Transcriptional reprogramming post-peripheral nerve injury: A systematic review.

Neuropathic pain is characterised by periodic or continuous hyperalgesia, numbness, or allodynia, and results from insults to the somatosensory nervous system. Peripheral nerve injury induces transcriptional reprogramming in peripheral sensory neurons, contributing to increased spinal nociceptive input and the development of neuropathic pain. Effective treatment for neuropathic pain remains an unmet medical need as current therapeutics offer limited effectiveness and have undesirable effects. Understanding transcriptional changes in peripheral nerve injury-induced neuropathy might offer a path for novel analgesics. Our literature search identified 65 papers exploring transcriptomic changes post-peripheral nerve injury, many of which were conducted in animal models. We scrutinize their transcriptional changes data and conduct gene ontology enrichment analysis to reveal their common functional profile. Focusing on genes involved in 'sensory perception of pain' (GO:0019233), we identified transcriptional changes for different ion channels, receptors, and neurotransmitters, shedding light on its role in nociception. Examining peripheral sensory neurons subtype-specific transcriptional reprograming and regeneration-associated genes, we delved into downstream regulation of hypersensitivity. Identifying the temporal program of transcription regulatory mechanisms might help develop better therapeutics to target them effectively and selectively, thus preventing the development of neuropathic pain without affecting other physiological functions.

Verification of lifetime and mechanical load aspects for ITER diagnostic pressure gauges based on ZrC emitter.

Hot cathode ionization gauges will measure the neutral gas pressure in the vacuum vessel of ITER. Overall, 52 gauge heads based on the concept of the ASDEX pressure gauge but using novel ZrC emitters are located in the divertor, in equatorial ports and in pumping ducts. The initial lifetime tests of the novel gauge design have raised the concern that the pyrolytic graphite used to indirectly heat the ceramic ZrC emitter erodes too fast during operation. This effect might limit the lifetime of the gauges below the limits acceptable according to the inherent availability (ignoring operational delays) requirement of 99.8% for the diagnostic system over the lifetime of ITER. Long term operation tests have been performed using 0.1 mm thick W, Ir, and Mo foils as an interlayer between the pyrolytic graphite and the ZrC within a constant atmosphere of 20 Pa H2. The longest lifetime of 860 h has been achieved with the Ir foil. Subsequent vibration tests applying accelerations on a shaker with magnitudes typical for seismic and ITER disruption loads demonstrated that the emitter can survive such demanding loads even after far-progressed erosion of the pyrolytic graphite. Additional ON/OFF cycle tests demonstrated that the gauge is still fully operational. In combination with a revision and consolidation of the operational plan and the reliability, accessibility, maintainability, and inspectability (RAMI) analysis, ITER's inherent availability requirement for the diagnostic system could be demonstrated successfully.

Impact of future scenarios of climate change on lignin dynamics in soil: A case study in a Mediterranean savannah.

Lignin is an abundant and recalcitrant biopolymer of major relevance as soil organic matter (SOM) component playing a significant role in its stabilization. In this work, a factorial field experiment was established, where three climatic treatments (W, warming; D, drought; W + D, warming + drought), mimicking future climate change scenarios were installed over five years in a Mediterranean savannah "dehesa", accounting for its landscape diversity (under the tree canopy and in open grassland). A combination of analytical pyrolysis (Py-GC/MS) and the study of biogeochemical proxies based on lignin monomers is used for the direct detection of lignin-derived phenols and to infer possible shifts in lignin dynamics in soil. A total of 27 main lignin-derived methoxyphenols were identified, exhibiting different patterns and proportions, mainly driven by the effect of habitat, hence biomass inputs to SOM. An accelerated decomposition of lignin moieties -(exhibited by higher LG/LS and Al/K + Ac ratios)- is particularly exacerbated by the effect of all climatic treatments. There is also an overall effect on increasing lignin oxidation of side chain in syringyl units, especially under the tree canopy due to the alteration in biomass degradation and potential stimulation of enzyme activities. Conversely, in open grassland these effects are slower since the microbial community is expected to be already adapted to harsher conditions. Our findings suggests that climate change-related temperature and soil moisture deviations impact soil lignin decomposition in dehesas threatening this productive Mediterranean agroecosystem and affecting the mechanism of soil carbon storage.

Phycobiliprotein from Arthrospira maxima: Conversion to nanoparticles by high-energy ball milling, structural characterization, and evaluation of their anti-inflammatory effect.

Arthrospira maxima is a source of phycobiliproteins with different nutraceutical properties, e.g. antioxidant and anti-inflammatory activities. The current study was aimed at the elaboration, characterization, and evaluation of the anti-inflammatory effect of the phycobiliprotein nanoparticles extracted from Arthrospira maxima. Previously freeze-dried phycobiliproteins were milled by high-energy ball milling until reaching a nanometric size (optimal time: 4 h). Microscopy techniques were used for the characterization of the size and morphology of phycobiliproteins nanoparticles. Additionally, a spectroscopic study evidenced that nanosized reduction induced an increase in the chemical functional groups associated with its anti-inflammatory activity that was tested in a murine model, showing an immediate inflammatory effect. The novelty and importance of this contribution was to demonstrate that high energy ball milling is an emerging and green technology that can produce phycobiliprotein nanoparticles on a large-scale, without the use of organic solvents, to test their nutraceutical properties in a biological model by intragastric administration.

[Translated article] Efficacy of early versus delayed spinal cord decompression in neurological recovery after traumatic spinal cord injury: Systematic review and meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To compare early (<24h) versus late (>24h) spinal cord decompression on neurological recovery in patients with acute spinal cord injury. METHODS: A systematic review was performed according to the PRISMA protocol to identify studies published up to December 2022. Prospective cohort studies and controlled trials comparing early versus delayed decompression on neurological recovery were included. Variables included number of patients, level of injury, treatment time, ASIA grade, neurological recovery, use of corticosteroids, and complications. For the meta-analysis, the "forest plot" graph was developed. The risk of bias of the included studies was assessed using the ROBINS-I22 and Rob223 tools. RESULTS: Six of the seven studies selected for our review were included in the meta-analysis, with a total of 1188 patients (592 patients in the early decompression group and 596 in the delayed decompression group), the mean follow-up was 8 months, in 5 studies used methylprednisolone, the most reported complications were thromboembolic cardiopulmonary events. Five studies showed significant differences in favour of early decompression (risk difference 0.10, 95% confidence interval 0.07-0.14, heterogeneity 46%). The benefit was greatest in cervical and incomplete injuries. CONCLUSION: There is scientific evidence to recommend early decompression in the first 24h after traumatic spinal cord injury, as it improves final neurological recovery, and it should be recommended whenever the patient and hospital conditions allow it to be safely done.

Environmental stressor assessment of hydrocarbonoclastic bacteria biofilms from a marine oil spill.

The environmental and economic impact of an oil spill can be significant. Biotechnologies applied during a marine oil spill involve bioaugmentation with immobilised or encapsulated indigenous hydrocarbonoclastic species selected under laboratory conditions to improve degradation rates. The environmental factors that act as stressors and impact the effectiveness of hydrocarbon removal are one of the challenges associated with these applications. Understanding how native microbes react to environmental stresses is necessary for effective bioaugmentation. Herein, Micrococcus luteus and M. yunnanensis isolated from a marine oil spill mooring system showed hydrocarbonoclastic activity on Maya crude oil in a short time by means of total petroleum hydrocarbons (TPH) at 144 h: M. luteus up to 98.79 % and M. yunnanensis 97.77 % removal. The assessment of Micrococcus biofilms at different temperature (30 °C and 50 °C), pH (5, 6, 7, 8, 9), salinity (30, 50, 60, 70, 80 g/L), and crude oil concentration (1, 5, 15, 25, 35 %) showed different response to the stressors depending on the strain. According to response surface analysis, the main effect was temperature > salinity > hydrocarbon concentration. The hydrocarbonoclastic biofilm architecture was characterised using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Subtle but significant differences were observed: pili in M. luteus by SEM and the topographical differences measured by AFM Power Spectral Density (PSD) analysis, roughness was higher in M. luteus than in M. yunnanensis. In all three domains of life, the Universal Stress Protein (Usp) is crucial for stress adaptation. Herein, the uspA gene expression was analysed in Micrococcus biofilm under environmental stressors. The uspA expression increased up to 2.5-fold in M. luteus biofilms at 30 °C, and 1.3-fold at 50 °C. The highest uspA expression was recorded in M. yunnanensis biofilms at 50 °C with 2.5 and 3-fold with salinities of 50, 60, and 80 g/L at hydrocarbon concentrations of 15, 25, and 35 %. M. yunnanensis biofilms showed greater resilience than M. luteus biofilms when exposed to harsh environmental stressors. M. yunnanensis biofilms were thicker than M. luteus biofilms. Both biofilm responses to environmental stressors through uspA gene expression were consistent with the behaviours observed in the response surface analyses. The uspA gene is a suitable biomarker for assessing environmental stressors of potential microorganisms for bioremediation of marine oil spills and for biosensing the ecophysiological status of native microbiota in a marine petroleum environment.

From Immunity to Neurogenesis: Toll-like Receptors as Versatile Regulators in the Nervous System.

Toll-like receptors (TLRs) are among the main components of the innate immune system. They can detect conserved structures in microorganisms and molecules associated with stress and cellular damage. TLRs are expressed in resident immune cells and both neurons and glial cells of the nervous system. Increasing evidence is emerging on the participation of TLRs not only in the immune response but also in processes of the nervous system, such as neurogenesis and cognition. Below, we present a review of the literature that evaluates the expression and role of TLRs in processes such as neurodevelopment, behavior, cognition, infection, neuroinflammation, and neurodegeneration.

Characterization of workers or population percentage affected by low-back pain (LPB), sciatica and herniated disc due to whole-body vibrations (WBV).

Whole-body vibrations have several harmful effects on the population's health. The most suitable way to characterize the vibrations is to use the daily vibration exposure A (8) and Vibration Dose Value as specified in Directive 2002/44/EC. Therefore, based on the existing literature, we propose Probit equations that allow us to relate the population percentage affected by the vibration effects (low-back pain, sciatica, and herniated disc) with the A (8) and the Vibration Dose Value. It is worth noting that there is a good correlation between the experimental data and the expressions obtained, especially for low-back pain and herniated discs. Once the expressions have been validated, we analyze the limit values given in the aforementioned legislation, showing that the percentage of the affected population is significant for them. Therefore, this study also proposes new limits based on their own definitions, which are more in line with the results shown in the bibliography.

Candida albicans natural diversity: a resource to dissect fungal commensalism and pathogenesis.

Candida albicans is a ubiquitous fungus of humans. It is not only a component of the oral and intestinal microbiota of most healthy adults but also a major cause of mucosal disorders and life-threatening disseminated infections. Until recently, research on the biology and pathogenesis of the fungus was largely based on a single clinical isolate. We review investigations that have started to dissect a diverse set of C. albicans strains. Using different approaches to leverage the species' phenotypic and/or genetic diversity, these studies illuminate the wide range of interactions between fungus and host. While connecting genetic variants to phenotypes of interest remains challenging, research on C. albicans' natural diversity is central to understand fungal commensalism and pathogenesis.

Postoperative pain in dogs undergoing either laparoscopic or open ovariectomy.

A prospective, quasi-experimental, clinical trial was performed to assess acute postoperative pain in healthy female dogs following elective ovariectomy by either laparoscopy (n=13) or laparotomy (n=14). Pain was assessed by both a veterinarian at the hospital, and by the owner once the patient was discharged. The Spanish version of the short form of the Glasgow Composite Measuring Pain Scale (CMPS-SF) was used. Pain scores were assessed by the veterinarian preoperatively and at 1, 2, 4, and 6 h after extubation, whilst owner-assessed scores were performed preoperatively and at postoperative days 0, 1, 2, 3, 5 and 7. Data were compared with Mann-Whitney-U test. Veterinarian-assessed CMPS-SF scores were different between both groups at all postoperative times but not at baseline, being below 6/24 in all dogs in the laparoscopy group, but equal to or greater than 6/24 in the laparotomy group at 1 h (n=12), and 4 h (n=4) (P<0.001 and P=0.029, respectively). There were also differences in pain scores between both groups at 2 h (P=0.012) and 6 h (P=0.007), being below 6/24 in all of them. However, there were no differences in owner assessments between groups. In conclusion, ovariectomy performed by laparoscopy induced lower pain scores that were below the pain threshold set by the CMPS-SF during the first 6 h postoperatively. After discharge, and up to one week later, ongoing owner-assessed scores suggest no pain was induced with neither of the techniques. Owners were proactive allowing real-time pain assessment to be reported. The development and validation of instruments for acute pain assessment by owners is warranted, as these tools are currently lacking.

Impact of device resistances in the performance of graphene-based terahertz photodetectors.

In recent years, graphene field-effect-transistors (GFETs) have demonstrated an outstanding potential for terahertz (THz) photodetection due to their fast response and high-sensitivity. Such features are essential to enable emerging THz applications, including 6G wireless communications, quantum information, bioimaging and security. However, the overall performance of these photodetectors may be utterly compromised by the impact of internal resistances presented in the device, so-called access or parasitic resistances. In this work, we provide a detailed study of the influence of internal device resistances in the photoresponse of high-mobility dual-gate GFET detectors. Such dual-gate architectures allow us to fine tune (decrease) the internal resistance of the device by an order of magnitude and consequently demonstrate an improved responsivity and noise-equivalent-power values of the photodetector, respectively. Our results can be well understood by a series resistance model, as shown by the excellent agreement found between the experimental data and theoretical calculations. These findings are therefore relevant to understand and improve the overall performance of existing high-mobility graphene photodetectors.

Memory and language risk assessment with Wada test in patients candidates for epilepsy surgery. / Evaluación de la memoria y el lenguaje mediante el test de Wada en pacientes candidatos a cirugía de epilepsia.

AIM: To determine post-surgical cognitive risk and associated factors according to lesion location in a sample of patients evaluated for epilepsy surgery with Wada test at the Fundacion Instituto Neurologico de Colombia. MATERIALS AND METHODS: An observational, retrospective, analytical study was completed in patients with drug-resistant temporal lobe epilepsy candidates for epilepsy surgery treated from 2001 to 2021, who completed the Wada test as part of the pre-surgical evaluation. A descriptive analysis of sociodemographic, clinical, imaging and neuropsychological variables was completed; a multivariate logistic regression was performed analyzing factors associated with resection risk in patients with left lesions. RESULTS A total of 369 patients were included, 54.74% of the cases were women, with a median age of seizure onset of 11 years. 92.66% of the cases had lesional epilepsy and 68.56% were secondary to hippocampal sclerosis. Left hemisphere was the most frequently affected (65.68%) being dominant for memory and language in most of the patients with a proportion of 42.82% and 81.3%, respectively. The median functional adequacy was 43.75 (IQR 0-75) and the functional reserve was 75 (IQR 25 -93.75). In 104 patients, the Wada test determined a resection risk. In patients with a left lesion, it was found that functional reserve (PRadjusted 0.99, CI 95% 0.9997-0.9998) and having a right hemispheric dominance for memory (PRadjusted 0.92, CI 95% 0.547-0.999) were protective factors for post-surgical resection risk. CONCLUSION: Wada test is a useful tool for surgical decision-making in patients with drug-resistant temporal lobe epilepsy. When considering cognitive risk, components such as memory dominance and functional reserve should be considered as protective factors for postsurgical cognitive function preservation in patients with left lesions.

TITLE: Evaluación de la memoria y el lenguaje mediante el test de Wada en pacientes candidatos a cirugía de epilepsia.Objetivo. Determinar el riesgo cognitivo posquirúrgico y factores asociados según la localización de la lesión en una muestra de pacientes evaluados para cirugía de epilepsia con el test de Wada en la Fundación Instituto Neurológico de Colombia. Materiales y métodos. Se realizó un estudio observacional, retrospectivo y analítico en pacientes con epilepsia farmacorresistente del lóbulo temporal candidatos a cirugía de epilepsia tratados entre 2001 y 2021, que completaron el test de Wada como parte de la evaluación prequirúrgica. Se realizó un análisis descriptivo de variables sociodemográficas, clínicas, imagenológicas y neuropsicológicas. Se realizó una regresión logística multivariada analizando factores asociados al riesgo de resección en pacientes con lesiones izquierdas. Resultados. Se incluyó a 369 pacientes, el 54,74% de los casos fueron mujeres, con una mediana de edad de inicio de las convulsiones de 11 años. El 92,66% de los casos presentó epilepsia lesional; de éstos, el 68,56% fue secundario a esclerosis hipocampal. El hemisferio izquierdo fue el más frecuentemente afectado (65,68%), y éste fue dominante para la memoria y el lenguaje en la mayoría de los pacientes, con una proporción del 42,82 y el 81,3%, respectivamente. La mediana de adecuación funcional fue de 43,75 (rango intercuartílico: 0-75) y la reserva funcional de 75 (rango intercuartílico: 25-93,75). En 104 pacientes, el test de Wada determinó un riesgo de resección. En pacientes con lesiones izquierdas se encontró que la reserva funcional (razón de prevalencia ajustada: 0,99; intervalo de confianza al 95%: 0,9997-0,9998) y tener dominancia del hemisferio derecho para la memoria (razón de prevalencia ajustada: 0,92; intervalo de confianza al 95%: 0,547-0,999) fueron factores asociados para determinar el riesgo de resección posquirúrgico en el test de Wada. Conclusión. El test de Wada es una herramienta útil para la toma de decisiones quirúrgicas en pacientes con epilepsia del lóbulo temporal farmacorresistente. Componentes como la dominancia de la memoria y la reserva funcional en el test de Wada deben considerarse como factores que se deben tener en cuenta en la predicción de la preservación de la función cognitiva posquirúrgica en pacientes con lesiones izquierdas.

Combined optimization of spot positions and weights for better FLASH proton therapy.

Objective.In Intensity Modulated Proton Therapy (IMPT), the weights of individual pencil-beams or spots are optimized to fulfil dosimetric constraints. Theses spots are usually located on a regular lattice and their positions are fixed during optimization. In many cases, the range of spot weights may however be limited, leading sometimes to sub-optimal plan quality. An emblematic use case is the delivery of a plan at ultra-high dose rate (FLASH-RT), for which the spot weights are typically constrained to high values.Approach. To improve further the quality of IMPT FLASH plans, we propose here a novel algorithm to optimize both the spot weights and positions directly based on the objectives defined by the treatment planner.Main results. For all cases considered, optimizing the spot positions lead to an enhanced dosimetric score, while maintaining a high dose rate.Significance. Overall, this approach resulted in a substantial plan quality improvement compared to optimizing only the spot weights, and in a similar execution time.

Identification of Prominin-2 as a new player of cardiomyocyte senescence in the aging heart.

The aging heart is characterized by a number of structural changes leading to ventricular stiffness, impaired resistance to stress and increased risk of developing heart failure (HF). Genetic or pharmacological removal of senescent cells has recently demonstrated the possibility to relieve some cardiac aging features such as hypertrophy and fibrosis. However, the contribution of the different cell types in cardiac aging remains fragmentary due to a lack of cell-specific markers. Cardiomyocytes undergo post-mitotic senescence in response to telomere damage, characterized by persistent DNA damage response and expression of the classical senescence markers p21 and p16, which are shared by many other cell types. In the present study, we used transcriptomic approaches to discover new markers specific for cardiomyocyte senescence. We identified Prominin2 (Prom2), encoding a transmembrane glycoprotein, as the most upregulated gene in cardiomyocytes of aged mice compared to young mice. We showed that Prom2 was upregulated by a p53-dependent pathway in stress-induced premature senescence. Prom2 expression correlated with cardiomyocyte hypertrophy in the hearts of aged mice and was increased in atrial samples of patients with HF with preserved ejection fraction. Consistently, Prom2 overexpression was sufficient to drive senescence, hypertrophy and resistance to cytotoxic stress while Prom2 shRNA silencing inhibited these features in doxorubicin-treated cardiac cells. In conclusion, we identified Prom2 as a new player of cardiac aging, linking cardiomyocyte hypertrophy to senescence. These results could provide a better understanding and targeting of cell-type specific senescence in age-associated cardiac diseases.

Comparing two vascular division techniques in laparoscopic varicocelectomy. A prospective study. / Comparación de dos técnicas de sección vascular en la varicocelectomía laparoscópica. Estudio prospectivo.

INTRODUCTION: Varicocele is the abnormal dilatation of the pampiniform plexus. It occurs in 15-20% of pre-adolescent/adult males. Varicocele diagnosis is important since it can induce testicular hypertrophy and fertility issues in adulthood. The objective of this study was to assess whether complications, including varicocele recurrence, depend on the vascular occlusion technique used -clipping + division vs. vascular sealer- in the laparoscopic Palomo technique used in our institution. MATERIALS AND METHODS: A longitudinal, prospective study was carried out from 2017 to 2021. Two therapeutic groups were created according to the vascular occlusion method used during laparoscopic varicocelectomy -clipping + division vs. vascular sealer. Patients were randomly allocated to the groups in a systematic alternating consecutive manner. Variables -age, varicocele grade according to the Dubin-Amelar classification, postoperative complications, follow-up, and varicocele recurrence- were analyzed according to the method employed. RESULTS: A total of 37 boys, with a mean age of 12 years (10-15 years) and a mean follow-up of 12 months, were studied. In 20 patients (54.1%), clipping + division was used, and in the remaining 17 (45.9%), the vascular sealer was employed. 24.3% had symptomatic Grade II varicocele and 75.7% had Grade III varicocele. 32.4% of the children had postoperative complications during follow-up. 29.7% of the patients had hydrocele following surgery -8 boys from the sealing group and 3 boys from the clipping group-, with 13.5% requiring re-intervention as a result of this. None of the patients had varicocele recurrence. CONCLUSIONS: The laparoscopic Palomo technique is safe and effective, with good results in pediatric patients and few postoperative complications, regardless of the vascular occlusion device used. In our study, no statistically significant differences regarding the use of clipping or vascular sealer in this laparoscopic technique were found. However, further studies with a larger sample size are required to find potential differences.

INTRODUCCION: El varicocele es la dilatación anormal del plexo pampiniforme. Puede afectar al 15-20% de los varones preadolescentes-adultos. La importancia de su diagnóstico radica en que puede inducir hipotrofia testicular y problemas de fertilidad en la etapa adulta. El objetivo de este estudio es evaluar si existe mayor índice de complicaciones, incluyendo la recurrencia del varicocele, dependiendo de la técnica de oclusión vascular utilizada: clip y sección o sellador vascular, en la técnica de Palomo laparoscópico en nuestro centro. MATERIAL Y METODOS: Estudio longitudinal prospectivo que se realiza de 2017 a 2021. Se crean dos grupos terapéuticos según el método de oclusión vascular utilizada durante la varicocelectomía laparoscópica: clip y sección o sellador vascular. Los pacientes son incluidos en un grupo mediante asignación sistemática consecutiva alternante. Se realiza el análisis de las variables: edad, grado de varicocele según la clasificación de Dubin-Amelar, complicaciones postquirúrgicas, seguimiento y recurrencia del varicocele, según el método empleado. RESULTADOS: Se intervinieron un total de 37 niños, con edad media de 12 años (10-15 años) y una media de seguimiento de 12 meses. En 20 pacientes (54,1%), se utilizó clip y sección, y en los 17 restantes (45,9%), sellador vascular. El 24,3% presentaba varicocele Grado II sintomático y el 75,7%, Grado III. El 32,4% de los niños presentó alguna complicación postquirúrgica durante el seguimiento. El 29,7% de los pacientes presentó hidrocele tras la intervención, perteneciendo 8 niños al grupo de sellado y 3 niños al de clipaje. El 13,5% de estos precisó reintervención por este motivo. Ningún paciente presentó recurrencia del varicocele. CONCLUSIONES: La técnica de Palomo laparoscópica es una técnica segura y efectiva que presenta buenos resultados en pacientes pediátricos, ya que presenta pocas complicaciones postquirúrgicas, independientemente del dispositivo de oclusión vascular que se utilice. En nuestro estudio, no se ha demostrado que existan diferencias estadísticamente significativas en cuanto al uso de clip o sellador vascular en esta técnica laparoscópica. No obstante, es preciso realizar más estudios con mayor tamaño muestral para hallar posibles diferencias.

Prevalence and prognostic meaning of interstitial lung abnormalities in remote CT scans of patients with interstitial lung disease treated with antifibrotic therapy.

OBJECTIVES: To describe the prevalence and characteristics of interstitial lung abnormalities (ILA) in CT scans performed prior to the initiation of antifibrotics in a series of patients with interstitial lung disease (ILD), and to identify characteristics apparent on early CT scans that could help to predict outcomes. METHODS: We conducted a retrospective observational study. The original cohort consisted of 101 patients diagnosed with ILD and treated with antifibrotics in a tertiary hospital. Patients were included if they had a thoracic CT scan performed at least one year before initiation of therapy. They were classified radiologically in three groups: without ILA, with radiological ILA and extensive abnormalities. ILA were classified as subpleural fibrotic, subpleural non-fibrotic and non-subpleural. The initial scan and the latest CT scan performed before treatment were read for assessing progression. The relationship between CT findings of fibrosis and the radiological progression rate and mortality were analyzed. RESULTS: We included 50 patients. Only 1 (2%) had a normal CT scan, 25 (50%) had extensive alterations and 24 (48%) had radiological criteria for ILA, a median of 98.2 months before initiation of antifibrotics, of them 18 (75%) had a subpleural fibrotic pattern. Significant bronchiectasis and obvious honeycombing in the lower zones were associated with shorter survival (p = 0.04). Obvious honeycombing in the lower zones was also significantly (p < 0.05) associated with a faster progression rate. CONCLUSIONS: Fibrotic ILAs are frequent in remote scans of patients with clinically relevant ILD, long before they require antifibrotics. Findings of traction bronchiectasis and honeycombing in the earliest scans, even in asymptomatic patients, are related to mortality and progression later on.

Standard and Expanded Series Patch Testing Update by the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC). / Actualización de la batería estándar y batería ampliada de pruebas alérgicas de contacto por el Grupo Español de Investigación en Dermatitis de Contacto y Alergia Cutánea (GEIDAC).

After the meeting held by the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) back in October 2021, changes were suggested to the Spanish standard series patch testing. Hydroxyethyl methacrylate (2% pet.), textile dye mixt (6.6% pet.), linalool hydroperoxide (1% pet.), and limonene hydroperoxide (0.3% pet.) were, then, added to the series that agreed upon in 2016. Ethyldiamine and phenoxyethanol were excluded. Methyldibromoglutaronitrile, the mixture of sesquiterpene lactones, and hydroxyisohexyl 3-cyclohexene (Lyral) were alo added to the extended Spanish series of 2022.

The hyphal-specific toxin candidalysin promotes fungal gut commensalism.

The fungus Candida albicans frequently colonizes the human gastrointestinal tract, from which it can disseminate to cause systemic disease. This polymorphic species can transition between growing as single-celled yeast and as multicellular hyphae to adapt to its environment. The current dogma of C. albicans commensalism is that the yeast form is optimal for gut colonization, whereas hyphal cells are detrimental to colonization but critical for virulence1-3. Here, we reveal that this paradigm does not apply to multi-kingdom communities in which a complex interplay between fungal morphology and bacteria dictates C. albicans fitness. Thus, whereas yeast-locked cells outcompete wild-type cells when gut bacteria are absent or depleted by antibiotics, hyphae-competent wild-type cells outcompete yeast-locked cells in hosts with replete bacterial populations. This increased fitness of wild-type cells involves the production of hyphal-specific factors including the toxin candidalysin4,5, which promotes the establishment of colonization. At later time points, adaptive immunity is engaged, and intestinal immunoglobulin A preferentially selects against hyphal cells1,6. Hyphal morphotypes are thus under both positive and negative selective pressures in the gut. Our study further shows that candidalysin has a direct inhibitory effect on bacterial species, including limiting their metabolic output. We therefore propose that C. albicans has evolved hyphal-specific factors, including candidalysin, to better compete with bacterial species in the intestinal niche.