The Potential of Chitosan-Based Composites for Adsorption of Diarrheic Shellfish Toxins.

Okadaic acid (OA) is one of the most potent marine biotoxins, causing diarrheal shellfish poisoning (DSP). The proliferation of microalgae that produce OA and its analogues is frequent, threatening human health and socioeconomic development. Several methods have been tested to remove this biotoxin from aquatic systems, yet none has proven enough efficacy to solve the problem. In this work, we synthesized and characterized low-cost composites and tested their efficacy for OA adsorption in saltwater. For the synthesis of the composites, the following starting materials were considered: chitosan of low and medium molecular weight (CH-LW and CH-MW, respectively), activated carbon (AC), and montmorillonite (MMT). Characterization by vibrational spectroscopy (FTIR), X-ray diffraction (XRD), and microscopy revealed differences in the mode of interaction of CH-LW and CH-MW with AC and MMT, suggesting that the interaction of CH-MW with MMT has mainly occurred on the surface of the clay particles and no sufficient intercalation of CH-MW into the MMT interlayers took place. Among the composites tested (CH-LW/AC, CH-MW/AC, CH-MW/AC/MMT, and CH-MW/MMT), CH-MW/MMT was the one that revealed lower OA adsorption efficiency, given the findings evidenced by the structural characterization. On the contrary, the CH-MW/AC composite revealed the highest average percentage of OA adsorption (53 ± 11%). Although preliminary, the results obtained in this work open up good perspectives for the use of this type of composite material as an adsorbent in the removal of OA from marine environments.

The role of botulinum toxin in the management of nonneurogenic overactive bladder in children: Highlights for clinical practice. A systematic review.

Overactive bladder (OAB) is the most common voiding dysfunction in children; however, nonneurogenic or idiopathic OAB remains poorly studied. First-line treatment includes conservative measures; however, as many patients are refractory, have adverse effects, or are contraindicated for anticholinergics, new options must be explored. This review covers the use of intravesical botulinum toxin (BoNT) for idiopathic OAB treatment in children, emphasizing its efficacy, safety, differences between toxins, doses, and injection techniques. Clinical results were promising, with all 8 studies reporting good results. All authors used BoNT type A (BoNT-A), either onabotulinum or abobotulinum toxin A. Response rates were variable, with full-response percentages of 32%-60%. As proven by the full-response rates of 50%, repeated injections are as safe and effective as first injections. Only a few cases of urinary tract infection, transient urinary retention, and hematuria have been reported, with no major local or systemic adverse effects. Despite these limitations, evidence encourages and supports BoNT-A use as a safe and effective treatment modality for refractory idiopathic OAB in pediatric settings, regardless of dosage and target toxin. To the best of our knowledge, this is the first systematic review of the use of intravesical BoNT-A for idiopathic OAB treatment in children.

Intrathecal baclofen for the management of hereditary spastic paraparesis: a systematic review.

This systematic review aims to evaluate the use of intrathecal baclofen (ITB) for hereditary spastic paraparesis (HSP) treatment. An extensive search in two electronical databases was performed. We identified articles published between 1990 and 2022 (PubMed, Scopus), and applied the following inclusion criteria: diagnosis of HSP at the time of the intervention, either familial or sporadic; report on the effect of ITB in patients with HSP; test trial via either bolus injections or continuous infusion tests; and ITB pump implantation. A data extraction sheet based on the Cochrane Consumers and Communication Review Group's data extraction template was created and adapted to collect relevant data. A qualitative analysis was performed to present the results in narrative summary fashion. A total of 6 studies met our inclusion criteria. 51 patients with HSP had a pre-implantation ITB trial. The time since the diagnosis until the pump implantation ranged from 5 to 30 years. The initial bolus ranged from 20 to 50 µg and the mean doses used at steady state ranged from 65 to 705 µg. An improvement in spasticity was observed on the modified Ashworth Scale in patients treated with ITB. Although all studies reported a subjective gait improvement, not all found an objective improvement in gait. The most common side effect reported was catheter-related problems. The findings of this review support the use of ITB as an effective and a viable option for the treatment of spasticity in HSP refractory to conservative therapies.

Cation-Exchange Resin Applied to Paralytic Shellfish Toxins Depuration from Bivalves Exposed to Gymnodinium catenatum.

The accumulation of marine biotoxins in shellfish and their consumption causes serious food safety problems, threatening human health and compromising the availability of protein-based food. It is thus urgent to develop methodologies for the detoxification of live bivalves, avoiding their economic and nutritional devaluation. In this context, we tested an adsorption mechanism of paralytic shellfish toxins (PST) based on a cation-exchange resin. The first studies using cultures of Gymnodinium catenatum (natural producers of PST) showed a decrease of about 80% in overall toxicity after 48 h. Interestingly, we found that the toxins are adsorbed differently, with toxins' structural features playing a part in the adsorption capacity via steric hindrance, electronic effects, or the extent of positive charge density (e.g., dcSTX). The positive effect of the resin in accelerating PST clearance from live mussels (Mytilus edulis) is not evident when compared to resin-free clearance; nevertheless, relevant information could be gathered that will facilitate further in vivo studies. Several factors appear to be at play, namely the competition of natural substances (e.g., salts, organic matter) for the same binding sites, the blocking of pores due to interactions between molecules, and/or difficulties in resin absorption by mussels. Additionally, the present work revealed the ability of mussels to neutralize pH and proposes bioconversion reactions among the PST molecules.

Post-stroke dysphagia: Clinical characteristics and evolution in a single-primary stroke center.

BACKGROUND: Dysphagia is a common manifestation after stroke and seems to play a major role in clinical and functional outcomes. OBJECTIVES: To identify clinical predictors of higher degrees of dysphagia, as well as assess its burden in our hospital, in order to understand how to improve the approach to this symptom. METHODS: We included 311 patients admitted in an acute stroke unit in a year-long period. The relationship of dysphagia with different outcomes, both in acute phase and within the first year after stroke, were investigated. RESULTS: Using the Pearson Correlation Coefficient, NIHSS score at admission was positively correlated with the degree of dysphagia (r = 0,783; p < 0,001) and total anterior circulation infarcts and age (> 70 years) were also associated with higher risk of dysphagia (p < 0.001). During hospitalization both respiratory infections and mortality occurred at significantly higher rates for dysphagic patients (p < 0.001) and we observed an increasing trend towards a higher mortality rate, the higher the degree of dysphagia. These patients stayed longer in the stroke unit, with less chance to be discharged home and more frequently transferred to inpatient rehabilitation care. One year after admission, dysphagic patients were more frequently readmitted due to pneumonia and we observed a higher mortality rate compared to patients without dysphagia (p < 0.001). CONCLUSION: The presence of the above-mentioned dysphagia predictive factors should alert us to the need for an early approach, starting in the stroke unit, but also after discharge, taking into account its impact on clinical outcomes, mortality and healthcare costs.

Toxin Profile of Two Gymnodinium catenatum Strains from Iberian Coastal Waters.

Gymnodinium catenatum has been the main species responsible for paralytic shellfish poisoning events along the Portuguese coast (Iberian Peninsula), causing bans on bivalve harvesting that result in huge economic losses. This work presents the characterization of two novel isolates of G. catenatum regarding their growth and toxin profiles. Laboratory growth experiments revealed that, although low growth rates were obtained during cultivation, the cell yields were high compared to those reported in the literature. Evaluation of the toxin profiles, by HPLC-FLD, essentially confirmed the typical composition of toxins of this regional population (Iberian Peninsula), namely, the absence or low representation of the toxins dcNEO, GTX1,4 and NEO and a higher ratio of the toxins C1,2, GTX6 and GTX5. However, the percentage of the identified toxins varied among the strains of this study (under the same isolation, growth, and analysis conditions), and also differed from that of other strains described in the literature. Interestingly, we found a comparatively high abundance of dcSTX in both strains, relative to the other toxins, and an unquantifiable amount of C3,4 toxins. In addition to the geographic relationship between toxin profiles, chemical conversions among toxins may explain some differences encountered in the toxin profiles of G. catenatum strains.

Revisiting the HPLC-FLD Method to Quantify Paralytic Shellfish Toxins: C3,4 Quantification and the First Steps towards Validation.

Paralytic shellfish toxins (PSTs) are a large group of biotoxins that cause paralytic shellfish poisoning. Their appearance in natural waters and their ingestion by aquatic species have a huge socio-economic impact, whereby their monitoring is of the upmost relevance to minimize the consequences. For earlier detection and faster response/action by stakeholders, validation of adjusted analytical methods, particularly for lower concentration levels, is important. This work proposes a derived High-Performance Liquid Chromatography method, with fluorescence detection (HPLC-FLD). The main differences from the official method are the size of the HPLC column and the gradient elution conditions. It covers the current eleven certified reference materials (CRM) available on the market, including the most recent-C3,4. This first calibration report for C3,4 suggests limits of detection (LOD) and limits of quantification (LOQ) of 6 nM and 19 nM (~5 µg STX.2HCl eqv./kg and 17 µg STX.2HCl eqv./kg), respectively. For the remaining CRM, LODs ranged between 3 and 28 nM (~0.9 and 127 µg STX.2HCl eqv./kg), while LOQs varied between 11 and 94 nM (~3 and 409 µg STX.2HCl eqv./kg, considering toxicity equivalency factors (TEFs) reported by EFSA).

Congenital Facial Paralysis Revealing an Aplasic Facial Nerve: A Report of Two Cases.

ABSTRACT: Congenital facial palsy is a rare condition, usually related to a traumatic event during birth or as a feature of a syndrome. In this report, two cases of infants with peripheral facial palsy since birth are described, in which magnetic resonance imaging demonstrated unilateral aplasia of the facial nerve. There are only a few cases with similar findings described in the literature. A multidisciplinary approach is recommended to provide the best care. Although no reinnervation of the facial muscles is likely to occur, rehabilitative therapies may be valuable as complementary treatments.

Marine paralytic shellfish toxins: chemical properties, mode of action, newer analogues, and structure-toxicity relationship.

Up to the end of 2020Every year, the appearance of marine biotoxins causes enormous socio-economic damage worldwide. Among the major groups of biotoxins, paralytic shellfish toxins, comprising saxitoxin and its analogues (STXs), are the ones that cause the most severe effects on humans, including death. However, the knowledge that currently exists on their chemistry, properties and mode of toxicological action is disperse and partially outdated. This review intends to systematically compile the dispersed information, updating and complementing it. With this purpose, it addresses several aspects related to the molecular structure of these toxins. Special focus is given to the bioconversion reactions that may occur in the different organisms (dinoflagellates, bivalves, and humans) and the possible mediators involved. A critical review of the most recently discovered analogues, the M-series toxins, is presented. Finally, a deep discussion about the relationship between the molecular structure (e.g., effect of the substituting groups and the net charge of the molecules) and the toxic activity of these molecules is performed, proposing the concept of "toxicological traffic light" based on the toxicity equivalency factors (TEFs).

On the Development of Selective Chelators for Cadmium: Synthesis, Structure and Chelating Properties of 3-((5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)amino)benzo[d]isothiazole 1,1-dioxide, a Novel Thiadiazolyl Saccharinate.

Aquatic contamination by heavy metals is a major concern for the serious negative consequences it has for plants, animals, and humans. Among the most toxic metals, Cd(II) stands out since selective and truly efficient methodologies for its removal are not known. We report a novel multidentate chelating agent comprising the heterocycles thiadiazole and benzisothiazole. 3-((5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)amino)benzo[d]isothiazole 1,1-dioxide (AL14) was synthesized from cheap saccharin and characterized by different techniques, including single crystal X-ray crystallography. Our studies revealed the efficiency and selectivity of AL14 for the chelation of dissolved Cd(II) (as compared to Cu(II) and Fe(II)). Different spectral changes were observed upon the addition of Cd(II) and Cu(II) during UV-Vis titrations, suggesting different complexation interactions with both metals.

l-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in rats.

We evaluated whether l-proline (Pro) supplementation improves redox status and nitric oxide (NO) bioavailability and prevents or delays angiotensin II (AngII)-induced hypertension. Male Sprague-Dawley rats were distributed to four experimental groups: Pro + AngII (Pro-Ang), Pro + Saline (Pro-Sal), Vehicle + AngII (Veh-Ang) and Veh + Saline (Veh-Sal). Pro solution (2 g.kg-1·day-1) or water (vehicle) were orally administered, from day 0 to day 21. AngII (200 ng.kg-1.min-1) or saline were infused (s.c.) from day 7 to day 21. Systolic blood pressure (SBP) was measured by the tail-cuff method. From day 20-21, animals were kept on metabolic cages for 24h-urine collection. On day 21, urine and blood were collected for further quantification of redox status biomarkers, NO-related markers (urinary nitrates and nitrites, U-NOx; plasma asymmetric dimethylarginine, P-ADMA), metabolic and renal parameters. Pro prevented the AngII-induced SBP rise [mean (95% CI), Day 19: Pro-AngII, 137 (131; 143) vs. Veh-AngII, 157 (151; 163) mm Hg, P < 0.001]. Pro-AngII rats also had increased values of U-NOx, systemic and urinary total antioxidant status (TAS), urinary H2O2 and plasma urea, as well as reduced P-ADMA and unaltered urinary isoprostanes. Plasma Pro was inversely correlated with P-ADMA (r = -0.52, p = 0.0009) and positively correlated with urinary TAS (r = 0.55, p = 0.0005) which, in turn, was inversely correlated with P-ADMA (r = -0.56, p = 0.0004). Furthermore, urinary H2O2 values decreased across P-ADMA tertiles (p for linear trend = 0.023). These results suggest that Pro reduces P-ADMA levels and improves redox status, thereby increasing NO bioavailability and counteracting the AngII-induced SBP rise. H2O2 and TAS modulation by Pro may contribute to the reduced P-ADMA concentration.

Measurement of myocardial native T1 in cardiovascular diseases and norm in 1291 subjects.

BACKGROUND: Native T1-mapping provides quantitative myocardial tissue characterization for cardiovascular diseases (CVD), without the need for gadolinium. However, its translation into clinical practice is hindered by differences between techniques and the lack of established reference values. We provide typical myocardial T1-ranges for 18 commonly encountered CVDs using a single T1-mapping technique - Shortened Look-Locker Inversion Recovery (ShMOLLI), also used in the large UK Biobank and Hypertrophic Cardiomyopathy Registry study. METHODS: We analyzed 1291 subjects who underwent CMR (1.5-Tesla, MAGNETOM-Avanto, Siemens Healthcare, Erlangen, Germany) between 2009 and 2016, who had a single CVD diagnosis, with mid-ventricular T1-map assessment. A region of interest (ROI) was placed on native T1-maps in the "most-affected myocardium", characterized by the presence of late gadolinium enhancement (LGE), or regional wall motion abnormalities (RWMA) on cines. Another ROI was placed in the "reference myocardium" as far as possible from LGE/RWMA, and in the septum if no focal abnormality was present. To further define normality, we included native T1 of healthy subjects from an existing dataset after sub-endocardial pixel-erosions. RESULTS: Native T1 of patients with normal CMR (938 ± 21 ms) was similar compared to healthy subjects (941 ± 23 ms). Across all patient groups (57 ± 19 yrs., 65% males), focally affected myocardium had significantly different T1 value compared to reference myocardium (all p < 0.001). In the affected myocardium, cardiac amyloidosis (1119 ± 61 ms) had the highest native T1 compared to normal and all other CVDs, while iron-overload (795 ± 58 ms) and Anderson-Fabry disease (863 ± 23 ms) had the lowest native reference T1 (all p < 0.001). Future studies designed to detect the large T1 differences between affected and reference myocardium are estimated to require small sample-sizes (n < 50). However, studies designed to detect the small T1 differences between reference myocardium in CVDs and healthy controls can require several thousand of subjects. CONCLUSIONS: We provide typical T1-ranges for common clinical cardiac conditions in the largest cohort to-date, using ShMOLLI T1-mapping at 1.5 T. Sample-size calculations from this study may be useful for the design of future studies and trials that use T1-mapping as an endpoint.

Facing a patient who seeks help after a suicide attempt: the difficulties of health professionals.

BACKGROUND: Although intervention with suicidal patients is one of the hardest tasks in clinical practice, little is known about health professionals' perceptions about the difficulties of working with suicidal patients. AIMS: The aims of this study were to: (1) describe the difficulties of professionals facing a suicidal patient; (2) analyze the differences in difficulties according to the sociodemographic and professional characteristics of the health professionals; and (3) identify the health professionals' perceived skills and thoughts on the need for training in suicide. METHOD: A self-report questionnaire developed for this purpose was filled out by 196 health professionals. Exploratory principal components analyses were used. RESULTS: Four factors were found: technical difficulties; emotional difficulties; relational and communicational difficulties; and family-approaching and logistic difficulties. Differences were found between professionals who had or did not have training in suicide, between professional groups, and between the number of patient suicide attempts. Sixty percent of the participants reported a personal need for training and 85% thought it was fundamental to implement training plans targeted at health professionals. CONCLUSION: Specific training is fundamental. Experiential and active methodologies should be used and technical, relational, and emotional questions must be included in the training syllabus.