Novel Lactone-Based Insecticides and Drosophila suzukii Management: Synthesis, Potential Action Mechanisms and Selectivity for Non-Target Parasitoids.

Drosophila suzukii, an invasive insect pest, poses a significant threat to various fruit crops. The use of broad-spectrum insecticides to control this pest can reduce the effectiveness of biological control agents, such as the parasitoid Trichopria anastrephae. Here, we evaluated the toxicity of newly synthesized lactone derivatives on D. suzukii and their selectivity towards T. anastrephae. We used in silico approaches to identify potential targets from the most promising molecules in the D. suzukii nervous system and to understand potential differences in susceptibilities between D. suzukii and its parasitoid. Of the nine molecules tested, (rac)-8 and compound 4 demonstrated efficacy against the fly. Exposure to the estimated LC90 of (rac)-8 and compound 4 resulted in a mortality rate of less than 20% for T. anastrephae without impairing the parasitoid's functional parasitism. The in silico predictions suggest that (rac)-8 and compound 4 target gamma amino butyric acid (GABA) receptors and transient receptor potential (TRP) channels of D. suzukii. However, only the reduced interaction with TRP channels in T. anastrephae demonstrated a potential reason for the selectivity of these compounds on the parasitoid. Our findings suggest the potential for integrating (rac)-8 and compound 4 into D. suzukii management practices.

First study demonstrating speckle tracking echocardiography has prognostic value in patients with idiopathic inflammatory myopathies.

To measure left ventricular (LV) global longitudinal strain (GLS) using speckle tracking echocardiography in idiopathic inflammatory myopathy (IIM) patients and to determine whether the LV GLS predicts outcomes in those patients. Prospective study consisted of a cross-sectional phase with 61 IIM patients and 32 individuals without IIM and longitudinal phase, in which patients were divided into two subgroups: 26 with reduced LV GLS and 35 with normal LV GLS; patients were followed for a mean of 25 months, and the occurrence of cardiovascular events and criteria for IIM activity were compared. The mean LV GLS (18.5 ± 2.9% vs. 21.6 ± 2.5%; p < 0.001) and right ventricle free wall strain (21.9 ± 6.1% vs. 27.5 ± 4.7%; p < 0.001) were lower in patients than in controls. The mean N-terminal pro B-type natriuretic peptide level was higher in patients than in controls. There were no differences regarding other cardiac involvement. Anti-Jo1 antibody was associated with general electrocardiographic abnormality and LV diastolic dysfunction. The subgroup with reduced GLS progressed with higher mean creatine phosphokinase, myositis disease activity assessment visual analogue scales, the physician's and patient's visual analogue scales, the health assessment questionnaire, and a higher proportion of relapses than the subgroup with normal GLS. There was no difference between the subgroups regarding cardiovascular events. The LV GLS appears to be useful for evaluating patients with IIM. Abnormal values are associated with more frequent relapses and increased disease activity during follow-up.

ROSEWOOD: A Phase II Randomized Study of Zanubrutinib Plus Obinutuzumab Versus Obinutuzumab Monotherapy in Patients With Relapsed or Refractory Follicular Lymphoma.

PURPOSE: The combination of zanubrutinib plus obinutuzumab (ZO) was found to be well tolerated with an early signal of efficacy in a phase Ib study. ROSEWOOD is a phase II, randomized study that assessed the efficacy and safety of ZO versus obinutuzumab in patients with relapsed/refractory (R/R) follicular lymphoma (FL). METHODS: Patients with R/R FL who had received ≥2 lines of therapy, including an anti-CD20 antibody and an alkylating agent, were randomly assigned 2:1 to receive ZO or obinutuzumab (O). The primary end point was overall response rate (ORR) by independent central review (ICR). Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival, and safety. RESULTS: A total of 217 patients were randomized (ZO, 145; O, 72). Median study follow-up was 20.2 months. The study met its primary end point: ORR by ICR was 69% (ZO) versus 46% (O; P = .001). Complete response rate was 39% (ZO) versus 19% (O); 18-month DOR rate was 69% (ZO) versus 42% (O). Median PFS was 28.0 months (ZO) versus 10.4 months (O; hazard ratio, 0.50 [95% CI, 0.33 to 0.75]; P < .001). The most common adverse events with ZO were thrombocytopenia, neutropenia, diarrhea, and fatigue; incidences of atrial fibrillation and major hemorrhage were 3% and 1%, respectively. CONCLUSION: The combination of ZO met its primary end point of a superior ORR versus O, and demonstrated meaningful activity and a manageable safety profile in patients with R/R FL. ZO had a favorable benefit-risk profile compared with O, and represents a potential combination therapy for patients with R/R FL.

Improving Functional Abilities in Children and Adolescents with Autism Spectrum Disorder Using Non-Invasive REAC Neuro Psycho Physical Optimization Treatments: A PEDI-CAT Study.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that affects communication, social interaction, and behavior. Non-invasive neuromodulation techniques, such as radioelectric asymmetric conveyer (REAC) technology, have gained attention for their potential to improve the endogenous bioelectric activity (EBA) and neurobiological processes underlying ASD. Neuro Postural Optimization (NPO) and Neuro Psycho Physical Optimization (NPPO) treatments are non-invasive and painless neuromodulation treatments that utilize REAC technology and have shown promising results in improving the symptoms of ASD. This study aimed to evaluate the effects of NPO and NPPO treatments on functional abilities in children and adolescents with ASD using the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT). The study consisted of 27 children and adolescents with ASD who underwent a single session of NPO followed by 18 sessions of NPPO treatment over a period of one week. The results showed significant improvements in the children's and adolescents' functional abilities across all domains of the PEDI-CAT. These findings suggest that NPO and NPPO may be effective treatments for improving functional abilities in children and adolescents with ASD.

Front-line fludarabine-cyclophosphamide-rituximab (FCR) in 110 patients with chronic lymphocytic leukaemia (CLL): real-life experience with long-term outcomes, toxicities and responses to second-line therapies.

Fludarabine-cyclophosphamide-rituximab (FCR) has been the gold standard front-line treatment for fit CLL patients until novel agent's introduction. Decision between either time-limited FCR or "endless" Bruton's tyrosine kinase inhibitor (BTKi) therapy may be difficult in fit IGHV-mutated-non-TP53 cases. We describe the outcomes after front-line FCR in 110 CLL patients from 5 centres in Catalonia, Spain, over a period of more than 10 years. ORR was 96.3% and CR 74.5%. Median second-treatment free survival (TFS1) was 6.2 years and median OS was 10.8 years. 50 (45.5%) patients required a subsequent therapy. Median third-treatment free survival was better for BTKi than for chemotherapy ± antiCD20 strategies (not reached vs 3.1 years, p = 0.003). Only 50 (45.5%) patients completed 6 cycles of FCR, and the main reason for discontinuation was cytopenia 29 (26.4%). 15 (13.6%) patients developed a second cancer, and 5 (4.5%) patients experienced a Richter's transformation (RT). At the end of follow-up, 50 (45.5%) patients remained in CR. Response rates, TFS1, OS, RT, and second cancers did not differ between patients treated with 6 vs 4 cycles of FCR. In conclusion, front-line FCR treatment leads to very long CR in almost half of patients, and BTKi yields excellent outcomes in relapsed patients.

Efficacy of Hip Strengthening on Pain Intensity, Disability, and Strength in Musculoskeletal Conditions of the Trunk and Lower Limbs: A Systematic Review with Meta-Analysis and Grade Recommendations.

To investigate the efficacy of hip strengthening on pain, disability, and hip abductor strength in musculoskeletal conditions of the trunk and lower limbs, we searched eight databases for randomized controlled trials up to 8 March 2022 with no date or language restrictions. Random-effect models estimated mean differences (MDs) with 95% confidence intervals (CIs), and the quality of evidence was assessed using the GRADE approach. Very low quality evidence suggested short-term effects (≤3 months) of hip strengthening on pain intensity (MD of 4.1, 95% CI: 2.1 to 6.2; two trials, n = 48 participants) and on hip strength (MD = 3.9 N, 95% CI: 2.8 to 5.1; two trials, n = 48 participants) in patellofemoral pain when compared with no intervention. Uncertain evidence suggested that hip strengthening enhances the short-term effect of the other active interventions on pain intensity and disability in low back pain (MD = -0.6 points, 95% CI: 0.1 to 1.2; five trials, n = 349 participants; MD = 6.2 points, 95% CI: 2.6 to 9.8; six trials, n = 389 participants, respectively). Scarce evidence does not provide reliable evidence of the efficacy of hip strengthening in musculoskeletal conditions of the trunk and lower limbs.

Impact of Gravity Compensation on Upper Extremity Movements in Harmony Exoskeleton.

Robots have been used to offset the limb weight through gravity compensation in upper body rehabilitation to delineate the effects of loss of strength and loss of dexterity, which are two common forms of post-stroke impairments. In this paper, we explored the impact of this anti-gravity support on the quality of movement during reaching and coordinated arm movements in a pilot study with two participants with chronic stroke. The subjects donned the Harmony exoskeleton which supported proper shoulder coordination in addition to providing gravity compensation. Participants had previously taken part in seven one-hour sessions with the Harmony exoskeleton, performing six sets of passive-stretching and active exercises. Pre- and post-training sessions included assessments of two separate tasks, planar reaching and a set of six coordinated arm movements, in two conditions, outside of and supported by the exoskeleton. The movements were recorded using an optical motion capture system and analyzed using spectral arc length (SPARC) and straight line deviation to quantify movement smoothness and quality. We observed that gravity compensation resulted in an increased smoothness for the subject with high level of impairment whereas compensation resulted in a reduction in smoothness for the subject with low level of impairment in the reaching task. Both participants demonstrated better coordination of the shoulder-arm joint with gravity compensation. This result motivates further studies into the role of gravity compensation during coordinated movement training and rehabilitation interventions.

Potential Action Mechanism and Inhibition Efficacy of Morinda citrifolia Essential Oil and Octanoic Acid against Stagonosporopsis cucurbitacearum Infestations.

The use of plant-based products has been shown to efficiently inhibit fungi-mediated diseases in agricultural crops. Here, we extracted and evaluated the composition of noni, Morinda citrifolia L., essential oil and assessed its activities against Stagonosporopsis cucurbitacearum in Cucumis melo L. Using in silico molecular approaches, potential interactions between the essential oil major components and S. cucurbitacearum tyrosine-tRNA ligase were predicted. Finally, we also measured the potential interference of plant physiology (the stomatal conductance and net photosynthesis) mediated by the application of the M. citrifolia essential oil. Chromatographic analysis revealed that octanoic acid (75.8%), hexanoic acid (12.8%), and isobutyl pent-4-enyl carbonate (3.1%) were the major essential oil compounds. Octanoic acid and noni essential oil, when used as preventive measures, reduce fungal mycelial growth at a concentration of 5 mg/mL without causing significant damage to the treated leaves, which reinforces their efficacies as preventive tools against S. cucurbitacearum. Molecular docking analyses predicted very stable interactions between the major essential oil constituents and S. cucurbitacearum tyrosine-tRNA ligase, suggesting the interference of these plant-based molecules upon enzyme activation. Octanoic acid and M. citrifolia essential oil at concentrations of 20 mg/mL decreased the stomatal conductance and net photosynthesis rate of melon plants, resulting in robust phytotoxicity. Collectively, our findings indicated that despite the phytotoxicity risks at higher concentrations, M. citrifolia essential oil and octanoic acid, have potential as alternative tools for the integrative management of S. cucurbitacearum.

Bacterial Co-Infection in Patients with COVID-19 Hospitalized (ICU and Not ICU): Review and Meta-Analysis.

The prevalence of patients hospitalized in ICUs with COVID-19 and co-infected by pathogenic bacteria is relevant in this study, considering the integrality of treatment. This systematic review assesses the prevalence of co-infection in patients admitted to ICUs with SARS-CoV-2 infection, using the PRISMA guidelines. We examined the results of the PubMed, Embase, and SciELO databases, searching for published English literature from December 2019 to December 2021. A total of 542 rec ords were identified, but only 38 were eligible and, and of these only 10 were included. The tabulated studies represented a sample group of 1394 co-infected patients. In total, 35%/138 of the patients were co-infected with Enterobacter spp., 27% (17/63) were co-infected with methicillin-sensitive Staphylococ cus aureus, 21% (84/404) were co-infected with Klebsiella spp., 16% (47/678) of patients were co-infected with coagulase-negative Staphylococcus, 13% (10/80) co-infected with Escherichia coli (ESBL), and 3% (30/1030) of patients were co-infected with Pseudomonas aeruginosa. The most common co-infections were related to blood flow; although in the urinary and respiratory tracts of patients Streptococcus pneumoniae was found in 57% (12/21) of patients, coagulase negative Staphylococcus in 44% (7/16) of patients, and Escherichia coli was found in 37% (11/29) of patients. The present research demonstrated that co-infections caused by bacteria in patients with COVID-19 are a concern.

Expression, purification and characterization of the transcription termination factor Rho from Azospirillum brasilense.

The Transcription Termination factor Rho is a ring-shaped, homohexameric protein that causes transcript termination by interaction with specific sites on nascent mRNAs. The process of transcription termination is essential for proper expression and regulation of bacterial genes. Although Rho has been extensively studied in the model bacteria Escherichia coli (EcRho), the properties of other Rho orthologues in other bacteria are poorly characterized. Here we present the heterologous expression and purification of untagged Rho protein from the diazotrophic environmental bacterium Azospirillum brasilense (AbRho). The AbRho protein was purified to >99% through a simple, reproducible and efficient purification protocol, a two-step chromatography procedure (affinity/gel filtration). By using analytical gel filtration and dynamic light scattering (DLS), we found that AbRho is arranged as an homohexamer as observed in the EcRho orthologue. Secondary structure and enzyme activity of AbRho was also evaluate indicating a properly folded and active protein after purification. Enzymatic assays indicate that AbRho is a RNA-dependent NTPase enzyme.

Impact of Two Whole-Body Vibration Exercise Protocols on Body Composition of Patients with Metabolic Syndrome: A Randomized Controlled Trial.

(1) Background: This study investigated the effects of two 6-week whole-body vibration exercise (WBVE) protocols on body composition in patients with metabolic syndrome (MSy). Thirty-three patients were allocated to either the Fixed Frequency WBVE Group (FFG-WBVE) or the Variable Frequency WBVE Group (VFG-WBVE). (2) Methods: A side-alternating vibration platform was used and the patients remained in the semi-squat position on this platform. In the FFG-WBVE (n = 12; median age = 50.50 years) and (body mass index BMI = 31.95 kg/m2), patients were exposed to 10 s of mechanical vibration at a fixed frequency of 5 Hz, followed by 50 s without vibration. In the VFG-WBVE (n = 10; median age = 57.50 years) and (BMI = 32.50 kg/m2), the patients performed 60 s of mechanical vibration at different frequencies from 5 to 16 Hz). Body composition evaluated through (bioelectrical impedance analysis and anthropometric measurements) were was evaluated before and after the all the interventions in each group. (3) Results: The VFG-WBVE decreased waist circumference, p = 0.01 and segmental fat mass [left arm, p = 0.01; right arm, p = 0.02 and trunk, p = 0.03]. Bone content increased, p = 0.01. No significant changes were observed in the FFG- WBVE. (4) Conclusions: In conclusion, this study demonstrated that 6 weeks of WBVE with a protocol with variable frequency can positively modify the body composition of MSY patients. These findings might contribute to improvements in the metabolic health of these patients.

Efficacy of Whole-Body Vibration Training on Brain-Derived Neurotrophic Factor, Clinical and Functional Outcomes, and Quality of Life in Women with Fibromyalgia Syndrome: A Randomized Controlled Trial.

This study aimed to investigate the efficacy of whole-body vibration training (WBVT) on blood brain-derived neurotrophic factor (BDNF) levels and determine the clinical and functional outcomes in patients with fibromyalgia syndrome (FMS). Thirty-two women with FMS were randomized into an intervention group (IG), receiving 6 weeks of WBVT, or a control group (CG) with no intervention. The outcomes at the baseline and follow-up in both groups included blood BDNF levels, sit-to-stand test (STS), 6-minute walk test (6MWT), Fibromyalgia Impact Questionnaire (FIQ), Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), and visual analogue scale (VAS). WBVT resulted in a group-by-time interaction effect. Thus, after the intervention time, the IG had increased blood BDNF levels (p=0.045), a higher number of repetitions on the STS test (p=0.011), and increased walking distance on the 6MWT (p=0.010), compared to CG. Moreover, there was a reduction in the scores of the FIQ (p=0.001), the PSQI (p=0.001), the BDI (p=0.017), and pain assessed using VAS (p=0.008) in IG. The results demonstrate that WBVT promotes an increase in blood BDNF levels, with concomitant improvement in lower limb muscle strength, aerobic capacity, clinical symptoms, and quality of life in women with FMS. This trial is registered with Brazilian Clinical Trials Registry (REBEC; RBR-38nbbx) (https://ensaiosclinicos.gov.br/rg/RBR-38nbbx).

Mussel-Inspired Catechol Functionalisation as a Strategy to Enhance Biomaterial Adhesion: A Systematic Review.

Biomaterials have long been explored in regenerative medicine strategies for the repair or replacement of damaged organs and tissues, due to their biocompatibility, versatile physicochemical properties and tuneable mechanical cues capable of matching those of native tissues. However, poor adhesion under wet conditions (such as those found in tissues) has thus far limited their wider application. Indeed, despite its favourable physicochemical properties, facile gelation and biocompatibility, gellan gum (GG)-based hydrogels lack the tissue adhesiveness required for effective clinical use. Aiming at assessing whether substitution of GG by dopamine (DA) could be a suitable approach to overcome this problem, database searches were conducted on PubMed® and Embase® up to 2 March 2021, for studies using biomaterials covalently modified with a catechol-containing substituent conferring improved adhesion properties. In this regard, a total of 47 reports (out of 700 manuscripts, ~6.7%) were found to comply with the search/selection criteria, the majority of which (34/47, ~72%) were describing the modification of natural polymers, such as chitosan (11/47, ~23%) and hyaluronic acid (6/47, ~13%); conjugation of dopamine (as catechol "donor") via carbodiimide coupling chemistry was also predominant. Importantly, modification with DA did not impact the biocompatibility and mechanical properties of the biomaterials and resulting hydrogels. Overall, there is ample evidence in the literature that the bioinspired substitution of polymers of natural and synthetic origin by DA or other catechol moieties greatly improves adhesion to biological tissues (and other inorganic surfaces).

A novel miniaturized electroanalytical device integrated with gas extraction for the voltammetric determination of sulfite in beverages.

Voltammetry and amperometry are inexpensive and high-performance analytical techniques. However, their lack of selectivity limits their use in complex matrices such as biological, environmental, and food samples. Therefore, voltammetric and amperometric analyses of these samples usually require time-consuming and laborious sample pretreatments. In this study, we present a simple and cost-effective approach to fabricate a miniaturized electrochemical cell that can be easily coupled to a head space-like gas extraction procedure in such a way the sample pretreatment and voltammetric detection are performed in a single step. As a proof of concept, we have used the proposed system to quantify sulfite in beverage samples after its conversion to SO2(g). Despite the simplicity and low cost of the proposed system, it provided good analytical performance and a limit of detection of 4.0 µmol L-1 was achieved after only 10 min of extraction. The proposed system is quite versatile since it can be applied to quantify any volatile electroactive species. Also, the proposed system provides a unique way to assess real-time extraction curves, which are essential to study and optimize new gas extraction procedures. Therefore, the approach described in this study could contribute to both applied and fundamental Analytical Chemistry.

Hemotropic Mycoplasma and Bartonella Species Diversity in Free-Roaming Canine and Feline from Luanda, Angola.

Free-roaming dogs and cats represent potential reservoirs for zoonotic vector-borne pathogens shedding to the human population. Given the health impact of these pathogens, we searched free-roaming dogs and cats included in an animal population control program from Luanda, Angola, for Bartonella and hemotropic mycoplasma infection. We report the detection of Bartonella henselae (2/66; 3%), Candidatus Mycoplasma haemominutum (5/66; 7.5%) and Mycoplasma haemofelis (1/66; 1.5%) in cats. One dog was found positive for Mycoplasma haemocanis (1/20; 5%). This is the first report of Bartonella henselae infections in stray cats and of hemotropic mycoplasmas in cats and dogs from Angola. Despite the relatively small sample size, our results sustain the hypothesis of uncontrolled circulation of these agents in highly mobile synanthropic animal populations of Luanda. Population and vector control could contribute to reducing the likelihood for animal-to-animal and animal-to-human transmission.

Assessment of Upper-Extremity Joint Angles Using Harmony Exoskeleton.

The biomechanical complexity of the human shoulder, while critical for functionality, poses a challenge for objective assessment during sensorimotor rehabilitation. With built-in sensing capabilities, robotic exoskeletons have the potential to serve as tools for both intervention and assessment. The bilateral upper-extremity Harmony exoskeleton is capable of full shoulder articulation, forearm flexion-extension, and wrist pronation-supination motions. The goal of this paper is to characterize Harmony's anatomical joint angle tracking accuracy towards its use as an assessment tool. We evaluated the agreement between anatomical joint angles estimated from the robot's sensor data and optical motion capture markers attached to the human user. In 9 healthy participants we examined 6 upper-extremity joint angles, including shoulder girdle angles, across 4 different motions, varying active/passive motion of the user and physical constraint of the trunk. We observed mostly good to excellent levels of agreement between measurement systems with for shoulder and distal joints, magnitudes of average discrepancies varying from 0.43° to 16.03° and width of LoAs ranging between 9.44° and 41.91°. Slopes were between 1.03 and 1.43 with r > 0.9 for shoulder and distal joints. Regression analysis suggested that discrepancies observed between measured robot and human motions were primarily due to relative motion associated with soft tissue deformation. The results suggest that the Harmony exoskeleton is capable of providing accurate measurements of arm and shoulder joint kinematics. These findings may lead to robot-assisted assessment and intervention of one of the most complex joint structures in the human body.

Exposure to tricyclic antidepressant nortriptyline affects early-life stages of zebrafish (Danio rerio).

Psychiatric drugs are among the leading medications prescribed for humans, with their presence in aquatic environments raising concerns relating to potentially harmful effects on non-target organisms. Nortriptyline (NTP) is a selective serotonin-norepinephrine reuptake inhibitor antidepressant, widely used in clinics and found in environmental water matrices. In this study, we evaluated the toxic effects of NTP on zebrafish (Danio rerio) embryos and early larval stages. Developmental and mortality analyses were performed on zebrafish exposed to NTP for 168 h at concentrations ranging from 500 to 46,900 µg/L. Locomotor behaviour and acetylcholinesterase (AChE) activity were evaluated by exposing embryos/larvae to lower NTP concentrations (0.006-500 µg/L). The median lethal NTP concentration after 168 h exposure was 2190 µg/L. Although we did not identify significant developmental changes in the treated groups, lack of equilibrium was already visible in surviving larvae exposed to ≥ 500 µg/L NTP. The behavioural analyses showed that NTP was capable of modifying zebrafish larvae swimming behaviour, even at extremely low (0.006 and 0.088 µg/L) environmentally relevant concentrations. We consistently observed a significant reduction in AChE activity in the animals exposed to 500 µg/L NTP. Our results highlight acute toxic effects of NTP on the early-life stages of zebrafish. Most importantly, exposure to environmentally relevant NTP concentrations may affect zebrafish larvae locomotor behaviour, which in turn could reduce the fitness of the species. More studies involving chronic exposure and sensitive endpoints are warranted to better understand the effect of NTP in a more realistic exposure scenario.

Malaria-induced Alterations of Drug Kinetics and Metabolism in Rodents and Humans.

BACKGROUND: Infections and inflammation lead to a downregulation of drug metabolism and kinetics in experimental animals. These changes in the expression and activities of drug-metabolizing enzymes may affect the effectiveness and safety of pharmacotherapy of infections and inflammatory conditions. OBJECTIVE: In this review, we addressed the available evidence on the effects of malaria on drug metabolism activity and kinetics in rodents and humans. RESULTS: An extensive literature review indicated that infection by Plasmodium spp consistently decreased the activity of hepatic Cytochrome P450s and phase-2 enzymes as well as the clearance of a variety of drugs in mice (lethal and non-lethal) and rat models of malaria. Malaria-induced CYP2A5 activity in the mouse liver was an exception. Except for paracetamol, pharmacokinetic trials in patients during acute malaria and in convalescence corroborated rodent findings. Trials showed that, in acute malaria, clearance of quinine, primaquine, caffeine, metoprolol, omeprazole, and antipyrine is slower and that AUCs are greater than in convalescent individuals. CONCLUSION: Notwithstanding the differences between rodent models and human malaria, studies in P. falciparum and P. vivax patients confirmed rodent data showing that CYP-mediated clearance of antimalarials and other drugs is depressed during the symptomatic disease when rises in levels of acute-phase proteins and inflammatory cytokines occur. Evidence suggests that inflammatory cytokines and the interplay between malaria-activated NF-kB-signaling and cell pathways controlling phase 1/2 enzyme genes transcription mediate drug metabolism changes. The malaria-induced decrease in drug clearance may exacerbate drug-drug interactions, and the occurrence of adverse drug events, particularly when patients are treated with narrow-margin-of-safety medicines.

Ontogenetic change in the diet of Semaprochilodus insignis (Characiformes: Prochilodontidae) during migration between two limnologically distinct environments in the Amazon Basin

Semaprochilodus insignis is an Amazonian migratory fish species, moving in large shoals between white- and black-water rivers. It has long been classified as a detritivorous fish. However, it is possible that the trophic plasticity of S. insignis could be higher than previously assumed. The objective of this study was to investigate the relative contributions of autotrophic energy sources to the diet of S. insignis in the Negro and Solimões rivers and to determine if the species undergoes an ontogenetic change in the diet. We found variations between the δ13C and δ15N values of S. insignis between the rivers. In the Negro River, periphyton (84%) was the principal energy source for adults, while juveniles in the Solimões River foraged predominantly on terrestrial plants/C3 macrophytes (50%) and phytoplankton (42%). These variations in isotopic signatures are likely associated with migratory movements of S. insignis at different life stages and hydrological periods. Instead of the previously assumed dietary classification, we suggest that S. insignis varies its diet ontogenetically, with adults acting as illiophagous in black-water while the young are detritivorous in white-water rivers. The results show that this species creates complex links between food chains, thus emphasizing the importance of conserving flooded areas.(AU)

Semaprochilodus insignis é uma espécie de peixe migratório da Amazônia, movendo-se em cardumes entre rios de água branca e preta. Tem sido classificado como um peixe detritívoro-iliófago. Porém, é possível que a plasticidade trófica de S. insignis seja maior do que se supunha. O objetivo deste estudo foi investigar as contribuições relativas de fontes de energia autotróficas para a dieta do S. insignis nos rios Negro e Solimões e se a espécie muda ontogenticamente a sua dieta. Encontramos variações entre os valores de δ13C e δ15N de S. insignis entre os rios: Negro, o perifíton (84%) foi a principal fonte de energia para adultos, enquanto para os juvenis do rio Solimões, foram predominantemente as plantas terrestres/macrófitas C3 (50%) e fitoplâncton (42%). Essas variações nas assinaturas isotópicas provavelmente estão associadas a movimentos migratórios do S. insignis em diferentes estágios da vida e períodos hidrológicos. Ao invés da classificação alimentar previamente assumida, sugerimos que o S. insignis varie sua dieta ontogeneticamente, os adultos são iliófagos em águas negras, enquanto os jovens são detritívoros em rios de águas brancas. Os resultados demonstram que essa espécie promove ligações complexas entre as cadeias alimentares enfatizando, dessa forma, a importância da conservação das áreas inundadas amazônicas.(AU)