Fluconazole-resistant Candida parapsilosis: fast detection of the Y132F ERG11p substitution, and a proposed microsatellite genotyping scheme.

OBJECTIVES: We propose fast and accurate molecular detection of the Y132F ERG11p substitution directly on pure-cultured C. parapsilosis isolates. We also assessed a discriminative genotyping scheme to track circulating genotypes. METHODS: A total of 223 C. parapsilosis isolates (one patient each) from 20 hospitals, located in Spain and Italy were selected. Isolates were fluconazole-resistant (n=94; harbouring the Y132F ERG11p substitution [n=85], the G458S substitution [n=6], the R398I substitution [n=2], or the wild-type ERG11 gene sequence) or fluconazole-susceptible (n=129). Two targeted-A395T-mutation PCR formats (conventional and real-time) were engineered and optimized on fluconazole-susceptible and fluconazole-resistant pure-cultured isolates, thus skipping DNA extraction. Two genotyping schemes were compared: Scheme 1 (CP1, CP4a, CP6, and B markers), and Scheme 2 (6A, 6B, 6C, CP1, CP4a, and CP6 markers). RESULTS: The screening performed using both PCR formats showed 100% specificity (fluconazole-susceptible isolates; n=129/129) and sensitivity (Y132F isolates; n=85/85) values, however, results were available in 3 and 1.5 hours with the conventional and real-time PCR formats, respectively. Overall, Scheme 1 showed higher genetic diversity than Scheme 2, as shown by the number of alleles detected (n=98; mean 23, range 13-38), the significantly higher observed and expected heterozygosity, and the probability of identity index (2.5x10-6). Scheme 2 markers did not provide further genotypic discrimination of Y132F fluconazole-resistant genotypes. CONCLUSION: Both proposed PCR formats allow to speed up the accurate detection of substitution Y132F ERG11p in C. parapsilosis isolates with 100% specificity and sensitivity. In addition, we recommend CP1, CP4a, CP6, and B microsatellite markers for genotyping fluconazole-resistant isolates.

Prevalence of Paslahepevirus balayani in commercial swine food products from Spain.

Paslahepevirus balayani (formerly known as hepatitis E virus) is an emerging cause of foodborne disease in Europe, transmitted mainly by the consumption of raw or undercooked pork. Since little is known about the presence of the virus in several pork products that are eaten uncooked, our aim was to evaluate the prevalence of Paslahepevirus balayani in groups of commercial pork products intended for human consumption subjected to different processing techniques. A total of 1265 samples of pork products from Spain were divided into four groups and tested for the presence of Paslahepevirus balayani RNA: unprocessed pig and wild boar meat frozen at -20 °C (n = 389), dry-cured pork products (n = 391), dry-cured and salted pork products (n = 219), and boiled products (n = 266) (none of these products contained pork liver). Five samples were positive for Paslahepevirus balayani RNA (overall prevalence: 0.4%; 95% CI: 0.17% - 0.92%). All positive samples were from unprocessed meat stored at -20 °C, with a prevalence in this group of 1.3% (95% CI: 0.42-3.44); two samples came from pigs (1.1%; 95% CI: 0.13-3.81) and three from wild boar (1.5%; 95% CI: 0.31-4.28). None of the pork samples in the other groups was positive. In conclusion, Paslahepevirus balayani was found in unprocessed swine products form Spain, but not in processed products intended to be consumed undercooked, demonstrating that transmission of this zoonotic virus by eating these pork products should be more seriously considered.

Psychological intervention in women victims of childhood sexual abuse: a randomized controlled clinical trial comparing EMDR psychotherapy and trauma-focused cognitive behavioral therapy.

Introduction: Childhood sexual abuse persists as a painful societal reality, necessitating responses from institutions and healthcare professionals to prevent and address its severe long-term consequences in victims. This study implements an intervention comprising two psychotherapeutic approaches recommended by the WHO and international clinical guidelines for addressing short-, medium-, and long-term posttraumatic symptomatology: Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) and Eye Movement Desensitization and Reprocessing (EMDR). Both approaches are adapted from group formats for implementation in small online groups via Zoom. Methods: The impact of both therapeutic approaches on trauma improvement was assessed in a sample of 19 women who were victims of childhood sexual abuse through a Randomized Clinical Trial comparing EMDR Psychotherapy and Trauma-Focused Cognitive Behavioral Therapy after a baseline period. Intra and inter comparison were made using statistics appropriate to the sample. Results: Both therapeutic approaches significantly reduced symptomatology across various evaluated variables, suggesting their efficacy in improving the quality of life for these individuals. Following CBT-FT treatment, patients exhibited enhanced emotional regulation, reduced reexperiencing, and avoidance. The EMDR group, utilizing the G-TEP group protocol, significantly improved dissociation, along with other crucial clinical variables and the perception of quality of life. Discussion: Although the limitations of this study must be taken into account due to the size of the sample and the lack of long-term follow-up, the results align with existing scientific literature, underscoring the benefits of trauma-focused psychological treatments. The online group format appears promising for enhancing the accessibility of psychological treatment for these women. Furthermore, the differential outcomes of each treatment support recent research advocating for the inclusion of both approaches for individuals with trauma-related symptomatology. Ethics and dissemination: The study has been approved by the Ethics Committee of the Valencian International University (VIU) (Valencia, Spain) (Ref. CEID2021_07). The results will be submitted for publication in peer-reviewed journals and disseminated to the scientific community. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04813224, identifier NCT04813224.

Ultrasound Cut-Off Values for Rectus Femoris for Detecting Sarcopenia in Patients with Nutritional Risk.

BACKGROUND: A nationwide, prospective, multicenter, cohort study (the Disease-Related caloric-protein malnutrition EChOgraphy (DRECO) study) was designed to assess the usefulness of ultrasound of the rectus femoris for detecting sarcopenia in hospitalized patients at risk of malnutrition and to define cut-off values of ultrasound measures. METHODS: Patients at risk of malnutrition according to the Malnutrition Universal Screening Tool (MUST) underwent handgrip dynamometry, bioelectrical impedance analysis (BIA), a Timed Up and Go (TUG) test, and rectus femoris ultrasound studies. European Working Group on Sarcopenia in Older People (EWGSOP2) criteria were used to define categories of sarcopenia (at risk, probable, confirmed, severe). Receiver operating characteristic (ROC) and area under the curve (AUC) analyses were used to determine the optimal diagnostic sensitivity, specificity, and predictive values of cut-off points of the ultrasound measures for the detection of risk of sarcopenia and probable, confirmed, and severe sarcopenia. RESULTS: A total of 1000 subjects were included and 991 of them (58.9% men, mean age 58.5 years) were evaluated. Risk of sarcopenia was detected in 9.6% patients, probable sarcopenia in 14%, confirmed sarcopenia in 9.7%, and severe sarcopenia in 3.9%, with significant differences in the distribution of groups between men and women (p < 0.0001). The cross-sectional area (CSA) of the rectus femoris showed a significantly positive correlation with body cell mass of BIA and handgrip strength, and a significant negative correlation with TUG. Cut-off values were similar within each category of sarcopenia, ranging between 2.40 cm2 and 3.66 cm2 for CSA, 32.57 mm and 40.21 mm for the X-axis, and 7.85 mm and 10.4 mm for the Y-axis. In general, these cut-off values showed high sensitivities, particularly for the categories of confirmed and severe sarcopenia, with male patients also showing better sensitivities than women. CONCLUSIONS: Sarcopenia in hospitalized patients at risk of malnutrition was high. Cut-off values for the better sensitivities and specificities of ultrasound measures of the rectus femoris are established. The use of ultrasound of the rectus femoris could be used for the prediction of sarcopenia and be useful to integrate nutritional study into real clinical practice.

The Weight of Bariatric Surgery: Wernicke-Korsakoff Syndrome after Vertical Sleeve Gastrectomy-A Case Series.

In this case series, the simultaneous occurrence of Wernicke's encephalopathy (WE) and dry beriberi was reported in three patients who underwent vertical sleeve gastrectomy (VSG) between May 2021 and May 2023. All patients were obese women who underwent vertical sleeve gastrectomy (VSG) without immediate postoperative complications, but two weeks later, hyperemesis and subsequent encephalopathy with ocular movement abnormalities and weakness were observed over the following thirty days. Patients were referred to neurology, where due to the high suspicion of WE, thiamine replacement therapy was initiated; meanwhile, diagnostic neuroimaging and blood tests were conducted. Neurological and psychiatric evaluations and neuroconduction studies were performed to assess the clinical evolution and present sequelae. One year after diagnosis, all patients exhibited affective and behavioral sequelae, anterograde memory impairment, and executive functioning deficits. Two patients met the criteria for Korsakoff syndrome. Additionally, peripheral nervous system sequelae were observed, with all patients presenting with sensorimotor polyneuropathy. In conclusion, Wernicke's encephalopathy requires a high diagnostic suspicion for timely intervention and prevention of irreversible sequelae, which can be devastating. Therefore, raising awareness among medical professionals regarding the significance of this disease is essential.

Perceived quality of life in patients with psoriasis treated with interleukin 17 or 23 inhibitors.

OBJECTIVE: To determine the effectiveness in terms of quality of life perceived by adult patients with moderate/severe plaque psoriasis treated with interleukin 17 or 23 inhibitors and to identify associated factors. METHOD: Cross-sectional observational study including adult patients diagnosed with moderate/severe plaque psoriasis treated with interleukin 17 or 23 inhibitors for at least 12 or 16 weeks in follow-up, respectively. RESULTS: Forty-one patients were included: 65% male, median age 54 years (SD=13). The included patients were treated with ixekizumab 35%, guselkumab 25%, secukinumab 17.5%, brodalumab 15%, and risankizumab 7.5%. Psoariasis area severity index (PASI) reduction was 94.6% (RIC 76.8-100%), DLQI of 1 (RIC 0-2.75), DLQI≤1 60%. The most affected health dimensions were symptoms and perceptions (57.5%), activities of daily living (27.5%), and discomfort caused with treatment (17.5%). No association was found between DLQI score <1 and demographic, comorbidities, and treatment-related variables. The median PASI reduction in patients with DLQI<1 was superior to patients with DLQI>1 (100% vs 90.2%, p=.025). CONCLUSIONS: Patients with moderate/severe plaque psoriasis treated with interleukin 17 or 23 inhibitors achieve adequate therapeutic targets achieving the target set according to clinical practice guideline recommendations (score ≤1 on the DLQI questionnaire and 90-100% reduction in the PASI index) and in accordance with the results of recent meta-analyses and real-life studies. A greater reduction of the PASI index is observed in the group reaching the quality of life target, there being the possibility of using patient-reported outcomes in the evaluation of treatment effectiveness.

[Abordaje y atención a la cronicidad con tecnologías digitales en las políticas sanitarias en España]. / Approach and attention to chronicity with digital technologies in health policies in Spain.

OBJECTIVE: From the healthcare policies that support Public Health strategies, technology implementation in healthcare is an innovative element to address chronicity. Its introduction is not uniform across Spain, despite of the existence of digital strategic implementation and national chronicity plans. The aim of this paper was to explore the current deployment of autonomic strategies for chronicity and the implementation of digital tools for telemonitoring and user support. METHODS: A descriptive cross-sectional study was conducted through documental review of autonomous strategies in digital health and chronicity care, available until 2020. Consequently, a consultation was carried out to eighteen experts addressing autonomic availability, benefits and barriers to healthcare digitalization. RESULTS: The expert consultation revealed that, in fifteen autonomous communities, the use and the enhancement of digital technologies were addressed and in nine the focus was on promoting digital transformation. Eleven communities are working on updates, fourteen have health-related digital applications, thirteen allow users checking their test results, ten allow them to carry out administrative procedures, nine deliver patient support resources, and three provide telematic communication channels. 38.89% of the consulted refered not knowing about the existence of any follow-up and monitoring programs in their community. The 60% identified a gap in digital competencies among citizens and the lack of resources, as main barriers to implementation. CONCLUSIONS: There exists disparity in the update of strategies to address chronicity and the introduction of digital technologies. Many of them are currently updating, which is an opportunity to provide efficient responses that incorporate digital tools.

OBJECTIVE: La implementación de tecnologías digitales supone un elemento innovador para el abordaje de la cronicidad, como parte de las estrategias de Salud Pública. Su implantación es variable a nivel autonómico, pese a existir un plan nacional. Este trabajo pretendió conocer el despliegue de las estrategias autonómicas sobre cronicidad, así como de la implementación de opciones de telemonitorización y apoyo al usuario. METHODS: Se realizó un estudio descriptivo transversal mediante revisión documental de las estrategias autonómicas de salud digital y abordaje de la cronicidad disponibles hasta 2020. Se realizó una posterior consulta a dieciocho personas expertas sobre disponibilidad autonómica, beneficios y barreras a la digitalización de la atención sanitaria. RESULTS: La consulta a personas expertas reveló que quince comunidades autónomas abordaron el uso y la potenciación de tecnologías digitales y nueve trabajaron en favorecer la trasformación digital. Once comunidades trabajan en actualizaciones, catorce tienen aplicaciones digitales de salud, trece permiten a los ciudadanos consultar resultados de pruebas, diez permiten trámites administrativos, nueve ofrecen recursos de apoyo al paciente y tres disponen de canales telemáticos de comunicación. El 38,89% de los consultados refirió no conocer los programas de seguimiento y monitorización en su comunidad. El 60% identificó a la falta de competencias digitales de la ciudadanía y a la falta de recursos como barreras de su implantación. CONCLUSIONS: Existe disparidad en la actualización de estrategias para el abordaje de la cronicidad y la implantación de tecnologías digitales. Muchas de ellas se están actualizando, lo que supone una oportunidad para dar respuestas eficientes que incorporen las herramientas digitales.

Postmortem imaging reveals patterns of medial temporal lobe vulnerability to tau pathology in Alzheimer's disease.

Our current understanding of the spread and neurodegenerative effects of tau neurofibrillary tangles (NFTs) within the medial temporal lobe (MTL) during the early stages of Alzheimer's Disease (AD) is limited by the presence of confounding non-AD pathologies and the two-dimensional (2-D) nature of conventional histology studies. Here, we combine ex vivo MRI and serial histological imaging from 25 human MTL specimens to present a detailed, 3-D characterization of quantitative NFT burden measures in the space of a high-resolution, ex vivo atlas with cytoarchitecturally-defined subregion labels, that can be used to inform future in vivo neuroimaging studies. Average maps show a clear anterior to poster gradient in NFT distribution and a precise, spatial pattern with highest levels of NFTs found not just within the transentorhinal region but also the cornu ammonis (CA1) subfield. Additionally, we identify granular MTL regions where measures of neurodegeneration are likely to be linked to NFTs specifically, and thus potentially more sensitive as early AD biomarkers.

Nanosilver-based materials as feed additives: Evaluation of their transformations along in vitro gastrointestinal digestion in pigs and chickens by using an ICP-MS based analytical platform.

The use of a new nanomaterial in the feed chain requires a risk assessment that involves in vitro gastrointestinal digestions to predict its degradation and oral exposure to nanoparticles. In this study, a nanosilver-based material was incorporated into pig and chicken feed as a growth-promoting additive and subjected to the corresponding in vitro gastrointestinal digestions. An inductively coupled plasma mass spectroscopy (ICP-MS) analytical platform was used to obtain information about the silver released in the different digestion phases. It included conventional ICP-MS for total silver determination, but also single particle ICP-MS and coupling to hydrodynamic chromatography for detection of dissolved and particulate silver. The bioaccessible fraction in the intestinal phase accounted for 8-13% of the total silver, mainly in the form of dissolved Ag(I) species, with less than 0.1% as silver-containing particles. Despite the additive behaving differently in pig and chicken digestions, the feed matrix played a relevant role in the fate of the silver.

Exploring the impact of silver-based nanomaterial feed additives on green algae through single-cell techniques.

Silver in its various forms, including dissolved silver ions (Ag+) and silver nanoparticles (AgNPs), is a promising alternative to traditional antibiotics, largely used in livestock as feed additives and could contribute to the decrease and avoidance of the development of antibiotic resistance. The present study aims to assess the potential ecotoxicity of a silver-based nanomaterial (Ag-kaolin), the feed supplemented with the nanomaterial and the faeces since the latter are the ones that finally reach the environment. To this end, green alga Raphidocellis subcapitata was exposed to the extracts of Ag-kaolin, supplemented feed, and pig faeces for 72 h, along with Ag+ and AgNPs as controls for comparison purposes. Given the complexity of the studied materials, single-cell techniques were used to follow the changes in the cell numbers and chlorophyll fluorescence by flow cytometry, and the accumulation of silver in the exposed cells by single cell inductively coupled plasma mass spectrometry (SC-ICP-MS). Changes in cell morphology were observed by cell imaging multimode reader. The results revealed a decrease in chlorophyll fluorescence, even at low concentrations of Ag-kaolin (10 µg L-1) after 48 h of exposure. Additionally, complete growth inhibition was found with this material like the results obtained by exposure to Ag+. For the supplemented feed, a concentration of 50 µg L-1 was necessary to achieve complete growth inhibition. However, the behaviour differed for the leachate of faeces, which released Ag2S and AgCl alongside Ag+ and AgNPs. At 50 µg L-1, inhibition was minimal, primarily due to the predominance of less toxic Ag2S in the leachate. The uptake of silver by the cells was confirmed with all the samples through SC-ICP-MS analysis. These findings demonstrate that the use of Ag-kaolin as a feed supplement will lead to a low environmental impact.

Evolutionary analysis of indeterminate cytology and risk of malignancy in a thyroid nodule unit.

OBJECTIVE: The objective of this study was to analyze the evolution in the diagnosis and management of indeterminate thyroid nodules over three time periods. METHODS: 3020 patients with thyroid nodules underwent cytological evaluation during three periods (2006-2008, 2012-2014, 2017-2019). Distribution of diagnostic cytologies, risk of malignancy, diagnostic performance indices of FNA, and cytologic-histologic correlation in indeterminate cytologies were analyzed. RESULTS: only 2.2% of cytology tests were insufficient for a diagnosis. 86.9% cytologies were benign, 1.7% malignant, and 11.4% indeterminate. Indeterminate cytology rates were 15.9% (2006-2008), 10.1% (2012-2014), and 10% (2017-2019). Surgery was performed in 13% of benign cytology, result-ing in malignant histology in 2.7%. All malignant and suspicious cytologies underwent surgery: malig-nancy confirmed in 98% and 77% of cases, respectively. All 'indeterminate with atypia' cytologies (2006-2008) and Bethesda IV (2012-2014; 2017-2019) un-derwent surgery, with malignancy confirmed in 19.6%, 43.8%, and 25.7%, respectively. In the 'inde-terminate without atypia' category (2006-2008) and Bethesda III (2012-2014; 2017-2019), diagnostic surgery was performed in 57.7%, 78.6%, and 59.4%, respectively, with malignancy confirmed in 3.3%, 20.5%, and 31.6%. The FNA sensitivity was 91.6% with a negative predictive value greater than 96% in all periods. The specificity exceeded 75% in the last two periods. CONCLUSION: Bethesda system reduces indeterminate cytologies and improves the accuracy of FNA diagnosis. We reported a higher proportion of malignancy than expected in Bethesda III, underscoring the importance of having institution-specific data to guide decision-making. However, there is a need for risk stratification tools that allow for conservative management in low-risk cases.

Synergistic Enhancement of Targeted Wound Healing by Near-Infrared Photodynamic Therapy and Silver Metal-Organic Frameworks Combined with S- or N-Doped Carbon Dots.

The literature data emphasize that nanoparticles might improve the beneficial effects of near-infrared light (NIR) on wound healing. This study investigates the mechanisms of the synergistic wound healing potential of NIR light and silver metal-organic frameworks combined with nitrogen- and sulfur-doped carbon dots (AgMOFsN-CDs and AgMOFsS-CDs, respectively), which was conducted by testing the fibroblasts viability, scratch assays, biochemical analysis, and synchrotron-based Fourier transform infrared (SR-FTIR) cell spectroscopy and imaging. Our findings reveal that the combined treatment of AgMOFsN-CDs and NIR light significantly increases cell viability to nearly 150% and promotes cell proliferation, with reduced interleukin-1 levels, suggesting an anti-inflammatory response. SR-FTIR spectroscopy shows this combined treatment results in unique protein alterations, including increased α-helix structures and reduced cross-ß. Additionally, protein synthesis was enhanced upon the combined treatment. The likely mechanism behind the observed changes is the charge-specific interaction of N-CDs from the AgMOFsN-CDs with proteins, enhanced by NIR light due to the nanocomposite's optical characteristics. Remarkably, the complete wound closure in the in vitro scratch assay was achieved exclusively with the combined NIR and AgMOFsN-CDs treatment, demonstrating the promising application of combined AgMOFsN-CDs with NIR light photodynamic therapy in regenerative nanomedicine and tissue engineering.

Epileptic encephalopathies secondary to hypothalamic hamartomas treated with radiosurgery: A case series.

OBJECTIVE: Hypothalamic hamartomas are congenital lesions that typically present with gelastic seizures, refractory epilepsy, neurodevelopmental delay, and severe cognitive impairment. Surgical procedures have been reported to be effective in removing the hamartomas, however, they are associated with significant morbidity. Therefore, it is not considered a safe therapeutic modality. Image-guided robotic radiosurgery (CyberKnife® Radiosurgery System) has been shown to provide good outcomes without lasting complications. METHODS: This series of cases describes the clinical, radiological, radiotherapeutic, and postsurgical outcomes of five patients with epileptic encephalopathies secondary to hypothalamic hamartomas who were treated with CyberKnife®. RESULTS: All patients exhibited refractory epilepsy with gelastic seizures and were unsuitable candidates for surgical resection The prescribed dose ranged between 16 and 25 Gy, delivered in a single fraction for four patients and five fractions for one patient while adhering strictly to visual pathway constraints. After radiosurgery, four patients maintained seizure control (one with an Engel class Ia, three with an Engel class 1d), and another presented sporadic, nondisabling gelastic seizures (with an Engel class IIa). After 24-26 months of follow-up, in three patients, their intelligence quotient scores increased. No complications were reported. SIGNIFICANCE: This report suggests that Cyberknife may be a good option for treating hypothalamic hamartoma, particularly in cases where other noninvasive alternatives are unavailable. Nevertheless, additional studies are essential in order to evaluate the effectiveness of the technique in these cases.

Carotid-femoral pulse wave velocity score, an estimator of cognitive performance in the elderly: results from the Toledo Study for Healthy Aging.

Ageing-related changes in the vascular wall influence the function of different organs; for this reason, we assessed how arterial stiffness measured by carotid-femoral pulse wave velocity (cf-PWV) modulates: the basal cognitive performance and the change in cognitive performance over the follow-up time. We developed a prospective, population-based cohort study with 1581 participants aged > 65 years were obtained from the Toledo Study for Healthy Aging. Participants from the second wave (2011-2013) were selected for the cross-sectional analysis. Those who also performed the cognitive assessment in the third wave (2015-2017) were selected for the prospective analysis. Arterial stiffness was evaluated by cf-PWV. Multivariate segmented regression models were used to evaluate the association between cf-PWV scores and basal neuropsychological evaluation scores and change of neuropsychological evaluation scores along follow-up. Cross-sectional analysis showed that as cf-PWV grew within the cf-PWV (5- < 10) category an improvement was observed in 7-min test, free short-term memory, and hole peg test. Furthermore, in the cf-PWV (> 13-18) category a decrease was observed in total short-term memory, free long-term memory, and total long-term memory. Prospective analysis showed a progressive worsening of cognitive function as cf-PWV increases within the cf-PWV (> 13-18) category in 7-min test, object denomination, immediate and short-term memory, and hole peg test, while in the cf-PWV (5- < 10) category, there was observed a decrease in Cumulative Executive Dysfunction Index score and short-term memory. In conclusion, a higher cf-PWV score is associated with worse cognitive performance, and with a worse evolution, reinforcing the need to plan interventions to delay arterial stiffness and its consequences.

Hereditary angioedema in Spain: medical care and patient journey.

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) is a genetic rare disease characterized by recurrent, transient and unpredictable episodes of cold, non-pruriginous oedema without associated urticaria. The characteristics of the disease have a considerable impact on the quality of life of patients. The aim of this study was to increase understanding of the patient journey of HAE in Spain. METHODS: A multidisciplinary committee of 16 HAE experts (allergy, immunology, emergency department, hospital pharmacy and nursing) and 3 representatives of the Spanish Hereditary Angioedema Patient Association (AEDAF) who were patients or caregivers participated in the study. A review of the publications on HAE treatment was performed. Semi-structured interviews were performed to HAE experts, patients, or caregivers. Three meetings with the experts, patients and caregivers were held to share, discuss, and validate data obtained from literature and interviews and to build the model. RESULTS: Throughout the project, the patient journey has been drawn up, dividing it into the stages of pre-diagnosis, diagnosis and treatment/follow-up. Some areas for improvement have been identified. Firstly, there is a need to enhance awareness and training on HAE among healthcare professionals, with a particular emphasis on primary care and emergency department personnel. Secondly, efforts should be made to minimize patient referral times to allergy/immunology specialists, ensuring timely access to appropriate care. Thirdly, it is crucial to encourage the study of the relatives of diagnosed patients to early identify potential cases. Fourthly, equitable access to self-administered treatments should be ensured, facilitated by systems that enable medication delivery at home and proper education and training for patients. Equitable access to long-term prophylactic treatment should also be prioritized for all patients in need. To standardize HAE management, the development of consensus guidelines that reduce variability in clinical practice is essential. Lastly, promoting research studies to enhance knowledge of the disease and align its treatment with new developments in the healthcare field should be encouraged. CONCLUSIONS: The knowledge of the patient journey in HAE allowed us to identify improvement areas with the final aim to optimize the disease management.

Acute Hepatitis in Children Due to Rat Hepatitis E Virus.

Two of 11 children with acute hepatitis of unknown origin were found to have rat hepatitis E virus infection. This infection should be considered in the differential diagnosis of children with acute hepatitis of unknown origin.

Nivel de ansiedad y miedo al covid-19 en médicos de la contingencia respiratoria del Hospital de Clínicas, durante la pandemia por el SARS-COV-2 / Anxiety and covid-19 fear in respiratory contingency of Clinical Hospital physicians during SARS-COV-2 pandemic

Introducción: Como ocurrió en todos los hospitales, los profesionales del Hospital de Clínicas sufrieron elevada presión física y psicológica. Estudios previos, sobre todo realizados en China, ya sugerían que los profesionales sanitarios eran especialmente vulnerables al malestar psicológico derivado de la pandemia. Objetivos: Determinar el nivel de ansiedad y miedo al COVID 19 en los médicos del área de Contingencia respiratoria del Hospital de Clínicas. Materiales y métodos: Se realizó un estudio observacional, descriptivo, de corte transverso, de muestreo no probabilístico por conveniencia, en individuos de ambos sexos, mayores de 18 años, en médicos del área de Contingencia respiratoria del Hospital de Clínicas de San Lorenzo durante la pandemia por el SARS-COV2. Resultados: Fueron encuestados 68 médicos, de los cuales el 63% fueron del sexo femenino, la edad promedio de los participantes fue de 31 años (±4,48). La mayoría de los encuestados fueron residentes. El 75% pertenecen a la especialidad de Medicina Interna. El 30.8% cuenta con 4 dosis de vacuna contra el SARSCOV 2. Presentaron síntomas de miedo al COVID-19 el 44,1%, de los cuales, los síntomas más frecuentes fueron: miedo a infectarse con el COVID-19 48,5%; incomodidad al pensar en el COVID19 39,7%; perder la vida a causa del COVID-19 el 30,8%. El 66,1% tiene criterios de Trastorno de Ansiedad Generalizada, de los cuales la mayoría sufre de Ansiedad Leve. Conclusión: Se observa una alta prevalencia de síntomas de Ansiedad y Miedo al COVID-19 en médicos de la Contingencia Respiratoria del Hospital de Clínicas.

Introduction: As happened in all hospitals, the professionals at the Hospital de Clínicas suffered high physical and psychological pressure. Previous studies, especially carried out in China, already suggested that health professionals were especially vulnerable to psychological distress derived from the pandemic. Objectives: Determine the level of anxiety and fear of COVID 19 in doctors of the Respiratory Contingency area of the Hospital de Clínicas. Materials and methods: An observational, descriptive, cross-sectional, non-probabilistic convenience sampling study was carried out in individuals of both sexes, over 18 years of age, in doctors from the Respiratory Contingency area of the Hospital de Clínicas de San Lorenzo during the SARS-COV2 pandemic. Results: 68 doctors were surveyed, of which 63% were female; the average age of the participants was 31 years (±4.48). The majority of respondents were residents. 75% belong to the specialty of Internal Medicine. 30.8% have 4 doses of vaccine against SARSCOV 2. 44.1% presented symptoms of fear of COVID-19, of which the most frequent symptoms were: fear of becoming infected with COVID-19 48. 5%; discomfort when thinking about COVID19 39.7%; 30.8% lose their lives due to COVID-19. 66.1% have criteria for Generalized Anxiety Disorder, of which the majority suffer from Mild Anxiety. Conclusion: A high prevalence of symptoms of Anxiety and Fear of COVID-19 is observed in Respiratory Contingency doctors at the Hospital de Clínicas.

Propiedades psicométricas de las versiones larga y corta del cuestionario de agresión AQ en una muestra de presos españoles / Psychometric properties of the long and short forms of the AQ aggression questionnaire in a sample of Spanish inmates

Objetivos: El cuestionario de agresión (AQ) de Buss-Perry (Buss-Perry Aggression Questionnaire; Buss y Perry, 1992) es una medida utilizada en la población en general. Existe un debate sobre la interpretación de las puntuaciones y la utilidad de una versión más breve (AQ-SV [short version]). El objetivo de este estudio es analizar y comparar las propiedades psicométricas de la versión larga (AQ-LV [long version]) y la breve y comprobar la fiabilidad de la versión breve en una muestra de varones encarcelados. Material y método: La muestra estaba formada por 236 varones encarcelados (edad media de 40,4 años) del Centro Penitenciario Ocaña I (Toledo), que se ofrecieron a participar en el estudio. La muestra se seleccionó mediante la técnica de muestreo aleatorio por niveles, basada en el número de reclusos internos. También se incluyó una lista aleatoria de posibles sustitutos en caso de negativa a ser entrevistados, interrumpiéndose la sustitución en caso de dos negaciones consecutivas. Este estudio es un diseño descriptivo transversal. Resultados: La versión breve de la escala demostró un mejor ajuste que la versión larga, como indican los valores mayores del índice de ajuste comparativo (CFI, comparative fit index) y los menores del cuadrado medio residual ponderado (WRMR, weighted root mean square residual). El número de penas de prisión se asoció positivamente con la agresión física, la agresión verbal, la ira y la hostilidad. Los coeficientes fueron ligeramente superiores para la versión breve que para la versión larga. Discusión: La versión breve del cuestionario AQ es un instrumento válido y de utilidad para medir la agresividad en contextos penitenciarios en relación con la versión larga, y se correlaciona con subescalas de agresión con más fuerza que la versión larga.(AU)

Objectives: The Buss-Perry Aggression Questionnaire (AQ; Buss & Perry, 1992) is a broad measurement tool used with the general public in Spain. There is some debate regarding the interpretation of AQ scores and the usefulness of a shorter version. The aim is to study and compare the psychometric properties of the long and short version of the AQ and check the reliability of the short version in a sample of male prisoners. Material and method: The sample was composed of 236 incarcerated males (mean age of 40.4 years of age) from Ocaña 1 prison center who volunteered to participate in the study. The sample was selected by using the tiered random sampling technique based on the internal inmate number. A random list of possible substitutes was also included in the event of refusal to be interviewed, with replacement being discontinued in the event of two consecutive refusals. This study is a descriptive cross-sectional design. Results: The short version of the scale demonstrated better adjustment than the long version, as indicated by the larger CFI and smaller WRMR values. The number of prison sentences was positively associated with physical aggression, verbal aggression, anger, and hostility. The coefficients were slightly higher for the short version of the scale than the long one. Discussion: The short version of the AQ is a valid instrument for measuring aggressiveness in prison contexts in relation to the long version, and correlates with subscales of aggression more strongly than the long one.(AU)

Dual FGFR-targeting and pH-activatable ruthenium-peptide conjugates for targeted therapy of breast cancer.

Dysregulation of Fibroblast Growth Factor Receptors (FGFRs) signaling has been associated with breast cancer, yet employing FGFR-targeted delivery systems to improve the efficacy of cytotoxic agents is still sparsely exploited. Herein, we report four new bi-functional ruthenium-peptide conjugates (RuPCs) with FGFR-targeting and pH-dependent releasing abilities, envisioning the selective delivery of cytotoxic Ru complexes to FGFR(+)-breast cancer cells, and controlled activation at the acidic tumoral microenvironment. The antiproliferative potential of the RuPCs and free Ru complexes was evaluated in four breast cancer cell lines with different FGFR expression levels (SKBR-3, MDA-MB-134-VI, MCF-7, and MDA-MB-231) and in human dermal fibroblasts (HDF), at pH 6.8 and pH 7.4 aimed at mimicking the tumor microenvironment and normal tissues/bloodstream pHs, respectively. The RuPCs showed higher cytotoxicity in cells with higher level of FGFR expression at acidic pH. Additionally, RuPCs showed up to 6-fold higher activity in the FGFR(+) breast cancer lines compared to the normal cell line. The release profile of Ru complexes from RuPCs corroborates the antiproliferative effects observed. Remarkably, the cytotoxicity and releasing ability of RuPCs were shown to be strongly dependent on the conjugation of the peptide position in the Ru complex. Complementary molecular dynamic simulations and computational calculations were performed to help interpret these findings at the molecular level. In summary, we identified a lead bi-functional RuPC that holds strong potential as a FGFR-targeted chemotherapeutic agent.