Nanofibrous ε-Polycaprolactone Matrices Containing Nano-Hydroxyapatite and Humulus lupulus L. Extract: Physicochemical and Biological Characterization for Oral Applications.

Oral bone defects occur as a result of trauma, cancer, infections, periodontal diseases, and caries. Autogenic and allogenic grafts are the gold standard used to treat and regenerate damaged or defective bone segments. However, these materials do not possess the antimicrobial properties necessary to inhibit the invasion of the numerous deleterious pathogens present in the oral microbiota. In the present study, poly(ε-caprolactone) (PCL), nano-hydroxyapatite (nHAp), and a commercial extract of Humulus lupulus L. (hops) were electrospun into polymeric matrices to assess their potential for drug delivery and bone regeneration. The fabricated matrices were analyzed using scanning electron microscopy (SEM), tensile analysis, thermogravimetric analysis (TGA), FTIR assay, and in vitro hydrolytic degradation. The antimicrobial properties were evaluated against the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. The cytocompatibility was proved using the MTT assay. SEM analysis established the nanostructured matrices present in the three-dimensional interconnected network. The present research provides new information about the interaction of natural compounds with ceramic and polymeric biomaterials. The hop extract and other natural or synthetic medicinal agents can be effectively loaded into PCL fibers and have the potential to be used in oral applications.

Total sleep deprivation effects on the attentional blink.

The Attentional Blink (AB) is a phenomenon that reflects difficulty in detecting or identifying the second of two successive targets (T1 and T2) that are presented in rapid succession, between 200-500ms apart. The AB involves indicators of attentional and temporal integration mechanisms related to the early stages of visual processing. The aim of this study was to identify the effects of 24-h of sleep deprivation (total sleep deprivation, TSD) on the attentional and temporal integration mechanisms of the AB. Twenty-two undergraduate students were recorded during five successive days, in these three conditions: baseline (two days), TSD (one day), and recovery (two days). Each day, at around 12:00 h, participants responded to a Rapid Serial Visual Presentation task (RSVP) that presented two targets separated by random intervals from 100 to 1000ms. The attentional mechanisms were assessed by the AB presence, the AB magnitude, and the AB interval, while the temporal integration mechanisms were evaluated by lag-1 sparing and order reversal responses. TSD negatively affected the attentional mechanisms, which is expressed by an overall reduction in performance, an extended AB interval, and a reduced AB magnitude. TSD also negatively affected the temporal integration mechanisms, manifested by an absence of lag-1 sparing and an increase in order reversals. These results suggest that people are still able to respond to two successive stimuli after 24 h without sleep. However, it becomes more difficult to respond to both stimuli because the attentional and temporal integration mechanisms of the AB are impaired.

Fluconazole-resistant Candida parapsilosis genotypes from hospitals located in five Spanish cities and one in Italy: Description of azole-resistance profiles associated with the Y132F ERG11p substitution.

BACKGROUND: Fluconazole-resistant Candida parapsilosis is a matter of concern. OBJECTIVES: To describe fluconazole-resistant C. parapsilosis genotypes circulating across hospitals in Spain and Rome and to study their azole-resistance profile associated with ERG11p substitutions. PATIENTS/METHODS: We selected fluconazole-resistant C. parapsilosis isolates (n = 528 from 2019 to 2023; MIC ≥8 mg/L according to EUCAST) from patients admitted to 13 hospitals located in five Spanish cities and Rome. Additionally, we tested voriconazole, posaconazole, isavuconazole, amphotericin B, micafungin, anidulafungin and ibrexafungerp susceptibility. RESULTS: Of the 53 genotypes found, 49 harboured the Y132F substitution, five of which were dominating city-specific genotypes involving almost half the isolates. Another genotype involved isolates harbouring the G458S substitution. Finally, we found two genotypes with the wild-type ERG11 gene sequence and one with the R398I substitution. All isolates were fully susceptible/wild-type to amphotericin B, anidulafungin, micafungin and ibrexafungerp. The azole-resistance patterns found were: voriconazole-resistant (74.1%) or voriconazole-intermediate (25.2%), posaconazole-resistant (10%) and isavuconazole non-wild-type (47.5%). Fluconazole-resistant and voriconazole non-wild-type isolates were likely to harbour substitution Y132F if posaconazole was wild type; however, if posaconazole was non-wild type, substitution G458S was indicated if isavuconazole MIC was >0.125 mg/L or substitution Y132F if isavuconazole MIC was ≤0.125 mg/L. CONCLUSIONS: We detected a recent clonal spread of fluconazole-resistant C. parapsilosis across some cities in Spain, mostly driven by dominating city-specific genotypes, which involved a large number of isolates harbouring the Y132F ERG11p substitution. Isolates harbouring substitution Y132F can be suspected because they are non-susceptible to voriconazole and rarely posaconazole-resistant.

Trends in antifungal resistance in Candida from a multicenter study conducted in Madrid (CANDIMAD study): fluconazole-resistant C. parapsilosis spreading has gained traction in 2022.

We previously conducted a multicenter surveillance study on Candida epidemiology and antifungal resistance in Madrid (CANDIMAD study; 2019-2021), detecting an increase in fluconazole-resistant Candida parapsilosis. We here present data on isolates collected in 2022. Furthermore, we report the epidemiology and antifungal resistance trends during the entire period, including an analysis per ward of admission. Candida spp. incident isolates from blood cultures and intra-abdominal samples from patients cared for at 16 hospitals in Madrid, Spain, were tested with the EUCAST E.Def 7.3.2 method against amphotericin B, azoles, micafungin, anidulafungin, and ibrexafungerp and were molecularly characterized. In 2022, we collected 766 Candida sp. isolates (686 patients; blood cultures, 48.8%). Candida albicans was the most common species found, and Candida auris was undetected. No resistance to amphotericin B was found. Overall, resistance to echinocandins was low (0.7%), whereas fluconazole resistance was 12.0%, being higher in blood cultures (16.0%) mainly due to fluconazole-resistant C. parapsilosis clones harboring the Y132F-R398I ERG11p substitutions. Ibrexafungerp showed in vitro activity against the isolates tested. Whereas C. albicans was the dominant species in most hospital wards, we observed increasing C. parapsilosis proportions in blood. During the entire period, echinocandin resistance rates remained steadily low, while fluconazole resistance increased in blood from 6.8% (2019) to 16% (2022), mainly due to fluconazole-resistant C. parapsilosis (2.6% in 2019 to 36.6% in 2022). Up to 7 out of 16 hospitals were affected by fluconazole-resistant C. parapsilosis. In conclusion, rampant clonal spreading of C. parapsilosis fluconazole-resistant genotypes is taking place in Madrid.

[Pruebas diagnósticas in vivo en alergia inmediata a penicilina: estudio piloto].

Background: The most commonly reported antibiotic allergy is penicillin. The false label of "allergy" to penicillin negatively affects the patient's quality of life and medical care. Objective: To determine the frequency of allergy to penicillin and amoxicillin by in vivo exposure tests in patients with a history of immediate reaction to this class of medicinal products. Methods: Observational, cross-sectional, descriptive and prolective study in patients between 12 and 60 years of age with a history of immediate reaction to penicillin and/or amoxicillin. Prick and intradermal skin tests were performed with benzylpenicilloyl polylysine (Pre-Pen), penicillin G and oral challenge test with amoxicillin. The frequency of positivity and negativity in these tests was calculated with a 95% CI. Results were analyzed in Epi info 7.2.5.0. Results: In total 13 patients (10 women) were included, with a mean age of 39 years (SD 12.14). In 84.6% the last adverse drug reaction occurred 10 years ago and in all manifested with urticaria. The 38.4% confirmed penicillin allergy and the most frequent adverse reaction after in vivo tests was pruritus. Conclusions: The clinical history alone is not sufficient, all patients with suspected penicillin allergy should be evaluated by in vivo exposure tests with major and minor determinants to corroborate or rule out allergy to this pharmacological class.

Antecedentes: La alergia a antibióticos notificada con más frecuencia es la penicilina. La falsa etiqueta de "alergia" a la penicilina afecta negativamente la calidad de vida del paciente y la atención médica. Objetivo: Determinar la frecuencia de alergia a penicilina y amoxicilina mediante pruebas de exposición in vivo, en pacientes con antecedente de reacción inmediata a esta clase de medicamentos. Métodos: Estudio observacional, transversal, descriptivo y prolectivo en pacientes entre 12 y 60 años con antecedente de reacción inmediata a penicilina y/o amoxicilina. Se realizaron pruebas cutáneas por prick e intradérmicas con bencilpeniciloil polilisina y penicilina G, y prueba de reto oral con amoxicilina. La frecuencia de positividad y negatividad en estas pruebas fue calculado con un IC del 95%. Los resultados se analizaron en Epi info 7.2.5.0. Resultados: Se incluyeron 13 pacientes (10 mujeres), con una media de edad de 39 años (DE 12.14) y diagnóstico predominante de rinitis alérgica (61,5%). En 84,6% de casos la última reacción adversa a medicamentos ocurrió 10 años atrás y en todos se manifestó con urticaria. Sólo en cinco pacientes (38,4%) se corroboró alergia a penicilina y la reacción adversa más frecuente tras las pruebas in vivo fue prurito (23 %). Conclusiones: La historia clínica por sí sola no es suficiente, todos los pacientes con sospecha de alergia a penicilina deben ser evaluados mediante pruebas de exposición in vivo con los determinantes mayores y menores para corroborar o descartar alergia a esta clase farmacológica.

[Diagnóstico de alergia inmediata para penicilina: estudio piloto].

Objectives: To confirm the presence of allergy to penicillin and amoxicillin by in vivo exposure tests in patients with a history of immediate reaction to these drugs. Methods: Observational, cross-sectional, descriptive and prolective study. Patients between 12 and 60 years old with a history of immediate reaction after administration of penicillin and/or amoxicillin were included. Skin prick and intradermal tests were performed with benzylpenicilloyl polylysine and penicillin G, as well as oral challenge with amoxicillin. Results: Ten female and 3 male patients were included. The mean age was 39 years. In 84.6% of the cases the last adverse drug reaction occurred 10 years ago and in all cases it manifested with urticaria. Allergy to penicillin was corroborated in only 38.4% of cases. The most frequent adverse reaction after in vivo exposure tests was pruritus in 23%. Conclusions: Patients with suspected penicillin allergy should be evaluated by in vivo exposure testing with major and minor determinants to corroborate or rule out allergic reactions and improve treatment conditions.

Objetivos: Confirmar la presencia de alergia a penicilina y amoxicilina mediante pruebas de exposición in vivo, en pacientes que refieren antecedente de reacción inmediata con estos medicamentos. Métodos: Estudio observacional, transversal, descriptivo y prolectivo. Se incluyeron pacientes entre 12 y 60 años con antecedente de reacción inmediata tras administración de penicilina y/o amoxicilina. Se realizaron pruebas cutáneas por prick e intradérmicas con bencilpeniciloil polilisina y penicilina G, así como desafío oral con amoxicilina. Resultados: Se incluyeron 10 pacientes femeninos y 3 masculinos. La edad promedio fue 39 años. En 84,6% de los casos la última reacción adversa a medica- mentos ocurrió 10 años atrás y en todos los casos se manifestó con urticaria. Sólo en el 38,4% se corroboró alergia a penicilina. La reacción adversa más frecuen- te, tras las pruebas de exposición in vivo fue prurito en el 23%. Conclusiones: Los pacientes con sospecha de alergia a penicilina se deben evaluar mediante pruebas de exposición in vivo con los determinantes mayores y menores, para corroborar o descartar reacciones alérgicas y mejorar las condiciones de tratamiento.

Target Genes of c-MYC and MYCN with Prognostic Power in Neuroblastoma Exhibit Different Expressions during Sympathoadrenal Development.

Deregulation of the MYC family of transcription factors c-MYC (encoded by MYC), MYCN, and MYCL is prevalent in most human cancers, with an impact on tumor initiation and progression, as well as response to therapy. In neuroblastoma (NB), amplification of the MYCN oncogene and over-expression of MYC characterize approximately 40% and 10% of all high-risk NB cases, respectively. However, the mechanism and stage of neural crest development in which MYCN and c-MYC contribute to the onset and/or progression of NB are not yet fully understood. Here, we hypothesized that subtle differences in the expression of MYCN and/or c-MYC targets could more accurately stratify NB patients in different risk groups rather than using the expression of either MYC gene alone. We employed an integrative approach using the transcriptome of 498 NB patients from the SEQC cohort and previously defined c-MYC and MYCN target genes to model a multigene transcriptional risk score. Our findings demonstrate that defined sets of c-MYC and MYCN targets with significant prognostic value, effectively stratify NB patients into different groups with varying overall survival probabilities. In particular, patients exhibiting a high-risk signature score present unfavorable clinical parameters, including increased clinical risk, higher INSS stage, MYCN amplification, and disease progression. Notably, target genes with prognostic value differ between c-MYC and MYCN, exhibiting distinct expression patterns in the developing sympathoadrenal system. Genes associated with poor outcomes are mainly found in sympathoblasts rather than in chromaffin cells during the sympathoadrenal development.

Antifungal resistance in Candida spp within the intra-abdominal cavity: study of resistance acquisition in patients with serial isolates.

OBJECTIVES: Antifungal susceptibility testing is mostly conducted on blood-cultured Candida spp isolates. Because the intra-abdominal cavity has been highlighted as a hidden echinocandin-resistant C. glabrata reservoir, we assessed whether testing sequential isolates from a given patient might increase the chances of detecting antifungal resistance. METHODS: Intra-abdominal initial and sequential isolates from the same species from patients included in the CANDIdaemia in MADrid study (January 2019 to June 2022) were studied. We assessed antifungal susceptibility to amphotericin B, azoles, anidulafungin, micafungin, and ibrexafungerp using European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology and molecularly characterized resistant isolates. RESULTS: We collected 308 isolates (C. albicans [n = 179/308; 58.1%], C. glabrata [n = 101/308; 32.8%], C. tropicalis [n = 17/308; 5.5%], and C. parapsilosis [n = 11/308; 3.6%]) from 112 patients distributed as incident (n = 125/308) and sequential (n = 183/308). Per patient resistance rates of fluconazole (13.4% [15/112] vs. 8% [9/112]); 5.4% proportions difference (95% CI, -2.7% to 13.5%, p 0.09) and echinocandins (8.9% [10/112] vs. 1.8% [2/112]); 7.1% proportions difference (95% CI; 1.2-12.9%; p 0.01) were higher when considering all available isolates than only incident isolates. Resistance was detected in 18 of 112 patients and would have been overlooked in 11 of 18 (61.1%) patients if only incident isolates had been studied. Of the patients who harboured fluconazole or echinocandin-resistant isolates, 14 of 15 and 8 of 10 had received or were receiving fluconazole or echinocandins, respectively. DISCUSSION: Testing sequential Candida isolates from intra-abdominal samples is required to detect antifungal resistance, particularly to echinocandins, in patients whose incident isolates turned out to be susceptible. Furthermore, patients with echinocandin-resistant infections had frequently used echinocandins and had common secondary resistance acquisition.

Breast cancer genomes from CHEK2 c.1100delC mutation carriers lack somatic TP53 mutations and display a unique structural variant size distribution profile.

BACKGROUND: CHEK2 c.1100delC was the first moderate-risk breast cancer (BC) susceptibility allele discovered. Despite several genomic, transcriptomic and functional studies, however, it is still unclear how exactly CHEK2 c.1100delC promotes tumorigenesis. Since the mutational landscape of a tumor reflects the processes that have operated on its development, the aim of this study was to uncover the somatic genomic landscape of CHEK2-associated BC. METHODS: We sequenced primary BC (pBC) and normal genomes of 20 CHEK2 c.1100delC mutation carriers as well as their pBC transcriptomes. Including pre-existing cohorts, we exhaustively compared CHEK2 pBC genomes to those from BRCA1/2 mutation carriers, those that displayed homologous recombination deficiency (HRD) and ER- and ER+ pBCs, totaling to 574 pBC genomes. Findings were validated in 517 metastatic BC genomes subdivided into the same subgroups. Transcriptome data from 168 ER+ pBCs were used to derive a TP53-mutant gene expression signature and perform cluster analysis with CHEK2 BC transcriptomes. Finally, clinical outcome of CHEK2 c.1100delC carriers was compared with BC patients displaying somatic TP53 mutations in two well-described retrospective cohorts totaling to 942 independent pBC cases. RESULTS: BC genomes from CHEK2 mutation carriers were most similar to ER+ BC genomes and least similar to those of BRCA1/2 mutation carriers in terms of tumor mutational burden as well as mutational signatures. Moreover, CHEK2 BC genomes did not show any evidence of HRD. Somatic TP53 mutation frequency and the size distribution of structural variants (SVs), however, were different compared to ER+ BC. Interestingly, BC genomes with bi-allelic CHEK2 inactivation lacked somatic TP53 mutations and transcriptomic analysis indicated a shared biology with TP53 mutant BC. Moreover, CHEK2 BC genomes had an increased frequency of > 1 Mb deletions, inversions and tandem duplications with peaks at specific sizes. The high chromothripsis frequency among CHEK2 BC genomes appeared, however, not associated with this unique SV size distribution profile. CONCLUSIONS: CHEK2 BC genomes are most similar to ER+ BC genomes, but display unique features that may further unravel CHEK2-driven tumorigenesis. Increased insight into this mechanism could explain the shorter survival of CHEK2 mutation carriers that is likely driven by intrinsic tumor aggressiveness rather than endocrine resistance.

An origami-based technique for simple, effective and inexpensive fabrication of highly aligned far-field electrospun fibers.

Fabrication of highly aligned fibers by far-field electrospinning is a challenging task to accomplish. Multiple studies present advances in the alignment of electrospun fibers which involve modification of the conventional electrospinning setup with complex additions, multi-phased fabrication, and expensive components. This study presents a new collector design with an origami structure to produce highly-aligned far-field electrospun fibers. The origami collector mounts on the rotating drum and can be easily attached and removed for each round of fiber fabrication. This simple, effective, and inexpensive technique yields high-quality ultra-aligned fibers while the setup remains intact for other fabrication types. The electrospun poly(ɛ-caprolactone) (PCL) fibers were assessed by scanning electron microscope (SEM), fiber diameter distribution, water contact angle (WCA), Fast Fourier Transform analysis (FFT), surface plot profile, and pixel intensity plots. We thoroughly explored the impact of influential parameters, including polymer concentration, injection rate, collector rotation speed, distance from the collector to the tip, and needle gauge number on fibers' quality and alignment. Moreover, we employed machine learning algorithms to predict the outcomes and classify the high-quality fibers instead of low-quality productions.

Papel de la empatía en los agresores y las víctimas del acoso escolar: un estudio transversal / Role of empathy in aggressors and victims of bullying: A cross-sectional study

El acoso escolar es un fenómeno que está presente en las aulas. Las competencias emocionales que desarrollan los niños en su crecimiento pueden tener relación con la participación en este proceso. La empatía es una competencia que se ve afectada en agresores y víctimas. Este trabajo analizó si existen diferencias en el nivel de empatía en función de los participantes del acoso escolar (víctimas y acosadores). Además, se estudiasi hay diferencias en empatía en función del sexo de la persona hacia quien va dirigida la acción empática y de quién la ejerce. La muestra estuvo compuesta por 180 niños siendo el 50% chicas y 50% chicos de entre 10 y 12 años, encontrando la media en 11,23 años y la desviación típica de .914. reclutados en cinco colegios de la provincia de Alicante (Petrel, Ibi y Alicante), en España. Los niños respondieron al Cuestionario de Índice de Empatía para Niños y Adolescentes (Index of Empaty for Children and Adolescents, IECA) para evaluar la empatía y al Test Bull-S paraevaluar los posibles perfiles de agresor y víctima en las aulas. Los agresores y las víctimas obtuvieron un menor índice de empatía con respecto a la media global de la muestra; aunque no hubo diferencia en empatía entre agresores y víctimas. Las chicas puntuaron más alto en empatía que los chicos. Las chicas mostraron ser más empáticas con las chicas, que con los chicos. Se concluye que las competencias emocionales pueden verse afectadas en personas involucradas en situaciones de acoso. Por tanto, se debe dar prioridad a programas de prevención basados en mejorar las competencias emocionales y así evitar el problema del acoso escolar antes de que ocurra. (AU)

Bullying is a phenomenon that is present in the classroom. The emotional competences that children develop as they grow up may be related to their participation in this process. Empathy is a competence thatis affected in aggressors and victims. This paper analysed whether there are differences in the level of empathy depending on the participants in bullying (victims and bullies). In addition, we studied whether there are differences in empathy according to the gender of the person towards whomthe empathic action is directed and who is exercising it. The sample consisted of 180 children, 50% girls and 50% boys between 10 and 12 years of age, with a mean of 11.23 years and a standard deviation of .914, recruited from five schools in the province of Alicante (Petrel, Ibi and Alicante),Spain. The children responded to the Index of Empathy for Children and Adolescents (IECA) questionnaire to assess empathy and to the Bull-S test to assess possible aggressor and victim profiles in the classroom. Bullies and victims scored lower on empathy than the overall sample mean, although there was no difference in empathy between bullies and victims. Girls scored higher on empathy than boys. Girls were more empathetic towards girls than boys. It is concluded that emotional competences may be affected in people involved in bullying situations. Therefore, priority should be given to prevention programmes based on improving emotional competences in order to prevent the problem of bullying before it occurs. (AU)

Correction: Díaz-García et al. Candida Genotyping of Blood Culture Isolates from Patients Admitted to 16 Hospitals in Madrid: Genotype Spreading during the COVID-19 Pandemic Driven by Fluconazole-Resistant C. parapsilosis. J. Fungi 2022, 8, 1228.

In the original publication [...].

Metabolic rewiring in MYC-driven medulloblastoma by BET-bromodomain inhibition.

Medulloblastoma (MB) is the most common malignant brain tumour in children. High-risk MB patients harbouring MYC amplification or overexpression exhibit a very poor prognosis. Aberrant activation of MYC markedly reprograms cell metabolism to sustain tumorigenesis, yet how metabolism is dysregulated in MYC-driven MB is not well understood. Growing evidence unveiled the potential of BET-bromodomain inhibitors (BETis) as next generation agents for treating MYC-driven MB, but whether and how BETis may affect tumour cell metabolism to exert their anticancer activities remains unknown. In this study, we explore the metabolic features characterising MYC-driven MB and examine how these are altered by BET-bromodomain inhibition. To this end, we employed an NMR-based metabolomics approach applied to the MYC-driven MB D283 and D458 cell lines before and after the treatment with the BETi OTX-015. We found that OTX-015 triggers a metabolic shift in both cell lines resulting in increased levels of myo-inositol, glycerophosphocholine, UDP-N-acetylglucosamine, glycine, serine, pantothenate and phosphocholine. Moreover, we show that OTX-015 alters ascorbate and aldarate metabolism, inositol phosphate metabolism, phosphatidylinositol signalling system, glycerophospholipid metabolism, ether lipid metabolism, aminoacyl-tRNA biosynthesis, and glycine, serine and threonine metabolism pathways in both cell lines. These insights provide a metabolic characterisation of MYC-driven childhood MB cell lines, which could pave the way for the discovery of novel druggable pathways. Importantly, these findings will also contribute to understand the downstream effects of BETis on MYC-driven MB, potentially aiding the development of new therapeutic strategies to combat medulloblastoma.

Re-irradiation in patients with progressive or recurrent brain metastases from extracranial solid tumors: A novel prognostic index.

BACKGROUND: Most studies evaluating factors associated with the survival of patients with brain metastases (BM) have focused on patients with newly diagnosed BM. This study aimed to identify prognostic factors associated with survival after brain re-irradiation in order to develop a new prognostic index. METHODS: This 5-year retrospective study included patients treated with repeat-radiotherapy for recurrent BM at the "Instituto Nacional de Cancerología" of Mexico between 2015 and 2019. Significant variables in the multivariate Cox regression analysis were used to create the brain re-irradiation index (BRI). Survival and group comparisons were performed using the Kaplan-Meier method and the log-rank test. RESULTS: Fifty-seven patients receiving brain re-irradiation were identified. Most patients were women (75.4%) with a mean age at BM diagnosis of 51.4 years. Lung and breast cancer were the most prevalent neoplasms (43.9% each). Independent prognostic factors for shorter survival after re-irradiation were: Age >50 years (hazard ratio [HR]:2.5 [95% confidence interval [CI], 1.1-5.8]; p = 0.026), uncontrolled primary tumor (HR:5.5 [95% CI, 2.2-13.5]; p < 0.001), lesion size >20 mm (4.6 [95% CI, 1.7-12.2]; p = 0.002), and an interval <12 months between radiation treatments (HR:4.3 [95% CI, 1.7-10.6]; p = 0.001). Median survival (MS) after re-irradiation was 14.6 months (95% CI, 8.2-20.9).MS of patients stratified according to the BRI score was 17.38, 10.34, and 2.82 months, with significant differences between all groups. CONCLUSIONS: The new BRI can be easily implemented for the prognostic classification of cancer patients with progressive or recurrent BM from extracranial solid tumors.

Candida Genotyping of Blood Culture Isolates from Patients Admitted to 16 Hospitals in Madrid: Genotype Spreading during the COVID-19 Pandemic Driven by Fluconazole-Resistant C. parapsilosis.

BACKGROUND: Candidaemia and invasive candidiasis are typically hospital-acquired. Genotyping isolates from patients admitted to different hospitals may be helpful in tracking clones spreading across hospitals, especially those showing antifungal resistance. METHODS: We characterized Candida clusters by studying Candida isolates (C. albicans, n = 1041; C. parapsilosis, n = 354, and C. tropicalis, n = 125) from blood cultures (53.8%) and intra-abdominal samples (46.2%) collected as part of the CANDIMAD (Candida in Madrid) study in Madrid (2019-2021). Species-specific microsatellite markers were used to define the genotypes of Candida spp. found in a single patient (singleton) or several patients (cluster) from a single hospital (intra-hospital cluster) or different hospitals (widespread cluster). RESULTS: We found 83 clusters, of which 20 were intra-hospital, 49 were widespread, and 14 were intra-hospital and widespread. Some intra-hospital clusters were first detected before the onset of the COVID-19 pandemic, but the number of clusters increased during the pandemic, especially for C. parapsilosis. The proportion of widespread clusters was significantly higher for genotypes found in both compartments than those exclusively found in either the blood cultures or intra-abdominal samples. Most C. albicans- and C. tropicalis-resistant genotypes were singleton and presented exclusively in either blood cultures or intra-abdominal samples. Fluconazole-resistant C. parapsilosis isolates belonged to intra-hospital clusters harboring either the Y132F or G458S ERG11p substitutions; the dominant genotype was also widespread. CONCLUSIONS: the number of clusters-and patients involved-increased during the COVID-19 pandemic mainly due to the emergence of fluconazole-resistant C. parapsilosis genotypes.

Drug-Eluting, Bioresorbable Cardiovascular Stents─Challenges and Perspectives.

Globally, the leading causes of natural death are attributed to coronary heart disease and type 1 and type 2 diabetes. High blood pressure levels, high cholesterol levels, smoking, and poor eating habits lead to the agglomeration of plaque in the arteries, reducing the blood flow. The implantation of devices used to unclog vessels, known as stents, sometimes results in a lack of irrigation due to the excessive proliferation of endothelial tissue within the blood vessels and is known as restenosis. The use of drug-eluting stents (DESs) to deliver antiproliferative drugs has led to the development of different encapsulation techniques. However, due to the potency of the drugs used in the initial stent designs, a chronic inflammatory reaction of the arterial wall known as thrombosis can cause a myocardial infarction (MI). One of the most promising drugs to reduce this risk is everolimus, which can be encapsulated in lipid systems for controlled release directly into the artery. This review aims to discuss the current status of stent design, fabrication, and functionalization. Variables such as the mechanical properties, metals and their alloys, drug encapsulation and controlled elution, and stent degradation are also addressed. Additionally, this review covers the use of polymeric surface coatings on stents and the recent advances in layer-by-layer coating and drug delivery. The advances in nanoencapsulation techniques such as liposomes and micro- and nanoemulsions and their functionalization in bioresorbable, drug-eluting stents are also highlighted.

Blood and intra-abdominal Candida spp. from a multicentre study conducted in Madrid using EUCAST: emergence of fluconazole resistance in Candida parapsilosis, low echinocandin resistance and absence of Candida auris.

OBJECTIVES: We prospectively monitored the epidemiology and antifungal susceptibility of Candida spp. from blood cultures and intra-abdominal samples in patients admitted to hospitals in the Madrid area. METHODS: Between 2019 and 2021, we prospectively collected incident isolates [one per species, patient and compartment (blood cultures versus intra-abdominal samples)] from patients admitted to any of 16 hospitals located in Madrid. We studied the antifungal susceptibilities to amphotericin B, triazoles, micafungin, anidulafungin and ibrexafungerp following the EUCAST E.Def 7.3.2 procedure. RESULTS: A total of 2107 Candida spp. isolates (1895 patients) from blood cultures (51.7%) and intra-abdominal samples were collected. Candida albicans, the Candida glabrata complex, the Candida parapsilosis complex, Candida tropicalis and Candida krusei accounted for 96.9% of the isolates; in contrast, Candida auris was undetected. Fluconazole resistance in Candida spp. was higher in blood cultures than in intra-abdominal samples (9.1% versus 8.2%; P > 0.05), especially for the C. parapsilosis complex (16.6% versus 3.6%, P < 0.05), whereas echinocandin resistance tended to be lower in blood cultures (0.5% versus 1.0%; P > 0.05). Resistance rates have risen, particularly for fluconazole in blood culture isolates, which increased sharply in 2021. Ibrexafungerp showed in vitro activity against most isolates. Species distributions and resistance rates varied among hospitals. CONCLUSIONS: Whereas no C. auris isolates were detected, fluconazole-resistant C. parapsilosis isolates have been spreading across the region and this has pulled up the rate of fluconazole resistance. In contrast, the rate of echinocandin resistance continues to be low.

The evolution of nutrition intervention during the COVID-19 pandemic / A evolução da intervenção nutricional durante a pandemia de COVID-19

Abstract COVID-19 has challenged health professionals in widely divergent areas, including innovation of practice, communication, multidisciplinary activities, broader use of technology, and adaptability. The role of the dietitian and other health professionals in dealing with the evolving crisis might be considered essential in treating patients. Given the limited access to various food options, nutrition screening and assessment deserves a high priority to complete a comprehensive nutrition evaluation, identify nutrition risks, prioritize care, and provide early nutrition intervention and support to all patients with or who have had, COVID-19 and are experiencing ongoing symptoms. Such an intervention would benefit the patients and the health system by reducing the length of hospital stay, ameliorating further complications, limiting hospital readmission, enhancing recovery, and assisting in the management of comorbidities and their metabolic alterations. This brief overview outlines the essential role of nutrition intervention and support as part of an integrated, multidisciplinary treatment program for the care of COVID-19 patients during the pandemic. Restrictive movements have changed consultative approaches, and the importance of Telenutrition for the effective communication of health status and recommendations.

Resumo A COVID-19 desafiou profissionais de saúde em diversas áreas, incluindo inovação da prática, comunicação, atividades multidisciplinares, uso amplo de tecnologia e adaptabilidade. O papel do nutricionista e de outros profissionais de saúde para lidar com a crise em expansão pode ser considerado essencial no tratamento de pacientes. Devido ao acesso limitado a várias opções de alimentos, a triagem e a avaliação nutricional devem ser priorizadas para a obtenção de uma avaliação nutricional abrangente, a fim de identificar riscos nutricionais, priorizar atendimento e possibilitar a intervenção nutricional precoce e o apoio a todos os pacientes com, ou que tiveram, COVID-19 e apresentem sintomas contínuos. Tal intervenção traria grande benefício aos pacientes e ao sistema de saúde, ao reduzir o tempo de internação, amenizar complicações posteriores, limitar a readmissão hospitalar, potencializar a recuperação e auxiliar no manejo das comorbidades e suas alterações metabólicas. Esta breve descrição elucida o papel essencial da intervenção nutricional e do apoio como parte de um programa de tratamento multidisciplinar para o cuidado de pacientes com COVID-19 durante a pandemia. Movimentos restritivos mudaram as abordagens consultivas e a importância da telenutrição para a comunicação eficaz do estado de saúde e das recomendações.

COVID-19: the impact on oral health care / COVID-19: o impacto na saúde bucal

Abstract The COVID-19 pandemic has highlighted the economic, social, and oral care health inequities in societies, especially in the developing world. Severe restrictions have been imposed on dental practices, limiting prophylactic and routine oral care health, allowing treatment only for emergencies. Since dental care includes procedures that generate aerosols, the risk of infection for dental personnel has increased significantly. In this review, a comprehensive and updated source of information about SARS-CoV-2/COVID-19 and the impacts it is having on oral health care is presented. The ongoing repercussions in dental practice and in dental education, including the opportunities for practice innovation that are evolving, are also indicated. Also, a discussion of the psychosocial factors that affect health and the quality of life of an individual, such as stress, depression, and anxiety, is provided. This pandemic may be an opportunity to promote the inclusion of well-established prevention measures, together with the use of teledentistry in academic dental curricula, encourage the implementation of new perspectives for the effective instruction and interactions with students, and foster the transition toward e-learning strategies in dental education.

Resumo A pandemia COVID-19 destacou as desigualdades econômicas, sociais e de saúde bucal, especialmente no mundo em desenvolvimento. Severas restrições têm sido impostas para a prática odontológica, limitando a rotina de saúde bucal, permitindo o tratamento apenas em emergências. Como o atendimento odontológico inclui procedimentos que geram aerossóis, o risco de infecção para a equipe odontológica aumentou significativamente. Nesta revisão, é abordada uma fonte abrangente e atualizada de informações sobre o SARS-CoV-2/COVID-19 e os impactos que têm nos cuidados de saúde bucal. As repercussões contínuas na profissão odontológica e na educação odontológica, incluindo as oportunidades de inovação da prática. Além disso, é fornecido o efeito de fatores psicossociais que afetam a saúde e a qualidade de vida, como estresse, depressão e ansiedade. Esta pandemia pode ser uma oportunidade para promover a inclusão de medidas de prevenção bem estabelecidas, juntamente com o uso da teledontologia nos currículos acadêmicos de odontologia, trazendo novas perspectivas sobre a forma de ensinar e interagir com os alunos, com a transição para estratégias de e-learning na educação odontológica.

Evidence of Fluconazole-Resistant Candida parapsilosis Genotypes Spreading across Hospitals Located in Madrid, Spain and Harboring the Y132F ERG11p Substitution.

We have been monitoring the antifungal resistance in Candida parapsilosis isolates collected from inpatients at Madrid metropolitan area hospitals for the last 3 years. The study aimed to elucidate the presence of fluconazole-resistant C. parapsilosis genotypes in Madrid. From January 2019 to December 2021, a total of 354 C. parapsilosis isolates (n = 346 patients) from blood (76.6%) or intraabdominal samples were collected and genotyped using species-specific microsatellite markers. Antifungal susceptibilities to amphotericin B, the triazoles, micafungin, anidulafungin, and ibrexafungerp were performed according to EUCAST E.Def 7.3.2; the ERG11 gene was sequenced in fluconazole-resistant isolates. A total of 13.6% (n = 48/354) isolates (one per patient) were found to be resistant to fluconazole and non-wild-type to voriconazole but fully susceptible to ibrexafungerp. Resistant isolates were mostly sourced from blood (n = 45/48, 93.8%) and were detected in five hospitals. Two hospitals accounted for a high proportion of resistant isolates (n = 41/48). Resistant isolates harbored either the Y132F ERG11p amino acid substitution (n = 43) or the G458S substitution (n = 5). Isolates harboring the Y132F substitution clustered into a clonal complex involving three genotypes (one genotype accounted for n = 39/43 isolates) that were found in four hospitals. Isolates harboring the G458S substitution clustered into another genotype found in a fifth hospital. C. parapsilosis genotypes demonstrating resistance to fluconazole have been spreading across hospitals in Madrid, Spain. Over the last 3 years, the frequency of isolation of such isolates and the number of hospitals affected is on the rise.