Fear of illness in Kafka's Metamorphosis.

This year marks 100 years since the death of Franz Kafka. Often in general medicine, and internal medicine in particular, doctors face situations in which they position themselves as the only guarantor of the patient in relation to society and how it conceives the disease. Many times, patients come to us without a diagnosis or with the fear of it; sometimes also rejected by their environment. This short text addresses this current topic, paying tribute to the brilliant writer and his best-known work, Metamorphosis.

A full-head model to investigate intra and extracochlear electric fields in cochlear implant stimulation.

Objective.Despite the widespread use and technical improvement of cochlear implant (CI) devices over past decades, further research into the bioelectric bases of CI stimulation is still needed. Various stimulation modes implemented by different CI manufacturers coexist, but their true clinical benefit remains unclear, probably due to the high inter-subject variability reported, which makes the prediction of CI outcomes and the optimal fitting of stimulation parameters challenging. A highly detailed full-head model that includes a cochlea and an electrode array is developed in this study to emulate intracochlear voltages and extracochlear current pathways through the head in CI stimulation.Approach.Simulations based on the finite element method were conducted under monopolar, bipolar, tripolar (TP), and partial TP modes, as well as for apical, medial, and basal electrodes. Variables simulated included: intracochlear voltages, electric field (EF) decay, electric potentials at the scalp and extracochlear currents through the head. To better understand CI side effects such as facial nerve stimulation, caused by spurious current leakage out from the cochlea, special emphasis is given to the analysis of the EF over the facial nerve.Main results.The model reasonably predicts EF magnitudes and trends previously reported in CI users. New relevant extracochlear current pathways through the head and brain tissues have been identified. Simulated results also show differences in the magnitude and distribution of the EF through different segments of the facial nerve upon different stimulation modes and electrodes, dependent on nerve and bone tissue conductivities.Significance.Full-head models prove useful tools to model intra and extracochlear EFs in CI stimulation. Our findings could prove useful in the design of future experimental studies to contrast FNS mechanisms upon stimulation of different electrodes and CI modes. The full-head model developed is freely available for the CI community for further research and use.

[Interlevel incident management: The experience of a primary care district]. / Gestión de incidencias interniveles. La experiencia de un distrito de atención primaria.

AIM: Determine the prevalence and define the profile of interlevel incidences (ININ) between primary care (PC) and hospital (HC). DESIGN: Multicenter cross-sectional descriptive study. SITE: Primary care. PARTICIPANTS: Professionals from a Health District and its reference hospitals. INTERVENTIONS: ININ are errors in communication between PC and HC professionals derived from administrative, pharmaceutical or clinical procedures not resolved during the formal interlevel communication processes, which requires a coordinated and validated response from the health care directions to not overload the family physician. MAIN MEASUREMENTS: ININ by category, hospital services and health centers, total and validated, relative to the total number of referrals, and the reason for the ININ. RESULTS: We detected 2011 ININs (3.36%) among the 59.859 referrals, although only 1684 were validated (83.7%). Most were administrative (59.5%), followed by pharmaceutical (24.2%), clinical (10.2%) and reverse (6.1%). 41.3% of the clinical ININs were grouped around 5 hospital specialties, and 45.9% in 5 health centers. The main reasons for clinical ININ were non-prescription of the recommended pharmacological treatment in outpatient clinics or on hospital discharge (27.3%), request for referral to another hospital specialist (27.9%), or request to referral in person to patients who had already been referred by teleconsultation (17.8%). CONCLUSIONS: 3.36% of interlevel referrals are accompanied by incidents and 83.7% are validated and processed. It is necessary to develop ININ management tools to guarantee safe healthcare and debureaucratize PC.

Accumulation of polyethylene microplastics in river biofilms and effect on the uptake, biotransformation and toxicity of the antimicrobial triclosan.

The interaction of multiple stressors in freshwater ecosystems may lead to adverse effects on aquatic communities and their ecological functions. Microplastics (MPs) are a class of contaminants of emerging concern that can exert both direct and indirect ecotoxicological effects. A growing number of studies have investigated MPs-attached microbial communities, but the interaction between MPs and substrate-associated biofilm (i.e., on natural river substrates, such as stones and sediments) remains poorly studied. In this work, the combined effects of polyethylene MPs (PE-MPs) with a particle size of 10-45 µm (2 mg/L) and the antimicrobial triclosan (TCS) (20 µg/L) were investigated on river biofilms through a short-term exposure experiment (72 h). To the best of authors' knowledge, this is the first time that the combined effects of MPs and chemical contaminants in substrate-associated river biofilms were assessed. Different response parameters were evaluated, including (i) exposure assessment and ii) contaminants effects at different levels: bacterial community composition, antibiotic resistance, extracellular polymeric substances (EPS), photosynthetic efficiency (Yeff), and leucine aminopeptidase activity (LAPA). Triclosan was accumulated in river biofilms (1189-1513 ng/g dw) alongside its biotransformation product methyl-triclosan (20-29 ng/g dw). Also, PE-MPs were detected on biofilms (168-292 MP/cm2), but they had no significant influence on the bioaccumulation and biotransformation of TCS. A moderate shift in bacterial community composition was driven by TCS, regardless of PE-MPs co-exposure (e.g., increased relative abundance of Sphingomonadaceae family). Additionally, Yeff and EPS content were significantly disrupted in TCS-exposed biofilms. Therefore, the most remarkable effects on river biofilms were related to the antimicrobial TCS, whereas single PE-MPs exposure did not alter any of the evaluated parameters. These results demonstrate that biofilms might act as environmental sink of MPs. Although no interaction between PE-MPs and TCS was observed, the possible indirect impact of other MPs-adsorbed contaminants on biofilms should be further assessed.

Four-year Epidemiological Surveillance of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy: Current Situation and Trends. / Vigilancia epidemiológica en los últimos 4 años del Registro Español de Investigación en Dermatitis de Contacto y Alergia Cutánea: situación actual y tendencias.

BACKGROUND: The epidemiological surveillance of contact dermatitis is one of the objectives of the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. Knowing whether the prevalence of positive tests to the different allergens changes over time is important for this monitoring process. OBJECTIVES: To describe the various temporary trends in allergen positivity in the GEIDAC standard series from 2018 through December 31, 2022. METHODS: This was a multicenter, observational trial of consecutive patients analyzed via patch tests as part of the study of possible allergic contact dermatitises collected prospectively within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy. The data was analyzed using 2 statistical tests: one homogeneity test (to describe the changes seen over time) and one trend test (to see whether the changes described followed a linear trend). RESULTS: A total of 11327 patients were included in the study. Overall, the allergens associated with a highest sensitization were nickel sulfate, methylisothiazolinone, cobalt chloride, methylchloroisothiazolinone/methylisothiazolinone, and fragrance mix i. A statistically significant decrease was found in the percentage of methylisothiazolinone positive tests across the study years with an orderly trend. CONCLUSIONS: Although various changes were seen in the sensitizations trends to several allergens of the standard testing, it became obvious that a high sensitization to nickel, methylchloroisothiazolinone/methylisothiazolinone and fragrances mix i remained. Only a significant downward trend was seen for methylisothiazolinone.

The triglycerides and glucose index is more strongly associated with metabolically healthy obesity phenotype than the lipid and obesity indices.

PURPOSE: The triglycerides and glucose (TyG) index is a reliable biomarker for estimating insulin resistance; however, evidence regarding the use of the TyG index in individuals with metabolically healthy obesity (MHO) is scarce. Thus, we examined the association between the TyG index and the MHO phenotype. METHODS: Apparently healthy men and women aged 18 years or more with obesity (body mass index [BMI] ≥ 30 kg/m2) were allocated into the following groups: MHO and metabolically unhealthy obesity (MUO). The MHO phenotype was defined by obesity and the absence of the following metabolic disorders: elevated triglyceride concentrations, elevated glucose levels, elevated blood pressure, and low HDL-C. The MUO was defined by individuals with obesity and at least one of the aforementioned cardiovascular risk factors. RESULTS: A total 827 individuals, 605 (73.1%) women and 222 (26.9%) men were enrolled and allocated into the MHO (n = 104) and MUO (n = 723) groups. The adjusted regression analysis by age, sex, BMI, and waist circumference showed that fasting glucose (OR = 0.90; 95% CI: 0.88-0.93), and triglycerides (OR = 0.97; 95% CI: 0.96-0.98), as well as the triglycerides/HDL-C (OR = 0.18; 95% CI: 0.13-0.26), lipid accumulation product (OR = 0.95; 95% CI: 0.93-0.96), visceral adipose index (OR = 0.38; 95% CI: 0.31-0.46), and TyG index (OR = 0.001; 95% CI: 0.000-0.004) are inversely associated with the MHO, while the HDL-C (OR = 1.10; 95% CI: 1.07-1.12) had a direct association. CONCLUSIONS: Our results show that the TyG index is more strongly associated with the MHO phenotype than the lipid and obesity indices.

Ultrasonic spectroscopy of sessile droplets coupled to optomechanical sensors.

We describe a system for interrogating the acoustic properties of sub-nanoliter liquid samples within an open microfluidics platform. Sessile droplets were deposited onto integrated optomechanical sensors, which possess ambient-medium-noise-limited sensitivity and can thus passively sense the thermally driven acoustic spectrum of the droplets. The droplet acoustic breathing modes manifest as resonant features in the thermomechanical noise spectrum of the sensor, in some cases hybridized with the sensor's own vibrational modes. Excellent agreement is found between experimental observations and theoretical predictions, over the entire ∼0-40 MHz operating range of our sensors. As an application example, we used the technique to monitor the temporal evolution of evaporating droplets. With suitable control over droplet size and morphology, this technique has the potential for precision acoustic sensing of small-volume biological and chemical samples.

[Anogenital lesions produced by Human Papillomavirus. Prevalence study in children and adolescent not vaccinated]. / Lesiones anogenitales por Virus Papiloma Humano. Estudio de prevalencia en niños, niñas y adolescentes no vacunados.

In Chilean children and adolescents, human papillomavirus (HPV) infection prevalence is unknown. In 2014, the HPV vaccine was incorporated into the National Immunization Program for girls, and since 2019 for boys. OBJECTIVE: To determine the prevalence, genotypes, and characteristics of HPV infection in children and adolescents with anogenital lesions not vaccinated against HPV. PATIENTS AND METHOD: Children and adolescents with anogenital lesions who consulted at the Luis Calvo Mackenna Children's Hospital between 2013 and 2017 were studied. The reason for consultation, age, sex, family history of HPV lesions, history of sexual abuse, and consensual sexual activity were recorded. HPV was detected by PCR and typification by reverse hybridization of the L1 gene. The samples were analyzed in the Oncogenic Virus Section of the Institute of Public Health. RESULTS: 110 patients were studied; 44.5% were children. HPV was detected in 34 cases (30.9% [CI95% 22.4- 40.4]), 22 (44.9%) were children and 12 (19.7%) adolescents. Eleven (91.7%) adolescents had a history of sexual con tact (p < 0.005); 4 (18.2%) children disclosed sexual abuse. HPV was found in 25% of patients with genital lesions and 50% with perianal lesions (p < 0.015). The most frequent genotypes were 59, 58, 16, 18, 6, and 11. Only low-risk genotypes were detected in children and high-risk genotypes were detected in 11/12 (91.7%) of HPV (+) adolescents. CONCLUSION: The prevalence of HPV infection was 30%. In adolescents, the infection was related to sexual contact and high-risk HPV. In children, it was associated with low-risk genotypes. Perianal lesions are more frequently associated with HPV infec tion than genital lesions in children and adolescents. The visual inspection does not allow to specify the etiology of the genital lesions, so it is necessary to perform a PCR test for HPV.

Perspectives on scientific error.

Theoretical arguments and empirical investigations indicate that a high proportion of published findings do not replicate and are likely false. The current position paper provides a broad perspective on scientific error, which may lead to replication failures. This broad perspective focuses on reform history and on opportunities for future reform. We organize our perspective along four main themes: institutional reform, methodological reform, statistical reform and publishing reform. For each theme, we illustrate potential errors by narrating the story of a fictional researcher during the research cycle. We discuss future opportunities for reform. The resulting agenda provides a resource to usher in an era that is marked by a research culture that is less error-prone and a scientific publication landscape with fewer spurious findings.

Analysis of headache management in Andalusia.

INTRODUCTION AND OBJECTIVE: Headache is a frequent reason for consultation between primary care physicians, emergency services physicians, and neurology specialists; however, it is not always well managed. The Andalusian Society of Neurology's Headache Study Group (SANCE) aimed to analyse headache management at different levels of care. MATERIAL AND METHODS: We conducted a descriptive cross-sectional study with data gathered through a retrospective survey in July 2019. Participants completed a series of structured questionnaires on different social and work-related variables from 4 different groups of healthcare professionals (primary care [PC], emergency departments, neurology departments, headache units). RESULTS: A total of 204 healthcare professionals completed the survey: 35 emergency department physicians, 113 PC physicians, 37 general neurologists, and 19 neurologists specialising in headache. Eighty-five percent of PC physicians reported prescribing preventive drugs, which were maintained for at least 6 months (59%), with flunarizine and amitriptyline being the most commonly used. Most patients attended at neurology consultations (65%) are referred by PC physicians, with changes in the headache pattern being the main reason for referral (74%). Healthcare professionals across all levels of care showed great interest in headache and in receiving training in headache management (97% of PC physicians, 100% of emergency services physicians, 100% of general neurologists). CONCLUSIONS: Migraine sparks great interest among healthcare professionals from different levels of care. Our results also reveal a lack of resources for headache management, which is reflected in the long waiting times. Other means of bilateral communication between different levels of care should be explored (eg, e-mail).

Spanish Version of the RECAP Questionnaire to Assess Control of Atopic Eczema: Translation, Cultural Adaptation, Validation, and Correlations with Other Patient-Reported Outcome Measures. / Traducción, adaptación transcultural, correlación con otros PRO y validación del cuestionario RECAP sobre el grado de control de la dermatitis atópica.

BACKGROUND: The 7-item RECAP (Recap of Atopic Eczema) questionnaire is used to assess the control of different degrees of eczema severity in patients of all ages. Long-term control of eczema is one of the 4 core outcome domains to be assessed in clinical trials of eczema therapies. After the RECAP was developed in the United Kingdom, it was translated into Chinese, German, Dutch, and French. OBJECTIVES: To produce a validated Spanish version of the RECAP questionnaire and, secondarily, to test its content validity in a group of Spanish patients with atopic eczema. MATERIAL AND METHODS: In a 7-step process we produced 2forward translations and 1back translation of the RECAP questionnaire. Experts then held two meetings to reach consensus and draft a Spanish version of the questionnaire. Fifteen adult patients with atopic eczema were interviewed to evaluate the comprehensibility, comprehensiveness, and relevance of the drafted items. These patients also completed the Atopic Dermatitis Control Tool (ADCT), the Dermatology Life Quality Index (DLQI), and the Patient-Oriented Eczema Measure (POEM). Stata software (version 16) was then used to explore the correlations between the patients' scores on these tools and the RECAP. RESULTS: The patients found the Spanish version of the RECAP to be comprehensible and easy to answer. We observed a strong correlation between results on the Spanish RECAP and the ADCT, and highly significant correlations between the RECAP and the DLQI and POEM tools. CONCLUSIONS: The culturally adapted Spanish version of the RECAP is linguistically equivalent to the original version of the questionnaire. RECAP scores correlate highly with other patient-reported outcome measures.

GNE-064: A Potent, Selective, and Orally Bioavailable Chemical Probe for the Bromodomains of SMARCA2 and SMARCA4 and the Fifth Bromodomain of PBRM1.

Bromodomains are acetyllysine recognition domains present in a variety of human proteins. Bromodomains also bind small molecules that compete with acetyllysine, and therefore bromodomains have been targets for drug discovery efforts. Highly potent and selective ligands with good cellular permeability have been proposed as chemical probes for use in exploring the functions of many of the bromodomain proteins. We report here the discovery of a class of such inhibitors targeting the family VIII bromodomains of SMARCA2 (BRM) and SMARCA4 (BRG1), and PBRM1 (polybromo-1) bromodomain 5. We propose one example from this series, GNE-064, as a chemical probe for the bromodomains SMARCA2, SMARCA4, and PBRM1(5) with the potential for in vivo use.

[Adaptation of headache units in Andalusia to the COVID-19 pandemic. Analysis of the Andalusian Neurology Society's Headache Study Group]. / Adaptación de las unidades de cefalea de Andalucía a la pandemia por COVID-19. Análisis del Grupo de Estudio de Cefaleas de la Sociedad Andaluza de Neurología.

INTRODUCTION: The SARS-CoV-2 pandemic has given rise to a major change in healthcare and brought teleconsultation to the forefront. In neurology, headaches are the most frequent reason for visits. AIM: To assess the impact of the COVID-19 pandemic on the structure of headache units in Andalusia and the adaptations made to healthcare that are potentially useful innovations that can continue to be developed when the pandemic is over. MATERIALS AND METHODS: Cross-sectional observational study using an online survey of neurologists responsible for headache units and specialised consultations in Andalusia. RESULTS: During the state of alarm, all respondents used teleconsultation. The vast majority (92.8%) maintained some face-to-face activity, mostly for invasive techniques and new patients, using individual protection measures and as a way to avoid crowds. Half of them (50%) maintained botulinum toxin administrations at the scheduled times and 78.6% continued to prescribe monoclonal antibodies against calcitonin gene-related peptide. Altogether 78.5% are generally satisfied with the use of teleconsultation and 57.1% think it could be quite useful in the future. The main advantages reported were avoiding the need for the patient to travel and time savings; the disadvantages were the absence of physical examinations and difficulties in communicating. The most frequently expressed need for improvement was the use of video-calls. CONCLUSIONS: Some of the changes adopted during this time could continue to be useful in the future and, in the case of headaches, teleconsultation could be used as an option for following up patients who have already been diagnosed and do not require any invasive techniques.

TITLE: Adaptación de las unidades de cefalea de Andalucía a la pandemia por COVID-19. Análisis del Grupo de Estudio de Cefaleas de la Sociedad Andaluza de Neurología.Introducción. La pandemia por SARS-CoV-2 ha supuesto un gran cambio en la atención sanitaria y ha dado protagonismo a la teleconsulta. En neurología, las cefaleas constituyen el motivo más frecuente de consulta. Objetivo. Evaluar el impacto de la pandemia por COVID-19 en la estructura de las unidades de cefaleas de Andalucía y las adaptaciones asistenciales potencialmente útiles tras ella. Materiales y métodos. Estudio observacional transversal mediante encuesta en línea a los neurólogos responsables de las unidades y consultas monográficas de cefaleas de Andalucía. Resultados. Durante el estado de alarma, todos los encuestados usaron teleconsulta. El 92,8% mantuvo alguna actividad presencial, fundamentalmente para técnicas invasivas y pacientes nuevos, utilizando medidas de protección individual y para evitar aglomeraciones. El 50% mantuvo las administraciones de toxina botulínica en los tiempos adecuados y el 78,6% siguió prescribiendo anticuerpos monoclonales frente al péptido relacionado con el gen de la calcitonina. El 78,5% se encuentra globalmente satisfecho con el uso de la teleconsulta y el 57,1% considera que podría ser bastante útil de cara al futuro. Las principales ventajas expresadas fueron evitar el desplazamiento de los pacientes y el ahorro de tiempo; los inconvenientes, la ausencia de exploración física y la dificultad de comunicación. La necesidad de mejora más expresada fue el uso de videollamada. Conclusiones. Algunos de los cambios adoptados en este tiempo podrían seguir siendo útiles en el futuro y, en el caso de las cefaleas, la teleconsulta se podría emplear como opción para el seguimiento de pacientes ya diagnosticados y que no requieran técnicas invasivas.

Comorbidity and prognostic factors on admission in a COVID-19 cohort of a general hospital.

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 2020, 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-CoV2 in 92 (92.5%). The mean age was 63 years, and 66% were male. The most frequent comorbidities were hypertension (40%), diabetes mellitus (16%) y 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 335 UI/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≥345 IU/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≥345 IU/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.

Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions.

The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-ß and α-synuclein pathology were rated on a scale of 0 (absent)-3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman's rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = - 0.27 to r = - 0.46), and (2) tau with BA35 (r = - 0.31) and SRLM thickness (r = - 0.33). In amyloid-ß and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = - 0.40), BA35 (r = - 0.55), subiculum (r = - 0.42) and CA1 thickness (r = - 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-ß suggests a role of Primary Age-Related Tauopathy in neurodegeneration.

A guideline to frame stressor effects in freshwater ecosystems.

Environmental policies fall short in protecting freshwater ecosystems, which are heavily threatened by human pressures and their associated stressors. One reason is that stressor effects depend on the context in which they occur and it is difficult to extrapolate patterns to predict the effect of stressors without these being contextualized in a general frame. This study aims at improving existing decision-making frameworks such as the DPSIR approach (Driver-Pressure-State-Impact-Response) or ERA (Environmental Risk Assessment) in the context of stressors. Here, we delve into stressor-impact relationships in freshwater ecosystems and develop a guideline which includes key characteristics such as stressor type, stressor duration, location, the natural levels of environmental variables to which each ecosystem is used to, among others. This guideline is intended to be useful in a wide range of ecosystem conditions and stressors. Incorporating these guidelines may favor the comparability of scientific results and may lead to a substantial advancement in the efficacy of diagnosis and predictive approaches of impacts.