The Effects of Vestibular Rehabilitation and Manual Therapy on Patients with Unilateral Vestibular Dysfunction: A Randomized and Controlled Clinical Study.

(1) Objective: To determine the effect of a directed vestibular rehabilitation therapy (VRT) program with manual therapy (MT) on dizziness-related disability and imbalance symptoms among patients with peripheral unilateral vestibular dysfunction. (2) Methods: Eighty patients (54.75 ± 1.34 years) were allocated either to a control group (n = 40), who underwent a directed VRT program, or to an experimental group (n = 40), who received the same program plus MT once a week/4 weeks. We assessed their level of disability (Dizziness Handicap Inventory, DHI), balance confidence (the Activities-specific Balance Confidence scale-16 items), postural balance (resistive multisensor platform), and the frequency and intensity of dizziness symptoms (visual analog scale). (3) Results: Post-intervention between-group improvements were observed regarding DHI total score and intensity in the experimental group (p < 0.001), as well as four weeks later. Six months after, the experimental group exhibited improvements in the center of pressure velocity with eyes open (p = 0.019), DHI total score (p = 0.001) and subscales (all p < 0.05), and intensity (p = 0.003) and frequency (p = 0.010) of dizziness. Balance confidence improvements were observed 1 month (p = 0.035) and 6 months (p = 0.038) post-intervention. (4) Conclusions: Directed VRT plus MT is a safe and beneficial intervention that speeds up recovery for patients suffering from dizziness and instability derived from unilateral vestibular dysfunction.

Healthy Zerumbone: From Natural Sources to Strategies to Improve Its Bioavailability and Oral Administration.

Zerumbone is a multifunctional compound with antimicrobial, antitumor, hyperalgesic, antioxidant and anti-inflammatory applications, and constitutes a point molecule for the future synthesis of derivatives with improved efficiency. This monocyclic sesquiterpenoid is found in high content in wild ginger (Zingiber zerumbet Smith), a perennial herb with economic importance as an ornamental as well as a medicinal plant. The presence of zerumbone is a distinctive feature that allows identification and differentiation from other species, not only in Zingiber, but also in Curcuma, Alpinia, Boesenbergia, Ethlingera and Ammomum spp., as well as related families (Costaceaee). To successfully use zerumbone in areas such as medicine, food and agriculture, further research on improving its low solubility and bioavailability, as well as its preservation, is a major current priority. In addition, despite its promising pharmacological activities, preclinical and clinical studies are required to demonstrate and evaluate the in vivo efficacy of zerumbone.

[Effect of omega-3 fatty acids on hypoalbuminemia in acute heart failure patients with increased inflammatory activity]. / Efecto de los ácidos grasos omega-3 sobre la hipoalbuminemia en pacientes con insuficiencia cardiaca aguda y actividad inflamatoria elevada.

INTRODUCTION: Introduction: inflammatory activity (IA) is a cause of hypoalbuminemia in patients with acute heart failure (AHF). Objectives: the main objective of this study was to evaluate whether an AI modulator treatment contributes to correcting albuminemia in this context. Methods: in this clinical trial 43 patients with AHF, hypoalbuminemia (serum albumin  3.4 g/dl), and elevated IA [C-reactive protein (CRP)  25 mg/l] were randomly assigned to receive omega-3 fatty acids (4 g daily) or placebo for 4 weeks. Albuminemia and CRP were reassessed at weeks 1 and 4. An analysis of variance for repeated measures was performed. Results: mean age was 75.6 ± 8.8 years, 72.1 % were male, and the most frequent etiology was ischemic (46.5 %). The two groups were homogeneous in their baseline characteristics. A significant increase in albumin concentration was found at week 4 from baseline (p for the effect of time < 0.001), with no differences between groups at week 1 or week 4. CRP decreased significantly in week 1 (p for the effect of time < 0.001), with no differences between groups in either week 1 or week 4. Conclusion: in patients with AHF, hypoalbuminemia, and elevated AI albuminemia normalizes in week 4, while CRP already drops significantly during the first week. In this context both effects are independent of the addition of high doses of omega-3 fatty acids.

INTRODUCCIÓN: Introducción: la actividad inflamatoria (AI) es causa de hipoalbuminemia en los pacientes con insuficiencia cardiaca aguda (ICA). Objetivos: el objetivo principal de este estudio fue evaluar si un tratamiento modulador de la AI contribuye a corregir la albuminemia en este contexto. Métodos: en este ensayo clínico, 43 pacientes con ICA, hipoalbuminemia (albúmina sérica ≤ 3,4 g/dl) y AI elevada [proteína C-reactiva (PCR)  25 mg/l] fueron asignados aleatoriamente a recibir ácidos grasos omega-3 (4 g diarios) o placebo durante 4 semanas. La albuminemia y la PCR se reevaluaron en las semanas 1 y 4. Se realizó un análisis de la varianza para medidas repetidas. Resultados: la edad media era de 75,6 ± 8,8 años, el 72,1 % eran varones y la etiología más frecuente era la isquémica (46,5 %). Los dos grupos fueron homogéneos en sus características basales. Se encontró un incremento significativo de la concentración de albúmina en la semana 4 con respecto a la basal (p del efecto tiempo < 0,001), sin que se hallaran diferencias entre los grupos ni en la semana 1 ni en la 4. La PCR descendió significativamente ya en la semana 1 (p del efecto tiempo < 0,001), sin que se encontraran diferencias entre los grupos ni en la semana 1 ni en la 4. Conclusión: en los pacientes con ICA, hipoalbuminemia y AI elevada, la albuminemia se normaliza en la semana 4 mientras que la PCR desciende significativamente en la primera semana. En este contexto, ambos efectos son independientes de la adición de altas dosis de ácidos grasos omega-3.

Characterization of an Agarophyton chilense Oleoresin Containing PPARγ Natural Ligands with Insulin-Sensitizing Effects in a C57Bl/6J Mouse Model of Diet-Induced Obesity and Antioxidant Activity in Caenorhabditis elegans.

The biomedical potential of the edible red seaweed Agarophyton chilense (formerly Gracilaria chilensis) has not been explored. Red seaweeds are enriched in polyunsaturated fatty acids and eicosanoids, which are known natural ligands of the PPARγ nuclear receptor. PPARγ is the molecular target of thiazolidinediones (TZDs), drugs used as insulin sensitizers to treat type 2 diabetes mellitus. Medical use of TZDs is limited due to undesired side effects, a problem that has triggered the search for selective PPARγ modulators (SPPARMs) without the TZD side effects. We produced Agarophyton chilense oleoresin (Gracilex®), which induces PPARγ activation without inducing adipocyte differentiation, similar to SPPARMs. In a diet-induced obesity model of male mice, we showed that treatment with Gracilex® improves insulin sensitivity by normalizing altered glucose and insulin parameters. Gracilex® is enriched in palmitic acid, arachidonic acid, oleic acid, and lipophilic antioxidants such as tocopherols and ß-carotene. Accordingly, Gracilex® possesses antioxidant activity in vitro and increased antioxidant capacity in vivo in Caenorhabditis elegans. These findings support the idea that Gracilex® represents a good source of natural PPARγ ligands and antioxidants with the potential to mitigate metabolic disorders. Thus, its nutraceutical value in humans warrants further investigation.

Discovery of Novel Substituted N-(4-Amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide Analogues as Potent Human Adenovirus Inhibitors.

An effective therapy for human adenovirus (HAdV) infections in immunocompromised patients and healthy individuals with community-acquired pneumonia remains an unmet medical need. We herein reported a series of novel substituted N-(4-amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide analogues as potent HAdV inhibitors. Compounds 6, 15, 29, 40, 43, 46, 47, and 54 exhibited increased selectivity indexes (SI > 100) compared to the lead compound niclosamide, while maintaining sub-micromolar to low micromolar potency against HAdV. The preliminary mechanistic studies indicated that compounds 6 and 43 possibly target the HAdV DNA replication process, while compounds 46 and 47 suppress later steps of HAdV life cycle. Notably, among these derivatives, compound 15 showed improved anti-HAdV activity (IC50 = 0.27 µM), significantly decreased cytotoxicity (CC50 = 156.8 µM), and low in vivo toxicity (maximum tolerated dose = 150 mg/kg in hamster) as compared with niclosamide, supporting its further in vivo efficacy studies for the treatment of HAdV infections.

Exploration of piperazine-derived thioureas as antibacterial and anti-inflammatory agents. In vitro evaluation against clinical isolates of colistin-resistant Acinetobacter baumannii.

A. baumannii is one of the most important multidrug-resistant microorganisms in hospital units. It is resistant to many classes of antibiotics and the development of new therapeutic strategies is necessary. The aim of this study was to evaluate the antibacterial activity of a set of piperazine-derived thioureas against 13 clinical strains of colistin-resistant A. baumannii. Six derivatives were identified to inhibit bacterial growth of 46% of the A. baumannii strains at low micromolar concentrations (Minimum Inhibitory Concentration from 1.56 to 6.25 µM). A common structural feature in most active compounds was the presence of a 3,5-bis-trifluoromethyl phenyl ring at the thiourea function. In addition, the ability of the compounds to inhibit production of nitric oxide (NO) was examined in RAW 264.7 murine macrophages, highlighting the potential of piperazine-derived thioureas as promising scaffolds for the design of new combined anti-bacterial/anti-inflammatory agents.

Direct and Fast Screening of New Psychoactive Substances Using Medical Swabs and Atmospheric Solids Analysis Probe Triple Quadrupole with Data-Dependent Acquisition.

New psychoactive substances (NPS) have become a serious public health problem, as they are continuously changing their structures and modifying their potency and effects on humans, and therefore, novel compounds are unceasingly appearing. One of the major challenges in forensic analysis, particularly related to the problem of NPS, is the development of fast screening methodologies that allow the detection of a wide variety of compounds in a single analysis. In this study, a novel application of the atmospheric solids analysis probe (ASAP) using medical swabs has been developed. The swab-ASAP was coupled to a triple quadrupole mass analyzer working under a data-dependent acquisition mode in order to perform a suspect screening of NPS in different types of samples as well as on surfaces. The compounds were automatically identified based on the observed fragmentation spectra using an in-house built MS/MS spectra library. The developed methodology was applied for the identification of psychoactive substances in research chemicals and herbal blends. The sensitivity of the method, as well as its applicability for surface analysis, was also assessed by identifying down to 1 µg of compound impregnated onto a laboratory table. Another remarkable application was the identification of cathinones and synthetic cannabinoids on the fingers of potential consumers. Interestingly, our data showed that NPS could be identified on the fingers after being in contact with the product and even after cleaning their hands by shaking off with a cloth. The methodology proposed in this paper can be applied for routine analyses of NPS in different matrix samples without the need to establish a list of target compounds prior to analysis.

Investigation on the consumption of synthetic cannabinoids among teenagers by the analysis of herbal blends and urine samples.

The use of synthetic cannabinoids (SCs), which escape conventional detection systems, may be a good alternative to elude routine drug analysis for cannabis. The detection of these drugs in urine is unusual due to their complete and fast metabolism, therefore requiring alternative strategies. In this work, an investigation has been made on SCs consumption by minors (less than 18 years old) in juvenile offenders' centres. 667 urine samples (from 127 minors) were collected after their permits with stay at home. We also studied the SCs from 7 herbal blends available at the smartshop frequented by the minors. Both, urine and herbal blends, were analysed by liquid chromatography coupled to high resolution mass spectrometry. The analysis of urine confirmed the absence of more than 200 SCs investigated. Thus, the focus was made on metabolites reported for those SCs identified in the herbal blends collected from the smart-shop. The major metabolites of XLR-11 and UR-144 (N-pentanoic acid and N-(5-hydroxypentyl)) were found in several urine samples. Apart from the main metabolites included in the initial searching, a thorough investigation of more metabolites for these SCs was additionally performed, including MS/MS experiments for the tentative identification of compounds detected in the urine samples. The 16 samples positive to the XLR-11 metabolites were assigned to 6 minors, only 2 of which had recognized consumption. On the basis of the results obtained, preventive and therapeutic interventions must be implemented to reduce the consumption of psychoactive substances and to improve the risk-perception of these substances by minors.

[Content of discussions about cardiopulmonary resuscitation with elderly patients]. / Contenu des discussions concernant la réanimation cardiopulmonaire avec les patients âgés.

Openly talking with caregivers and physicians about medical decisions to prolong life, such as cardiopulmonary resuscitation, offers patients the opportunity to ensure that these decisions will be in line with their values and expectations, and thereby promote their autonomy and responsibility in health care. In order to support -informed and shared decision-making, it is important to share with the patient relevant information concerning their life-threatening condition (including risks of cardiac arrest, risks associated with the resuscitation procedure, immediate and long-term survival, and the impact of the procedure on quality of life), and encourage a -holistic discussion of the goals of care.

Le fait de discuter ouvertement avec leur médecin des décisions médicales concernant la prolongation de la vie, telle la réani­mation cardiopulmonaire, permet aux patients d'être rassurés sur le fait que ces décisions seront en conformité avec leurs ­valeurs et leurs attentes ; ceci favorise ainsi leur autonomie et leur responsabilité dans le projet de soins. Afin de soutenir une prise de décision informée et partagée, il est important de partager avec le patient les informations pertinentes par rapport à son pronostic vital (y compris les risques de subir un arrêt cardiaque, les risques associés à la procédure de réanimation, les chances de survie immédiate et à long terme, et l'impact de la procédure sur la qualité de vie), et d'encourager une discussion globale sur les objectifs des soins.

GRAZAX®: a sublingual immunotherapy vaccine for Hay fever treatment: from concept to commercialization.

Allergen immunotherapy has been used for more than 100 y, but only recently underlying immunological mechanisms have started to be understood. New Allergy vaccines are now considered to be full pharmaceutical products, that should comply with general as well as specific pharmaceutical legal framework. GRAZAX® is the first global allergy vaccine developed in compliance with the new legal environment and is thus a reference for developing new allergy vaccines. Here, we provide a rationale description of GRAZAX®, providing a sequential description of its pharmaceutical and clinical development. With more than 25 clinical trials, involving more than 8000 patients, including as well three 5-y prospective clinical trials, GRAZAX® is a key product to understand the unique position of allergen-specific immunotherapy as a disease-modifying intervention.

Has the clinical profile of patients with nonvalvular atrial fibrillation treated with rivaroxaban changed in the last 5 years of use?

AIM: To analyze the evolution of clinical profile of patients with nonvalvular atrial fibrillation treated with rivaroxaban. METHODS: Retrospective study in which patients treated with rivaroxaban were divided into two groups according to the data in which the initial prescription was performed (November 2012-December 2013 and January 2014-January 2017). RESULTS: 211 patients (mean age 76.7 ± 9.2 years; CHA2DS2-VASc 3.8 ± 1.5; HAS-BLED 2.0 ± 0.8.) were included. Age and bleeding risk were higher in those subjects in which the prescription started earlier. Rates of stroke/TIA, major bleeding and intracranial hemorrhage were 2.3/4.2/0.6 events/100 patient-years, respectively. CONCLUSION: Although, the initial prescription of rivaroxaban was mainly performed in very elderly patients and/or with a higher bleeding risk, this has been extended to the overall nonvalvular atrial fibrillation population.

Nutritional intervention in acute heart failure patients with undernutrition and normalbuminemia: A subgroup analysis of PICNIC study.

BACKGROUND & AIMS: Hypoalbuminemia is common in acute heart failure (HF) patients and has been associated with increased hospital mortality and long-term mortality. Undernutrition is a factor causing hypoalbuminemia. The PICNIC study results show that a nutritional intervention in undernourished acute HF patients reduces the risks of all-cause death and of readmission for HF. We aimed to investigate whether the efficacy of a nutritional intervention is consistent among the subgroups of patients with and without hypoalbuminemia. METHODS: In PICNIC study, a total of 120 malnourished hospitalized patients due to acute HF were randomized to conventional HF treatment or conventional HF treatment combined with an individualized nutritional intervention. The primary endpoint was a composite of all-cause death or readmission for worsening of HF, with a maximum follow-up of 12 months. In this post-hoc sub-analysis we assessed the interaction of the effects of a nutritional intervention among patients with and without hypoalbuminemia. Analysis was by intention to treat. RESULTS: 59 (49,2%) patients demonstrated hypoalbuminemia and 61 (50,8%) had normalbuminemia. At 12 months, the number of events for the primary endpoint in the intervention group compared with the control group was consistent among patients with hypoalbuminemia (28.6% intervention vs 61.3% control, HR 0,35, 95% CI 0,15-0,81) and those without (25.8% intervention vs 60% control, HR 0,35, 95% CI 0,15-0,79; interaction p = 0,86). CONCLUSION: There was no evidence that the relative efficacy of a nutritional intervention in undernourished acute HF patients was different between patients with normalbuminemia and those with hypoalbuminemia.

Endoscopically placed stents: a useful alternative for the management of refractory benign cervical esophageal stenosis.

INTRODUCTION: Benign esophageal strictures are relatively frequent and can severely affect the quality of life of a patient. Stenting has been proposed for the treatment of refractory cases. Lesions affecting the cervical esophagus are more difficult to treat, and the placement of stents in this location has traditionally been restricted due to potential adverse events. The aim of this study was to describe the efficacy and safety of endoscopic stenting in the management of refractory benign cervical esophageal strictures (RBCES) in a single-center cohort study. METHODS: We analyzed 12 patients with RBCES (Kochman's criteria) and severe dysphagia. We recorded previous endoscopic treatments, stricture characteristics and demographic data. The two types of stents used were fully covered self-expandable metallic stents (FCSEMS) and uncovered biodegradable stents (BDS). FCSEMS were removed eight weeks after placement, and BDS were followed-up until degradation. We assessed technical and clinical success, rate of stricture recurrence and adverse events. RESULTS: The mean age of participants was 64 years (range 30-85). A total of 23 stents (13 FCSEMS and 10 BDS) were placed in 12 patients (median 1.92, range 1-4). The technical success rate was 96% (22/23 stents). Eight patients (66.6%) maintained adequate oral intake at the end of follow-up (median 33.3 months, range 3-84 months). Migration was recorded in 7/23 stents (30.4%) and epithelial hyperplasia in 4/23 stents (17.4%). No severe adverse events were noted. All patients complained of minor cervical pain after placement that was well controlled with mild analgesia. CONCLUSIONS: Endoscopic stent therapy seems to be effective and safe in the management of RBCES.

Perspectives for clinical use of engineered human host defense antimicrobial peptides.

Infectious diseases caused by bacteria, viruses or fungi are among the leading causes of death worldwide. The emergence of drug-resistance mechanisms, especially among bacteria, threatens the efficacy of all current antimicrobial agents, some of them already ineffective. As a result, there is an urgent need for new antimicrobial drugs. Host defense antimicrobial peptides (HDPs) are natural occurring and well-conserved peptides of innate immunity, broadly active against Gram-negative and Gram-positive bacteria, viruses and fungi. They also are able to exert immunomodulatory and adjuvant functions by acting as chemotactic for immune cells, and inducing cytokines and chemokines secretion. Moreover, they show low propensity to elicit microbial adaptation, probably because of their non-specific mechanism of action, and are able to neutralize exotoxins and endotoxins. HDPs have the potential to be a great source of novel antimicrobial agents. The goal of this review is to provide an overview of the advances made in the development of human defensins as well as the cathelicidin LL-37 and their derivatives as antimicrobial agents against bacteria, viruses and fungi for clinical use.

Occurrence and fate of illicit drugs and pharmaceuticals in wastewater from two wastewater treatment plants in Costa Rica.

Chemical analysis of raw wastewater in order to assess the presence of biological markers entering a wastewater treatment plant can provide objective information about the health and lifestyle of the population connected to the sewer system. This work was performed in a tropical country of Central America, Costa Rica, with the aim of extending this knowledge to new world regions. This work is the first to report wastewater-based epidemiological data on the use of illicit drugs in this region of the world. Composite wastewater samples from the influents of two different wastewater treatment facilities and surface water samples from surrounding areas were collected applying the best practice protocol and analysed to investigate the occurrence and fate of selected illicit drugs of abuse and pharmaceuticals. Results showed the presence of chemical indicators of the classic drugs cocaine and cannabis at high concentration levels, besides the moderate presence of the opiates codeine and morphine. Neither the worldwide commonly used psychoactive substances of abuse such as synthetic phenethylamines, nor pharmaceuticals from the family of benzodiazepines were detected, demonstrating the spatial differences in drug use among different world regions. In addition, effluent wastewater samples were analysed and compared to influent concentrations in order to evaluate the decrease in concentration of the targeted analytes through two treatment technologies. As a final step, a wide-scope qualitative screening, including hundreds of suspect compounds, was applied in order to have a better knowledge on the presence of pharmaceuticals in waters and to assess the potential impact of the treated wastewater into the receiving aquatic ecosystems.

New molecules and adjuvants in the treatment of infections by Acinetobacter baumannii.

INTRODUCTION: The current problems of the treatment of infections by Acinetobacter baumannii are linked with the increase of multidrug- and extensive-drug resistance and the lack of development of new antimicrobial drugs for Gram-negative bacilli. For these reasons, new alternatives for the treatment and control of severe infections by A. baumannii are necessary. Several studies have reported the effect of adjuvants to restore the efficacy of existing antimicrobial agents. AREAS COVERED: In the present review, the authors describe the main results in the development of adjuvant drugs as well as new data on antimicrobial peptides, in monotherapy or in combination therapy with existing antimicrobial agents, which have shown promising preclinical results in vitro and in vivo. EXPERT OPINION: The preclinical evaluation of adjuvants and antimicrobial peptides, in monotherapy or in combination therapy, for A. baumannii infections has shown promising results. However, caution is needed and further extensive in vivo studies and clinical trials have to be performed to confirm the potential use of these adjuvants as true therapeutic alternatives.

Comprehensive monitoring of organic micro-pollutants in surface and groundwater in the surrounding of a solid-waste treatment plant of Castellón, Spain.

The solid-waste treatment plant of RECIPLASA is located in the municipality of Onda (Castellón province), which is an important agricultural area of Spain, with predominance of citrus crops. In this plant, all urban solid wastes from the town of Castellón (around 200,000 inhabitants) and other smaller towns as Almassora, Benicàssim, Betxí, Borriana, L'Alcora, Onda and Vila-Real are treated. In order to evaluate the potential impact of this plant on the surrounding water, both surface and groundwater, a comprehensive monitoring of organic pollutants has been carried out along 2011, 2012 and 2013. To this aim, an advanced analytical strategy was applied for wide-scope screening, consisting on the complementary use of liquid chromatography (LC) and gas chromatography (GC) coupled to mass spectrometry (MS) with quadrupole (Q)-time of flight analyser (TOF). A generic solid-phase extraction with Oasis HLB cartridges was applied prior to the chromatographic analysis. The screening included more than 1500 organic pollutants as target compounds, such as pesticides, pharmaceuticals, veterinary drugs, drugs of abuse, UV-filters, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), among others. Pesticides, mainly herbicides, were the compounds more frequently detected. Other compounds as antioxidants, cosmetics, drugs of abuse, PAHs, pharmaceuticals and UV filters, were also identified in the screening though at much lower frequency. Once the screening was made, quantitative analysis focused on the compounds more frequently detected was subsequently applied using LC coupled to tandem MS with triple quadrupole analyser. In this way, up to 24 pesticides and transformation products (TPs), 7 pharmaceuticals, one drug of abuse and its metabolite could be quantified at sub-ppb concentrations. Along the three years of study, ten compounds were found at concentrations higher than 0.1µg/L. Most of them were pesticides and TPs, a fact that illustrates that the main source of pollution seems to be the agricultural activities in this area.

Analysis of comorbidities and therapeutic approach for allergic rhinitis in a pediatric population in Spain.

BACKGROUND: Allergic rhinitis (AR) is the most common chronic disease in children. The main objective of this study was to analyze the comorbidities and therapeutic approaches for AR in a Spanish pediatric population. METHODS: Children aged 6 to 12 years with AR were included in an observational, cross-sectional, multicenter study. RESULTS: 1,275 children were recruited from 271 centers. AR was intermittent in 59.5% of cases, persistent in 40.5%, seasonal in 60.7%, and perennial in 39.3% of patients. The most frequent comorbidities were conjunctivitis (53.6%), asthma (49.5%), atopic dermatitis (40%), rhinosinusitis(26.1%), otitis media (23.8%), and adenoid hypertrophy (17.3%). Overall, patients with persistent, moderate or severe, AR were more likely to present comobidities, except for food allergy and urticaria. The most common drugs used for treatment of AR were oral antihistamines(76%), nasal corticosteroids(49%) and a combination of both (45%). Antihistamines and nasal corticosteroids were used on demand (<18 days) in 38 and 41% of patients, respectively; for 18-30 days in 22 and 27%; for 1-3 months in 31 and 29%; and for more than 3 months in 8 and 3%, respectively. Eye drops were used in 32% and specific immunotherapy in 21% of patients. CONCLUSION: Comorbidities are frequent in children with AR, supporting the notion of allergy as a systemic disease. Severity and duration of AR were significantly associated with presence of most of comorbidities. The most common drugs used for AR treatment were oral antihistamines, followed by nasal corticosteroids and a combination of both used on demand.

Quadrupole-time-of-flight mass spectrometry screening for synthetic cannabinoids in herbal blends.

'Legal highs' are novel substances which are intended to elicit a psychoactive response. They are sold from 'head shops', the internet and from street suppliers and may be possessed without legal restriction. Several months ago, a 19-year-old woman came searching for medical treatment as she had health problems caused by smoking legal highs. The substances were sold as herbal blends in plastic bags under four different labels. In this work, samples of these herbal blends have been analysed to investigate the presence of psychoactive substances without any reference standard being available at the laboratory. A screening strategy for a large number of synthetic and natural cannabinoids has been applied based on the use of ultra-high pressure liquid chromatography coupled to quadrupole-time of flight mass spectrometry (UHPLC-QTOF MS) under MS(E) mode. A customized home-made database containing literature-based exact masses for parent and product ions of around 200 synthetic and natural cannabinoids was compiled. The presence of the (de)protonated molecule measured at its accurate mass was evaluated in the samples. When a peak was detected, collision-induced dissociation fragments and characteristic isotopic ions were also evaluated and used for tentative identification. After this tentative identification, four synthetic cannabinoids (JWH-081, JWH-250, JWH-203 and JWH-019) were unequivocally confirmed by subsequent acquisition of reference standards. The presence in the herbal blends of these synthetic cannabinoids might explain the psychotic and catatonic symptoms observed in the patient, as JWH compounds could act as potent agonists of CB1 and CB2 receptors located in the Limbic System and Basal ganglia of the human brain.

CuTe nanocrystals: shape and size control, plasmonic properties, and use as SERS probes and photothermal agents.

We report a procedure to prepare highly monodisperse copper telluride nanocubes, nanoplates, and nanorods. The procedure is based on the reaction of a copper salt with trioctylphosphine telluride in the presence of lithium bis(trimethylsilyl)amide and oleylamine. CuTe nanocrystals display a strong near-infrared optical absorption associated with localized surface plasmon resonances. We exploit this plasmon resonance for the design of surface-enhanced Raman scattering sensors for unconventional optical probes. Furthermore, we also report here our preliminary analysis of the use of CuTe nanocrystals as cytotoxic and photothermal agents.