Mindfulness training for reducing anger, anxiety, and depression in fibromyalgia patients

Fibromyalgia is a disabling syndrome. Results obtained with different therapies are very limited to date.The goal of this study was to verify whether the application of a mindfulnessbased training program was effective in modifying anger, anxiety, and depression levels in a group of women diagnosed with fibromyalgia. This study is an experimental trial that employed a waiting list control group. Measures were taken at three different times: pretest, posttest, and follow-up. The statistical analyses revealed a significant reduction of anger (trait) levels, internal expression of anger, state anxiety, and depression in the experimental group as compared to the control group, as well as a significant increase in internal control of anger. It can be concluded that the mindfulness-based treatment was effective after 7 weeks. These results were maintained 3 months after the end of the intervention.Fibromyalgia Association of Almeria (AFIAL

Involvement of ANXA5 and ILKAP in Susceptibility to Malignant Melanoma

Single nucleotide-polymorphisms (SNPs) are a source of diversity among human population, which may be responsible for the different individual susceptibility to diseases and/or response to drugs, among other phenotypic traits. Several low penetrance susceptibility genes associated with malignant melanoma (MM) have been described, including genes related to pigmentation, DNA damage repair and oxidative stress pathways. In the present work, we conducted a candidate gene association study based on proteins and genes whose expression we had detected altered in melanoma cell lines as compared to normal melanocytes. The result was the selection of 88 loci and 384 SNPs, of which 314 fulfilled our quality criteria for a case-control association study. The SNP rs6854854 in ANXA5 was statistically significant after conservative Bonferroni correction when 464 melanoma patients and 400 controls were analyzed in a discovery Phase I. However, this finding could not be replicated in the validation phase, perhaps because the minor allele frequency of SNP rs6854854 varies depending on the geographical region considered. Additionally, a second SNP (rs6431588) located on ILKAP was found to be associated with melanoma after considering a combined set of 1,883 MM cases and 1,358 disease-free controls. The OR was 1.29 (95% CI 1.12–1.48; p-value = 4×10−4). Both SNPs, rs6854854 in ANXA5 and rs6431588 in ILKAP, show population structure, which, assuming that the Spanish population is not significantly structured, suggests a role of these loci on a specific genetic adaptation to different environmental conditions. Furthermore, the biological relevance of these genes in MM is supported by in vitro experiments, which show a decrease in the transcription levels of ANXA5 and ILKAP in melanoma cells compared to normal melanocyte

The Interplay between Natural Selection and Susceptibility to Melanoma on Allele 374F of SLC45A2 Gene in a South European Population

We aimed to study the selective pressures interacting on SLC45A2 to investigate the interplay between selection and susceptibility to disease. Thus, we enrolled 500 volunteers from a geographically limited population (Basques from the North of Spain) and by resequencing the whole coding region and intron 5 of the 34 most and the 34 least pigmented individuals according to the reflectance distribution, we observed that the polymorphism Leu374Phe (L374F, rs16891982) was statistically associated with skin color variability within this sample. In particular, allele 374F was significantly more frequent among the individuals with lighter skin. Further genotyping an independent set of 558 individuals of a geographically wider population with known ancestry in the Spanish population also revealed that the frequency of L374F was significantly correlated with the incident UV radiation intensity. Selection tests suggest that allele 374F is being positively selected in South Europeans, thus indicating that depigmentation is an adaptive process. Interestingly, by genotyping 119 melanoma samples, we show that this variant is also associated with an increased susceptibility to melanoma in our populations. The ultimate driving force for this adaptation is unknown, but it is compatible with the vitamin D hypothesis. This shows that molecular evolution analysis can be used as a useful technology to predict phenotypic and biomedical consequences in humans

Pluripotency factors regulate the onset of Hox cluster activation in the early embryo

Pluripotent cells are a transient population of the mammalian embryo dependent on transcription factors, such as OCT4 and NANOG, which maintain pluripotency while suppressing lineage specification. However, these factors are also expressed during early phases of differentiation, and their role in the transition from pluripotency to lineage specification is largely unknown. We found that pluripotency factors play a dual role in regulating key lineage specifiers, initially repressing their expression and later being required for their proper activation. We show that Oct4 is necessary for activation of HoxB genes during differentiation of embryonic stem cells and in the embryo. In addition, we show that the HoxB cluster is coordinately regulated by OCT4 binding sites located at the 3′ end of the cluster. Our results show that core pluripotency factors are not limited to maintaining the precommitted epiblast but are also necessary for the proper deployment of subsequent developmental programs.This work was funded by the Spanish government (grants BFU2017-84914-P and PID2020-115755GB-I00 to M.M.; BFU2016-74961-P and BFU2016-81887-REDT to J.L.G.-S.), the Andalusian government (grant BIO-396 to J.L.G.-S.), and the European Research Council (ERC; grant agreement 740041 to J.L.G.-S.). M.T. held Juan de la Cierva fellowships from the Spanish government (FJCI-2017-31791 and IJC2019-038897-I), R.R. and R.D.A. held FPU fellowships from the government, and J.V. was the recipient of a “La Caixa” fellowship. Work in the laboratory of J.L.G.-S. was supported by a María de Maetzu Unit of Excellence Grant (MDM-2016-0687) to the Department of Gene Regulation and Morphogenesis of the CABD. The CBMSO is supported by an institutional grant from the Fundación Ramon Areces, and the CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN), and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). : With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2020-001041-S)

Terfenadine induces apoptosis and autophagy in melanoma cells through ROS-dependent and -independent mechanisms

Previously we found that terfenadine, an H1 histamine receptor antagonist, acts as a potent apoptosis inducer in melanoma cells through modulation of Ca2+ homeostasis. In this report, focusing our attention on the apoptotic mechanisms activated by terfenadine, we show that this drug can potentially activate distinct intrinsic signaling pathways depending on culture conditions. Serum-deprived conditions enhance the cytotoxic effect of terfenadine and caspase-4 and -2 are activated upstream of caspase-9. Moreover, although we found an increase in ROS levels, the apoptosis was ROS independent. Conversely, terfenadine treatment in complete medium induced ROS-dependent apoptosis. Caspase-4, -2, and -9 were simultaneously activated and p73 and Noxa induction were involved. ROS inhibition prevented p73 and Noxa expression but not p53 and p21 expression, suggesting a role for Noxa in p53-independent apoptosis in melanoma cells. Finally, we found that terfenadine induced autophagy, that can promote apoptosis. These findings demonstrate the great potential of terfenadine to kill melanoma cells through different cellular signaling pathways and could contribute to define new therapeutic strategies in melanoma

Seroprevalence and Associated Risk Factors for Toxoplasma gondii Infection in Healthy Blood Donors: A Cross-Sectional Study in Sonora, Mexico

Toxoplasma gondii (T. gondii) can be transmitted by blood transfusion. We determined the prevalence of T. gondii infection in healthy blood donors in Hermosillo city, Mexico, and the association of infection with T. gondii with the sociodemographic, clinical, and behavioral characteristics of blood donors. Four hundred and eight blood donors who attended two public blood banks in Hermosillo city were examined for anti-T. gondii IgG and IgM antibodies by using enzyme-linked immunoassays. Of the 408 blood donors (mean age 31.77±9.52; range 18–60 years old) studied, 55 (13.5%) were positive for anti-T. gondii IgG antibodies, and 12 (21.8%) of them were also positive for anti-T. gondii IgM antibodies. Multivariate analysis showed that seropositivity to T. gondii was associated with age (OR = 1.74; 95% CI: 1.03–2.94; P=0.03) and tobacco use (OR = 2.09; 95% CI: 1.02–4.29; P=0.04). Seropositivity to T. gondii was correlated with the number of pregnancies, deliveries, and cesarean sections. The seroprevalence of T. gondii infection in blood donors in Sonora is the highest reported in blood donors in northern Mexico so far. This is the first report of an association of T. gondii exposure and tobacco use. Further research to confirm this association is needed

Seroprevalence and Associated Risk Factors for Toxoplasma gondii Infection in Healthy Blood Donors: A Cross-Sectional Study in Sonora, Mexico

Toxoplasma gondii (T. gondii) can be transmitted by blood transfusion. We determined the prevalence of T. gondii infection in healthy blood donors in Hermosillo city, Mexico, and the association of infection with T. gondii with the sociodemographic, clinical, and behavioral characteristics of blood donors. Four hundred and eight blood donors who attended two public blood banks in Hermosillo city were examined for anti-T. gondii IgG and IgM antibodies by using enzyme-linked immunoassays. Of the 408 blood donors (mean age 31.77 ± 9.52; range 18-60 years old) studied, 55 (13.5%) were positive for anti-T. gondii IgG antibodies, and 12 (21.8%) of them were also positive for anti-T. gondii IgM antibodies. Multivariate analysis showed that seropositivity to T. gondii was associated with age (OR = 1.74; 95% CI: 1.03-2.94; = 0.03) and tobacco use (OR = 2.09; 95% CI: 1.02-4.29; = 0.04). Seropositivity to T. gondii was correlated with the number of pregnancies, deliveries, and cesarean sections. The seroprevalence of T. gondii infection in blood donors in Sonora is the highest reported in blood donors in northern Mexico so far. This is the first report of an association of T. gondii exposure and tobacco use. Further research to confirm this association is needed

Data of the SNPs analyzed in Phase II.

<p>Chrom. Chromosome; OR (95% CI) Odds ratio (95% confidence interval).</p

SNP association results.

<p>The –log10 of the allelic p-values from 314 SNPs comparing 464 melanoma patients and 400 controls of Spanish origin at Phase I are represented. The chromosomal SNP distribution is shown. The SNP rs6854854 in <i>ANXA5</i> remained statistically significant after Bonferroni correction (p-<i>value</i> <0.00015).</p

Polymorphisms and alleles identified in the promoter region of <i>ILKAP</i> gene in each cell line studied.

<p>The SNPs are numbered according to their appearance in the promoter region of <i>ILKAP</i> from the position Chr 2∶239,114,642 to the position Chr 2∶239,113,023 according to NCBI dbSNP 138. The ancestral allele is in black and the derived allele in bold.</p