The effect of aging temperature on martensite reversion and mechanical behavior of a 2304-lean duplex stainless steel (LDSS) was analyzed after cold rolling to 74% reduction and aging at 400–600 °C ...for 1800 s. Strain-induced martensite (SIM) formation results from cold rolling. After cold rolling, the results revealed a Nishiyama–Wasser (N–W) relationship between the
∝
'-martensite laths and the metastable austenite. Increasing the aging temperature led to a rise in the steel strength, resulting in very low ductility, but with high yield and tensile strength of the specimens. The SIM reversion started between 500 and 550 °C for 1800 s soaking time. At temperatures between 400 and 500 °C, substantial embrittlement occurred. Precipitation of the
∝
+
∝
′ (spinodal decomposition) in solid solution in ferrite was not observed. Hence, it is not the cause of the steel embrittlement. The mechanisms involved in the increase of strength and embrittlement were the aging of the austenite phase due to the formation of a substructure with ultrafine or nano-deformation twins, stacking faults, and shear bands in a lamellar array, and possibly Suzuki effect mechanism occurrence.
Recently, a link between the biological activity of CD73 and tumorigenicity in solid tumors has been proposed. We previously reported that the generation of adenosine (Ado) by the activity of CD73 in ...cervical cancer (CC) cells induces transforming growth factor‐beta 1 (TGF‐β1) production to maintain CD73 expression. In the present study, we analyzed the participation of TGF‐β1 in CD73 expression and the development of protumoral characteristics in CaSki CC cells cultured as tumorspheres (CaSki‐T) and in monolayers (CaSki‐M). Compared with those in CaSki‐M cells, CD73 expression and Ado generation ability were significantly increased in CaSki‐T cells. CaSki‐T cells exhibited enrichment in the CSC‐like phenotype due to increases in the expression levels of stem cell markers (CD49f, CK17, and P63; OCT4 and SOX2), greater sphere formation efficiency (SFE), and an increase in the percentage of side population (SP) cells. Interestingly, compared with CaSki‐M cells, CaSki‐T cells produced a greater amount of TGF‐β1 and presented a marked protumor phenotype characterized by a significant decrease in the expression of major histocompatibility complex class‐I (MHC‐I) molecules, an increase in the expression of multidrug resistance protein‐I (MRP‐I) and vimentin, and an increase in the protein expression levels of Snail‐1 and Twist, which was strongly reversed with TGF‐β1 inhibition. These results suggest that the presence of TGF‐β1−CD73–Ado feedback loop can promote protumoral characteristics in the CC tumor microenvironment.
Significance statement
This study provided the first evidence that high CD73 expression associated with high TGF‐β1 production by cervical cancer cells cultured as tumorspheres strongly contributes to the induction of protumoral characteristics related to tumor progressions, such as migration and invasiveness, immune evasion, immunosuppression, and chemoresistance.
Background
The distribution of
RUNX1-RUNXT1
,
PML-RARA
,
CBFB-MYH11
,
BCR-ABL1
p210
, and
KMT2A-MLLT3
in the pediatric population with acute myeloid leukemia (AML) in many countries of Latin America ...is largely unknown. Therefore, we aimed to investigate the frequency of these fusion genes in children with
de novo
AML from Mexico City, which has one of the highest incidence rates of acute leukemia in the world. Additionally, we explored their impact in mortality during the first year of treatment.
Methods
We retrospectively analyzed the presence of
RUNX1-RUNXT1
,
PML-RARA
,
CBFB-MYH11
,
BCR-ABL1
p210
, and
KMT2A-MLLT3
by RT-PCR among 77 patients (<18 years) diagnosed with
de novo
AML between 2019 and 2021 in nine Mexico City hospitals.
Results
The overall frequency of the fusion genes was 50.7%;
RUNX1-RUNXT1
(22.1%) and
PML-RARA
(20.8%) were the most prevalent, followed by
CBFB-MYH11
(5.2%) and
BCR-ABL1
p210
(2.4%).
KMT2A-MLLT3
was not detected. Patients with
PML-RARA
showed the lowest survival with high early mortality events. However, more studies are required to evaluate the impact of analyzed fusion genes on the overall survival of the Mexican child population with AML.
Conclusion
The pediatric population of Mexico City with AML had frequencies of
AML1-ETO
,
PML-RARA
,
CBFB-MYH11
, and
BCR-ABL1
p210
similar to those of other populations around the world. Patients with
BCR-ABL1
p210
and
CBFB-MYH11
were few or did not die, while those with
MLL-AF9
was not detected. Although patients with
PML-RARA
had a low survival and a high early mortality rate, further studies are needed to determine the long-term impacts of these fusion genes on this Latino population.
The oral administration of vitamin B12 offers a potentially simpler and cheaper alternative to parenteral administration, but its effectiveness has not been definitively demonstrated. The following ...protocol was designed to compare the effectiveness of orally and intramuscularly administered vitamin B12 in the treatment of patients ≥65 years of age with vitamin B12 deficiency.
The proposed study involves a controlled, randomised, multicentre, parallel, non-inferiority clinical trial lasting one year, involving 23 primary healthcare centres in the Madrid region (Spain), and patients ≥65 years of age. The minimum number of patients required for the study was calculated as 320 (160 in each arm). Bearing in mind an estimated 8-10% prevalence of vitamin B12 deficiency among the population of this age group, an initial sample of 3556 patients will need to be recruited. Eligible patients will be randomly assigned to one of the two treatment arms. In the intramuscular treatment arm, vitamin B12 will be administered as follows: 1 mg on alternate days in weeks 1 and 2, 1 mg/week in weeks 3-8,and 1 mg/month in weeks 9-52. In the oral arm, the vitamin will be administered as: 1 mg/day in weeks 1-8 and 1 mg/week in weeks 9-52. The main outcome variable to be monitored in both treatment arms is the normalisation of the serum vitamin B12 concentration at weeks 8, 26 and 52; the secondary outcome variables include the serum concentration of vitamin B12 (in pg/ml), adherence to treatment, quality of life (EuroQoL-5D questionnaire), patient 3satisfaction and patient preferences. All statistical tests will be performed with intention to treat and per protocol. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in analyses.
The results of this study should help establish, taking quality of life into account, whether the oral administration of vitamin B12 is an effective alternative to its intramuscular administration. If this administration route is effective, it should provide a cheaper means of treating vitamin B12 deficiency while inducing fewer adverse effects. Having such an alternative would also allow patient preferences to be taken into consideration at the time of prescribing treatment.
This trial has been registered with ClinicalTrials.gov, number NCT 01476007, and under EUDRACT number 2010-024129-20.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The elongase of long chain fatty acids family 6 (ELOVL6) is an enzyme that specifically catalyzes the elongation of saturated and monounsaturated fatty acids with 12, 14 and 16 carbons. ELOVL6 is ...expressed in lipogenic tissues and it is regulated by sterol regulatory element binding protein 1 (SREBP-1).
We investigated whether ELOVL6 genetic variation is associated with insulin sensitivity in a population from southern Spain.
We undertook a prospective, population-based study collecting phenotypic, metabolic, nutritional and genetic information. Measurements were made of weight and height and the body mass index (BMI) was calculated. Insulin resistance was measured by homeostasis model assessment. The type of dietary fat was assessed from samples of cooking oil taken from the participants' kitchens and analyzed by gas chromatography. Five SNPs of the ELOVL6 gene were analyzed by SNPlex.
Carriers of the minor alleles of the SNPs rs9997926 and rs6824447 had a lower risk of having high HOMA_IR, whereas carriers of the minor allele rs17041272 had a higher risk of being insulin resistant. An interaction was detected between the rs6824447 polymorphism and the intake of oil in relation with insulin resistance, such that carriers of this minor allele who consumed sunflower oil had lower HOMA_IR than those who did not have this allele (P = 0.001).
Genetic variations in the ELOVL6 gene were associated with insulin sensitivity in this population-based study.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•STESS is a valuable tool to predict mortality in patients with status epilepticus.•A cutoff point ≥3 discriminates well survivors and nonsurvivors in Medellin.•STESS-3 is better to justify treatment ...with fewer side effects than anaesthetics.
The Status Epilepticus Severity Score (STESS) is one of the most well-known clinical scoring systems to predict mortality in status epilepticus (SE). The objective of this study was to validate STESS in a Colombian population.
We evaluated historical data of adult patients (age ≥16 years) with a clinical or electroencephalographic diagnosis of SE admitted between 2014 and 2017. Prospectively, we included patients admitted from January to June of 2018. The primary outcome was in-hospital mortality. Receiver operating characteristic (ROC)-analysis, determination of best cutoff values, sensitivity, specificity, and positive and negative likelihood ratios were performed.
The sample was 395 patients, with in-hospital mortality of 16.8 %. The area under the ROC curve for STESS was 0.84. A cutoff point of ≥3 produced the highest sensitivity of 84.9 % (95 % CI 73.9 %-92.5 %) and a specificity of 65.7 % (95 % CI 60.2 %–70.8 %), with a positive likelihood ratio of 2.5 and a negative likelihood ratio of 0.2.
STESS is a useful tool to predict mortality in patients with SE. In Medellin, Colombia, a STESS < 3 allows the identification of the patients who survive reliably. Those patients with a score <3 may have a better prognosis, and treatment with fewer side effects than anaesthetics could be suggested, always remembering the importance of the treating physician's clinical judgement.
Peace can be built from the ground up. Moreover, peacebuilding is future-orientated and thus calls for a focus on children and youth. This approach involves a need to adapt methods to respond to the ...needs and abilities of young people, building their agency and capacities. Qualitative, participatory, arts-based methods offer such an approach, allowing for creativity, hope, and change for the future. This article will present qualitative data from 75 children and young people between the ages of 7 and 18 across three urban settings in Colombia and qualitative interviews with the adult stakeholders involved in the intervention, such as theater teachers and auxiliary researchers. A thematic analysis identified three major themes relating to peace: educating for peace, everyday peacebuilding, and building sustainable peace. From these categories, a textual data analysis was conducted using KH-Coder software to find co-occurrence networks. The implications for this article serve to further reinforce United Nations Resolutions 2250 (2015), 2419 (2018), and 2535 (2020), recognizing the essential role of children and youth in peacebuilding processes.
Public Significance Statement
The findings of this study suggest that children and youth should be integrated into peacebuilding processes. To enable their contribution of perspectives, opinions, and actions to peacebuilding, it is crucial to develop strategies such as theater or other artistic expressions.
Background Information
Autophagy is a conserved process that functions as a cytoprotective mechanism; it may function as a cell death process called programmed cell death type II. There is ...considerable evidence for the presence of autophagic cell death during oocyte elimination in prepubertal rats. However, the mechanisms involved in this process have not been deciphered.
Results
Our observations revealed autophagic cell death in oocytes with increased labeling of the autophagic proteins Beclin 1, light chain 3 A (LC3 A), and lysosomal‐associated membrane protein 1 (Lamp1). Furthermore, mTOR and phosphorylated (p)‐mTOR (S2448) proteins were significantly decreased in oocytes with increased levels of autophagic proteins, indicating autophagic activation. Moreover, phosphorylated protein kinase B (p‐AKT) was not expressed by oocytes, but mitogen‐activated protein kinase/extracellular signalregulated kinase (MAPK/ERK) signaling was observed. Additionally, selective and elevated mitochondrial degradation was identified in altered oocytes.
Conclusions
All these results suggest that mTOR downregulation, which promotes autophagy, could be mediated by low energy levels and sustained starvation involving the phosphoinositide 3‐kinase (PI3K)/AKT/mTOR and MAPK/ERK pathways.
Significance
In this work, we analyzed the manner in which autophagy is carried out in oocytes undergoing autophagic cell death by studying the behavior of proteins involved in different steps of the autophagic pathway.
Autophagy in oocytes from atretic follicles is influenced by nutrients limitation and energy lowering. TSC1‐TSC2 signaling pathway is influenced by pAkt reduction. TSC2 protein serves as an inhibitor of mammalian target of rapamycin (mTOR) signaling inducing low p‐Ulk1 (S757) to stimulate autophagy. Simultaneously, low energy levels induce AMPK to phosphorylate p‐Ulk1 (S555) to promote autophagy, by increasing Beclin 1, LC3 A, and Lamp1 proteins, and lowering p62 protein levels.
While foraging, it is critical for a predator to detect and recognize its prey quickly in order to optimize its energy investment. In response, prey can use low-cost energy strategies such as crypsis ...and immobility that operate early in the detection–attack sequence. Mesopredators, such as spiders, are themselves attacked by visually oriented predators such as mud-dauber wasps. However, it is not known which colour cues are used by wasps to detect and capture their spider prey or whether there are biases towards such cues. In this study, we evaluated the prey colour biases of two mud-dauber wasps (Trypoxylon tridentatum and Trypoxylon bridwelli) using full-spectrum digital photography and visual modelling. We compared the colour contrast of spiders that were preyed upon with that of the spiders in the surrounding habitat. We show that the spiders captured by the wasps had higher chromatic contrast with their typical backgrounds compared with other co-occurring spider species not found in Trypoxylon nests. Our results suggest that Trypoxylon wasps may exhibit colour biases and/or preferences when hunting their spider prey. Our study highlights the importance of considering the perceptual abilities and biases of predators when studying predator–prey interactions.
•We evaluated mud-dauber wasps' colour biases for spider prey.•Araneophagic wasp species showed distinct preferences when foraging for spiders.•Spiders with higher colour contrast with the background were captured more often.•Wasps may use chromatic cues at different stages during detection and attack.
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