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1.
Infect Dis (Lond) ; 56(7): 575-580, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38743059

RESUMO

OBJECTIVE: To study the effect of plitidepsin antiviral treatment in immunocompromised COVID-19 patients with underlying haematological malignancies or solid tumours, particularly those who have undergone anti-CD20 therapies. DESIGN: We conducted a retrospective observational study, involving 54 adults treated with plitidepsin on compassionate use as an antiviral drug. Our analysis compared outcomes between patients with solid tumours and those with haematological malignancies, and a cohort of cases treated or not with anti-CD20 monoclonal antibodies. RESULTS: Patients with a history of anti-CD20 therapies showed a prolonged time-to-negative RT-PCR for SARS-CoV-2 infection compared to non-treated patients (33 d (28;75) vs 15 (11;25); p = .002). Similar results were observed in patients with solid tumours in comparison to those with haematological malignancies (13 (10;16) vs 26 (17;50); p < .001). No serious adverse events were documented. CONCLUSIONS: Patients with haematological malignancies appear to be at a heightened risk for delayed SARS-CoV-2 clearance and subsequent clinical complications. These findings support plitidepsin as a well-tolerated treatment in this high-risk group. A phase II clinical trial (NCT05705167) is ongoing to evaluate plitidepsin as an antiviral drug in this population.KEY POINTSHaematological patients face an increased risk for severe COVID-19.Anti-CD20 therapies could increase fatal outcomes in COVID-19 patients.Persistent viral replication is increased in immunocompromised patients.Plitidepsin does not lead to new serious adverse events in immunocompromised patients.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Depsipeptídeos , Neoplasias Hematológicas , Neoplasias , Peptídeos Cíclicos , SARS-CoV-2 , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/complicações , Idoso , Depsipeptídeos/uso terapêutico , Depsipeptídeos/efeitos adversos , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Peptídeos Cíclicos/uso terapêutico , Antivirais/uso terapêutico , Resultado do Tratamento , Adulto , Ensaios de Uso Compassivo , Hospedeiro Imunocomprometido , Antígenos CD20/imunologia , Idoso de 80 Anos ou mais
2.
Environ Sci Pollut Res Int ; 30(58): 121794-121806, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37962756

RESUMO

Shrimp production is an important industry for many countries and shrimp consumption is increasing worldwide. Shrimps are a highly nutritional food, but can pose a risk for human health if subject to high levels of environmental contaminants. This work studies the presence of As, Cd, Co, Cr, Cu, Hg, Ni, Pb and Zn in shrimps from Ecuador and compares them to such contents noted in other shrimp-production areas in the world to evaluate the possible risks associated with these elements for consumer health, and to relate them to potentially toxic element (PTE) contents in water, sediments and diets, and also to animal biometric parameters. The PTE levels (mg kg-1 DM) obtained are as follows: in the head-As (3.52-6.11), Cd (0.02-0.10), Co (0.14-0.49) Cr (0.23-4.89), Cu (99.9--233.0), Ni (0.52-1.86), Pb (0.24-1.09), Zn (51.8-100.5) and Hg (µg kg-1 DM) (10.00-66.81); in the tail-(0.91-3.21), Cd (0.01-0.02), Co (0.01-0.43) Cr (0.01-6.52), Cu (20.0-72.44), Ni (0.15-2.03), Pb (0.01-0.69), Zn (31.2-66.1) and Hg (µg kg-1 DM) (10.00-67.18). The concentration of all the PTEs is generally lower than the limits set for seafood by European regulations, except for As in the cephalothorax (4.63 mg kg-1). Different behaviours for PTE accumulation in shrimps were found, which preferentially tend to accumulate in the cephalothorax, except for Hg (40.13 µg kg-1 DM), which accumulates in muscle (body) and is associated with contents of proteins, lipids and total shrimp weight. Nonetheless, the target hazard quotient (THQ) values for PTEs indicate that the consumption of shrimp muscles from Ecuador does not pose a human health risk because the values of these indices are below 1 in all cases.


Assuntos
Mercúrio , Metais Pesados , Poluentes Químicos da Água , Animais , Humanos , Metais Pesados/análise , Cádmio , Água , Bioacumulação , Chumbo , Monitoramento Ambiental , Mercúrio/análise , Alimentos Marinhos/análise , Fazendas , Dieta , Medição de Risco , Poluentes Químicos da Água/análise
3.
Eur Heart J Open ; 3(5): oead095, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37829559

RESUMO

Aims: The fragmentation and loss of elastic fibre in the tunica media of the aorta are pathological hallmarks of Marfan syndrome (MFS) but the dynamics of elastin degradation and its relationship to aortic size and physiological growth remain poorly understood. Methods and results: In this post hoc analysis of the AIMS randomized controlled trial, the association of plasma desmosine (pDES)-a specific biomarker of mature elastin degradation-with age and aortic size was analysed in 113 patients with MFS and compared to 109 healthy controls. There was a strong association between age and pDES in both groups, with higher pDES levels in the lower age groups compared to adults. During childhood, pDES increased and peaked during early adolescence, and thereafter decreased to lower adult levels. This trend was exaggerated in young individuals with MFS but in those above 25 years of age, pDES levels were comparable to controls despite the presence of aortic root dilation. In MFS children, increased aortic diameter relative to controls was seen at an early age and although the increase in diameter was less after adolescence, aortic root size continued to increase steadily with age. In MFS participants, there was an indication of a positive association between baseline pDES levels and aortic root dilatation during up to 5 years of follow-up. Conclusion: This study has shown that developmental age has a significant effect on levels of elastin turnover as measured by pDES in MFS individuals as well as healthy controls. This effect is exaggerated in those with MFS with increased levels seen during the period of physiologic development that plateaus towards adulthood. This suggests an early onset of pathophysiology that may present an important opportunity for disease-modifying intervention.

4.
Front Cell Dev Biol ; 11: 1190258, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576597

RESUMO

Ellis van Creveld syndrome and Weyers acrofacial dysostosis are two rare genetic diseases affecting skeletal development. They are both ciliopathies, as they are due to malfunction of primary cilia, microtubule-based plasma membrane protrusions that function as cellular antennae and are required for Hedgehog signaling, a key pathway during skeletal morphogenesis. These ciliopathies are caused by mutations affecting the EVC-EVC2 complex, a transmembrane protein heterodimer that regulates Hedgehog signaling from inside primary cilia. Despite the importance of this complex, the mechanisms underlying its stability, targeting and function are poorly understood. To address this, we characterized the endogenous EVC protein interactome in control and Evc-null cells. This proteomic screen confirmed EVC's main known interactors (EVC2, IQCE, EFCAB7), while revealing new ones, including USP7, a deubiquitinating enzyme involved in Hedgehog signaling. We therefore looked at EVC-EVC2 complex ubiquitination. Such ubiquitination exists but is independent of USP7 (and of USP48, also involved in Hh signaling). We did find, however, that monoubiquitination of EVC-EVC2 cytosolic tails greatly reduces their protein levels. On the other hand, modification of EVC-EVC2 cytosolic tails with the small ubiquitin-related modifier SUMO3 has a different effect, enhancing complex accumulation at the EvC zone, immediately distal to the ciliary transition zone, possibly via increased binding to the EFCAB7-IQCE complex. Lastly, we find that EvC zone targeting of EVC-EVC2 depends on two separate EFCAB7-binding motifs within EVC2's Weyers-deleted peptide. Only one of these motifs had been characterized previously, so we have mapped the second herein. Altogether, our data shed light on EVC-EVC2 complex regulatory mechanisms, with implications for ciliopathies.

5.
Int J Infect Dis ; 135: 12-17, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37481109

RESUMO

OBJECTIVES: To evaluate the compassionate use of plitidepsin as an antiviral treatment in hospitalized immunocompromised adult patients with moderate-to-severe COVID-19. DESIGN: Retrospective observational study of data -collected from January 01, 2021 to April 30, 2022- from 35 immunocompromised adult patients with COVID-19 non-eligible for other available antiviral treatments. Main outcome measures were time to respiratory recovery (SpFi ≥ 315); COVID-19-related 30-day-cumulative mortality after first plitidepsin infusion; and time to undetectable levels of viral RNA. RESULTS: Thirty-three patients receiving a full course of plitidepsin (2.5 mg [n = 29] or 1.5 mg [n = 4]) were included. Most (69.7%) had a malignant hematologic disease and 27.3% had solid tumors. A total of 111 infusions were administered with lack of relevant safety events. Median time from plitidepsin initiation to SpFi ≥315 was 8 days (95% confidence interval [CI], 7-19). Median time to first negative reverse transcription-polymerase chain reaction for SARS-CoV-2 (cycle threshold >36) was 17 days (95% CI 13-25). Mortality rate was 16.3% (95% CI 3-37.3). CONCLUSION: These data support plitidepsin as a well-tolerated treatment that might have potential clinical and antiviral efficacy in COVID-19 immunocompromised patients.


Assuntos
COVID-19 , Neoplasias , Humanos , Adulto , SARS-CoV-2 , Ensaios de Uso Compassivo , Neoplasias/tratamento farmacológico , Antivirais/uso terapêutico
6.
Biomater Adv ; 150: 213426, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37104961

RESUMO

Acquired muscle diseases such as cancer cachexia are responsible for the poor prognosis of many patients suffering from cancer. In vitro models are needed to study the underlying mechanisms of those pathologies. Extrusion bioprinting is an emerging tool to emulate the aligned architecture of fibers while implementing additive manufacturing techniques in tissue engineering. However, designing bioinks that reconcile the rheological needs of bioprinting and the biological requirements of muscle tissue is a challenging matter. Here we formulate a biomaterial with dual crosslinking to modulate the physical properties of bioprinted models. We design 3D bioprinted muscle models that resemble the mechanical properties of native tissue and show improved proliferation and high maturation of differentiated myotubes suggesting that the GelMA-AlgMA-Fibrin biomaterial possesses myogenic properties. The electrical stimulation of the 3D model confirmed the contractile capability of the tissue and enhanced the formation of sarcomeres. Regarding the functionality of the models, they served as platforms to recapitulate skeletal muscle diseases such as muscle wasting produced by cancer cachexia. The genetic expression of 3D models demonstrated a better resemblance to the muscular biopsies of cachectic mouse models. Altogether, this biomaterial is aimed to fabricate manipulable skeletal muscle in vitro models in a non-costly, fast and feasible manner.


Assuntos
Caquexia , Neoplasias , Camundongos , Animais , Caquexia/etiologia , Caquexia/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/etiologia , Atrofia Muscular/metabolismo , Neoplasias/complicações , Neoplasias/metabolismo , Materiais Biocompatíveis
7.
Nat Commun ; 13(1): 6278, 2022 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-36271011

RESUMO

Desmoid fibromatosis (DF) are mesenchymal neoplasms, with potential aggressive course and relevant clinical impact. New systemic therapy modalities are needed in this symptomatic/progressive population. In this multicenter, phase II trial (NCT03275818), patients with symptomatic/progressing DF received three cycles of weekly nab-paclitaxel. Brief pain inventory short form (BPI-SF) was collected at baseline and in every visit. MRI was performed every 3 months. Primary composite endpoint was RECIST 1.1 overall response rate (ORR) and/or clinical response (improvement ≥ 2 points in BPI-SF). If 40% of patients achieved clinical/radiological response, further investigation would be warranted. Toxicity, progression-free survival (PFS), pattern of response and its correlation with clinical best response and BPI, variation of physical function, and analgesic consumption were secondary endpoints. The translational research reported was not a pre-specified secondary outcome. Forty eligible patients started therapy, being 35 radiologically and clinically evaluable. The study achieved its primary endpoint, as 7(20%) patients obtained RECIST partial response, whereas 31(89%) experienced pain reduction of ≥2 points in BPI-SF worst pain. Therapy was well tolerated. With a median follow-up of 30(14-44) months, median 12 and 24-months PFS rates were 91%(CI 95%, 82-100) and 84%(CI 95%, 71-97). For clinical progression, 12 and 24-months PFS rates were 85% (CI 95%, 73-97) and 74% (CI 95%, 58-90) respectively. Short course of nab-paclitaxel is active, safe and achieves quick and durable responses in progressing/symptomatic DF patients.


Assuntos
Fibromatose Agressiva , Humanos , Fibromatose Agressiva/diagnóstico por imagem , Fibromatose Agressiva/tratamento farmacológico , Fibromatose Agressiva/induzido quimicamente , Paclitaxel/efeitos adversos , Albuminas/efeitos adversos , Dor/tratamento farmacológico
8.
Toxics ; 10(7)2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35878280

RESUMO

Albufera Natural Park (ANP) (Valencia, Spain) is one of the most important wetland areas of the Mediterranean coast subject to high anthropogenic pressure, on whose soils a battery of bioassays has never been applied to evaluate the ecotoxicological risk. The present study determined available and water-soluble heavy metal content in four paddy soils used in the ANP, and the ecotoxicological effect on these soils was evaluated by performing the bioassays regulated in Spanish Royal Decree 9/2005. Soil properties and extractable Co, Cr, Cu, Ni, Pb and Zn (EDTA pH = 7) were analyzed in soils. These elements and macro- and micronutrients were also assessed in soil leachate. A test battery covering the following was needed: acute toxicity test in Eisenia foetida (OECD TG 207); mineralization tests of nitrogen (OECD TG 2016) and carbon (OECD TG 217); growth inhibition test in Raphidocelis subcapitata (OECD TG 201); mobility inhibition test in Daphnia magna (OECD TG 202). The soils found in the most anthropized areas to the north of the ANP (Massanassa and Alfafar) demonstrated a higher concentration of available heavy metals than in the southern ones (Sueca and Sollana). The aqueous leachate of the studied soils contained very low concentrations, which would be related to soil properties. Despite the high concentration of available potentially toxic elements (PTEs) in the Massanassa and Alfafar soils, the studied soils showed no toxicity during the performed battery bioassays. Therefore, soils can be considered non-toxic despite the obtained PTEs available concentration.

9.
Int J Cardiol ; 366: 1-9, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35830949

RESUMO

OBJECTIVES: This study aims to identify the clinical utility of targeted-genetic sequencing in a cohort of patients with TAA and establish a new method for regional histological characterisation of TAA disease. METHODS: Fifty-four patients undergoing surgery for proximal TAA were recruited. EXCLUSIONS: connective tissue disease, bicuspid aortic valves, redo surgery. All patients underwent next generation sequencing (NGS) using a custom gene panel containing 63 genes previously associated with TAA on Illumina MiSeqor NextSeq550 platforms. Explanted TAA tissue was obtained en-bloc from 34/54 patients, and complete circumferential strips of TAA tissue processed into whole slides which were subsequently digitalised. Computational pathology methods were employed to quantify elastin, cellularity and collagen in six equally divided regions across the whole aneurysm circumference. RESULTS: Of 54 patients, clearly pathogenic or potentially pathogenic variants were found in 7.4%: namely LOX, PRKG1, TGFBR1 and SMAD3 genes. 55% had at least one variant of unknown significance (VUS) and seven of the VUSs were in genes with a strong disease association (category A) genes, whilst 15 were from moderate risk (category B) genes. Elastin and collagen abundance displayed high regional variation throughout the aneurysm circumference. In patients with <60% total elastin, the loss of elastin was more significant on the outer curve (38.0% vs 47.4%, p = 0.0094). The presence of VUS, higher pulse wave velocity and advancing age were predictors of elastin loss (regression analysis: p < 0.05). CONCLUSIONS: These findings demonstrate the heterogeneity of TAA disease microstructure and the potential link between histological appearance and clinical factors, including genetic variation.


Assuntos
Aneurisma da Aorta Torácica , Doença da Válvula Aórtica Bicúspide , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/genética , Aneurisma da Aorta Torácica/patologia , Colágeno , Elastina/genética , Humanos , Análise de Onda de Pulso
10.
Australas J Dermatol ; 63(3): e231-e237, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35567765

RESUMO

Down syndrome (DS) has been related to a higher risk of hidradenitis suppurativa (HS). This cross-sectional study assessed DS patients with HS in a Spanish single-centre sample. DS participants presented a lower age of onset, age at diagnosis and time to diagnosis. Also, DS was not associated with the severity of HS measured by baseline IHS4 .


Assuntos
Síndrome de Down , Hidradenite Supurativa , Estudos Transversais , Síndrome de Down/complicações , Hidradenite Supurativa/complicações , Hidradenite Supurativa/diagnóstico , Hidradenite Supurativa/epidemiologia , Humanos , Índice de Gravidade de Doença
11.
J Clin Med ; 11(7)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35407672

RESUMO

Comparable outcomes were published using a buccal mucosa graft (BMG) from the cheek and a lingual mucosa graft (LMG) from the sublingual area, for urethral augmentation or substitution. To date, no histological comparison between both grafts has been conducted. We histologically assessed BMG and LMG harvested during urethral surgeries, aiming to compare graft properties and vascular support. We conducted a prospective single cohort study, including oral mucosa urethroplasty patients. During surgery, graft dimensions and donor sites were collected, and a 0.5 × 0.5 cm sample was obtained from the prepared graft. Formalin-fixed paraffin-embedded samples were sliced at 4 micrometres (µm) and hematoxylin-eosin stained. Using a telepathology tool, all slides were digitalized and measured from 10× to 40× magnification. In each graft, global and individual layers thicknesses were assessed, including vascular density and area. Descriptive and comparative (parametrical and non-parametrical) statistical analysis occurred. We collected 57 grafts during 33 urethroplasties, with 30 BMG and 22 LMG, finally, included. The mean age was 56.6 (SD 15.2) years, and the mean graft length was 5.8 (SD 1.7) cm and the width was 1.7 (SD 0.4) cm. The median graft thickness was 1598.9 (IQR 1200-2100) µm, the mean epithelium layer was 510.2 (SD 223.7) µm, the median submucosa was 654 (IQR 378-943) µm. the median muscular was 477.6 (IQR 286-772) µm, the median vascular area was 5% (IQR 5-10), and the median adipose tissue area was 5% (IQR 0-20). LMG were significantly longer and narrower than BMG. Total graft thickness was similar between LMG and BMG, but the epithelium and submucosa layers were significantly thinner in LMG. The muscular layer was significantly thicker in LMG. Vascular density and vascular areas were not significantly different between both types of grafts. LMG showed significantly less adipose tissue compared with BMG. Our findings show LMG and BMG for urethroplasty surgeries share the same thickness and blood supply, despite having significantly different graft sizes as well as mucosal and submucosal layers thickness.

12.
Nat Commun ; 12(1): 7008, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34853302

RESUMO

Combination treatment with BRAF (BRAFi) plus MEK inhibitors (MEKi) has demonstrated survival benefit in patients with advanced melanoma harboring activating BRAF mutations. Previous preclinical studies suggested that an intermittent dosing of these drugs could delay the emergence of resistance. Contrary to expectations, the first published phase 2 randomized study comparing continuous versus intermittent schedule of dabrafenib (BRAFi) plus trametinib (MEKi) demonstrated a detrimental effect of the "on-off" schedule. Here we report confirmatory data from the Phase II randomized open-label clinical trial comparing the antitumoral activity of the standard schedule versus an intermittent combination of vemurafenib (BRAFi) plus cobimetinib (MEKi) in advanced BRAF mutant melanoma patients (NCT02583516). The trial did not meet its primary endpoint of progression free survival (PFS) improvement. Our results show that the antitumor activity of the experimental intermittent schedule of vemurafenib plus cobimetinib is not superior to the standard continuous schedule. Detection of BRAF mutation in cell free tumor DNA has prognostic value for survival and its dynamics has an excellent correlation with clinical response, but not with progression. NGS analysis demonstrated de novo mutations in resistant cases.


Assuntos
Antineoplásicos/farmacologia , Melanoma/tratamento farmacológico , Melanoma/genética , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Idoso , Antineoplásicos/uso terapêutico , Azetidinas/farmacologia , Humanos , Imidazóis/farmacologia , Mutação , Oximas/farmacologia , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Piridonas/farmacologia , Pirimidinonas/farmacologia , Vemurafenib/farmacologia
13.
Genes (Basel) ; 12(7)2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34356048

RESUMO

Adolescent idiopathic scoliosis (AIS) is a complex common disorder of multifactorial etiology defined by a deviation of the spine in three dimensions that affects approximately 2% to 4% of adolescents. Risk factors include other affected family members, suggesting a genetic component to the disease. The POC5 gene was identified as one of the first ciliary candidate genes for AIS, as three variants were identified in large families with multiple members affected with idiopathic scoliosis. To assess the prevalence of p.(A429V), p.(A446T), and p.(A455P) POC5 variants in patients with AIS, we used next-generation sequencing in our cohort of French-Canadian and British families and sporadic cases. Our study highlighted a prevalence of 13% for POC5 variants, 7.5% for p.(A429V), and 6.4% for p.(A446T). These results suggest a higher prevalence of the aforementioned POC5 coding variants in patients with AIS compared to the general population.


Assuntos
Proteínas de Transporte/genética , Variação Genética , Escoliose/genética , Adolescente , Canadá , Proteínas de Transporte/classificação , Estudos de Coortes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Linhagem , Prevalência , Fatores de Risco , Escoliose/epidemiologia , Sequenciamento do Exoma
14.
Eur J Case Rep Intern Med ; 8(7): 002652, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268272

RESUMO

Dermal fillers are applied using a minimally invasive technique with a good safety profile. However, they can have side effects. We present the case of a patient who, 2 months after undergoing polycaprolactone (Ellansé®) injections, developed nodular facial and nodal lesions that were compatible with sarcoidosis on histology. This complication has not been previously described for polycaprolactone and could be the expression of an autoimmune syndrome induced by adjuvants. LEARNING POINTS: Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) is a recently devised umbrella term for autoimmune diseases caused by adjuvants.Aesthetic procedures, which are increasingly common, may be a cause of ASIA syndrome.Polycaprolactone is a bioabsorbable polymer with a safe profile but can have adverse events, including systemic sarcoidosis.

15.
Sci Rep ; 11(1): 11026, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34040021

RESUMO

Idiopathic scoliosis (IS) is a complex 3D deformation of the spine with a strong genetic component, most commonly found in adolescent girls. Adolescent idiopathic scoliosis (AIS) affects around 3% of the general population. In a 5-generation UK family, linkage analysis identified the locus 9q31.2-q34.2 as a candidate region for AIS; however, the causative gene remained unidentified. Here, using exome sequencing we identified a rare insertion c.1569_1570insTT in the tubulin tyrosine ligase like gene, member 11 (TTLL11) within that locus, as the IS causative gene in this British family. Two other TTLL11 mutations were also identified in two additional AIS cases in the same cohort. Analyses of primary cells of individuals carrying the c.1569_1570insTT (NM_194252) mutation reveal a defect at the primary cilia level, which is less present, smaller and less polyglutamylated compared to control. Further, in a zebrafish, the knock down of ttll11, and the mutated ttll11 confirmed its role in spine development and ciliary function in the fish retina. These findings provide evidence that mutations in TTLL11, a ciliary gene, contribute to the pathogenesis of IS.


Assuntos
Ligação Genética , Escoliose , Coluna Vertebral , Adolescente , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único , Reino Unido
16.
Artigo em Inglês | MEDLINE | ID: mdl-33946837

RESUMO

This paper aims to measure disparities among the variables associated with Sustainable Development Goal (SDG) 3 defined by the United Nations (UN) in the least developed countries (LDCs) of Asia. In the terms of the UN Conference on Trade and Development, LDCs are countries with profound economic and social inequalities. The indicator was constructed using a set of variables associated with SDG3: Good Health and Wellbeing. Applying Pena's DP2 distance method to the most recent data available (2018) enables regional ordering of Asia's LDCs based on the values of these variables. The index integrates socioeconomic variables that permit examination of the impact of each individual indicator to determine territorial disparities in terms of the partial indicators of SDG3. "Maternal education," "Proportion of women who make their own informed decisions regarding sexual relations, contraceptive use, and reproductive health care," and "Gender parity index in primary education" are the most important variables in explaining spatial disparities in good health and wellbeing in the LDCs of Asia.


Assuntos
Países em Desenvolvimento , Desenvolvimento Sustentável , Ásia , Economia , Feminino , Objetivos , Direitos Humanos , Humanos , Fatores Socioeconômicos
17.
Environ Pollut ; 283: 117397, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34030063

RESUMO

Hg is a global concern given its adverse effects on human health, food security and the environment, and it requiring actions to identify major local Hg sources and to evaluate pollution. Our study provides the first assessment of Hg stock trends on the entire Majorca surface, identifying major Hg sources by studying the spatiotemporal soil Hg variation at two successive times (2006 and 2016-17). The Hg soil concentration ranged from 14 to 258 µg kg-1 (mean 52 µg kg-1). Higher concentrations (over 100 µg kg-1) were found in two areas: (i) close to the Alcudia coal-fired power plant; (ii) in the city of La Palma. During the 11-year, the total Hg stock in Majorcan soil increased from 432.96 tons to 493.18 tones (14% increase). Based on a block kriging analysis, soil Hg enrichment due to power plant emissions was clearly detectable on a local scale (i.e. a shorter distance than 18 km from the power plant). Nonetheless, a significant island-wide Hg increase due to diffuse pollution was reported. This result could be extrapolated to other popular tourist destinations in the Mediterranean islands where tourism has increased in recent decades In short, more than 60 tons of Hg have accumulated on Majorca island in 11 years.


Assuntos
Mercúrio , Poluentes do Solo , Carvão Mineral/análise , Monitoramento Ambiental , Humanos , Ilhas , Ilhas do Mediterrâneo , Mercúrio/análise , Centrais Elétricas , Solo , Poluentes do Solo/análise , Espanha
18.
Environ Sci Technol ; 55(11): 7327-7334, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34009978

RESUMO

Copper-based fungicides (Cuf) are used in European (EU) vineyards to prevent fungal diseases. Soil physicochemical properties locally govern the variation of the total copper content (Cut) in EU vineyards. However, variables controlling Cut distribution at a larger scale are poorly known. Here, machine learning techniques were used to identify governing variables and to predict the Cut distribution in EU vineyards. Precipitation, aridity and soil organic carbon are key variables explaining together 45% of Cut distribution across EU vineyards. This underlines the effect of both climate and soil properties on Cut distribution. The average net export of Cu at the EU scale is 0.29 kg Cu ha-1, which is 2 orders of magnitude less than the net accumulation of Cu (24.8 kg Cu ha-1). Four scenarios of Cuf application were compared. The current EU regulation with a maximum of 4 kg Cu ha-1 year-1 may increase by 2% of the EU vineyard area, exceeding the predicted no-effect concentration (PNEC) in soil in the next 100 years. Overall, our results highlight the vineyard areas requiring specific remediation measures and strategies of Cuf use to manage a trade-off between pest control and soil and water contamination.


Assuntos
Poluentes do Solo , Solo , Agricultura , Carbono , Cobre/análise , Fazendas , Poluentes do Solo/análise
19.
Chemosphere ; 268: 129347, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33359986

RESUMO

In this study, concentrations of cadmium using 3778 samples encompassing the total size of Spain (about 505 km2) were investgated. Two novel spatial methods namely Moran eigenvector spatially varying coefficient (MESVC) and spatially filtered unconditional quantile regression (SF-UQR) were employed with the aim of avoiding the problem of local collinearity which is prevalent in regression models. Additionally, the spatially varying coefficients methods were applied to assess the influence of soil properties together with soil texture on the spatial variations of cadmium. It was indicated that the overall level of cadmium is low compared to the concentrations found around the world. In particular, the values of Cd varied between 0.01 and 2.00 mgkg-1, with the median of 0.23 mgkg-1. The residual standard error and adjusted R2 produced by MESVC were 0.16 and 0.69, respectively which are better than 0.21 and 0.39 yielded by the SF-UQR model. Both of these models outperformed compared to the geographically weighted regression (GWR) and the performance of MESVC was also better than the traditional method of kriging. For instance, in terms of willmott index (d) and root mean squared relative error (RMSRE), the MESVC had superior performance with values equal to 0.612 and 0.275 compared to 0.399 and 0.379 obtained for the ordinary kriging. The MESVC and GWR demonstrated that CaCO3, sand, silt and clay had a negligible influence on spatial variations of cadmium whereas, EC had the largest contribution followed by SOM and pH.


Assuntos
Poluentes do Solo , Solo , Cádmio/análise , Poluentes do Solo/análise , Espanha , Análise Espacial
20.
Ther Adv Rare Dis ; 2: 26330040211055738, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-37181104

RESUMO

Marfan syndrome (MFS) is an autosomal dominantly inherited disorder affecting the cardiovascular, ocular and musculoskeletal systems. Frequently, clinical suspicion and subsequent diagnosis begins in the ophthalmology clinic. Importantly, the ophthalmologist has a responsibility to cater not only to the eye, but also to be involved in a holistic approach for these patients. In this review, we discuss how MFS may present to an eye clinic, including clinical features, ocular morbidity, genetic diagnosis and management. Although this condition is ideally managed by a multidisciplinary team, our focus will be on MFS and the eye, including other conditions which may present with similar phenotypes. The ophthalmologist's role as the potential first contact for a patient with suspected MFS is crucial in making the proper investigations and referral, with the knowledge that not all ectopia lentis cases are MFS and vice versa. Management of ocular conditions in MFS may range from simple observation to surgical intervention; current options will be discussed.


Eye problems in Marfan Syndrome ­ A Review Marfan syndrome (MFS) is an inherited disorder that affects many systems of the body, including the heart, joints, skeleton, skin and eyes. Although the more dangerous problems caused by this are to do with the heart and blood vessels, it is quite often that such patients are first found by eye doctors. They are either seen due to being very short-sighted or with dislocated lenses which can cause major problems in the eye. Eye problems can be managed by regular observation, although they often require surgery. Because eye doctors are often the first to see these patients, they must involve other doctors of different specialities to help in diagnosing and managing important issues these patients may have, especially affecting the heart and major blood vessels. Confirmation of diagnosis is done through genetic testing, which has advanced greatly, finding new mutations which may contribute to this disorder. Genetic counselling services can help families in understanding their diagnosis and making better informed decisions about future family planning as well as screening other family members. The eye is just one part of this complex genetic disease. We look in detail at how eye doctors can best approach such patients.

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