This work reports the synthesis of kappa-carrageenan aerogels using different dissolution and crosslinking media in order to evaluate its effects on the textural properties of the matrixes and ...further on the drug loading and release performance. The different aerogel samples were produced through the dissolution of the biopolymer in water with addition of potassium salts as crosslinking agents and, in two different ionic liquids (ILs) derived from imidazolium ion, being further dried with supercritical CO2. The samples were characterized by Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), Scanning Electron Microscopy (SEM), Nitrogen Adsorption-Desorption Analysis, Thermogravimetry (TGA) and Differential Scanning Calorimetry (DSC). The synthesized samples presented surface areas similar to the carrageenan aerogels being their structure constituted mainly by meso and macropores. The absence of ionic liquid in samples was demonstrated by DSC analysis and was corroborated by the cytotoxicity assays which revealed that cellular viability in Caco-2 cells was preserved. Tetracycline was used as a model drug and loaded in two of the prepared aerogels samples. The release experiments were performed with the composites to test in vitro drug release at physiologic pH. With a higher macroporosity, the kappa-carrageenan aerogel prepared by dissolution into ionic liquid showed a higher loading capacity than the one prepared by dissolution into water and a slightly higher release rate. The matrixes were considered to present a good potential to be used as biocompatible carriers on drug controlled delivery.
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•Kappa-carrageenan aerogel materials were successfully prepared by dissolution into ionic liquids.•Dissolution into ionic liquids allows for a lower volume shrinkage with repercussions on the porosity of the aerogels.•Aerogel matrixes prepared by dissolution into ionic liquids showed to not reduce Caco-2 cell viability.•Controlled release of tetracycline from kappa-carrageenan matrixes was achieved at pH 7.4.•The synthesized matrixes are promissory to be used on biocompatible controlled delivery formulations.
Past climate changes provide important clues for advancement of studies on current global change biology. We have tested large-scale biogeographic patterns through four marine groups from twelve ...Atlantic Ocean archipelagos and searched for patterns between species richness/endemism and littoral area, age, isolation, latitude and mean annual sea-surface temperatures. Species richness is strongly correlated with littoral area. Two reinforcing effects take place during glacial episodes: i) species richness is expected to decrease (in comparison with interglacial periods) due to the local disappearance of sandy/muddy-associated species; ii) because littoral area is minimal during glacial episodes, area per se induces a decrease on species richness (by extirpation/extinction of marine species) as well as affecting speciation rates. Maximum speciation rates are expected to occur during the interglacial periods, whereas immigration rates are expected to be higher at the LGM. Finally, sea-level changes are a paramount factor influencing marine biodiversity of animals and plants living on oceanic islands.
•We tested large-scale biogeographic patterns on 4 marine groups in 12 Atlantic Ocean archipelagos.•Species richness is strongly correlated with littoral area.•Species richness decreases during glacial episodes, in comparison with interglacial periods.•Maximum speciation rates are expected to occur during interglacial periods.•Sea-level changes are a paramount factor influencing marine biodiversity around oceanic islands.
Opsoclonus-myoclonus syndrome (OMS) is a very rare neurological disorder thought to be the result of autoimmune responses in the nervous system. The relationship between this disorder and anesthesia ...procedures has not been studied in detail. To our knowledge, there are only 4 case reports, none of them with epidural-general combined anesthesia.
We present a 9-year-old female with OMS due to low-grade neuroblastoma, for 7 years, who underwent tumor remotion due to the large size. Intravenous induction was done with alfentanil, lidocaine, propofol and rocuronium and ropivacaine was administered via lumbar epidural catheter. Adding to the sparse anesthetic management information in OMS, we now show one more possible approach, that can be valuable in high-risk cases, where general anesthesia can be involved with higher risk for the patient.
Anti-obesity drugs in the amphetamine (AMPH) class act in the brain to reduce appetite and increase locomotion. They are also characterized by adverse cardiovascular effects with origin that, despite ...absence of any in vivo evidence, is attributed to a direct sympathomimetic action in the heart. Here, we show that the cardiac side effects of AMPH originate from the brain and can be circumvented by PEGylation (PEGyAMPH) to exclude its central action. PEGyAMPH does not enter the brain and facilitates SNS activity via theβ2-adrenoceptor, protecting mice against obesity by increasing lipolysis and thermogenesis, coupled to higher heat dissipation, which acts as an energy sink to increase energy expenditure without altering food intake or locomotor activity. Thus, we provide proof-of-principle for a novel class of exclusively peripheral anti-obesity sympathofacilitators that are devoid of any cardiovascular and brain-related side effects.
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•PEGylated amphetamine (PEGyAMPH) does not enter the brain, nor has behavioral effects•PEGyAMPH promotes weight loss, by coupling thermogenesis to heat dissipation•PEGyAMPH is a sympathofacilitator, requiring β2-adrenoceptor function•PEGyAMPH is cardioprotective, unless directly delivered into the brain
PEGyAMPH is a brain-sparing modified amphetamine that is a cardioneutral anti-obesity drug. Unlike amphetamines, which act in the brain to increase satiety and locomotion, PEGyAMPH couples thermogenesis to heat dissipation, activating a whole-body energy sink by simultaneously promoting vasodilation and facilitating the activity of sympathetic neurons.
Objectives
There is a growing interest in mindfulness-based programs. Yet, research in the area is limited, and little is known about the factors that moderate the effects of these programs. The ...two-fold aim of this study was (1) to examine the effects of a mindfulness-based program on dispositional mindfulness, inattention and emotional lability, handwriting fluency, spelling accuracy, and composing quality, as well as school achievement; and (2) to evaluate the moderating role of lesson absences, intervention-related knowledge, and social validity.
Method
Using a quasi-experimental design, 257 fourth graders were assigned to an experimental group receiving a mindfulness-based program (
n
= 130) or an active control group receiving a health-based program (
n
= 127). Both programs were implemented in the classroom for 8 weekly units, which included two 30-min sessions delivered by psychologists, followed by three 5-min sessions delivered by teachers. All children were evaluated before and after the programs.
Results
Compared to the control condition, the mindfulness-based program resulted in higher levels of internal and external awareness, and decentering and nonreactivity, as well as better composing quality and mathematics grades. Lesson absences, intervention-related knowledge, and social validity did not moderate the effects of the mindfulness-based program.
Conclusions
These findings support the integration of mindfulness practices in primary school as a means to improve children’s academic-related skills and ability to be mindful.
In contrast to adult-onset inflammatory bowel disease (IBD), where many genetic loci have been shown to be involved in complex disease etiology, early-onset IBD (eoIBD) and associated syndromes can ...sometimes present as monogenic conditions. As a result, the clinical phenotype and ideal disease management in these patients often differ from those in adult-onset IBD. However, due to high costs and the complexity of data analysis, high-throughput screening for genetic causes has not yet become a standard part of the diagnostic work-up of eoIBD patients.
We selected 28 genes of interest associated with monogenic IBD and performed targeted panel sequencing in 71 patients diagnosed with eoIBD or early-onset chronic diarrhea to detect causative variants. We compared these results to whole-exome sequencing (WES) data available for 25 of these patients.
Target coverage was significantly higher in the targeted gene panel approach compared with WES, whereas the cost of the panel was considerably lower (approximately 25% of WES). Disease-causing variants affecting protein function were identified in 5 patients (7%), located in genes of the IL10 signaling pathway (3), WAS (1), and DKC1 (1). The functional effects of 8 candidate variants in 5 additional patients (7%) are under further investigation. WES did not identify additional causative mutations in 25 patients.
Targeted gene panel sequencing is a fast and effective screening method for monogenic causes of eoIBD that should be routinely established in national referral centers.
X-linked severe combined immunodeficiency disease (SCID) is caused by mutations in the interleukin (IL)-2 receptor γ (IL2RG) gene and patients usually present with a TBNK SCID phenotype. ...Nevertheless, a minority of these patients present with a TBNK phenotype, similar to the IL-7R-deficient patients. We report a patient with a novel missense p.Glu297Gly mutation in the IL2RG gene presenting with a leaky TBNK SCID with delayed onset, moderate susceptibility to infections, and nodular regenerative hyperplasia. He presents with preserved STAT5 tyrosine phosphorylation in response to IL-15 stimulation but not in response to IL-2 and IL-7, resulting in the NK phenotype.
Background. homB codes for a putative Helicobacter pylori outer membrane protein and has previously been associated with peptic ulcer disease (PUD) in children. Methods. A total of 190 H. pylori ...strains isolated from children and adults were studied to evaluate the clinical importance of the homB gene. In vitro experiments were performed to identify HomB mechanisms of bacterial pathogenicity. Results. Characterization of the isolates demonstrated that homB was significantly associated with PUD in 86 children (odds ratio OR, 7.64 95% confidence interval {CI{, 2.65–22.05) and in 32 adults ⩽40 years of age (OR, 11.25 95% CI, 1.86–68.13). homB was correlated with the presence of cagA, babA2, vacAs1, hopQI, and oipA “on” genotype (P < .001). The HomB protein was found to be expressed in the H. pylori outer membrane and was noted to be antigenic in humans. H. pylori homB knockout mutant strains presented reduced ability to induce interleukin-8 secretion from human gastric epithelial cells, as well as reduced capacity to bind to these cells. Both of these functions correlated with the number of homB copies present in a strain. Conclusion. homB can be considered a comarker of H. pylori strains associated with PUD. Moreover, results strongly suggest that HomB is involved in the inflammatory response and in H. pylori adherence, constituting a novel putative virulence factor.
Abstract Closing the gap between adverse health effects of aluminum and its mechanisms of action still represents a huge challenge. Cholinergic dysfunction has been implicated in neuronal injury ...induced by aluminum. Previously reported data also indicate that in vivo and in vitro exposure to aluminum inhibits the mammalian (Na+ /K+ )ATPase, an ubiquitous plasma membrane pump. This study was undertaken with the specific aim of determining whether in vitro exposure to AlCl3 and ouabain, the foremost utilized selective inhibitor of (Na+ /K+ )ATPase, induce similar functional modifications of cholinergic presynaptic nerve terminals, by comparing their effects on choline uptake, acetylcholine release and (Na+ /K+ )ATPase activity, on subcellular fractions enriched in synaptic nerve endings isolated from rat brain, cuttlefish optic lobe and torpedo electric organ. Results obtained show that choline uptake by rat synaptosomes was inhibited by submillimolar AlCl3 , whereas the amount of choline taken up by synaptosomes isolated from cuttlefish and torpedo remained unchanged. Conversely, choline uptake was reduced by ouabain to a large extent in all synaptosomal preparations analyzed. In contrast to ouabain, which modified the K+ depolarization evoked release of acetylcholine by rat, cuttlefish and torpedo synaptosomal fractions, AlCl3 induced reduction of stimulated acetylcholine release was only observed when rat synaptosomes were challenged. Finally, it was observed that the aluminum effect on cuttlefish and torpedo synaptosomal (Na+ /K+ )ATPase activity was slight when compared to its inhibitory action on mammalian (Na+ /K+ )ATPase. In conclusion, inhibition of (Na+ /K+ )ATPase by AlCl3 and ouabain jeopardized the high-affinity (Na+ -dependent, hemicholinium-3 sensitive) uptake of choline and the Ca2+ -dependent, K+ depolarization evoked release of acetylcholine by rat, cuttlefish and torpedo synaptosomal fractions. The effects of submillimolar AlCl3 on choline uptake and acetylcholine release only resembled those of ouabain when rat synaptosomes were assayed. Therefore, important differences were found between the species regarding the cholinotoxic action of aluminum. The variability of (Na+ /K+ )ATPase sensitivity to aluminum of cholinergic neurons might contribute to their differential susceptibility to this neurotoxic agent.
Ectodermal dysplasias Ana L. João; Sofia Antunes-Duarte; Ana I. Cordeiro ...
Revista da Sociedade Portuguesa de Dermatologia e Venereologia,
11/2022, Letnik:
80, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Ectodermal dysplasias are a heterogeneous group of rare inherited disorders. Molecular findings and clarification of cell signaling processes and ectodermal-mesenchyme interaction enabled the ...development of a clinical-functional model, which in turn helps to explain clinical signs, with variability in severity, associated non-ectodermal abnormalities and overlap seen in many patients. We herein review the current state of knowledge regarding this distinct entity and illustrate with an elucidative case report. The need for early multidisciplinary intervention is highlighted, and further studies will focus on genetically-target therapeutic approaches.
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