Applications of RNA-based molecular logic have been hampered by sequence constraints imposed on the input and output of the circuits. Here we show that the sequence constraints can be substantially reduced by appropriately encoded multi-arm junctions of single-stranded RNA structures. To conditionally activate RNA translation, we integrated multi-arm junctions, self-assembled upstream of a regulated gene and designed to unfold sequentially in response to different RNA inputs, with motifs of loop-initiated RNA activators that function independently of the sequence of the input RNAs and that reduce interference with the output gene. We used the integrated RNA system and sequence-independent input RNAs to execute two-input and three-input OR and AND logic in Escherichia coli, and designed paper-based cell-free colourimetric assays that accurately identified two human immunodeficiency virus (HIV) subtypes (by executing OR logic) in amplified synthetic HIV RNA as well as severe acute respiratory syndrome coronavirus-2 (via two-input AND logic) in amplified RNA from saliva samples. The sequence-independent molecular logic enabled by the integration of multi-arm junction RNAs with motifs for loop-initiated RNA activators may be broadly applicable in biotechnology.
1 March 2021 in International Journal of Infectious Diseases
The COVID-19 diagnosis is difficult and ambiguous due to nonspecific symptoms. Further, data from Mexico arehospitable population-based without signs and symptoms information. Thus, this work aims to provide epidemiology information about the burden of COVID-19 in Mexican outpatients and to identify symptomatic COVID-19 profiles that could help in the early diagnosis of the disease. From June to September, epidemiological, clinical, and demographic data of 482,413 individuals diagnosed by RT-PCR test for SARS-CoV-2 in Salud Digna clinics were collected. We observed a 41% incidence of SARS-CoV-2 infections with a mean age of 36 years and with young adults (20-40 years) being the most affected. Among occupations, delivery persons (OR 1.38) or informal traders (OR 1.33) had a higher risk of COVID-19. Moreover, 13% of SARS-CoV-2 infections were in presymptomatic patients. Finally, we identified three different symptomatic profiles (common, respiratory, and gastrointestinal) associated with COVID-19. The incidence of SARS-CoV-2 was high among outpatients with a significant proportion of presymptomatic carriers, and thus it is necessary to increase testing and continue SARS-CoV-2 surveillance with a better description of signs and symptoms; in this regard, we identified three symptomatic profiles that could help in the diagnosis of COVID-19.
Omicron is the most mutated SARS-CoV-2 variant—a factor that can affect transmissibility, disease severity, and immune evasiveness. Its genomic surveillance is important in cities with millions of inhabitants and an economic center, such as Mexico City. Results. From 16 November to 31 December 2021, we observed an increase of 88% in Omicron prevalence in Mexico City. We explored the R346K substitution, prevalent in 42% of Omicron variants, known to be associated with immune escape by monoclonal antibodies. In a phylogenetic analysis, we found several independent exchanges between Mexico and the world, and there was an event followed by local transmission that gave rise to most of the Omicron diversity in Mexico City. A haplotype analysis revealed that there was no association between haplotype and vaccination status. Among the 66% of patients who have been vaccinated, no reported comorbidities were associated with Omicron; the presence of odynophagia and the absence of dysgeusia were significant predictor symptoms for Omicron, and the RT-qPCR Ct values were lower for Omicron. Conclusions. Genomic surveillance is key to detecting the emergence and spread of SARS-CoV-2 variants in a timely manner, even weeks before the onset of an infection wave, and can inform public health decisions and detect the spread of any mutation that may affect therapeutic efficacy.
Objective. To determine the frequency and distribution of ABO and Rh (D) antigens and, additionally, investigate gene diversity and the structure of Mexican populations.Materials and Methods. Blood groups were tested in 271,164 subjects from 2014 to 2016. The ABO blood group was determined by agglutination using the antibodies anti-A, Anti-B, and Anti-D for the Rh factor, respectively.Results. The overall distribution of ABO and Rh (D) groups in the population studied was as follows: O: 61.82%; A: 27.44%; B: 8.93%; and AB: 1.81%. For the Rh group, 95.58% of people were Rh (D), and 4.42% were Rh (d). Different distributions of blood groups across regions were found; additionally, genetic analysis revealed that theandallele showed an increasing trend from the north to the center, while theandallele tended to increase from the center to the north. Also, we found more gene diversity in bothlociin the north compared with the center, suggesting population structure in Mexico.Conclusion. This work could help health institutions to identify where they can obtain blood products necessary for medical interventions. Moreover, this piece of information contributes to the knowledge of the genetic structure of the Mexican populations which could have significant implications in different fields of biomedicine.
In Mexico, HPV vaccines available immunize against genotypes 16/18 and 16/18/6/11; however, there is limited surveillance about carcinogenic subtypes in different states of the country that allow evaluating the effectiveness of vaccination and cervical cancer screening programs. Here, we report the regional and age-specific prevalence of 14 hr-HPV genotypes as well as their prevalence in abnormal cytology (from ASCUS to cervical cancer) among Mexican women which were undergoing from cervical cancer screening in the Salud Digna clinics in 20 states of the country. This study includes women with social security from the majority of public health institutions (IMSS, ISSSTE, SEMAR, and PEMEX), and women without social security. For cervical cancer screening, we used the SurePath liquid-based cytology and the BD Onclarity HPV Assay. From December 1, 2016, to August 2, 2018, the hr-HPV prevalence among 60,135 women was 24.78%, the most prevalent types were HPV 16 (4.13%), HPV 31 (4.12%) and HPV 51 (3.39%), while HPV 18 (1.70%) was less prevalent among infected women. Interestingly, the genotypes not covered by current vaccines in Mexico were commonly found in precancerous lesions, evidencing their carcinogenic potential, so it is necessary to increase their surveillance and inclusion in cervical cancer screening triage.
To validate the performance, reproducibility, and reliability of BD automated instruments in order to establish a fully automated clinical microbiology laboratory. We used control strains and clinical samples to assess the accuracy, reproducibility, and reliability of the BD Kiestra WCA, the BD Phoenix, and BD Bruker MALDI-Biotyper instruments and compared them to previously established conventional methods. The following processes were evaluated: sample inoculation and spreading, colony counts, sorting of cultures, antibiotic susceptibility test, and microbial identification. The BD Kiestra recovered single colonies in less time than conventional methods (e.g. E. coli, 7h vs 10h, respectively) and agreement between both methodologies was excellent for colony counts (κ=0.824) and sorting cultures (κ=0.821). Antibiotic susceptibility tests performed with BD Phoenix and disk diffusion demonstrated 96.3% agreement with both methods. Finally, we compared microbial identification in BD Phoenix and Bruker MALDI-Biotyper and observed perfect agreement (κ=1) and identification at a species level for control strains. Together these instruments allow us to process clinical urine samples in 36h (effective time). The BD automated technologies have improved performance compared with conventional methods, and are suitable for its implementation in very busy microbiology laboratories.