Why Is Cardiac Morbidity and Mortality Greater Around Christmas, New Year’s, Monday Mornings and in the Morning Hours: Potential Roles of Unrecognized Ionized Hypomagnesemia and Release of Ceramides?

The following is the introduction to this article: There is a growing incidence of lethal cardiac events around Christmas, New Year’s and in the morning hours from 4:00 to 10:00 a.m. which is well-established in the USA and in The Southern Hemisphere [1-7]. In addition, many cardiac deaths often occur on Mondays with no satisfactory explanation [2,3]. Many of these deaths are, for the most part, unexplained and listed as “death from “natural causes”. Although in the USA, the deaths which occur around Christmas and New Years happen in the cold –winter months, this does not account for many cardiac incidences which occur throughout the year in the early a.m. hours or on Mondays. A number of explanations have been offered to explain the higher morbidities and mortalities at these special times of the year, morning hours and on Mondays, such as emotional stresses, too much ingestion of alcoholic beverages, improper medical facilities, diet, and/or changes in the physical environments [1-7]

How brain-computer interface technology may improve the diagnosis of the disorders of consciousness: A comparative study

ObjectiveClinical assessment of consciousness relies on behavioural assessments, which have several limitations. Hence, disorder of consciousness (DOC) patients are often misdiagnosed. In this work, we aimed to compare the repetitive assessment of consciousness performed with a clinical behavioural and a Brain-Computer Interface (BCI) approach. Materials and methodsFor 7 weeks, sixteen DOC patients participated in weekly evaluations using both the Coma Recovery Scale-Revised (CRS-R) and a vibrotactile P300 BCI paradigm. To use the BCI, patients had to perform an active mental task that required detecting specific stimuli while ignoring other stimuli. We analysed the reliability and the efficacy in the detection of command following resulting from the two methodologies. ResultsOver repetitive administrations, the BCI paradigm detected command following before the CRS-R in seven patients. Four clinically unresponsive patients consistently showed command following during the BCI assessments. ConclusionBrain-Computer Interface active paradigms might contribute to the evaluation of the level of consciousness, increasing the diagnostic precision of the clinical bedside approach. SignificanceThe integration of different diagnostic methods leads to a better knowledge and care for the DOC

Arginine Depletion Attenuates Renal Cystogenesis in Tuberous Sclerosis Complex Model

Cystic kidney disease is a leading cause of morbidity in patients with tuberous sclerosis complex (TSC). We characterize the misregulated metabolic pathways using cell lines, a TSC mouse model, and human kidney sections. Our study reveals a substantial perturbation in the arginine biosynthesis pathway in TSC models with overexpression of argininosuccinate synthetase 1 (ASS1). The rise in ASS1 expression is dependent on the mechanistic target of rapamycin complex 1 (mTORC1) activity. Arginine depletion prevents mTORC1 hyperactivation and cell cycle progression and averts cystogenic signaling overexpression of c-Myc and P65. Accordingly, an arginine-depleted diet substantially reduces the TSC cystic load in mice, indicating the potential therapeutic effects of arginine deprivation for the treatment of TSC-associated kidney disease

Evolution of Linear Absorption and Nonlinear Optical Properties in V-Shaped Ruthenium(II)-Based Chromophores

In this article, we describe a series of complexes with electron-rich cis-{Ru^(II)(NH_3)_4}^(2+) centers coordinated to two pyridyl ligands bearing N-methyl/arylpyridinium electron-acceptor groups. These V-shaped dipolar species are new, extended members of a class of chromophores first reported by us (Coe, B. J. et al. J. Am. Chem. Soc. 2005, 127, 4845−4859). They have been isolated as their PF_6− salts and characterized by using various techniques including ^1H NMR and electronic absorption spectroscopies and cyclic voltammetry. Reversible Ru^(III/II) waves show that the new complexes are potentially redox-switchable chromophores. Single crystal X-ray structures have been obtained for four complex salts; three of these crystallize noncentrosymmetrically, but with the individual molecular dipoles aligned largely antiparallel. Very large molecular first hyperpolarizabilities β have been determined by using hyper-Rayleigh scattering (HRS) with an 800 nm laser and also via Stark (electroabsorption) spectroscopic studies on the intense, visible d → π^* metal-to-ligand charge-transfer (MLCT) and π → π^* intraligand charge-transfer (ILCT) bands. The latter measurements afford total nonresonant β_0 responses as high as ca. 600 × 10^(−30) esu. These pseudo-C_(2v) chromophores show two substantial components of the β tensor, β_(zzz) and β_(zyy), although the relative significance of these varies with the physical method applied. According to HRS, β_(zzz) dominates in all cases, whereas the Stark analyses indicate that β_(zyy) is dominant in the shorter chromophores, but β_(zzz) and β_(zyy) are similar for the extended species. In contrast, finite field calculations predict that β_(zyy) is always the major component. Time-dependent density functional theory calculations predict increasing ILCT character for the nominally MLCT transitions and accompanying blue-shifts of the visible absorptions, as the ligand π-systems are extended. Such unusual behavior has also been observed with related 1D complexes (Coe, B. J. et al. J. Am. Chem. Soc. 2004, 126, 3880−3891)

The effect of nasal provocation with a single-dose allergen on the physical and cognitive performance of patients with ragweed allergy

Purpose This study aims to compare the impact of active allergic rhinitis on physical and cognitive abilities of trained allergic athletes to untrained allergic patients. Methods Cognitive, respiratory, and fitness functions were assessed before and after allergen exposure. Participants in both groups were provoked intranasally with ragweed allergen. Results The group of athletes revealed significantly higher average values in peak inspiratory flow and fitness index before and after provocation. In neuropsychological assessments, athletes performed significantly better after allergen provocation in complex working memory capacity. Due to single acute allergen exposure, the size of the nasal cavity and nasal inspiratory peak flow significantly decreased in both groups. The physical performance of both groups did not change after provocation. Executive functions and complex working memory capacity of athletes significantly improved resulting from provocation. Conclusions A single-shot allergen in high dose might cause an increase in mental concentration, which was more pronounced in the group of athletes. This study indicates that acute exposure to allergen cannot affect the physical performance and may result in increased mental focus in patients with allergy notwithstanding the declining respiratory functions

Diquat Derivatives: Highly Active, Two-Dimensional Nonlinear Optical Chromophores with Potential Redox Switchability

In this article, we present a detailed study of structure−activity relationships in diquaternized 2,2′-bipyridyl (diquat) derivatives. Sixteen new chromophores have been synthesized, with variations in the amino electron donor substituents, π-conjugated bridge, and alkyl diquaternizing unit. Our aim is to combine very large, two-dimensional (2D) quadratic nonlinear optical (NLO) responses with reversible redox chemistry. The chromophores have been characterized as their PF_6^− salts by using various techniques including electronic absorption spectroscopy and cyclic voltammetry. Their visible absorption spectra are dominated by intense π → π^* intramolecular charge-transfer (ICT) bands, and all show two reversible diquat-based reductions. First hyperpolarizabilities β have been measured by using hyper-Rayleigh scattering with an 800 nm laser, and Stark spectroscopy of the ICT bands affords estimated static first hyperpolarizabilities β_0. The directly and indirectly derived β values are large and increase with the extent of π-conjugation and electron donor strength. Extending the quaternizing alkyl linkage always increases the ICT energy and decreases the E_(1/2) values for diquat reduction, but a compensating increase in the ICT intensity prevents significant decreases in Stark-based β_0 responses. Nine single-crystal X-ray structures have also been obtained. Time-dependent density functional theory clarifies the molecular electronic/optical properties, and finite field calculations agree with polarized HRS data in that the NLO responses of the disubstituted species are dominated by ‘off-diagonal’ β_(zyy) components. The most significant findings of these studies are: (i) β_0 values as much as 6 times that of the chromophore in the technologically important material (E)-4′-(dimethylamino)-N-methyl-4-stilbazolium tosylate; (ii) reversible electrochemistry that offers potential for redox-switching of optical properties over multiple states; (iii) strongly 2D NLO responses that may be exploited for novel practical applications; (iv) a new polar material, suitable for bulk NLO behavior

Assessment of Potential Companies Based on Performance and Financial Component under Conditions of New Economic Growth Model

In the article there are presented the features of the components that make up the economic capacity of the organization, improve the ability to deepen the analysis of their impact on the effectiveness of and prospects for stable development of the business entity in the new paradigm of economic development. Also, it the authors have developed the technique of evaluating the economic potential of the entertainment, through the application of the component approach and integrated rating. The complex analysis of the economic potential of "Istochnik" based on the proposed method of scoring production and financial potential of the company. Keywords: Economic potential, financial strength, system, production, finance, numerical score, a technique JEL Classification: O1

A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis

The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 [odds ratio (OR) = 1.17 and 1.18, and P-values = 6.98 x 10–7 and 1.16 x 10–6], were located on chromosome 7p13.3 within a 175 kb linkage disequilibrium block containing the SUNC1, HUS1 and C7orf57 genes. These associations did not achieve genome-wide significance in the original cohort and failed to replicate in an additional independent cohort of 989 US cases and 327 controls (OR = 1.18 and 1.19, P-values = 0.08 and 0.06, respectively). Thus, we chose to cautiously interpret our data as hypothesis-generating requiring additional confirmation, especially as all previously reported loci for ALS have failed to replicate successfully. Indeed, the three loci (FGGY, ITPR2 and DPP6) identified in previous GWAS of sporadic ALS were not significantly associated with disease in our study. Our findings suggest that ALS is more genetically and clinically heterogeneous than previously recognized. Genotype data from our study have been made available online to facilitate such future endeavors