Design and evaluation of a mobile-based intervention for Maya adults during the COVID-19 pandemic

Introduction: The COVID-19 pandemic has had a direct impact on mental health. Inter national organisations have emphasised the vulnerability of indigenous people. Digital Mental Health approaches deliver online therapy as an evidence-based, effective, and accessible treat ment option for common mental health problems. However, the evidence regarding these ap proaches is limited in indigenous populations. The objective of this study is to describe the design, development, and evaluation of the efficacy of a self-applied online intervention regarding the psychological symptoms of depression, anxiety, and fear of COVID-19 in a sample of the Maya population. Method: A prospective longitudinal quantitative study was designed, where a single group was measured before and after receiving the online intervention. This study took place from April to September 2021 and consisted of six sessions delivered via WhatsApp in Spanish and Mayan. Results: The initial assessment was implemented with 82 participants who were evaluated using the Patient Health Questionnaire, Scale for Generalised Anxiety Disorder and the Fear of COVID-19 Scale; 18 participants remained in the intervention for the post-as sessment. Statistical differences were observed in PRE and POST measures of depression and anxiety, but not in fear of COVID-19. Conclusions: This study produced positive results for the first online mental health intervention implemented in the Latin American indigenous pop ulation. Future studies might consider developing similar interventions for other indigenous communities in Latin America.

Introducción: La pandemia de COVID-19 tuvo impacto directo en la salud mental. Organizaciones internacionales han enfatizado la vulnerabilidad de los pueblos indígenas. Los enfoques de salud mental digital brindan terapia en línea como una opción de tratamiento basada en evidencia, efectiva y accesible; sin embargo, los datos son limitados en población indígena. El objetivo de este estudio fue describir el diseño, desarrollo y evaluación de la eficacia de una intervención en línea autoaplicada sobre síntomas psicológicos de depresión, ansiedad y miedo al COVID-19 en una muestra de población maya. Método: Se diseñó un es tudio cuantitativo longitudinal prospectivo, donde se midió a un solo grupo antes y después de recibir la intervención en línea, implementada de abril a septiembre de 2021, que constó de seis sesiones impartidas vía WhatsApp, en español y maya. Resultados: La evaluación inicial se implementó con 82 participantes que fueron evaluados mediante el Cuestionario de Salud del Paciente, Escala para el Trastorno de Ansiedad Generalizada y Escala de Miedo al COVID-19; 18 participantes permanecieron para la evaluación posterior. Se observaron di ferencias estadísticas en las medidas pre- y post- de depresión y ansiedad, pero no miedo al COVID-19. Conclusiones: Este estudio arrojó resultados positivos de la primera intervención de salud mental en línea implementada en la población indígena latinoamericana. Estudios futuros podrían considerar el desarrollo de intervenciones similares para otras comunidades indígenas en América Latina.

Polluted wetlands contain multidrug-resistance plasmids encoding CTX-M-type extended-spectrum ß-lactamases.

While most detailed analyses of antibiotic resistance plasmids focus on those found in clinical isolates, less is known about the vast environmental reservoir of mobile genetic elements and the resistance and virulence factors they encode. We selectively isolated three strains of cefotaxime-resistant Escherichia coli from a wastewater-impacted coastal wetland. The cefotaxime-resistant phenotype was transmissible to a lab strain of E. coli after one hour, with frequencies as high as 10-3 transconjugants per recipient. Two of the plasmids also transferred cefotaxime resistance to Pseudomonas putida, but these were unable to back-transfer this resistance from P. putida to E. coli. In addition to the cephalosporins, E. coli transconjugants inherited resistance to at least seven distinct classes of antibiotics. Complete nucleotide sequences revealed large IncF-type plasmids with globally distributed replicon sequence types F31:A4:B1 and F18:B1:C4 carrying diverse antibiotic resistance and virulence genes. The plasmids encoded extended-spectrum ß-lactamases blaCTX-M-15 or blaCTX-M-55, each associated with the insertion sequence ISEc9, although in different local arrangements. Despite similar resistance profiles, the plasmids shared only one resistance gene in common, the aminoglycoside acetyltransferase aac(3)-IIe. Plasmid accessory cargo also included virulence factors involved in iron acquisition and defense against host immunity. Despite their sequence similarities, several large-scale recombination events were detected, including rearrangements and inversions. In conclusion, selection with a single antibiotic, cefotaxime, yielded conjugative plasmids conferring multiple resistance and virulence factors. Clearly, efforts to limit the spread of antibiotic resistance and virulence among bacteria must include a greater understanding of mobile elements in the natural and human-impacted environments.

Redundant mechanisms driven independently by RUNX1 and GATA2 for hematopoietic development.

RUNX1 is essential for the generation of hematopoietic stem cells (HSCs). Runx1-null mouse embryos lack definitive hematopoiesis and die in mid-gestation. However, although zebrafish embryos with a runx1 W84X mutation have defects in early definitive hematopoiesis, some runx1W84X/W84X embryos can develop to fertile adults with blood cells of multilineages, raising the possibility that HSCs can emerge without RUNX1. Here, using 3 new zebrafish runx1-/- lines, we uncovered the compensatory mechanism for runx1-independent hematopoiesis. We show that, in the absence of a functional runx1, a cd41-green fluorescent protein (GFP)+ population of hematopoietic precursors still emerge from the hemogenic endothelium and can colonize the hematopoietic tissues of the mutant embryos. Single-cell RNA sequencing of the cd41-GFP+ cells identified a set of runx1-/--specific signature genes during hematopoiesis. Significantly, gata2b, which normally acts upstream of runx1 for the generation of HSCs, was increased in the cd41-GFP+ cells in runx1-/- embryos. Interestingly, genetic inactivation of both gata2b and its paralog gata2a did not affect hematopoiesis. However, knocking out runx1 and any 3 of the 4 alleles of gata2a and gata2b abolished definitive hematopoiesis. Gata2 expression was also upregulated in hematopoietic cells in Runx1-/- mice, suggesting the compensatory mechanism is conserved. Our findings indicate that RUNX1 and GATA2 serve redundant roles for HSC production, acting as each other's safeguard.

A Self-Administered Multicomponent Web-Based Mental Health Intervention for the Mexican Population During the COVID-19 Pandemic: Protocol for a Randomized Controlled Trial.

BACKGROUND: The COVID-19 pandemic has become a public health emergency of international concern; it has not only threatened people's physical health but has also affected their mental health and psychological well-being. It is necessary to develop and offer strategies to reduce the psychological impact of the outbreak and promote adaptive coping. OBJECTIVE: This study protocol aims to describe a self-administered web-based intervention (Mental Health COVID-19) based on the principles of positive psychology supported by elements of cognitive behavioral therapy and behavioral activation therapy to reduce the symptoms of anxiety and depression and increase positive emotions and sleep quality during and after the COVID-19 outbreak through a telepsychology system. METHODS: A randomized controlled clinical superiority trial with two independent groups will be performed, with intrasubject measures at four evaluation periods: pretest, posttest, 3-month follow-up, and 6-month follow-up. Participants will be randomly assigned to one of two groups: self-administered intervention with assistance via chat or self-administered intervention without assistance via chat. The total required sample size will be 166 participants (83 per group). RESULTS: The clinical trial is ongoing. This protocol was approved by the Research Ethics Board of the Free School of Psychology-University of Behavioral Sciences (Escuela libre de Psicología-Universidad de Ciencias del Comportamiento). The aim is to publish the preliminary results in December 2020. A conservative approach will be adopted, and the size effect will be estimated using the Cohen d index with a significance level (α) of .05 (95% reliability) and a conventional 80% power statistic. CONCLUSIONS: The central mechanism of action will be to investigate the effectiveness of an intervention based on positive psychology through a web platform that can be delivered through computers and tablets, with content that has been rigorously contextualized to the Mexican culture to provide functional strategies to help the target users cope with the COVID-19 pandemic. TRIAL REGISTRATION: ClinicalTrials.gov NCT04468893; https://clinicaltrials.gov/ct2/show/NCT04468893. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/23117.

MicroRNA-18a-5p Suppresses Tumor Growth via Targeting Matrix Metalloproteinase-3 in Cisplatin-Resistant Ovarian Cancer.

Cumulating evidence indicates that dysregulation of microRNAs (miRNAs) plays a central role in the initiation, progression, and drug resistance of cancer cells. However, the specific miRNAs contributing to drug resistance in ovarian cancer cells have not been fully elucidated. Aimed to identify potential miRNAs involved in platinum resistance, we performed a miRNA expression profile in cisplatin-sensitive and cisplatin-resistant ovarian cancer cells, and we found several differentially abundant miRNAs in the pair of cell lines. Notably, miR-18a-5p (miR-18a), a member of the oncogenic associated miR-17-92 cluster, was decreased in cisplatin-resistant as compared with cisplatin-sensitive cells. Real-time PCR analysis confirmed these findings. We then studied the biological, molecular, and therapeutic consequences of increasing the miR-18a levels with oligonucleotide microRNA mimics (OMM). Compared with a negative control OMM, transient transfection of a miR-18a-OMM reduced cell growth, cell proliferation, and cell invasion. Intraperitoneal injections of miR-18a-OMM-loaded folate-conjugated liposomes significantly reduced the tumor weight and the number of nodules in ovarian cancer-bearing mice when compared with a control-OMM group. Survival analysis using the Kaplan-Meier plotter database showed that ovarian cancer patients with high miR-18a levels live longer in comparison to patients with lower miR-18a levels. Bioinformatic analyses, real-time-PCR, Western blots, and luciferase reporter assays revealed that Matrix Metalloproteinase-3 (MMP-3) is a direct target of miR-18a. Small-interfering RNA (siRNA)-mediated silencing of MMP-3 reduced cell viability, cell growth, and the invasiveness potential of cisplatin-resistant ovarian cancer cells. Our study suggests that targeting miR-18a is a plausible therapeutic strategy for cisplatin-resistant ovarian cancer.

The apical annuli of Toxoplasma gondii are composed of coiled-coil and signalling proteins embedded in the inner membrane complex sutures.

The apical annuli are among the most intriguing and understudied structures in the cytoskeleton of the apicomplexan parasite Toxoplasma gondii. We mapped the proteome of the annuli in Toxoplasma by reciprocal proximity biotinylation (BioID), and validated five apical annuli proteins (AAP1-5), Centrin2, and an apical annuli methyltransferase. Moreover, inner membrane complex (IMC) suture proteins connecting the alveolar vesicles were also detected and support annuli residence within the sutures. Super-resolution microscopy identified a concentric organisation comprising four rings with diameters ranging from 200 to 400 nm. The high prevalence of domain signatures shared with centrosomal proteins in the AAPs together with Centrin2 suggests that the annuli are related and/or derived from the centrosomes. Phylogenetic analysis revealed that the AAPs are conserved narrowly in coccidian, apicomplexan parasites that multiply by an internal budding mechanism. This suggests a role in replication, for example, to provide pores in the mother IMC permitting exchange of building blocks and waste products. However, presence of multiple signalling domains and proteins are suggestive of additional functions. Knockout of AAP4, the most conserved compound forming the largest ring-like structure, modestly decreased parasite fitness in vitro but had no significant impact on acute virulence in vivo. In conclusion, the apical annuli are composed of coiled-coil and signalling proteins assembled in a pore-like structure crossing the IMC barrier maintained during internal budding.

Improved annotation of the insect vector of citrus greening disease: biocuration by a diverse genomics community.

Database URL: https://citrusgreening.org/.

Characterization of Four Multidrug Resistance Plasmids Captured from the Sediments of an Urban Coastal Wetland.

Self-transmissible and mobilizable plasmids contribute to the emergence and spread of multidrug-resistant bacteria by enabling the horizontal transfer of acquired antibiotic resistance. The objective of this study was to capture and characterize self-transmissible and mobilizable resistance plasmids from a coastal wetland impacted by urban stormwater runoff and human wastewater during the rainy season. Four plasmids were captured, two self-transmissible and two mobilizable, using both mating and enrichment approaches. Plasmid genomes, sequenced with either Illumina or PacBio platforms, revealed representatives of incompatibility groups IncP-6, IncR, IncN3, and IncF. The plasmids ranged in size from 36 to 144 kb and encoded known resistance genes for most of the major classes of antibiotics used to treat Gram-negative infections (tetracyclines, sulfonamides, ß-lactams, fluoroquinolones, aminoglycosides, and amphenicols). The mobilizable IncP-6 plasmid pLNU-11 was discovered in a strain of Citrobacter freundii enriched from the wetland sediments with tetracycline and nalidixic acid, and encodes a novel AmpC-like ß-lactamase (blaWDC-1), which shares less than 62% amino acid sequence identity with the PDC class of ß-lactamases found in Pseudomonas aeruginosa. Although the IncR plasmid pTRE-1611 was captured by mating wetland bacteria with P. putida KT2440 as recipient, it was found to be mobilizable rather than self-transmissible. Two self-transmissible multidrug-resistance plasmids were also captured: the small (48 kb) IncN3 plasmid pTRE-131 was captured by mating wetland bacteria with Escherichia coli HY842 where it is seemed to be maintained at nearly 240 copies per cell, while the large (144 kb) IncF plasmid pTRE-2011, which was isolated from a cefotaxime-resistant environmental strain of E. coli ST744, exists at just a single copy per cell. Furthermore, pTRE-2011 bears the globally epidemic blaCTX-M-55 extended-spectrum ß-lactamase downstream of ISEcp1. Our results indicate that urban coastal wetlands are reservoirs of diverse self-transmissible and mobilizable plasmids of relevance to human health.