Purpose
Familial papillary thyroid microcarcinoma (FPTMC) can present a more aggressive behavior than the sporadic microcarcinoma. However, few studies have analyzed this situation. The objective is ...to analyze the recurrence rate of FPTMC and the prognostic factors which determine that recurrence in Spain.
Methods
Spanish multicenter longitudinal analytical observational study was conducted. Patients with FPTMC received treatment with curative intent and presented cure criteria 6 months after treatment. Recurrence rate and disease-free survival (DFS) were analyzed. Two groups were analyzed: group A (no tumor recurrence) vs. group B (tumor recurrence).
Results
Ninety-four patients were analyzed. During a mean follow-up of 73.3 ± 59.3 months, 13 recurrences of FPTMC (13.83%) were detected and mean DFS was 207.9 ± 11.5 months. There were multifocality in 56%, bilateral thyroid involvement in 30%, and vascular invasion in 7.5%; that is to say, they are tumors with histological factors of poor prognosis in a high percentage of cases. The main risk factors for recurrence obtained in the multivariate analysis were the tumor size (OR: 2.574, 95% CI 1.210–5.473;
p
= 0.014) and the assessment of the risk of recurrence of the American Thyroid Association (ATA), both intermediate risk versus low risk (OR: 125, 95% CI 10.638–1000;
p
< 0.001) and high risk versus low risk (OR: 45.454, 95% CI 5.405–333.333;
p
< 0.001).
Conclusion
FPTMC has a recurrence rate higher than sporadic cases. Poor prognosis is mainly associated with the tumor size and the risk of recurrence of the ATA.
Graphical abstract
Transcription Factors (TFs) are DNA‐specific binding proteins that regulate gene expression and other biological processes like cell differentiation. For example, the cardiac TF NKX2‐5 has been ...proven to be a master regulator in the transcriptional network needed for heart development. Mutations in NKX2‐5 have been shown to cause congenital heart diseases (CHDs), the most common birth defect that result in structural abnormalities in the heart. However, ~95% of disease‐associated mutations occur within the non‐coding genome, such as promoters and enhancers. The molecular mechanism of these genetic variations and their role in many diseases has remained unexplored. We hypothesize that non‐coding variants within NKX2‐5 binding sites will affect DNA recognition and alter TF‐DNA binding. First, using ~84 million Single Nucleotide Polymorphisms (SNPs) reported in the 1000 Genomes Project, I identified 8,475 that are predicted to affect NKX2‐5 binding. After filtering these variants, I found 901 SNPs localized in cardiac enhancers, and 30 disease‐associated SNPs from the GWAS catalog predicted to affect NKX2‐5 binding sites. Using position weight matrix (PWM) DNA‐specificity models, binding scores for the identified mutations were calculated. The variants rs7350789 and rs7719885 were predicted to have the greatest impact in NKX2‐5 binding affinity with ΔPWM scores of 258 and ‐212 respectively. These variants were prioritized for in vitro validation through Electrophoretic Mobility Shift Assay (EMSA) using purified full‐length NKX2‐5 to evaluate TF‐DNA complex formation. After performing an EMSA, both variants resulted in an increase in TF‐DNA binding even though rs7719885 had a negative ΔPWM score which predicts a decrease in binding affinity. Although not as expected, two of the variants predicted to impact TF‐DNA binding were successfully validated.
Mitochondria-associated membranes (MAMs) are structures that regulate physiological functions between endoplasmic reticulum (ER) and mitochondria in order to maintain calcium signaling and ...mitochondrial biogenesis. Several proteins located in MAMs, including those encoded by
PARK
genes and some of neurodegeneration-related proteins (huntingtin, presenilin, etc.), ensure this regulation. In this regard, MAM alteration is associated with neurodegenerative diseases such as Parkinson’s (PD), Alzheimer’s (AD), and Huntington’s diseases (HD) and contributes to the appearance of the pathogenesis features, i.e., autophagy dysregulation, mitochondrial dysfunction, oxidative stress, and lately, neuronal death. Moreover,, ER stress and/or damaged mitochondria can be the cause of these disruptions. Therefore, ER-mitochondria contact structure and function are crucial to multiple cellular processes. This review is focused on the molecular interaction between ER and mitochondria indispensable to MAM formation and on MAM alteration-induced etiology of neurodegenerative diseases.
Some medical applications of magnetic nanoparticles require direct contact with healthy tissues and blood. If nanoparticles are not designed properly, they can cause several problems, such as ...cytotoxicity or hemolysis. A strategy for improvement the biological proprieties of magnetic nanoparticles is their functionalization with biocompatible polymers and nonionic surfactants. In this study we compared bare magnetite nanoparticles against magnetite nanoparticles coated with a combination of polyethylene glycol 3350 (PEG 3350) and polysorbate 80 (Tween 80). Physical characteristics of nanoparticles were evaluated. A primary culture of sheep adipose mesenchymal stem cells was developed to measure nanoparticle cytotoxicity. A sample of erythrocytes from a healthy donor was used for the hemolysis assay. Results showed the successful obtention of magnetite nanoparticles coated with PEG 3350-Tween 80, with a spherical shape, average size of 119.2 nm and a zeta potential of +5.61 mV. Interaction with mesenchymal stem cells showed a non-cytotoxic propriety at doses lower than 1000 µg/mL. Interaction with erythrocytes showed a non-hemolytic propriety at doses lower than 100 µg/mL. In vitro information obtained from this work concludes that the use of magnetite nanoparticles coated with PEG 3350-Tween 80 is safe for a biological system at low doses.
Background
Familial papillary thyroid microcarcinoma (FPTMC) appears to be more aggressive than sporadic papillary thyroid microcarcinoma (SPTMC). However, there are authors who indicate that ...unicentric FPTMC has a similar prognosis to SPTMC. The objective is to analyze whether unicentric FPTMC has a better prognosis than multicentric FPTMC.
Design and methods
Type of study: National multicenter longitudinal analytical observational study. Study population: Patients with FPTMC. Study groups: Two groups were compared: Group A (unicentric FPTMC) vs. Group B (multicentric FPTMC). Study variables: It is analyzed whether between the groups there are: a) differentiating characteristics; and b) prognostic differences. Statistical analysis: Cox regression analysis and survival analysis.
Results
Ninety-four patients were included, 44% (
n
= 41) with unicentric FPTMC and 56% (
n
= 53) with multicentric FPTMC. No differences were observed between the groups according to socio-familial, clinical or histological variables. In the group B a more aggressive treatment was performed, with higher frequency of total thyroidectomy (99 vs. 78%;
p
= 0.003), lymph node dissection (41 vs. 15%;
p
= 0.005) and therapy with radioactive iodine (96 vs. 73%;
p
= 0.002). Tumor stage was similar in both groups (
p
= 0.237), with a higher number of T3 cases in the group B (24 vs. 5%;
p
= 0.009). After a mean follow-up of 90 ± 68.95 months, the oncological results were similar, with a similar disease persistence rate (9 vs. 5%;
p
= 0.337), disease recurrence rate (21 vs. 8%;
p
= 0.159) and disease-free survival (
p
= 0.075).
Conclusions
Unicentric FPTMC should not be considered as a SPTMC due to its prognosis is similar to multicentric FPTMC.
Graphical Abstract
Vaccination is a widely used therapeutical strategy in aquaculture, but whether vaccination elicits stress responses in the central neuroendocrine system and enhances the crosstalk between the immune ...and endocrine systems in the brain or pituitary after vaccination is unclear. To answer this question two experiments using two different vaccine exposure routes, i.e., bath or intraperitoneal (i.p.) injection, were carried out on gilthead seabream (
L.). In the first one, the stress responses of fish subjected to waterborne
bacterin were compared with responses after air exposure or their combination. In the second experiment, fish were subjected to an intraperitoneal injection of
bacterin and we assessed the central stress response and also whether or not a significant immune response was induced in brain and pituitary. In both experiments, blood, brain and pituitary tissues were collected at 1, 6, and 24 h post stress for plasma hormone determination and gene expression analysis, respectively. Results indicated that bath vaccination induced a decreased central stress response compared to air exposure which stimulated both brain and pituitary stress genes. In the second experiment, injection vaccination kept unchanged plasma stress hormones except cortisol that raised at 6 and 24 h. In agreement, non-significant or slight changes on the transcription of stress-related genes were recorded, including the hormone genes of the hypothalamic pituitary interrenal (HPI) axis and other stress markers such as
,
, and
genes in either brain or pituitary. Significant changes were observed, however, in
and
. In this second experiment the immune genes
,
, and
, showed a strong expression in both brain and pituitary after vaccination, notably
which showed more than 10 fold raise. Overall, vaccination procedures, although showing a cortisol response, did not induce other major stress response in brain or pituitary, regardless the administration route. Other than main changes, the alteration of
and
suggests that these genes could play a relevant role in the feedback regulation of HPI axis after vaccination. In addition, from the results obtained in this work, it is also demonstrated that the immune system maintains a high activity in both brain and pituitary after vaccine injection.
In0.145Ga0.855AsySb1−y semiconductor alloys were grown on GaSb(100) substrates by varying the As content by liquid phase epitaxy (LPE). We demonstrated that the growth mechanism of these quaternary ...alloys is mainly constituted by two stable bonding configurations, Ga−Sb and In−As. These quaternary alloys showed a high crystalline quality due to the nearly lattice-matched epitaxial growth to the GaSb substrate. We identified a tensile strain of the In0.145Ga0.855AsySb1−y alloys on the GaSb substrate, strain that increases with the As content. In the bulk region of these crystalline alloys it was noticed a greater fonon-plasmon coupling than in the surface space-charge region. In addition, we found that the band gap energy of the In0.145Ga0.855AsySb1−y alloys can be easily engineered in the near infrared by varying the As content. Excitonic transitions were observed in these quaternary alloys, whose energy decreases with the As content. We employed a theoretical method that considers spin-orbit coupling for the determination of the band gap energy, which is in agreement with experimental results. These findings provide an important understanding of the growth dynamics, and of the optical and structural properties of the In0.145Ga0.855AsySb1−y crystalline alloys by varying the As content for near infrared applications using the band gap engineering.
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•In0.145Ga0.855AsySb1−y alloys were grown on GaSb substrate by varying the As content.•The quaternary alloys were grown by Liquid Phase Epitaxy (LPE).•The growth mechanism of these alloys is mainly constituted by Ga−Sb and In−As.•The excitonic transition energies of the alloys decrease with the As content.
In January 2020, the Chinese authorities identified a new virus of the Coronaviridae family as the cause of several cases of pneumonia of unknown aetiology. The outbreak was initially confined to ...Wuhan City, but then spread outside Chinese borders. On 31 January 2020, the first case was declared in Spain. On 11 March 2020, The World Health Organization (WHO) declared the coronavirus outbreak a pandemic. On 16 March 2020, there were 139 countries affected. In this situation, the Scientific Societies SEMICYUC and SEEIUC have decided to draw up this Contingency Plan to guide the response of the Intensive Care Services. The objectives of this plan are to estimate the magnitude of the problem and identify the necessary human and material resources. This is to provide the Spanish Intensive Medicine Services with a tool to programme optimal response strategies.
The regulation of circadian gene expression remains largely unknown in farmed fish larvae. In this study, a high-density oligonucleotide microarray was used to examine the daily expression of 13,939 ...unique genes in whole gilthead sea bream (Sparus aurata) larvae with fast growth potentiality. Up to 2,229 genes were differentially expressed, and the first two components of Principal Component Analysis explained more than 81% of the total variance. Clustering analysis of differentially expressed genes identified 4 major clusters that were triggered sequentially, with a maximum expression at 0 h, 3 h, 9-15 h and 18-21 h zeitgeber time. Various core clock genes (per1, per2, per3, bmal1, cry1, cry2, clock) were identified in clusters 1-3, and their expression was significantly correlated with several genes in each cluster. Functional analysis revealed a daily consecutive activation of canonical pathways related to phototransduction, intermediary metabolism, development, chromatin remodeling, and cell cycle regulation. This daily transcriptome of whole larvae resembles a cell cycle (G1/S, G2/M, and M/G1 transitions) in synchronization with multicellular processes, such as neuromuscular development. This study supports that the actively feeding fish larval transcriptome is temporally organized in a 24-h cycle, likely for maximizing growth and development.
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