Effects of chronic hydrogen peroxide exposure on mitochondrial oxidative stress genes, ROS production and lipid peroxidation in HL60 cells.

Hydrogen peroxide (H2O2) is a reactive species that is also involved in the redox regulation of cells because of it is relative stability. In numerous pathological situations, a chronic increase in the production of reactive species is observed, which is related to oxidative stress and cellular damage. This study aimed to evaluate the effects of long-term exposure to different H2O2 concentrations on oxidative stress biomarkers and mitochondrial dynamics in HL60 cells. HL60 cells were treated with a sustained production (0.1, 1.0 and 10.0 nM/s) of H2O2 for one hour. H2O2 production and malondialdehyde (MDA) levels, as a lipid peroxidation marker, increased progressively in HL60 cells in accordance with higher H2O2 exposure, with significant differences between the 10 nM/s H2O2 group and the control and 0.1 nM/s groups. Similarly, progressive increased expression in genes related to the mitochondrial antioxidant defences and mitochondrial dynamics were also observed. Significantly increased gene expression in the 10 nM/s H2O2 with respect to the control group was observed for manganese superoxide dismutase (MnSOD), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PCG1α), nuclear respiratory factor 2 (Nrf2), mitochondrial transcription factor A (Tfam), mitofusins 1 and 2 (Mfn1 and Mfn2) and uncoupling protein 3 (UCP3), whereas no significant changes were observed in the cytochrome c oxidase subunit IV (COXIV) gene expression. In conclusion, exposure to different sustained production of H2O2 is related to a progressive increase in the gene expression of mitochondrial dynamics and redox processes in HL60 cells, but also to oxidative damage at higher H2O2 production levels.

Costs and resource utilization patterns in surgical site infections: a pre-COVID-19 perspective from France, Germany, Spain, and the UK.

BACKGROUND: Surgical site infections (SSIs), mainly caused by Staphylococcus aureus, pose a significant economic burden in Europe, leading to increased hospitalization duration, mortality, and treatment costs, particularly with drug-resistant strains such as meticillin-resistant S. aureus. AIM: To conduct a case-control study on the economic impact of S. aureus SSI in adult surgical patients across high-volume centres in France, Germany, Spain, and the UK, aiming to assess the overall and procedure-specific burden across Europe. METHODS: The SALT study is a multinational, retrospective cohort study with a nested case-control analysis focused on S. aureus SSI in Europe. The study included participants from France, Germany, Italy, Spain, and the UK who underwent invasive surgery in 2016 and employed a micro-costing approach to evaluate health economic factors, matching S. aureus SSI cases with controls. FINDINGS: In 2016, among 178,904 surgical patients in five European countries, 764 developed S. aureus SSI. Matching 744 cases to controls, the study revealed that S. aureus SSI cases incurred higher immediate hospitalization costs (€8,810), compared to controls (€6,032). Additionally, S. aureus SSI cases exhibited increased costs for readmissions within the first year post surgery (€7,961.6 versus €5,298.6), with significant differences observed. Factors associated with increased surgery-related costs included the cost of hospitalization immediately after surgery, first intensive care unit (ICU) admission within 12 months, and hospital readmission within 12 months, as identified through multivariable analysis. CONCLUSION: The higher rates of hospitalization, ICU admissions, and readmissions among S. aureus SSI cases highlight the severity of these infections and their impact on healthcare costs, emphasizing the potential benefits of evidence-based infection control measures and improved patient care to mitigate the economic burden.

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.

Risk model of seizure cluster or status epilepticus and intervention in the emergency department.

OBJECTIVES: To identify possible predictors of seizure cluster or status epilepticus (SE) and to evaluate whether these patients receive greater interventions in emergency departments. METHODOLOGY: We conducted a secondary analysis of the ACESUR Registry, a multipurpose, observational, prospective, multicentre registry of adult patients with seizures from 18 emergency departments. Clinical and care-related variables were collected. We identified risk factors and risk models for seizure cluster or SE and assessed the effect of interventions by prehospital emergency services and the hospital emergency department. RESULTS: We identified a total of 186 (28%) patients from the ACESUR registry with seizure cluster (126 [19%]) or SE (60 [9%]); the remaining 478 patients (72%) had isolated seizures. The risk model for seizure cluster or SE in the emergency department included Charlson Comorbidity Index scores ≥ 3 (OR: 1.60; 95% CI, 1.05-2.46; P=.030), ≥ 2 habitual antiepileptic drugs (OR: 2.29; 95% CI, 1.49-3.51; P<.001), and focal seizures (OR: 1.56; 95% CI, 1.05-2.32; P=.027). The area under the curve of the model was 0.735 (95% CI, 0.693-0.777; P=.021). Patients with seizure cluster and SE received more aggressive interventions both by prehospital emergency services (OR: 2.89; 95% CI, 1.91-4.36; P<.001) and at the emergency department (OR: 4.41; 95% CI, 2.69-7.22; P<.001). CONCLUSIONS: This risk model may be of prognostic value in identifying adult patients at risk of presenting seizure cluster or SE in the emergency department. In our sample, these patients received more aggressive treatment than adult patients with isolated seizures before arriving at hospital, and even more so in the emergency department.

Patient-reported outcomes before treatment for localized prostate cancer: are there differences among countries? Data from the True North Global Registry.

INTRODUCTION: Similar Patient-Reported Outcomes (PROs) at diagnosis for localized prostate cancer among countries may indicate that different treatments are recommended to the same profile of patients, regardless the context characteristics (health systems, medical schools, culture, preferences…). The aim of this study was to assess such comparison. METHODS: We analyzed the EPIC-26 results before the primary treatment of men diagnosed of localized prostate cancer from January 2017 onwards (revised data available up to September 2019), from a multicenter prospective international cohort including seven regions: Australia/New Zealand, Canada, Central Europe (Austria / Czech Republic / Germany), United Kingdom, Italy, Spain, and the United States. The EPIC-26 domain scores and pattern of three selected items were compared across regions (with Central Europe as reference). All comparisons were made stratifying by treatment: radical prostatectomy, external radiotherapy, brachytherapy, and active surveillance. RESULTS: The sample included a total of 13,483 men with clinically localized or locally advanced prostate cancer. PROs showed different domain patterns before treatment across countries. The sexual domain was the most impaired, and the one with the highest dispersion within countries and with the greatest medians' differences across countries. The urinary incontinence domain, together with the bowel and hormonal domains, presented the highest scores (better outcomes) for all treatment groups, and homogeneity across regions. CONCLUSIONS: Patients with localized or locally advanced prostate cancer undergoing radical prostatectomy, EBRT, brachytherapy, or active surveillance presented mainly negligible or small differences in the EPIC-26 domains before treatment across countries. The results on urinary incontinence or bowel domains, in which almost all patients presented the best possible score, may downplay the baseline data role for evaluating treatments' effects. However, the heterogeneity within countries and the magnitude of the differences found across countries in other domains, especially sexual, support the need of implementing the PRO measurement from diagnosis.

[Translated article] Overview of systematic reviews of risk factors for prosthetic joint infection.

BACKGROUND: Prosthetic joint infection is one of the most serious complications in orthopedics. Prognostic systematic reviews (SRs) detecting and assessing factors related to prosthetic joint infection, allow better prediction of risk and implementation of preventive measures. Although prognostic SRs are increasingly frequent, their methodological field presents some knowledge gaps. PURPOSE: To carry out an overview of SR assessing risk factors for prosthetic joint infection, describing and synthesizing their evidence. Secondarily, to assess the risk of bias and methodological quality. MATERIAL AND METHODS: We conducted a bibliographic search in 4 databases (May 2021) to identify prognostic SR evaluating any risk factor for prosthetic joint infection. We evaluated risk of bias with the ROBIS tool, and methodological quality with a modified AMSTAR-2 tool. We computed the overlap degree study between included SR. RESULTS: Twenty-three SRs were included, studying 15 factors for prosthetic joint infection, of which, 13 had significant association. The most frequently studied risk factors were obesity, intra-articular corticosteroids, smoking and uncontrolled diabetes. Overlapping between SR was high for obesity and very high for intra-articular corticoid injection, smoking and uncontrolled diabetes. Risk of bias was considered low in 8 SRs (34.7%). The modified AMSTAR-2 tool showed important methodological gaps. CONCLUSIONS: Identification of procedural-modifiable factors, such as intra-articular corticoids use, can give patients better results. Overlapping between SR was very high, meaning that some SRs are redundant. The evidence on risk factors for prosthetic joint infection is weak due to high risk of bias and limited methodological quality.

Overview of systematic reviews of risk factors for prosthetic joint infection. / Revisión de revisiones sistemáticas de factores pronóstico para infección protésica.

BACKGROUND: Prosthetic joint infection is one of the most serious complications in orthopedics. Prognostic systematic reviews (SR) detecting and assessing factors related to prosthetic joint infection, allow better prediction of risk and implementation of preventive measures. Although prognostic SR are increasingly frequent, their methodological field presents some knowledge gaps. PURPOSE: To carry out an overview of SR assessing risk factors for prosthetic joint infection, describing and synthesizing their evidence. Secondarily, to assess the risk of bias and methodological quality. MATERIAL AND METHODS: We conducted a bibliographic search in 4databases (May 2021) to identify prognostic SR evaluating any risk factor for prosthetic joint infection. We evaluated risk of bias with the ROBIS tool, and methodological quality with a modified AMSTAR-2 tool. We computed the overlap degree study between included SR. RESULTS: Twenty-three SR were included, studying 15 factors for prosthetic joint infection, of which, 13 had significant association. The most frequently studied risk factors were obesity, intra-articular corticosteroids, smoking and uncontrolled diabetes. Overlapping between SR was high for obesity and very high for intra-articular corticoid injection, smoking and uncontrolled diabetes. Risk of bias was considered low in 8SRs (34.7%). The modified AMSTAR-2 tool showed important methodological gaps. CONCLUSIONS: Identification of procedural-modifiable factors, such as intra-articular corticoids use, can give patients better results. Overlapping between SR was very high, meaning that some SR are redundant. The evidence on risk factors for prosthetic joint infection is weak due to high risk of bias and limited methodological quality.

Benefits in quality of life following an obstructive sleep apnea screening and treatment program in patients with acute ischemic stroke. / Beneficios en la calidad de vida de un programa de cribado y tratamiento de apnea obstructiva del sueño en pacientes con ictus isquémico agudo.

INTRODUCTION: Obstructive sleep apnea (OSA) has been proposed as a factor that worsens stroke prognosis. Our aim was to determine if an OSA intervention could improve quality of life (QOL, first objective) and modified Rankin score (mRS, second objective). PATIENTS AND METHODS: The intervention group of this quasi-experimental study included patients with acute ischemic stroke <72 hours who underwent polygraphy and Continuous Positive Airway Pressure (CPAP) and hygienic-dietary measures if required. The control group followed routine clinical practice. The Short Form 36 Health Survey (SF-36) and mRS were applied at the sixth month after stroke in both groups. RESULTS: Fifty-five vs. sixty-two patients were included in the intervention and control group respectively. In the intervention group, 64.71% of patients accepted the proposed CPAP (16 cases with a good adherence). An improvement in SF-36 items was detected in the intervention group: physical functioning (p = 0.008), role physical (p = 0.002), bodily pain (p = 0.008), general health (p <0.001), vitality (p = 0.001) and role emotional (p = 0.015). In a per-protocol analysis, all these improvements were verified in the group of patients treated with good CPAP adherence (p < 0.05 in all the same SF-36 items). The percentage of patients with physical component summatory = 50 was higher in the intervention group (p = 0.003). There were no differences in the median of mRS (p = 0.262). CONCLUSIONS: Although more evidence is needed, a significant improvement in QOL was suggested after our OSA intervention, particularly in patients with good CPAP adherence.

TITLE: Beneficios en la calidad de vida de un programa de cribado y tratamiento de apnea obstructiva del sueño en pacientes con ictus isquémico agudo.Introducción. La apnea obstructiva del sueño (AOS) se ha propuesto como un factor de mal pronóstico en el ictus. Pretendemos determinar si una intervención sobre la AOS puede mejorar las escalas de calidad de vida (primer objetivo) y de discapacidad (segundo objetivo). Pacientes y métodos. El grupo de intervención de este estudio cuasi experimental incluye a pacientes con ictus isquémico agudo menor de 72 horas de evolución a quienes se les realizó poligrafía, así como presión positiva continua en las vías aéreas (CPAP) y medidas higienicodietéticas si se requerían. En el grupo de control se siguió la práctica clínica habitual. Se aplicaron las escalas Short Form 36 Health Survey (SF-36) y modified Rankin Score (mRS) en el sexto mes del ictus en ambos grupos. Resultados. Se incluyó a 55 y a 62 pacientes en el grupo de intervención y en el de control, respectivamente. En el grupo de intervención, el 64,71% de los pacientes aceptó la CPAP indicada (16 casos con buena adhesión). Se detectó una mejoría en los ítems de la escala SF-36 en el grupo de intervención: funcionamiento físico (p = 0,008), rol físico (p = 0,002), dolor corporal (p = 0,008), salud general (p menor de 0,001), vitalidad (p = 0,001) y rol emocional (p = 0,015). En un análisis por protocolo, todas estas mejorías se comprobaron en el grupo de pacientes tratados con CPAP con buena adhesión (p menor de 0,05 en todos los ítems de la SF-36). El porcentaje de pacientes con el sumatorio del componente físico = 50 fue más alto en el grupo de intervención (p = 0,003). No había diferencias en la mediana de la mRS (p = 0,262). Conclusiones. Aunque se necesitan más evidencias, nuestro estudio sugiere una mejoría significativa de la calidad de vida tras nuestra intervención en la AOS, especialmente en pacientes con buena adhesión a la CPAP.

Covid-19 en trabajadores de la Salud: Experiencia en la Residencia de Pediatría de un hospital de La Plata, Argentina / Covid-19 in health workers: Experience in the Pediatric Residence of a hospital in La Plata, Argentina

Introducción: Los trabajadores de la salud (TS) poseen la mayor exposición laboral al contagio SARS-CoV-2. Los residentes forman parte fundamental de los servicios de salud por lo que no se encuentran exentos del impacto físico, psíquico, social y económico negativo producido por la pandemia por COVID-19. Objetivo: : Describir el impacto epidemiológico de la enfermedad profesional por COVID-19 en médicos residentes de pediatría. Material y métodos: Estudio descriptivo de corte transversal en médicos residentes de pediatría del H.I.A.E.P "Sor María Ludovica". El período comprendido en el estudio fue del 01/10/2020 al 30/09/2021. Se evaluaron los siguientes datos: género, edad, antecedentes personales, vacunación, cuadro clínico, métodos diagnósticos, aislamientos epidemiológicos, evolución y licencias tramitadas. Los datos fueron registrados por la jefatura de residentes. Resultados: 143 casos sospechosos de COVID-19, de ellos 30 resultaron confirmados de COVID-19. La edad media de los enfermos fue de 31 años (26-46 años) de los cuales 14 (47%) no estaban vacunados contra SARS COV-2, 11 (36%) estaban completamente inmunizados y 5 (17%) tenían calendario incompleto. 2 casos (6,6%) reportaron comorbilidad previa. Se realizaron pruebas de laboratorio en 130 de los 143 casos. 13 casos se descartaron por criterio clínico. La tasa de positividad fue 23,1%. 26 casos fueron confirmados por laboratorio y 4 casos mediante criterio clínico epidemiológico. Todos los casos fueron leves y evolucionaron favorablemente. Fueron gestionadas 326 licencias relacionadas a la pandemia por COVID-19 que significaron la pérdida de 2.830 días laborales. Conclusión: En el presente estudio se evidenció una alta tasa de incidencia de COVID-19 en residentes de pediatría en un año: 23,1%

Introduction: Health workers (HCWs) have the highest occupational exposure to SARS-CoV-2 contagion. Residents are a fundamental part of health services, so they are not exempt from the negative physical, psychological, social and economic impact caused by the COVID-19 pandemic. Objectives: To describe the epidemiological impact of the occupational disease by COVID-19 in resident pediatricians. Material and methods: Descriptive cross-sectional study in pediatric residents of the H.I.A.E.P "Sor María Ludovica". The period covered by the study was from 10/01/2020 to 09/30/2021. The following data were evaluated: gender, age, personal history, vaccination, clinical picture, diagnostic methods, epidemiological isolates, evolution and licenses processed. The data was recorded by the head of residents. Results: 143 suspected cases of COVID-19, of which 30 were confirmed to be COVID-19. The mean age of the patients was 31 years (26-46 years), of which 14 (47%) were not vaccinated against SARS COV.-2, 11 (36%) were fully immunized and 5 (17%) had an incomplete schedule. 2 cases (6.6%) reported previous comorbidity. Laboratory tests were performed in 130 of the 143 cases. 13 cases were ruled out based on clinical criteria. The positivity rate was 23.1%. 26 cases were confirmed by laboratory and 4 cases by clinical epidemiological criteria. All cases were mild and evolved favorably. 326 licenses related to the COVID-19 pandemic were managed, which meant the loss of 2,830 working days. Conclusion: In the present study, a high rate of incidence of COVID-19 was evidenced in pediatric residents in one year: 23.1%

Differences in Linear Epitopes of Ara h 9 Recognition in Peanut Allergic and Tolerant, Peach Allergic Patients.

Background: Peanut-allergic patients from the Mediterranean region are predominantly sensitized to the lipid transfer protein (LTP) Ara h 9, and the peach LTP Pru p 3 seems to be the primary sensitizer. However, LTP sensitization in peanut allergy is not a predictive marker for clinically relevant symptoms. Objective: We aimed to identify sequential epitopes of IgE and IgG4 from Pru p 3 and Ara h 9 in peach-allergic patients sensitized to peanuts. We also sought to determine the differences in IgE and IgG4 binding between patients who had developed peanut allergy and those tolerating peanuts. Methods: A total of 46 peach-allergic patients sensitized to peanuts were selected. A total of 35 patients were allergic to peanuts (peanut-allergic group) and 11 were tolerant to peanuts (peanut-tolerant group). We measured sIgE and sIgG4 in peanut, peach, and their recombinant allergen (Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Ara h 9) with fluorescence enzyme immunoassay. We examined the IgE and IgG4 binding to sequential epitopes using a peptide microarray corresponding to linear sequences of the LTPs Ara h 9 and Pru p 3 with a library of overlapping peptides with a length of 20 amino acids (aa) and an offset of 3 aa. Results: The frequency and the intensity of IgE recognition of Ara h 9 and Pru p 3 peptides were higher in the peanut-tolerant group than in the peanut-allergic group. We found four Ara h 9 peptides (p4, p14, p21, and p25) and four Pru p 3 peptides (p1, p3, p21, and p24) with a significantly elevated IgE recognition in peanut-tolerant patients. Only one peptide of Ara h 9 (p4) recognized by IgG4 was significantly elevated in the peanut-tolerant group. The IgG4/IgE ratio of Ara h 9 peptide 4 was significantly higher in peanut-tolerant patients than in peanut-allergic patients, while no significant differences were observed in the IgG4/IgE ratio of this peptide in Pru p 3. Conclusion: Although we found significant differences in IgE and IgG4 recognition of Ara h 9 and Pru p 3 between peanut-tolerant and peanut-allergic patients (all of whom were allergic to peach), polyclonal IgE peptide recognition of both LTPs was observed in peach-allergic patients tolerating peanuts. However, the IgG4 blocking antibodies against Ara h 9 peptide 4 could provide an explanation for the absence of clinical reactivity in peanut-tolerant peach-allergic patients. Further studies are needed to validate the usefulness of IgG4 antibodies against Ara h 9 peptide 4 for peanut allergy diagnosis.

Effects of ascorbic acid addition on the oxidative stress response of Oryza sativa L. plants to As(V) exposure.

Accumulation of noxious elements in the edible part of crops and its impact on food safety is of increasing concern. Rice is one of the major staple food crops worldwide, including arsenic (As)-polluted areas, in which dietary As exposure is becoming a widespread health threat. Plant chemical priming has been shown to be an effective strategy to enhance tolerance to environmental stresses, including metal(loid) exposure. The priming effect of ascorbic acid (AsA) was assessed in rice seedlings exposed to As(V) in a hydroponics experiment. AsA treatment (co-addition to the growing media concomitantly (t0) or 24 h in advance (t24)) prevented an excessive accumulation of As in the roots (that decreased âˆ¼ 60%) and stimulated the activities of photosynthetic and antioxidant attributes (∼1.2-fold) in the aerial part of the plants. The increase in proline levels in both shoots (∼2.1-fold) and roots (∼2.4-fold) was found to be the most sensitive stress parameter, and was able to reflect the AsA-induced reduction of As toxic effects (concentrations back to Control levels, both simultaneously added or added as a pretreatment) in the aerial part of the plants. However, the phytotoxic effects related to As exposure were not fully prevented by priming with AsA, and further research is needed to find alternative priming approaches.

Mechanical ventilation in Spain, 1998-2016: Changes in the disconnection of mechanical ventilation.

PURPOSE: To evaluate changes in the disconnection of mechanical ventilation in Spain from 1998 to 2016. DESIGN: Post-hoc analysis of four cohort studies. AMBIT: 138 Spanish ICUs. PATIENTS: 2141 patients scheduled extubated. INTERVENTIONS: None. VARIABLES OF INTEREST: Demographics, reason for mechanical ventilation, complications, methods for disconnection, failure on the first attempt at disconnection, duration of weaning, reintubation, post-reintubation tracheotomy, ICU stay and mortality. RESULTS: There was a significant increase (p < 0.001) in the use of gradual reduction of support pressure. The adjusted probability of using the gradual reduction in pressure support versus a spontaneous breathing trial has increased over time, both for the first attempt at disconnection (taking the 1998 study as a reference: odds ratio 0.99 in 2004, 0.57 in 2010 and 2.43 in 2016) and for difficult/prolonged disconnection (taking the 1998 study as a reference: odds ratio 2.29 in 2004, 1.23 in 2010 and 2.54 in 2016). The proportion of patients extubated after the first attempt at disconnection has increased over time. There is a decrease in the ventilation time dedicated to weaning (from 45% in 1998 to 36% in 2016). However, the duration in difficult/prolonged weaning has not decreased (median 3 days in all studies, p = 0.435). CONCLUSIONS: There have been significant changes in the mode of disconnection of mechanical ventilation, with a progressive increase in the use of gradual reduction of pressure support. No relevant changes in outcomes have been observed.

Consensus on the Definition of Control and Remission in Chronic Urticaria.

The terms control and remission and other key terms used in chronic urticaria (CU) such as flare-up, relapse, exacerbation, and recurrence have not been fully defined in the literature. Disease monitoring and treatment goals in clinical practice are not well established. After a qualitative appraisal of available evidence, we aimed to find a consensus definition of control and remission, clarify key terminology, provide guidance on how to monitor the disease, and establish treatment goals in clinical practice. A modified Delphi consensus approach was used. Based on a literature review, a scientific committee provided 137 statements addressing controversial definitions and terms, available patient-reported outcomes (PROs), and recommendations on how to measure therapeutic objectives in CU. The questionnaire was evaluated by 138 expert allergists and dermatologists. A consensus was reached on 105 out of the 137 proposed items (76.6%). The experts agreed that complete control and remission of CU could be defined as the absence of signs or symptoms while on treatment and in the absence of treatment, respectively. Consensus was not reached on the definition of other key terms such as flare-up, exacerbation, and recurrence. The panel agreed that the objective of therapy in CU should be to achieve complete control. PROs that define the degree of control (complete, good, partial, or absence) were established. An algorithm for disease assessment is provided. In conclusion, this work offers consensus definitions and tools that may be useful in the management of patients with CU.

Mental impact of Covid-19 among Spanish healthcare workers. A large longitudinal survey.

AIMS: Longitudinal data on the mental health impact of the coronavirus disease 2019 (Covid-19) pandemic in healthcare workers is limited. We estimated prevalence, incidence and persistence of probable mental disorders in a cohort of Spanish healthcare workers (Covid-19 waves 1 and 2) -and identified associated risk factors. METHODS: 8996 healthcare workers evaluated on 5 May-7 September 2020 (baseline) were invited to a second web-based survey (October-December 2020). Major depressive disorder (PHQ-8 ≥ 10), generalised anxiety disorder (GAD-7 ≥ 10), panic attacks, post-traumatic stress disorder (PCL-5 ≥ 7), and alcohol use disorder (CAGE-AID ≥ 2) were assessed. Distal (pre-pandemic) and proximal (pandemic) risk factors were included. We estimated the incidence of probable mental disorders (among those without disorders at baseline) and persistence (among those with disorders at baseline). Logistic regression of individual-level [odds ratios (OR)] and population-level (population attributable risk proportions) associations were estimated, adjusting by all distal risk factors, health care centre and time of baseline interview. RESULTS: 4809 healthcare workers participated at four months follow-up (cooperation rate = 65.7%; mean = 120 days s.d. = 22 days from baseline assessment). Follow-up prevalence of any disorder was 41.5%, (v. 45.4% at baseline, p < 0.001); incidence, 19.7% (s.e. = 1.6) and persistence, 67.7% (s.e. = 2.3). Proximal factors showing significant bivariate-adjusted associations with incidence included: work-related factors [prioritising Covid-19 patients (OR = 1.62)], stress factors [personal health-related stress (OR = 1.61)], interpersonal stress (OR = 1.53) and financial factors [significant income loss (OR = 1.37)]. Risk factors associated with persistence were largely similar. CONCLUSIONS: Our study indicates that the prevalence of probable mental disorders among Spanish healthcare workers during the second wave of the Covid-19 pandemic was similarly high to that after the first wave. This was in good part due to the persistence of mental disorders detected at the baseline, but with a relevant incidence of about 1 in 5 of HCWs without mental disorders during the first wave of the Covid-19 pandemic. Health-related factors, work-related factors and interpersonal stress are important risks of persistence of mental disorders and of incidence of mental disorders. Adequately addressing these factors might have prevented a considerable amount of mental health impact of the pandemic among this vulnerable population. Addressing health-related stress, work-related factors and interpersonal stress might reduce the prevalence of these disorders substantially. Study registration number: NCT04556565.

Long non-coding RNA H19 as a biomarker for hepatocellular carcinoma.

BACKGROUND AND AIMS: Liver cancer stem cells (CSCs) could be involved in the carcinogenesis, recurrence, metastasis and chemoresistance of hepatocellular carcinoma (HCC). The aim of this study was to explore the role of lncRNA-H19 as a biomarker for liver cancer. METHODS: LncRNA-H19 expression levels and the functional assays were conducted in EpCAM+ CD133+ CSCs and C57BL/6J mice fed with a high-fat high-cholesterol carbohydrate (HFHCC) or standard diet for 52 weeks. Liver tissue and plasma samples from patients with cirrhosis, with or without HCC, were used for the analyses of gene expression and circulating lncRNA-H19 levels in an estimation and validation cohort. RESULTS: EpCAM+ CD133+ cells showed a stem cell-like phenotype, self-renewal capacity, upregulation of pluripotent gene expression and overexpressed lncRNA-H19 (p < .001). Suppression of lncRNA-H19 by antisense oligonucleotide treatment significantly reduced the self-renewal capacity (p < .001). EpCAM, CD133 and lncRNA-h19 expression increased accordingly with disease progression in HFHCC-fed mice (p < .05) and also in liver tissue from HCC patients (p = .0082). Circulating lncRNA-H19 levels were significantly increased in HCC patients in both cohorts (p = .013; p < .0001). In addition, lncRNA-H19 levels increased accordingly with BCLC staging (p < .0001) and decreased after a partial and complete therapeutic response (p < .05). In addition, patients with cirrhosis who developed HCC during follow-up showed higher lncRNA-H19 levels (p = .0025). CONCLUSION: LncRNA-H19 expression was increased in CSCs, in liver tissue and plasma of patients with HCC and decreased after partial/complete therapeutic response. Those patients who developed HCC during the follow-up showed higher levels of lncRNA-H19. LncRNA-H19 could constitute a new biomarker of HCC.

Discovery of a functionally selective ghrelin receptor (GHSR1a) ligand for modulating brain dopamine.

SignificanceThe modulation of growth hormone secretagogue receptor-1a (GHSR1a) signaling is a promising strategy for treating brain conditions of metabolism, aging, and addiction. GHSR1a activation results in pleiotropic physiological outcomes through distinct and pharmacologically separable G protein- and ß-arrestin (ßarr)-dependent signaling pathways. Thus, pathway-selective modulation can enable improved pharmacotherapeutics that can promote therapeutic efficacy while mitigating side effects. Here, we describe the discovery of a brain-penetrant small molecule, N8279 (NCATS-SM8864), that biases GHSR1a conformations toward Gαq activation and reduces aberrant dopaminergic behavior in mice. N8279 represents a promising chemical scaffold to advance the development of better treatments for GHSR1a-related brain disorders involving the pathological dysregulation of dopamine.

Four-month incidence of suicidal thoughts and behaviors among healthcare workers after the first wave of the Spain COVID-19 pandemic.

Healthcare workers (HCW) are at high risk for suicide, yet little is known about the onset of suicidal thoughts and behaviors (STB) in this important segment of the population in conjunction with the COVID-19 pandemic. We conducted a multicenter, prospective cohort study of Spanish HCW active during the COVID-9 pandemic. A total of n = 4809 HCW participated at baseline (May-September 2020; i.e., just after the first wave of the pandemic) and at a four-month follow-up assessment (October-December 2020) using web-based surveys. Logistic regression assessed the individual- and population-level associations of separate proximal (pandemic) risk factors with four-month STB incidence (i.e., 30-day STB among HCW negative for 30-day STB at baseline), each time adjusting for distal (pre-pandemic) factors. STB incidence was estimated at 4.2% (SE = 0.5; n = 1 suicide attempt). Adjusted for distal factors, proximal risk factors most strongly associated with STB incidence were various sources of interpersonal stress (scaled 0-4; odds ratio [OR] range = 1.23-1.57) followed by personal health-related stress and stress related to the health of loved ones (scaled 0-4; OR range 1.30-1.32), and the perceived lack of healthcare center preparedness (scaled 0-4; OR = 1.34). Population-attributable risk proportions for these proximal risk factors were in the range 45.3-57.6%. Other significant risk factors were financial stressors (OR range 1.26-1.81), isolation/quarantine due to COVID-19 (OR = 1.53) and having changed to a specific COVID-19 related work location (OR = 1.72). Among other interventions, our findings call for healthcare systems to implement adequate conflict communication and resolution strategies and to improve family-work balance embedded in organizational justice strategies.

A Specialized Therapeutic Approach to Chronic Urticaria Refractory to H1-Antihistamines Improves Disease Burden: The Spanish AWARE Experience.

OBJECTIVE: During its first year, the AWARE study assessed disease activity, patient quality of life (QOL), and treatment patterns in chronic urticaria (CU) refractory to H1-antihistamines (H1-AH) in clinical practice. METHODS: We performed an observational, prospective (24 months), international, multicenter study. The inclusion criteria were age ≥18 years and H1-AH-refractory CU (>2 months). At each visit, patients completed questionnaires to assess disease burden (Urticaria Control Test [UCT]), disease activity (7 day-Urticaria Activity Score [UAS7]), and QOL (Dermatology Life Quality index [DLQI], Chronic Urticaria Quality of Life Questionnaire [CU-Q2oL], and Angioedema Quality of Life Questionnaire [AE-QoL]). We present data for Spain. RESULTS: The study population comprised 270 evaluable patients (73.3% female, mean [SD] age, 48.9 [14.7] years). At baseline, 89.3% were prescribed a CU treatment. After 1 year, first- and second-line treatments became less frequent and third-line treatments became more frequent. At baseline, 47.0% of patients experienced angioedema; at 1 year, this percentage had fallen to 11.8%. The mean (SD) AE-QoL score decreased from 45.2 (28.7) to 24.0 (25.8). The mean (SD) UCT score decreased from 7.0 (4.5) to 12.1 (4.1). According to UAS7, 38.2% of patients reported absence of wheals and itch in the previous 7 days at 1 year compared with 8.3% at baseline. The mean (SD) DLQI score decreased from 8.0 (7.4) to 2.8 (4.6). At the 1-year visit, the percentage of patients reporting a high or very high impact on QOL fell from 29.9% to 9.6%. CONCLUSION: H1-AH-refractory CU in Spain is characterized by absence of control of symptoms and a considerable impact on QOL. Continuous follow-up of CU patients and third-line therapies reduce disease burden and improve patients' QOL.

Changes in serum testosterone and anti-Müllerian hormone concentration in bulls undergoing scrotal insulation.

While changes in semen quality after heat stress are well characterized in the bull, changes in endocrine function have not been critically evaluated. It was hypothesized here that scrotal insulation results in alterations in Sertoli cell and Leydig cell function, as measured by changes in serum testosterone and anti-Müllerian hormone (AMH) concentration. Scrotal insulation bags were placed in 10 bulls for 8 d. Blood was collected on days -22 and -2, and weekly from days 5 to 96 (day 0 = first day of scrotal insulation) for measurement of serum concentration of AMH and testosterone using ELISA. The concentration of AMH decreased on day 5, followed by an increase on day 54 (P = 0.014). When AMH concentration was normalized to pre-insulation values, the percent increase in serum concentration of AMH was significant between days 26 and 54, with another peak at 75 d (P = 0.031). The serum concentration of testosterone (P = 0.0001) and the percentage of change in testosterone concentration (P < 0.0001) increased on day 5, followed by a decrease from days 33 to 96. Scrotal insulation was associated with Sertoli and Leydig cell dysfunction, as measured by serum testosterone and AMH concentration. The persistently low concentration of testosterone at the end of the study suggests a long term effect of scrotal insulation on Leydig cell function.

Unraveling the Diagnosis of Kiwifruit Allergy: Usefulness of Current Diagnostic Tests.

OBJECTIVES: To determine the usefulness of the in vitro and in vivo methods used in the diagnosis of kiwifruit allergy and to specifically assess the impact of seed proteins on sensitivity. METHODS: We performed skin prick tests (SPTs) using various commercial extracts, homemade pulp, and seed extracts and prick-prick tests with kiwifruit on 36 allergic patients. The presence of specific IgE (sIgE) was assessed using the ImmunoCAP (kiwifruit extract), ELISA (Act d 1, Act d 2), ISAC, and FABER assays. Immunoblotting of seed extract was carried out, and a single-blind oral food challenge was performed with whole seeds in seed-sensitized individuals. RESULTS: The prick prick test with kiwifruit demonstrated the highest diagnostic capacity (81.8% sensitivity and 94.1% specificity) among the in vivo tests. The sIgE levels measured using ImmunoCAP (kiwifruit extract) showed a similar sensitivity to that of global ISAC and FABER (63.9%, 59.5%, and 58.3%, respectively). Act d 1 was the major allergen. Sensitization to Act d 1 was associated with positive sIgE results to whole kiwifruit extract detected by ImmunoCAP (P<.000). A positive SPT result to kiwifruit seeds was associated with severe symptoms induced by kiwifruit (P=.019) as a marker of advanced disease, but not with clinically relevant sensitization. Challenge testing with kiwifruit seeds performed on 8 seed-sensitized patients yielded negative results. CONCLUSION: Sensitization to Act d 1 is associated with a positive result in conventional diagnostic techniques, whereas kiwifruit seed sensitization does not increase the sensitivity of the diagnostic techniques evaluated.