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El lupus eritematoso discoide lineal es una enfermedad crónica de etiología desconocida. Se caracteriza por placas eritematosas que siguen las líneas de Blaschko y constituye una variante inusual del lupus eritematoso discoide. En la presente revisión, se describe el caso de una paciente femenina que consultó por lesiones en la cara, área alopécica en el cuero cabelludo asociado a manifestaciones de lupus eritematoso sistémico, quien obtuvo una adecuada respuesta al tratamiento farmacológico. La búsqueda de los artículos científicos para el desarrollo de este reporte se realizó en las siguientes bases de datos: ClinicalKey, Ovid y PubMed. En la actualidad, es el primer reporte de caso clínico descrito de lupus eritematoso discoide lineal asociado a lupus eritematoso sistémico; se realizará una revisión de la literatura.

Connecting the gas in H ii regions to the underlying source of the ionizing radiation can help us constrain the physical processes of stellar feedback and how H ii regions evolve over time. With PHANGS–MUSE, we detect nearly 24 000 H ii regions across 19 galaxies and measure the physical properties of the ionized gas (e.g. metallicity, ionization parameter, and density). We use catalogues of multiscale stellar associations from PHANGS–HST to obtain constraints on the age of the ionizing sources. We construct a matched catalogue of 4177 H ii regions that are clearly linked to a single ionizing association. A weak anticorrelation is observed between the association ages and the $\mathrm{H}\, \alpha$ equivalent width $\mathrm{EW}(\mathrm{H}\, \alpha)$, the $\mathrm{H}\, \alpha/\mathrm{FUV}$ flux ratio, and the ionization parameter, log q. As all three are expected to decrease as the stellar population ages, this could indicate that we observe an evolutionary sequence. This interpretation is further supported by correlations between all three properties. Interpreting these as evolutionary tracers, we find younger nebulae to be more attenuated by dust and closer to giant molecular clouds, in line with recent models of feedback-regulated star formation. We also observe strong correlations with the local metallicity variations and all three proposed age tracers, suggestive of star formation preferentially occurring in locations of locally enhanced metallicity. Overall, $\mathrm{EW}(\mathrm{H}\, \alpha)$ and log q show the most consistent trends and appear to be most reliable tracers for the age of an H ii region.

This study uses data collected by Australia’s vaccine safety surveillance system to examine the adverse event profile of the modified vaccinia Ankara–Bavarian Nordic vaccine.

Las causales de justificación de la antijuridicidad penal no son reconocidas de forma expresa en el ámbito civil, creando la posibilidad de demandar por esta última vía a una persona absuelta de un delito que ha ocasionado daños. Ante este supuesto, es necesario establecer una línea de defensa en lo civil para aquel cuya inocencia haya sido ratificada en el ámbito penal. Lo que, argumentamos, se podría lograr con la aplicación de eximentes reconocidos en el Derecho de Daños en aquellos casos que hayan sido justificados por medio de la legítima defensa, el estado de necesidad, el mandato de ley, la orden de autoridad y el consentimiento del titular del bien jurídico protegido. El resultado, en este caso, sería la total exención de responsabilidad, tanto civil como penal.

Modernization of 3D printing has allowed for the production of porous titanium interbody cages (3D-pTi) which purportedly optimize implant characteristics and increase osseointegration; however, this remains largely unstudied in vivo.To compare osseointegration of three-dimensional (3D) titanium cages without bone graft and Polyether-ether-ketone (PEEK) interbody cages with autologous iliac crest bone graft (AICBG).Animal study utilizing an ovine in vivo model of lumbar fusion.Interbody cages of PEEK or 3D-pTi supplied by Spineart SA (Geneva, Switzerland) were implanted in seven living sheep at L2-L3 and L4-L5, leaving the intervening disc space untreated. Both implant materials were used in each sheep and randomized to the aforementioned disc spaces. Computed tomography (CT) was obtained at 4 weeks and 8 weeks. MicroCT and histological sections were obtained to evaluate osseointegration.MicroCT demonstrated osseous in-growth of native cancellous bone in the trabecular architecture of the 3D-pTi interbody cages and no interaction between the PEEK cages with the surrounding native bone. Qualitative histology revealed robust osseointegration in 3D-pTi implants and negligible osseointegration with localized fibrosis in PEEK implants. Evidence of intramembranous and endochondral ossification was apparent with the 3D-pTi cages. Quantitative histometric bone implant contact demonstrated significantly more contact in the 3D-pTi implants versus PEEK (p.001); region of interest calculations also demonstrated significantly greater osseous and cartilaginous interdigitation at the implant-native bone interface with the 3D-pTi cages (p=.008 and p=.015, respectively).3D-pTi interbody cages without bone graft outperform PEEK interbody cages with AICBG in terms of osseointegration at 4 and 8 weeks postoperatively in an ovine lumbar fusion model.3D-pTi interbody cages demonstrated early and robust osseointegration without any bone graft or additive osteoinductive agents. This may yield early stability in anterior lumbar arthrodesis and potentially bolster the rate of successful fusion. This could be of particular advantage in patients with spinal neoplasms needing post-ablative arthrodesis, where local autograft use would be ill advised.

This paper describes the adaptation of a self-management program for chronic conditions - DECIDE (Decision-making Education for Choices in Diabetes Everyday) to focus on mental health and be both trauma-informed and culturally appropriate for Latina immigrant ACE survivors with depression and/or anxiety symptoms.

first_pagesettingsOrder Article Reprints Open AccessArticle Metabolic Disturbance of High-Saturated Fatty Acid Diet in Cognitive Preservation by Antonio Rivas-Domínguez 1ORCID,Himan Mohamed-Mohamed 2,Margarita Jimenez-Palomares 3ORCID,Victoria García-Morales 3ORCID,Laura Martinez-Lopez 1,Manuel Luis Orta 1,Juan José Ramos-Rodriguez 2,*,†ORCID andBeatriz Bermudez-Pulgarin 1,† 1 Department of Cellular Biology, University of Seville, 41009 Seville, Spain 2 Department of Physiology, Faculty of Health Sciences (Ceuta), University of Granada, 51001 Ceuta, Spain 3 Department of Biomedicine, Biotechnology and Public Health, University of Cádiz, 11003 Cádiz, Spain * Author to whom correspondence should be addressed. † These authors contributed equally to this work. Int. J. Mol. Sci. 2023, 24(9), 8042; https://doi.org/10.3390/ijms24098042 Received: 31 March 2023 / Revised: 16 April 2023 / Accepted: 26 April 2023 / Published: 28 April 2023 (This article belongs to the Special Issue Research on Neural and Cognitive Molecular Mechanisms of Memory and Executive Control) Download Browse Figures Review Reports Versions Notes Abstract Aging continues to be the main cause of the development of Alzheimer’s, although it has been described that certain chronic inflammatory pathologies can negatively influence the progress of dementia, including obesity and hyperlipidemia. In this sense, previous studies have shown a relationship between low-density lipoprotein receptor (LDLR) and the amyloid-beta (Aβ) binding activity, one of the main neuropathological features of Alzheimer’s disease (AD). LDLR is involved in several processes, including lipid transport, regulation of inflammatory response and lipid metabolism. From this perspective, LDLR−/− mice are a widely accepted animal model for the study of pathologies associated with alterations in lipid metabolism, such as familial hypercholesterolemia, cardiovascular diseases, metabolic syndrome, or early cognitive decline. In this context, we induced hyperlipidemia in LDLR−/− mice after feeding with a high-saturated fatty acid diet (HFD) for 44 weeks. LDLR−/−-HFD mice exhibited obesity, hypertriglyceridemia, higher glucose levels, and early hepatic steatosis. In addition, HFD increased plasmatic APOE and ubiquitin 60S levels. These proteins are related to neuronal integrity and health maintenance. In agreement, we detected mild cognitive dysfunctions in mice fed with HFD, whereas LDLR−/−-HFD mice showed a more severe and evident affectation. Our data suggest central nervous system dysfunction is associated with a well-established metabolic syndrome. As a late consequence, metabolic syndrome boots many behavioral and pathological alterations recognized in dementia, supporting that the control of metabolic parameters could improve cognitive preservation and prognosis., Junta de Andalucía, Spain, grant number P18-RT-3324, P20-01061 from Junta de Andalucía, Spain, PID2019- 110960GB-I00 from the Ministry of Science and Innovation, Spain

Background: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking.Methods: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, Results: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups.Conclusions: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.). Background The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. Methods In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age

Supplementary Table S2. Small-molecule library.

Pediatric tumors harbor very low numbers of somatic mutations and therefore offer few targets to improve therapeutic management with targeted drugs. In particular, outcomes remain dismal for patients with metastatic alveolar rhabdomyosarcoma (aRMS), where the chimeric transcription factor PAX3/7-FOXO1 has been implicated but problematic to target. In this report, we addressed this challenge by developing a two-armed screen for druggable upstream regulatory kinases in the PAX3/7-FOXO1 pathway. Screening libraries of kinome siRNA and small molecules, we defined PLK1 as an upstream-acting regulator. Mechanistically, PLK1 interacted with and phosphorylated PAX3-FOXO1 at the novel site S503, leading to protein stabilization. Notably, PLK1 inhibition led to elevated ubiquitination and rapid proteasomal degradation of the PAX3-FOXO1 chimeric oncoprotein. On this basis, we embarked on a preclinical validation of PLK1 as a target in a xenograft mouse model of aRMS, where the PLK1 inhibitor BI 2536 reduced PAX3-FOXO1–mediated gene expression and elicited tumor regression. Clinically, analysis of human aRMS tumor biopsies documented high PLK1 expression to offer prognostic significance for both event-free survival and overall survival. Taken together, these preclinical studies validate the PLK1–PAX3-FOXO1 axis as a rational target to treat aRMS. Cancer Res; 75(1); 98–110. ©2014 AACR.

Supplementary Table S1. PAX3-FOXO1 regulating kinases identified by siRNA screen.

Supplementary Figure Legends. Legend for Supplementary Figures S1-S7.

Supplementary Table S3. PAX3-FOXO1 phospho-peptides identified by mass spectrometry.

Supplementary Materials and Methods. Description of additional methods and procedures used in the study.

The surveillance of arboviruses in mangrove mosquitoes is a neglected topic in Mexico. The Yucatan State is part of a peninsula and, therefore, is rich in mangroves along its coast. The purpose of the study was to identify alphavirus in the mosquito fauna of mangroves. Mosquitoes were captured in mangrove settings in seven communities in Yucatan between June 2019 and August 2021. From 1900 to 2200 h and from 0500 to 0800 h, mosquitoes were captured with a backpack-mounted aspirator. In total, 3,167 female mosquitoes of five genera and nine species were captured. Aedes taeniorhynchus and Anopheles crucians were the most abundant mosquitoes collected. Mosquitoes were sorted into 210 pools and tested by reverse transcription-polymerase chain reaction for alphavirus ribonucleic acid (RNA). Alphavirus RNA was found in Ae. taeniorhynchus, An. pseudopunctipennis, and An. crucians collected in the Celestun Mangrove. The community is part of the Ria Celestun Biosphere Reserve, and the presence arbovirus-infected mosquitoes could pose a health risk to residents and visitors alike in the area.

(1) Background: In the mHeart trial, we showed that an eHealth intervention, mHeart, improved heart transplant (HTx) recipients’ adherence to immunosuppressive therapy compared with the standard of care. Herein, we present the analysis assessing whether mHeart reduces complication frequency and healthcare resource use, and whether this reduction depends on patients’ adherence. (2) Methods: The mHeart was a single-center randomized-controlled trial (IIBSP-MHE-2014-55) in 134 adult HTx recipients (n = 71 intervention; n = 63 controls). The endpoints were mortality, complications, and resource use during follow-up (mean 1.6 ± 0.6 years). (3) Results: A significantly lower proportion of HTx recipients in mHeart had echocardiographic alteration (2.8% vs. 13.8%; p = 0.02), cardiovascular events (0.35% vs. 2.4%; p = 0.006), infections (17.2% vs. 56%; p = 0.03), and uncontrolled Hba1c (40.8% vs. 59.6%; p = 0.03) than controls. In addition, a significantly lower proportion of patients in the intervention needed hospital (32.4% vs. 56.9%; p = 0.004) or urgent admissions (16.9% vs. 41.4%; p = 0.002) and emergency room visits (50.7% vs. 69.0%; p = 0.03). Adherence status (measured by the self-reported SMAQ) influenced only controls regarding hospitalizations and emergency room visits. Differences were not significant on deaths (intervention 4.2% vs. control 9.5%; p = 0.4) (4) Conclusions: the mHeart strategy significantly reduced the occurrence of the studied post-transplant complications and the need for medical attention in HTx recipients. Adherence status influenced controls in their need for medical care.

OBJECTIVE Ultrasound is considered a real-time imaging method in neuro-oncology because of its highly rapid image acquisition time. However, to our knowledge, there are no studies that analyze the additional surgical time that it requires. METHODS A prospective study of 100 patients who underwent intra-axial brain tumor resection with navigated intraoperative ultrasound. The primary outcomes were lesion visibility grade on ultrasound and concordance with preoperative magnetic resonance imaging (MRI) scan, intraoperative ultrasound usage time, and percentage of tumor resection on ultrasound and comparison with postoperative MRI scan. RESULTS The breakdown of patients included the following: 53 high-grade gliomas, 26 metastases, 14 low-grade gliomas, and 7 others. Ninety-six percent of lesions were clearly visualized. The tumor border was clearly delimited in 71%. Concordance with preoperative MRI scan was 78% (P < 0.001). The mean time ± SD for sterile covering of the probe was 2.16 ± 0.5 minutes, and the mean image acquisition time was 2.49 ± 1.26 minutes. Insular tumor location, low-grade glioma, awake surgery, and recurrent tumor were statistically associated with an increased ultrasound usage time. Ultrasound had a sensitivity of 94.4% and a specificity of 100% for residual tumor detection. CONCLUSIONS Neuronavigated ultrasound can be considered a truly real-time intraoperative imaging method because it does not increase surgical time significantly and provides optimal visualization of intra-axial brain lesions and residual tumor.

Rheumatoid arthritis (RA) associates with cardiovascular risk factors (CVRF) such as dyslipidemias and systemic inflammation. Cardiovascular Disease (CVD) is the leading cause of mortality. The hypertriglyceridemic waist phenotype (HTWP) identifies increased CVRF; however, information about HTWP on RA is scarce. Objective: To evaluate the association of HTWP with CVRF in RA. Material and methods: Cross-sectional study. Women (125) with RA were included (ACR, 1987). Anthropometry, bioimpedance, body mass index (BMI), disease activity score 28 (DAS28), and health assessment questionnaire disability index (HAQ-Di) were determined. The lipid profile determination includes the atherogenic index (AI) (TC/HDL) and Framingham Risk Score. HTWP is defined as a waist circumference ≥88 cm and triglycerides ≥ 150 mg/dL. Chi-squared and Student’s t-tests were applied for comparisons. Results: HTWP was found in 38 (30.4%) patients. The subgroup with HTWP had a greater frequency of arterial hypertension (AHT) (57.9 vs. 37.9, p = 0.04), Type 2 DM (23.7 vs. 8.0, p= 0.02), BMI (29.7 ± 3.2, vs. 26.8 ± 4.3, p < 0.001), fat mass (39.3 ± 4.8 vs. 34.7 ± 6.8, p < 0.001), and AI (4.7 ± 1.2 vs. 3.7 ± 1.0, p < 0.001). No differences between DAS28 and HAQ-Di were found. HTWP was associated with the presence of MetS and CVR (p < 0.001 and p = 0.012, respectively). Conclusion: The HTWP in RA is associated with CVRF, and its potential predictive role should be evaluated in longitudinal studies.

We present maps of the 3.3 micron polycyclic aromatic hydrocarbon (PAH) emission feature in NGC 628, NGC 1365, and NGC 7496 as observed with the Near-Infrared Camera (NIRCam) imager on JWST from the PHANGS-JWST Cycle 1 Treasury project. We create maps that isolate the 3.3 micron PAH feature in the F335M filter (F335M$_{\rm PAH}$) using combinations of the F300M and F360M filters for removal of starlight continuum. This continuum removal is complicated by contamination of the F360M by PAH emission and variations in the stellar spectral energy distribution slopes between 3.0 and 3.6 micron. We modify the empirical prescription from Lai et al. (2020) to remove the starlight continuum in our highly resolved galaxies, which have a range of starlight- and PAH-dominated lines-of-sight. Analyzing radially binned profiles of the F335M$_{\rm PAH}$ emission, we find that between 5-65% of the F335M intensity comes from the 3.3 micron feature within the inner 0.5 $r_{25}$ of our targets. This percentage systematically varies from galaxy to galaxy, and shows radial trends within the galaxies related to each galaxy's distribution of stellar mass, interstellar medium, and star formation. The 3.3 micron emission is well correlated with the 11.3 micron PAH feature traced with the MIRI F1130W filter, as is expected, since both features arise from C-H vibrational modes. The average F335M$_{\rm PAH}$/F1130W ratio agrees with the predictions of recent models by Draine et al. (2021) for PAHs with size and charge distributions shifted towards larger grains with normal or higher ionization., Comment: submitted to AAS journals and revised according to referee comments, part of a PHANGS-JWST Focus Issue to appear in ApJ

BackgroundTo determine whether depressive symptoms in traumatic brain injury (TBI) patients were associated with altered resting-state functional connectivity (rs-fc) or voxel-based morphology in brain regions involved in emotional regulation and associated with depression.MethodsIn the present study, we examined 79 patients (57 males; age range = 17–70 years, M ± s.d. = 38 ± 16.13; BDI-II, M ± s.d. = 9.84 ± 8.67) with TBI. We used structural MRI and resting-state fMRI to examine whether there was a relationship between depression, as measured with the Beck Depression Inventory (BDI-II), and the voxel-based morphology or functional connectivity in regions previously identified as involved in emotional regulation in patients following TBI. Patients were at least 4 months post-TBI (M ± s.d. = 15.13 ± 11.67 months) and the severity of the injury included mild to severe cases [Glasgow Coma Scale (GCS), M ± s.d. = 6.87 ± 3.31].ResultsOur results showed that BDI-II scores were unrelated to voxel-based morphology in the examined regions. We found a positive association between depression scores and rs-fc between limbic regions and cognitive control regions. Conversely, there was a negative association between depression scores and rs-fc between limbic and frontal regions involved in emotion regulation.ConclusionThese findings lead to a better understanding of the exact mechanisms that contribute to depression following TBI and better inform treatment decisions.

Introduction Although endonasal endoscopic approaches (EEA) to the orbit have been previously reported, a didactic resource for educating neurosurgery and otolaryngology trainees regarding the pertinent anatomy, techniques, and decision-making pearls is lacking. Methods Six sides of three formalin-fixed, color latex–injected cadaveric specimens were dissected using 4-mm 0- and 30-degree rigid endoscopes, as well as standard endoscopic equipment, and a high-speed surgical drill. The anatomical dissection was documented in stepwise three-dimensional (3D) endoscopic images. Following dissection, representative case applications were reviewed. Results EEA to the orbit provides excellent access to the medial and inferior orbital regions. Key steps include positioning and preoperative considerations, middle turbinate medialization, uncinate process and ethmoid bulla removal, complete ethmoidectomy, sphenoidotomy, maxillary antrostomy, lamina papyracea resection, orbital apex and optic canal decompression, orbital floor resection, periorbita opening, dissection of the extraconal fat, and final exposure of the orbit contents via the medial-inferior recti corridor. Conclusion EEA to the orbit is challenging, in particular for trainees unfamiliar with nasal and paranasal sinus anatomy. Operatively oriented neuroanatomy dissections are crucial didactic resources in preparation for practical endonasal applications in the operating room (OR). This approach provides optimal exposure to the inferior and medial orbit to treat a wide variety of pathologies. We describe a comprehensive step-by-step curriculum directed to any audience willing to master this endoscopic skull base approach.

Tomando como eje la representación de personas que encarnaban enfermedades congénitas visibles, examinamos los intereses particulares que estas imágenes han suscitado desde el siglo XVI, desde la Medicina y la Historia del Arte. Mediante diferentes tipos de medios visuales –tratados médicos, pintura y cine–, estudiamos los valores que revelan según los contextos en los que se crearon y publicaron. Como enfoque metodológico, planteamos un análisis transdisciplinar, centrándonos en personas a las que la medicina contemporánea habría asignado diagnósticos de origen genético-cromosómico. ¿Quiénes y en qué contextos se encargaron estas representaciones? ¿A qué función estaban destinadas? ¿Qué intereses tienen quienes las crean? ¿Qué papel tienen las personas representadas? Los grabados en tratados médicos en los siglos XVI y XVII muestran representaciones para la comprensión científica del cuerpo expuesto, tipifican el sujeto y no se otorga relevancia personal. En la pintura y el cine, a pesar de sus notables diferencias, se subraya la identidad personal en un contexto social particular, expresada con profundidad psicológica y sensibilidad. Es el cruce de miradas entre el arte y la medicina donde se puede apreciar cómo se van expandiendo las fronteras inteligibles del cuerpo.

Tomando como eje la representación de personas que encarnaban enfermedades congénitas visibles, examinamos los intereses particulares que estas imágenes han suscitado desde el siglo XVI, desde la Medicina y la Historia del Arte. Mediante diferentes tipos de medios visuales –tratados médicos, pintura y cine–, estudiamos los valores que revelan según los contextos en los que se crearon y publicaron. Como enfoque metodológico, planteamos un análisis transdisciplinar, centrándonos en personas a las que la medicina contemporánea habría asignado diagnósticos de origen genético-cromosómico. ¿Quiénes y en qué contextos se encargaron estas representaciones? ¿A qué función estaban destinadas? ¿Qué intereses tienen quienes las crean? ¿Qué papel tienen las personas representadas? Los grabados en tratados médicos en los siglos XVI y XVII muestran representaciones para la comprensión científica del cuerpo expuesto, tipifican el sujeto y no se otorga relevancia personal. En la pintura y el cine, a pesar de sus notables diferencias, se subraya la identidad personal en un contexto social particular, expresada con profundidad psicológica y sensibilidad. Es el cruce de miradas entre el arte y la medicina donde se puede apreciar cómo se van expandiendo las fronteras inteligibles del cuerpo.

We compare mid-infrared (mid-IR), extinction-corrected H$\alpha$, and CO (2-1) emission at 70--160 pc resolution in the first four PHANGS-JWST targets. We report correlation strengths, intensity ratios, and power law fits relating emission in JWST's F770W, F1000W, F1130W, and F2100W bands to CO and H$\alpha$. At these scales, CO and H$\alpha$ each correlate strongly with mid-IR emission, and these correlations are each stronger than the one relating CO to H$\alpha$ emission. This reflects that mid-IR emission simultaneously acts as a dust column density tracer, leading to the good match with the molecular gas-tracing CO, and as a heating tracer, leading to the good match with the H$\alpha$. By combining mid-IR, CO, and H$\alpha$ at scales where the overall correlation between cold gas and star formation begins to break down, we are able to separate these two effects. We model the mid-IR above $I_\nu = 0.5$~MJy sr$^{-1}$ at F770W, a cut designed to select regions where the molecular gas dominates the interstellar medium (ISM) mass. This bright emission can be described to first order by a model that combines a CO-tracing component and an H$\alpha$-tracing component. The best-fitting models imply that $\sim 50\%$ of the mid-IR flux arises from molecular gas heated by the diffuse interstellar radiation field, with the remaining $\sim 50\%$ associated with bright, dusty star forming regions. We discuss differences between the F770W, F1000W, F1130W bands and the continuum dominated F2100W band and suggest next steps for using the mid-IR as an ISM tracer., Comment: 49 pages, 17 figures, Section 8 provides a detailed summary, accepted for publication in ApJ Letters, part of a PHANGS-JWST Focus Issue to appear in ApJ

We compare embedded young massive star clusters (YMCs) to (sub-)millimeter line observations tracing the excitation and dissociation of molecular gas in the starburst ring of NGC 1365. This galaxy hosts one of the strongest nuclear starbursts and richest populations of YMCs within 20 Mpc. Here we combine near-/mid-IR PHANGS-JWST imaging with new ALMA multi-J CO (1-0, 2-1 and 4-3) and [CI](1-0) mapping, which we use to trace CO excitation via R42 = I_CO(4-3)/I_CO(2-1) and R21 = I_CO(2-1)/I_CO(1-0) and dissociation via RCICO = I_[CI](1-0)/I_CO(2-1) at 330 pc resolution. We find that the gas flowing into the starburst ring from northeast to southwest appears strongly affected by stellar feedback, showing decreased excitation (lower R42) and increased signatures of dissociation (higher RCICO) in the downstream regions. There, radiative transfer modeling suggests that the molecular gas density decreases and temperature and [CI/CO] abundance ratio increase. We compare R42 and RCICO with local conditions across the regions and find that both correlate with near-IR 2 um emission tracing the YMCs and with both PAH (11.3 um) and dust continuum (21 um) emission. In general, RCICO exhibits ~ 0.1 dex tighter correlations than R42, suggesting CI to be a more sensitive tracer of changing physical conditions in the NGC 1365 starburst than CO (4-3). Our results are consistent with a scenario where gas flows into the two arm regions along the bar, becomes condensed/shocked, forms YMCs, and then these YMCs heat and dissociate the gas., 19 pages, 7 figures and 2 tables in total (12 pages and 6 figures in main text). Accepted as part of a PHANGS-JWST Focus Issue to appear in ApJL

The PHANGS collaboration has been building a reference data set for the multiscale, multiphase study of star formation and the interstellar medium (ISM) in nearby galaxies. With the successful launch and commissioning of JWST, we can now obtain high-resolution infrared imaging to probe the youngest stellar populations and dust emission on the scales of star clusters and molecular clouds (∼5–50 pc). In Cycle 1, PHANGS is conducting an eight-band imaging survey from 2 to 21 μm of 19 nearby spiral galaxies. Optical integral field spectroscopy, CO(2–1) mapping, and UV-optical imaging for all 19 galaxies have been obtained through large programs with ALMA, VLT-MUSE, and Hubble. PHANGS–JWST enables a full inventory of star formation, accurate measurement of the mass and age of star clusters, identification of the youngest embedded stellar populations, and characterization of the physical state of small dust grains. When combined with Hubble catalogs of ∼10,000 star clusters, MUSE spectroscopic mapping of ∼20,000 H II regions, and ∼12,000 ALMA-identified molecular clouds, it becomes possible to measure the timescales and efficiencies of the earliest phases of star formation and feedback, build an empirical model of the dependence of small dust grain properties on local ISM conditions, and test our understanding of how dust-reprocessed starlight traces star formation activity, all across a diversity of galactic environments. Here we describe the PHANGS–JWST Treasury survey, present the remarkable imaging obtained in the first few months of science operations, and provide context for the initial results presented in the first series of PHANGS–JWST publications., La lista completa de autores que integran el documento puede consultarse en el archivo., Instituto de Astrofísica de La Plata

[EN] Proteases are abundant in prokaryotic genomes (~10 per genome), but their recovery encounters expression problems, as only 1% can be produced at high levels; this value differs from that of similarly abundant esterases (1–15 per genome), 50% of which can be expressed at good levels. Here, we design a catalytically efficient artificial protease that can be easily produced. The PluriZyme EH with two active sites supporting the esterase activity was employed. A Leu24Cys mutation in EH, remodelled one of the esterase sites into a proteolytic one through the incorporation of a catalytic dyad (Cys24 and His214). The resulting artificial enzyme, EH, efficiently hydrolysed (azo)casein at pH 6.5–8.0 and 60–70 °C. The presence of both esterase and protease activities in the same scaffold allowed the one-pot cascade synthesis (55.0 ± 0.6% conversion, 24 h) of L-histidine methyl ester from the dipeptide L-carnosine in the presence of methanol. This study demonstrates that active sites supporting proteolytic activity can be artificially introduced into an esterase scaffold to design easy-to-produce in-one protease-esterase PluriZymes for cascade reactions, namely, the synthesis of amino acid esters from dipeptides. It is also possible to design artificial proteases with good production yields, in contrast to natural proteases that are difficult to express., This research was funded by the FuturEnzyme Project, funded by the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 101000327 and 101000607. We also acknowledge the financial support under Grants PID2020-112758RB-I00 (M.F.), PID2019-106370RB-I00 (V.G.), PDC2021-121534-I00 (M.F.), and PID2019-105838RB-C31 (F.J.P.), from the Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación (AEI) (Digital Object Identifier 10.13039/501100011033), Fondo Europeo de Desarrollo Regional (FEDER) and the European Union (“NextGenerationEU/PRTR”), and Grant 2020AEP061 (M.F.) from the Agencia Estatal CSIC. SR thanks the Spanish Ministry of Science and Innovation for a PhD fellowship (FPU19/00608).

Background. Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. Methods. Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. Results. The RA + osteoporosis group had elevated sRANKL levels ( p = 0.005 ), higher sRANKL/OPG ratio ( p = 0.017 ), decreased DKK-1 ( p = 0.028 ), and lower SOST levels ( p < 0.001 ). Low total hip BMD correlated with high sRANKL ( p = 0.001 ) and sRANKL/OPG ratio ( p = 0.005 ). Total hip and lumbar spine BMD correlated with DKK-1 ( p = 0.009 and p = 0.05 , respectively) and SOST levels ( p < 0.001 and p < 0.001 , respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures ( p = 0.003 and p = 0.003 , respectively) and hip fracture ( p = 0.002 and p = 0.006 , respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture ( p = 0.003 ) and hip fracture ( p = 0.009 ). Conclusion. High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.

The discovery of new enzymes is strongly enabled by the implementation of high-throughput screening methods to detect enzymatic activity in single organisms or clone expression libraries, or to benchmark their performances against known prototypes. In this chapter, a number of methods, applicable at high-throughput scale, are described that allow the screening and characterization of enzymes relevant to biotechnology, particularly, ester-hydrolases (esterases, lipases, phospholipases, and polyester hydrolases).

Currently, demand for functional foods is increasing in the public interest in order to improve life expectations and general health. Food matrices containing probiotic microorganisms and active compounds encapsulated into carrier agents are essential in this context. Encapsulation via the lyophilisation method is widely used because oxidation reactions that affect physicochemical and nutritional food properties are usually avoided. Encapsulated functional ingredients, such as quercetin and

Background: Muscle wasting, also known as myopenia, is frequent in rheumatoid arthritis (RA). To date, it is still unknown if the failure of pharmacologic therapies increases the risk of myopenia in RA. Objective: To identify if treatment failure with conventional synthetic DMARDs (csDMARDs) constitutes an independent risk factor of muscle wasting in women with RA. Methods: This was a cross-sectional study. We included 277 women with RA. Assessments in RA patients included: clinical, epidemiological, and therapeutic variables. The skeletal muscle index (SMI) was estimated by DXA, and myopenia was diagnosed if they had an SMI < 5.45 kg/m2. Multivariable logistic regression models identified risk factors of myopenia. Results: Muscle wasting was observed in 28.2% of patients with RA. The risk factors of myopenia in RA were menopausal (OR: 4.45, 95% CI: 1.86 to 10.64) and failure of combined therapy with csDMARDs (OR: 2.42, 95% CI: 1.15 to 5.07). The increased body mass index was protective (OR:0.81, 95% CI: 0.75 to 0.87). Conclusions: Around one of four patients with RA presented muscle wasting. Muscle wasting is related to treatment failure of combined csDMARDs; other factors influencing the presence of muscle wasting is being postmenopausal, whereas, the body mass index was a protective factor.

Backyard animal husbandry is common in rural communities in developing countries and, given the conditions in which it occurs, it can increase the risk of disease transmission, such as arboviruses. To determine the presence of the Zika virus (ZIKV) and abundance of its arthropod vectors we evaluated the socioeconomic implications involved in its transmission in two highly vulnerable Mayan communities in the state of Yucatan that practice backyard farming. An analytical cross-sectional study was carried out throughout 2016 to understand socioeconomic variables and seasonal patterns in mosquito populations. We selected 20 households from each community. Social exclusion indicators were analyzed, human and domestic animals were sampled, and mosquitoes were collected and identified. Four out of eight indicators of social exclusion were higher than the reported national averages. We captured 5,825 mosquitoes from 16 species being Culex quinquefasciatus and Aedes aegypti the most abundant. The presence of chickens and human overcrowding in dwellings were the most significant factors (P = 0.026) associated with the presence of Ae. aegypti. Septic tanks (odds ratio = 6.64) and chickens (odds ratio = 27.41) in backyards were the main risk factors associated with the presence of immature states of Ae. aegypti in both communities. Molecular analysis to detect ZIKV was performed in blood samples from 416 humans, 1,068 backyard animals and 381 mosquito pools. Eighteen humans and 10 pig pools tested positive for ZIKV. Forty-three mosquito pools tested positive for flavivirus. Ten of the 43 pools of positive mosquitoes were sequenced, corresponding 3/10 to ZIKV and 1/10 to Dengue virus type 2. The findings obtained indicate the continuous circulation of Flavivirus (including ZIKV) in backyard environments in vulnerable communities, highlighting the importance of studying their transmission and maintenance in these systems, due that backyard animal husbandry is a common practice in these vulnerable communities with limited access to health services.

We analyze image and spectral data from $\approx$365~ks of observations from the {\it Chandra} X-ray Observatory of the nearby, edge-on starburst galaxy NGC 253 to constrain properties of the hot phase of the outflow. We focus our analysis on the $-$1.1 to $+$0.63 kpc region of the outflow and define several regions for spectral extraction where we determine best-fit temperatures and metal abundances. We find that the temperatures and electron densities peak in the central $\sim$250 pc region of the outflow and decrease with distance. These temperature and density profiles are in disagreement with an adiabatic spherically expanding starburst wind model and suggest the presence of additional physics such as mass loading and non-spherical outflow geometry. Our derived temperatures and densities yield few-Myr cooling times in the nuclear region, which may imply that the hot gas can undergo bulk radiative cooling as it escapes along the minor axis. Our metal abundances of O, Ne, Mg, Si, S, and Fe all peak in the central region and decrease with distance along the outflow, with the exception of Ne which maintains a flat distribution. The metal abundances indicate significant dilution outside of the starburst region. We also find estimates on the mass outflow rates which are $2.8\:M_{\odot}/\rm{yr}$ in the northern outflow and $3.2\:M_{\odot}/\rm{yr}$ in the southern outflow. Additionally, we detect emission from charge exchange and find it has a significant contribution ($20-42$\%) to the total broad-band ($0.5-7$ keV) X-ray emission in the central and southern regions of the outflow., 15 pages, 9 figures; submitted (19 September 2022), accepted ApJ (22 November 2022)

Sarcomas of the uterus are a group of tumors that make up 1% of neoplasms of the female genital tract.1 The global incidence is 0.5 to 3.3 cases per 100,000 women per year 1 the rarity of this tumor, and its histological diversity, contributes to the lack of consensus on diagnostic behavior and timely treatment.1 The incidence increases in ages over 40years, tied to other risk factors.1 The preoperative diagnosis is a challenge, since the clinical presentation is variable, it frequently presents with transvaginal bleeding and a rapid increase in the size of the uterus,2 accompanied by symptoms of pelvic pressure, anemic syndrome stands out in these women in different degrees.2 however there are high frequency pathologies that share clinical characteristics that direct the diagnosis and is easily confused with benign leiomyoma and adenomyosis3 The objective of this presentation of the case is to take into account as a differential diagnosis in abnormal uterine bleeding and constitutional syndrome,2 due to the rarity of this tumor, only some articles of review and report of cases have been published.3

AusVaxSafety (Australia’s active safety surveillance system) used SMS/email delivered surveys to actively solicit the short-term (within first 3 days after vaccination) adverse event profile of mRNA COVID-19 vaccines in children (aged 5–15 years) by age, dose, brand and pre-existing comorbidity.392,268 survey responses for children aged 5–15 who received a COVID-19 vaccine between July 2021–May 2022 (211,994 following BNT162b2 10mcg in children aged 5–11 years, 173,329 following BNT162b2 30mcg and 6,945 following mRNA-1273 100mcg in adolescents aged 12–15 years) were analysed.Adverse event rates were higher following dose 2 and 3 compared to dose 1 after all vaccines and highest following dose 2 of mRNA-1273 in 12–15 years. Fever was low in the youngest children (5 years old, any dose; 1,090/26,181 (4%)). Medical review rates remained low (0.3% overall) and impact on daily activities was also low (7% overall). No self-reported cases of myocarditis or pericarditis were identified.Ongoing active safety surveillance of lower dose mRNA vaccines in children under 5 years old is required to better understand safety as the vaccines roll out into this population age-group.

In nature, plants experience rapid changes in light intensity and quality throughout the day. To maximize growth, they have established molecular mechanisms to optimize photosynthetic output while protecting components of the light-dependent reaction and CO

Aluminum (Al), antimony (Sb), and lithium (Li) are relatively common toxic metal(oid)s that can be transferred into breast milk and potentially to the nursing infant. This study assessed concentrations of Al, Sb, and Li in breast milk samples collected from donor mothers and explored the predictors of these concentrations. Two hundred forty-two pooled breast milk samples were collected at different times post-partum from 83 donors in Spain (2015-2018) and analyzed for Al, Sb, and Li concentrations. Mixed-effect linear regression was used to investigate the association of breast milk concentrations of these elements with the sociodemographic profile of the women, their dietary habits and utilization of personal care products (PCPs), the post-partum interval, and the nutritional characteristics of milk samples, among other factors. Al was detected in 94% of samples, with a median concentration of 57.63 μg/L. Sb and Li were detected in 72% and 79% of samples at median concentrations of 0.08 μg/L and 0.58 μg/L, respectively. Concentrations of Al, Sb, and Li were not associated with post-partum time. Al was positively associated with total lipid content of samples, weight change since before pregnancy, and coffee and butter intakes and inversely with meat intake. Li was positively associated with intake of chocolate and use of face cream and eyeliner and inversely with year of sample collection, egg, bread, and pasta intakes, and use of hand cream. Sb was positively associated with fatty fish, yoghurt, rice, and deep-fried food intakes and use of eyeliner and inversely with egg and cereal intakes and use of eyeshadow. This study shows that Al, Sb, and Li, especially Al, are widely present in donor breast milk samples. Their concentrations in the milk samples were most frequently associated with dietary habits but also with the lipid content of samples and the use of certain PCPs.

To describe the severity and clinical spectrum of coronavirus disease 2019 (COVID-19) in children during the 2021 New South Wales outbreak of the Delta variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Prospective cohort study in three metropolitan Sydney local health districts, 1 June - 31 October 2021.Children under 16 years of age with positive SARS-CoV-2 nucleic acid test results admitted to hospital or managed by the Sydney Children's Hospital Network (SCHN) virtual care team.Age-specific SARS-CoV-2 infection frequency, overall and separately for SCHN virtual and hospital patients; rates of medical and social reason admissions, intensive care admissions, and paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 per 100 SARS-CoV-2 infections; demographic and clinical factors that influenced likelihood of hospital admission.A total of 17 474 SARS-CoV-2 infections in children under 16 were recorded in NSW, of whom 11 985 (68.6%) received SCHN-coordinated care, including 459 admitted to SCHN hospitals: 165 for medical reasons (1.38 [95% CI, 1.17-1.59] per 100 infections), including 15 admitted to intensive care, and 294 (under 18 years of age) for social reasons (2.45 [95% CI, 2.18-2.73] per 100 infections). In an analysis that included all children admitted to hospital and a random sample of those managed by the virtual team, having another medical condition (adjusted odds ratio [aOR], 7.42; 95% CI, 3.08-19.3) was associated with increased likelihood of medical admission; in univariate analyses, non-asthmatic chronic respiratory disease was associated with greater (OR, 9.21; 95% CI, 1.61-174) and asthma/viral induced wheeze with lower likelihood of admission (OR, 0.38; 95% CI, 0.18-0.78). The likelihood of admission for medical reasons declined from infancy to 5-11 years, but rose again for those aged 12-15 years. Sex and Indigenous status did not influence the likelihood of admission.Most SARS-CoV-2 infections (Delta variant) in children were asymptomatic or associated with mild disease. Hospitalisation was relatively infrequent, and most common for infants, adolescents, and children with other medical conditions. More children were hospitalised for social than for medical reasons.

Adipokines, especially chemerin, can interact with cytokines and other molecules in inflammation. To date, there is insufficient information regarding a possible correlation between functional disability and chemerin and other pro-inflammatory molecules in rheumatoid arthritis (RA). To identify the association of functional disability with serum chemerin and other pro-inflammatory molecules, including other adipokines, cytokines and E-selectin, in patients with RA. Cross-sectional study. Assessment: disease activity (DAS28-ESR) and functional disability (HAQ-DI). We compared the adipokines (chemerin, leptin, adiponectin, resistin, and visfatin), cytokines (TNF-α, IL-6, IL-1β, and IL-18) and E-selectin levels between RA with functional disability and RA non-disabled patients. Of 82 patients with RA, 43 (52%) had functional disability. The RA with functional disability group had higher chemerin (140 vs. 112 ng/mL, p = 0.007) than the non-disabled RA group. Chemerin correlated with the HAQ-DI (rho = 0.27, p = 0.02) and DAS28-ESR (rho = 0.21, p = 0.05). Severe activity correlated with IL-6 (rho = 0.33, p = 0.003) and E-selectin (rho = 0.23, p = 0.03) but not with disability. No other pro-inflammatory molecules correlated with HAQ-DI. High chemerin levels were associated with functional disability in RA, whereas no other molecules correlated with loss of function. These results encourage further studies assessing new roles of chemerin as a marker of impairment in RA.

Introduction The middle fossa (MF) approaches encompass a group of versatile surgical accesses to pathologies in the MF, internal auditory canal (IAC), and superomedial aspect of the posterior fossa. Although many descriptions of the MF approaches have been published, a practical surgical guide that allows an easy understanding for Skull Base trainees is needed. Methods Three formalin-fixed, colored-injected specimens were dissected under microscopic magnification (six sides). A MF craniotomy followed by IAC drilling was performed on three sides, and anterior petrosectomy (AP) was performed in the remaining three sides. The anatomical dissection was documented in stepwise three-dimensional photographic images. Following dissection, representative case applications were reviewed. Results The MF approach provides direct access to the MF structures and IAC. The AP provides excellent access to the superomedial aspect of the posterior fossa. Key common steps include: positioning and skin incision; scalp and muscle flaps; burr holes; craniotomy flap elevation; dural dissection along the petrous ridge; division of the middle meningeal artery; and exposure of the greater superficial petrosal nerve, tegmen tympani, and V3. Then, to approach the IAC: superior IAC drilling, and longitudinal dura opening. The area drilled in the AP approach forms a pentagon limited by the petrous internal carotid artery, cochlea, IAC, petrous ridge, and lateral border of V3. Conclusion The MF approaches are challenging. Operatively oriented skull base dissections provide a crucial foundation for learning these techniques. We describe comprehensive step-by-step approaches intended to develop familiarity in the cadaver laboratory and facilitate understanding of their potential for skull base disorders. Basic surgical principles are described to help in the operating room as well as illustrative cases.

[EN] Enzymes with a broad substrate specificity are of great interest both at the basic and applied level. Understanding the main parameters that make an enzyme substrate ambiguous could be thus important not only for their selection from the ever-increasing amount of sequencing data but also for engineering a more substrate promiscuous variant. This issue, which remains unresolved, was herein investigated by targeting a serine ester hydrolase (EH102), which exhibits a narrow substrate spectrum, being only capable of hydrolyzing 16 out of 96 esters tested. By using a modeling approach, we demonstrated that one can rationalize active site parameters defining substrate promiscuity, and that based on them the substrate specificity can be significantly altered. This was accomplished by designing two variants, EH102 and EH102, that hydrolyze 51 and 63 esters, respectively, while maintaining similar or higher turnover rates compared to the original enzyme. We hypothesized that the parameters identified here (the volume, size, exposure, enclosure, hydrophobicity, and hydrophilicity of the active site cavity and its tightness) can serve in the future to expand the substrate spectra of esterases and thus expand their use in biotechnology and synthetic chemistry., This work was funded by grant “INMARE” from the European Union’s Horizon 2020 (grant agreement no. 634486), grant PCIN-2017-078 (within the Marine Biotechnology ERA-NET), and BIO2017-85522-R and PID2019-106370RB-I00/AEI/10.13039/501100011033 grants from the Spanish Ministry of Science and Innovation, Ministerio de Economía, Industria y Competitividad, Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación (AEI), Fondo Europeo de Desarrollo Regional (FEDER), and European Union (EU). This work has also been supported by a predoctoral fellowship from the Spanish Ministry of Science and Innovation (FPU19/00608)

Systemic lupus erythematosus is a systemic autoimmune disease that affects the central nervous system, either by direct neuronal damage, injury to brain vessels, or by pathogenic mechanisms indirectly induced by immune mechanisms related to the production and deposition of immune complexes. The prevalence of explicit episodes of seizures among SLE patients, varies from 2 to 8%. In some cases, patients with positivity for antiphospholipid or anti-β2 glycoprotein antibodies are found to be more prone to exhibit seizures compared to seronegative patients, other subjects at risk are carries of gene abnormalities codifying for ion channels. The exclusion of vasculitis or thrombosis is required for accurate treatment, imaging studies and alternative sequences are mandatory in patients with known SLE who present with a seizure. Several statements regarding SLE-related seizure remain to be decoded. In this scoping review we analyzed published information about prevalence, pathogenesis, clinical characteristics, diagnostic and therapeutic SLE patients that manifest a seizure, our objective is to provide with useful information for prompt diagnosis and individualized treatment.