National Diagnostic Reference Levels for Standard Descending Thoracic Endovascular Aortic Repair and Optimisation Strategies.

OBJECTIVE: The International Commission on Radiological Protection has highlighted the large number of medical specialties that use fluoroscopy outside diagnostic imaging departments without radiation protection programmes for patients and staff. Vascular surgery is one of these specialties. Thoracic endovascular aortic repair (TEVAR) is a complicated procedure requiring radiation protection guidance and optimisation. The recent EU Basic Safety Standards Directive requires the use and periodic updating of diagnostic reference levels (DRLs) for interventional procedures. The aim of this study was to determine doses for patients undergoing TEVAR with mobile X-ray systems and hybrid rooms (fixed X-ray systems) to obtain national DRLs and to suggest optimisation actions. METHODS: This was a retrospective cross-sectional study. The Spanish Chapter of Endovascular Surgery conducted a national survey in 11 autonomous communities representing around 77.6% of the Spanish population (47.33 million inhabitants). A total of 266 TEVAR procedures from 17 Spanish centres were analysed, of which 50.2% were performed in hybrid operating rooms. National DRLs were obtained and defined as the third quartile of the median values from the different participating centres. RESULTS: The proposed national DRLs are: for kerma area product (KAP), 113.81 Gy·cm2 for mobile X-ray systems and 282.59 Gy·cm2 for hybrid rooms; and for cumulative air kerma (CAK) at the patient entry reference point, 228.38 mGy for mobile systems and 910.64 mGy for hybrid rooms. CONCLUSION: Based on the requirement to know radiation doses for standard endovascular procedures, this study of TEVARs demonstrated that there is an increased factor of 2.48 in DRLs for KAP when the procedure is performed in a hybrid room compared with mobile C-arm systems, and an increased factor of 3.98 in DRLs for CAK when the procedure is performed with hybrid equipment. These results will help to optimise strategies to reduce radiation doses during TEVAR procedures.

The mutation R107Q alters mtSSB ssDNA compaction ability and binding dynamics.

Mitochondrial single-stranded DNA-binding protein (mtSSB) is essential for mitochondrial DNA (mtDNA) replication. Recently, several mtSSB variants have been associated with autosomal dominant mitochondrial optic atrophy and retinal dystrophy. Here, we have studied at the molecular level the functional consequences of one of the most severe mtSSB variants, R107Q. We first studied the oligomeric state of this variant and observed that the mtSSBR107Q mutant forms stable tetramers in vitro. On the other hand, we showed, using complementary single-molecule approaches, that mtSSBR107Q displays a lower intramolecular ssDNA compaction ability and a higher ssDNA dissociation rate than the WT protein. Real-time competition experiments for ssDNA-binding showed a marked advantage of mtSSBWT over mtSSBR107Q. Combined, these results show that the R107Q mutation significantly impaired the ssDNA-binding and compacting ability of mtSSB, likely by weakening mtSSB ssDNA wrapping efficiency. These features are in line with our molecular modeling of ssDNA on mtSSB showing that the R107Q mutation may destabilize local interactions and results in an electronegative spot that interrupts an ssDNA-interacting-electropositive patch, thus reducing the potential mtSSB-ssDNA interaction sites.

Unveiling the Molecular Mechanisms of the Type-IX Secretion System's Response Regulator: Structural and Functional Insights.

The Type-IX secretion system (T9SS) is a nanomachinery utilized by bacterial pathogens to facilitate infection. The system is regulated by a signaling cascade serving as its activation switch. A pivotal member in this cascade, the response regulator protein PorX, represents a promising drug target to prevent the secretion of virulence factors. Here, we provide a comprehensive characterization of PorX both in vitro and in vivo . First, our structural studies revealed PorX harbours a unique enzymatic effector domain, which, surprisingly, shares structural similarities with the alkaline phosphatase superfamily, involved in nucleotide and lipid signaling pathways. Importantly, such pathways have not been associated with the T9SS until now. Enzymatic characterization of PorX's effector domain revealed a zinc-dependent phosphodiesterase activity, with active site dimensions suitable to accommodate a large substrate. Unlike typical response regulators that dimerize via their receiver domain upon phosphorylation, we found that zinc can also induce conformational changes and promote PorX's dimerization via an unexpected interface. These findings suggest that PorX can serve as a cellular zinc sensor, broadening our understanding of its regulatory mechanisms. Despite the strict conservation of PorX in T9SS-utilizing bacteria, we demonstrate that PorX is essential for virulence factors secretion in Porphyromonas gingivalis and affects metabolic enzymes secretion in the non-pathogenic Flavobacterium johnsoniae , but not for the secretion of gliding adhesins. Overall, this study advances our structural and functional understanding of PorX, highlighting its potential as a druggable target for intervention strategies aimed at disrupting the T9SS and mitigating virulence in pathogenic species.

Orthopantomography Detection of Atheroma Plaques and Its Relationship with Periodontal Disease and Missing Teeth.

Background: The aim of this study is to determine the atheromatous plaques' prevalence in orthopantomography and their relationship with periodontal disease and missing teeth. Material and Methods. Orthopantomographs of 1,254 patients over 18 years of age from Clínica Arlanza in Lerma, Burgos, were examined between 2017 and 2021. A Planmeca ProOne® orthopantomograph (68 kV, 7 mA, and 10 sg) was used. Statistical analysis was carried out using SPSS Statistics® version 25. The results of the categorical variables were described as frequencies (%). Contingency tables were made with the qualitative variables, and the chi-square test was applied to study the relationship among them. The measure of statistical power used was the relative risk (RR), which was described with its respective 95% confidence interval (CI). Student's t-test was applied to study the relationship between the qualitative variable "presence or absence of atheroma plaque" and the quantitative variable "number of teeth." Results: A 6.2% prevalence of atheroma plaques was obtained from 1,079 selected X-rays. The risk in patients with periodontal disease increased as periodontal disease worsened. The risk in patients with periodontal disease increased as periodontal disease worsened as follows: healthy patients vs. periodontal patients with less than 30% bone loss in radiography: RR 0.434, 95% CI 0.181-1.041, p = 0.053 healthy patients vs. patients with between 30%-60% bone loss: RR 0.177, 95% CI 0.075-0.418, p < 0.05 healthy patients vs. patients with more than 60% bone loss: RR 0.121, 95% CI 0.041-0.355, p < 0.05. Patients with calcifications on their orthopantomograms had a lower mean teeth number (20.9 teeth) compared to patients without calcifications (24 teeth), which was statistically significant, t (1077) = -3.125, p < 0.05. Conclusions: Orthopantomography can be considered a screening method to detect patients at increased cardiovascular risk who are referred for individualized study. It is important to continue research to know the real significance of these findings. Dentists should be aware of the importance of our work in our patients' systemic health.

Effectiveness and Safety of Teriflunomide in Relapsing-Remitting Multiple Sclerosis and Improvements in Quality of Life: Results from the Real-World TERICARE Study.

INTRODUCTION: Teriflunomide is a once-daily oral immunomodulator approved for relapsing forms of multiple sclerosis (MS) or relapsing-remitting multiple sclerosis (RRMS; depending on the local label), based on extensive evidence from clinical trials and a real-world setting on efficacy, tolerability and patient-reported benefits. The TERICARE study assessed the impact of teriflunomide treatment over 2 years on health-related quality of life (HRQoL) and some of the most common and disabling symptoms of MS, such as fatigue and depression. METHODS: This prospective observational study in Spain included RRMS patients treated with teriflunomide for ≤ 4 weeks. The following patient-reported outcomes (PROs) were collected at baseline and every 6 months for 2 years: the 29-item Multiple Sclerosis Impact Scale version 2 (MSIS-29), the 21-item Modified Fatigue Impact Scale (MFIS-21), the Beck Depression Inventory (BDI-II), the Short Form (SF)-Qualiveen and the Treatment Satisfaction Questionnaire for Medication v1.4 (TSQM). Annualised relapse rate (ARR), disability progression according to the Expanded Disability Status Scale (EDSS), and no evidence of disease activity (NEDA-3) were also assessed. RESULTS: A total of 325 patients were analysed. Patients had a mean (SD) age of 43.2 years (10.4), a mean baseline EDSS score of 1.75 (1.5), a mean number of relapses in the past 2 years of 1.5 (0.7), and 64% had received prior disease-modifying therapy (DMT). Patients showed significant improvements in the psychological domain of MSIS-29 from 35.9 (26.6) at baseline to 29.4 (25.5) at 18 months (p = 0.004) and 29.0 (24.6) at 24 months (p = 0.002). Levels of fatigue and depression were also reduced. After 2 years of treatment with teriflunomide, ARR was reduced to 0.17 (95% CI 0.14-0.21) from the baseline of 0.42 (95% CI 0.38-0.48), representing a 60.1% reduction. Mean EDSS scores remained stable during the study, and 79.9% of patients showed no disability progression. 54.7% of patients achieved NEDA-3 in the first 12 months, which increased to 61.4% during months 12-24. Patients reported increased satisfaction with treatment over the course of the study, regardless of whether they were DMT naive or not. CONCLUSION: Teriflunomide improves psychological aspects of HRQoL and maintains low levels of fatigue and depression. Treatment with teriflunomide over 2 years is effective in reducing ARR and disability progression.

Enfermedad de Still del adulto: serie de casos / Adult Still's disease: case series

Resumen La enfermedad de Still del adulto (ESA) es una enfermedad reumática e inflamatoria, infrecuente, de etiología desconocida. Su presentación clínica es variada y sus síntomas más frecuentes son fiebre, artralgias, exantema asalmonado evanescente, odinofagia, adenopatías, hepatoesplenomegalia, serositis y presencia en laboratorio de leucocitosis (neutrofilia), hiperferritinemia asociado a ausencia de anticuerpos. El diagnóstico es clínico y por exclusión. Existen criterios clasificatorios como son los de Yamaguchi1, Cush y Fautrel2,3 que ayudan a la orientación diagnóstica. El tratamiento se define según la presentación y la evolución clínica1. Se describen las características clínicas, diagnósticas, tratamiento y evolución de siete pacientes con ESA.

Abstract Adult Still's disease (ASD) is an uncommon rheumatic and inflammatory disorder of unknown etiology. The major clinical features include fever, arthralgia, transient salmon-pink rash, odynophagia, lymphadenopathy, hepatosplenomegaly, serositis, and laboratory findings such as leukocytosis with neutrophilia, hyperferritinemia, and negative immunologic laboratory testing. ASD diagnosis is reached by exclusion. Different classification criteria such as Yamaguchi, Cush and Fautrel have been developed for the identification of ASD. Treatment is based on the degree of disease activity and clinical response1. We describe clinical manifestations, diagnosis, treatment, and prognosis of seven patients with adult's Still disease.

Bitter taste receptors along the gastrointestinal tract: comparison between humans and rodents.

For decades bitter taste receptors (TAS2R) were thought to be located only in the mouth and to serve as sensors for nutrients and harmful substances. However, in recent years Tas2r have also been reported in extraoral tissues such as the skin, the lungs, and the intestine, where their function is still uncertain. To better understand the physiological role of these receptors, in this paper we focused on the intestine, an organ in which their activation may be similar to the receptors found in the mouth. We compare the relative presence of these receptors along the gastrointestinal tract in three main species of biomedical research (mice, rats and humans) using sequence homology. Current data from studies of rodents are scarce and while more data are available in humans, they are still deficient. Our results indicate, unexpectedly, that the reported expression profiles do not always coincide between species even if the receptors are orthologs. This may be due not only to evolutionary divergence of the species but also to their adaptation to different dietary patterns. Further studies are needed in order to develop an integrated vision of these receptors and their physiological functionality along the gastrointestinal tract.

Plastic degradation by insect hexamerins: Near-atomic resolution structures of the polyethylene-degrading proteins from the wax worm saliva.

Plastic waste management is a pressing ecological, social, and economic challenge. The saliva of the lepidopteran Galleria mellonella larvae is capable of oxidizing and depolymerizing polyethylene in hours at room temperature. Here, we analyze by cryo-electron microscopy (cryo-EM) G. mellonella's saliva directly from the native source. The three-dimensional reconstructions reveal that the buccal secretion is mainly composed of four hexamerins belonging to the hemocyanin/phenoloxidase family, renamed Demetra, Cibeles, Ceres, and a previously unidentified factor termed Cora. Functional assays show that this factor, as its counterparts Demetra and Ceres, is also able to oxidize and degrade polyethylene. The cryo-EM data and the x-ray analysis from purified fractions show that they self-assemble primarily into three macromolecular complexes with striking structural differences that likely modulate their activity. Overall, these results establish the ground to further explore the hexamerins' functionalities, their role in vivo, and their eventual biotechnological application.

Trends in stroke mortality in La Rioja (Spain) from 1999 to 2022.

INTRODUCTION: Stroke mortality has declined in recent decades, but there appears to be a slowdown in the decline in recent years. We analyze the trends in stroke mortality in La Rioja (Spain) for the period 1999-2022. METHODS: We evaluated stroke mortality using statistical data from the mortality registry of La Rioja (Spain). We adjusted the rates by age and sex and analyzed both overall strokes and subtypes: hemorrhagic and ischemic. To analyze the trend in mortality rates we constructed joinpoint regression models, with associated annual percentage change (APC) RESULTS: Age-standardized stroke mortality declined between 1999 and 2022: females from 98.0 to 29.2 per 100 000; males, from 131.6 to 44.8 per 100 000. We found a decrease in overall stroke mortality in all age groups, except those under 65 years old. Ischemic stroke mortality showed declines in the first decade (APC: 7.3%, CI95%: 4.1-19.1%) and increases in the second decade (APC: 1.6%, CI95%: -1.6-11.7%) among men. In women, the rates declined between 2018 and 2022(APC: -6.6%, CI95%: -5.1-30.6%) after an increase between 2015 and 2017 (APC: 23.5%, CI95%: -20.2-38.3%). For hemorrhagic stroke, we found a consistent rate of decline throughout the entire time period in men (APC: 2.4%, CI95%: 0.9 a 4.0%). In women, rates increased during the period 1999-2009(APC: 1.9%, CI95%: -2.1-22.8%) and decreased 2010-2022 (APC: 6.5%, CI95%: 4.0-25.6%). CONCLUSIONS: Stroke mortality rates have decreased, more so for haemorrhagic than ischaemic strokes.

Bloqueo anestésico del nervio occipital mayor en el tratamiento de las cefaleas. Revisión de la evidencia / Greater occipital nerve block in the treatment of headaches. Review of evidence

Introducción Los bloqueos anestésicos de nervios pericraneales han constituido un tratamiento habitual de múltiples cefaleas. El más utilizado en la práctica clínica habitual y que cuenta con mayor evidencia que avale su efectividad es el bloqueo del nervio occipital mayor. Métodos búsqueda en Pubmed de Meta-Analysis/Systematic Review de los últimos 10 años, seleccionando para su revisión aquellos metaanálisis, y en su defecto revisiones sistemáticas, acerca del bloqueo del nervio occipital mayor en el tratamiento de las cefaleas. Resultados Se obtuvieron 95 trabajos, 13 incluyeron los criterios de inclusión. Conclusión El bloqueo del occipital mayor es una técnica eficaz y segura, fácil de realizar, y que ha mostrado su utilidad en migraña, cefalea en racimos, cefalea cervicogénica y pospunción lumbar. No obstante, hacen falta más estudios que aclaren su eficacia a largo plazo, su lugar en el tratamiento habitual, la posible diferencia entre diversos anestésicos, la posología más conveniente y el papel del uso concomitante de corticoides (AU)

Introduction Peripheral nerve blocks have been a common treatment for multiple headaches. By far, the greater occipital nerve block is the most used and with the stronger body of evidence in routine clinical practice. Methods We searched Pubmed Meta-Analysis/Systematic Review, in the last 10 years. Of these results, meta-analyses, and in the absence of these systematic reviews, assessing Greater Occipital Nerve Block in headache has been selected for review. Results We identified 95 studies in Pubmed, 13 that met the inclusion criteria. Conclusion Greater occipital block is an effective and safe technique, easy to perform and which has shown its usefulness in migraine, cluster headache, cervicogenic headache and Post-dural puncture headache. However, more studies are needed to clarify its long-term efficacy, its place in clinical treatment, the possible difference between different anaesthetics, the most convenient dosage and the role of concomitant use of corticosteroids (AU)

Estudio y manejo de casos y contactos en el ámbito escolar, análisis del impacto de las medidas aplicadas al alumnado / Study and management of cases and contacts in the school environment, analysis of the impact of measures applied to students

Fundamento: Desde septiembre de 2020, los centros escolares permanecieron abiertos bajomedidas de prevención de la infección por COVID-19 y una estrecha vigilancia y control porparte de Salud Pública. Métodos: Se describió la organización y el procedimiento de rastreo escolar durante la pande-mia de COVID-19 en Navarra. Se estudió el alumnado rastreado, cuarentenas escolares, trans-misión en el aula, e impacto en la actividad educativa. Resultados: El rastreo fue desarrollado por el Departamento de Salud en coordinación con elDepartamento de Educación. Durante el curso 2020/21, la incidencia en escolares fue similar oinferior a la población general y las ondas epidémicas no mostraron relación con los periodoslectivos. El 26% del alumnado, mayormente de educación infantil y primaria, estuvo en cuaren-tena. La tasa de ataque secundaria (TAS) en las aulas fue inferior al 5%. En el curso 2021/22, laincidencia aumentó con la entrada de la variante Ómicron. Se indicó cuarentena en el 17% delalumnado de infantil y primaria durante el primer trimestre, y en el 11% durante el segundo. LaTAS ascendió al 18% en el primer trimestre, y la transmisión alcanzó niveles muy altos en el se-gundo, con grandes brotes. Las cuarentenas tuvieron un gran impacto en la actividad lectiva. Conclusiones: La gestión de casos y contactos en el ámbito escolar resultó de suma importan-cia para mantener un balance equilibrado entre la seguridad y el control de la pandemia en lasaulas, y asegurar las garantías pedagógicas y el bienestar de la infancia.(AU)

Dolor local durante la administración de paracetamol endovenoso que tiene como excipiente ácido acético / Local pain during the administration of intravenous paracetamol with acetic acid as excipient

Objetivo: evaluar la presencia de dolor local durante la administración endovenosa de paracetamol con ácido acético respecto a la administración de paracetamol sin ácido acético en los pacientes intervenidos en el bloque quirúrgico.Métodos: se realizó un ensayo clínico controlado aleatorizado doble ciego de dos grupos. Se incluyeron los pacientes mayores de edad intervenidos en el bloque quirúrgico de la Fundació Salut Empordà (Girona, España) durante los meses de agosto a noviembre de 2020, que precisaron administración de paracetamol endovenoso. Se requerían 60 pacientes por grupo (paracetamol con acetato frente a paracetamol sin acetato). Se recogieron variables sociodemográficas, relativas al catéter venoso, tratamiento, presencia de dolor y momento, valoración del dolor según escala numérica verbal (0 sin dolor a 10 peor dolor imaginable). Análisis descriptivo y bivariado. Comparación de grupos según el protocolo asignado.Resultados: se incluyeron 60 pacientes en cada grupo. La media de edad fue de 56,6 años (DE=15,6), el 56,7% fue varón. Los grupos fueron homogéneos y comparables en el momento basal. Se identificó presencia de dolor en el 48,3% (n= 29) de los pacientes del grupo de infusión de paracetamol con ácido acético, mientras que en el grupo sin acetato no se dio ningún caso de dolor (p< 0,001).Conclusiones: se observaron diferencias estadísticamente significativas entre el grupo de pacientes intervenidos del bloque quirúrgico a los que se les administró paracetamol sin ácido acético, que no presentaron dolor, frente al grupo de paracetamol con ácido acético, con presencia de dolor casi en la mitad de los pacientes.(AU)

Objective: to evaluate the presence of local pain during the intravenous administration of paracetamol with acetic acid compared with the administration of paracetamol without acetic acid in patients undergoing a procedure in the surgical unit.Methods: a double-blind randomized controlled clinical trial was conducted on two groups. All patients of age who underwent a procedure in the surgical unit of the Fundació Salut Empordà (Girona, Spain) from August to November 2020 and who needed the administration of intravenous paracetamol were included in the study. Sixty (60) patients were required per group (paracetamol with acetate vs. paracetamol without acetate). Sociodemographic variables were collected, as well as those related to the venous catheter, treatment, presence and time of pain, pain assessment according to the verbal numerical scale (from 0=no pain to 10=the worst pain imaginable). Descriptive and bivariate analysis. Comparison between arms according to the assigned protocol.Results: sixty (60) patients were included in each arm. Their mean age was 56.6 years (SD =15.6), and 56.7% were male. Arms were homogeneous and comparable at baseline. The presence of pain was detected in 48.3% (n= 29) of patients in the group receiving infusion of paracetamol with acetic acid, while there were no cases of pain in the group without acetate (p< 0.001).Conclusions: statistically significant differences were observed between the group of patients undergoing procedures in the surgical unit who were administered paracetamol without acetic acid, who did not present pain, vs. the group receiving paracetamol with acetic acid, where pain was present in almost half of the patients.(AU)

Structural analysis of the Candida albicans mitochondrial DNA maintenance factor Gcf1p reveals a dynamic DNA-bridging mechanism.

The compaction of mitochondrial DNA (mtDNA) is regulated by architectural HMG-box proteins whose limited cross-species similarity suggests diverse underlying mechanisms. Viability of Candida albicans, a human antibiotic-resistant mucosal pathogen, is compromised by altering mtDNA regulators. Among them, there is the mtDNA maintenance factor Gcf1p, which differs in sequence and structure from its human and Saccharomyces cerevisiae counterparts, TFAM and Abf2p. Our crystallographic, biophysical, biochemical and computational analysis showed that Gcf1p forms dynamic protein/DNA multimers by a combined action of an N-terminal unstructured tail and a long helix. Furthermore, an HMG-box domain canonically binds the minor groove and dramatically bends the DNA while, unprecedentedly, a second HMG-box binds the major groove without imposing distortions. This architectural protein thus uses its multiple domains to bridge co-aligned DNA segments without altering the DNA topology, revealing a new mechanism of mtDNA condensation.

[Greater occipital nerve block in the treatment of headaches. Review of evidence]. / Bloqueo anestésico del nervio occipital mayor en el tratamiento de las cefaleas. Revisión de la evidencia.

INTRODUCTION: Peripheral nerve blocks have been a common treatment for multiple headaches. By far, the greater occipital nerve block is the most used and with the stronger body of evidence in routine clinical practice. METHODS: We searched Pubmed Meta-Analysis/Systematic Review, in the last 10 years. Of these results, meta-analyses, and in the absence of these systematic reviews, assessing Greater Occipital Nerve Block in headache has been selected for review. RESULTS: We identified 95 studies in Pubmed, 13 that met the inclusion criteria. CONCLUSION: Greater occipital block is an effective and safe technique, easy to perform and which has shown its usefulness in migraine, cluster headache, cervicogenic headache and Post-dural puncture headache. However, more studies are needed to clarify its long-term efficacy, its place in clinical treatment, the possible difference between different anaesthetics, the most convenient dosage and the role of concomitant use of corticosteroids.