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1.
Dalton Trans ; 52(41): 14762-14773, 2023 Oct 24.
Article in English | MEDLINE | ID: mdl-37548588

ABSTRACT

A new series of Zn(II) and Cu(II)-based porphyrin complexes 5a and 5b doubly functionalised with carbazole units were developed to be used as hole-transporting materials (HTMs) in perovskite solar cells (PSCs). These complexes were obtained via a nucleophilic substitution reaction mediated by PhI(OAc)2/NaAuCl4·2H2O, or using C-N transition metal-assisted coupling. The hole extraction capability of 5a and 5b was assessed using cyclic voltammetry; this study confirmed the better alignment of the Zn(II) complex 5a with the perovskite valence band level, compared to the Cu(II) complex 5b. The optimised geometry and molecular orbitals of both complexes also corroborate the higher potential of 5a as a HTM. Photoluminescence characterisation showed that the presence of 5a and 5b as HTMs on the perovskite surface resulted in the quenching of the emission, matching the hole transfer phenomenon. The photovoltaic performance was evaluated and compared with those of reference cells made with the standard HTM spiro-OMeTAD. The optimised 5-based devices showed improvements in all photovoltaic characteristics; their open circuit voltage (Voc) reached close to 1 V and short-circuit current density (Jsc) values were 13.79 and 9.14 mA cm-2 for 5a and 5b, respectively, disclosing the effect of the metallic centre. A maximum power conversion efficiency (PCE) of 10.01% was attained for 5a, which is 65% of the PCE generated by using the spiro-OMeTAD reference. This study demonstrates that C-N linked donor-type porphyrin derivatives are promising novel HTMs for developing efficient and reproducible PSCs.

2.
Allergy ; 78(10): 2581-2595, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37641384

ABSTRACT

Eight million Ukrainians have taken refuge in the European Union. Many have asthma and/or allergic rhinitis and/or urticaria, and around 100,000 may have a severe disease. Cultural and language barriers are a major obstacle to appropriate management. Two widely available mHealth apps, MASK-air® (Mobile Airways Sentinel NetworK) for the management of rhinitis and asthma and CRUSE® (Chronic Urticaria Self Evaluation) for patients with chronic spontaneous urticaria, were updated to include Ukrainian versions that make the documented information available to treating physicians in their own language. The Ukrainian patients fill in the questionnaires and daily symptom-medication scores for asthma, rhinitis (MASK-air) or urticaria (CRUSE) in Ukrainian. Then, following the GDPR, patients grant their physician access to the app by scanning a QR code displayed on the physician's computer enabling the physician to read the app contents in his/her own language. This service is available freely. It takes less than a minute to show patient data to the physician in the physician's web browser. UCRAID-developed by ARIA (Allergic Rhinitis and its Impact on Asthma) and UCARE (Urticaria Centers of Reference and Excellence)-is under the auspices of the Ukraine Ministry of Health as well as European (European Academy of Allergy and Clinical immunology, EAACI, European Respiratory Society, ERS, European Society of Dermatologic Research, ESDR) and national societies.

3.
Int J Mol Sci ; 24(2)2023 Jan 14.
Article in English | MEDLINE | ID: mdl-36675195

ABSTRACT

Obesity is associated with complex adipose tissue energy metabolism remodeling. Whether AT metabolic reprogramming differs according to body mass index (BMI) and across different obesity classes is unknown. This study's purpose was to evaluate and compare bioenergetics and energy substrate preference of visceral adipose tissue (VAT) pertaining to individuals with obesity class 2 and class 3. VAT obtained from patients with obesity (n = 15) class 2 (n = 7; BMI 37.53 ± 0.58 kg/m2) or class 3 (n = 8; BMI 47.79 ± 1.52 kg/m2) was used to assess oxygen consumption rate (OCR) bioenergetics and mitochondrial substrate preferences. VAT of patients with obesity class 3 presented significantly higher non-mitochondrial oxygen consumption (p < 0.05). In VAT of patients with obesity class 2, inhibition of pyruvate and glutamine metabolism significantly decreased maximal respiration and spare respiratory capacity (p < 0.05), while pyruvate and fatty acid metabolism inhibition, which renders glutamine the only available substrate, increased the proton leak with a protective role against oxidative stress (p < 0.05). In conclusion, VAT bioenergetics of patients with obesity class 2 depicts a greater dependence on glucose/pyruvate and glutamine metabolism, suggesting that patients within this BMI range are more likely to be responsive to interventions based on energetic substrate modulation for obesity treatment.


Subject(s)
Glutamine , Intra-Abdominal Fat , Humans , Glutamine/metabolism , Intra-Abdominal Fat/metabolism , Obesity/metabolism , Energy Metabolism , Pyruvates/metabolism , Adipose Tissue/metabolism
4.
Laryngoscope ; 133(6): 1321-1327, 2023 06.
Article in English | MEDLINE | ID: mdl-35912902

ABSTRACT

OBJECTIVES: Allergic rhinitis (AR) has been associated with anxiety and depression. A possible influence of frequency and intensity of the AR symptoms has remained unclear. Therefore, we evaluated the association between AR, as well as its control, seasonality and severity, and the presence of anxiety and depression. METHODS: Participants were selected from a preexistent national database and consecutively contacted by phone. AR was classified according to Allergic Rhinitis and its Impact on Asthma. Presence of anxiety and depression was identified by Hospital Anxiety and Depression Scale (HADS), Beck Anxiety Inventory (BAI), and Beck Depression Inventory-II (BDI-II). We built linear regression models assessing the association between any of the assessed anxiety or depression scores and the occurrence, degree of control, seasonality or severity of AR. RESULTS: We analyzed 115 participants with AR and 38 participants with no respiratory symptoms. Patients with AR presented higher scores of anxiety (HADS: 3.1; 95% confidence interval [CI] = 1.9; 4.3; p < 0.001) and depression (HADS: 3.8; 95% CI = 2.5; 5.0; p < 0.001). Poorer AR control was positively associated with higher prevalence and scores of anxiety (HADS: 3.0; 95% CI = 1.5; 4.5; p < 0.001) and depression (HADS: 1.8; 95% CI = 0.2; 3.4; p = 0.031). Similar results were obtained with BAI and BDI-II scales. A moderate/severe presentation of AR were also related with higher scores of anxiety (HADS: 1.7; 95% CI = 0.1; 3.2; p = 0.040) and depression (HADS: 1.7; 95% CI = 0.1; 3.3; p = 0.037). CONCLUSION: The presence of AR, a poorer control, and a moderate/severe presentation of the disease were significantly associated with higher scores of anxiety and depression. Thus, it is important to alert to this association to allow a quick diagnosis of AR-associated pathologies. Laryngoscope, 133:1321-1327, 2023.


Subject(s)
Asthma , Rhinitis, Allergic , Humans , Depression/epidemiology , Depression/etiology , Depression/diagnosis , Anxiety/epidemiology , Anxiety/etiology , Anxiety/diagnosis , Anxiety Disorders/diagnosis , Rhinitis, Allergic/complications , Rhinitis, Allergic/epidemiology , Asthma/complications , Asthma/epidemiology
5.
Foods ; 11(23)2022 Nov 22.
Article in English | MEDLINE | ID: mdl-36496561

ABSTRACT

Mannans are outstanding polysaccharides that have gained exponential interest over the years. These polysaccharides may be extracted from the cell wall of Saccharomyces cerevisiae, and recovered from the brewing or synthetic biology industries, among others. In this work, several extraction processes-physical, chemical and enzymatic-were studied, all aiming to obtain mannans from spent yeast S. cerevisiae. Their performance was evaluated in terms of yield, mannose content and cost. The resultant extracts were characterized in terms of their structure (FT-IR, PXRD and SEM), physicochemical properties (color, molecular weight distribution, sugars, protein, ash and water content) and thermal stability (DSC). The biological properties were assessed through the screening of prebiotic activity in Lactobacillus plantarum and Bifidobacterium animalis. The highest yield (58.82%) was achieved by using an alkaline thermal process, though the correspondent mannose content was low. The extract obtained by autolysis followed by a hydrothermal step resulted in the highest mannose content (59.19%). On the other hand, the extract obtained through the enzymatic hydrolysis displayed the highest prebiotic activity. This comparative study is expected to lay the scientific foundation for the obtention of well-characterized mannans from yeast, which will pave the way for their application in various fields.

6.
Oncogene ; 41(32): 3969-3977, 2022 08.
Article in English | MEDLINE | ID: mdl-35768547

ABSTRACT

HORMAD1 expression is usually restricted to germline cells, but it becomes mis-expressed in epithelial cells in ~60% of triple-negative breast cancers (TNBCs), where it is associated with elevated genomic instability (1). HORMAD1 expression in TNBC is bimodal with HORMAD1-positive TNBC representing a biologically distinct disease group. Identification of HORMAD1-driven genetic dependencies may uncover novel therapies for this disease group. To study HORMAD1-driven genetic dependencies, we generated a SUM159 cell line model with doxycycline-inducible HORMAD1 that replicated genomic instability phenotypes seen in HORMAD1-positive TNBC (1). Using small interfering RNA screens, we identified candidate genes whose depletion selectively inhibited the cellular growth of HORMAD1-expressing cells. We validated five genes (ATR, BRIP1, POLH, TDP1 and XRCC1), depletion of which led to reduced cellular growth or clonogenic survival in cells expressing HORMAD1. In addition to the translesion synthesis (TLS) polymerase POLH, we identified a HORMAD1-driven dependency upon additional TLS polymerases, namely POLK, REV1, REV3L and REV7. Our data confirms that out-of-context somatic expression of HORMAD1 can lead to genomic instability and reveals that HORMAD1 expression induces dependencies upon replication stress tolerance pathways, such as translesion synthesis. Our data also suggest that HORMAD1 expression could be a patient selection biomarker for agents targeting replication stress.


Subject(s)
Triple Negative Breast Neoplasms , Cell Cycle Proteins/genetics , DNA Damage/genetics , DNA Repair , DNA Replication/genetics , DNA-Binding Proteins/genetics , DNA-Directed DNA Polymerase/genetics , Genomic Instability/genetics , Humans , Nucleotidyltransferases/genetics , Phosphoric Diester Hydrolases/genetics , Phosphoric Diester Hydrolases/metabolism , X-ray Repair Cross Complementing Protein 1/genetics
7.
Front Psychol ; 12: 596434, 2021.
Article in English | MEDLINE | ID: mdl-33868076

ABSTRACT

Esports, including virtual football, are a worldwide phenomenon. Yet, little is known about the physical activity levels of individuals engaged in virtual football game play. Therefore, we aimed to perform a preliminary evaluation of the levels of physical activity, sedentarism, and habits of physical training of adults engaged with virtual football in Portugal. This was a cross-sectional investigation based on a structured online survey using the International Physical Activity Questionnaire (IPAQ) and a set of questions regarding habits of physical training. The participants (n = 433) reported spending a median of 5,625 MET-min⋅week-1 being physically active. Still, the participants spent 320 min/day sitting, and 150 min/day practicing virtual football. According to the IPAQ scores, high physical activity levels were reported by 84.5% of the participants, and 87.1% were considered physically active considering the WHO guidelines on physical activity and sedentary behavior. Overall, 60.0% of the participants reported planning their own physical training. Maintaining or improving overall physical health was one of the main reasons for doing physical training (66.7%), with only 6.1% responding being active to improve virtual football performance. Overall, the results showed that virtual football players accomplished the standard recommendations for physical activity, with high levels of physical activity, and encompassing regular physical training focused mostly on health promotion, rather than improved virtual football performance.

8.
Allergy ; 76(10): 3041-3052, 2021 10.
Article in English | MEDLINE | ID: mdl-33492738

ABSTRACT

BACKGROUND: Pollen food allergy syndrome (PFAS) is a frequently underdiagnosed disease due to diverse triggers, clinical presentations, and test results. This is especially relevant in geographic areas with a broad spectrum of pollen sensitization, such as Southern Europe. OBJECTIVES: To elucidate similarities and differences of PFAS in nine Southern European centers and identify associated characteristics and unique markers of PFAS. METHODS: As part of the @IT.2020 Multicenter Study, 815 patients with seasonal allergic rhinitis (SAR), aged 10-60 years, were recruited in seven countries. They completed questionnaires regarding SAR, comorbidities, family history, and PFAS, and underwent skin prick testing (SPT) and serum IgE testing. RESULTS: Of the 815 patients, 167 (20.5%) reported PFAS reactions. Most commonly, eliciting foods were kiwi (58, 34.7%), peach (43, 25.7%), and melon (26, 15.6%). Reported reactions were mostly local (216/319, 67.7%), occurring within 5 min of contact with elicitors (209/319, 65.5%). Associated characteristics included positive IgE to at least one panallergen (profilin, PR-10, or nsLTP) (p = 0.007), maternal PFAS (OR: 3.716, p = 0.026), and asthma (OR: 1.752, p = 0.073). Between centers, heterogeneity in prevalence (Marseille: 7.5% vs. Rome: 41.4%, p < 0.001) and of clinical characteristics was apparent. Cypress played a limited role, with only 1/22 SPT mono-sensitized patients reporting a food reaction (p < 0.073). CONCLUSIONS: PFAS is a frequent comorbidity in Southern European SAR patients. Significant heterogeneity of clinical characteristics in PFAS patients among the centers was observed and may be related to the different pollen sensitization patterns in each geographic area. IgE to panallergen(s), maternal PFAS, and asthma could be PFAS-associated characteristics.


Subject(s)
Food Hypersensitivity , Rhinitis, Allergic, Seasonal , Allergens , Cross Reactions , Food Hypersensitivity/diagnosis , Food Hypersensitivity/epidemiology , Humans , Pollen , Rhinitis, Allergic, Seasonal/diagnosis , Rhinitis, Allergic, Seasonal/epidemiology , Skin Tests
9.
ACS Biomater Sci Eng ; 7(2): 451-461, 2021 02 08.
Article in English | MEDLINE | ID: mdl-33492122

ABSTRACT

The increasing bacterial resistance to antibiotics is driving strong demand for new antimicrobial biomaterials. This work describes the fabrication of free-standing films exhibiting antimicrobial properties by combining, in the same polypeptide chain, an elastin-like recombinamer comprising 200 repetitions of the pentamer VPAVG (A200) and an 18-amino-acid truncated variant of the antimicrobial peptide BMAP-28, termed BMAP-18. The fusion protein BMAP-18A200 was overexpressed and conveniently purified by a simplified and scalable nonchromatographic process. Free-standing films of BMAP-18A200 demonstrated to be stable without requiring cross-linking agents and displayed high antimicrobial activity against skin pathogens including Gram-negative and Gram-positive bacteria as well as unicellular and filamentous fungi. The antimicrobial activity of the films was mediated by direct contact of cells with the film surface, resulting in compromised structural integrity of microbial cells. Furthermore, the BMAP-18A200 films showed no cytotoxicity on normal human cell lines (skin fibroblasts and keratinocytes). All of these results highlight the potential of these biotechnological multifunctional polymers as new drug-free materials to prevent and treat microbial infections.


Subject(s)
Anti-Infective Agents , Amino Acid Sequence , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Gram-Positive Bacteria , Humans , Pore Forming Cytotoxic Proteins
10.
J Anal Methods Chem ; 2020: 8821809, 2020.
Article in English | MEDLINE | ID: mdl-32953194

ABSTRACT

Zinc is an essential trace element for animals in several biological processes, particularly in energy production, and it is acquired from food ingestion. In this context, a microplate-based fluorimetric assay was developed for simple, fast, and low-cost determination of zinc in pet food using 2,2'-((4-(2,7-difluoro-3,6-dihydroxy-4aH-xanthen-9-yl)-3-methoxyphenyl)azanediyl)diacetic acid (FluoZin-1) as fluorescent probe. Several aspects were studied, namely, the stability of the fluorescent product over time, the FluoZin-1 concentration, and the pH of reaction media. The developed methodology provided a limit of detection of 1 µg L-1 in sample acid digests, with a working range of 10 to 200 µg L-1, corresponding to 100-2000 mg of Zn per kg of dry dog food samples. Intraday repeatability and interday repeatability were assessed, with relative standard deviation values < 3.4% (100 µg L-1) and <11.7% (10 µg L-1). Sample analysis indicated that the proposed fluorimetric assay provided results consistent with ICP-MS analysis. These results demonstrated that the developed assay can be used for rapid determination of zinc in dry dog food.

11.
Eur J Pharmacol ; 885: 173390, 2020 Oct 15.
Article in English | MEDLINE | ID: mdl-32735983

ABSTRACT

Erythrinian alkaloids ((+)-erythravine and (+)-11-α-hydroxy-erythravine) have been pointed as the main responsible agents for the anticonvulsant and anxiolytic properties of Erythrina mulungu Mart ex Benth. The present work provides a new set of information about the mode of action of these alkaloids by the use of a complementary approach of neurochemical and electrophysiological assays. We propose here that the antiepileptic and anxiolytic properties exhibited by both alkaloids appear not to be related to the inhibition of glutamate binding or GABA uptake, or even to the increase of glutamate uptake or GABA binding, as investigated here by the use of rat cortical synaptosomes. Similarly, and even in a high concentration, (+)-erythravine and (+)-11-α-hydroxy-erythravine did not modulate the main sodium and potassium channel isoforms checked by the use of voltage-clamp studies on Xenopus laevis oocytes. However, unlike (+)-11-α-hydroxy-erythravine, which presented a little effect, it was possible to observe that the (+)-erythravine alkaloid produced a significant inhibitory modulation on α4ß2, α4ß4 and α7 isoforms of nicotinic acetylcholine receptors also checked by the use of voltage-clamp studies, which could explain at least partially its anxiolytic and anticonvulsant properties. Since (+)-11-α-hydroxy-erythravine and (+)-erythravine modulated nicotinic acetylcholine receptors to different extents, it is possible to reinforce that small differences between the chemical structure of these alkaloids can affect the selectivity and affinity of target-ligand interactions, conferring distinct potency and/or pharmacological properties to them, as previously suggested by differential experimental comparison between different erythrinian alkaloids.


Subject(s)
Anti-Anxiety Agents/pharmacology , Anticonvulsants/pharmacology , Heterocyclic Compounds, 4 or More Rings/pharmacology , Animals , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Erythrina/chemistry , Glutamic Acid/metabolism , Nicotinic Antagonists/pharmacology , Oocytes , Patch-Clamp Techniques , Potassium/metabolism , Receptors, Nicotinic/drug effects , Sodium Channels/metabolism , Synaptosomes/drug effects , Synaptosomes/metabolism , Xenopus laevis , gamma-Aminobutyric Acid/metabolism
12.
Obes Surg ; 30(10): 4019-4028, 2020 10.
Article in English | MEDLINE | ID: mdl-32564307

ABSTRACT

PURPOSE: Biliopancreatic diversion with duodenal switch (BPD-DS) is an effective weight loss surgical procedure. Yet, BPD-DS is technically difficult to perform and carries a higher risk of nutrient deficiencies as compared with other surgical interventions. Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a modified BPD-DS procedure conceived with the aim of decreasing the technical complexity, while retaining the weight loss efficiency. Whether the two surgical procedures diverge in nutrient absorption rates and malnutrition risk is still matter of debate. Our aim was to determine if postprandial nutrient absorption rates are different in patients subjected to BPD-DS or SADI-S for weight loss. MATERIALS AND METHODS: Plasma amino acid metabolomic profiling during mixed-meal tolerance test (MMTT) was performed in subjects (N = 18) submitted to BPD-DS (n = 9) or SADI-S (n = 9) 1.6 ± 0.1 years earlier. RESULTS: Patients submitted to SADI-S or BPD-DS presented distinct postprandial metabolomic profiles. Postprandial excursions of total and essential amino acids-leucine, isoleucine, and valine-were higher after SADI-S as compared with BPD-DS. CONCLUSION: Our study demonstrates that a simplified malabsorptive bariatric surgery procedure SADI-S results in greater essential branched-chain amino acid absorption when compared with the classical BPD-DS intervention. These findings suggest that SADI-S can potentially lower lifetime risk of postoperative protein malnutrition, as well as have a positive impact on systemic metabolism and glucose homeostasis.


Subject(s)
Bariatric Surgery , Biliopancreatic Diversion , Obesity, Morbid , Amino Acids , Duodenum , Gastrectomy , Humans , Obesity, Morbid/surgery
13.
J Nat Prod ; 83(5): 1409-1415, 2020 05 22.
Article in English | MEDLINE | ID: mdl-32372647

ABSTRACT

Citrus sinensis and Citrus limonia were obtained by germination from seeds, and isotopic-labeling experiments using d-[1-13C]glucose were performed with the seedlings. After 60 days, the seedlings were analyzed by high-performance liquid chromatography-ultraviolet-solid-phase extraction-nuclear magnetic resonance, data and the 13C enrichment patterns of xanthyletin and seselin indicated that the pyran ring was formed by the methylerythritol phosphate pathway and that the coumarin moiety was derived from the shikimate pathway in both compounds. This information regarding the biosynthetic pathway can be used to increase resistance against phytopathogens, because xanthyletin and seselin are reported to have antimicrobial activity on the growth of Xylella fastidiosa, which causes citrus variegated chlorosis in orange.


Subject(s)
Isotope Labeling/methods , Pyranocoumarins/metabolism , Carbon Isotopes , Chromatography, High Pressure Liquid , Citrus/metabolism , Citrus sinensis/metabolism , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Diseases/microbiology , Pyranocoumarins/chemistry , Pyranocoumarins/isolation & purification , Shikimic Acid/metabolism , Solid Phase Extraction , Spectrophotometry, Ultraviolet , Xylella/drug effects
14.
Rev. psicol. clín. niños adolesc ; 7(2): 22-31, mayo 2020. tab, graf
Article in English | IBECS | ID: ibc-193690

ABSTRACT

Children and adolescents living in residential childcare have a higher prevalence of mental health problems as a result of a history of adverse childhood experiences. Therefore, this population should be a priority target for mental health preventive interventions. The current study analyses the effectiveness of the Wave by Wavesurf therapy program, that combines surfing with a psychological group intervention, through a randomized controlled trial. Seventy-three youth (7-17 years) living in residential care participated in the study. Main mental health outcomes (adjustment problems, depression, anxiety, and wellbeing) and secondary outcomes (self-efficacy, self-regulation, sleep quality, physical activity, pro-social behavior, and social connectivity) were assessed at pre- and post-intervention. The results indicated a significant impact of the intervention on mental health outcomes reported by the key residential worker, with medium to large effect sizes. Specifically, after the intervention, there was a significant reduction in the total emotional and behavioural problems, and a significant increase of youth pro-social behaviour and quality of life that was not observed for the waiting list group. There were no significant effects on other measures reported by the children (e.g., depression and anxiety, self-esteem, emotion regulation, social connectedness, sleep quality, physical activity) and on executive functions measures. The Wave by Wave program seems to be an effective intervention to reduce behavior problems and to promote pro-social behavior in a high-risk sample. The absence of significant effects on other dimensions may indicate the need of some complementary support to address specific difficulties of this population


Los niños y adolescentes que viven en acogimiento residencial tienen una mayor prevalencia de problemas de salud mental. Por lo tanto, esta población debe ser un objetivo prioritario para las intervenciones preventivas de salud mental. El estudio actual analiza la efectividad del programa Wave by Wave, que combina el surf con una intervención psicológica grupal, a través de un ensayo controlado aleatorio. Setenta y tres jóvenes (7-17 años) que viven en acogimiento residencial participaron en el estudio. Los principales resultados de salud mental (problemas de ajuste, depresión, ansiedad y bienestar) y los resultados secundarios (autoeficacia, autorregulación, calidad del sueño, actividad física, comportamiento prosocial y conectividad social) se evaluaron antes y después de intervención. Los resultados indicaron un impacto significativo de la intervención sobre los resultados de salud mental reportados por el cuidador en la residencia. Específicamente, después de la intervención, hubo una reducción significativa en los problemas emocionales y conductuales totales, y un aumento significativo del comportamiento prosocial de los jóvenes y de la calidad de vida que no se observó en el grupo control. No hubo efectos significativos en otras medidas reportadas por los niños (ex., depresión y ansiedad, autoestima) y en las medidas de las funciones ejecutivas. El programa Wave by Wave parece ser una intervención efectiva para reducir los problemas de comportamiento y promover el comportamiento prosocial en una muestra de alto riesgo. La ausencia de efectos significativos en otras dimensiones puede indicar la necesidad de algún apoyo complementario para abordar las dificultades específicas de esta población


Subject(s)
Humans , Male , Female , Child , Adolescent , Child Behavior Disorders/therapy , Residential Facilities , Child, Abandoned/psychology , User Embracement , Adolescent Behavior/psychology , Primary Prevention/methods , Treatment Outcome
15.
J Appl Biomater Funct Mater ; 17(4): 2280800019848923, 2019.
Article in English | MEDLINE | ID: mdl-31623515

ABSTRACT

INTRODUCTION: The success of a bioartificial pancreas crucially depends on ameliorating encapsulated beta cells survival and function. By mimicking the cellular in vivo niche, the aim of this study was to develop a novel model for beta cells encapsulation capable of establishing an appropriate microenvironment that supports interactions between cells and extracellular matrix (ECM) components. METHODS: ECM components (Arg-Gly-Asp, abbreviated as RGD) were chemically incorporated in alginate hydrogels (alginate-RGD). After encapsulation, INS-1E beta cells outcome was analyzed in vitro and after their implantation in an animal model of diabetes. RESULTS: Our alginate-RGD model demonstrated to be a good in vitro niche for supporting beta cells viability, proliferation, and activity, namely by improving the key feature of insulin secretion. RGD peptides promoted cell-matrix interactions, enhanced endogenous ECM components expression, and favored the assembly of individual cells into multicellular spheroids, an essential configuration for proper beta cell functioning. In vivo, our pivotal model for diabetes treatment exhibited an improved glycemic profile of type 2 diabetic rats, where insulin secreted from encapsulated cells was more efficiently used. CONCLUSIONS: We were able to successfully introduce a novel valuable function in an old ally in biomedical applications, the alginate. The proposed alginate-RGD model stands out as a promising approach to improve beta cells survival and function, increasing the success of this therapeutic strategy, which might greatly improve the quality of life of an increasing number of diabetic patients worldwide.


Subject(s)
Diabetes Mellitus, Experimental/metabolism , Extracellular Matrix/chemistry , Hydrogels/chemistry , Insulin Secretion , Oligopeptides/chemistry , Pancreas, Artificial , Animals , Cell Line, Tumor , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Experimental/therapy , Rats
16.
Molecules ; 24(18)2019 Sep 10.
Article in English | MEDLINE | ID: mdl-31510078

ABSTRACT

Uncaria tomentosa (Rubiaceae) has a recognized therapeutic potential against various diseases associated with oxidative stress. The aim of this research was to evaluate the antioxidant potential of an aqueous leaf extract (ALE) from U. tomentosa, and its major alkaloids mitraphylline and isomitraphylline. The antioxidant activity of ALE was investigated in vitro using standard assays (DPPH, ABTS and FRAP), while the in vivo activity and mode of action were studied using Caenorhabditis elegans as a model organism. The purified alkaloids did not exhibit antioxidant effects in vivo. ALE reduced the accumulation of reactive oxygen species (ROS) in wild-type worms, and was able to rescue the worms from a lethal dose of the pro-oxidant juglone. The ALE treatment led to a decreased expression of the oxidative stress response related genes sod-3, gst-4, and hsp-16.2. The treatment of mutant worms lacking the DAF-16 transcription factor with ALE resulted in a significant reduction of ROS levels. Contrarily, the extract had a pro-oxidant effect in the worms lacking the SKN-1 transcription factor. Our results suggest that the antioxidant activity of ALE in C. elegans is independent of its alkaloid content, and that SKN-1 is required for ALE-mediated stress resistance.


Subject(s)
Antioxidants/chemistry , Cat's Claw/chemistry , Indole Alkaloids/pharmacology , Oxindoles/pharmacology , Alkaloids/chemistry , Animals , Antioxidants/isolation & purification , Antioxidants/pharmacology , Caenorhabditis elegans/drug effects , Longevity/drug effects , Oxidative Stress/drug effects , Oxindoles/chemistry , Plant Extracts/chemistry , Plant Leaves/chemistry , Reactive Oxygen Species/metabolism
17.
Sci Rep ; 9(1): 12911, 2019 09 09.
Article in English | MEDLINE | ID: mdl-31501484

ABSTRACT

Induced morphology changes of cells and organelles are by far the easiest way to determine precise protein sub-locations and organelle quantities in light microscopy. By using hypotonic solutions to swell mammalian cell organelles we demonstrate that precise membrane, lumen or matrix protein locations within the endoplasmic reticulum, Golgi and mitochondria can reliably be established. We also show the benefit of this approach for organelle quantifications, especially for clumped or intertwined organelles like peroxisomes and mitochondria. Since cell and organelle swelling is reversible, it can be applied to live cells for successive high-resolution analyses. Our approach outperforms many existing imaging modalities with respect to resolution, ease-of-use and cost-effectiveness without excluding any co-utilization with existing optical (super)resolution techniques.


Subject(s)
Cell Shape , Hypotonic Solutions , Organelles , Animals , Cell Line , Humans , Microscopy, Fluorescence , Optical Imaging , Organelles/metabolism , Protein Transport
18.
Clin Transl Allergy ; 9: 17, 2019.
Article in English | MEDLINE | ID: mdl-30918624

ABSTRACT

BACKGROUND: Half of the adults with current asthma among the US National Health and Nutrition Examination Survey (NHANES) participants could be classified in more than one hypothesis-driven phenotype. A data-driven approach applied to the same subjects may allow a more useful classification compared to the hypothesis-driven one. AIM: To compare previously defined hypothesis-driven with newly derived data-driven asthma phenotypes, identified by latent class analysis (LCA), in adults with current asthma from NHANES 2007-2012. METHODS: Adults (≥ 18 years) with current asthma from the NHANES were included (n = 1059). LCA included variables commonly used to subdivide asthma. LCA models were derived independently according to age groups: < 40 and ≥ 40 years old. RESULTS: Two data-driven phenotypes were identified among adults with current asthma, for both age groups. The proportions of the hypothesis-driven phenotypes were similar among the two data-driven phenotypes (p > 0.05). Class A < 40 years (n = 285; 75%) and Class A ≥ 40 years (n = 462; 73%), respectively, were characterized by a predominance of highly symptomatic asthma subjects with poor lung function, compared to Class B < 40 years (n = 94; 25%) and Class B ≥ 40 years (n = 170; 27%). Inflammatory biomarkers, smoking status, presence of obesity and hay fever did not markedly differ between the phenotypes. CONCLUSION: Both data- and hypothesis-driven approaches using clinical and physiological variables commonly used to characterize asthma are suboptimal to identify asthma phenotypes among adults from the general population. Further studies based on more comprehensive disease features are required to identify asthma phenotypes in population-based studies.

19.
Allergy ; 74(4): 698-708, 2019 04.
Article in English | MEDLINE | ID: mdl-30447164

ABSTRACT

BACKGROUND: Refined phenotyping of allergic diseases may unravel novel phenotypes. Conjunctivitis as an independent disorder has never been approached. AIM: To identify distinct classes of allergic respiratory diseases using latent class analysis (LCA) and distinguish each class using classification and regression tree (CART) analysis. METHODS: Seven hundred and twenty-eight adults from the Portuguese general population study ICAR had a structured medical interview combined with blood collection, skin prick tests, spirometry with bronchodilation, and exhaled nitric oxide. LCA was applied to 19 variables. The CART algorithm selected the most likely variables distinguishing LCA-classes. RESULTS: A six-class model was obtained. Class 1 (25%): nonallergic participants without bronchial or ocular symptoms. Classes 2 (22%) and 3 (11%): nasal and ocular (low levels) symptoms without nasal impairment, monosensitized (Class 2) or polysensitized (Class 3). Class 4 (13%): polysensitized participants with high levels of nasal and ocular symptoms, and nasal impairment. Classes 5 (16%) and 6 (14%): high level of nasal, bronchial and ocular symptoms with nasal impairment (non-allergic or polysensitized, respectively). Participants in classes 5 and 6 had more bronchial exacerbations and unscheduled medical visits (P < 0.001). Ocular symptoms were significantly higher in classes with nasal impairment, compared to those without impairment (P < 0.001) or no nasal symptom (P < 0.001). CART highlighted ocular symptoms as the most relevant variable in distinguishing LCA-classes. CONCLUSION: Novel severe phenotypes of participants with co-occurrence of ocular, nasal and bronchial symptoms, and exacerbation-prone were identified. The tree algorithm showed the importance of the ocular symptoms in the expression of allergic diseases phenotypes.


Subject(s)
Asthma/diagnosis , Eye Diseases/immunology , Latent Class Analysis , Adult , Algorithms , Asthma/classification , Conjunctivitis , Eye Diseases/pathology , Female , Humans , Male , Middle Aged , Phenotype , Portugal
20.
Int J Obes (Lond) ; 43(12): 2518-2527, 2019 12.
Article in English | MEDLINE | ID: mdl-30538284

ABSTRACT

BACKGROUND/OBJECTIVE: Biliopancreatic diversion with duodenal switch (BPD-DS) is the most effective bariatric intervention to treat morbid obesity and related disorders. Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a new bariatric procedure devised with the purpose of simplifying the complexity of the BPD-DS technique while maintaining its efficacy. However, whether BPD-DS and SADI-S result in similar fasting and post-prandial hormone profiles has not yet been studied. Therefore, the purpose of this study was to assess and compare the hormone response to a standardized mixed meal in subjects operated with BPD-DS or SADI-S. SUBJECTS/METHODS: Subjects submitted to BPD-DS (n = 9) or SADI-S (n = 9) 1.5 years earlier on average, with no past nor current diabetes diagnosis underwent a liquid mixed-meal tolerance test (MMTT) to assess the baseline and post-prandial profile of glucose, enteropancreatic hormones and total bile acids. RESULTS: Fasting glucose, enteropancreatic hormones and total bile acids levels after BPD-DS and SADI-S were similar. After the MMTT, the response of subjects who underwent SADI-S was characterized by higher glucose (t = 30 min: p < 0.05; iAUC: 156.1 ± 46.2 vs. 103.4 ± 35.8 mmol/L × min, p = 0.02), GLP-1 (t = 30 min: p < 0.05; iAUC: 5388 ± 3010 vs. 2959.0 ± 2146 pmol/L × min, p = 0.02), glucagon (t = 30 min: p < 0.05; iAUC: 678.7 ± 295.2 vs. 376.9 ± 215.7 pmol/L × min, p = 0.02), insulin (t = 30 and 45 min: p < 0.05); and C-peptide levels (t = 30 and 45 min: p < 0.05), when compared to BPD-DS. CONCLUSIONS: The post-prandial hormone secretion profile after SADI-S is characterized by increased GLP-1, glucagon and insulin secretion, when compared to BPD-DS, which suggests the existence of different endocrine driven mechanisms leading to weight loss and metabolic improvement after the two procedures.


Subject(s)
Bariatric Surgery/methods , Biliopancreatic Diversion/methods , Gastrointestinal Hormones/blood , Postprandial Period/physiology , Adult , Anastomosis, Surgical , Cohort Studies , Duodenum/surgery , Female , Gastrectomy , Humans , Ileum/surgery , Male , Middle Aged , Obesity, Morbid/surgery , Treatment Outcome , Young Adult
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