Quantum Markovian activated surface diffusion of interacting adsorbates.
A quantum Markovian activated atom-surface diffusion model with interacting adsorbates is proposed for the intermediate scattering function, which is shown to be complex-valued and factorizable into a classical-like and a quantum-mechanical factor. Applications to the diffusion of Na atoms on flat (weakly corrugated) and corrugated-Cu(001) surfaces at different coverages and surface temperatures are analyzed. Quantum effects are relevant to diffusion at low surface temperatures and coverages even for relatively heavy particles, such as Na atoms, where transport by tunneling is absent.


[Rapid spontaneous resolution of an acute epidural hematoma].
The rapid spontaneous resolution of an acute epidural hematoma within a one hour is reported in a 8 year-old boy. The literature is reviewed and the potential communication between intracranial and epicranial spaces through a fracture is emphasized in very rapid spontaneous resolution of epidural hematomas.


Osteoporosis and sarcopenia: two diseases or one?
This article reviews recently published evidence for common pathways explaining bone and muscle wasting in normal ageing and pathological conditions. Numerous studies support the concept of a bone-muscle unit, where constant cross-talking between the two tissues takes place, involving molecules released by the skeletal muscle secretome, which affects bone, and osteokines secreted by the osteoblasts and osteocytes, which, in turn, impact muscle cells. New chemical entities aiming at concomitantly treating osteoporosis and sarcopenia could be developed by targeting pathways that centrally regulate bone and muscle or emerging pathways that facilitate the communication between the two tissues.


Studies on supercapacitor electrode material from activated lignin-derived mesoporous carbon.
We synthesized mesoporous carbon from pre-cross-linked lignin gel impregnated with a surfactant as the pore-forming agent and then activated the carbon through physical and chemical methods to obtain activated mesoporous carbon. The activated mesoporous carbons exhibited 1.5- to 6-fold increases in porosity with a maximum Brunauer-Emmett-Teller (BET) specific surface area of 1148 m(2)/g and a pore volume of 1.0 cm(3)/g. Both physical and chemical activation enhanced the mesoporosity along with significant microporosity. Plots of cyclic voltammetric data with the capacitor electrode made from these carbons showed an almost rectangular curve depicting the behavior of ideal double-layer capacitance. Although the pristine mesoporous carbon exhibited a range of surface-area-based capacitance similar to that of other known carbon-based supercapacitors, activation decreased the surface-area-based specific capacitance and enhanced the gravimetric specific capacitance of the mesoporous carbons. A vertical tail in the lower-frequency domain of the Nyquist plot provided additional evidence of good supercapacitor behavior for the activated mesoporous carbons. We have modeled the equivalent circuit of the Nyquist plot with the help of two constant phase elements (CPE). Our work demonstrated that biomass-derived mesoporous carbon materials continue to show potential for use in specific electrochemical applications.


Modelling bioelectrochemical denitrification in absence of electron donors for groundwater treatment.
Microbial electrochemical technologies (METs) have become a widely studied technology in recent years due to the need for sustainable biotechnologies. The scope of this work is the development of a mechanistic biokinetic model, based on first principles and a robust thermodynamic basis, to provide a theoretical accurate description of a MET system that would treat water contaminated with nitrate, the most common aquifer water pollutant, in absence of external electron donors. The model aims at describing the complex processes occurring including the competition between bioelectroactive and non-bioelectroactive reactions as well as the dynamics and kinetics of multiple bioelectrochemical reactions (both in series and in parallel) taking place in the same electrode. The bioelectrochemical denitrification of groundwater was then evaluated using the model as a case study. The evaluation focused on theoretical removal rates and energy expenditure, as well as the effect of key design parameters on the system's performance. The model successfully described how changes in the applied voltage and/or hydraulic retention time may impact the performance in terms of removal rate and effluent quality. The theoretical results also predict that the impact of electrode area is potentially more significant on the energy efficiency rather than on the effluent quality.


Design and Fabrication of a Three-Dimensional In Vitro System for Modeling Vascular Stenosis.
Vascular stenosis, the abnormal narrowing of blood vessels, arises from defective developmental processes or atherosclerosis-related adult pathologies. Stenosis triggers a series of adaptive cellular responses that induces adverse remodeling, which can progress to partial or complete vessel occlusion with numerous fatal outcomes. Despite its severity, the cellular interactions and biophysical cues that regulate this pathological progression are poorly understood. Here, we report the design and fabrication of a three-dimensional (3D) in vitro system to model vascular stenosis so that specific cellular interactions and responses to hemodynamic stimuli can be investigated. Tubular cellularized constructs (cytotubes) were produced, using a collagen casting system, to generate a stenotic arterial model. Fabrication methods were developed to create cytotubes containing co-cultured vascular cells, where cell viability, distribution, morphology, and contraction were examined. Fibroblasts, bone marrow primary cells, smooth muscle cells (SMCs), and endothelial cells (ECs) remained viable during culture and developed location- and time-dependent morphologies. We found cytotube contraction to depend on cellular composition, where SMC-EC co-cultures adopted intermediate contractile phenotypes between SMC- and EC-only cytotubes. Our fabrication approach and the resulting artery model can serve as an in vitro 3D culture system to investigate vascular pathogenesis and promote the tissue engineering field.


Burden of Cancer Among Syrian Refugees in Jordan.
The Syrian crisis, which started in 2011, has had a profound impact on the entire region. Jordan, with its limited resources, now has the second highest ratio of refugees to inhabitants in the world (89 to 1,000). The actual number of Syrians in Jordan is hotly contested: more than 630,776 refugees registered in November 2015 compared with 1,265,514 reported by the national census conducted at the same time. Although the numbers are slowly but steadily increasing, the number of patients with cancer who were registered by the Jordan Cancer Registry peaked in 2013 at 510 patients reported and subsequently slumped downward, which coincided with changes in funding as a result of the increasing strains on the Ministry of Health. Older individuals, women, and patients with advanced diseases were less likely to be registered. These findings overlap with data obtained from the authors' own center registry. Using age- and sex-specific population-based incidence rates, we estimated that 869 Syrians are diagnosed with cancer in Jordan annually. Using diagnosis-specific cost records of the King Hussein Cancer Foundation, we estimated that the cost of their treatments is 15.6 million Jordan dinars (US$22.1 million).


Gender dimorphism of macrophage response to GMCSF and IL-4 for differentiation into dendritic cells.
We previously demonstrated the existence of gender dimorphism in a murine tumor model with respect to the growth of a spontaneous T-cell lymphoma designated as Dalton's lymphoma and several aspects of host-tumor interaction. We also demonstrated the involvement of macrophages in manifestation of gender-dependent differential tumor growth [J Reprod Immunol 2005; 65:17, Cancer Invest 2006; 24:1, J Biomed Sci 2007 (in press), J Reprod Immunol 2007; 74:90]. Although monocytes/macrophages of tumor-bearing hosts have been used to differentiate into macrophage-derived dendritic cells for various applications in the immunotherapy of cancer, it remains unclear if macrophages show a gender-dependent differential response to the signals of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for differentiation to cells with dendritic cell morphology (MO-DC) and if these MO-DC have a gender-dependent differential therapeutic efficacy in inhibiting tumor growth. Peritoneal macrophage obtained from male and female mice were incubated in vitro for a period of 7 days in a medium containing GM-CSF (800 IU/mL) and IL-4 (500 IU/mL) followed by incubation for further 24 hr in medium alone or containing lipopolysaccharide (LPS; 10 ng/mL) to differentiate into cells with DC morphology (MO-DC). The MO-DC thus obtained were used to check a variety of phenotypic and functional parameters related to their gender-dependent anti-tumor activity. The MO-DC obtained from male mice showed a better response to GM-CSF and IL-4 treatment and activation by LPS for differentiating into cells with DC phenotype compared with that of female mice. MO-DC of male mice showed a comparatively higher tumoricidal activity, expression of DC markers [chemokine receptor-5 (CCR-5), ICAM-1 (CD-54) and CD-80], MLR, pinocytosis and production of NO, IFN-gamma and TNF-alpha. Adoptive transfer of MO-DC obtained from male mice to tumor-bearing mice resulted in a longer prolongation of survival duration and a better retardation of tumor growth compared with the MO-DC obtained from female mice. To the best of our knowledge, this is the first report of its kind to demonstrate the existence of gender dimorphism in the antitumor and other accessory functions of macrophages differentiated in vitro into cells with DC morphology. These observations may have long lasting clinical significance in developing gender-specific protocols regarding the use of MO-DC in cancer immunotherapy.


miRBaseMiner, a tool for investigating miRBase content.
microRNAs are small non-coding RNA molecules playing a central role in gene regulation. miRBase is the standard reference source for analysis and interpretation of experimental studies. However, the richness and complexity of the annotation is often underappreciated by users. Moreover, even for experienced users, the size of the resource can make it difficult to explore annotation to determine features such as species coverage, the impact of specific characteristics and changes between successive releases. A further consideration is that each new miRBase release contains entries that have had limited review and which may subsequently be removed in a future release to ensure the quality of annotation. To aid the miRBase user, we developed a software tool, miRBaseMiner, for investigating miRBase annotation and generating custom annotation sets. We apply the tool to characterize each release from v9.2 to v22 to examine how annotation has changed across releases and highlight some of the annotation features that users should keep in mind when using for miRBase for data analysis. These include: (1) entries with identical or very similar sequences; (2) entries with multiple annotated genome locations; (3) hairpin precursor entries with extremely low-estimated minimum free energy; (4) entries possessing reverse complementary; (5) entries with 3' poly(A) ends. As each of these factors can impact the identification of dysregulated features and subsequent clinical or biological conclusions, miRBaseMiner is a valuable resource for any user using miRBase as a reference source.


Cranial reconstruction after a post-craniotomy empyema.
This article presents a case report of a cranioplasty performed after a post-craniotomy empyema with osteitis. The skull reconstruction was performed using a bioceramic implant and a combined muscular free flap of latissimus dorsi and serratus anterior. This procedure not only provided coverage of a wide skull defect but also allowed the filling of the intracranial dead space. Clinically, we observed an improvement of the patient's preoperative neurological status with a near-complete correction of her right hemiparaesis and phasic disorders. Eight months after the cranioplasty, (1) no recurrence of infection was noticed; (2) no distortion of the skull was noticeable and (3) the patient again experienced a normal social life. Using computed tomography (CT) scan images, we observed a re-expansion of the left cerebral hemisphere without any dead space or extradural collection. The only observable sequelae were a temporoparietal alopecia (10 cm x 4 cm) and a winging of the scapula, induced by the skin graft and the removal of the lower-third of the serratus anterior muscle, respectively. The use of a muscular free flap associated with a customised biomaterial allows a single-stage reconstruction of extensive skull defect (120 cm(2)) in a previously infected area.


The susceptible HLA class II alleles and their presenting epitope(s) in Goodpasture's disease.
Goodpasture's disease is closely associated with HLA, particularly DRB1*1501. Other susceptible or protective HLA alleles are not clearly elucidated. The presentation models of epitopes by susceptible HLA alleles are also unclear. We genotyped 140 Chinese patients and 599 controls for four-digit HLA II genes, and extracted the encoding sequences from the IMGT/HLA database. T-cell epitopes of α3(IV)NC1 were predicted and the structures of DR molecule-peptide-T-cell receptor were constructed. We confirmed DRB1*1501 (OR = 4·6, P = 5·7 × 10-28 ) to be a risk allele for Goodpasture's disease. Arginine at position 13 (ARG13) (OR = 4·0, P = 1·0 × 10-17 ) and proline at position 11 (PRO11) (OR = 4·0, P = 2·0 × 10-17 ) on DRβ1, encoded by DRB1*1501, were associated with disease susceptibility. α134-148 (HGWISLWKGFSFIMF) was predicted as a T-cell epitope presented by DRB1*1501. Isoleucine137 , tryptophan140 , glycine142 , phenylalanine143 and phenylalanine145 , were presented in peptide-binding pockets 1, 4, 6, 7 and 9 of DR2b, respectively. ARG13 in pocket 4 interacts with tryptophan140 and forms a hydrogen bond. In conclusion, we propose a mechanism for DRB1*1501 susceptibility for Goodpasture's disease through encoding ARG13 and PRO11 on MHC-DRβ1 chain and presenting T-cell epitope, α134-148 , with five critical residues.


Lipolysis in cheddar cheese made from raw, thermized, and pasteurized milks.
The evolution of free fatty acids (FFA) was monitored over 168 d of ripening in Cheddar cheeses manufactured from good quality raw milk (RM), thermized milk (TM; 65 degrees C x 15 s), and pasteurized milk (PM; 72 degrees C x 15 s). Heat treatment of the milk reduced the level and diversity of raw milk microflora and extensively or wholly inactivated lipoprotein lipase (LPL) activity. Indigenous milk enzymes or proteases from RM microflora influenced secondary proteolysis in TM and RM cheeses. Differences in FFA in the RM, TM, and PM influenced the levels of FFA in the subsequent cheeses at 1 d, despite significant losses of FFA to the whey during manufacture. Starter esterases appear to be the main contributors of lipolysis in all cheeses, with LPL contributing during production and ripening in RM and, to a lesser extent, in TM cheeses. Indigenous milk microflora and nonstarter lactic acid bacteria appear to have a minor contribution to lipolysis particularly in PM cheeses. Lipolytic activity of starter esterases, LPL, and indigenous raw milk microflora appeared to be limited by substrate accessibility or environmental conditions over ripening.


Global transmission/disequilibrium tests based on haplotype sharing in multiple candidate genes.
It is well recognized that multiple genes are likely contributing to the susceptibility of most common complex diseases. Studying one gene at a time might reduce our chance to identify disease susceptibility genes with relatively small effect sizes. Therefore, it is crucial to develop statistical methods that can assess the effect of multiple genes collectively. Motivated by the increasingly available high-density markers across the whole human genome, we propose a class of TDT-type methods that can jointly analyze haplotypes from multiple candidate genes (linked or unlinked). Our approach first uses a linear signed rank statistic to compare at an individual gene level the structural similarity among transmitted haplotypes against that among non-transmitted haplotypes. The results of the ranked comparisons from all considered genes are subsequently combined into global statistics, which can simultaneously test the association of the set of genes with the disease. Using simulation studies, we find that the proposed tests yield correct type I error rates in stratified populations. Compared with the gene-by-gene test, the new global tests appear to be more powerful in situations where all candidate genes are associated with the disease.


Crosstalk between bone niche and immune system: osteoimmunology signaling as a potential target for cancer treatment.
There is a well recognized link between the bone and the immune system and in recent years there has been a major effort to elucidate the multiple functions of the molecules expressed in both bone and immune cells. Several molecules that were initially identified and studied in the immune system have been shown to have essential functions also in the bone. An interdisciplinary field embracing immune and bone biology has been brought together and called "osteoimmunology". The co-regulation of the skeletal and immune systems strikingly exemplifies the extreme complexity of such an interaction. Their interdependency must be considered in designing therapeutic approaches for either of the two systems. In other words, it is necessary to think of the osteoimmune system as a complex physiological unit. Denosumab was originally introduced to specifically target bone resorption, but it is now under evaluation for its effect on the long term immune response. Similarly, our current and still growing knowledge of the intimate link between the immune system and bone will be beneficial for the safety of drugs targeting either of these integrated systems. Given the large number of molecules exerting functions on both the skeletal and immune systems, osteoimmunological understanding is becoming increasingly important. Both bone and immune systems are frequently disrupted in cancer; and they may be crucial in regulating tumor growth and progression. Some therapies - such as bisphosphonates and receptor activator of NF-κB ligand (RANKL) targeted drugs - that aim at reducing pathologic osteolysis in cancer may interact with the immune system, thus providing potential favorable effects on survival.


Synthesis of the parent and substituted tetracyclic ABCD ring cores of camptothecins via 1-(3-aryl-2-propynyl)- 1,6-dihydro-6-oxo-2-pyridinecarbonitriles.
A new synthetic pathway to the parent and substituted ABCD ring cores of the camptothecin family of alkaloids was developed. The N-alkylation of 1,6-dihydro-6-oxo-2-pyridinecarbonitrile (2) with 3-bromo-1-phenylpropyne provided 3a using Curran's protocol. Treatment of 3a with a catalytic amount of DBU (5 mol %) at 110 degrees C for 12 h produced indolizino[1,2-b]quinolin-9(11H)-one (6a), the parent ABCD ring core of camptothecin, in essentially quantitative yield.


Model Fractional Chern Insulators.
We devise local lattice models whose ground states are model fractional Chern insulators-Abelian and non-Abelian topologically ordered states characterized by exact ground state degeneracies at any finite size and infinite entanglement gaps. Most saliently, we construct exact parent Hamiltonians for two distinct families of bosonic lattice generalizations of the Z_{k} parafermion quantum Hall states: (i) color-entangled fractional Chern insulators at band filling fractions ν=k/(C+1) and (ii) nematic states at ν=k/2, where C is the Chern number of the lowest band. In spite of a fluctuating Berry curvature, our construction is partially frustration free: the ground states reside entirely within the lowest band and exactly minimize a local (k+1) body repulsion term by term. In addition to providing the first known models hosting intriguing states such as higher Chern number generalizations of the Fibonacci anyon quantum Hall states, the remarkable stability and finite-size properties make our models particularly well suited for the study of novel phenomena involving, e.g., twist defects and proximity induced superconductivity, as well as being a guide for designing experiments.


Compact folded metasurface spectrometer.
An optical design space that can highly benefit from the recent developments in metasurfaces is the folded optics architecture where light is confined between reflective surfaces, and the wavefront is controlled at the reflective interfaces. In this manuscript, we introduce the concept of folded metasurface optics by demonstrating a compact spectrometer made from a 1-mm-thick glass slab with a volume of 7 cubic millimeters. The spectrometer has a resolution of ~1.2 nm, resolving more than 80 spectral points from 760 to 860 nm. The device is composed of three reflective dielectric metasurfaces, all fabricated in a single lithographic step on one side of a substrate, which simultaneously acts as the propagation space for light. The folded metasystem design can be applied to many optical systems, such as optical signal processors, interferometers, hyperspectral imagers, and computational optical systems, significantly reducing their sizes and increasing their mechanical robustness and potential for integration.


Anomalous thermalization of nonlinear wave systems.
We report theoretically and experimentally in an optical system a process of anomalous thermalization of one-dimensional nonlinear Hamiltonian waves. It is characterized by an irreversible evolution of the waves towards a specific equilibrium state of a fundamental different nature than the expected thermodynamic equilibrium state. A kinetic approach of the problem reveals that this phenomenon is due to the existence of a local invariant in frequency space. A novel family of equilibrium distributions is discovered, which is found in quantitative agreement with the numerical simulations.


High-Performance Organic Vertical Thin Film Transistor Using Graphene as a Tunable Contact.
Here we present a general strategy for the fabrication of high-performance organic vertical thin film transistors (OVTFTs) based on the heterostructure of graphene and different organic semiconductor thin films. Utilizing the unique tunable work function of graphene, we show that the vertical carrier transport across the graphene-organic semiconductor junction can be effectively modulated to achieve an ON/OFF ratio greater than 10(3). Importantly, with the OVTFT design, the channel length is determined by the organic thin film thickness rather than by lithographic resolution. It can thus readily enable transistors with ultrashort channel lengths (<200 nm) to afford a delivering current greatly exceeding that of conventional planar TFTs, thus enabling a respectable operation frequency (up to 0.4 MHz) while using low-mobility organic semiconductors and low-resolution lithography. With this vertical device architecture, the entire organic channel is sandwiched and naturally protected between the source and drain electrodes, which function as the self-passivation layer to ensure stable operation of both p- and n-type OVTFTs in ambient conditions and enable complementary circuits with voltage gain. The creation of high-performance and highly robust OVTFTs can open up exciting opportunities in large-area organic macroelectronics.


Swiss consensus recommendations on urinary tract infections in children.
The kidneys and the urinary tract are a common source of infection in children of all ages, especially infants and young children. The main risk factors for sequelae after urinary tract infections (UTI) are congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction. UTI should be considered in every child with fever without a source. The differentiation between upper and lower UTI is crucial for appropriate management. Method of urine collection should be based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture. Treatment of UTI should be based on practical considerations regarding age and presentation with adjustment of the initial antimicrobial treatment according to antimicrobial sensitivity testing. All children, regardless of age, should have an ultrasound of the urinary tract performed after pyelonephritis. In general, antibiotic prophylaxis is not recommended.Conclusion: Based on recent data and in line with international guidelines, multidisciplinary Swiss consensus recommendations were developed by members of Swiss pediatric infectious diseases, nephrology, and urology societies giving the clinician clear recommendations in regard to diagnosis, type and duration of therapy, antimicrobial treatment options, indication for imaging, and antibiotic prophylaxis. What is Known: • Urinary tract infections (UTI) are a common and important clinical problem in childhood. Although children with pyelonephritis tend to present with fever, it can be difficult on clinical grounds to distinguish cystitis from pyelonephritis, particularly in young children less than 2 years of age. • Method of urine collection is based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture. What is New: • Vesicoureteric reflux (VUR) remains a risk factor for UTI but per se is neither necessary nor sufficient for the development of renal scars. Congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction play a more important role as causes of long-term sequelae. In general, antibiotic prophylaxis is not recommended. • A switch to oral antibiotics should be considered already in young infants. Indications for invasive imaging are more restrictive and reserved for patients with abnormal renal ultrasound, complicated UTI, and infections with pathogens other than E. coli.


[Association between polymorphisms in the gene coding for glutathione S-transferase P1 and chronic obstructive pulmonary disease].
To investigate the association between polymorphisms in the gene coding for glutathione S-transferase P1 (GSTP1) and susceptibility to chronic obstructive pulmonary disease (COPD) in a Chinese population. This was a pilot study of the molecular epidemiology in patients with COPD. The research design was a case-control study. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to genotype GSTP1 polymorphisms in exon 5 in 100 COPD patients and 100 age and sex matched healthy controls. Logistic regression analysis method was used to calculate the odds ratio (OR) and the 95% confidence interval (CI). There was no significant difference in GSTP1 polymorphisms adjusted by age, sex, body mass index and smoking between COPD patients and controls. The gene polymorphism for GSTP1 was not associated with susceptibility to COPD in the Chinese population.


MERS coronavirus neutralizing antibodies in camels, Eastern Africa, 1983-1997.
To analyze the distribution of Middle East respiratory syndrome coronavirus (MERS-CoV)-seropositive dromedary camels in eastern Africa, we tested 189 archived serum samples accumulated during the past 30 years. We identified MERS-CoV neutralizing antibodies in 81.0% of samples from the main camel-exporting countries, Sudan and Somalia, suggesting long-term virus circulation in these animals.


Identification and Characteristics of Lactic Acid Bacteria Isolated from Sour Dough Sponges.
Lactic acid bacteria in four samples of sour dough sponges were studied quantitatively and qualitatively. In each sponge, there were one or two species of the genus Lactobacillus: L. reuteri and L. curvatus in San Francisco sour dough sponge, L. brevis and L. hilgardii in panettone sour dough sponge produced in Italy, L. sanfrancisco from a rye sour dough sponge produced in Germany, and L. casei and L. curvatus from a rye sour dough sponge produced in Switzerland. For all isolates except the L. reuteri strains oleic acid, a component of the Tween 80 added to the medium, was essential for growth. It was of interest that lactobacilli requiring oleic acid were the predominant flora of lactic acid bacteria in the microbial environment of sour dough sponges.


Body composition and circulating levels of insulin, insulin-like growth factor-binding protein-1 and growth hormone (GH)-binding protein affect the pharmacokinetics of GH in adults independently of age.
The aim of our study was to scrutinize the association among age, body composition, and GH status in healthy adults. Using two-step, primed constant infusions of GH during suppression of endogenous GH secretion with octreotide in a group of 26 healthy nonobese men [mean age, 37.3 yr (range, 22-55 yr); body mass index, 24.6 +/- 0.4 kg/m(-2)] we investigated the contributions of age, body composition, insulin, and binding proteins to the variability in the pharmacokinetics and acute actions of GH. All subjects were investigated twice, with the infusion rates of GH calculated according to either total body weight or intraabdominal fat mass. Body composition was determined using computed tomography and bioimpedance measurements. There was no correlation between age and body weight, yet strong positive correlations were observed between age and intraabdominal fat area (r = 0.78; P < 0.0001) and waist to hip ratio (r = 0.71; P < 0.0001) and to a lesser degree to sc fat area (r = 0.42; P < 0.03). The between-subject variability in steady state GH levels was significantly larger when GH was administered per cm(2) intraabdominal fat area than per kg BW (P < 0.001). During primed constant infusions of GH at rates of 1.5 and 3.0 microg/kg x h, the corresponding MCRs of GH were 148.8 +/- 5.4 and 89.8 +/- 2.4 ml/min x m(-2), respectively, and the MCRs were inversely related to the achieved steady state GH levels (P < 0.0001). The MCR was unrelated to age, but was negatively correlated to baseline concentrations of IGF-binding protein-1 (IGFBP-1; r = -0.53, P < 0.01) and positively correlated to basal levels of insulin (r = 0.46; P < 0.05), GH-binding protein (GHBP; r = 0.52; P < 0.01), IGFBP-3 (r = 0.47; P < 0.05), and total body fat (r = 0.44; P < 0.05). GH infusion caused significant changes in the concentrations of IGF-I, free fatty acids, GHBP, IGFBP-1, and insulin, but none of these effects was correlated to age. Based on our results we conclude that 1) the clearance of GH is concentration dependent; 2) the pharmacokinetics and acute effects of GH are not affected by age per se; and 3) basal levels of insulin, IGFBP-1, and GHBP as well as age-related changes in body composition are important predictors of GH pharmacokinetics.


Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part I-Psychiatric and Behavioral Interventions.
This article outlines the consensus guidelines for symptomatic treatment for children with Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Syndrome Associated with Streptococcal Infection (PANDAS). Extant literature on behavioral, psychotherapeutic, and psychopharmacologic treatments for PANS and PANDAS was reviewed. Members of the PANS Research Consortium pooled their clinical experiences to find agreement on treatment of PANS and PANDAS symptoms. Current guidelines result from consensus among the Consortium members. While underlying infectious and inflammatory processes in PANS and PANDAS patients are treated, psychiatric and behavioral symptoms need simultaneous treatment to decrease suffering and improve adherence to therapeutic intervention. Psychological, behavioral, and psychopharmacologic interventions tailored to each child's presentation can provide symptom improvement and improve functioning during both the acute and chronic stages of illness. In general, typical evidence-based interventions are appropriate for the varied symptoms of PANS and PANDAS. Individual differences in expected response to psychotropic medication may require marked reduction of initial treatment dose. Antimicrobials and immunomodulatory therapies may be indicated, as discussed in Parts 2 and 3 of this guideline series.


Modulation of local field potentials by high-frequency stimulation of afferent axons in the hippocampal CA1 region.
Modulation of the rhythmic activity of local field potentials (LFP) in neuronal networks could be a mechanism of deep brain stimulation (DBS). However, exact changes of LFP during the periods of high-frequency stimulation (HFS) of DBS are unclear because of the interference of dense stimulation artifacts with high amplitudes. In the present study, we investigated LFP changes induced by HFS of afferent axons in the hippocampal CA1 region of urethane-anesthetized rats by using a proper algorithm of artifact removal. Afterward, the LFP changes in the frequency bands of [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] rhythms were studied by power spectrum analysis and coherence analysis for the recorded signals collected in the pyramidal layer and in the stratum radiatum of CA1 region before, during and after 1-min long 100 and 200[Formula: see text]Hz HFS. Results showed that the power of LFP rhythms in higher-frequency band ([Formula: see text] rhythm) increased in the pyramidal layer and the power of LFP rhythms in lower-frequency bands ([Formula: see text], [Formula: see text] and [Formula: see text] rhythms) decreased in the stratum radiatum during HFS. The synchronization of [Formula: see text] rhythm decreased and the synchronization of [Formula: see text] rhythm increased during HFS in the stratum radiatum. These results suggest that axonal HFS could modulate LFP rhythms in the downstream brain areas with a plausible underlying mechanism of partial axonal blockage induced by HFS. The study provides new evidence to support the mechanism of DBS modulating rhythmic activity of neuronal populations.


Monitoring disease in lymphoma and CLL patients using molecular techniques.
Over the past decade considerable advances have been made in the sensitivity of detection of residual lymphoma and leukaemia cells. Assays based on the polymerase chain reaction (PCR) can detect one tumour cell in up to 10(5) to 10(6) normal cells. The identification and cloning of breakpoints associated with specific chromosomal translocations has made possible the application of these techniques to a variety of lymphoid malignancies. In parallel, B cell malignancies exhibit rearrangements of their immunoglobulin genes that are also suitable targets for PCR amplification to identify residual cells. Although these techniques provide a useful adjunct to standard methods of detection and diagnosis, their role in determining disease outcome remains investigational. There is confusion as to whether it is necessary to eradicate PCR-detectable lymphoma cells for cure, so it is not yet possible to determine whether the detection of residual lymphoma cells by PCR is an indication to continue therapy.


Single-stage reconstruction of key pinch and extension of the elbow in tetraplegic patients.
The results in ten arms of nine patients who had post-traumatic tetraplegia at the fifth or sixth cervical level were reviewed after combined transfer of the brachioradialis to the flexor pollicis longus and of the posterior part of the deltoid to the triceps tendon to restore key pinch and extension of the elbow. The average age of the patients was twenty-nine years, the average time from the injury to the operation was five years, and the average duration of follow-up was thirty-one months. Key pinch improved from essentially none preoperatively to an average of 2.0 pounds (0.9 kilogram) postoperatively: an average of 3.0 pounds (1.4 kilograms) for the patients who had tetraplegia at the sixth cervical level and an average of 0.9 pound (0.4 kilogram) for those who had tetraplegia at the fifth cervical level. Key pinch was favorably influenced by extension of the wrist, while the position of the elbow had no effect. Maximum active extension of the elbow against gravity was within 20 degrees of full extension in eight of the ten arms. There was an improvement in the performance of activities of daily living, including wheelchair use, and most of the patients discontinued use of special equipment for the upper extremity. The results of this study, when compared with those of each procedure performed separately, suggest that a combination of the operations improves function of the upper extremity and shortens the duration of dependence postoperatively.


Substrate utilization by Clostridium estertheticum cultivated in meat juice medium.
Blown pack spoilage of vacuum packaged beef, which results in packs being grossly distended with gas, is caused by the psychrophile Clostridium estertheticum. To determine what substrates are utilized by C. estertheticum during growth on beef, C. estertheticum subsp. estertheticum ATCC 51377, the type strain for that organism, and two isolates from blown pack spoiled beef that were identified as C. estertheticum by 16 S rRNA gene sequencing were grown in meat juice medium at 10 degrees C for up to 14 days. Analysis of the growth media showed that all three organisms grew exponentially on glucose with simultaneous hydrolysis of glycogen. Growth ceased when glucose in the media was depleted; but hydrolysis of glycogen continued at a reduced rate, and lactate was consumed rapidly. The pH values of media fell during growth of the organisms, but rose as the concentrations of lactate subsequently decreased. The major products of fermentation during utilization of glucose were butyrate and acetate, with butyrate greatly predominating. During fermentation of lactate the major products were butyrate and butanol, which were produced in similar amounts. The findings suggest that growth of C. estertheticum on vacuum packaged beef may be limited by the availability of glucose, as is the growth of other organisms that usually predominate in the flora of vacuum packaged meat. However, production of gas by fermentation of lactate will likely continue after growth ceases.


Effect of parental coronary artery disease on adverse effects of the metabolic syndrome and aging on carotid artery intima-media thickness (from the Bogalusa Heart Study).
Genetic susceptibility is considered an important predictor of coronary artery disease (CAD) and its risk factors. This study was conducted to assess the hypothesis that parental CAD, a surrogate measure of genetic susceptibility, increases the vulnerability of the arterial wall to adverse effects of the metabolic syndrome and the aging process in asymptomatic young adults. The study cohort consisted of 1,073 black and white subjects (29.1% black, 43.7% male) aged 25 to 44 years. Carotid intima-media thickness (IMT) of the common carotid, carotid bulb, and internal carotid segments was measured using B-mode ultrasound. Subjects with parental CAD had greater composite (average of 3 segments) carotid IMT (0.839 vs 0.802 mm, p = 0.04) and a higher prevalence of the metabolic syndrome (20.7% vs 13.3%, p <0.01) compared with those without such a history. Furthermore, the association of the metabolic syndrome with composite, carotid bulb, and internal carotid IMT was significantly stronger in subjects with parental CAD than those without such a history (p = 0.022, p = 0.032, and p = 0.035 for comparison of slopes, respectively). After adjusting for race, gender, and the metabolic syndrome components, only internal carotid IMT showed significantly more increase with age in subjects with parental CAD compared with those without such a history (regression coefficient: beta = 0.014 vs beta = 0.006, p = 0.010 for comparison of slopes). In conclusion, parental CAD amplifies the adverse effects of the metabolic syndrome and aging on carotid artery IMT, especially internal carotid IMT, in asymptomatic young adults. These findings reinforce the value of using family history of CAD in risk assessment algorithm.


mTORC1 activity repression by late endosomal phosphatidylinositol 3,4-bisphosphate.
Nutrient sensing by mechanistic target of rapamycin complex 1 (mTORC1) on lysosomes and late endosomes (LyLEs) regulates cell growth. Many factors stimulate mTORC1 activity, including the production of phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] by class I phosphatidylinositol 3-kinases (PI3Ks) at the plasma membrane. We investigated mechanisms that repress mTORC1 under conditions of growth factor deprivation. We identified phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2], synthesized by class II PI3K β (PI3KC2β) at LyLEs, as a negative regulator of mTORC1, whereas loss of PI3KC2β hyperactivated mTORC1. Growth factor deprivation induced the association of PI3KC2β with the Raptor subunit of mTORC1. Local PI(3,4)P2 synthesis triggered repression of mTORC1 activity through association of Raptor with inhibitory 14-3-3 proteins. These results unravel an unexpected function for local PI(3,4)P2 production in shutting off mTORC1.


[Not Available].
The paper attempts to conceptualise the observations made in therapies of Holocaust survivors. The first case studies of child therapies were published in 1982, demonstrating the induced trauma transference and the three-generational neurosis model, i.e. the transfer of the trauma from the traumatised grandparent through his/her child to the grandchild. The first generation survivor syndrome was first experienced with patients who themselves had suffered deportation or had survived the ghetto, and after several decades, came for treatment to the KUT Psychotherapeutical Clinic. that has been operating for 4 years now.


Analysis of COVID-19 outbreak origin in China in 2019 using differentiation method for unusual epidemiological events.
Origin of outbreaks could be natural, accidental, deliberate, and caused by a new or re-emerging bioagent. The aim of this study was the retrospective analysis of whether the COVID-19 outbreak was natural, accidental, deliberate one, or caused by a new or re-emerging bioagent. Analysis was performed according to the Radosavljevic-Belojevic method for outbreak scoring and differentiation. Data for the application of this method were obtained by literature review in the Medline database for the period from 2000 to 2020. The analysis of the unusual COVID-19 outbreak shows that the present official assumption of its natural origin is questionable and pointed out to a probability that the pathogen could have also been accidentally introduced in the human population. There are no conclusive pieces of evidence about the reservoir of the pathogen or the source of infection. These parameters are essential for the final clarification of the outbreak origin. This study suggests that the COVID-19 outbreak is a consequence of an accidental release of a new COVID-19 virus, probably during the technical accident and/or negligent violation of hygienic norms in the laboratory facility. Further epidemiological, microbiological, and forensic analyses are needed to clarify the COVID-19 outbreak.


Glycal assembly by the in situ generation of glycosyl dithiocarbamates.
Glycal assembly offers an expedient entry into β-linked oligosaccharides, but epoxyglycal donors can be capricious in their reactivities. Treatment with Et(2)NH and CS(2) enables their in situ conversion into glycosyl dithiocarbamates, which can be activated by copper triflate for coupling with complex or sterically congested acceptors. The coupling efficiency can be further enhanced by in situ benzoylation, as illustrated in an 11-step synthesis of a branched hexasaccharide from glucals in 28% isolated yield and just four chromatographic purifications.


Herb-induced liver injury (HILI) with 12,068 worldwide cases published with causality assessments by Roussel Uclaf Causality Assessment Method (RUCAM): an overview.
Herbal products including herbal medicines are worldwide used in large amounts for treating minor ailments and for disease prevention. However, efficacy of most herbal products has rarely been well documented through randomized controlled trials in line with evidence-based medicine concepts, which could be used to estimate the benefit/risk ratio. Instead, much better documented are adverse reactions such as liver injury associated with the consumption of some herbal products, so called herb-induced liver injury (HILI), which represents a clinical challenge. In order to establish HILI as valid diagnosis, the use of a diagnostic algorithms such as Roussel Uclaf Causality Assessment Method (RUCAM) is widely recommended, although physicians in some countries are reluctant to use RUCAM for their HILI cases. This review on worldwide HILI and RUCAM, developed as part of the artificial intelligence ideas, reveals that China is the leading country with 24 publications on HILI cases that were all assessed for causality using RUCAM, followed by Korea with 15 reports, Germany with 9 reports, the US with 7 reports, and Spain with 6 reports, whereas the remaining countries provided less than 4 reports. The total number of assessed HILI cases is 12,068 worldwide derived from 80 publications but in each report HILI case numbers were variable in a range from 1 up to 6,971. This figure compares with 46,266 cases of drug-induced liver injury (DILI) published worldwide from 2014 to early 2019 also assessed for causality by RUCAM. The original version of RUCAM was validated and established in 1993 and updated in 2016 that should be used in future HILI cases. RUCAM is an objective, structured, and validated method, specifically designed for liver injury. It is a scoring system including case data elements to be assessed and scored individually to provide a final score in five causality gradings. Among the 11,404/12,068 HILI (94.5%) cases assessable for evaluation, causality gradings were highly probable in 4.2%, probable in 15.5%, possible in 70.3%, and unlikely or excluded in 10.0%. To improve the future reporting of RUCAM based HILI cases, recommendations include the strict adherence to instructions outlined in the updated RUCAM and, in particular, to follow prospective data collection on the cases to ensure completeness of case data. In conclusion, RUCAM can well be used to assess causality in suspected HILI cases, and additional efforts are now required to increase the quality of the reported cases.


Dissociative adsorption of methyl chloride on Si(001) studied by scanning tunneling microscopy.
Chemical reactions of methyl chloride (CH3Cl) on a clean Si(001) surface at approximately 300 K are studied by means of scanning tunneling microscopy (STM) under ultra-high-vacuum conditions. The features appearing in the STM images are identified with the possible products of dissociated CH3 and Cl, and their distribution is also evaluated as well as the development of their distribution with increasing CH(3)Cl doses. The amount of Cl atoms found on the surface is approximately twice as large as that of the CH3 molecules. This leads to the conclusion that dissociative adsorption of CH3Cl on Si occurs in different processes: CH3Cl(precursor) --> CH3(ad) + Cl(ad) and CH3Cl(precursor) --> CH3(gas) + Cl(ad).


Alterations of Ca(v)1.2 and 5-hydroxytryptamine in rat hearts after positional asphyxia.
We investigated alterations of cardiac Ca(v)1.2 and 5-hydroxytryptamine (5-HT) associated with positional asphyxia. Male rats were divided into five groups: a control group with no restraint, group 1 restrained for 1 h, group 2 restrained for 2 h, group 3 restrained for 4 h, and group 4 restrained for 8 h. The rats that were restrained for 8 h ultimately suffered fatal asphyxia. After the restraint periods, the rats were sacrificed and immunohistochemistry was performed to evaluate the expressions of Ca(v)1.2 and 5-HT in the heart. Sections were analyzed by digital image analysis. Cardiac expression of Ca(v)1.2 and 5-HT proteins were significantly decreased by positional asphyxia in the rat, shown by integrated optical density (IOD) compared to controls. Our findings indicate that Ca(v)1.2 and 5-HT alterations could cause abnormal cardiac function, and the proteins investigated here may be useful for investigating the mechanisms underlying positional asphyxia.


[Removing a femoral catheter].
Nurses at the University of Ottawa Heart Institute are removing femoral sheaths on post-angioplasty patients. The authors describe this new technique and explain how nurses can benefit by doing it. They discuss practical considerations before delegating this sanctioned medical act to nurses. Prevention and management of complications are also discussed as are research projects to evaluate the technique.


Effect of postexposure vaccination in a chimpanzee model of hepatitis A virus infection.
Passive transfer of antibodies to hepatitis A virus (HAV) in immune globulin (IG) effectively prevents hepatitis A when given after exposure, but does not provide lasting protection from infection. Hepatitis A vaccines have been shown to generate quickly levels of antibody equivalent to those found after IG administration. The effect of hepatitis A vaccine in preventing infection following fecal-oral exposure was evaluated in a chimpanzee model of HAV infection. Two animals were vaccinated 1 and 3 days, respectively following inoculation and two inoculated animals served as unprotected controls. Of the two immunized animals, one had no evidence of HAV infection, while the other had an attenuated infection with no evidence of virus shedding. These results suggest that while postexposure hepatitis A vaccination may be infection permissive, it attenuates disease expression and prevents virus shedding.


Stakeholder interactions and the development of functional foods.
This paper investigates the roles of the individual stakeholders involved in the development of functional foods and the implications of their actions for public perception of this new food concept. At a time when consumer awareness of the link between diet and health is strong, a new food concept incorporating of a wide spectrum of foods has captured the imagination of the food industry and consumers alike. Functional foods provide a new category of foods that appear to be offering the public the opportunity to achieve a healthy lifestyle with minimal effort. Public perception may determine whether this new food concept is to become the next successful breakthrough in nutritional science or just another marketing gimmick devised by food manufacturers. The paper also addresses issues that arise directly as a result of the emergence of functional foods, such as appropriate legislation in connection to health claims in order to ensure consumer protection and also the lack of clarity in relation to definitions of what constitutes a functional food. The paper concludes that functional foods can only reach their maximum potential if the food industry, government and health professionals work together to improve communication between themselves and consumers and also to educate consumers, thereby allowing them to make informed decisions about dietary choices.


Multiplexed Isobaric Tagging Protocols for Quantitative Mass Spectrometry Approaches to Auditory Research.
Modern biologists have at their disposal a large array of techniques used to assess the existence and relative or absolute quantity of any molecule of interest in a sample. However, implementing most of these procedures can be a daunting task for the first time, even in a lab with experienced researchers. Just choosing a protocol to follow can take weeks while all of the nuances are examined and it is determined whether a protocol will (a) give the desired results, (b) result in interpretable and unbiased data, and (c) be amenable to the sample of interest. We detail here a robust procedure for labeling proteins in a complex lysate for the ultimate differential quantification of protein abundance following experimental manipulations. Following a successful outcome of the labeling procedure, the sample is submitted for mass spectrometric analysis, resulting in peptide quantification and protein identification. While we will concentrate on cells in culture, we will point out procedures that can be used for labeling lysates generated from tissues, along with any minor modifications required for such samples. We will also outline, but not fully document, other strategies used in our lab to label proteins prior to mass spectrometric analysis, and describe under which conditions each procedure may be desirable. What is not covered in this chapter is anything but the most brief introduction to mass spectrometry (instrumentation, theory, etc.), nor do we attempt to cover much in the way of software used for post hoc analysis. These two topics are dependent upon one's resources, and where applicable, one's collaborators. We strongly encourage the reader to seek out expert advice on topics not covered here.


Quality of life and sexual function in patients with benign prostatic hyperplasia.
Incidence of benign prostatic hyperplasia (BPH), one of the most common conditions affecting adult men, increases dramatically after the age of 50. The various symptoms of BPH, which include lower urinary tract symptoms (LUTS), can adversely affect quality of life (QOL). Many men with BPH and LUTS wait until symptoms become significantly bothersome before seeking medical attention. Evaluating the exact severity and significance of symptoms has been difficult with previous methodology. Over the last decade, assessment tools have become available to quantify the symptoms of BPH and LUTS. This article addresses the impact of BPH, its management, and the overall effects it has on QOL.


Understanding the role of amphipathic helices in N-BAR domain driven membrane remodeling.
Endophilin N-BAR (N-terminal helix and Bin/amphiphysin/Rvs) domain tubulates and vesiculates lipid membranes in vitro via its crescent-shaped dimer and four amphipathic helices that penetrate into membranes as wedges. Like F-BAR domains, endophilin N-BAR also forms a scaffold on membrane tubes. Unlike F-BARs, endophilin N-BARs have N-terminal H0 amphipathic helices that are proposed to interact with other N-BARs in oligomer lattices. Recent cryo-electron microscopy reconstructions shed light on the organization of the N-BAR lattice coats on a nanometer scale. However, because of the resolution of the reconstructions, the precise positioning of the amphipathic helices is still ambiguous. In this work, we applied a coarse-grained model to study various membrane remodeling scenarios induced by endophilin N-BARs. We found that H0 helices of N-BARs prefer to align in an antiparallel manner at two ends of the protein to form a stable lattice. The deletion of H0 helices causes disruption of the lattice. In addition, we analyzed the persistence lengths of the protein-coated tubes and found that the stiffness of endophilin N-BAR-coated tubules qualitatively agrees with previous experimental work studying N-BAR-coated tubules. Large-scale simulations on membrane liposomes revealed a systematic relation between H0 helix density and local membrane curvature fluctuations. The data also suggest that the H0 helix is required for BARs to form organized structures on the liposome, further illustrating its important function.


[Adverse cutaneous reactions to drugs].
Adverse cutaneous reactions to drugs are any undesirable change in the structure or function of the skin. These are among the adverse side effects to common drugs. The most commonly implicated drugs are antibiotics and anticonvulsants. Cutaneous clinical manifestations are diverse ranging from mild or moderate reactions, such as urticaria and maculopapular rash, to severe cutaneous adverse reactions (SCAR), which are known due to their high morbidity and mortality (among these: Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). The clinical pattern, etiology, prognosis and treatment differ among these skin reactions, which is why it is necessary a clear diagnosis based on a comprehensive clinical examination, skin biopsy, and specific laboratory tests. The therapeutic options depend on the clinical diagnosis. For all reactions, a symptomatic and adequate supportive therapy is necessary; in some cases, a systemic immunomodulatory therapy can be useful.


Manufactured nanomaterials (fullerenes, C60) induce oxidative stress in the brain of juvenile largemouth bass.
Although nanotechnology has vast potential in uses such as fuel cells, microreactors, drug delivery devices, and personal care products, it is prudent to determine possible toxicity of nanotechnology-derived products before widespread use. It is likely that nanomaterials can affect wildlife if they are accidentally released into the environment. The fullerenes are one type of manufactured nanoparticle that is being produced by tons each year, and initially uncoated fullerenes can be modified with biocompatible coatings. Fullerenes are lipophilic and localize into lipid-rich regions such as cell membranes in vitro, and they are redox active. Other nano-sized particles and soluble metals have been shown to selectively translocate into the brain via the olfactory bulb in mammals and fish. Fullerenes (C60) can form aqueous suspended colloids (nC60); the question arises of whether a redox-active, lipophilic molecule could cause oxidative damage in an aquatic species. The goal of this study was to investigate oxyradical-induced lipid and protein damage, as well as impacts on total glutathione (GSH) levels, in largemouth bass exposed to nC60. Significant lipid peroxidation was found in brains of largemouth bass after 48 hr of exposure to 0.5 ppm uncoated nC60. GSH was also marginally depleted in gills of fish, and nC60 increased water clarity, possibly due to bactericidal activity. This is the first study showing that uncoated fullerenes can cause oxidative damage and depletion of GSH in vivo in an aquatic species. Further research needs to be done to evaluate the potential toxicity of manufactured nanomaterials, especially with respect to translocation into the brain.


An innovative intervention for the treatment of cognitive impairment-Emisymmetric bilateral stimulation improves cognitive functions in Alzheimer's disease and mild cognitive impairment: an open-label study.
In the last decade, the development of different methods of brain stimulation by electromagnetic fields (EMF) provides a promising therapeutic tool for subjects with impaired cognitive functions. Emisymmetric bilateral stimulation (EBS) is a novel and innovative EMF brain stimulation, whose working principle is to introduce very weak noise-like stimuli through EMF to trigger self-arrangements in the cortex of treated subjects, thereby improving cognitive faculties. The aim of this pilot study was to investigate in patients with cognitive impairment the effectiveness of EBS treatment with respect to global cognitive function, episodic memory, and executive functions. Fourteen patients with cognitive decline (six with mild cognitive impairment and eight with Alzheimer's disease) underwent three EBS applications per week to both the cerebral cortex and auricular-specific sites for a total of 5 weeks. At baseline, after 2 weeks and 5 weeks, a neuropsychological assessment was performed through mini-mental state examination, free and cued selective reminding tests, and trail making test. As secondary outcomes, changes in behavior, functionality, and quality of life were also evaluated. After 5 weeks of standardized EBS therapy, significant improvements were observed in all neurocognitive assessments. Mini-mental state examination score significantly increased from baseline to end treatment (+3.19, P=0.002). Assessment of episodic memory showed an improvement both in immediate and delayed recalls (immediate recall =+7.57, P=0.003; delayed recall =+4.78, P<0.001). Executive functions significantly improved from baseline to end stimulation (trail making test A -53.35 seconds; P=0.001). Of note, behavioral disorders assessed through neuropsychiatric inventory significantly decreased (-28.78, P<0.001). The analysis concerning the Alzheimer's disease and mild cognitive impairment group confirmed a significant improvement of cognitive functions and behavior after EBS treatment. This pilot study has shown EBS to be a promising, effective, and safe tool to treat cognitive impairment, in addition to the drugs presently available. Further investigations and controlled clinical trials are warranted.


Advances in myocardial protection.
The success of cardiac surgery is due in large part to the myocardial protection techniques employed to maintain cardiac viability during the period of induced ischemic arrest. As the number of older, high-risk cardiac surgical patients increases, advances in myocardial protection have become necessary to achieve a quiet, bloodless operative field without the production of irreversible intraoperative myocardial damage. Current efforts to provide optimal myocardial protection have focused on the effects of cardioplegic perfusate temperature, distribution of cardioplegia flow, and components of the arresting solution. Minimally invasive techniques have expanded surgical options and have led to the development of new methods to protect the myocardium.


The development of a learning management system for dental radiology education: A technical report.
This study was conducted to suggest the development of a learning management system for dental radiology education using the Modular Object-Oriented Dynamic Learning Environment (Moodle). Moodle is a well-known and verified open-source software-learning management system (OSS-LMS). The Moodle software was installed on a server computer and customized for dental radiology education. The system was implemented for teaching undergraduate students to diagnose dental caries in panoramic images. Questions were chosen that could assess students' diagnosis ability. Students were given several questions corre-sponding to each of 100 panoramic images. The installation and customization of Moodle was feasible, cost-effective, and time-saving. By having students answer questions repeatedly, it was possible to train them to examine panoramic images sequentially and thoroughly. Based on its educational efficiency and efficacy, the adaptation of an OSS-LMS in dental school may be highly recommended. The system could be extended to continuing education for dentists. Further studies on the objective evaluation of knowledge acquisition and retention are needed.


Sight-threatening retinopathy is associated with lower mortality in type 2 diabetic subjects: a 10-year observation study.
To study associations between diabetic retinopathy and development of stroke, myocardial infarction and death in type 2 diabetic patients. During a 10-year observation period, 363 type 2 diabetic patients (diagnosis > or =30 years of age) attending an outpatient clinic were studied regarding the prevalence and incidence of retinopathy and associated risk factors, i.e., (HbA(1c), blood pressure, albuminuria, plasma creatinine, age, sex and diabetes duration) in relation to the development of myocardial infarction, stroke and death. The degree of retinopathy was classified as no retinopathy, background or sight-threatening retinopathy, i.e., clinically significant macular edema, severe non-proliferative or proliferative retinopathy. During the study period, 62 patients had had myocardial infarction, 54 stroke and 99 patients died. Patients with sight-threatening retinopathy at baseline (n=41) had a 2.2-fold increased (p<0.01) risk for death compared to patients with no or background retinopathy, even when controlled for medical risk factors. When adjusted for medical risk factors, patients with no retinopathy at baseline (n=226) who remained without retinopathy or developed background retinopathy (n=187) during the study period, had a 3.6-fold increased risk for death (95% CI, 1.1, 11.8), (p=0.03), compared to patients who developed sight-threatening retinopathy (n=39), while the incidence of myocardial infarction did not differ. More patients who developed sight-threatening retinopathy were treated with ACE inhibitors than patients who did not (41% versus 24%; p=0.03). Despite more medical risk factors, patients who developed sight-threatening retinopathy had lower mortality compared to patients with no or background retinopathy at follow-up. More patients who developed sight-threatening retinopathy were treated with ACE inhibitors but this seemed not to have influenced the lower mortality rate in this group, whereas the use of ACE inhibitors in patients who did not develop sight-threatening retinopathy was connected with lower mortality rate.


Managing patients with vulvovaginal candidiasis.
Epidemiologic studies have demonstrated a continuing increase in the prevalence of vulvovaginal candidiasis. Although in the past most of these infections were caused by Candida albicans, an increasing percentage are caused by non-albicans Candida species that are less sensitive to the most frequently used antifungal agents. An accurate diagnosis of these infections and the subsequent choice of the most appropriate therapy can only be made after a thorough evaluation of the patient. Successful treatment of vulvovaginal candidiasis is dependent on compliance with therapy; thus, the treatment regimen chosen should fit the patient's daily lifestyle. Newer single-dose regimens offer the option of completing therapy with a single treatment for most patients with uncomplicated vaginal candidiasis. Use of topical agents avoids the potential systemic adverse effects and drug interactions that have been noted with oral antifungals. Patient education and support can also enhance satisfaction with the treatment plan and promote compliance.


The two-box model of climate: limitations and applications to planetary habitability and maximum entropy production studies.
The 'two-box model' of planetary climate is discussed. This model has been used to demonstrate consistency of the equator-pole temperature gradient on Earth, Mars and Titan with what would be predicted from a principle of maximum entropy production (MEP). While useful for exposition and for generating first-order estimates of planetary heat transports, it has too low a resolution to investigate climate systems with strong feedbacks. A two-box MEP model agrees well with the observed day : night temperature contrast observed on the extrasolar planet HD 189733b.


Treatment of ureterovaginal fistula using a Memokath stent.
Ureterovaginal fistula (UVF) is a challenging problem for patients and doctors, especially in patients who have been treated by radiation for malignancy. UVF may occur in conjunction with surgeries involving the uterus. A success rate of 70-100% has been reported for fistula repair with the best results in non-radiated patients. Meanwhile, conservative treatment using ureteral stents in selected patients has resulted in reported success rates of 71%. We present the case of a 24-year-old woman with UVF due to surgery and radiotherapy for cervix cancer. The patient has been successfully treated with the insertion of a Memokath 051 stent (PNN Medical A/S, Denmark), which is a thermoexpandable, nickel-titanium alloy stent. The patient has been totally continent during a follow-up period of 3 years. The Memokath stent has been changed twice within this period due to dysfunction.


["Blue eyes"-case report about the risks of cosmetic iris implants].
A 24-year-old Iranian woman presented to our department for routine eye control. She had had cosmetic iris implants (BrightOcular©) implanted 5 years before in a Tunisian eye clinic in order to change the color of her eyes. Despite subjective freedom of symptoms, a dramatically reduced corneal endothelial cell count was measured in the left eye. Therefore, surgical removal of the angle-supported cosmetic iris implants was necessary. Cosmetic iris implants are associated with sight-threatening complications-even years after their implantation. We report on a case of cosmetic iris implants inserted for alteration of eye color only, which gave rise to serious complications for our patient.


pH-Dependent solution dynamics of a manganese(II) polyoxometalate, [Mn4(H2O)2(P2W15O56)2](16-), and [Mn(H2O)6](2+).
The aqueous reaction dynamics of the manganese(II)-functionalised Wells-Dawson polyoxometalate [Mn4(H2O)2(P2W15O56)2](16-) has been determined as a function of pH using variable temperature (17)O NMR, and compared with that of the well-studied monomeric manganese(II) hexa-aqua ion, [Mn(H2O)6](2+). While the rate of aquo-ligand exchange on the hexa-aqua ion remains independent of pH in the range 3.2-6.0, the rate of water exchange of the polyoxometalate ion varies by a factor of fifteen, from 1.98 × 10(7) s(-1) at pH 3.2 to 1.3 × 10(6) s(-1) at pH 6.0. This decrease in the rate of exchange correlates with the deprotonation of the polyoxometalate framework.


Studies on the influence of pH and pancreatin on 13C-formaldehyde-induced gelatin cross-links using nuclear magnetic resonance.
Carbon-13 nuclear magnetic resonance (13C-NMR) and 13C-enriched formaldehyde (13CH2O) were utilized to observe cross-linking in gelatin. Thus, when a 6% solution of gelatin in water was treated with 2000 ppm 13CH2O at 20 degrees C, the 15 hr 13C-NMR spectrum of the crosslinked gel showed peaks representing carbinolamines (methylols) of arginine and lysine, as well as a peak ascribed to a methylene cross-link between arginine and lysine. Similar results were obtained when these cross-linking reactions were conducted using only 100 ppm 13CH2O. When pancreatin (1% w/v) was added to the solution of 6% gelatin cross-linked with 2000 ppm 13CH2O, the gel began to revert to a clear fluid solution. After incubation for 24 hr at 37 degrees C, the 13C-NMR spectrum of this solution confirmed the presence of the methylols of lysine and arginine, and the lysine-arginine cross-link. When 13CH2O (2000 ppm) was added to a 6% solution of gelatin at pH 13.0, the arginine methylol and the lysine-arginine crosslinks were produced. The 13CH2O-induced crosslinking of gelatin at pH 2.0, however, yielded the lysine methylol as the sole product.


[Oxidative stress in nephrology].
The effect of reactive oxygen species (ROS) on pathophysiology of many diseases is widely documented in numerous scientific publications. Nephropathies belong to pathologies in which ROS undoubtedly play a role. Imbalance between ROS and antioxidants results in destructive effect on mesangial cells by altering lipid metabolism. This phenomenon is frequently observed in patients with glomerulonephritis and nephritic syndrome. Accumulation of hypoxanthine and oxygen in the mechanism of reperfusion damages renal cells by the produced ROS in patients with acute renal failure. Inactivation of nitric oxide by superoxide anion radical increases vascular resistance in renal arteries and contributes to the development of hypertensive nephropathy. Diabetic nephropathy, in which a significant role is ascribed to glycation end products, oxidative stress and decrease of antioxidant mechanisms, is another nephropathy associated with oxidant/antioxidant imbalance. Pro-inflammatory processes with activation of nonspecific system cells and destruction of kidney structure by free radical processes play an important role in urinary system infections. Similar phenomena are observed in patients with urinary system neoplastic diseases. Each of the above pathological conditions may in consequence lead to chronic renal failure (CRF) requiring nephro-substitute therapy. The therapy substituting for normal kidney function but not devoid of disadvantages. Despite of the application of numerous techniques of detoxification in patients with CRF, none of them has become the "gold standard" yet, because according to the so far carried out research they all induce free radical reactions in the course of dialysis and decrease total antioxidant potential of plasma. It is a very crucial problem of nephro-substitute therapy which will be developed in our next review paper.


Formation of massive black holes in rapidly growing pre-galactic gas clouds.
The origin of the supermassive black holes that inhabit the centres of massive galaxies remains unclear1,2. Direct-collapse black holes-remnants of supermassive stars, with masses around 10,000 times that of the Sun-are ideal seed candidates3-6. However, their very existence and their formation environment in the early Universe are still under debate, and their supposed rarity makes modelling their formation difficult7,8. Models have shown that rapid collapse of pre-galactic gas (with a mass infall rate above some critical value) in metal-free haloes is a requirement for the formation of a protostellar core that will then form a supermassive star9,10. Here we report a radiation hydrodynamics simulation of early galaxy formation11,12 that produces metal-free haloes massive enough and with sufficiently high mass infall rates to form supermassive stars. We find that pre-galactic haloes and their associated gas clouds that are exposed to a Lyman-Werner intensity roughly three times the intensity of the background radiation and that undergo at least one period of rapid mass growth early in their evolution are ideal environments for the formation of supermassive stars. The rapid growth induces substantial dynamical heating13,14, amplifying the Lyman-Werner suppression that originates from a group of young galaxies 20 kiloparsecs away. Our results strongly indicate that the dynamics of structure formation, rather than a critical Lyman-Werner flux, is the main driver of the formation of massive black holes in the early Universe. We find that the seeds of massive black holes may be much more common than previously considered in overdense regions of the early Universe, with a co-moving number density up to 10-3 per cubic megaparsec.


Hydroxychloroquine directly reduces the binding of antiphospholipid antibody-beta2-glycoprotein I complexes to phospholipid bilayers.
Treatment with the antimalarial drug hydroxychloroquine (HCQ) has been associated with reduced risk of thrombosis in the antiphospholipid (aPL) syndrome (APS) and, in an animal model of APS, with reduction of experimentally induced thrombosis. Recognition of beta2-glycoprotein I (beta2GPI) by aPL antibodies appears to play a major role in the disease process. We therefore used the techniques of ellipsometry and atomic force microscopy (AFM) to investigate whether HCQ directly affects the formation of aPL IgG-beta2GPI complexes on phospholipid bilayers. HCQ, at concentrations of 1 mug/mL and greater, significantly reduced the binding of aPL-beta2GPI complexes to phospholipid surfaces and THP-1 (human acute monocytic leukemia cell line) monocytes. The drug also reduced the binding of the individual proteins to bilayers. This HCQ-mediated reduction of binding was completely reversed when the HCQ-protein solutions were dialyzed against buffer. HCQ also caused modest, but statistically significant, reductions of clinical antiphospholipid assays. In conclusion, HCQ reduces the formation of aPL-beta2GPI complexes to phospholipid bilayers and cells. This effect appears to be due to reversible interactions between HCQ and the proteins and may contribute to the observed reduction of thrombosis in human and experimental APS. These results support the possibility that HCQ, or analogous molecules, may offer novel nonanticoagulant therapeutic strategies for treating APS.


[The use of ribonucleic acids as markers for the measuring of microbial protein yield in the rumen. 2. The effect of sample treatment, the time of sampling and the composition of the ration on the RNA:N ratio in rumen microbes].
In two experiments the influence of the treatment of samples, the sampling time and the composition of the rations on the RNA: N ratio in the rumen microbes was checked. Experiment I proved that freezing (-21 degrees C), thawing and freeze-drying of isolated bacteria and protozoa from the rumen fluid and from the duodenal content did not result in a change of the RNA content and the RNA-N: total N relation. If, however, the rumen fluid is stored deep-frozen before the isolation of the bacteria the N content in the DM of the bacteria decreases by 17% and that of RNA by 30%. This results in a change of the RNA: N relation of 16%. In conclusion, the bacteria are to be isolated immediately after rumen fluid sampling. Isolated bacteria can be stored deep-frozen before RNA determination and then freeze-dried. Experiment II showed that the RNA content of the rumen protozoa varies according to the period after feeding. The RNA: N relation was 0.50, 0.92, 0.70 and 0.58 on average 0, 3, 6 and 8 h after feeding, in which the 3rd hour after feeding can obviously be considered the time of increased microbial activity. The conclusion from this variation is that more than one isolation of microbes must be carried out in the course of the day in order to achieve representative samples. These statements apply to easily and not easily fermentable protein as N source in the feed. It could also be proved that no essential variation is to be expected in the RNA: N relation in the microbes isolated from the rumen fluid in the range of 8-21% crude protein in the DM of the ration (roughage: concentrate = 55: 45). On average the rumen microbes contained 1.7 g RNA-N/16 g N, essential differences between bacteria and protozoa could not be ascertained. From the slight variation of the RNA-N: N relation in the isolated bacteria from various cows one can conclude that there is no need to isolate the microbes of each individual animal.


Impact of a Community-Based Healthy Lifestyle Program on Individuals With Traumatic Brain Injury.
To examine adherence with and effect of an evidence-based healthy lifestyle intervention modified for individuals with traumatic brain injury (TBI). Pre-/postintervention without control. Community. Eighteen individuals with TBI: primarily male (61%), white (67%), with private insurance (50%). Mean age was 45.6 ± 12.3 years, weight 210 ± 42.6 lb, and body mass index 31.8 ± 4.6 (obese category) at baseline. The primary goal of the Diabetes Prevention Program Group Lifestyle Balance program is 5% to 7% weight loss through increased physical activity and improved dietary behaviors. Adherence (ie, session attendance and self-monitoring of dietary behaviors), physiologic changes (ie, weight loss, blood pressure; waist and arm circumference; and lipid profile), and quality of life (ie, self-reported health, quality of life, and step count). Average participant attendance (85% over 12 months) and self-monitoring (90% over 6 months) were high. Significant decreases were observed in diastolic blood pressure and waist and arm circumference from baseline through 12 months and from baseline to 3 months only for weight and total cholesterol. No significant changes were observed in self-reported health, quality of life, or step count. Participants demonstrated high adherence with the program, suggesting that individuals with TBI are able to successfully engage in the program and achieve significant weight loss and changes in key physiologic outcomes.


Evolutionary dynamics of populations with conflicting interactions: classification and analytical treatment considering asymmetry and power.
Evolutionary game theory has been successfully used to investigate the dynamics of systems, in which many entities have competitive interactions. From a physics point of view, it is interesting to study conditions under which a coordination or cooperation of interacting entities will occur, be it spins, particles, bacteria, animals, or humans. Here, we analyze the case, where the entities are heterogeneous, particularly the case of two populations with conflicting interactions and two possible states. For such systems, explicit mathematical formulas will be determined for the stationary solutions and the associated eigenvalues, which determine their stability. In this way, four different types of system dynamics can be classified and the various kinds of phase transitions between them will be discussed. While these results are interesting from a physics point of view, they are also relevant for social, economic, and biological systems, as they allow one to understand conditions for (1) the breakdown of cooperation, (2) the coexistence of different behaviors ("subcultures"), (3) the evolution of commonly shared behaviors ("norms"), and (4) the occurrence of polarization or conflict. We point out that norms have a similar function in social systems that forces have in physics.


Rates of clinically apparent heparin-induced thrombocytopenia for unfractionated heparin vs. low molecular weight heparin in non-surgical patients are low and similar.
With the growing use of low-molecular-weight heparins (LMWH) for the treatment and prevention of venous thromboembolism (VTE), it is important to provide an evidence-based comparison with unfractionated heparin (UFH) concerning rates of heparin-induced thrombocytopenia (HIT). Such comparisons are essential in clinical decision-making and cost-modeling. In this paper we review data regarding non-surgical (medical) patients. We conclude that the lack of uniform evaluation and standardized testing for HIT in the current literature precludes making a reliable estimate of the relative risk of HIT in UFH vs. LMWH in either the treatment or prevention of VTE in non-surgical patients. However, current data suggest that the risk of thrombocytopenia and HIT is low and similar for non-surgical patients who receive either LMWH or UFH.


Alternaria toxins in wheat during the 2004 to 2005 Argentinean harvest.
The natural occurrence of Alternaria mycotoxins in Argentinean wheat from the zone 5 South during the 2004 to 2005 harvest was investigated in 64 wheat samples. All samples were highly contaminated with a wide range of fungal species. Alternaria was found as the main component of the mycota, with an infection percentage of 100%. Three mycotoxins produced by species of Alternaria were determined in wheat: alternariol, alternariol monomethyl ether, and tenuazonic acid. Alternariol was detected in 4 (6%) of 64 samples, with a range of 645 to 1,388 microg/kg (mean of 1,054 microg/kg); alternariol monomethyl ether, with a range of 566 to 7,451 microg/kg (mean of 2,118 microg/kg) in 15 (23%) of 64 samples; and tenuazonic acid in 12 (19%) of 64 samples, with a range of 1,001 to 8,814 microg/kg (mean, 2,313 microg/kg). Alternariol monomethyl ether was the predominant toxin, but tenuazonic acid was detected in higher concentrations. Alternariol was present in fewer samples and in lower levels than were the other toxins. Tenuazonic acid and alternariol monomethyl ether occurred together in four samples, while tenuazonic acid and alternariol co-occurred in one sample. This the first report of the natural occurrence of Alternaria mycotoxins in Argentinean wheat. Toxin levels were high, probably due to the heavy infection with Alternaria species found in the samples.


Endonasal endoscopic approaches to the paramedian skull base.
To describe the technical and anatomic nuances related to endoscopic endonasal approaches (EEAs) to the paramedian skull base. Surgical indications, limitations, and technical aspects pertaining to EEAs designed to access areas oriented in the coronal plane are systematically reviewed with special attention to caveats, pitfalls, and common complications and how to avoid them. Case examples are presented. The paramedian skull base may be divided into anterior (corresponding to the orbit and its contents), middle (corresponding to the middle cranial, pterygopalatine, and infratemporal fossae), and posterior (includes the craniovertebral junction lateral to the occipital condyles and the jugular foramen) segments. EEAs to the anterior segment offer access to the intraconal orbital space and the optic canal. A transpterygoid corridor typically precedes EEAs to the middle and posterior paramedian approaches. EEAs to the middle segment provide wide exposure of the petrous apex, middle cranial fossa (including cavernous sinus and Meckel cave), and infratemporal and pterygopalatine fossae. Finally, EEAs to the posterior segment access the hypoglossal canal, occipital condyle, and jugular foramen. Approaches to the paramedian skull base are the most challenging and complex of all endoscopic endonasal techniques. Because of their technical complexity, it is recommended that surgeons master endoscopic endonasal anatomic approaches oriented to median structures (sagittal plane) before approaching paramedian (coronal plane) pathologies.


Dermatitis Herpetiformis: Novel Perspectives.
Dermatitis herpetiformis (DH) is an inflammatory disease of the skin, considered the specific cutaneous manifestation of celiac disease (CD). Both DH and CD occur in gluten-sensitive individuals, share the same Human Leukocyte Antigen (HLA) haplotypes (DQ2 and DQ8), and improve following the administration of a gluten-free diet. Moreover, almost all DH patients show typical CD alterations at the small bowel biopsy, ranging from villous atrophy to augmented presence of intraepithelial lymphocytes, as well as the generation of circulating autoantibodies against tissue transglutaminase (tTG). Clinically, DH presents with polymorphic lesions, including papules, vesicles, and small blisters, symmetrically distributed in typical anatomical sites including the extensor aspects of the limbs, the elbows, the sacral regions, and the buttocks. Intense pruritus is almost the rule. However, many atypical presentations of DH have also been reported. Moreover, recent evidence suggested that DH is changing. Firstly, some studies reported a reduced incidence of DH, probably due to early recognition of CD, so that there is not enough time for DH to develop. Moreover, data from Japanese literature highlighted the absence of intestinal involvement as well as of the typical serological markers of CD (i.e., anti-tTG antibodies) in Japanese patients with DH. Similar cases may also occur in Caucasian patients, complicating DH diagnosis. The latter relies on the combination of clinical, histopathologic, and immunopathologic findings. Detecting granular IgA deposits at the dermal-epidermal junction by direct immunofluorescence (DIF) from perilesional skin represents the most specific diagnostic tool. Further, assessing serum titers of autoantibodies against epidermal transglutaminase (eTG), the supposed autoantigen of DH, may also serve as a clue for the diagnosis. However, a study from our group has recently demonstrated that granular IgA deposits may also occur in celiac patients with non-DH inflammatory skin diseases, raising questions about the effective role of eTG IgA autoantibodies in DH and suggesting the need of revising diagnostic criteria, conceivably emphasizing clinical aspects of the disease along with DIF. DH usually responds to the gluten-free diet. Topical clobetasol ointment or dapsone may be also applied to favor rapid disease control. Our review will focus on novel pathogenic insights, controversies, and management aspects of DH.


Hyperthyroidism with concurrent FMS-like tyrosine kinase 3-internal tandem duplication-positive acute promyelocytic leukemia: A case report and review of the literature.
Neutropenia is a common side-effect in hyperthyroid patients with long-term use of antithyroid drugs. This may be caused by drug-induced immune dysfunction or increased thyroxine hematologic toxicity, which usually returns to normal after medication is discontinued or the hyperthyroidism becomes well controlled. However, hyperthyroidism with pancytopenia is extremely rare. The current case report presents a hyperthyroid patient complicated with pancytopenia who had taken antithyroid drugs for 14 years. Bone marrow analysis revealed primary leuokocytes, indicating M3 acute leukemia. Genetic analysis revealed promyelocytic leukemia-retinoic acid receptor α fusion and FMS-like tyrosine kinase 3-internal tandem duplication. The genetic abnormality was also associated with thyroid hormonal functions. After a standard anti-M3 regimen was administed, the patient achieved complete remission and maintained stable thyroid functions. To the best of our knowledge, this is the first reported case of a patient with hyperthyroidism acquiring M3 leukemia harboring the FMS-like tyrosine kinase 3-internal tandem duplication.


Densified vertically lamellar electrode architectures for compact energy storage.
As one of the most compact electrochemical energy storage systems, lithium-ion batteries (LIBs) are playing an indispensable role in the process of vehicle electrification to accelerate the shift to sustainable mobility. Making battery electrodes thicker is a promising strategy for improving the energy density of LIBs which is essential for applications with weight or volume constraints, such as electric-powered transportation; however, their power densities are often significantly restricted due to elongated and tortuous charge traveling distances. Here, we propose an effective methodology that couples bidirectional freeze-casting and compression-induced densification to create densified vertically lamellar electrode architectures for compact energy storage. The vertically lamellar architectures not only overcome the critical thickness limit for conventional electrodes but also facilitate and redistribute the lithium-ion flux enabling both high rate capability and stable cyclability. Furthermore, this proposed methodology is universal as demonstrated in various electrochemical active material systems. This study offers a facile approach that realizes simultaneous high energy and high power in high-loading battery electrodes and provides useful rationales in designing electrode architectures for scalable energy storage systems.


A new xyelotomid (Hymenoptera) from the Middle Jurassic of China displaying enigmatic venational asymmetry.
Pterygota insects typically have symmetric veins in left and right wings. For studying taxonomy and phylogeny of fossil insects, venational patterns are commonly used as diagnostic characters, in conjunction with preserved body characters. Some examples of asymmetrical venation are known among extant insects, but only a few fossil insects with asymmetric wings have been reported, among which a previously described xyelotomid of Hymenoptera, Xyelocerus diaphanous, displays an unusual, small cell of vein Rs in the left forewing, but not in the right. Herein we report a new sawfly of the family Xyelotomidae, Aethotoma aninomorpha gen. et sp. nov., from the late Middle Jurassic of China having a simple Sc in the forewing and Sc with two branches in the hind wing. In additional, the new specimen exhibits an enigmatic venational asymmetry. In the right forewing, crossvein 2r-rs of forms a loop, then forks into 2 long branches reaching Rs, while 2r-rs of the left forewing forks into 2 short branches reaching Rs, in contrast to a linear 2r-rs in typical fossil and extant sawflies. Such rare asymmetrical venation found from fossil sawflies provides a glance at early occurrences of venational variability and instability, or possibly aberrational development, for insects in the late Middle Jurassic.


A transfer learning approach based on gradient boosting machine for diagnosis of Alzheimer's disease.
Early detection of Alzheimer's disease (AD) during the Mild Cognitive Impairment (MCI) stage could enable effective intervention to slow down disease progression. Computer-aided diagnosis of AD relies on a sufficient amount of biomarker data. When this requirement is not fulfilled, transfer learning can be used to transfer knowledge from a source domain with more amount of labeled data than available in the desired target domain. In this study, an instance-based transfer learning framework is presented based on the gradient boosting machine (GBM). In GBM, a sequence of base learners is built, and each learner focuses on the errors (residuals) of the previous learner. In our transfer learning version of GBM (TrGB), a weighting mechanism based on the residuals of the base learners is defined for the source instances. Consequently, instances with different distribution than the target data will have a lower impact on the target learner. The proposed weighting scheme aims to transfer as much information as possible from the source domain while avoiding negative transfer. The target data in this study was obtained from the Mount Sinai dataset which is collected and processed in a collaborative 5-year project at the Mount Sinai Medical Center. The Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset was used as the source domain. The experimental results showed that the proposed TrGB algorithm could improve the classification accuracy by 1.5 and 4.5% for CN vs. MCI and multiclass classification, respectively, as compared to the conventional methods. Also, using the TrGB model and transferred knowledge from the CN vs. AD classification of the source domain, the average score of early MCI vs. late MCI classification improved by 5%.


Potential activity of Linezolid against SARS-CoV-2 using electronic and molecular docking study.
The crescent evolution of a global pandemic COVID-19 and its respiratory syndrome (SARS-Cov-2) has been a constant concern (Ghosh 2021; Khan et al. 2021; Alazmi and Motwalli 2020; Vargas et al. 2020). The absence of a proven and effective medication has compelled all the scientific community to search for a new drug. The use of known drugs is a faster way to develop new therapies. Molecular docking is a powerful tool (Gao et al. J Mol Model 10: 44-54, 2004; Singh et al. J Mol Model 18: 39-51, 2012; Schulz-Gasch and Stahl J Mol Model 9:47-57, 2003) to study the interaction of potential drugs with SARS-CoV-2, Alsalme et al. (2020) and Sanders et al. (2020) spike protein as a consequence the main goal of this article is to present the result of the study of an interaction between (R and S)-Linezolid with receptor-binding domain (RBD) of SARS-Cov-2 spike protein complexed with human Angiostensin-converting enzyme 2 (ACE2) (6vW1 - from PDB). The Linezolid enantiomers were optimized at B3LYP/6-311++G(2d,p) level of theory. Molecular docking of the system (S)-Linezolid⋯RBD⋯ACE2 and (R)-Linezolid⋯RBD⋯ACE2 was performed, the analysis was made using LigPlot+ and NCIplot software packages, to understand the intermolecular interactions. The UV-Vis and ECD of the complexes - (R and S)-Linezolid⋯RBD⋯ACE2 were performed in two layers with DFT/6-311++G(3df,2p) and DFT/6-31G(d), respectively. The results showed that only the (S)-Linezolid had a stable interaction with - 8.05 kcal.mol- 1, whereas all the R-enantiomeric configurations had positive values of binding energy. The (S)-Linezolid had the same interactions as in the (S)-Linezolid ⋯ Haluarcula morismortui Ribosomal system, where it is well-known the fact that the latter has biological activity. A specific interaction on the fluorine ring justified an attenuation on the ECD signal, in comparison to isolated species. Therefore, some biological activity of (S)-Linezolid with SARS-CoV-2 RBD was expected, indicated by the modification of its ECD signal and justified by a similar interaction in the S-Linezolid⋯Haluarcula marismortui Ribosomal system.


Back schools for the treatment of chronic low back pain: possibility of benefit but no convincing evidence after 47 years of research-systematic review and meta-analysis.
Back schools are interventions that comprise exercise and education components. We aimed to systematically review the randomized controlled trial evidence on back schools for the treatment of chronic low back pain. By searching MEDLINE, Embase, and Cochrane Central as well as bibliographies, we identified 31 studies for inclusion in our systematic review and 5 of these for inclusion in meta-analyses. Meta-analyses for pain scores and functional outcomes revealed statistical superiority of back schools vs no intervention for some comparisons but not others. No meta-analysis was feasible for the comparison of back schools vs other active treatments. Adverse events were poorly reported so that no reliable conclusions regarding the safety of back schools can be drawn, although some limited reassurance in this regard may be derived from the fact that few adverse events and no serious adverse events were reported in the back school groups in the studies that did report on safety. Overall, the evidence base for the use of back schools to treat chronic low back pain is weak; in nearly a half-century since back schools were first trialled, no unequivocal evidence of benefit has emerged.


Recurrent erysipelas: 47 cases.
Recurrence is a common complication of erysipelas (cellulitis). Todescribe the characteristics of patients with recurrent erysipelas and thereby, identify potential risk factors and evaluate prophylaxis efficacy. Data were retrospectively recorded from the files of 47 patients admitted to hospital between 1995 and 2003 for erysipelas recurrence. Studied variables included: general condition, regional and local factors, e.g. broken cutaneous barrier. Patient characteristics were used to construct tree-based models according to the classification and regression tree methodology. Our patients suffered a mean of 4.1 recurrences. Cutaneous barrier disruption was observed in 81%, mainly intertrigo (60%). Antibiotic prophylaxis was taken by 68% of the patients for 30.6 months. After 1 and 2 years, 84 and 72% of the patients, respectively, were recurrence-free. Our results showed that erysipelas recurrence has the same risk factors as single episodes and underlines the potential benefit of oral or parenteral antibiotic prophylaxis to prevent recurrences.