Extensive Phylogenomic Discordance and the Complex Evolutionary History of the Neotropical Cat Genus Leopardus.

Even in the genomics era, the phylogeny of Neotropical small felids comprised in the genus Leopardus remains contentious. We used whole-genome resequencing data to construct a time-calibrated consensus phylogeny of this group, quantify phylogenomic discordance, test for interspecies introgression, and assess patterns of genetic diversity and demographic history. We infer that the Leopardus radiation started in the Early Pliocene as an initial speciation burst, followed by another in its subgenus Oncifelis during the Early Pleistocene. Our findings challenge the long-held notion that ocelot (Leopardus pardalis) and margay (L. wiedii) are sister species and instead indicate that margay is most closely related to the enigmatic Andean cat (L. jacobita), whose whole-genome data are reported here for the first time. In addition, we found that the newly sampled Andean tiger cat (L. tigrinus pardinoides) population from Colombia associates closely with Central American tiger cats (L. tigrinus oncilla). Genealogical discordance was largely attributable to incomplete lineage sorting, yet was augmented by strong gene flow between ocelot and the ancestral branch of Oncifelis, as well as between Geoffroy's cat (L. geoffroyi) and southern tiger cat (L. guttulus). Contrasting demographic trajectories have led to disparate levels of current genomic diversity, with a nearly tenfold difference in heterozygosity between Andean cat and ocelot, spanning the entire range of variability found in extant felids. Our analyses improved our understanding of the speciation history and diversity patterns in this felid radiation, and highlight the benefits to phylogenomic inference of embracing the many heterogeneous signals scattered across the genome.

Genotyping Hepatitis B virus by Next-Generation Sequencing: Detection of Mixed Infections and Analysis of Sequence Conservation.

Our aim was to develop an accurate, highly sensitive method for HBV genotype determination and detection of genotype mixtures. We examined the preS and 5' end of the HBV X gene (5X) regions of the HBV genome using next-generation sequencing (NGS). The 1852 haplotypes obtained were subjected to genotyping via the Distance-Based discrimination method (DB Rule) using two sets of 95 reference sequences of genotypes A-H. In clinical samples from 125 patients, the main genotypes were A, D, F and H in Caucasian, B and C in Asian and A and E in Sub-Saharan patients. Genotype mixtures were identified in 28 (22.40%) cases, and potential intergenotypic recombination was observed in 29 (23.20%) cases. Furthermore, we evaluated sequence conservation among haplotypes classified into genotypes A, C, D, and E by computing the information content. The preS haplotypes exhibited limited shared conserved regions, whereas the 5X haplotypes revealed two groups of conserved regions across the genotypes assessed. In conclusion, we developed an NGS-based HBV genotyping method utilizing the DB Rule for genotype classification. We identified two regions conserved across different genotypes at 5X, offering promising targets for RNA interference-based antiviral therapies.

Neuropsychiatric adverse reactions in patients treated with denosumab: two case reports and a review of data from the FDA Adverse Event Reporting System (FAERS).

Denosumab is a human monoclonal antibody indicated for patients with osteoporosis and a high risk of fractures. It targets RANKL, the receptor activator of NF-κB (RANK) ligand, blocking RANKL-RANK interaction and leading to rapid osteoclast-mediated bone resorption inhibition. But RANK is widely expressed in neurons, microglia, and astrocytes. RANKL/RANK/NF-κB system can play an important role in the neuroinflammatory response, depressive behavior, memory impairments, and neurotrophism. We present two well-documented case reports of recurrent neuropsychiatric manifestations in patients treated with denosumab and a descriptive review of similar cases reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database between 2012 and 2022. Only those reported by healthcare professionals, coding denosumab as the only suspected drug, were retained. An 81-year-old woman with pre-existing mild cognitive impairment suffered two acute confusional episodes and another 81-year-old woman with depression in remission suffered two depressive recurrences with anxiety and psychomotor inhibition, in both cases following sequential administrations of denosumab without underlying calcium/phosphate imbalance. Scores on Naranjo Adverse Drug Reaction Probability Scale were 6 and 7, respectively, suggesting a probable causal relationship. Of the 91,151 cases with denosumab exposure reported to FAERS, 5.7% were related to psychiatric/neurological disorders and 23.8% of these corresponded to cognitive impairment, depressive/mood disturbances, or psychomotor retardation. Denosumab may cause transient but severe neuropsychiatric symptoms by several mechanisms involving RANKL blockade and subsequent immuno-inflammatory changes, at least in subjects with pre-existing neurobiological vulnerability. We recommend caution and careful monitoring of these patients following denosumab administrations.

[18F]FNDP PET neuroimaging test-retest repeatability and whole-body dosimetry in humans.

PURPOSE: Soluble epoxide hydrolase (sEH) is an enzyme that shapes immune signaling through its role in maintaining the homeostasis of polyunsaturated fatty acids and their related byproducts. [18F]FNDP is a radiotracer developed for use with positron emission tomography (PET) to image sEH, which has been applied to imaging sEH in the brains of healthy individuals. Here, we report the test-retest repeatability of [18F]FNDP brain PET binding and [18F]FNDP whole-body dosimetry in healthy individuals. METHODS: Seven healthy adults (4 men, 3 women, ages 40.1 ± 4.6 years) completed [18F]FNDP brain PET on two occasions within a period of 14 days in a test-retest study design. [18F]FNDP regional total distribution volume (VT) values were derived from modeling time-activity data with a metabolite-corrected arterial input function. Test-retest variability, mean absolute deviation, and intraclass correlation coefficient (ICC) were investigated. Six other healthy adults (3 men, 3 women, ages 46.0 ± 7.0 years) underwent [18F]FNDP PET/CT for whole-body dosimetry, which was acquired over 4.5 h, starting immediately after radiotracer administration. Organ-absorbed doses and the effective dose were then estimated. RESULTS: The mean test-retest difference in regional VT (ΔVT) was 0.82 ± 5.17%. The mean absolute difference in regional VT was 4.01 ± 3.33%. The ICC across different brain regions ranged from 0.92 to 0.99. The organs with the greatest radiation-absorbed doses included the gallbladder (0.081 ± 0.024 mSv/MBq), followed by liver (0.077 ± 0.018 mSv/MBq) and kidneys (0.063 ± 0.006 mSv/MBq). The effective dose was 0.020 ± 0.003 mSv/MBq. CONCLUSION: These data support a favorable test-retest repeatability of [18F]FNDP brain PET regional VT. The radiation dose to humans from each [18F]FNDP PET scan is similar to that of other 18F-based PET radiotracers.

Molecular characterization and clinical impact of human bocavirus at a tertiary hospital in Barcelona (Catalonia, Spain) during the 2014-2017 seasons.

PURPOSE: The aim was to describe the prevalence, molecular epidemiology and clinical manifestations of human bocavirus (HBoV) in patients attended at a tertiary hospital in Barcelona, Spain. METHODS: From October 2014 to May 2017, respiratory specimens from paediatric patients were collected for respiratory viruses' laboratory-confirmation. Phylogenetic analyses from partial VP1 sequences were performed from all HBoV laboratory-confirmed specimens. Clinical features were retrospectively studied. RESULTS: 178/10271 cases were HBoV laboratory-confirmed. The median age was 1.53 (IQR 1.0-2.3). Co-detection was highly reported (136; 76%). All viruses belonged into HBoV1 genotype but one into HBoV2. Non-reported mutations were observed and two sites were suggestive to be under negative selection. 61% (109/178) cases had lower RTI (LRTI), of whom 84 had co-detections (77%) and 76 had comorbidities (70%). LRTI was the cause of hospitalization in 85 out of 109 cases (78%), and no differences were found regarding severity factors during hospitalization between co- and single-detections, except for median length of respiratory support, which was longer in cases with co-detections. CONCLUSIONS: Close monitoring of predominant HBoV1 showed a high similarity between viruses. The presence of comorbidities might explain the high prevalence of LRTI. Symptomatology in HBoV single-detected cases suggest that HBoV is a true pathogen.

Loss ratio of the capitation payment unit of the health-promoting entities in Colombia between 2017 and 2021: a financial-actuarial approach.

BACKGROUND: Because of a change of government, the Colombian Ministry of Health and Social Protection is in the process of presenting a structural reform for the General System of Social Security in Health (GSSSH), in order to implement a 'preventive and predictive health model'. However, it will always be relevant to review and analyze the fiscal implications of any proposed public policy program, to protect financial sustainability and to promote the better functioning of the system in question. METHODS: To contribute to this topic, we have calculated, using a financial-actuarial approach, the loss ratio for the years 2017 to 2021 for the Capitation Payment Unit (CPU) for all the Health-Promoting Entities (HPE) for both contributory and subsidized schemes. This information, derived from public reports available on the official website of the National Health Superintendency, allows us to estimate the financial burden of the institutions that guarantee access to and provision of health services and technologies in Colombia. RESULTS: The study shows that close to half of the HPEs in Colombia (which represent 11.6 million affiliates) have CPU loss ratios of more than 100% for the year 2021, evidencing insufficient resources for the operation of health insurance. CONCLUSIONS: Finally, we propose some policy recommendations regarding the strengthening of informed decision-making to allow the healthy financial sustainability of the Colombian GSSSH.

Crowding out and impoverishing effect of tobacco in Mexico.

INTRODUCTION: Tobacco is one of the world's largest preventable causes of premature death, accounting for more than 8 million deaths and costing the global economy US$1.4 trillion each year. Smoking is a global problem with 1.3 billion people using tobacco worldwide, who will face harmful effects on health and on people's current and future financial situations and quality of life.This article aims to be the first study to generate evidence on the effects of smoking on household expenditure and the number of people living under the poverty threshold by studying the crowding out and impoverishing effect in Mexico. METHODS: Through econometric methods and maximising a household utility function we estimate the crowding out and impoverishing effect of tobacco consumption in México based on household's income and spending survey from 2020. RESULTS: Spending on tobacco crowds out household spending on other goods and services. In Mexico, spending on tobacco results in decreased spending on essential goods and services, like education and healthcare, and increased spending on harmful goods such as alcoholic beverages. These effects are common across all income levels but are more pronounced in low-income households. When spending on tobacco increases, for example, following regular price increases made by the tobacco industry, the crowding out effect is exacerbated.In addition, smoking has an impoverishing effect on the population. This is because some families find that their remaining income level falls below the poverty line after deducting money spent on tobacco (a concept known as secondary poverty). In Mexico, 909 132 people are left with a disposable income level below the extreme poverty line because of expenditure on tobacco and smoking-related diseases. CONCLUSIONS: Smoking affects individual health and the finances of households in Mexico, particularly those of low-income people. By increasing tobacco taxes, those who quit smoking increase their quality of life and well-being. However, those who continue to smoke and increase their tobacco spending are affected by a shift in their spending on other goods and services.The increase in tobacco taxes must be accompanied by public policies that help reduce tobacco consumption and compensate the crowding out on goods and services relevant to the development of households.

First report of Nalanthamala vermoesenii causing pink rot of Phoenix canariensis in Mexico.

In Mexico City, the Canary Island date palm (Phoenix canariensis Chabaud) is an important plant forming part of its landscape identity. In February 2022, pink rot disease symptoms were observed on 16 P. canariensis plants in Mexico City (19°25'43.98"N, 99° 9'49.41"W). The incidence was 27%, while the severity 12%. External symptoms included necrotic lesions that advanced from the petiole towards the rachis. Internal symptoms were rotted, dark brown discoloration in bud, petiole, and rachis. Abundant conidial masses were developed on the infected tissues. Pieces of diseased tissues (5-mm cubes) were surface sterilized for 2 min in 3% sodium hypochlorite, rinsed with sterilized distilled water, plated onto potato dextrose agar (PDA), and incubated at 24°C and 12-h photoperiod, 20 pink fungal colonies were developed with sparse aerial mycelia on PDA. Conidiophores were hyaline, dimorphic, penicillate, and Acremonium-like. Conidia were dimorphic, typically with somewhat truncated ends, 4.5 to 5.7 × 1.9 to 2.3 µm (mean 4.99 × 2.15, n = 100), borne in long chains on penicillate conidiophores; on Acremonium-like conidiophores conidia were cylindrical, straight, and slightly curved, 4.55 to 10.1 × 1.2 to 2.35 µm (mean 8.2 × 1.7, n = 100). These morphological characteristics resembled those of Nalanthamala vermoesenii (Biourge) Schroers (Schroers et al. 2005). Genomic DNA was extracted from the mycelia of a representative isolate CP-SP53. The internal transcribed spacer (ITS) region and the large subunit of ribosomal ribonucleic acid (LSU) were amplified and sequenced. The sequences were deposited in GenBank with accession numbers OQ581472 (ITS) and OQ581465 (LSU). Phylogenetic trees based on ITS and LSU sequences of Nalanthamala species were reconstructed using maximum likelihood and Bayesian inference methods. Isolate CP-SP53 was placed in the clade of Nalanthamala vermoesenii. The pathogenicity test was carried out twice with isolate CP-SP53 on five 3-year-old P. canariensis plants. Four petioles per plant were surface disinfected with 75% ethanol, and wounded with a sterilized scalpel (shallow cuts 0.5 cm wide). A mycelial plug (5 mm in diam.) of a 1-week-old PDA culture was placed on each wounded site. Sterile PDA plugs were used for five non-inoculated control plants. All plants were maintained at 22 ± 2°C and a 12-h photoperiod. Twenty-five days after inoculation (dai), wounded petioles showed the same symptoms observed in the field, whereas control plants remained healthy. Forty-five dai, all inoculated plants died. Pink conidial masses developed on symptomatic tissues. To fulfill Koch's postulates, the pathogen was reisolated by placing the pink conidial masses onto PDA. The colony characteristics and morphometric measurements were identical to those of isolate CP-SP53. Nalanthamala vermoesenii has been reported on P. canariensis in Greece and United States (Feather et al. 1979; Ligoxigakis et al. 2013) and Syagrus romanzoffiana in Egypt (Mohamed et al. 2016). To our knowledge, this is the first report of Nalanthamala vermoesenii as the causal agent of pink rot on P. canariensis in Mexico. This plant is the most commonly planted ornamental palm in Mexico City. The spread of N. vermoesenii could be a threat for the estimated 15 thousand palms, therefore dramatically change the urban landscape.

Enterovirus D68 in Hospitalized Children, Barcelona, Spain, 2014-2021.

To determine molecular epidemiology and clinical features of enterovirus D68 (EV-D68) infections, we reviewed EV-D68-associated respiratory cases at a hospital in Barcelona, Spain, during 2014-2021. Respiratory samples were collected from hospitalized patients or outpatients with symptoms of acute respiratory tract infection or suggestive of enterovirus infection. Enterovirus detection was performed by real-time multiplex reverse transcription PCR and characterization by phylogenetic analysis of the partial viral protein 1 coding region sequences. From 184 patients with EV-D68 infection, circulating subclades were B3 (80%), D1 (17%), B2 (1%), and A (<1%); clade proportions shifted over time. EV-D68 was detected mostly in children (86%) and biennially (2016, 2018, 2021). In patients <16 years of age, the most common sign/symptom was lower respiratory tract infection, for which 11.8% required pediatric intensive care unit admission and 2.3% required invasive mechanical ventilation; neurologic complications developed in 1. The potential neurotropism indicates that enterovirus surveillance should be mandatory.

Long-Term Sebelipase Alfa Treatment in Children and Adults With Lysosomal Acid Lipase Deficiency.

OBJECTIVES: Sebelipase alfa is approved for treatment of lysosomal acid lipase deficiency (LAL-D). This single-arm, open-label study (NCT02112994) evaluated sebelipase alfa efficacy and safety in patients with LAL-D. METHODS: Patients >8 months of age diagnosed with LAL-D received sebelipase alfa 1.0 mg/kg by intravenous infusion every other week (qow) for up to 144 weeks. Dose escalation to 3.0 mg/kg qow and subsequently to 3.0 mg/kg weekly was permitted, per protocol; dose reductions for tolerability were permitted to 0.35 mg/kg qow. Descriptive statistical analyses were conducted. RESULTS: Thirty-one patients were enrolled and treated. Baseline median alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were 63.5 and 65.5 U/L, respectively. Twenty-eight patients completed 96 weeks of treatment, and 25 continued into the extended treatment period; 19 completed 144 weeks. From baseline to week 144, median ALT and AST levels changed by -42.0 and -22.0 U/L, respectively, median liver and spleen volumes changed from 1.4 to 1.3 and from 2.6 to 2.3 multiples of normal, respectively, median low-density lipoprotein cholesterol levels decreased by 52.6 mg/dL, and median high-density lipoprotein cholesterol increased by 9.8 mg/dL. Liver biopsies showed mostly improved or stable histopathology at 48 and 96 weeks versus baseline. Infusion-associated reactions were mild (n = 1) or moderate (n = 2). One patient (a candidate for liver transplant at baseline) discontinued treatment because of liver transplant (unrelated to treatment). Two patients tested positive for nonneutralizing, anti-drug antibodies on 1 occasion each. CONCLUSION: Sebelipase alfa was well tolerated and resulted in sustained improvements in liver and lipid parameters.

Supporting the mental health needs of underserved communities: A qualitative study of barriers to accessing community resources.

This study examined the accessibility of community resources (e.g., welfare programs and afterschool programs) for underserved youth and families with mental health needs. Mental health professionals (n = 52) from a large community mental health and welfare agency serving predominantly low-income, Latinx families completed a semistructured interview that asked about the accessibility of community resources. Participant responses were coded using an inductive thematic analysis. Results showed that 71% of participants endorsed availability barriers (e.g., limited local programs), 37% endorsed logistical barriers (e.g., waitlists), 27% endorsed attitudinal barriers (e.g., stigmatized beliefs about help-seeking), and 23% endorsed knowledge barriers (e.g., lacking awareness about local programs). Professionals' perceived availability barriers were mostly consistent with the actual availability of community resources. Findings highlight the compounding challenges that underserved communities face and point to opportunities for promoting enhanced well-being and functioning for youth and families with mental health needs.

Hundreds of nuclear and plastid loci yield novel insights into orchid relationships.

PREMISE: The inference of evolutionary relationships in the species-rich family Orchidaceae has hitherto relied heavily on plastid DNA sequences and limited taxon sampling. Previous studies have provided a robust plastid phylogenetic framework, which was used to classify orchids and investigate the drivers of orchid diversification. However, the extent to which phylogenetic inference based on the plastid genome is congruent with the nuclear genome has been only poorly assessed. METHODS: We inferred higher-level phylogenetic relationships of orchids based on likelihood and ASTRAL analyses of 294 low-copy nuclear genes sequenced using the Angiosperms353 universal probe set for 75 species (representing 69 genera, 16 tribes, 24 subtribes) and a concatenated analysis of 78 plastid genes for 264 species (117 genera, 18 tribes, 28 subtribes). We compared phylogenetic informativeness and support for the nuclear and plastid phylogenetic hypotheses. RESULTS: Phylogenetic inference using nuclear data sets provides well-supported orchid relationships that are highly congruent between analyses. Comparisons of nuclear gene trees and a plastid supermatrix tree showed that the trees are mostly congruent, but revealed instances of strongly supported phylogenetic incongruence in both shallow and deep time. The phylogenetic informativeness of individual Angiosperms353 genes is in general better than that of most plastid genes. CONCLUSIONS: Our study provides the first robust nuclear phylogenomic framework for Orchidaceae and an assessment of intragenomic nuclear discordance, plastid-nuclear tree incongruence, and phylogenetic informativeness across the family. Our results also demonstrate what has long been known but rarely thoroughly documented: nuclear and plastid phylogenetic trees can contain strongly supported discordances, and this incongruence must be reconciled prior to interpretation in evolutionary studies, such as taxonomy, biogeography, and character evolution.

Quality of life evaluation in Mexican patients with severe obesity before and after bariatric surgery.

INTRODUCTION: In Mexico, neither the 36-item Short Form Health Survey (SF-36) nor the Bariatric Analysis and Reporting Outcome System (BAROS) instruments have been used to assess quality of life (QoL) before and after bariatric surgery (BS). OBJECTIVE: To describe changes in QoL using the SF-36 and BAROS questionnaires in patients with severe obesity before and after BS. METHODS: Clinical and anthropometric data of patients undergoing bariatric surgery between 2015 and 2016 were collected. Statistical significance was considered with a p-value < 0.05. RESULTS: 230 patients were analyzed, 98 before and 132 and after BS; most were females (81 %). Initial body mass index was 48 kg/m2 (44-53). SF-36-measured QoL showed an increase in the physical component score from 43 to 54.2 points (p < 0.001), and in the mental component, from 53.3 to 56.6 points after BS. With BAROS, 98.5 % showed good to excellent QoL results within the first three months after BS. CONCLUSION: When measured with the SF-36 and BAROS questionnaires, QoL of Mexican patients with severe obesity was found to improve after BS.

INTRODUCCIÓN: En México no se han utilizado los instrumentos Shorth Form 36 Items (SF-36) ni Baryatric Assesment Reporting Outcomes System (BAROS) para evaluar la calidad de vida (CV) antes y después de la cirugía bariátrica (CB). OBJETIVO: Describir los cambios en la CV con los cuestionarios SF-36 y BAROS, en pacientes con obesidad severa antes y después de la CB. MÉTODOS: Se recolectaron los datos clínicos y antropométricos de pacientes sometidos a cirugía baríatrica entre 2015 y 2016. Se consideró con significación estadística una p < 0.05. RESULTADOS: Se analizaron 230 pacientes, 98 y 132 antes y después de la CB; la mayoría fue del sexo femenino (81 %). El índice de masa corporal inicial fue de 48 kg/m2 (44-53). La CV medida con el SF-36 demostró un incremento en la puntuación del componente físico de 43 a 54.2 (p < 0.001) y en el componente mental, de 53.3 a 56.6 después de la CB. Con BAROS, en 98.5 % se registraron resultados buenos a excelentes en la CV en los primeros tres meses. CONCLUSIÓN: Al ser medida con los cuestionarios SF-36 y BAROS se definió que la CV de los pacientes mexicanos con obesidad severa mejora después de la CB.

Are there really any predictive factors for a successful weight loss after bariatric surgery?

BACKGROUND: Currently, bariatric surgery is the most effective treatment for severe obesity and its metabolic complications; however, 15-35% of the patients that undergo bariatric surgery do not reach their goal for weight loss. The aim of this study was to determine the proportion of patients that didn't reach the goal of an excess weight loss of 50% or more during the first 12 months and determine the factors associated to this failure. METHODS: We obtained the demographic, anthropometric and biochemical information from 130 patients with severe obesity who underwent bariatric surgery in our institution between 2012 and 2017. We used self-reports of physical activity, caloric intake and diet composition. An unsuccessful weight loss was considered when the patient lost < 50% or more of the excess weight 12 months after surgery. We compared the characteristics between the successful and unsuccessful groups in order to find the factors associated with success. RESULTS: We included 130 patients (mean age 48 ± 9 years, 81.5% were women). One year after surgery, 26 (20%) had loss < 50% EBW. Unsuccessful surgery was associated with an older age, previous history of hypertension, abdominal surgery or depression/anxiety, also the number of comorbidities and unemployment affected the results. These patients loss enough weight to improve some of their comorbidities, but they are more prone to regain weight 2 years after surgery. CONCLUSIONS: A fifth of the patients undergoing bariatric surgery may not lose enough weight to be considered successful by current standards. Some patients may benefit from the surgery in the short term, but they are more likely to regain weight after 2 years. The factors influencing this result are still controversial but may be population-specific. Early detection of the patients that are more likely to fail is imperative to establish additional therapeutic strategies, without denying them the opportunity of surgery or waiting for weight re-gain to occur.

Serological and molecular study of Hepatitis E virus in pediatric patients in Mexico.

INTRODUCTION AND OBJECTIVES: Cases of viral hepatitis reported in Mexico are typically identified as hepatitis A, B and C. However, unspecified cases are reported annually. Hepatitis E virus (HEV) is an emergent agent that causes a self-limiting infection that can evolve to chronic in immunosuppressed individuals. In Mexico, HEV genotype 2 is considered endemic, though it's the prevalence is not well known. Therefore, the present study was designed to determine the prevalence of HEV among patients at the "Hospital Infantil de Mexico Federico Gomez". MATERIALS AND METHODS: The study included 99 patients, anti-HEV antibody (IgG and IgM) were detected by indirect ELISA and viral genome was identified using RT-PCR technique. Two PCR products of positive cases were sequenced. RESULTS: ELISA results were positive in 3% and 6%, for IgG and IgM respectively, 54.5% prevalence was found by PCR. Low lymphocyte count (p<0.05) and malnutrition (p<0.005) were significant factors for high PCR prevalence and could increase the possibility of infection. Two samples were sequenced and confirmed the presence of HEV genotype 3. CONCLUSIONS: This report reveals the incidence of HEV in pediatric patients in Mexico. Moreover, the identification of HEV genotype 3 in human samples suggests a potential zoonotic risk that requires further research.

Impaired pesticide removal and detoxification by biomixtures during the simulated pesticide application cycle of a tropical agricultural system.

Biopurification systems (BPS) or biobeds have been developed to attenuate point-source contamination due to inappropriate pesticide handling or disposal of agricultural wastewaters. The biomixture used for this strategy should be able to remove different active ingredients but its efficiency can vary due to the constant load of pesticides from crop application programs. For that reason, the performance of biomixtures in conditions that mimic the real pesticide treatment before their implementation in field settings should be assayed. This study aimed to evaluate the removal and detoxifying capacity of a previously formulated biomixture (coconut fiber, 50% v/v; compost, 25%; and soil pre-exposed to pesticides, 25%) during a simulated cycle of pesticide application (93 days) for potato production. The scheme included a first application of linuron followed by a weekly alternated treatment of the mixtures chlorpyrifos/metalaxyl and malathion/dimethomorph, and antibiotics at day 72. The biomixture showed efficient removal of linuron (half-life <15 days), and a fluctuating transformation rate for the other compounds. A constant and sustained removal was observed for malathion and methalaxyl. In contrast, lower efficiency and accumulation was described for chlorpyrifos and dimethomorph. Following antibiotic treatment, changes on pesticide removal were observed only in the case of chlorpyrifos, whose removal was slightly enhanced. Furthermore, acute toxicity assays showed limited detoxification of the matrix, especially when compounds began to accumulate. Summarizing, our experiments showed that the proposed biomixture does not support a proper removal of the pesticides during the simulated application cycle of potato production. Further optimization of a biopurification system is required to guarantee the successful elimination of pesticide combinations when applied in field conditions.

Association of neutrophil-to-lymphocyte and lymphocyte-to-C-reactive protein ratios with COVID-19-related mortality.

INTRODUCTION: Neutrophil-to-lymphocyte (NLR) and lymphocyte-to-C-reactive protein (LCR) ratios are used to predict severity and mortality in various infections. OBJECTIVE: To establish the best NLR and LCR cutoff point to predict mortality in patients hospitalized for COVID-19 in Mexico. METHOD: Analytical cross-sectional study of patients hospitalized for severe COVID-19 in a specialty hospital. RESULTS: Out of 242 analyzed patients, 34 % died. The deceased subjects were older (62 vs. 51 years; p < 0.001), had a higher prevalence of > 10 years with systemic arterial hypertension (59.4 vs. 45.1 %, p = 0.022), as well as a higher NLR (17.66 vs. 8.31, p < 0.001) and lower LCR (0.03 vs. 0.06, p < 0.002) with regard to those who survived. The cutoff points to predict mortality were NLR > 12 and LCR < 0.03. The combination of NLR/LCR had a sensitivity of 80 %, specificity of 74 %, positive predictive value of 46.15 %, negative predictive value of 93.02 % and an odds ratio of 11.429 to predict mortality. CONCLUSION: NLR > 12 and LCR < 0.03 are useful biomarkers to evaluate the risk of mortality in Mexican patients with severe COVID- 19. INTRODUCCIÓN: Los índices neutrófilo/linfocito (INL) y linfocito/proteína C reactiva (ILR) se usan para predecir severidad y mortalidad en diversas infecciones. OBJETIVO: Establecer en México el mejor punto de corte de INL e ILR para predecir la mortalidad en pacientes hospitalizados por COVID-19. MÉTODO: Estudio transversal analítico de pacientes hospitalizados por COVID-19 grave en un hospital de especialidades. RESULTADOS: Falleció 34 % de 242 pacientes analizados. Los sujetos fallecidos tenían mayor edad (62 versus 51 años, p < 0.001), mayor prevalencia de hipertensión arterial sistémica > 10 años (59.4 versus 45.1 %, p = 0.022), así como INL más alto (17.66 versus 8.31, p < 0.001) e ILR más bajo (0.03 versus 0.06, p < 0.002) respecto a quienes sobrevivieron. Los puntos de corte para predecir mortalidad fueron INL > 12 e ILR < 0.03. La combinación de INL e ILR tuvo sensibilidad de 80 %, especificidad de 74 %, valor predictivo positivo de 46.15 %, valor predictivo negativo de 93.02 % y razón de momios de 11.429 para predecir la mortalidad. CONCLUSIÓN: INL > 12 e ILR < 0.03 son biomarcadores útiles para evaluar el riesgo de mortalidad en pacientes mexicanos con COVID-19 grave.

Inference from the analysis of genetic structure of Helicobacter pylori strains isolates from two paediatric patients with recurrent infection.

BACKGROUND: Helicobacter pylori recurrence after successful eradication is an important problem. Children are particularly vulnerable to reinfection, by intrafamilial transmission which facilitates the acquisition or recombination of new genetic information by this bacterium. We investigated the evolutionary dynamics of 80 H. pylori strains isolated from two paediatric patients with recurrent infection (recrudescence and reinfection). RESULTS: We characterized the virulence genes vacA (s1, m1, s2, and m2), cagA, cagE, and babA2 and performed multilocus sequence typing (MLST) on 7 housekeeping genes (atpA, efp, ureI, ppa, mutY, trpC, and yphC) to infer the evolutionary dynamics of the H. pylori strains through phylogenetic and genealogic inference analyses, genetic diversity analysis and the exploration of recombination events during recurrent infections. The virulence genotype vacAs1m1/cagA+/cagE+/babA2 was present at a high frequency, as were the EPIYA motifs EPIYA-A, -B and -C. Furthermore, the housekeeping genes of the H. pylori strains exhibited high genetic variation, comprising 26 new alleles and 17 new Sequence Type (ST). In addition, the hpEurope (76.5%) and hspWAfrica (23.5%) populations predominated among the paediatric strains. All strains, regardless of their ancestral affiliation, harboured western EPIYA motifs. CONCLUSIONS: This study provides evidence of the evolutionary dynamics of the H. pylori strains in two paediatric patients during recrudescence and reinfection events. In particular, our study shows that the strains changed during these events, as evidenced by the presence of different STs that emerged before and after treatment; these changes may be due to the accumulation of mutations and recombination events during the diversification process and recolonization of the patients by different genotypes.

Clinical and genetic characteristics of ankylosing spondylitis patients with peripheral arthritis at disease onset.

OBJECTIVES: The aim of this study was to assess the clinical and genetic characteristics associated with the presence of peripheral arthritis (PA) at disease onset in patients with ankylosing spondylitis (AS). METHODS: 456 Spanish AS patients, diagnosed according to the modified New York Criteria, who had at least ten years of follow-up since initial disease onset were selected from the National Spondyloarthropathies Registry (REGISPONSER). 18.9% of AS patients initially presented PA. Clinical variables and 384 single nucleotide polymorphisms (SNPs) distributed in 190 genes were analysed. SNP genotyping was performed using the Illumina GoldenGate genotyping platform. Association tests for allele frequencies and for categorical clinical variables were performed by the χ2 test and with the unpaired t-test for continuous variables. p-values of <0.05 were considered statistically significant. RESULTS: AS patients with PA showed an earlier age of disease onset (p=0.021), longer disease duration (p=0.020) and longer duration of AS symptoms from onset (p=0.034) than AS patients without PA. We found significant associations with the presence of PA at disease onset in 14 SNPs located in 10 genes: HLA-DQB2 (rs2857210 and rs9276615), HLA-DOB (rs2857151, rs2621332 and rs1383261), JAK2 (rs7857730), IL-23R (rs11209008 and rs10489630), CYP1B1 (rs1056836), NELL1 (rs8176786), KL (rs564481), and MEFV (rs224204), IL-2RB (rs743777) and IL-1A (rs1800587). CONCLUSIONS: Both clinical and genetic factors are associated with the presence of PA at disease onset in Spanish AS patients. The results suggest that this subset of AS patients with PA at disease onset might have differentiation factors involved in disease pathogenesis.

A Microsatellite Analysis Used to Identify Global Pathways of Movement of Phytophthora cinnamomi and the Likely Sources of Wildland Infestations in California and Mexico.

The genetic structure of a sample of isolates of the oomycete plant pathogen Phytophthora cinnamomi from natural and agricultural outbreaks and the long-distance movement of individual genotypes were studied using four microsatellite markers to genotype 159 isolates of Californian, Mexican, and worldwide origins. Allelic profiles identified 75 multilocus genotypes. A STRUCTURE analysis placed them in three groups characterized by different geographic and host ranges, different genic and genotypic diversity, and different reproductive modes. When relationships among genotypes were visualized on a minimum spanning network (MSN), genotypes belonging to the same STRUCTURE group were contiguous, with rare exceptions. A putatively ancestral group 1 had high genic diversity, included all A1 mating type isolates and all Papuan isolates in the sample, was rarely isolated from natural settings in California and Mexico, and was positioned at the center of the MSN. Putatively younger groups 2 and 3 had lower genic diversity, were both neighbors to group 1 but formed two distinct peripherical sectors of the MSN, and were equally present in agricultural commodities and natural settings in Mexico and California. A few genotypes, especially in groups 2 and 3, were isolated multiple times in different locations and settings. The presence of identical genotypes from the same hosts in different continents indicated that long-distance human-mediated movement of P. cinnamomi had occurred. The presence of identical genotypes at high frequencies in neighboring wildlands and agricultural settings suggest that specific commodities may have been the source of recent wild infestations caused by novel invasive genotypes.