Case Report: Congenital Arthrogryposis and Unilateral Absences of Distal Arm in Congenital Zika Syndrome.

Zika virus was recognized as a teratogen in 2015, when prenatal Zika infection was associated with neonatal microcephaly. The transmission, virulence, tropism, and consequences of Zika virus infection during pregnancy are currently studied. Decreased neural progenitor cells, arrest in neuronal migration and/or disruption of the maturation process of the fetus central nervous system have been associated. Congenital Zika Syndrome produces a fetal brain disruption sequence resulting in structural brain abnormalities, microcephaly, intracranial calcifications, fetal akinesia and arthrogryposis. Vascular abnormalities like unique umbilical artery and decreased cerebral vascular flow have been described in some patients. This article reports a Zika positive patient with sequence of fetal brain disruption, arthrogryposis and absence of distal third of the right forearm. This report expands the clinical observations of congenital Zika syndrome that may be related to disruptive vascular events.

Insecticide-treated house screening protects against Zika-infected Aedes aegypti in Merida, Mexico.

BACKGROUND: The integration of house-screening and long-lasting insecticidal nets, known as insecticide-treated screening (ITS), can provide simple, safe, and low-tech Aedes aegypti control. Cluster randomised controlled trials in two endemic localities for Ae. aegypti of south Mexico, showed that ITS conferred both, immediate and sustained (~2 yr) impact on indoor-female Ae. aegypti infestations. Such encouraging results require further validation with studies quantifying more epidemiologically-related endpoints, including arbovirus infection in Ae. aegypti. We evaluated the efficacy of protecting houses with ITS on Ae. aegypti infestation and arbovirus infection during a Zika outbreak in Merida, Yucatan, Mexico. METHODOLOGY/PRINCIPAL FINDINGS: A two-arm cluster-randomised controlled trial evaluated the entomological efficacy of ITS compared to the absence of ITS (with both arms able to receive routine arbovirus vector control) in the neighbourhood Juan Pablo II of Merida. Cross-sectional entomological surveys quantified indoor adult mosquito infestation and arbovirus infection at baseline (pre-ITS installation) and throughout two post-intervention (PI) surveys spaced at 6-month intervals corresponding to dry/rainy seasons over one year (2016-2017). Household-surveys assessed the social reception of the intervention. Houses with ITS were 79-85% less infested with Aedes females than control houses up to one-year PI. A similar significant trend was observed for blood-fed Ae. aegypti females (76-82%). Houses with ITS had significantly less infected female Ae. aegypti than controls during the peak of the epidemic (OR = 0.15, 95%CI: 0.08-0.29), an effect that was significant up to a year PI (OR = 0.24, 0.15-0.39). Communities strongly accepted the intervention, due to its perceived mode of action, the prevalent risk for Aedes-borne diseases in the area, and the positive feedback from neighbours receiving ITS. CONCLUSIONS/SIGNIFICANCE: We show evidence of the protective efficacy of ITS against an arboviral disease of major relevance, and discuss the relevance of our findings for intervention adoption.

Data on a genome-wide association study of type 2 diabetes in a Maya population.

Maya communities have been shown to exhibit type 2 diabetes (T2D) with high prevalence compared with Mexican mestizo populations. Furthermore, some variants associated with the risk for T2D have been described. In this study, we describe the results of a pilot genome wide association study (GWAS) using 817,823 single nucleotide polymorphisms (SNPs) to identify candidate variants for replication in future studies. Herein, we present the GWAS study data, which were divided into three parts: first, 1289 ancestry informative markers (AIMs) were selected for Latino populations containing European, African, and Native American SNPs obtained from the literature; second, a GWAS hypothesis free to select candidate genes associated with T2D was performed, which identified 24 candidate genes; and third, 39 SNPs previously associated with T2D or related traits were replicated. This article is associated with the original article published in "Gene" under the title "Pilot genome-wide association study identifying novel risk loci for type 2 diabetes in a Maya population".

Maya gene variants related to the risk of type 2 diabetes in a family-based association study.

Mexican Maya populations have a notably high prevalence of type 2 diabetes (T2D) as a consequence of the interaction between environmental factors and a genetic component. To assess the impact of 24 single nucleotide variants (SNVs) located in 18 T2D risk genes, we conducted a family-based association evaluation in samples from Maya communities with a high incidence of the disease. A total of four hundred individuals were recruited from three Maya communities with a high T2D incidence. Family pedigrees (100) and 49 nuclear families were included. Genotyping was performed by allelic discrimination with TaqMan probes. This study also included the family-based association test (FBAT) statistic U to assess the genetic associations with T2D, and the multivariate statistical and haplotype analyses. A positive association with TD2 risk was found for WFS1 rs6446482 (p = 0.046, Z = 1.994) under an additive model, and SIRT1 rs7896005 (p = 0.038, Z = 2.073) under the dominant model. Multivariate model analysis, including T2D status, age, and body mass index (BMI), displayed significant covariance in PPARGC-1α rs8192678; SIRT1 rs7896005; TCF7L2 rs7903146 and rs122243326; UCP3 rs3781907; and HHEX rs1111875 with a P < 0.05. This study revealed an association of SIRT1 and WFS1 with T2D risk.

Zika Virus Infection in Pregnant Women, Yucatan, Mexico.

We report demographic, epidemiologic, and clinical findings for a prospective cohort of pregnant women during the initial phase of Zika virus introduction into Yucatan, Mexico. We monitored 115 pregnant women for signs of active or recent Zika virus infection. The estimated cumulative incidence of Zika virus infection was 0.31 and the ratio of symptomatic to asymptomatic cases was 1.7 (range 1.3-4.0 depending on age group). Exanthema was the most sensitive clinical sign but also the least specific. Conjunctival hyperemia, joint edema, and exanthema were the combination of signs that had the highest specificity but low sensitivity. We did not find evidence of vertical transmission or fetal anomalies, likely because of the low number of pregnant women tested. We also did not find evidence of congenital disease. Our findings emphasize the limited predictive value of clinical features in areas where Zika virus cocirculates with other flaviviruses.

Pilot genome-wide association study identifying novel risk loci for type 2 diabetes in a Maya population.

Type 2 diabetes mellitus (T2D) is one of the two leading causes of mortality in Mexico. However, most studies have focused on Caucasians or Asians, and there are a small number of studies investigating Maya populations. Furthermore, to the best of our knowledge, there is no information on isolated Maya communities with T2D frequencies of 20% that are primarily attributed to ethnicity. Consequently, this study focused on assessing which genetic risk variants could be involved in the high rates of T2D in 92 individuals with Maya ancestry; 47 were diagnosed with T2D, and 45 were classified as healthy individuals. A pilot genome-wide association study was performed using the Affymetrix Axiom Genome-wide LAT1 array. The population structure was determined with the ADMIXTURE software using 1289 Latin American selected polymorphisms, and 39 polymorphisms associated with T2D were included for replication. Association tests were performed using the Statistical Analysis System (SAS) using the allelic, genotype and Armitage trend tests. The results indicated that population structure analysis displayed no differences between T2D patients and healthy individuals; 24 loci located were identified for probable association with T2D (p > 1.288 × 10-7 and p < 1.348 × 10-4); the polymorphism AGTR2 rs1914711 in chromosome X was identified by the allele test (OR = 6.824; p = 1.448 × 10-9) as a candidate gene for association with T2D; and ARL15 rs4311394 was associated as a T2D protector by genotype and the Armitage trend test (OR = 0.318; p = 0.001). In conclusion, this study proposes 24 candidate SNPs associated with T2D for replication studies and one for protective association with T2D.

Birth Defects Associated With Congenital Zika Virus Infection in Mexico.

Part of the work agenda of international health authorities is to define the clinical spectrum of the congenital Zika syndrome (CZS) in different territories. We describe the clinical variability that gave rise to the suspicion of CZS in 3 newborn patients in the south of Mexico with active transmission of Zika. All of them presented Zika RNA by reverse transcription-polymerase chain reaction and positive antibodies for IgM by enzyme-linked immunosorbent assay. None of the mothers tested positive for active viremia, only one mother had Zika-symptoms and titers of Zika-positive IgM. Intrauterine growth restriction, brain disruption sequence, and intracranial calcifications are the clinical characteristics common in all. One patient had neural tube defect and other, arthrogryposis. Because the majority of pregnant women will be asymptomatic to Zika, we must be alert to the clinical variability of the birth defects associated to pregnancy Zika infection. Reports of clinical cases encourage the medical community to make diagnostic decisions.

Diets containing sea cucumber (Isostichopus badionotus) meals are hypocholesterolemic in young rats.

Sea cucumber is widely consumed as a putative functional food. It contains many biologically-active substances, but only limited research on its properties in vivo has been done. The effects of different meals containing Isostichopus badionotus, a sea cucumber from southeast Mexico, on growth performance and body lipid profile in young rats were analyzed. Sea cucumber body wall was either lyophilized, cooked (100 °C, 1 h in water) and lyophilized, or oven-dried (70 °C for 12 h). It was then ground and incorporated into cholesterol-containing diets. I. badionotus meals supported growth and improved lipid profile in rats. In particular, serum cholesterol, low density lipoproteins, triglycerides concentration and atherogenic index values were greatly reduced by some I. badionotus containing diets. Liver total lipids, triglycerides and cholesterol were also reduced. Cooking or heat-treatment of the meals lowered but did not abolish their hypolipidemic potency. Gene expression analysis of several key genes involved in cholesterol and lipid metabolism in liver showed that diets containing I. badionotus repressed the induction of key genes associated with dyslipidemia exerted by cholesterol supplementation. Consumption of I. badionotus from the Yucatan Peninsula is beneficial for dyslipidemia, although biological effect is clearly dependent on preparation method.

Implicación del alelo CCR5-Δ32 en la progresión clínica de pacientes VIH-1+ en Yucatán, México / CCR5-Δ32 allele involvement in the clinical evolution of HIV1+ patients in Yucatán, Mexico

OBJETIVO: Establecer la frecuencia y la relación del alelo CCR5-Δ32 con la infección y la progresión clínica de pacientes VIH+ y en individuos expuestos seronegativos. MATERIAL Y MÉTODOS: Se analizaron 355 muestras, 62 VIH+, 51 individuos expuestos seronegativos y 242 de la población general. Los VIH+ se subdividieron en: a) progresores normales n= 49; b) progresores lentos n= 10, y c) no progresores n= 3. RESULTADOS: Se identificó el genotipo wt/Δ32 en 17.7 por ciento de los VIH+, 13.7 por ciento de los individuos expuestos seronegativos y 6.2 por ciento en la población general. El genotipo Δ32/Δ32 se encontró en 3.9 por ciento de los individuos expuestos seronegativos. Según la progresión clínica de los VIH+, se identificó el genotipo wt/Δ32 en 10.2 por ciento de los progresores normales, 30 por ciento de los progresores lentos y en 100 por ciento de los no progresores. CONCLUSIÓN: El genotipo wt/Δ32 se observó en todos los no progresores, lo que apoya su papel en esta forma de progresión clínica en este grupo.

OBJECTIVE: CCR5-Δ32 allele frequency needs to be identified in HIV+ patients and exposed seronegative individuals in Yucatan, Mexico, to understand this mutation's relationship to infection and disease progression. MATERIAL AND METHODS: A total of 355 samples were analyzed: 62 from HIV+ patients, 51 from exposed seronegative individuals and 242 from general population. Infected patients were subdivided into a) normal progressors n= 49; b) slow progressors n= 10, and c) non-progressors n= 3. RESULTS: Genotype wt/Δ32 was identified in 17.7 percent of HIV+, 13.7 percent of exposed seronegative individuals and 6.2 percent of general population. Genotype Δ32/Δ32 was identified in 3.9 percent of exposed seronegative individuals. In infected patients, wt/Δ32 was identified in 10.2 percent of normal progressors, 30 percent of slow progressors and 100 percent of non-progressors. CONCLUSION: Genotype wt/Δ32 was observed in all non-progressing HIV+ patients, supporting its role in this group's disease development and clinical evolution.

[CCR5-Δ32 allele involvement in the clinical evolution of HIV1+ patients in Yucatán, Mexico]. / Implicación del alelo CCR5-Δ32 en la progresión clínica de pacientes VIH-1+ en Yucatán, México.

OBJECTIVE: CCR5-Δ32 allele frequency needs to be identified in HIV+ patients and exposed seronegative individuals in Yucatan, Mexico, to understand this mutation's relationship to infection and disease progression. MATERIAL AND METHODS: A total of 355 samples were analyzed: 62 from HIV+ patients, 51 from exposed seronegative individuals and 242 from general population. Infected patients were subdivided into a) normal progressors n= 49; b) slow progressors n= 10, and c) non-progressors n= 3. RESULTS: Genotype wt/Δ32 was identified in 17.7% of HIV+, 13.7% of exposed seronegative individuals and 6.2% of general population. Genotype Δ32/Δ32 was identified in 3.9% of exposed seronegative individuals. In infected patients, wt/Δ32 was identified in 10.2% of normal progressors, 30% of slow progressors and 100% of non-progressors. CONCLUSION: Genotype wt/Δ32 was observed in all non-progressing HIV+ patients, supporting its role in this group's disease development and clinical evolution.

Tipificación del virus del papiloma humano en mujeres con lesión escamosa intraepitelial de bajo grado / Human Papillomavirus DNA in women having low-grade squamous intraepithelial lesion

El embarazo ectópico bilateral espontáneo es una condición clínica infrecuente que ocurre en 1 de cada 1.580 embarazos ectópicos. En los últimos 25 años se han reportado 72 casos de embarazo ectópico bilateral, 31 de los cuales han sido espontáneos y en ninguno de ellos se ha logrObjetivo: determinar la prevalencia y los genotipos de los papillomavirus humanos (PVH) en mujeres con lesiones escamosas intraepiteliales de bajo grado (LEIBG). Métodos: noventa y seis mujeres de la clínica e colposcopia fueron incluidas. La presencia de los PVH en las biopsias fue determinada por ensayo de reacción en cadena de la polimerasa (RCP) con oligonucleótidos para el gen L1. Las muestras fueron coamplificadas con MY09/MY11/HMB01 e iniciadores para betaglobina GH20/PC04. Para tipificar se utilizó hibridación reversa en línea. Resultados: el ADN de PVH fue detectado en 28/96 (29,1 por ciento) pacientes, de las cuales 21/28 (75 por ciento) tuvieron infección con un sólo tipo y 7/28 (25 por ciento); infección múltiple. En 29/39 (74,3 por ciento) fueron de alto riesgo y 10/39 (25,7 por ciento) de bajo riesgo. Encontramos 13 diferentes tipos 9/13 (69,2 por ciento) de ellos de alto riesgo. PVH 58 fue el tipo más frecuente. Conclusiones: la prevalencia de VPH en mujeres con diagnóstico citológico de LEIBG fue menor que la esperada; este resultado sugiere una clasificación inadecuada de los diagnósticos.

Transmembtane glycoprotein cross reactive HIV-1/HIV-2 epitope / Epítopo de reactividad cruzada en las glicoproteínas transmembranales de HIV-1/HIV-2

Epítopo de reactividad cruzada en las glicoproteínas transmembranales de HIV-1/HIV-2. Introducción. En México se ha reportado una alta reactividad cruzada (24 por ciento) entre las glicoproteínas transmembranales del HIV-1 y HIV-2. Material y métodos. En este estudio, se sintetizó y se utilizó como antígeno para un ELISA, el péptido UIRH1 que corresponde a la región aminoterminal de la glicoproteína transmembranal del HIV-2 (aa629-652). La especificidad de la reacción se confirmó mediante un ensayo de competencia. Resultados. Los sueros de personas infectadas con el HIV-1 que no presentaron reacción cruzada con la gp32 del HIV-2 dieron valores de absorbancias similares a los que se obtuvieron de las personas seronegativas (1.1 veces) mientras que los sueros positivos al HIV-1 que presentaron reactividad cruzada dieron 2.8 veces la absorbancia de los negativos. Discusión. Proponemos que esta región transmembranal es responsable de la reactividad cruzada observada en ensayos de inmunoblot en individuos infectados con el HIV-1 en México.

Picobirnavirus: nuevo agente viral como probable causante de la diarrea infecciosa aguda en lechones lactantes de granjas porcícolas del estado de Yucatán, México / picobirnaviruses: new viral agent as cause of acute infection disease in pig farms in the state of Yucatan, Mexico

En 1988, en Brasil, Pereira describió un nuevo grupo de virus con genoma bisegmentado de ácido ribonucleico (ARN), al que nombró picobirnavirus (PBV), desde entonces éste se ha localizado en animales y en humanos de todo el mundo. En México no existe ningún dato sobre este virus, por lo que al encontrar patrones electroforéticos semejantes a los mencionados en tres muestras de heces de lechones con diarrea infecciosa aguda(DIA), se decidió identificar este hallazgo de dos segementos de ARN encontrando por medio de la técnica de electroforesis en geles de poliacrilamida (PAGE) con tinción de nitrato de plata. De las muestras analizadas, 74 presentaron un patrón electroforético de 11 segmentos de ARN característico de los rotavirus (RV) y en 3 muestras se observaron únicamente 2 bandas con distribución diferente a los RV. A estas 3 muestras se les realizó digestión enzimática con DNAsa I y RNAsa A, encontrándose que corresponden a segmentos de ARN de doble cadena de aproximadamente 2600-1600 pares de bases, semejante a lo que se ha informado para los "picobirnavirus"; por lo que estos hallazgos sugieren la existencia de un virus con dos segmentos de doble cadena de ARN, que son partículas representativas de un nuevo virus intestinal, asociado con gastroenteritis en lechones, aunque no se conoce el papel que desempeña en ellas