Clinical and economic hospital burden of acute respiratory infection (BARI) due to respiratory syncytial virus in Spanish children, 2015-2018.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection (ALRI) in children, causing frequent outpatient visits and hospitalizations. Our study aimed to describe the clinical and direct economic burden of ALRI hospitalizations related to RSV in children in Spain and the characteristics of patients and their episodes. In this retrospective study, ALRI hospitalizations in children aged < 5 years for 2015-2018 were reviewed using anonymized administrative public hospital discharge data from Spain. Three case definitions were considered: (a) RSV-specific; (b) RSV-specific and unspecified acute bronchiolitis (RSV-specific and bronchiolitis); and (c) RSV-specific and unspecified ALRI (RSV-specific and ALRI). The study reported a mean of 36,743 yearly admissions potentially due to RSV, resulting in a mean annual cost of €87.1 million. RSV-specific codes accounted for 39.2% of cases, unspecified acute bronchiolitis for 20.1%, and other unspecified ALRI codes for the remaining 40.6%. The mean hospitalization rate per 1,000 children was 55.5 in the first year of life, 16.0 in the second, and 5.4 between 24 and 59 months. A considerable proportion of cases occurred in children under two years old (> 80.4%) and even during the first year of life (> 61.7%). Otherwise healthy children accounted for 92.9% of hospitalizations and 83.3% of costs during the period. Children born preterm accounted for 1.3% of hospitalizations and 5.7% of costs. The findings revealed that RSV still contributes to a high burden on the Spanish health care system. Children under one year of age and otherwise healthy term infants accounted for most of the substantial clinical and economic burden of RSV. Current evidence potentially underestimates the true epidemiology and burden of severe RSV infection; thus, further studies focusing on the outpatient setting are needed.

Excess hospitalizations and mortality associated with seasonal influenza in Spain, 2008-2018.

BACKGROUND: Influenza may trigger complications, particularly in at-risk groups, potentially leading to hospitalization or death. However, due to lack of routine testing, influenza cases are infrequently coded with influenza-specific diagnosis. Statistical models using influenza activity as an explanatory variable can be used to estimate annual hospitalizations and deaths associated with influenza. Our study aimed to estimate the clinical and economic burden of severe influenza in Spain, considering such models. METHODS: The study comprised ten epidemic seasons (2008/2009-2017/2018) and used two approaches: (i) a direct method of estimating the seasonal influenza hospitalization, based on the number of National Health Service hospitalizations with influenza-specific International Classification of Diseases (ICD) codes (ICD-9: 487-488; ICD-10: J09-J11), as primary or secondary diagnosis; (ii) an indirect method of estimating excess hospitalizations and deaths using broader groups of ICD codes in time-series models, computed for six age groups and four groups of diagnoses: pneumonia or influenza (ICD-9: 480-488, 517.1; ICD-10: J09-J18), respiratory (ICD-9: 460-519; ICD-10: J00-J99), respiratory or cardiovascular (C&R, ICD-9: 390-459, 460-519; ICD-10: I00-I99, J00-J99), and all-cause. Means, excluding the H1N1pdm09 pandemic (2009/2010), are reported in this study. RESULTS: The mean number of hospitalizations with a diagnosis of influenza per season was 13,063, corresponding to 28.1 cases per 100,000 people. The mean direct annual cost of these hospitalizations was €45.7 million, of which 65.7% was generated by patients with comorbidities. Mean annual influenza-associated C&R hospitalizations were estimated at 34,894 (min: 16,546; max: 52,861), corresponding to 75.0 cases per 100,000 (95% confidence interval [CI]: 63.3-86.3) for all ages and 335.3 (95% CI: 293.2-377.5) in patients aged ≥ 65 years. We estimate 3.8 influenza-associated excess C&R hospitalizations for each hospitalization coded with an influenza-specific diagnosis in patients aged ≥ 65 years. The mean direct annual cost of the estimated excess C&R hospitalizations was €142.9 million for all ages and €115.9 million for patients aged ≥ 65 years. Mean annual influenza-associated all-cause mortality per 100,000 people was estimated at 27.7 for all ages. CONCLUSIONS: Results suggest a relevant under-detected burden of influenza mostly in the elderly population, but not neglectable in younger people.

Revisiting the bonding of the pentagonal-pyramidal C6H62+ and C6(CH3)62+ dications.

This work delves into the bonding nature of the pentagonal-pyramidal benzene and hexamethylbenzene dications, C6R62+ (R = H and CH3), which contain a hexacoordinate carbon. The study employs a range of methodologies to analyze a series of scalar fields, including electron density, electron localization function, local momentum representation, and the evaluation of the Coulomb hole through information theory-derived functions. The findings unveil that electron density undergoes transfer from the pentagonal ring to the apical group. As a result, the base of the complex accumulates the positive charge. Moreover, an extended electron density domain emerges between the carbon pentagon and the apical carbon atom. This phenomenon is related to the molecular orbitals with a dipolar character aligned with the principal axis of the molecule. The results also indicate an electron density polarization towards the apical carbon, coupled with an exclusion of electron density surrounding both the apical carbon and the lower portion of the pentagonal ring. These provide valuable insights into the complex bonding nature of hexacoordinate carbon and its implications for organic chemistry.

Na⋯B bond in NaBH 3 - : An induced spin-polarized bond.

The nature of the Na⋯B bond, in the recently synthesized NaBH 3 - adduct, is analyzed on the light of the Na- propensity to polarize along the bond axis as a consequence of the electric field produced by the BH3 fragment. The observed induced polarization has two consequences: (i) the energetic stabilization of the Na- , and (ii) the split of its valence electrons into two opposite lobes along the bond axis. Additionally, an analysis of the electron localization is presented using the information content of the correlated conditional pair density that reveals a significant delocalization between one lobe of the polarized Na- anion and the BH3 fragment at the equilibrium distance. Our findings reported here complement previous works on this system.

Clinical and economic burden of respiratory syncytial virus in Spanish children: the BARI study.

Respiratory syncytial virus (RSV) infection is a major cause of morbidity in children. However, its disease burden remains poorly understood, particularly outside of the hospital setting. Our study aimed to estimate the burden of medically attended acute lower respiratory infection (ALRI) cases potentially related to RSV in Spanish children. Longitudinal data from September 2017 to June 2018 of 51,292 children aged < 5 years old from the National Healthcare System (NHS) of two Spanish regions were used. Three case definitions were considered: (a) RSV-specific; (b) RSV-specific and unspecified acute bronchiolitis (RSV-specific and Bronchiolitis), and; (c) RSV-specific and unspecified ALRI (RSV-specific and ALRI). A total of 3460 medically attended ALRI cases potentially due to RSV were identified, of which 257 (7.4%), 164 (4.7%), and 3039 (87.8%) coded with RSV-specific, unspecific bronchiolitis, and unspecific ALRI codes, respectively. Medically attended RSV-specific and ALRI cases per 1000 children was 134.4 in the first year of life, 119.4 in the second, and 35.3 between 2 and 5 years old. Most cases were observed in otherwise healthy children (93.1%). Mean direct healthcare cost per medically attended RSV-specific and ALRI case was €1753 in the first year of life, €896 in the second, and €683 between 2 and 5 years old. Hospitalization was the main driver of these costs, accounting for 55.6%, 38.0% and 33.4%, in each respective age group. In RSV-specific cases, mean direct healthcare cost per medically attended case was higher, mostly due to hospitalization: €3362 in the first year of life (72.9% from hospitalizations), €3252 in the second (72.1%), and €3514 between 2 and 5 years old (74.2%). These findings suggest that hospitalization data alone will underestimate the RSV infections requiring medical care, as will relying only on RSV-specific codes. RSV testing and codification must be improved and preventive solutions adopted, to protect all infants, particularly during the first year of life.

Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics.

There is abundant epidemiological data indicating that the incidence of severe cases of coronavirus disease (COVID-19) is significantly higher in males than females worldwide. Moreover, genetic variation at the X-chromosome linked TLR7 gene has been associated with COVID-19 severity. It has been suggested that the sex-biased incidence of COVID-19 might be related to the fact that TLR7 escapes X-chromosome inactivation during early embryogenesis in females, thus encoding a doble dose of its gene product compared to males. We analyzed TLR7 expression in two acute phase cohorts of COVID-19 patients that used two different technological platforms, one of them in a multi-tissue context including saliva, nasal, and blood samples, and a third cohort that included different post-infection timepoints of long-COVID-19 patients. We additionally explored methylation patterns of TLR7 using epigenomic data from an independent cohort of COVID-19 patients stratified by severity and sex. In line with genome-wide association studies, we provide supportive evidence indicating that TLR7 has altered CpG methylation patterns and it is consistently downregulated in males compared to females in the most severe cases of COVID-19.

Utility of the combination of hederagenin glucoside saponins and chromane hydrazone in the topical treatment of canine cutaneous leishmaniasis. An observational study.

Canine cutaneous leishmaniasis (CCL) is an emerging zoonotic infection endemic in several countries of the world. Due to variable response to therapy and frequency of relapses, a more effective, safer, and inexpensive treatment is needed. Recently, it was reported that the hederagenin glucoside saponins (SS) and chromane-derived hydrazone (TC2) combined in a 1:1 ratio has high potential in antileishmanial therapy since both compounds alter the survival of Leishmania and the ability to infect adjacent macrophage. Not only the skin permeation and the absorption of an ointment containing 2% TC2 and 2% SS (w/w) was determined in this work, but also the acute dermal toxicity in both in vitro and in vivo assays. Last, the effectiveness and safety of the topical therapy with 2% TC2-2% SS ointment was evaluated in an observational study in dogs with diagnosis of cutaneous leishmaniasis (CL). Both TC2 and SS diffused through pig ear skin and traces of TC2 (but not SS) were detected in the stratum corneum of mice at 6-24 h. Neither TC2 nor SS was detected in plasma. The acute dermal toxicity was negative. Treatment with 2% TC2-2% SS ointment produced a complete long-term clinical cure in 56 dogs (24 females and 32 males) from the Orinoco and Amazonas regions in southeastern Colombia without adverse effects. All dogs have remained disease-free for the last 24 months. In conclusion, these results support the use of this topical therapy as a safer and new first-line local treatment of CCL that could help limit the spread of CL from dogs to humans.

A Theoretical Study of the C-X Bond Cleavage Mediated by Cob(II)Aloxime.

The C-X bond cleavage in different methyl halides (CH3X; X = Cl, Br, I) mediated by 5,6-dimethylbenzimidazole-bis(dimethylglyoximate)cobalt(II) (CoIICbx) was theoretically investigated in the present work. An SN2-like mechanism was considered to simulate the chemical process where the cobalt atom acts as the nucleophile and the halogen as the leaving group. The reaction path was computed by means of the intrinsic reaction coordinate method and analyzed in detail through the reaction force formalism, the quantum theory of atoms in molecules (QTAIM), and the calculation of one-electron density derived quantities, such as the source function (SF) and the spin density. A thorough comparison of the results with those obtained in the same reaction occurring in presence of 5,6-dimethylbenzimidazole-bis(dimethylglyoximate)cobalt(I) (CoICbx) was conducted to reveal the main differences between the two cases. The reactions mediated by CoIICbx were observed to be endothermic and possess higher activation energies in contrast to the reactions where the CoICbx complex is present. The latter was supported by the reaction force results, which suggest a relationship between the activation energy and the ionization potentials of the different nucleophiles present in the cleavage reaction. Moreover, the SF results indicates that the lower axial ligand (i.e., 5,6-dimethylbenzimidazole) exclusively participates on the first stage of the reaction mediated by the CoIICbx complex, while for the CoICbx case, it appears to have an important role along the whole process. Finally, the QTAIM charge analysis indicates that oxidation of the cobalt atom occurs in both cases; at the same time, it suggests the formation of an uncommon two-center one-electron bond in the CoIICbx case. The latter was confirmed by means of electron localization calculations, which resulted in a larger electron count at the Co-C interatomic region for the CoICbx case upon comparison with its CoIICbx counterpart.

A computational study of the reaction mechanism involved in the fast cleavage of an unconstrained amide bond assisted by an amine intramolecular nucleophilic attack.

In the present work, the fast amide bond cleavage of [3-((1R,5S,7s)-3-azabicyclo[3.3.1]nonane-7-carbonyl)-3-azabicyclo[3.3.1]nonane-7-carboxylic acid (bi-ATDO)], through an intramolecular nucleophilic attack of an amine group is evaluated. First, six possible peptide bond cleavage mechanisms, two of them including a water molecule, are described at the ωB97XD/6-311 + G(d,p)//MP2/6-311 + G(d,p) level of theory. The reaction consisting of an intramolecular nitrogen nucleophilic attack followed by a proton transfer and the amide bond cleavage is determined as the most favorable mechanism. The activation free energy computed for the latter is 20.5 kcal mol-1 , which agrees with the reported experimental result of 24.8 kcal mol-1 . Inclusion of a water molecule to assist the first step of the reaction results in an activation free energy increase of about 17 kcal mol-1 . All the steps in the most favorable mechanism are studied more in detail employing intrinsic reaction coordinate as well as the reaction force and reaction electronic flux analysis.

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) vs. a licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine in meningococcal vaccine-naïve and meningococcal C conjugate vaccine-primed toddlers: a phase III randomised study.

Vaccination remains the best strategy to reduce invasive meningococcal disease. This study evaluated an investigational tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MenACYW-TT) vs. a licensed tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MCV4-TT) (NCT02955797). Healthy toddlers aged 12-23 months were included if they were either meningococcal vaccine-naïve or MenC conjugate (MCC) vaccine-primed (≥1 dose of MCC prior to 12 months of age). Vaccine-naïve participants were randomised 1:1 to either MenACYW-TT (n = 306) or MCV4-TT (n = 306). MCC-primed participants were randomised 2:1 to MenACYW-TT (n = 203) or MCV4-TT (n = 103). Antibody titres against each of the four meningococcal serogroups were measured by serum bactericidal antibody assay using the human complement. The co-primary objectives of this study were to demonstrate the non-inferiority of MenACYW-TT to MCV4-TT in terms of seroprotection (titres ≥1:8) at Day 30 in both vaccine-naïve and all participants (vaccine-naïve and MCC-primed groups pooled). The immune response for all four serogroups to MenACYW-TT was non-inferior to MCV4-TT in vaccine-naïve participants (seroprotection: range 83.6-99.3% and 81.4-91.6%, respectively) and all participants (seroprotection: range 83.6-99.3% and 81.4-98.0%, respectively). The safety profiles of both vaccines were comparable. MenACYW-TT was well-tolerated and demonstrated non-inferior immunogenicity when administered to MCC vaccine-primed and vaccine-naïve toddlers.

Beyond taxonomy: species complexes in New World phlebotomine sand flies.

A species complex (= species group, species series) is an assemblage of species, which are related morphologically and phylogenetically. Recent research has revealed several arthropod vector species that were believed to be a single nominal species actually representing a group of closely related species, which are sometimes morphologically indistinguishable at one or more developmental stages. In some instances, differences in terms of vector competence, capacity, or both have been recorded. It highlights the importance of detecting and studying species complexes to improve our understanding of pathogen transmission patterns, which may be vectored more or less efficiently by different species within the complex. Considering more than 540 species, about one-third of the phlebotomine sand flies in the New World present males and/or females morphologically indistinguishable to one or more species. Remarkably, several of these species may act in transmission of pathogenic agents. In this article, we review recent research on species complexes in phlebotomine sand flies from the Americas. Possible practical implications of recently acquired knowledge and future research needs are also discussed.

A Theoretical and Experimental Study on the Potential Luminescent and Biological Activities of Diaminodicyanoquinodimethane Derivatives.

Recently, several studies have demonstrated that diaminodicyanoquinone derivatives (DADQs) could present interesting fluorescence properties. Furthermore, some DADQs under the solid state are capable of showing quantum yields that can reach values of 90%. Besides, the diaminodiacyanoquinone core represents a versatile building block propense either to modification or integration into different systems to obtain and provide them unique photophysical features. Herein, we carried out a theoretical study on the fluorescence properties of three different diaminodicyanoquinodimethane systems. Therefore, time-dependent density functional theory (TD-DFT) was used to obtain the values associated with the dipole moments, oscillator strengths, and the conformational energies between the ground and the first excited states of each molecule. The results suggest that only two of the three studied systems possess significant luminescent properties. In a further stage, the theoretical insights were confirmed by means of experimental measurements, which not only retrieved the photoluminescence of the DADQs, but also suggest a preliminary and promising antibacterial activity of these systems.

Effect of the Nucleophile's Nature on Chloroacetanilide Herbicides Cleavage Reaction Mechanism. A DFT Study.

In this study, the degradation mechanism of chloroacetanilide herbicides in the presence of four different nucleophiles, namely: Br-, I-, HS-, and S2O3-2, was theoretically evaluated using the dispersion-corrected hybrid functional wB97XD and the DGDZVP as a basis set. The comparison of computed activation energies with experimental data shows an excellent correlation (R2 = 0.98 for alachlor and 0.97 for propachlor). The results suggest that the best nucleophiles are those where a sulfur atom performs the nucleophilic attack, whereas the other species are less reactive. Furthermore, it was observed that the different R groups of chloroacetanilide herbicides have a negligible effect on the activation energy of the process. Further insights into the mechanism show that geometrical changes and electronic rearrangements contribute 60% and 40% of the activation energy, respectively. A deeper analysis of the reaction coordinate was conducted, employing the evolution chemical potential, hardness, and electrophilicity index, as well as the electronic flux. The charge analysis shows that the electron density of chlorine increases as the nucleophilic attack occurs. Finally, NBO analysis indicates that the nucleophilic substitution in chloroacetanilides is an asynchronous process with a late transition state for all models except for the case of the iodide attack, which occurs through an early transition state in the reaction.

Electricity demand during pandemic times: The case of the COVID-19 in Spain.

Electricity demand and its typical load pattern are usually affected by many endogenous and exogenous factors to which the generation system must accordingly respond through utility operators. Lockdown measures to prevent the spread of COVID-19 imposed by many countries have led to sudden changes in socioeconomic habits which have had direct effects on the electricity systems. Therefore, a detailed analysis of how confinement measures have modified the electricity consumption in Spain, one of the countries most affected by this pandemic, has been performed in this work. Its electricity consumption has decreased by 13.49% from March 14 to April 30, compared to the average value of five previous years. Daily power demand profiles, especially morning and evening peaks, have been modified at homes, hospitals, and in the total power demand. These changes generate a greater uncertainty for the System Operator when making demand forecasts, but production deviations have increased by only 0.1%, thanks to the presence of a diversified generation mix, which has been modified during this period, increasing the proportion of renewable sources and decreasing CO2 emissions.

Shannon Entropy and Fisher Information from a Non-Born-Oppenheimer Perspective.

We study the Shannon entropy and the Fisher information in a non-Born-Oppenheimer (nBO) regime, where these quantities are constructed from one-particle densities obtained from an exact nBO analytic wave function for a Coulomb-Hooke model of a four-particle system. This model consists of two electrons and two protons with Coulombic interactions between like particles and Hookean interactions otherwise [ Becerra , M. et al. Int. J. Quantum Chem 2013 , 113 ( 10 ), 1584 - 1590 ]. In the nBO case, there arise densities for both the nuclei and electrons. Furthermore, these densities vary with respect to a particular point of reference from which they are calculated. We consider, in the present work, electron and nuclear densities calculated from the following reference points: a global center of mass, the geometric center between the electrons, and the geometric center between the protons. A comparison of the nBO Shannon entropy and Fisher information, with respect to their counterparts computed from Born-Oppenheimer densities, suggests that the former quantities provide more insights into the chemical reactivity because of the nonuniqueness nature of the nBO electron density as well as the availability and access to the nBO nuclear density. Finally, some comments are made concerning the nBO vs the BO regimes in relation to this particular chemical reactivity indicator.

When global and local molecular descriptors are more than the sum of its parts: Simple, But Not Simpler?

In this report, we introduce a set of aggregation operators (AOs) to calculate global and local (group and atom type) molecular descriptors (MDs) as a generalization of the classical approach of molecular encoding using the sum of the atomic (or fragment) contributions. These AOs are implemented in a new and free software denominated MD-LOVIs ( http://tomocomd.com/md-lovis ), which allows for the calculation of MDs from atomic weights vector and LOVIs (local vertex invariants). This software was developed in Java programming language and employed the Chemical Development Kit (CDK) library for handling chemical structures and the calculation of atomic weights. An analysis of the complexities of the algorithms presented herein demonstrates that these aspects were efficiently implemented. The calculation speed experiments show that the MD-LOVIs software has satisfactory behavior when compared to software such as Padel, CDKDescriptor, DRAGON and Bluecal software. Shannon's entropy (SE)-based variability studies demonstrate that MD-LOVIs yields indices with greater information content when compared to those of popular academic and commercial software. A principal component analysis reveals that our approach captures chemical information orthogonal to that codified by the DRAGON, Padel and Mold2 software, as a result of the several generalizations in MD-LOVIs not used in other programs. Lastly, three QSARs were built using multiple linear regression with genetic algorithms, and the statistical parameters of these models demonstrate that the MD-LOVIs indices obtained with AOs yield better performance than those obtained when the summation operator is used exclusively. Moreover, it is also revealed that the MD-LOVIs indices yield models with comparable to superior performance when compared to other QSAR methodologies reported in the literature, despite their simplicity. The studies performed herein collectively demonstrated that MD-LOVIs software generates indices as simple as possible, but not simpler and that use of AOs enhances the diversity of the chemical information codified, which consequently improves the performance of traditional MDs.

Effect of immersion in distilled water or phosphate-buffered saline on the solubility, volumetric change and presence of voids within new calcium silicate-based root canal sealers.

AIM: To assess the effect of immersion in distilled water or phosphate-buffered saline (PBS) on the solubility, volumetric change and presence of voids of calcium silicate-based root canal sealers (TotalFill BC, Sealer Plus BC and Bio-C), in comparison with the gold standard epoxy resin-based sealer (AH Plus). METHODOLOGY: All properties were evaluated after immersion in distilled water or PBS. Solubility was determined by the percentage of mass loss, whereas volumetric change and presence of voids were evaluated by micro-computed tomography, after 7 days of immersion. The volumetric change and percentage of voids between the baseline (after setting) and the experimental period were calculated. Statistical analysis was performed using one-way anova and Tukey's or Student's t-tests (α = 0.05). RESULTS: The calcium silicate-based sealers had significantly greater solubility and volumetric loss than AH Plus, after immersion in distilled water or PBS (P < 0.05). Bio-C had the greatest solubility (P < 0.05), followed by TotalFill BC and Sealer Plus BC, which were similar (P > 0.05). Regarding the volumetric change, AH Plus had a volume increase, with similar values in distilled water and PBS (P > 0.05). TotalFill BC, Sealer Plus BC and Bio-C had a similar volumetric change (P > 0.05). The calcium silicate-based materials had the greatest solubility and volume loss after immersion in distilled water (P < 0.05). There was no difference in the percentage of voids amongst the sealers, before and after immersion in distilled water or PBS (P > 0.05). CONCLUSIONS: TotalFill BC, Sealer Plus BC and Bio-C had significantly greater solubility and volumetric loss than AH Plus. Although storage in PBS significantly reduced the solubility and volumetric change of calcium silicate-based sealers, their solubility remained above that recommend by ISO 6876. All the sealers evaluated had low and similar voids, even after immersion in distilled water or PBS.

Theoretical Description of R-X⋯NH3 Halogen Bond Complexes: Effect of the R Group on the Complex Stability and Sigma-Hole Electron Depletion.

In the present work, a number of R-X⋯NH3 (X = Cl, Br, and I) halogen bonded systems were theoretical studied by means of DFT calculations performed at the ωB97XD/6-31+G(d,p) level of theory in order to get insights on the effect of the electron-donating or electron-withdrawing character of the different R substituent groups (R = halogen, methyl, partially fluorinated methyl, perfluoro-methyl, ethyl, vinyl, and acetyl) on the stability of the halogen bond. The results indicate that the relative stability of the halogen bond follows the Cl < Br < I trend considering the same R substituent whereas the more electron-withdrawing character of the R substituent the more stable the halogen bond. Refinement of the latter results, performed at the MP2/6-31+G(d,p) level showed that the DFT and the MP2 binding energies correlate remarkably well, suggesting that the Grimme's type dispersion-corrected functional produces reasonable structural and energetic features of halogen bond systems. DFT results were also observed to agree with more refined calculations performed at the CCSD(T) level. In a further stage, a more thorough analysis of the R-Br⋯NH3 complexes was performed by means of a novel electron localization/delocalization tool, defined in terms of an Information Theory, IT, based quantity obtained from the conditional pair density. For the latter, our in-house developed C++/CUDA program, called KLD (acronym of Kullback-Leibler divergence), was employed. KLD results mapped onto the one-electron density plotted at a 0.04 a.u. isovalue, showed that (i) as expected, the localized electron depletion of the Br sigma-hole is largely affected by the electron-withdrawing character of the R substituent group and (ii) the R-X bond is significantly polarized due to the presence of the NH3 molecule in the complexes. The afore-mentioned constitutes a clear indication of the dominant character of electrostatics on the stabilization of halogen bonds in agreement with a number of studies reported in the main literature. Finally, the cooperative effects on the [Br-CN]n system (n = 1-8) was evaluated at the MP2/6-31+G(d,p) level, where it was observed that an increase of about ~14.2% on the complex stability is obtained when going from n = 2 to n = 8. The latter results were corroborated by the analysis of the changes on the Fermi-hole localization pattern on the halogen bond zones, which suggests an also important contribution of the electron correlation in the stabilization of these systems.

Utility of point-of-care vs reference laboratory testing for the evaluation of glucose levels.

AIMS: To assess the level of agreement between point-of-care and laboratory reference glucose values in defining glycaemic status. METHODS: We analysed 1292 overweight/obese, non-institutionalized participants, aged 40-65 years, in the San Juan Overweight Adults Longitudinal Study. Fasting venous blood glucose was determined using a point-of-care Bayer Contour Blood Glucose Meter and by Vitros System 250 instrument (laboratory). American Diabetes Association thresholds were used to classify participants into normoglycaemia (< 5.6 mmol/l), prediabetes (5.6 to 6.9 mmol/l), or diabetes groups (≥ 7 mmol/l). RESULTS: Bland-Altman plot analysis showed a slope of 0.04 (P=0.002) for the regression between the mean difference and the average of the two methods. The slopes were significantly different from zero among people with normoglycaemia (ß=-0.57, P<0.001), and prediabetes (ß=-0.75, P<0.001) but not among people with diabetes (ß=-0.02, P=0.68). When the prediabetes and diabetes groups were merged into one group, the slope was 0.01, and the glucose values remained similar using the two methods (P=0.76). CONCLUSION: Point-of-care blood glucose measurement may be useful to screen people with diabetes, and to assess glucose among individuals with diabetes where blood can be drawn, but laboratory tests are unavailable or untimely.

Comparison of two high doses of oral methylprednisolone for multiple sclerosis relapses: a pilot, multicentre, randomized, double-blind, non-inferiority trial.

BACKGROUND AND PURPOSE: Oral or intravenous methylprednisolone (≥500 mg/day for 5 days) is recommended for multiple sclerosis (MS) relapses. Nonetheless, the optimal dose remains uncertain. We compared clinical and radiological effectiveness, safety and quality of life (QoL) of oral methylprednisolone [1250 mg/day (standard high dose)] versus 625 mg/day (lesser high dose), both for 3 days] in MS relapses. METHODS: A total of 49 patients with moderate to severe MS relapse within the previous 15 days were randomized in a pilot, double-blind, multicentre, non-inferiority trial (ClinicalTrial.gov, NCT01986998). The primary endpoint was non-inferiority of the lesser high dose by Expanded Disability Status Scale (EDSS) score improvement on day 30 (non-inferiority margin, 1 point). The secondary endpoints were EDSS score change on days 7 and 90, changes in T1 gadolinium-enhanced and new/enlarged T2 lesions on days 7 and 30, and safety and QoL results. RESULTS: The primary outcome was achieved [mean (95% confidence interval) EDSS score difference, -0.26 (-0.7 to 0.18) at 30 days (P = 0.246)]. The standard high dose yielded a superior EDSS score improvement on day 7 (P = 0.028). No differences were observed in EDSS score on day 90 (P = 0.352) or in the number of T1 gadolinium-enhanced or new/enlarged T2 lesions on day 7 (P = 0.401, 0.347) or day 30 (P = 0.349, 0.529). Safety and QoL were good at both doses. CONCLUSIONS: A lesser high-dose oral methylprednisolone regimen may not be inferior to the standard high dose in terms of clinical and radiological response.