Design of a brain-machine interface for reducing false activations of a lower-limb exoskeleton based on error related potential.

BACKGROUND AND OBJECTIVE: Brain-Machine Interfaces (BMIs) based on a motor imagination paradigm provide an intuitive approach for the exoskeleton control during gait. However, their clinical applicability remains difficulted by accuracy limitations and sensitivity to false activations. A proposed improvement involves integrating the BMI with methods based on detecting Error Related Potentials (ErrP) to self-tune erroneous commands and enhance not only the system accuracy, but also its usability. The aim of the current research is to characterize the ErrP at the beginning of the gait with a lower limb exoskeleton to reduce the false starts in the BMI system. Furthermore, this study is valuable for determining which type of feedback, Tactile, Visual, or Visuo-Tactile, achieves the best performance in evoking and detecting the ErrP. METHODS: The initial phase of the research concentrates on detecting ErrP at the beginning of gait to improve the efficiency of an asynchronous BMI based on motor imagery (BMI-MI) to control a lower limb exoskeleton. Initially, an experimental protocol is designed to evoke ErrP at the start of gait, employing three different stimuli: Tactile, Visual, and Visuo-Tactile. An iterative selection process is then utilized to characterize ErrP in both time and frequency domains and fine-tune various parameters, including electrode distribution, feature combinations, and classifiers. A generic classifier with 6 subjects is employed to configure an ensemble classification system for detecting ErrP and reducing the false starts. RESULTS: The ensembled system configured with the selected parameters yields an average correction of false starts of 72.60 % ± 10.23, highlighting its corrective efficacy. Tactile feedback emerges as the most effective stimulus, outperforming Visual and Visuo-Tactile feedback in both training types. CONCLUSIONS: The results suggest promising prospects for reducing the false starts when integrating ErrP with BMI-MI, employing Tactile feedback. Consequently, the security of the system is enhanced. Subsequent, further research efforts will focus on detecting error potential during movement for gait stop, in order to limit undesired stops.

Clinical-haematological changes and predictors of severity in acute food protein-induced enterocolitis syndrome reactions at oral food challenge: a multicentre observational study.

BACKGROUND: Oral food challenge (OFC) is the gold standard for diagnosis of acute Food Protein-Induced Enterocolitis Syndrome (FPIES). No diagnostic/prognostic biomarkers are available, and OFC assessment criteria are not validated. OBJECTIVE: To assess clinical-haematological changes and predictors of severity of FPIES reactions at OFC. METHODS: Observational multicentre prospective study. Children aged 0-18 years diagnosed with acute FPIES were recruited at follow-up OFC in 12 tertiary centres in Spain and Italy. OFC Outcomes (as positive/negative/inconclusive and mild/moderate/severe) were assessed based on published '2017 FPIES Consensus' criteria. Clinical characteristics were recorded, and full blood count was done at baseline, reaction onset and 4 hours later. Regression analysis was performed to assess predictors of severe reactions at OFC. RESULTS: 81 children had positive OFC (mild in 11% (9/81), moderate in 61% (49/81), severe in 28% (23/81)). Increase in neutrophils and reduction in eosinophils, basophils and lymphocytes was observed (P-value<0.05). OFC was inconclusive in 19 cases despite objective signs or neutrophilia. Regression analysis showed a 2-day OFC protocol where only 25% of an age-appropriate portion is given on day 1 (not gender, age, culprit food, cumulative dose and previous reaction severity) was associated with reduced odds of severe reaction compared to giving multiple doses in a single day. CONCLUSION: Distinct haematological changes may help support FPIES diagnosis. Current OFC assessment criteria may not capture the broad spectrum of acute FPIES presentations. This 2-day protocol may associate a reduced risk of severe reactions. Future work should aim to develop safer OFC and non-OFC diagnostics for FPIES.

Combined application of high pressure and ultrasound in fig paste: effect on bioactive and volatile compounds.

The combined impact of high-hydrostatic pressure (HHP) and ultrasound (US) on the cyanidin-3-O-rutinoside (C3R), quercetin-3-O-rutinoside (Q3R), and volatile compounds from fig (Ficus carica) paste was investigated. The HHP increased the content of C3R and Q3R, from 70 to 133 mg/kg fw and 31 to 44 mg/kg fw, respectively. The combination of HHP and US further enhanced the extraction of these bioactive compounds. Specifically, processing fig paste with US for 5 min at 40 °C yielded approximately 250 mg of C3R/kg fw and 45 mg of Q3R/kg fw, after 20 min. More than 25 volatile compounds were identified, with benzaldehyde being the predominant compound, accounting > 75%. Trace amounts of hydroxymethylfurfural (< 0.36 mg/100 g fw) were detected in HHP-processed fig paste. The application of HHP at mild temperatures and short time, combined with US, effectively promotes the content of bioactive compounds present in fig paste without adversely affecting the fruit's volatile compounds. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01410-1.

The mediating role of reflective functioning in the association between childhood trauma and suicide attempt.

BACKGROUND: Childhood trauma is intimately related with suicidal behaviour. Patients who have suffered childhood trauma develop impaired Reflective Functioning (RF), which refers to the capacity to understand ourselves and others in terms of intentional mental states. An improvement in RF has been associated with a reduction in suicidal attempts, but the mediating role of RF between childhood trauma and suicidal behaviour has not been addressed so far. OBJECTIVE: We aim to examine the potential mediating effect of RF among childhood trauma and suicide attempts. METHOD: We included 748 patients who had attempted suicide at least once. They were asked to complete the Reflective Functioning Questionnaire (RFQ-8), the Columbia-Suicide Severity Rating scale (CSSRS), and the Childhood Trauma Questionnaire-Short Form (CTQ-SF). We conducted linear regressions by simple mediating model to examine the role of RF in the indirect association between childhood trauma and the number of suicide attempts. RESULTS: Our results show significant indirect effects through hypo and hypermentalizing between Emotional Abuse (EA) and Sexual Abuse (SA) in childhood and the number of suicide attempts in lifetime. These results indicate that ineffective RF significantly mediates the association between childhood trauma and suicidality. CONCLUSION: This is the first study supporting the mediational role of RF in the relationship between EA and SA, and the number of suicide attempt in lifetime. These findings have important implications for reducing suicide rates and preventing future re-attempts. Further studies analysing this mediating role and focusing efforts on increasing RF-based interventions are required.

Diagnosis of multiple sclerosis using optical coherence tomography supported by explainable artificial intelligence.

BACKGROUND/OBJECTIVES: Study of retinal structure based on optical coherence tomography (OCT) data can facilitate early diagnosis of relapsing-remitting multiple sclerosis (RRMS). Although artificial intelligence can provide highly reliable diagnoses, the results obtained must be explainable. SUBJECTS/METHODS: The study included 79 recently diagnosed RRMS patients and 69 age matched healthy control subjects. Thickness (Avg) and inter-eye difference (Diff) features are obtained in 4 retinal layers using the posterior pole protocol. Each layer is divided into six analysis zones. The Support Vector Machine plus Recursive Feature Elimination with Leave-One-Out Cross Validation (SVM-RFE-LOOCV) approach is used to find the subset of features that reduces dimensionality and optimises the performance of the classifier. RESULTS: SVM-RFE-LOOCV was used to identify OCT features with greatest capacity for early diagnosis, determining the area of the papillomacular bundle to be the most influential. A correlation was observed between loss of layer thickness and increase in functional disability. There was also greater functional deterioration in patients with greater asymmetry between left and right eyes. The classifier based on the top-ranked features obtained sensitivity = 0.86 and specificity = 0.90. CONCLUSIONS: There was consistency between the features identified as relevant by the SVM-RFE-LOOCV approach and the retinotopic distribution of the retinal nerve fibres and the optic nerve head. This simple method contributes to implementation of an assisted diagnosis system and its accuracy exceeds that achieved with magnetic resonance imaging of the central nervous system, the current gold standard. This paper provides novel insights into RRMS affectation of the neuroretina.

Analysis of Error Potentials generated by a lower limb exoskeleton feedback in a BMI for gait control.

Brain-machine interfaces (BMIs) based on motor imagery (MI) for controlling lower-limb exoskeletons during the gait have been gaining importance in the rehabilitation field. However, these MI-BMI are not as precise as they should. The detection of error related potentials (ErrP) as a self-tune parameter to prevent wrong commands could be an interesting approach to improve their performance. For this reason, in this investigation ErrP elicited by the movement of a lower-limb exoskeleton against subject's will is analyzed in the time, frequency and time-frequency domain and compared with the cases where the exoskeleton is correctly commanded by motor imagery (MI). The results of the ErrP study indicate that there is statistical significative evidence of a difference between the signals in the erroneous events and the success events. Thus, ErrP could be used to increase the accuracy of BMIs which commands exoskeletons.Clinical Relevance- This investigation has the purpose of improving brain-machine interfaces (BMIs) based on motor imagery (MI) by means of the detection of error potentials. This could promote the adoption of robotic exoskeletons commanded by BMIs in rehabilitation therapies.

Transfer Learning with CNN Models for Brain-Machine Interfaces to command lower-limb exoskeletons: A Solution for Limited Data.

This study evaluates the performance of two convolutional neural networks (CNNs) in a brain-machine interface (BMI) based on motor imagery (MI) by using a small dataset collected from five participants wearing a lower-limb exoskeleton. To address the issue of limited data availability, transfer learning was employed by training models on EEG signals from other subjects and subsequently fine-tuning them to specific users. A combination of common spatial patterns (CSP) and linear discriminant analysis (LDA) was used as a benchmark for comparison. The study's primary aim is to examine the potential of CNNs and transfer learning in the development of an automatic neural classification system for a BMI based on MI to command a lower-limb exoskeleton that can be used by individuals without specialized training.Clinical Relevance- BMI can be used in rehabilitation for patients with motor impairment by using mental simulation of movement to activate robotic exoskeletons. This can promote neural plasticity and aid in recovery.

High endoreduplication after drought-related conditions in haploid but not diploid mosses.

BACKGROUND AND AIMS: Endoreduplication, the duplication of the nuclear genome without mitosis, is a common process in plants, especially in angiosperms and mosses. Accumulating evidence supports the relationship between endoreduplication and plastic responses to stress factors. Here, we investigated the level of endoreduplication in Ceratodon (Bryophyta), which includes the model organism Ceratodon purpureus. METHODS: We used flow cytometry to estimate the DNA content of 294 samples from 67 localities and found three well-defined cytotypes, two haploids and one diploid, the haploids corresponding to C. purpureus and Ceratodon amazonum, and the diploid to Ceratodon conicus, recombination occurring between the former two. KEY RESULTS: The endoreduplication index (EI) was significantly different for each cytotype, being higher in the two haploids. In addition, the EI of the haploids was higher during the hot and dry periods typical of the Mediterranean summer than during spring, whereas the EI of the diploid cytotype did not differ between seasons. CONCLUSIONS: Endopolyploidy may be essential in haploid mosses to buffer periods of drought and to respond rapidly to desiccation events. Our results also suggest that the EI is closely related to the basic ploidy level, but less so to the nuclear DNA content as previously suggested.

Attitudes scale toward cancer-related cognitive changes - an initial Colombian validation.

OBJECTIVE: The aim of this study was to develop an initial valid tool to measure attitudes toward cancer-related cognitive changes. SUBJECTS AND METHODS: After revising the literature, three main dimensions were hypothesized. Eight judges were contacted to obtain content validity evidence. A robust Exploratory Factor Analysis (EFA) was performed via a parallel analysis with an Unweighted Least Squares (ULS) estimator and polychoric correlations. The results were crossed with sociodemographic variables to find possible statistical differences and estimate the size effect. Analysis was performed in the software Factor and the statistical package R. RESULTS: A sample of 374 participants was obtained, involving oncology patients, their caregivers, and people from the general community. A statistical fit was found in two dimensions: Awareness and Judgments [root mean squared error of approximation (RMSEA) = 0.042, standardized root mean square residual (SRMR) = 0.02, comparative fit index (CFI) = 0.99, Tucker-Lewis index (TLI) = 0.98] with a moderate correlation between them (r = 0.612). Optimal reliability indices were obtained for the total scale and its dimensions. No real statistical difference was found between sociodemographic variables; the interpretation norms were established via the quartiles. CONCLUSIONS: The first attempt to measure the construct of interest was developed with two primary validity evidence based on the content and its internal structure. This instrument could help strengthen the prevention of cancer-related cognitive changes. More research is needed to adhere more valid evidence to the scale.

The inversion of multiresponse partial least squares models, a useful tool to improve analytical methods in the framework of analytical quality by design.

Analytical Quality by Design (AQbD) is the adaptation of Quality by Design (QbD) when it is applied to the development of an analytical method. The main idea is to develop the analytical method in such a way that the desired quality of the Critical Quality Attributes (CQAs), stated via the analytical target profile (ATP), is maintained while allowing some variation in the Control Method Parameters (CMPs). The paper presents a general procedure for selecting factor levels in the CMPs to achieve the desired responses, characterized by the CQAs, when liquid chromatographic methods are to be used for the simultaneous determination of several analytes. In such a case, the CMPs are usually the composition of the ternary mobile phase, its flow rate, column temperature, etc., while typical CQAs refer to the quality of the chromatograms in terms of the resolution between each pair of consecutive peaks, initial and final chromatographic time, etc. The analytical target profile in turn defines the desired characteristics for the CQAs, the reason for the whole approach. The procedure consists of four steps. The first is to construct a D-optimal combined design (mixture-process design) to select the domain and levels of the CMPs. The second step is to fit a PLS2 model to predict the analytical responses expressed in the ATP (the good characteristics of the chromatogram) as a function of the CMPs. The third step is the inversion of the PLS2 model to obtain the conditions necessary to obtain the preset ATP in the corresponding CQAs. The inversion is performed computationally in order to estimate the Pareto front of these responses, namely, a set of experimental conditions to perform the chromatographic determination for which the desired critical quality attributes are met. The fourth final step is to obtain the Method Operable Design Region (MODR), that is, the region where the CMPs can vary while maintaining the quality of the CQAs. The procedure has been applied to some cases involving different analytes, all of which are regulated by the European Union due to their toxicity to human health, namely five bisphenols and ten polycyclic aromatic hydrocarbons.

A bit of medical paternalism? A qualitative study on power relations between women and healthcare providers when deciding on mode of birth in five public maternity wards of Argentina.

BACKGROUND: Whether women should be able to decide on mode of birth in healthcare settings has been a topic of debate in the last few decades. In the context of a marked increase in global caesarean section rates, a central dilemma is whether pregnant women should be able to request this procedure without medical indication. Since 2015, Law 25,929 of Humanised Birth is in place in Argentina. This study aims at understanding the power relations between healthcare providers, pregnant women, and labour companions regarding decision-making on mode of birth in this new legal context. To do so, central concepts of power theory are used. METHODS: This study uses a qualitative design. Twenty-six semi-structured interviews with healthcare providers were conducted in five maternity wards in different regions of Argentina. Participants were purposively selected using heterogeneity sampling and included obstetrician/gynaecologists (heads of department, specialists working in 24-h shifts, and residents) and midwives where available. Reflexive thematic analysis was used to inductively develop themes and categories. RESULTS: Three themes were developed: (1) Healthcare providers reconceptualize decision-making processes of mode of birth to make women's voices matter; (2) Healthcare providers feel powerless against women's request to choose mode of birth; (3) Healthcare providers struggle to redirect women's decision regarding mode of birth. An overarching theme was built to explain the power relations between healthcare providers, women and labour companions: Healthcare providers' loss of beneficial power in decision-making on mode of birth. CONCLUSIONS: Our analysis highlights the complexity of the healthcare provider-woman interaction in a context in which women are, in practice, allowed to choose mode of birth. Even though healthcare providers claim to welcome women being an active part of the decision-making processes, they feel powerless when women make autonomous decisions regarding mode of birth. They perceive themselves to be losing beneficial power in the eyes of patients and consider fruitful communication on risks and benefits of each mode of birth to not always be possible. At the same time, providers perform an increasing number of CSs without medical indication when it is convenient for them, which suggests that paternalistic practices are still in place.

In the last few decades, there has been a debate on whether women should be able to choose if they haver a vaginal birth or a caesarean section. This debate has been framed by the fact that an increasing number of caesarean sections are being performed. Since 2015, Argentina has a Law of Humanised Birth. We conducted a study to understand the power relations between healthcare providers, pregnant women and labour companions in decision making on mode of birth in this new legal context. To do so, we used central concepts of power theory. We conducted 26 semi-structured interviews with healthcare providers in five maternity wards of Argentina. The interviewees were obstetrician/gynaecologists (heads of department, specialists working in 24-h shifts, and residents) and midwives where available. We used thematic analysis to build themes from the data. We discovered that healthcare providers perceive themselves to be losing beneficial power in decision-making on mode of birth. Even though they claim to want women to make autonomous decisions, they feel frustrated when this happens. They also perceive it to be more difficult to communicate with patients regarding the risks and benefits of vaginal birth and caesarean section. At the same time, providers carry out an increasing number of CSs without medical indication when it is convenient for them, which suggests that paternalistic practices are still in place.

A new bathyal species of Pardaliscoides (Amphipoda, Amphilochidea, Pardaliscidae) from off the southwestern Gulf of Mexico.

A new species of pardaliscid amphipod is described and illustrated from a single male specimen collected from bathyal sediments (2125 m depth) in the southern Gulf of Mexico. The new species is morphologically closest to Pardaliscoides fictotelson Barnard, 1966, previously documented from Southern California, at 218 m depth. The new pardaliscid differs from other species in the genus in having antenna 1 with a 10-articulate accessory flagellum; maxilliped palp very long; pereopods 5-7 elongate, slender; basis pereopod 7 expanded; telson with a short U-shaped cleft and pointed lobes; uropods 1-2 outer ramus curved, peduncle flat, longer than rami; uropod 3 rami flat, fleshy-lined, with marginal distal short robust setae. An identification key for all known species in the Pardaliscoides genus is also provided. The new species increase the number of Pardaliscoides species documented to six worldwide.

Limbic encephalitis secondary to neuro-Behcet disease: an uncommon presentation. / Encefalitis límbica secundaria a neuro-Behçet: una presentación insólita.

INTRODUCTION: Limbic encephalitis (LE) can have a wide range of etiologies, most frequently infectious (especially viral) or autoimmune. Behcet's disease (BD) can present with heterogeneous neurological manifestations. However, LE is not considered a typical presentation of neuro-Behcet's disease (NBD). CASE REPORT: A 40-years-old male presented with new-onset subacute headaches, memory problems and apathy. A review of systems revealed an unrecorded past history of recurrent oral sores for years, recent malaise and fever, as well as an episode of bilateral panuveitis four months before presentation. His general and neurologic examination revealed slight fever, an isolated oral aphtha, anterograde amnesia and signs of bilateral retinal vasculitis. Brain magnetic resonance imaging displayed a pattern of limbic meningoencephalitis, and his cerebrospinal fluid showed mononuclear inflammation. The patient met BD diagnostic criteria. Considering LE is a very rare presentation of NBD, alternative etiologies were thoroughly assessed and excluded, including infectious, autoimmune and paraneoplastic encephalitis. Therefore, he was diagnosed with NBD, and he recovered well after immunosuppression. DISCUSSION: Only two cases of NBD presenting with LE have been previously reported. We report a third case of this rare presentation and compare it with the previous two. We aim to highlight this association and contribute to enlarge the rich clinical spectrum of NBD.

TITLE: Encefalitis límbica secundaria a neuro-Behçet: una presentación insólita.Introducción. La encefalitis límbica (EL) puede tener un amplio abanico de etiologías, más frecuentemente la infecciosa (sobre todo viral) o autoinmune. La enfermedad de Behçet (EB) puede presentarse con manifestaciones neurológicas heterogéneas. Sin embargo, la EL no se considera una presentación típica del neuro-Behçet (NB). Caso clínico. Varón de 40 años que consultó por cefalea de novo subaguda, problemas de memoria y apatía. La anamnesis por sistemas reveló una historia no conocida previamente de aftas orales recurrentes durante años, fiebre y afectación general reciente, así como un episodio de panuveítis bilateral cuatro meses antes de la presentación. Su exploración general y neurológica reveló febrícula, una afta oral aislada, amnesia anterógrada y signos de vasculitis retiniana bilateral. La resonancia magnética mostró un patrón de afectación de meningoencefalitis límbica y su líquido cefalorraquídeo presentaba inflamación mononuclear. El paciente cumplía los criterios diagnósticos de la EB. Considerando que la EL es una presentación muy rara del NB, se buscaron exhaustivamente y se excluyeron otras etiologías alternativas, incluyendo las encefalitis infecciosas, autoinmunes y paraneoplásicas. En consecuencia, el paciente se diagnosticó de NB y mostró una buena recuperación con tratamiento inmunosupresor. Discusión. Sólo dos casos de NB con presentación en forma de EL se han publicado previamente. Comunicamos el tercer caso de esta rara manifestación clínica de la EB y lo comparamos con los dos anteriores, con el objetivo de destacar dicha asociación y contribuir a expandir el rico espectro clínico del NB.

Lychnophora pinaster in endangered campos rupestres: phenolic compounds and population ecogeography.

Lychnophora pinaster, known as arnica-mineira, is endemic to campos rupestres, at risk of extinction. The present study aimed to characterize the ecogeography and phenolic constituents of 11 L. pinaster populations collected in the mesoregions North, Jequitinhonha, Metropolitan of Belo Horizonte and Campos das Vertentes in the state of Minas Gerais, Brazil. Phenolic constituents were identified and quantified by Ultra-high performance liquid chromatography- mass spectrometry. Lychnophora pinaster occurs in sites at high altitude (700 and 1498 m), annual rainfall of up to 1455 m, soils with low fertility and predominantly loamy texture. Therefore, it can be considered tolerant to acidic soils, with low availability of nutrient. The most abundant substances in all populations were vitexin (18 - 1345 ng/g) and chlorogenic acid (60 - 767 ng/g). The 11 populations formed four groups in relation to the phenolic constituents, with group 1 consisting of the populations of the North Mesoregion (GM, OD) and Jetiquinhonha (DIMa), group 2, the Metropolitan of Belo Horizonte (SRM, NLSC, SM, RPS, CTRA), group 3, the North Mesoregion (ODMa and DI), and group 4, the Campos das Vertentes (CC). Among the populations, only those from the Metropolitan of Belo Horizonte showed correlation of soil properties with phenolic constituents.

Soil fungal diversity and assembly along a xeric stress gradient in the central Namib Desert.

The Namib Desert of south-western Africa is one of the oldest deserts in the world and possesses unique geographical, biological and climatic features. While research through the last decade has generated a comprehensive survey of the prokaryotic communities in Namib Desert soils, little is yet known about the diversity and function of edaphic fungal communities, and even less of their responses to aridity. In this study, we have characterized soil fungal community diversity across the longitudinal xeric gradient across the Namib desert (for convenience, divided into the western fog zone, the central low-rainfall zone and the eastern high-rainfall zone), using internal transcribed sequence (ITS) metabarcoding. Ascomycota, Basidiomycota and Chytridiomycota consistently dominated the Namib Desert edaphic fungal communities and a core mycobiome composed of only 15 taxa, dominated by members of the class Dothideomycetes (Ascomycota), was identified. However, fungal community structures were significantly different in the fog, low-rainfall and high-rainfall zones. Furthermore, Namib Desert gravel plain fungal community assembly was driven by both deterministic and stochastic processes; the latter dominating in the all three xeric zones. We also present data that suggest that the inland limit of fog penetration represents an ecological barrier to fungal dispersal across the Namib Desert.

[Guilt and well-being in institutionalized family caregivers of dependent older adult people]. / Culpa y bienestar en cuidadores familiares de personas mayores dependientes institucionalizadas.

INTRODUCTION AND OBJECTIVE: The experience of family caregivers after nursing home admission has received much less attention, probably because many caregivers experience an initial sense of initial emotional relief. However, for some caregivers nursing home admission is a stressor despite the reduced physical burden of caregiving. Caregiver distress following institutionalization has been related to the new burdens and challenges encountered in the nursing home. Ambivalence and guilt related to the institutionalization decision have been identified as sources of stress. Therefore, this study examined the effect of guilt and well-being on the perceived stress of family caregivers of institutionalized dependent persons. MATERIALS AND METHODS: Two hundred and one family caregivers of institutionalized persons in a nursing home (La Rioja, Spain) participated. Perceived stress, caregiving guilt and subjective well-being, sociodemographic and caregiving-related variables were assessed. Linear regression analyses and correlations between variables were performed. RESULTS: Guilt and five dimensions of well-being (anxiety, vitality, self-control and depression, except general health) significantly predicted stress (R2adj=.552 (F (6, 198)=41.71, P<.001)). The effect size was large (95% CI=.461). CONCLUSIONS: Paying attention to family caregivers' feelings of guilt during institutionalization is important. This will enable the design and implementation of psychosocial interventions that improve caregiver adjustment immediately after institutionalization.

Correlation between imaging findings and hormonal markers at the onset of puberty in girls.

INTRODUCTION: This study aimed to determine the diagnostic performance of transabdominal pelvic ultrasonography and bone age in identifying the onset of puberty in girls at the Clínica Las Américas in Medellín, Colombia. METHODS: We included girls aged ≤11 years referred to our clinic between March 2016 and March 2019 for signs of puberty. We compared the findings on pelvic and breast ultrasonography and bone age versus the baseline measurement of luteinizing hormone (LH) in serum, used as the reference standard for identifying the onset of puberty. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios, analyzing subgroups of patients of different ages. RESULTS: We analyzed 43 patients. Ultrasound assessment of breast development had the highest sensitivity (94.1%) of all the imaging parameters evaluated, but its specificity was low. However, characteristics such as the length of the body of the uterus >3.0 cm and the presence of endometrial echoes were highly specific for identifying the onset of puberty, particularly in patients aged ≤8 years. CONCLUSION: Pelvic ultrasonography, ultrasonographic assessment of Tanner stage of breast development, and the evaluation of bone age are useful tools for the imaging confirmation of the onset of puberty. The results of this study support the use of these techniques in clinical practice in the workup for pubertal disorders in girls.

A signature of circulating microRNAs predicts the response to treatment with FOLFIRI plus aflibercept in metastatic colorectal cancer patients.

The benefit of adding the antiangiogenic drug aflibercept to FOLFIRI regime in metastatic colorectal cancer (CRC) patients resistant to or progressive on an oxaliplatin-based therapy has been previously demonstrated. However, the absence of validated biomarkers to predict greater outcomes is a major challenge encountered when using antiangiogenic therapies. In this study we investigated profiles of circulating microRNAs (miRNAs) to build predictive models of response to treatment and survival. Plasma was obtained from 98 metastatic CRC patients enrolled in a clinical phase II trial before receiving FOLFIRI plus aflibercept treatment, and the circulating levels of 754 individual miRNAs were quantified using real-time PCR. A distinct signature of circulating miRNAs differentiated responder from non-responder patients. Remarkably, most of these miRNAs were found to target genes that are involved in angiogenic processes. Accordingly, some of these miRNAs had predictive value and entered in predictive models of response to therapy, progression of disease, and survival of patients treated with FOLFIRI plus aflibercept. Among these miRNAs, circulating levels of hsa-miR-33b-5p efficiently discriminated between responder and non-responder patients and predicted the risk of disease progression. Moreover, the combination of circulating VEGF-A and miR-33b-5p levels improved clinical stratification of metastatic CRC patients who were to receive FOLFIRI plus aflibercept treatment. In conclusion, our study supports circulating miRNAs as valuable biomarkers for predicting better outcomes in metastatic CRC patients treated with FOLFIRI plus aflibercept.

Essential Oils of Aromatic Plant Species from the Atlantic Rainforest Exhibit Extensive Chemical Diversity and Antimicrobial Activity.

Microbial resistance, caused by the overuse or inadequate application of antibiotics, is a worldwide crisis, increasing the risk of treatment failure and healthcare costs. Plant essential oils (EOs) consist of hydrophobic metabolites with antimicrobial activity. The antimicrobial potential of the chemical diversity of plants from the Atlantic Rainforest remains scarcely characterized. In the current work, we determined the metabolite profile of the EOs from aromatic plants from nine locations and accessed their antimicrobial and biocidal activity by agar diffusion assays, minimum inhibitory concentration, time-kill and cell-component leakage assays. The pharmacokinetic properties of the EO compounds were investigated by in silico tools. More than a hundred metabolites were identified, mainly consisting of sesqui and monoterpenes. Individual plants and botanical families exhibited extensive chemical variations in their EO composition. Probabilistic models demonstrated that qualitative and quantitative differences contribute to chemical diversity, depending on the botanical family. The EOs exhibited antimicrobial biocidal activity against pathogenic bacteria, fungi and multiple predicted pharmacological targets. Our results demonstrate the antimicrobial potential of EOs from rainforest plants, indicate novel macromolecular targets, and contribute to highlighting the chemical diversity of native species.

Sialyltransferase Inhibitor Ac53FaxNeu5Ac Reverts the Malignant Phenotype of Pancreatic Cancer Cells, and Reduces Tumor Volume and Favors T-Cell Infiltrates in Mice.

Hypersialylation is a feature of pancreatic ductal adenocarcinoma (PDA) and it has been related to tumor malignancy and immune suppression. In this work, we have evaluated the potential of the sialyltransferase inhibitor, Ac53FaxNeu5Ac, to decrease tumor sialoglycans in PDA and to revert its malignant phenotype. Sialoglycans on PDA cells were evaluated by flow cytometry, and the functional impact of Ac53FaxNeu5Ac was assessed using E-selectin adhesion, migration, and invasion assays. PDA tumors were generated in syngeneic mice from KC cells and treated with Ac53FaxNeu5Ac to evaluate tumor growth, mice survival, and its impact on blocking sialic acid (SA) and on the tumor immune component. Ac53FaxNeu5Ac treatment on human PDA cells decreased α2,3-SA and sialyl-Lewisx, which resulted in a reduction in their E-selectin adhesion, and in their migratory and invasive capabilities. Subcutaneous murine tumors treated with Ac53FaxNeu5Ac reduced their volume, their SA expression, and modified their immune component, with an increase in CD8+ T-lymphocytes and NK cells. In conclusion, Ac53FaxNeu5Ac treatment weakened PDA cells' malignant phenotype, thereby reducing tumor growth while favoring anti-tumor immune surveillance. Altogether, these results show the positive impact of reducing SA expression by inhibiting cell sialyltransferases and open the way to use sialyltransferase inhibitors to target this dismal disease.