Genotypic characterization and antimicrobial susceptibility of human Campylobacter jejuni isolates in Southern Spain.

Campylobacter jejuni is the main cause of bacterial gastroenteritis and a public health problem worldwide. Little information is available on the genotypic characteristics of human C. jejuni in Spain. This study is based on an analysis of the resistome, virulome, and phylogenetic relationship, antibiogram prediction, and antimicrobial susceptibility of 114 human isolates of C. jejuni from a tertiary hospital in southern Spain from October 2020 to June 2023. The isolates were sequenced using Illumina technology, and a bioinformatic analysis was subsequently performed. The susceptibility of C. jejuni isolates to ciprofloxacin, tetracycline, and erythromycin was also tested. The resistance rates for each antibiotic were 90.3% for ciprofloxacin, 66.7% for tetracycline, and 0.88% for erythromycin. The fluoroquinolone resistance rate obtained is well above the European average (69.1%). CC-21 (n = 23), ST-572 (n = 13), and ST-6532 (n = 13) were the most prevalent clonal complexes (CCs) and sequence types (STs). In the virulome, the cadF, ciaB, and cdtABC genes were detected in all the isolates. A prevalence of 20.1% was obtained for the genes wlaN and cstIII, which are related to the pathogenesis of Guillain-Barré syndrome (GBS). The prevalence of the main antimicrobial resistance markers detected were CmeABC (92.1%), RE-cmeABC (7.9%), the T86I substitution in gyrA (88.9%), blaOXA-61 (72.6%), tet(O) (65.8%), and ant (6)-Ia (17.1%). High antibiogram prediction rates (>97%) were obtained, except for in the case of the erythromycin-resistant phenotype. This study contributes significantly to the knowledge of C. jejuni genomics for the prevention, treatment, and control of infections caused by this pathogen.IMPORTANCEDespite being the pathogen with the greatest number of gastroenteritis cases worldwide, Campylobacter jejuni remains a poorly studied microorganism. A sustained increase in fluoroquinolone resistance in human isolates is a problem when treating Campylobacter infections. The development of whole genome sequencing (WGS) techniques has allowed us to better understand the genotypic characteristics of this pathogen and relate them to antibiotic resistance phenotypes. These techniques complement the data obtained from the phenotypic analysis of C. jejuni isolates. The zoonotic transmission of C. jejuni through the consumption of contaminated poultry supports approaching the study of this pathogen through "One Health" approach. In addition, due to the limited information on the genomic characteristics of C. jejuni in Spain, this study provides important data and allows us to compare the results with those obtained in other countries.

The integrated genomic surveillance system of Andalusia (SIEGA) provides a One Health regional resource connected with the clinic.

The One Health approach, recognizing the interconnectedness of human, animal, and environmental health, has gained significance amid emerging zoonotic diseases and antibiotic resistance concerns. This paper aims to demonstrate the utility of a collaborative tool, the SIEGA, for monitoring infectious diseases across domains, fostering a comprehensive understanding of disease dynamics and risk factors, highlighting the pivotal role of One Health surveillance systems. Raw whole-genome sequencing is processed through different species-specific open software that additionally reports the presence of genes associated to anti-microbial resistances and virulence. The SIEGA application is a Laboratory Information Management System, that allows customizing reports, detect transmission chains, and promptly alert on alarming genetic similarities. The SIEGA initiative has successfully accumulated a comprehensive collection of more than 1900 bacterial genomes, including Salmonella enterica, Listeria monocytogenes, Campylobacter jejuni, Escherichia coli, Yersinia enterocolitica and Legionella pneumophila, showcasing its potential in monitoring pathogen transmission, resistance patterns, and virulence factors. SIEGA enables customizable reports and prompt detection of transmission chains, highlighting its contribution to enhancing vigilance and response capabilities. Here we show the potential of genomics in One Health surveillance when supported by an appropriate bioinformatic tool. By facilitating precise disease control strategies and antimicrobial resistance management, SIEGA enhances global health security and reduces the burden of infectious diseases. The integration of health data from humans, animals, and the environment, coupled with advanced genomics, underscores the importance of a holistic One Health approach in mitigating health threats.

The physiological quality of Vigna unguiculata L. seeds shows tolerance to salinity.

Salinity reduces feijão-caupi production, and the search for tolerant varieties becomes important within the agricultural context, as, in addition to being used in the field, they can be used in genetic improvement. The objective was to for a identify variety that is tolerant to salinity considering the physiological quality of seeds and seedling growth. A 2 × 4 factorial scheme was used, referring to the varieties Pingo-de-ouro and Coruja, and four electrical conductivities of water (0; 3.3; 6.6 and 9.9 dS m-1). The physiological quality of seeds and the growth of seedlings were analyzed, in addition to the cumulative germination. The Pingo-de-ouro variety showed no germination, length of the shoot and root, dry mass of the shoot and root compromised up to electrical conductivity of 6 dS m-1 in relation to 0.0 dS m-1. On the other hand, the Coruja variety showed reduced germination, increased shoot and root length. The creole variety Pingo-de-ouro proved to be tolerant to salinity.

A multicenter, randomized phase 2 study to establish combinations of CBP501, cisplatin and nivolumab for ≥3rd-line treatment of patients with advanced pancreatic adenocarcinoma.

BACKGROUND: There is no standard of care for ≥ 3rd-line treatment of metastatic pancreatic adenocarcinoma (PDAC). CBP501 is a novel calmodulin-binding peptide that has been shown to enhance the influx of platinum agents into tumor cells and tumor immunogenicity. This study aimed to (1) confirm efficacy of CBP501/cisplatin/nivolumab for metastatic PDAC observed in a previous phase 1 study, (2) identify combinations that yield 35% 3-month progression-free survival rate (3MPFS) and (3) define the contribution of CBP501 to the effects of combination therapy. METHODS: CBP501 16 or 25 mg/m2 (CBP(16) or CBP(25)) was combined with 60 mg/m2 cisplatin (CDDP) and 240 mg nivolumab (nivo), administered at 3-week intervals. Patients were randomized 1:1:1:1 to (1) CBP(25)/CDDP/nivo, (2) CBP(16)/CDDP/nivo, (3) CBP(25)/CDDP and (4) CDDP/nivo, with randomization stratified by ECOG PS and liver metastases. A Fleming two-stage design was used, yielding a one-sided type I error rate of 2.5% and 80% power when the true 3MPFS is 35%. RESULTS: Among 36 patients, 3MPFS was 44.4% in arms 1 and 2, 11.1% in arm 3% and 33.3% in arm 4. Two patients achieved a partial response in arm 1 (ORR 22.2%; none in other arms). Median PFS and OS were 2.4, 2.1, 1.5 and 1.5 months and 6.3, 5.3, 3.7 and 4.9 months, respectively. Overall, all treatment combinations were well tolerated. Most treatment-related adverse events were grade 1-2. CONCLUSIONS: The combination CBP(25)/(16)/CDDP/nivo demonstrated promising signs of efficacy and a manageable safety profile for the treatment of advanced PDAC. CLINICAL TRIAL REGISTRATION: NCT04953962.

Resistance determinants of emerging pathogens isolated from an intensive care unit as a parameter of population health conditions of the Legal Amazon microregion.

Bacteria responsible for causing infections are common in hospital environments, water, soil, and food products. The infection risk is intensified by the absence of public sanitation, poor quality of life, and food scarcity. These external factors promote the dissemination of pathogens by direct contamination or biofilm formation. In this work, we identified bacterial isolates obtained from intensive care units in the southern region of Tocantins, Brazil. We compared matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) techniques and 16S ribosomal ribonucleic acid (rRNA) molecular analysis; we also performed phenotypic characterization. Fifty-six isolates characterized using morphotinctorial tests were classified as gram-positive (80.4%; n = 45) and gram-negative (19.6%; n = 11) and were resistant to several antibiotic classes; notably, we identified the blaOXA-23 resistance gene in the ILH10 isolate. Microbial identification using MALDI-TOF MS resulted in the identification of Sphingomonas paucimobilis and Bacillus circulans. 16S rRNA sequencing revealed four isolates belonging to the genera Bacillus and Acinetobacter. The similarity was superior to 99% for Acinetobacter schindleri in the Basic Local Alignment Search Tool (BLAST), grouped in the clade superior to 90%. Several strains isolated from intensive care units (ICU) were resistant to various antibiotic classes. These techniques allowed for the identification of several microorganisms of importance in public health, enabling improvements in human infection control and proving the quality of inputs, food, and water.

Listeriosis outbreak caused by contaminated stuffed pork, Andalusia, Spain, July to October 2019.

Between 1 July and 26 October 2019 in Andalusia, Spain, a large outbreak with 207 confirmed cases of listeriosis was identified. Confirmed cases had a median age of 44 years (range: 0-94) and 114 were women (55.1%). Most cases (n = 154) had mild gastroenteritis, 141 (68.1%) required hospitalisation and three died; five of 34 pregnant women had a miscarriage. The median incubation period was 1 day (range: 0-30), and was significantly shorter in cases presenting with gastroenteritis compared to those presenting without gastroenteritis (1 day vs. 3 days, respectively, p value < 0.001). Stuffed pork, a ready-to-eat product consumed unheated, from a single producer contaminated with Listeria monocytogenes ST388 was identified as the source of infection. The outbreak strain was identified in 189 human samples and 87 non-human (82 food and 5 environmental) samples. Notification of new cases declined abruptly after control measures were implemented. These included contaminated food recall, protocols for clinical management of suspected cases and for post-exposure prophylaxis in pregnant women and communication campaigns with concise messages to the population through social media. Given that there were 3,059 probable cases, this was the largest L. monocytogenes outbreak ever reported in Europe.

[Mirror writing in epilepsy]. / Escritura en espejo en epilepsia.

TITLE: Escritura en espejo en epilepsia.

Circulating microRNAs as potential biomarkers for genetic generalized epilepsies: a three microRNA panel.

BACKGROUND AND PURPOSE: Genetic generalized epilepsies (GGEs) encompass a group of syndromes of mainly genetic causes, characterized by the involvement of both hemispheres. MicroRNAs (miRNAs) are small non-coding RNAs with a critical role in the regulation of neuronal biological processes through gene expression modulation. Dysregulated miRNA expression has been shown in epilepsy. Due to their stability in biological fluids like serum, miRNAs have assumed a prominent role in biomarker research. Our aim was to evaluate circulating levels of three miRNAs in GGE patients and assess their putative diagnostic value. METHODS: MiR-146a, miR-155 and miR-132 were quantified by real-time polymerase chain reaction in the serum of 79 GGE patients (47 women, 32 men, 35.1 ± 12.4 years) and 67 healthy individuals (41 women, 26 men, 42.4 ± 10.1 years). Relative expression values were calculated using the 2-ΔΔCt method. Receiver operating characteristic curve analysis was performed to assess diagnostic value. MiRNA expression was correlated with clinicopathological features. RESULTS: Serum levels of miR-146a and miR-155 were significantly upregulated in GGE patients relative to controls (3.13 and 6.05, respectively). Combined miR-146a, miR-155 and miR-132 serum levels performed well as a diagnostic biomarker, discriminating GGE patients from controls with an area under the curve of 0.85, 80% specificity and 73% sensitivity. CONCLUSIONS: Our results indicate that miR-146a, miR-155 and miR-132 may partake in GGE epileptogenesis. A panel of three circulating miRNAs with potential value as a GGE biomarker is reported for the first time. Novel biomarkers may help to identify new treatment targets and contribute to improved patients' quality of life through earlier diagnosis and a more precise prognosis.

First Measurement of the Total Neutron Cross Section on Argon between 100 and 800 MeV.

We report the first measurement of the neutron cross section on argon in the energy range of 100-800 MeV. The measurement was obtained with a 4.3-h exposure of the Mini-CAPTAIN detector to the WNR/LANSCE beam at LANL. The total cross section is measured from the attenuation coefficient of the neutron flux as it traverses the liquid argon volume. A set of 2631 candidate interactions is divided in bins of the neutron kinetic energy calculated from time-of-flight measurements. These interactions are reconstructed with custom-made algorithms specifically designed for the data in a time projection chamber the size of the Mini-CAPTAIN detector. The energy averaged cross section is 0.91±0.10(stat)±0.09(syst) b. A comparison of the measured cross section is made to the GEANT4 and FLUKA event generator packages, where the energy averaged cross sections in this range are 0.60 and 0.68 b, respectively.

Magnetoliposomes as model for signal transmission.

Liposomes containing magnetic nanoparticles (magnetoliposomes) have been extensively explored for targeted drug delivery. However, the magnetic effect of nanoparticles movement is also an attractive choice for the conduction of signals in communication systems at the nanoscale level because of the simple manipulation and efficient control. Here, we propose a model for the transmission of electrical and luminous signals taking advantage of magnetophoresis. The study involved three steps. Firstly, magnetite was synthesized and incorporated into fusogenic large unilamellar vesicles (LUVs) previously associated with a fluorescent label. Secondly, the fluorescent magnetite-containing LUVs delivered their contents to the giant unilamellar vesicles (GUVs), which were corroborated by magnetophoresis and fluorescence microscopy. In the third step, magnetophoresis of magnetic vesicles was used for the conduction of the luminous signal from a capillary to an optical fibre connected to a fluorescence detector. Also, the magnetophoresis effects on subsequent transmission of the electrochemical signal were demonstrated using magnetite associated with CTAB micelles modified with ferrocene. We glimpse that these magnetic supramolecular systems can be applied in micro- and nanoscale communication systems.

Profiling of patients with non-valvular atrial fibrillation and moderate-to-high risk of stroke not receiving oral anticoagulation in Spain.

OBJECTIVE: In non-valvular atrial fibrillation (NVAF) with embolic risk, the guidelines recommend oral anticoagulation (OAC), although not all patients receive it. In this study, an attempt is made to identify these patients, and to study factors related to non-anticoagulation. MATERIAL AND METHODS: Non-interventional, cross-sectional, multicentre study was performed on a population of patients ≥18 years with a NVAF diagnosis, moderate-high embolic risk (CHADS2 score≥2), not treated with OAC. Atrial fibrillation (AF) prevalence was also collected. RESULTS: AF prevalence was 4.5%, and 80.7% of the patients had NVAF (20.0% did not receive OAC). A total of 1310 non-OAC-treated patients were included (51.8% male, mean age: 76.0 years). The mean time since AF diagnosis was 58.4 months. The main therapeutic decision for stroke prevention was prescription of antiplatelet agents (82.4%, n=1078), and the main reasons were: patient refusal to monitoring (37.3%), high bleeding risk (31.1%), uncontrolled hypertension (27.9%), and frequent falls (27.6%). The mean CHA2DS2-VASc score was 4.6, and the HAS-BLED was 2.7 (55.9% of patients scoring HAS-BLED≥3). The most common thromboembolic risk factors were: hypertension (89.1%), age≥75 years (61.5%); the haemorrhagic factors: use of drugs increasing the bleeding risk (41.2%), uncontrolled blood pressure (33.7%). CONCLUSIONS: About 20% of Spanish NVAF patients do not receive OAC in the clinical practice and are treated with antiplatelet agents, which do not reduce haemorrhagic risk. Most patients do not clearly show a contraindication to OACs, particularly considering that there are other available options (direct oral anticoagulant drugs [DOACs]).

Deadbeat-fuzzy controller for the power control of a Doubly Fed Induction Generator based wind power system.

This paper proposes a Fuzzy Logic Controller for improvement of the steady-state response of a Doubly Fed Induction Generator used in a wind energy system, and governed by means of a Deadbeat Power Controller. The generator mathematical model is consistent with the Stator Flux oriented strategy in the synchronous reference frame. Different simulation scenarios were developed in Matlab/Simulink to evaluate the dynamic and the steady-state responses. In order to obtain experimental results, the simulated scenarios were repeated by means of a test bench and a Digital Signal Processor board. These results demonstrate that the response still follows the power references imposed, despite the fact that the generator parameters ( Rr, Ls and Lm) were varied in a 30%. A lower steady-state error is also achieved when compared with a Deadbeat and a classical PI controller. All the aforementioned evidence the proper application of this Fuzzy Controller in a wind power system based on a Doubly Fed Induction Generator.

Measurement of Final-State Correlations in Neutrino Muon-Proton Mesonless Production on Hydrocarbon at ⟨E_{ν}⟩=3 GeV.

Final-state kinematic imbalances are measured in mesonless production of ν_{µ}+A→µ^{-}+p+X in the MINERvA tracker. Initial- and final-state nuclear effects are probed using the direction of the µ^{-}-p transverse momentum imbalance and the initial-state momentum of the struck neutron. Differential cross sections are compared to predictions based on current approaches to medium modeling. These models underpredict the cross section at intermediate intranuclear momentum transfers that generally exceed the Fermi momenta. As neutrino interaction models need to correctly incorporate the effect of the nucleus in order to predict neutrino energy resolution in oscillation experiments, this result points to a region of phase space where additional cross section strength is needed in current models, and demonstrates a new technique that would be suitable for use in fine-grained liquid argon detectors where the effect of the nucleus may be even larger.

The clinical outcome of skeletal anchorage in interceptive treatment (in growing patients) for class III malocclusion.

A systematic review of the literature was performed regarding the clinical outcome (effectiveness) of bone anchorage devices in interceptive treatment for class III malocclusion. A search of Embase, PubMed and Web of Science databases yielded 285 papers. An additional two articles were retrieved through manual searching of the reference lists. After initial abstract selection, 32 potentially eligible articles were screened in detail, resulting in a final number of eight articles included in this review. Insufficient evidence was found regarding the effects of skeletal anchorage in interceptive class III treatment to support definitive conclusions on long-term skeletal effects and stability. In the short term, it seems that bone anchors can provide more skeletal effect with less dentoalveolar compensations and less unwanted vertical changes. This does not always exclude the use of a face mask. The use of miniscrews as skeletal anchorage device does not seem to provide more skeletal effect, although it could minimize the unwanted dental effects in the upper jaw. No information regarding the need for orthognathic surgery, orthodontic treatment time or patient compliance and complications was found in the selected articles.

Post-translationally modified human lens crystallin fragments show aggregation in vitro.

BACKGROUND: Crystallin fragments are known to aggregate and cross-link that lead to cataract development. This study has been focused on determination of post-translational modifications (PTMs) of human lens crystallin fragments, and their aggregation properties. METHODS: Four crystallin fragments-containing fractions (Fraction I [∼3.5 kDa species], Fraction II [∼3.5-7 kDa species], Fraction III [∼7-10 kDa species] and Fraction IV [>10-18 kDa species]), and water soluble high molecular weight (WS-HMW) protein fraction were isolated from water soluble (WS) protein fraction of human lenses of 50-70 year old-donors. The crystallin fragments of the Fractions I-IV were separated by two-dimensional (2D)-gel electrophoresis followed by analysis of their gel-spots by mass spectrometry. The Fractions I-IV were examined for their molecular mass, particle-diameters, amyloid fibril formation, and for their aggregation by themselves and with WS-HMW proteins. RESULTS: Crystallin fragments in Fractions I-IV were derived from α-, ß- and γ-crystallins, and their 2D-gel separated spots contained multiple crystallins with PTMs such as oxidation, deamidation, methylation and acetylation. Crystallin fragments from all the four fractions exhibited self-aggregated complexes ranging in Mr from 5.5×105 to 1.0×108 Da, with diameters of 10-28 nm, and amyloid fibril-like formation, and aggregation with WS-HMW proteins. CONCLUSION: The crystallin fragments exhibited several PTMs, and were capable of forming aggregated species by themselves and with WS-HMW proteins, suggesting their potential role in aggregation process during cataract development. GENERAL SIGNIFICANCE: Crystallin fragments play a major role in human cataract development.

Eslicarbazepine acetate as adjunctive therapy in clinical practice: ESLADOBA study.

OBJECTIVE: To assess seizure control and tolerability of eslicarbazepine acetate (ESL) as adjunctive therapy to one baseline antiepileptic drug (AED), in adults with partial-onset seizures (POS) with or without secondary generalization. METHODS: Multicenter, non-interventional, prospective cohort study conducted between March 2012 and September 2014 at 12 neurology departments in Portugal. Adults with POS not controlled with one AED who had initiated ESL as adjunctive treatment were enrolled. Retention rate was defined at the final visit (Vfinal) 6-9 months of follow-up. Proportion of responders, seizure-free, changes in seizure frequency were evaluated using patients' diaries. Clinical Global Impression of Change (CGI-C) and Clinical Global Impression of Severity (CGI-S) were assessed by the neurologist. RESULTS: Fifty-two patients (48.1% male) were included with mean age 41.5±13.3 years. Mean epilepsy duration was 18.5±14.8 years; mean seizure frequency in the four previous weeks to baseline was 7.5±12.7. At Vfinal, retention rate was 73.0%; responder rate and seizure-free rates were 71.1% and 39.5%, respectively. The median relative reduction in seizure frequency between baseline and Vfinal was 82.2%. A reduction in epilepsy severity (CGI-S) was observed in 42.1%. According to CGI-C, 73.6% patients had their epilepsy "much improved" or "very much improved". Twelve patients (23.1%) had at least one adverse event (AE), two (3.9%) had one serious AE, and five (9.6%) discontinued due to AE. CONCLUSIONS: Eslicarbazepine acetate showed good retention rates, elicited a significant reduction in seizure frequency, and was well tolerated when used in the clinical practice.

Period of Hyperbaric Oxygen Delivery Leads to Different Degrees of Hepatic Ischemia/Reperfusion Injury in Rats.

BACKGROUND: This study evaluated the morphology of the rat liver when hyperbaric oxygen (HBO) was used at various stages of ischemia and reperfusion. METHODS: Thirty-two male Wistar rats, subjected to 30 minutes of hepatic ischemia and 30 minutes of reperfusion, were randomly assigned as follows: GIR (n = 8), control without HBO; GHBO/I (n = 8), in which HBO was applied only during ischemia; GHBO/R (n = 8), HBO only during reperfusion; and GHBO/IR (n = 8), HBO during both ischemia and reperfusion. Feasibility scores of hepatocytes were determined by assessing 8 items related to liver injury. RESULTS: The histologic injury score of the hepatic specimens was significantly lower in the GHBO/I group (79.0 ± 0.1) compared with the GIR group (135.0 ± 0.1). HBO was not effective when applied during reperfusion (GHBO/R, 151.3 ± 0.1) or during the ischemia plus reperfusion period (GHBO/IR, 131.0 ± 0.1). The sum was significantly higher (P < .05) in HBO-treated animals during the reperfusion period (ie, in the GHBO/R group compared with any of the other groups). CONCLUSIONS: A favorable effect was obtained when HBO was administered early during ischemia. HBO given in later periods of reperfusion was associated with a more severe sum index percentage of liver damage.

Compact étendue-preserving light-mixing optics.

We present a compact freeform optic, called "Freeform Shell-Mixer", which, when placed on top of a multicolor light source (particularly, a multi-chip LED), turns it into a virtual source in which colors are uniformly mixed. The optic, compatible with injection molding, makes use of étendue-conserving Köhler integration to provide homogeneous mixing of light. Its minimal size (just 2x larger than the source) makes the concept compatible with many luminaries, as ray tracing models show. Simulations indicate that the Freeform Shell-Mixer can reach efficiencies above 95% and both the size of the virtual source and its emission pattern are very similar to the ones of the original source, so the correct performance of the luminaire is secured.

Comparison of findings using ultrasonography and cystoscopy in urogenital schistosomiasis in a public health centre in rural Angola.

BACKGROUND: Schistosomiasis is a chronic disease caused by infection with parasitic worms of the genus Schistosoma. In sub-Saharan Africa, infections with S. haematobium are most common. Cystoscopic examination (CE) has been accepted as the goldstandard test for detecting the late manifestations of schistosomiasis, including urothelial cancer of the bladder. However, this procedure is invasive and 10-40% of tumours may remain undetected. A non-invasive examination and a new generation of biomarkers are needed for better monitoring of the disease. OBJECTIVE: To assess the usefulness of ultrasound (US) scans for monitoring of structural urinary tract disease by local public health services in areas of Angola in which urogenital schistosomiasis is endemic. METHODS: A cohort of 80 S. haematobium-infected patients was selected in order to compare changes in the bladder wall detected by US with those observed on CE. RESULTS: There was a notable correlation between the findings observed on CE and US. Patients with lesions of the bladder mucosa such as neoplasms, ulcers or granulomas detected by CE also had changes in bladder wall thickness on US. The results support increased use of portable US machines for non-invasive examination of the bladder by local general practitioners. CONCLUSION: US examination should be an integral part of the investigation of haematuria and used in all S. haematobium control programmes. General practitioners may find it useful for more accurate diagnosis of haematuria and to identify bladder wall alterations in both adults and children in schistosomiasis-endemic regions.