UV and Visible Spectrum LED Lighting as Abiotic Elicitors of Bioactive Compounds in Sprouts, Microgreens, and Baby Leaves-A Comprehensive Review including Their Mode of Action.
Background: According to social demands, the agri-food industry must elaborate convenient safe and healthy foods rich in phytochemicals while minimising processing inputs like energy consumption. Young plants in their first stages of development represent great potential. Objective: This review summarises the latest scientific findings concerning the use of UV and visible spectrum LED lighting as green, sustainable, and low-cost technologies to improve the quality of sprouts, microgreens, and baby leaves to enhance their health-promoting compounds, focusing on their mode of action while reducing costs and energy. Results: These technologies applied during growing and/or after harvesting were able to improve physiological and morphological development of sprouted seeds while increasing their bioactive compound content without compromising safety and other quality attributes. The novelty is to summarise the main findings published in a comprehensive review, including the mode of action, and remarking on the possibility of its postharvest application where the literature is still scarce. Conclusions: Illumination with UV and/or different regions of the visible spectrum during growing and shelf life are good abiotic elicitors of the production of phytochemicals in young plants, mainly through the activation of specific photoreceptors and ROS production. However, we still need to understand the mechanistic responses and their dependence on the illumination conditions.


Video-assisted instruction improves the success rate for tracheal intubation by novices.
Tracheal intubation via laryngoscopy is a fundamental skill, particularly for anaesthesiologists. However, teaching this skill is difficult since direct laryngoscopy allows only one individual to view the larynx during the procedure. The purpose of this study was to determine if video-assisted laryngoscopy improves the effectiveness of tracheal intubation training. In this prospective, randomized, crossover study, 37 novices with less than six prior intubation attempts were randomized into two groups, video-assisted followed by traditional instruction (Group V/T) and traditional instruction followed by video-assisted instruction (Group T/V). Novices performed intubations on three patients, switched groups, and performed three more intubations. All trainees received feedback during the procedure from an attending anaesthesiologist based on standard cues. Additionally, during the video-assisted part of the study, the supervising anaesthesiologist incorporated feedback based on the video images obtained from the fibreoptic camera located in the laryngoscope. During video-assisted instruction, novices were successful at 69% of their intubation attempts whereas those trained during the non-video-assisted portion were successful in 55% of their attempts (P=0.04). Oesophageal intubations occurred in 3% of video-assisted intubation attempts and in 17% of traditional attempts (P<0.01). The improved rate of successful intubation and the decreased rate of oesophageal intubation support the use of video laryngoscopy for tracheal intubation training.


Evaluating oral flavorant effects on nicotine self-administration behavior and phasic dopamine signaling.
Understanding how tobacco product flavor additives, such as flavorants in electronic cigarettes, influence smoking behavior and addiction is critical for informing public health policy decisions regarding tobacco product regulation. Here, we developed a combined intraoral (i.o.) and intravenous (i.v.) self-administration paradigm in rats to determine how flavorants influence self-administration behavior. By combining i.o. flavorant delivery with fast scan cyclic voltammetry (FSCV) or i.v. nicotine self-administration in adult, male rats, we examined whether flavors alter phasic dopamine (DA) signaling and nicotine self-administration. Oral administration of 10% sucrose or 0.32% saccharin, but not 0.005% menthol, increased phasic DA release in the nucleus accumbens (NAc). Oral sucrose or saccharin, when combined with i.v. nicotine delivery, also led to increased self-administration behavior. Specifically, combined i.o. sucrose and i.v. nicotine decreased responding compared to sucrose alone, and increased responding compared to nicotine alone. In contrast, i.o. flavorants did not alter motivational breakpoint in a progressive ratio task. Oral menthol, which did not alter i.v. nicotine administration, reversed oral nicotine aversion (50 and 100 mg/L) in a two-bottle choice test. Here, we demonstrate that i.o. appetitive flavorants that increase phasic DA signaling also increase self-administration behavior when combined with i.v. nicotine delivery. Additionally, oral menthol effects were specific to oral nicotine, and were not observed with i.v. nicotine-mediated reinforcement. Together, these preclinical findings have important implications regarding menthol and sweet flavorant additive effects on tobacco product use and can be used to inform policy decisions on tobacco product flavorant regulation.


Vestibulodynia: synergy between palmitoylethanolamide + transpolydatin and transcutaneous electrical nerve stimulation.
The study aimed to assess the effect of palmitoylethanolamide + transpolydatin combination in patients with vestibulodynia undergoing transcutaneous electrical nerve stimulation (TENS) therapy and to confirm the effectiveness of TENS also in a domiciliary protocol. The study is based on the premise that palmitoylethanolamide + transpolydatin combination may contribute to a down-regulation of mast cell hyperactivity, which is believed to be responsible for the proliferation and sprouting of vestibular pain fibers and the associated hyperalgesia and allodynia. Twenty women with vestibulodynia were randomly assigned to receive oral palmitoylethanolamide (PEA) 400 mg and transpolydatin 40 mg or placebo, twice daily for 60 days. All patients underwent TENS therapy in a self-administered home protocol. Visual analogue scale (VAS), Marinoff score for dyspareunia, and current perception threshold obtained from the vulvar vestibule were assessed at baseline and at the end of treatment. The patients received a mean of 26.7 TENS sessions. All scores in the 2 groups improved significantly, although the level of improvement was similar between the groups (VAS, p < .57; dyspareunia, p < .38). Nevertheless, the analysis of regression of symptoms related to the duration of disease revealed the therapy to be more effective when PEA + transpolydatin is included in cases with more recent disease onset, as compared with the placebo group (PEA: VAS, p < .01; dyspareunia, p < .01) (placebo: VAS, p = nonsignificant; dyspareunia, p = nonsignificant). This study confirms that TENS is of significant benefit in the management of vestibulodynia, also in a home environment. PEA + transpolydatin can be a value-added treatment adjunct when the onset of vestibulodynia is more recent or when the disease relapses.


Economic analysis of palivizumab in infants with congenital heart disease.
Palivizumab has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations by 45% in children with congenital heart disease (CHD). The American Academy of Pediatrics has recommended that infants with hemodynamically significant CHD be considered for palivizumab. However, the economic implications of palivizumab prophylaxis in the CHD population have not been evaluated. In the present study, we sought to examine the cost savings and cost utility of RSV prophylaxis with palivizumab in children with CHD. Probabilities of hospitalization and efficacy of prophylaxis were based on published results. Costs of hospitalization were derived from a published analysis of bronchiolitis hospitalization costs from a consortium of children's hospitals. A hypothetical cohort of 10,000 CHD patients (half of whom would receive palivizumab) was created to calculate cost-savings and cost-utility. To assess cost utility, we assumed that by reducing hospitalization, palivizumab would reduce RSV-related hospital mortality, generally reported to be 3% in CHD patients. Sensitivity analysis was performed. On the basis of a protocol of 5 monthly doses of palivizumab, the cost of prophylaxis for 1 RSV season was calculated as 6160 dollars per patient. After accounting for impact on direct and indirect costs of hospitalization, administration of palivizumab to 5000 CHD patients would result in a net loss of 20,415,753 dollars. If one assumes that palivizumab confers a survival benefit, then the cost of life-year saved is 100,338 dollars and cost of quality-adjusted life-year saved is 114,337 dollars. The cost of palivizumab prophylaxis was high relative to benefits realized. Given the large number of CHD patients who might be considered candidates for RSV prophylaxis (>6000 patients per year in United States) routine use of palivizumab in young children with hemodynamically significant CHD needs to be evaluated further.


Role of phosphoglucomutase of Bordetella bronchiseptica in lipopolysaccharide biosynthesis and virulence.
The phosphoglucomutase (PGM)-encoding gene of Bordetella bronchiseptica is required for lipopolysaccharide (LPS) biosynthesis. An insertion mutant of the wild-type B. bronchiseptica strain BB7865 which disrupted LPS biosynthesis was created and characterized (BB7865pgm). Genetic analysis of the mutated gene showed it shares high identity with PGM genes of various bacterial species and forms part of an operon which also encompasses the gene encoding phosphoglucose isomerase. Functional assays for PGM revealed that enzyme activity is expressed in both bvg-positive and bvg-negative strains of B. bronchiseptica and is substantially reduced in BB7865pgm. Complementation of the mutated PGM gene with that from BB7865 restored the wild-type condition for all phenotypes tested. The ability of the mutant BB7865pgm to survive within J774. A1 cells was significantly reduced at 2 h (40% reduction) and 24 h (56% reduction) postinfection. BB7865pgm was also significantly attenuated in its ability to survive in vivo following intranasal infection of mice, being effectively cleared from the lungs within 4 days, whereas the wild-type strain persisted at least 35 days. The activities of superoxide dismutase, urease, and acid phosphatase were unaffected in the PGM-deficient strain. In contrast, the inability to produce wild-type LPS resulted in a reduced bacterial resistance to oxidative stress and a higher susceptibility to the antimicrobial peptide cecropin P.


Thematic Analysis of Mental Health Nurses' Views of Contributing Factors Fueling Workplace Violence in Psychiatric Hospitals: Insights From Unsung Soldiers.
Workplace violence against mental health nurses is an international phenomenon that sparks concerns for nurses' safety and mental health. This phenomenon has recently arisen as a crucial concern in the Middle East as it has become pervasive and has negative implications, causing nurses to accumulate psychological and emotional distress. However, no research has yet investigated the contributing factors of this phenomenon in Jordanian psychiatric hospitals from the nurses' perspectives. This study aimed to explore the factors contributing to workplace violence in Jordanian psychiatric hospitals from the perspective of mental health nurses. An exploratory, qualitative design was utilized. Using audio-recorded, semi-structured, face-to-face interviews, a purposive sample of 24 mental health nurses were interviewed to collect data. Thematic analysis was used to analyze the data. Four overarching themes were identified: Peak Time of Violence, Unavoidable Part of the Job, Poor Organization and Lack of Policy, and Bite the Bullet. From nurses' perspectives, an in-depth understanding of factors contributing to workplace violence provides a foundation for developing preventive interventions, improving work environment safety, and promoting nurses' mental health. Prevention strategies and further studies are warranted to limit this phenomenon.


Elucidation of the calcineurin-Crz1 stress response transcriptional network in the human fungal pathogen Cryptococcus neoformans.
Calcineurin is a highly conserved Ca2+/calmodulin-dependent serine/threonine-specific protein phosphatase that orchestrates cellular Ca2+ signaling responses. In Cryptococcus neoformans, calcineurin is activated by multiple stresses including high temperature, and is essential for stress adaptation and virulence. The transcription factor Crz1 is a major calcineurin effector in Saccharomyces cerevisiae and other fungi. Calcineurin dephosphorylates Crz1, thereby enabling Crz1 nuclear translocation and transcription of target genes. Here we show that loss of Crz1 confers phenotypes intermediate between wild-type and calcineurin mutants, and demonstrate that deletion of the calcineurin docking domain results in the inability of Crz1 to translocate into the nucleus under thermal stress. RNA-sequencing revealed 102 genes that are regulated in a calcineurin-Crz1-dependent manner at 37°C. The majority of genes were down-regulated in cna1Δ and crz1Δ mutants, indicating these genes are normally activated by the calcineurin-Crz1 pathway at high temperature. About 58% of calcineurin-Crz1 target genes have unknown functions, while genes with known or predicted functions are involved in cell wall remodeling, calcium transport, and pheromone production. We identified three calcineurin-dependent response element motifs within the promoter regions of calcineurin-Crz1 target genes, and show that Crz1 binding to target gene promoters is increased upon thermal stress in a calcineurin-dependent fashion. Additionally, we found a large set of genes independently regulated by calcineurin, and Crz1 regulates 59 genes independently of calcineurin. Given the intermediate crz1Δ mutant phenotype, and our recent evidence for a calcineurin regulatory network impacting mRNA in P-bodies and stress granules independently of Crz1, calcineurin likely acts on factors beyond Crz1 that govern mRNA expression/stability to operate a branched transcriptional/post-transcriptional stress response network necessary for fungal virulence. Taken together, our findings reveal the core calcineurin-Crz1 stress response cascade is maintained from ascomycetes to a pathogenic basidiomycete fungus, but its output in C. neoformans appears to be adapted to promote fungal virulence.


Heat shock protein 90 mediates efficient antigen cross presentation through the scavenger receptor expressed by endothelial cells-I.
Ag cross presentation is an important mechanism for CD8(+) T cell activation by APCs. We have investigated mechanisms involved in heat shock protein 90 (Hsp90) chaperone-mediated cross presentation of OVA-derived Ags. Hsp90-OVA peptide complexes bound to scavenger receptor expressed by endothelial cells (SREC-I) on the surface of APCs. SREC-I then mediated internalization of Hsp90-OVA polypeptide complexes through a Cdc42-regulated, dynamin-independent endocytic pathway known as the GPI-anchored protein-enriched early endosomal compartment to recycling endosomes. Peptides that did not require processing could then be loaded directly onto MHC class I in endosomes, whereas longer peptides underwent endosomal and cytosomal processing by aminopeptidases and proteases. Cross presentation of Hsp90-chaperoned peptides through this pathway to CD8(+) T cells was highly efficient compared with processing of free polypeptides. In addition, Hsp90 also activated c-Src kinase associated with SREC-I, an activity that we determined to be required for effective cross presentation. Extracellular Hsp90 can thus convey antigenic peptides through an efficient endocytosis pathway in APCs and facilitate cross presentation in a highly regulated manner.


Multi-stage carcinogenesis in the urinary bladder.
Sodium saccharin has been shown to be a promoting substance for urinary bladder carcinogenesis in the rat following initiation with N-methyl-N-nitrosourea, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), or N-butyl-N-(4-hydroxybutyl)nitrosamine. It has been shown to have many of the properties of promoting substances in other animal models, such as the mouse skin; it lacks mutagenic activity, induces hyperplasia in the target tissue, and does not bind DNA. It has recently been demonstrated to be co-carcinogenic for the rat bladder. It has also been shown that the administration of sodium saccharin during the regenerative hyperplasia observed after freeze ulceration or cyclophosphamide administration resulted in the induction of bladder tumours, even without pre-initiation with FANFT or other known initiating substances. This model appears to be analogous to the administration of sodium saccharin to animals with a rapidly proliferating bladder mucosa as occurs in utero during the two-generation carcinogenesis experiments and in the pellet-insertion experiments in which a cholesterol pellet containing sodium saccharin is inserted into the bladder. To enhance our understanding of the complex interaction of the many variables involved in two-stage bladder carcinogenesis, a stochastic model has been formulated based on long-term carcinogenicity and in vivo tissue kinetic studies. This model indicates the importance of cell proliferation and the development of hyperplasia in carcinogenesis.


Drug overdose among women in intimate relationships: The role of partner violence, adversity and relationship dependencies.
This study examines the relationship between experiencing intimate partner violence (IPV), exposure to prior childhood adversity, lifetime adverse experiences, drug-related relationship dependencies with intimate partners and overdose, hospitalization for drug use, friends and family members who overdosed and witnessing overdose. This paper included a sample of 201 women who use drugs in heterosexual relationships with criminal justice-involved men in New York City. We included measures of experiencing overdose, hospitalization for drug use, witnessing overdose, and having friends and family who overdosed. Intimate partner violence consisted of either 1) none/verbal only, 2) moderate and 3) severe abuse. Dichotomous indicators of drug-related relationship dependencies included financial support, drug procurement, splitting and pooling drugs. A scale measured cumulative exposure to childhood adversity and lifetime exposures to adverse events. This paper hypothesized that experiencing moderate and severe IPV, drug-related dependencies and exposure to prior childhood and lifetime adversity would be associated with a greater risk of experiencing overdose, hospitalization for drug use, witnessing overdose and having friends and family members who overdosed. Generalized linear modeling with robust variance estimated relative risk ratios that accounted for potential bias in confidence intervals and adjusted for race, ethnicity, education and marital status. We found experiencing moderate or severe IPV was associated with ever being hospitalized for drug use and having a family member who experienced overdose. Experiencing moderate IPV was associated with increased risk of witnessing overdose, Partner drug dependencies were associated with overdose, ever being hospitalized for drug use, witnessing overdose, and having a family member or friend who experienced overdose. Childhood and lifetime adversity exposures were significantly associated with increased risk of overdose, ever being hospitalized for drug use, ever witnessing overdose and having a friend and family member who overdosed. Findings underscore the intersection of experiencing IPV and drug-related relationship dependencies, childhood adversity and lifetime adversity in shaping experiences of and witnessing overdose among women who use drugs. They highlight the urgent need to address IPV, adversity experiences and drug-related relationship dependencies in overdose prevention for women who use drugs.


The health economic impact of disease management programs for COPD: a systematic literature review and meta-analysis.
There is insufficient evidence of the cost-effectiveness of Chronic Obstructive Pulmonary Disease (COPD) Disease Management (COPD-DM) programs. The aim of this review is to evaluate the economic impact of COPD-DM programs and investigate the relation between the impact on healthcare costs and health outcomes. We also investigated the impact of patient-, intervention, and study-characteristics. We conducted a systematic literature review to identify cost-effectiveness studies of COPD-DM. Where feasible, results were pooled using random-effects meta-analysis and explorative subgroup analyses were performed. Sixteen papers describing 11 studies were included (7 randomized control trials (RCT), 2 pre-post, 2 case-control). Meta-analysis showed that COPD-DM led to hospitalization savings of €1060 (95% CI: €2040 to €80) per patient per year and savings in total healthcare utilization of €898 (95% CI: €1566 to €231) (excl. operating costs). In these health economic studies small but positive results on health outcomes were found, such as the St Georges Respiratory Questionnaire (SGRQ) score, which decreased with 1.7 points (95% CI: 0.5-2.9). There was great variability in DM interventions-, study- and patient-characteristics. There were indications that DM showed greater savings in studies with: severe COPD patients, patients with a history of exacerbations, RCT study design, high methodological quality, few different professions involved in the program, and study setting outside Europe. COPD-DM programs were found to have favourable effects on both health outcomes and costs, but there is considerable heterogeneity depending on patient-, intervention-, and study-characteristics.


Prevalence of Cardiovascular Risk Factors among Executive and Nonexecutive Workers in an Urban Public Sector Office Setting: A Cross-Sectional Epidemiological Study from Eastern India.
The aim of the study is to determine the prevalence of cardiovascular risk factors among executive and nonexecutive workers in an urban public sector office setting. A prospective, cross-sectional survey of employees in a public sector office in Eastern India was done using a structured questionnaire to collect data on demographic and lifestyle details and health conditions. Clinical examination, anthropometric measurements, blood sugar, and lipid levels were measured. The employees were divided as executives and nonexecutives based on whether they held gazetted or nongazetted posts. A total of 502 participants were surveyed - 140 executives and 362 nonexecutives; majority were male (88.23%). The executive group had a significantly greater number of participants with older age, hypertension (57.9% vs. 39%), and overweight (40% vs. 30.6%) than the nonexecutive group. Significantly, more nonexecutives had a physically active lifestyle and relatively less presence of conventional cardiovascular risk factors such as tobacco use, hypertension, diabetes, hypercholesterolemia, and weight. The prevalence of ≥3 cardiovascular risk factors was significantly high in executives (27.9%) as compared to nonexecutives (14.1%). A higher prevalence of mostly lifestyle-related modifiable cardiovascular risk factors was seen among the executives in an urban public sector office setting in Eastern India.


Genetic variation and risks of introgression in the wild Coffea arabica gene pool in south-western Ethiopian montane rainforests.
The montane rainforests of SW Ethiopia are the primary centre of diversity of Coffea arabica and the origin of all Arabica coffee cultivated worldwide. This wild gene pool is potentially threatened by forest fragmentation and degradation, and by introgressive hybridization with locally improved coffee varieties. We genotyped 703 coffee shrubs from unmanaged and managed coffee populations, using 24 microsatellite loci. Additionally, we genotyped 90 individuals representing 23 Ethiopian cultivars resistant to coffee berry disease (CBD). We determined population genetic diversity, genetic structure, and admixture of cultivar alleles in the in situ gene pool. We found strong genetic differentiation between managed and unmanaged coffee populations, but without significant differences in within-population genetic diversity. The widespread planting of coffee seedlings including CBD-resistant cultivars most likely offsets losses of genetic variation attributable to genetic drift and inbreeding. Mixing cultivars with original coffee genotypes, however, leaves ample opportunity for hybridization and replacement of the original coffee gene pool, which already shows signs of admixture. In situ conservation of the wild gene pool of C. arabica must therefore focus on limiting coffee production in the remaining wild populations, as intensification threatens the genetic integrity of the gene pool by exposing wild genotypes to cultivars.


Fingolimod Limits Acute Aβ Neurotoxicity and Promotes Synaptic Versus Extrasynaptic NMDA Receptor Functionality in Hippocampal Neurons.
Fingolimod, also known as FTY720, is an analogue of the sphingolipid sphingosine, which has been proved to be neuroprotective in rodent models of Alzheimer's disease (AD). Several cellular and molecular targets underlying the neuroprotective effects of FTY720 have been recently identified. However, whether the drug directly protects neurons from toxicity of amyloid-beta (Aβ) still remains poorly defined. Using a combination of biochemical assays, live imaging and electrophysiology we demonstrate that FTY720 induces a rapid increase in GLUN2A-containing neuroprotective NMDARs on the surface of dendritic spines in cultured hippocampal neurons. In addition, the drug mobilizes extrasynaptic GLUN2B-containing NMDARs, which are coupled to cell death, to the synapses. Altered ratio of synaptic/extrasynaptic NMDARs decreases calcium responsiveness of neurons to neurotoxic soluble Aβ 1-42 and renders neurons resistant to early alteration of calcium homeostasis. The fast defensive response of FTY720 occurs through a Sphingosine-1-phosphate receptor (S1P-R) -dependent mechanism, as it is lost in the presence of S1P-R1 and S1P-R3 antagonists. We propose that rapid synaptic relocation of NMDARs might have direct impact on amelioration of cognitive performance in transgenic APPswe/PS1dE9 AD mice upon sub-chronic treatment with FTY720.


Ab Initio Vibro-Polaritonic Spectra in Strongly Coupled Cavity-Molecule Systems.
Recent experiments have revealed the profound effect of strong light-matter interactions in optical cavities on the electronic ground state of molecular systems. This phenomenon, known as vibrational strong coupling, can modify reaction rates and induce the formation of molecular vibrational polaritons, hybrid states involving both photon modes, and vibrational modes of molecules. We present an ab initio methodology based on the cavity Born-Oppenheimer Hartree-Fock ansatz, which is specifically powerful for ensembles of molecules, to calculate vibro-polaritonic IR spectra. This method allows for a comprehensive analysis of these hybrid states. Our semiclassical approach, validated against full quantum simulations, reproduces key features of the vibro-polaritonic spectra. The underlying analytic gradients also allow for optimization of cavity-coupled molecular systems and performing semiclassical dynamics simulations.


Analysis of fast excitatory postsynaptic currents in bullfrog parasympathetic ganglion cells.
Excitatory postsynaptic currents (EPSCs), miniature excitatory postsynaptic currents (MEPSCs), and acetylcholine-induced current fluctuations (noise) have been studied in voltage-clamped bullfrog parasympathetic ganglion cells of the atrial septum. EPSCs were also recorded from voltage-clamped sympathetic B cells and, in general, it was found that the basic properties of the EPSCs are similar in both parasympathetic and sympathetic B cells. For parasympathetic cells, the EPSC reached a peak amplitude of several nanoamperes within 3 msec and decayed exponentially. For 31 cells voltage-clamped to -50 mV (22 to 23 degrees C), peak amplitude was -4.3 +/- 1.4 nA (mean +/- SD) and the decay time constant, tau, was 5.6 +/- 1.0 msec. tau was independent of EPSC amplitude at a set voltage but increased with hyperpolarization, the coefficient of voltage dependence being -0.0070 +/- 0.0025 mV-1 in 13 cells (21 to 23 degrees C). The EPSC amplitude-voltage relationship was linear between -30 and -90 mV. The reversal potential, determined by interpolation, was -4.0 +/- 6.7 mV (n = 11). The EPSC tau had a Q10 equal to 2.9. Blocking the acetylcholinesterase with methane sulfonyl fluoride (MSF) pretreatment prolonged EPSC decay but decreased EPSC amplitude. In addition, EPSC decay after MSF treatment deviated from a single exponential function. MEPSCs exhibited decay characteristics very similar to those of EPSCs recorded at the same voltage and temperature. Acetylcholine-induced current fluctuations were well described by a single Lorentzian function with the estimated mean channel open time (tau noise) very similar to the EPSC decay time constant.(ABSTRACT TRUNCATED AT 250 WORDS)


Short-term effects of non-surgical periodontal therapy on clinical measures of impaired glucose tolerance in people with prediabetes and chronic periodontitis.
Diabetes and periodontal disease are conditions considered to be biologically linked. Prediabetes is a condition in which individuals have blood glucose levels, impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) or glycated hemoglobin (A1C) levels higher than normal but not high enough to be classified as diabetes. Few human studies address the relationship between periodontitis and prediabetes or clarify an association between periodontitis and prediabetes. The purpose of this pilot study was to examine the impact of non-surgical periodontal therapy (NSPT) on clinical measures of glycemic control in prediabetes. Prediabetes measures of IFG, IGT, A1C and periodontal measures of pocket depth (PD), clinical attachment level (CAL), plaque index (PI) and gingival index (GI) were taken at baseline and 3 months in 12 subjects with prediabetes and chronic slight to moderate periodontitis. Blood samples were taken from each subject following an 8 hour fast. This study controlled for changes in medications, body-mass index, physical activity and diet. Comparison of mean prediabetes and periodontal measures from baseline and post-treatment at 3 months demonstrated clinical improvement for both periodontal and prediabetes measures. A mean reduction in PD of 0.27 (p=0.003), CAL of 0.32 (p=0.050) and A1C of 0.19 (p=0.015) reached statistical significance. This pilot study suggests NSPT improves A1C and periodontal measures at 3 months. The robustness of measures is limited due to the small sample size and lack of a control group. Further larger scale studies using a randomized control design would be informative.


Reappraisal of the role of dolasetron in prevention and treatment of nausea and vomiting associated with surgery or chemotherapy.
Chemotherapy-induced nausea and vomiting and postoperative nausea and vomiting are one of the most frequent but also very concerning consequences for patients undergoing chemotherapy or surgical procedures under general anesthesia. There are a variety of mechanisms involved in the activation of nausea and vomiting. Serotonin, a ubiquitous central and peripheral neurotransmitter, is thought to be the predominant mediator of the perception of nausea and triggering of the vomiting response in both the brain and the periphery via the 5-hydroxytryptamine type 3 (5-HT(3)) receptor pathways. 5-HT(3) receptor antagonists disrupt this pathway, largely at the level of the vagal afferent pathways, to decrease nausea and vomiting. This review will focus on dolasetron, an older but sill commonly used 5-HT(3) receptor antagonist and its multimodal mechanism of action, safety and tolerability, patient considerations, and a review of the current literature on its use to combat both chemotherapy-induced and postoperative nausea and vomiting in these two important patient populations.


Cloning and sequence analysis of a trans-regulatory locus required for exoenzyme S synthesis in Pseudomonas aeruginosa.
Exoenzyme S is an ADP-ribosyltransferase enzyme distinct from exotoxin A that is synthesized and secreted by Pseudomonas aeruginosa. Yields of exoenzyme S are variable and depend on strain and growth conditions. Since certain medium additives are required for exoenzyme S production, its regulation may be influenced by environmental stimuli. In this study, we have cloned a region that complements the exoenzyme S-deficient phenotype of strain 388 exs1::Tn1, a chromosomal Tn1 insertional mutation. A large clone (28 kb) was shown to restore both synthesis and secretory functions to the mutant strain. Subcloning and Tn501 mutagenesis experiments localized the region required for exoenzyme S synthesis to a 3.2-kb fragment. Nucleotide sequence analysis demonstrated several open reading frames. Comparison of the N-terminal amino acid sequence of purified exoenzyme S with predicted amino acid sequences of all open reading frames indicated that the structural gene was not encoded within the sequenced region. Homology studies suggested that the region encoded three regulatory genes, exsC, exsB, and exsA. ExsA was homologous to the AraC family of transcriptional activator proteins, with extensive homology being found with one member of this family, VirF of Yersinia enterocolitica. VirF and ExsA both contain carboxy-terminal domains with the helix-turn-helix motif of DNA-binding proteins. The ExsA gene product appeared to be required for induction of exoenzyme S synthesis above a low basal level. Expression of ExsA was demonstrated by cloning the region under the control of the T7 promoter. Gene replacement experiments suggested that the expression of ExsC affects the final yield of exoenzyme S.


Failed attempts to improve the reliability of the alcohol visual probe task following empirical recommendations.
The visual probe task (VPT) is a computerized task used to measure attentional bias to substance-related stimuli. Little research has examined the psychometric properties of the VPT, despite concerns it demonstrates poor test-retest reliability and internal consistency. These issues can reduce confidence in inferences based on VPT performance. As such, we attempted to identify parameters under which the reliability of the alcohol VPT might be improved by applying recent empirical recommendations for outlier handling, bias calculation, and task design from the anxiety literature. We reanalyzed data from 3 previously published studies in our laboratory and 2 newly collected data sets. We compared tasks which presented images on the left/right of the screen to above/below, whether participants responded to the location or content of the probe, and whether general alcohol-related images or images personalized to the individual were used. In each VPT we also applied a priori outlier removal (2 and 3 standard deviations and median absolute difference) and data-driven outlier removal (winsorizing), in addition to calculating trial-level bias scores. Across all studies and tasks internal consistency and test-retest reliability of attentional bias measures were inadequate. There was no consistent improvement in internal consistency or test-retest reliability as a function of outlier removal methods. We were unable to demonstrate adequate reliability of the alcohol VPT, which further supports observations that these tasks may not yield reliable measures. Future research should focus on improving the reliability of these tasks or abandoning them in favor of more reliable alternatives. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Repeated Impact-Based Capture of a Spinning Object by a Dual-Arm Space Robot.
This paper presents detumbling and capture of space debris by a dual-arm space robot for active space debris removal missions. Space debris, such as a malfunctioning satellite or a rocket upper stage, often has uncontrolled tumbling motion. It also has uncertainties in its parameters, such as inertial characteristics or surface frictional roughness. These factors make the debris capture missions difficult to accomplish. To cope with such challenging missions, we propose a detumbling and capture control method for a dual-arm robot based on repeated impact capable of suppressing the debris motion by repeatedly utilizing an effect of a passive damping factor in the contact characteristics. In this paper, as the initial step of a study on the repeated impact-based capture method, we assume that the capture target is a rocket upper stage that can be simply modeled as a cylindrical body and mainly has angular velocity motion in its principle axis of inertia. A motion tracking control law of an end-effector of the robot arm is introduced to maintain the repeated impact. The proposed control method enables the robot to accomplish the detumbling and capture without precise estimation of the inertial characteristics and surface frictional roughness of the debris. The validity of the proposed method is presented by numerical simulations and planar microgravity experiments using an air-floating system. In particular, the experimental evaluation shows the fundamental feasibility of the proposed method, and thus, the result contributes to a practical application.


Analgesic efficacy of cerebral and peripheral electrical stimulation in chronic nonspecific low back pain: a randomized, double-blind, factorial clinical trial.
Chronic non-specific low back pain is a major socioeconomic public health issue worldwide and, despite the volume of research in the area, it is still a difficult-to-treat condition. The conservative analgesic therapy usually comprises a variety of pharmacological and non-pharmacological strategies, such as transcutaneous electrical nerve stimulation. The neuromatrix pain model and the new findings on the process of chronicity of pain point to a higher effectiveness of treatments that address central rather than peripheral structures. The transcranial direct current stimulation is a noninvasive technique of neuromodulation that has made recent advances in the treatment of chronic pain. The simultaneous combination of these two electrostimulation techniques (cerebral and peripheral) can provide an analgesic effect superior to isolated interventions. However, all the evidence on the analgesic efficacy of these techniques, alone or combined, is still fragmented. This is a protocol for a randomized clinical trial to investigate whether cerebral electrical stimulation combined with peripheral electrical stimulation is more effective in relieving pain than the isolated application of electrical stimulations in patients with chronic nonspecific low back pain. Ninety-two patients will be randomized into four groups to receive transcranial direct current stimulation (real/sham) + transcutaneous electrical nerve stimulation (real/sham) for 12 sessions over a period of four weeks. The primary clinical outcome (pain intensity) and the secondary ones (sensory and affective aspects of pain, physical functioning and global perceived effect) will be recorded before treatment, after four weeks, in Month 3 and in Month 6 after randomization. Confounding factors such as anxiety and depression, the patient's satisfaction with treatment and adverse effects will also be listed. Data will be collected by an examiner unaware of (blind to) the treatment allocation. The results of this study may assist in clinical decision-making about the combined use of cerebral and peripheral electrical stimulation for pain relief in patients with chronic low back pain. NCT01896453.


Telemedicine to deliver diabetes care in low- and middle-income countries: a systematic review and meta-analysis.
To determine the effectiveness of telemedicine in the delivery of diabetes care in low- and middle-income countries. We searched seven databases up to July 2020 for randomized controlled trials investigating the effectiveness of telemedicine in the delivery of diabetes care in low- and middle-income countries. We extracted data on the study characteristics, primary end-points and effect sizes of outcomes. Using random effects analyses, we ran a series of meta-analyses for both biochemical outcomes and related patient properties. We included 31 interventions in our meta-analysis. We observed significant standardized mean differences of -0.38 for glycated haemoglobin (95% confidence interval, CI: -0.52 to -0.23; I 2 = 86.70%), -0.20 for fasting blood sugar (95% CI: -0.32 to -0.08; I 2 = 64.28%), 0.81 for adherence to treatment (95% CI: 0.19 to 1.42; I 2 = 93.75%), 0.55 for diabetes knowledge (95% CI: -0.10 to 1.20; I 2 = 92.65%) and 1.68 for self-efficacy (95% CI: 1.06 to 2.30; I 2 = 97.15%). We observed no significant treatment effects for other outcomes, with standardized mean differences of -0.04 for body mass index (95% CI: -0.13 to 0.05; I 2 = 35.94%), -0.06 for total cholesterol (95% CI: -0.16 to 0.04; I 2 = 59.93%) and -0.02 for triglycerides (95% CI: -0.12 to 0.09; I 2 = 0%). Interventions via telephone and short message service yielded the highest treatment effects compared with services based on telemetry and smartphone applications. Although we determined that telemedicine is effective in improving several diabetes-related outcomes, the certainty of evidence was very low due to substantial heterogeneity and risk of bias.


High-quality reflection separation using polarized images.
In this paper, we deal with a problem of separating the effect of reflection from images captured behind glass. The input consists of multiple polarized images captured from the same view point but with different polarizer angles. The output is the high quality separation of the reflection layer and the background layer from the images. We formulate this problem as a constrained optimization problem and propose a framework that allows us to fully exploit the mutually exclusive image information in our input data. We test our approach on various images and demonstrate that our approach can generate good reflection separation results.


Is 1-stage Posterior Corpectomy More Favorable Compared With Decompression With Fusion to Control Thoracic Cord Compression by Metastasis?
A retrospective comparative study OBJECTIVE:: To compare 1-stage posterior corpectomy to decompression with fusion for the control of thoracic cord compression due to a metastatic tumor. Thoracic cord compression by a metastatic tumor can cause back pain, paralysis, and urinary/bowel dysfunction and is generally treated by palliative decompressive surgery. However, no studies have assessed the advantages of 1-stage posterior corpectomy compared with decompression with fusion. We studied 18 patients who underwent surgery for thoracic cord compression due to metastatic tumors between September 2009 and August 2013. Neurological examination was performed preoperatively and postoperatively. Data on operative time, blood loss during surgery, postoperative complications, and survival time were retrospectively retrieved from electronic medical records. Patients were divided into 2 groups based on treatment: decompression and corpectomy (corpectomy group, n=8) and decompression with fusion (decompression-fusion group, n=10). Data were statistically compared between the 2 groups. The mean age of the patients was 61±12 years. Motor weakness and urinary/bowel dysfunction were observed in 15 and 9 cases, respectively. Five patients, who could walk before surgery, could walk at 1 month following surgery. However, only 3 of the 13 patients who could not walk before surgery regained the ability to walk. No difference was found in the degree of muscle strength recovery between the 2 groups. However, the corpectomy group showed higher blood loss (2200 vs. 710 mL, P=0.037) and longer operative time (281 vs. 217 min, P=0.029) than the decompression-fusion group. There is no significant advantage of 1-stage posterior corpectomy over decompression with fusion. Furthermore, more blood loss and longer operative time may increase the risk of postoperative complications following corpectomy. For this reason, 1-stage posterior corpectomy to control thoracic metastasis should be considered with caution.


Electro--optical simulation of diffraction in solar cells.
A simulation method is presented and evaluated for simulating two- and three dimensional wave optical effects in crystalline silicon solar cells. Due to a thickness in the 100 µm range, optical properties of these solar cells typically are simulated, primarily through the use of ray-tracing. Recently, diffractive elements such as gratings or photonic crystals have been investigated for their application in crystalline silicon solar cells, making it necessary to consider two- and three dimensional wave optical effects. The presented approach couples a rigorous wave optical simulation to a semiconductor device simulation. In a first step, characteristic parameters, simulated for a reference setup using the electro-optical method and the standard procedure are compared. Occurring differences provide a measure to quantify the errors of the electro-optical method. These errors are below 0.4% relative. In a second step the electro-optical method is used to simulate a crystalline silicon solar cell with a back side diffractive grating. It is found that the grating enhances to short circuit current density jSC of the solar cell by more than 1 mA/cm².


Demonstration of using two aperture pairs combined with multiple-mode receivers and MIMO signal processing for enhanced tolerance to turbulence and misalignment in a 10 Gbit/s QPSK FSO link.
We utilize aperture diversity combined with multiple-mode receivers and multiple-input-multiple-output (MIMO) digital signal processing (DSP) to demonstrate enhanced tolerance to atmospheric turbulence and spatial misalignment in a 10 Gbit/s quadrature-phase-shift-keyed (QPSK) free-space optical (FSO) link. Turbulence and misalignment could cause power coupling from the fundamental Gaussian mode into higher-order modes. Therefore, we detect power from multiple modes and use MIMO DSP to enhance the recovery of the original data. In our approach, (a) each of multiple transmitter apertures transmits a single fundamental Gaussian beam carrying the same data stream, (b) each of multiple receiver apertures detects the signals that are coupled from the fundamental Gaussian beams to multiple orbital angular momentum (OAM) modes, and (c) MIMO DSP is used to recover the data over multiple modes and receivers. Our simulation shows that the outage probability could be reduced from >0.1 to <0.01. Moreover, we experimentally demonstrate the scheme by transmitting two fundamental Gaussian beams carrying the same data stream and recovering the signals on OAM modes 0 and +1 at each receiver aperture. We measure an up to ∼10dB power-penalty reduction for a bit error rate (BER) at the 7% forward error correction limit for a 10 Gbit/s QPSK signal.


Sharing the costs and benefits of climate change mitigation via Shapley value.
This paper examines the free rider problem that exists in the joint effort to mitigate climate change. There is a need to develop a model that is stable and that provides evidence of an objective burden sharing rule so that the environmental agreement is more acceptable. This study approaches this problem via a cooperative game at the global level to make International Environmental Agreements (IEA) more stable. For this purpose, we apply the Shapley value transfer mechanism and find that under the commitment scenario, some regions attain the maximum benefits by joining the coalition. Shapley value transfer improves the coalition size and increases the global benefits at a certain level of abatement under perfect cooperation. Imperfect cooperation leads to lower levels of global benefits. Our findings offer new implications on how to improve the international cooperation for climate change. Commitments by major regions could activate the IEA (e.g., Paris agreement) efficiently. For the maximum global response to climate change, the national governments must reformulate and implement policies to meet their intended nationally determined contributions (INDCs). The results of this study also help the national governments to set their implementation priorities to implement the Paris Accord at global level.


Gated mesoporous silica nanoparticles for the controlled delivery of drugs in cancer cells.
In recent years, mesoporous silica nanoparticles (MSNs) have been used as effective supports for the development of controlled-release nanodevices that are able to act as multifunctional delivery platforms for the encapsulation of therapeutic agents, enhancing their bioavailability and overcoming common issues such as poor water solubility and poor stability of some drugs. In particular, redox-responsive delivery systems have attracted the attention of scientists because of the intracellular reductive environment related to a high concentration of glutathione (GSH). In this context, we describe herein the development of a GSH-responsive delivery system based on poly(ethylene glycol)- (PEG-) capped MSNs that are able to deliver safranin O and doxorubicin in a controlled manner. The results showed that the PEG-capped systems designed in this work can be maintained closed at low GSH concentrations, yet the cargo can be delivered when the concentration of GSH is increased. Moreover, the efficacy of the PEG-capped system in delivering the cytotoxic agent doxorubicin in cells was also demonstrated.


Myeloproliferative neoplasms can be initiated from a single hematopoietic stem cell expressing JAK2-V617F.
The majority of patients with myeloproliferative neoplasms (MPNs) carry a somatic JAK2-V617F mutation. Because additional mutations can precede JAK2-V617F, it is questioned whether JAK2-V617F alone can initiate MPN. Several mouse models have demonstrated that JAK2-V617F can cause MPN; however, in all these models disease was polyclonal. Conversely, cancer initiates at the single cell level, but attempts to recapitulate single-cell disease initiation in mice have thus far failed. We demonstrate by limiting dilution and single-cell transplantations that MPN disease, manifesting either as erythrocytosis or thrombocytosis, can be initiated clonally from a single cell carrying JAK2-V617F. However, only a subset of mice reconstituted from single hematopoietic stem cells (HSCs) displayed MPN phenotype. Expression of JAK2-V617F in HSCs promoted cell division and increased DNA damage. Higher JAK2-V617F expression correlated with a short-term HSC signature and increased myeloid bias in single-cell gene expression analyses. Lower JAK2-V617F expression in progenitor and stem cells was associated with the capacity to stably engraft in secondary recipients. Furthermore, long-term repopulating capacity was also present in a compartment with intermediate expression levels of lineage markers. Our studies demonstrate that MPN can be initiated from a single HSC and illustrate that JAK2-V617F has complex effects on HSC biology.


Low mid-upper arm circumference, calf circumference, and body mass index and mortality in older persons.
Low body mass index is a general measure of thinness. However, its measurement can be cumbersome in older persons and other simple anthropometric measures may be more strongly associated with mortality. Therefore, associations of low mid-upper arm circumference, calf circumference, and body mass index with mortality were examined in older persons. Data of the Longitudinal Aging Study Amsterdam, a population-based cohort study in the Netherlands, were used. The present study included community-dwelling persons 65 years and older in 1992-1993 (n = 1,667), who were followed until 2007 for their vital status. Associations between anthropometric measures and 15-year mortality were examined by spline regression models and, below the nadir, Cox regression models, transforming all measures to sex-specific Z scores. Mortality rates were 599 of 826 (73%) in men and 479 of 841 (57%) in women. Below the nadir, the hazard ratio of mortality per 1 standard deviation lower mid-upper arm circumference was 1.79 (95% confidence interval, 1.48-2.16) in men and 2.26 (1.71-3.00) in women. For calf circumference, the hazard ratio was 1.45 (1.22-1.71) in men and 1.30 (1.15-1.48) in women and for body mass index 1.38 (1.17-1.61) in men and 1.56 (1.10-2.21) in women. Excluding deaths within the first 3 years after baseline did not change these associations. Excluding those with a smoking history, obstructive lung disease, or cancer attenuated the associations of calf circumference (men) and body mass index (women). Based on the stronger association with mortality and given a more easy assessment in older persons, mid-upper arm circumference seems a more feasible and valid anthropometric measure of thinness than body mass index in older men and women.


A retrospective analysis of referral patterns for oral radiologic consultation over 3 years in Ontario, Canada.
To determine the types of practitioners who most commonly refer and the film type and diagnostic entities that are most frequently submitted for oral radiologic consultation in Ontario, Canada. A total of 430 referral letters and responses from 2 Ontario oral radiologists from 2003 to 2005 were analyzed. Data collected included the specialty of the referring practitioner, the film type(s) submitted, the radiographic density of the entity of interest, and the interpretation by the radiologist. General practitioners (58.9%) and oral surgeons (21.5%) were the most frequently referring practitioner types, representing 1.2% and 17.1% respectively of each group practicing in Ontario. Also, 18.2% of oral pathologists referred. Panoramic radiographs (79.5%) were included in referrals more often than intraoral radiographs (46.0%). Of the entities, 37.0% were radiopacities, 27.4% were radiolucencies, and 13.5% had mixed radiopaque-radiolucent density. The radiologists interpreted normal features (55.6%) most often. Panoramic radiographs with normal findings were submitted to oral radiologists for consultation most frequently in Ontario.


Two different tetrodotoxin-separable inward sodium currents in the membrane of isolated cardiomyocytes.
Isolated ventricular myocytes of 3 to 5 weeks old rats were studied under conditions of intracellular perfusion and voltage clamp. The existence of two inward sodium currents with different TTX-sensitivities and different properties was shown. The fast sodium current was more sensitive to TTX (Kd about 8 X 10(-8) mol/l). The block of the slow sodium current by TTX was less specific (Kd about 7 X 10(-6) mol/l). There was an about four fold difference in the inactivation time constants between these currents. The maximum on the I-V curve of the slow sodium current was shifted along the voltage axis by about 15 mV in the positive direction as compared with that of the fast sodium current. A slow current carried by calcium ions was observed in sodium-free solution. The kinetics and TTX-sensitivity of this current were similar to those of the slow sodium current. The amplitude of this current was 15 to 20 times lower as compared with the slow sodium current observed in Na-containing solution with 10(-6) mol/l TTX (a concentration which completely blocked the fast sodium current). It is suggested that the slow voltage-gated TTX-sensitive channels described are not highly selective and pass both sodium and calcium ions.


State Mindfulness During Meditation Predicts Enhanced Cognitive Reappraisal.
Putatively, mindfulness meditation involves generation of a state of "nonappraisal", yet, little is known about how mindfulness may influence appraisal processes. We investigated whether the state and practice of mindfulness could enhance cognitive reappraisal. Participants (N = 44; M age = 24.44, SD = 4.00, range 19 - 38, 82.2% female) were randomized to either 1) mindfulness, 2) suppression, or 3) mind-wandering induction training conditions. Cognitive reappraisal was assessed with the Emotion Regulation Questionnaire (ERQ) prior to experimental induction, and state mindfulness was assessed immediately following induction using the Toronto Mindfulness Scale (TMS). Participants practiced their assigned strategy for one week and then were reassessed with the ERQ reappraisal subscale. Participants receiving mindfulness training reported significantly higher levels of state mindfulness than participants in the thought suppression and mind wandering conditions. Although brief mindfulness training did not lead to significantly greater increases in reappraisal than the other two conditions, state mindfulness during mindfulness meditation was prospectively associated with increases in reappraisal. Path analysis revealed that the indirect effect between mindfulness training and reappraisal was significant through state mindfulness. Degree of state mindfulness achieved during the act of mindfulness meditation significantly predicted increases in reappraisal over time, suggesting that mindfulness may promote emotion regulation by enhancing cognitive reappraisal.


Brain activity associated with placebo suppression of the urge-to-cough in humans.
Antitussive therapies are accompanied by a substantial placebo effect, indicating that inhibitory circuits in the brain have a significant capacity to regulate cough neural processing. However, essentially nothing is known about the identity of these inhibitory circuits or how they reduce coughing. Understanding these processes may help develop more effective antitussive therapies in the future. To identify regional changes in human brain activity related to the urge-to-cough after placebo antitussive administration. Seventeen healthy participants undertook functional magnetic resonance imaging while completing a series of inhalations of capsaicin to induce the urge-to-cough. The resultant brain responses associated with capsaicin inhalation without any treatment were compared with those induced by capsaicin after placebo antitussive administration. There was a significant decrease in participants' ratings of urge-to-cough after the placebo antitussive administration. Brain activity associated with capsaicin inhalation was less in the somatosensory, primary motor, insula, and cingulate cortices during placebo antitussive trials compared with no treatment control subjects. By contrast, placebo trials were associated with increased activation in the prefrontal and left parietal cortices. Placebo-related decreases in urge-to-cough are accompanied by commensurate decreases in several brain regions activated during capsaicin inhalation, suggesting that beliefs about treatment can modify the central processing of inputs arising from the airways. The prefrontal cortex and posterior parietal cortex are likely to play an active role in the modification of airway sensory processing after administration of a placebo.


HMGN1 modulates nucleosome occupancy and DNase I hypersensitivity at the CpG island promoters of embryonic stem cells.
Chromatin structure plays a key role in regulating gene expression and embryonic differentiation; however, the factors that determine the organization of chromatin around regulatory sites are not fully known. Here we show that HMGN1, a nucleosome-binding protein ubiquitously expressed in vertebrate cells, preferentially binds to CpG island-containing promoters and affects the organization of nucleosomes, DNase I hypersensitivity, and the transcriptional profile of mouse embryonic stem cells and neural progenitors. Loss of HMGN1 alters the organization of an unstable nucleosome at transcription start sites, reduces the number of DNase I-hypersensitive sites genome wide, and decreases the number of nestin-positive neural progenitors in the subventricular zone (SVZ) region of mouse brain. Thus, architectural chromatin-binding proteins affect the transcription profile and chromatin structure during embryonic stem cell differentiation.


Unconventional fermi surface instabilities in the kagome Hubbard model.
We investigate the competing Fermi surface instabilities in the kagome tight-binding model. Specifically, we consider on-site and short-range Hubbard interactions in the vicinity of van Hove filling of the dispersive kagome bands where the fermiology promotes the joint effect of enlarged density of states and nesting. The sublattice interference mechanism devised by Kiesel and Thomale [Phys. Rev. B 86, 121105 (2012)] allows us to explain the intricate interplay between ferromagnetic fluctuations and other ordering tendencies. On the basis of the functional renormalization group used to obtain an adequate low-energy theory description, we discover finite angular momentum spin and charge density wave order, a twofold degenerate d-wave Pomeranchuk instability, and f-wave superconductivity away from van Hove filling. Together, this makes the kagome Hubbard model the prototypical scenario for several unconventional Fermi surface instabilities.


Cross-modal enhancement of speech detection in young and older adults: does signal content matter?
The purpose of the present study was to examine the effects of age and visual content on cross-modal enhancement of auditory speech detection. Visual content consisted of three clearly distinct types of visual information: an unaltered video clip of a talker's face, a low-contrast version of the same clip, and a mouth-like Lissajous figure. It was hypothesized that both young and older adults would exhibit reduced enhancement as visual content diverged from the original clip of the talker's face, but that the decrease would be greater for older participants. Nineteen young adults and 19 older adults were asked to detect a single spoken syllable (/ba/) in speech-shaped noise, and the level of the signal was adaptively varied to establish the signal-to-noise ratio (SNR) at threshold. There was an auditory-only baseline condition and three audiovisual conditions in which the syllable was accompanied by one of the three visual signals (the unaltered clip of the talker's face, the low-contrast version of that clip, or the Lissajous figure). For each audiovisual condition, the SNR at threshold was compared with the SNR at threshold for the auditory-only condition to measure the amount of cross-modal enhancement. Young adults exhibited significant cross-modal enhancement with all three types of visual stimuli, with the greatest amount of enhancement observed for the unaltered clip of the talker's face. Older adults, in contrast, exhibited significant cross-modal enhancement only with the unaltered face. Results of this study suggest that visual signal content affects cross-modal enhancement of speech detection in both young and older adults. They also support a hypothesized age-related deficit in processing low-contrast visual speech stimuli, even in older adults with normal contrast sensitivity.


Fight, Flight, - Or Grab a Bite! Trait Emotional and Restrained Eating Style Predicts Food Cue Responding Under Negative Emotions.
In today's society, obesity rates are rising as food intake is no longer only a response to physiological hunger signals that ensure survival. Eating can represent a reward, a response to boredom, or stress reduction and emotion regulation. While most people decrease food intake in response to stress or negative emotions, some do the opposite. Yet, it is unclear who shows emotional overeating under which circumstances. Emotion regulation theories describe emotional overeating as a learned strategy to down-regulate negative emotions. Cognitive theories, by contrast, attribute emotional overeating to perceived diet breaches in individuals who chronically attempt to diet. After consuming "forbidden foods", they eat more than individuals who do not restrict their food intake. This laboratory study investigated emotional overeating by exposing individuals to a personalized emotion induction while showing images of palatable foods. Outcome variables indexed cue reactivity to food images through picture ratings (valence, desire to eat), facial expressions (electromyography of the corrugator supercilii muscle), and brain reactivity by detecting event-related potentials (ERPs) by means of electroencephalography (EEG). The influence of emotion condition (negative, neutral) and individual differences (self-reported trait emotional and restrained eating) on outcome variables was assessed. Valence ratings and appetitive reactions of the corrugator muscle to food pictures showed a relative increase in the negative condition for individuals with higher emotional eating scores, with the opposite pattern in lower scores. Desire to eat ratings showed a similar pattern in individuals who showed a strong response to the emotion induction manipulation, indicative of a dose-response relationship. Although no differences between conditions were found for ratings or corrugator activity with restrained eating as a predictor, an ERP at P300 showed increased activation when viewing food compared to objects in the negative condition. Findings support emotion regulation theories: Emotional eaters showed an appetitive reaction in rating patterns and corrugator activity. EEG findings (increased P300) suggest a motivated attention toward food in restrained eaters, which supports cognitive theories. However, this did not translate to other variables, which might demonstrate successful restraint. Future studies may follow up on these findings by investigating eating disorders with emotion regulation difficulties.


Biomechanical analysis suggests early rehabilitation is possible after single-incision EndoButton distal biceps repair with FiberWire.
Previous studies that have encouraged early postoperative motion after distal biceps repair shows little agreement on exactly when activity should be resumed after surgery or on the level of weight restriction that should be used. The aim of the current study was to define a service load that would permit, without failure, 2,000 cycles of immediate motion after single-incision EndoButton distal biceps repair with FiberWire. In each of 15 cadaveric elbows, the distal biceps tendon was divided at its insertion and then repaired using a single-incision EndoButton technique with FiberWire. The repairs were then challenged according to the "staircase method" by cyclically loading the biceps tendon, so that the forearm flexed between 0° and 90°. The mean failure load of the repair was 166.7 N (95% confidence interval, 132.6-200.8). The data suggested that a 0.9 kg (9-N) weight at the hand was the limit for a 2,000-cycle early rehabilitation protocol after repair of a ruptured distal biceps tendon via a single-incision EndoButton repair technique. Early active motion with a 0.9-kg weight restriction may therefore be possible in those patients undergoing distal biceps tendon repair using this technique.


The Socioeconomic and Institutional Determinants of Participation in India's Health Insurance Scheme for the Poor.
The Rashtriya Swasthya Bima Yojana (RSBY), which was introduced in 2008 in India, is a social health insurance scheme that aims to improve healthcare access and provide financial risk protection to the poor. In this study, we analyse the determinants of participation and enrolment in the scheme at the level of districts. We used official data on RSBY enrolment, socioeconomic data from the District Level Household Survey 2007-2008, and additional state-level information on fiscal health, political affiliation, and quality of governance. Results from multivariate probit and OLS analyses suggest that political and institutional factors are among the strongest determinants explaining the variation in participation and enrolment in RSBY. In particular, districts in state governments that are politically affiliated with the opposition or neutral parties at the centre are more likely to participate in RSBY, and have higher levels of enrolment. Districts in states with a lower quality of governance, a pre-existing state-level health insurance scheme, or with a lower level of fiscal deficit as compared to GDP, are significantly less likely to participate, or have lower enrolment rates. Among socioeconomic factors, we find some evidence of weak or imprecise targeting. Districts with a higher share of socioeconomically backward castes are less likely to participate, and their enrolment rates are also lower. Finally, districts with more non-poor households may be more likely to participate, although with lower enrolment rates.


The use of foundational ontologies in biomedical research.
The FAIR principles recommend the use of controlled vocabularies, such as ontologies, to define data and metadata concepts. Ontologies are currently modelled following different approaches, sometimes describing conflicting definitions of the same concepts, which can affect interoperability. To cope with that, prior literature suggests organising ontologies in levels, where domain specific (low-level) ontologies are grounded in domain independent high-level ontologies (i.e., foundational ontologies). In this level-based organisation, foundational ontologies work as translators of intended meaning, thus improving interoperability. Despite their considerable acceptance in biomedical research, there are very few studies testing foundational ontologies. This paper describes a systematic literature mapping that was conducted to understand how foundational ontologies are used in biomedical research and to find empirical evidence supporting their claimed (dis)advantages. From a set of 79 selected papers, we identified that foundational ontologies are used for several purposes: ontology construction, repair, mapping, and ontology-based data analysis. Foundational ontologies are claimed to improve interoperability, enhance reasoning, speed up ontology development and facilitate maintainability. The complexity of using foundational ontologies is the most commonly cited downside. Despite being used for several purposes, there were hardly any experiments (1 paper) testing the claims for or against the use of foundational ontologies. In the subset of 49 papers that describe the development of an ontology, it was observed a low adherence to ontology construction (16 papers) and ontology evaluation formal methods (4 papers). Our findings have two main implications. First, the lack of empirical evidence about the use of foundational ontologies indicates a need for evaluating the use of such artefacts in biomedical research. Second, the low adherence to formal methods illustrates how the field could benefit from a more systematic approach when dealing with the development and evaluation of ontologies. The understanding of how foundational ontologies are used in the biomedical field can drive future research towards the improvement of ontologies and, consequently, data FAIRness. The adoption of formal methods can impact the quality and sustainability of ontologies, and reusing these methods from other fields is encouraged.


Formin-g muscle cytoarchitecture.
Striated muscle cells display an extremely regular assembly of their actin cytoskeleton that contributes to the contractile elements, the myofibrils. How this assembly is initiated and how these structures are maintained is still unclear. We have recently shown that striated muscle expresses a specific isoform of the formin protein family member FHOD3, which is characterised by the presence of a CK2 phosphorylation site at the C-terminal end of the formin homology domain 2 (FH2). Phosphorylated muscle FHOD3 displays a different subcellular localisation, namely to the myofibrils, and also has increased stability compared to un-phosphorylated or non muscle FHOD3. In addition, we could show that muscle FHOD3 is involved in myofibril maintenance in cultured cardiomyocytes and that its presence dramatically enhances the reconstitution of cardiac actin filaments after depolymerisation. Since FHOD3 expression levels and in particular that of the muscle isoform are also decreased in different types of cardiomyopathy, we postulate a crucial role for this protein in the maintenance of a fully functional cardiac cytoarchitecture.


Patterns of species richness and the center of diversity in modern Indo-Pacific larger foraminifera.
Symbiont-bearing Larger Benthic Foraminifera (LBF) are ubiquitous components of shallow tropical and subtropical environments and contribute substantially to carbonaceous reef and shelf sediments. Climate change is dramatically affecting carbonate producing organisms and threatens the diversity and structural integrity of coral reef ecosystems. Recent invertebrate and vertebrate surveys have identified the Coral Triangle as the planet's richest center of marine life delineating the region as a top priority for conservation. We compiled and analyzed extensive occurrence records for 68 validly recognized species of LBF from the Indian and Pacific Ocean, established individual range maps and applied Minimum Convex Polygon (MCP) and Species Distribution Model (SDM) methodologies to create the first ocean-wide species richness maps. SDM output was further used for visualizing latitudinal and longitudinal diversity gradients. Our findings provide strong support for assigning the tropical Central Indo-Pacific as the world's species-richest marine region with the Central Philippines emerging as the bullseye of LBF diversity. Sea surface temperature and nutrient content were identified as the most influential environmental constraints exerting control over the distribution of LBF. Our findings contribute to the completion of worldwide research on tropical marine biodiversity patterns and the identification of targeting centers for conservation efforts.


Magnesium deficiency promotes muscle weakness, contributing to the risk of sudden infant death (SIDS) in infants sleeping prone.
A review was published (1991) of 19 retrospective case-control studies that had investigated the relationship between prone sleeping position (on the stomach) and the sudden infant death syndrome (SIDS). These studies, which had been conducted between 1965 and 1990 in New Zealand, Australia, England, France and the Netherlands, showed an overall higher rate of SIDS in infants who usually slept prone. In those countries, vigorous community intervention to change babies' sleep position away from the prone has resulted in marked declines of 50 per cent or more in the rate of SIDS. Such encouraging reports from many countries prompted the American Academy of Pediatrics to recommend that infants be placed to sleep on their backs to reduce the risk of SIDS. This was followed by a successful campaign in the United States between mid-1994 and 1998. Despite the decreased incidence, SIDS remains the leading cause of death in infants 1 month to 1 year of age of industrialized nations of the world. Studies have been conducted in human infants, mechanical models and animal models to learn the role of risk factors in prone sleeping infants. Soft bedding, thermal stress and biologic risk factors such as impaired ventilatory and arousal responsiveness are among many factors that have been investigated. Hunt states that there is not a single unifying factor that explains increased SIDS in prone sleeping infants. Two major studies conducted in the 1970s showed: (1) muscle weakness in the upper half of the body in infants who subsequently died of SIDS, and (2) shoulder hypotonia in near-miss for SIDS infants. An infant sleeping face-down in the prone position could be jeopardized if he lacked the muscle strength to shift his position or turn his head to rescue himself from a life-threatening situation. In contrast, recent studies in neonates sleeping in the prone position report that normal infants can spontaneously arouse and turn their heads. Some data support the hypothesis that magnesium deficiency contributes to SIDS. Muscle strength is seriously impaired in the young magnesium deficient subject, while magnesium rapidly reverses muscle weakness. In rats, marginal deprivation in dietary magnesium reduces exercise capacity, an early effect of magnesium deficiency which is preventable by consuming magnesium-enriched mineral water. It is concluded that magnesium deficiency is at least one major unifying factor that explains increased SIDS in prone sleeping infants.


The epidemiology of human hookworm infections in the southern region of Mali.
Two surveys of hookworm (Necator americanus) infections, conducted three years apart (December 1994 and January 1998) in a village in the Sikasso region of Mali, revealed that overall prevalence of infection was 68.7% and 53%, respectively. In both years there was a highly significant difference between the sexes in the prevalence and abundance of infection, with male subjects carrying heavier infections than females. Both prevalence and abundance of infection increased with age, although in 1998 there was a strong interaction between sex and age, arising from the declining egg counts among 16-20-year-old females and the continuing increase among males, reinforced by the subsequent reduction among the older males (> or = 61 years) and concomitant increase among females. After controlling for the effects of age, sex and their interaction, a highly significant positive relationship was detected between faecal egg counts of individuals who were examined in both 1994 and 1998 (n = 134), indicating predisposition to infection. This relationship remained significant in each of 4 age classes spanning 7-79 years. The members of some family compounds were shown to carry heavier infections than expected whilst others were less infected, suggesting compound-related clustering of hookworm infections. The use of footwear increased with age but there was no significant relationship between the extent of use of footwear and the abundance of hookworm infection. Eyesight deteriorated with age and impaired vision was particularly prominent among the older sectors of the community, a legacy from the time when onchocerciasis was widely prevalent in the region. Although men with partially damaged eyes carried lower infections than expected for their age, no overall significant relationship was found between quality of vision and hookworm infections. These results are discussed in relation to hookworm epidemiology in general and in Mali in particular.


Ethically incentivising healthy behaviours: views of parents and adolescents with type 1 diabetes.
To assess ethical concerns associated with participation in a financial incentive (FI) programme to help adolescents with type 1 diabetes improve diabetes self-management. Focus groups with 46 adolescents with type 1 diabetes ages 12-17 and 38 of their parents were conducted in the Seattle, Washington metropolitan area. Semistructured focus group guides addressed ethical concerns related to the use of FI to promote change in diabetes self-management. Qualitative data were analysed and emergent themes identified. We identified three themes related to the ethical issues adolescents and parents anticipated with FI programme participation. First, FI programmes may variably change pressure and conflict in different families in ways that are not necessarily problematic. Second, the pressure to share FIs in some families and how FI payments are structured may lead to unfairness in some cases. Third, some adolescents may be likely to fabricate information in any circumstances, not simply because of FIs, but this could compromise the integrity of FI programmes relying on measures that cannot be externally verified. Many adolescents with type 1 diabetes and their parents see positive potential of FIs to help adolescents improve their self-management. However, ethical concerns about unfairness, potentially harmful increases in conflict/pressure and dishonesty should be addressed in the design and evaluation of FI programmes.


A Phase II Study of Dovitinib in Patients with Recurrent or Metastatic Adenoid Cystic Carcinoma.
Purpose: Genetic and preclinical studies have implicated FGFR signaling in the pathogenesis of adenoid cystic carcinoma (ACC). Dovitinib, a suppressor of FGFR activity, may be active in ACC.Experimental Design: In a two-stage phase II study, 35 patients with progressive ACC were treated with dovitinib 500 mg orally for 5 of 7 days continuously. The primary endpoints were objective response rate and change in tumor growth rate. Progression-free survival, overall survival, metabolic response, biomarker, and quality of life were secondary endpoints.Results: Of 34 evaluable patients, 2 (6%) had a partial response and 22 (65%) had stable disease >4 months. Median PFS was 8.2 months and OS was 20.6 months. The slope of the overall TGR fell from 1.95 to 0.63 on treatment (P < 0.001). Toxicity was moderate; 63% of patients developed grade 3-4 toxicity, 94% required dose modifications, and 21% stopped treatment early. An early metabolic response based on 18FDG-PET scans was seen in 3 of 15 patients but did not correlate with RECIST response. MYB gene translocation was observed and significantly correlated with overexpression of MYB but did not correlate with FGFR1 phosphorylation or clinical response to dovitinib.Conclusions: Dovitinib produced few objective responses in patients with ACC but did suppress the TGR with a PFS that compares favorably with those reported with other targeted agents. Future studies of more potent and selective FGFR inhibitors in biomarker-selected patients will be required to determine whether FGFR signaling is a valid therapeutic target in ACC. Clin Cancer Res; 23(15); 4138-45. ©2017 AACR.


Community Care for People with Complex Care Needs: Bridging the Gap between Health and Social Care.
A growing number of people are living with complex care needs characterized by multimorbidity, mental health challenges and social deprivation. Required is the integration of health and social care, beyond traditional health care services to address social determinants. This study investigates key care components to support complex patients and their families in the community. Expert panel focus groups with 24 care providers, working in health and social care sectors across Toronto, Ontario, Canada were conducted. Patient vignettes illustrating significant health and social care needs were presented to participants. The vignettes prompted discussions on i) how best to meet complex care needs in the community and ii) the barriers to delivering care to this population. Categories to support care needs of complex patients and their families included i) relationships as the foundation for care, ii) desired processes and structures of care, and iii) barriers and workarounds for desired care. Meeting the needs of the population who require health and social care requires time to develop authentic relationships, broadening the membership of the care team, communicating across sectors, co-locating health and social care, and addressing the barriers that prevent providers from engaging in these required practices.


Diagnostic Pitfalls in Papillary Lesions of the Breast: Experience from a Single Tertiary Care Center.
Papillary neoplasms are a group of lesions that are characterized by presence of papillae supported by fibrovascular cores lined by epithelial cells with or without myoepithelial cell layer. These neoplasms may be benign, atypical or malignant. This study was conducted to analyse the clinicopathological characteristics of papillary lesions of the breast. A retrospective and prospective analysis of 34 cases of papillary lesions received over a period of 7 years from 2009 to 2015 was done. The patient's clinical details were collected from medical archives and the histopathological findings were reviewed. The lesions were classified into benign, atypical and malignant categories. During the study period, there were 34 cases of papillary lesions of breast. The mean age was 58 years. The central quadrant was the most common location (66.6%). The most common presenting complaint was lump (76.5% cases). Papillary lesions presented more commonly as solitary lump (82.4%) rather than multifocal disease. Benign papillary lesions were more common than the atypical and malignant lesions. The most common papillary lesion accounting for 43% of the cases was intraductal papilloma. Malignant lesions accounted for 41.2% cases with intraductal papillary carcinoma and invasive papillary carcinoma constituting 14.7% cases each. Diagnosis of papillary carcinoma is challenging and its classification includes different entities that have specific diagnostic criteria. Due to their heterozygosity in morphology with benign, atypical and malignant subtypes, morphological features such as type of fibrovascular core and continuity of myoepithelial layer along with immunohistochemical stains for myoepithelial cells should be considered for proper and accurate diagnosis.


Measurement of intracellular pH with microelectrodes in rat kidney in vivo.
The construction of two types of double-barreled microelectrodes of sufficiently small tip size to record cytosolic pH (pHc) in renal tubular epithelial cells is described. Mean pHc in control anesthetized rats was 7.10 and mean basolateral membrane potential (Em) was -51.8 mV. These results suggest that hydrogen ions are actively extruded from either or both poles of the proximal tubular cell but that bicarbonate exit across the basolateral membrane is passive. In animals treated with acetazolamide, pHc was significantly elevated (mean 7.35) but Em was unchanged, suggesting that proton extrusion continues but that the rate of reaction of OH- with CO2 is diminished due to carbonic anhydrase inhibition. A pH higher than that of arterial blood was obtained from sites presumed to be in the interstitium. The evidence for the various assignments of microelectrode tip position is discussed.


Pattern recognition of forced oscillation technique measurement results using deep learning can identify asthmatic patients more accurately than setting reference ranges.
No official clinical reference values have been established for MostGraph, which measures total respiratory resistance and reactance using the forced oscillation technique, complicating result interpretation. This study aimed to establish a reference range for MostGraph measurements and examine its usefulness in discriminating participants with asthma from controls (participants without any respiratory diseases). The study also aimed to investigate the effectiveness of deep learning in discriminating between the two aforementioned groups. To establish reference ranges, the MostGraph measurements of healthy controls (n = 215) were power-transformed to distribute the data more normally. After inverse transformation, the mean ± standard deviation × 2 of the transformed values were used to establish the reference ranges. The number of measured items outside the reference ranges was evaluated to discriminate patients with asthma (n = 941) from controls. Additionally, MostGraph measurements were evaluated using deep learning. Although reference ranges were established, patients with asthma could not be discriminated from controls. However, with deep learning, we could discriminate between the two groups with 78% accuracy. Therefore, deep learning, which considers multiple measurements as a whole, was more effective in interpreting MostGraph measurement results than use of reference ranges, which considers each result individually.


Apolipoprotein CIII promotes Ca2+-dependent beta cell death in type 1 diabetes.
In type 1 diabetes (T1D), there is a specific destruction of the insulin secreting pancreatic beta cell. Although the exact molecular mechanisms underlying beta cell destruction are not known, sera from T1D patients have been shown to promote Ca(2+)-induced apoptosis. We now demonstrate that apolipoprotein CIII (apoCIII) is increased in serum from T1D patients and that this serum factor both induces increased cytoplasmic free intracellular Ca(2+) concentration ([Ca(2+)](i)) and beta cell death. The apoCIII-induced increase in [Ca(2+)](i) reflects an activation of the voltage-gated L-type Ca(2+) channel. Both the effects of T1D sera and apoCIII on the beta cell are abolished in the presence of antibody against apoCIII. Increased serum levels of apoCIII can thus account for the increase in beta cell [Ca(2+)](i) and thereby beta cell apoptosis associated with T1D.


Polyphosphazene polymers: The next generation of biomaterials for regenerative engineering and therapeutic drug delivery.
The demand for new biomaterials in several biomedical applications, such as regenerative engineering and drug delivery, has increased over the past two decades due to emerging technological advances in biomedicine. Degradable polymeric biomaterials continue to play a significant role as scaffolding materials and drug devices. Polyphosphazene platform is a subject of broad interest, as it presents an avenue for attaining versatile polymeric materials with excellent structure and property tunability, and high functional diversity. Macromolecular substitution enables the facile attachment of different organic groups and drug molecules to the polyphosphazene backbone for the development of a broad class of materials. These materials are more biocompatible than traditional biomaterials, mixable with other clinically relevant polymers to obtain new materials and exhibit unique erosion with near-neutral degradation products. Hence, polyphosphazene represents the next generation of biomaterials. In this review, the authors systematically discuss the synthetic design, structure-property relationships, and the promising potentials of polyphosphazenes in regenerative engineering and drug delivery.


Polarization-maintaining buffered Fourier domain mode-locked swept source for optical coherence tomography.
A polarization-maintaining buffered Fourier domain mode-locked (FDML) swept source with a center wavelength of 1300 nm is demonstrated. The scanning rate of the buffered FDML swept source is doubled without sacrificing the output power of the swept source by combining two orthogonally polarized outputs with a polarization beam combiner. The stability of the swept source is improved because the polarization state of the laser beam inside the laser cavity is maintained without the use of any polarization controllers. The swept source is capable of an edge-to-edge tuning range of more than 150 nm and a FWHM range of 95 nm at a 102 kHz sweeping rate and with an average power of 12 mW. A swept source optical coherence tomography (SSOCT) system is developed utilizing this buffered FDML swept source. The axial resolution of the SSOCT system is measured to be 9.4 µm in air. The sensitivity of the SSOCT system is 107.5 dB at a depth of 0.25 mm with a 6 dB roll-off at a depth of 2.25 mm.


Effect of partial substitution of NaCl with KCl on proteolysis of halloumi cheese.
The effect of substitution of NaCl with Potassium chloride (KCl) in brine solution on proteolysis of halloumi cheese was investigated. Halloumi cheeses were made and kept in 4 different brine solutions (18% w/w), including only NaCl (HA; control); 3NaCl:1KCl (w/w) (HB); 1NaCl:1KCl (w/w) (HC); 1NaCl:3KCl (w/w) (HD); and stored for 56 d at 4 °C. Proteolysis was assessed using water-soluble nitrogen (WSN), trichloroacetic acid-soluble nitrogen (TCA-SN), phosphotungstic-soluble nitrogen (PTA-SN), urea polyacrylamide gel electrophoresis (urea-PAGE), and peptide patterns. WSN and TCA-SN contents were similar in all experimental cheeses. Peptide patterns of the pH 4.6 N fraction and urea-PAGE showed no significant difference between halloumi cheeses kept in various NaCl/KCl mixtures (HB, HC, HD) and control (HA). Sodium and potassium contents showed positive correlations with WSN and PTA-SN. There was an inverse correlation between calcium (Ca) contents and WSN and PTA-SN. Correlations between Ca and Na or K were negative at the same salt treatment.


Effects of mean arterial pressure target on mottling and arterial lactate normalization in patients with septic shock: a post hoc analysis of the SEPSISPAM randomized trial.
In patients with septic shock, the impact of the mean arterial pressure (MAP) target on the course of mottling remains uncertain. In this post hoc analysis of the SEPSISPAM trial, we investigated whether a low-MAP (65 to 70 mmHg) or a high-MAP target (80 to 85 mmHg) would affect the course of mottling and arterial lactate in patients with septic shock. The presence of mottling was assessed every 2 h from 2 h after inclusion to catecholamine weaning. We compared mottling and lactate time course between the two MAP target groups. We evaluated the patient's outcome according to the presence or absence of mottling. We included 747 patients, 374 were assigned to the low-MAP group and 373 to the high-MAP group. There was no difference in mottling and lactate evolution during the first 24 h between the two MAP groups. After adjustment for MAP and confounding factors, the presence of mottling ≥ 6 h during the first 24 h was associated with a significantly higher risk of death at day 28 and 90. Patients without mottling or with mottling < 6 h and lactate ≥ 2 mmol/L have a higher probability of survival than those with mottling ≥ 6 h and lactate < 2 mmol/L. Compared with low MAP target, higher MAP target did not alter mottling and lactate course. Mottling lasting for more than 6 h was associated with higher mortality. Compared to arterial lactate, mottling duration appears to be a better marker of mortality.


Oxygen-inducible glutamate oxaloacetate transaminase as protective switch transforming neurotoxic glutamate to metabolic fuel during acute ischemic stroke.
This work rests on our previous report (J Cereb Blood Flow Metab 30: 1275-1287, 2010) recognizing that glutamate (Glu) oxaloacetate transaminase (GOT) is induced when brain tissue hypoxia is corrected during acute ischemic stroke (AIS). GOT can metabolize Glu into tricarboxylic acid cycle intermediates and may therefore be useful to harness excess neurotoxic extracellular Glu during AIS as a metabolic substrate. We report that in cultured neural cells challenged with hypoglycemia, extracellular Glu can support cell survival as long as there is sufficient oxygenation. This effect is abrogated by GOT knockdown. In a rodent model of AIS, supplemental oxygen (100% O(2) inhaled) during ischemia significantly increased GOT expression and activity in the stroke-affected brain tissue and prevented loss of ATP. Biochemical analyses and in vivo magnetic resonance spectroscopy during stroke demonstrated that such elevated GOT decreased Glu levels at the stroke-affected site. In vivo lentiviral gene delivery of GOT minimized lesion volume, whereas GOT knockdown worsened stroke outcomes. Thus, brain tissue GOT emerges as a novel target in managing stroke outcomes. This work demonstrates that correction of hypoxia during AIS can help clear extracellular neurotoxic Glu by enabling utilization of this amino acid as a metabolic fuel to support survival of the hypoglycemic brain tissue. Strategies to mitigate extracellular Glu-mediated neurodegeneration via blocking receptor-mediated excitotoxicity have failed in clinical trials. We introduce the concept that under hypoglycemic conditions extracellular Glu can be transformed from a neurotoxin to a survival factor by GOT, provided there is sufficient oxygen to sustain cellular respiration.


Immunotherapy of idiopathic inflammatory neuropathies.
Evaluation of peripheral neuropathy is a common reason for referral to a neurologist. Recent advances in immunology have identified an inflammatory component in many neuropathies and have led to treatment trials using agents that attenuate this response. This article reviews the clinical presentation and treatment of the most common subacute inflammatory neuropathies, Guillain-Barré syndrome (GBS) and Fisher syndrome, and describes the lack of response to corticosteroids and the efficacy of treatment with plasma exchange and intravenous immunoglobulin (IVIG). Chronic inflammatory demyelinating polyneuropathy, although sharing some clinical, electrodiagnostic, and pathologic similarities to GBS, improves after treatment with plasma exchange and IVIG and numerous immunomodulatory agents. Controlled trials in multifocal motor neuropathy have shown benefit after treatment with IVIG and cyclophosphamide. Also discussed is the treatment of less common inflammatory neuropathies whose pathophysiology involves monoclonal proteins or antibodies directed against myelin-associated glycoprotein or sulfatide. Little treatment data exist to direct the clinician to proper management of rare inflammatory neuropathies resulting from osteosclerotic myeloma; POEMS syndrome; vasculitis; Sjögren's syndrome; and neoplasia (paraneoplastic neuropathy).


Inosine monophosphate dehydrogenase intranuclear inclusions are markers of aging and neuronal stress in the human substantia nigra.
We explored mechanisms involved in the age-dependent degeneration of human substantia nigra (SN) dopamine (DA) neurons. Owing to its important metabolic functions in post-mitotic neurons, we investigated the developmental and age-associated changes in the purine biosynthetic enzyme inosine monophosphate dehydrogenase (IMPDH). Tissue microarrays prepared from post-mortem samples of SN from 85 neurologically intact participants humans spanning the age spectrum were immunostained for IMPDH combined with other proteins. SN DA neurons contained two types of IMPDH structures: cytoplasmic IMPDH filaments and intranuclear IMPDH inclusions. The former were not age-restricted and may represent functional units involved in sustaining purine nucleotide supply in these highly metabolically active cells. The latter showed age-associated changes, including crystallization, features reminiscent of pathological inclusion bodies, and spatial associations with Marinesco bodies; structures previously associated with SN neuron dysfunction and death. We postulate dichotomous roles for these two subcellularly distinct IMPDH structures and propose a nucleus-based model for a novel mechanism of SN senescence that is independent of previously known neurodegeneration-associated proteins.