GEIDIS is a national-based research-net registry of patients with bronchopulmonary dysplasia (BPD) from public and private Spanish hospitals. It was created to provide data on the clinical ...characterization and follow-up of infants with BPD until adulthood. The purpose of this observational study was to analyze the characteristics and the impact of perinatal risk factors on BPD severity. The study included 1755 preterm patients diagnosed with BPD. Of the total sample, 90.6% (
n
= 1591) were less than 30 weeks of gestation. The median gestational age was 27.1 weeks (25.8–28.5) and median birth weight 885 g (740–1,070 g). A total of 52.5% (
n
= 922) were classified as mild (type 1), 25.3% (
n
= 444) were moderate (type 2), and 22.2% (
n
= 389) were severe BPD (type 3). In patients born at under 30 weeks’ gestation, most pre-and postnatal risk factors for type 2/3 BPD were associated with the length of exposure to mechanical ventilation (MV). Independent prenatal risk factors were male gender, oligohydramnios, and intrauterine growth restriction. Postnatal risk factors included the need for FiO
2
of > 0.30 in the delivery room, nosocomial pneumonia, and the length of exposure to MV.
Conclusion
: In this national-based research-net registry of BPD patients, the length of MV is the most important risk factor associated with type 2/3 BPD. Among type 3 BPD patients, those who required an FiO
2
> .30 at 36 weeks’ postmenstrual age had a higher morbidity, during hospitalization and at discharge, compared to those with nasal positive pressure but FiO
2
< .30.
What is Known:
• BPD is a highly complex multifactorial disease associated with preterm birth.
What is New:
• The length of exposure to mechanical ventilation is the most important postnatal risk factor associated to bronchopulmonary severity which modulate the effect of most pre and postnatal risk factors.
• Among patients with BPD, the requirement for FiO2 >.30% at 36 weeks of postmenstrual age is associated with greater morbidity during hospitalization and at discharge.
Patients with ESRD undergoing peritoneal dialysis develop progressive peritoneal fibrosis, which may lead to technique failure. Recent data point to Th17-mediated inflammation as a key contributor in ...peritoneal damage. The leukocyte antigen CD69 modulates the setting and progression of autoimmune and inflammatory diseases by controlling the balance between Th17 and regulatory T cells (Tregs). However, the relevance of CD69 in tissue fibrosis remains largely unknown. Thus, we explored the role of CD69 in fibroproliferative responses using a mouse model of peritoneal fibrosis induced by dialysis fluid exposure under either normal or uremic status. We found that cd69
mice compared with wild-type (WT) mice showed enhanced fibrosis, mesothelial to mesenchymal transition, IL-17 production, and Th17 cell infiltration in response to dialysis fluid treatment. Uremia contributed partially to peritoneal inflammatory and fibrotic responses. Additionally, antibody-mediated CD69 blockade in WT mice mimicked the fibrotic response of cd69
mice. Finally, IL-17 blockade in cd69
mice decreased peritoneal fibrosis to the WT levels, and mixed bone marrow from cd69
and Rag2
c
mice transplanted into WT mice reproduced the severity of the response to dialysis fluid observed in cd69
mice, showing that CD69 exerts its regulatory function within the lymphocyte compartment. Overall, our results indicate that CD69 controls tissue fibrosis by regulating Th17-mediated inflammation.
The purpose of this study was to investigate the association between the reception zone and the spiking performance in each of the game rotations in top level men's volleyball teams. The sample ...consisted of 29 men´s matches of final phases in Olympic Games, World League and World Cup between 2012 and 2016, obtaining a sample of 3,689 spikes in the K1 phase. The variables analyzed were: the rotation of the reception team, the reception area and the spike performance. Ordinal regression models were used to determine the influence of the receiving zone and the interaction of rotation on spike performance. The results show significant interaction between the rotation and the reception area on spike performance (X²₄₆ = 127.885; p <.001; r2 = .036), which allow us to understand the greater or lesser probability of achieving a better spike performance in some of the rotations. In conclusion, the performance of the spike varies depending on the interaction of the rotation of the team and the reception area, but this relation in global level, only explain 3.6% of the variance of the spike. The analysis of the situations in which significance has been found could be associated with strategic decisions in the execution of the serve and the training of the K1.
El objetivo de este estudio, fue investigar la asociación de la zona de recepción con el rendimiento del remate considerando el impacto de la rotación, en equipos de voleibol masculino de alto nivel. Fueron analizados 29 partidos de selecciones internacionales masculinas de máximo nivel, obteniendo una muestra de 3689 remates en la fase de KI. Las variables analizadas fueron: la rotación del equipo en recepción, la zona de recepción y el rendimiento del remate. Se emplearon modelos de regresión ordinales para determinar la influencia de la zona de recepción y la interacción de la rotación en el rendimiento del remate. Los resultados mostraron interacciones significativas entre la rotación y la zona de recepción, que permiten entender la mayor o menor probabilidad de conseguir un mejor rendimiento en remate (p<0.001) en algunas de las rotaciones. En conclusión, el rendimiento del remate es diferente en función de la interacción de la rotación del equipo y de la zona de recepción, lo que podría asociarse con decisiones tácticas en la ejecución del saque.
Evidence implicating p38γ and p38δ (p38γ/p38δ) in inflammation are mainly based on experiments using
deficient (p38γ/δKO) mice, which show low levels of TPL2, the kinase upstream of MKK1-ERK1/2 in ...myeloid cells. This could obscure p38γ/p38δ roles, since TPL2 is essential for regulating inflammation. Here we generated a
/
(p38γ/δKIKO) mouse, expressing kinase-inactive p38γ and lacking p38δ. This mouse exhibited normal TPL2 levels, making it an excellent tool to elucidate specific p38γ/p38δ functions. p38γ/δKIKO mice showed a reduced inflammatory response and less susceptibility to LPS-induced septic shock and
infection than wild-type mice. Gene expression analyses in LPS-activated WT and p38γ/δKIKO macrophages revealed that p38γ/p38δ regulated numerous genes implicated in innate immune response. Additionally, phospho-proteomic analyses and
kinase assays showed that the transcription factor myocyte enhancer factor-2D (MEF2D) was phosphorylated at Ser444 via p38γ/p38δ. Mutation of MEF2D Ser444 to the non-phosphorylatable residue Ala increased its transcriptional activity and the expression of
and
mRNA. These results suggest that p38γ/p38δ govern innate immune responses by regulating MEF2D phosphorylation and transcriptional activity.
Increased amounts of protein, in particular albumin within renal tubular cells (TBCs), induce the expression of inflammatory and fibrogenic mediators, which are adverse prognostic factors in ...tubulointerstitial fibrosis and diabetic nephropathy (DN). We sought to assess the participation of the thiol-linked tertiary structure of albumin in the mechanism of protein toxicity in a model of TBCs.
Cultured human renal proximal tubular cells, HK-2, were exposed to isolated albumin from patients with and without DN (Stages 0, 1 and 4). The magnitude of change of the albumin tertiary structure, cell viability (LDH leakage), apoptosis (Annexin V), transdifferentiation and reticulum endoplasmic stress (Western blot and flow cytometry) and lysosomal enzyme activity were assessed.
We found that albumin from Stage 4 patients presented >50% higher thiol-dependent changes of tertiary structure compared to Stages 0 and 1. Cells incubated with Stage 4 albumin displayed 5 times less viability, accompanied by an increased number of apoptotic cells; evidence of profibrogenic markers E-cadherin and vimentin and higher expression of epithelial-to-mesenchymal transition markers α-SMA and E-cadherin and of endoplasmic reticulum stress protein GRP78 were likewise observed. Moreover, we found that cathepsin B activity in isolated lysosomes showed a significant inhibitory effect on albumin from patients in advanced stages of DN and on albumin that was intentionally modified.
Overall, this study showed that thiol-dependent changes in albumin's tertiary structure interfere with the lysosomal proteolysis of renal TBCs, inducing molecular changes associated with interstitial fibrosis and DN progression.
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Sex hormones play a role in gastric cancer and colorectal cancer etiology, however, epidemiological evidence is inconsistent. This study examines the influence of menstrual and reproductive factors ...over the risk of both tumors.
In this case-control study 128 women with gastric cancer and 1293 controls, as well as 562 female and colorectal cancer cases and 1605 controls were recruited in 9 and 11 Spanish provinces, respectively. Population controls were frequency matched to cases by age and province. Demographic and reproductive data were directly surveyed by trained staff. The association with gastric, colon and rectal cancer was assessed using logistic and multinomial mixed regression models.
Our results show an inverse association of age at first birth with gastric cancer risk (five-year trend: OR = 0.69; p-value = 0.006). Ever users of hormonal contraception presented a decreased risk of gastric (OR = 0.42; 95%CI = 0.26-0.69), colon (OR = 0.64; 95%CI = 0.48-0.86) and rectal cancer (OR = 0.61; 95%CI = 0.43-0.88). Postmenopausal women who used hormone replacement therapy showed a decreased risk of colon and rectal tumors. A significant interaction of educational level with parity and months of first child lactation was also observed.
These findings suggest a protective role of exogenous hormones in gastric and colorectal cancer risk. The role of endogenous hormones remains unclear.
To explore the association of colorectal cancer with environmental solar radiation and sun exposure behavior, considering phenotypic variables (eye color, hair color and skin phenotype), dietary ...intake of vitamin D and calcium, and socio-demographic factors.
Multicenter population-based frequency matched case-control study in Spain (MCC-Spain), with 2140 CRC cases and 3950 controls.
Data were obtained through personal interviews using a structured epidemiological questionnaire that included socio-demographic data, residential history, environmental exposures, behavior, phenotypic and dietary information. An environmental-lifetime sun exposure score was constructed combining residential history and average daily solar radiation, direct and diffuse. Logistic regression was used to explore the association between different variables. A structural equation model was used to verify the associations of the conceptual model.
We found a lower risk of CRC in subjects frequently exposed to sunlight during the previous summer and skin burning due to sun exposure. No association was observed in relation to the residential solar radiation scores. Subjects with light eye or light hair colors had a lower risk of CRC that those with darker colors. Dietary calcium and vitamin D were also protective factors, but not in the multivariate model. The structural equation model analysis suggested that higher sun exposure was associated with a decreased risk of CRC, as well as dietary intake of calcium and vitamin D, and these factors are correlated among themselves and with environmental solar radiation and skin phenotypes.
The results agree with previous observations that sun exposure, dietary vitamin D and calcium intake, and serum 25(OH)D concentration reduce the risk of CRC and indicate that these factors may be relevant for cancer prevention.
•Sunlight, dietary intake of vitamin D and calcium were associated with a reduced risk of colorectal cancer•Risk of CRC was higher for individuals with dark hair or eyes, though these effects could be related to sun exposure habits•Our model indicates that vitamin D and calcium, sun exposure and skin phenotype, coordinately contribute to CRC prevention•Weaker associations were observed in women, possible related to differential adiposity that influence vitamin D availability
Reproductive factors are well known risk factors for breast cancer; however, little is known about how genetic variants in hormonal pathways interact with that relationship.
One thousand one hundred ...thirty nine cases of breast cancer in women and 1322 frequency-matched controls were compared. Genetic variants in hormonal pathways (identified in the Kyoto Encyclopedia of Genes and Genomes) were screened according to their relationship with breast cancer using the Cochran-Armitage statistic. Information on reproductive factors was obtained using a face-to-face questionnaire. The interaction among the selected genetic variants and reproductive factors was tested with logistic regression.
Concerning C allele in rs2229712, compared to nulliparity in non-carriers the ORs for 1-2 and > 2 deliveries were 0.48 (0.28-0.81) and 0.34 (0.19-0.59), and in C carriers they were 0.92 (0.42-1.98) and 0.71 (0.31-1.61). Similar results were found in women carrying the C allele in rs1269851. Carriers of Allele T in rs35652107 and allele C in rs6018027 had the delivery number effect more pronounced.
The number of deliveries had a dose-response protective effect on breast cancer; women carrying C allele in rs2229712 did not benefit from this protective effect.
Abstract
Within the context of complex sexual signaling, most research has focused on exploring the associations between several signals and/or their relationships with different proxies of ...individual quality. However, very few studies have focused on checking whether the expression of one signal is conditioned by the expression of the others. Here, by experimentally shortening the throat feathers of male spotless starlings (Sturnus unicolor), we evaluated the influence of this trait on the color expression of the beak base. In addition, we tested the relationship between these two sexually dimorphic characters with traits indicating individual qualities, such as body condition and color reflectance at the wavelength related to carotenes in the tip of the beak. Our results show that the coloration of the beak base in males, but not in females, is positively related to body condition and to the length of ornamental throat feathers. Moreover, the experimental shortening of throat feathers in males had a negative effect on the blue chroma intensity of their beak base 1 year after manipulation. These results support for the first time a causal link between the expression of two sexually dimorphic characters, which is essential to understand their functionality in a multiple signaling framework.
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