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Nanocarriers, and especially nanostructured lipid carriers (NLC), represent one of the most effective systems for topical drug administration. NLCs are biodegradable, biocompatible and provide a prolonged drug release. The glutamate release inhibitor Riluzole (RLZ) is a drug currently used for amyotrophic lateral sclerosis (ALS), with anti-proliferative effects potentially beneficial for diseases with excessive cell turnover. However, RLZ possesses low water solubility and high light-sensibility. We present here optimized NLCs loaded with RLZ (RLZ-NLCs) as a potential topical treatment. RLZ-NLCs were prepared by the hot-pressure homogenization method using active essential oils as liquid lipids, and optimized using the design of experiments approach. RLZ-NLCs were developed obtaining optimal properties for dermal application (mean size below 200 nm, negative surface charge and high RLZ entrapment efficacy). In vitro release study demonstrates that RLZ-NLCs allow the successful delivery of RLZ in a sustained manner. Moreover, RLZ-NLCs are not angiogenic and are able to inhibit keratinocyte cell proliferation. Hence, a NLCs delivery system loading RLZ in combination with natural essential oils constitutes a promising strategy against keratinocyte hyperproliferative conditions., This research was funded by the Spanish Ministry of Science and Innovation (PID2021-122187NB-C32 to M.G., PID2020-114477RB-I00 to C.S. and PID2021-126249OA-I00 to J.M. from the MCIN/ AEI /10.13039/501100011033).

Introduction Pneumocystis jirovecii pneumonia (PJP) is a life-threatening condition in immunocompromised children. Our aim is to analyze the epidemiologic and clinical characteristics of PJP cases in our setting, describing the prognosis and related risk factors. Methods Retrospective study including all pediatric patients (≤18 years) with PJP admitted to our hospital (January 1989–December 2016). Case definition: patient with acute pneumonitis and P. jirovecii detection in bronchoalveolar lavage or tracheal aspirate using methenamine silver or direct antibody fluorescence staining, or Real-Time Polymerase Chain Reaction. Results Twenty-five cases (0.9 cases/year) were identified. Median age was 2.2 years (interquartile range: 0.5–12.3), 64% were male, and 12% were receiving appropriate antimicrobial prophylaxis. Cytomegalovirus coinfection was detected in 26% cases. The most common underlying diseases were primary immunodeficiencies (36%) and 16% were human immunodeficiency virus (HIV)-infected children. Eighteen were admitted to the pediatric intensive care unit (PICU) and overall 30-day mortality was 20% (31.25% in HIV non-infected vs 0% in HIV-infected patients; OR: 0.33, 95% CI: 0.02–7.24, p = 0.55). Clinical outcome was worse in girls and those patients requiring adjuvant steroid therapy. HIV non-infected patients, higher initial LDH, younger age and shorter time elapsed between diagnosis of PJP and the underlying disease were identified as risk factors to be admitted to the PICU (p = 0.05, p = 0.026, p = 0.04 and p = 0.001 respectively). Conclusion Accompanying the widespread use of combined antiretroviral therapy, PJP has been diagnosed almost exclusively in HIV non-infected children at our institution. Moreover, significant higher morbidity rates associated with PJP are seen in this group of patients.

STUDY OBJECTIVES: The majority of studies investigating the association between sleep and Alzheimer's disease (AD) biomarkers have been performed in healthy participants. Our objective was to investigate the association between sleep and several biomarkers that reflect distinct aspects of AD physiopathology. METHODS: The cohort included 104 individuals with mild-moderate AD. The participants were submitted to one-night polysomnography, and cerebrospinal fluid was collected in the following morning to measure the selected biomarkers associated with amyloid deposition, tau pathology, neurodegeneration, axonal damage, synaptic integrity, neuroinflammation, and oxidative damage. RESULTS: There was a positive correlation between neurofilament light (NF-L) and the time spent in stage 1 of non-rapid eyes movement (NREM) (N1) sleep and a negative correlation between this marker and the time spent in stage 3 of NREM (N3) sleep. Accordingly, we observed that deep sleep was associated with lower levels of NF-L, whereas light sleep increased the probability of having higher levels of this marker. Furthermore, chitinase-3-like-1 (YKL-40) was negatively correlated with sleep efficiency, the time spent in stage 2 of NREM (N2) sleep, and the time spent in N3 sleep. Conversely, there was a positive correlation between N3 sleep and the oxidative protein damage markers N-ε-(carboxyethyl)lysine and N-ε-(malondialdehyde)lysine. CONCLUSIONS: There were significant correlations between sleep parameters and AD biomarkers related to axonal damage and neuroinflammation, such as NF-L and YKL-40. A lack of deep sleep was associated with higher levels of NF-L. This highlights a potential role for NF-L as a biomarker of sleep disruption in patients with mild-moderate AD in addition to its role in predicting neurodegeneration and cognitive decline. This study was supported by the Generalitat of Catalonia, Department of Health (PERIS 2019 SLT008/18/00050) and “Fundació La Marató TV3” (464/C/2014) to G.P.R.; by the Spanish Ministry of Economy and Competitiveness, Institute of Health Carlos III (grant number P114/00328), the Spanish Ministry of Science, Innovation and University (RTI 2018–099) of Catalonia, and Agency for Management of University and Research grants (2017 SGR696) to R.P. This study has been co-financed by FEDER funds from the European Union (“A way to build Europe”). IRBLleida is a CERCA Programme/Generalitat of Catalonia. F.D. was supported by the Agency for Management of University and Research grants (FI_B100153).

This study is an extension of our previous paper on the interaction of AcP6-2 and the VIR576 peptides with DPPC: DPPS (3:2) and DMPC: DMPS (3:2) model membranes [Colloids and Surfaces A. 532 (2017) 483–492]. In the present contribution, the temperature effect and the role of the lipid phase in the lipid-peptide interaction were investigated. Moreover at the same time, relating them to HIV-1 FP inhibition. Several biophysics experiments as lipid-peptide binding, Trp fluorescence quenching and Atomic Force Microscopy (AFM) visualization were used to evidence the different interaction of the peptide depending on the physical state of the lipids. In addition, the inhibition effect of HIV-1 FP by P6-2 VIR576 peptide was conducted by fluorescence resonance energy transfer (FRET) and also by AFM microscopy. P6-2VIR576 showed a preference to the liquid crystalline phases from where the peptide can diffuse and interact with the gel phases. Firstly, P6-2VIR576 induces a rigidifying of the membrane to finally, promote the vanishing of these gel phases. Concerning to the inhibition of HIV-1 FP peptide by P6-2VIR576 peptide, FRET and AFM results evidencing P6-2VIR576 peptide is a promising structure to be in mind in the development of new or improved drugs in HIV therapies.

Puntos clave • Se estima que un 10% de la poblacion adulta padece insomnio cronico. • Ante un paciente que consulta por insomnio de reciente aparicion, el medico de familia debe plantearse su tratamiento etiologico. • Es importante realizar una correcta anamnesis de la persona con insomnio para poder saber que es lo que puede estar causando el insomnio. • El insomnio es causa, efecto y comorbilidad frecuente de padecimientos medicos, psiquiatricos y de consumo de sustancias. • El insomnio puede ser el resultado del tratamiento de otros padecimientos. • La intervencion terapeutica temprana es crucial para limitar las consecuencias negativas que puede suponer la cronificacion del insomnio. • El primer paso del tratamiento del insomnio consiste en informar al paciente, para que comprenda el origen de su problema y para que conozca las medidas que se pueden llevar a cabo para resolverlo. • Los hipnoticos son de utilidad si se usan en la dosis minima efectiva y por el menor tiempo necesario. Su funcion es el alivio sintomatico y prevenir la accion de los factores perpetuantes. • El tratamiento del insomnio cronico es complejo y debe incluir obligatoriamente metodos no farmacologicos, en especial la explicacion de habitos correctos de sueno. • La terapia cognitivo-conductual (TCC) ha demostrado ser, al menos, tan efectiva como los farmacos, y sus beneficios se mantienen en el tiempo una vez que finaliza la administracion activa de la TCC.

The interaction of P6-2VIR576, a peptide derived from the GBV-C E2 structural protein, with anionic lipid membranes (DMPC:DMPS (3:2) and DPPC:DPPS (3:2)) and its effect on HIV-1 fusion peptide (HIV-1 FP) binding with the membrane were studied. P6-2VIR576 showed higher surface activity than its parent peptide AcP6-2, with an area per molecule value in π-A compression isotherms approximately twice that of AcP6-2. Interaction studies, involving penetration experiments in lipid monolayers and lipid bilayer binding assays, demonstrated that P6-2VIR576 interacted better with the more rigid membrane DPPC:DPPS (3:2), with an exclusion pressure slightly lower than the biological membrane pressure (24–30 mN m−1). This, together with the results of the binding experiments and considering the effect of ionic strength and changes in membrane dipole potential, indicate a lipid-peptide interaction driven by electrostatic forces followed by hydrophobic interactions. Morphological surface analysis by fluorescence microscopy of Langmuir-Blodgett monolayers revealed that P6-2VIR576 suppressed the interaction of HIV-1 FP with the membrane.

Rehabilitation for return to training is an interdisciplinary, specific and individualised process that is geared towards the sportsman's optimal availability for competition after a sports injury. This process begins after medical discharge and continues up to the return to play, involving the different professionals in the field of healthcare and led by the sports physician. Planning consists of three phases, defined by muscular action (isometric, concentric and eccentric); kinetic chain (closed or open); range of movement (internal, medial, external and total); and exercise orientation (general, directed and specific). Return to play must be agreed upon on the basis of objective information on the recovery stage of the injury, the state of fitness, and the sportsman's own perception.

Background Pantothenate kinase-associated neurodegeneration is a progressive neurological disorder occurring in both childhood and adulthood. The objective of this study was to design and pilot-test a disease-specific clinical rating scale for the assessment of patients with pantothenate kinase-associated neurodegeneration. Methods In this international cross-sectional study, patients were examined at the referral centers following a standardized protocol. The motor examination was filmed, allowing 3 independent specialists in movement disorders to analyze 28 patients for interrater reliability assessment. The scale included 34 items (maximal score, 135) encompassing 6 subscales for cognition, behavior, disability, parkinsonism, dystonia, and other neurological signs. Results Forty-seven genetically confirmed patients (30 ± 17 years; range, 6-77 years) were examined with the scale (mean score, 62 ± 21; range, 20-106). Dystonia with prominent cranial involvement and atypical parkinsonian features were present in all patients. Other common signs were cognitive impairment, psychiatric features, and slow and hypometric saccades. Dystonia, parkinsonism, and other neurological features had a moderate to strong correlation with disability. The scale showed good internal consistency for the total scale (Cronbach's α = 0.87). On interrater analysis, weighted kappa values (0.30-0.93) showed substantial or excellent agreement in 85% of the items. The scale also discriminated a subgroup of homozygous c.1583C>T patients with lower scores, supporting construct validity for the scale. Conclusions The proposed scale seems to be a reliable and valid instrument for the assessment of pediatric and adult patients with pantothenate kinase-associated neurodegeneration. Additional validation studies with a larger sample size will be required to confirm the present results and to complete the scale validation testing. © 2017 International Parkinson and Movement Disorder Society

Summary Objective To reduce ventilator-associated infections (VARI) and improve outcomes for children. Methods This prospective interventional cohort study was conducted in a paediatric intensive care unit (PICU) over three periods: pre-intervention, early post-intervention, and late post-intervention. These children were on mechanical ventilation (MV) for ≥48h. Results Overall, 312 children (11.9% of whom underwent tracheostomy) and 6187 ventilator-days were assessed. There was a significant reduction in ventilator-associated pneumonia (VAP) among tracheostomized patients (8.16, 3.27, and 0.65 per 1000 tracheostomy ventilation-days before the intervention, after the general bundle implementation, and after the tracheostomy intervention, respectively). The median time from onset of MV to diagnosis of ventilator-associated tracheobronchitis (VAT) increased from 5.5 to 48 days in the late post-intervention period ( p =0.004), and was associated with a significant increase in median 28-day ventilator-free days and PICU-free days. Tracheostomy (odds ratio 7.44) and prolonged MV (odds ratio 2.75) were independent variables significantly associated with VARI. A trend towards a reduction in PICU mortality was observed, from 28.4% to 16.6% (relative risk 0.58). Conclusions The implementation of a care bundle to prevent VARI in children had a different impact on VAP and VAT, diminishing VAP rates and delaying VAT onset, resulting in reduced healthcare resource use. Tracheostomized children were at increased risk of VARI, but preventive measures had a greater impact on them.

Introduction: Neuroinflammation is a potential player in neurodegenerative conditions, particularly the aggressive ones, such as multiple system atrophy (MSA). Previous reports on cytokine levels in MSA using serum or cerebrospinal fluid (CSF) have been inconsistent, including small samples and a limited number of cytokines, often without comparison to Parkinson's disease (PD), a main MSA differential diagnosis. Methods: Cross-sectional study of CSF levels of 38 cytokines using a multiplex assay in 73 participants: 39 MSA patients (19 with parkinsonian type [MSAp], 20 with cerebellar type [MSAc]; 31 probable, 8 possible), 19 PD patients and 15 neurologically unimpaired controls. None of the participants was under non-steroidal anti-inflammatory drugs at the time of the lumbar puncture. Results: There were not significant differences in sex and age among participants. In global non-parametric comparisons FDR-corrected for multiple comparisons, CSF levels of 5 cytokines (FGF-2, IL-10, MCP-3, IL-12p40, MDC) differed among the three groups. In pair-wise FDR-corrected non-parametric comparisons 12 cytokines (FGF-2, eotaxin, fractalkine, IFN-α2, IL-10, MCP-3, IL-12p40, MDC, IL-17, IL-7, MIP-1β, TNF-α) were significantly higher in MSA vs. non-MSA cases (PD + controls pooled together). Of these, MCP-3 and MDC were the most significant ones, also differed in MSA vs. PD, and were significant MSA-predictors in binary logistic regression models and ROC curves adjusted for age. CSF levels of fractalkine and MIP-1α showed a strong and significant positive correlation with UMSARS-2 scores. Conclusion: Increased CSF levels of cytokines such as MCP-3, MDC, fractalkine and MIP-1α deserve consideration as potential diagnostic or severity biomarkers of MSA. info:eu-repo/semantics/publishedVersion

Introduction The finding of mutations of the COQ2 gene and reduced coenzyme Q10 levels in the cerebellum in multiple system atrophy (MSA) suggest that coenzyme Q10 is relevant to MSA pathophysiology. Two recent studies have reported reduced coenzyme Q10 levels in plasma and serum (respectively) of MSA patients compared to Parkinson's disease and/or control subjects, but with largely overlapping values, limited comparison with other parkinsonisms, or dependence on cholesterol levels. We hypothesized that cerebrospinal fluid (CSF) is reliable to assess reductions in coenzyme Q10 as a candidate biomarker of MSA. Methods In this preliminary cross-sectional study we assessed CSF coenzyme Q10 levels in 20 patients with MSA from the multicenter Catalan MSA Registry and of 15 PD patients, 10 patients with progressive supranuclear palsy (PSP), and 15 control subjects from the Movement Disorders Unit Biosample Collection of Hospital Clinic de Barcelona. A specific ELISA kit was used to determine CSF coenzyme Q10 levels. CSF coenzyme Q10 levels were compared in MSA vs. the other groups globally, pair-wise, and by binary logistic regression models adjusted for age, sex, disease severity, disease duration, and dopaminergic treatment. Results CSF coenzyme Q10 levels were significantly lower in MSA than in other groups in global and pair-wise comparisons, as well as in multivariate regression models. Receiver operating characteristic curve analyses yielded significant areas under the curve for MSA vs. PD, PSP and controls. Conclusions These findings support coenzyme Q10 relevance in MSA. Low CSF coenzyme Q10 levels deserve further consideration as a biomarker of MSA.

Objectives To assess the prediction accuracy of the 2008 US Centers for Disease Control and Prevention (CDC) definitions for ventilator-associated pneumonia (VAP)/ventilator-associated tracheobronchitis (VAT), 2013 CDC definitions for ventilator-associated events (VAE) and a new VAE algorithm in the paediatric (Ped) population, the Ped-VAE. Methods We performed a prospective 13-month cohort study at a multidisciplinary paediatric intensive care unit (PICU). Primary endpoints were duration of ventilation episode, PICU or hospitalization length of stay from episode and episode mortality. Episodes without VAE (or VAP/VAT) served as comparison groups. Results One hundred eight episodes of ventilation (99 children) with 2554 ventilator-days were assessed. In episodes not meeting 2008 CDC definitions, a median of 6 ventilator-days (PICU stay 11 days) was documented (with eight deaths), not significantly different from episodes not meeting VAE or Ped-VAE definitions. Using 2008 CDC criteria, 11 (10.2%) respiratory infections (eight tracheobronchitis) were identified, seven VAEs using 2013 CDC criteria (6.4%) and 29 (26.8%) using Ped-VAE criteria (relative risk vs. 2008 CDC criteria 2.58; 95% confidence interval 1.36–4.91). In contrast with their comparison groups, episodes meeting 2008 CDC criteria did not significantly predict outcomes, whereas VAEs (only four possible VAPs) were associated with significantly more ventilation and PICU length of stay (12-day/8-day increase) and sevenfold increase in mortality. Ped-VAE did not increase mortality, but it was associated with 4-day increase in ventilation and PICU length of stay, with ten possible VAPs, and atelectasis (9/12) as the main paediatric ventilator-associated condition. Conclusions The 2008 CDC criteria did not predict outcomes, whereas VAE only identified very severe events. The Ped-VAE algorithm had more accuracy predicting outcomes by characterizing lower oxygenation changes and identifying hypoxaemia severity, a major driver of management.

Objective To examine the presence and characteristics of idiopathic REM sleep behavior disorder (IRBD) in a representative Caucasian sample from the elderly community of Lleida, Spain, attending primary care centers. Methods Participants were individuals aged 60 years or older who underwent routine visits in two primary care centers. They underwent a two-stage study; a validated screening single question for IRBD diagnosis (RBD1Q) followed by, in those who endorsed positive answer, clinical assessment by a neurologist plus video-polysomnography (V-PSG). Results Of 539 individuals (56.4% women, mean age 72.86 ± 8.20 years), 28 (5.2%) endorsed positively the RBD1Q. Four of these 28 refused further assessments. Four of the 24 remaining subjects underwent clinical assessment but refused V-PSG. Of the 20 who underwent clinical assessment plus V-PSG, REM sleep was not recorded in four (20%, all four taking antidepressants). V-PSG ruled out RBD in 12 subjects who had obstructive sleep apnea (n = 9), periodic limb movement disorder in sleep (n = 2) and normal sleep (n = 1). IRBD was diagnosed in four individuals giving an estimated prevalence of 0.74% (95% CI = 0.29–1.89). They were three men and one woman between 74 and 82 years of age who never reported dream-enacting behaviors to their doctors because they thought they represented a normal phenomenon despite suffering sleep-related injuries. These patients had history of violent sleep behaviors with an interval between estimated RBD onset and V-PSG of 4.5 ± 4.2 years. Conclusions IRBD is not uncommon in the elderly community and its demographic and clinical profile is similar to those diagnosed in sleep centers.

Study objectives To describe a group of patients referred because of abnormal sleep behaviors that were suggestive of rapid eye movement (REM) sleep behavior disorder (RBD) in whom video-polysomnography ruled out RBD and showed the reported behaviors associated with vigorous periodic limb movements during sleep (PLMS). Aims and methods Clinical history and video-polysomnography review of patients identified during routine visits in a sleep center. Results Patients were 15 men and 2 women with a median age of 66 (range: 48-77) years. Reported sleep behaviors were kicking (n = 17), punching (n = 16), gesticulating (n = 8), falling out of bed (n = 5), assaulting the bed partner (n = 2), talking (n = 15), and shouting (n = 10). Behaviors resulted in injuries in 3 bed partners and 1 patient. Twelve (70.6%) patients were not aware of displaying abnormal sleep behaviors that were only noticed by their bed partners. Ten (58.8%) patients recalled unpleasant dreams such as being attacked or chased. Video-polysomnography showed (1) frequent and vigorous stereotyped PLMS involving the lower limbs, upper limbs, and trunk (median PLMS index 61.2; median PLMS index in NREM sleep 61.9; during REM sleep only 8 patients had PLMS and their median PLMS index in REM sleep was 39.5); (2) abnormal behaviors (e.g., punching, groaning) during some of the arousals that immediately followed PLMS in NREM sleep; and (3) ruled out RBD and other sleep disorders such as obstructive sleep apnea. Dopaminergic agents were prescribed in 14 out of the 17 patients and resulted in improvement of abnormal sleep behaviors and unpleasant dreams in all of them. After dopaminergic treatment, follow-up video-polysomnography in 7 patients showed a decrease in the median PLMS index from baseline (108.9 vs. 19.2, p = .002) and absence of abnormal behaviors during the arousals. Conclusions Abnormal sleep behaviors and unpleasant dreams simulating RBD symptomatology may occur in patients with severe PLMS. In these cases, video-polysomnography ruled out RBD and identified prominent PLMS followed by arousals containing abnormal behaviors. Our cases represent an objectively documented subtype of periodic limb movement disorder causing abnormal sleep behaviors.

Sleep-related movement and behaviour disorders may have an impact on sleep quality and lead to daytime symptoms. These groups of conditions include diseases such as restless legs syndrome, periodic leg movements, and REM and NREM parasomnias. The knowledge of their clinical features and management is of utmost importance for the neurologist and sleep specialist. Frequently, these patients are referred to such specialists and it is relevant to know that certain sleep disorders may be associated with other neurological conditions.

Three synthetic peptide sequences of 18 amino acid each, corresponding to different fragments of the E2 capsid protein of GB virus C (GBV-C): SDRDTVVELSEWGVPCAT (P45), GSVRFPFHRCGAGPKLTK (P58) and RFPFHRCGAGPKLTKDLE (P59) have been characterized in order to find a relationship between their physicochemical properties and the results obtained in cellular models. Experiments were performed in presence and absence of the HIV fusion peptide (FP-HIV) due to the evidences that GBV-C inhibits AIDS progression. P45 peptide showed lower surface activity and less extent of penetration into 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (DMPS) (3:2, mol/mol) lipid monolayers than P58 and P59. However, P45 peptide presented higher capacity to inhibit FP-HIV induced cell–cell fusion than the other two sequences. These results were supported by fluorescence anisotropy measurements which indicated that P45 had a significant effect on the inhibition of FP-HIV perturbation of liposomes of the same lipid composition. Finally, atomic force microscopy (AFM) studies have evidenced the modification of the changes induced by the FP-HIV in the morphology of lipid bilayers when P45 was present in the medium.

Rehabilitation for return to training is an interdisciplinary, specific and individualised process to achieve optimal availability for competition after an athlete’s sports injury. This process requires a transversal, specific, progressive and previously planned design. The model will be individualized according to the injury, the athlete, the sport and its competitive schedule. The design is divided into 3 different phases and the duration of each one will be determined by premises previously set out for the achievement of specific clinical and conditional goals. Decision making process is assessed by objective information, but performance on professional context is a key factor to consider.

BACKGROUND: Pantothenate kinase-associated neurodegeneration is a progressive neurological disorder occurring in both childhood and adulthood. The objective of this study was to design and pilot-test a disease-specific clinical rating scale for the assessment of patients with pantothenate kinase-associated neurodegeneration. METHODS: In this international cross-sectional study, patients were examined at the referral centers following a standardized protocol. The motor examination was filmed, allowing 3 independent specialists in movement disorders to analyze 28 patients for interrater reliability assessment. The scale included 34 items (maximal score, 135) encompassing 6 subscales for cognition, behavior, disability, parkinsonism, dystonia, and other neurological signs. RESULTS: Forty-seven genetically confirmed patients (30 ± 17 years; range, 6-77 years) were examined with the scale (mean score, 62 ± 21; range, 20-106). Dystonia with prominent cranial involvement and atypical parkinsonian features were present in all patients. Other common signs were cognitive impairment, psychiatric features, and slow and hypometric saccades. Dystonia, parkinsonism, and other neurological features had a moderate to strong correlation with disability. The scale showed good internal consistency for the total scale (Cronbach's a = 0.87). On interrater analysis, weighted kappa values (0.30-0.93) showed substantial or excellent agreement in 85% of the items. The scale also discriminated a subgroup of homozygous c.1583C>T patients with lower scores, supporting construct validity for the scale. CONCLUSIONS: The proposed scale seems to be a reliable and valid instrument for the assessment of pediatric and adult patients with pantothenate kinase-associated neurodegeneration. Additional validation studies with a larger sample size will be required to confirm the present results and to complete the scale validation testing. © 2017 International Parkinson and Movement Disorder Society.

Introduction This study objective was to identify, select, and define a basic set of quality indicators for pediatric intensive care in Spain. Methods (1) Review of the literature to identify quality indicators and their defining elements and (2) selection of indicators by consensus of a group of experts using basic Delphi methodology (2 rounds) and forms distributed by email among experts from the Spanish society of pediatric intensive care. Results We selected quality indicators according to their relevance and feasibility and the experts' agreement on their incorporation in the final set. We included only those indicators whose assessment was within the highest tertile and greater than or equal to 70% evaluator agreement in the final selection. Starting from an initially proposed set of 136 indicators, 31 experts first selected 43 indicators for inclusion in the second round. Twenty indicators were selected for the final set. This "top 20" set comprised 9 process indicators, 9 of results (especially treatment-associated adverse effects), and 2 indicators of structure. Several of them are classical indicators in intensive care medicine (rates of hospital-acquired infections, pressure ulcers, etc.), whereas others are specifically pediatric (eg, unrestricted parent visitation or training the parents of technology-dependent children). Conclusions We reached a consensus on a set of 20 essential quality indicators for pediatric intensive care in Spain. A significant subset reflects the peculiarities of pediatric care. We consider this subset as a starting point for future projects of network collaboration between pediatric intensive care units in Spain.

The Hepatitis G virus (GBV-C/HGV) is a parenterally transmitted virus that is frequently associated with the Hepatitis C virus (HCV) infection. In people co-infected with GBV-C/HGV and human immunodeficiency virus (HIV), a delayed progression of acquired immunodeficiency syndrome (AIDS) has been observed. The liver disease caused by GBV-C/HGV and the mechanism by which this virus may inhibit the progression of AIDS remain to be elucidated. Given that GBV-HGV is an enveloped RNA virus similar to HIV and Hepatitis B viruses, we hypothesize that, as in those viruses, capside assembly is crucial for viral infection. Thus, the study of peptides from capside proteins may help us to understand the mechanism of viral infection which takes place. Here we studied the surface behaviour of E1(3-17)R and E1(3-17)G peptides from HGV by means of the Langmuir-monolayer technique, in order to examine the peptide–membrane interaction. Both peptides showed spontaneous adsorption at the air–water interface but adsorption process was faster for E1(3-17)G peptide. In both cases, the maximum pressure reached ( π max ) and molecular areas at maximal packing, calculated from compression isotherms of pure peptide monolayers, were in good agreement with previous reports for peptides with α-helical structures at the interface. E1(3-17)R and E1(3-17)G interacted with l -α-phosphatidylcholine (PC) and l -α-phophatidylserine (PS). Miscibility studies indicated that the two peptides interact with PC and PS; the presence of a peptide altered the shape of the compression isotherms. BAM images revealed that E1(3-17)G is immiscible with the lipids assayed. In contrast, E1(3-17)R disrupted the PS lipid film.

CPT-11 and SN-38 are camptothecins with strong antitumor activity. Nevertheless, their severe side effects and the chemical instability of their lactone ring have questioned the usual forms for its administration and have focused the current research on the development of new suitable pharmaceutical formulations. This work presents a biophysical study of the interfacial interactions of CPT-11 and SN-38 with membrane mimetic models by using monolayer techniques and Differential Scanning Calorimetry. The aim is to get new insights for the understanding of the bilayer mechanics after drug incorporation and to optimize the design of drug delivery systems based on the formation of stable bilayer structures. Moreover, from our knowledge, the molecular interactions between camptothecins and phospholipids have not been investigated in detail, despite their importance in the context of drug action. The results show that neither CPT-11 nor SN-38 disturbs the structure of the complex liposome bilayers, despite their different solubility, that CPT-11, positively charged in its piperidine group, interacts electrostatically with DOPS, making stable the incorporation of a high percentage of CPT-11 into liposomes and that SN-38 establishes weak repulsive interactions with lipid molecules that modify the compressibility of the bilayer without affecting significantly neither the lipid collapse pressure nor the miscibility pattern of drug-lipid mixed monolayers. The suitability of a binary and a ternary lipid mixture for encapsulating SN-38 and CPT-11, respectively, has been demonstrated.

Background: Twenty-four-hour ambulatory blood pressure monitoring (ABPM) provides the most accurate efficacy assessment of an antihypertensive agent throughout a 24-hour dosing interval. The objective of this prospective, randomised, double-blind, parallel-group, multicentre study was to compare the antihypertensive efficacy of imidapril versus candesartan cilexetil using ABPM. Methods: After screening and a single-blind, placebo run-in phase, ambulatory adult patients with mild to moderate hypertension (defined as a mean office sitting diastolic BP [DBP] and systolic BP [SBP], respectively, of 90–109mm Hg and 140–179mm Hg, and a mean ABPM DBP and SBP, respectively, of ≥80mm Hg and ≥125mm Hg) were randomised to once-daily treatment with imidapril or candesartan cilexetil for 12 weeks. ABPM was performed at baseline and at the end of the 12-week treatment period in 112 patients (imidapril group, n = 55; candesartan cilexetil group, n = 57). To achieve the target BP of ≤140/90mm Hg, imidapril was titrated from 5 mg/day to 20 mg/day and candesartan cilexetil was titrated from 4 mg/day to 16 mg/day. Results: Significant (p < 0.001) and similar decreases from baseline in clinic mean DBP and SBP, in mean 24-hour ABPM, DBP and SBP awake and asleep, and in mean BP (MBP) were observed in both treatment groups. In addition, significant and similar reductions in DBP and SBP were observed during the early morning acceleration period in both treatments. The reduction in BP load was higher with imidapril than with candesartan cilexetil: 44.6% versus 34.5% reduction in DBP load and 38.0% versus 32.9% reduction in SBP load, respectively. With respect to the average deviation index expressing a load index, the reduction with imidapril was 41.0% versus 33.6% with candesartan cilexetil. The percentage of DBP dipper patients remained identical before and after treatment in both groups. With regard to SBP, the percentage of dippers increased from 38.2% to 45.5% in the imidapril group and decreased from 54.4% to 42.1% in the candesartan cilexetil group. The incidence of adverse events was similar between the treatment groups and no cases of dry cough were reported. Conclusion: Imidapril in once-daily doses of up to 20mg was shown to be at least as effective as candesartan cilexetil given in once-daily doses of up to 16mg in reducing BP throughout the entire 24-hour dosing interval. Both drugs were well tolerated.

Antimicrobial peptides offer a new class of therapeutic agents to which bacteria may not be able to develop genetic resistance, since their main activity is in the lipid component of the bacterial cell membrane. We have developed a series of synthetic cationic cyclic lipopeptides based on natural polymyxin, and in this work we explore the interaction of sp-85, an analog that contains a C12 fatty acid at the N-terminus and two residues of arginine. This analog has been selected from its broad spectrum antibacterial activity in the micromolar range, and it has a disruptive action on the cytoplasmic membrane of bacteria, as demonstrated by TEM. In order to obtain information on the interaction of this analog with membrane lipids, we have obtained thermodynamic parameters from mixed monolayers prepared with POPG and POPE/POPG (molar ratio 6:4), as models of Gram positive and Gram negative bacteria, respectively. Langmuir–Blodgett films have been extracted on glass plates and observed by confocal microscopy, and images are consistent with a strong destabilizing effect on the membrane organization induced by sp-85. The effect of sp-85 on the membrane is confirmed with unilamelar lipid vesicles of the same composition, where biophysical experiments based on fluorescence are indicative of membrane fusion and permeabilization starting at very low concentrations of peptide and only if anionic lipids are present. Overall, results described here provide strong evidence that the mode of action of sp-85 is the alteration of the bacterial membrane permeability barrier.

The development of peptide fusion inhibitors based on short synthetic peptides represents a promising option in the fight against HIV-1 infection, especially in individuals infected with multiresistant HIV-1 strains. GBV-C has the beneficial effect of retarding the progression of AIDS in people who are co-infected with both the GBV-C and HIV viruses. In previous works, the E1(22–39) GBV-C sequence (E1P8lin) was found to be capable of inhibiting the interaction of HIV-1 FP with bilayers and its cyclic analogue (E1P8cyc) showed a higher anti-HIV-1 activity. In the present work, in an attempt to gain a better understanding of the interaction of E1P8 peptides with HIV-1 FP, we analyzed direct interactions between peptides at the molecular level. Our results support that E1P8cyc might be more potent at blocking HIV-1 entry than E1P8lin as a consequence of the structure induced in the complex formed with HIV-1 FP, which is able to modify the conformation adopted by this functional domain of the HIV-1 gp41 protein in target cell membranes.

STUDY OBJECTIVES To measure the sleep spindle characteristics in patients with unilateral thalamic stroke. DESIGN A prospective study of patients with thalamic stroke and age-matched healthy controls. SETTING Department of Neurology of a University Hospital. PARTICIPANTS Thirteen patients (mean age: 67 years, SD: 13,44) with an isolated, unilateral acute thalamic stroke and 18 healthy age-matched volunteers. INTERVENTIONS A polysomnogram recording from 14 scalp EEG electrodes performed during 2 consecutive nights, the second or third week after the stroke. Only the sleep of the second night was analyzed. MEASUREMENTS AND RESULTS Sleep spindles were counted during two separate 10-minute epochs of stage II. Spindles appearing synchronously in both sides with similar amplitude were called "bilateral." Spindles with twice the amplitude in one side than the other were "right" or "left-side predominant". There were 8 patients with posterolateral, 3 with global and 2 with anterior lesions. Eight were right and 5 left-sided. The number of spindles was similar in patients (39.8 +/- 23.4 in 20 minutes) than controls (26.07 +/- 29.07; p=0.173). Spindles with a centroparietal (34%) and centroparieto-occipital localization (22%) were the most frequent. In controls approximately 66% of the spindles had a bilateral and symmetric distribution over the scalp, 23% of the spindles were predominantly left-sided and 5% were predominantly right-sided. In patients, bilateral spindles decreased (p

Aims and topics The international symposium on luminescence spectrometry (ISLS) series started in 1984 when Willy Bayens organized the first six editions at Ghent University. From 1996, the ISLS has been conducted periodically every 2 years in different countries. The main purpose of the conference is to provide a forum to present new developments and innovations in the field of luminescence spectroscopy and their main applications, from photoluminescence and electrogenerated luminescence to bioluminescence and chemiluminescence, regarding both basic science and applications in biosciences and pharmaceutical, environmental, and food analysis. The 2012 meeting was mainly focused on “Luminescence spectroscopy: bioanalytical and biophysical aspects.” Symposium sessions took place in the Historic Building of the University of Barcelona (Fig. 1), which was raised in 1871 by Elies Rogent (it is possible to have a virtual look at http://www.ub.edu/museuvirtual/visitavirtualEH/ index_es.html).

Esmolol is a cardioselective beta-blocker with very rapid onset of action and short half-life due to its metabolism by blood-borne esterases. This unique profile among currently available beta-blockers renders esmolol highly useful in critical care situations. However, published experience with the use of esmolol in critically ill children is scant. The case of a 4-year-old boy with secondary long QT syndrome and ventricular tachycardia successfully treated with esmolol is presented.

Four peptide sequences corresponding to the E1 protein of GBV-C: NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCLVALGCTICTD (P10) and QAGLAVRPGKSAAQLVGE (P18) were studied as they were capable of interfering with the HIV-1 fusion peptide (HIV-1 FP). In this work, the surface properties of the E1 peptide sequences are investigated and their physicochemical characterization is done by studying their interaction with model membranes; moreover, their mixtures with HIV-1 FP were also studied in order to observe whether they are capable to modify the HIV-1 FP interaction with model membranes as liposomes or monolayers. Physicochemical properties of peptides (pI and net charge) were predicted showing similarities between P7 and P8, and P10 and HIV-1 FP, whereas P18 appears to be very different from the rest. Circular dichroism experiments were carried out showing an increase of the percentage of α-helix of P7 and P8 when mixed with HIV-1 FP corroborating a conformational change that could be the cause of their inhibition ability. Penetration experiments show that all the peptides can spontaneously insert into phospholipid membranes. Analysis of compression isotherms indicates that the peptides interact with phospholipids and the E1 peptides modify the compression isotherms of HIV-1 FP, but there is one of the peptides that excelled as the best candidate for inhibiting the activity of HIV-1 FP, P7, and therefore, that could be potentially used in future anti-HIV-1 research.

One way to gain information about the fusogenic potential of virus-derived synthetic peptides is to examine their interfacial properties and subsequently to study them in monolayers and bilayers. Here, we characterize the physicochemical surface properties of the peptide E1(64–81), whose sequence is AQLVGELGSLYGPLSVSA. This peptide is derived from the E1 structural protein of GBV-C/HGV which was previously shown to inhibit leakage of vesicular contents caused by the HIV-1 fusion peptide (HIV-1 FP). Mixed isotherms of E1(64–81) and HIV-1 FP were obtained and their Brewster angle microscopy (BAM) and atomic force microscopy (AFM) images showed that the peptide mixture forms a different structure that is not present in the pure peptide images. Studies with lipid monolayers (1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DMPG) and 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG)) show that both peptides interact with all the lipids assayed but the effect that HIV-1 FP has on the monolayers is reduced in the presence of E1(64–81). Moreover, differential scanning calorimetry (DSC) experiments show the capacity of HIV-1 FP to modify the properties of the bilayer structure and the capacity of E1(64–81) to inhibit these modifications. Our results indicate that E1(64–81) interacts with HIV-1 FP to form a new structure, and that this may be the cause of the previously observed inhibition of the activity of HIV-1 FP by E1(64–81)., This work was supported by project CTQ2006-15396-C02-02/01-BQU from the Secretaría de Estado de Investigación, Ministerio de Ciencia e Innovación, Dirección General de Programas y transferencia de conocimiento, Subdirección General de Proyectos de Investigación (Spain). M.J. Sánchez-Martín is a recipient of an FPI programme pre-doctoral grant. The authors are members of the consolidated research group recognized by the Generalitat de Catalunya “Peptides and Proteins: physicochemical studies” (2005SGR00278).

The stability of carboplatin in aqueous solutions at different experimental conditions was studied. It was observed that the degradation rate of carboplatin under illumination increases notably with respect to the rate obtained in the dark. The time course of carboplatin in solution follows a first-order kinetics with rate constants that depend on the incident light intensity and little with temperature. The quantum yield of the carboplatin degradation lies between 0.05 and 0.2 depending on the experimental conditions. From the results obtained in the present work it is concluded that carboplatin is degraded under illumination by means of a photoaquation process.

A functional disorder of facial muscle activity commonly occurs in patients after recovery from Bell's palsy with axonal degeneration. The postparalytic facial dysfunction is probably related to the aberrant growing of regenerating axons, although other theories such as ephaptic transmission, spontaneous generation of impulses, and enhancement of motoneuron excitability should also be considered. In this work, we have carried out a comparative electrophysiological study of both sides of the face in 23 patients who had recovered from a unilateral Bell's palsy with axonal degeneration. At rest, spontaneous firing of motor units was observed in muscles of the previously paralyzed side. Direct motor responses to facial nerve stimulation were smaller in the muscles of the previously paralyzed side, but reflex responses obtained in the same muscles by stimulation of either the facial or trigeminal nerve were larger when compared with those of the contralateral side. These data indicate that patients with "postparalytic facial dysfunction" may have an increased background muscle activity, as well as an enhanced recruitment of facial motoneurons to reflex activation in the side of the previous paralysis. These findings are compatible with an enhanced level of motoneuron excitability in the facial nucleus.

E1(145-162), a peptide corresponding to the structural protein E1 of the GB virus C, has been shown earlier to bind at pH 7.4 to vesicles containing 1,2-dimyiristoyl-sn-glycero-3-phospho-rac-(1-glycerol)] (DMPG) and 1,2-dimyiristoyl-sn-glycero-3-phosphocholine (DMPC) phospholipids. To deepen the understanding of the interaction of E1(145-162) with the lipid membrane, in this paper, we report a detailed study of the surface properties of peptide, miscibility properties, and behavior of mixed monomolecular films of it and three phospholipids DMPG, DMPC, and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPG). These studies were performed using the Langmuir balance by means of surface adsorption studies, surface pressure-mean molecular area compression isotherms, and penetration kinetics. The Brewster angle microscopy (BAM) was used to study the morphological properties of pure peptide and the mixed monolayers. The results show us that the peptide showed surface activity concentration dependent when injected beneath a buffered solution (HEPES/NaCl, pH 7.4). This tendency to accumulate into the air/water interface confirms its potential capacity to interact with membranes; the higher penetration of peptide into phospholipids is attained when the monolayers are in the liquid expanded state and the lipids are charged negatively maybe due to its negative electric charge that interacts with the positive global charge of the peptide sequence. The area per molecule values obtained suggested that the main arrangement structure for E1(145-162) peptide is the alpha-helical at the air-water interface that agreed with computational prediction calculations. Miscibility studies indicated that mixtures become thermodynamically favored at low peptide molar fraction.

Fragile X syndrome is the most common form of hereditary mental retardation. The molecular basis of this syndrome is mainly a CGG expansion in the 5' untranslated region of the FMR1 gene. Expansions with more than 200 CGG repeats abolish gene expression causing the classical fragile X phenotype. Premutation carriers (55-200 CGG) have normal cognitive function with increased risk of developing premature ovarian failure and fragile X-associated tremor-ataxia syndrome (FXTAS). Some clinical features associated with FXTAS, such as tremor, gait ataxia, cognitive decline, and generalized brain atrophy, are also seen in other movement disorders. Ninety-five patients referred for HD, who tested negative for the expansion in the IT15 gene, were screened for FMR1 CGG-repeat expansion. One FMR1 premutation male carrier was detected, giving an FXTAS frequency of 1.6%. Our results highlight that FXTAS is still not well diagnosed; therefore, we recommend FMR1 premutation screenings in all patients with late-onset tremor, ataxia, and cognitive dysfunction.

The incidence and prevalence of immunocompromised patients has increased (higher number of transplantations and improved management of primary immunodeficiencies). Nevertheless, the management strategies of these patients in the pediatric ICU (PICU) remain a challenge because of their important death rate. The study objective was to analyse the morbimortality and prognosis of immunosuppressed patients requiring critical care due to a medical cause.

Acute respiratory failure (ARF) in immunocompromised patients is associated with a high mortality rate. The aim of this investigation is to study these patients' behavior patterns to collect data that can allow us to improve their survival rate.

© 2014 Elsevier B.V. All rights reserved. The interaction between a peptide sequence from GB virus C E1 protein (E1P8) and its structural analogs (E1P8-12), (E1P8-13), and (E1P8-21) with anionic lipid membranes (POPG vesicles and POPG, DPPG or DPPC/DPPG (2:1) monolayers) and their association with HIV-1 fusion peptide (HIV-1 FP) inhibition at the membrane level were studied using biophysical methods. All peptides showed surface activity but leakage experiments in vesicles as well as insertion kinetics in monolayers and lipid/peptide miscibility indicated a low level of interaction: neither E1P8 nor its analogs induced the release of vesicular content and the exclusion pressure values (πe) were clearly lower than the biological membrane pressure (24-30 mN m- 1) and the HIV-1 FP (35 mN m- 1). Miscibility was elucidated in terms of the additivity rule and excess free energy of mixing (GE). E1P8, E1P8-12 and E1P8-21 (but not E1P8-13) induced expansion of the POPG monolayer. The mixing process is not thermodynamically favored as the positive GE values indicate. To determine how E1 peptides interfere in the action of HIV-1 FP at the membrane level, mixed monolayers of HIV-1 FP/E1 peptides (2:1) and POPG were obtained. E1P8 and its derivative E1P8-21 showed the greatest HIV-1 FP inhibition. The LC-LE phase lipid behavior was morphologically examined via fluorescence microscopy (FM) and atomic force microscopy (AFM). Images revealed that the E1 peptides modify HIV-1 FP-lipid interaction. This fact may be attributed to a peptide/peptide interaction as indicated by AFM results. Finally, hemolysis assay demonstrated that E1 peptides inhibit HIV-1 FP activity.