Egg-laying by female Aedes aegypti shapes the bacterial communities of breeding sites.

BACKGROUND: Aedes aegypti, the main arboviral mosquito vector, is attracted to human dwellings and makes use of human-generated breeding sites. Past research has shown that bacterial communities associated with such sites undergo compositional shifts as larvae develop and that exposure to different bacteria during larval stages can have an impact on mosquito development and life-history traits. Based on these facts, we hypothesized that female Ae. aegypti shape the bacteria communities of breeding sites during oviposition as a form of niche construction to favor offspring fitness. RESULTS: To test this hypothesis, we first verified that gravid females can act as mechanical vectors of bacteria. We then elaborated an experimental scheme to test the impact of oviposition on breeding site microbiota. Five different groups of experimental breeding sites were set up with a sterile aqueous solution of larval food, and subsequently exposed to (1) the environment alone, (2) surface-sterilized eggs, (3) unsterilized eggs, (4) a non-egg laying female, or (5) oviposition by a gravid female. The microbiota of these differently treated sites was assessed by amplicon-oriented DNA sequencing once the larvae from the sites with eggs had completed development and formed pupae. Microbial ecology analyses revealed significant differences between the five treatments in terms of diversity. In particular, between-treatment shifts in abundance profiles were detected, showing that females induce a significant decrease in microbial alpha diversity through oviposition. In addition, indicator species analysis pinpointed bacterial taxa with significant predicting values and fidelity coefficients for the samples in which single females laid eggs. Furthermore, we provide evidence regarding how one of these indicator taxa, Elizabethkingia, exerts a positive effect on the development and fitness of mosquito larvae. CONCLUSIONS: Ovipositing females impact the composition of the microbial community associated with a breeding site, promoting certain bacterial taxa over those prevailing in the environment. Among these bacteria, we found known mosquito symbionts and showed that they can improve offspring fitness if present in the water where eggs are laid. We deem this oviposition-mediated bacterial community shaping as a form of niche construction initiated by the gravid female.

Impairments in fine motor skills in children with Acute Lymphoblastic Leukaemia. A cross-sectional study.

AIM: We evaluated fine motor skills; precision, motor integration, manual dexterity, and upper-limb coordination according to sex and risk stratification in children with Acute Lymphoblastic Leukaemia (ALL). METHODS: We evaluated twenty-nine children in the maintenance phase aged 6 to 12 years with the Bruininks-Oseretsky Test of Motor Proficiency-second edition (BOT-2), and sex and age-specific norm values of BOT-2 were used to compare our results. RESULTS: We found lower scores on the upper-limb coordination subtest, p = 0.003 and on the manual coordination composite, p = 0.008, than normative values. Most boys performed "average" on both the subtests and the composites, but girls showed lower scores with a mean difference of 7.69 (95%CI; 2.24 to 3.14), p = 0.009. Girls' scale scores on the upper-limb coordination subtest were lower than normative values, with mean difference 5.08 (95%CI; 2.35 to 7.81), p = 0.006. The mean standard score difference in high-risk patients was lower than normative on the manual coordination composite, 8.18 (95%CI; 2.26 to 14.1), p = 0.015. High-risk children also performed below the BOT-2 normative on manual dexterity 2.82 (95%CI; 0.14 to 5.78), p = 0.035 and upper limb coordination subtest 4.10 (95%CI; 1.13 to 7.05), p = 0.028. We found a decrease in fine motor precision in children with a higher BMI, rho= -0.87, p = 0.056 and a negative correlation between older age and lower manual dexterity, r= -0.41 p = 0.026; however, we did not find any correlation with the weeks in the maintenance phase. CONCLUSIONS: Fine motor impairments are common in children with ALL in the maintenance phase; it is important to identify these impairments to early rehabilitation.

Syndemic Conditions and Their Association with HIV/STI Sexual Risk Behaviors Among Transgender Women and Cisgender Men Sex Workers in Catalonia: The SexCohort Project.

BACKGROUND: Transgender women and cisgender men sex workers are vulnerable to HIV and sexually transmitted infections (STIs). This study aimed to explore in depth the prevalence of syndemic conditions and their association with the sexual risk behaviors for HIV/STI acquisition in cis men and trans women sex workers in Barcelona (Catalonia, Spain). METHOD: We conducted a study between 2014 and 2018 to determine whether syndemic conditions (frequent alcohol consumption and polydrug use (> 2) during sex with clients; experience of violence; and lack of healthcare access) are associated with HIV/STI sexual risk behaviors. A "syndemic index" was calculated based on the cumulative number of syndemic conditions (0 to 4). RESULTS: In the last year (2018), 78.8% of cisgender men and 68.1% of transgender women reported at least one syndemic condition. The most prevalent syndemic factor in both cisgender men and transgender women was violence (38.8% and 43.6% respectively). In multivariable analysis, an association was found between condomless anal sex and violence (aOR = 1.81), and frequent alcohol consumption and violence with reporting > 10 clients/week (aOR = 2.73 and 1.88, respectively). The higher the number of syndemic factors, the greater probability of having > 10 clients/week and reporting condomless anal sex with clients. CONCLUSION: Psychosocial conditions have a syndemic effect on risky sexual behaviors highlighting the need for a more holistic approach to HIV/STI prevention targeting these populations.

Chemsex in Barcelona: A qualitative study of factors associated with the practice, the perception of the impact on health and prevention needs. / Chemsex en Barcelona: Estudio cualitativo sobre factores asociados a la práctica, percepción del impacto en salud y necesidades de prevención.

Chemsex is defined as use of psychoactive drugs with the aim of having sexual relations between gay men, bisexuals and men who have sex with men for a long period of time. To study this phenomenon, this qualitative descriptive study was proposed with the objective of describing the practice of chemsex from the perspective of users, to determine the main factors associated with its practice, the perception of the impact on their health and to establish prevention needs. Data were obtained using conversational techniques: 12 semi-structured interviews and 3 focus groups. The purposive sample was made up of GBMSM with a mean age of 40.1 years, 78% born in Spain, and 68% with completed university studies. The qualitative analysis focused on three thematic areas: factors associated with the practice of chemsex, the impact of chemsex on health, and prevention and risk reduction needs. It is concluded that the practice of chemsex should be understood as multifactorial and multicausal, associated with the sociocultural context. Sexual satisfaction, increased libido and the search for more intense pleasure are identified as key factors among people who practice it. These men are still scared of being judged, even by specialists who may lack knowledge or training. A reanalysis and rethinking of the interventions and policies directed towards this population is necessary, putting the focus of action on shared decision-making, self-care, cultural competence and the humanization of care.

El chemsex se define como el uso de drogas psicoactivas con el objetivo de mantener relaciones sexuales entre hombres gay, bisexuales y otros hombres que tienen sexo con hombres (GBHSH), por un largo periodo de tiempo. El objetivo de este estudio cualitativo exploratorio es describir la práctica del chemsex desde la perspectiva de los usuarios, determinar los principales factores asociados a su práctica, la percepción del impacto en su salud y establecer necesidades de prevención. Se obtuvieron los datos mediante técnicas conversacionales: 12 entrevistas semiestructuradas y 3 grupos focales. El análisis cualitativo se centró en tres áreas temáticas: factores asociados a la práctica de chemsex, impacto del chemsex en la salud y necesidades prevención y reducción de riesgos. La muestra intencionada fue conformada por hombres GBHSH con una edad media de 40,1 años, 78% nacidos en España, y 68% con estudios universitarios finalizados. Los resultados del estudio ponen de manifiesto que la práctica de chemsex debe comprenderse como multifactorial y multicausal, y asociada al contexto sociocultural. La satisfacción sexual, del aumento de la libido y de la búsqueda de placer más intenso se identifican como factores clave entre las personas que lo practican. Sigue existiendo miedo en estos hombres a ser juzgados, incluso por los especialistas que pueden carecer de conocimiento o formación. Es necesario un reanálisis y replanteamiento de las intervenciones y políticas dirigidas hacia esta población, poniendo el foco de acción en la toma de decisiones compartidas, el autocuidado, la competencia cultural y la humanización del cuidado.

High occurrence of CRLF2 abnormalities in Mexican children with B-cell acute lymphoblastic leukemia.

The P2RY8-CRLF2 and IGH-CRLF2 rearrangements induce the overexpression of cytokine receptor-like factor 2 (CRLF2) and have been associated with relapse and poor prognosis in B-cell acute lymphoblastic leukemia (B-ALL). Additionally, they are frequently documented in high-risk Hispanic populations. To better understand the potential causes of the adverse prognosis of childhood B-ALL in Mexico, we analyzed these rearrangements and the CRLF2 mRNA and protein levels in 133 Mexican children with B-ALL. We collected bone marrow samples at diagnosis and evaluated the CRLF2 gene expression by qRT-PCR and the total CRLF2 protein by flow cytometry. P2RY8-CRLF2 and IGH-CRLF2 were detected by RT-PCR and FISH, respectively. The median time of follow-up to determine the prognostic significance of the CRLF2 abnormalities was three years. In 82% of the participants, the mRNA levels correlated with the cell-surface and intracellular CRLF2 protein levels. The P2RY8-CRLF2 rearrangement was present in 31.5% (42/133) of the patients, while the IGH-CRLF2 rearrangement was detected in 13.5% (9/67) of patients with high expression of CRLF2 (6.8% of the total sample). CRLF2 copy number variations (gain) were also detected in 7.5% (5/67) of patients with high protein levels. The overall survival (OS) presented significantly lower rates in patients with high white blood cell count (≥50x109/L) regardless of CRLF2 expression, but high levels of CRLF2 gene expression appears to contribute to the reduction of OS within this group of patients. In conclusion, in our cohort, a high occurrence of CRLF2 abnormalities was documented, particularly the P2RY8-CRLF2 rearrangement, which might represent a characteristic of the Mexican population. Targeted therapy to treat this group of patients could improve OS.

Costs associated with adverse events from remission induction for children with Acute Lymphoblastic Leukemia (ALL).

BACKGROUND: ALL is the most frequent hematological tumor in children, so during remission induction chemotherapy protocol (RICP) adverse events (AEs) may appear. The public program in Mexico in charge of financial support to oncologic children without social security delivered a fix amount for ALL chemotherapy, but additional money needed to treat any other unexpected condition should be taken from the budget of the oncologic healthcare providers. So the purpose of our study was to estimate and evaluate the direct medical costs associated to EAs during RICP in children with ALL. METHODS: This study was retrospective, longitudinal, and observational based on medical records review of patients in RICP. The CTCAE was used to identify and classify AEs according to a SOC category. We focused on extracting resources data that were consumed both for inpatients and outpatients AEs. A micro-costing approach was adopted which involve quantification of each healthcare resource consumed by the hospital multiplying them by unit cost. The probability distributions of data were evaluated to identify the appropriated statistical tests to be used for comparisons between groups that were performed with Wilcoxon rank sum test. Generalized linear models (GLM) were adjusted to evaluate the effects of patient characteristics on total cost. RESULTS: Forty patients accumulated 204 inpatient and 81 outpatient AEs during RICP. Comparison of total costs between groups showed an incremental cost of $7,460.23 likewise attributable to AEs. The total cost of a pediatric patient undergoing RICP without adverse events was $3,078.36 and the total cost of a patient with AEs exceeds it threefold. CONCLUSIONS: The costs associated with AEs during RICP in Mexican children with ALL representing a high burden for the healthcare provider. Generalized linear models showed that variables such as sex, risk category and alive status are associated with the total costs of AEs. This is the first study aiming to analyze the effect of ALL-related AEs on health care costs in pediatric population, so our results may help not only to local decision making but also it may contribute to the research agenda in this field.

Characterization of Philadelphia-like Pre-B Acute Lymphoblastic Leukemia: Experiences in Mexican Pediatric Patients.

Ph-like subtypes with CRLF2 abnormalities are frequent among Hispano-Latino children with pre-B ALL. Therefore, there is solid ground to suggest that this subtype is frequent in Mexican patients. The genomic complexity of Ph-like subtype constitutes a challenge for diagnosis, as it requires diverse genomic methodologies that are not widely available in diagnostic centers in Mexico. Here, we propose a diagnostic strategy for Ph-like ALL in accordance with our local capacity. Pre-B ALL patients without recurrent gene fusions (104) were classified using a gene-expression profile based on Ph-like signature genes analyzed by qRT-PCR. The expressions of the CRLF2 transcript and protein were determined by qRT-PCR and flow cytometry. The P2RY8::CRLF2, IGH::CRLF2, ABL1/2 rearrangements, and Ik6 isoform were screened using RT-PCR and FISH. Surrogate markers of Jak2-Stat5/Abl/Ras pathways were analyzed by phosphoflow. Mutations in relevant kinases/transcription factors genes in Ph-like were assessed by target-specific NGS. A total of 40 patients (38.5%) were classified as Ph-like; of these, 36 had abnormalities associated with Jak2-Stat5 and 4 had Abl. The rearrangements IGH::CRLF2,P2RY8::CRLF2, and iAMP21 were particularly frequent. We propose a strategy for the detection of Ph-like patients, by analyzing the overexpression/genetic lesions of CRLF2, the Abl phosphorylation of surrogate markers confirmed by gene rearrangements, and Sanger sequencing.

Patient and health service factors associated with delays in cancer treatment for children without social security in Mexico.

BACKGROUND: The objective was to investigate factors associated with patient-related timing (PRT) to seek healthcare and health service-related timing (HSRT) to diagnose cancer and provide treatment to children without social security in Mexico. PROCEDURE: A cross-sectional survey was conducted in 13 Ministry of Health hospitals in the states of Chihuahua, Jalisco, Mexico City, Morelos, Oaxaca, Puebla, Queretaro, State of Mexico, and Tlaxcala. Study participants were parents of recently diagnosed pediatric cancer patients (≤ 17 years of age). Three groups of factors were investigated: (1) patients (child and parent characteristics); (2) healthcare providers (HCPs) (first-contact HCP, institution, perceptions of barriers to healthcare, etc.); and (3) disease factors (cancer type/site, stage/risk at diagnosis). PRT and HSRT-associated factors were identified using multiple negative binomial regressions. RESULTS: The study included 265 children; 49% sought care when symptoms first appeared. The median PRT was seven days, and the median HSRT was 40 days. Parents' perceptions of long wait times for appointments were associated with longer PRT and HSRT. Residing in the lowest or highest socioeconomic regions and persistent or worsening symptoms increased the probability of longer PRT. Older patient age, HCP requests for imaging tests or prescription for steroids, a higher number of doctors consulted, having a urinary tract cancer, and having an advanced stage or high-risk cancer increased the probability of longer HSRT. CONCLUSION: Strategies to shorten lag time from symptom onset to diagnosis and treatment are urgently needed for childhood cancers in Mexico.

Safety and efficacy of step-down to oral outpatient treatment versus inpatient antimicrobial treatment in pediatric cancer patients with febrile neutropenia: A noninferiority multicenter randomized clinical trial.

BACKGROUND: It has been suggested that low-risk febrile neutropenia (FN) episodes can be treated in a step-down manner in the outpatient setting. This recommendation has been limited to implementation in middle-income countries due to concerns about infrastructure and lack of trained personnel. We aimed to determine whether early step-down to oral antimicrobial outpatient treatment is not inferior in safety and efficacy to inpatient intravenous treatment in children with low-risk FN. PROCEDURE: A noninferiority randomized controlled clinical trial was conducted in three hospitals in Mexico City. Low-risk FN was identified in children younger than 18 years. After 48 to 72 hours of intravenous treatment, children were randomly allocated to receive outpatient oral treatment (experimental arm, cefixime) or to continue inpatient treatment (standard of care, cefepime). Daily monitoring was performed until neutropenia resolution. The presence of any unfavorable clinical outcome was the endpoint of interest. We performed a noninferiority test for comparison of proportions. RESULTS: We identified 1237 FN episodes; 117 cases were randomized: 60 to the outpatient group and 57 for continued inpatient treatment. Of the FN episodes, 100% in the outpatient group and 93% in the inpatient group had a favorable outcome (P < 0.001). The mean duration of antibiotics was 4.1 days (SD 2.5; 95% CI, 3.4-4.8 days) in the outpatient group and 4.4 days (SD 2.5; 95% CI, 3.7-5.0 days) in the inpatient group (P = 0.70). CONCLUSIONS: In our population, step-down oral outpatient treatment of low-risk FN was as safe and effective as inpatient intravenous treatment. Clinical Trials Identifier: NCT04000711.

Expression of YY1 in Wilms tumors with favorable histology is a risk factor for adverse outcomes.

AIM: To investigate the role of the transcription factor YY1 in Wilms tumor (WT). PATIENTS & METHODS: We measured YY1 expression using tissue microarray from patients with pediatric renal tumors, mainly WT and evaluated correlations with the predicted clinical evolution. YY1 expression was measured using immunohistochemical and protein expression was determined by digital pathology. RESULTS & CONCLUSION: YY1 significantly increased in WT patients. In addition, an increase in YY1 expression had a greater risk of adverse outcomes in WT patients with favorable histology. YY1 expression was higher in the blastemal component of tumors, and high nuclear expression positively correlated with metastasis. YY1 may be considered as a metastasis risk factor in WT.

Species-specific escape of Plasmodium sporozoites from oocysts of avian, rodent, and human malarial parasites.

BACKGROUND: Malaria is transmitted when an infected mosquito delivers Plasmodium sporozoites into a vertebrate host. There are many species of Plasmodium and, in general, the infection is host-specific. For example, Plasmodium gallinaceum is an avian parasite, while Plasmodium berghei infects mice. These two parasites have been extensively used as experimental models of malaria transmission. Plasmodium falciparum and Plasmodium vivax are the most important agents of human malaria, a life-threatening disease of global importance. To complete their life cycle, Plasmodium parasites must traverse the mosquito midgut and form an oocyst that will divide continuously. Mature oocysts release thousands of sporozoites into the mosquito haemolymph that must reach the salivary gland to infect a new vertebrate host. The current understanding of the biology of oocyst formation and sporozoite release is mostly based on experimental infections with P. berghei, and the conclusions are generalized to other Plasmodium species that infect humans without further morphological analyses. RESULTS: Here, it is described the microanatomy of sporozoite escape from oocysts of four Plasmodium species: the two laboratory models, P. gallinaceum and P. berghei, and the two main species that cause malaria in humans, P. vivax and P. falciparum. It was found that sporozoites have species-specific mechanisms of escape from the oocyst. The two model species of Plasmodium had a common mechanism, in which the oocyst wall breaks down before sporozoites emerge. In contrast, P. vivax and P. falciparum sporozoites show a dynamic escape mechanism from the oocyst via polarized propulsion. CONCLUSIONS: This study demonstrated that Plasmodium species do not share a common mechanism of sporozoite escape, as previously thought, but show complex and species-specific mechanisms. In addition, the knowledge of this phenomenon in human Plasmodium can facilitate transmission-blocking studies and not those ones only based on the murine and avian models.

An overview of malaria transmission from the perspective of Amazon Anopheles vectors.

In the Americas, areas with a high risk of malaria transmission are mainly located in the Amazon Forest, which extends across nine countries. One keystone step to understanding the Plasmodium life cycle in Anopheles species from the Amazon Region is to obtain experimentally infected mosquito vectors. Several attempts to colonise Anopheles species have been conducted, but with only short-lived success or no success at all. In this review, we review the literature on malaria transmission from the perspective of its Amazon vectors. Currently, it is possible to develop experimental Plasmodium vivax infection of the colonised and field-captured vectors in laboratories located close to Amazonian endemic areas. We are also reviewing studies related to the immune response to P. vivax infection of Anopheles aquasalis, a coastal mosquito species. Finally, we discuss the importance of the modulation of Plasmodium infection by the vector microbiota and also consider the anopheline genomes. The establishment of experimental mosquito infections with Plasmodium falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide interesting models for studying malaria in the Amazonian scenario is important. Understanding the molecular mechanisms involved in the development of the parasites in New World vectors is crucial in order to better determine the interaction process and vectorial competence.

Metagenomics, paratransgenesis and the Anopheles microbiome: a portrait of the geographical distribution of the anopheline microbiota based on a meta-analysis of reported taxa.

Anophelines harbour a diverse microbial consortium that may represent an extended gene pool for the host. The proposed effects of the insect microbiota span physiological, metabolic and immune processes. Here we synthesise how current metagenomic tools combined with classical culture-dependent techniques provide new insights in the elucidation of the role of the Anopheles-associated microbiota. Many proposed malaria control strategies have been based upon the immunomodulating effects that the bacterial components of the microbiota appear to exert and their ability to express anti-Plasmodium peptides. The number of identified bacterial taxa has increased in the current "omics" era and the available data are mostly scattered or in "tables" that are difficult to exploit. Published microbiota reports for multiple anopheline species were compiled in an Excel® spreadsheet. We then filtered the microbiota data using a continent-oriented criterion and generated a visual correlation showing the exclusive and shared bacterial genera among four continents. The data suggested the existence of a core group of bacteria associated in a stable manner with their anopheline hosts. However, the lack of data from Neotropical vectors may reduce the possibility of defining the core microbiota and understanding the mosquito-bacteria interactive consortium.

The microbiota of Amblyomma americanum reflects known westward expansion.

Amblyomma americanum, a known vector of multiple tick-borne pathogens, has expanded its geographic distribution across the United States in the past decades. Tick microbiomes may play a role shaping their host's life history and vectorial capacity. Bacterial communities associated with A. americanum may reflect, or enable, geographic expansion and studying the microbiota will improve understanding of tick-borne disease ecology. We examined the microbiota structure of 189 adult ticks collected in four regions encompassing their historical and current geographic distribution. Both geographic region of origin and sex were significant predictors of alpha diversity. As in other tick models, within-sample diversity was low and uneven given the presence of dominant endosymbionts. Beta diversity analyses revealed that bacterial profiles of ticks of both sexes collected in the West were significantly different from those of the Historic range. Biomarkers were identified for all regions except the historical range. In addition, Bray-Curtis dissimilarities overall increased with distance between sites. Relative quantification of ecological processes showed that, for females and males, respectively, drift and dispersal limitation were the primary drivers of community assembly. Collectively, our findings highlight how microbiota structural variance discriminates the western-expanded populations of A. americanum ticks from the Historical range. Spatial autocorrelation, and particularly the detection of non-selective ecological processes, are indicative of geographic isolation. We also found that prevalence of Ehrlichia chaffeensis, E. ewingii, and Anaplasma phagocytophilum ranged from 3.40-5.11% and did not significantly differ by region. Rickettsia rickettsii was absent from our samples. Our conclusions demonstrate the value of synergistic analysis of biogeographic and microbial ecology data in investigating range expansion in A. americanum and potentially other tick vectors as well.

Mosquito abundance and diversity in central Ohio, USA vary among stormwater wetlands, retention ponds, and detention ponds and their associated environmental parameters.

Mosquitoes (Diptera: Culicidae) are one of the most impactful pests to human society, both as a nuisance and a potential vector of human and animal pathogens. Mosquito larvae develop in still aquatic environments. Eliminating these habitats near high human density or managing them to reduce the suitability for mosquitoes will reduce mosquito populations in these human environments and decrease the overall negative impact of mosquitoes on humans. One common source of standing water in urban and suburban environments is the water that pools in stormwater control measures. Previous studies have shown that some stormwater control measures generate large numbers of mosquitoes while others harbor none, and the reason for this difference remains unclear. Our study focuses on elucidating the factors that cause a stormwater control measure to be more or less suitable for mosquitoes. During the summers of 2021 and 2022, we collected and identified mosquito larvae from thirty stormwater control measures across central Ohio to assess variation in mosquito abundance and diversity among sites. Our goal was to determine if specific types of stormwater control measures (retention ponds, detention ponds, or constructed wetlands) harbored different abundances of mosquitoes or different community structures. We also assessed environmental parameters of these sites to elucidate their effects on mosquito abundance and diversity. Overall, we recorded the highest number of mosquito larvae and species in constructed wetlands. However, these sites were dominated by the innocuous species, Culex territans. Conversely, detention ponds held fewer mosquitoes but a higher proportion of known vector species, including Culex pipiens and Aedes vexans. The total number of mosquitoes across all sites was correlated with higher vegetation, more shade, lower water temperatures, and lower pH, suggesting stormwater control measures with these features may also be hotspots for mosquito proliferation.

Germline mutations in pediatric cancer cohort with mixed-ancestry Mexicans.

BACKGROUND: Childhood cancer is one of the primary causes of disease-related death in 5- to 14-year-old children and currently no prevention strategies exist to reduce the incidence of this disease. Childhood cancer has a larger hereditary component compared with cancer in adults. Few genetic studies have been conducted on children with cancer. Additionally, Latin American populations are underrepresented in genomic studies compared with other populations. Therefore, the aim of this study is to analyze germline mutations in a group of mixed-ancestry Mexican pediatric patients with solid and hematological cancers. METHODS: We analyzed genetic variants from 40 Mexican childhood cancer patients and their relatives. DNA from saliva or blood samples was used for whole-exome sequencing. All variants were identified following GATK best practices. RESULTS: We found that six patients (15%) were carriers of germline mutations in CDKN2A, CHEK2, DICER1, FANCA, MSH6, MUTYH, NF1, and SBDS cancer predisposition genes, and additional new variants predicted to be deleterious by in silico algorithms. A population genetics analysis detected five components consistent with the demographic models assumed for modern mixed-ancestry Mexicans. CONCLUSIONS: This report identifies potential genetic risk factors and provides a better understanding of the underlying mechanisms of childhood cancer in this population.

Phase 1 study of epigenetic priming with decitabine prior to standard induction chemotherapy for patients with AML.

We conducted an open-label phase 1 study exploring the feasibility, safety, and biologic activity of epigenetic priming with decitabine before standard induction chemotherapy in patients with less-than-favorable risk of acute myelogenous leukemia (AML). We directly compared the clinical and DNA-hypomethylating activity of decitabine delivered at 20 mg/m² by either a 1-hour infusion (Arm A) or a continuous infusion (Arm B) for 3, 5, or 7 days before a single, standard induction with infusional cytarabine (100 mg/m² for 7 days) and daunorubicin (60 mg/m² × 3 doses). Toxicity was similar to that of standard induction chemotherapy alone. Although we did not identify a maximum tolerated dose, there was more gastro-intestinal toxicity with 7 days of decitabine priming. Decitabine induced DNA hypomethylation at all dose levels and there was a trend toward greater hypomethylation in CD34(+) bone marrow cells when decitabine was delivered by a short pulse (Arm A). Twenty-seven subjects (90%) responded to therapy: 17 with complete remission (57%) and 10 with partial remission (33%). Of the patients with partial remission to protocol treatment, 8 achieved remission to their next therapy, bringing the overall complete remission rate to 83%. We conclude that epigenetic priming of intensive chemotherapy can be safely delivered in an attempt to improve response rates. This trial was registered at www.clinicaltrials.gov as NCT00538876.

Bacterial communities of Aedes aegypti mosquitoes differ between crop and midgut tissues.

Microbiota studies of Aedes aegypti and other mosquitoes generally focus on the bacterial communities found in adult female midguts. However, other compartments of the digestive tract maintain communities of bacteria which remain almost entirely unstudied. For example, the Dipteran crop is a food storage organ, but few studies have looked at the microbiome of crops in mosquitoes, and only a single previous study has investigated the crop in Ae. aegypti. In this study, we used both culture-dependent and culture-independent methods to compare the bacterial communities in midguts and crops of laboratory reared Ae. aegypti. Both methods revealed a trend towards higher abundance, but also higher variability, of bacteria in the midgut than the crop. When present, bacteria from the genus Elizabethkingia (family Weeksellaceae) dominated midgut bacterial communities. In crops, we found a higher diversity of bacteria, and these communities were generally dominated by acetic acid bacteria (family Acetobacteriaceae) from the genera Tanticharoenia and Asaia. These three taxa drove significant community structure differences between the tissues. We used FAPROTAX to predict the metabolic functions of these communities and found that crop bacterial communities were significantly more likely to contain bacteria capable of methanol oxidation and methylotrophy. Both the presence of acetic acid bacteria (which commonly catabolize sugar to produce acetic acid) and the functional profile that includes methanol oxidation (which is correlated with bacteria found with natural sources like nectar) may relate to the presence of sugar, which is stored in the mosquito crop. A better understanding of what bacteria are present in the digestive tract of mosquitoes and how these communities assemble will inform how the microbiota impacts mosquito physiology and the full spectrum of functions provided by the microbiota. It may also facilitate better methods of engineering the mosquito microbiome for vector control or prevention of disease transmission.

Long-term experience in treatment of acute promyelocytic leukemia in Mexican children in a tertiary care hospital.

Introduction: Acute promyelocytic leukemia (APL) is a rare myeloid leukemia subtype affecting adult and pediatric populations. APL constitutes 15-20% of all childhood AML in Latin America, compared to 7% in the non-Latino population. This leukemia has unique characteristics, such as its association with chromosomal translocations involving the retinoid acid receptor α (RARA) gene on chromosome 17. In addition, APL is also distinct from other AML subtypes due to its response to all-trans-retinoic acid (ATRA), which induces terminal granulocytic differentiation of blasts. Overall 5-year survival rates are generally reported to be greater than 80%. Materials and methods: A study was conducted from January 2008 to December 2022 applying the IC-APL 2006 treatment protocol. This case series reports the clinical results of 22 children with APL. In all cases, the diagnosis was made by bone marrow aspiration and evaluation of the t(15:17) or t(11:17) transcripts. Results: We identified 22 patients with APL, of whom 10 were female and 12 were male. Twelve patients debuted with coagulation abnormalities. The doses of anthracyclines varied according to the risk, with an average of 496.8 mgm2. The cardiological assessment was performed before and after chemotherapy, finding 2/22 patients with moderate sisto-diastolic dysfunction and one with mild pulmonary insufficiency at the end of treatment. There were 6/22 patients with complications related to ATRA treatment, the most frequent being pseudotumor cerebri. All complications were transitory and treated immediately without complications. In this series of cases, an overall survival of 90.6% and a relapse-free survival of 90.6% were recorded. The follow-up mean was 9.1 ± 3.8 years. Conclusion: APL is a highly curable disease when combined with ATRA and anthracyclines. In this series of cases, good long-term results were observed with the IC-APL 2006 protocol. However, in Latin America, the availability of drugs such as arsenic trioxide as the first line of treatment is an unresolved challenge.