DNA damage reduces heterogeneity and coherence of chromatin motions.

Chromatin motions depend on and may regulate genome functions, in particular the DNA damage response. In yeast, DNA double-strand breaks (DSBs) globally increase chromatin diffusion, whereas in higher eukaryotes the impact of DSBs on chromatin dynamics is more nuanced. We mapped the motions of chromatin microdomains in mammalian cells using diffractive optics and photoactivatable chromatin probes and found a high level of spatial heterogeneity. DNA damage reduces heterogeneity and imposes spatially defined shifts in motions: Distal to DNA breaks, chromatin motions are globally reduced, whereas chromatin retains higher mobility at break sites. These effects are driven by context-dependent changes in chromatin compaction. Photoactivated lattices of chromatin microdomains are ideal to quantify microscale coupling of chromatin motion. We measured correlation distances up to 2 µm in the cell nucleus, spanning chromosome territories, and speculate that this correlation distance between chromatin microdomains corresponds to the physical separation of A and B compartments identified in chromosome conformation capture experiments. After DNA damage, chromatin motions become less correlated, a phenomenon driven by phase separation at DSBs. Our data indicate tight spatial control of chromatin motions after genomic insults, which may facilitate repair at the break sites and prevent deleterious contacts of DSBs, thereby reducing the risk of genomic rearrangements.

Current iron therapy in the light of regulation, intestinal microbiome, and toxicity: are we prescribing too much iron?

Iron deficiency is a widespread global health concern with varying prevalence rates across different regions. In developing countries, scarcity of food and chronic infections contribute to iron deficiency, while in industrialized nations, reduced food intake and dietary preferences affect iron status. Other causes that can lead to iron deficiency are conditions and diseases that result in reduced intestinal iron absorption and blood loss. In addition, iron absorption and its bioavailability are influenced by the composition of the diet. Individuals with increased iron needs, including infants, adolescents, and athletes, are particularly vulnerable to deficiency. Severe iron deficiency can lead to anemia with performance intolerance or shortness of breath. In addition, even without anemia, iron deficiency leads to mental and physical fatigue, which points to the fundamental biological importance of iron, especially in mitochondrial function and the respiratory chain. Standard oral iron supplementation often results in gastrointestinal side effects and poor compliance. Low-dose iron therapy seems to be a valid and reasonable therapeutic option due to reduced hepatic hepcidin formation, facilitating efficient iron resorption, replenishment of iron storage, and causing significantly fewer side effects. Elevated iron levels influence gut microbiota composition, favoring pathogenic bacteria and potentially disrupting metabolic and immune functions. Protective bacteria, such as bifidobacteria and lactobacilli, are particularly susceptible to increased iron levels. Dysbiosis resulting from iron supplementation may contribute to gastrointestinal disorders, inflammatory bowel disease, and metabolic disturbances. Furthermore, gut microbiota alterations have been linked to mental health issues. Future iron therapy should consider low-dose supplementation to mitigate adverse effects and the impact on the gut microbiome. A comprehensive understanding of the interplay between iron intake, gut microbiota, and human health is crucial for optimizing therapeutic approaches and minimizing potential risks associated with iron supplementation.

Azithromycin resistance in Escherichia coli and Salmonella from food-producing animals and meat in Europe.

OBJECTIVES: To characterize the genetic basis of azithromycin resistance in Escherichia coli and Salmonella collected within the EU harmonized antimicrobial resistance (AMR) surveillance programme in 2014-18 and the Danish AMR surveillance programme in 2016-19. METHODS: WGS data of 1007 E. coli [165 azithromycin resistant (MIC > 16 mg/L)] and 269 Salmonella [29 azithromycin resistant (MIC > 16 mg/L)] were screened for acquired macrolide resistance genes and mutations in rplDV, 23S rRNA and acrB genes using ResFinder v4.0, AMRFinder Plus and custom scripts. Genotype-phenotype concordance was determined for all isolates. Transferability of mef(C)-mph(G)-carrying plasmids was assessed by conjugation experiments. RESULTS: mph(A), mph(B), mef(B), erm(B) and mef(C)-mph(G) were detected in E. coli and Salmonella, whereas erm(C), erm(42), ere(A) and mph(E)-msr(E) were detected in E. coli only. The presence of macrolide resistance genes, alone or in combination, was concordant with the azithromycin-resistant phenotype in 69% of isolates. Distinct mph(A) operon structures were observed in azithromycin-susceptible (n = 50) and -resistant (n = 136) isolates. mef(C)-mph(G) were detected in porcine and bovine E. coli and in porcine Salmonella enterica serovar Derby and Salmonella enterica 1,4, [5],12:i:-, flanked downstream by ISCR2 or TnAs1 and associated with IncIγ and IncFII plasmids. CONCLUSIONS: Diverse azithromycin resistance genes were detected in E. coli and Salmonella from food-producing animals and meat in Europe. Azithromycin resistance genes mef(C)-mph(G) and erm(42) appear to be emerging primarily in porcine E. coli isolates. The identification of distinct mph(A) operon structures in susceptible and resistant isolates increases the predictive power of WGS-based methods for in silico detection of azithromycin resistance in Enterobacterales.

Divergence and gene flow history at two large chromosomal inversions underlying ecotype differentiation in the long-snouted seahorse.

Chromosomal inversions can play an important role in divergence and reproductive isolation by building and maintaining distinct allelic combinations between evolutionary lineages. Alternatively, they can take the form of balanced polymorphisms that segregate within populations until one arrangement becomes fixed. Many questions remain about how inversion polymorphisms arise, how they are maintained over the long term, and ultimately, whether and how they contribute to speciation. The long-snouted seahorse (Hippocampus guttulatus) is genetically subdivided into geographic lineages and marine-lagoon ecotypes, with shared structural variation underlying lineage and ecotype divergence. Here, we aim to characterize structural variants and to reconstruct their history and suspected role in ecotype formation. We generated a near chromosome-level genome assembly and described genome-wide patterns of diversity and divergence through the analysis of 112 whole-genome sequences from Atlantic, Mediterranean, and Black Sea populations. By also analysing linked-read sequencing data, we found evidence for two chromosomal inversions that were several megabases in length and showed contrasting allele frequency patterns between lineages and ecotypes across the species range. We reveal that these inversions represent ancient intraspecific polymorphisms, one likely being maintained by divergent selection and the other by pseudo-overdominance. A possible selective coupling between the two inversions was further supported by the absence of specific haplotype combinations and a putative functional interaction between the two inversions in reproduction. Lastly, we detected gene flux eroding divergence between inverted alleles at varying levels for the two inversions, with a likely impact on their dynamics and contribution to divergence and speciation.

Unidirectional trans-Atlantic gene flow and a mixed spawning area shape the genetic connectivity of Atlantic bluefin tuna.

The commercially important Atlantic bluefin tuna (Thunnus thynnus), a large migratory fish, has experienced notable recovery aided by accurate resource assessment and effective fisheries management efforts. Traditionally, this species has been perceived as consisting of eastern and western populations, spawning respectively in the Mediterranean Sea and the Gulf of Mexico, with mixing occurring throughout the Atlantic. However, recent studies have challenged this assumption by revealing weak genetic differentiation and identifying a previously unknown spawning ground in the Slope Sea used by Atlantic bluefin tuna of uncertain origin. To further understand the current and past population structure and connectivity of Atlantic bluefin tuna, we have assembled a unique dataset including thousands of genome-wide single-nucleotide polymorphisms (SNPs) from 500 larvae, young of the year and spawning adult samples covering the three spawning grounds and including individuals of other Thunnus species. Our analyses support two weakly differentiated but demographically connected ancestral populations that interbreed in the Slope Sea. Moreover, we also identified signatures of introgression from albacore (Thunnus alalunga) into the Atlantic bluefin tuna genome, exhibiting varied frequencies across spawning areas, indicating strong gene flow from the Mediterranean Sea towards the Slope Sea. We hypothesize that the observed genetic differentiation may be attributed to increased gene flow caused by a recent intensification of westward migration by the eastern population, which could have implications for the genetic diversity and conservation of western populations. Future conservation efforts should consider these findings to address potential genetic homogenization in the species.

Role of gene sequencing in classifying struma ovarii: BRAF p.G469A mutation and TERT promoter alterations favour malignant struma ovarii.

AIMS: Struma ovarii (SO) are rare, accounting for 0.3-1% of ovarian tumours, and include benign and malignant lesions. In most cases, histology is not predictive of clinical outcome and prognosis. The prognosis of histologically malignant thyroid-type carcinomas can indeed be excellent, while SO, composed of normal thyroid tissue, can recur and are designated highly differentiated follicular carcinoma of the ovary. Clearer diagnostic criteria are therefore required. METHODS AND RESULTS: We retrospectively studied 31 SO using DNA and RNA sequencing with pan-cancer gene panels, including eight biologically malignant SO (BMSO) defined based on ovarian serosal or extra-ovarian dissemination at presentation or during follow-up, 10 stage IA histologically malignant SO (HMSO) with thyroid-type carcinoma morphology and 13 biologically and histologically benign SO (BSO), with none of the above-mentioned characteristics. Molecular alterations were observed in 87.5% of BMSO, 70% of HMSO and 7.7% of BSO (P < 0.001). All patients with a peritoneal dissemination at presentation or during follow-up had at least one gene alteration. BRAF mutations (44.5%) were only observed in malignant forms (HMSO and BMSO) and TERT promoter alterations (25%) only in cases of BMSO. The BRAF p.G469A mutation, which is extremely rare in thyroid carcinomas, was the molecular alteration most frequently associated with malignant SO (28.5%). CONCLUSION: Our results highlight the clinical utility of molecular sequencing in SO, based on this limited number of cases. However, as malignant SO evolve slowly, more extensive molecular studies in SO with more than 10 years' follow-up are required to draw any conclusions on the prognostic value of the associated gene alterations.

Feasibility of Prone Positioning for Brain-injured Patients with Severe Acute Respiratory Distress Syndrome: A Systematic Review and Pilot Study (ProBrain).

BACKGROUND: Prone position is a key component to treat hypoxemia in patients with severe acute respiratory distress syndrome. However, most studies evaluating it exclude patients with brain injuries without any medical evidence. METHODS: This study includes a systematic review to determine whether brain-injured patients were excluded in studies evaluating prone position on acute respiratory distress syndrome; a prospective study including consecutive brain-injured patients needing prone position. The primary endpoint was the evaluation of cerebral blood flow using transcranial Doppler after prone positioning. Secondary outcomes were intracranial pressure, cerebral perfusion pressure, and tissue oxygen pressure. RESULTS: From 8,183 citations retrieved, 120 studies were included in the systematic review. Among them, 90 studies excluded brain-injured patients (75%) without any justification, 16 included brain-injured patients (4 randomized, 7 nonrandomized studies, 5 retrospective), and 14 did not retrieve brain-injured data. Eleven patients were included in the authors' pilot study. No reduction of cerebral blood flow surrogates was observed during prone positioning, with diastolic speed values (mean ± SD) ranging from 37.7 ± 16.2 cm/s to 45.2 ± 19.3 cm/s for the right side (P = 0.897) and 39.6 ± 18.2 cm/s to 46.5 ± 21.3 cm/s for the left side (P = 0.569), and pulsatility index ranging from 1.14 ± 0.31 to 1.0 ± 0.32 for the right side (P = 0.145) and 1.14 ± 0.31 to 1.02 ± 0.2 for the left side (P = 0.564) before and during prone position. CONCLUSIONS: Brain-injured patients are largely excluded from studies evaluating prone position in acute respiratory distress syndrome. However, cerebral blood flow seems not to be altered considering increasing of mean arterial pressure during the session. Systematic exclusion of brain-injured patients appears to be unfounded, and prone position, while at risk in brain-injured patients, should be evaluated on these patients to review recommendations, considering close monitoring of neurologic and hemodynamic parameters.

Dorsal wrist ganglion: clinical and imaging correlation in symptomatic population based on high-field MRI.

OBJECTIVES: To determine prevalence in the symptomatic population of dorsal mucoid cysts centered on dorsal capsuloscapholunate septum (DCSS) using high-field magnetic resonance imaging (MRI) for anatomoclinical and epidemiological correlations. MATERIALS AND METHODS: This single-center retrospective study analyzed all 3-Tesla MRIs consecutively performed for painful wrists in 295 patients. Two blinded readers performed measurements. The protocol included T1 spin echo and 3D proton density sequences with fat saturation. Inter-observer reliability was assessed using kappa and intra-class correlation coefficients for cyst detection and volumetry, respectively. Disagreements concerning cyst detection were resolved by a consensus reading. Cyst size, relationship to extrinsic and scapholunate ligaments (SL), continuity of SL, minimum distance to the posterior interosseous nerve (PIN), cyst communication with joint, and anatomical classifications of cysts were analyzed. Correlation tests were performed to assess associations. RESULTS: Two-hundred ninety-five patients (mean age 39.6 +/- 15.6 (standard deviation), 161 males) were evaluated for detection of dorsal wrist cysts identified in 150/295. In this subgroup, the mean age was 38.7 years (15-75), the sex ratio of 0.6 (59% women), and the median volume cyst of 8.7 mm3 (0.52-2555). Cyst detection, volume, and major axis measurements showed very high agreement between observers, respectively, 0.89, 0.96, and 0.91. 42 patients had dorsal SL pain. A weak negative correlation was found between distance to PIN and dorsal SL pain (r = -0.2415; p < 0.05) and a weak positive correlation between Guérini's classification and dorsal SL pain (r = 0.2466; p < 0.05). CONCLUSION: High-field MRI is the modality of choice for the detection, anatomical, and volumetric assessment of dorsal cysts. Preoperative assessment will be aided by the proposed revised anatomical classification. CLINICAL RELEVANCE STATEMENT: High-field MRI is the modality of choice for the anatomical study of dorsal ganglion cysts. It allows the radiologist to accurately describe the anatomical relationships, size, and visibility of the pedicle, essential information for the surgeon's preoperative assessment. KEY POINTS: Dorsal mucoid wrist ganglion is a condition for which prevalence remains to be determined. High-field MRI is a reproducible imaging modality for the detection and assessment of dorsal wrist cysts. High-field MRI has a key role in the preoperative management of dorsal mucoid cysts.

Digital Holography and 3D Imaging: introduction to the joint feature issue in Applied Optics and Journal of the Optical Society of America A.

The Optica Topical Meeting on Digital Holography and 3D Imaging (DH) was held 14-17 August 2023 in Boston, Massachusetts. The meeting was organized co-jointly with the Optica Imaging Congress. Feature issues based on the DH meeting series have been released by Applied Optics (AO) since 2007. Since 2017, AO and the Journal of the Optical Society of America A (JOSA A) have presented a feature issue in each journal. This feature issues includes 17 papers in AO and 9 in JOSA A. Together they cover a large range of topics, reflecting the rapidly expanding techniques and applications of digital holography and 3D imaging. The upcoming DH Conference (DH 2024) will be held from 3 to 6 June in Paestum, Italy.

Digital Holography and 3D Imaging 2023: introduction to the joint feature issue in Applied Optics and Journal of the Optical Society of America A.

The Optica Topical Meeting on Digital Holography and 3D Imaging (DH) was held 14-17 August 2023 in Boston, Massachusetts. The meeting was organized co-jointly with the Optica Imaging Congress. Feature issues based on the DH meeting series have been released by Applied Optics (AO) since 2007. Since 2017, AO and the Journal of the Optical Society of America A (JOSA A) have presented a feature issue in each journal. This feature issues includes 17 papers in AO and 9 in JOSA A. Together they cover a large range of topics, reflecting the rapidly expanding techniques and applications of digital holography and 3D imaging. The upcoming DH Conference (DH 2024) will be held from 3 to 6 June in Paestum, Italy.

Pixel-based open-space microfluidics for versatile surface processing.

An increasing number of applications in biology, chemistry, and material sciences require fluid manipulation beyond what is possible with current automated pipette handlers, such as gradient generation, interface reactions, reagent streaming, and reconfigurability. In this article, we introduce the pixelated chemical display (PCD), a scalable strategy for highly parallel, reconfigurable liquid handling on open surfaces. Microfluidic "pixels" are created when a fluid stream injected above a surface is confined by neighboring identical fluid streams, forming a repeatable flow unit that can be used to tesselate a surface. PCDs generating up to 144 pixels are fabricated and used to project "chemical moving pictures" made of several reagents over both immersed and dry surfaces, without any physical barrier or wall. This work distinguishes itself from previous work in open-space microfluidics by presenting a device architecture where the number of confinement areas can be scaled to any size. Furthermore, it challenges the open-space tenet that the aspiration rate must be higher than the injection rate for reagents to be confined. Overall, this article sets the foundation for massively parallel surface processing using continuous flow streams and showcases possibilities in both wet and dry surface patterning and roll-to-roll processes.

The CovR regulatory network drives the evolution of Group B Streptococcus virulence.

Virulence of the neonatal pathogen Group B Streptococcus is under the control of the master regulator CovR. Inactivation of CovR is associated with large-scale transcriptome remodeling and impairs almost every step of the interaction between the pathogen and the host. However, transcriptome analyses suggested a plasticity of the CovR signaling pathway in clinical isolates leading to phenotypic heterogeneity in the bacterial population. In this study, we characterized the CovR regulatory network in a strain representative of the CC-17 hypervirulent lineage responsible of the majority of neonatal meningitis. Transcriptome and genome-wide binding analysis reveal the architecture of the CovR network characterized by the direct repression of a large array of virulence-associated genes and the extent of co-regulation at specific loci. Comparative functional analysis of the signaling network links strain-specificities to the regulation of the pan-genome, including the two specific hypervirulent adhesins and horizontally acquired genes, to mutations in CovR-regulated promoters, and to variability in CovR activation by phosphorylation. This regulatory adaptation occurs at the level of genes, promoters, and of CovR itself, and allows to globally reshape the expression of virulence genes. Overall, our results reveal the direct, coordinated, and strain-specific regulation of virulence genes by the master regulator CovR and suggest that the intra-species evolution of the signaling network is as important as the expression of specific virulence factors in the emergence of clone associated with specific diseases.

A novel VCP::TFE3 gene fusion resulting from t(X;9)(p11.23;p13.3) chromosome translocation in TFE3 rearranged renal cancer cell carcinoma.

Renal cell carcinoma (RCC) with rearrangement of transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3; TFE3-rearranged RCC) at Xp11.2 is a rare tumor entity but the most frequent among the microphthalmia transcription factor family translocation RCCs. Here, we report the identification of a new VCP::TFE3 fusion gene as the result of a t(X;9)(p11.23;p13.3) translocation identified by whole transcriptome sequencing. No other relevant molecular alteration was identified by whole exome sequencing. This case showed typical morphological features of TFE3-rearranged RCC with positive TFE3 immunostaining and positive TFE3 break-apart fluorescence in situ hybridization. MET was also overexpressed on immunohistochemistry. The patient had metastatic disease and was treated by surgery and five lines of therapy, including 24 months of stable disease on the mesenchymal epithelial transition (MET) inhibitor cabozantinib, with an overall survival of 7 years. In addition to expanding the spectrum of TFE3 rearrangement partners, this report highlights the complexity of these tumors and supports the development of translational programs in renal cancer.

Proposed DRLs for mammography in Switzerland.

The aim of this study is to propose diagnostic reference levels (DRLs) values for mammography in Switzerland. For the data collection, a survey was conducted among a sufficient number of centres, including five University hospitals, several cantonal hospitals, and large private clinics, covering all linguistic regions of Switzerland to be representative of the clinical practice. The data gathered contained the mean glandular dose (MGD), the compressed breast thickness (CBT), the mammography model and the examination parameters for each acquisition. The data collected was sorted into the following categories: 2D or digital breast tomosynthesis (DBT) examination, craniocaudal (CC) or mediolateral oblique (MLO) projection, and eight categories of CBT ranging from 20 mm to 100 mm in 10 mm intervals. A total of 24 762 acquisitions were gathered in 31 centres on 36 mammography units from six manufacturers. The analysis showed that the data reflects the practice in Switzerland. The results revealed that the MGD is larger for DBT than for 2D acquisitions for the same CBT. From 20-30 mm to 90-100 mm of CBT, the 75th percentile of the MGD values obtained increased from 0.81 mGy to 2.55 mGy for 2D CC acquisitions, from 0.83 mGy to 2.96 mGy for 2D MLO acquisitions, from 1.22 mGy to 3.66 mGy for DBT CC acquisitions and from 1.33 mGy to 4.04 mGy for DBT MLO acquisitions. The results of the survey allow us to propose Swiss DRLs for mammography according to the examination type (2D/DBT), projection (CC/MLO) and CBT. The proposed values are very satisfactory in comparison with other studies.

COVID-19 rapidly increases MDSCs and prolongs innate immune dysfunctions.

We used unsupervised immunophenotyping of blood leukocytes and measured cytokine production by innate immune cell exposed to LPS and R848. We show that COVID-19 induces a rapid, transient upregulation of myeloid-derived suppressor cells (MDSCs) accompanied by a rapid, sustained (up to 3 months) hyporesponsiveness of dendritic cells and monocytes. Blood MDSCs may represent biomarkers and targets for intervention strategies in COVID-19 patients.

Sequence and vector shapes vaccine induced antibody effector functions in HIV vaccine trials.

Despite the advent of long-acting anti-retroviral therapy able to control and prevent infection, a preventative vaccine remains a global priority for the elimination of HIV. The moderately protective RV144 vaccine trial suggested functional IgG1 and IgG3 antibodies were a potential correlate of protection, but the RV144-inspired HVTN702 validation trial failed to demonstrate efficacy despite inducing targeted levels of IgG1/IgG3. Alterations in inserts, and antigens, adjuvant, and regimen also resulted in vaccine induced target quantitative levels of the immune correlates, but drove qualitative changes to the humoral immune response, pointing to the urgent need to define the influence of vaccine strategies on shaping antibody quality, not just quantity. Thus, defining how distinct prime/boost approaches tune long-lived functional antibodies represents an important goal in vaccine development. Here, we compared vaccine responses in Phase I and II studies in humans utilizing various combinations of DNA/vector, vector/vector and DNA/protein HIV vaccines. We found that adenoviral vector immunization, compared to pox-viral vectors, resulted in the most potent IgG1 and IgG3 responses, linked to highly functional antibody activity, including assisting NK cell related functions. Minimal differences were observed in the durability of the functional humoral immune response across vaccine regimens, except for antibody dependent phagocytic function, which persisted for longer periods in the DNA/rAd5 and rAd35/rAd5 regimen, likely driven by higher IgG1 levels. Collectively, these findings suggest adenoviral vectors drive superior antibody quality and durability that could inform future clinical vaccine studies. Trial registration: ClinicalTrials.gov NCT00801697, NCT00961883, NCT02207920, NCT00125970, NCT02852005).

S100A alarmins and thymic stromal lymphopoietin (TSLP) regulation in severe asthma following bronchial thermoplasty.

RATIONALE: Severe asthma affects a small proportion of asthmatics but represents a significant healthcare challenge. Bronchial thermoplasty (BT) is an interventional treatment approach preconized for uncontrolled severe asthma after considering biologics therapy. It was showed that BT long-lastingly improves asthma control. These improvements seem to be related to the ability of BT to reduce airway smooth muscle remodeling, reduce the number of nerve fibers and to modulate bronchial epithelium integrity and behavior. Current evidence suggest that BT downregulates epithelial mucins expression, cytokine production and metabolic profile. Despite these observations, biological mechanisms explaining asthma control improvement post-BT are still not well understood. OBJECTIVES: To assess whether BT affects gene signatures in bronchial epithelial cells (BECs). METHODS: In this study we evaluated the transcriptome of cultured bronchial epithelial cells (BECs) of severe asthmatics obtained pre- and post-BT treatment using microarrays. We further validated gene and protein expressions in BECs and in bronchial biopsies with immunohistochemistry pre- and post-BT treatment. MEASUREMENTS AND MAIN RESULTS: Transcriptomics analysis revealed that a large portion of differentially expressed genes (DEG) was involved in anti-viral response, anti-microbial response and pathogen induced cytokine storm signaling pathway. S100A gene family stood out as five members of this family where consistently downregulated post-BT. Further validation revealed that S100A7, S100A8, S100A9 and their receptor (RAGE, TLR4, CD36) expressions were highly enriched in severe asthmatic BECs. Further, these S100A family members were downregulated at the gene and protein levels in BECs and in bronchial biopsies of severe asthmatics post-BT. TLR4 and CD36 protein expression were also reduced in BECs post-BT. Thymic stromal lymphopoietin (TSLP) and human ß-defensin 2 (hBD2) were significantly decreased while no significant change was observed in IL-25 and IL-33. CONCLUSIONS: These data suggest that BT might improve asthma control by downregulating epithelial derived S100A family expression and related downstream signaling pathways.

Clinical outcomes of 3T magnetic resonance imaging-guided lumbar and sacral foraminal injections.

PURPOSE: This article evaluates the feasibility, safety, and efficacy of MRI-guided lumbar or sacral nerve root infiltration for chronic back pain. We compared the outcomes of our MRI-guided infiltrations with data from CT-guided infiltrations reported in the literature and explored the potential advantages of MRI guidance. METHOD: Forty-eight MRI-guided nerve root infiltrations were performed using a 3 T MRI machine. The optimal needle path was determined using breathhold T2-weighted sequences, and the needle was advanced under interleaved guidance based on breathhold PD-weighted images. Pain levels were assessed using a numeric rating scale (NRS) before the procedure and up to 5 months after, during follow-up. Procedure success was evaluated by comparing patients' pain levels before and after the infiltration. RESULTS: The MRI-guided infiltrations yielded pain reduction 1 week after the infiltration in 92% of cases, with an average NRS substantial change of 3.9 points. Pain reduction persisted after 5 months for 51% of procedures. No procedure-related complications occurred. The use of a 22G needle and reconstructed subtraction images from T2 FatSat sequences improved the workflow. CONCLUSION: Our study showed that MRI-guided nerve root infiltration is a feasible, safe, and effective treatment option for chronic back pain. Precise positioning of the needle tip and accurate distribution of the injected solution contributed to the effectiveness of MRI-guided infiltration, which appeared to be as accurate as CT-guided procedures. Further research is needed to explore the potential benefits of metal artifact reduction sequences to optimize chronic back pain management.

Final Size for Epidemic Models with Asymptomatic Transmission.

The final infection size is defined as the total number of individuals that become infected throughout an epidemic. Despite its importance for predicting the fraction of the population that will end infected, it does not capture which part of the infected population will present symptoms. Knowing this information is relevant because it is related to the severity of the epidemics. The objective of this work is to give a formula for the total number of symptomatic cases throughout an epidemic. Specifically, we focus on different types of structured SIR epidemic models (in which infected individuals can possibly become symptomatic before recovering), and we compute the accumulated number of symptomatic cases when time goes to infinity using a probabilistic approach. The methodology behind the strategy we follow is relatively independent of the details of the model.

Identification of novel genes influencing eosinophil-specific protein levels in asthma families.

BACKGROUND: Eosinophils play a key role in the asthma allergic response by releasing cytotoxic molecules such as eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) that generate epithelium damages. OBJECTIVE: We sought to identify genetic variants influencing ECP and EDN levels in asthma-ascertained families. METHODS: We performed univariate and bivariate genome-wide association analyses of ECP and EDN levels in 1018 subjects from the EGEA study with follow-up in 153 subjects from the Saguenay-Lac-Saint-Jean study and combined the results of these 2 studies through meta-analysis. We then conducted Bayesian statistical fine mapping together with quantitative trait locus and functional annotation analyses to identify the most likely functional genetic variants and candidate genes. RESULTS: We identified 5 genome-wide significant loci (P &lt; 5 × 10^-8) including 7 distinct signals associated with ECP and/or EDN levels. The genes targeted by our fine mapping and functional search include RNASE2 and RNASE3 (14q11), which encode EDN and ECP, respectively, and 4 other genes that regulate ECP and EDN levels. These 4 genes were JAK1 (1p31), a transcription factor that plays a key role in the immune response and acts as a potential therapeutic target for eosinophilic asthma; ARHGAP25 (2p13), which is involved in leukocyte recruitment to inflammatory sites; NDUFA4 (7p21), which encodes a component of the mitochondrial respiratory chain and is involved in cellular response to stress; and CTSL (9q22), which is involved in immune response, extracellular remodeling, and allergic inflammation. CONCLUSION: Analysis of specific phenotypes produced by eosinophils allows the identification of genes that play a major role in allergic response and inflammation, and offers potential therapeutic targets for asthma.