Evolutionary Pathways and Trajectories in Antibiotic Resistance.

Evolution is the hallmark of life. Descriptions of the evolution of microorganisms have provided a wealth of information, but knowledge regarding "what happened" has precluded a deeper understanding of "how" evolution has proceeded, as in the case of antimicrobial resistance. The difficulty in answering the "how" question lies in the multihierarchical dimensions of evolutionary processes, nested in complex networks, encompassing all units of selection, from genes to communities and ecosystems. At the simplest ontological level (as resistance genes), evolution proceeds by random (mutation and drift) and directional (natural selection) processes; however, sequential pathways of adaptive variation can occasionally be observed, and under fixed circumstances (particular fitness landscapes), evolution is predictable. At the highest level (such as that of plasmids, clones, species, microbiotas), the systems' degrees of freedom increase dramatically, related to the variable dispersal, fragmentation, relatedness, or coalescence of bacterial populations, depending on heterogeneous and changing niches and selective gradients in complex environments. Evolutionary trajectories of antibiotic resistance find their way in these changing landscapes subjected to random variations, becoming highly entropic and therefore unpredictable. However, experimental, phylogenetic, and ecogenetic analyses reveal preferential frequented paths (highways) where antibiotic resistance flows and propagates, allowing some understanding of evolutionary dynamics, modeling and designing interventions. Studies on antibiotic resistance have an applied aspect in improving individual health, One Health, and Global Health, as well as an academic value for understanding evolution. Most importantly, they have a heuristic significance as a model to reduce the negative influence of anthropogenic effects on the environment.

Acute-onset smell and taste disorders in the context of COVID-19: a pilot multicentre polymerase chain reaction based case-control study.

BACKGROUND AND PURPOSE: Specific respiratory tract infections, including COVID-19, may cause smell and/or taste disorders (STDs) with increased frequency. The aim was to determine whether new-onset STDs are more frequent amongst COVID-19 patients than influenza patients. METHOD: This was a case-control study including hospitalized patients of two tertiary care centres. Consecutive patients positive for COVID-19 polymerase chain reaction (cases) and patients positive for influenza polymerase chain reaction (historical control sample) were assessed during specific periods, employing a self-reported STD questionnaire. RESULTS: Seventy-nine cases and 40 controls were included. No significant differences were found in basal features between the two groups. New-onset STDs were significantly more frequent amongst cases (31, 39.2%) than in the control group (5, 12.5 %) [adjusted odds ratio 21.4 (2.77-165.4, P = 0.003)]. COVID-19 patients with new-onset STDs were significantly younger than COVID-19 patients without STDs (52.6 ± 17.2 vs. 67.4 ± 15.1, P < 0.001). Amongst COVID-19 patients who presented STDs, 22 (70.9%) recalled an acute onset and it was an initial manifestation in 11 (35.5%). Twenty-five (80.6%) presented smell disorders (mostly anosmia, 14, 45.2%) and 28 (90.3%) taste disorders (mostly ageusia, 14, 45.2%). Only four (12.9 %) reported concomitant nasal obstruction. The mean duration of STD was 7.5 ± 3.2 days and 12 patients (40%) manifested complete recovery after 7.4 ± 2.3 days of onset. CONCLUSION: New-onset STDs were significantly more frequent amongst COVID-19 patients than influenza patients; they usually had an acute onset and were commonly an initial manifestation. The use of STD assessment in anamnesis as a hint for COVID-19 and to support individuals' self-isolation in the current epidemic context is suggested.

Impact of COVID-19 outbreak in reperfusion therapies of acute ischaemic stroke in northwest Spain.

BACKGROUND AND PURPOSE: Spain has been one of the countries more heavily stricken by SARS-CoV-2, which has had huge implications for stroke care. The aim was to analyse the impact of the COVID-19 epidemic outbreak on reperfusion therapies for acute ischaemic stroke in the northwest of Spain. METHODS: This was a Spanish multicentre retrospective observational study based on data from tertiary hospitals of the NORDICTUS network. All patients receiving reperfusion therapy for ischaemic stroke between 30 December 2019 and 3 May 2020 were recorded, and their baseline, clinical and radiological characteristics, extra- and intra-hospital times of action, Code Stroke activation pathway, COVID-19 status, reperfusion rate, and short-term outcome before and after the setting of the emergency state were analysed. RESULTS: A total of 796 patients received reperfusion therapies for ischaemic stroke. There was a decrease in the number of patients treated per week (46.5 patients per week vs. 39.0 patients per week, P = 0.043) and a delay in out-of-hospital (95.0 vs. 110.0 min, P = 0.001) and door-to-needle times (51.0 vs. 55.0, P = 0.038). Patients receiving endovascular therapy obtained less successful reperfusion rates (92.9% vs. 86.6%, P = 0.016). COVID-19 patients had more in-hospital mortality. CONCLUSION: A decrease in the number of patients benefiting from reperfusion therapies was found, with a delay in out-of-hospital and door-to-needle times and worse reperfusion rates in northwest Spain. COVID-19 patients had more in-hospital mortality.

ATP5H/KCTD2 locus is associated with Alzheimer's disease risk.

To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 × 10(-6) were genotyped in an independent Stage III sample (the Fundació ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H+ transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)=1.58, P=2.6 × 10(-7) in discovery and OR=1.43, P=0.004 in Fundació ACE data set; combined OR=1.53, P=4.7 × 10(-9)). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation.

Consumption of a dark roast coffee decreases the level of spontaneous DNA strand breaks: a randomized controlled trial.

PURPOSE: Coffee consumption has been reported to decrease oxidative damage in peripheral white blood cells (WBC). However, effects on the level of spontaneous DNA strand breaks, a well established marker of health risk, have not been specifically reported yet. We analyzed the impact of consuming a dark roast coffee blend on the level of spontaneous DNA strand breaks. METHODS: Healthy men (n = 84) were randomized to consume daily for 4 weeks either 750 ml of fresh coffee brew or 750 ml of water, subsequent to a run in washout phase of 4 weeks. The study coffee was a blend providing high amounts of both caffeoylquinic acids (10.18 ± 0.33 mg/g) and the roast product N-methylpyridinium (1.10 ± 0.05 mg/g). Before and after the coffee/water consumption phase, spontaneous strand breaks were determined by comet assay. RESULTS: At baseline, both groups exhibited a similar level of spontaneous DNA strand breaks. In the intervention phase, spontaneous DNA strand breaks slightly increased in the control (water only) group whereas they significantly decreased in the coffee group, leading to a 27% difference within both arms (p = 0.0002). Food frequency questionnaires indicated no differences in the overall diet between groups, and mean body weight during the intervention phases remained stable. The consumption of the study coffee substantially lowered the level of spontaneous DNA strand breaks in WBC. CONCLUSION: We conclude that regular coffee consumption contributes to DNA integrity.

Search for solar axions by the CERN axion solar telescope with 3He buffer gas: closing the hot dark matter gap.

The CERN Axion Solar Telescope has finished its search for solar axions with (3)He buffer gas, covering the search range 0.64 eV ≲ ma ≲ 1.17 eV. This closes the gap to the cosmological hot dark matter limit and actually overlaps with it. From the absence of excess x rays when the magnet was pointing to the Sun we set a typical upper limit on the axion-photon coupling of gaγ ≲ 3.3 × 10(-10) GeV(-1) at 95% C.L., with the exact value depending on the pressure setting. Future direct solar axion searches will focus on increasing the sensitivity to smaller values of gaγ, for example by the currently discussed next generation helioscope International AXion Observatory.

Dye adsorption onto mesoporous materials: pH influence, kinetics and equilibrium in buffered and saline media.

Mesoporous materials were used as adsorbents for dye removal in different media: non-ionic, buffered and saline. The mesoporous materials used were commercial (silica gel) as well as as-synthesised materials (SBA-15 and a novel mesoporous carbon). Dye adsorption onto all the materials was very fast and the equilibrium was reached before 1 h. The pH has a significant influence on the adsorption capacity for the siliceous materials since the electrostatic interactions are the driving forces. However, the influence of the pH on the adsorption capacity of the carbonaceous material was lower, since the van der Waals interactions are the driving forces. The ionic strength has a great impact on the siliceous materials adsorption capacity, being their adsorption capacity in a buffered medium six times higher than the corresponding to a non-ionic medium. Nevertheless, ionic strength does not influence on the dye adsorption on the mesoporous carbon. Overall, the as-synthesised carbon material presents a clear potential to treat dye effluents, showing high adsorption capacity (q(e) ≈ 200 mg/g) in all the pH range studied (from 3 to 11); even at low concentrations (C(e) ≈ 10 mg/L) and at short contact times (t(e) < 30 min).

Euthanasia and assisted suicide in neurological diseases: a systematic review.

OBJECTIVE: To identify the neurological diseases for which euthanasia and assisted suicide are most frequently requested in the countries where these medical procedures are legal and the specific characteristics of euthanasia in some of these diseases, and to show the evolution of euthanasia figures. METHODS: We conducted a systematic literature review. RESULTS: Dementia, motor neuron disease, multiple sclerosis, and Parkinson's disease are the neurological diseases that most frequently motivate requests for euthanasia or assisted suicide. Requests related to dementia constitute the largest group, are growing, and raise additional ethical and legal issues due to these patients' diminished decision-making capacity. In some countries, the ratios of euthanasia requests to all cases of multiple sclerosis, motor neuron disease, or Huntington disease are higher than for any other disease. CONCLUSIONS: After cancer, neurological diseases are the most frequent reason for requesting euthanasia or assisted suicide.

Odours in sewer networks: nuisance assessment.

As odour nuisance can affect the quality of life, the population is more and more demanding and in many cities sewers are a critical source of odours. Both factors can lead to increasing numbers of complaints due to the odour nuisance perceived by the residents, affecting also the public image of the sewer management companies. Odours associated with sewer networks are very heterogeneous, in as much as the different 'types of odours' encountered are sewer site specific. The state of the art indicates that there are three parameters that play an important role with the nuisance generated by an odour: hedonic odour tone, odour concentration and odour intensity. This paper presents the results of the study on odour nuisance carried out in different points of the sewer network, with the aim to assess the nuisance generated and identify which points of the sewer should be targeted to implement corrective actions. Considering the different parameters assessed, pumping stations have been identified as critical points of odour nuisance in the sewers, being recommended to implement an odour treatment system in order to guarantee the odour comfort of residents.

[Telephone assistance for neurological diseases: a systematic review]. / La asistencia telefónica de las enfermedades neurológicas: una revisión sistemática.

INTRODUCTION AND OBJECTIVE: While part of the care for neurological patients is done by telephone, it is not well known what neurological diseases and which part of that care is provided by telephone. Our goal is to find it out through a bibliographic review. MATERIALS AND METHODS: References on telephone care for neurological diseases accessible through the PubMed, Embase, and Cochrane platforms have been systematically reviewed, with an unspecified start date and up to March 2022. We found 618 references, and as 219 did not pass the exclusion criteria, 399 were finally included in the review. RESULTS: Dementia is the area of neurology with more publications about its telephone assistance. It is followed by stroke, head trauma, multiple sclerosis, Parkinson's disease and movement disorders, epilepsy, neuromuscular disorders, and others. DISCUSSION AND CONCLUSIONS: Dementias are the diseases with more bibliographic references on their telephone assistance despite not being the most prevalent. The telephone is frequently used to administer diagnostic scales or support caregivers and is particularly useful in diseases that limit mobility and attending a medical practice.

TITLE: La asistencia telefónica de las enfermedades neurológicas: una revisión sistemática.Introducción y objetivo. Es conocido que parte de la asistencia a los pacientes neurológicos se presta por teléfono, pero desconocemos las enfermedades que se atienden de esta manera y qué partes de la asistencia se proporcionan así. Pretendemos averiguarlo a través de esta revisión bibliográfica. Materiales y métodos. Se han revisado sistemáticamente las referencias sobre asistencia telefónica a enfermedades neurológicas accesibles a través de las plataformas PubMed, Embase y Cochrane, sin fecha de inicio y hasta el 3 de abril de 2022. Se encontraron 618 referencias, de las que 219 no pasaron los criterios de exclusión, por lo que se revisaron 399. Resultados. Hay un aumento de publicaciones en los últimos años y, aunque la demencia no es la enfermedad más prevalente, es el área de la neurología con más publicaciones sobre asistencia telefónica. Le siguen los ictus, el traumatismo craneoencefálico, la esclerosis múltiple, la enfermedad de Parkinson y trastornos del movimiento, la epilepsia, las enfermedades neuromusculares y otras. Discusión y conclusiones. Las demencias son las enfermedades con más referencias bibliográficas sobre su asistencia telefónica a pesar de no ser las más prevalentes. Con frecuencia, el teléfono se utiliza para administrar escalas diagnósticas o apoyar a los cuidadores, y es especialmente útil en enfermedades que dificultan la movilidad y acudir presencialmente.

Benchmarking in the process of donation after brain death: a methodology to identify best performer hospitals.

A benchmarking approach was developed in Spain to identify and spread critical success factors in the process of donation after brain death. This paper describes the methodology to identify the best performer hospitals in the period 2003-2007 with 106 hospitals throughout the country participating in the project. The process of donation after brain death was structured into three phases: referral of possible donors after brain death (DBD) to critical care units (CCUs) from outside units, management of possible DBDs within the CCUs and obtaining consent for organ donation. Indicators to assess performance in each phase were constructed and the factors influencing these indicators were studied to ensure that comparable groups of hospitals could be established. Availability of neurosurgery and CCU resources had a positive impact on the referral of possible DBDs to CCUs and those hospitals with fewer annual potential DBDs more frequently achieved 100% consent rates. Hospitals were grouped into each subprocess according to influencing factors. Hospitals with the best results were identified for each phase and hospital group. The subsequent study of their practices will lead to the identification of critical factors for success, which implemented in an adapted way should fortunately lead to increasing organ availability.

Continuously evaluating performance in deceased donation: the Spanish quality assurance program.

The Spanish Quality Assurance Program applied to the process of donation after brain death entails an internal stage consisting of a continuous clinical chart review of deaths in critical care units (CCUs) performed by transplant coordinators and periodical external audits to selected centers. This paper describes the methodology and provides the most relevant results of this program, with information analyzed from 206,345 CCU deaths. According to the internal audit, 2.3% of hospital deaths and 12.4% of CCU deaths in Spain yield potential donors (clinical criteria consistent with brain death). Out of the potential donors, 54.6% become actual donors, 26% are lost due to medical unsuitability, 13.3% due to refusals to donation, 3.1% due to maintenance problems and 3% due to other reasons. Although the national pool of potential donors after brain death has progressively decreased from 65.2 per million population (pmp) in 2001 to 49 pmp in 2010, the number of actual donors after brain death has remained at about 30 pmp. External audits reveal that the number of actual donors could be 21.6% higher if all potential donors were identified and preventable losses avoided. We encourage other countries to develop similar comprehensive approaches to deceased donation performance.

Anxiety as a marker of severity in acute mania.

OBJECTIVE: Anxiety has scarcely been studied in acute mania. The aim of this study was to assess anxiety symptoms during manic episodes and their impact on clinical outcomes. METHOD: Observational, cross-sectional multicentre study. Anxiety was measured using the Hamilton Anxiety Rating Scale (HARS). Bivariate and multiple linear regression analyses were performed using the HARS score as the dependent variable. RESULTS: Two hundred and forty-two patients admitted with a diagnosis of acute manic episode according to DSM-IV TR criteria and a Young Mania Rating Scale>20 were analysed. Mean age was 43 years (SD=11.9) and 57% were women. Forty-six per cent of patients (n=104) presented moderate to severe anxiety symptoms (HARS score>14). Anxiety was significantly associated with severity of manic symptoms (P<0.0001). Patients with anxiety had 20% longer hospitalizations (mean 21 days, CI95% 19.7-23.7). CONCLUSION: An association of anxiety symptoms with greater severity in acute mania was demonstrated. The close relationship between anxiety and manic symptoms highlights the need for greater clinical attention to anxiety in this population. Further studies are necessary to determine whether effective treatment of anxiety symptoms could improve clinical and care outcomes.

Assessment of odour and H(2)S impact in WWTPs by cryo-condensation.

Stability of gaseous samples is a major concern when dealing with odours and airborne pollutants sampling. In terms of odours, the representativeness of the sample can be very seriously compromised, despite the rigorous application of the maximum storage time established by EN-13725. The present paper is focused on the use of the cryo-condensation technique (Cryocore) for time-weighted-average (TWA) sampling in waste water treatment plants (WWTPs), with the aim of comparing the values of TWA odour and H(2)S concentration when using the Cryocore system and other well established sampling methods, such as those described in EN-13725 and passive sampling. The study showed comparable results when comparing all the methodologies tested.

Phases in the decision to request euthanasia and brain structures involved. / Fases en la decisión de solicitar la eutanasia y estructuras cerebrales involucradas.

INTRODUCTION: Euthanasia laws do not mention as an obstacle brain diseases other than dementia that damage circuits involved in decision-making. DEVELOPMENT: Narrative review of the stages of the decision to request euthanasia and the brain areas involved. The amygdala, the cingulate and insular cortex, and different parts of the prefrontal lobes are activated during decisions with similarities to that of requesting euthanasia. CONCLUSIONS: When an injury or malfunction of any of the structures involved in making decisions is known, a specific evaluation should be made of the influence it may have on the competence of the patient to request euthanasia.

TITLE: Fases en la decisión de solicitar la eutanasia y estructuras cerebrales involucradas.Introducción. Las leyes de eutanasia no mencionan como obstáculo las enfermedades cerebrales diferentes de la demencia, pero que dañan los circuitos involucrados en la toma de decisiones. Desarrollo. Revisión narrativa de las etapas de la decisión de solicitar la eutanasia y las áreas cerebrales involucradas. La amígdala, la corteza cingulada, la ínsula y distintas partes de los lóbulos prefrontales se activan durante decisiones con similitudes a la de solicitar la eutanasia. Conclusiones. Cuando se conoce una lesión o mal funcionamiento de alguna de las estructuras involucradas en la toma de decisiones, se debe realizar una evaluación específica de la influencia que pueda tener en la competencia del paciente para solicitar la eutanasia.

Immune surveillance for six vaccinable pathogens using paired plasma and dried blood spots in HIV infected and uninfected children in Kinshasa.

Child vaccination reduces infant mortality rates. HIV-infected children present higher risk of diseases than non-infected. We report the protection coverage rates for 6 vaccine-preventable diseases in a paediatric population from the Democratic Republic of the Congo (DRC) and the impact of HIV infection, providing the first data on the validity of dried blood samples (DBS) to monitor the immune protection. During 2016-2018 DBS from 143 children/adolescents were collected in Kinshasa (DRC), being 52 HIV-infected. Forty-two had a paired plasma sample. Protective IgG was quantified (VirClia-IgG,VIRCELL) to obtain the optimal cut-off in IgG detection in DBS. ROC curves were generated with R software and statistical analyses with Stata. Protective IgG levels varied across pathogens, not reaching herd immunity. HIV-infected presented lower vaccine protection than uninfected for all analyzed pathogens, except rubella, with statistically significant differences for measles (30.8% vs. 53.8%; p = 0.008) and tetanus (3.8% vs. 22%; p = 0.0034). New cut-offs were calculated when using DBS to improve test performance. We reinforce the necessity to increase pediatric vaccination coverage in Kinshasa, especially in HIV seropositive, with less capacity to maintain adequate antibody levels. DBS were useful to monitor vaccination coverage in seroprevalence studies in resource-limited settings, after optimizing the cut-off value for each pathogen.

Search for Dark Matter Axions with CAST-CAPP.

The CAST-CAPP axion haloscope, operating at CERN inside the CAST dipole magnet, has searched for axions in the 19.74 µeV to 22.47 µeV mass range. The detection concept follows the Sikivie haloscope principle, where Dark Matter axions convert into photons within a resonator immersed in a magnetic field. The CAST-CAPP resonator is an array of four individual rectangular cavities inserted in a strong dipole magnet, phase-matched to maximize the detection sensitivity. Here we report on the data acquired for 4124 h from 2019 to 2021. Each cavity is equipped with a fast frequency tuning mechanism of 10 MHz/ min between 4.774 GHz and 5.434 GHz. In the present work, we exclude axion-photon couplings for virialized galactic axions down to gaγγ = 8 × 10-14 GeV-1 at the 90% confidence level. The here implemented phase-matching technique also allows for future large-scale upgrades.

Squeezing and expanding light without reflections via transformation optics.

We study the reflection properties of squeezing devices based on transformation optics. An analytical expression for the angle-dependent reflection coefficient of a generic three-dimensional squeezer is derived. In contrast with previous studies, we find that there exist several conditions that guarantee no reflections so it is possible to build transformation-optics-based reflectionless squeezers. Moreover, it is shown that the design of antireflective coatings for the non-reflectionless case can be reduced to matching the impedance between two dielectrics. We illustrate the potential of these devices by proposing two applications in which a reflectionless squeezer is the key element: an ultra-short perfect coupler for high-index nanophotonic waveguides and a completely flat reflectionless hyperlens. We also apply our theory to the coupling of two metallic waveguides with different cross-section. Finally, we show how the studied devices can be implemented with non-magnetic isotropic materials by using a quasi-conformal mapping technique.

Search for sub-eV mass solar axions by the CERN Axion Solar Telescope with 3He buffer gas.

The CERN Axion Solar Telescope (CAST) has extended its search for solar axions by using (3)He as a buffer gas. At T=1.8 K this allows for larger pressure settings and hence sensitivity to higher axion masses than our previous measurements with (4)He. With about 1 h of data taking at each of 252 different pressure settings we have scanned the axion mass range 0.39 eV≲m(a)≲0.64 eV. From the absence of excess x rays when the magnet was pointing to the Sun we set a typical upper limit on the axion-photon coupling of g(aγ)≲2.3×10(-10) GeV(-1) at 95% C.L., the exact value depending on the pressure setting. Kim-Shifman-Vainshtein-Zakharov axions are excluded at the upper end of our mass range, the first time ever for any solar axion search. In the future we will extend our search to m(a)≲1.15 eV, comfortably overlapping with cosmological hot dark matter bounds.