A prion-like domain in ELF3 functions as a thermosensor in Arabidopsis.

Temperature controls plant growth and development, and climate change has already altered the phenology of wild plants and crops1. However, the mechanisms by which plants sense temperature are not well understood. The evening complex is a major signalling hub and a core component of the plant circadian clock2,3. The evening complex acts as a temperature-responsive transcriptional repressor, providing rhythmicity and temperature responsiveness to growth through unknown mechanisms2,4-6. The evening complex consists of EARLY FLOWERING 3 (ELF3)4,7, a large scaffold protein and key component of temperature sensing; ELF4, a small α-helical protein; and LUX ARRYTHMO (LUX), a DNA-binding protein required to recruit the evening complex to transcriptional targets. ELF3 contains a polyglutamine (polyQ) repeat8-10, embedded within a predicted prion domain (PrD). Here we find that the length of the polyQ repeat correlates with thermal responsiveness. We show that ELF3 proteins in plants from hotter climates, with no detectable PrD, are active at high temperatures, and lack thermal responsiveness. The temperature sensitivity of ELF3 is also modulated by the levels of ELF4, indicating that ELF4 can stabilize the function of ELF3. In both Arabidopsis and a heterologous system, ELF3 fused with green fluorescent protein forms speckles within minutes in response to higher temperatures, in a PrD-dependent manner. A purified fragment encompassing the ELF3 PrD reversibly forms liquid droplets in response to increasing temperatures in vitro, indicating that these properties reflect a direct biophysical response conferred by the PrD. The ability of temperature to rapidly shift ELF3 between active and inactive states via phase transition represents a previously unknown thermosensory mechanism.

The pathogenicity of Plasmopara viticola: a review of evolutionary dynamics, infection strategies and effector molecules.

Oomycetes are filamentous organisms that resemble fungi in terms of morphology and life cycle, primarily due to convergent evolution. The success of pathogenic oomycetes lies in their ability to adapt and overcome host resistance, occasionally transitioning to new hosts. During plant infection, these organisms secrete effector proteins and other compounds during plant infection, as a molecular arsenal that contributes to their pathogenic success. Genomic sequencing, transcriptomic analysis, and proteomic studies have revealed highly diverse effector repertoires among different oomycete pathogens, highlighting their adaptability and evolution potential.The obligate biotrophic oomycete Plasmopara viticola affects grapevine plants (Vitis vinifera L.) causing the downy mildew disease, with significant economic impact. This disease is devastating in Europe, leading to substantial production losses. Even though Plasmopara viticola is a well-known pathogen, to date there are scarce reviews summarising pathogenicity, virulence, the genetics and molecular mechanisms of interaction with grapevine.This review aims to explore the current knowledge of the infection strategy, lifecycle, effector molecules, and pathogenicity of Plasmopara viticola. The recent sequencing of the Plasmopara viticola genome has provided new insights into understanding the infection strategies employed by this pathogen. Additionally, we will highlight the contributions of omics technologies in unravelling the ongoing evolution of this oomycete, including the first in-plant proteome analysis of the pathogen.

Differences in whole blood before and after hemodialysis session of subjects with chronic kidney disease measured by Raman spectroscopy.

This study aimed to identify differences in the composition of whole blood of patients with chronic kidney disease (CKD), before and after a hemodialysis session (HDS), and possible differences in blood composition between stages and between genders using Raman spectroscopy and principal component analysis (PCA). Whole blood samples were collected from 40 patients (20 women and 20 men), before and after a HDS. Raman spectra were obtained and the spectra were evaluated by PCA and partial least squares (PLS) regression. Mean spectra and difference spectrum between the groups were calculated: stages Before and After HDS, and gender Women and Men, which had their most intense peaks identified. Stage: mean spectra and difference spectrum indicated positive peaks that could be assigned to red blood cells, hemoglobin and deoxi-hemoglobin in the group Before HDS. There was no statistically significant difference by PCA. Gender: mean spectra and difference spectrum Before HDS indicated positive peaks that could be assigned to red blood cells, hemoglobin and deoxi-hemoglobin with greater intensity in the group Women, and negative peaks to white blood cells and serum, with greater intensity in the group Men. There was statistically significant difference by PCA, which also identified the peaks assigned to white blood cells, serum and porphyrin for Women and red blood cells and amino acids (tryptophan) for Men. PLS model was able to classify the spectra of the gender with 83.7% accuracy considering the classification per patient. The Raman technique highlighted gender differences in pacients with CKD.

Preliminary study: cognitive behavioural therapy for insomnia in adolescents with anorexia nervosa.

PURPOSE: Insomnia and anorexia nervosa (AN) are frequently comorbid, negatively affecting the evolution and the prognosis of AN. Within this framework, the management of sleep disorders appears as critical. The aim of this retrospective study is to assess, for the first time, the efficacy of cognitive and behavioural therapy for insomnia (CBT-I) on sleep disturbances in adolescents with AN. To do so, we investigated the impact of CBT-I on sleep disturbances and sleep-related outcomes, in BMI, AN symptoms, anxiety and depressive symptoms, emotionality and quality of life. These features were compared between two groups of patients with AN, one following CBT-I, and the other receiving the regular treatment at the psychiatric unit. METHODS: Data collection occurred between January and May 2022. The study included 42 adolescents in-treatment at the Eating Disorders care specialised unit at Salvator Hospital in Marseille. They were randomly assigned to the CBT-I group (N = 31) or the control group (N = 11). Several clinical elements were assessed using sleep diaries and self-report questionnaires. RESULTS: Participants undergoing CBT-I showed a significant improvement in sleep latency, total wake time and sleep efficacy, as well as in physical well-being. No significant effects were found regarding AN symptoms. CONCLUSION: These preliminary findings provide support for CBT-I effectiveness in adolescents with AN, as shown by significant improvements in several sleep parameters, as well as in physical well-being. These promising results, underline the relevance of this topic and its potential benefits for a more appropriate treatment for adolescents with AN. LEVEL OF EVIDENCE: Level V, retrospective study.

Imaging characterization of the fellow eye in patients with unilateral polypoidal choroidal vasculopathy.

INTRODUCTION: New insights on polypoidal choroidal vasculopathy (PCV) have shed light regarding its pathophysiology and associations. However, PCV characterization is still incomplete in Caucasians, which is due to presumed lower prevalence in this population. Features typically associated with AMD such as drusen, retinal pigmentary changes or atrophy are seen in PCV, as precursors and in the fellow eye. Pachychoroid spectrum, predisposing to PCV, also presents with chronic changes in the retinal pigment epithelium (RPE), such as drusen-like deposits (DLD), and in the choroid. The purpose of this study is to perform a multimodal imaging characterization of unaffected fellow eyes in a sample of Caucasian patients with unilateral PCV. METHODS: Multicenter retrospective cohort study with a sample of 55 unaffected fellow eyes from patients diagnosed with unilateral PCV confirmed by indocyanine green angiography. The sample was characterized in the baseline by color fundus photography, spectral domain optical coherence tomography (SD-OCT), fluorescein angiography and indocyanine green angiography. Morphological characteristics of both the retina and the choroid were evaluated. The SD-OCT of the last follow-up visit was also evaluated in order to exclude evolution to PCV or choroidal neovascularization. All images captured underwent evaluation by two independent graders. Informed consent was obtained from all participants. RESULTS: Fifty-five patients (median age, 74 ± 15 years) were included. After 15.5 ± 6.4 months of follow-up, only one developed disease (1.9%). Soft and/or hard drusen were present in 60% and pachydrusen in 23.6%. Pachychoroid signs were present in 47.2%, the double-layer sign in 36.4%, disruption of the RPE changes in 16.4% and RPE atrophy in 10.9%. ICGA revealed choroidal vascular dilation in 63.6% and punctiform hyperfluorescence in 52.7%. Branching vascular networks were identified in only 1.9% of cases. CONCLUSION: The identification of pachychoroid signs in the OCT and ICGA were present in over half of the cases and the presence of the double-layer sign in more than a third provide crucial insights for enhanced characterization of this pathology and deeper understanding of its pathogenesis. These findings contribute significantly to the current knowledge, offering valuable markers to discern various phases of the pathology's progression.

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction.

We describe the use of bismuth(III) triflate as an efficient and environmentally friendly catalyst for the Nazarov reaction of aryl vinyl ketones, leading to the synthesis of 3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones. By changing the temperature and reaction time, it was possible to modulate the reactivity, allowing the synthesis of two distinct product classes (3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones) in good to excellent yield. The reaction did not require additives and was insensitive to both air and moisture. Preliminary biological evaluation of some indanones showed a promising profile against some human cancer line cells.

Genomic insights of evolutionary divergence and life history innovations in Antarctic brittle stars.

Understanding the drivers of evolutionary innovation provides a crucial perspective of how evolutionary processes unfold across taxa and ecological systems. It has been hypothesised that the Southern Ocean provided ecological opportunities for novelty in the past. However, the drivers of innovation are challenging to pinpoint as the evolutionary genetics of Southern Ocean fauna are influenced by Quaternary glacial-interglacial cycles, oceanic currents and species ecology. Here we examined the genome-wide single nucleotide polymorphisms of the Southern Ocean brittle stars Ophionotus victoriae (five arms, broadcaster) and O. hexactis (six arms, brooder). We found that O. victoriae and O. hexactis are closely-related species with interspecific gene flow. During the late Pleistocene, O. victoriae likely persisted in a connected deep water refugium and in situ refugia on the Antarctic continental shelf and around Antarctic islands; O. hexactis persisted exclusively within in situ island refugia. Within O. victoriae, contemporary gene flow linking to the Antarctic Circumpolar Current, regional gyres and other local oceanographic regimes was observed. Gene flow connecting West and East Antarctic islands near the Polar Front was also detected in O. hexactis. A strong association was detected between outlier loci and salinity in O. hexactis. Both O. victoriae and O. hexactis are associated with genome-wide increase in alleles at intermediate-frequencies; the alleles associated with this peak appear to be species specific, and these intermediate-frequency variants are far more excessive in O. hexactis. We hypothesise that the peak in alleles at intermediate frequencies could be related to adaptation in the recent past, linked to evolutionary innovations of increase in arm number and a switch to brooding from broadcasting, in O. hexactis.

Epidemiology and genetic diversity of invasive Neisseria meningitidis strains circulating in Portugal from 2003 to 2020.

Invasive meningococcal disease (IMD) continues to be a public health problem due to its epidemic potential, affecting mostly children. We aimed to present a detailed description of the epidemiology of IMD in Portugal, including insights into the genetic diversity of Neisseria meningitidis strains. Epidemiological analysis included data from the Portuguese National Reference Laboratory of Neisseria meningitidis during 2003 to 2020. Since 2012, N. meningitidis isolates have also been assessed for their susceptibility to antibiotics and were characterized by whole genome sequencing. During 2003-2020, 1392 confirmed cases of IMD were analyzed. A decrease in the annual incidence rate was observed, ranging from 1.99 (2003) to 0.39 (2020), with an average case fatality rate of 7.1%. Serogroup B was the most frequent (69.7%), followed by serogroups C (9.7%), Y (5.7%), and W (2.6%). Genomic characterization of 329 isolates identified 20 clonal complexes (cc), with the most prevalent belonging to serogroup B cc41/44 (26.3%) and cc213 (16.3%). Isolates belonging to cc11 were predominantly from serogroups W (77.3%) and C (76.5%), whereas cc23 was dominant from serogroup Y (65.7%). Over the past 4 years (2017-2020), we observed an increasing trend of cases assigned to cc213, cc32, and cc11. Regarding antimicrobial susceptibility, all isolates were susceptible to ceftriaxone and 61.8% were penicillin-nonsusceptible, whereas 1.4% and 1.0% were resistant to ciprofloxacin and rifampicin. This is the first detailed study on the epidemiology and genomics of invasive N. meningitidis infections in Portugal, providing relevant data to public health policy makers for a more effective control of this disease.

Influence of fasting during the night shift on next day eating behavior, hunger, and glucose and insulin levels: a randomized, three-condition, crossover trial.

AIMS: To investigate the influence of fasting during the night shift on eating behavior, hunger, glucose and insulin levels the following day. METHODS: Study with 10 male police officers who have been working at night. Participants were tested under three different conditions separated by at least 6 days of washout in a randomized, crossover design: "Night Shift Fasting" (NSF)-two nights of fasting during the night shift; "Night Shift Eating" (NSE)-two nights with the consumption of a standardized meal during the night shift (678 ± 42 kcal consumed at ~ 0200 h); and "Nighttime Sleep" (NS)-two nights of sleep. The morning after, blood glucose and insulin and hunger ratings were assessed, and food intake was assessed with an ad libitum test meal. Food intake was also assessed throughout the remainder of the day using a food record. Generalized Estimating Equations were used to analyze the effect of experimental condition. RESULTS: Food intake during the test meal, especially of proteins and fats, was higher after fasting during the night shift compared to the other conditions (p < 0.05), whereas desire to eat scores were lower after the NSF compared to NSE condition (p = 0.043). Hunger levels were lower after the NSF compared to the NS condition (p = 0.012). Insulin and HOMA-IR were also lower in the morning after NSF (p < 0.001). CONCLUSION: Fasting during the night shift leads to not only a higher intake of energy and macronutrients both in the early morning after work and throughout the next day, but also lower insulin levels and HOMA-IR in the morning. REGISTRATION NUMBER OF CLINICAL TRIAL: NCT03800732. Initial release: 01/09/2019. Last release: 02/23/2022.

Time perception and pain: Can a temporal illusion reduce the intensity of pain?

It is commonly known-and previous studies have indicated-that time appears to last longer during unpleasant situations. This study examined whether a reciprocal statement can be made-that is, whether changes in the perception of time can influence our judgment (or rating) of a negative event. We used a temporal illusion method (Pomares et al. Pain 152, 230-234, 2011) to induce distortions in the perception of time. Two stimuli were presented for a constant time: a full clock, which stayed on the screen until its clock hand completed a full rotation (360°); and a short clock, in which the clock hand moved just three-quarters of the way (270°), thus suggesting a reduced interval duration. However, both stimuli were shown for the same amount of time. We specifically investigated (a) whether we could induce a temporal illusion with this simple visual manipulation, and (b) whether this illusion could change participants' ratings of a painful stimulus. In Experiment I (n = 22), to answer (a) above, participants were asked to reproduce the duration in which the different clocks were presented. In Experiment II (n = 30), a painful thermal stimulation was applied on participants' hands while the clocks were shown. Participants were asked to rate the perceived intensity of their pain, and to reproduce its duration. Results showed that, for both experiments, participants reproduced a longer interval after watching the full clock compared with the short clock, confirming that the clock manipulation was able to induce a temporal illusion. Furthermore, the second experiment showed that participants rated the thermal stimuli as less painful when delivered with the short clock than with the full clock. These findings suggest that temporal distortions can modulate the experience of pain.

Implementation determinants of physical activity interventions in primary health care settings using the TICD framework: a systematic review.

BACKGROUND: Translation into practice of effective physical activity interventions in primary care is difficult, due to a complex interaction of implementation determinants. We aimed to identify implementation barriers and facilitators of four primary care interventions: physical activity assessment, counselling, prescription, and referral. METHODS: A systematic review of qualitative, quantitative and mixed-methods studies published since 2016 was conducted. The "Tailored Implementation for Chronic Diseases" (TICD) framework was adapted to extract and synthesize barriers and facilitators. RESULTS: Sixty-two studies met the inclusion criteria. Barriers (n = 56) and facilitators (n = 55) were identified across seven domains, related to characteristics of the intervention, individual factors of the implementers and receivers, organizational factors, and political and social determinants. The five most frequently reported determinants were: professionals' knowledge and skills; intervention feasibility/compatibility with primary health care routine; interventions' cost and financial incentives; tools and materials; and professionals' cognitions and attitudes. "Social, political and legal factors" domain was the least reported. Physical activity counselling, prescription, and referral were influenced by determinants belonging to all the seven domains. CONCLUSION: The implementation of physical activity interventions in primary care is influenced by a broader range of determinants. Barriers and facilitators related with health professionals, intervention characteristics, and available resources were the most frequently reported. A deep understanding of the local context, with particularly emphasis on these determinants, should be considered when preparing an intervention implementation, in order to contribute for designing tailored implementation strategies and optimize the interventions' effectiveness.

Prevalence of and factors associated with unmanageable pain levels in people with knee or hip osteoarthritis: a cross-sectional population-based study.

BACKGROUND: Pain due to knee and / or hip osteoarthritis (HKOA) is the most common symptom for seeking healthcare. Pain interferes on daily activities, social and occupational participation in people with HKOA. The goal of this study is to estimate the prevalence of unmanageable pain levels (UPL) among people with HKOA), characterize this population and identify factors associated with UPL, and compare therapeutic strategies used by people with UPL versus manageable pain levels (MPL). METHODS: We analysed data from the EpiReumaPt study (n = 10,661), that included a representative sample of the Portuguese population. Among these, 1081 participants had a validated diagnosis of HKOA by a rheumatologist.. Sociodemographic, lifestyle and health-related data were collected in a structured interview. Pain intensity (NPRS) data were collected in a medical appointment. Painmedication (last month), physiotherapy and surgery were considered as therapies for pain management. UPL was defined as a mean pain intensity in the previous week of ≥5 points on 11-point numeric pain rating scale. The factors associated with UPL were analyzed with logistic regression (p < 0.05, 95%CI). The effect of unmanageable pain levels was assessed by the HOOS/KOOS activities of daily living and quality of life subscales. Symptoms of anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS). Analysis was completed with linear and logistic regression. All analysis were weighted. RESULTS: The estimated prevalence of UPL among people with HKOA was 68.8%. UPL was associated with being female (odds ratio (OR) = 2.36, p < 0.001), being overweight (OR = 1.84, p = 0.035) or obese (OR = 2.26, p = 0.006), and having multimorbidity (OR = 2.08, p = 0.002). People with UPL reported worse performance in activities of daily living and lower quality of life (ß = - 21.28, p < 0.001 and ß = - 21.19, p < 0.001, respectively) than people with MPL. People with UPL consumed more NSAIDs (22.0%, p = 0.003), opioids (4.8%, p = 0.008), paracetamol (2.7%, p = 0.033), and overall analgesics (7.3%, p = 0.013) than people with MPL. A higher proportion of people with UPL underwent physiotherapy (17.5%, p = 0.002) than people with MPL. CONCLUSION: Two-thirds of people with HKOA in Portugal have poor management of their pain levels. Clinical and lifestyle factors, that are highly presented in individuals with HKOA, are associated with unmanageable pain. Our results highlighting the need for further research and implementation of effective interventions to improve pain, function and quality of life in people with HKOA.

Molecular mechanisms of Evening Complex activity in Arabidopsis.

The Evening Complex (EC), composed of the DNA binding protein LUX ARRHYTHMO (LUX) and two additional proteins EARLY FLOWERING 3 (ELF3) and ELF4, is a transcriptional repressor complex and a core component of the plant circadian clock. In addition to maintaining oscillations in clock gene expression, the EC also participates in temperature and light entrainment, acting as an important environmental sensor and conveying this information to growth and developmental pathways. However, the molecular basis for EC DNA binding specificity and temperature-dependent activity were not known. Here, we solved the structure of the DNA binding domain of LUX in complex with DNA. Residues critical for high-affinity binding and direct base readout were determined and tested via site-directed mutagenesis in vitro and in vivo. Using extensive in vitro DNA binding assays of LUX alone and in complex with ELF3 and ELF4, we demonstrate that, while LUX alone binds DNA with high affinity, the LUX-ELF3 complex is a relatively poor binder of DNA. ELF4 restores binding to the complex. In vitro, the full EC is able to act as a direct thermosensor, with stronger DNA binding at 4 °C and weaker binding at 27 °C. In addition, an excess of ELF4 is able to restore EC binding even at 27 °C. Taken together, these data suggest that ELF4 is a key modulator of thermosensitive EC activity.

Monitoring Sensors for Urban Air Quality: The Case of the Municipality of Lisbon.

Air pollution is a global issue that impacts environmental inequalities, and air quality sensors can have a decisive role in city policymaking for future cities. Science and society are already aware that during the most challenging times of COVID-19, the levels of air pollution in cities decreased, especially during lockdowns, when road traffic was reduced. Several pollution parameters can be used to analyse cities' environmental challenges, and it is more pressing than ever to have city climate decisions supported by sensor data. We have applied a data science approach to understand the evolution of the levels of carbon monoxide, nitrogen dioxide, particulate matter 2.5, and particulate matter 10 between August 2021 and July 2022. The analysis of the air quality levels, captured for the first time via 80 monitoring stations distributed throughout the municipality of Lisbon, has allowed us to realize that nitrogen dioxide and particulate matter 10 exceed the levels that are recommended by the World Health Organization, thereby increasing the health risk for those who live and work in Lisbon. Supported by these findings, we propose a central role for air quality sensors for policymaking in future cities, taking as a case study the municipality of Lisbon, Portugal, which is among the European cities that recently proposed be climate-neutral and smart city by 2030.

Sleep and emotionality in adolescents with anorexia nervosa during the Covid-19 pandemic.

PURPOSE: The recent Covid-19 pandemic and its lockdown measures raised concerns about people's mental health, leading to an increased interest in identifying vulnerable groups especially at risk for mental distress. This cross-sectional study investigated the impact of this unprecedented situation on sleeping patterns and emotionality in adolescents with anorexia nervosa (AN). METHODS: Variations in sleeping patterns and emotionality of two groups of adolescents with AN, assessed before (N = 50) and during (N = 51) the Covid-19 lockdown were analysed. We further investigated these variations over time, considering the two lockdown periods in France. RESULTS: Adolescents self-reported significantly more sleep difficulties and lower rates of positive emotions during lockdown, compared to those evaluated before it. Furthermore, present findings overall suggest that as the lockdown progresses, adolescents with AN show an increased deterioration of sleep quality, as indicated by greater insomnia severity levels. They also show a significant decrease in the subjective experience of positive emotionality, in particular in feelings of tenderness. CONCLUSIONS: These sleep and emotionality alterations may have amplified the severity and the incidence of AN in adolescents during the Covid-19 pandemic. These features may therefore represent therapeutic targets to optimise care of adolescents with AN. This is particularly urgent, considering kinetics of the deterioration. Tools such as those provided by cognitive behavioural therapy for insomnia and by the positive psychology framework seem appropriate to guide clinicians in this context. LEVEL OF EVIDENCE: Level V, descriptive study (evaluation data retrospectively studied).

Comprehensive Metabolomics and Lipidomics Profiling of Prostate Cancer Tissue Reveals Metabolic Dysregulations Associated with Disease Development.

Prostate cancer (PCa) is a global health problem that affects millions of men every year. In the past decade, metabolomics and related subareas, such as lipidomics, have demonstrated an enormous potential to identify novel mechanisms underlying PCa development and progression, providing a good basis for the development of new and more effective therapies and diagnostics. In this study, a multiplatform metabolomics and lipidomics approach, combining untargeted mass spectrometry (MS) and nuclear magnetic resonance (NMR)-based techniques, was applied to PCa tissues to investigate dysregulations associated with PCa development, in a cohort of 40 patients submitted to radical prostatectomy for PCa. Results revealed significant alterations in the levels of 26 metabolites and 21 phospholipid species in PCa tissue compared with adjacent nonmalignant tissue, suggesting dysregulation in 13 metabolic pathways associated with PCa development. The most affected metabolic pathways were amino acid metabolism, nicotinate and nicotinamide metabolism, purine metabolism, and glycerophospholipid metabolism. A clear interconnection between metabolites and phospholipid species participating in these pathways was observed through correlation analysis. Overall, these dysregulations may reflect the reprogramming of metabolic responses to produce high levels of cellular building blocks required for rapid PCa cell proliferation.

Protein fucosylation is required for Notch dependent vascular integrity in zebrafish.

The onset of circulation in a developing embryo requires intact blood vessels to prevent hemorrhage. The development of endothelial cells, and their subsequent recruitment of perivascular mural cells are important processes to establish and maintain vascular integrity. These processes are genetically controlled during development, and mutations that affect endothelial cell specification, pattern formation, or maturation through the addition of mural cells can result in early developmental hemorrhage. We created a strong loss of function allele of the zebrafish GDP-mannose 4,6 dehydratase (gmds) gene that is required for the de novo synthesis of GDP-fucose, and homozygous embryos display cerebral hemorrhages. Our data demonstrate that gmds mutants have early defects in vascular patterning with ectopic branches observed at time of hemorrhage. Subsequently, defects in the number of mural cells that line the vasculature are observed. Moreover, activation of Notch signaling rescued hemorrhage phenotypes in gmds mutants, highlighting a potential downstream pathway that requires protein fucosylation for vascular integrity. Finally, supplementation with fucose can rescue hemorrhage frequency in gmds mutants, demonstrating that synthesis of GDP-fucose via an alternative (salvage) pathway may provide an avenue toward therapeutic correction of phenotypes observed due to defects in de novo GDP-fucose synthesis. Together, these data are consistent with a novel role for the de novo and salvage protein fucosylation pathways in regulating vascular integrity through a Notch dependent mechanism.

Metronidazole Delivery Nanosystem Able To Reduce the Pathogenicity of Bacteria in Colorectal Infection.

Metronidazole (MTZ) is a drug potentially used for the treatment of intestinal infections, namely, the ones caused by colorectal surgery. The traditional routes of administration decrease its local effectiveness and present off-site effects. To circumvent such limitations, herein a drug delivery system (DDS) based on MTZ-loaded nanoparticles (NPs) immobilized at the surface of electrospun fibrous meshes is proposed. MTZ at different concentrations (1, 2, 5, and 10 mg mL-1) was loaded into chitosan-sodium tripolyphosphate NPs. The MTZ loaded into NPs at the highest concentration showed a quick release in the first 12 h, followed by a gradual release. This DDS was not toxic to human colonic cells. When tested against different bacterial strains, a significant reduction of Escherichia coli and Staphylococcus aureus was observed, but no effect was found against Enterococcus faecalis. Therefore, this DDS offers high potential to locally prevent the occurrence of infections after colorectal anastomosis.

Trisomy 18-when the diagnosis is compatible with life.

Trisomy 18 is an autosomal chromosomal disorder characterized by the presence of an extra 18 chromosome. In the last decades, and as novel therapeutic options emerged, a paradigm shift on the treatments available to these children occurred, establishing the need to deepen the knowledge regarding the management/treatment of children diagnosed with trisomy 18. This retrospective cohort study sought to characterize the clinical path and survival of the children with the diagnosis of trisomy 18 followed in a tertiary pediatric hospital between 1995 and 2020. Medical records were reviewed, and epidemiological and clinical features and follow-up data were collected. Six patients were identified, two with mosaicism (33.3%) and four were female (66.7%). All had cardiovascular, cognitive, and physical development anomalies or minor congenital anomalies. Most presented neurological anomalies (n = 4, 66.7%) and feeding difficulties (n = 4, 66.7%). Four children (66.7%) required medical devices or equipment and all required chronic medication. Two children (33.3%) underwent surgical interventions. Four children (66.7%) were hospitalized in the last year of life. Three patients had a do not resuscitate order (50%) but only one child was referred to a pediatric palliative care team (16.7%). One-month, 1-year, and 10-year survival were 66.7% (n = 4), 33.3% (n = 2, both with mosaicism), and 16.7% (n = 1, with mosaicism) respectively. CONCLUSIONS: Knowledge of the multiple comorbidities and complex care needs of children with this syndrome is crucial. Every-day care and decisions about invasive treatments may raise ethical issues. Early referral to pediatric palliative care teams is essential to promote a holistic advanced care plan for both the patient and his family. WHAT IS KNOWN: • The increase in survival and the high morbimortality that trisomy 18 still entails demands a careful deliberation on the use of invasive treatment. WHAT IS NEW: • Recent studies show that the labels of "incompatible with life"/"lethal" are not adequate, establishing a need to change this mindset. • The development of pediatric palliative care teams in the last decade and early referral allow for an optimal individualized advanced care plan. Under-referral to pediatric palliative care teams persists and efforts must be made to increase awareness of their existence and role in patient care.

Contact dermatitis in children caused by diabetes devices.

BACKGROUND: Insulin pumps and glucose monitoring devices improve diabetes mellitus control and enhance patients' quality of life. However, a growing number of adverse cutaneous reactions related to the use of these devices have been reported. OBJECTIVE: To investigate the culprits of localized contact dermatitis in paediatric patients with diabetes caused by insulin pumps and glucose monitoring devices. METHODS: Retrospective analysis of 15 paediatric patients patch tested as part of a clinical investigation for skin reactions associated with insulin pumps and glucose monitoring devices. RESULTS: Seven patients had positive patch test reactions to isobornyl acrylate (IBOA) and five had positive reactions to benzoyl peroxide (BP). Positive patch test reactions to materials from the glucose sensor and/or insulin pump were seen in 10 of the 15 patients. Three had positive reactions to adhesive remover wipe from Smith and Nephew Remove and four had reactions to EMLA plaster. CONCLUSION: A high share of patients showed positive reactions to IBOA and/or their medical devices (insulin pumps or glucose devices). A third of patients showed positive reactions to BP. The presence of additional unidentified allergens cannot be excluded, highlighting the importance of access to a full description of the chemical composition of the devices.