A callosal biomarker of behavioral intervention outcomes for autism spectrum disorder? A case-control feasibility study with diffusion tensor imaging

Tentative results from feasibility analyses are critical for planning future randomized control trials (RCTs) in the emerging field of neural biomarkers of behavioral interventions. The current feasibility study used MRI-derived diffusion imaging data to investigate whether it would be possible to identify neural biomarkers of a behavioral intervention among people diagnosed with autism spectrum disorder (ASD). The corpus callosum has been linked to cognitive processing and callosal abnormalities have been previously found in people diagnosed with ASD. We used a case-control design to evaluate the association between the type of intervention people diagnosed with ASD had previously received and their current white matter integrity in the corpus callosum. Twenty-six children and adolescents with ASD, with and without a history of parent-managed behavioral intervention, underwent an MRI scan with a diffusion data acquisition sequence. We conducted tract-based spatial statistics and a region of interest analysis. The fractional anisotropy values (believed to indicate white matter integrity) in the posterior corpus callosum was significantly different across cases (exposed to parent-managed behavioral intervention) and controls (not exposed to parent-managed behavioral intervention). The effect was modulated by the intensity of the behavioral intervention according to a dose-response relationship. The current feasibility case-control study provides the basis for estimating the statistical power required for future RCTs in this field. In addition, the study demonstrated the effectiveness of purposely-developed motion control protocols and helped to identify regions of interest candidates. Potential clinical applications of diffusion tensor imaging in the evaluation of treatment outcomes in ASD are discussed

A callosal biomarker of behavioral intervention outcomes for autism spectrum disorder? A case-control feasibility study with diffusion tensor imaging

Tentative results from feasibility analyses are critical for planning future randomized control trials (RCTs) in the emerging field of neural biomarkers of behavioral interventions. The cur rent feasibility study used MRI-derived diffusion imaging data to investigate whether it would be possible to identify neural biomarkers of a behavioral intervention among people diag nosed with autism spectrum disorder (ASD). The corpus callosum has been linked to cogni tive processing and callosal abnormalities have been previously found in people diagnosed with ASD. We used a case-control design to evaluate the association between the type of intervention people diagnosed with ASD had previously received and their current white matter integrity in the corpus callosum. Twenty-six children and adolescents with ASD, with and without a history of parent-managed behavioral intervention, underwent an MRI scan with a diffusion data acquisition sequence. We conducted tract-based spatial statistics and a region of interest analysis. The fractional anisotropy values (believed to indicate white mat ter integrity) in the posterior corpus callosum was significantly different across cases (exposed to parent-managed behavioral intervention) and controls (not exposed to parent managed behavioral intervention). The effect was modulated by the intensity of the behav ioral intervention according to a dose-response relationship. The current feasibility case control study provides the basis for estimating the statistical power required for future RCTs in this field. In addition, the study demonstrated the effectiveness of purposely-developed motion control protocols and helped to identify regions of interest candidates. Potential clini cal applications of diffusion tensor imaging in the evaluation of treatment outcomes in ASD are discussedThis study was supported by grants from Oakley Mental Health Foundation (project no. 3705925), The University of Auckland (Marsden Fund Near Miss Support Program), and through a research contract between ABA España and The University of Auckland (project no. CON02739); all awarded to JV

Loss of myocardial LIF receptor in experimental heart failure reduces cardiotrophin-1 cytoprotection. A role for neurohumoral agonists?

OBJECTIVES: Cardiomyocyte loss is involved in the transition from compensatory left ventricular hypertrophy (LVH) to heart failure (HF). Our aim was to investigate the status of the leukaemia inhibitory factor receptor (LIFR)/gp130 survival pathway and its cytoprotective activity in intact cardiac tissue and in cardiomyocytes obtained from adult spontaneously hypertensive rats (SHR) with LVH (non-failing SHR) and from aged SHR with overt HF (failing SHR). METHODS: Cardiac morphometry was assayed by planimetry in an image analysis system. mRNA and protein expression were quantified by real time RT-PCR and Western blotting. Receptors were localized by immunocytochemistry. Trypan blue staining, TUNEL, and MTT cell viability assays were employed to study the cytoprotective activity of cardiotrophin-1 (CT-1) in isolated caridomyocytes. RESULTS: Compared to non-failing SHR, failing SHR exhibited enhanced myocardial cell death (p<0.01) demonstrated by the increase in Bax/Bcl-2 ratio, caspase-3 activation and poly (ADP-ribose) polymerase (PARP) fragmentation. Failing SHR had a 7-fold diminished expression (p<0.01) of LIFR, no changes in gp130, and 1.6-fold increased myocardial expression (p<0.01) of CT-1. In cardiomyocytes isolated from non-failing SHR, recombinant CT-1 inhibited apoptotic and non-apoptotic cell death induced by angiotensin II or hydrogen peroxide. LIFR protein was entirely absent in cardiomyocytes isolated from failing SHR, which were resistant to the cytoprotective effects of CT-1. Finally, stimulation of non-failing SHR cardiomyocytes with angiotensin II, aldosterone, norepinephrine or endothelin-1 significantly decreased (p<0.01) LIFR expression. CONCLUSIONS: These data suggest that loss of CT-1-dependent survival mechanisms may contribute to the increase of cell death associated with HF in SHR. Neurohumoral activation may contribute to this alteration via suppression of LIFR

Extended-Spectrum β-Lactam Resistant Klebsiella pneumoniae and Escherichia coli in Wild European Hedgehogs (Erinaceus europeus) Living in Populated Areas

Wildlife has been suggested to be a good sentinel of environmental health because of its close interaction with human populations, domestic animals, and natural ecosystems. The alarming emergence of antimicrobial resistance (AMR) in human and veterinary medicine has activated/triggered the awareness of monitoring the levels of AMR pollution in wildlife. European hedgehogs (Erinaceus europaeus) are common wild species habiting urban areas in Europe. However, there are few studies conducted in hedgehogs as reservoirs of AMR bacteria or genes. The aim of this study was to assess the occurrence and distribution of ESBL, AmpC, and carbapenem-resistant enterobacteria and AMR genes in wild European hedgehogs in Catalonia, a densely populated region of NE Spain. A total of 115 hedgehogs admitted at the Wildlife Rehabilitation Center of Torreferrussa were studied. To our knowledge, this is the first description of β-lactam resistant enterobacteria in wild hedgehogs. Interestingly, 36.8% (42/114) of the animals were detected as carriers of β-lactamase/carbapenemase resistance genes. Klebsiella spp. (59.6%), and specifically K. pneumoniae (84.6%), were the bacteria with the highest proportion of resistance genes, followed by E. coli (34.6%) and C. freundii (5.8%). The most frequently detected genetic variants were blaCTX-M-15 (19.3%), blaSHV-28 (10.5%), blaCMY-1 (9.7%), blaCMY-2 (8.8%), and blaOXA-48 (1.7%). In addition, 52% (27/52) of the isolates presented a multidrug resistance (MDR) phenotype and 31% had an extended drug resistance (XDR) profile. No clustering of animals with AMR genes within the study region was shown in the spatial analysis, nor differences in the proportion of positive animals among Animals 2021, 11, 2837. https://doi.org/10.3390/ani11102837 https://www.mdpi.com/journal/animals Animals 2021, 11, 2837 2 of 13 regions, were detected. The results of this study suggest that wild European hedgehogs could be good sentinels of AMR environmental pollution, especially in areas with a high human population density, because they either inhabit and/or feed in an anthropogenic environment. In conclusion, it is crucial to raise awareness of the strong interconnection between habitats and compartments, and therefore this implies that AMR issues must be tackled under the One Health approachinfo:eu-repo/semantics/publishedVersio

Biochemical Diagnosis of Hypertensive Myocardial Fibrosis

A substantial increase in fibrillar collagen has been observed in the left cardiac ventricle of animals and humans with arterial hypertension. Hypertensive myocardial fibrosis is the result of both increased collagen types I and III due to the fact that its synthesis by fibroblasts and myofibroblasts is stimulated and its extracellular collagen degradation unchanged or decreased extracellular collagen degradation. Hemodynamic and non-hemodynamic factors may be involved in the disequilibrium between collagen synthesis and degradation that occurs in hypertension. As shown experimentally and clinically, an exaggerated rise in fibrilar collagen content promotes abnormalities of cardiac function, contributes to the decrease in coronary reserve and facilitates alterations in the electrical activity of the left ventricle. Although microscopic examination of cardiac biopsies is the most reliable method for documenting and measuring myocardial fibrosis, the development of non-invasive methods to indicate the presence of myocardial fibrosis in hypertensive patients would be useful. We have therefore applied a biochemical method based on the measurement of serum peptides derived from the tissue formation when synthesized and degradation of fibrillar collagens to monitor the turnover of these molecules in rats with spontaneous hypertension and patients with essential hypertension

The Influence of Coronary Artery Disease in the Development of Aortic Stenosis and the Importance of the Albumin Redox State.

Calcific aortic valve and coronary artery diseases are related cardiovascular pathologies in which common processes lead to the calcification of the corresponding affected tissue. Among the mechanisms involved in calcification, the oxidative stress that drives the oxidation of sulfur-containing amino acids such ascysteines is of particular interest. However, there are important differences between calcific aortic valve disease and coronary artery disease, particularly in terms of the reactive oxygen substances and enzymes involved. To evaluate what effect coronary artery disease has on aortic valves, we analyzed valve tissue from patients with severe calcific aortic stenosis with and without coronary artery disease. Proteins and peptides with oxidized cysteines sites were quantified, leading to the identification of 16 proteins with different levels of expression between the two conditions studied, as well as differences in the redox state of the tissue. We also identified two specific sites of cysteine oxidation in albumin that have not been described previously. These results provide evidence that coronary artery disease affects valve calcification, modifying the molecular profile of aortic valve tissue. In addition, the redox proteome is also altered when these conditions coincide, notably affecting human serum albumin.This research was funded by the Junta de Comunidades de Castilla-La Mancha (JCCM, co-funded by the European Social Fund, SBPLY/19/180501/000226), the Instituto de Salud Carlos III through the project PI18/00995, PI21/00384 (co-funded by European Regional Development Fund/European Social Fund—“Investing in your future”) Sociedad Española de Cardiología, 2020, Grant PRB3 (IPT17/0019—ISCIII-SGEFI/ERDF), Spanish Ministry of Science, Innovation and Universities (PGC2018-097019-B-I00) and “la Caixa” Banking Foundation (project code HR17-00247). These results are aligned with the Spanish initiative on the Human Proteome Project (SpHPP).S

Route Towards a Label-free Optical Waveguide Sensing Platform Based on Lossy Mode Resonances

According to recent market studies of the North American company Allied Market Research, the field of photonic sensors is an emerging strategic field for the following years and it is expected to garner $18 billion by 2021. The integration of micro and nanofabrication technologies in the field of sensors has allowed the development of new technological concepts such as lab-on-a-chip, which have achieved extraordinary advances in terms of detection and applicability, for example in the field of biosensors. This continuous development has allowed that equipment consisting of many complex devices that occupied a whole room a few years ago, at present it is possible to handle them in the palm of the hand; that formerly long duration processes are carried out in a matter of milliseconds and that a technology previously dedicated solely to military or scientific uses is available to the vast majority of consumers. The adequate combination of micro and nanostructured coatings with optical fiber sensors has permitted us to develop novel sensing technologies, such as the first experimental demonstration of lossy mode resonances (LMRs) for sensing applications, with more than one hundred citations and related publications in high rank journals and top conferences. In fact, fiber optic LMR-based devices have been proven as devices with one of the highest sensitivity for refractometric applications. Refractive index sensitivity is an indirect and simple indicator of how sensitive the device is to chemical and biological species, topic where this proposal is focused. Consequently, the utilization of these devices for chemical and biosensing applications is a clear opportunity that could open novel and interesting research lines and applications as well as simplify current analytical methodologies. As a result, on the basis of our previous experience with LMR based sensors to attain very high sensitivities, the objective of this paper is presenting the route for the development of label-free optical waveguide sensing platform based on LMRs that enable to explore the limits of this technology for bio-chemosensing applications

The BIDIAP index: a clinical, analytical and ultrasonographic score for the diagnosis of acute appendicitis in children

Background: Pediatric acute appendicitis (PAA) continues to be a diagnostic challenge today. The diagnostic performance of classical indices is only moderate, especially in pediatric population. This study aimed to define a clinical, radiological and analytical index for the diagnosis of PAA. Materials and methods: This prospective study included 151 patients divided into two groups: (1) 53 patients with non-surgical abdominal pain (NSAP) and (2) 98 patients with a confirmed PAA. Sociodemographic and clinical characteristics were compared between groups using the Mann-Whitney U test and the Fisher exact test. To identify the predictors of PAA, we performed a multivariable logistic regression using a forward stepwise analysis and we assigned multiples of integer values to the selected variables. The diagnostic performance of the index was assessed by calculating the area under the receiver operating characteristic curve. Intra-cohort calibration was assessed with the Hosmer-Lemeshow test. Results: We developed the BIDIAP index (BIomarkers for the DIagnosis of Appendicitis in Pediatrics), which included three variables that independently predicted higher odds of PAA: appendiceal caliber (≥ 6.9 mm), systemic immune-inflammation index (≥ 890) and peritoneal irritation, which scored 4, 3 and 2 points, respectively. Mean (SD) score of the participants was 2.38 (2.06) in group 1 and 7.89 (1.50) in group 2. The area under the ROC was 0.97 (95% CI 0.95-0.99). The cut-off point was established at 4 points, resulting in a sensitivity of 98.98% and a specificity of 77.78%. Conclusions: The BIDIAP index has an exceptional diagnostic performance in PAA. The importance of these results lies in its novelty and in the simplicity of the index. Although external validation will be necessary, initial results look promising

Alterations and diagnostic performance of capillary ketonemia in pediatric acute appendicitis: a pilot study

Introduction: The diagnostic performance of capillary ketonemia (CK) has been previously evaluated in context of pediatric acute gastroenteritis. To our knowledge, there is no literature on its performance in the setting of pediatric acute appendicitis (PAA). Materials and methods: In this study, 151 patients were prospectively included and divided into two groups: (1) patients with non-surgical abdominal pain in whom the diagnosis of PAA was excluded (n : 53) and (2) patients with a confirmed diagnosis of PAA (n : 98). In 80 patients (Group 1, n : 23 and group 2, n : 57) a CK was measured at the time of diagnosis. The PAA group was further classified into complicated (n : 18) and uncomplicated PAA (n : 39). Quantitative variables were compared between groups using the Mann-Whitney U test. Diagnostic performance of CK was evaluated with ROC curves. Results: CK values were 0.3 [0.1-0.9] mmol/L in group 1 and 0.7 [0.4-1.4] mmol/L in group 2 (p = 0.01). Regarding the type of PAA, CK values were 0.6 [0.4-0.9] mmol/L in uncomplicated PAA and 1.2 [0.8-1.4] mmol/L in complicated PAA (p : 0.02). The AUC for the discrimination between groups 1 and 2 was 0.68 (95/100 IC 0.53-0.82) (p : 0.24) and the AUC for the discrimination between uncomplicated PAA and complicated PAA was 0.69 (95/100 IC 0.54-0.85) (p : 0.04). The best cut-off point (group 1 vs group 2) resulted in 0.4 mmol/L, with a sensitivity of 80.7/100 and a specificity of 52.2/100. The best cut-off point (non-complicated vs complicated PAA) resulted in 1.1 mmol/L, with a sensitivity of 61.1/100 and a specificity of 76.9/100. Conclusions: This study found significantly higher levels of CK in patients with PAA than in those with NSAP. Similarly, significantly higher levels were observed in patients with complicated than in those with uncomplicated PAA. Nevertheless, the diagnostic performance of CK was only moderate in the two settings analyzed. The potential usefulness of CK determination as a tool to guide the preoperative rehydration regimen of patients with PAA to prevent postoperative hyporexia and vomiting is a promising line of research and should be evaluated in future studies

Leucine-Rich Alpha-2-Glycoprotein as a non-invasive biomarker for pediatric acute appendicitis: a systematic review and meta-analysis

The aim of this study was to analyze the diagnostic performance of Leucine-Rich Alpha-2-Glycoprotein (LRG1) in pediatric acute appendicitis (PAA). We conducted a systematic review of the literature in the main databases of medical bibliography. Two independent reviewers selected the articles and extracted relevant data. Methodological quality was assessed using the QUADAS2 index. A synthesis of the results, standardization of the metrics and 4 random-effect meta-analyses were performed. Eight studies with data from 712 participants (305 patients with confirmed diagnosis of PAA and 407 controls) were included in this review. The random-effect meta-analysis of serum LRG1 (PAA vs control) resulted in a significant mean difference (95% CI) of 46.76 μg/mL (29.26–64.26). The random-effect meta-analysis for unadjusted urinary LRG1 (PAA vs control) resulted in a significant mean difference (95% CI) of 0.61 μg/mL (0.30–0.93). The random-effect metaanalysis (PAA vs control) for urinary LRG1 adjusted for urinary creatinine resulted in a significant mean difference (95% CI) of 0.89 g/mol (0.11–1.66). Conlusion: Urinary LRG1 emerges as a potential non-invasive biomarker for the diagnosis of PAA. On the other hand, due to the high between-study heterogeneity, the results on serum LRG1 should be interpreted with caution. The only study that analyzed salivary LRG1 showed promising results. Further prospective studies are needed to confirm these findings