Microscopic fractional anisotropy outperforms multiple sclerosis lesion assessment and clinical outcome associations over standard fractional anisotropy tensor.

We aimed to compare the ability of diffusion tensor imaging and multi-compartment spherical mean technique to detect focal tissue damage and in distinguishing between different connectivity patterns associated with varying clinical outcomes in multiple sclerosis (MS). Seventy-six people diagnosed with MS were scanned using a SIEMENS Prisma Fit 3T magnetic resonance imaging (MRI), employing both conventional (T1w and fluid-attenuated inversion recovery) and advanced diffusion MRI sequences from which fractional anisotropy (FA) and microscopic FA (µFA) maps were generated. Using automated fiber quantification (AFQ), we assessed diffusion profiles across multiple white matter (WM) pathways to measure the sensitivity of anisotropy diffusion metrics in detecting localized tissue damage. In parallel, we analyzed structural brain connectivity in a specific patient cohort to fully grasp its relationships with cognitive and physical clinical outcomes. This evaluation comprehensively considered different patient categories, including cognitively preserved (CP), mild cognitive deficits (MCD), and cognitively impaired (CI) for cognitive assessment, as well as groups distinguished by physical impact: those with mild disability (Expanded Disability Status Scale [EDSS] <=3) and those with moderate-severe disability (EDSS >3). In our initial objective, we employed Ridge regression to forecast the presence of focal MS lesions, comparing the performance of µFA and FA. µFA exhibited a stronger association with tissue damage and a higher predictive precision for focal MS lesions across the tracts, achieving an R-squared value of .57, significantly outperforming the R-squared value of .24 for FA (p-value <.001). In structural connectivity, µFA exhibited more pronounced differences than FA in response to alteration in both cognitive and physical clinical scores in terms of effect size and number of connections. Regarding cognitive groups, FA differences between CP and MCD groups were limited to 0.5% of connections, mainly around the thalamus, while µFA revealed changes in 2.5% of connections. In the CP and CI group comparison, which have noticeable cognitive differences, the disparity was 5.6% for FA values and 32.5% for µFA. Similarly, µFA outperformed FA in detecting WM changes between the MCD and CI groups, with 5% versus 0.3% of connections, respectively. When analyzing structural connectivity between physical disability groups, µFA still demonstrated superior performance over FA, disclosing a 2.1% difference in connectivity between regions closely associated with physical disability in MS. In contrast, FA spotted a few regions, comprising only 0.6% of total connections. In summary, µFA emerged as a more effective tool than FA in predicting MS lesions and identifying structural changes across patients with different degrees of cognitive and global disability, offering deeper insights into the complexities of MS-related impairments.

Synergistic Effect of SOS Response and GATC Methylome Suppression on Antibiotic Stress Survival in Escherichia coli.

The suppression of the SOS response has been shown to enhance the in vitro activity of quinolones. Furthermore, Dam-dependent base methylation has an impact on susceptibility to other antimicrobials affecting DNA synthesis. Here, we investigated the interplay between these two processes, alone and in combination, in terms of antimicrobial activity. A genetic strategy was used employing single- and double-gene mutants for the SOS response (recA gene) and the Dam methylation system (dam gene) in isogenic models of Escherichia coli both susceptible and resistant to quinolones. Regarding the bacteriostatic activity of quinolones, a synergistic sensitization effect was observed when the Dam methylation system and the recA gene were suppressed. In terms of growth, after 24 h in the presence of quinolones, the Δdam ΔrecA double mutant showed no growth or delayed growth compared to the control strain. In bactericidal terms, spot tests showed that the Δdam ΔrecA double mutant was more sensitive than the ΔrecA single mutant (about 10- to 102-fold) and the wild type (about 103- to 104-fold) in both susceptible and resistant genetic backgrounds. Differences between the wild type and the Δdam ΔrecA double mutant were confirmed by time-kill assays. The suppression of both systems, in a strain with chromosomal mechanisms of quinolone resistance, prevents the evolution of resistance. This genetic and microbiological approach demonstrated the enhanced sensitization of E. coli to quinolones by dual targeting of the recA (SOS response) and Dam methylation system genes, even in a resistant strain model.

Midbrain and pons MRI shape analysis and its clinical and CSF correlates in degenerative parkinsonisms: a pilot study.

OBJECTIVES: To conduct brainstem MRI shape analysis across neurodegenerative parkinsonisms and control subjects (CS), along with its association with clinical and cerebrospinal fluid (CSF) correlates. METHODOLOGY: We collected demographic and clinical variables, performed planimetric and shape MRI analyses, and determined CSF neurofilament-light chain (NfL) levels in 84 participants: 11 CS, 12 with Parkinson's disease (PD), 26 with multiple system atrophy (MSA), 21 with progressive supranuclear palsy (PSP), and 14 with corticobasal degeneration (CBD). RESULTS: MSA featured the most extensive and significant brainstem shape narrowing (that is, atrophy), mostly in the pons. CBD presented local atrophy in several small areas in the pons and midbrain compared to PD and CS. PSP presented local atrophy in small areas in the posterior and upper midbrain as well as the rostral pons compared to MSA. Our findings of planimetric MRI measurements and CSF NfL levels replicated those from previous literature. Brainstem shape atrophy correlated with worse motor state in all parkinsonisms and with higher NfL levels in MSA, PSP, and PD. CONCLUSION: Atypical parkinsonisms present different brainstem shape patterns which correlate with clinical severity and neuronal degeneration. In MSA, shape analysis could be further explored as a potential diagnostic biomarker. By contrast, shape analysis appears to have a rather limited discriminant value in PSP. KEY POINTS: • Atypical parkinsonisms present different brainstem shape patterns. • Shape patterns correlate with clinical severity and neuronal degeneration. • In MSA, shape analysis could be further explored as a potential diagnostic biomarker.

Integrated full-scale solar CPC/UV-LED-filtration system as a tertiary treatment in a conventional WWTP for agricultural reuse purposes.

Today, the emergence of increasingly restrictive treatment and reuse policies make the implementation of full-scale tertiary treatment, capable of improving the quality of water, a priority. Full-scale TiO2 photocatalysis systems are resulting in a promising option, since TiO2 is commercially available. However, questions such as how to work continuously during day/night irradiation cycle, or the removing of TiO2 in outlet flow are still unresolved. In this work, a full-scale system integrating a solar CPC/UV-LED step combined with commercial microfiltration membranes was installed in a conventional WWTP for agricultural reuse purposes. After optimization, 0.5 g/L of catalyst and combined SOLAR + UV-LED showing the highest pharmaceutical removal percentages, while a self-designed UV-LED included in the own reaction tank resulting in higher efficiencies compared with commercial lamps. Longer membrane surface area decreased fouling problems in the system. However, 60 min of irradiation time was necessary to reach the most restrictive water quality values according with (EU 2020/741). After optimization step, total costs were reduced by 45%. However, it was shown that a reduction in operating and maintenance costs, along with the development of more effective and economical commercial filtration membranes is a key factor; therefore, working on these aspects is essential in the treated water cost reduction.

Effect of RecA inactivation and detoxification systems on the evolution of ciprofloxacin resistance in Escherichia coli.

BACKGROUND: Suppression of SOS response and overproduction of reactive oxygen species (ROS) through detoxification system suppression enhance the activity of fluoroquinolones. OBJECTIVES: To evaluate the role of both systems in the evolution of resistance to ciprofloxacin in an isogenic model of Escherichia coli. METHODS: Single-gene deletion mutants of E. coli BW25113 (wild-type) (ΔrecA, ΔkatG, ΔkatE, ΔsodA, ΔsodB), double-gene (ΔrecA-ΔkatG, ΔrecA-ΔkatE, ΔrecA-ΔsodA, ΔrecA-ΔsodB, ΔkatG-ΔkatE, ΔsodB-ΔsodA) and triple-gene (ΔrecA-ΔkatG-ΔkatE) mutants were included. The response to sudden high ciprofloxacin pressure was evaluated by mutant prevention concentration (MPC). The gradual antimicrobial pressure response was evaluated through experimental evolution and antibiotic resistance assays. RESULTS: For E. coli BW25113 strain, ΔkatE, ΔsodB and ΔsodB/ΔsodA mutants, MPC values were 0.25 mg/L. The ΔkatG, ΔsodA, ΔkatG/katE and ΔrecA mutants showed 2-fold reductions (0.125 mg/L). The ΔkatG/ΔrecA, ΔkatE/ΔrecA, ΔsodA/ΔrecA, ΔsodB/ΔrecA and ΔkatG/ΔkatE/ΔrecA strains showed 4-8-fold reductions (0.03-0.06 mg/L) relative to the wild-type. Gradual antimicrobial pressure increased growth capacity for ΔsodA and ΔsodB and ΔsodB/ΔsodA mutants (no growth in 4 mg/L) compared with the wild-type (no growth in the range of 0.5-2 mg/L). Accordingly, increased growth was observed with the mutants ΔrecA/ΔkatG (no growth in 2 mg/L), ΔrecA/ΔkatE (no growth in 2 mg/L), ΔrecA/ΔsodA (no growth in 0.06 mg/L), ΔrecA/ΔsodB (no growth in 0.25 mg/L) and ΔrecA/ΔkatG/ΔkatE (no growth in 0.5 mg/L) compared with ΔrecA (no growth in the range of 0.002-0.015 mg/L). CONCLUSIONS: After RecA inactivation, gradual exposure to ciprofloxacin reduces the evolution of resistance. After suppression of RecA and detoxification systems, sudden high exposure to ciprofloxacin reduces the evolution of resistance in E. coli.

Does exposure to greenness improve children's neuropsychological development and mental health? A Navigation Guide systematic review of observational evidence for associations.

BACKGROUND: Contact with nature may have a key role in child brain development. Recent observational studies have reported improvements in children's neuropsychological development and mental health associated with greenness exposure. In a rapidly urbanizing word, researchers, policymakers, healthcare workers and urban planners need to work together to elaborate evidence-based policies and interventions to increase the availability of quality green space with the potential to enhance childhood development. OBJECTIVE: To review the observational evidence assessing the effect of exposure to greenness on children's neuropsychological development and mental health. METHODS: The protocol for the review was preregistered at PROSPERO (CRD42020213838). The Navigation Guide systematic review methodology was followed. Search strategies were formulated and adapted to each database. Searches were performed in PubMed, Scopus, Web of Science and EBSCO's GreenFILE on October 5, 2021. Additional articles were further identified by hand-searching reference lists of included papers. RESULTS: A systematic search of 4 databases identified 621 studies, of which 34 were included in the review. The studies included investigated diverse domains within neuropsychological development and mental health, such as attention, working memory, intelligence, cognitive development, academic performance, well-being, attention-deficit/hyperactivity disorder symptoms, and behavior. Most of the studies were rated as having high or probably high risk of bias in the assessment. DISCUSSION: Although nearly all studies showed a positive association between greenness exposure and the outcomes studied, the heterogeneity in the methods used to assess exposure and the diversity of domains within each main outcome has made it difficult to draw clear conclusions. Future studies should adopt a longitudinal design to confirm the causality of the associations and include measures to determine which characteristics of greenness have the greatest influence on each domain. Researchers should also try to explore pathways linking exposure to greenness with the neuropsychological development and mental health, by implementing mechanistic studies.

Folic acid enhances proinflammatory and antiviral molecular pathways in chicken B-lymphocytes infected with a mild infectious bursal disease virus.

1. This study evaluated the effect of folic acid (FA) supplementation on the proinflammatory and antiviral molecular pathways of B-lymphocytes infected with a modified live IBDV (ST-12) mild vaccine strain during a timed post-infection analysis.2. A chicken B-lymphocytes (DT-40) cell line was cultured in triplicate at a concentration of 5 × 105 cells per well in 24-well plates; and was divided into three groups: 1: No virus, FA; 2: Virus, no FA; 3: Virus + FA at a concentration of 3.96 mM. The experiment was repeated three times.3. Cells in groups 2 and 3 were infected with a modified live IBDV (ST-12) mild vaccine strain at one multiplicity of infection (MOI: 1). After 1 hour of virus adsorption, samples were collected at 0, 3, 6, 12, 24 and 36 hours post-infection (hpi).4. The modified live IBDV (ST-12) mild vaccine strain triggered a B-lymphocyte specific immune response associated with the upregulation of genes involved in virus recognition (Igß), virus sensing (TLR-2, TLR-3, TLR-4 and MDA5), signal transduction and regulation (TRIF, MyD88 and IRF7), and the antiviral effector molecules (IFN-α, OAS, PKR, and viperin).5. FA supplementation modulated IBDV replication and regulated the proinflammatory and antiviral downstream molecular pathways.6. In conclusion, the low virulent pathotype serotype I modified live IBDV (ST-12) mild vaccine strain was able to trigger and mount an immune response in chicken B-lymphocytes without affecting B-cell viability. FA supplementation modulated B lymphocytes response and improved their innate immune proinflammatory and antiviral response molecular pathways.

Synergistic Quinolone Sensitization by Targeting the recA SOS Response Gene and Oxidative Stress.

Suppression of the recA SOS response gene and reactive oxygen species (ROS) overproduction have been shown, separately, to enhance fluoroquinolone activity and lethality. Their putative synergistic impact as a strategy to potentiate the efficacy of bactericidal antimicrobial agents such as fluoroquinolones is unknown. We generated Escherichia coli mutants that exhibited a suppressed ΔrecA gene in combination with inactivated ROS detoxification system genes (ΔsodA, ΔsodB, ΔkatG, ΔkatE, and ΔahpC) or inactivated oxidative stress regulator genes (ΔoxyR and ΔrpoS) to evaluate the interplay of both DNA repair and detoxification systems in drug response. Synergistic sensitization effects, ranging from 7.5- to 30-fold relative to the wild type, were observed with ciprofloxacin in double knockouts of recA and inactivated detoxification system genes. Compared to recA knockout, inactivation of an additional detoxification system gene reduced MIC values up to 8-fold. In growth curves, no growth was evident in mutants doubly deficient for recA gene and oxidative detoxification systems at subinhibitory concentrations of ciprofloxacin, in contrast to the recA-deficient strain. There was a marked reduction of viable bacteria in a short period of time when the recA gene and other detoxification system genes (katG, sodA, or ahpC) were inactivated (using absolute ciprofloxacin concentrations). At 4 h, a bactericidal effect of ciprofloxacin was observed for ΔkatG ΔrecA and ΔahpC ΔrecA double mutants compared to the single ΔrecA mutant (Δ3.4 log10 CFU/ml). Synergistic quinolone sensitization, by targeting the recA gene and oxidative detoxification stress systems, reinforces the role of both DNA repair systems and ROS in antibiotic-induced bacterial cell death, opening up a new pathway for antimicrobial sensitization.

Effect of RecA inactivation on quinolone susceptibility and the evolution of resistance in clinical isolates of Escherichia coli.

BACKGROUND: SOS response suppression (by RecA inactivation) has been postulated as a therapeutic strategy for potentiating antimicrobials against Enterobacterales. OBJECTIVES: To evaluate the impact of RecA inactivation on the reversion and evolution of quinolone resistance using a collection of Escherichia coli clinical isolates. METHODS: Twenty-three E. coli clinical isolates, including isolates belonging to the high-risk clone ST131, were included. SOS response was suppressed by recA inactivation. Susceptibility to fluoroquinolones was determined by broth microdilution, growth curves and killing curves. Evolution of quinolone resistance was evaluated by mutant frequency and mutant prevention concentration (MPC). RESULTS: RecA inactivation resulted in 2-16-fold reductions in fluoroquinolone MICs and modified EUCAST clinical category for several isolates, including ST131 clone isolates. Growth curves and time-kill curves showed a clear disadvantage (up to 10 log10 cfu/mL after 24 h) for survival in strains with an inactivated SOS system. For recA-deficient mutants, MPC values decreased 4-8-fold, with values below the maximum serum concentration of ciprofloxacin. RecA inactivation led to a decrease in mutant frequency (≥103-fold) compared with isolates with unmodified SOS responses at ciprofloxacin concentrations of 4×MIC and 1 mg/L. These effects were also observed in ST131 clone isolates. CONCLUSIONS: While RecA inactivation does not reverse existing resistance, it is a promising strategy for increasing the effectiveness of fluoroquinolones against susceptible clinical isolates, including high-risk clone isolates.

Autosomal Recessive Cerebellar Ataxia 1: First Case Report Depicting a Variant in SYNE1 Gene in a Chilean Patient.

Autosomal recessive cerebellar ataxia type 1 (ARCA-1) or spinocerebellar ataxia autosomal recessive type 8 (SCAR8) is a slowly progressive neurodegenerative disorder that occurs due to mutations in the spectrin repeat containing nuclear envelope protein 1 (SYNE1) gene. Previously considered a rare cause of ARCA, related to French-Canadian patients from Beauce, Quebec, Canada, SYNE1 ataxia is now known to be of worldwide distribution. We present the case report of a 54-year-old male patient with the genetic diagnosis of SYNE1 ataxia, presenting with a SYNE1 gene mutation never described in Chilean population before.

Antimicrobial peptides as an alternative to relieve antimicrobial growth promoters in poultry.

1. This review describes different classes of antimicrobial peptides (AMP) found in the gastrointestinal (GI) tract of avian species, and their antimicrobial and immunomodulatory activities. The potential benefits of synthetic AMP in poultry production are examined, in the context of the use of AMP as alternatives to antimicrobial growth promoters (AGP).2. Since the mid-1950s, antibiotic growth promoters (AGP) have been used in feed at low prophylactic doses to modulate the homoeostasis of intestinal microbiota, decreasing the risk of intestinal dysbacteriosis and the growth of pathogens within the avian gut. Over the last three decades, AGP have faced major regulatory restrictions due to concerns of generating antimicrobial resistance (AMR). It is now well documented that the rate of infectious disease outbreaks is higher in flocks that are not fed prophylactic antibiotics, resulting in a compensatory increase in antimicrobial use for therapeutic purposes.3. Endogenous natural AMP production is associated with the presence of microbiota and their interaction with the intestinal epithelial and lamina propria lymphoid cells. Their antimicrobial activity shapes the beneficial microbiota population and controls intestinal pathogens such Clostridium and Salmonella spp., and stimulates the development and maturation of the local immune system.4. Similar to AGP, AMP can establish a well-balanced gut beneficial microbiota for adequate immune-competence, animal health and high growth performance parameters such as feed intake, daily weight, feed conversion and accumulated mortality.5. Antimicrobial proteins and peptides constitute an essential part of the innate immune system of all organisms and protect the host from invading pathogenic bacteria, viruses, fungi, and parasites by interacting with the negatively charged pathogen membranes.

Role of low-level quinolone resistance in generating tolerance in Escherichia coli under therapeutic concentrations of ciprofloxacin.

BACKGROUND: Tolerance (including persistence) and resistance result in increased survival under antibiotic pressure. OBJECTIVES: We evaluated the interplay between resistance and tolerance to ciprofloxacin under therapeutic and killing conditions to determine the contribution of low-level quinolone resistance (LLQR) mechanisms to tolerance. We also determined how the interaction between resistance (LLQR phenotypes) and tolerance was modified under SOS response suppression. METHODS: Twelve isogenic Escherichia coli strains harbouring quinolone resistance mechanisms combined with SOS response deficiency and six clinical E. coli isolates (LLQR or non-LLQR) were evaluated. Survival (tolerance or persistence) assays were used to measure surviving bacteria after a short period (up to 4 h) of bactericidal antibiotic treatment under therapeutic and killing concentrations of ciprofloxacin [1 mg/L, EUCAST/CLSI breakpoint for resistance; and 2.5 mg/L, peak serum concentration (Cmax) of this drug]. RESULTS: QRDR substitutions (S83L in GyrA alone or combined with S80R in ParC) significantly increased the fraction of tolerant bacteria (2-4 log10 cfu/mL) after exposure to ciprofloxacin at clinically relevant concentrations. The impact on tolerant bacteria due to SOS response suppression (including persistence mediated by the tisB gene) was reversed by LLQR mechanisms at therapeutic concentrations. Furthermore, no reduction in the fraction of tolerant bacteria due to SOS response suppression was observed when S83L in GyrA plus S80R in ParC were combined. CONCLUSIONS: Tolerance and quinolone resistance mutations interact synergistically, giving LLQR mechanisms an additional role in allowing bacterial survival and evasion of therapeutic antimicrobial conditions by a combination of the two strategies. At clinically relevant concentrations, LLQR mechanisms reverse further impact of SOS response suppression in reducing bacterial tolerance.

A Be-type star with a black-hole companion.

Stellar-mass black holes have all been discovered through X-ray emission, which arises from the accretion of gas from their binary companions (this gas is either stripped from low-mass stars or supplied as winds from massive ones). Binary evolution models also predict the existence of black holes accreting from the equatorial envelope of rapidly spinning Be-type stars (stars of the Be type are hot blue irregular variables showing characteristic spectral emission lines of hydrogen). Of the approximately 80 Be X-ray binaries known in the Galaxy, however, only pulsating neutron stars have been found as companions. A black hole was formally allowed as a solution for the companion to the Be star MWC 656 (ref. 5; also known as HD 215227), although that conclusion was based on a single radial velocity curve of the Be star, a mistaken spectral classification and rough estimates of the inclination angle. Here we report observations of an accretion disk line mirroring the orbit of MWC 656. This, together with an improved radial velocity curve of the Be star through fitting sharp Fe II profiles from the equatorial disk, and a refined Be classification (to that of a B1.5-B2 III star), indicates that a black hole of 3.8 to 6.9 solar masses orbits MWC 656, the candidate counterpart of the γ-ray source AGL J2241+4454 (refs 5, 6). The black hole is X-ray quiescent and fed by a radiatively inefficient accretion flow giving a luminosity less than 1.6 × 10(-7) times the Eddington luminosity. This implies that Be binaries with black-hole companions are difficult to detect in conventional X-ray surveys.

Cross-cultural adaptation and validation of the RhinAsthma Patient Perspective (RAPP) in Spanish.

OBJECTIVE: the RhinAsthma Patient Perspective (RAPP) is the only available tool to assess HRQoL in daily practice. The aim of this study is to cross-culturally validate the RAPP in Spanish. METHODS: The RAPP was translated into Spanish. Adult patients receiving usual care for asthma and allergic rhinitis (AR) were recruited consecutively and assessed twice with a four-week interval between visits to test the psychometric properties of the questionnaire. RESULTS: 149 patients (62.8% female) with a mean age of 37.7 years completed the study. Exploratory and confirmatory factor analysis confirmed the uni-dimensional structure of the questionnaire. Internal consistency (0.73 at visit 1; 0.87 at visit 2), convergent and discriminant validity (p<.05 at both visits) were satisfactory. Reliability was confirmed by an ICC of 0.69 and a CCC of 0.74. Responsiveness was supported by a significant association with VAS (r=0.28, p<0.003) and ACT (r=-0.35, p<0.01). The minimal clinical difference (MID) value in the analyzed population was 2. CONCLUSIONS: The Spanish version of RAPP was demonstrated to have satisfactory psychometric properties and is a valid, reliable and responsive tool for the assessment of asthma and AR HRQoL in clinical practice.

Epigenetic effect of folic acid (FA) on the gene proximal promoter area and mRNA expression of chicken B cell as antigen presenting cells.

1. This study evaluated and characterised the effect of folic acid (FA) on chromosomal DNA methylation and the epigenetic result on gene expression control mechanisms in chicken B cells as a model of antigen presenting cells. 2. After FA supplementation, the methylation pattern on the proximal promoter area and mRNA expression of toll-like receptor (TLR) 2b, TLR4, B cell receptor (BCR) immunoglobulin (Ig) ß and major histocompatibility complex (MHC) II ß chain genes in chicken B cells was observed 3. Chicken B cell line (DT40) cultures were incubated with 0, 1.72 or 3.96 mM of FA for 4 and 8 h and samples were taken at specific time points. After 4 h of incubation, cells were challenged with 0, 1 or 10 µg/ml of lipopolysaccharide (LPS) and samples were collected 4 h post-challenge. 4. FA supplementation modified the methylation patterns of the proximal promoter regions of TLR4, Igß, and MHCII ß chain at 4 and 8 hours of incubation; however, the single CpG dinucleotide of TLR2b remained methylated regardless of the treatment. 5. A positive association was found between FA concentration and percentage DNA methylation on the promoter area of Igß and TLR2b. However, there was a negative association between FA and MHCII ß chain. 6. There were downregulatory effects in TLR4, Igß and MHCII ß chain gene expression after 8 h of incubation, nut not at 4 h. Although incubation time did not affect TLR2b gene expression, FA concentration did, whereby it increased TLR2b expression at 1.72 mM FA (P < 0.05). 7. LPS significant downregulated TLR2b expression, while an interaction between FA and LPS concentration affected TLR4 and Igß gene expression. 8. In conclusion, the results showed that FA can have an immunomodulatory effect on chicken B cells, possibly affecting their ability to both recognise antigens through the TLR and BCR pathways, and to present it via the MHCII presentation pathway.

Prevalence of Apical Periodontitis in patients with Multiple Myeloma.

BACKGROUND: Aim Previous reports have been analyzed the prevalence/association of apical periodontitis (AP) with systemic diseases. The present study aims to analyze the prevalence of healthy/diseased periapex and endodontic treatments in patients with Multiple Myeloma (MM) and compare the results with those of control subjects. MATERIAL AND METHODS: Methodology Panoramic radiographs of 50 individuals with MM were evaluated and compared with 50 controls that were sex and age matched exactly with the diseased group. Radiographic analysis was performed by 2 two experienced endodontists under standardized conditions. The periapical status (presence or not of AP) was assessed using the periapical index (PAI). Data included systemic health, technical quality of root fillings, total number of teeth, quality of restoration, and periapical status. Statistical evaluation of differences between groups included used chi-squared tests and Fisher's exact tests. RESULTS: The prevalence of root canal-treated teeth was 10.11% in the MM group and 12.05% in the control group (p=0.90). The average root canal-treated teeth in the test group was 2,34 and 2.48 in the control group, where the difference was statistically significant (p=0.05). AP in 1 or more teeth was found in 86 % and in 78% of the patients in the MM and the control groups, respectively. When analyzed by subject, there was no statistically significant difference in the prevalence of AP (p>0.72). Similarly there was also no statistically significant difference in the prevalence of PA (p=0.85), when analyzed by tooth, AP was found in 63.2% and 62.9% in MM and control groups. CONCLUSIONS: The presence of AP and endodontic treatment was not significantly different in individuals with MM compared with control subjects. Future studies are needed to elucidate and confirm the association between MM and AP.

Suppression of the SOS response modifies spatiotemporal evolution, post-antibiotic effect, bacterial fitness and biofilm formation in quinolone-resistant Escherichia coli.

Background: Suppression of the SOS response has been proposed as a therapeutic strategy for potentiating quinolones against susceptible, low-level quinolone-resistant (LLQR) and resistant Enterobacteriaceae. Objectives: To monitor the functionality of the SOS response in the evolution towards clinical quinolone resistance and study its impact on the evolution of spatiotemporal resistance. Methods: An isogenic collection of Escherichia coli (derived from the strain ATCC 25922) carrying combinations of chromosomally and plasmid-mediated quinolone resistance mechanisms (including susceptible, LLQR and resistant phenotypes) and exhibiting a spectrum of SOS activity was used. Relevant clinical parameters such as mutation rate, mutant prevention concentration (MPC), bacterial fitness, biofilm formation and post-antibiotic effect (PAE) were evaluated. Results: Inactivating the SOS response (recA deletion) led to a decrease in mutation rate (∼103 fold) in LLQR compared with WT strains at ciprofloxacin concentrations of 1 mg/L (the EUCAST breakpoint for resistance) and 2.5 mg/L (Cmax), as well as a remarkable delay in the spatiotemporal evolution of quinolone resistance. For all strains, there was an 8-fold decrease in MPC in RecA-deficient strains, with values for LLQR strains decreasing below the Cmax of ciprofloxacin. Inactivation of the SOS response reduced competitive fitness by 33%-50%, biofilm production by 22%-80% and increased the PAE by ∼3-4 h at sub-MIC concentrations of ciprofloxacin. Conclusions: Our data indicate that suppression of the SOS response affects key bacterial traits and is a promising strategy for reversing and tackling the evolution of antibiotic resistance in E. coli, including low-level and resistant phenotypes at therapeutic quinolone concentrations.

Effect of CRHR1 and CRHR2 gene polymorphisms and childhood trauma in suicide attempt.

Family, twin, and adoption studies have suggested that genetic factors might be involved in suicidal behavior. Corticotropin-releasing receptor type 1 (CRHR1) and 2 (CRHR2) genes play a key role in the activation and modulation of the hypothalamic-pituitary-adrenal (HPA) axis, which is considered a major stress regulator. Childhood trauma is an environmental risk factor associated with suicide attempt (SA) and it has been related to HPA axis dysregulation. This study aimed at analyzing the relationship of CRHR1 and CRHR2 genes with childhood trauma concerning the development of SA. In this study, we included 366 affective disorder patients. Among them, 183 patients had SA at least once and 183 had not SA. Information regarding SA and childhood trauma was obtained from medical records. Multifactor Dimensionality Reduction program was used to detect gene-environment interactions between CRHR1 (rs110402, rs242924, and rs16940665) and CRHR2 (rs2190242, rs2284217, and rs2014663) with childhood trauma in SA. The analysis showed an interaction of CRHR1 and CRHR2 with childhood trauma, thus conferring increased risk of having presented at least one SA (OR 7.44; 95% CI 4.58-12.07; p < 0.0001). In addition, we observed the following in the trauma subtypes analysis: physical negligence (OR 4.72; 95% CI 3.01-7.40; p < 0.0001), emotional abuse (OR 5.76; 95% CI 3.67-9.05; p < 0.0001), and sexual abuse (OR 5.70; 95% CI 3.62-8.97; p < 0.0001). Our results suggested that genetic variants of CRHR1 and CRHR2 genes in addition to physical negligence, and emotional and sexual abuse, contribute to increase risk of presented at least one SA.

Advantages and challenges of the implementation of a low-cost particulate matter monitoring system as a decision-making tool.

The integration of monitoring technologies in the last decades has been a key factor in the development of new ways to track air pollutants and supplementing the network of traditional monitoring systems. In this regard, the appearance of affordable and accurate sensor devices to monitor air quality has made possible to obtain relevant data about the state of the air, and moreover, eminent institutions are interested in promoting the use of novel and more affordable tools for air pollution, such as the United States Environmental Protection Agency and European institutions, within a new approach to environmental surveillance, known as Next Generation Compliance and Enforcement technologies. On other hand, in order to get more reliable measurements, the use of machine learning to support adjustment or calibration process has been used in some studies to improve the performance of monitoring devices. On this paper, led by a group of specialists of the Chilean Superintendence of Environment (henceforth, SMA from its Spanish initials), a first approach case study related to the convenience of the usage of low-cost devices in environmental enforcement will be presented. The study was made in the Metropolitan Region of Santiago and considers the spatial distribution of different particulate matter sensors in the region. Some aspects regarding communication and technical issues are presented as well as the main findings about their performance. Results illustrate that low-cost sensors, aided by machine learning algorithms, could provide a reliable enough general screening of particulate matter within a large city, constituting a valuable decision-making tool for environmental oversight, as well as a powerful preventive and deterrent approach for compliance.