Metabolic effects of switching to Biktarvy (B/F/TAF) in patients with HIV-1 treated with antiretroviral regimens that do not include tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF): The Metabic study.

BACKGROUND: Studies on switching to tenofovir alafenamide (TAF)-based regimens raise concerns about a worse metabolic profile in people with HIV, even though most received tenofovir disoproxil fumarate (TDF) in their previous regimen. This study aims to evaluate changes in lipid fractions, glucose, and serum markers for hepatic steatosis (HS) after switching from a TDF- or TAF-sparing regimen to bictegravir/emtricitabine/TAF (B/F/TAF). METHODS: We performed a retrospective cohort study of people with HIV who switched to B/F/TAF from TDF- or TAF-sparing regimens between January 2019 and May 2022 with at least 6 months of follow-up. The primary endpoint was the absolute change in lipid fractions at 6 months. Secondary outcomes were changes in lipid fractions at 12 months and changes in other metabolic parameters (glucose, creatinine, and HS based on the triglyceride-to-glucose [TyG] ratio at 6 and 12 months). Changes were analysed using mixed linear regression models with random intercept and time as a fixed effect. RESULTS: The study included 259 people with HIV (median age 55 [interquartile range (IQR) 47-60] years; 80% male; 88% Caucasian; CD4+ T-cell count 675 [IQR 450-880] cells/mm3; 84.3% HIV-RNA <50 copies/mL). In total, 63 patients (30%) had hypertension, 93 (44%) dyslipidaemia, 30 (14%) diabetes, and 45% obesity/overweight. Most (60%) switched from integrase inhibitor-based regimens, and 21% switched from a boosted regimen. At 6 months, significant reductions were observed in total cholesterol (-7.64 mg/dL [95% confidence interval (CI) -13.52 to -1.76; p = 0.002]), triglycerides (-23.4 [95% CI -42.07 to -4.65]; p = 0.003), and TyG ratio (-0.14 [95% CI -0.23 to -0.05]; p < 0.001). CONCLUSION: In our real-life cohort, the effect of switching TDF-/TAF-sparing regimens to triple therapy with B/F/TAF improved total cholesterol, triglycerides, and serum markers of HS at 6 months and was neutral for the remaining metabolic parameters at 12 months.

The role of viral diagnostic tests in respiratory tract infections: moving forward.

The increased knowledge on virology and the increased potential of their diagnostic has risen several relevant question about the role of an early viral diagnosis and potential early treatment on the management of respiratory tract infections (RTI). In order to further understand the role of viral diagnostic tests in the management of RTI, a panel of experts was convened to discuss about their potential role, beyond what had been agreed in Influenza. The objective of this panel was to define the plausible role of aetiologic viral diagnostic into clinical management; make recommendations on the potential expanded use of such tests in the future and define some gaps in the management of RTI. Molecular Infection Viral Diagnostic (mIVD) tests should be used in all adult patients admitted to Hospital with RTI, and in paediatric patients requiring admission or who would be referred to another hospital for more specialised care. The increased use of mIVD will not only reduce the inappropriate use of antibiotics so reducing the antibiotic microbe resistance, but also will improve the outcome of the patient if an aetiologic viral therapy can be warranted, saving resource requirements and improving patient flows. Implementing IVD testing in RTI has various organizational benefits as well, but expanding its use into clinical settings would need a cost-effectiveness strategy and budget impact assessment.

Description of Saccocoelioides miguelmontesi n. sp. (Digenea: Haploporidae) from characid fishes in the Iguazu River Basin based on morphological and molecular evidence.

Here we describe a new species of the genus Saccocoelioides found parasitizing Astyanax dissimilis Garavello & Sampaio, Psalidodon bifasciatus (Garavello and Sampaio) and Bryconamericus ikaa Casciotta, Almirón & Azpelicueta from the Iguazu National Park, Misiones province, Argentina. Saccocoelioides miguelmontesi n. sp. was studied based on morphological and molecular (28S rDNA and COI mtDNA sequences) data. The COI mtDNA tree indicated that the specimens collected from the three fish hosts are conspecific, with an intragroup p-distance of 0%. The new species shows an intermediate morphological configuration between the diminutive and robust forms described for Saccocoelioides by Curran (2018). Although, in the 28S rDNA tree, it is placed in a well-supported clade with the two robust species analysed (S. elongatus and S. magnus; p-distance of 1 and 2%, respectively), it differs from the robust group by the range of body size, mature egg size, oral and ventral sucker size, sucker ratio, oral sucker to pharynx ratio, and post-cecal or post-testis/body length percentage. Our results led us to redefine the robust group as having eggs shorter or equal in length to the pharynx. Saccocoelioides miguelmontesi n. sp. the 10th species reported from Argentina and the 7th species within the robust group.

Reduced genetic diversity and the success of the invasive peacock bass (Cichliformes: Cichlidae)

Abstract Several species of Cichla successfully colonized lakes and reservoirs of Brazil, since the 1960s, causing serious damage to local wildlife. In this study, 135 peacock bass were collected in a reservoir complex in order to identify if they represented a single dominant species or multiple ones, as several Cichla species have been reported in the basin. Specimens were identified by color pattern, morphometric and meristic data, and using mitochondrial markers COI, 16S rDNA and Control Region (CR). Overlapping morphological data and similar coloration patterns prevented their identification using the taxonomic keys to species identification available in the literature. However, Bayesian and maximum likelihood from sequencing data demonstrated the occurrence of a single species, Cichla kelberi. A single haplotype was observed for the 16S and CR, while three were detected for COI, with a dominant haplotype present in 98.5% of the samples. The extreme low diversity of the transplanted C. kelberi evidenced a limited number of founding maternal lineages. The success of this colonization seems to rely mainly on abiotic factors, such as increased water transparency of lentic environments that favor visual predators that along with the absence of predators, have made C. kelberi a successful invader of these reservoirs.

Resumo Muitas espécies de Cichla colonizaram com sucesso lagos e reservatórios do Brasil desde os anos 1960, causando graves prejuízos à vida selvagem nesses locais. Neste estudo, 135 tucunarés foram coletados em um complexo de reservatórios a fim de identificar se representavam uma espécie dominante ou múltiplas espécies, uma vez que diversas espécies de Cichla foram registradas na bacia. Os espécimes foram identificados com base na coloração, dados morfométricos e merísticos, e por marcadores mitocondriais COI, 16S rDNA e Região Controle (RC). A sobreposição dos dados morfométricos e o padrão similar de coloração impediram a identificação utilizando as chaves de identificação disponíveis na literatura. Entretanto, as análises bayesiana e de máxima verossimilhança de dados moleculares demonstraram a ocorrência de uma única espécie, Cichla kelberi. Um único haplótipo foi observado para o 16S e RC, enquanto três foram detectados para o COI, com um haplótipo dominante presente em 98,5% das amostras. A baixa diversidade nos exemplares introduzidos de C. kelberi evidenciou um número limitado de linhagens maternas fundadoras. O sucesso da invasão parece depender de fatores abióticos, como a maior transparência da água de ambientes lênticos que favorece predadores visuais que, atrelado à ausência de predadores, fez do C. kelberi um invasor bem-sucedido nesses reservatórios.

Reduced genetic diversity and the success of the invasive peacock bass (Cichliformes: Cichlidae) / Diversidade genética reduzida e o sucesso da espécie invasora tucunaré (Cichliformes: Cichlidae)

Abstract Several species of Cichla successfully colonized lakes and reservoirs of Brazil, since the 1960's, causing serious damage to local wildlife. In this study, 135 peacock bass were collected in a reservoir complex in order to identify if they represented a single dominant species or multiple ones, as several Cichla species have been reported in the basin. Specimens were identified by color pattern, morphometric and meristic data, and using mitochondrial markers COI, 16S rDNA and Control Region (CR). Overlapping morphological data and similar coloration patterns prevented their identification using the taxonomic keys to species identification available in the literature. However, Bayesian and maximum likelihood from sequencing data demonstrated the occurrence of a single species, Cichla kelberi. A single haplotype was observed for the 16S and CR, while three were detected for COI, with a dominant haplotype present in 98.5% of the samples. The extreme low diversity of the transplanted C. kelberi evidenced a limited number of founding maternal lineages. The success of this colonization seems to rely mainly on abiotic factors, such as increased water transparency of lentic environments that favor visual predators that along with the absence of predators, have made C. kelberi a successful invader of these reservoirs.

Resumo Muitas espécies de Cichla colonizaram com sucesso lagos e reservatórios do Brasil desde os anos 1960, causando graves prejuízos à vida selvagem nesses locais. Neste estudo, 135 tucunarés foram coletados em um complexo de reservatórios a fim de identificar se representavam uma espécie dominante ou múltiplas espécies, uma vez que diversas espécies de Cichla foram registradas na bacia. Os espécimes foram identificados com base na coloração, dados morfométricos e merísticos, e por marcadores mitocondriais COI, 16S rDNA e Região Controle (RC). A sobreposição dos dados morfométricos e o padrão similar de coloração impediram a identificação utilizando as chaves de identificação disponíveis na literatura. Entretanto, as análises bayesiana e de máxima verossimilhança de dados moleculares demonstraram a ocorrência de uma única espécie, Cichla kelberi. Um único haplótipo foi observado para o 16S e RC, enquanto três foram detectados para o COI, com um haplótipo dominante presente em 98,5% das amostras. A baixa diversidade nos exemplares introduzidos de C. kelberi evidenciou um número limitado de linhagens maternas fundadoras. O sucesso da invasão parece depender de fatores abióticos, como a maior transparência da água de ambientes lênticos que favorece predadores visuais que, atrelado à ausência de predadores, fez do C. kelberi um invasor bem-sucedido nesses reservatórios.

Phylogenetic position of the Neotropical Family Zonocotylidae (Paramphistomoidea) using partial 28S rDNA sequences.

Six families belonging to the Paramphistomoidea superfamily have been reported in South America, with only Zonocotylidae and Balanorchiidae being endemic. The Zonocotylidae was initially classified as Aspidogastrea and then as a paramphistomoid. This family comprises a single genus, Zononocotyle, with two species. It is primarily characterized by having an attachment organ with transverse ridges and a single testis. The placement of Zonocotylidae within Paramphistomoidea is controversial, as some researchers speculate that this genus is the most primitive member of the superfamily, while others consider it an aberrant form. The main objectives of our study were to provide the first sequences of Zonocotylidae and elucidate its phylogenetic position. We amplified the 28S gene from two parasites from Cyphocharax sp. from Punta Lara, Buenos Aires. Newly generated sequences were used to infer the phylogenetic relationships with other Paramphistomoidea species using a Bayesian approach. Zonocotylidae were clustered with Dadayiinae and Kalitrematinae (Cladorchiidae) species found in freshwater fishes from South America. Genetic analyses revealed that they formed a well-supported clade with cladorchiids in freshwater hosts from South America. However, the occurrence of genera of Cladorchiidae in North America, Middle America, Asia, and Australia suggested its polyphyletic nature and may indicate the need for the erection of new families. Other Paramphistomoidea families may also require further revision. The addition of new sequences to phylogenetic analyses along with a comprehensive and more detailed description of the genera will help resolve the relationships within this group.

Integrative analysis of new Clinostomum metacercariae (Digenea, Clinostomidae) using COI mtDNA and morphology rises the number of lineages found in South American freshwater fishes.

Clinostomidae is a diverse family of digenean parasitizing fish-eating birds as adults and fishes as metacercariae. The species composition, within the genus Clinostomum has been steadily increasing in recent years. In Argentina, four named species of Clinostomum have been documented, accompanied by four metacercariae representing distinct genetic lineages whose adults have not been identified. This study focused on examining clinostomids in three fish species - Australoheros scitulus (ASI), Cichlasoma dimerus (CDIM), and Pimelodella laticeps (PLA) - at various localities in Argentina. We conducted both morphological and molecular characterizations of the Clinostomum metacercariae collected from these fish species. Molecular phylogenetic analyses using COI mtDNA were performed to determine the placement of these metacercariae within the clinostomid phylogenetic tree. Clinostomum ASC represents a distinct lineage, morphologically distinguishable from other sequenced metacercariae due to its body shape (widest anteriorly and becoming slender towards the posterior end); this lineage was found to be closely related to C. caffarae. While Clinostomum CDIM and Clinostomum PLA exhibited morphological differences, they clustered together genetically with metacercariae reported in previous studies as Clinostomum L3 and Clinostomum CVI. This outcome, coupled with a low genetic distance (0 to 3%), suggests that they are conspecific with metacercariae found in fish across Mexico, Costa Rica, and Argentina. In light of the extensive diversity of fish species in Argentine freshwater ecosystems (over 500 species), and considering the relatively constrained extent of prior investigations, the anticipation of unearthing additional Clinostomum species or lineages is plausible.

Three-year efficacy of switching to dolutegravir plus lamivudine: A real-world study.

BACKGROUND: Dolutegravir (DTG) plus lamivudine (3TC) has proven highly efficacious as a switching strategy in virologically suppressed people with HIV (PWH). As this strategy was introduced relatively recently, real-world, long-term durability studies are lacking. METHODS: We performed a retrospective review of treatment-experienced patients who started DTG + 3TC in a cohort of PWH. HIV-RNA <50 copies/mL was analysed at 144 weeks in an intention-to-treat (ITT) analysis (missing = failure) and a per-protocol (PP) analysis (patients with missing data or changes for reasons other than virological failure were excluded). RESULTS: The study population comprised 358 PWH (19% women). Median age and time with HIV infection were 51.7 and 13.4 years, respectively. The median number of previous antiretroviral combinations was three. Previous virological failure was reported in 27.1% of patients, and the M184V resistance mutation was detected in 17 patients. At 144 weeks, the percentage of individuals with HIV-RNA <50 copies/mL was 77.4% (277/358) in the ITT analysis and 95.5% (277/290) in the PP analysis. A total of 68 participants were excluded from the PP analysis (data missing, 25, discontinuation due to toxicity, 19; other, 16; death, 8). Two people with virological failure selected resistance-associated mutations (M184V and M184V + R263K). HIV-RNA remained undetectable in 17 patients with a previous history of the M184V mutation. CONCLUSION: Our results confirm the real-world, long-term efficacy, tolerability and high genetic barrier of DTG + 3TC in treatment-experienced PWH. Although scarce, mutations causing resistance to nucleosides and integrase can emerge.

Efficacy and safety of dolutegravir/rilpivirine in real-world clinical practice. GeSIDA study 1119.

INTRODUCTION: Dolutegravir/rilpivirine (DTG/RPV) is an effective antiretroviral (ART) regimen endorsed by clinical trials as a switch therapy. The aim of our study was to analyse the efficacy and safety of DTG/RPV in real-world clinical practice. METHODS: Observational, multicentre study of patients who started DTG/RPV. Efficacy, adverse events and metabolic changes at 48 weeks were analysed. RESULTS: A total of 348 patients were included; median time of HIV infection was 21.1 years, 33.7% were AIDS cases; median nadir CD4 was 160 cells/µL; 90.5% had received ≥3 lines of ART and 179 (53.8%) had prior virological failure. Convenience (43.5%), toxicity/intolerance (28.4%) and interactions (17.0%) were the main reasons for starting DTG/RPV. Previous regimens were protease inhibitors (PI) (31.6%), non-nucleoside reverse transcriptase inhibitors (NNRTI) (20.4%) and integrase strand transfer inhibitors (INSTI) (14.9%). Efficacy (HIV-RNA <50 copies/mL) at 48 weeks was 89.7% (95% CI 86.1-92.6) by intention-to-treat (ITT) and 94.2% (95% CI 91.3-96.4) by on treatment (OT); 10 patients (3.1%) were not suppressed (3 had abandoned ART). There was a mean decrease in triglycerides, total cholesterol, low-density lipoprotein-cholesterol, glutamic-pyruvic transaminase (GPT), gamma-glutamyl transferase (GGT) and alkaline phosphatase; creatinine increased with a decrease in glomerular filtration rate. CONCLUSIONS: This study confirms the effectiveness, tolerability and safety of DTG/RPV in real-world clinical practice in a different population from clinical trials, with many years of infection, low CD4 nadir, several previous treatment lines, more than half with virological failures, and one-third diagnosed with AIDS. The switch to DTG/RPV was safe with few discontinuations due to adverse effects. Modifications of the lipid and liver profiles were favourable. There were no relevant changes in kidney function.

Proctitis in patients with monkeypox infection: a single-center analysis of 42 consecutive cases from a multidisciplinary observational study on monkeypox proctitis.

BACKGROUND: The current monkeypox (MP) virus outbreak was declared an international emergency in July 2022. The aim of this report is to describe our initial experience with patients with MP, focusing on proctitis. METHODS: We conducted an observational study between 20 May and 31 July 2022, on patients with MP at a reference tertiary center in Madrid, Spain. A descriptive analysis on MP was performed, focusing on its characteristics, symptoms, diagnosis, and outcomes. RESULTS: A total of 143 positive MP cases were diagnosed in our center; 42 of them [all male, median age 39 years (range: 22-57 years)] had proctitis (29.37%), and 3 patients (2.09%/MP total cases and 7.14%/MP proctitis) required surgical drainage of a perianal abscess. CONCLUSIONS: General and digestive surgeons must be aware of the presence of proctological impairment and complications due to MP virus.

[Myelination as a modulating factor in memory circuitry]. / La mielinización como un factor modulador de los circuitos de memoria.

INTRODUCTION: Myelin has been understood for many years as a static component that regulates the speed of electrical impulse transmission. However, multiple works defend a dynamic role dependent on experience. This has allowed the development of a new concept called myelin plasticity that contributes, together with synaptic plasticity, to the long-term changes that occur in neuronal circuits during learning and memory. Therefore, this review will address the latest published data regarding the role of myelination with memory. DEVELOPMENT: Evidence from human neuroimaging studies demonstrates that myelination can change due to activity-dependent modulation, such that learning can modify the axon myelination. Alternatively, it has also been shown that interfering with myelination, using transgenic rodent models, significantly impairs memory processes. This has important implications in alterations as severe as Alzheimer's disease, where transcriptional changes and in the phenotype of cells associated with the myelination process begin to be described. CONCLUSIONS: The new knowledge supports the concept of myelin plasticity and its implications for memory, which opens a new opportunity for the treatment of deficits that affect this cognitive function.

TITLE: La mielinización como un factor modulador de los circuitos de memoria.Introducción. La mielina se ha conceptualizado durante muchos años como un componente estático que regula la velocidad de transmisión del impulso nervioso. Sin embargo, cada vez son más los trabajos que defienden un papel dinámico y dependiente de la experiencia. Esto ha permitido el desarrollo de un nuevo concepto denominado plasticidad mielínica, que contribuye, junto con la plasticidad sináptica, a los cambios a largo plazo que se dan en los circuitos neuronales durante el aprendizaje y la memoria. Por tanto, en esta revisión se abordarán los últimos datos publicados en relación con el papel de la mielinización con la memoria. Desarrollo. La evidencia a partir de estudios de neuroimagen en humanos demuestra que la mielinización puede cambiar debido a la modulación dependiente de la actividad, de forma que los aprendizajes pueden modificar la mielinización de los axones. Alternativamente, también se ha demostrado que interferir sobre la mielinización, utilizando para ello modelos transgénicos de roedores, deteriora significativamente los procesos de memoria. Esto tiene importantes implicaciones en alteraciones tan graves como la enfermedad de Alzheimer, en la que comienzan a describirse cambios transcripcionales y en el fenotipo de las células asociadas al proceso de mielinización. Conclusiones. Los nuevos descubrimientos apoyan el concepto de plasticidad mielínica y sus implicaciones con la memoria, lo que abre una nueva oportunidad para el tratamiento de los déficits que afectan a esta función cognitiva.

Description of Diegoglossidium maradonai n. g. and n. sp. (Digenea: Alloglossidiidae) through an integrative taxonomy approach, with an amended diagnosis of the family.

This paper describes Diegloglossidium maradonai n. g., n. sp. a parasite of the intestine of Hoplosternum littorale (Hancock) from La Plata River basin. The new genus is morphologically similar to members of Alloglossidiidae and Macroderoidiidae although they also share some traits observed in both families. Those families can be differentiated from each other by the combination of morphological features, including the density and distribution of the tegumental spines, the distribution of the vitelline follicles and the extent of the post-testicular space. The molecular analyses based on the large subunit of the ribosomal RNA gene, and the internal transcribed spacer (ITS) regions including ITS1, 5.8S and ITS2 unequivocally place the new genus in the family Alloglossidiidae which is amended based on new observed features. Diegoglossidium n. g. is characterized by a combination of characteristics, being most notably the presence of a deeply lobed ovary. Lastly, the geographical distribution and host associations of the two closely related Neotropical genera of Alloglossidiidae: Magnivitellinum and Diegoglossidium are discussed, and the host and distribution range of Magnivitellinum saltaensis is expanded into Argentina.

Estabilidad, función, alineación y lesiones asociadas después de una intervención quirúrgica y rehabilitación de fractura de platillos tibiales / Stability, function, alignment and associated injuries after surgical intervention and rehabilitation of tibial plate fracture

Resumen: Introducción: las fracturas de los platillos tibiales afectan la funcionalidad de una gran articulación de carga como la rodilla debido a sus múltiples compromisos no sólo articulares, sino también de tejidos blandos. Este estudio tiene como objetivo evaluar la estabilidad, función, alineación, lesiones asociadas y complicaciones de la rodilla después de intervención quirúrgica y rehabilitación de fractura de platillos tibiales. Material y métodos: se realizó estudio observacional prospectivo descriptivo, donde se incluyeron los pacientes con fractura de platillos tibiales intervenidos quirúrgicamente que cumplieran los criterios de inclusión en el período comprendido entre Abril de 2018 y Junio de 2019. Se hizo análisis de variables con pruebas t para muestras independientes. Resultados: de un total de 92 pacientes con fractura de platillos tibiales, 66 (71%) lograron completar los seis meses mínimos de seguimiento. La fractura más común según la clasificación de Schatzker fue tipo II con 33.3% y la más común según la clasificación de Luo fue la de tres columnas medial, lateral y posterior con 39.4%. Más de 70% de los pacientes intervenidos por fracturas de platillos tibiales presentaron lesión de tejidos blandos, por ende, una inestabilidad de rodilla, especialmente con mayor índice de lesiones del ligamento cruzado anterior e inestabilidad anterior. Conclusión: una proporción importante de los pacientes intervenidos por fractura de platillos tibiales tienen lesión ligamentaria de rodilla.

Abstract: Introduction: tibial plateau fractures affect functionality of a large load bearing joint such as the knee, due to its multiple compromises, not only articular but also the ones including soft tissues. This study aims to evaluate the stability, function, alignment, associated injuries and complications of the knee after surgery and tibial plateau fractures rehabilitation. Material and methods: a descriptive prospective observational study was carried out where patients with a tibial plateau fracture who had undergone surgery, that accomplish the inclusion criteria were included, in the period from April 2018 to June 2019. Analysis of variables was performed with t tests for independent samples. Results: from a total of 92 patients with tibial plateau fracture, 66 (71%) were able to achieve the minimum six months follow-up. The most common fracture according to Schatzker classification was type II with 33.3%, and the most common according to Luo classification was the medial, lateral and posterior three column with 39.4%. More than 70% of patients who underwent surgery due to tibial plateau fractures developed soft tissue injury, therefore knee instability, specially with a higher rate of anterior cruciate ligament injuries or anterior instability. Conclusion: an important proportion of patients who underwent surgery for tibial plateau fractures have knee ligament injuries.

Genetic variants associated with steatohepatitis and liver fibrosis in HIV-infected patients with NAFLD.

Background and aims: Nonalcoholic fatty liver disease (NAFLD) is a common cause of liver damage in people living with HIV (PLWHIV). Several studies have investigated candidate genes for susceptibility to NAFLD and to steatohepatitis. PNPLA3, TM6SF2, and MBOAT7-TMC4 have been reported to be associated with elevated ALT levels and the histologic parameters of nonalcoholic steatohepatitis and severity of fibrosis. Our objective was to analyze the relationship between PNPLA3, TM6SF2, and MBOAT7-TMC4 and steatosis, steatohepatitis, and liver fibrosis in PLWHIV with NAFLD. Method: A cohort of PLWHIV with persistently elevated aminotransferase levels and suspected NAFLD who underwent liver biopsy and determination of genetic variants was assessed at two large centers in Spain. All participants included in the current study were genotyped for rs738409 (PNPLA3), rs58542926 (TM6SF2), and rs641738 (MBOAT7-TMC4). Results: The study population comprised PLWHIV who were on stable antiretroviral therapy [7.7% women; median age, 49.3 years (44-53.4)]. The median CD4 count was 829 (650-980), 60% had metabolic syndrome, and 18.5% were diabetic. The median BMI was 28.9 (25.5-30.8). Patients with liver steatosis (any grade) vs. nonsteatosis tended to harbor the PNPLA3 G allele variant [57.6% vs. 16.7% (p = 0.09)], but not TM6SF2 or MBOAT7-TMC4 variants. However, those with steatohepatitis vs. nonsteatohepatitis significantly more frequently had the PNPLA3 G allele variant [69.4% vs. 39.1% (p < 0.05)] and the MBOAT7-TMC4 A allele variant [75% vs. 42% (p < 0.05)]. In our cohort, the TM6SF2 gene variant was not associated with steatosis or steatohepatitis. The PNPLA3 G allele variant was associated with steatohepatitis [OR 4.9 (1.3-18); p 0.02] and liver fibrosis [OR 4.3 (1.1-17.4); p 0.04], and the MBOAT7-TMC4 A allele variant was associated with steatohepatitis [OR 6.6 (1.6-27.6); p 0.01]. Conclusion: The PNPLA3 G allele variant and MBOAT7-TMC4 A allele variant were associated with steatohepatitis and liver fibrosis in PLWHIV with persistently elevated aminotransferases and NAFLD. We recommend routine genotyping for PNPLA3 and MBOAT7-TMC4 in PLWHIV with NAFLD to identify those at higher risk of progression.

Metacercariae in the brain of Erythrinus cf. erythrinus (Characiformes: Erythrinidae) from Iguazú National Park (Argentina): do they belong to Dolichorchis lacombeensis (Digenea, Diplostomidae)?

In Argentina, the family Diplostomidae is composed of eight genera: Austrodiplostomum Szidat & Nani; Diplostomum von Nordmann; Dolichorchis Dubois; Hysteromorpha Lutz; Neodiplostomum Railliet; Posthodiplostomum Dubois; Sphincterodiplostomum Dubois; and Tylodelphys Diesing. During a parasitological survey of fishes from the Iguazú National Park we detected diplostomid metacercariae in the brain of Erythrinus cf. erythrinus. Fish were caught using crab traps, transported alive to the field laboratory, cold-anaesthetized and euthanized by cervical dissection. Some metacercariae were heat-killed in water and fixed in 10% formalin and others were preserved in alcohol 96% for DNA extraction. They were sequenced for the partial segment of the 28S rDNA, internal transcribed spacer (ITS) rDNA and cytochrome c oxidase subunit I (COI) mtDNA genes. Phylogenetic reconstruction was carried out using Bayesian inference and the proportion (p) of absolute nucleotide sites (p-distance) was obtained. In the 28S rDNA tree, the metacercaria sequenced grouped as Dolichorchis sp. The COI mtDNA p-distance between the metacercariae with Dolichorchis lacombeensis was 0.01. There is a small number of ITS sequences for the Diplostomidae family deposited in the GenBank. The oral sucker, ventral sucker, holdfast organ and the distance between oral and ventral suckers are larger in the adult compared with the metacercariae. Additionally, hind-body length and width are larger in the adult due to the development of the genital complex. Further studies using an integrative approach will help confirm the affiliation of other species to the genus Dolichorchis.

Assessment of Noninvasive Markers of Steatosis and Liver Fibrosis in Human Immunodeficiency Virus-Monoinfected Patients on Stable Antiretroviral Regimens.

Background: Nonalcoholic fatty liver disease (NAFLD) is a major nonacquired immune deficiency syndrome-defining condition for persons with human immunodeficiency virus (PWH). We aimed to validate noninvasive tests for the diagnosis of NAFLD in PWH. Methods: This is a cross-sectional study of PWH on stable antiretroviral therapy with persistently elevated transaminases and no known liver disease. The area under the receiver operating characteristic curve (AUROC) was calculated to compare the diagnostic accuracy of liver biopsy with abdominal ultrasound, transient elastography (TE) (including controlled attenuation parameter [CAP]), and noninvasive markers of steatosis (triglyceride and glucose index [TyG], hepatic steatosis index [HSI], fatty liver index [FLI]) and fibrosis ([FIB]-4, aminotransferase-to-platelet ratio index [APRI], NAFLD fibrosis score). We developed a diagnostic algorithm with serial combinations of markers. Results: Of 146 patients with increased transaminase levels, 69 underwent liver biopsy (90% steatosis, 61% steatohepatitis, and 4% F ≥3). The AUROC for steatosis was as follows: ultrasound, 0.90 (0.75-1); CAP, 0.94 (0.88-1); FLI, 0.81 (0.58-1); HSI, 0.74 (0.62-0.87); and TyG, 0.75 (0.49-1). For liver fibrosis ≥F3, the AUROC for TE, APRI, FIB-4, and NAFLD fibrosis score was 0.92 (0.82-1), 0.96 (0.90-1), 0.97 (0.93-1), and 0.85 (0.68-1). Optimal diagnostic performance for liver steatosis was for 2 noninvasive combined models of tests with TyG and FLI/HSI as the first tests and ultrasound or CAP as the second tests: AUROC = 0.99 (0.97-1, P < .001) and 0.92 (0.77-1, P < .001). Conclusions: Ultrasound and CAP performed best in diagnosing liver steatosis, and FLI, TyG, and HSI performed well. We propose an easy-to-implement algorithm with TyG or FLI as the first test and ultrasound or CAP as the second test to accurately diagnose or exclude NAFLD.

The transported cations impose differences in the thermostability of the gastric H,K-ATPase. A kinetic analysis.

This work analyses the thermostability of a membrane protein, the gastric H,K-ATPase, by means of a detailed kinetic characterization of its inactivation process, which showed to exhibit first-order kinetics. We observed parallel time courses for the decrease of ATPase activity, the decrease of the autophosphorylation capacity and the loss of tertiary structure at 49 °C. Higher temperatures were required to induce a significant change in secondary structure. The correspondence between the kinetics of Trp fluorescence measured at 49 °C and the decrease of the residual activity after heating at that temperature, proves the irreversibility of the inactivation process. Inactivation proceeds at different rates in E1 or E2 conformations. The K+-induced E2 state exhibits a lower inactivation rate; the specific effect is exerted with a K0.5 similar to that found at 25 °C, providing a further inkling that K+ occlusion by the H,K-ATPase is not really favoured. Increasing [H+] from pH 8 to pH 7, which possibly shifts the protein to E1, produces a subtle destabilizing effect on the H,K-ATPase. We performed a prediction of potential intramolecular interactions and found that the differential stability between E1 and E2 may be mainly explained by the higher number of hydrophobic interactions in the α- and ß-subunits of E2 conformation.

Improvement of Mueller-Kauffman Tetrathionate-Novobiocin (MKTTn) enrichment medium for the detection of Salmonella enterica by the addition of ex situ-generated tetrathionate.

The detection of Salmonella in food is based on the use of a selective enrichment broth such as Muller-Kauffman Tetrathionate-Novobiocin (MKTTn), in which tetrathionate plays a key role by providing Salmonella with a growth advantage. As sodium tetrathionate is unstable, it is generated in situ by the addition of iodine (Lugol's solution) before seeding. This step is cumbersome as the solution is easily spilled, compromising the performance of the medium and hindering the work of technicians. The aim of this study was to optimize MKTTn broth by generating tetrathionate ex situ through an external reaction between iodine and thiosulphate followed by lyophilization. Quality control procedures were performed to compare the modified and original media, testing pure productivity (enrichment with 50-120 CFU of Salmonella Thyphimurium ATCC 14028 and Salmonella Enteritidis ATCC 13076 and plating on Xylose Lysine Deoxycholate agar, XLD), mixed productivity (50-120 CFU of Salmonella strains and Pseudomonas aeruginosa and Escherichia coli at ≥104 CFU and XLD plating) and selectivity (≥104 CFU of P. aeruginosa and Enterococcus faecalis and plating on Tryptone Casein Soy agar, TSA). The modified MKTTn medium (S/L) performed comparably with the original medium in terms of growth of both Salmonella strains (>300 colonies in XLD), alone or with P. aeruginosa and E. coli. Quantitative assays showed no statistically significant differences in the number of colonies grown on XLD after 10-5 dilution (p = 0.7015 with S. Thyphimurium ATCC 14028 and p = 0.2387 with S. Enteritidis ATCC 13076; ANOVA test). MKTTn medium (S/L) was also selective against E. coli (≤100 colonies) and E. faecalis (<10 colonies). These results suggest that adding tetrathionate as a lyophilisate (S/L) is a feasible alternative to the use of Lugol's solution for the preparation of MKTTn enrichment broth and does not affect the properties of the medium.

Saccocoelioides kirchneri n. sp. (Digenea: Haploporidae) from the killifish Cnesterodon decemmaculatus (Cyprinodontiformes: Poeciliidae) from Argentina, morphological and molecular description.

This paper presents a new haploporid digenean that expands the number of species of Saccoccoelioides to 27. The new species, Saccocoelioides kirchneri n. sp. was collected from the intestine of Cnesterodon decemmaculatus (Poeciliidae: Cyprinodontiformes) from Lago del Bosque, La Plata, Argentina. The new species possesses the diagnostic features for Saccocoelioides: a sac like ceca; the vitellarium confined in two irregular groups of follicles distributed between the ventral sucker and the anterior margin of the testis; and a uterus confined largely in the hind-body, but encroaching into the range of the ventral sucker. The new species is differentiated from the 26 congeners by the body size, pharynx size, ventral sucker size, posterior extent of ceca, posterior extent of uterus and egg size. S. kirchneri n. sp. also is supported by the molecular analysis.