No evidence for a modulating effect of continuous transcutaneous auricular vagus nerve stimulation on markers of noradrenergic activity.

Although transcutaneous auricular vagus nerve stimulation (taVNS) is thought to increase central noradrenergic activity, findings supporting such mechanism are scarce and inconsistent. This study aimed to investigate whether taVNS modulates indirect markers of phasic and tonic noradrenergic activity. Sixty-six healthy participants performed a novelty auditory oddball task twice on separate days: once while receiving taVNS (left cymba concha), once during sham (left earlobe) stimulation. To maximize potential effects, the stimulation was delivered continuously (frequency: 25 Hz; width: 250 µs) at an intensity individually calibrated to the maximal level below pain threshold. The stimulation was administered 10 min before the oddball task and maintained throughout the session. Event-related pupil dilation (ERPD) to target stimuli and pre-stimulus baseline pupil size were assessed during the oddball task as markers of phasic and tonic noradrenergic activity, respectively. Prior to and at the end of stimulation, tonic pupil size at rest, cortisol, and salivary alpha-amylase were assessed as markers of tonic noradrenergic activity. Finally, we explored the effect of taVNS on cardiac vagal activity, respiratory rate, and salivary flow rate. Results showed a greater ERPD to both target and novelty compared to standard stimuli in the oddball task. In contrast to our hypotheses, taVNS did not impact any of the tested markers. Our findings strongly suggest that continuous stimulation of the cymba concha with the tested stimulation parameters is ineffective to increase noradrenergic activity via a vagal pathway.

A Brief History of Cerebellar Neurostimulation.

The first attempts at using electric stimulation to study human brain functions followed the experiments of Luigi Galvani and Giovanni Aldini on animal electricity during the eighteenth century. Since then, the cerebellum has been among the areas that have been studied by invasive and non-invasive forms of electrical and magnetic stimulation. During the nineteenth century, animal experiments were conducted to map the motor-related regions of cerebellar cortex by means of direct electric stimulation. As electric stimulation research on the cerebellum moved into the twentieth century, systematic research of electric cerebellar stimulation led to a better understanding of its effects and mechanism of action. In addition, the clinical potential of cerebellar stimulation in the treatment of motor diseases started to be explored. With the introduction of transcranial electric and magnetic stimulation, cerebellar research moved to non-invasive techniques. During the twenty-first century, following on groundbreaking research that linked the cerebellum to non-motor functions, non-invasive techniques have facilitated research into different aspects of cerebellar functioning. The present review provides a brief historical account of cerebellar neurostimulation and discusses current challenges and future direction in this field of research.

Parallel evolution of vgsc mutations at domains IS6, IIS6 and IIIS6 in pyrethroid resistant Aedes aegypti from Mexico.

Aedes aegypti is the primary urban mosquito vector of viruses causing dengue, Zika and chikungunya fevers -for which vaccines and effective pharmaceuticals are still lacking. Current strategies to suppress arbovirus outbreaks include removal of larval-breeding sites and insecticide treatment of larval and adult populations. Insecticidal control of Ae. aegypti is challenging, due to a recent rapid global increase in knockdown-resistance (kdr) to pyrethroid insecticides. Widespread, heavy use of pyrethroid space-sprays has created an immense selection pressure for kdr, which is primarily under the control of the voltage-gated sodium channel gene (vgsc). To date, eleven replacements in vgsc have been discovered, published and shown to be associated with pyrethroid resistance to varying degrees. In Mexico, F1,534C and V1,016I have co-evolved in the last 16 years across Ae. aegypti populations. Recently, a novel replacement V410L was identified in Brazil and its effect on vgsc was confirmed by electrophysiology. Herein, we screened V410L in 25 Ae. aegypti historical collections from Mexico, the first heterozygote appeared in 2002 and frequencies have increased in the last 16 years alongside V1,016I and F1,534C. Knowledge of the specific vgsc replacements and their interaction to confer resistance is essential to predict and to develop strategies for resistance management.

Population genetics and ecological niche of invasive Aedes albopictus in Mexico.

The Asian tiger mosquito Aedes albopictus (Skuse), is one of the most invasive mosquito species worldwide. In Mexico it is now recorded in 12 states and represents a serious public health problem, given the recent introduction of Chikungunya on the southern border. The aim of this study was to analyze the population genetics of A. albopictus from all major recorded foci, and model its ecological niche. Niche similarity with that from its autochthonous distribution in Asia and other invaded countries were analyzed and its potential future expansion and potential human exposure in climate change scenarios measured. We analyzed 125 sequences of a 317 bp fragment of the cyt b gene from seven A. albopictus populations across Mexico. The samples belong to 25 haplotypes with moderate population structuring (Fst=0.081, p<0.02) and population expansion. The most prevalent haplotype, found in all principal sites, was shared with the USA, Brazil, France, Madagascar, and Reunion Island. The ecological niche model using Mexican occurrence records covers 79.7% of the country, and has an 83% overlap with the Asian niche projected to Mexico. Both Neotropical and Nearctic regions are included in the Mexican niche model. Currently in Mexico, 38.6 million inhabitants are exposed to A. albopictus, which is expected to increase to 45.6 million by 2070. Genetic evidence supports collection information that A. albopictus was introduced to Mexico principally by land from the USA and Central and South America. Prevalent haplotypes from Mexico are shared with most invasive regions across the world, just as there was high niche similarity with both natural and invaded regions. The important overlap with the Asian niche model suggests a high potential for the species to disperse to sylvatic regions in Mexico.

Effect of Photoperiod On Permethrin Resistance In Aedes aegypti.

Living organisms have been exposed to light-dark cycles that allowed them to adapt to different ecological niches. Circadian cycles affect hormone release, metabolism, and response to xenobiotic compounds. Current studies have shown that insect susceptibility to toxic agents depends on circadian cycles, mainly because the biochemical processes involved in detoxification and responses to oxidative stress are modulated by this process. The goal of this study was to determine the effect of photoperiod on resistance to permethrin in Aedes aegypti . Collections of Ae. aegypti from 4 locations in Yucatan, southern Mexico, were subjected to 2 different photoperiod schemes: dark (0 h light:24 h dark) and natural photoperiod (12 h light:12 h dark). The comparison of both photoperiods was evaluated with respect to permethrin resistance using bottle bioassays and by monitoring the possible mechanism related such as enzymatic activity and by the frequency of 2 knockdown resistance mutations in the voltage-dependent sodium channel gene (V1016I and F1534C). The susceptible strain was used as a reference. The mosquitoes in dark photoperiod showed a reduction in resistance to the pyrethroid. The α-esterases and glutathione S-transferase enzymatic activities showed lower levels in the dark photoperiod, and the frequencies of V1016I knockdown resistance mutation showed significant difference between photoperiod schemes.

First report of L1014F kdr mutation in Culex quinquefasciatus in Mexico.

The L1014F mutation in the voltage-sodium channel gene has been associated with resistance to DDT and pyrethroids in various arthropod species including mosquitoes. We determined the frequency of the L1014F kdr mutation in 16 field populations of Culex quinquefasciatus from Northeastern Mexico collected between 2008 and 2013. The L1014F was present in all populations analyzed with the lowest frequency (3.33%) corresponding to the population from Monclova collected in 2012, and the highest frequency (63.63%) from the Monterrey population collected in 2012. The presence of a kdr mutation in populations of Cx. quinquefasciatus from northeastern Mexico provides evidence of pyrethroid resistance. This requires a special attention, considering that pyrethroid-based insecticides are commonly used in vector-control campaigns, especially against Aedes aegypti (L.).

Frequency of V1016I and F1534C mutations in the voltage-gated sodium channel gene in Aedes aegypti in Venezuela.

BACKGROUND: The V1016I and F1534C mutations in the voltage-gated sodium channel gene have been associated with resistance to pyrethroids and DDT in Aedes aegypti mosquitoes. A study was carried out to determine the frequency of I1016 and C1534 by real-time PCR in five natural populations of Ae. aegypti in Venezuela during 2008, 2010 and 2012, as well as in a strain selected with 0.14 µg of deltamethrin for 15 generations. RESULTS: In natural populations, frequencies of I1016 varied between 0.01 and 0.37, and frequencies of C1534 between 0.35 and 1.0. In the Pampanito strain, the frequency of I1016 increased from 0.02 in F1 up to 0.5 in F15 and from 0.35 up to fixation for C1534 after selection with deltamethrin. CONCLUSION: The results showed that C1534 frequencies are higher than I1016 frequencies in natural populations of Ae. aegypti in Venezuela, and that deltamethrin selected the C1534 more rapidly than I1016.

Susceptibility to chlorpyrifos in pyrethroid-resistant populations of Aedes aegypti (Diptera: Culicidae) from Mexico.

Resistance to the organophosphate insecticide chlorpyrifos was evaluated in females from six strains of Aedes aegypti (L.) that expressed high levels of cross-resistance to eight pyrethroid insecticides. Relative to LC50 and LC90 at 24 h of a susceptible New Orleans (NO) strain, three strains were highly resistant to chlorpyrifos (Coatzacoalcos, resistance ratio [RRLC90 = 11.97; Pozarica, RRLC90 = 12.98; and Cosoleacaque, RRLC50 = 13.94 and RRLC90 = 17.57), one strain was moderately resistant (Veracruz, RRLC90 = 5.92), and two strains were susceptible (Tantoyuca and Martinez de la Torre, RRLC50 and RRLC90 < 5) in bottle bioassays according to Centers for Disease Control and Prevention. Furthermore, high levels of alpha- or beta-esterase activity in the sample populations were correlated with resistance, suggesting that esterase activity may be a mechanism causing the development of organophosphate resistance in these populations. Overall, the populations in this study were less resistant to chlorpyrifos than to pyrethroids. Rotation of insecticides used in control activities is recommended to delay or minimize the occurrence of high levels of resistance to chlorpyrifos among local populations of Ae. aegypti. The diagnostic dose and diagnostic time for chlorpyrifos resistance monitoring was determined to be 85 microg per bottle and 30 min, respectively, using the susceptible NO strain.

Susceptibility status of Aedes aegypti (L.) (Diptera: Culicidae) to temephos in Venezuela.

BACKGROUND: Temephos is an insecticide widely used in Venezuela to control the proliferation of the larvae of Aedes aegypti (L.), the principal vector of dengue virus. The aim of this study was to identify the susceptibility to temephos of Ae. aegypti in four locations in western Venezuela: Lara, Tres Esquinas, Ureña and Pampanito. Larval bioassays were conducted on samples collected in 2008 and 2010, and the levels of α- and ß-esterases, mixed-function oxidases, glutathione-S-transferase and insensitive acethyl cholinesterase were determined. RESULTS: Larval populations from western Venezuela obtained during 2008 and 2010 were found to be susceptible to temephos, with low resistance ratios and without overexpression of enzymes. CONCLUSIONS: The low RR values reveal the effectiveness of temephos in controlling the larval populations of Ae. aegypti. Control strategies must be vigorously monitored to maintain the susceptibility to temephos of these populations of Ae. aegypti.

Resistance to malathion and deltamethrin in Aedes aegypti (Diptera: Culicidae) from western Venezuela.

Resistance to the insecticides deltamethrin and malathion and the enzymes associated with metabolic resistance mechanisms were determined in four field populations of Aedes aegypti (L.) from western Venezuela during 2008 and 2010 using the bottle assay and the microplate biochemical techniques. For deltamethrin, mortality rates after 1 h exposure and after a 24-h recovery period were determined to calculate the 50% knock-downconcentration (KC50) and the lethal concentration (LC50), respectively. For malathion, mortality was recorded at 24 h to determine the LC50. For deltamethrin, resistance ratios of knock-down resistance and postrecovery were determined by calculating the RRKC50 and RRLC50, comparing the KC50 and LC50 values of the field populations and those of the susceptible New Orleans strain. Knock-down resistance to deltamethrin was moderate in the majority of the populations in 2008 (RRKC50 values were between 5- and 10-fold), and only one population showed high resistance in 2010 (RRKC50 > 10-fold). Moderate and high postrecovery resistance to deltamethrin was observed in the majority of the populations for 2008 and 2010, respectively. There was significantly increased expression of glutathione-S-tranferases and mixed-function oxidases. All populations showed low resistance to malathion in 2008 and 2010 with significantly higher levels of alpha-esterases for 2008 and 2010 and beta-esterases for 2008.

Wide spread cross resistance to pyrethroids in Aedes aegypti (Diptera: Culicidae) from Veracruz state Mexico.

Seven F1 strains of Aedes aegypti (L.) were evaluated by bottle bioassay for resistance to the pyrethroids d-phenothrin, permethrin, deltamethrin, lambda-cyalothrin, bifenthrin, cypermethrin, alpha-cypermethrin, and z-cypermethrin. The New Orleans strain was used as a susceptible control. Mortality rates after a 1 h exposure and after a 24 h recovery period were determined. The resistance ratio between the 50% knockdown values (RR(KC50)) of the F1 and New Orleans strains indicated high levels of knockdown resistance. The RR(KC50) with alpha-cypermethrin varied from 10 to 100 among strains indicating high levels of knockdown resistance. Most of the strains had moderate resistance to d-phenothrin. Significant but much lower levels of resistance were detected for lambda-cyalothrin, permethrin, and cypermethrin. For zeta-cypermethrin and bifenthrin, only one strain exhibited resistance with RR(KC50) values of 10- and 21-fold, respectively. None of the strains showed RR(KC50) >10 with deltamethrin, and moderate resistance was seen in three strains, while the rest were susceptible. Mosquitoes from all strains exhibited some recovery from all pyrethroids except d-phenothrin. Regression analysis was used to analyze the relationship between RR(LC50) and RR(KC50). Both were highly correlated (R2 = 0.84-0.97) so that the slope could be used to determine how much additional pyrethroid was needed to ensure lethality. Slopes ranged from 0.875 for d-phenothrin (RR(LC50) approximately equal to RR(KC50)) to 8.67 for lambda-cyalothrin (-8.5-fold more insecticide needed to kill). Both RR(LC50) and RR(KC50) values were highly correlated for all pyrethroids except bifenthrin indicating strong cross-resistance. Bifenthrin appears to be an alternative pyrethroid without strong cross-resistance that could be used as an alternative to the current widespread use of permethrin in Mexico.

Genetic variation in Bactericera cockerelli (Hemiptera: Triozidae) from Mexico.

Bactericera cockerelli (Sulc) is a significant pest of several solanacious crops in Mexico and the United States since 1970. In 2001 significant outbreaks of outstanding importance were observed for the first time in areas where infestations of this insect were historically rare. Molecular studies revealed that this was because of the development of a new biotype of B. cockerelli that had become adapted to south-western United States, further demonstrating that this genetic differentiation was reflected in the survival, development cycle, fertility, and growth rate of both the native biotype as well as the one recently reported. To determine genetic variation in populations of B. cockerelli from Mexico, inter simple sequence repeat were used. Results showed that populations of B. cockerelli from central and northeastern Mexico (Guanajuato, Morelos, Estado de Mexico, and Nuevo Leon states) are genetically similar, meanwhile B. cockerelli from northwest, southwest, and southeast of the country (Sinaloa, Michoacan, and Oaxaca states) are genetically distinct from each other and from the rest of the populations included in the study.

Update on the frequency of Ile1016 mutation in voltage-gated sodium channel gene of Aedes aegypti in Mexico.

We analyzed 790 Aedes aegypti from 14 localities of Mexico in 2009 to update information on the frequency of the Ile1016 allele in the voltage-gated sodium channel gene that confers resistance to pyrethroids and DDT. The Ile1016 mutation was present in all 17 collections, and was close to fixation in Acapulco (frequency = 0.97), Iguala (0.93), and San Nicolas (0.90). Genotypes at the 1016 locus were not in Hardy-Weinberg proportions in collections from Panuco, Veracruz, Cosoleacaque, Coatzacoalcos, Tantoyuca, and Monterrey due in every case to an excess of homozygotes. The high frequencies of this mutation in Ae. aegypti are probably due to selection pressure from pyrethroid insecticides, particularly permethrin, which has been used in mosquito control programs for >10 years in Mexico.

A novel amino acid substitution in the para-sodium channel gene in Rhipicephalus microplus (Acari: Ixodidae) associated with knockdown resistance.

Resistance acquired by the tick Rhipicephalus microplus (Canestrini) to different types of ixodicides in Mexico has had a negative impact on national and local livestock, mainly due to the transmission of diseases such as babesiosis and anaplasmosis, among others. The technique used for the diagnosis of resistance was that in the bioassays noted in the Norma Oficial Mexicana (NOM-006-ZOO-1994). The purpose of this investigation was the determination of resistance to pyrethroids through isoleucine-phenylalanine mutation in the gene KDR, in a population of ticks from Montemorelos, NL, Mexico. Preliminary bioassays demonstrated resistance to cypermethrin and deltamethrin (27.4%) and flumethrin (36.7-34.7%). To identify the mutation, DNA was extracted from 100 mg of larvae (pools), 10 pools were assessed by PCR, in which a pair of primers designed with the program Oligo 2.0 and Amplify 1.2 amplified a 136 bp fragment containing the mutation. The PCR product was subsequently sequenced to confirm the presence of the mutation. A strain susceptible to pyrethroid insecticides (Mora strain) was used as control, but it did not show the mutation. However, the mutation was detected in 4 out of 10 samples of the strain Montemorelos.

Carcinoma del tracto biliar / Biliary duct carcinoma

Se revisaron 6 casos de carcinoma de vías biliares extrahepáticas, confirmados histológicamente, operados en el Hospital México, C.C.S.S. En el tercio superior se presentaron 3 casos; 2 casos en el tercio inferior y 1 caso en el tercio medio. Se encontró un promedio de 2 mujeres por 1 hombre. Se presentaron 4 pacientes en la sétima década de la vida. El 100% de los casos se reportaron como adenocarcinomas. Ictericia, dolor en C.S.D. y pérdida de peso fueron los síntomas y signos más frecuentes. La E.R.C.P. correlacionó bien en todos los casos en que se efectuó, con los hallazgos operatorios. En los 6 casos se documentó elevación de la fosfatasa alcalina e hiperbilirrubinemia directa. La fístula pancreática y la sepsis son las 2 principales complicaciones postoperatorias. La mejor sobrevida se ha encontrado en los 2 casos del tercio inferior, con uno de ellos vivo a los 3 años de operado. Se hace una revisión comparativa de la literatura