Unravelling the clinical heterogeneity of undefined recurrent fever over time in the European registries on Autoinflammation.

BACKGROUND: Systemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries. METHODS: Data of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients. RESULTS: Clinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria. CONCLUSIONS: Patients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes.

Thresholds and interactive effects of BPA-gradient and temperature on life history traits of Daphnia magna.

Bisphenol A (BPA), a synthetic organic compound widely used in the production of plastics, is recognized as an emerging contaminant because of its toxicity and the potential risks associated with bioaccumulation in organisms. Despite potential environmental hazards, there is a lack of studies examining BPA toxicity mechanisms and its potential impact on various trophic levels, with even fewer exploring whether global stressors such as temperature can affect the toxicity of BPA in organisms. Our aim was to assess the combined impact of BPA and varying temperature regimes on life-history traits in Daphnia magna. Our results revealed a significant impact of BPA on the growth, reproduction, and accumulated moulting of D. magna, with adverse effects primarily associated with the assimilation of BPA in algae rather than the BPA present in the medium, pointing to a trophic transfer mechanism. The interactive effect between BPA and temperature demonstrated a slight stimulatory effect of low BPA level on D. magna growth rate under warming constant conditions, but an inhibitory under warming fluctuating temperatures. Additionally, a BPA threshold was identified, below which growth became temperature-dependent. This study emphasizes the crucial role of considering temperature in predicting how toxins may affect Daphnia within aquatic food webs.

Changes in the location of cutaneous melanoma over the past 30 years. A retrospective observational study. / Cambios en la localización del melanoma cutáneo en los últimos 30 años. Estudio observacional retrospectivo.

BACKGROUND: The location of cutaneous melanoma is associated with photoexposure. OBJECTIVES: To retrospectively analyze changes in the location of cutaneous melanoma over the past 30 years. PATIENTS AND METHODS: All patients treated at our hospital for cutaneous melanoma from 1988 through 2017 were prospectively collected. Data obtained in cases diagnosed from 1988 through June 2006 were compared to those diagnosed from July 2006 through 2017. RESULTS: A total of 1937 patients (876 men and 1061 women; median age, 57 years; interquartile range 27) were diagnosed with primary cutaneous melanoma. The location of melanoma was head and neck (470 cases), trunk (745 cases), upper limbs (239 cases), and lower limbs (483 cases). From July 2006 through 2017 we detected an increase in the incidence of head and neck melanomas (19.9% vs 28.6%, p < 0.001). A drop in the incidence of melanomas located in the lower extremities was also seen in women (39.8% vs 30.4%, p < 0.001), and in men (trunks) (57.5% vs 47.3%, p = 0.003). In the multivariate analyses, only the decrease in melanomas located in lower extremities in women remained significant. CONCLUSION: The increased incidence of head and neck melanomas in both sexes and the decrease in trunk melanomas in men can be attributed to the aging of our population. The reduction in the incidence of melanomas in the lower extremities in women could be associated with changes in photoexposure patterns. Analyzing the factors possibly associated with these changes would contribute to better understanding the pathogenesis of cutaneous melanoma for prevention purposes.

Twenty-first century antiepileptic drugs. An overview of their targets and synthetic approaches.

The therapeutic use of the traditional drugs against epilepsy has been hindered by their toxicity and low selectivity. These limitations have stimulated the design and development of new generations of antiepileptic drugs. This review explores the molecular targets and synthesis of the antiepileptic drugs that have entered the market in the 21st century, with a focus on manufacturer synthesis.

Evaluation of guidelines line-care approach to the treatment of chronic inducible urticaria.

BACKGROUND: Chronic Inducible Urticaria (CIndU) management often follows Chronic Spontaneous Urticaria (CSU) guidelines, but a step-by-step evaluation of their effectiveness in CIndU is lacking. OBJECTIVE: To assess the clinical impact of adapting CSU international guidelines for CIndU management. METHODS: We conducted a prospective cohort study involving patients diagnosed with CIndU based on challenge tests and a Urticaria Control Test (UCT) score of <11 points. Following the guidelines, a stepwise approach was used: avoidance measures, antihistamines, omalizumab, and cyclosporine. Treatment steps were added based on individual response, with control defined as UCT >12 points. Pharmacological steps were evaluated for at least one month, with the next step initiated in case of a UCT score <11 points. RESULTS: We enrolled 194 patients with CIndU. One hundred and thirty-four patients had CIndU with concomitant CSU and 60 had CIndU only. Following the step-by-step approach outlined in the guidelines, a total of 159 (81.9%) patients reaches a UCT >12 points; With avoidance measures 23 (11.8%) patients; antihistamines 84 (43.2%); omalizumab 35 (18%); and with cyclosporine 17 (8.7%). CONCLUSIONS: This study supports the use of a stepwise approach based on CSU guidelines for CIndU management. However, a significant proportion of patients, particularly those with CIndU only, did not achieve adequate control. This highlights the heterogeneity within CIndU and the need for further research to develop new therapies for CIndU patients who remain uncontrolled.

Uric acid and acute kidney injury in high-risk patients for developing acute kidney injury undergoing cardiac surgery: A prospective multicenter study.

PURPOSE: It is unclear whether preoperative serum uric acid (SUA) elevation may play a role in the development of acute kidney injury (AKI) associated with cardiac surgery (CSA-AKI). We conducted a cohort study to evaluate the influence of preoperative hyperuricemia on AKI in patients at high risk for developing SC-AKI. DESIGN: Multicenter prospective international cohort study. SETTING: Fourteen university hospitals in Spain and the United Kingdom. PARTICIPANTS: We studied 261 consecutive patients at high risk of developing CSA-AKI, according to a Cleveland score ≥ 4 points, from July to December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AKIN criteria were used for the definition of AKI. Multivariable logistic regression models and propensity score-matched pairwise analysis were used to determine the adjusted association between preoperative hyperuricemia (≥7 mg/dL) and AKI. Elevated preoperative AUS (≥7 mg/dL) was present in 190 patients (72.8%), whereas CSA-AKI occurred in 145 patients (55.5%). In multivariable logistic regression models, hyperuricemia was not associated with a significantly increased risk of AKI (adjusted Odds Ratio [OR]: 1.58; 95% confidence interval [CI]: 0.81-3; P = .17). In propensity score-matched analysis of 140 patients, the hyperuricemia group experienced similar adjusted odds of AKI (OR 1.05, 95%CI 0.93-1.19, P = .37). CONCLUSIONS: Hyperuricemia was not associated with an increased risk of AKI in this cohort of patients undergoing cardiac surgery at high risk of developing CSA-AKI.

Paediatric interventional radiology: it's not child's play.

Pediatric interventional radiology is a dynamic and growing subspecialty. The new training pathways in interventional radiology, the maintenance of skills with a small volume of cases or complex procedures, the limited availability of specific pediatric equipment and materials pose significant challenges and opportunities.

RFX6 regulates human intestinal patterning and function upstream of PDX1.

The gastrointestinal (GI) tract is complex and consists of multiple organs with unique functions. Rare gene variants can cause congenital malformations of the human GI tract, although the molecular basis of these has been poorly studied. We identified a patient with compound-heterozygous variants in RFX6 presenting with duodenal malrotation and atresia, implicating RFX6 in development of the proximal intestine. To identify how mutations in RFX6 impact intestinal patterning and function, we derived induced pluripotent stem cells from this patient to generate human intestinal organoids (HIOs). We identified that the duodenal HIOs and human tissues had mixed regional identity, with gastric and ileal features. CRISPR-mediated correction of RFX6 restored duodenal identity. We then used gain- and loss-of-function and transcriptomic approaches in HIOs and Xenopus embryos to identify that PDX1 is a downstream transcriptional target of RFX6 required for duodenal development. However, RFX6 had additional PDX1-independent transcriptional targets involving multiple components of signaling pathways that are required for establishing early regional identity in the GI tract. In summary, we have identified RFX6 as a key regulator in intestinal patterning that acts by regulating transcriptional and signaling pathways.

Recent Advances in Closed-Tube Barcoding for FastFish-ID.

FastFish-ID for rapid and accurate identification of fish species was conceived at Brandeis University based on pioneering work on Closed-Tube Barcoding (Rice et al., Mitochondrial DNA Part A 27(2):1358-1363, 2016; Sirianni et al., Genome 59:1049-1061, 2016). FastFish-ID was subsequently validated and commercialized at Thermagenix, Inc. using a portable device and high-precision PCR (Naaum et al., Food Res Int 141:110035, 2021). The motivation for these efforts was the pressing need for a technology that could be widely used throughout the seafood supply chain to combat IUU Fishing (Helyar et al., PLOS ONE 9, 2014) and overfishing (FAO, State of the World Fisheries and Aquaculture 2018. http://www.fao.org/documents/card/en/c/I9540EN/ , 2018), along with seafood fraud and mislabeling (Watson et al., Fish Fish 17:585-595, 2015). These destructive practices are wasting fish stocks, frustrating attempts to achieve seafood sustainability, endangering oceanic ecosystems, and causing consumers billions of dollars each year (Porterfield et al., Oceana: February, 2022). During the past three Covid19 pandemic years, EcologeniX, LLC has taken over further development and optimization of FastFish-ID. The present chapter provides an overview of the improvements introduced throughout the FastFish-ID process.

Recent Applications of FastFish-ID.

FastFish-ID via Closed-Tube barcoding is a portable platform for rapid and accurate identification of fish species that was conceived at Brandeis University, commercialized at Thermagenix, Inc., and further improved at Ecologenix, LLC (see Chap. 17 in this volume). This chapter focuses on the use of FastFish-ID for (1) identification of intraspecies variants, (2) quantitative use of FastFish-ID to measure the decay of fresh fish, and (3) use of FastFish-ID for the identification of dried and processed shark fins.

Ammonium depletion associated with the COVID-19 pandemic in the Mexican Caribbean.

The Mexican Caribbean contributes significantly to Mexico's gross national product. The number of tourists declined from 16.7 million in 2019 to 8.8 million in 2020 due to the COVID-19 pandemic, with a rapid recovery of 13.5 million in 2021. Wastewater discharge is the primary contamination source associated with the tourism sector's demand for goods and services. Water quality could improve due to fewer tourists arriving during the COVID-19 sanitary emergency. This study aimed to quantify ammonium concentrations at eleven locations to evaluate water quality during the sanitary restriction due to the pandemic in the Mexican Caribbean. The ammonium concentrations were 85 % (Nov-2019), 89 % (Feb-2020), and 86 % (Feb-2021) higher than in Nov-2020, where six of the eleven sampled stations were below the detection limit (0.15 µM). Lower ammonium concentrations coincide with the sanitary restriction period and a decrease in affluent tourists.

Radiología intervencionista en pediatría: no es un juego de niños / Pediatric interventional radiology: It's not a child's play

La radiología intervencionista pediátrica es una subespecialidad dinámica y en crecimiento. Las nuevas vías de formación en radiología intervencionista, el mantenimiento de las competencias con un pequeño volumen de casos o procedimientos complejos, la disponibilidad limitada de equipos y material pediátrico específico, los efectos de la sedación o de la anestesia sobre el neurodesarrollo y la protección radiológica suponen importantes retos y oportunidades.(AU)

Pediatric interventional radiology is a dynamic and growing subspecialty. The new training pathways in interventional radiology, the maintenance of skills with a small volume of cases or complex procedures, the limited availability of specific pediatric equipment and materials, the effects of sedation or anesthesia on neurodevelopment or radiological on neurodevelopment or radiation protection pose significant challenges and opportunities.(AU)

Combined application of high pressure and ultrasound in fig paste: effect on bioactive and volatile compounds.

The combined impact of high-hydrostatic pressure (HHP) and ultrasound (US) on the cyanidin-3-O-rutinoside (C3R), quercetin-3-O-rutinoside (Q3R), and volatile compounds from fig (Ficus carica) paste was investigated. The HHP increased the content of C3R and Q3R, from 70 to 133 mg/kg fw and 31 to 44 mg/kg fw, respectively. The combination of HHP and US further enhanced the extraction of these bioactive compounds. Specifically, processing fig paste with US for 5 min at 40 °C yielded approximately 250 mg of C3R/kg fw and 45 mg of Q3R/kg fw, after 20 min. More than 25 volatile compounds were identified, with benzaldehyde being the predominant compound, accounting > 75%. Trace amounts of hydroxymethylfurfural (< 0.36 mg/100 g fw) were detected in HHP-processed fig paste. The application of HHP at mild temperatures and short time, combined with US, effectively promotes the content of bioactive compounds present in fig paste without adversely affecting the fruit's volatile compounds. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01410-1.

3D volume growth rate evaluation in the EORTC-BTG-1320 clinical trial for recurrent WHO grade 2 and 3 meningiomas.

BACKGROUND: We previously reported that tumor 3D volume growth rate (3DVGR) classification could help in the assessment of drug activity in patients with meningioma using three main classes and a total of five subclasses: class 1: decrease; 2: stabilization or severe slowdown; 3: progression. The EORTC-BTG-1320 clinical trial was a randomized phase II trial evaluating the efficacy of trabectedin for recurrent WHO 2 or 3 meningioma. Our objective was to evaluate the discriminative value of 3DVGR classification in the EORTC-BTG-1320. METHODS: All patients with at least one available MRI before trial inclusion were included. 3D volume was evaluated on consecutive MRI until progression. 2D imaging response was centrally assessed by MRI modified Macdonald criteria. Clinical benefit was defined as neurological or functional status improvement or steroid decrease or discontinuation. RESULTS: Sixteen patients with a median age of 58.5 years were included. Best 3DVGR classes were: 1, 2A, 3A and 3B in 2 (16.7%), 4 (33.3%), 2 (16.7%) and 4 (33.3%) patients, respectively. All patients with progression-free survival longer than 6 months had best 3DVGR class 1 or 2. 3DVGR classes 1 and 2 (combined) had a median overall survival of 34.7 months versus 7.2 months for class 3 (p=0.061). All class 1 patients (2/2), 75% of class 2 patients (3/4) and only 10% of class 3 patients (1/10) had clinical benefit. CONCLUSIONS: Tumor 3DVGR classification may be helpful to identify early signals of treatment activity in meningioma clinical trials.

Mortality and cardiovascular risk in vasculitis ANCA. Importance of hypertension and renal function. Experience from southern Spain / Mortalidad y riesgo cardiovascular en vasculitis ANCA. Importancia de la hipertension y funcion renal. Experiencia del sur de España

Background: Cardiovascular disease (CVD) is one of the principal causes of death in antineutrophil cytoplasmic antibody-(ANCA)-associated vasculitis (AAV). Objectives: To evaluate the mortality and it's causes and CVD and its vascular risk factors (VRFs) in AAV patients in Andalusia. Methods: A multicenter cohort of 220 AAV patients followed-up from 1979 until June 2020 was studied in Andalussia, south of Spain. The information, including socio-demographic and clinical data was recorded retrospectively through chart review. Data was analysed using Chi2, ANOVA and Cox proportional hazards regresion as uni and multivariate test with a 95% confidence interval (CI). Results: During a mean ± standard deviation follow-up of 96.79 ± 75.83 months, 51 patients died and 30 presented at least one CVE. Independent prognostic factors of mortality were age (HR 1.083, p=0.001) and baseline creatinine (HR 4.41, p=0.01). Independent prognostic factors of CVE were age [hazard ratio (HR) 1.042, p=0.005] and the presence of hypertension (HTN) six months after diagnosis (HR 4.641, p=0.01). HTN, diabetes and renal failure, all of these important VRFs, are more prevalent in AAV patients than it is described in matched general population. Conclusions: Age and baseline renal function, but not CVEs, are predictors of mortality and age and early HTN are independent predictors for having a CVE. CVD screening in AAV patients is demanded.(AU)

Introducción: La enfermedad cardiovascular (ECV) es una de las principales causas de muerte en las vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos (ANCA) (VAA). Objetivos: Evaluar la mortalidad y sus causas, entre ellas la ECV y sus factores de riesgo vascular (FRV) en pacientes con VAA en Andalucía. Métodos: Se estudió una cohorte multicéntrica de 220 pacientes con VAA seguidos desde 1979 hasta junio de 2020 en Andalucía. La información, incluidos los datos sociodemográficos y clínicos, se registró retrospectivamente a través de la revisión de historias clínicas. Los datos se analizaron mediante Chi2, ANOVA y regresión de riesgos proporcionales de Cox de forma uni y multivariante con un intervalo de confianza (IC) del 95%. Resultados: Durante un seguimiento medio y desviación estándar de 96,79 ± 75,83 meses, 51 pacientes fallecieron y 30 presentaron al menos un ECV. Los factores pronósticos independientes de mortalidad fueron la edad (HR 1,083, p=0,001) y la creatinina basal (HR 4,41, p=0,01). Los factores pronósticos independientes de ECV fueron la edad [hazard ratio (HR) 1,042, p=0,005] y la presencia de hipertensión arterial (HTA) seis meses después del diagnóstico (HR 4,641, p=0,01). La prevalencia de HTA, diabetes e insuficiencia renal fue elevada o muy elevada en comparación con la población general emparentada, todos FRCV determinantes para el pronóstico de estos pacientes. Conclusiones: La edad y la función renal basal son predictores de mortalidad y la edad y la HTA de aparición precoz son predictores independientes de tener ECV. Se recomienda el cribado de FRCV en pacientes con vasculitis ANCA.(AU)

n/p-Doping in a buckled honeycomb InAs monolayer using IVA-group impurities.

In this work, the effects of n/p-doping on the electronic and magnetic properties of a low-buckled honeycomb InAs monolayer are investigated using first-principles calculations. Herein, IVA-group atoms (C, Si, Ge, Sn, and Pb) are selected as impurities for n-doping in the In sublattice and p-doping in the As sublattice. The pristine monolayer is a semiconductor with a band gap of 0.77(1.41) as determined using the PBE(HSE06) functional. A single In vacancy induces magnetic semiconductor behavior with a large total magnetic moment of 2.98 µB, while a single As vacancy preserves the non-magnetic nature. The monolayer is not magnetized by n-doping with C and Si atoms due to the strong ionic interactions, while the magnetic semiconducting nature is induced with Ge, Sn, and Pb impurities. In these cases, magnetic properties are produced by IVA-group impurities and their neighboring As atoms. Furthermore, either a magnetic semiconducting or half-metallic nature is obtained via p-doping, whereas magnetism originates mainly from C, Si, Ge, and Sn dopants, and the As atoms closest to a Pb dopant. Further investigation indicates that the magnetization becomes stronger upon increasing the doping level, with a total magnetic moment of up to 3.92 µB with 25% Sn impurity. In addition, the thermal stability of the doped systems at room temperature is also confirmed by ab initio molecular-dynamics (AIMD) simulations. The results introduce IVA-group-assisted functionalization as an efficient way to make prospective 2D InAs-based spintronic materials.

In vitro evaluation of methanol extracts of edible fungi Pleurotus ostreatus and Lentinula edodes against Rhyssomatus nigerrimus Fahraeus.

The study aimed to evaluate the insecticidal activity of extracts of edible mushrooms Pleurotus ostreatus and Lentinula edodes against Rhyssomatus nigerrimus. Methanol:water extracts (70:30) of P. ostreatus and L. edodes were made and evaluated in two in vitro tests (exposure and immersion toxic effect) against R. nigerrimus. Subsequently, the toxicity test of the extracts against Artemia salina was evaluated. These extracts were subjected to colorimetric tests and gas chromatography-mass spectrometry. The results showed a mortality effect against R. nigerrimus of 50% for the P. ostreatus 2 extracts at a concentration of 20% in the immersion test. Likewise, in the toxic effect test, 90% mortality was observed after five days of exposure to a concentration of 10%. On the other hand, for the toxicity test, the extract that showed the values with the highest mortality against A. salina was P. ostreatus, starting with 80% mortality at 100µg/mL. The functional groups present in the extracts were saponins, coumarins, and alkaloids. Furthermore, the presence of more than 7 compounds in the mushroom extracts evaluated is reported. This study demonstrates the insecticidal activity of P. ostreatus and L. edodes fungal extracts and indicates the importance of using different in vitro tests to elucidate the mechanism of action for future studies.

Impact of an educational intervention about healthy lifestyles in teenagers.

BACKGROUND: During the last years, lifestyle has worsened along the entire European population, causing an alarming boom-up regarding overweight and obese people. Pediatric population is also influenced in this sense, which may predispose to suffer from several diseases in adulthood. Educational interventions at early ages could be an effective strategy to face this situation. AIM: To describe the impact of an educational intervention about healthy lifestyle in adolescents. METHODS: A quasi-experimental study analyzing the knowledge of high school students, before and after a brief educational intervention based on a self-elaborated questionnaire including questions from the validated questionnaire CAPA (from Spanish, Conocimientos en Alimentación de Personas Adolescentes). RESULTS: The results of this study show a significant increase in knowledge about healthy lifestyles in the study population after the educational intervention (14.3±3.8 vs. 16.5±4.5; p<0.001). In addition, this improvement presents an asymmetric distribution according to gender (13.2±3.6 vs. 14.9±4.6; p=0.002 in men; 15.6±3 vs. 18.1±3.6; p<0.001 in women) and the type of educational center (14.17±3.6 vs. 16.48±4.17; p<0.001 in public schools and 14.86±4.15 vs. 16.54±5.32; p=0.047 in private schools). Parents' educational level was associated with improvement in knowledge about healthy lifestyles (13.44±2.9 vs. 15.67±5.37; p=0.132 at low level, 14.22±3.42 vs. 16.9±4.68; p<0.001 at medium level and 15.75±3.3 vs. 17.39±4.5; p=0.022 at high level). CONCLUSION: Educational intervention taught by primary health care professionals is a useful and efficient tool for the acquisition of nutritional and healthy lifestyle knowledge in adolescents.

Diagnostic accuracy of patch testing based in clinical response to contact allergen restrictions in allergic contact dermatitis.

Summary: Background. Patch testing (PT) is used to identify substances that cause allergic contact dermatitis (ACD). However, the clinical effects of allergen restrictions following PT have not been thoroughly investigated. This study aims to assess the diagnostic accuracy of PT in patients suspected of having ACD. Methods. Prospective study. PT were performed in patients with clinical diagnosis of ACD. Patients with a positive PT (case group) had a strict restriction of the suspected substance for one month. In patients with negative patch testing (control group), allergen restriction was based in clinical history. Clinical reduction (CR) of at least 50% in disease activity (CR50%) after one month of allergen restriction was considered clinically relevant. Total control was defined as clinical reduction of at least 90% (CR90%). Results. From 400 patients, 66.2% had a positive PT. The sensitivity of PT to identify CR50% was 84%, specificity 47%, PPV 53%, and NPV 81%. Only 10.5% of patients achieved CR90%. Conclusions. The PT had moderate diagnostic accuracy. It could be useful as a screening, but a positive result should be confirmed with controlled allergen restriction. The low number of patients who achieved a 90% CR invites to reconsider the allergens included in PT and the mechanistic processes of the disease.