Crohn's disease and the NOD2 gene: a role for paneth cells.
The NOD2 gene, which is strongly associated with susceptibility to Crohn's disease (CD) of the terminal ileum, interacts with bacterial lipopolysaccharide (LPS), inducing cellular activation. However, the mechanisms by which NOD2 mutations cause terminal ileitis are unknown, and NOD2 is expressed most highly by peripheral blood monocytes, which are distributed ubiquitously and readily respond to LPS via cell-surface receptors. Paneth cells on the other hand, are most numerous in the terminal ileum, are critically important in enteric antibacterial defense, and respond to LPS through as yet undefined pathways. We therefore determined if these specialized intestinal epithelial cells also expressed the NOD2 gene. In situ hybridization, immunohistochemistry, and laser-capture microdissection were used to determine RNA and protein expression in tissue sections, and real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to quantitate gene expression in intestinal epithelial cells and peripheral blood mononuclear cells. NOD2 was detected readily in monocytes, but not in mature macrophages in the lamina propria or within granulomas, and levels declined as monocytes differentiated into macrophages in vitro, so that Caco-2 cells expressed more NOD2 mRNA than macrophages. NOD2 mRNA was enriched in crypts compared with villi, and in situ, Paneth cells were the most prominent cells expressing NOD2 in normal and CD-affected intestinal tissue, where they also strongly expressed tumor necrosis factor alpha (TNFalpha) RNA. The NOD2 gene product is most abundant in Paneth cells in the terminal ileum, which could therefore play a critical and hitherto unrecognized role in the pathogenesis of NOD2-associated CD.


The Postpartum Maternal and Newborn Microbiomes.
Biological and environmental changes to maternal and newborn microbiomes in the postnatal period can affect health outcomes for the mother-baby dyad. Postpartum sleep deprivation and unmet dietary needs can alter commensal bacteria within the body and disrupt gut-brain communication. Perineal injury and breast infections also change microbial community composition, potentiating an environment favoring pathogen growth. The gut microbiome refers to the collection of microorganisms working in harmony. Disruptions within the gut microbiome and gut-brain communication may lead to postpartum depression, a potentially devastating sequela. Postnatal newborn changes to the gut and skin microbiome materialize quickly after birth and are profoundly influenced by mode of birth, feeding method, and bathing and skin care practices. During the newborn period, infant microbiomes are highly vulnerable and susceptible to multiple influences. Maternal-newborn nurses have a valuable role in helping mothers and newborns promote healthy microbiomes. Factors that influence the rapidly changing postnatal microbiome of the mother and her newborn, and the role nurses have to positively influence immediate and long-term health outcomes are presented.


Impact of the baseline temporal selection on the ERD/ERS analysis for Motor Imagery-based BCI.
Motor Imagery-based Brain-Computer Interfaces (MI-BCIs) are neurotechnologies that exploit the modulation of sensorimotor rhythms over the motor cortices, respectively known as Event-Related Desynchronization (ERD) and Synchronization (ERS). The interpretation of ERD/ERS is directly related to the selection of the baseline used to estimate them, and might result in a misleading ERD/ERS visualization. In fact, in BCI paradigms, if two trials are separated by a few seconds, taking a baseline close to the end of the previous trial could result in an over-estimation of the ERD, while taking a baseline too close to the upcoming trial could result in an under-estimation of the ERD. This phenomenon may cause a functional misinterpretation of the ERD/ERS phenomena in MI-BCI studies. This may also impair BCI performances for MI vs Rest classification, since such baselines are often used as resting states. In this paper, we propose to investigate the effect of several baseline time window selections on ERD/ERS modulations and BCI performances. Our results show that considering the selected temporal baseline effect is essential to analyze the modulations of ERD/ERS during MI-BCI use.


TAK1 plays a major role in growth factor-induced phenotypic modulation of airway smooth muscle.
Increased airway smooth muscle (ASM) mass is a major feature of airway remodeling in asthma and chronic obstructive pulmonary disease. Growth factors induce a proliferative ASM phenotype, characterized by an increased proliferative state and a decreased contractile protein expression, reducing contractility of the muscle. Transforming growth factor-β-activated kinase 1 (TAK1), a mitogen-activated protein kinase kinase kinase, is a key enzyme in proinflammatory signaling in various cell types; however, its function in ASM is unknown. The aim of this study was to investigate the role of TAK1 in growth factor-induced phenotypic modulation of ASM. Using bovine tracheal smooth muscle (BTSM) strips and cells, as well as human tracheal smooth muscle cells, we investigated the role of TAK1 in growth factor-induced proliferation and hypocontractility. Platelet-derived growth factor- (PDGF; 10 ng/ml) and fetal bovine serum (5%)-induced increases in DNA synthesis and cell number in bovine and human cells were significantly inhibited by pretreatment with the specific TAK1 inhibitor LL-Z-1640-2 (5Z-7-oxozeaenol; 100 nM). PDGF-induced DNA synthesis and extracellular signal-regulated kinase-1/2 phosphorylation in BTSM cells were strongly inhibited by both LL-Z-1640-2 pretreatment and transfection of dominant-negative TAK1. In addition, LL-Z-1640-2 inhibited PDGF-induced reduction of BTSM contractility and smooth muscle α-actin expression. The data indicate that TAK1 plays a major role in growth factor-induced phenotypic modulation of ASM.


Does survival context enhance memory for source? A within-subjects comparison.
Nairne, Thompson, and Pandeirada [2007. Adaptive memory: Survival processing enhances retention. Journal of Experimental Psychology: Learning, Memory, and Cognition, 33, 263-273] demonstrated that processing words according to their relevance to a survival scenario enhanced their subsequent retrieval in recall and recognition tasks compared to a variety of control scenarios. From an adaptive perspective, it is maintained that processing words in a survival context should also enhance memory for source; however, evidence in the literature is rather mixed regarding a survival context advantage for source memory. In the current study, we conducted four experiments to systematically investigate the survival advantage in source memory, when the context itself is the source, with both recall (Experiments 1A and 1B) and recognition tests (Experiments 2A and 2B). Results showed a survival advantage for item memory over the control contexts in all experiments. The survival context advantage was not extended to source memory performance in Experiment 1A. Results from all other experiments, however, indicated a survival context advantage for both item and source memory. Findings are discussed in relation to possible proximate mechanisms underlying the survival processing effect.


Encrypted imaging based on algebraic implementation of double random phase encoding.
The security of important information captured by sensors and cameras is currently a growing concern as information theft via techniques such as side-channel attacks become increasingly more prevalent. Double random phase encoding (DRPE) is an optical encryption method based on optical Fourier transform that is currently being used to implement secure coherent optical systems. In this paper, we propose a new DRPE implementation for incoherent optical systems based on integral photography that can be applied to "encrypted imaging (EI)" to optically encrypt an image before it is captured by an image sensor. Because the proposed incoherent DRPE is constituted from conventional DRPE by rewriting the optical encryption via discretization and Euler's formula, its security level is the same as that of conventional DRPE. The results of an experiment in which we encrypted a plaintext image optically and then decrypted it numerically demonstrate that our proposed incoherent optical security system is feasible.


Viscosity of Lennard-Jones mixtures: A systematic study and empirical law.
A systematic study of the viscosity of the binary Lennard-Jones (LJ) mixtures is carried out by equilibrium molecular dynamics simulations via the Green-Kubo relation. The effects of mass, size, and energy-parameter asymmetries on the viscosity and the self-diffusion coefficients are examined separately, both in equimolar mixtures and by varying the molar fractions. The systems are mapped into an effective one-component model according to the van der Waals one-fluid (vdW1) model. Furthermore, using an empirical law for pure LJ liquids, similar to the one proposed recently for liquid sodium, it is shown that the viscosity of the mixtures studied here are well-predicted by the combination of vdW1 fluid and empirical law. The Stokes-Einstein relation in the mixtures has also been investigated. A possible simple extension of this relation, from pure liquids to mixtures, has been proposed and tested.


[Experimental measles infection in rodents].
The sensitivity of newborn hamsters to inoculation with the vaccine L-16 strain of measles virus and the Lec strain isolated from a patient with subacute sclerosing panencephalitis as well as the possibility of persistence of these viruses in the animals were studied. Intracerebral inoculation of the L-15 strain was shown to produce in hamsters acute meningoencephalitis leading to death in 85%-100% of cases. Over 30 days after inoculation, the infectious virus, the virus-specific antigen and virus genome were found in the brain. In the brains of the sick animals, all the structural proteins of measles virus with the exception of hemagglutinin were expressed. After inoculation with the Lec strain, the clinical signs of the disease were less manifest, and mortality was 40%. The infectious virus could be detected in the brain up to 20 days postinoculation, the genome, up to 31 days. All the structural proteins of measles virus were expressed in the brains of the inoculated animals. No persistence of L-16 and Lec strains of measles virus could be demonstrated at langer intervals after inoculation (90-180 days) in the brains of hamsters.


Borg scores before and after challenge with adenosine 5'-monophosphate and methacholine in subjects with COPD and asthma.
Dyspnoea differs between subjects with chronic obstructive pulmonary disease (COPD) and asthma, partly because the underlying mechanisms for bronchoconstriction differ. This study investigated the possible role of inflammation and the contribution of clinical variables on dyspnoea in subjects with COPD and asthma. Forty-eight smoking subjects with COPD and 21 nonsmoking subjects with asthma, were challenged with adenosine 5'-monophosphate (AMP) and methacholine. The Borg score was assessed before and after each challenge. Mean increases in Borg score (per percentage decrease in baseline forced expiratory volume in one second (FEV1)) were significantly smaller in COPD than in asthma (p<0.01), values being 0.055 and 0.045 in COPD and 0.122 and 0.093 in asthma respectively. This difference was largely due to the fact that one-third of the subjects with COPD did not increase their Borg score during bronchoconstriction. The increase in Borg tended to be larger during AMP than during methacholine challenge, both in asthma and COPD. Changes in Borg scores were explained by age in COPD and by the Borg score before AMP challenge in asthma. The authors conclude that perception of dyspnoea during adenosine 5'-monophosphate and methacholine induced bronchoconstriction is lower in chronic obstructive pulmonary disease than in asthma and that age contributes to this difference. As adenosine 5'-monophosphate is regarded as an indirect marker of airway inflammation, the results suggest that inflammation is not important because both groups showed similar responses on such provocations.


Understanding growth and age of red tree corals (Primnoa pacifica) in the North Pacific Ocean.
Massive, long-lived deep-sea red tree corals (Primnoa pacifica) form a solid, layered axis comprised of calcite and gorgonin skeleton. They are abundant on the outer continental shelf and upper slope of the Northeast Pacific, providing habitat for fish and invertebrates. Yet, their large size and arborescent morphology makes them susceptible to disturbance from fishing activities. A better understanding of their growth patterns will facilitate in-situ estimates of population age structure and biomass. Here, we evaluated relationships between ages, growth rates, gross morphological characteristics, and banding patterns in 11 colonies collected from depths of ~141-335 m off the Alaskan coast. These corals ranged in age from 12 to 80 years old. They grew faster radially (0.33-0.74 mm year-1) and axially (2.41-6.39 cm year-1) than in previously measured older colonies, suggesting that growth in P. pacifica declines slowly with age, and that basal diameter and axial height eventually plateau. However, since coral morphology correlated with age in younger colonies (< century), we developed an in-situ age estimation technique for corals from the Northeast Pacific Ocean providing a non-invasive method for evaluating coral age without removing colonies from the population. Furthermore, we determined that annual bands provided the most accurate means for determining coral age in live-collected corals, relative to radiometric dating. Taken together, this work provides insight into P. pacifica growth patterns to inform coastal managers about the demographics of this ecologically important species. With this new ability to estimate the age of red tree corals in-situ, we can readily determine the age-class structure and consequently, the maturity status of thickets, using non-invasive video survey techniques when coupled with mensuration systems such as lasers or stereo-cameras. Enhanced surveys could identify which populations are most vulnerable to disturbance from human activities, and which should be highlighted for protection.


A glycoconjugate from corms of saffron plant (Crocus sativus L.) inhibits root growth and affects in vitro cell viability.
A glycoconjugate has been characterized from saffron corms (Crocus sativus L.) that inhibits the growth of roots of Nicotiana tabacum and Arabidopsis thaliana, at concentrations ranging from 1-100 micrograms m-3. Roots of seedlings grown in the presence 0.1 microgram m-3 glycoconjugate showed bulging of epidermal cells, whereas at 10 micrograms m-3, roots were completely devoid of hairs. At 100 micrograms m-3 glycoconjugate the cell walls of the root vascular tissues were thicker and, overall, the vascular tissue was enlarged. In addition, this glycan is cytotoxic to isolated tobacco cells and protoplasts, with 50% cell death induced by 0.5 and 2 micrograms m-3 glycoconjugate, respectively. Morphological and biochemical changes induced by the exposure to the glycoconjugate included cell size decrease, loss of regular cell shape, cytoplasm collapse, and release of intracellular proteins. This molecule at low concentrations (0.1 microgram m-3) mimics the effects of Yariv phenylglycosides and of mutant Arabidopsis which present defective or missing arabinogalactan-proteins (AGPs) in roots, indicating the glycoconjugate might interact with cell surface AGPs.


Expression of the Escherichia coli NRZ nitrate reductase is highly growth phase dependent and is controlled by RpoS, the alternative vegetative sigma factor.
In the absence of oxygen, many bacteria preferentially use nitrate as a terminal electron acceptor for anaerobic respiration. In Escherichia coli, there are two membrane-bound, differentially regulated nitrate reductases. While the physiological basis for this metabolic redundancy is not completely understood, during exponential growth, synthesis of NRA is greatly induced by anaerobiosis plus nitrate, whereas NRZ is expressed at a low level that is not influenced by anaerobiosis or nitrate. In the course of identifying genes controlled by the stationary phase regulatory factor RpoS (sigmas), we found that the expression of NRZ is induced during entry into stationary phase and highly dependent on this alternative sigma factor. Expression studies, using operon fusions and nitrate reductase assays, revealed that the NRZ operon is controlled mainly at the level of transcription and is induced 10-fold at the onset of stationary phase in rich media. Consistent with previous reports of RpoS expression, the RpoS dependency of NRZ in minimal media was very high (several hundredfold). We also observed a fivefold stationary phase induction of NRZ in an rpoS background, indicating that other regulatory factors, besides RpoS, are probably involved in transcriptional control of NRZ. The RpoS dependence of NRZ expression was confirmed by Northern analyses using RNA extracted from wild-type and rpoS- strains sampled in exponential and stationary phase. In toto, these data indicate that RpoS-mediated regulation of NRZ may be an important physiological adaptation that allows the cell to use nitrate under stress-associated conditions.


Lyme disease in children in southeastern Connecticut. Pediatric Lyme Disease Study Group.
Although the incidence of Lyme disease is highest in children, there are few prospective data on the clinical manifestations and outcomes in children. We conducted a prospective, longitudinal, community-based cohort study of children with newly diagnosed Lyme disease in an area of Connecticut in which the disease is highly endemic. We obtained clinical and demographic information and performed serial antibody tests and follow-up evaluations. Over a period of 20 months, 201 consecutive patients were enrolled; their median age was 7 years (range, 1 to 21). The initial clinical manifestations of Lyme disease were a single erythema migrans lesion in 66 percent, multiple erythema migrans lesions in 23 percent, arthritis in 6 percent, facial-nerve palsy in 3 percent, aseptic meningitis in 2 percent, and carditis in 0.5 percent. At presentation, 37 percent of the patients with a single erythema migrans lesion and 89 percent of those with multiple erythema migrans lesions had antibodies against Borrelia burgdorferi. All but 3 of the 201 patients were treated for two to four weeks with conventional antimicrobial therapy, which was administered orally in 96 percent. All had prompt clinical responses. After four weeks, 94 percent were completely asymptomatic (including the two patients whose parents had refused to allow antimicrobial treatment). At follow-up a mean of 25.4 months later, none of the patients had evidence of either chronic or recurrent Lyme disease. Six patients subsequently had a new episode of erythema migrans. About 90 percent of children with Lyme disease present with erythema migrans, which is an early stage of the disease. The prognosis is excellent for those with early Lyme disease who are treated promptly with conventional courses of antimicrobial agents.


Uteroglobin and related biochemical changes in the reproductive tract during early pregnancy in the rabbit.
The macromolecular secretion products of the rabbit uterus are described. The biochemical and biological properties of uteroglobin are considered, and its synthesis and secretion in various endocrinological conditions are described. The release of uteroglobin from the endometrial epithelium is stimulated by progestagens such as progesterone and its synthetic analogues, although its synthesis has not yet been shown to be entirely dependent on progesterone. The biological function of uteroglobin is obscure. Several approaches to this long-standing probelm are discussed, including the passage of uteroglobin into the blastocyst. It is suggested that interference with the passage of uterine components into the blastocyst may inhibit implantation and provide a means of contraception.


Self-sustaining limbic status epilepticus. I. Acute and chronic cerebral metabolic studies: limbic hypermetabolism and neocortical hypometabolism.
Regional cerebral glucose utilization (RCGU) increases during seizures whereas hypometabolism occurs in postictal and interictal states. Recently, we developed a model of nonconvulsive, self-sustaining limbic status epilepticus (SSLSE) in which electrographic seizures persist 12 to 24 hours after 90 minutes of continuous hippocampal stimulation. The present studies define the functional anatomy of SSLSE and the states thereafter. RCGU was studied by 2-deoxyglucose autoradiography in (1) a group of rats acutely (1 hour after induction) during SSLSE, and (2) two groups of rats chronically (1 week or 1 month) after SSLSE. RCGU measurements in these groups were compared with those obtained in naive and electrode-implanted control rats. In the acute group, there were bilateral increases in RCGU in the hippocampus, retrohippocampal structures, and associated limbic and subcortical nonlimbic regions; hypometabolism was found in several neocortical structures. Chronically, RCGU was elevated in certain limbic areas at 7 days but returned to control values at 30 days. On the basis of our findings, we postulate a feedback network involving the hippocampus and neighboring parahippocampal structures (the hippocampal-parahippocampal "loop") as a critical substrate for establishing limbic system status epilepticus. In addition, the results indicate that metabolic responses can persist long after the cessation of status epilepticus and that both increases and decreases in RCGU can be seen in acute limbic status epilepticus.


Tissue-specific and developmentally regulated expression of a chimeric actin-globin gene in transgenic mice.
A chimeric plasmid containing about 2/3 of the rat skeletal muscle actin gene plus 730 base pairs of its 5' flanking sequences fused to the 3' end of a human embryonic globin gene (D. Melloul, B. Aloni, J. Calvo, D. Yaffe, and U. Nudel, EMBO J. 3:983-990, 1984) was inserted into mice by microinjection into fertilized eggs. Eleven transgenic mice carrying the chimeric gene with or without plasmid pBR322 DNA sequences were identified. The majority of these mice transmitted the injected DNA to about 50% of their progeny. However, in transgenic mouse CV1, transmission to progeny was associated with amplification or deletion of the injected DNA sequences, while in transgenic mouse CV4 transmission was distorted, probably as a result of insertional mutagenesis. Tissue-specific expression was dependent on the removal of the vector DNA sequences from the chimeric gene sequences prior to microinjection. None of the transgenic mice carrying the chimeric gene together with plasmid pBR322 sequences expressed the introduced gene in striated muscles. In contrast, the six transgenic mice carrying the chimeric gene sequences alone expressed the inserted gene specifically in skeletal and cardiac muscles. Moreover, expression of the chimeric gene was not only tissue specific, but also developmentally regulated. Similar to the endogenous skeletal muscle actin gene, the chimeric gene was expressed at a relatively high level in cardiac muscle of neonatal mice and at a significantly lower level in adult cardiac muscle. These results indicate that the injected DNA included sufficient cis-acting control elements for its tissue-specific and developmentally regulated expression in transgenic mice.


Obesity, inflammation, and the gut microbiota.
As the prevalence of obesity and associated disease continues to rise and concerns for the spiralling economic and social costs also escalate, innovative management strategies beyond primary prevention and traditional lifestyle interventions are urgently needed. The biological basis of disease is one avenue for further exploration in this context. Several key inflammatory markers have been consistently associated with both obesity and risk of adverse outcomes in obesity-associated diseases, which suggests that a persistent, low-grade, inflammatory response is a potentially modifiable risk factor. In this Review, we provide evidence supporting perturbation of the intestinal microbiota and changes in intestinal permeability as potential triggers of inflammation in obesity. Further characterisation of the mechanisms underpinning the triggers of such inflammatory responses in overweight and obese individuals could offer unique opportunities for intervention strategies to help ameliorate the risk of obesity-associated disease.


Acute myeloid leukemia concurrent with spinal epidural extramedullary myeloid sarcoma accompanied by a high CD25 expression and the FLT3-ITD mutation.
Myeloid sarcoma (MS) is an extramedullary myeloid tumor that sometimes presents with antedating systemic leukemia, leading physicians to the misdiagnosis of lymphoma. CD25 is expressed in 13% of patients with acute myeloid leukemia (AML), and its expression is associated with FLT3-ITD mutations, an elevated serum soluble interleukin 2 receptor (sIL-2R) level and a lower survival rate. However, there are no reports concerning the relationship between MS and the CD25 expression. We herein report a case of AML accompanied by thoracic epidural MS with a high CD25 expression, the FLT3-ITD mutation and an extremely elevated serum sIL-2R level in a 59-year-old man who presented with paraplegia.


Atrial natriuretic factor and cyclic guanosine 3',5'-monophosphate in vascular smooth muscle.
To elucidate the molecular mechanism of the vascular action of atrial natriuretic factor (ANF), we investigated the effects of synthetic ANF and sodium nitroprusside on the levels of intracellular cyclic nucleotides and prostacyclin (measured as its stable metabolite 6-keto-prostaglandin F1 alpha) in cultured vascular smooth muscle cells from rat mesenteric artery and, in some experiments, from rat renal artery. Both ANF and sodium nitroprusside increased intracellular cyclic guanosine 3',5'-monophosphate (cGMP) levels in a dose-dependent manner but did not affect cyclic adenosine 3',5'-monophosphate levels or 6-keto-prostaglandin F1 alpha synthesis. The stimulatory effect of ANF and sodium nitroprusside on cGMP levels were additive. Neither the deprivation of extracellular Ca2+ nor calcium entry blockers affected ANF-stimulated cGMP levels. Preincubation of ANF or sodium nitroprusside with kallikrein attenuated only the effect of ANF on cGMP levels. The effect of kallikrein was abolished by serine protease inhibitors. In contrast, the oxidant methylene blue inhibited the effect of sodium nitroprusside on cGMP levels, but not that of ANF. The stimulatory effect of ANF on cGMP levels was greater in cells from renal artery than in those from mesenteric artery. These results in cultured vascular smooth muscle cells further support the hypothesis that cGMP mediates the vasorelaxant action of ANF.


Quality of life in diabetic recipients of kidney transplants is better with the addition of the pancreas.
The present study is an evaluation of the quality of life of 32 patients following successful pancreatic transplantation. These patients were studied at from 6 months to 5 years post-transplantation. Over one-half of them were beyond the 21/2-yr mark. A questionnaire was developed that focused on symptoms of neuropathy, enteropathy, and retinopathy. All of the patients evaluated had completely normal carbohydrate metabolism, as evidenced by normal fasting blood sugars and hemoglobin A1C levels. Twenty-one of the 32 patients had symptomatic neuropathy pre-operatively, and 11 of these reported substantial subjective improvement. Eight remained unchanged and 2 became worse. Twenty-four patients had symptoms of enteropathy and 23 noted improvement post-transplantation. Retinopathy symptoms were not improved, but there was a suggestion that after 3 or 31/2 yr progression did not occur as rapidly as earlier. Virtually all of the patients had mood improvements and considerably less fatigue. We have determined that the risk of the procedure when receiving simultaneous renal and pancreas grafts is not significantly greater than that associated with a kidney transplant alone. Patients who are not uremic, either those with a successful kidney graft or those preuremic patients, are better candidates if symptoms are present. The risk of immunosuppression is insignificant in those patients who already have a successful renal transplant and are already on immunosuppressant drugs. Pancreatic transplantation can substantially improve the quality of life in diabetic patients, and should be considered as a therapeutic measure.


Script-driven imagery of self-injurious behavior in patients with borderline personality disorder: a pilot FMRI study.
Self-injurious behavior (SIB) is one of the most distinctive features of borderline personality disorder (BPD) and related to impulsivity and emotional dysregulation. Female patients with BPD (n = 11) and healthy controls (n = 10) underwent functional magnetic resonance imaging while listening to a standardized script describing an act of self-injury. Experimental sections of the script were contrasted to the neutral baseline section and group-specific brain activities were compared. While imagining the reactions to a situation triggering SIB, patients with BPD showed significantly less activation in the orbitofrontal cortex compared with controls. Furthermore, only patients with BPD showed increased activity in the dorsolateral prefrontal cortex during this section and a decrease in the mid-cingulate while imagining the self-injurious act itself. This pattern of activation preliminary suggests an association with diminished emotion regulation, impulse control as well as with response selection and reappraisal during the imagination of SIB.


Highly enantioselective synthesis of 3-amino-2-oxindole derivatives: catalytic asymmetric alpha-amination of 3-substituted 2-oxindoles with a chiral scandium complex.
A highly enantioselective alpha-amination of 3-substituted oxindoles with azodicarboxylates catalyzed by a chiral Sc(OTf)(3)/N,N'-dioxide complex (Tf: triflate) has been developed and affords the corresponding 3-amino-2-oxindole derivatives in high yields (up to 98%) with excellent enantioselectivities (up to 99% ee). The procedure is capable of tolerating a relatively wide range of substrates, and excellent results (92-96% ee) can also be obtained, even in the presence of 0.5 mol % of catalyst loading under mild conditions. These results showed the potential value of the catalytic approach. Moreover, with high synthetic versatility, the product could be easily transformed into optically active 3-amino-3-methyloxindole bearing a chiral quaternary stereogenic center.


Heterogeneous catalytic ozonation of hydroquinone using sewage sludge-derived carbonaceous catalysts.
This study converted sewage sludge into a carbonaceous catalyst via pyrolysis and employed it in the ozonation of hydroquinone. The catalyst was characterized by Mössbauer spectroscopy, X-ray photoelectron spectroscopy, temperature programmed desorption, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy and X-ray diffraction. Intermediate products were detected by gas chromatography-mass spectrometry, and a pathway for hydroquinone degradation was proposed. The results showed that sludge pyrolyzed at 700 °C promoted hydroquinone degradation, compared with commercial activated carbon derived from coal. When the catalyst dose was 0.5 g/L, the hydroquinone (200 mg/L) removal rate reached 97.86% after exposure to ozone (the ozone concentration was 17 mg/L and the flow rate was 50 mL/min) for 60 min. The results indicated that basic groups contributed to the catalysis.


Salmonella enterica serovar Cerro displays a phylogenetic structure and genomic features consistent with virulence attenuation and adaptation to cattle.
Salmonella enterica subsp. enterica (S.) serovar Cerro is rarely isolated from human clinical cases of salmonellosis but represents the most common serovar isolated from cattle without clinical signs of illness in the United States. In this study, using a large, diverse set of 316 isolates, we utilized genomic methods to further elucidate the evolutionary history of S. Cerro and to identify genomic features associated with its apparent virulence attenuation in humans. Phylogenetic analyses showed that within this polyphyletic serovar, 98.4% of isolates (311/316) represent a monophyletic clade within section Typhi and the remaining 1.6% of isolates (5/316) form a monophyletic clade within subspecies enterica Clade A1. Of the section Typhi S. Cerro isolates, 93.2% of isolates (290/311) clustered into a large clonal clade comprised of predominantly sequence type (ST) 367 cattle and environmental isolates, while the remaining 6.8% of isolates (21/311), primarily from human clinical sources, clustered outside of this clonal clade. A tip-dated phylogeny of S. Cerro ST367 identified two major clades (I and II), one of which overwhelmingly consisted of cattle isolates that share a most recent common ancestor that existed circa 1975. Gene presence/absence and rarefaction curve analyses suggested that the pangenome of section Typhi S. Cerro is open, potentially reflecting the gain/loss of prophage; human isolates contained the most open pangenome, while cattle isolates had the least open pangenome. Hypothetically disrupted coding sequences (HDCs) displayed clade-specific losses of intact speC and sopA virulence genes within the large clonal S. Cerro clade, while loss of intact vgrG, araH, and vapC occurred in all section Typhi S. Cerro isolates. Further phenotypic analysis suggested that the presence of a premature stop codon in speC does not abolish ornithine decarboxylase activity in S. Cerro, likely due to the activity of the second ornithine decarboxylase encoded by speF, which remained intact in all isolates. Overall, our study identifies specific genomic features associated with S. Cerro's infrequent isolation from humans and its apparent adaptation to cattle, which has broader implications for informing our understanding of the evolutionary events facilitating host adaptation in Salmonella.


Higher income and uninsured: common or rare?
Massachusetts plans to penalize those who do not have health insurance, targeting higher-income people. Are higher-income Americans a small or substantial share of the uninsured? The U.S. Census Bureau reports that one in three Americans without health insurance lived in a household with income greater than $50,000 in 2005. Many of these higher-income uninsured people do not fit the profile of free-riders who have the money but are unwilling to buy coverage. A majority have lower incomes but live with others; only together are they higher income. For others, higher income or lack of insurance is transient.


High-frequency stimulation of the subthalamic nucleus suppresses oscillatory beta activity in patients with Parkinson's disease in parallel with improvement in motor performance.
High-frequency stimulation (HFS) of the subthalamic nucleus (STN) is a well-established therapy for patients with severe Parkinson's disease (PD), but its mechanism of action is unclear. Exaggerated oscillatory synchronization in the beta (13-30 Hz) frequency band has been associated with bradykinesia in patients with PD. Accordingly, we tested the hypothesis that the clinical benefit exerted by STN HFS is accompanied by suppression of local beta activity. To this end, we explored the after effects of STN HFS on the oscillatory local field potential (LFP) activity recorded from the STN immediately after the cessation of HFS in 11 PD patients. Only patients that demonstrated a temporary persistence of clinical benefit after cessation of HFS were analyzed. STN HFS led to a significant reduction in STN LFP beta activity for 12 s after the end of stimulation and a decrease in motor cortical-STN coherence in the beta band over the same time period. The reduction in LFP beta activity correlated with the movement amplitude during a simple motor task, so that a smaller amount of beta activity was associated with better task performance. These features were absent when power in the 5-12 Hz frequency band was considered. Our findings suggest that HFS may act by modulating pathological patterns of synchronized oscillations, specifically by reduction of pathological beta activity in PD.


Mechanisms of Action of Cassiae Semen for Weight Management: A Computational Molecular Docking Study of Serotonin Receptor 5-HT2C.
Overweight and obesity is a growing global health concern. Current management of obesity includes lifestyle intervention, bariatric surgery and medication. The serotonin receptor, 5-HT2C, is known to mediate satiety, appetite and consumption behaviour. Lorcaserin, an appetite control drug, has demonstrated efficacy in appetite control by targeting 5-HT2C but causes undesirable side effects. This study aimed to explore the potential usage of Cassiae semen (CS), a well-known traditional Chinese medicine used to treat obesity. A computational molecular docking study was performed to determine the binding mechanism of CS compounds to the 5-HT2C receptors in both active, agonist-bound and inactive, antagonist-bound conformations. By comparing binding poses and predicted relative binding affinities towards the active or inactive forms of the receptor, we hypothesise that two of the CS compounds studied may be potent agonists which may mimic the appetite suppression effects of lorcaserin: obtusifoliol and cassiaside B2. Furthermore, two ligands, beta-sitosterol and juglanin, were predicted to bind favourably to 5-HT2C outside of the known agonist binding pocket in the active receptor, suggesting that such ligands may serve as positive allosteric modulators of 5-HT2C receptor function. Overall, this study proposed several CS compounds which may be responsible for exerting anti-obesity effects via appetite suppression by 5-HT2C receptor activation.


Intake of wholegrain products is associated with dietary, lifestyle, anthropometric and socio-economic factors in Denmark.
To evaluate the association between wholegrain products intake and other dietary, lifestyle, anthropometric and socio-economic factors. Cross-sectional study, with data on diet, lifestyle and socio-economic factors obtained from questionnaires. Anthropometric measurements were collected by trained professionals. Multiple linear and principal components regression analyses were used in statistical analyses. Part of the Diet, Cancer and Health study, a prospective cohort study to evaluate the aetiological role of diet on cancer risk, conducted in the greater Copenhagen and Aarhus area, Denmark. Men and women (n 54,720) aged 50-64 years. In multiple linear regression analyses focusing on individual dietary factors, intake of wholegrain products was associated with intake of all dietary factors studied (fish, red meat, poultry, processed meat, dairy products, fruits, vegetables, cakes and refined-grain products). The strongest positive associations were seen for intake of vegetables and processed meat, whereas the strongest negative associations were seen for intake of red meat and refined-grain products. Regression analyses on dietary patterns identified by principal components analysis yielded similar results. Also, wholegrain products intake was positively associated with cycling, taking dietary supplements and high school education, and negatively associated with intake of alcohol, BMI and smoking. Intake of wholegrain products is associated with other dietary factors, healthier lifestyle habits and higher socio-economic status. Therefore future studies need to account for the possible confounding by other dietary and lifestyle-related parameters when investigating relationships between wholegrain products intake and disease risk.


Binaural coherence edge pitch.
The binaural coherence edge pitch (BICEP) is a dichotic broadband noise pitch effect similar to the binaural edge pitch (BEP). The BICEP stimulus is made by summing spectrally dense sine wave components with random phases. The interaural phase angle is a constant (0 or pi) for components with frequencies below (or above) a chosen edge frequency, and it is a random variable for the remaining components. The chosen edge frequency is a coherence edge because the noises to the two ears are mutually coherent within any band of frequencies on one side of the edge and they are mutually incoherent in any band on the other side. Pitch-matching experiments show that the BICEP exists for coherence edge frequencies between about 300 and 1000 Hz. It is matched by a pure-tone frequency that differs from the edge frequency by 5% to 10%. The matching frequency lies on the incoherent side of the edge, an important result that is consistent with the way that the equalization-cancellation model has been applied to binaural pitch effects, especially the BEP. The results of BICEP experiments depend upon whether the coherent components are presented in 0 or pi interaural phase for some listeners but not for all. The BICEP persists if the noise to one of the ears is delayed, but it becomes weaker and less well matched as the delay increases beyond 2 ms. The BICEP does not depend on whether the component amplitudes are all created equal or are given a Rayleigh distribution. Some reliable pitch sensation exists even when the component amplitudes are entirely independent in the two ears, so long as the phase coherence conditions of the BICEP stimulus are maintained. The existence of the BICEP is a challenge for current models of dichotic pitch because none of them predicts all its features.


Functional Mammalian Amyloids and Amyloid-Like Proteins.
Amyloids are highly ordered fibrous cross-β protein aggregates that are notorious primarily because of association with a variety of incurable human and animal diseases (termed amyloidoses), including Alzheimer's disease (AD), Parkinson's disease (PD), type 2 diabetes (T2D), and prion diseases. Some amyloid-associated diseases, in particular T2D and AD, are widespread and affect hundreds of millions of people all over the world. However, recently it has become evident that many amyloids, termed "functional amyloids," are involved in various activities that are beneficial to organisms. Functional amyloids were discovered in diverse taxa, ranging from bacteria to mammals. These amyloids are involved in vital biological functions such as long-term memory, storage of peptide hormones and scaffolding melanin polymerization in animals, substrate attachment, and biofilm formation in bacteria and fungi, etc. Thus, amyloids undoubtedly are playing important roles in biological and pathological processes. This review is focused on functional amyloids in mammals and summarizes approaches used for identifying new potentially amyloidogenic proteins and domains.


Temporal Trends in the Incidence, Characteristics, and Outcomes of Hanging-Related Out-of-Hospital Cardiac Arrest.
Aim: The aim of this study was to describe temporal trends in the incidence, characteristics, and outcomes of hanging-related out-of-hospital cardiac arrest (OHCA). Method: A retrospective study of all hanging-related OHCA in Victoria, Australia, between 2000 and 2017 was conducted. Trends in incidence, characteristics, and outcomes were assessed using linear regression and a non-parametric test for trend, as appropriate. Predictors of survival to hospital discharge were identified using multivariable logistic regression. Results: Between 2000 and 2017, emergency medical services (EMS)-attended 3,891 cases of hanging-related OHCA, of which 876 cases (23%) received an attempted resuscitation. The overall incidence rate of EMS-attended cases was 3.8 cases per 100,000 person-years increasing from 2.3 cases per 100,000 person-years in 2000 to 4.7 cases in 2017 (p for trend <0.001). Incidence rates increased approximately two-fold in young adults (18-44 years) and three-fold in middle aged adults (45-64 years). Despite improvement in the rate of bystander cardiopulmonary resuscitation (from 49% in 2000-2005 to 75% in 2012-2017), the survival to hospital discharge rate remained unchanged (3% overall). Among adult survivors with 12-month follow-up (n = 10), five patients responded to telephone interviews. Of those, three (60%) reported severe functional disability. Five patients responded to telephone interviews, of which 3 patients reported severe functional disability. An initial shockable rhythm (OR 23.17, 95% CI: 5.75, 93.36) or pulseless electrical activity (OR 13.14, 95% CI: 4.79, 36.03) were associated with survival. Conclusion: The incidence of hanging-related OHCA doubled over the 18 year period with no change to survival rates. New preventative strategies are needed to reduce the community burden of these events.


Myoepithelioma of the soft palate: a case report giving special attention to the differential diagnosis.
Myoepitheliomas are rare tumours that may generally arise from the minor or major salivary glands. The differential diagnosis of this tumour should be performed along with several benign and malignant soft tissue neoplasms. The present case report describes an asymptomatic mass that arose in the soft palate of 42 year old black woman with duration of the six months. An incisional biopsy of soft palate lesion was carried out and submitted for histological evaluation under the clinical hypothesis of salivary gland tumour. To confirm the myoepithelial nature of neoplastic cells the immunohistochemical reactions for smooth-muscle actin, cytokeratins and S100 were performed. The histological examination revealed the presence of tumour originating from a minor salivary gland and covered by a stratified squamous oral epithelium. The tumour cells were arranged in order to form a myxoid pattern and, individually, small and/or medium spindle-shaped cells with predominantly round or ovoid nuclei, as well as epithelioid and plasmocytoid cells were noted. The stroma was myxomatous and no ductal or syringomatous epithelial structures were observed. Following the histological and immunohistochemical diagnosis of myoepithelioma, the lesion was surgically removed. After the surgery, a follow-up of one year showed no signs and symptoms of reccurrence. The myoepithelioma should be carefully distinguished from the other soft tissue tumours, especially those arising from salivary glands, such as pleomorphic adenoma and adenoid-cystic carcinoma.


Evaluation of the nasopalatine canal with cone-beam computed tomography in an Iranian population.
Implant placement plays a vital role in oral rehabilitation following loss of the incisors. Thus, having knowledge of anatomical variations of adjacent neurovascular structures especially the nasopalatine canal (NPC) is essential. Due to the lack of basic information in Iran about the morphology of this canal and the probability of its variety in different populations, this study was designed on an Iranian population. In this descriptive study, we selected cone-beam computed tomography images of 198 patients comprising of 98 males and 100 females in two dental groups (edentulous or dentate). The shape of the nasopalatine foramen and the form of the canal in axial views were assessed. Then, the canal height and its diameter at the palatal, middle and nasal levels in cross-sectional images were measured. The available bone in the buccal and palatal sides of the canal was assessed. Data analysis was carried out using a Chi-square test and an independent t-test (P ≤ 0.05). The majority of the samples (81.8%) presented a single foramen. Cylindrical shape (57.6%) was the most frequently detected canal form. The mean of the estimated canal height was 12.84 ± 2.88 mm. The canal diameter at the palatal level between the sexes and dental groups showed statistically significant differences. In our investigated population, the NPC form was mainly cylindrical with a single opening foramen. The mean of the canal height was higher than that found in other populations. Furthermore, the canal diameter in the edentulous group was greater than that observed in the other group.


Understanding the Surprising Ionic Conductivity Maximum in Zn(TFSI)2 Water/Acetonitrile Mixture Electrolytes.
Aqueous electrolytes composed of 0.1 M zinc bis(trifluoromethylsulfonyl)imide (Zn(TFSI)2) and acetonitrile (ACN) were studied using combined experimental and simulation techniques. The electrolyte was found to be electrochemically stable when the ACN V% is higher than 74.4. In addition, it was found that the ionic conductivity of the mixed solvent electrolytes changes as a function of ACN composition, and a maximum was observed at 91.7 V% of ACN although the salt concentration is the same. This behavior was qualitatively reproduced by molecular dynamics (MD) simulations. Detailed analyses based on experiments and MD simulations show that at high ACN composition the water network existing in the high water composition solutions breaks. As a result, the screening effect of the solvent weakens and the correlation among ions increases, which causes a decrease in ionic conductivity at high ACN V%. This study provides a fundamental understanding of this complex mixed solvent electrolyte system.


Alteration of membrane barrier in stripped rough microsomes from rat liver on incubation with GTP: its relevance to the stimulation by this nucleotide of the dolichol pathway for protein glycosylation.
The membrane barrier of stripped rough microsomes from rat liver is markedly altered on incubation with GTP at 37 degrees C: after 30 min the structure-linked latency of mannose-6-phosphatase was considerably reduced, and esterase and nucleoside diphosphatase were partly released into the suspension medium. This phenomenon was already maximal with 30 microM GTP and was specific for this nucleotide. Similar conditions enhance the dolichol-mediated glycosylation of protein in microsomes incubated with uridine diphosphate N-acetylglucosamine and guanosine diphosphate mannose (Godelaine, D., H. Beaufay, M. Wibo, and A. Amar-Costesec, 1979, Eur. J. Biochem., 96:17-26; Godelaine, D., H. Beaufay, and M. Wibo, 1979, Eur. J. Biochem., 96:27-34). The GTP-induced permeability and glycosylation activities evolved in parallel in rough microsomes subjected to various treatments to detach the ribosomes and were maximal after removal of congruent to 60% of the RNA. In addition, GTP had no effect of this type in smooth microsome subfractions. Triton X-100, in spite of complex inhibitory effects on glycosylation reactions, mimicked the action of GTP by increasing the amount of microsomal dolichylphosphate that reacts with uridine diphosphate N-acetylglucosamine and by enhancing synthesis of dolichylpyrophosphoryl-chitobiose at concentrations greater than 2 mg/ml. Thus, GTP may activate dolichol-mediated glycosylation reactions in stripped microsomes by lowering the permeability barrier that prevents access of sugar nucleotides to the inner aspect of the membrane. The genuine role of GTP in the functioning of the endoplasmic reticulum membrane in situ remains unknown. Because GTP seems to act only on rough microsomes, we hypothesize that this role is somehow related to biosynthesis of protein by the rough endoplasmic reticulum.


Are retinal arteriolar abnormalities related to atherosclerosis?: The Atherosclerosis Risk in Communities Study.
The objective of this study was to describe associations of retinal arteriolar abnormalities with clinical and subclinical manifestations of atherosclerosis and a broad group of risk factors for vascular disease. A biracial population of 8772 adults (aged 48 to 72 years) living in 4 communities was examined from 1993 to 1995 were studied for that purpose. Retinal arteriovenous nicking and focal arteriolar narrowing were determined by light-box grading of a 45 degrees fundus photograph by use of a standardized protocol. Diameters of arterioles and venules were measured in digitized photographs, and a summary arteriolar-to-venular ratio was derived as an index of generalized arteriolar narrowing. Focal arteriolar narrowing was associated only with hypertension. Generalized arteriolar narrowing was associated with carotid plaque but not with any other evidence of atherosclerosis, either clinical (cardiovascular disease or stroke) or subclinical (carotid or popliteal artery thickness or lower limb obstructive disease), or with plasma cholesterol. It was also associated with smoking, with inflammatory markers (white blood cell count, fibrinogen, and reduced albumin), and with the triglyceride and high density lipoprotein cholesterol changes associated with inflammation. Arteriovenous nicking was inconsistently associated with subclinical atherosclerosis. It was not associated with cardiovascular disease, stroke, or plasma cholesterol. Arteriovenous nicking was associated with markers of inflammation and vascular endothelial dysfunction (von Willebrand factor and factor VIII). Arteriolar narrowing and nicking appear to be related to hypertension and inflammatory factors. Nicking may also be related to endothelial dysfunction. Results suggest that these arteriolar changes are pathologically distinct from atherosclerosis. Including their measurement in population studies may permit evaluation of the independent contribution of arteriolar disease to various ischemic diseases of the heart, brain, and other organs.


5-HT receptors couple to activation of Akt, but not extracellular-regulated kinase (ERK), in cultured hippocampal neurons.
5-HT(1A) receptors have been hypothesized to mediate some of the neuronal plasticity and behavioral responses stimulated by serotonin selective reuptake inhibitors. Although the cellular signaling pathways required for inducing these actions have not yet been determined, roles for the neuroprotective extracellular-regulated kinase (ERK) mitogen-activated protein (MAP) kinase and Akt pathways have been suggested. In the current studies we have utilized primary cultures to directly determine whether hippocampal 5-HT(1A) receptors couple to activation of Akt and ERK. We found that E18 hippocampal neurons exhibit a twofold activation of Akt when exposed to nanomolar concentrations of 5-HT. The 5-HT(1/7) receptor-selective agonist 5-carboxamidotryptamine maleate (5-CT) and the 5-HT(1A/7) receptor-selective agonist 8-hydroxy-N,N-dipropyl-aminotetralin (8-OH-DPAT) maleate were found to activate Akt with equal efficacy, and similar potency, to 5-HT. p-MPPI and WAY-100635, antagonists selective for 5-HT(1A) receptors, completely inhibited 5-CT- stimulated Akt activation. Activation of Akt was also inhibited by pretreatment with pertussis toxin as well as the phosphatidylinositol 3-kinase inhibitors, wortmannin and LY294002. In contrast, the 5-HT selective antagonist, SB269970, caused no inhibition. Although the density of 5-HT(1A) receptors expressed by cultured neurons was sufficient to activate Akt, no activation of ERK was observed. These findings suggest that Akt, and not ERK, may be relevant to previous reports of hippocampal 5-HT(1A) receptors mediating neurotrophic responses.


Educational strategies: Kaiser Permanente of Ohio shares its successful techniques.
What strategies are effective for educating your medical staff about medications and medication-related issues? Kaiser Permanente of Ohio has developed an educational program for its medical staff that involves four key components: a custom-designed formulary handbook, drug fairs, traditional letter/newsletter communication pieces and educational meetings, and collaborative projects between its pharmacy and medical staffs. These educational techniques--many of which have been successfully adapted from the pharmaceutical industry--can be adopted for use at your institution.


Analysis of protein interactions using fluorescence technologies.
Biophotonics techniques, especially those involving fluorescence, are widely used in proteomics to characterize the in vitro interactions between proteins in high-throughput mode. On the other hand, fluorescence-based imaging studies often show that protein activity is regulated through large protein complexes that transiently form at specific sites in the cell. One could therefore argue that a systematic functional analysis of the human proteome requires technologies that are capable of time and spatially resolved, multiplexed analysis of protein interactions within cells.


Association of Body Mass Index With Blood Pressure Among 1.7 Million Chinese Adults.
Body mass index (BMI) is positively associated with blood pressure (BP); this association has critical implications for countries like China, where hypertension is highly prevalent and obesity is increasing. A greater understanding of the association between BMI and BP is required to determine its effect and develop strategies to mitigate it. To assess the heterogeneity in the association between BMI and BP across a wide variety of subgroups of the Chinese population. In this cross-sectional study, data were collected at 1 time point from 1.7 million adults (aged 35-80 years) from 141 primary health care sites (53 urban districts and 88 rural counties) from all 31 provinces in mainland China who were enrolled in the China PEACE (Patient-Centered Evaluative Assessment of Cardiac Events) Million Persons Project, conducted between September 15, 2014, and June 20, 2017. A comprehensive subgroup analysis was performed by defining more than 22 000 subgroups of individuals based on covariates, and within each subgroup, linearly regressing BMI to BP. Systolic BP was measured twice with the participant in a seated position, using an electronic BP monitor. The study included 1 727 411 participants (1 027 711 women and 699 700 men; mean [SD] age, 55.7 [9.8] years). Among the study sample, the mean (SD) BMI was 24.7 (3.5), the mean (SD) systolic BP was 136.5 (20.4) mm Hg, and the mean (SD) diastolic BP was 81.1 (11.2) mm Hg. The increase of BP per unit BMI ranged from 0.8 to 1.7 mm Hg/(kg/m2) for 95% of the subgroups not taking antihypertensive medication. The association between BMI and BP was substantially weaker in subgroups of patients taking antihypertensive medication compared with those who were untreated. In untreated subgroups, 95% of the coefficients varied by less than 1 mm Hg/(kg/m2). The association between BMI and BP is positive across tens of thousands of individuals in population subgroups, and, if causal, given its magnitude, would have significant implications for public health.


Exploring consistency between stated and revealed preferences for the plastic bag ban policy in Chile.
This paper exploits individual-level data before the implementation of a national policy to understand the factors driving avoidance of plastic consumption and explore potential inconsistencies between revealed and stated preferences for a plastic bag ban policy. We estimate a bivariate ordered probit model that allows us to account for a potential correlation between these types of preferences. The data reveals that while 71% of respondents take a reusable bag for shopping, only 58% of the sample state to strongly agree with prohibiting plastic bags. We find that gender, age, environmental concerns, environmental efforts, participation in environmental causes and pro-environmental behavior determine avoidance of plastic consumption, but no effects are found for being in favor of the prohibition. We also find inconsistencies decrease for individuals demonstrating higher pro-environmental behavior in related domains. This indicates waste management policies may benefit from local grounded knowledge from related environmental initiatives.


Sequence Variations Among 17 New Radish Isolates of Turnip mosaic virus Showing Differential Pathogenicity and Infectivity in Nicotiana benthamiana, Brassica rapa, and Raphanus sativus.
Infectious clones were generated from 17 new Korean radish isolates of Turnip mosaic virus (TuMV). Phylogenetic analysis indicated that all new isolates, and three previously characterized Korean radish isolates, belong to the basal-BR group (indicating that the pathotype can infect both Brassica and Raphanus spp.). Pairwise analysis revealed genomic nucleotide and polyprotein amino acid identities of >87.9 and >95.7%, respectively. Five clones (HJY1, HJY2, KIH2, BE, and prior isolate R007) had lower sequence identities than other isolates and produced mild symptoms in Nicotiana benthamiana. These isolates formed three distinct sequence classes (HJY1/HJY2/R007, KIH2, and BE), and several differential amino acid residues (in P1, P3, 6K2, and VPg) were present only in mild isolates HJY1, HJY2, and R007. The remaining isolates all induced systemic necrosis in N. benthamiana. Four mild isolates formed a phylogenetic subclade separate from another subclade including all of the necrosis-inducing isolates plus mild isolate KIH2. Symptom severity in radish and Chinese cabbage genotypes was not correlated with pathogenicity in N. benthamiana; indeed, Chinese cabbage cultivar Norang was not infected by any isolate, whereas Chinese cabbage cultivar Chusarang was uniformly susceptible. Four isolates were unable to infect radish cultivar Iljin, but no specific amino acid residues were correlated with avirulence. These results may lead to the identification of new resistance genes against TuMV.


[Management of levodopa-induced dyskinesia].
There are three main therapeutic strategies to manage levodopa-induced dyskinesias in parkinsonian patients: (1) prevent the occurrence of the priming phenomenon which generates the abnormal movements, (2) avoid the expression of dyskinesias in already primed brain with antidyskinetic symptomatic interventions and (3) reverse, once primed, the changes that occurred in the basal ganglia to induce dyskinesias. To prevent, at least partly, priming for dyskinesias is attempted by the early use of dopamine D2 agonists, which delays the need for levodopa. To avoid the expression of dyskinesias in already primed patients, amantadine is presently the most efficacious symptomatic medication, while functional stereotactic surgery is required in the most severe cases. There are several ways to try to reverse, at least partly, dyskinesia priming. The strategy is to reduce as much as possible (ideally completely) the daily dose of levodopa, by the mean of adjunct interventions like high doses of oral agonists, or more efficiently, with apormorphine subcutaneous infusion or subthalamic deep brain stimulation.


Encouraging physical activity--five steps for GPs.
Over half of Australians do not meet physical activity recommendations. General practitioners can play an important role in encouraging physical activity, which would significantly reduce the burden of chronic disease. This article outlines steps to guide GPs in their efforts to promote greater physical activity participation among their patients, and identifies resources that will assist GPs to incorporate this into routine practice. The 'five As' model for preventive counselling is applied to the problem of physical inactivity. General practitioners first need to Ask about physical activity at an opportune time during consultations, Assess the patient's physical activity level, and then Advise about the recommended type, intensity and amount of physical activity that is relevant to their needs and life circumstances. An achievable plan for increasing physical activity can be prepared and GPs can Assist by discussing strategies to maintain this and tackle the barriers to activity that may arise. It is also useful to Arrange follow up contact and ongoing support through the practice or external programs and exercise professionals.


The Effectiveness of Spinal Cord Stimulation for the Treatment of Axial Low Back Pain: A Systematic Review with Narrative Synthesis.
Determine the effectiveness of spinal cord stimulation (SCS) for the treatment of axial low back pain (LBP) with or without leg pain. Systematic review. Persons aged ≥18 with axial LBP with or without accompanying leg pain. Traditional low-frequency, burst, or high-frequency SCS. Sham, active standard of care treatment, or none. The primary outcome was ≥50% pain improvement, and the secondary outcome was functional improvement measured six or more months after treatment intervention. Publications in PubMed, MEDLINE, and Cochrane databases were reviewed through September 19, 2019. Randomized or nonrandomized comparative studies and nonrandomized studies without internal controls were included. The Cochrane Risk of Bias Tool and GRADE system were used to assess individual study characteristics and overall quality. Query identified 262 publications; 17 were suitable for inclusion. For high-frequency SCS, the only level 1 study showed that 79% (95% confidence interval = 70-87%) of patients reported ≥50% pain improvement. For low-frequency SCS, the only level 1 study reported no categorical data for axial LBP-specific outcomes; axial LBP improved by a mean 14 mm on the visual analog scale at six months. Meta-analysis was not performed due to study heterogeneity. According to GRADE, there is low-quality evidence that high-frequency SCS compared with low-frequency SCS is effective in patients with axial LBP with concomitant leg pain. There is very low-quality evidence for low-frequency SCS for the treatment of axial LBP in patients with concomitant leg pain. There is insufficient evidence addressing the effectiveness of burst SCS to apply a GRADE rating.


Intramolecular distances between tryptophan residues and the active-site serine residue in alkaline bacterial proteinases as measured by fluorescence energy-transfer studies.
Singlet-singlet energy transfer from the tryptophan residues to an active-site-serine-bound 5-dimethylaminonaphthalene-1-sulphonyl group was investigated in four subtilisins. The transfer distances for subtilisin Novo and mesentericopeptidase are 1.93 +/- 0.20 nm (19.3 +/- 2.0 A) and 1.81 +/- 0.20 nm (18.1 +/- 2.0 A) respectively. The positions of the indole groups in the three-dimensional structures of the two pairs of proteinases, namely subtilisin Novo and mesentericopeptidase on the one hand and subtilisins Carlsberg and DY on the other, are essentially identical.


Risk of Cancer Recurrence Among Individuals Exposed to Antitumor Necrosis Factor Therapy: A Systematic Review and Meta-Analysis of Observational Studies.
Patients with immune-mediated disorders such as ankylosing spondylitis, inflammatory bowel disease, psoriasis and rheumatoid arthritis are increasingly treated with tumor necrosis factor (TNF) inhibitors. The safety of anti-TNF therapy in patients with a history of cancer requires further evaluation. We conducted a systematic review and a meta-analysis of observational studies including patients with a history of cancer exposed to anti-TNF therapy assessing for a risk of new cancer or cancer recurrence. A computerized literature search of MEDLINE, Google scholar, and Cochrane Database of Systematic Reviews was performed through September 1, 2015. Study characteristics, quality, and risk of bias were assessed. Random-effects model meta-analyses were used to estimate the risk of new cancer development or cancer recurrence. Nine English-language observational studies including patients with a history of cancer and exposed to anti-TNF therapy were idenitifed. The pooled incidence rate ratio of new or recurrent cancer among individuals with a history of cancer exposed to anti-TNF therapy was not significantly different compared with control therapies (incidence rate ratio, 0.90; 95% confidence interval, 0.59-1.37). Subgroup analyses were performed according to disease type, underlying cancer diagnosis, time to initiation of anti-TNF therapy and study quality. Heterogeneity of study populations, heterogeneity of the included cancer subtypes and utilization of observational studies limits the study quality. The risk of new cancer or cancer recurrence among patients with a history of cancer and use of anti-TNF therapy is similar to the risk with nonbiological disease modifying therapies. These results support the use of anti-TNF medications in select populations despite prior diagnosis of cancer.


Melatonin ameliorates bisphenol A-induced perturbations of the prostate gland of adult Wistar rats.
Bisphenol A (BPA) is an endocrine disrupting chemical (EDC) that has been demonstrated to induce alterations in reproductive organs while melatonin (ML), an antioxidant, present in plants and animals, is capable of protecting against EDC-induced alterations. Adult male Wistar rats (average weight, 240 + 10 g) were divided into four groups of ten animals each: Rats in group I (control) received oral 0.2 ml 1% dimethyl sulfoxide (DMSO)/99% canola oil as vehicle; group II received intra-peritoneal 10 mg/kg BW/day ML. Group III received oral BPA dissolved in DMSO and solubilized in canola oil at 10 mg/kg BW/day. Group IV were treated with same dose of BPA as group III with a concomitant intra-peritoneal 10 mg/kg BW/day ML. All treatments lasted for 14 days. BPA significantly increased the prostatic index of the rats while ML ameliorated it. BPA significantly increased serum levels of estrogen as well as prostate-specific antigen but decreased serum testosterone in the rats while concomitant treatment with ML ameliorated these alterations. Also, BPA caused vascular congestion, hyperplasia (functional, reactive and atypical) of prostatic epithelium as well as tubular atrophy the rats while ML attenuated the observed lesions. Decreased localization of αSmooth muscle actin, vimentin and S100 proteins were observed in the BPA-treated rats while these decreases were ameliorated by ML. The present study has shown that sub-acute oral administration of BPA induced alterations in prostatic index, serum hormone levels, down-regulated protein localization and induced morphological lesions of the prostate gland in rats while concomitant treatment with intra-peritoneal ML ameliorated these conditions. Hence, low dose of ML can protect against BPA-induced toxicity of the prostate gland of rats.


Capsule Dynamics, Implantation, and Explantation of the Smaller Incision, New-Generation Implantable Miniature Telescope: a Miyake-Apple Study.
The smaller incision, new-generation implantable miniature telescope is a novel implant to optimize vision in retinal patients with central vision loss. Using Miyake-Apple techniques we visualized the device implantation, repositioning, and explantation, while noting capsular bag dynamics. Using the Miyake-Apple technique, we assessed capsular bag deformation after successful implantation of the device in human autopsy eyes. We assessed rescue strategies for converting a sulcus implantation to a capsular implantation and explantation strategies. We noted the occurrence of posterior capsule striae, zonular stress, and the haptics' arc of contact with the capsular bag after implantation. Acceptable zonular stress was observed during the successful implantation of the SING IMT. When it was implanted in the sulcus, one could reposition the haptics into the bag with two spatulas using counter-pressure in an effective strategy despite inducing tolerable, medium zonular stress. A similar technique, in reverse, allows safe explantation without damaging the rhexis or the bag, while inducing similar medium, tolerable zonular stress. In all eyes we examined, the implant considerably stretches the bag, inducing a capsular bag deformation and posterior capsule striae. The SING IMT can be safely implanted without significant zonular stress. In sulcus implantation and explantation, repositioning of the haptic is achievable without perturbing zonular stress using the presented approaches. It stretches average-sized capsular bags to support its weight. This is achieved by an increased arc of contact of the haptics with the capsular equator.


Bis(phenylethynyl)arene Linkers in Tetracationic Bis-triarylborane Chromophores Control Fluorimetric and Raman Sensing of Various DNAs and RNAs.
We report four new luminescent tetracationic bis-triarylborane DNA and RNA sensors that show high binding affinities, in several cases even in the nanomolar range. Three of the compounds contain substituted, highly emissive and structurally flexible bis(2,6-dimethylphenyl-4-ethynyl)arene linkers (3: arene=5,5'-2,2'-bithiophene; 4: arene=1,4-benzene; 5: arene=9,10-anthracene) between the two boryl moieties and serve as efficient dual Raman and fluorescence chromophores. The shorter analogue 6 employs 9,10-anthracene as the linker and demonstrates the importance of an adequate linker length with a certain level of flexibility by exhibiting generally lower binding affinities than 3-5. Pronounced aggregation-deaggregation processes are observed in fluorimetric titration experiments with DNA for compounds 3 and 5. Molecular modelling of complexes of 5 with AT-DNA, suggest the minor groove as the dominant binding site for monomeric 5, but demonstrate that dimers of 5 can also be accommodated. Strong SERS responses for 3-5 versus a very weak response for 6, particularly the strong signals from anthracene itself observed for 5 but not for 6, demonstrate the importance of triple bonds for strong Raman activity in molecules of this compound class. The energy of the characteristic stretching vibration of the C≡C bonds is significantly dependent on the aromatic moiety between the triple bonds. The insertion of aromatic moieties between two C≡C bonds thus offers an alternative design for dual Raman and fluorescence chromophores, applicable in multiplex biological Raman imaging.


[Molecular mechanism of vitamin E transport in the body].
Vitamin E occurs in nature in eight different forms, but animal body is enriched in alpha-tocopherol compared with other forms. alpha-Tocopherol transfer protein (alpha-TTP) is a liver cytosolic protein, which specifically binds alpha-tocopherol, and plays an important role in the discrimination of various tocopherols in the body. Furthermore, alpha-TTP is a product of the causative gene for familial isolated vitamin E deficiency. Using cell culture system, it was shown that alpha-TTP functions to enhance secretion of alpha-tocopherol from liver cells and that the reaction utilizes a novel non-Golgi mediated pathway which may be linked to cellular cholesterol metabolism and/or transport.


A theoretical model for Zika virus transmission.
In this paper, we present and analyze an SEIR Zika epidemic model. Firstly, we investigate the model with constant controls. The steady states of the model is found to be locally and globally asymptotically stable. Thereafter, we incorporate time dependent controls into the model in order to investigate the optimal effects of bednets, treatments of infective and spray of insecticides on the disease spread. Furthermore, we used Pontryagin's Maximum Principle to determine the necessary conditions for effective control of the disease. Also, the numerical results were presented.


Silicon photonic wire biosensor array for multiplexed real-time and label-free molecular detection.
We demonstrate a silicon photonic wire waveguide biosensor array chip for the simultaneous monitoring of different molecular binding reactions. The chip is compatible with automated commercial spotting tools and contains a monolithically integrated microfluidic channel for sample delivery. Each array sensor element is a 1.8-mm-long spiral waveguide folded within a 130 microm diameter spot and is incorporated in a balanced Mach-Zehnder interferometer with a near temperature independent response. The sensors are arranged in a 400 microm spacing grid pattern and are addressed through cascaded 1x2 optical power splitters using light from a single input fiber. We demonstrate the real-time monitoring of antibody-antigen reactions using complementary and mismatched immunoglobulin G receptor-analyte pairs and bovine serum albumin. The measured level of detection for each sensor element corresponds to a surface coverage of less than 0.3 pg/mm(2).


Caring through activities.
Home care patients require help with health-related activities, but they also want to engage in activities that they like to do, such as reminiscing or listening to music. Home care professionals can improve the lives of their patients by integrating some special activities into daily caregiving activities and teaching these activities to informal caregivers.


Family interaction in pediatric diabetes.
Adaptation to type 1 diabetes is optimized in the presence of ongoing family support and supervision. Therefore, it is particularly important to understand how family interactions influence adaptation to the illness. The purpose of this paper is to review the current literature on family interaction in youth with type 1 diabetes. Recent advancements in the literature include greater specificity of types of parental involvement, attention to the role of fathers, acknowledgment of the impact of parental distress, increased use of observational methods, and awareness of the impact of culture. Continued parental involvement-particularly monitoring-in the management of diabetes care is important as children transition into adolescence, and the best outcomes are evident when this involvement occurs in a warm, collaborative manner. Parents need support in managing their own distress to maintain this type of involvement.


Estimates of dietary exposure to bisphenol A (BPA) from light metal packaging using food consumption and packaging usage data: a refined deterministic approach and a fully probabilistic (FACET) approach.
The FACET tool is a probabilistic model to estimate exposure to chemicals in foodstuffs, originating from flavours, additives and food contact materials. This paper demonstrates the use of the FACET tool to estimate exposure to BPA (bisphenol A) from light metal packaging. For exposure to migrants from food packaging, FACET uses industry-supplied data on the occurrence of substances in the packaging, their concentrations and construction of the packaging, which were combined with data from a market research organisation and food consumption data supplied by national database managers. To illustrate the principles, UK packaging data were used together with consumption data from the UK National Diet and Nutrition Survey (NDNS) dietary survey for 19-64 year olds for a refined deterministic verification. The UK data were chosen mainly because the consumption surveys are detailed, data for UK packaging at a detailed level were available and, arguably, the UK population is composed of high consumers of packaged foodstuffs. Exposures were run for each food category that could give rise to BPA from light metal packaging. Consumer loyalty to a particular type of packaging, commonly referred to as packaging loyalty, was set. The BPA extraction levels used for the 15 types of coating chemistries that could release BPA were in the range of 0.00005-0.012 mg dm(-2). The estimates of exposure to BPA using FACET for the total diet were 0.0098 (mean) and 0.0466 (97.5th percentile) mg/person/day, corresponding to 0.00013 (mean) and 0.00059 (97.5th percentile) mg kg(-1) body weight day(-1) for consumers of foods packed in light metal packaging. This is well below the current EFSA (and other recognised bodies) TDI of 0.05 mg kg(-1) body weight day(-1). These probabilistic estimates were compared with estimates using a refined deterministic approach drawing on the same input data. The results from FACET for the mean, 95th and 97.5th percentile exposures to BPA lay between the lowest and the highest estimates from the refined deterministic calculations. Since this should be the case, for a fully probabilistic compared with a deterministic approach, it is concluded that the FACET tool has been verified in this example. A recent EFSA draft opinion on exposure to BPA from different sources showed that canned foods were a major contributor and compared results from various models, including those from FACET. The results from FACET were overall conservative.


Vortioxetine as adjunctive therapy to risperidone for treatment of patients with chronic schizophrenia: A randomised, double-blind, placebo-controlled clinical trial.
Vortioxetine, a novel antidepressant, may be an interesting candidate for adjunctive therapy of schizophrenia. Our primary objective was to investigate the effect of vortioxetine on negative symptoms, with the assessment of positive, general psychopathology and total symptoms as our secondary goal. This was an eight-week randomised, double-blind, placebo-controlled, parallel-group clinical trial, in which 78 inpatients with chronic schizophrenia were stabilised with risperidone (4-6 mg/day) for two months before being assigned to adjunctive vortioxetine (10 mg b.i.d.) or placebo. The patients were assessed using the Positive and Negative Syndrome Scale (PANSS), Extrapyramidal Symptom Rating Scale and Hamilton Depression Rating Scale during the study course. All participants had a PANSS negative symptoms subscale score of ⩾16 at baseline. Sixty-eight patients completed the trial. Vortioxetine improved the negative symptoms score as the primary outcome and total PANSS score as a secondary outcome significantly better than placebo from baseline to end point at week 8, accompanied by significant time × treatment interactions and effect sizes (negative symptoms: mean difference (95% confidence interval (CI)) = -1.82 (-2.73 to -0.92); total scores: mean difference (95% CI) = -2.09 (-3.16 to -1.01). No significant difference was detected for changes in positive symptoms score or PANSS general psychopathology score as the other secondary outcomes from baseline to end point between the two treatment arms. The incidence of adverse events was comparable between groups. This is the first study to provide evidence for the therapeutic effect of vortioxetine on negative symptoms as an adjunctive to treatment with antipsychotics in patients with schizophrenia.


Brain atrophy correlates with functional outcome in a murine model of multiple sclerosis.
White matter (WM) lesions are the classic pathological hallmarks of multiple sclerosis (MS). However, MRI-based WM lesion load shows relatively poor correlation with functional outcome, resulting in the "clinico-radiological paradox" of MS. Unlike lesion based measures, volumetric MRI assessment of brain atrophy shows a strong correlation with functional outcome, and the presence of early atrophy predicts a worse disease course. While extensive literature exists describing MRI characteristics of atrophy in MS, the exact pathogenesis and the substrate of atrophy-gray vs. WM loss, axonal/neuronal damage vs. demyelination, or a combination of the above-remain unclear. Animal models of atrophy would allow for detailed investigations of the pathomechanism, and would contribute to an enhanced understanding of structural-functional connections in this complex disease. We now report that in the Theiler's Murine Encephalitis Virus (TMEV) model of MS in SJL/J mice, significant brain atrophy accompanies the development of the progressive MS-like disease. We conducted volumetric MRI studies in 8 cases and 4 age, gender- and strain-matched control mice. While in controls we did not detect any brain atrophy, significant atrophy developed as early as 3 months into the disease course, and reached its peak by 6 months, resulting in ventricular enlargement by 118% (p=0.00003). A strong correlation (r=-0.88) between atrophy and disability, as assessed by rotarod assay, was also demonstrated. We earlier reported another neurodegenerative feature in this model, the presence of deep gray matter T2 hypointensity in thalamic nuclei. Future studies utilizing this model will allow us to investigate key components of MRI detectable neurodegenerative feature development, their tissue correlations and associations with functional outcome measures. These studies are expected to pave the way to a better understanding of the substrate of disability in MS models.


Myopia and Late-Onset Progressive Cone Dystrophy Associate to LVAVA/MVAVA Exon 3 Interchange Haplotypes of Opsin Genes on Chromosome X.
Rare interchange haplotypes in exon 3 of the OPN1LW and OPN1MW opsin genes cause X-linked myopia, color vision defect, and cone dysfunction. The severity of the disease varies on a broad scale from nonsyndromic high myopia to blue cone monochromatism. Here, we describe a new genotype-phenotype correlation attributed to rare exon 3 interchange haplotypes simultaneously present in the long- and middle-wavelength sensitive opsin genes (L- and M-opsin genes). A multigenerational family with X-linked high myopia and cone dystrophy was investigated. Affected male patients had infantile onset myopia with normal visual acuity and color vision until their forties. Visual acuity decreased thereafter, along with the development of severe protan and deutan color vision defects. A mild decrease in electroretinography response of cone photoreceptors was detected in childhood, which further deteriorated in middle-aged patients. Rods were also affected, however, to a lesser extent than cones. Clinical exome sequencing identified the LVAVA and MVAVA toxic haplotypes in the OPN1LW and OPN1MW opsin genes, respectively. Here, we show that LVAVA haplotype of the OPN1LW gene and MVAVA haplotype of the OPN1MW gene cause apparently nonsyndromic high myopia in young patients but lead to progressive cone-rod dystrophy with deuteranopia and protanopia in middle-aged patients corresponding to a previously unknown disease course. To the best of our knowledge, this is the first report on the joint effect of these toxic haplotypes in the two opsin genes on chromosome X.


Genome mining and biosynthesis of kitacinnamycins as a STING activator.
Cinnamoyl-containing nonribosomal peptides (CCNPs) are a small group of secondary metabolites with potent biological activities produced by actinobacteria. Two remarkable features in the biosynthesis of CCNPs include the nonribosomal peptide synthases (NRPSs) for assembly of the depsipeptide backbone and the type II polyketide synthases (PKSs) for N-terminal cinnamoyl moiety construction. Here, we present a genome mining approach targeting both NRPS and type II PKS for discovery of new CCNPs, which led to the identification of 51 putative CCNP gene clusters from public bacterial genome databases. After strain prioritization, a novel class of CCNP-type glycopeptides named kitacinnamycins, one of which showing potent activation ability towards the stimulator of interferon genes (STING) protein, was identified. Bioinformatic, genetic and biochemical analysis revealed the use of the NRPS assembly line to form the macrocyclic peptide backbone, followed by a P450 monooxygenase to generate terminal oxidized groups. A glycosyltransferase with relatively broad substrate specificity transfers sugars to the newly generated OH/COOH group. The protein crystallographic study further provided structural insights into this glycosylation. Our results not only demonstrated the feasibility of genome mining and strain prioritization for the discovery of new bioactive natural products but also disclosed the biosynthetic pathway for kitacinnamycins.


Multiregional Utilization of a Mobile Device App for Triage and Transfer of Burn Patients.
Technology and telehealth have the potential to optimize burn care in areas limited by lack of expertise and geographic distance from a Burn Center. This study reports a multicenter, multiregional experience using a mobile phone app to facilitate triage of patients by allowing referring providers to send encrypted photos, thus enhancing the telephone consultation process. A retrospective review was conducted on referrals from August 2016 to July 2017 at three regional Burn Centers that utilize the same mobile phone app. Centers studied are located in the Western, Northeastern, and Southern regions of the United States. Data on numbers of admissions, consults, referral facilities, type of wounds, disposition, and distance from the Burn Centers were recorded. A total of 2011 consults were placed using the mobile phone app from 294 different referring facilities spanning seven states. Utilization of the mobile phone app ranged from 20.4% to 84% among centers. All three centers demonstrated a similar range of consult distances (0-289 miles). Overall, the top three referral diagnoses were scald, contact, and flame burns. Regional differences included a higher percentage of frostbite in the Western region (P < 0.001) and a higher percentage of scald burns in the Northeastern and Southern regions (P < 0.001). The majority of patients at all centers were referred to outpatient clinics for ongoing burn care. Utilization of a mobile phone app appears to be a useful tool in the triage of patients, but further studies are warranted to assess the impact on accuracy of triage, patient outcomes, and reduction of costs.


Prediction and Analysis of Autism Spectrum Disorder Using Machine Learning Techniques.
Autism spectrum disorder is a severe, life-prolonged neurodevelopmental disease typified by disabilities that are chronic or limited in the development of socio-communication skills, thinking abilities, activities, and behavior. In children aged two to three years, the symptoms of autism are more evident and easier to recognize. The major part of the existing literature on autism spectrum disorder is covered by a prediction system based on traditional machine learning algorithms such as support vector machine, random forest, multiple layer perceptron, naive Bayes, convolution neural network, and deep neural network. The proposed models are validated by using performance measurement parameters such as accuracy, precision, and recall. In this research, autism spectrum disorder prediction has been investigated and compared using common parameters such as application type, simulation method, comparison methodology, and input data. The key purpose of this study is to give a centralized framework to use for researchers working on autism spectrum disorder prediction. The best results were obtained by using the random forest algorithm as it performs better than other traditional machine learning algorithms. The achieved accuracy is 89.23%. The workflow representations of the investigated frameworks assist readers in comprehending the fundamental workings and architectures of these frameworks.


2-Oxoadenosine induces cytotoxicity through intracellular accumulation of 2-oxo-ATP and depletion of ATP but not via the p38 MAPK pathway.
2-Oxoadenosine (2-oxo-Ado), an oxidized form of adenosine, is cytotoxic and induces growth arrest and cell death, which has potential as an anti-cancer drug. However, it is not well understood how 2-oxo-Ado exerts its cytotoxicity. We examined the effects of 2-oxo-Ado on non-tumour cells, namely immortalized mouse embryonic fibroblast lines, and investigated mechanisms by which 2-oxo-Ado exerts its cytotoxicity. We found that cell death induced by 2-oxo-Ado is classical caspase-dependent apoptosis, and requires its sequential intracellular phosphorylation catalysed by adenosine kinase (ADK) and adenylate kinase 2, resulting in intracellular accumulation of 2-oxo-ATP accompanied by accumulation of 2-oxo-Ado in RNA and depletion of ATP. Moreover, we showed that overexpression of MTH1, an oxidized purine nucleoside triphosphatase, prevents 2-oxo-Ado-induced cytotoxicity accompanied by suppression of accumulation of both intracellular 2-oxo-ATP and 2-oxo-Ado in RNA and recovery of ATP levels. We also found that 2-oxo-Ado activates the p38 MAPK pathway. However, siRNAs against Mkk3 and Mkk6, or treatment with several p38 MAPK inhibitors, except SB203580, did not prevent the cytotoxicity. SB203580 prevented intracellular phosphorylation of 2-oxo-Ado to 2-oxo-AMP, and an in vitro ADK assay revealed that SB203580 directly inhibits ADK activity, suggesting that some of the effects of SB203580 may depend on ADK inhibition.


Hypogonadism after traumatic brain injury.
Traumatic brain injury (TBI) is the most common cause of death and disability in young adults. Post-TBI neuroendocrine disorders have been increasingly acknowledged in recent years due to their potential contribution to morbidity and, probably, to mortality after trauma. Marked alterations of the hypothalamic-pituitary axis during the post-TBI acute and chronic phases have been reported. Prospective and longitudinal studies have shown that some abnormalities are transitory. On the other hand, there is a high frequency (15% to 68%) of pituitary hormone deficiency among TBI survivors in a long term setting. Post-TBI hypogonadism is a common finding after cranial trauma, and it is predicted to develop in 16% of the survivors in the long term. Post-TBI hypogonadism has been associated with adverse results in the acute and chronic phases after injury. These data reinforce the need for identification of hormonal deficiencies and their proper treatment, in order to optimize patient recovery, improve their life quality, and avoid the negative consequences of non-treated hypogonadism in the long term.


Experimental evolution of resistance in Paramecium caudatum against the bacterial parasite Holospora undulata.
Host-parasite coevolution is often described as a process of reciprocal adaptation and counter adaptation, driven by frequency-dependent selection. This requires that different parasite genotypes perform differently on different host genotypes. Such genotype-by-genotype interactions arise if adaptation to one host (or parasite) genotype reduces performance on others. These direct costs of adaptation can maintain genetic polymorphism and generate geographic patterns of local host or parasite adaptation. Fixation of all-resistant (or all-infective) genotypes is further prevented if adaptation trades off with other host (or parasite) life-history traits. For the host, such indirect costs of resistance refer to reduced fitness of resistant genotypes in the absence of parasites. We studied (co)evolution in experimental microcosms of several clones of the freshwater protozoan Paramecium caudatum, infected with the bacterial parasite Holospora undulata. After two and a half years of culture, inoculation of evolved and naive (never exposed to the parasite) hosts with evolved and founder parasites revealed an increase in host resistance, but not in parasite infectivity. A cross-infection experiment showed significant host clone-by-parasite isolate interactions, and evolved hosts tended to be more resistant to their own (local) parasites than to parasites from other hosts. Compared to naive clones, evolved host clones had lower division rates in the absence of the parasite. Thus, our study indicates de novo evolution of host resistance, associated with both direct and indirect costs. This illustrates how interactions with parasites can lead to the genetic divergence of initially identical populations.


Acupuncture and immunomodulation.
Acupuncture is a well-known form of Asian medical treatment and it is used not only as an effective curative method but also to prevent illness and maintain health. It is used for the production of analgesic effect; stress related physical-mental disorders and homeostasis. Electroacupuncture (EA) stimulation, an application of electrical current on acupuncture needles, is one of the most popular types of this traditional therapy. In recent years, intensive studies have been carried out to explain the underlying mechanisms of the efficacy of acupuncture. An increase in the release of endogen opioid peptides is generally accepted to be a keystone pathway that affects the immune system after the acupuncture application. To understand the huge gap between specific skin point applications and immune responses, a vast number of accumulating data of experimental and clinical studies in the literature have been collected. This paper reviews the data to explain the updated mechanisms related to immune modulation via acupuncture therapy.


Responsible vendors, intelligent consumers: Silk Road, the online revolution in drug trading.
Silk Road is located on the Deep Web and provides an anonymous transacting infrastructure for the retail of drugs and pharmaceuticals. Members are attracted to the site due to protection of identity by screen pseudonyms, variety and quality of product listings, selection of vendors based on reviews, reduced personal risks, stealth of product delivery, development of personal connections with vendors in stealth modes and forum activity. The study aimed to explore vendor accounts of Silk Road as retail infrastructure. A single and holistic case study with embedded units approach (Yin, 2003) was chosen to explore the accounts of vendor subunits situated within the Silk Road marketplace. Vendors (n=10) completed an online interview via the direct message facility and via Tor mail. Vendors described themselves as 'intelligent and responsible' consumers of drugs. Decisions to commence vending operations on the site centred on simplicity in setting up vendor accounts, and opportunity to operate within a low risk, high traffic, high mark-up, secure and anonymous Deep Web infrastructure. The embedded online culture of harm reduction ethos appealed to them in terms of the responsible vending and use of personally tested high quality products. The professional approach to running their Silk Road businesses and dedication to providing a quality service was characterised by professional advertising of quality products, professional communication and visibility on forum pages, speedy dispatch of slightly overweight products, competitive pricing, good stealth techniques and efforts to avoid customer disputes. Vendors appeared content with a fairly constant buyer demand and described a relatively competitive market between small and big time market players. Concerns were evident with regard to Bitcoin instability. The greatest threat to Silk Road and other sites operating on the Deep Web is not law enforcement or market dynamics, it is technology itself.