Not all severe malaria cases are severe: Is it time to redefine severity criteria for malaria in non-endemic regions?

BACKGROUND: The current definition of severe malaria in non-endemic areas follows WHO criteria, which mainly target children in malaria-endemic areas, potentially misclassifying cases in non-endemic regions. We assessed the performance of a modified severe malaria classification criteria within our patient cohort. METHODS: A cohort study of patients managed for malaria in a non-endemic setting (2005-2023) was analyzed. We classified patients into severe malaria (SM) using WHO 2013 criteria except for hyperparasitemia, where 2 % threshold was applied. Patients with SM were distinguished as very severe malaria (VSM) when presenting at least one of the following conditions: parasitemia >10 %, pulmonary edema, impaired consciousness, seizures, renal failure, metabolic acidosis or hyperlactatemia, shock or hypoglycemia. In patients with SM and no criteria for VSM, less severe malaria (LSM) was defined by: 2-10 % parasitemia, hyperbilirubinemia, prostration, anemia or minor bleeding. The primary composite outcome was death or the need for a life-saving intervention, as analyzed in the three comparative groups. Secondary outcome was the prevalence of co-infections. RESULTS: Among 506 patients with malaria, 176 (34.8 %) presented with SM. A total of 37 (7.3 %) patients developed a life-threatening condition, namely death (n = 4) and/or the need for life-saving interventions (n = 34). All fatalities and 33 out of the 34 life-saving interventions occurred in the VSM group. Patients in LSM group did not develop any life-threatening conditions. As to co-infections, 28 (5.5 %) patients had a community-acquired co-infection, with no differences between groups (p = 0.763). CONCLUSIONS: Severity criteria definitions would benefit from a review when assessing patients with malaria in non-endemic areas. Within the spectrum of SM, patients reclassified as LSM have a low risk of developing a life-threatening condition and present low co-infection incidence and could benefit from management out of intensive care units and a restrictive use of empirical antibiotics.

Host biomarkers for early identification of severe imported Plasmodium falciparum malaria.

BACKGROUND: Severe imported P. falciparum malaria is a source of morbi-mortality in non-endemic regions. WHO criteria don't accurately classify patients at risk of complications. There is a need to evaluate new tools such as biomarkers to better identify patients with severe imported malaria. METHODS: A case-control study was conducted in Barcelona, from January 2011-January 2021. Adult patients with microbiologically confirmed P. falciparum malaria were classified according to WHO criteria. Patients with imported non-malarial fevers were included as controls. In each group, angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), soluble triggering receptor expressed on myeloid cells (sTREM-1), C-reactive protein (CRP) and platelets were measured and their concentrations were compared between groups. New groups were made with a modified WHO severity classification and biomarkers' performance was evaluated using multiple imputation models. RESULTS: 131 participants were included: 52 severe malaria, 30 uncomplicated malaria and 49 non-malarial fever cases. All biomarkers except sTREM-1 showed significant differences between groups. Using the modified WHO severity classification, Ang-2 and CRP presented the best AUROC; 0.79 (95%CI 0.64-0.94) and 0.80(95%CI 0.67-0.93). A model combining CRP and Ang-2 showed the best AUROC, of 0.84(95%CI 0.68-0.99), with the highest sensitivity and specificity: 84.6%(95%CI 58.9-98.1) and 77.4% (95%CI 65.9-87.7), respectively. CONCLUSIONS: The combination of Ang-2 and CRP may be a reliable tool for the early identification of severe imported malaria. The use of a rapid prognostic test including the mentioned biomarkers could optimize imported malaria management, with the potential to decrease the rate of complications and hospitalizations in patients with imported malaria.

Cross-sectional and longitudinal relationships between cardiorespiratory fitness and health-related quality of life in primary school children in England: the mediating role of psychological correlates of physical activity.

AIMS: The aims were (1) to analyse the cross-sectional and longitudinal associations between children's cardiorespiratory fitness (CRF) and health-related quality of life (HRQoL) and (2) to examine whether these associations were mediated by physical activity self-efficacy and physical activity enjoyment. METHODS: This study involved 383 children (10.0 ± 0.5 years) recruited from 20 primary schools in northwest England. Data were collected on two occasions 12 weeks apart. The number of laps completed in the 20-m Shuttle Run Test was used as the CRF indicator. HRQoL was assessed using the KIDSCREEN-10 questionnaire. Physical activity self-efficacy and enjoyment were assessed with the social-cognitive and Physical Activity Enjoyment Scale questionnaires, respectively. Linear mixed models with random intercepts (schools) assessed associations between CRF and HRQoL cross-sectionally, and longitudinally. Boot-strapped mediation procedures were performed, and indirect effects (IE) with 95% confidence intervals (CI) not including zero considered as statistically significant. Analyses were adjusted for sex, time of the year, socioeconomic status, waist-to-height ratio, maturation, and physical activity. RESULTS: CRF was cross-sectionally associated with HRQoL (ß = 0.09, 95% CI = 0.02, 0.16; p = .015). In the longitudinal analysis, CRF at baseline was associated with HRQoL at 12 weeks after additionally controlling for baseline HRQoL (ß = 0.08, 95% CI = 0.002; p = .15, p = .045). Cross-sectionally, physical activity self-efficacy and enjoyment acted individually as mediators in the relationship between CRF and HRQoL (IE = 0.069, 95% CI = 0.038; p = .105 and IE = 0.045, 95% CI = 0.016; p = .080, respectively). In the longitudinal analysis, physical activity self-efficacy showed a significant mediating effect (IE = 0.025, 95% CI = 0.004; p = .054). CONCLUSION: Our findings highlight the influence of CRF on children's psychological correlates of physical activity and their overall HRQoL.

Improved diagnosis of gastrointestinal infections using a semi-automated multiplex real-time PCR for detection of enteropathogens.

Introduction. The identification of enteropathogens is critical for the clinical management of patients with suspected gastrointestinal infection. The FLOW multiplex PCR system (FMPS) is a semi-automated platform (FLOW System, Roche) for multiplex real-time PCR analysis.Hypothesis/Gap Statement. FMPS has greater sensitivity for the detection of enteric pathogens than standard methods such as culture, biochemical identification, immunochromatography or microscopic examination.Aim.The diagnostic performance of the FMPS was evaluated and compared to that of traditional microbiological procedures.Methodology. A total of 10 659 samples were collected and analysed over a period of 7 years. From 2013 to 2018 (every July to September), samples were processed using standard microbiological culture methods. In 2019, the FMPS was implemented using real-time PCR to detect the following enteropathogens: Shigella spp., Salmonella spp., Campylobacter spp., Giardia intestinalis, Entamoeba histolytica, Blastocystis hominis, Cryptosporidum spp., Dientamoeba fragilis, adenovirus, norovirus and rotavirus. Standard microbiological culture methods (2013-2018) included stool culture, microscopy and immunochromatography.Results. A total of 1078 stool samples were analysed prospectively using the FMPS from July to September (2019): bacterial, parasitic and viral pathogens were identified in 15.3, 9.71 and 5.29 % of cases, respectively. During the same period of 6 years (2013-2018), the proportion of positive identifications using standard microbiological methods from 2013 to 2018 was significantly lower. A major significant recovery improvement was observed for all bacteria species tested: Shigella spp./enteroinvasive Escherichia coli (EIEC) (P <0.05), Salmonella spp. (P <0.05) and Campylobacter spp. (P <0.05). Marked differences were also observed for the parasites G. intestinalis, Cryptosporidium spp. and D. fragilis.Conclusion. These results support the value of multiplex real-time PCR analysis for the detection of enteric pathogens in laboratory diagnosis with outstanding performance in identifying labile micro-organisms. The identification of unsuspected micro-organisms for less specific clinical presentations may also impact on clinical practice and help optimize patient management.

Dynamic expression of Ralstonia solanacearum virulence factors and metabolism-controlling genes during plant infection.

BACKGROUND: Ralstonia solanacearum is the causal agent of bacterial wilt, a devastating plant disease responsible for serious economic losses especially on potato, tomato, and other solanaceous plant species in temperate countries. In R. solanacearum, gene expression analysis has been key to unravel many virulence determinants as well as their regulatory networks. However, most of these assays have been performed using either bacteria grown in minimal medium or in planta, after symptom onset, which occurs at late stages of colonization. Thus, little is known about the genetic program that coordinates virulence gene expression and metabolic adaptation along the different stages of plant infection by R. solanacearum. RESULTS: We performed an RNA-sequencing analysis of the transcriptome of bacteria recovered from potato apoplast and from the xylem of asymptomatic or wilted potato plants, which correspond to three different conditions (Apoplast, Early and Late xylem). Our results show dynamic expression of metabolism-controlling genes and virulence factors during parasitic growth inside the plant. Flagellar motility genes were especially up-regulated in the apoplast and twitching motility genes showed a more sustained expression in planta regardless of the condition. Xylem-induced genes included virulence genes, such as the type III secretion system (T3SS) and most of its related effectors and nitrogen utilisation genes. The upstream regulators of the T3SS were exclusively up-regulated in the apoplast, preceding the induction of their downstream targets. Finally, a large subset of genes involved in central metabolism was exclusively down-regulated in the xylem at late infection stages. CONCLUSIONS: This is the first report describing R. solanacearum dynamic transcriptional changes within the plant during infection. Our data define four main genetic programmes that define gene pathogen physiology during plant colonisation. The described expression of virulence genes, which might reflect bacterial states in different infection stages, provides key information on the R. solanacearum potato infection process.

Effects of a Tapering Period on Physical Condition in Soccer Players.

Beltran-Valls, MR, Camarero-López, G, Beltran-Garrido, JV, and Cecilia-Gallego, P. Effects of a tapering period on physical condition in soccer players. J Strength Cond Res 34(4): 1086-1092, 2020-The aim of this research was to analyze the effects of a 2-week step tapering period on lower-limb muscle power, change of direction (COD) and acceleration capacities, and on the stress-recovery state in an amateur soccer team. Twenty-two male players were included in the study. After a 6-week progressive training, the sample was divided into experimental group (EG) (n = 11), which did a 2-week period of taper in which training volume was 50% reduced (intensity was kept high) and control group (CG) (n = 11), which kept on with the training. Muscle power (countermovement jump test), acceleration (10-m sprint test), COD (Illinois test), and stress and recovery perceptions (RESTQ questionnaire) were evaluated before training, at the end of it (pretapering, PRE-TP) and after the tapering period (posttapering, POST-TP). After the taper, the EG in comparison with the CG showed significantly improved power (1,029.71 ± 108.51 W·kg vs. 1,084.21 ± 110.87 W·kg; p ≤ 0.01), acceleration (1.72 ± 0.09 seconds vs. 1.67 ± 0.07 seconds; p ≤ 0.05), and lower stress levels (1.9 ± 0.5 vs. 1.6 ± 0.5; p ≤ 0.01) (PRE-TP vs. POST-TP, respectively). Change of direction did not show significant changes. In conclusion, a 2-week step tapering program was found to be an effective periodization strategy to increase muscle power and acceleration, and to reduce stress perception in soccer amateur players.

Prevalence and Factors Associated With Fatigue in Patients With Inflammatory Bowel Disease: A Multicentre Study.

BACKGROUND AND AIMS: The aims of this study were to determine the prevalence of fatigue in patients with inflammatory bowel disease [IBD], to identify the factors associated with fatigue and its severity, to assess the impact of fatigue on quality of life [QoL], and to evaluate the relationship between fatigue and sleep disorders. METHODS: This was a prospective multicentre study conducted at 22 Spanish centres. Consecutive patients followed at IBD Units were included. Fatigue was evaluated with the Fatigue Severity Scale [FSS] and the Fatigue Impact Scale [FIS]. Quality of life and sleep quality were assessed using the IBD Questionnaire-Short Form [IBDQ-9] and the Pittsburgh Sleep Quality Index [PSQI], respectively. RESULTS: A total of 544 consecutive adult IBD patients were included [50% women, mean age 44 years, 61% Crohn's disease]. The prevalence of fatigue was 41% (95% confidence interval [CI] = 37-45%). The variables associated with an increased risk of fatigue were: anxiety [OR = 2.5, 95% CI = 1.6-3.7], depression [OR = 2.4, 95% CI = 1.4-3.8], presence of extraintestinal manifestations [EIMs] [OR = 1.7, 95% CI = 1.1-2.6], and treatment with systemic steroids [OR = 2.8, 95% CI = 1.4-5.7]. The presence of EIMs [regression coefficient, RC = 8.2, 95% CI = 2.3-14.2], anxiety [RC = 25.8, 95% CI = 20.0-31.5], depression [RC = 30.6, 95% CI = 24.3-37.0], and sleep disturbances [RC = 15.0, 95% CI = 9.3-20.8] were associated with severity of fatigue. Patients with fatigue had a significantly decreased IBDQ-9 score [p < 0.001]. CONCLUSIONS: The prevalence of fatigue in IBD patients is remarkably high and has a negative impact on QoL. Therapy with systemic steroids is associated with an increased risk of fatigue. The severity of fatigue is associated with anxiety, depression, sleep disorders, and the presence of EIMs. Fatigue was not associated with anaemia, disease activity or anti-TNF therapy.

Association Between Objectively Measured Physical Activity and Plasma BDNF in Adolescents: DADOS Study.

Brain-derived neurotrophic factor (BDNF) is suggested to play a key role in moderating the benefits of physical activity (PA) on cognition. Previous research found that PA may have an impact on peripheral BDNF expression. The aim of our study was to analyze the association between objectively measured PA with circulating BDNF in a group of active adolescents. Two hundred thirty-four adolescents (132 boys) aged 13.9 ± 0.3 years old from the DADOS study were included in this cross-sectional analysis. PA was assessed by GENEActiv triaxial accelerometer. Participants wore the accelerometer on their non-dominant wrist for 6 consecutive 24-h days, including weekends. PA was expressed as the average (min/day) of light, moderate, and vigorous PA. Fasting plasma BDNF concentrations at rest were measured using an enzyme-linked immunosorbent assay. Partial correlations and linear regression analyses were performed with a significance level established at p < 0.05. No correlations were found between BDNF and PA variables. Plasma levels of BDNF at rest were not significantly associated with daily PA in either boys or girls (p > 0.05). Based on previous research and our own data, the association between daily PA and baseline levels of BDNF remains inconclusive. Further research is needed to shed light on the relationship between regular PA and BDNF in adolescents.

Adipokines, cytokines and body fat stores in hepatitis C virus liver steatosis.

AIM: To identify patients with or without liver steatosis and its severity in treatment-naïve patients affected by hepatitis C virus (HCV) infection. METHODS: We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body (by densitometry), hormones [insulin, homeostatic model assessment (HOMA)], adipokines (resistin, adiponectin, leptin), and cytokines (tumor necrosis factor α, interleukin-6). RESULTS: Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunk fat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. No differences were observed in leptin and resistin. CONCLUSION: Steatosis in HCV infection is common (67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines.

Long-lasting concentrations of cefovecin after subcutaneous and intramuscular administration to Patagonian sea lions (Otaria flavescens).

Cefovecin is a third-generation cephalosporin developed as an aqueous solution for use by the subcutaneous route in dogs and cats. This study evaluated the duration of cefovecin plasma concentrations after single intramuscular (IM) or subcutaneous (SC) injection at different doses in 10 Patagonian sea lions (Otaria flavescens). Blood samples were collected serially from the day of the injection up to 60-90 days post-injection. Plasma drug concentrations were determined by high performance liquid chromatography-UV detection and pharmacokinetic parameters were calculated by non-compartmental analysis. No reactions or side effects associated with the drug were observed in any of the studied animals. Both routes showed very similar pharmacokinetic behaviour. Elimination half-life (11.3-21.6 days, SC; 13.1-15.9 days, IM) and mean residence time (17.6-36.8 days SC; 16.5-25.4 days IM) were, in all cases and doses, considerably longer than those previously reported for any other species. Based on these findings, and preliminary data on specific pathogen sensitivity, cefovecin was found to be a very promising antimicrobial for Patagonian sea lions, in particular those that are difficult to access or that are under certain rehabilitation conditions.

Diet specialization in a generalist population: the case of breeding great tits Parus major in the Mediterranean area.

The analysis of diet specialization provides key information on how different individuals deal with similar food and habitat constraints within populations. Characterizing parental diet specialization at the moment of breeding, and the consistency of these preferences under different levels of effort, may help us to understand why parents exploit alternative resources. We investigated these questions in a species commonly considered a generalist: a breeding population of Mediterranean great tits Parus major. Our aim was to determine whether they are specialists or generalists at the pair level, and the consistency of this behaviour under different levels of effort. Using proportional similarity and mean pairwise overlap indices, we found that parents showed great variability in prey selection between territories. That is, they displayed a small niche overlap. Interestingly, the most specialized breeding pairs showed a tendency to have larger broods. Additionally, we experimentally manipulated brood size and found that parents showed high short-term consistency in their foraging behaviour. They precisely adjusted the number of provisioning trips to the number of nestlings, while they were unable to modify prey proportions or prey size after brood size was changed. We can therefore characterize their foraging strategies as highly consistent. Our results suggest that although the great tit may be considered a generalist at the species or population level, there was a tendency for trophic specialization among breeding pairs. This high inter- and intrapopulation plasticity could account for their great success and wide distribution.

[Acculturation orientations and psychosocial adaptation among adolescents with immigrant background]. / Orientations d'acculturation et adaptation psychosociale des adolescents issus de l'immigration.

OBJECTIVE: The aim of the study was to explore the typology of adolescents with immigrant background based on the orientations of acculturation and to estimate the psychosocial adaptation of the various subtypes. METHOD: A sample of 228 French high school students with an immigrant background completed a questionnaire assessing acculturation orientations (Immigrant Acculturation Scale; Barrette et al., 2004), antisocial behaviors, depressive symptoms and self-esteem. Cluster analysis based on acculturation orientations was performed using the k-means method. RESULTS: Cluster analysis produced four distinct acculturation profiles: bicultural (31%), separated (28%), marginalized (21%), and assimilated-individualistic (20%). Adolescents in the separated and marginalized clusters, both characterized by rejection of the host culture, reported higher levels of antisocial behavior. Depressive symptoms and self-esteem did not differ between clusters. DISCUSSION: Several hypotheses may explain the association between separation and delinquency. First, separation and rejection of the host culture may lead to rebellious behavior such as delinquency. Conversely, delinquent behavior may provoke rejection or discrimination by peers or school, or legal sanctions that induce a reciprocal process of rejection of the host culture and separation. The relationship between separation and antisocial behavior may be bidirectional, each one reinforcing the other, resulting in a negative spiral. This study confirms the interest of the study of the orientations of acculturation in the understanding of the antisocial behavior of adolescents with immigrant background.

[Cannabis use and antisocial behaviors in high-school students]. / Consommation de cannabis et comportements antisociaux dans un échantillon d'adolescents scolarisés.

OBJECTIVE: The aim of the study was to evaluate the contribution of cannabis to the prediction of delinquent behaviors. METHOD: Participants were 312 high-school students who completed self-report questionnaires measuring antisocial behaviors, the frequency of cannabis and alcohol use, psychopathic traits using the Youth Psychopathic traits Inventory, borderline traits, depressive symptoms, socio-economic status, life events, attachment to parents, and low academic achievement. Hierarchical multiple regression analyses were conducted to investigate the contribution of cannabis use and potential confounding variables to antisocial behaviors. RESULTS: Boys reported a greater number of delinquent behaviors than girls (10.2±9.2 vs. 5.4±5.3, t=9.2, P<0.001). Thirty-seven percent of boys and 24 % of girls reported having used cannabis at least once during the last six months (P<0.001). Among cannabis users, boys reported a greater frequency of use than girls: average use for boys was 2-3 times per month whereas average use for girls was once a month (3.4±2.3 vs. 2.6±2, t=2.9, P=0.004). Cannabis users reported a greater number of antisocial behaviors than non-users (13.2±9.9 vs. 6.1±6.3, t=13.6, P<0.001). Multiple regression analyses showed that cannabis use was a significant independent predictor of antisocial behaviors in both gender (ß=.35, P<.001 in boys, ß=.29, P<.001 in girls) after adjustment for alcohol use, psychopathological and sociofamilial variables. DISCUSSION: The unique and independent association between frequency of cannabis use and antisocial behaviors does not indicate the causal direction of the relationship. It may be that cannabis use induces antisocial behaviors by enhancing impulsivity or irritability or by the need for money to buy cannabis. Conversely, antisocial behaviors may lead to cannabis use either through becoming used to transgressions or through the influence of delinquent peers using cannabis. This link is probably bidirectional, cannabis use and antisocial behaviors influencing mutually in a negative interactive spiral. This association suggests that these two problems are to be jointly approached when treating adolescents using cannabis or having antisocial behaviors.

The plant metacaspase AtMC1 in pathogen-triggered programmed cell death and aging: functional linkage with autophagy.

Autophagy is a major nutrient recycling mechanism in plants. However, its functional connection with programmed cell death (PCD) is a topic of active debate and remains not well understood. Our previous studies established the plant metacaspase AtMC1 as a positive regulator of pathogen-triggered PCD. Here, we explored the linkage between plant autophagy and AtMC1 function in the context of pathogen-triggered PCD and aging. We observed that autophagy acts as a positive regulator of pathogen-triggered PCD in a parallel pathway to AtMC1. In addition, we unveiled an additional, pro-survival homeostatic function of AtMC1 in aging plants that acts in parallel to a similar pro-survival function of autophagy. This novel pro-survival role of AtMC1 may be functionally related to its prodomain-mediated aggregate localization and potential clearance, in agreement with recent findings using the single budding yeast metacaspase YCA1. We propose a unifying model whereby autophagy and AtMC1 are part of parallel pathways, both positively regulating HR cell death in young plants, when these functions are not masked by the cumulative stresses of aging, and negatively regulating senescence in older plants.

Serum sclerostin in hepatitis C virus infected patients.

BACKGROUND: Sclerostin inhibits osteoblast functions, differentiations, and survival rates. As an endogenous inhibitor of the Wnt/ß-catenin pathway, the sclerostin should be related to decreased bone masses, although several studies indicate opposite results. In addition, it may be related to insulin resistances and carbohydrate metabolisms, a relation shared with other markers of bone metabolisms, such as osteocalcin. Hepatitis C virus (HCV) infected patients may present osteoporosis, and frequently show liver steatosis, which is a consequence of insulin resistance. The behaviour of sclerostin in these patients is yet unknown. The aim of this work is to analyse the relationships between serum sclerostin and osteocalcin levels and bone mineral density (BMD), liver functions, the intensity of liver steatosis and biochemical markers of bone homeostasis and insulin resistance in HCV-infected patients. METHODS: Forty HCV patients with 20 years of age and gender-matching controls were included in this study and underwent bone densitometry. Serum sclerostin, osteocalcin, collagen telopeptide, adiponectin, leptin, insulin, resistin, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were determined. Liver fat was histomorphometrically assessed. RESULTS: Sclerostin levels were slightly higher in patients than in controls, and were directly related to BMD at different parts of the skeleton, also to the serum telopeptide, and to the liver steatosis and TNF-α. On the contrary, osteocalcin showed a significant direct relationship with serum adiponectin, and an inverse one with IL-6. CONCLUSIONS: Serum sclerostin levels were within the normal range in HCV patients, and correlated directly with BMD and serum telopeptide. In addition, the relationships of sclerostin and osteocalcin with variables associated with insulin resistance suggested the role of bones for intermediary metabolisms.