Ney Bienvenido Arias Lora (1926-2007): The Dominican Republic's First Neurosurgeon.

BACKGROUND: Dr. Ney Bienvenido Arias Lora emerged not only as a pioneer in neurosurgery but a community leader in the Dominican Republic, contributing significantly to a region where both fundamental and neurosurgical resources were scarce. This account aims to shed light on the remarkable life and career of Dr. Arias Lora, emphasizing the critical role he played in establishing and advancing neurosurgery in the Dominican Republic. METHODS: This paper relies on original bibliographic materials, providing an in-depth analysis of Dr. Arias Lora's life. Through a thorough examination of his career, we aim to highlight his pioneering efforts in the Caribbeans where neurosurgical expertise was nearly non-existent during his time. RESULTS: Dr. Arias Lora, born in 1926, and became the first neurosurgeon in the Dominican Republic in 1959. He played a pivotal role in establishing the Neurosurgery Residency Program at the Hospital Salvador B. Gautier and was instrumental in the development of neurosurgery training in his home country and the Caribbeans. Beyond his medical contributions, Dr. Arias Lora served as an educator, authoring significant works, and holding prestigious academic positions. His legacy is reflected in the "Dr. Ney Arias Lora Traumatology Hospital" in Santo Domingo, a testament to his dedication to neurosurgery and public service. CONCLUSIONS: Dr. Ney Bienvenido Arias Lora's life and achievements stand as a testament to the transformative impact dedicated individuals can have on the advancement of neurosurgery. Despite the intricacies inherent in the field of neurosurgery and broader societal challenges, his story serves as an inspiration.

Atlas of fetal metabolism during mid-to-late gestation and diabetic pregnancy.

Mounting evidence suggests metabolism instructs stem cell fate decisions. However, how fetal metabolism changes during development and how altered maternal metabolism shapes fetal metabolism remain unexplored. We present a descriptive atlas of in vivo fetal murine metabolism during mid-to-late gestation in normal and diabetic pregnancy. Using 13C-glucose and liquid chromatography-mass spectrometry (LC-MS), we profiled the metabolism of fetal brains, hearts, livers, and placentas harvested from pregnant dams between embryonic days (E)10.5 and 18.5. Our analysis revealed metabolic features specific to a hyperglycemic environment and signatures that may denote developmental transitions during euglycemic development. We observed sorbitol accumulation in fetal tissues and altered neurotransmitter levels in fetal brains isolated from hyperglycemic dams. Tracing 13C-glucose revealed disparate fetal nutrient sourcing depending on maternal glycemic states. Regardless of glycemic state, histidine-derived metabolites accumulated in late-stage fetal tissues. Our rich dataset presents a comprehensive overview of in vivo fetal tissue metabolism and alterations due to maternal hyperglycemia.

SPH simulations and experimental investigation of water flow through a Venturi meter of rectangular cross-section.

The flow of water through a horizontal small-scale Venturi tube of rectangular cross-section is simulated using a modified version of the open-source code DualSPHysics, which is based on Smoothed Particle Hydrodynamics (SPH) methods. Water is simulated using the Murnaghan-Tait equation of state so that weak compressibility is allowed. The hydrodynamics is coupled to a Large-Eddy Simulation (LES) turbulence model. The convergence properties of SPH are improved by adopting a C[Formula: see text] Wendland function as the interpolation kernel, increased number of neighboring particles and non-reflective open boundary conditions at the outlet of the Venturi tube. The flow structure and differential pressure as well as the mainstream velocity profiles at different stations are compared with calibrated experimental data. A resolution independence test shows that good convergence to the experimental measurements is achieved using four million particles. At this resolution the simulations predict the experimental centerline velocity profile along the Venturi meter for a volumetric flow rate of ten liters per minutes (lpm) with a root-mean-square error of 4.3%. This error grows to 7.1% when the volumetric flow rate increases to 25 lpm. The predicted differential pressure matches the experimental data with errors varying from 1.4% (for 10 lpm) to 6.8% (for 25 lpm). Cross-sectional velocity profiles within the throat and divergent sections differ from the experimental measurements in less than 5.5%. In general, it is shown that the SPH model can provide an efficient and accurate method for recalibrating flow meters at moderately high Reynolds numbers instead of using costly experimental tests.

GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration.

The mammalian heart switches its main metabolic substrate from glucose to fatty acids shortly after birth. This metabolic switch coincides with the loss of regenerative capacity in the heart. However, it is unknown whether glucose metabolism regulates heart regeneration. Here, we report that glucose metabolism is a determinant of regenerative capacity in the neonatal mammalian heart. Cardiac-specific overexpression of Glut1, the embryonic form of constitutively active glucose transporter, resulted in an increase in glucose uptake and concomitant accumulation of glycogen storage in postnatal heart. Upon cryoinjury, Glut1 transgenic hearts showed higher regenerative capacity with less fibrosis than non-transgenic control hearts. Interestingly, flow cytometry analysis revealed two distinct populations of ventricular cardiomyocytes: Tnnt2-high and Tnnt2-low cardiomyocytes, the latter of which showed significantly higher mitotic activity in response to high intracellular glucose in Glut1 transgenic hearts. Metabolic profiling shows that Glut1-transgenic hearts have a significant increase in the glucose metabolites including nucleotides upon injury. Inhibition of the nucleotide biosynthesis abrogated the regenerative advantage of high intra-cardiomyocyte glucose level, suggesting that the glucose enhances the cardiomyocyte regeneration through the supply of nucleotides. Our data suggest that the increase in glucose metabolism promotes cardiac regeneration in neonatal mouse heart.

Challenges in Studying Stem Cell Metabolism.

The expanding field of stem cell metabolism has been supported by technical advances in metabolite profiling and novel functional analyses. While use of these methodologies has been fruitful, many challenges are posed by the intricacies of culturing stem cells in vitro, along with the distinctive scarcity of adult tissue stem cells and the complexities of their niches in vivo. This review provides an examination of the methodologies used to characterize stem cell metabolism, highlighting their utility while placing a sharper focus on their limitations and hurdles the field needs to overcome for the optimal study of stem cell metabolic networks.

Dipeptidyl peptidase 3, a novel protease from Leishmania braziliensis.

The increase of leishmaniasis cases worldwide and the emergence of Leishmania strains resistant to current treatments make necessary to find new therapeutic targets. Proteases are appealing drug targets because they play pivotal roles in facilitating parasite survival and promoting pathogenesis. Enzymes belonging to the dipeptidyl peptidase 3 (DPP3) group have been described in different organisms such as mammals, insects and yeast, in which these enzymes have been involved in both protein turnover and protection against oxidative damage. The aim of this work was to characterize the structure and function of the Leishmania braziliensis DPP3 (LbDPP3) protein as the first step to elucidate its suitability as a potential drug target. Sequence alignment showed 43% of identity between LbDPP3 and its human orthologous (hDPP3) enzyme. Although the modeled protein adopted a globally conserved three-dimensional (3D) structure, structural differences were found in the vicinity of the active site and the substrate binding-cleft. In addition, the Leishmania protein was expressed as a soluble recombinant protein and its kinetics parameters were determined using the z-Arginine-Arginine-AMC substrate. The LbDPP3 activity was maximal at pH values between 8.0-8.5. Interestingly, classical enzyme inhibitors such as the tynorphin and its derivative peptide IVYPW were found to actively inhibit the LbDPP3 activity. Moreover, these DPP3 inhibitors showed a detrimental effect upon parasite survival, decreasing the viability of promastigotes by up to 29%. Finally, it was observed that LbDPP3 was equally expressed along the in vitro differentiation from promastigotes to axenic amastigotes. In conclusion, these findings suggest that the L. brazileinsis DPP3 could be a promising drug target.

Leishmania braziliensis SCD6 and RBP42 proteins, two factors with RNA binding capacity.

BACKGROUND: The study of RNA binding proteins (RBPs) is of great relevance for understanding processes like post-transcriptional control of gene expression. The post-transcriptional mechanisms are particularly important in Leishmania parasites and related trypanosomatids since transcriptional regulation is almost absent in them. Thus, RBPs should be essential during the development of these parasites and for survival strategies against the adverse conditions that they face during their life-cycle. This work was aimed to do a structural and biochemical characterization of two Leishmania braziliensis proteins, which were previously found in pull-down assays using an HSP70 RNA as bait. At that time, these proteins were annotated as hypothetical proteins (LbrM.25.2210 and LbrM.30.3080) in the GeneDB database. RESULTS: Structural analysis indicated that these two proteins belong to evolutionarily conserved families; thus, they have been renamed accordingly as LbSCD6 (LbrM.25.2210) and LbRBP42 (LbrM.30.3080). We have demonstrated experimentally that these proteins are RBPs, in agreement with their structural features. Both proteins were able to bind to the complete 3' UTR-II region of HSP70-type II mRNA, and to an A + U rich element (ARE) present in that UTR. Cellular localization assays suggested that both proteins are mainly distributed in the cytoplasm of promastigotes growing at 26 °C, but they accumulate in foci around the nucleus when the parasites are under heat-shock conditions. Also, our study showed that steady-state levels of LbSCD6 and LbRBP42 transcripts decreased significantly during incubation of L. braziliensis promastigotes at heat-shock temperatures. However, in these conditions, the cellular content of both proteins remained unaltered. CONCLUSIONS: Our data suggest that LbSCD6 and LbRBP42, as occurs for their orthologues in other organisms, are involved in mRNA regulation, and probably they have a relevant role facing the stress conditions that L. braziliensis encounters during insect-to-mammalian transmission.

Leishmania braziliensis replication protein A subunit 1: molecular modelling, protein expression and analysis of its affinity for both DNA and RNA.

BACKGROUND: Replication factor A (RPA) is a single-strand DNA binding protein involved in DNA replication, recombination and repair processes. It is composed by the subunits RPA-1, RPA-2 and RPA-3; the major DNA-binding activity resides in the subunit 1 of the heterotrimeric RPA complex. In yeast and higher eukaryotes, besides the three basic structural DNA-binding domains, the RPA-1 subunit contains an N-terminal region involved in protein-protein interactions with a fourth DNA-binding domain. Remarkably, the N-terminal extension is absent in the RPA-1 of the pathogenic protozoan Leishmania (Leishmania) amazonensis; however, the protein maintains its ability to bind ssDNA. In a recent work, we identify Leishmania (Viannia) braziliensis RPA-1 by its specific binding to the untranslated regions of the HSP70 mRNAs, suggesting that this protein might be also an RNA-binding protein. METHODS: Both rLbRPA-1 purified by His-tag affinity chromatography as well as the in vitro transcribed L. braziliensis 3' HSP70-II UTR were used to perform pull down assays to asses nucleic acid binding properties. Also, homology modeling was carried out to construct the LbRPA-1 tridimensional structure to search relevant amino acid residues to bind nucleic acids. RESULTS: In this work, after obtaining the recombinant L. braziliensis RPA-1 protein under native conditions, competitive and non-competitive pull-down assays confirmed the single-stranded DNA binding activity of this protein and demonstrated its interaction with the 3' UTR from the HSP70-II mRNA. As expected, this protein exhibits a high affinity for ssDNA, but we have found that RPA-1 interacts also with RNA. Additionally, we carried out a structural analysis of L. braziliensis RPA-1 protein using the X-ray diffraction structure of Ustilago maydis homologous protein as a template. Our results indicate that, in spite of the evolutionary divergence between both organisms, the structure of these two RPA-1 proteins seems to be highly conserved. CONCLUSION: The LbRPA-1 protein is a ssDNA binding protein, but also it shows affinity in vitro for the HSP70 mRNA; this finding supports a possible in vivo role in the HSP70 mRNA metabolism. On the other hand, the three dimensional model of Leishmania RPA-1 serves as a starting point for both functional analysis and its exploration as a chemotherapeutic target to combat leishmaniasis.

DFT and docking studies of rhodostreptomycins A and B and their interactions with solvated/nonsolvated Mg²âº and Ca²âº ions.

The interactions of L-aminoglucosidic stereoisomers such as rhodostreptomycins A (Rho A) and B (Rho B) with cations (Mg(2+), Ca(2+), and H(+)) were studied by a quantum mechanical method that utilized DFT with B3LYP/6-311G. Docking studies were also carried out in order to explore the surface recognition properties of L-aminoglucoside with respect to Mg(2+) and Ca(2+) ions under solvated and nonsolvated conditions. Although both of the stereoisomers possess similar physicochemical/antibiotic properties against Helicobacter pylori, the thermochemical values for these complexes showed that its high affinity for Mg(2+) cations caused the hydration of Rho B. According to the results of the calculations, for Rho A-Ca(2+)(H2O)6, ΔH = -72.21 kcal mol(-1); for Rho B-Ca(2+)(H2O)6, ΔH = -72.53 kcal mol(-1); for Rho A-Mg(2+)(H2O)6, ΔH = -72.99 kcal mol(-1) and for Rho B-Mg(2+)(H2O)6, ΔH = -95.00 kcal mol(-1), confirming that Rho B binds most strongly with hydrated Mg(2+), considering the energy associated with this binding process. This result suggests that Rho B forms a more stable complex than its isomer does with magnesium ion. Docking results show that both of these rhodostreptomycin molecules bind to solvated Ca(2+) or Mg(2+) through hydrogen bonding. Finally, Rho B is more stable than Rho A when protonation occurs.

Alpha tubulin genes from Leishmania braziliensis: genomic organization, gene structure and insights on their expression.

BACKGROUND: Alpha tubulin is a fundamental component of the cytoskeleton which is responsible for cell shape and is involved in cell division, ciliary and flagellar motility and intracellular transport. Alpha tubulin gene expression varies according to the morphological changes suffered by Leishmania in its life cycle. However, the objective of studying the mechanisms responsible for the differential expression has resulted to be a difficult task due to the complex genome organization of tubulin genes and to the non-conventional mechanisms of gene regulation operating in Leishmania. RESULTS: We started this work by analyzing the genomic organization of α-tubulin genes in the Leishmania braziliensis genome database. The genomic organization of L. braziliensis α-tubulin genes differs from that existing in the L. major and L. infantum genomes. Two loci containing α-tubulin genes were found in the chromosomes 13 and 29, even though the existence of sequence gaps does not allow knowing the exact number of genes at each locus. Southern blot assays showed that α-tubulin locus at chromosome 13 contains at least 8 gene copies, which are tandemly organized with a 2.08-kb repetition unit; the locus at chromosome 29 seems to contain a sole α-tubulin gene. In addition, it was found that L. braziliensis α-tubulin locus at chromosome 13 contains two types of α-tubulin genes differing in their 3' UTR, each one presumably containing different regulatory motifs. It was also determined that the mRNA expression levels of these genes are controlled by post-transcriptional mechanisms tightly linked to the growth temperature. Moreover, the decrease in the α-tubulin mRNA abundance observed when promastigotes were cultured at 35°C was accompanied by parasite morphology alterations, similar to that occurring during the promastigote to amastigote differentiation. CONCLUSIONS: Information found in the genome databases indicates that α-tubulin genes have been reorganized in a drastic manner along Leishmania speciation. In the L. braziliensis genome database, two loci containing α-tubulin sequences were found, but only the locus at chromosome 13 contains the prototypic α-tubulin genes, which are repeated in a head-to-tail manner. Also, we determined that the levels of α-tubulin mRNAs are down-regulated drastically in response to heat shock by a post-transcriptional mechanism which is dependent upon active protein synthesis.

Identification of the HSP70-II gene in Leishmania braziliensis HSP70 locus: genomic organization and UTRs characterization.

BACKGROUND: The heat stress suffered by Leishmania sp during its digenetic life-cycle is a key trigger for its stage differentiation. In Leishmania subgenera two classes of HSP70 genes differing in their 3' UTR were described. Although the presence of HSP70-I genes was previously suggested in Leishmania (Viannia) braziliensis, HSP70-II genes had been reluctant to be uncovered. RESULTS: Here, we report the existence of two types of HSP70 genes in L. braziliensis and the genomic organization of the HSP70 locus. RT-PCR experiments were used to map the untranslated regions (UTR) of both types of genes. The 3' UTR-II has a low sequence identity (55-57%) when compared with this region in other Leishmania species. In contrast, the 5' UTR, common to both types of genes, and the 3' UTR-I were found to be highly conserved among all Leishmania species (77-81%). Southern blot assays suggested that L. braziliensis HSP70 gene cluster may contain around 6 tandemly-repeated HSP70-I genes followed by one HSP70-II gene, located at chromosome 28. Northern blot analysis indicated that levels of both types of mRNAs are not affected by heat shock. CONCLUSIONS: This study has led to establishing the composition and structure of the HSP70 locus of L. braziliensis, complementing the information available in the GeneDB genome database for this species. L. braziliensis HSP70 gene regulation does not seem to operate by mRNA stabilization as occurs in other Leishmania species.

Frequency and behavior of Salmonella and Escherichia coli on whole and sliced jalapeño and serrano peppers.

The frequencies of coliform bacteria (CB), thermotolerant coliforms (TC), Escherichia coli, and Salmonella were determined for jalapeño and serrano peppers. In addition, the behavior of four serotypes of Salmonella and three E. coli strains on whole and sliced jalapeño and serrano peppers as well as in blended sauce at 25 ± 2°C and 3 to 5°C was investigated. Chili peppers were collected from markets in the city of Pachuca, Hidalgo, Mexico. CB, TC, E. coli, and Salmonella were detected on serrano peppers in 100, 90, 50, and 10 % of the samples, and on jalapeño peppers in 100, 86, 32, and 12 % of the samples. Concentrations of CB ranged from 3.8 to 7.9 log CFU per serrano sample and from 5.3 to 8.2 log CFU per jalapeño sample, whereas concentrations of TC and E. coli were between < 3 and 1,100 most probable number per serrano and jalapeño samples. On whole serrano and jalapeño peppers stored at 25 ± 2°C or 3 to 5°C, no growth was observed for rifampin-resistant strains of Salmonella and E. coli. After 6 days at 25 ± 2°C, the tested Salmonella serotypes and E. coli strains had decreased from an initial inoculum level of 5 log CFU to 1 and 2.5 log on serrano and jalapeño peppers, respectively, and at 3 to 5°C they decreased to approximately 1.8 and 1.2 log, respectively, on serrano and jalapeño. Both the Salmonella serotypes and E. coli grew on sliced chili peppers and in blended sauce; after 24 h at 25 ± 2°C, both bacteria types had grown to approximately 4 and 5 log CFU on pepper slices and in sauce, respectively. At 3 to 5°C the bacterial growth was inhibited.

Mortalidad materna. Evolución de su estudio en México en los 25 años / Maternal mortality. Evolution of its study during the last 20 years

Tradicionalmente se ha considerado que el embarazo y el parto son procesos naturales, fisiológicos que deberían desarrollarse sin problemas para la madre. Sin embargo, tanto uno como el otro pueden ser motivo de complicaciones graves que pueden conducir a la muerte de la mujer con frecuencia variable, según diversos factores tales como la disponibilidad y calidad de la atención obstétrica así como las características de la población que en nuestro país son especiales, ya que en su mayoría corresponde a la llamada población abierta por no disponer de los servicios médicos asistenciales de instituciones de seguridad social y de la medicina privada y que es por lo tanto la de más baja condición socio-ecónomica motivos por los cuales la incidencia de mortalidad es alta, teniéndose tasas comprendidas entre 90.30 y 57.15 por 100,000 nacidos vivos, que difieren bastante de los de países desarrollados que varían entre 9 y 30 por 100,000 recién nacidos vivos, pudiéndose por lo tanto afirmar que las tasas de mortalidad materna de un país demuestran su grado de desarrollo

Ruptura Uterina: revisión de 5 años 1981-1985 en el Hospital de la Mujer / Uterine rupture: 5 year review at the Hospital de la Mujer

Se revisaron 20 casos de ruptura uterina atendidos en el Hospital de la Mujer de la S. S., en el periodo del 10. de enero de 1981 al 31 de diciembre de 1985. Se encontró un caso por cada 2,717 partos atendidos. La edad promedio en que ocurrió el accidente fue de 30 años, y la multiparidad fue factor predisponente. La cesárea previa se encontró en 50% de los casos y en 100% de éstos se tuvo ruptura uterina. Se clasificaron las causas en espontáneas, traumáticas e iatrogénicas; se analizó la profundidad, localización y cronología. La duración promedio del trabajo de parto en el momento de la ruptura fue de 10.38 horas. La presentación cefálica fue la más frecuente, seguida por el sufrimiento fetal el signo principal. el procedimiento anestseico predominante fue el bloqueo peridural. Se resolvieron cinco caoss por vía vaginal (25%), detectándose la ruptura al efectuarse revisión de cavidad. La mortalidad materna fue de 10% (2 casos) de los cuales solamente 1 (5%) fue atribuido directamente a la ruptura, la mortalidad fetal corregida fue de 15%