Biomarkers predicting the controller dose of omalizumab in patients with chronic spontaneous urticaria.

BACKGROUND: Clinical trials showed the efficacy of 300 mg/4 weeks of omalizumab (OMA) during 6 months in patients with severe chronic spontaneous urticaria (CSU). Nevertheless, in real life, many patients require higher doses and/or longer treatment. This study assesses the real-life performance of OMA in severe CSU and identifies factors associated with the response. METHODS: CSU patients eligible for OMA were recruited prospectively. Clinical data and a blood test were collected before OMA initiation. Urticaria Activity Score 7 (UAS7) was calculated at baseline and every 3 months during OMA treatment. CSU control was defined as UAS7 <7 points. This work was partially sponsored by OMA manufacturer. RESULTS: Eighty-nine adults (19.1% males) with severe CSU were recruited. Median duration of CSU prior to OMA initiation was 2 years, and median severity by UAS7 at baseline was 24 points (range 10-42 points). OMA controlled 94.4% of patients, but 17.9% of responders required doses >300 mg/4 weeks. A blood basophil count >20 cells/µL (OR 13.33; 95% CI 3.32-52.63; p < .001) and the absence of hypothyroidism (OR 3.65; 95% CI 0.78-16.95; p = .099) were identified as predictive factors to achieve control with 300 mg/4 weeks. Twelve patients were able to stop OMA during the study (responders in remission, RR). RR had received OMA for a median of 29 months (12-53 months). Conversely, 32 patients had been on OMA for >29 months at the end of the study (active responders, AR). AR had received OMA for a median of 45 months (30-100 months). There were no significant differences in clinical or analytical factors between RR and AR patients. CONCLUSIONS: Low blood basophil count and the presence of hypothyroidism might serve as biomarkers for the controller dose of OMA in severe CSU patients.

Impact of First Wave of COVID-19 Pandemic on Mortality at Emergency Department in Older Patients with COVID and Non-COVID Diagnoses.

INTRODUCTION: Mortality in emergency departments (EDs) is not well known. This study aimed to assess the impact of the first-wave pandemic on deaths accounted in the ED of older patients with COVID and non-COVID diseases. METHODS: We used data from the Emergency Department and Elderly Needs (EDEN) cohort (pre-COVID period) and from the EDEN-COVID cohort (COVID period) that included all patients ≥65 years seen in 52 Spanish EDs from April 1 to 7, 2019, and March 30 to April 5, 2020, respectively. We recorded patient characteristics and final destination at ED. We compared older patients in the pre-COVID period, with older patients with non-COVID and with COVID-19. ED-mortality (before discharge or hospitalization) is the prior outcome and is expressed as an adjusted odds ratio (aOR) with 95% interval confidence. RESULTS: We included 23,338 older patients from the pre-COVID period (aged 78.3 [8.1] years), 6,715 patients with non-COVID conditions (aged 78.9 [8.2] years) and 3,055 with COVID (aged 78.3 [8.3] years) from the COVID period. Compared to the older patients, pre-COVID period, patients with non-COVID and with COVID-19 were more often male, referred by a doctor and by ambulance, with more comorbidity and disability, dementia, nursing home, and more risk according to qSOFA, respectively (p < 0.001). Compared to the pre-COVID period, patients with non-COVID and with COVID-19 were more often to be hospitalized from ED (24.8% vs. 44.3% vs. 79.1%) and were more often to die in ED (0.6% vs. 1.2% vs. 2.2%), respectively (p < 0.001). Compared to the pre-COVID period, aOR for age, sex, comorbidity and disability, ED mortality in elderly patients cared in ED during the COVID period was 2.31 (95% confidence interval [CI]: 1.76-3.06), and 3.75 (95% CI: 2.77-5.07) for patients with COVID. By adding the variable qSOFA to the model, such OR were 1.59 (95% CI: 1.11-2.30) and 2.16 (95% CI: 1.47-3.17), respectively. CONCLUSIONS: During the early first pandemic wave of COVID-19, more complex and life-threatening older with COVID and non-COVID diseases were seen compared to the pre-COVID period. In addition, the need for hospitalization and the ED mortality doubled in non-COVID and tripled in COVID diagnosis. This increase in ED mortality is not only explained by the complexity or severity of the elderly patients but also because of the system's overload.

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.

Activity of fosfomycin and amikacin against fosfomycin-heteroresistant Escherichia coli strains in a hollow-fiber infection model.

Objectives:To evaluate human-like intravenous doses of fosfomycin (8g/Q8h) and amikacin (15mg/kg/Q24h) efficacy in monotherapy and in combination against six fosfomycin-heteroresistant Escherichia coli isolates using a hollow-fiber infection model (HFIM).Materials and methods:Six fosfomycin-heteroresistant E. coli isolates (4 with strong mutator phenotype) and the control strain E. coli ATCC 25922 were used. Mutant frequencies for rifampin (100mg/L), fosfomycin (50 and 200mg/L) and amikacin (32mg/L) were determined. Fosfomycin and amikacin MICs were assessed by agar dilution (AD), gradient strip (GSA) and broth microdilution (BMD) assays. Fosfomycin and amikacin synergies were studied by checkerboard and time-kill assays at different concentrations. Fosfomycin (8g/Q8h) and amikacin (15mg/kg/Q24h) efficacy alone and in combination were assessed using a HFIM.Results:Five isolates were resistant to fosfomycin by AD and BMD, but all susceptible by GSA. All isolates were considered susceptible to amikacin. Antibiotic combinations were synergistic in two isolates and no antagonism was detected. In time-kill assays, all isolates survived under fosfomycin at 64mg/L, although, at 307mg/L, only the normomutators and two hypermutators survived. Four isolates survived under 16mg/L amikacin and none at 45mg/L. No growth was detected under combination conditions. In HFIM, fosfomycin and amikacin monotherapies failed to sterilise bacterial cultures, however, fosfomycin and amikacin combination showed a rapid eradication.Conclusions.There may be a risk of treatment failure of fosfomycin-heteroresistant E. coli isolates using either amikacin or fosfomycin in monotherapy. These results support that the combination amikacin-fosfomycin can rapidly decrease bacterial burden and prevent the emergence of resistant subpopulations against fosfomycin-heteroresistant strains.

Epidemiology, oncologic results and risk stratification model for metachronous peritoneal metastases after surgery for pT4 colon cancers: results from an observational retrospective multicentre long-term follow-up study.

PURPOSE: Metachronous peritoneal metastases (MPM) following a curative surgery procedure for pT4 colon cancer is a challenging condition. Current epidemiological studies on this topic are scarce. METHODS: A retrospective multicentre trial was designed. All consecutive patients who underwent operations to treat pT4 cancers between 2015 and 2017 were reviewed. Demographic, clinical, operative, pathological and oncological follow-up variables were included. MPM were described as any oncological disease at the peritoneum, clearly different from a local recurrence. Univariate and multivariate Cox regression models were constructed. A risk stratification model was created on a cumulative factor basis. According to the calculated hazard ratio (HR), a scoring system was designed (HR < 3, 1 point; HR > 3, 2 points) and a scale from 0 to 6 was calculated for peritoneal disease-free rate (PDF-R). A risk stratification model was also created on the basis of these calculations. RESULTS: Fifty different hospitals were involved, which included a total of 1356 patients. Incidence of MPM was 13.6% at 50 months median follow-up. The strongest independent risk factors for MPM were positive pN stage [HR 3.72 (95% CI 2.56-5.41; p < 0.01) for stage III disease], tumour perforation [HR 1.91 (95% CI 1.26-2.87; p < 0.01)], mucinous or signet ring cell histology [HR 1.68 (95% CI 1.1-2.58; p = 0.02)], poorly differentiated tumours [HR 1.54 (95% CI 1.1-2.2; p = 0.02)] and emergency surgery [HR 1.42 (95% CI 1.01-2.01; p = 0.049)]. In the absence of additional risk factors, pT4 tumours showed 98% and 96% PDF-R in 1-year and 5-year periods based on Kaplan-Meier curves. CONCLUSIONS: Cumulative MPM incidence was 13.6% at 5-year follow-up. The sole presence of a pT4 tumour resulted in high rates of PDF-R at 1-year and 5-year follow-up (98% and 96% respectively). Five additional risk factors different from pT4 status itself were identified as possible MPM indicators during follow-up.

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.

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.

Interplay among Different Fosfomycin Resistance Mechanisms in Klebsiella pneumoniae.

The objectives of this study were to characterize the role of the uhpT, glpT, and fosA genes in fosfomycin resistance in Klebsiella pneumoniae and evaluate the use of sodium phosphonoformate (PPF) in combination with fosfomycin. Seven clinical isolates of K. pneumoniae and the reference strain (ATCC 700721) were used, and their genomes were sequenced. ΔuhpT, ΔglpT, and ΔfosA mutants were constructed from two isolates and K. pneumoniae ATCC 700721. Fosfomycin susceptibility testing was done by the gradient strip method. Synergy between fosfomycin and PPF was studied by checkerboard assay and analyzed using SynergyFinder. Spontaneous fosfomycin mutant frequencies at 64 and 512 mg/liter, in vitro activity using growth curves with fosfomycin gradient concentrations (0 to 256mg/liter), and time-kill assays at 64 and 307 mg/liter were evaluated with and without PPF (0.623 mM). The MICs of fosfomycin against the clinical isolates ranged from 16 to ≥1,024 mg/liter. The addition of 0.623 mM PPF reduced fosfomycin MIC between 2- and 8-fold. Deletion of fosA led to a 32-fold decrease. Synergistic activities were observed with the combination of fosfomycin and PPF (most synergistic area at 0.623 mM). The lowest fosfomycin-resistant mutant frequencies were found in ΔfosA mutants, with decreases in frequency from 1.69 × 10-1 to 1.60 × 10-5 for 64 mg/liter of fosfomycin. In the final growth monitoring and time-kill assays, fosfomycin showed a bactericidal effect only with the deletion of fosA and not with the addition of PPF. We conclude that fosA gene inactivation leads to a decrease in fosfomycin resistance in K. pneumoniae The pharmacological approach using PPF did not achieve enough activity, and the effect decreased with the presence of fosfomycin-resistant mutations.

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.

3D trapping of microbubbles by the Marangoni force.

In this Letter, we show 3D steady-state trapping and manipulation of vapor bubbles in liquids employing a low-power continuous-wave laser using the Marangoni effect. Light absorption from photodeposited silver nanoparticles on the distal end of a multi-mode optical fiber is used to produce bubbles of different diameters. The thermal effects produced by either the nanoparticles on the fiber tip or the light bulk absorption modulate the surface tension of the bubble wall and creates both longitudinal and transversal forces just like optical forces, effectively creating a 3D potential well. Using numerical simulations, we obtain expressions for the temperature profiles and present analytical expressions for the Marangoni force. In addition, using an array of three fibers with photodeposited nanoparticles is used to demonstrate the transfer of bubbles from one fiber to another by sequentially switching on and off the lasers.

Intraventricular hemorrhage as clinical presentation of herpes simplex virus encephalitis. A case report and review of the literature.

OBJECTIVE: Herpes simplex virus encephalitis (HSVE) represents the most common cause of sporadic encephalitis in humans. The development of intracerebral hematomas is rare and late during the course of HSVE. To report a case of a patient with HSVE who initially presented a diffuse intracranial hemorrhage with predominant intraventricular bleeding. CASE REPORT: A 66-year-old man was admitted to the Emergency Department with acute headache. Antecedents: alcohol consumption and ethylic hepatopathy. The brain computed tomography showed acute tetraventricular hemorrhage and hydrocephalus. The blood analysis showed pancytopenia and alteration of all hepatic parameters. After external drainage of cerebrospinal fluid the patient presented a worsening of headache, disorientation, mild left hemiparesis, neck stiffness and temperature of 37.6 °C. The cerebrospinal fluid was hemorrhagic, with 3 lymphocytes/mm3, 60 mg/dL of proteins and PCR positive for Herpes simplex virus type 1. The patient improved with intravenous acyclovir, however he experienced several medical complications which caused his dead. DISCUSSION: The patient presented an atypical cerebral bleeding related to HSVE because the development of hematoma was early and the topography of hemorrhage was basically intraventricular. Probably, both atypical characteristics were related to thrombocytopenia and severe coagulation disorder. This case expands the spectrum of cerebrovascular disorders associated with HSVE.

Artificial Intelligence DENTOMO: Opportunities and Prospects for Interpretation of Cone Beam CT in Dentistry.

The model of artificial intelligence DENTOMO, which allows automated deciphering the CT in maxillofacial area, was developed and implemented in practical dentistry. The presented model is based on two convolutional neural networks, includes a database and knowledge base, harmonized with SNOMED Clinical Terms is a systematically organized computer processable collection of medical terms providing codes, terms, synonyms and definitions used in clinical documentation and reporting. The developed model automatically decodes cone beam CT images, identifies and classifies the anatomical structures of the human dental system, and reveals the pathological processes and their dynamics in dentistry system. This model generates the medical reports automatically. Testing of DENTOMO model demonstrated a reasonable effectiveness in deciphering the CT of dental system. The developed technology allows computerizing and objectifying interpretation of CT of the dental system.

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.

Optothermal generation, trapping, and manipulation of microbubbles.

The most common approach to optically generate and manipulate bubbles in liquids involves temperature gradients induced by CW lasers. In this work, we present a method to accomplish both the generation of microbubbles and their 3D manipulation in ethanol through optothermal forces. These forces are triggered by light absorption from a nanosecond pulsed laser (λ = 532 nm) at silver nanoparticles photodeposited at the distal end of a multimode optical fiber. Light absorbed from each laser pulse quickly heats up the silver-ethanol interface beyond the ethanol critical-point (∼ 243 °C) before the heat diffuses through the liquid. Therefore, the liquid achieves a metastable state and owing to spontaneous nucleation converted to a vapor bubble attached to the optical fiber. The bubble grows with semi-spherical shape producing a counterjet in the final stage of the collapse. This jet reaches the hot nanoparticles vaporizing almost immediately and ejecting a microbubble. This microbubble-generation mechanism takes place with every laser pulse (10 kHz repetition rate) leading to the generation of a microbubbles stream. The microbubbles' velocities decrease as they move away from the optical fiber and eventually coalesce forming a larger bubble. The larger bubble is attracted to the optical fiber by the Marangoni force once it reaches a critical size while being continuously fed with each bubble of the microbubbles stream. The balance of the optothermal forces owing to the laser-pulse drives the 3D manipulation of the main bubble. A complete characterization of the trapping conditions is provided in this paper.

Laser-Plasma Interaction Experiment for Solar Burst Studies.

A new experimental platform based on laser-plasma interaction is proposed to explore the fundamental processes of wave coupling at the origin of interplanetary radio emissions. It is applied to the study of electromagnetic (EM) emission at twice the plasma frequency (2ω_{p}) observed during solar bursts and thought to result from the coalescence of two Langmuir waves (LWs). In the interplanetary medium, the first LW is excited by electron beams, while the second is generated by electrostatic decay of Langmuir waves. In the present experiment, instead of an electron beam, an energetic laser propagating through a plasma excites the primary LW, with characteristics close to those at near-Earth orbit. The EM radiation at 2ω_{p} is observed at different angles. Its intensity, spectral evolution, and polarization confirm the LW-coalescence scenario.

Results on Low-Mass Weakly Interacting Massive Particles from an 11 kg d Target Exposure of DAMIC at SNOLAB.

We present constraints on the existence of weakly interacting massive particles (WIMPs) from an 11 kg d target exposure of the DAMIC experiment at the SNOLAB underground laboratory. The observed energy spectrum and spatial distribution of ionization events with electron-equivalent energies >200 eV_{ee} in the DAMIC CCDs are consistent with backgrounds from natural radioactivity. An excess of ionization events is observed above the analysis threshold of 50 eV_{ee}. While the origin of this low-energy excess requires further investigation, our data exclude spin-independent WIMP-nucleon scattering cross sections σ_{χ-n} as low as 3×10^{-41} cm^{2} for WIMPs with masses m_{χ} from 7 to 10 GeV c^{-2}. These results are the strongest constraints from a silicon target on the existence of WIMPs with m_{χ}<9 GeV c^{-2} and are directly relevant to any dark matter interpretation of the excess of nuclear-recoil events observed by the CDMS silicon experiment in 2013.

Quality of information about oral cancer in Brazilian Portuguese available on Google, Youtube, and Instagram.

BACKGROUND: To evaluate the quality of oral cancer information in Brazilian Portuguese on Google, YouTube, and Instagram. MATERIAL AND METHODS: The first 100 links of each platform characterized the initial sample. The websites and Instagram were evaluated using the JAMA benchmarks, the Discern instrument, and the Flesch readability index (Flesch Reading Ease). The existence of Health on the Net (HON) code was also registered on websites. The usefulness of each video on YouTube was classified as not useful, slightly useful, moderately useful, or very useful. RESULTS: Thirty-four websites, 39 Instagram posts, and 57 videos were evaluated, of which 18 (33.3%) websites and 19 (48.7%) Instagram posts covered only 2 of the 4 JAMA benchmarks. For the Discern instrument, 20 (37%) and 18 (33.3%) websites exhibited low and moderate reliability, respectively, while 26 (66.7%) Instagram posts were of low confidence. The level of intelligibility of both websites and Instagram was difficult. Only three websites exhibited the HONcode. Forty-one (71.9%) videos on YouTube were moderately useful. CONCLUSIONS: Information on oral cancer on the Internet in Brazilian Portuguese is of low quality. Thus, educational and governmental institutions have a responsibility to produce and indicate reliable sources of information for the population.

A Spanish Sign Language (LSE) Adaptation of the Communicative Development Inventories.

This article presents the adaptation of the MacArthur Communicative Development Inventory (CDI; Fenson et al., 1993, Guide and technical manual for the MacArthur Communicative Development Inventories. San Diego, CA: Singular Press; Fenson et al. 1994, Variability in early communicative development. Monographs of the Society for Research in Child Development, 59, 1-173) to Spanish Sign Language (LSE). Data were collected from 55 participants (32 boys and 23 girls; 17 deaf signers, 38 hearing signers) who, evaluated by their caregivers every 4 months, presented a total of 170 records. The parents reported the signs that the children could understand or produce between 8 and 36 months. Results suggested that the CDI adapted to LSE is a valid and reliable instrument. Signing children could understand more signs than they produced at this early developmental stage. There were no significant differences between boys and girls, or between deaf and hearing children. The development of LSE is similar to other sign languages, although with a lower production of signs in the early stages, perhaps due to the bilingualism of most of the children of our study.

Comorbidity and prognostic factors on admission in a COVID-19 cohort of a general hospital. / Comorbilidad y factores pronósticos al ingreso en una cohorte COVID-19 de un hospital general.

ANTECEDENTS AND OBJECTIVE: To describe clinical features, comorbidity, and prognostic factors associated with in-hospital mortality in a cohort of COVID-19 admitted to a general hospital. MATERIAL AND METHODS: Retrospective cohort study of patients with COVID-19 admitted from 26th February, who had been discharged or died, up to 29th April, 2020. A descriptive study and an analysis of factors associated with intrahospital mortality were performed. RESULTS: Out of the 101 patients, 96 were analysed. Of these, 79 (82%) recovered and were discharged, and 17 (18%) died in the hospital. Diagnosis of COVID-19 was confirmed by polymerase chain reaction to SARS-CoV-2 in 92 (92.5%). The mean age was 63 years, and 66% were male. The most frequent comorbidities were hypertension (40%), diabetes mellitus (16%) and cardiopathy (14%). Patients who died were older (mean 77 vs 60 years), had higher prevalence of hypertension (71% vs 33%), and cardiopathy (47% vs 6%), and higher levels of lactate dehydrogenase (LDH) and reactive C protein (mean 662 vs 335UI/L, and 193 vs 121mg/L respectively) on admission. In a multivariant analysis the variables significantly associated to mortality were the presence of cardiopathy (CI 95% OR 2,58-67,07), levels of LDH≥345IU/L (CI 95% OR 1,52-46,00), and age≥65 years (CI 95% OR 1,23-44,62). CONCLUSIONS: The presence of cardiopathy, levels of LDH≥345IU/L and age ≥65 years are associated with a higher risk of death during hospital stay for COVID-19. This model should be validated in prospective cohorts.

Pheochromocytoma: A three-decade clinical experience in a multicenter study. / Feocromocitoma: experiencia clínica de tres décadas en un estudio multicéntrico.

OBJECTIVE: To analyze the clinical and analytical features, diagnostic tests, therapies, and outcomes of pheochromocytoma (PCC). DESIGN AND METHODS: A multicenter retrospective study in surgically treated patients with PCC followed in 3 Spanish tertiary referral hospitals. RESULTS: A total of 106 patients (61 [57.5%] women, mean age 52.3 ± 14.8 years) were evaluated. At diagnosis, PCC was symptomatic in 62% and sporadic in 83%. Patients with familial PCC were significantly younger than those with sporadic disease (40.8 ± 14.2 years vs. 54.5 ± 13.9 years, p<.001). Familial PCCs were more frequently associated with MEN2A (n=8). Levels of 24-h urinary fractionated metanephrines were positively related to tumor size. The maximum tumor diameter was 4.3cm (3-6cm); 27.7% of the patients had tumors ≥6cm. Incidental PCCs were significantly smaller than symptomatic PCCs (3.4cm [2.4-5.0cm] vs. 5.6cm [4.0-7.0cm], p<.001). Scintigraphy by 123I-metaiodobenzylguanidine showed a high sensitivity (81.9%). Preoperative alpha blockade with phenoxybenzamine was used in 93.6% and doxazosin in the rest. Laparoscopic surgery was used in 2/3 of the patients, with a low conversion (1.9%) to open surgery. Perioperative complications appeared in approximately 20% of patients, mainly hypertensive crisis (9.4%). Recurrent disease appeared in 10%, and malignant PCC was uncommon (6.3%). CONCLUSIONS: PCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low.