Neonatal screening program for five conditions in Honduras.

We present the initial results of a neonatal screening program in part of the public health system in Honduras, that is, the Honduran Social Security Institute. The program design includes steps from neonatal bloodspot in the first newborn days to evaluation and treatment when necessary. In 2018 and 2019, 19,911 newborns were tested for hypothyroidism, cystic fibrosis, galactosemia, phenylketonuria, and adrenal hyperplasia. Abnormalities were identified in 18 newborns, corresponding to a prevalence of 9:10,000. Considering all births in Honduras, the estimated coverage of screening ranged between 4.4 and 5.7%. These results reinforce the need to expand and consolidate neonatal screening.

Revisiting the Teleost Thymus: Current Knowledge and Future Perspectives.

The thymus in vertebrates plays a critical role in producing functionally competent T-lymphocytes. Phylogenetically, the thymus emerges early during evolution in jawed cartilaginous fish, and it is usually a bilateral organ placed subcutaneously at the dorsal commissure of the operculum. In this review, we summarize the current understanding of the thymus localization, histology studies, cell composition, and function in teleost fishes. Furthermore, we consider environmental factors that affect thymus development, such as seasonal changes, photoperiod, water temperature fluctuations and hormones. Further analysis of the thymus cell distribution and function will help us understand how key stages for developing functional T cells occur in fish, and how thymus dynamics can be modulated by external factors like photoperiod. Overall, the information presented here helps identify the knowledge gaps and future steps needed for a better understanding of the immunobiology of fish thymus.

Single-Nucleotide Polymorphisms (SNP) Mining and Their Effect on the Tridimensional Protein Structure Prediction in a Set of Immunity-Related Expressed Sequence Tags (EST) in Atlantic Salmon (Salmo salar).

Single-nucleotide polymorphisms (SNPs) are single genetic code variations considered one of the most common forms of nucleotide modifications. Such SNPs can be located in genes associated to immune response and, therefore, they may have direct implications over the phenotype of susceptibility to infections affecting the productive sector. In this study, a set of immune-related genes (cc motif chemokine 19 precursor [ccl19], integrin ß2 (itß2, also named cd18), glutathione transferase omega-1 [gsto-1], heat shock 70 KDa protein [hsp70], major histocompatibility complex class I [mhc-I]) were analyzed to identify SNPs by data mining. These genes were chosen based on their previously reported expression on infectious pancreatic necrosis virus (IPNV)-infected Atlantic salmon phenotype. The available EST sequences for these genes were obtained from the Unigene database. Twenty-eight SNPs were found in the genes evaluated and identified most of them as transition base changes. The effect of the SNPs located on the 5'-untranslated region (UTR) or 3'-UTR upon transcription factor binding sites and alternative splicing regulatory motifs was assessed and ranked with a low-medium predicted FASTSNP score risk. Synonymous SNPs were found on itß2 (c.2275G > A), gsto-1 (c.558G > A), and hsp70 (c.1950C > T) with low FASTSNP predicted score risk. The difference in the relative synonymous codon usage (RSCU) value between the variant codons and the wild-type codon (ΔRSCU) showed one negative (hsp70 c.1950C > T) and two positive ΔRSCU values (itß2 c.2275G > A; gsto-1 c.558G > A), suggesting that these synonymous SNPs (sSNPs) may be associated to differences in the local rate of elongation. Nonsynonymous SNPs (nsSNPs) in the gsto-1 translatable gene region were ranked, using SIFT and POLYPHEN web-tools, with the second highest (c.205A > G; c484T > C) and the highest (c.499T > C; c.769A > C) predicted score risk possible. Using homology modeling to predict the effect of these nonsynonymous SNPs, the most relevant nucleotide changes for gsto-1 were observed for the nsSNPs c.205A > G, c484T > C, and c.769A > C. Molecular dynamics was assessed to analyze if these GSTO-1 variants have significant differences in their conformational dynamics, suggesting these SNPs could have allosteric effects modulating its catalysis. Altogether, these results suggest that candidate SNPs identified may play a crucial potential role in the immune response of Atlantic salmon.

Carbon dioxide emission in relation with irrigation and organic amendments from a sweet corn field.

Soil moisture and organic matter level affects soil respiration and microbial activities, which in turn impact greenhouse gas (GHG) emissions. This study was conducted to evaluate the effect of irrigation levels (75% [deficit], 100% [full], and 125% [excess] of reference crop evapotranspiration requirements), and organic amendments (OA) type (chicken manure [CM] and bone meal [BM]) and OA application rates (0,168, 336 and 672 kg total N ha-1) on (i) soil physical properties (bulk density, organic matter content and soil moisture content) and (ii) soil carbon dioxide (CO2) emissions from a highly weathered tropical Hawai'ian soil. Carbon dioxide readings were consistently taken once or twice a week for the duration of the cropping season. A drip irrigation system was used to apply the appropriate amount of irrigation water to the treatment plots. Treatments were randomly selected and corresponding organic amendments were manually incorporated into the soil. Plots were cultivated with sweet corn (Zea mays 'SS-16'). Soil moisture content within and below the rootzone was monitored using a TDR 300 soil moisture sensor (Spectrum Technologies, Inc., Plainfield, IL, USA) connected with 12 cm long prongs. Soil bulk density and organic matter content were determined at the end of the cropping season. Analysis of variance results revealed that OA type, rate, and their interaction had significant effect on soil CO2 flux (P < 0.05). Among the OA rates, all CM mostly resulted in significantly higher soil CO2 fluxes compared to BM and control treatment (p < 0.05). The two highest rates of BM treatment were not significantly different from the control with regard to soil CO2 flux. In addition, organic amendments affected soil moisture dynamics during the crop growing season and organic matter content measured after the crop harvest. While additional studies are needed to further investigate the effect of irrigation levels on soil CO2 flux, it is recommended that in order to minimize soil CO2 emissions, BM soil amendments could be a potential option to reduce soil CO2 fluxes from agricultural fields similar to the one used in this study.

Functional assessment of pharmacological telomerase activators in human T cells.

Telomeres are structures at the ends of chromosomes that shorten during cell division and eventually signal an irreversible state of growth arrest known as cellular senescence. To delay this cellular aging, human T cells, which are critical in the immune control over infections and cancer, activate the enzyme telomerase, which binds and extends the telomeres. Several different extracts from the Astragalus membranaceus root have been documented to activate telomerase activity in human T cells. The objective of this research was to compare two extracts from Astragalus membranaceus, TA-65 and HTA, for their effects on both telomerase and proliferative activity of human CD4 and CD8 T cells. Our results demonstrate that, TA-65 increased telomerase activity significantly (1.3 to 3.3-fold relative to controls) in T cell cultures from six donors tested, whereas HTA only increased telomerase levels in two out of six donors. We also demonstrate that TA-65 activates telomerase by a MAPK- specific pathway. Finally, we determine that during a three-day culture period, only the T cells treated with the TA-65 extract showed a statistically significant increase in proliferative activity. Our results underscore the importance of comparing multiple telomerase activators within the same experiment, and of including functional assays in addition to measuring telomerase activity.

[The use of the Health Popular Insurance Program in pregnant women]. / Utilización del Seguro Popular de Salud en mujeres embarazadas.

OBJECTIVE: To evaluate the use of the Popular Insurance of health (PIH) during the pregnancy and the factors associated with its adquisicition. METHODS: From November of 2006 to January of the 2007, women in puerperal immediate hospitalized in the General Hospital of Tijuana, BC were invited to participate in the study. A direct interrogation through a structured questionnaire was applied, exploring sociodemographic variables, variables related to the pregnancy, trimester in which SPS was acquired, consumption of tobacco and alcohol, drug use, prenatal control, complications during the pregnancy, childbirth and time of hospital stay. Descriptive and bivaried analysis was performed to identify association between variables and the use of PIH. RESULTS: 730 women where studied. The average age was of 23-6 +/- 6.3, schooling 7.4 +/- 2.8 years and 72 % cohabitated. Five hundred and forty women (74 %) acquired PIH during pregnancy, 36 women never assist to antennal visits despite to have PIH and only 15 % already had it from the first trimester of pregnancy. Women with SPS had statically significant higher levels of schooling (7.8 versus. 6.8 p = 0.003), minor smoker frequency during pregnancy (1.5 % versus 4.2 %, p = 0.002) and minor rate of premature childbirth (3.7 versus 8.9, p=. 005). The mean catasthropic expenditure in women with not PIH was 2546 +/- 131 Mexican pesos. CONCLUSIONS: Fifty per cent of women acquired the PIH in the third trimester of pregnancy this could be related more to protecting households during periods of financial crisis than for utilization of prenatal care services.

O-glycosylation regulates LNCaP prostate cancer cell susceptibility to apoptosis induced by galectin-1.

Resistance to apoptosis is a critical feature of neoplastic cells. Galectin-1 is an endogenous carbohydrate-binding protein that induces death of leukemia and lymphoma cells, breast cancer cells, and the LNCaP prostate cancer cell line, but not other prostate cancer cell lines. To understand the mechanism of galectin-1 sensitivity of LNCaP cells compared with other prostate cancer cells, we characterized glycan ligands that are important for conferring galectin-1 sensitivity in these cells, and analyzed expression of glycosyltransferase genes in galectin-1-sensitive, prostate-specific antigen-positive (PSA(+)) LNCaP cells compared with a galectin-1-resistant PSA(-) LNCaP subclone. We identified one glycosyltransferase, core 2 N-acetylglucosaminyltransferase, which is down-regulated in galectin-1-resistant PSA(-) LNCaP cells compared with galectin-1-sensitive PSA(+) LNCaP cells. Intriguingly, this is the same glycosyltransferase required for galectin-1 susceptibility of T lymphoma cells, indicating that similar O-glycan ligands on different polypeptide backbones may be common death trigger receptors recognized by galectin-1 on different types of cancer cells. Blocking O-glycan elongation by expressing alpha2,3-sialyltransferase 1 rendered LNCaP cells resistant to galectin-1, showing that specific O-glycans are critical for galectin-1 susceptibility. Loss of galectin-1 susceptibility and synthesis of endogenous galectin-1 has been proposed to promote tumor evasion of immune attack; we found that galectin-1-expressing prostate cancer cells killed bound T cells, whereas LNCaP cells that do not express galectin-1 did not kill T cells. Resistance to galectin-1-induced apoptosis may directly contribute to the survival of prostate cancer cells as well as promote immune evasion by the tumor.

In vitro senescence of immune cells.

Immune cells are eminently suitable model systems in which to address the possible role of replicative senescence during in vivo aging. Since there are more than 10(8) unique antigen specificities present within the total T lymphocyte population of each individual, the immune response to any single antigen requires massive clonal expansion of the small proportion of T cells whose receptors recognize that antigen. The Hayflick Limit may, therefore, constitute a barrier to effective immune function, at least for those T cells that encounter their specific antigen more than once over the life course. Application of the fibroblast replicative senescence model to the so-called cytotoxic or CD8 T cell, the class of T cells that controls viral infection and cancer, has revealed certain features in common with other cell types as well as several characteristics that are unique to T cells. One senescence-associated change that is T cell-specific is the complete loss of expression of the activation signaling surface molecule, CD28, an alteration that enabled the documentation of high proportions of senescent T cells in vivo. The T cell model has also provided the unique opportunity to analyze telomere dynamics in a cell type that has the ability to upregulate telomerase yet nevertheless undergoes senescence. The intimate involvement of the immune system in the control of pathogens and cancer as well as in modulation of bone homeostasis suggests that more extensive analysis of the full range of characteristics of senescent T cells may help elucidate a broad spectrum of age-associated physiological changes.

Divergent telomerase and CD28 expression patterns in human CD4 and CD8 T cells following repeated encounters with the same antigenic stimulus.

Induction of telomerase, the enzyme that extends telomeres, accompanies human T lymphocyte activation. Nevertheless, high proportions of memory T cells with shortened telomeres are present in vivo during HIV infection and aging. To elucidate the long-term telomerase dynamics in human T cells, longitudinal analyses were performed on T cells subjected to repeated encounters with an allogeneic cell line in long-term culture. Whereas CD4(+) and CD8(+) T cells showed similarly dramatic increases in telomerase activity following primary stimulation, by the fourth stimulation, telomerase activity was nearly undetectable in the CD8(+) subset, but remained high in the CD4(+) subset. In addition, we document the dependence of antigen-specific telomerase inducibility on CD28 and that the decline in telomerase activity parallels the loss of CD28 expression. These findings suggest stringent telomerase regulation in human T cells, a property that may ultimately contribute to telomere shortening, finite replicative potential, and loss of control over certain pathogens.