Through CPMS, it is possible to both discuss patient cases and to make patients’ data available for registries and databases in a secure way. In this view, CPMS may be considered a sort of a temporary storage for patients’ data and an effective tool for data sharing; it facilitates specialists’ consultation since rare diseases (RDs) require multidisciplinary skills, specific, and outstanding clinical experience. Following European Union (EU) recommendation, and to promote the use of CPMS platform among EURO-NMD members, a twelve-month pilot project was set up to train the 15 Italian Health Care Providers (HCPs). In this paper, we report the structure, methods, and results of the teaching course, showing that tailored, ERN-oriented, training can significantly enhance the profitable use of the CPMS. Results Throughout the training course, 45 professionals learned how to use the many features of the CPMS, eventually opening 98 panels of discussion—amounting to 82% of the total panels included in the EURO-NMD. Since clinical, genetic, diagnostic, and therapeutic data of patients can be securely stored within the platform, we also highlight the importance of this platform as an effective tool to discuss and share clinical cases, in order to ease both case solving and data storing. Conclusions In this paper, we discuss how similar course could help implementing the use of the platform, highlighting strengths and weaknesses of e-health for ERNs. The expected result is the creation of a “map” of neuromuscular patients across Europe that might be improved by a wider use of CPMS.

Since becoming an independent country in 1991, Kazakhstan has demonstrated a strong desire for international status and recognition by, for example, hosting numerous international events, such as chairing the OSCE and hosting EXPO 2017; creating the Conference on Interaction and Confidence Building Measures in Asia; and, most notably, presenting the abandonment of its nuclear weapons as a model for other states to emulate. Surprisingly, Kazakhstan has received scant attention by scholars regarding its desire for status, especially considering how the government has framed its decision to relinquish its nuclear weapons in terms of advancing international peace at the expense of its own security self-interest. Kazakhstan’s status-seeking raises two questions. First, how can a mid-level power strategically frame its foreign and domestic policies in order to improve its global status? And second, how can it improve its international status when domestic priorities (such as economic development and political stability) lead to policies that meet disapproval abroad? In this article, we answer these questions by examining issue areas (security, democratization, and the environment) that contain variation in our dependent variable, Kazakhstan’s quest for status. In doing so, we reveal patterns of how a secondary or mid-level state lacking substantial material capabilities can, through its words and actions, construct an image that may enhance its international status. We also show variation by issue area in the reception of these efforts by developed and developing countries. Lastly, we reveal in what issue areas Kazakhstan’s desire for status internationally is constrained by the government’s desire to maintain power domestically.

Abstract Mitochondrial diseases are a heterogeneous group of monogenic disorders that result from impaired oxidative phosphorylation (OXPHOS). As neuromuscular tissues are highly energy‐dependent, mitochondrial diseases often affect skeletal muscle. Although genetic and bioenergetic causes of OXPHOS impairment in human mitochondrial myopathies are well established, there is a limited understanding of metabolic drivers of muscle degeneration. This knowledge gap contributes to the lack of effective treatments for these disorders. Here, we discovered fundamental muscle metabolic remodeling mechanisms shared by mitochondrial disease patients and a mouse model of mitochondrial myopathy. This metabolic remodeling is triggered by a starvation‐like response that evokes accelerated oxidation of amino acids through a truncated Krebs cycle. While initially adaptive, this response evolves in an integrated multiorgan catabolic signaling, lipid store mobilization, and intramuscular lipid accumulation. We show that this multiorgan feed‐forward metabolic response involves leptin and glucocorticoid signaling. This study elucidates systemic metabolic dyshomeostasis mechanisms that underlie human mitochondrial myopathies and identifies potential new targets for metabolic intervention.

Funded by a Teaching Innovation Grant designed to transform traditional in-person courses into engaging and equitable online spaces, we designed the introductory anthropology course, Plagues, Pathogens, and Public Policy. The course is 15 weeks and is organized thematically around pressing topics and conversations concerning the social, political, and cultural dimensions of pandemics. While the COVID-19 global pandemic has intensified the pertinence of the course’s content, recent discourse on systemic racism and police brutality in the United States has also drawn renewed attention to the lack of inclusivity and accessibility within anthropological academia. Thus, with the design of this syllabus, we sought to decolonize our course content and pedagogy as a means of contributing to ongoing efforts towards inclusivity in academia. Our approach to a decolonized and inclusive syllabus included diversifying course content as well as constructing accessible language, assignments, and course policies. The following commentary outlines our goals for this endeavor and describes the process of creating this course. We detail our experiences with employing a decolonizing framework and present a guide for reading our completed syllabus so that we may encourage the development of more spaces where students can engage with and understand the benefits of decolonized scholarship.

The COVIVAX study assessed the association between COVID-19 vaccination and the risk of common neurological disorders in a multicenter case-control design. Vaccination exposure was compared between individuals with a first diagnosis of a neurological disorder (cases) and age- and sex-matched controls. A total of 624 participants were enrolled, and after random 1:1 matching 265 cases and 265 matched controls (total 530 participants) were included in the analyses. The most frequent neurological diagnosis in cases were stroke (60.4%), multiple sclerosis (11.3%) and seizures (6.4%). The proportion of vaccinated participants was 72.1% among cases and 79.6% among controls. A protective role of vaccination on the risk of developing a new neurological disorder was detected in the unadjusted analysis (OR 0.50; 95% CI 0.29–0.86; p = 0.0114). After adjustment for confounders, the number of vaccination doses received was associated with a reduced risk of developing new neurological disorders for participants aged over 60 years (p = 0.0472; OR 0.14, 95% CI 0.03–0.68), with pre-existing comorbidities (p = 0.0122; OR 0.04, 95% CI 0.01–0.99) and for stroke (p = 0.0232; OR 0.04, 95% CI 0.02–0.97). The COVIVAX study provided no warning sign regarding an increase in the risk of developing new neurological disorders following COVID-19 vaccination of any type or doses. A potentially protective effect of multiple doses of COVID-19 vaccines against the risk of stroke in people aged over 60 needs to be confirmed by further studies. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid Arthritis (RA) is among the most prevalent chronic inflammatory diseases affecting millions of people with a significant expenditure of resources by National Healthcare Systems. This study aimed to analyze all available treatments exclusively for RA to highlight the costs of each treatment type and raise awareness of the use of biosimilar drugs. Methods: In an Italian healthcare authority, all prescriptions made for the diagnosis of RA were extracted to verify consumption expressed in Defined Daily Dose (DDD) and the expenditure incurred expressed in euros. Consequently, a grouping into three major drug categories has been performed: anti – tumor necrosis factor alpha agents (TNFα), other injectable formulations, and novel oral formulations. Results: Prescriptions for the second half-year 2022 and 2023 have been analyzed, with a total cost of almost 7 million euros in the sample considered. All pharmaceutical categories showed an increase in consumption, but only anti- TNFα recorded a decrease in costs from 25% in 2022 to 22% in 2023, thanks to the lower cost of the biosimilar drug. Conclusion: The costs of RA may represent a significant spending commitment for central governments. As a result, actions are needed to encourage the preferential use of biosimilar drugs. [ABSTRACT FROM AUTHOR]

Abstract Background We believe that our experience with patients presenting with Coats disease and macular sparing should be shared with our colleagues. We would like to show the effect of posture and prompt intervention in cases with fovea-threatening and/or fovea-involving peripheral Coats disease (FTPCD). This association has been poorly debated in our specialty and literature. We call the attention for the unexpexted scenario of observing the lost of the fovea during some types of traditional and prompt interventional treatments of these cases with previous 20/20 vision (something that we have been studying and observing for many years). In order to publish our best representative cases, we have chosen 8 Brazilian patients (age range, 7–62 years; 5 male) with FTPCD. All patients underwent multimodal imaging and different treatments (observation, sleep-posture repositioning, laser, intraocular steroids, and/or anti-vascular endothelial growth factor therapy). All patients, initially, informed to adopt a sleeping lateral-down position, favoring exudation shifting to the fovea pre-treatment. Most promptly-treated patients in this way (n = 4), developed subretinal fluid and exudates in the macula and some had irreversible central visual loss (n = 3). Patients with recent fovea-involving exudation who changed postural sleep position (to protect the foveal area) before and during treatment fared better, with some preserved central vision and an intact fovea (n = 5). The fundus status was correlated with the gravitational effects of posture before and after treatment. Despite prepared as an observational/interventional study, with a small number of cases, the most difficult part is documenting the sleep position of these patients and its influence in the outcomes as there is not good way to prove how well or poorly the positioning occurred in our cases. Finally, we also intended to call the attention to the fact that Coats disease must be studied in all its clinical stage variants and not only seen as a potential blinding and incurable ocular disease. Case presentation This study is a retrospective and/or interventional analysis of eight cases with a less severe clinical variant of classic Coats disease that we refer to as fovea-threatening and fovea-involving peripheral Coats disease (FTPCD). All cases were unilateral with no systemic disease or family history of Coats disease. The bilateral anterior segment and intraocular pressure were normal in all patients. The characteristics of all patients are shown in the Table. Conclusion The funduscopic features of FTPCD are fundamental to disease understanding and optimal management. Habitual posturing may affect the fundus morphologic features of retinal exudation as observed in all current patients with exudative peripheral Coats disease. When sleep habitual posture is not observed in patients with FTPCD, the effects of prompt invasive treatments can cause rapid visual loss because of foveal subretinal pooling of exudates post-treatment. Initial vigilant adjusting of the habitual sleep posture for several patients with FTPCD, before the indication of traditional invasive treatments (laser and/or pharmacologic medications) can result in improved vision and fundoscopic morphologic features.

Abstract Background Guideline adaptation provides an important alternative to de novo guideline development by making the process more efficient and reducing unnecessary duplication. The quality evaluation of international guidelines is an essential part of the adaptation process. The study aims at describing the development and validation of a new tool to screen trustworthy Clinical Practice Guidelines (CPGs) for their adoption/adaption: the International Guideline Evaluation Screening Tool (IGEST). Methods The process of developing the IGEST involved two main phases: 1) tool development and 2) content validation. The tool development phase comprised three stages, where the scope of the IGEST was defined and the item pool was generated and refined. The content validation was performed through the computation of a content validity index (CVI) based on the opinions of an expert panel. Results All the items obtained a CVI >0.78, which resulted in the validation of the instrument. The final instrument comprised four preliminary conditions and 12 criteria organised into three dimensions: (i) the management of conflict of interest; (ii) the quality of evidence and the coherence between evidence and recommendations; and (iii) the panel composition. Conclusion The IGEST showed good content validity for assessing the quality of international guidelines. Using the new tool to select trustworthy guidelines might increase the likelihood that international clinical practice guidelines will be adopted/adapted to the local context by allowing a quick screening of existing guidelines trustworthiness and providing an acceptability threshold that supports the decision-making process.