Intrauterine Transmission of Zika and Vertical Transfer of Neutralizing Antibodies Detected Immediately at Birth in Oaxaca, Mexico: An Analysis in the Context of Microcephaly.

Zika virus (ZIKV) can cause neurological issues in infants. To provide protection, neutralizing antibodies should be transferred from the mother to the infant. We conducted a study at the Hospital General de Pochutla, Oaxaca, Mexico. Samples were collected from mothers (blood and breast milk) and infants (saliva and dried blood spots) within the first 12 postnatal hours (December 2017 to February 2018) and tested for ZIKV total and neutralizing antibodies as well as ZIKV-PCR. Microcephaly was evaluated according to INTERGROWTH-21st standards. Maternal IgG seroprevalence was 28.4% with 10.4% active infection, while infant IgG seroprevalence was 5.5% with 2.4% active infection. There were two cases of virolactia, and 6.3% of the infant saliva samples tested positive for ZIKV. Additionally, 18.3% of the infants were in a cephalic perimeter percentile lower than 10 and had an association between microcephaly and serology or a PCR between 8.6 and 60.9%. The infant blood samples had neutralizing antibodies, indicating intrauterine protection. Microcephaly was correlated with serology or PCR, but in our study population, non-ZIKV factors may be involved as well. Low ZIKV infection values in breast milk mean that breastfeeding is safe in most of the mothers and infants of the endemic area studied.

Heavy Metal Pollution From a Major Earthquake and Tsunami in Chile Is Associated With Geographic Divergence of Clinical Isolates of Methicillin-Resistant Staphylococcus aureus in Latin America.

Methicillin-resistant Staphylococcus aureus (MRSA) is a priority pathogen listed by the World Health Organization. The global spread of MRSA is characterized by successive waves of epidemic clones that predominate in specific geographical regions. The acquisition of genes encoding resistance to heavy-metals is thought to be a key feature in the divergence and geographical spread of MRSA. Increasing evidence suggests that extreme natural events, such as earthquakes and tsunamis, could release heavy-metals into the environment. However, the impact of environmental exposition to heavy-metals on the divergence and spread of MRSA clones has been insufficiently explored. We assess the association between a major earthquake and tsunami in an industrialized port in southern Chile and MRSA clone divergence in Latin America. We performed a phylogenomic reconstruction of 113 MRSA clinical isolates from seven Latin American healthcare centers, including 25 isolates collected in a geographic area affected by an earthquake and tsunami that led to high levels of heavy-metal environmental contamination. We found a divergence event strongly associated with the presence of a plasmid harboring heavy-metal resistance genes in the isolates obtained in the area where the earthquake and tsunami occurred. Moreover, clinical isolates carrying this plasmid showed increased tolerance to mercury, arsenic, and cadmium. We also observed a physiological burden in the plasmid-carrying isolates in absence of heavy-metals. Our results are the first evidence that suggests that heavy-metal contamination, in the aftermath of an environmental disaster, appears to be a key evolutionary event for the spread and dissemination of MRSA in Latin America.

Gratitud eterna para los fundadores de la docencia médica en Cienfuegos

En el marco de los 40 años de la docencia médica en Cienfuegos, este artículo constituye un pequeño, pero sincero, homenaje para sus fundadores. El primer grupo de alumnos de 3er año de la carrera de Medicina, llegó en septiembre de 1980 al Hospital Dr. Gustavo Aldereguía Lima, de Cienfuegos. En este trabajo se hace una relatoría de los primeros trabajadores de la Unidad Docente, que radicó donde se encuentra hoy la oficina del Consejo Científico, la distribución de los alumnos y profesores por salas, la ubicación de los primeros albergues, las primeras actividades científicas, hoy Fórum Científico Estudiantil, el Movimiento de alumnos ayudantes, actividades extracurriculares: la primera actividad por el día de la mujer, las primeras celebraciones por el día del Educador, el primer chequeo de emulación de los tres centros de educación superior de la provincia, el inicio de las manifestaciones de la cultura, entre otros aspectos, anécdotas y comentarios.

Within the framework of 40 years of medical teaching in Cienfuegos, this article constitutes a small, but sincere, tribute to its founders. The first group of 3rd year Medicine students arrived in September 1980 at the Dr. Gustavo Aldereguía Lima Hospital in Cienfuegos. In this work, a report is made of the first workers of the Teaching Unit, which was located where the office of the Scientific Council is today, the distribution of students and teachers by rooms, the location of the first hostels, the first scientific activities, today the Student Scientific Forum, the Movement of student assistants, extracurricular activities: the first activity for Women's Day, the first celebrations for Educator's Day, the first emulation check of the three higher education centers in the province, the beginning of the manifestations of culture, among other aspects, anecdotes and comments.

Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries.

Objectives: Identify molecular mechanisms responsible for the in vitro non-susceptibility to ceftolozane/tazobactam (TOL) in a group of 158 clinical isolates of Pseudomonas aeruginosa from five Latin American countries collected before the introduction of TOL into the clinical practice. Methods: Clinical isolates of P. aeruginosa (n = 504) were collected between January 2016 and October 2017 from 20 hospitals located in Argentina, Brazil, Chile, Colombia, and Mexico. Minimum inhibitory concentrations (MICs) to TOL were determined by standard broth microdilution and interpreted according to CLSI breakpoints. Initially, production of carbapenemases in TOL non-susceptible isolates was assessed by Rapidec® followed by qPCR to detect bla KPC, bla NDM-1, bla VIM, and bla IMP. Illumina® WGS was performed for isolates in which non-susceptibility to TOL was not mediated by carbapenemases. Results: A total of 158 (31.3%) isolates were non-susceptible to TOL. In 74 (46.8%) of these isolates, non-susceptibility to TOL was explained by the production of at least one carbapenemase. WGS revealed that some isolates carried ESBLs, mutated bla PDC and ampD, associated with decreased susceptibility to TOL. Conclusion: Substitutions found in PDC and carbapenemase production were the most common presumed mechanisms of resistance to TOL detected in this study. This study shows that epidemiological surveillance is warranted to monitor the emergence of novel mechanisms of resistance to TOL that might compromise its clinical utility.

Multiomics characterization of methicillin-resistant Staphylococcus aureus (MRSA) isolates with heterogeneous intermediate resistance to vancomycin (hVISA) in Latin America.

BACKGROUND: Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) compromise the clinical efficacy of vancomycin. The hVISA isolates spontaneously produce vancomycin-intermediate Staphylococcus aureus (VISA) cells generated by diverse and intriguing mechanisms. OBJECTIVE: To characterize the biomolecular profile of clinical hVISA applying genomic, transcriptomic and metabolomic approaches. METHODS: 39 hVISA and 305 VSSA and their genomes were included. Core genome-based Bayesian phylogenetic reconstructions were built and alterations in predicted proteins in VISA/hVISA were interrogated. Linear discriminant analysis and a Genome-Wide Association Study were performed. Differentially expressed genes were identified in hVISA-VSSA by RNA-sequencing. The undirected profiles of metabolites were determined by liquid chromatography and hydrophilic interaction in six CC5-MRSA. RESULTS: Genomic relatedness of MRSA associated to hVISA phenotype was not detected. The change Try38 → His in Atl (autolysin) was identified in 92% of the hVISA. We identified SNPs and k-mers associated to hVISA in 11 coding regions with predicted functions in virulence, transport systems, carbohydrate metabolism and tRNA synthesis. Further, capABCDE, sdrD, esaA, esaD, essA and ssaA genes were overexpressed in hVISA, while lacABCDEFG genes were downregulated. Additionally, valine, threonine, leucine tyrosine, FAD and NADH were more abundant in VSSA, while arginine, glycine and betaine were more abundant in hVISA. Finally, we observed altered metabolic pathways in hVISA, including purine and pyrimidine pathway, CoA biosynthesis, amino acid metabolism and aminoacyl tRNA biosynthesis. CONCLUSIONS: Our results show that the mechanism of hVISA involves major changes in regulatory systems, expression of virulence factors and reduction in glycolysis via TCA cycle. This work contributes to the understanding of the development of this complex resistance mechanism in regional strains.

Differences in the subgingival microbiome according to stage of periodontitis: A comparison of two geographic regions.

No microbiological criteria were included in the 2018 EFP-AAP classification of periodontal diseases that could be used to differentiate between stages and grades. Furthermore, differences in the subgingival microbiome depending on stage and grade have not been established. Sixty subgingival biofilm samples were collected in Spain (n = 30) and Colombia (n = 30) from three distinct patient categories: those with periodontal health/gingivitis (n = 20), those with stage I-II periodontitis (n = 20), and those with stage III-IV periodontitis (n = 20). Patients were evaluated by 16S rRNA gene amplification sequencing. Amplicon sequence variants were used to assign taxonomic categories compared to the Human Oral Microbiome Database (threshold ≥97% identity). Alpha diversity was established by Shannon and Simpson indices, and principal coordinate analysis, ANOSIM, and PERMANOVA of the UNIFRAC distances were performed using QIIME2. Although differences in the alpha diversity were observed between samples according to country, Filifactor alocis, Peptostreptococcaceae [XI][G-4] bacterium HMT 369, Fretibacterium fastidiosum, Lachnospiraceae [G-8] bacterium HMT 500, Peptostreptococcaceae [XI][G-5] [Eubacterium] saphenum, Peptostreptococcus stomatis, and Tannerella forsythia were associated with periodontitis sites in all stages. However, only F. alocis, Peptostreptococcaceae [XI][G-4] bacterium HMT 369, Peptostreptococcaceae [XI][G-9] [Eubacterium] brachy, Peptostreptococcaceae [XI][G-5] [Eubacterium] saphenum, and Desulfobulbus sp. HMT 041 were consistent in stage III-IV periodontitis in both countries. Porphyromonas gingivalis and Tannerella forsythia were differentially expressed in severe lesions in the countries studied. Although some non-cultivable microorganisms showed differential patterns between the different stages of periodontitis, they were not the same in the two countries evaluated. Further studies using larger samples with advanced next-generation techniques for high-throughput sequencing of phyla and non-cultivable bacteria within the subgingival microbiome could provide more insight into the differences between stages of periodontitis.

Structural and ultrastructural renal lesions in rats fed high-fat and high-phosphorus diets.

BACKGROUND: Foods prone to deteriorate renal function are rich in fat and in phosphorus (P), but the interaction between these two factors is not well studied. METHOD: Detailed structural and ultrastructural histopathological studies were performed on the kidneys of rats fed different amounts of fat and P: low (4%) fat (LF) and normal (0.6%) P (NP), LF and high (1.2%) P (HP), high (35%) fat (HF) and NP, HF and HP, and HF with low (0.2%) P (LP) for 28 weeks. RESULTS: Glomeruli of the HF groups showed segmental areas of retraction, sclerosis and thickening of the Bowman's capsule and basal membranes, which were more accentuated in the HF-HP group. Ultrastructural lesions in the glomeruli also were prominent in rats fed HF, particularly in the HF-HP group, and included thickening of the capillary membrane, endothelial damage, mesangial matrix hypercellularity and podocyte effacement. P restriction reduced the severity of endothelial damage, mesangial matrix hypercellularity, thickening of capillary basement membrane and podocyte effacement. The kidneys of rats fed HP showed significant tubular atrophy and dilatation, focal tubular hyperplasia, thickening of the tubular basal membrane, interstitial edema, inflammation and calcification. All groups fed HF also showed tubular lesions that were more prominent in the HF-HP group. P restriction had a beneficial effect on inflammation and calcification. CONCLUSIONS: Intake of both HF and HP damages the kidneys and their noxious effects are additive. HF intake was preferentially associated with glomerular lesions, while lesions related to HP intake were located mainly in the tubuli and in the interstitium.

A Test for the Rapid Detection of the Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus.

The cefazolin inoculum effect (CzIE) has been associated with therapeutic failures and mortality in invasive methicillin-susceptible Staphylococcus aureus (MSSA) infections. A diagnostic test to detect the CzIE is not currently available. We developed a rapid (∼3 h) CzIE colorimetric test to detect staphylococcal-ß-lactamase (BlaZ) activity in supernatants after ampicillin induction. The test was validated using 689 bloodstream MSSA isolates recovered from Latin America and the United States. The cefazolin MIC determination at a high inoculum (107 CFU/ml) was used as a reference standard (cutoff ≥16 µg/ml). All isolates underwent genome sequencing. A total of 257 (37.3%) of MSSA isolates exhibited the CzIE by the reference standard method. The overall sensitivity and specificity of the colorimetric test was 82.5% and 88.9%, respectively. Sensitivity in MSSA isolates harboring type A BlaZ (the most efficient enzyme against cefazolin) was 92.7% with a specificity of 87.8%. The performance of the test was lower against type B and C enzymes (sensitivities of 53.3% and 72.3%, respectively). When the reference value was set to ≥32 µg/ml, the sensitivity for isolates carrying type A enzymes was 98.2%. Specificity was 100% for MSSA lacking blaZ The overall negative predictive value ranged from 81.4% to 95.6% in Latin American countries using published prevalence rates of the CzIE. MSSA isolates from the United States were genetically diverse, with no distinguishing genomic differences from Latin American MSSA, distributed among 18 sequence types. A novel test can readily identify most MSSA isolates exhibiting the CzIE, particularly those carrying type A BlaZ. In contrast to the MIC determination using high inoculum, the rapid test is inexpensive, feasible, and easy to perform. After minor validation steps, it could be incorporated into the routine clinical laboratory workflow.

Evaluation of aquafitness exercise on the physical and mental health of older women: a pilot study.

Physical activity is a priority to improve health. However, a sedentary lifestyle is increasingly becoming the norm. For example, in Mexico, sedentarism has increased, especially among older women. This study evaluated the effects of aquafitness on the health of older women in Mexico. Healthy older women performed aquafitness exercise and were compared to a control group of comparable women. Outcome assessments performed at baseline and after 17-weeks included psychological and physical/anthropometric measures. Participants in aquafitness became more optimistic, lost more weight, body fat, and a subsequent decrease in BMI, compared to controls. The results suggest important avenues for future research.

Dynamics of blaKPC-2 Dissemination from Non-CG258 Klebsiella pneumoniae to Other Enterobacterales via IncN Plasmids in an Area of High Endemicity.

Carbapenem-resistant Enterobacterales (CRE) pose a significant threat to global public health. The most important mechanism for carbapenem resistance is the production of carbapenemases. Klebsiella pneumoniae carbapenemase (KPC) represents one of the main carbapenemases worldwide. Complex mechanisms of blaKPC dissemination have been reported in Colombia, a country with a high endemicity of carbapenem resistance. Here, we characterized the dynamics of dissemination of blaKPC gene among CRE infecting and colonizing patients in three hospitals localized in a highly endemic area of Colombia (2013 and 2015). We identified the genomic characteristics of KPC-producing Enterobacterales recovered from patients infected/colonized and reconstructed the dynamics of dissemination of blaKPC-2 using both short and long read sequencing. We found that spread of blaKPC-2 among Enterobacterales in the participating hospitals was due to intra- and interspecies horizontal gene transfer (HGT) mediated by promiscuous plasmids associated with transposable elements that was originated from a multispecies outbreak of KPC-producing Enterobacterales in a neonatal intensive care unit. The plasmids were detected in isolates recovered in other units within the same hospital and nearby hospitals. The gene "epidemic" was driven by IncN-pST15-type plasmids carrying a novel Tn4401b structure and non-Tn4401 elements (NTEKPC) in Klebsiella spp., Escherichia coli, Enterobacter spp., and Citrobacter spp. Of note, mcr-9 was found to coexist with blaKPC-2 in species of the Enterobacter cloacae complex. Our findings suggest that the main mechanism for dissemination of blaKPC-2 is HGT mediated by highly transferable plasmids among species of Enterobacterales in infected/colonized patients, presenting a major challenge for public health interventions in developing countries such as Colombia.

Case Report: Gestational Melioidosis through Perinatal Transmission.

Burkholderia pseudomallei is an emerging pathogen in the Americas. Cases of mother-to-child transmission of B. pseudomallei are rare and probably occur by placental or perinatal infection. We report the first case of native gestational and neonatal melioidosis in the Western hemisphere. The isolated strains in the mother and newborn were confirmed by whole-genome sequencing and identified as a novel sequence type ST1748. The comparison of both genomes revealed a nucleotide similarity of 100%. Melioidosis should be considered within the differential diagnosis of febrile illness or pneumonia in pregnant women and newborns from endemic areas of the Americas.

Detection of heterogeneous vancomycin intermediate resistance in MRSA isolates from Latin America.

BACKGROUND: Vancomycin is a common first-line option for MRSA infections. The heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) phenotype is associated with therapeutic failure. However, hVISA isolates are usually reported as vancomycin susceptible by routine susceptibility testing procedures. OBJECTIVES: To detect and characterize the hVISA phenotype in MRSA isolates causing infections in nine Latin American countries. METHODS: We evaluated a total of 1189 vancomycin-susceptible MRSA isolates recovered during 2006-08 and 2011-14. After an initial screening of hVISA using glycopeptide-supplemented agar strategies, the detection of hVISA was performed by Etest (GRD) and Macro-method (MET). Isolates deemed to be hVISA were subjected to population analysis profile/AUC (PAP/AUC) and WGS for further characterization. Finally, we interrogated alterations in predicted proteins associated with the development of the VISA phenotype in both hVISA and vancomycin-susceptible S. aureus (VSSA) genomes. RESULTS: A total of 39 MRSA isolates (3.3%) were classified as hVISA (1.4% and 5.6% in MRSA recovered from 2006-08 and 2011-14, respectively). Most of the hVISA strains (95%) belonged to clonal complex (CC) 5. Only 6/39 hVISA isolates were categorized as hVISA by PAP/AUC, with 6 other isolates close (0.87-0.89) to the cut-off (0.9). The majority of the 39 hVISA isolates exhibited the Leu-14→Ile (90%) and VraT Glu-156→Gly (90%) amino acid substitutions in WalK. Additionally, we identified 10 substitutions present only in hVISA isolates, involving WalK, VraS, RpoB and RpoC proteins. CONCLUSIONS: The hVISA phenotype exhibits low frequency in Latin America. Amino acid substitutions in proteins involved in cell envelope homeostasis and RNA synthesis were commonly identified. Our results suggest that Etest-based methods are an important alternative for the detection of hVISA clinical isolates.

A Young Diabetic Patient With Sepsis After Gardening.

We report a case of soft tissue infection, sepsis, and bacteremia due to Burkholderia pseudomallei (melioidosis) in a diabetic young patient and the genomic characterization of Burkholderia pseudomallei isolate (COL-5428).

Genomic Epidemiology of Vancomycin-Resistant Enterococcus faecium (VREfm) in Latin America: Revisiting The Global VRE Population Structure.

Little is known about the population structure of vancomycin-resistant Enterococcus faecium (VREfm) in Latin America (LATAM). Here, we provide a complete genomic characterization of 55 representative Latin American VREfm recovered from 1998-2015 in 5 countries. The LATAM VREfm population is structured into two main clinical clades without geographical clustering. Using the LATAM genomes, we reconstructed the global population of VREfm by including 285 genomes from 36 countries spanning from 1946 to 2017. In contrast to previous studies, our results show an early branching of animal related isolates and a further split of clinical isolates into two sub-clades within clade A. The overall phylogenomic structure of clade A was highly dependent on recombination (54% of the genome) and the split between clades A and B was estimated to have occurred more than 2,765 years ago. Furthermore, our molecular clock calculations suggest the branching of animal isolates and clinical clades occurred ~502 years ago whereas the split within the clinical clade occurred ~302 years ago (previous studies showed a more recent split between clinical an animal branches around ~74 years ago). By including isolates from Latin America, we present novel insights into the population structure of VREfm and revisit the evolution of these pathogens.

Novel Insights into the Classification of Staphylococcal ß-Lactamases in Relation to the Cefazolin Inoculum Effect.

Cefazolin has become a prominent therapy for methicillin-susceptible Staphylococcus aureus (MSSA) infections. However, an important concern is the cefazolin inoculum effect (CzIE), a phenomenon mediated by staphylococcal ß-lactamases. Four variants of staphylococcal ß-lactamases have been described based on serological methodologies and limited sequence information. Here, we sought to reassess the classification of staphylococcal ß-lactamases and their correlation with the CzIE. We included a large collection of 690 contemporary bloodstream MSSA isolates recovered from Latin America, a region with a high prevalence of the CzIE. We determined cefazolin MICs at standard and high inoculums by broth microdilution. Whole-genome sequencing was performed to classify the ß-lactamase in each isolate based on the predicted full sequence of BlaZ. We used the classical schemes for ß-lactamase classification and compared it to BlaZ allotypes found in unique sequences using the genomic information. Phylogenetic analyses were performed based on the BlaZ and core-genome sequences. The overall prevalence of the CzIE was 40%. Among 641 genomes, type C was the most predominant ß-lactamase (37%), followed by type A (33%). We found 29 allotypes and 43 different substitutions in BlaZ. A single allotype, designated BlaZ-2, showed a robust and statistically significant association with the CzIE. Two other allotypes (BlaZ-3 and BlaZ-5) were associated with a lack of the CzIE. Three amino acid substitutions (A9V, E112A, and G145E) showed statistically significant association with the CzIE (P = <0.01). CC30 was the predominant clone among isolates displaying the CzIE. Thus, we provide a novel approach to the classification of the staphylococcal ß-lactamases with the potential to more accurately identify MSSA strains exhibiting the CzIE.

Home chemical and microbial transitions across urbanization.

Urbanization represents a profound shift in human behaviour, and has considerable cultural and health-associated consequences1,2. Here, we investigate chemical and microbial characteristics of houses and their human occupants across an urbanization gradient in the Amazon rainforest, from a remote Peruvian Amerindian village to the Brazilian city of Manaus. Urbanization was found to be associated with reduced microbial outdoor exposure, increased contact with housing materials, antimicrobials and cleaning products, and increased exposure to chemical diversity. The degree of urbanization correlated with changes in the composition of house bacterial and microeukaryotic communities, increased house and skin fungal diversity, and an increase in the relative abundance of human skin-associated fungi and bacteria in houses. Overall, our results indicate that urbanization has large-scale effects on chemical and microbial exposures and on the human microbiota.

Extensively Drug-Resistant Pseudomonas aeruginosa ST309 Harboring Tandem Guiana Extended Spectrum ß-Lactamase Enzymes: A Newly Emerging Threat in the United States.

BACKGROUND: Treatment of serious infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa remains a challenge, despite the introduction of novel therapeutics. In this study, we report 2 extensively drug-resistant clinical isolates of sequence type (ST) 309 P aeruginosa resistant to all ß-lactams, including the novel combinations ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam. METHODS: Isolates were sequenced using both short-read (Illumina) and long-read technology to identify resistance determinants, polymorphisms (compared with P aeruginosa PAO1), and reconstruct a phylogenetic tree. A pair of ß-lactamases, Guiana extended spectrum ß-lactamase (GES)-19 and GES-26, were cloned and expressed in a laboratory strain of Escherichia coli to examine their relative impact on resistance. Using cell lysates from E coli expressing the GES genes individually and in tandem, we determined relative rates of hydrolysis for nitrocefin and ceftazidime. RESULTS: Two ST309 P aeruginosa clinical isolates were found to harbor the extended spectrum ß-lactamases GES-19 and GES-26 clustered in tandem on a chromosomal class 1 integron. The presence of both enzymes in E coli was associated with significantly elevated minimum inhibitory concentrations to aztreonam, cefepime, meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam, compared with those expressed individually. The combination of ceftazidime/avibactam plus aztreonam was active in vitro and used to achieve cure in one patient. Phylogenetic analysis revealed ST309 P aeruginosa are closely related to MDR strains from Mexico also carrying tandem GES. CONCLUSIONS: The presence of tandem GES-19 and GES-26 is associated with resistance to all ß-lactams, including ceftolozane/tazobactam. Phylogenetic analysis suggests that ST309 P aeruginosa may be an emerging threat in the United States.

Circulating miR-141-3p, miR-143-3p and miR-200c-3p are differentially expressed in colorectal cancer and advanced adenomas.

Colorectal cancer (CRC) is one of the prominent causes of cancer related deaths because, in part, there is not an early, non-invasive, effective detection strategy. Circulating microRNAs (miRNAs) have been proposed as potential non-invasive biomarkers for CRC. In this study, we evaluated the miRNA profile in sixteen CRC tissues by Next-Generation-Sequencing and compared the circulating expression levels of 22 miRNAs among 45 CRC, 14 hyperplastic polyps, 11 advanced adenoma patients and 45 control subjects, by reverse transcription-quantitative PCR, to search for miRNAs which could be potential biomarkers. In total, nine of them represented 70% of total read counts (miR-10a-5p, miR-192-5p, miR-10b-5p, miR-22-3p, miR-26a-5p, miR-148a-3p, miR-181a-5p, miR-92a-3p and miR-143-5p). In silico analysis found eight candidates to mature miRNAs. With respect to circulating miRNA, we found higher serum expression levels of miR-143-3p, miR-141-3p and miR-200c-3p in the CRC and adenoma groups compared with controls (P<0.002), and we also found significant higher levels of miR-141-3p and miR-200c-3p in serum of adenoma patients compared with the CRC group. In conclusion, the measurement of miRNAs in the blood could complement current screening methods for CRC and might provide new insights into mechanisms of tumorigenesis. miR-143-3p, miR-141-3p and miR-200c-3p could be interesting miRNAs to study as potential biomarkers for CRC.

Low birth weight and PM2.5 in Puerto Rico.

BACKGROUND: Low birth weight (LBW) has been associated with adverse health outcomes across the lifespan. Among ethnic/racial minority populations, few studies have examined the association between LBW (<2,500 or ≥2,500 g) and prenatal exposure to air pollution, a key modifiable environmental risk factor. METHODS: We examined the association between LBW and prenatal exposure to PM2.5 in a Hispanic and black population in Puerto Rico between 1999 and 2013, adjusting for individual and municipality-level confounders. We used modified Poisson regression to estimate the association and performed sensitivity analyses treating birth weight as continuous or polychotomous. In secondary analyses, we applied a 2-stage mixed effects model suitable for longitudinally measured exposures and binary outcomes. RESULTS: Among 332,129 total and 275,814 term births, 12.2% and 6.3% of infants had LBW, respectively. Eighty-eight percent of mothers were Hispanic. Mean (SD) PM2.5 concentrations declined from 9.9 (1.7) µg/m3 in 1999 to 6.1 (1.1) µg/m3 in 2013. Mean birth weights dropped to 3,044 g in 2010 and rose steadily afterward. Among term births, a SD increase in PM2.5 was associated with a 3.2% (95% CI = -1.0%, 6.3%) higher risk of LBW. First (risk ratio, 1.02; 95% CI = 1.00, 1.04) and second (1.02; 95% CI = 1.01, 1.05) trimester exposures were associated with increased LBW risk. In a 2-stage approach that longitudinally modeled monthly prenatal exposure levels, a standard deviation increase in average PM2.5 was associated with higher risk of LBW (odds ratio, 1.04; 95% CI = 1.01, 1.08). CONCLUSIONS: In Puerto Rico, LBW is associated with prenatal PM2.5 exposure.

Terapia hormonal en la transición femenino a masculino (ftm), androgénica, para trans masculino o para hombre transgénero / Hormone Therapy in Female to Male Transition (FTM), Androgenic, Trans Male, or Transgender Male

RESUMEN La transexualidad, o el ser transgénero según la nomenclatura actual, describe a personas que persistentemente buscan ser aceptados como miembros del sexo opuesto, desean cambiar sus caracteres sexuales primarios y/o secundarios a través de intervenciones médicas tanto hormonales como quirúrgicas para feminizarse o masculinizarse. (Tabla 1) Esta discordancia entre su "sexo biológico" y "psicológico" genera estrés clínicamente significativo con rechazo profundo al cuerpo del sexo anatómico, al género asignado al nacer y, por ende, alteración persistente en el funcionamiento diario (mayor a 6 meses), se denomina disforia de género, sienten que nacieron en el "cuerpo equivocado". El objetivo de la intervención médica es mejorar la disforia de género y, por consiguiente, mejora el bienestar y la calidad de vida de las personas trans. En Revista de la Sociedad Chilena de Obstetricia y Ginecología Infantil y de la Adolescencia, recientemente hemos publicado dos artículos de revisión sobre la introducción a la Hormonoterapia en personas transexuales, objetivos de la terapia, transición en la adolescencia, y la transición masculino a femenino, por lo que éste escrito se concentrará sólo en la Terapia Hormonal de la transición femenino a Masculino (FTM), son personas que transitan de Mujer a Hombre, o transgénero masculino o trans masculino. (1,2)

ABSTRACT Transsexuality, or being transgender according to the current nomenclature, describes people who persistently seek to be accepted as members of the opposite sex, wish to change their primary and / or secondary sexual characteristics through both hormonal and surgical medical interventions to feminize or masculinize themselves. (Table 1) This discordance between their "biological" and "psychological" sex, generates clinically significant stress with profound rejection of the body of the anatomical sex, the gender assigned at birth and, therefore, persistent alteration in daily functioning (more than 6 months), is called gender dysphoria feel that they were born in the "wrong Body". The goal of medical intervention is to improve gender dysphoria and, consequently, improve the well-being and quality of life of transgender people. In the Journal of the Chilean Society of Obstetrics and Child and Adolescent Gynecology, we have recently published two review articles on the introduction of Hormonotherapy in transgender people, goals of therapy, transition in adolescence, and the male-to-female transition, so this paper will focus only on Hormonal Therapy of the female to male transition (FTM), are people who transit from woman to man, or male trans, male transgender. (1,2)