Caracterización del bienestar en hogares mexicanos de niñas y niños con diarrea, Ensanut Continua 2022.

OBJETIVO: Analizar el nivel de bienestar en los hogares mexicanos de niñas y niños menores de cinco años que presentaron enfermedad diarreica aguda (EDA) en las últimas dos semanas en México, según la Encuesta Nacional de Salud y Nutrición Continua 2022 (Ensanut Continua 2022). Material y métodos. La encuesta se realizó entre julio y diciembre de 2022. Variable dependiente: ocurrencia de EDA. Variable independiente: nivel de bienestar de los hogares. Se realizó análisis bivariado y regresiones logísticas crudas y ajustadas. RESULTADOS: Se estima que 9.4% de los menores de cinco años presentaron EDA, de quienes 76.4% (IC95%: 69.0,82.5) pertenecía a hogares con nivel de bienestar bajo-medio. La EDA fue más frecuente en los niños y niñas de un año de edad (razón de momios ajustada [RMa] 3.00; IC95%: 1.76,5.11), en comparación con quienes tenían menor edad y en los hogares donde el agua para beber no es tratada (RMa 2.13; IC95%: 1.11,4.08). CONCLUSIONES: Se requiere fortalecer las medidas sanitarias preventivas de EDA en niñas y niños de un año de edad, principalmente implementar acciones para asegurar la disponibilidad de agua potable o el tratamiento adecuado para beberla, y planear, ejecutar y evaluar acciones de política pública integrales y multisectoriales para coadyuvar en garantizar el derecho humano a la salud durante la niñez.

Cobertura de vacunación en niños, niñas y adolescentes en México.

OBJETIVO: Describir las coberturas de vacunación en 2022 en niñas, niños y en adolescentes, así como comparar las prevalencias observadas con los datos de la Encuesta Nacional de Salud y Nutrición 2021 (Ensanut 2021). Material y métodos. Análisis de datos obtenidos de la Ensanut 2022. RESULTADOS: En los niños menores de cinco años, las coberturas de vacuna con Bacilo de Calmette y Guérin (BCG), hepatitis B, pentavalente o hexavalente, neumocócica, antirotavirus y triple viral (SRP) fueron de 78.5% (IC95%: 70.8,84.6), 65.1% (IC95%: 58.4,71.2), 69.0% (IC95%: 61.8,75.4), 88.0% (IC95%: 83.0,91.7), 81.6% (IC95%: 75.7,86.2) y 61.8% (IC95%: 55.6,67.6), respectivamente. Al primer y segundo año de vida, 42.6% (IC95%: 34.3,51.4) y 26.6% (IC95%: 22.1,31.5) habían recibido el esquema correspondiente. Se redujo la cobertura estimada para primera dosis de SRP 72.6% (IC95%: 67.5,77.1) vs. 61.8% (IC95%: 55.6,67.5). En adolescentes, el antecedente de vacunación contra VPH, hepatitis B, tétanos y doble viral (SR) lo refirieron en 43.7% (IC95%: 39.9,47.6), 31.8% (IC95%: 29.8,34.0), 38.5% (IC95%: 35.9,41.2) y 32.6% (IC95%: 30.15,35.1). Conclusión. No se alcanza la meta de cobertura de 90% para ningún inmunógeno investigado. La cobertura para primera dosis de SRP se ha reducido.

Porcentaje de infección respiratoria aguda en menores de cinco años en México. Ensanut Continua 2022.

OBJETIVO: Estimar el porcentaje de infección respiratoria aguda (IRA) en menores de cinco años en las últimas dos semanas en México, de acuerdo con los datos de la Encuesta Nacional de Salud y Nutrición Continua 2022 (Ensanut Continua 2022). Material y métodos. Se analizaron datos de la Ensanut Continua 2022. RESULTADOS: El porcentaje de IRA fue de 27.6% (IC95%: 25.2,30.1). La prevalencia fue mayor en el primer tercil socioeconómico (44.1% [IC95%: 38.0,50.4]). El signo de alarma IRA más identificado fue "verse más enfermo" 33.0% (IC95%: 30.1,36.0) y el menos identificado fue "salir pus del oído" (1.5% [IC95%: 0.9,2.7]). CONCLUSIONES: Las IRA afectan cerca de una tercera parte de los niños y las niñas menores de cinco años en México, particularmente de los hogares con menores capacidades económicas. Es necesario fortalecer las estrategias de prevención, entre ellas la vacunación, el control y la promoción de la salud.

Porcentaje de enfermedad diarreica aguda en menores de cinco años en México. Ensanut Continua 2022.

OBJETIVO: Estimar el porcentaje de enfermedad diarreica aguda (EDA) en menores de cinco años en las últimas dos semanas, de acuerdo con los datos de la Encuesta Nacional de Salud y Nutrición Continua 2022. Material y métodos. Se analizaron los datos de menores de cinco años incluidos en la Encuesta Nacional de Salud y Nutrición Continua 2022 respecto a la EDA en las últimas dos semanas. Se compararon los datos con los de ediciones previas de la encuesta. RESULTADOS: El porcentaje de EDA en México fue de 9.4% (IC95%: 7.9,11.2), similar al de 2000, con diferencias por grupo etario. Durante el episodio de EDA, 38.7% (IC95%: 27.7,51.0) de las personas cuidadoras ofrecen menor cantidad de alimentos a la habitual. CONCLUSIONES: El elevado porcentaje de EDA en menores de cinco años en México en el 2022 evidencia la necesidad de fortalecer estrategias de prevención y promoción de la salud.

Vacunación en adultos y adultos mayores en México.

OBJETIVO: Estimar la prevalencia del antecedente de vacunación en adultos de 20 a 59 años y mayores de 60 años mediante autorreporte. Material y métodos. Análisis de datos obtenidos de la Encuesta Nacional de Salud y Nutrición 2022 (Ensanut 2022). RESULTADOS: El 27.4% de los adultos de 20-39 años refirió haber recibido vacuna doble viral (sarampión y rubeola [SR]) y 57.3% de adultos de 20-59 años cualquier vacuna con toxoide tetánico (Td) en los últimos diez años. En mujeres de 29 a 49 años, 18.7% (IC95%: 17.0,20.5) y 58.46% (IC95%: 56.2,60.7) habían sido vacunadas con vacuna SR y Td, respectivamente. En mayores de 60 años, 48.8% (IC95%: 45.9,51.7), 24.4% (IC95%: 22.2,26.8) y 49.1% (IC95%: 46.1,52.2) informaron haber recibido cualquier vacuna conteniendo Td, vacuna antineumococo y vacuna antiinfluenza estacional desde septiembre del año anterior a la encuesta, respectivamente. Conclusión. Los resultados de este estudio muestran que una proporción considerable de adultos, mujeres en edad fértil y adultos mayores no estaban protegidos contra enfermedades prevenibles por vacunación en 2022.

Mexican Biobank advances population and medical genomics of diverse ancestries.

Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories and complex trait architectures remain hidden owing to insufficient data1. To fill this gap, the Mexican Biobank project genotyped 6,057 individuals from 898 rural and urban localities across all 32 states in Mexico at a resolution of 1.8 million genome-wide markers with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database. Here, using ancestry deconvolution and inference of identity-by-descent segments, we inferred ancestral population sizes across Mesoamerican regions over time, unravelling Indigenous, colonial and postcolonial demographic dynamics2-6. We observed variation in runs of homozygosity among genomic regions with different ancestries reflecting distinct demographic histories and, in turn, different distributions of rare deleterious variants. We conducted genome-wide association studies (GWAS) for 22 complex traits and found that several traits are better predicted using the Mexican Biobank GWAS compared to the UK Biobank GWAS7,8. We identified genetic and environmental factors associating with trait variation, such as the length of the genome in runs of homozygosity as a predictor for body mass index, triglycerides, glucose and height. This study provides insights into the genetic histories of individuals in Mexico and dissects their complex trait architectures, both crucial for making precision and preventive medicine initiatives accessible worldwide.

Demographic modeling of admixed Latin American populations from whole genomes.

Demographic models of Latin American populations often fail to fully capture their complex evolutionary history, which has been shaped by both recent admixture and deeper-in-time demographic events. To address this gap, we used high-coverage whole-genome data from Indigenous American ancestries in present-day Mexico and existing genomes from across Latin America to infer multiple demographic models that capture the impact of different timescales on genetic diversity. Our approach, which combines analyses of allele frequencies and ancestry tract length distributions, represents a significant improvement over current models in predicting patterns of genetic variation in admixed Latin American populations. We jointly modeled the contribution of European, African, East Asian, and Indigenous American ancestries into present-day Latin American populations. We infer that the ancestors of Indigenous Americans and East Asians diverged ∼30 thousand years ago, and we characterize genetic contributions of recent migrations from East and Southeast Asia to Peru and Mexico. Our inferred demographic histories are consistent across different genomic regions and annotations, suggesting that our inferences are robust to the potential effects of linked selection. In conjunction with published distributions of fitness effects for new nonsynonymous mutations in humans, we show in large-scale simulations that our models recover important features of both neutral and deleterious variation. By providing a more realistic framework for understanding the evolutionary history of Latin American populations, our models can help address the historical under-representation of admixed groups in genomics research and can be a valuable resource for future studies of populations with complex admixture and demographic histories.

Safety and Tolerability of Six Months of Isoniazid Plus Pyridoxine or Three Months of Rifampicin for Tuberculosis among Subjects with Diabetes Mellitus: A Randomized Trial.

Tuberculosis (TB) associated with diabetes mellitus (DM) is a growing problem, particularly in low- and medium-resource countries. We conducted an open-label, parallel-group, randomized, and controlled trial in a tertiary care center in Mexico City to assess TB preventive treatment (TPT) with isoniazid (INH) or rifampicin (RIF) in people with type 2 DM. Participants were assigned six months of INH 300 mg/day plus pyridoxine 75 mg or three months of RIF 600 mg/day. The primary outcomes were adverse events resulting in permanent treatment cessation and considered possibly or probably related to study drugs. We included 130 subjects, 68 randomized to INH and 62 to RIF. We prematurely halted the study based on recommendations of the Adverse Event Safety Panel. There was no difference between arms in the overall frequency of adverse events. However, the INH group had significantly more permanent treatment interruptions due to grade 2 recurrent or grade 3 or 4 hepatoxicity. In comparison, the RIF arm had more treatment interruptions due to grade 3 or 4 gastrointestinal intolerance. TPT using INH or RIF is not safe enough to be considered a universal indication to patients with type 2 DM and TB infection. These results underline the need to search for alternative TB preventions with better safety profiles for type 2 DM patients.

Vertical transmission of African-lineage Zika virus through the fetal membranes in a rhesus macaque (Macaca mulatta) model.

Zika virus (ZIKV) can be transmitted vertically from mother to fetus during pregnancy, resulting in a range of outcomes including severe birth defects and fetal/infant death. Potential pathways of vertical transmission in utero have been proposed but remain undefined. Identifying the timing and routes of vertical transmission of ZIKV may help us identify when interventions would be most effective. Furthermore, understanding what barriers ZIKV overcomes to effect vertical transmission may help improve models for evaluating infection by other pathogens during pregnancy. To determine the pathways of vertical transmission, we inoculated 12 pregnant rhesus macaques with an African-lineage ZIKV at gestational day 30 (term is 165 days). Eight pregnancies were surgically terminated at either seven or 14 days post-maternal infection. Maternal-fetal interface and fetal tissues and fluids were collected and evaluated for ZIKV using RT-qPCR, in situ hybridization, immunohistochemistry, and plaque assays. Four additional pregnant macaques were inoculated and terminally perfused with 4% paraformaldehyde at three, six, nine, or ten days post-maternal inoculation. For these four cases, the entire fixed pregnant uterus was evaluated with in situ hybridization for ZIKV RNA. We determined that ZIKV can reach the MFI by six days after infection and infect the fetus by ten days. Infection of the chorionic membrane and the extraembryonic coelomic fluid preceded infection of the fetus and the mesenchymal tissue of the placental villi. We did not find evidence to support a transplacental route of ZIKV vertical transmission via infection of syncytiotrophoblasts or villous cytotrophoblasts. The pattern of infection observed in the maternal-fetal interface provides evidence of paraplacental vertical ZIKV transmission through the chorionic membrane, the outer layer of the fetal membranes.

Mycobacterium tuberculosis lineage 4 associated with cavitations and treatment failure.

BACKGROUND: Mycobacterium tuberculosis genotyping has been crucial to determining the distribution and impact of different families on disease clinical presentation. The aim of the study was to evaluate the associations among sociodemographic and clinical characteristics and M. tuberculosis lineages from patients with pulmonary tuberculosis in Orizaba, Veracruz, Mexico. METHODS: We analyzed data from 755 patients whose isolates were typified by 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR). The associations among patient characteristics and sublineages found were evaluated using logistic regression analysis. RESULTS: Among M. tuberculosis isolates, 730/755 (96.6%) were assigned to eight sublineages of lineage 4 (Euro-American). Alcohol consumption (adjusted odds ratio [aOR] 1.528, 95% confidence interval (CI) 1.041-2.243; p = 0.030), diabetes mellitus type 2 (aOR 1.625, 95% CI 1.130-2.337; p = 0.009), sputum smear positivity grade (3+) (aOR 2.198, 95% CI 1.524-3.168; p < 0.001) and LAM sublineage isolates (aOR 1.023, 95% CI 1.023-2.333; p = 0.039) were associated with the presence of cavitations. Resistance to at least one drug (aOR 25.763, 95% CI 7.096-93.543; p < 0.001) and having isolates other than Haarlem and LAM sublineages (aOR 6.740, 95% CI 1.704-26.661; p = 0.007) were associated with treatment failure. In a second model, multidrug resistance was associated with treatment failure (aOR 31.497, 95% CI 5.119-193.815; p < 0.001). Having more than 6 years of formal education was not associated with treatment failure. CONCLUSIONS: Knowing M. tuberculosis genetic diversity plays an essential role in disease development and outcomes, and could have important implications for guiding treatment and improving tuberculosis control.

Stimulation of natural killer cells with small molecule inhibitors of CD38 for the treatment of neuroblastoma.

High-risk neuroblastoma (NB) accounts for 15% of all pediatric cancer deaths. Refractory disease for high-risk NB patients is attributed to chemotherapy resistance and immunotherapy failure. The poor prognosis for high-risk NB patients demonstrates an unmet medical need for the development of new, more efficacious therapeutics. CD38 is an immunomodulating protein that is expressed constitutively on natural killer (NK) cells and other immune cells in the tumor microenvironment (TME). Furthermore, CD38 over expression is implicated in propagating an immunosuppressive milieu within the TME. Through virtual and physical screening, we have identified drug-like small molecule inhibitors of CD38 with low micromolar IC50 values. We have begun to explore structure activity relationships for CD38 inhibition through derivatization of our most effective hit molecule to develop a new compound with lead-like physicochemical properties and improved potency. We have demonstrated that our derivatized inhibitor, compound 2, elicits immunomodulatory effects in NK cells by increasing cell viability by 190 ± 36% in multiple donors and by significantly increasing interferon gamma. Additionally, we have illustrated that NK cells exhibited enhanced cytotoxicity toward NB cells (14% reduction of NB cells over 90 minutes) when given a combination treatment of our inhibitor and the immunocytokine ch14.18-IL2. Herein we describe the synthesis and biological evaluation of small molecule CD38 inhibitors and demonstrate their potential utility as a novel approach to NB immunotherapy. These compounds represent the first examples of small molecules that stimulate immune function for the treatment of cancer.

Differential affinity chromatography reveals a link between Porphyromonas gingivalis-induced changes in vascular smooth muscle cell differentiation and the type 9 secretion system.

Porphyromonas gingivalis is implicated in adverse pregnancy outcome. We previously demonstrated that intrauterine infection with various strains of P. gingivalis impairs the physiologic remodeling of the uterine spiral arteries (IRSA) during pregnancy, which underlies the major obstetrical syndromes. Women diagnosed with IRSA also have a greater risk for premature cardiovascular disease in later life. The dysregulated plasticity of vascular smooth muscle cells (VSMCs) is present in both IRSA and premature cardiovascular events. We hypothesized that VSMCs could serve as a bait to identify P. gingivalis proteins associated with dysregulated VSMC plasticity as seen in IRSA. We first confirmed that dams with P. gingivalis A7UF-induced IRSA also show perturbed aortic smooth muscle cell (AoSMC) plasticity along with the P. gingivalis colonization of the tissue. The in vitro infection of AoSMCs with IRSA-inducing strain A7UF also perturbed AoSMC plasticity that did not occur with infection by non-IRSA-inducing strain W83. Far-Western blotting with strain W83 and strain A7UF showed a differential binding pattern to the rat aorta and primary rat AoSMCs. The affinity chromatography/pull-down assay combined with mass spectrometry was used to identify P. gingivalis/AoSMC protein interactions specific to IRSA. Membrane proteins with a high binding affinity to AoSMCs were identified in the A7UF pull-down but not in the W83 pull-down, most of which were the outer membrane components of the Type 9 secretion system (T9SS) and T9SS cargo proteins. Additional T9SS cargo proteins were detected in greater abundance in the A7UF pull-down eluate compared to W83. None of the proteins enriched in the W83 eluate were T9SS components nor T9SS cargo proteins despite their presence in the prey preparations used in the pull-down assay. In summary, differential affinity chromatography established that the components of IRSA-inducing P. gingivalis T9SS as well as its cargo directly interact with AoSMCs, which may play a role in the infection-induced dysregulation of VSMC plasticity. The possibility that the T9SS is involved in the microbial manipulation of host cell events important for cell differentiation and tissue remodeling would constitute a new virulence function for this system.

Knowledge, attitudes, perceptions, and COVID-19 hesitancy in a large public university in Mexico city during the early vaccination rollout.

BACKGROUND: Vaccination against COVID-19 is a primary tool for controlling the pandemic. However, the spread of vaccine hesitancy constitutes a significant threat to reverse progress in preventing the disease. Studies conducted in Mexico have revealed that vaccination intention in Mexico among the general population ranges from 62 to 82%. OBJECTIVE: To know the prevalence of COVID-19 vaccine hesitancy and associated factors among academics, students, and administrative personnel of a public university in Mexico City. METHODS: We administered an online survey investigating sociodemographic aspects, knowledge, attitudes, practices, and acceptance/hesitancy regarding the COVID-19 vaccine. Using generalized linear Poisson models, we analyzed factors associated with vaccine hesitancy, defined as not intending to be vaccinated within the following six months or refusing vaccination. RESULTS: During May and June 2021, we studied 840 people, prevalence of vaccine hesitancy was 6%. Hesitancy was significantly associated with fear of adverse effects, distrust of physician's recommendations, lack of knowledge regarding handwashing, age younger than 40 years, refusal to use face masks, and not having received influenza vaccination during the two previous seasons. CONCLUSIONS: Vaccine hesitancy in this population is low. Furthermore, our results allowed us the identification of characteristics that can improve vaccine promotion.

Porphyromonas gingivalis-mediated disruption in spiral artery remodeling is associated with altered uterine NK cell populations and dysregulated IL-18 and Htra1.

Impaired spiral artery remodeling (IRSA) underpins the great obstetrical syndromes. We previously demonstrated that intrauterine infection with the periodontal pathogen, Porphyromonas gingivalis, induces IRSA in rats. Since our previous studies only examined the end stage of arterial remodeling, the aim of this study was to identify the impact of P. gingivalis infection on the earlier stages of remodeling. Gestation day (GD) 11 specimens, a transition point between trophoblast-independent remodeling and the start of extravillous trophoblast invasion, were compared to late stage GD18 tissues. P. gingivalis was found in decidual stroma of GD11 specimens that already had reduced spiral artery remodeling defined as smaller arterial lumen size, increased retention of vascular smooth muscle, and decreased invasion by extravillous trophoblasts. At GD11, P. gingivalis-induced IRSA coincided with altered uterine natural killer (uNK) cell populations, decreased placental bed expression of interleukin-18 (IL-18) with increased production of temperature requirement A1 (Htra1), a marker of oxidative stress. By GD18, placental bed IL-18 and Htra1 levels, and uNK cell numbers were equivalent in control and infected groups. However, infected GD18 placental bed specimens had decreased TNF + T cells. These results suggest disturbances in placental bed decidual stroma and uNK cells are involved in P. gingivalis-mediated IRSA.

Evaluating the impact of mobility in COVID-19 incidence and mortality: A case study from four states of Mexico.

Introduction: The COVID-19 pandemic in Mexico began at the end of February 2020. An essential component of control strategies was to reduce mobility. We aimed to evaluate the impact of mobility on COVID- incidence and mortality rates during the initial months of the pandemic in selected states. Methods: COVID-19 incidence data were obtained from the Open Data Epidemiology Resource provided by the Mexican government. Mobility data was obtained from the Observatory for COVID-19 in the Americas of the University of Miami. We selected four states according to their compliance with non-pharmaceutical interventions and mobility index. We constructed time series and analyzed change-points for mobility, incidence, and mortality rates. We correlated mobility with incidence and mortality rates for each time interval. Using mixed-effects Poisson models, we evaluated the impact of reductions in mobility on incidence and mortality rates, adjusting all models for medical services and the percentage of the population living in poverty. Results: After the initial decline in mobility experienced in early April, a sustained increase in mobility followed during the rest of the country-wide suspension of non-essential activities and the return to other activities throughout mid-April and May. We identified that a 1% increase in mobility yielded a 5.2 and a 2.9% increase in the risk of COVID-19 incidence and mortality, respectively. Mobility was estimated to contribute 8.5 and 3.8% to the variability in incidence and mortality, respectively. In fully adjusted models, the contribution of mobility to positive COVID-19 incidence and mortality was sustained. When assessing the impact of mobility in each state compared to the state of Baja California, increased mobility conferred an increased risk of incident positive COVID-19 cases in Mexico City, Jalisco, and Nuevo León. However, for COVID-19 mortality, a differential impact of mobility was only observed with Jalisco and Nuevo León compared to Baja California. Conclusion: Mobility had heterogeneous impacts on COVID-19 rates in different regions of Mexico, indicating that sociodemographic characteristics and regional-level pandemic dynamics modified the impact of reductions in mobility during the COVID-19 pandemic. The implementation of non-pharmaceutical interventions should be regionalized based on local epidemiology for timely response against future pandemics.

PDI inhibitor LTI6426 enhances panobinostat efficacy in preclinical models of multiple myeloma.

The histone deacetylase inhibitor (HDACi), panobinostat (Pano), is approved by the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) for treatment of relapsed/refractory multiple myeloma (MM). Despite regulatory approvals, Pano is used on a limited basis in MM due largely to an unfavorable toxicity profile. The MM treatment landscape continues to evolve, and for Pano to maintain a place in that paradigm it will be necessary to identify treatment regimens that optimize its effectiveness, particularly those that permit dose reductions to eliminate unwanted toxicity. Here, we propose such a regimen by combining Pano with LTI6426, a first-in-class orally bioavailable protein disulfide isomerase (PDI) inhibitor. We show that LTI6426 dramatically enhances the anti-MM activity of Pano in vitro and in vivo using a proteasome inhibitor resistant mouse model of MM and a low dose of Pano that exhibited no signs of toxicity. We go on to characterize a transcriptional program that is induced by the LTI6426/Pano combination, demonstrating a convergence of the two drugs on endoplasmic reticulum (ER) stress pathway effectors ATF3 (Activating Transcription Factor 3), DDIT3/CHOP (DNA Damage Inducible Transcript 3, a.k.a. C/EBP Homologous Protein), and DNAJB1 (DnaJ homolog subfamily B member 1, a.k.a. HSP40). We conclude that LTI6426 may safely enhance low-dose Pano regimens and that ATF3, DDIT3/CHOP, and DNAJB1 are candidate pharmacodynamic biomarkers of response to this novel treatment regimen.

Seudoaneurisma de la arteria femoral lateral: revisión sistemática a propósito de una complicación infrecuente en pacientes con fracturas pertrocantéricas / Lateral femoral artery pseudoaneurisms: A case report and systematic review of a rare complication of pertrochanteric fractures

Introducción: Se presenta un caso clínico de seudoaneurisma de la arteria femoral circunfleja lateral secundario a una fractura pertrocantérica de cadera. Materiales y métodos: Como el cuadro y su localización son infrecuentes, se llevó a cabo una revisión bibliográfica sistematizada que incluyó todos los casos publicados sobre esta enfermedad (n = 40) en los últimos 15 años. Resultados: No se hallaron asociaciones estadísticamente significativas entre ninguna de las variables estudiadas. Sin embargo, parece existir cierto consenso en mantener una alta sospecha clínica para una intervención precoz y así obtener mejores resultados. Tanto su etiología como su localización se relacionan con la morfología de la fractura, el gesto quirúrgico y el material de osteosíntesis. Asimismo, hay una tendencia mayor a utilizar la angiotomografía para el diagnóstico y la localización del seudoaneurisma. Conclusiones: Nuestra paciente es el primer caso de resolución espontánea. Es fundamental conocer esta complicación tan poco frecuente para optimizar los resultados terapéuticos. Esta revisión, la más reciente sobre el tema, es muy útil para enumerar y subrayar los aspectos más importantes sobre el manejo y la prevención de los seudoaneurismas secundarios a una fractura de cadera. Nivel de Evidencia: IV

Introduction: We present a case of a lateral circumflex femoral artery pseudoaneurysm associated with pertrochanteric hip fracture. Materials and methods: We performed a systematic review considering all cases published in the last 15 years about this pathology (n=40). Results: No statistically significant associations were found between any of the variables studied. However, there seems to be some consensus in maintaining a high clinical suspicion for early intervention, thus obtaining better outcomes. Both its etiology and location are related to the morphology of the fracture, the surgical procedure, and the osteosynthesis material. Likewise, there is a greater tendency to use CT angiography for the diagnosis and localization of the pseudoaneurysm. Conclusion: Our patient is the first reported case of spontaneous resolution. Knowing this rare complication is essential to optimize therapeutic results. This review, the most recent on the subject, is very useful in listing and highlighting the most important aspects of the management and prevention of pseudoaneurysms secondary to hip fracture. Level of Evidence: IV

Genetic diversity and primary drug resistance transmission in Mycobacterium tuberculosis in southern Mexico.

Tuberculosis is a global human health threat, especially in developing countries. The present study aimed to describe the genetic diversity of Mycobacterium tuberculosis and to measure the transmission rates of primary and acquired resistance. A total of 755 M. tuberculosis isolates from a cohort study of patients with culture-confirmed pulmonary tuberculosis in Orizaba, Veracruz, performed between 1995 and 2010 were genotyped by the 24-locus mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) method. Drug susceptibility was determined. Logistic regression models were constructed to identify the variables associated with resistance and clusters. The recent transmission index (RTI), the Hunter-Gaston discrimination index (HGDI) for the MIRU-VNTR test and allelic diversity (h) were calculated. The Haarlem and LAM lineages were the most common in the population. A total of 519 isolates were grouped into 128 clusters. The overall drug resistance rate was 19%, isoniazid monoresistance (10%) was the most common, and 3.4% of the isolates were multidrug resistant. Among the 116 isolates resistant to at least one drug, the primary and acquired resistance rates were 81.9% and 18.1%, respectively. Primary resistance was associated with belonging to a cluster (aOR 4.05, 95% CI 1.5-11.2, p = 0.007). Previous treatment history (aOR 9.05, 95% CI 3.6-22.5, p < 0.001) and LAM lineage (aOR 4.25, 95% CI 1.4-12.7, p = 0.010) were associated with multidrug-resistant tuberculosis (MDR-TB). The RTI was 51.7%, and the 24-locus MIRU-VNTR HGDI was 0.98. The alleles with the greatest diversity were 4056-QUB26 (h = 0.84), 2163b-QUB11b (h = 0.79), and 424-Mtub04 (h = 0.72). Primary resistance transmission, high LAM lineage prevalence and its association with MDR-TB represent public health problems. The implementation of molecular tools is needed to improve the existing control surveillance tuberculosis program.

Nicotine Induces Maternal and Fetal Inflammatory Responses Which Predispose Intrauterine Infection Risk in a Rat Model.

INTRODUCTION: Both smoking and infection adversely impact pregnancy. Previously, our group identified in a rodent model that 6 mg/kg/d nicotine increased the risk of fetal infection at gestation day (GD) 18. Here, we investigate lower nicotine doses. METHODS: Pregnant Sprague-Dawley rats received nicotine infusion at 0, 1, or 3 mg/kg/d (no, low-, and mid-dose nicotine, respectively) from GD 6, with intravenous inoculation with Mycoplasma pulmonis (MP) at 107 CFU (N = 20) or sterile broth (sham) (N = 11) on GD 14. Uterus and fetuses were retrieved on GD 18 for MP culture and histopathologic evaluation of maternal and fetal inflammatory responses (MIR and FIR). RESULTS: At 1 mg/kg/d nicotine, MP colonization rates were decreased, from 100% (9 of 9) to 40% (2 of 5) of MP-inoculated dams (p = .03), and 59% (66 of 111) to 39% (24 of 62) of fetuses (p = .01), versus no nicotine. Low-dose nicotine resulted in increased MIR and FIR in the sham-inoculated group; in the MP-inoculated group, this resulted in reduced relative risk (RR) for placental colonization (RR, 95% CI with high MIR = 0.14, 0.02 to 0.65; FIR = 0.38, 0.12 to 0.93). In contrast, 3 mg/kg/d nicotine treatment did not alter colonization rates; furthermore, FIR was completely suppressed, even in the face of placental or amniotic fluid colonization. CONCLUSION: The 1 mg/kg/d nicotine dose decreased risk of intrauterine infection, with increased MIR and FIR. The 3 mg/kg/d nicotine dose inhibited FIR, and increased risk for intrauterine infection. Nicotine alterations of the intrauterine environment were markedly dose-dependent. IMPLICATIONS: Nicotine exposure alters intrauterine infection and inflammation in a dose-dependent manner, potentially impacting fetal development and programming. Previous work in a rodent model showed that high-dose nicotine (6 mg/kg/d) exposure exacerbated intrauterine infection during pregnancy. The current study found that low-dose nicotine (1 mg/kg/d) exposure reduced colonization of placenta and amniotic fluid; this decrease was associated with increased intrauterine inflammation. Exposure to mid-dose nicotine (3 mg/kg/d) suppressed fetal inflammation. Elucidation of underlying mechanisms of these phenomena will inform public health and clinical care decisions, particularly in the context of risk assessment of nicotine replacement therapy during pregnancy for smoking cessation.