Workflow to facilitate the detection of new psychoactive substances and drugs of abuse in influent urban wastewater.

The complexity around the dynamic markets for new psychoactive substances (NPS) forces researchers to develop and apply innovative analytical strategies to detect and identify them in influent urban wastewater. In this work a comprehensive suspect screening workflow following liquid chromatography - high resolution mass spectrometry analysis was established utilising the open-source InSpectra data processing platform and the HighResNPS library. In total, 278 urban influent wastewater samples from 47 sites in 16 countries were collected to investigate the presence of NPS and other drugs of abuse. A total of 50 compounds were detected in samples from at least one site. Most compounds found were prescription drugs such as gabapentin (detection frequency 79%), codeine (40%) and pregabalin (15%). However, cocaine was the most found illicit drug (83%), in all countries where samples were collected apart from the Republic of Korea and China. Eight NPS were also identified with this protocol: 3-methylmethcathinone 11%), eutylone (6%), etizolam (2%), 3-chloromethcathinone (4%), mitragynine (6%), phenibut (2%), 25I-NBOH (2%) and trimethoxyamphetamine (2%). The latter three have not previously been reported in municipal wastewater samples. The workflow employed allowed the prioritisation of features to be further investigated, reducing processing time and gaining in confidence in their identification.

Study on the relation of the characteristics of the capture sites with the Leptospira spp. occurrence in bats and rodents from Yucatan, Mexico.

This study aims to describe the natural Leptospira occurrence in small mammals from Yucatan, Mexico, and to explore the relation between the characteristics of the capture sites and the Leptospira occurrence. Bats and rodents were captured in five sites of Yucatan state, and from them, a kidney fragment was collected that was used in the genomic DNA extraction. Leptospira DNA was identified by PCR targeting the 16S-rRNA and LipL32 genes. Additionally, a bioinformatic analysis was carried out to know the Leptospira species and was corroborated with a phylogenetic tree. The assemblage of small mammals was compound of 82 (51.2 %) bats and 78 (48.8 %) rodents. A global frequency (bats plus rodents) of Leptospira occurrence of 21.2 % (34/160) was observed; in bats, it was 21.9 % (18/82), and in rodents, 20.5 % (16/78). The phylogenetic trees based on LipL32 gene showed that the recovered sequences most closely resemble the species L. borgpetersenii and L. noguchii. The ordination of the capture sites with tropical deciduous forests as original vegetation is more related to the abundance of Leptospira-infected rodents. The ordination of the capture sites with tropical sub-deciduous forests as original vegetation is more related to the diversity of Leptospira-infected bat species. The canonical ordering of the capture sites is by the original vegetation type and the diversity and abundance of Leptospira-infected bat and rodent species.

Unraveling the diversity of Trypanosoma species from Central Mexico: Molecular confirmation on the presence of Trypanosoma dionisii and novel Neobat linages.

Bats are one of the groups of mammals with the highest number of associated Trypanosoma taxa. There are 50 Trypanosoma species and genotypes infecting more than 75 species of bats across five continents. However, in Mexico, the inventory of species of the genus Trypanosoma associated with bats is limited to only two species (Trypanosoma vespertilionis and Trypanosoma cruzi) even though 140 species of bats inhabit this country. Specifically, 91 bat species have been recorded in the state of Veracruz, but records of trypanosomatids associated with this mammalian group are absent. Due to the complex Trypanosoma-bat relationship, the high diversity of bat species in Veracruz, as well as the lack of records of trypanosomatids associated with bats for this state, the aim of this work was to analyze the diversity of species of the genus Trypanosoma and their presence from a bat community in the central area of the state of Veracruz, Mexico. During the period of January to August 2022 in the Tequecholapa Environmental Management Unit where bats were collected using mist nets and blood samples were obtained from their thumbs. We extracted genetic material and amplified a fragment of 800 bp of the 18S ribosomal gene of the genus Trypanosoma by conventional PCR. The positive amplicons were sequenced, and phylogenetic reconstruction was performed to identify the parasite species. A total of 285 bats (149♀, 136♂) belonging to 13 species from 10 genera and a single family (Phyllostomidae) were collected. Twenty-three specimens from six species tested positive for the presence of Trypanosoma dionisii, Trypanosoma sp. Neobat 4, and a potential novelty species provisionally named as Trypanosoma sp. Neobat 6. The results of the present work increase the number of species of the genus Trypanosoma infecting bats in Mexico and in the Neotropical region.

Exposure to Trypanosoma cruzi and Leishmania parasites in dogs from a rural locality of Yucatan, Mexico. A serological survey.

Trypanosoma cruzi, the causal agent of American trypanosomiasis, and Leishmania spp., the causal agents of Leishmaniasis, are prevalent in more than 20 American countries, including Mexico. Dogs have been reported as incidental hosts for both parasites and may be helpful as transmission sentinels. We surveyed the dog population in a rural locality of the Merida municipality in Yucatan, Mexico, to evaluate the seroreactivity against T. cruzi and Leishmania spp. using two antigens, parasite homogenate (H) and iron superoxide dismutase extract (FeSODe), with two serological techniques (ELISA and Western Blot). Our study found that 3.33% of the tested dogs were seroreactive to T. cruzi using ELISA-H, and 29.5% were seroreactive to FeSODe antigen, with a 94.4% consistency between the two tests. Similarly, for L. mexicana, 1.6% were seroreactive using ELISA-H, and 9.8% were seroreactive using ELISA-FeSODe, with an 83.3% consistency between tests. For L. braziliensis, no dogs were seroreactive using ELISA-H, but 16.4% were seroreactive using ELISA-FeSODe, with a 90% consistency between tests. Finally, for L. infantum, 4.9% were seropositive using ELISA-H, and 6.6% were seropositive using ELISA-FeSODe, with a 75% consistency between tests. These results show noticeable evidence of exposure of dogs to trypanosomatid parasites and highlight the potential disease risk for the people and their companion animals in the region.

An unusual identification of Rickettsia parkeri in synanthropic rodents and domiciliated dogs of a rural community from Yucatán, Mexico.

Rickettsia parkeri belongs to the spotted fever group (SFG) of the Rickettsia genus. This bacterium causes mild rickettsiosis in humans and is mainly transmitted by Amblyomma ticks. Its medical importance is emerging in the Americas, including Mexico. Synanthropic rodents and domiciled dogs participate as accidental hosts in epidemiological cycles of Rickettsia of the SFG. The aim is to report the presence of R. parkeri in synanthropic rodents and domiciled dogs from a rural community of Yucatán, Mexico. Rodents were captured, and plasma samples were taken from dogs in 48 households from Ucú, Yucatán, Mexico. A spleen sample (rodents) and plasma (dogs) were used in the propagation of Rickettsia on Vero cells. These infected cells were used in the extraction of genomic DNA. Rickettsia DNA was identified using a semi-nested PCR (snPCR); some products were sent for sequencing. The recovered sequences were analysed with bioinformatics programs, and a phylogenetic tree was built to determine the Rickettsia species. One hundred animals were sampled: 36 synanthropic rodents and 64 dogs. The snPCR evidenced the presence of Rickettsia DNA in 10 rodents (10/36, 27.8%) and 18 dogs (18/64, 28.1%), which represents a global frequency of 28% (28/100) in this study. The bioinformatics analysis yielded homology to R. parkeri and was demonstrated in the phylogenetic tree. The first evidence of the presence of R. parkeri in synanthropic rodents (Mus musculus) from Mexico is presented; likewise, the participation of domestic dogs in the transmission cycle of this bacterium with potential importance in public health is confirmed.

Three years of wastewater surveillance for new psychoactive substances from 16 countries.

The proliferation of new psychoactive substances (NPS) over recent years has made their surveillance complex. The analysis of raw municipal influent wastewater can allow a broader insight into community consumption patterns of NPS. This study examines data from an international wastewater surveillance program that collected and analysed influent wastewater samples from up to 47 sites in 16 countries between 2019 and 2022. Influent wastewater samples were collected over the New Year period and analysed using validated liquid chromatography - mass spectrometry methods. Over the three years, a total of 18 NPS were found in at least one site. Synthetic cathinones were the most found class followed by phenethylamines and designer benzodiazepines. Furthermore, two ketamine analogues, one plant based NPS (mitragynine) and methiopropamine were also quantified across the three years. This work demonstrates that NPS are used across different continents and countries with the use of some more evident in particular regions. For example, mitragynine has highest mass loads in sites in the United States, while eutylone and 3-methylmethcathinone increased considerably in New Zealand and in several European countries, respectively. Moreover, 2F-deschloroketamine, an analogue of ketamine, has emerged more recently and could be quantified in several sites, including one in China, where it is considered as one of the drugs of most concern. Finally, some NPS were detected in specific regions during the initial sampling campaigns and spread to additional sites by the third campaign. Hence, wastewater surveillance can provide an insight into temporal and spatial trends of NPS use.

Transcriptional analysis in bacteriophage Fc02 of Pseudomonas aeruginosa revealed two overlapping genes with exclusion activity.

Little is known about the gene expression program during the transition from lysogenic to lytic cycles of temperate bacteriophages in Pseudomonas aeruginosa. To investigate this issue, we developed a thermo-sensitive repressor mutant in a lysogen and analyzed the phage transcriptional program by strand-specific RNA-Seq before and after thermo-induction. As expected, the repressor gene located on the phage DNA forward strand is transcribed in the lysogen at the permissive temperature of 30°C. Upstream the repressor gene, we noticed the presence of two overlapped ORFs apparently in the same transcript. One ORF is a gene that encodes a protein of 7.9 kDa mediating the exclusion of various super-infecting phages. The other ORF, placed in an alternate reading frame with a possible AUG initiation codon at 25 nucleotide downstream of the AUG of the first gene, is expected to encode a 20.7 kDa polypeptide of yet an unknown function. Upon lifting repression at 40°C, the transcription of an operon which is involved in the lytic cycle is started from a promoter on the reverse phage DNA strand. The first gene in the operon is a homolog of the antirepresor ner, a common gene in the lysis-lysogeny regulation region of other phages. Interestingly, the next gene after ner is gene 10 that on the reverse strand overlaps the overlapped gene olg1 on the forward strand. Curiously, gene 10 expression also shows superinfection exclusion. Strand-specific RNA-Seq also has uncovered the transcription succession of gene modules expressed during the phage lytic stage. The conservation of overlapped genes with similar functions may be evolutionarily selected.

Survey on helminths of bats in the Yucatan Peninsula: infection levels, molecular information and host-parasite networks.

Helminth species of Neotropical bats are poorly known. In Mexico, few studies have been conducted on helminths of bats, especially in regions such as the Yucatan Peninsula where Chiroptera is the mammalian order with the greatest number of species. In this study, we characterized morphologically and molecularly the helminth species of bats and explored their infection levels and parasite­host interactions in the Yucatan Peninsula, Mexico. One hundred and sixty-three bats (representing 21 species) were captured between 2017 and 2022 in 15 sites throughout the Yucatan Peninsula. Conventional morphological techniques and molecular tools were used with the 28S gene to identify the collected helminths. Host­parasite network analyses were carried out to explore interactions by focusing on the level of host species. Helminths were found in 44 (26.9%) bats of 12 species. Twenty helminth taxa were recorded (7 trematodes, 3 cestodes and 10 nematodes), including 4 new host records for the Americas. Prevalence and mean intensity of infection values ranged from 7.1 to 100% and from 1 to 56, respectively. Molecular analyses confirmed the identity of some helminths at species and genus levels; however, some sequences did not correspond to any of the species available on GenBank. The parasite­host network suggests that most of the helminths recorded in bats were host-specific. The highest helminth richness was found in insectivorous bats. This study increases our knowledge of helminths parasitizing Neotropical bats, adding new records and nucleotide sequences.

Chlamydia trachomatis prevalence in females in São Paulo, Brazil: 11 years' surveillance of the infection.

BACKGROUND: Chlamydia trachomatis (CT) infection is the most prevalent sexually transmitted bacterial disease worldwide whose greatest impact is on the female reproductive system. The objective was to assess the prevalence of Chlamydia infection in a large population of female patients from a private health service in São Paulo (Brazil), identifying the main age groups affected by the agent and the evolution of the prevalence. METHODS: A cross-sectional study was conducted based on the results of all molecular biology tests. The tests were carried out between January 2005 and December 2015. The positivity of test results was determined by year and age group. RESULTS: A total of 85,292 patients who performed 103,576 tests for Chlamydia were considered eligible for the statistical data. The overall prevalence of C. trachomatis infection in the study population was 2.2% (95% CI: 2.07-2.25). A higher prevalence of infection was observed in the ≤ 25 years and ≤ 30 years age groups, with rates of 6.0% (95% CI: 5.59-6.35) and 4.4% (95% CI: 4.08-4.50), respectively. There was a significant increase in the positivity of the exams over time, especially in the ≤ 35 years age group. The prevalence at 26-30 years was 3.1% (95% CI: 2.82-3.30); 31-35 years 1.7% (95% CI: 1.50-1.82); 36-40 years 1.0% (95% CI: 0.86-1.16); 41-60 years 0.6% (95% CI: 0.50-0.70) and the prevalence at ≥ 61 years was 0.4% (95% CI: 0.11-0.75). CONCLUSION: The screening of asymptomatic young women would have the potential to reduce infection, transmission, and sequelae of infection by this agent.

Helminths of small rodents (Heteromyidae and Cricetidae) in the Yucatan Peninsula, Mexico: an integrative taxonomic approach to their inventory.

In this survey, we inventoried the helminths of heteromyid and cricetid rodents captured in the Yucatan Peninsula from 2017 to 2019. Helminths were identified using morphological techniques (clearing, staining, and scanning electron microscopy). Also, the 28S rRNA gene of individuals from several helminth taxa was successfully amplified and sequenced. To confirm the identification at the generic level, and in some cases at the specific level, and the genealogical relationships of the parasites, phylogenetic analyses were performed with the new 28S sequences. We identified 22 species of helminths including three trematodes (Brachylaimidae, Dicrocoeliidae, and Microphallidae), five cestodes (Davaineidae, Hymenolepididae, and Taeniidae), and 14 nematodes (Trichuridae, Ancylostomatidae, Ornithostrongylidae, Heligmonellidae, and Oxyuridae) from Heteromys gaumeri (Heteromyidae), Ototylomys phyllotis, Oligoryzomys fulvescens, Peromyscus yucatanicus, Sigmodon toltecus, and Reithrodontomys gracilis (Cricetidae). The overall frequency of infection in small rodents was 84.1% (143/170); all specimens of H. gaumeri, S. toltecus and Ol. fulvescens were infected with helminths. In total, we provided 46 new sequences of the 28S gene from 17 species of helminths. Seven species are likely undescribed species, six are reported for the first time in rodents from Mexico, and 12 are new host records in the Americas. Before this study, 87 taxa of helminths had been reported from 35 cricetid and 12 heteromyid species in 21 Mexican states. Our findings increase to 93 the helminth taxa in these rodents, and to 36 the cricetid species parasitized by helminths. This large scale-survey is the first to use an integrative approach to inventory the helminths of wild small rodents in Mexico.

Cutaneous Leishmaniasis Emergence in Southeastern Mexico: The Case of the State of Yucatan.

Environmental changes triggered by deforestation, urban expansion and climate change are present-day drivers of the emergence and reemergence of leishmaniasis. This review describes the current epidemiological scenario and the feasible influence of environmental changes on disease occurrence in the state of Yucatan, Mexico. Relevant literature was accessed through different databases, including PubMed, Scopus, Google, and Mexican official morbidity databases. Recent LCL autochthonous cases, potential vector sandflies and mammal hosts/reservoirs also have been reported in several localities of Yucatan without previous historical records of the disease. The impact of deforestation, urban expansion and projections on climate change have been documented. The current evidence of the relationships between the components of the transmission cycle, the disease occurrence, and the environmental changes on the leishmaniasis emergence in the state shows the need for strength and an update to the intervention and control strategies through a One Health perspective.

Epidemiological Study of the Occurrence of Typhus Group Rickettsia Natural Infection in Domiciliated Dogs from a Rural Community in South-Eastern Mexico.

The aim is to describe the Typhus group (TG) Rickettsia infection in dogs and to identify factors associated with this infection. We collected blood samples and gathered exposure and clinical data of 142 dogs from a rural community of Yucatan. The Rickettsia group was determined by semi-nested PCR. Generalized linear models with binomial error distribution were used to model the associated factors from the dog sample for risk ratio (RR) estimation. Thirty-four dogs (23.9%) showed molecular evidence of TG Rickettsia DNA. The multivariate model showed that mixed-breed dogs (RR = 0.06) and dogs that had received antiparasitic treatment (RR = 0.049) had a lower risk of getting infected, taking as reference the purebred group and the non-treated dogs, respectively. Looking at variable interactions, adult dogs without outdoor activities had a lower infection risk than puppies (RR = 0.26). Among dogs with antiparasitic treatment, females had a higher infection risk than male dogs (RR = 26.2). The results showed enzootic TG Rickettsia circulation in dogs of a rural community. The factors outdoor activities, age and previous antiparasitic treatment, as well as the clinical variables signs of hemorrhages and epistaxis, were associated with a less chance of natural infection in the studied dogs. Prevention and control of the enzootic transmission risk of TG Rickettsia should help to reduce the potential zoonotic transmission of this pathogen.

Primer registro de un caso de loxoscelismo cutáneo ocasionado por mordedura de araña violinista (Loxosceles yucatana) en Yucatán, México / First record of a case of cutaneous loxoscelism caused by violin spider (Loxosceles yucatana) bite in Yucatan, Mexico

El loxoscelismo es ocasionado cuando el veneno dermonecrótico producido por las arañas del género Loxosceles, conocidas como «arañas violinistas», ingresa al organismo de una persona a través de su mordida. En México ocurre un subregistro de los casos de loxoscelismo por la ausencia de pruebas de laboratorio para su diagnóstico y la dificultad del cuadro clínico. El objetivo de este trabajo es describir un caso de loxoscelismo cutáneo ocasionado por mordedura de Loxosceles yucatana en un residente de Yucatán, México. El loxoscelismo cutáneo es el tipo más frecuente y menos severo. El presente caso se diagnosticó por medio de la sintomatología registrada en la historia clínica, la lesión inicial y la identificación de arañas L. yucatana. Este trabajo representa la primera descripción de un caso de loxoscelismo cutáneo con resolución favorable en Yucatán.

Loxoscelism occurs when the dermonecrotic venom produced by spiders of the genus Loxosceles, known as "violin spiders," enters a person's organism through their bite. In Mexico there is an underreporting of loxoscelism cases due to the absence of laboratory tests for its diagnosis and the complexity of the clinical picture. The aim of this paper is to describe a case of cutaneous loxoscelism caused by the bite of Loxosceles yucatana in a resident of Yucatan, Mexico. Cutaneous loxoscelism is the most frequent and less severe type. This case was diagnosed by means of the symptomatology registered in the medical records, the initial lesion, and the identification of L. yucatana spiders. This study represents the first description of a case of cutaneous loxoscelism with favorable outcome in Yucatan.

Preditores de Mortalidade Hospitalar nos Pacientes Tratados por Angioplastia Primária: Um Estudo de Caso-Controle Multicêntrico / Predictors of Hospital Mortality Based on Primary Angioplasty Treatment: A Multicenter Case-Control Study

Resumo Fundamento A estratificação do risco de morte dos pacientes no contexto da angioplastia primária (ATC) é fundamental. Objetivo Identificar os fatores relacionados ao desfecho morte em pacientes submetidos a ATC. Métodos Estudo de caso-controle, utilizando como fonte de dados um registro brasileiro. A associação entre cada variável e o desfecho óbito foi avaliada via modelo de regressão logística binária. Consideramos significativo p<0,05. Resultados Foram analisados 26.990 registros, sendo 18.834 (69,8%) do sexo masculino, com idade mediana de 61 (17) anos. Na análise multivariada, as principais variáveis relacionadas ao desfecho óbito com seus respectivos odds ratio e intervalos de confiança (IC) com nível de significância de 95% foram a idade avançada 70 - 79 anos (2,46; 1,64 - 3,79) e ≥ 80 anos (3,68; 2,38 - 5,81), p<0,001, classificação de Killip II (2,71; 1,92 - 3,83), Killip III (8,14; 5,67 - 11,64), Killip IV (19,83; 14,85 - 26,69), p<0,001, disfunção global acentuada do ventrículo esquerdo (VE) (3,63; 2,39 - 5,68), p<0,001 e ocorrência de infarto após a intervenção (5,01; 2,57- 9,46), p<0,001. O principal fator protetor foi o fluxo TIMI III pós-intervenção (0,18; 0,13 - 0,24), p<0,001, seguido do TIMI II (0,59; 0,41 - 0,86), p=0,005, sexo masculino (0,79; 0,64 - 0,98), p= 0,032, dislipidemia (0,69; 0,59 - 0,85), p<0,001 e número de lesões tratadas (0,86; 0,9 - 0,94), p<0,001. Conclusão Os preditores de mortalidade nos pacientes submetidos a ATC foram: classificação de Killip, reinfarto, idade, disfunção global acentuada do VE, sexo feminino e fluxo TIMI 0/I pós-intervenção.

Abstract Background Identification of high-risk patients undergoing primary angioplasty (PCI) is essential. Objective Identify factors related to the causes of death in PCI patients. Methods This work consisted of a multicenter case-control study using a Brazilian registry of cardiovascular interventions as the data source. The association between each variable and death was assessed using a binary logistic regression model, p <0.05 was considered significant. Results A total of 26,990 records were analyzed, of which 18,834 (69.8%) were male patients, with a median age of 61 (±17) years. In the multivariate analysis, the main variables related to the causes of death with their respective odds ratios and 95%confidence intervals (CI) were advanced age, 70-79 years (2.46; 1.64-3.79) and ≥ 80 years (3.69; 2.38-5.81), p<0.001; the classification of Killip II (2.71; 1.92-3.83), Killip III (8.14; 5.67-11.64), and Killip IV (19.83; 14.85-26.69), p<0.001; accentuated global dysfunction (3.63; 2,39-5.68), p<0.001; and the occurrence of infarction after intervention (5.01; 2.57-9.46), p<0.001. The main protective factor was the post-intervention thrombolysis in myocardial infarction (TIMI) III flow (0.18; 0.13-0.24), p<0.001, followed by TIMI II (0.59; 0.41 -0.86), p=0.005, and male (0.79; 0.64-0.98), p = 0.032; dyslipidemia (0.69; 0.59-0.85), p<0.001; and number of lesions treated (0.86; 0.9-0.94), p<0.001. Conclusion The predictors of mortality in patients undergoing PCI were Killip's classification, reinfarction, advanced age, severe left ventricular dysfunction, female gender, and post-intervention TIMI 0 / I flow.

Predictors of Hospital Mortality Based on Primary Angioplasty Treatment: A Multicenter Case-Control Study. / Preditores de Mortalidade Hospitalar nos Pacientes Tratados por Angioplastia Primária: Um Estudo de Caso-Controle Multicêntrico.

BACKGROUND: Identification of high-risk patients undergoing primary angioplasty (PCI) is essential. OBJECTIVE: Identify factors related to the causes of death in PCI patients. METHODS: This work consisted of a multicenter case-control study using a Brazilian registry of cardiovascular interventions as the data source. The association between each variable and death was assessed using a binary logistic regression model, p <0.05 was considered significant. RESULTS: A total of 26,990 records were analyzed, of which 18,834 (69.8%) were male patients, with a median age of 61 (±17) years. In the multivariate analysis, the main variables related to the causes of death with their respective odds ratios and 95%confidence intervals (CI) were advanced age, 70-79 years (2.46; 1.64-3.79) and ≥ 80 years (3.69; 2.38-5.81), p<0.001; the classification of Killip II (2.71; 1.92-3.83), Killip III (8.14; 5.67-11.64), and Killip IV (19.83; 14.85-26.69), p<0.001; accentuated global dysfunction (3.63; 2,39-5.68), p<0.001; and the occurrence of infarction after intervention (5.01; 2.57-9.46), p<0.001. The main protective factor was the post-intervention thrombolysis in myocardial infarction (TIMI) III flow (0.18; 0.13-0.24), p<0.001, followed by TIMI II (0.59; 0.41 -0.86), p=0.005, and male (0.79; 0.64-0.98), p = 0.032; dyslipidemia (0.69; 0.59-0.85), p<0.001; and number of lesions treated (0.86; 0.9-0.94), p<0.001. CONCLUSION: The predictors of mortality in patients undergoing PCI were Killip's classification, reinfarction, advanced age, severe left ventricular dysfunction, female gender, and post-intervention TIMI 0 / I flow.

FUNDAMENTO: A estratificação do risco de morte dos pacientes no contexto da angioplastia primária (ATC) é fundamental. OBJETIVO: Identificar os fatores relacionados ao desfecho morte em pacientes submetidos a ATC. MÉTODOS: Estudo de caso-controle, utilizando como fonte de dados um registro brasileiro. A associação entre cada variável e o desfecho óbito foi avaliada via modelo de regressão logística binária. Consideramos significativo p<0,05. RESULTADOS: Foram analisados 26.990 registros, sendo 18.834 (69,8%) do sexo masculino, com idade mediana de 61 (17) anos. Na análise multivariada, as principais variáveis relacionadas ao desfecho óbito com seus respectivos odds ratio e intervalos de confiança (IC) com nível de significância de 95% foram a idade avançada 70 - 79 anos (2,46; 1,64 - 3,79) e ≥ 80 anos (3,68; 2,38 - 5,81), p<0,001, classificação de Killip II (2,71; 1,92 - 3,83), Killip III (8,14; 5,67 - 11,64), Killip IV (19,83; 14,85 - 26,69), p<0,001, disfunção global acentuada do ventrículo esquerdo (VE) (3,63; 2,39 - 5,68), p<0,001 e ocorrência de infarto após a intervenção (5,01; 2,57- 9,46), p<0,001. O principal fator protetor foi o fluxo TIMI III pós-intervenção (0,18; 0,13 - 0,24), p<0,001, seguido do TIMI II (0,59; 0,41 - 0,86), p=0,005, sexo masculino (0,79; 0,64 - 0,98), p= 0,032, dislipidemia (0,69; 0,59 - 0,85), p<0,001 e número de lesões tratadas (0,86; 0,9 - 0,94), p<0,001. CONCLUSÃO: Os preditores de mortalidade nos pacientes submetidos a ATC foram: classificação de Killip, reinfarto, idade, disfunção global acentuada do VE, sexo feminino e fluxo TIMI 0/I pós-intervenção.

Occurrence of legacy and replacement plasticizers, bisphenols, and flame retardants in potable water in Montreal and South Africa.

The occurrence of thirty-nine contaminants including plasticizers, bisphenols, and flame retardants in potable water from Montreal and South Africa was analyzed to determine their presence and concentrations in different water sources. In Montreal, five bottled water (BW) brands and three drinking water treatment plants (DWTP) were included. In South Africa, water was sampled from one urban DWTP located in Pretoria, Gauteng, and one rural DWTP located in Vhembe, along with water from the same rural DWTP which had been stored in small and large plastic containers. A combination of legacy compounds, typically with proven toxic effects, and replacement compounds was investigated. Bisphenols, Dechlorane-602, Dechlorane-603, and s-dechlorane plus (s-DP) were not detected in any water samples, and a-dechlorane plus (a-DP) was only detected in one sample from Pretoria at a concentration of 1.09 ng/L. Lower brominated polybrominated diphenyl ethers (PBDE)s were detected more frequently than higher brominated PBDEs, always at low concentrations of <2 ng/L, and total PBDE levels were statistically higher in South Africa than in Montreal. Replacement flame retardants, organophosphate esters (OPEs), were detected at statistically higher concentrations in Montreal's BW (68.56 ng/L), drinking water (DW) (421.45 ng/L) and Vhembe (198.33 ng/L) than legacy PBDEs. Total OPE concentrations did not demonstrate any geographical trend; however, levels were statistically higher in Montreal's DW than Montreal's BW. Plasticizers were frequently detected in all samples, with legacy compounds DEHP, DBP, and replacement DINCH being detected in 100 % of samples with average concentrations ranging from 6.89 ng/L for DEHP in Pretoria to 175.04 ng/L for DINCH in Montreal's DW. Total plasticizer concentrations were higher in Montreal than in South Africa. The replacement plasticizers (DINCH, DINP, DIDA, and DEHA) were detected at similar frequencies and concentrations as legacy plasticizers (DEHP, DEP, DBP, MEHP). For the compounds reported in earlier studies, the concentrations detected in the present study were similar to other locations. These compounds are not currently regulated in drinking water but their frequent detection, especially OPEs and plasticizers, and the presence of replacement compounds at similar or higher levels than their legacy compounds demonstrate the importance of further investigating the prevalence and the ecological or human health effects of these compounds.

Is vertical transmission the only pathway for Rickettsia felis?

The genus Rickettsia encompasses several species grouped into two main clusters, Typhus and the Transitional groups. The latter group contains Rickettsia felis, an endosymbiont of several arthropods with an uncertain human pathogenicity and whose most efficient transmission mechanism described thus far is transovarial. The aim of this study was to evaluate whether this pathway exists using phylogenetic analysis and partial sequences of the 17kDa and gltA genes and comparing them with host phylogeny using the cytb region. This is the first study that evaluates the vertical transmission of R. felis. In general, both phylogenies of R. felis showed no polytomies, as suspected if this pathway was the only pathway occurring. When phylogenies of the invertebrates and the gltA of R. felis were compared for strong coevolutionary insight, intricate relationships were observed, suggesting that other transmission pathways must occur, such as horizontal transmission. Further studies are needed to determine which other transmission routes occur in hematophagous arthropods.

A YAP/TAZ-TEAD signalling module links endothelial nutrient acquisition to angiogenic growth.

Angiogenesis, the process by which endothelial cells (ECs) form new blood vessels from existing ones, is intimately linked to the tissue's metabolic milieu and often occurs at nutrient-deficient sites. However, ECs rely on sufficient metabolic resources to support growth and proliferation. How endothelial nutrient acquisition and usage are regulated is unknown. Here we show that these processes are instructed by Yes-associated protein 1 (YAP)/WW domain-containing transcription regulator 1 (WWTR1/TAZ)-transcriptional enhanced associate domain (TEAD): a transcriptional module whose function is highly responsive to changes in the tissue environment. ECs lacking YAP/TAZ or their transcriptional partners, TEAD1, 2 and 4 fail to divide, resulting in stunted vascular growth in mice. Conversely, activation of TAZ, the more abundant paralogue in ECs, boosts proliferation, leading to vascular hyperplasia. We find that YAP/TAZ promote angiogenesis by fuelling nutrient-dependent mTORC1 signalling. By orchestrating the transcription of a repertoire of cell-surface transporters, including the large neutral amino acid transporter SLC7A5, YAP/TAZ-TEAD stimulate the import of amino acids and other essential nutrients, thereby enabling mTORC1 activation. Dissociating mTORC1 from these nutrient inputs-elicited by the loss of Rag GTPases-inhibits mTORC1 activity and prevents YAP/TAZ-dependent vascular growth. Together, these findings define a pivotal role for YAP/TAZ-TEAD in controlling endothelial mTORC1 and illustrate the essentiality of coordinated nutrient fluxes in the vasculature.

The blood-brain barrier-a metabolic ecosystem.

A functional blood-brain barrier relies on a tightly controlled interplay between endothelial cells, pericytes, and astrocytes, which together form the neurovascular unit. Recent work by Lee et al (2022) discovers endothelial cell-derived lactate as a crucial metabolic fuel for brain pericytes, revealing a new way of CNS vascular communication that links nutrient metabolism to blood-brain barrier function.