Albendazole metabolites excretion in human saliva as a biomarker to assess treatment compliance in mass drug administration (MDA) anthelmintic programs.

Soil-transmitted-helminth (STH) infections continue to be a persistent global public health problem. Control strategies for STH have been based on the use of mass drug administration (MDA). Coverage and compliance assessment is critical to understanding the true effectiveness of albendazole (ABZ) in those MDA programs. The aims of this work were to characterize the pattern of albendazole and metabolites excretion in human saliva, and to develop a saliva-based biomarker (HPLC drug/metabolite detection) useful to accurately estimate the coverage/compliance in MDA campaigns. The study subjects were 12 healthy volunteers treated with a single oral dose of ABZ (400 mg). Saliva and blood (dried blood spot, DBS) samples were taken previously and between 2 and 72 h post-treatment. The samples were analyzed by HPLC with UV detection, C18 reversed-phase column. ABZ sulphoxide was the main analyte recovered up to 72 h p.t. in blood and saliva. The concentration profiles measured in the blood (DBS samples) were higher (P < 0.05) than those in saliva, however, this ABZ-metabolite was recovered longer in saliva. The in vivo measurement of drugs/metabolites in saliva samples from ABZ-treated volunteers offers strong scientific evidence to support the use of saliva as a valid biological sample for assessing compliance in MDA programs.

Diagnostic accuracy of patch testing based in clinical response to contact allergen restrictions in allergic contact dermatitis.

Summary: Background. Patch testing (PT) is used to identify substances that cause allergic contact dermatitis (ACD). However, the clinical effects of allergen restrictions following PT have not been thoroughly investigated. This study aims to assess the diagnostic accuracy of PT in patients suspected of having ACD. Methods. Prospective study. PT were performed in patients with clinical diagnosis of ACD. Patients with a positive PT (case group) had a strict restriction of the suspected substance for one month. In patients with negative patch testing (control group), allergen restriction was based in clinical history. Clinical reduction (CR) of at least 50% in disease activity (CR50%) after one month of allergen restriction was considered clinically relevant. Total control was defined as clinical reduction of at least 90% (CR90%). Results. From 400 patients, 66.2% had a positive PT. The sensitivity of PT to identify CR50% was 84%, specificity 47%, PPV 53%, and NPV 81%. Only 10.5% of patients achieved CR90%. Conclusions. The PT had moderate diagnostic accuracy. It could be useful as a screening, but a positive result should be confirmed with controlled allergen restriction. The low number of patients who achieved a 90% CR invites to reconsider the allergens included in PT and the mechanistic processes of the disease.

Anthocyanin-Loaded Polymers as Promising Nature-Based, Responsive, and Bioactive Materials.

Anthocyanins are a specific group of molecules found in nature that have recently received increasing attention due to their interesting biological and colorimetric properties that have been successfully applied in several fields such as food preservation and biomedicine. Consequently, reviews devoted to a general overview of these flavonoids have proliferated in recent years. Meanwhile, the incorporation of anthocyanins into polymeric systems has become an interesting strategy to widen the applicability of these molecules and develop new smart and functional polymers in the above cited areas. However, anthocyanin-based polymers have been scarcely reviewed in the literature. Accordingly, this review aims to be a systematic summary of the most recent approaches for the incorporation of anthocyanins into macro-, micro-, or nanostructured polymers. Moreover, this work describes the fundamentals of the applicability of smart anthocyanin-based polymers and offers an updated review of their most interesting applications as sensors, biological regulators, and active materials.

Resultados quirúrgicos a corto y mediano plazo por enfermedad de Crohn ileocecal / Short and medium term results of the surgical management of ileocecal Crohn's disease

BACKGROUND: The treatment of Crohn's disease (CD) is based on medical therapy and surgery is reserved for failure of medical management or complications. AIM: To evaluate endoscopic, clinical, and surgical recurrence of CD after surgery. MATERIAL AND METHODS: In a prospectively maintained database, consecutive patients older than 15 years subjected to an ileocecal resection for ileocolic disease from January 2011 to April 2021, were identified. The diagnosis of CD was confirmed with the pathologic report. Patients with less than one year of follow-up were excluded. Information was obtained retrospectively from the database and clinical records. RESULTS: Fourteen patients were identified. The mean age at the time of surgery was 38 years. Surgery was performed at a median of 41.5 months (0-300) after the diagnosis of CD, nine elective and five emergency procedures. In five patients there were four major and two minor postoperative complications, with no anastomotic leakage. Six patients had endoscopic recurrence and seven had clinical recurrence (50%) at a mean of 15 months, one of whom required a second operation. There was no mortality. CONCLUSIONS: After the surgical treatment of CD, the clinical and endoscopic recurrence rate continues to be high.

Organic matter removal in a simultaneous nitrification-denitrification process using fixed-film system.

Swine wastewater treatment is a complex challenge, due to the high organic matter (OM) and nitrogen (N) concentrations which require an efficient process. This study focused on evaluating two different support media for OM and N removal from an Upflow Anaerobic Sludge Blanket (UASB) reactor fed with swine wastewater. Maximum specific nitrification (MSNA) and denitrification (MSDA) activity test for both biofilm and suspended biomass were carried out using as supports: polyurethane foam (R1) and polyethylene rings (R2). The results showed that R2 system was more efficiently than R1, reaching OM removal of 77 ± 8% and N of 98 ± 4%, attributed to higher specific denitrifying activity recorded (5.3 ± 0.34 g NO3-N/g TVS∙h). Furthermore, 40 ± 5% of the initial N in the wastewater could have been transformed into molecular nitrogen through SND, of which only 10 ± 1% was volatilized. In this sense, MSDA tests indicated that suspended biomass was responsible for at least 70% of N removal and only 20% can be attributed to biofilm. SND could be confirmed with the analysis of microbial diversity, due to the presence of the genus Pseudomonas dominated the prokaryotic community of the system in 54.4%.

ABC-transporter gene expression in ivermectin-susceptible and resistant Haemonchus contortus isolates.

Mammalian efflux transporters of the ATP-binding cassette (ABC) regulate cellular levels of endo- and xenobiotics by transporting molecules across cell membranes and are involved in diverse biological processes. Over-expression of these ABC transporters has been involved in macrocyclic lactone resistance. The main goal of this work was to compare the gene expression of the whole ABC-transporter superfamily in isolates of the sheep nematode Haemonchus contortus with different degrees of susceptibility to ivermectin (IVM). Additionally, the effects of in vivo IVM treatment were evaluated in the resistant isolates. Parasite-free Corriedale lambs were artificially infected with either IVM-susceptible or IVM-resistant H. contortus isolates. The differential expression of ABC transcripts in H. contortus female worms with differential susceptibility to IVM were assessed by RNA-seq. Additionally, the transcription levels of ABC-transporter genes in IVM-resistant adult worms recovered from treated sheep at 12 and 24 h after IVM administration were compared to those of IVM-R worms collected from untreated sheep. The comparative analysis of the ABC-transcripts revealed some minor differences in the expression levels of HCON_00042800 (pgp-3), HCON_00020200.mod (ced-7c), HCON_00085890 (abt-4), HCON_00063000 (pmp-5) and HCON_00116670 (wht-8), indicating that, at transcriptional level, these ABC-genes alone cannot explain resistance in H. contortus. HCON_00130060 (pgp-9.2) was highly differentially expressed in resistant isolates compared to susceptible ones, which agrees with previous reports suggesting that pgp-9 may be one of the most relevant candidates contributing to the multi-genic nature of the IVM resistance trait.

Feasibility of coronary blood flow simulations using mid-fidelity numeric and geometric models.

The fractional flow reserve index (FFR) is currently used as a gold standard to quantify coronary stenosis's functional relevance. Due to its highly invasive nature, the development of noninvasive surrogates based on simulations has drawn much attention in recent years, emphasizing efficient strategies that enable translational research. The focus of this work is twofold. First, to assess the feasibility of using a mid-fidelity numerical strategy (transversally enriched pipe element method, TEPEM), placed between low- and high-fidelity models, for the estimation of flow-related quantities, such as FFR and wall shear stress (WSS). Low-fidelity models, as zero- or one-dimensional models, are computationally inexpensive but in detriment of poorer spatially detailed predictions. On the other hand, high-fidelity models, such as classical three-dimensional numerical approximations, can provide detailed predictions but their transition to clinical application is prohibitive due to high computational costs. As a second goal, we quantify the impact of the length of lateral branches in the blood flow through the interrogated vessel of interest to further reduce the computational burden. Both studies are addressed considering a cohort of 17 coronary geometries. A total of 20 locations were selected to estimate the FFR index for a wide range of Coronary Flow Reserve (CFR) scenarios. Numerical results suggest that the mid-fidelity TEPEM model is a reliable approach for the efficient estimation of the FFR index and WSS, with an error in the order of [Formula: see text] and [Formula: see text], respectively, when compared to the high-fidelity prediction. Moreover, such mid-fidelity models require much less computational resources, in compliance with infrastructure frequently available in the clinic, by achieving a speedup between 30 and 60 times compared to a conventional finite element approach. Also, we show that shortening peripheral branches does not introduce considerable perturbations either in the flow patterns, in the wall shear stress, or the pressure drop. Comparing the different geometric models, the error in the estimation of FFR index and WSS is reduced to less than [Formula: see text] and [Formula: see text], respectively.

[Short and medium term results of the surgical management of ileocecal Crohn's disease]. / Resultados quirúrgicos a corto y mediano plazo por enfermedad de Crohn ileocecal.

BACKGROUND: The treatment of Crohn's disease (CD) is based on medical therapy and surgery is reserved for failure of medical management or complications. AIM: To evaluate endoscopic, clinical, and surgical recurrence of CD after surgery. MATERIAL AND METHODS: In a prospectively maintained database, consecutive patients older than 15 years subjected to an ileocecal resection for ileocolic disease from January 2011 to April 2021, were identified. The diagnosis of CD was confirmed with the pathologic report. Patients with less than one year of follow-up were excluded. Information was obtained retrospectively from the database and clinical records. RESULTS: Fourteen patients were identified. The mean age at the time of surgery was 38 years. Surgery was performed at a median of 41.5 months (0-300) after the diagnosis of CD, nine elective and five emergency procedures. In five patients there were four major and two minor postoperative complications, with no anastomotic leakage. Six patients had endoscopic recurrence and seven had clinical recurrence (50%) at a mean of 15 months, one of whom required a second operation. There was no mortality. CONCLUSIONS: After the surgical treatment of CD, the clinical and endoscopic recurrence rate continues to be high.

Enfoque del tromboembolismo pulmonar agudo desde el momento inicial en el servicio de urgencias / Initial Approach to Acute Pulmonary Embolism since the Initial Moment in the Emergency Department / Abordagem para tromboembolismo pulmonar agudo desde o momento inicial no departamento de emergência

El tromboembolismo pulmonar es la manifestación más grave de la enfermedad tromboembólica venosa y la tercera causa de mortalidad cardiovascular. Su sintomatología puede ir desde un cuadro asintomático o con síntomas leves, hasta el paro cardiaco. Dentro del enfoque de esta patología es importante tener en cuenta escalas que permiten estimar la probabilidad de que determinado paciente con ciertos signos, síntomas y factores de riesgo presente un tromboembolismo pulmonar, así como escalas diseñadas para valorar el riesgo de morir, en pacientes en los que ya se estableció este diagnóstico. Los pilares del tratamiento son la anticoagulación y la trombólisis, sin embargo, esta última está indicada únicamente en algunos casos. La presente revisión tiene como objetivo presentar una actualización de la evidencia sobre el enfoque diagnóstico y terapéutico del tromboembolismo pulmonar agudo, desde el ingreso del paciente al servicio de urgencias.

Pulmonary embolism is the most severe manifestation of venous thromboembolic disease and the third cause of cardiovascular mortality. Its symptoms can range from asymp-tomatic or mild symptoms to cardiac arrest. The approach to patients with suspected pulmonary embolism includes scores that allow estimating the clinical probability that a certain patient with certain signs, symptoms and risk factors will present a pulmonary thromboembolism, as well as scores that classify patients by severity and risk of hemody-namic decompensation. Treatment is based on anticoagulation and thrombolysis, which is used only in certain patients. The goal of this review is to present updated evidence regarding diagnosis and treatment of acute pulmonary embolism from the moment the patient arrives at the emergency room.

A embolia pulmonar é a manifestação mais grave da doença tromboembólica venosa e a terceira principal causa de mortalidade cardiovascular. Seus sintomas podem variar de sintomas assintomáticos ou leves a parada cardíaca. No enfoque desta patologia, é importante levar em consideração escalas que permitem estimar a probabilidade de um determinado paciente com determinados sinais, sintomas e fatores de risco apresentar tromboembolismo pulmonar, bem como escalas destinadas a avaliar o risco de morrer, em pacientes nos quais esse diagnóstico já foi estabelecido. Os pilares do tratamento são a anticoagulação e a trombólise, porém, esta última está indicada apenas em alguns casos. A presente revisão tem como objetivo apresentar uma atualização das evidências sobre a abordagem diagnóstica e terapêutica do tromboembolismo pulmonar agudo, desde a admissão do paciente no pronto-socorro.

Assessment of Diet-Related Changes on Albendazole Absorption, Systemic Exposure, and Pattern of Urinary Excretion in Treated Human Volunteers.

Soil-transmitted-helminth (STH) infections are a persistent global public health problem. Control strategies for STH have been based on the use of mass drug administration (MDA) mainly targeting preschool- and school-aged-children, although there is increasing interest in expanding treatment to include adults and others through community-wide MDA. Coverage assessment is critical to understanding the real effectiveness of albendazole (ALB) treatment in those MDA programs. The work described here aims to (i) evaluate the effect of type of diet (a heavy or light meal) and fasting before ALB treatment on the systemic disposition of ALB and its metabolites in treated human volunteers and (ii) evaluate the potential feasibility of detecting albendazole metabolites in urine. The data reported here demonstrate that the systemic availability of the active ALB-sulfoxide (ALBSO) metabolite was enhanced more than 2-fold after food ingestion (a heavy or light meal). ALB dissolution improvement related to the ingestion of food may modify the amount of drug/metabolites reaching the parasite, affecting drug efficacy and the overall success of MDA strategies. The measurement in urine samples of the amino-ALB-sulfone (NHALBSO2) derivative and ALBSO for up to 96 h suggests that it may be feasible to develop a noninvasive tool to evaluate compliance/adherence to ALB treatment.

Combined moxidectin-levamisole treatment against multidrug-resistant gastrointestinal nematodes: A four-year efficacy monitoring in lambs.

Nematicide combinations may be a valid strategy to achieve effective nematode control in the presence of drug resistance. The goal of the current trial was to evaluate the pharmaco-parasitological performance of the moxidectin (MOX) and levamisole (LEV) combination after four years of continuous use in lambs naturally parasitized with multi-resistant gastrointestinal nematodes. At the beginning of the trial, 40 lambs were divided into four groups (n = 10), which were untreated (control) or subcutaneously treated with MOX (0.2 mg/kg), LEV (8 mg/kg) or with the combination MOX + LEV (administered separately at 0.2 and 8 mg/kg, respectively). Blood samples were collected at different times post-treatment and LEV and MOX plasma concentrations were measured by HPLC. The clinical efficacy of the continuous use of MOX + LEV combination was assessed with the controlled efficacy test (CET), performed at the beginning and end of the study, and with the faecal egg count reduction (FECR) test, performed over the four-year study period. No significant adverse pharmacokinetic changes were observed either for MOX or LEV after their co-administration to infected lambs. The CET (first year) showed efficacies of 84.3 % (Haemonchus contortus), 100 % (Teladorsagia circumcincta and Trichostrongylus axei), and 97.4 % (T. colubriformis). After the repetitive use of the combined treatment for four years, those efficacies remained high (100 %) and only decreased to 58 % against T. colubriformis. The evaluation of the FECR over the study period showed fluctuations in the performance of the combined administration. The initial FECR (2014) was 99 % (MOX), 85 % (LEV) and 100 % (MOX + LEV). The co-administration of MOX + LEV during the four-year experimental period resulted in a significantly higher anthelmintic effect (87 %) than that of MOX (42 %) or LEV (69 %) given alone. The combined use of MOX + LEV to control resistant gastrointestinal nematodes appears to be a valid strategy under specific management conditions. A high initial therapeutic response to the combination would be a relevant feature for the success of this tool.