Modeling Glutaric Aciduria Type I in human neuroblastoma cells recapitulates neuronal damage that can be rescued by gene replacement.

Glutaric Aciduria type I (GA1) is a rare neurometabolic disorder caused by mutations in the GDCH gene encoding for glutaryl-CoA dehydrogenase (GCDH) in the catabolic pathway of lysine, hydroxylysine and tryptophan. GCDH deficiency leads to increased concentrations of glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA) in body fluids and tissues. These metabolites are the main triggers of brain damage. Mechanistic studies supporting neurotoxicity in mouse models have been conducted. However, the different vulnerability to some stressors between mouse and human brain cells reveals the need to have a reliable human neuronal model to study GA1 pathogenesis. In the present work we generated a GCDH knockout (KO) in the human neuroblastoma cell line SH-SY5Y by CRISPR/Cas9 technology. SH-SY5Y-GCDH KO cells accumulate GA, 3-OHGA, and glutarylcarnitine when exposed to lysine overload. GA or lysine treatment triggered neuronal damage in GCDH deficient cells. SH-SY5Y-GCDH KO cells also displayed features of GA1 pathogenesis such as increased oxidative stress vulnerability. Restoration of the GCDH activity by gene replacement rescued neuronal alterations. Thus, our findings provide a human neuronal cellular model of GA1 to study this disease and show the potential of gene therapy to rescue GCDH deficiency.

Primary intraosseous papillary intralymphatic angioendothelioma of the distal femoral epiphysis: a case report with literature review.

INTRODUCTION: Papillary intralymphatic angioendothelioma (PILA) is an exceptionally rare metastasizing soft tissue tumor. It tends to arise in the subcutaneous tissues of distal extremities in children. Only four intraosseous PILA cases have been reported until now in English language literature. CASE REPORT: We present a case of PILA arising in the distal femoral epiphysis of a 50-year-old female patient. It started as a relentless pain in her left knee. A plain radiography revealed a radiolucent area in the left internal femoral condyle. Computerized tomography revealed a 1-cm lytic lesion with a sclerotic rim. Magnetic resonance images showed a significant bone marrow edema signal focused on a 1-cm subchondral lesion suggestive of an intraarticular osteoid osteoma. Histologically, the tumor contained vascular channels covered by a single endothelial layer with intraluminal papillary endothelial structures lined with hobnail cells. Immunohistochemically, the cells were positive for ERG, CD31, and D2-40. The tumor underwent cryoablation and 6 months later, after local recurrence or tumor persistence, a wide tumor resection was referred. After 7 years of follow-up, the patient displayed neither local recurrence nor distant metastases. CONCLUSION: Primary intraosseous PILAs are exceedingly rare tumors that should be considered in the differential diagnosis of vascular bone tumors.

Inter-annual and spatial climatic variability have led to a balance between local fluctuating selection and wide-range directional selection in a perennial grass species.

BACKGROUND AND AIMS: The persistence of a plant population under a specific local climatic regime requires phenotypic adaptation with underlying particular combinations of alleles at adaptive loci. The level of allele diversity at adaptive loci within a natural plant population conditions its potential to evolve, notably towards adaptation to a change in climate. Investigating the environmental factors that contribute to the maintenance of adaptive diversity in populations is thus worthwhile. Within-population allele diversity at adaptive loci can be partly driven by the mean climate at the population site but also by its temporal variability. METHODS: The effects of climate temporal mean and variability on within-population allele diversity at putatively adaptive quantitative trait loci (QTLs) were evaluated using 385 natural populations of Lolium perenne (perennial ryegrass) collected right across Europe. For seven adaptive traits related to reproductive phenology and vegetative potential growth seasonality, the average within-population allele diversity at major QTLs (HeA) was computed. KEY RESULTS: Significant relationships were found between HeA of these traits and the temporal mean and variability of the local climate. These relationships were consistent with functional ecology theory. CONCLUSIONS: Results indicated that temporal variability of local climate has likely led to fluctuating directional selection, which has contributed to the maintenance of allele diversity at adaptive loci and thus potential for further adaptation.

Diagnostic accuracy of first-trimester combined screening for early-onset and preterm pre-eclampsia at 8-10 compared with 11-13 weeks' gestation.

OBJECTIVES: To compare the ability of first-trimester combined screening for pre-eclampsia (PE) to predict early-onset and preterm PE when pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) were assessed before vs after 11 weeks' gestation. METHODS: This was a secondary analysis of a prospective cohort study of singleton pregnancies undergoing routine first-trimester screening conducted at Vall d'Hebron University Hospital, Barcelona, Spain, between October 2015 and September 2017. Demographic characteristics, obstetric history, maternal history and biophysical markers (mean uterine artery pulsatility index and mean arterial blood pressure (MAP)) were recorded at the first-trimester scan (at 11 + 0 to 13 + 6 weeks' gestation). Maternal serum concentrations of PAPP-A and PlGF were assessed from the routine first-trimester blood test (at 8 + 0 to 13 + 6 weeks). Women were classified into two groups depending on whether serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks or at 11 + 0 to 13 + 6 weeks. Probability scores for early-onset and preterm PE were calculated by using two different algorithms: the multivariate Gaussian-distribution model and The Fetal Medicine Foundation (FMF) competing-risks model. Receiver-operating-characteristics (ROC) curves were produced and detection rates at fixed 5% and 10% false-positive rates were computed to compare the performance of these algorithms when PAPP-A and PlGF were assessed before vs after 11 weeks. RESULTS: Of the 2641 women included, serum biomarkers were assessed before 11 weeks in 1675 (63.4%) and at or after 11 weeks in 966 (36.6%). Of these, 90 (3.4%) women developed PE, including 11 (0.4%) cases of early-onset PE and 30 (1.1%) of preterm PE. Five (45.5%) cases of early-onset and 16 (53.3%) of preterm PE were identified in the group in which serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks and six (54.5%) cases of early-onset and 14 (46.7%) of preterm PE in the group in which serum biomarkers were assessed at 11 + 0 to 13 + 6 weeks. In the prediction of early-onset and preterm PE using the Gaussian algorithm, no differences were observed between the areas under the ROC curves (AUCs) when PAPP-A and PlGF were measured before or after 11 weeks. In the prediction of early-onset and preterm PE using the FMF algorithm, no differences were observed between AUCs for any of the combinations used for risk calculation when the serum biomarkers were obtained before vs after 11 weeks, except for the combination of PAPP-A and MAP, which showed a greater AUC for the prediction of early-onset PE when PAPP-A was measured at or after 11 weeks. CONCLUSIONS: The prediction of early-onset and preterm PE is similar when serum biomarkers are measured before or after 11 weeks. This allows the use of a two-step approach for PE risk assessment that permits immediate risk calculation at the time of the first-trimester scan. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Dysplasia in oral lichen planus: relevance, controversies and challenges. A position paper.

BACKGROUND: Patients with oral lichen planus (OLP) have an increased risk of oral cancer. For this reason, OLP is classified as an oral potentially malignant disorder. However, the precise personal (or individual) risk is unknown. Recent meta-analytical studies have reported that dysplastic OLP may transform to cancer in around 6% of cases, while the rate of transformation is lower (<1.5%) in non-dysplastic cases. The presence of epithelial dysplasia has emerged as the most powerful indicator for assessing cancer risk in oral potentially malignant disorders in routine practice. However, the general acceptance of epithelial dysplasia as an accompanying histologic feature in OLP is subject to great controversy. Many pathologists consider the presence of dysplasia as a criterion to exclude OLP when routinely reporting on this disease. This practice, widespread among oral pathology professionals, has resulted in the underestimation of the potential for malignancy of OLP. MATERIAL AND METHODS: A review of the literature was carried out in order to critically analyze the relevance, controversies and challenges encountered across the diagnosis of epithelial dysplasia in OLP. RESULTS: 12 studies have been published examining dysplastic changes in OLP, reporting figures ranging from 0.54% to 25% of cases with dysplasia in the first diagnostic biopsy. The diagnosis of dysplasia in the OLP poses an additional difficulty due to the fact that the affected oral epithelium per se develops changes related to autoimmune aggression. Among the most frequent histological features of OLP that develops dysplasia are basal cell hyperplasia with basaloid appearance, loss of basal cells polarity, cellular and nuclear pleomorphism and irregular stratification. CONCLUSIONS: Epithelial dysplasia should not be considered an exclusion criterion for OLP; its evaluation requires experienced pathologists in this field.

Pre-eclampsia-like syndrome induced by severe COVID-19: a prospective observational study.

OBJECTIVES: To investigate the incidence of clinical, ultrasonographic and biochemical findings related to pre-eclampsia (PE) in pregnancies with COVID-19, and to assess their accuracy to differentiate between PE and the PE-like features associated with COVID-19. DESIGN: A prospective, observational study. SETTING: Tertiary referral hospital. PARTICIPANTS: Singleton pregnancies with COVID-19 at >20+0  weeks. METHODS: Forty-two consecutive pregnancies were recruited and classified into two groups: severe and non-severe COVID-19, according to the occurrence of severe pneumonia. Uterine artery pulsatility index (UtAPI) and angiogenic factors (soluble fms-like tyrosine kinase-1/placental growth factor [sFlt-1/PlGF]) were assessed in women with suspected PE. MAIN OUTCOME MEASURES: Incidence of signs and symptoms related to PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, abnormal UtAPI and increased sFlt-1/PlGF. RESULTS: Thirty-four cases were classified as non-severe and 8 as severe COVID-19. Five (11.9%) women presented signs and symptoms of PE, all five being among the severe COVID-19 cases (62.5%). However, abnormal sFlt-1/PlGF and UtAPI could only be demonstrated in one case. One case remained pregnant after recovery from severe pneumonia and had a spontaneous resolution of the PE-like syndrome. CONCLUSIONS: Pregnant women with severe COVID-19 can develop a PE-like syndrome that might be distinguished from actual PE by sFlt-1/PlGF, LDH and UtAPI assessment. Healthcare providers should be aware of its existence and monitor pregnancies with suspected pre-eclampsia with caution. TWEETABLE ABSTRACT: This study shows that a pre-eclampsia-like syndrome could be present in some pregnancies with severe COVID-19.

Protein separation under a microfluidic regime.

Lab-on-a-Chip (LoC), or micro-Total Analysis Systems (µTAS), is recognized as a powerful analytical technology with high capabilities, though end-user products for protein purification are still far from being available on the market. Remarkable progress has been achieved in the separation of nucleic acids and proteins using electrophoretic microfluidic devices, while pintsize devices have been developed for protein isolation according to miniaturized chromatography principles (size, charge, affinity, etc.). In this work, we review the latest advances in the fabrication of components, detection methods and commercial implementation for the separation of biological macromolecules based on microfluidic systems, with some critical remarks on the perspectives of their future development towards standardized microfluidic systems and protocols. An outlook on the current needs and future applications is also presented.

Predictors of Mortality in Nondemented Patients With Parkinson Disease: Motor Symptoms Versus Nonmotor Symptoms.

BACKGROUND AND OBJECTIVE: The aim of this study is to identify risk factors for mortality in a community-based cohort of nondemented patients with Parkinson disease (PD) during prospective long-term follow-up, while also comparing the effect of motor complications to nonmotor symptoms (NMS) on risk of mortality. METHODS: One hundred forty seven nondemented patients with PD (57.1% males; 70.9 ± 8.6 years old) were included in this 48 month follow-up, longitudinal, single, evaluation study. Motor and therapy-related complications were assessed using the Unified Parkinson's Disease Rating Scale/part-IV (UPDRS-IV). Non-Motor Symptoms Scale (NMSS) total score was used to assess NMS burden. Cox proportional hazard models were applied to identify independent predictors of mortality during follow-up. RESULTS: Twenty-two patients of 146 (15.1%) died (1 case without information). Both UPDRS-IV and NMSS total scores were higher at baseline in patients with PD who died (3.5 ± 3.1 vs 2.4 ± 2.4, P = .049 and 96.9 ± 58.6 vs 61.9 ± 51.0, P = .004, respectively). Unadjusted hazard ratios (HRs) associated with UPDRS-IV and NMSS total scores among those who died during follow-up were 1.171 (95% confidence interval [CI]: 1.012-1.357; P = .035) and 1.008 (95% CI: 1.002-1.013; P = .006), respectively. Independent predictors of mortality during follow-up after adjusting for other covariates were UPDRS-IV (HR: 1.224; 95% CI: 1.002-1.494; P = .047), age (HR: 1.231; 95% CI: 1104-1.374; P < .0001), and comorbidity (Charlson Index; HR: 1.429; 95% CI: 1.023-1.994; P = .036), but not NMSS total score (HR: 1.005; 95% CI: 0.996-1.014; P = .263). CONCLUSIONS: Both motor complications (UPDRS-IV) and NMS (NMSS) were associated with mortality at 4 years, being motor complications an independent predictor of it.

Reason for immigration and immigrants' health.

OBJECTIVES: The existing literature on the health trajectories of the UK immigrants has mainly focussed on the relationship between ethnicity and health. There is little information on the role of immigration status and no previous information on the role of reason for immigration to the country. This study fills this gap in the literature by analysing the heterogeneity of immigrant-native differences in health by reason for immigration. STUDY DESIGN: Analysis of cross-sectional quarterly data from the UK Labour Force Survey covering the period of 2010 (quarter 1) to 2017 (quarter 2). The sample includes 345,086 observations. The dependent variables of interest include suffering from a long-lasting condition, the link between long-lasting conditions and labour market performance and the prevalence of 12 specific health conditions. METHODS: Data were analysed using linear probability models to adjust for differences in age, education, gender, ethnicity, local authority of residence and year of survey. The analysis also explores the role of length of stay in the UK and the percentage of current lifetime spent in the UK (duration in the UK/age). RESULTS: Results indicate that, in general, immigrants are less likely than natives to report suffering from a long-lasting (1 year or more) health problem. This pattern generally remains the same when we consider the specificity of the long-lasting health problem. However, there are key differences across the immigrant groups by reason for immigration. Those who migrated for employment, family and study reasons report better health outcomes than natives, while those who migrated to seek asylum report worse health outcomes than natives. There is convergence to natives' health outcomes over time for those who migrated for non-asylum reasons, but not for those who migrated to seek asylum. CONCLUSIONS: The findings show that the prevalence of health problems differs not only between natives and immigrants but also across groups of immigrants who moved to the UK for different reasons.

Context-dependent signal integration by the GLI code: the oncogenic load, pathways, modifiers and implications for cancer therapy.

Canonical Hedgehog (HH) signaling leads to the regulation of the GLI code: the sum of all positive and negative functions of all GLI proteins. In humans, the three GLI factors encode context-dependent activities with GLI1 being mostly an activator and GLI3 often a repressor. Modulation of GLI activity occurs at multiple levels, including by co-factors and by direct modification of GLI structure. Surprisingly, the GLI proteins, and thus the GLI code, is also regulated by multiple inputs beyond HH signaling. In normal development and homeostasis these include a multitude of signaling pathways that regulate proto-oncogenes, which boost positive GLI function, as well as tumor suppressors, which restrict positive GLI activity. In cancer, the acquisition of oncogenic mutations and the loss of tumor suppressors - the oncogenic load - regulates the GLI code toward progressively more activating states. The fine and reversible balance of GLI activating GLI(A) and GLI repressing GLI(R) states is lost in cancer. Here, the acquisition of GLI(A) levels above a given threshold is predicted to lead to advanced malignant stages. In this review we highlight the concepts of the GLI code, the oncogenic load, the context-dependency of GLI action, and different modes of signaling integration such as that of HH and EGF. Targeting the GLI code directly or indirectly promises therapeutic benefits beyond the direct blockade of individual pathways.

Circulating microRNAs in Huntington's disease: Emerging mediators in metabolic impairment.

Huntington's disease (HD) is a hereditary neurodegenerative disease, with peripheral consequences that negatively contribute to quality of life. Circulating microRNAs (cmiRNAs) are being explored for their roles in intercellular communication and gene expression regulation, which allows gaining insight into the regulation of crosstalk between neuronal and peripheral tissues. Here, we explore the cmiRNA profile of plasma samples from fifteen symptomatic patients, with 40-45 CAG repeats in the HTT gene, and seven healthy matched controls. Isolated miRNAs from plasma samples were run against human miRNome panels, which have sequences for 752 human mature miRNAs. We found that 168 cmiRNAs are altered in symptomatic patients. Considering Bonferroni's correction, miR-877-5p, miR-223-3p, miR-223-5p, miR-30d-5p, miR-128, miR-22-5p, miR-222-3p, miR-338-3p, miR-130b-3p, miR-425-5p, miR-628-3p, miR-361-5p, miR-942 are significantly increased in HD patients as compared with controls. Moreover, after patient's organization according to approved HD scales, miR-122-5p is significantly decreased in HD patients with Unified Huntington's Disease Rating Scale >24, whereas an increase in miR-100-5p levels and a decrease in miR-641 and miR-330-3p levels were recorded when patients were rearranged by Total Functional Capacity. These results suggest that cmiRNA profile could be further modified by disease progression, making cmiRNAs useful as monitoring biomarkers. Analysis of target genes indicated a general overexpression of cmiRNAs implicated in metabolism regulation. Profiling cmiRNA of HD subjects opens the possibility of personalized therapies for different groups of HD patients, based on disease modifiers: regulation of altered pathways might contribute to not only alleviate disease symptoms, but also influence HD progression.

[LH-FSH ratio and Polycystic Ovary Syndrome: A forgotten test?]. / Proporción LH-FSH y síndrome de ovario poliquístico: ¿prueba olvidada o no útil?

OBJECTIVE: To identify the predictive value of LH-FSH ratio in the Polycystic Ovary Syndrome diagnosis and to evaluate its role according PCOS phenotypes. MATERIAL AND METHOD: A descriptive, comparative, observational, prospective study of PCOS patients and its controls. All participants received a questionnaire and underwent a physical and transvaginal ultrasound examination. Blood samples were also collected for analysis of metabolic markers and hormones. PCOS was diagnosed according to Rotterdam criteria. RESULTS: A total of 267 women were included into the study. PCOS was diagnosed in 162 patients. There was statistical difference in: HOMA, 1.43 ± 1.06, 2.09 ± 1.96; Total Testosterone, 0.31 ± 0.14, 0.41 ± 0.19; and free Androgen index, 1.17 ± 1.30, 1.69 ± 1.18; for control and PCOS group, respectively. FSH, 6.55 ± 2.43 in controls and 5.30 ± 1.66 in PCOS patients (p = 0.001); LH, 4.34 ± 2.12 controls, 6.36 ± 4.61 PCOS patients (p = 0.001). LH-FSH ratio was 0.71 ± 0.39 for control group and 1.25 ± 0.85 in PCOS group, p = 0.001. A correlation was observed between LH-FSH ratio and total antral follicle count (p < 0.001) and with insulin resistance (p = 0.022). CONCLUSION: LH-FSH ratio, although it is a valuable test, it is not diagnostic of PCOS. A correlation was found with LH-FSH ratio and insulin resistance but we must not forget about its association with hyperandrogenism.

Wineries wastewater treatment by constructed wetlands: a review.

The application of wetland systems for the treatment of wineries wastewater started in the early 1990s in the USA followed a few years later by France, Italy, Germany and Spain. Various studies demonstrated the efficiency of constructed wetlands (CWs) as a low cost, low maintenance and energy-saving technology for the treatment of wineries wastewater. Several of these experiences have also shown lessons to be learnt, such as some limits in the tolerance of the horizontal subsurface flow and vertical subsurface flow classic CWs to the strength of the wineries wastewater, especially in the first stage for the multistage systems. This paper is presenting an overview of all the reported experiences at worldwide level during the last 15 years, giving particular attention and provision of details to those systems that have proven to get reliable and constant performances in the long-term period and that have been designed and realized as optimized solutions for the application of CW technology to this particular kind of wastewater. The organic loading rates (OLRs) applied to the examined 13 CW systems ranged from about 30 up to about 5,000 gCOD/m² d (COD: chemical oxygen demand), with the 80th percentile of the reported values being below 297 gCOD/m² d and the median at 164 gCOD/m² d; the highest OLR values have in all cases been measured during the peak season (vintage) and often have been linked to lower surface removal rates (SRRs) in comparison to the other periods of the year. With such OLRs the SRRs have ranged from a minimum of 15 up to 4,700 gCOD/m² d, with the 80th percentile of the reported values being below 308 gCOD/m² d and the median at 112 gCOD/m² d.

Transmission of Balamuthia mandrillaris through solid organ transplantation: utility of organ recipient serology to guide clinical management.

A liver, heart, iliac vessel and two kidneys were recovered from a 39-year-old man who died of traumatic head injury and were transplanted into five recipients. The liver recipient 18 days posttransplantation presented with headache, ataxia and fever, followed by rapid neurologic decline and death. Diagnosis of granulomatous amebic encephalitis was made on autopsy. Balamuthia mandrillaris infection was confirmed with immunohistochemical and polymerase chain reaction (PCR) assays. Donor and recipients' sera were tested for B. mandrillaris antibodies. Donor brain was negative for Balamuthia by immunohistochemistry and PCR; donor serum Balamuthia antibody titer was positive (1:64). Antibody titers in all recipients were positive (range, 1:64-1:512). Recipients received a four- to five-drug combination of miltefosine or pentamidine, azithromycin, albendazole, sulfadiazine and fluconazole. Nausea, vomiting, elevated liver transaminases and renal insufficiency were common. All other recipients survived and have remained asymptomatic 24 months posttransplant. This is the third donor-derived Balamuthia infection cluster described in solid organ transplant recipients in the United States. As Balamuthia serologic testing is only available through a national reference laboratory, it is not feasible for donor screening, but may be useful to determine exposure status in recipients and to help guide chemotherapy.

NANOG regulates glioma stem cells and is essential in vivo acting in a cross-functional network with GLI1 and p53.

A cohort of genes associated with embryonic stem (ES) cell behaviour, including NANOG, are expressed in a number of human cancers. They form an ES-like signature we first described in glioblastoma multiforme (GBM), a highly invasive and incurable brain tumour. We have also shown that HEDGEHOG-GLI (HH-GLI) signalling is required for GBM growth, stem cell expansion and the expression of this (ES)-like stemness signature. Here, we address the function of NANOG in human GBMs and its relationship with HH-GLI activity. We find that NANOG modulates gliomasphere clonogenicity, CD133(+) stem cell cell behavior and proliferation, and is regulated by HH-GLI signalling. However, GLI1 also requires NANOG activity forming a positive loop, which is negatively controlled by p53 and vice versa. NANOG is essential for GBM tumourigenicity in orthotopic xenografts and it is epistatic to HH-GLI activity. Our data establish NANOG as a novel HH-GLI mediator essential for GBMs. We propose that this function is conserved and that tumour growth and stem cell behaviour rely on the status of a functional GLI1-NANOG-p53 network.

Cold storage to overcome dormancy affects the carbon balance of azalea.

Flower bud dormancy in azalea (Rhododendron simsii) is broken by artificial cold treatment and this will have its consequences on carbon reserves and photosynthesis. The effect of cold storage at 7 °C on carbohydrate and starch content in leaves and flower buds of an early ('Nordlicht') and semi-early ('M. Marie) flowering cultivar was quantified. Carbon loss due to respiration was lowest for 'M. Marie'. Photosynthetic measurements on 'Nordlicht' showed that photosynthesis 3 days after cold treatment (plants ready to flower) was improved compared to before cold treatment (plants with dormant flower buds).

Nursing care plan for a patient with Fournier's gangrene: Clinical case.

INTRODUCTION: Fournier's gangrene, a relatively rare form of necrotizing fasciitis, is a rapidly progressive disease affecting the deep and superficial tissues of the perineal, anal, scrotal, and genital regions. Despite the significant evolution in medical knowledge, there is still scarce evidence regarding the nursing care plan in patients affected by this pathology, which hinders its correct management. For this reason, we present the following clinical case of a 53-year-old male patient with Fournier's gangrene who was admitted to the emergency department for 3 days of pain in the perineal area and fever. OBJECTIVE: The objective was to establish an individualized care plan for the patient detailing the diagnoses, expected outcomes and interventions through nursing taxonomies. CASE DEVELOPMENT: A systematic assessment was performed using Marjory Gordon's model of functional health patterns as a reference. After drawing inferences, three collaborative problems and two nursing diagnoses were established with their outcome criteria and interventions. Once the plan was executed, the results obtained highlighted that the interventions were consistent in achieving the objectives set out in the problems present in the case patient. CONCLUSIONS: The development of an individualized plan made it possible to detect problems, establish realistic objectives and define interventions that optimized nursing care in this patient with Fournier's gangrene.

Coastal current convergence structures in the Bay of Biscay from optimized high-frequency radar and satellite data.

The southeastern Bay of Biscay has been described as a "dead end" for floating marine litter, often accumulating along small-scale linear streaks. Coastal Current Convergence Structures (CCS), often associated with vertical motions at river plume edges, estuarine fronts, or other physical processes, can be at the origin of the accumulation. Understanding the formation of CCS and their role in the transport of marine litter is essential to better quantify and to help mitigate marine litter pollution. The Lagrangian framework, used to estimate the absolute dispersion, and the finite-size Lyapunov exponents (FSLE), have proved very effective for identifying CCS in the current velocity field. However, the quality of CCS identification depends strongly on the Eulerian fields. Two surface current velocity data sets were used in the analysis: the remotely sensed velocities from the EuskOOS High-Frequency Radar (HFR) network and velocities from three-dimensional model outputs. They were complemented by drifting buoy velocity measurements. An optimization method, involving the fusion of drifting buoys and HFR velocities is proposed to better reconstruct the fine-scale structure of the current velocity field. Merging these two sources of velocity data reduced the mean Lagrangian error and the Root Mean Square Error (RMSE) by 50 % and 30 % respectively, significantly improving velocity reconstruction. FSLE ridgelines obtained from the Lagrangian analysis of optimized velocities were compared with remotely sensed concentrations of Chlorophyll-a. It was shown that ridgelines control the spatial distribution of phytoplankton. They fundamentally represent the CCS which can potentially affect marine litter aggregation. Analysis of the absolute dispersion revealed large stirring in the alongshore direction which was also confirmed by spatial distribution of FSLE ridgelines. The alignment between FSLE ridgelines and patterns of high Chlorophyll-a concentration was observed, often determining the limits of river plume expansion in the study area.