The role of FDG-PET/CT imaging in early detection of extra-cardiac complications of infective endocarditis

AbstractThe exact incidence of extra-cardiac complications (ECC) in patients with infective endocarditis (IE) is unknown but presumed to be high. These patients, although mostly asymptomatic, may require a more aggressive therapeutic approach. 18fluorodeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) is used for the diagnosis of infections, but its role in the early diagnosis of IE complications is still unclear. This study aimed to evaluate the role of FDG-PET/CT in the early diagnosis of ECC in IE and its implications for medical management. We prospectively studied 40 consecutive patients with a confirmed diagnosis of IE (according to the modified Duke criteria) who underwent a whole body FDG-PET/CT study within 14 days from diagnosis. The FDG-PET/CT demonstrated ECC in 17 (42.5%) patients, while 8 (38.1%) of them were asymptomatic. The most frequent embolic sites were musculoskeletal and splenic. Owing to the FDG-PET/CT findings, treatment planning was modified in 14 (35%) patients. This included antibiotic treatment prolongation (27.5%), referral to surgical procedures (15%) and, most substantially, prevention of unnecessary device extraction (17.7%). According to our experiences, FDG-PET/CT imaging was useful in the detection of embolic and metastatic infections in IE. This clinical information had a significant diagnostic and therapeutic impact in managing IE disease

Does One Measure Fit All? The Role of Experimentally Induced Pain Tests in the Assessment of Women with Provoked Vestibular Pain

Ahinoam Lev-Sagie,1 Nosaiba Rayan-Gharra,2 Hadas Allouche-Kam,3 Michal Granot2 1Faculty of Medicine, Hebrew University of Jerusalem, Clalit Health Organization, Jerusalem, Israel; 2Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel; 3Department of Obstetrics and Gynecology, Hadassah Mount Scopus-Hebrew University Medical Center, Jerusalem, IsraelCorrespondence: Ahinoam Lev-Sagie, MD Faculty of Medicine,Hebrew University of Jerusalem, Israel, and Vulvovaginal Disorders Clinic, Clalit Health Organization, Jerusalem, Israel, Tel +972-52-5223933, Fax +972-74-7405516, Email [email protected]: A diagnostic algorithm was recently suggested to address the underlying mechanisms of provoked-vestibulodynia (PVD). It delineates four subgroups (Hormonal-associated, Augmented-anterior, Hymenal-associated and Hypertonicity-associated), each manifesting a distinctive vulvar pain-hypersensitivity regarding location (circumferential vs posterior-only vestibulodynia) and pain characteristics. We aimed to explore the significance of various experimentally induced vulvar pain measures in the manifestation of pain hypersensitivity in each subgroup.Methods: Women with PVD (n = 113) and 43 controls reported pain intensity provoked during vaginal penetration and tampon insertion. Vestibular tenderness (anterior and posterior) was assessed by Q-tip test, and pressure stimulation delivered to the puborectalis assessed muscle tenderness. Pain thresholds were measured using a vulvar-algesiometer. These measures were compared between patients and controls and among the PVD subgroups. Correlations between the clinical and experimentally induced-pain measures were assessed. Finally, to address whether the association between experimentally induced-pain measures and dyspareunia severity is mediated by hypertonicity, the conditional indirect effect was analyzed in each subgroup.Results: Compared to controls, augmented vulvar pain-hypersensitivity and hypertonicity were observed among patients (p < 0.001). ANOVA revealed no subgroup differences in dyspareunia severity. Nevertheless, some experimentally induced-pain measures were differently correlated with dyspareunia intensity in each subgroup, allowing discrimination of subgroups according to the unique findings of vulvar pain-hypersensitivity. The degree of pelvic floor muscle-hypertonicity mediated the association between vulvar pain-hypersensitivity and dyspareunia severity, emphasizing the key role of hypertonicity in distinguishing between subgroups.Conclusion: The findings offer more evidence of variations among PVD subtypes, demonstrating that insertional dyspareunia may originate from dissimilar alterations in the mucosal and muscular tissues. The results also emphasize the significance of utilizing a wide battery of tests to capture different experimentally induced-pain measures, revealing the unique patterns of vulvar pain-hypersensitivity in each subgroup.Keywords: vulvodynia, provoked vestibulodynia, insertional dyspareunia, experimentally induced pain measures, subgroup

Autoimmune Epilepsy: Some Epilepsy Patients Harbor Autoantibodies to Glutamate Receptors and dsDNA on both Sides of the Blood-brain Barrier, which may Kill Neurons and Decrease in Brain Fluids after Hemispherotomy

Purpose: Elucidating the potential contribution of specific autoantibodies (Ab's) to the etiology and/or pathology of some human epilepsies. Methods: Six epilepsy patients with Rasmussen's encephalitis (RE) and 71 patients with other epilepsies were tested for Ab's to the –B— peptide (amino acids 372-395) of the glutamate/AMPA subtype 3 receptor (GluR3B peptide), double-stranded DNA (dsDNA), and additional autoimmune disease-associated autoantigens, and for the ability of their serum and cerebrospinal-fluid (CSF) to kill neurons. Results: Elevated anti-GluR3B Ab's were found in serum and CSF of most RE patients, and in serum of 17/71 (24%) patients with other epilepsies. In two RE patients, anti-GluR3B Ab's decreased drastically in CSF following functional-hemispherotomy, in association with seizure cessation and neurological improvement. Serum and CSF of two RE patients, and serum of 12/71 (17%) patients with other epilepsies, contained elevated anti-dsDNA Ab's, the hallmark of systemic-lupus-erythematosus. The sera (but not the CSF) of some RE patients contained also clinically elevated levels of –classical— autoimmune Ab's to glutamic-acid-decarboxylase, cardiolipin, β2-glycoprotein-I and nuclear-antigens SS-A and RNP-70. Sera and CSF of some RE patients caused substantial death of hippocampal neurons. Conclusions: Some epilepsy patients harbor Ab's to GluR3 and dsDNA on both sides of the blood-brain barrier, and additional autoimmune Ab's only in serum. Since all these Ab's may be detrimental to the nervous system and/or peripheral organs, we recommend testing for their presence in epilepsy, and silencing their activity in Ab-positive patients

The Impact and Cost of Scaling up GeneXpert MTB/RIF in South Africa

We estimated the incremental cost and impact on diagnosis and treatment uptake of national rollout of Xpert MTB/RIF technology (Xpert) for the diagnosis of pulmonary TB above the cost of current guidelines for the years 2011 to 2016 in South Africa.We parameterised a population-level decision model with data from national-level TB databases (n = 199,511) and implementation studies. The model follows cohorts of TB suspects from diagnosis to treatment under current diagnostic guidelines or an algorithm that includes Xpert. Assumptions include the number of TB suspects, symptom prevalence of 5.5%, annual suspect growth rate of 10%, and 2010 public-sector salaries and drug and service delivery costs. Xpert test costs are based on data from an in-country pilot evaluation and assumptions about when global volumes allowing cartridge discounts will be reached.At full scale, Xpert will increase the number of TB cases diagnosed per year by 30%-37% and the number of MDR-TB cases diagnosed by 69%-71%. It will diagnose 81% of patients after the first visit, compared to 46% currently. The cost of TB diagnosis per suspect will increase by 55% to USD 60-61 and the cost of diagnosis and treatment per TB case treated by 8% to USD 797-873. The incremental capital cost of the Xpert scale-up will be USD 22 million and the incremental recurrent cost USD 287-316 million over six years.Xpert will increase both the number of TB cases diagnosed and treated and the cost of TB diagnosis. These results do not include savings due to reduced transmission of TB as a result of earlier diagnosis and treatment initiation

Detailed Analysis of <em>ITPR1 </em>Missense Variants Guides Diagnostics and Therapeutic Design

\ua9 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Background: The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP3) receptor type 1 (IP3R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood. Objectives: We aimed to identify novel SCA29 and GLSP cases to define core phenotypes, describe the spectrum of missense variation across ITPR1, standardize the ITPR1 variant nomenclature, and investigate disease progression in relation to cerebellar atrophy. Methods: Cases were identified using next-generation sequencing through the Deciphering Developmental Disorders study, the 100,000 Genomes project, and clinical collaborations. ITPR1 alternative splicing in the human cerebellum was investigated by quantitative polymerase chain reaction. Results: We report the largest, multinational case series of 46 patients with 28 unique ITPR1 missense variants. Variants clustered in functional domains of the protein, especially in the N-terminal IP3-binding domain, the carbonic anhydrase 8 (CA8)-binding region, and the C-terminal transmembrane channel domain. Variants outside these domains were of questionable clinical significance. Standardized transcript annotation, based on our ITPR1 transcript expression data, greatly facilitated analysis. Genotype–phenotype associations were highly variable. Importantly, while cerebellar atrophy was common, cerebellar volume loss did not correlate with symptom progression. Conclusions: This dataset represents the largest cohort of patients with ITPR1 missense variants, expanding the clinical spectrum of SCA29 and GLSP. Standardized transcript annotation is essential for future reporting. Our findings will aid in diagnostic interpretation in the clinic and guide selection of variants for preclinical studies. \ua9 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Association of Early Repolarization Pattern on ECG with Risk of Cardiac and All-Cause Mortality: A Population-Based Prospective Cohort Study (MONICA/KORA)

In a population-based cohort study of middle-aged people in Central Europe, Stefan Kääb and colleagues find an association between electrocardiographic early repolarization pattern and mortality risk

Detailed Analysis of ITPR1 Missense Variants Guides Diagnostics and Therapeutic Design

BACKGROUND: The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP3 ) receptor type 1 (IP3 R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood. OBJECTIVES: We aimed to identify novel SCA29 and GLSP cases to define core phenotypes, describe the spectrum of missense variation across ITPR1, standardize the ITPR1 variant nomenclature, and investigate disease progression in relation to cerebellar atrophy. METHODS: Cases were identified using next-generation sequencing through the Deciphering Developmental Disorders study, the 100,000 Genomes project, and clinical collaborations. ITPR1 alternative splicing in the human cerebellum was investigated by quantitative polymerase chain reaction. RESULTS: We report the largest, multinational case series of 46 patients with 28 unique ITPR1 missense variants. Variants clustered in functional domains of the protein, especially in the N-terminal IP3 -binding domain, the carbonic anhydrase 8 (CA8)-binding region, and the C-terminal transmembrane channel domain. Variants outside these domains were of questionable clinical significance. Standardized transcript annotation, based on our ITPR1 transcript expression data, greatly facilitated analysis. Genotype-phenotype associations were highly variable. Importantly, while cerebellar atrophy was common, cerebellar volume loss did not correlate with symptom progression. CONCLUSIONS: This dataset represents the largest cohort of patients with ITPR1 missense variants, expanding the clinical spectrum of SCA29 and GLSP. Standardized transcript annotation is essential for future reporting. Our findings will aid in diagnostic interpretation in the clinic and guide selection of variants for preclinical studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

How effective are on-farm conservation land management strategies for preserving ecosystem services in developing countries? A systematic map protocol

Background An extensive body of literature in the field of agro-ecology claims to show the positive effects that maintenance of ecosystem services can have on sustainably meeting future food demand, by making farms more productive and resilient, and contributing to better nutrition and livelihoods of farmers. In Africa alone, some research has estimated a two-fold yield increase if food producers capitalize on new and existing knowledge from science and technology. Site-specific strategies adopted with the aim of improving ecosystem services may incorporate principles of multifunctional agriculture, sustainable intensification and conservation agriculture. However, a coherent synthesis and review of the evidence of these claims is largely absent, and the quality of much of this literature is questionable. Moreover, inconsistent effects have commonly been reported, while empirical evidence to support assumed improvements is largely lacking. Objectives This systematic map is stimulated by an interest to (1) collate evidence on the effectiveness of on-farm conservation land management for preserving and enhancing ecosystem services in agricultural landscapes, by drawing together the currently fragmented and multidisciplinary literature base, and (2) geographically map what indicators have been used to assess on-farm conservation land management. For both questions, we will focus on 74 low-income and developing countries, where much of the world’s agricultural expansion is occurring, yet 80% of arable land is already used and croplands are yielding well below their potential. Methods/Design To this end, reviewers will systematically search bibliographic databases for peer-reviewed research from Web of Science, SCOPUS, AGRICOLA, AGRIS databases and CAB abstracts, and grey literature from Google Scholar, and 22 subject-specific or institutional websites. Boolean search operators will be used to create search strings where applicable. Ecosystem services included in the study are pollination services; pest-, carbon-, soil-, and water-regulation; nutrient cycling; medicinal and aromatic plants; fuel wood and cultural services. Outputs of the systematic map will include a database, technical report and an online interactive map, searchable by topic. The results of this map are expected to provide clarity about synergistic outcomes of conservation land management, which will help support local decision-making

Identification and functional characterization of small non-coding RNAs in Xanthomonas oryzae pathovar oryzae

<p>Abstract</p> <p>Background</p> <p>Small non-coding RNAs (sRNAs) are regarded as important regulators in prokaryotes and play essential roles in diverse cellular processes. <it>Xanthomonas oryzae </it>pathovar <it>oryzae </it>(<it>Xoo</it>) is an important plant pathogenic bacterium which causes serious bacterial blight of rice. However, little is known about the number, genomic distribution and biological functions of sRNAs in <it>Xoo</it>.</p> <p>Results</p> <p>Here, we performed a systematic screen to identify sRNAs in the <it>Xoo </it>strain PXO99. A total of 850 putative non-coding RNA sequences originated from intergenic and gene antisense regions were identified by cloning, of which 63 were also identified as sRNA candidates by computational prediction, thus were considered as <it>Xoo </it>sRNA candidates. Northern blot hybridization confirmed the size and expression of 6 sRNA candidates and other 2 cloned small RNA sequences, which were then added to the sRNA candidate list. We further examined the expression profiles of the eight sRNAs in an <it>hfq </it>deletion mutant and found that two of them showed drastically decreased expression levels, and another exhibited an Hfq-dependent transcript processing pattern. Deletion mutants were obtained for seven of the Northern confirmed sRNAs, but none of them exhibited obvious phenotypes. Comparison of the proteomic differences between three of the ΔsRNA mutants and the wild-type strain by two-dimensional gel electrophoresis (2-DE) analysis showed that these sRNAs are involved in multiple physiological and biochemical processes.</p> <p>Conclusions</p> <p>We experimentally verified eight sRNAs in a genome-wide screen and uncovered three Hfq-dependent sRNAs in <it>Xoo</it>. Proteomics analysis revealed <it>Xoo </it>sRNAs may take part in various metabolic processes. Taken together, this work represents the first comprehensive screen and functional analysis of sRNAs in rice pathogenic bacteria and facilitates future studies on sRNA-mediated regulatory networks in this important phytopathogen.</p