Functional analysis of expressed peptides that bind yeast STE proteins.
Peptides are potentially useful for target validation and other reverse genetic applications. For instance, if a specific protein is susceptible to peptide inhibition, it may have a higher probability of being vulnerable to small molecules. We used the yeast two-hybrid technique to identify and study peptide binders for three yeast proteins involved in pheromone response: Ste11p, Ste18p, and Ste50p. A subset of peptide binders was shown to inhibit pheromone response in cells using two different functional assays. In addition, we utilized a variant of the yeast two-hybrid method to examine relative binding affinities based on competitive interactions in yeast. Our results suggest that binding affinity and inhibitory potency of peptides do not correlate perfectly and that peptide-protein interactions can be complex and unpredictable. Taken together these results suggest that while peptides are useful as in vivo inhibitors of protein function, caution must be exercised when choosing peptides for further studies and when inferring affinities from expression phenotypes.


Sulphation of the salivary mucin MG1 (MUC-5B) is not correlated to the degree of its sialylation and is unaffected by cystic fibrosis.
Defective acidification of intracellular organelles, particularly the trans-Golgi network, has been proposed to explain the decreased sialylation and increased sulphation of secreted proteins in cystic fibrosis (CF). To test this hypothesis we compared expression of sulphate and sialic acid on three salivary mucins namely MG1 (MUC-5B), MG2 (MUC-7) and GL. Proteins in whole mouth saliva (WMS) from four individuals were separated by fast protein liquid chromatography (FPLC) on a Superdex 200 column and the partially purified mucins slot-blotted and assayed for sulphate content by staining with Alcian Blue. Sulphation varied with the individual and with the mucin: MG1 was the most sulphated and contributed almost the entire sulphate content of WMS. These results allowed us to test small volumes of WMS from 20 CF patients and age- and sex-matched controls for estimates of sulphate content on MG1. Wherever possible sulphate on MG1 was also visualised by staining washed SDS-PAGE gels with Alcian Blue at pH 1.0. To assess the sialic acid content of salivary mucins, electroblots of SDS-PAGE gels were probed with labelled Triticum vulgaris agglutinin. In summary, our results show MG1 to be the main sulphated protein in whole mouth saliva and there are large differences in the expression of sulphate and of sialic acid on this mucin, both in control and CF groups. CF led neither a decrease in sialylation nor an increase in sulphation and direct comparisons of sialic acid content with sulphate in MG1 failed to reveal any obvious link between the two in health or in disease. Our data thus do not support the hypothesis of defective acidification as the underlying cause of altered glycosylation in CF, but point instead to inter-individual differences in expression/functioning of terminal glycosyltransferases for published observations. We thank the European Union Biomed II programme for support.


Structural vaccinology: structure-based design of influenza A virus hemagglutinin subtype-specific subunit vaccines.
There is a great need for new vaccine development against influenza A viruses due to the drawbacks of traditional vaccines that are mainly prepared using embryonated eggs. The main component of the current split influenza A virus vaccine is viral hemagglutinin (HA) which induces a strong antibody-mediated immune response. To develop a modern vaccine against influenza A viruses, the current research has been focused on the universal vaccines targeting viral M2, NP and HA proteins. Crystallographic studies have shown that HA forms a trimer embedded on the viral envelope surface, and each monomer consists of a globular head (HA1) and a "rod-like" stalk region (HA2), the latter being more conserved among different HA subtypes and being the primary target for universal vaccines. In this study, we rationally designed the HA head based on the crystal structure of the 2009-pandemic influenza A (H1N1) virus HA as a model, tested its immunogenicity in mice, solved its crystal structure and further examined its immunological characteristics. The results show that the HA globular head can be easily prepared by in vitro refolding in an E. coli expression system, which maintains its intact structure and allows for the stimulation of a strong immune response. Together with recent reports on some similar HA globular head preparations we conclude that structure-based rational design of the HA globular head can be used for subtype-specific vaccines against influenza viruses.


Characterisation of poly(ADP-Rib) polymerase activity in nuclei from the slime mould Dictyostelium discoideum.
Nuclei isolated from D. discoideum and incubated in vitro with 3H-NAD synthesise poly(ADP-Rib). The optimum incubation conditions for the poly(ADP-Rib) polymerase were determined. The Km of the enzyme is 18 microM NAD and it is inhibited by nicotinamide. Most of the poly(ADP-Rib) synthesised is attached to nuclear proteins.


Aggressive recurrence of Non-Hodgkin's Lymphoma after successful clearance of hepatitis C virus with direct acting antivirals.
The association of Non-Hodgkin lymphomas and Hepatitis C virus is well documented and antiviral treatments facilitate a virological and hematological response in the majority of HCV related Non-Hodgkin lymphomas. The recent years, direct acting antivirals have made cure possible almost for every HCV patient. Some concerns were raised as regards the frequency and the pattern of recurrence in HCV patients with HCC, treated with these agents. We present a patient with DLBCL, in remission after appropriate treatment, HCV cirrhosis that was cured with the new antivirals and shortly after SVR, he experienced a lethal lymphoma recurrence.


Translating innate immunity into immunological memory: implications for vaccine development.
Vaccination is the most effective means of preventing infectious diseases. Despite the success of many vaccines, there is presently little knowledge of the immunological mechanisms that mediate their efficacy. Such information will be critical in the design of future vaccines against old and new infectious diseases. Recent advances in immunology are beginning to provide an intellectual framework with which to address fundamental questions about how the innate immune system shapes adaptive immunity. In this review, we summarize current knowledge about how the innate immune system modulates the quantity and quality of long-term T and B cell memory and protective immune responses to pathogens. In addition, we point out unanswered questions and identify critical challenges, the solution of which, we believe, will greatly facilitate the rational design of novel vaccines against a multitude of emerging infections.


Combined use of gray matter volume and neuropsychological test performance for classification of individuals with bipolar I disorder via artificial neural network method.
Diagnosis of patients with bipolar disorder may be challenging and delayed in clinical practice. Neuropsychological impairments and brain abnormalities are commonly reported in bipolar disorder (BD); therefore, they can serve as potential biomarkers of the disorder. Rather than relying on these predictors separately, using both structural and neuropsychiatric indicators together could be more informative and increase the accuracy of the automatic disorder classification. Yet, to our information, no Artificial Intelligence (AI) study has used multimodal data using both neuropsychiatric tests and structural brain changes to classify BD. In this study, we first investigated differences in gray matter volumes between patients with bipolar I disorder (n = 37) and healthy controls (n = 27). The results of the verbal and non-verbal memory tests were then compared between the two groups. Finally, we used the artificial neural network (ANN) method to model all the aforementioned values for group classification. Our voxel-based morphometry results demonstrated differences in the left anterior parietal lobule and bilateral insula gray matter volumes, suggesting a reduction of these brain structures in BD. We also observed a decrease in both verbal and non-verbal memory scores of individuals with BD (p < 0.001). The ANN model of neuropsychiatric test scores combined with gray matter volumes has classified the bipolar group with 89.5% accuracy. Our results demonstrate that when bilateral insula volumes are used together with neuropsychological test results the patients with bipolar I disorder and controls could be differentiated with very high accuracy. The findings imply that multimodal data should be used in AI studies as it better represents the multi-componential nature of the condition, thus increasing its diagnosability.


Clinical heterogeneity of glycine encephalopathy in three Palestinian siblings: A novel mutation in the glycine decarboxylase (GLDC) gene.
Glycine encephalopathy (GE), also known as non-ketotic hyperglycinemia (NKH), is a rare inborn error of glycine metabolism caused by a defect in glycine cleavage system, a multi-enzyme complex located in mitochondrial membrane. This defect results in elevated glycine concentration in plasma and cerebrospinal fluid (CSF). Clinical manifestations vary from severe lethargy, hypoactivity and apneic episodes in the neonatal form, mild or moderate psychomotor delay and seizures in the infantile form, and abnormal behaviors, ataxia and choreoathetoid movements in late onset form. More than 50 GLDC mutations were found, reflecting large heterogeneity of the gene. We describe the clinical, biochemical and molecular characteristics of three Palestinian siblings who have distinct clinical phenotypes. Molecular study was performed utilizing standard Polymerase Chain Reaction (PCR) amplification then direct DNA sequencing for the affected family members. Their phenotypes included severe symptoms in neonatal period, infantile onset of seizure and psychomotor delay and a mild late-onset form with speech delay at age 20months. All siblings were homozygous for a novel mutation Y164H in exon 4 of GLDC gene. The described novel homozygous variant in our study is predicted deleterious and pathogenic. This article further expands the genetic spectrum of glycine encephalopathy and adds an evidence of the clinical heterogeneity of glycine encephalopathy even in siblings with identical mutation.


Current status of hematopoietic stem cell transplantation for acute radiation syndromes.
Many people believe that hematopoietic stem cell transplantation (HSCT) together with various hematopoietic factors may aid or rescue victims of acute radiation exposure. However, nearly all patients who have received current HSCT for severe bone marrow damage in the past died relatively shortly after transplantation, even when engraftment followed by autologous blood cell recovery was observed. The causes of death in such cases involved rapidly progressing insults to many non-hematopoietic tissues, such as lung and gut, potentially exacerbated by the conditioning regimen and immune dysfunction. We should recognize that at present avoiding high-dose radiation exposure is the only safe option.


Cloning and characterization of a cdc25 phosphatase from mouse lymphocytes.
Members of the cdc25 phosphatase family are proposed to function as important regulators of the eukaryotic cell cycle, particularly in the induction of mitotic events. A new cdc25 tyrosine phosphatase, cdc25M1, has been cloned from a mouse pre-B cell cDNA library and characterized. The cdc25M1 protein consists of 465 amino acids with a predicted relative molecular mass (M(r)) of 51,750. Over the highly conserved carboxyl terminal region, the amino acid sequence similarity to the human cdc25 C or Hs1 isoform is 89%, while the overall similarity is 67%. The phosphatase active site is located within residues 367-374. Tissue expression of the cdc25M1 was highest in mouse spleen and thymus by northern blot analysis. The cdc25M1 mRNA was detected in a number of cloned mouse lymphocyte cell lines including both CD8+ and CD4+ cells. cdc25M1 mRNA was shown to be cell cycle-regulated in T cells following interleukin-2 (IL-2)-stimulation. Accumulation of cdc25M1 mRNA occurred at 48 h after IL-2 stimulation, when lymphocytes were progressing from S phase to G2/M phase of the cell cycle. This pattern of expression is in contrast to that observed for other protein tyrosine phosphatases expressed in T lymphocytes including CD45, LRP, SHP, and PEP. The elevation in cdc25M1 mRNA level occurred concomittant to the appearance of the hyperphosphorylated form of p34cdc2 protein kinase. A purified, bacterial-expressed recombinant cdc25M1 phosphatase domain catalyzed the dephosphorylation of p-nitrophenol phosphate, as well as [32P-Tyr] and [32P-Ser/Thr]-containing substrates. Preincubation of p34cdc2 kinase with cdc25M1 activated its histone H1 kinase activity in vitro. These results suggest that cdc25M1 may be involved in regulating the proliferation of mouse T lymphocytes following cytokine stimulation, through its action on p34cdc2 kinase.


Parasite-induced parthenogenesis in a freshwater snail: stable, persistent patterns of parasitism.
The role of parasites in the evolution of host reproductive modes has gained renewed interest in evolutionary ecology. It was previously argued that obligate parthenogenesis (all-female reproduction) arose in a freshwater snail, Campeloma decisum, as a consequence of severe sperm limitation caused by an unencysted trematode, Leucochloridiomorpha constantiae. In the present study, certain conditions are examined for parasitic castration to account for the maintenance of parthenogenesis: the spatial patterns of the prevalence and intensity of infection on a broad geographical scale and its relationship to host genotype; the recovery from infection after isolation from sources of infection; age-related patterns of infections; and the effects of L. constantiae on snail fecundity.In contrast to the common pattern of the aggregated distribution of parasites within host populations, many snail populations with high prevalence and intensity of infection have non-aggregated parasite distributions. Clonal genotype of the host explained little of the variation in intensity and prevalence of infection by the parasite. Female snails maintained similar prevalence and intensity of infection after isolation, and individuals accumulated parasites throughout their lifespan, both of which suggest there is no effective immune response to infection by L. constantiae. Snail fecundity is not significantly influenced by the intensity of infection. These results suggest that L. constantiae may have represented a strong selective force against males during the initial introduction of this parasite into sexual snail populations because of the persistent nature of infection.


Passive transfer of immunity of Mycobacterium avium in susceptible and resistant strains of mice.
Naturally susceptible mice (C57BL/6) infected with M. avium (strain Weybridge) developed a population of splenic T cells which, on transfer to syngeneic recipient mice, conferred significant protection against a subsequent challenge inoculum of M. avium. Similar T cells from naturally resistant mice (A/J) did not protect syngeneic recipient mice. Growth of M. avium in donor mice only occurred in the C57BL/6 strain. Replication of M. avium in donor mice was necessary for the development of protective T cells. High numbers of killed mycobacterium did not induce immune T cells. In addition, A/J mice inoculated with increasing numbers of viable M. avium (which still did not replicate) failed to develop protective T lymphocytes. Further studies indicated that no protective T cells were present in the M. avium-infected A/J mouse, although evidence for non-specific immunity in these mice was obtained. In addition, BCG (which grows progressively in A/J mice) stimulated a population of splenic T cells which protected recipient mice from subsequent infection with M. tuberculosis.


Targeted mutagenesis of ∆5 and ∆6 fatty acyl desaturases induce dysregulation of lipid metabolism in Atlantic salmon (Salmo salar).
With declining wild fish populations, farmed salmon has gained popularity as a source for healthy long-chain highly unsaturated fatty acids (LC-HUFA). However, the introduction of plant oil in farmed salmon feeds has reduced the content of these beneficial LC-HUFA. The synthetic capability for LC-HUFAs depends upon the dietary precursor fatty acids and the genetic potential, thus there is a need for in-depth understanding of LC-HUFA synthetic genes and their interactions with other genes involved in lipid metabolism. Several key genes of LC-HUFA synthesis in salmon belong to the fatty acid desaturases 2 (fads2) family. The present study applied whole transcriptome analysis on two CRISPR-mutated salmon strains (crispants), 1) Δ6abc/5Mt with mutations in Δ5fads2, Δ6fads2-a, Δ6fads2-b and Δ6fads2-c genes, and 2) Δ6bcMt with mutations in Δ6fads2-b and Δ6fads2-c genes. Our purpose is to evaluate the genetic effect fads2 mutations have on other lipid metabolism pathways in fish, as well as to investigate mosaicism in a commercial species with a very long embryonal period. Both Δ6abc/5Mt and Δ6bcMt crispants demonstrated high percentage of indels within all intended target genes, though different indel types and percentage were observed between individuals. The Δ6abc/5Mt fish displayed several disruptive indels which resulted in over 100 differentially expressed genes (DEGs) enriched in lipid metabolism pathways in liver. This includes up-regulation of srebp1 genes which are known key transcription regulators of lipid metabolism as well as a number of down-stream genes involved in fatty acid de-novo synthesis, fatty acid β-oxidation and lipogenesis. Both elovl5 and elovl2 genes were not changed, suggesting that the genes were not targeted by Srebp1. The mutation of Δ6bcMt surprisingly resulted in over 3000 DEGs which were enriched in factors encoding genes involved in mRNA regulation and stability. CRISPR-Cas9 can efficiently mutate multiple fads2 genes simultaneously in salmon. The results of the present study have provided new information on the transcriptional regulations of lipid metabolism genes after reduction of LC-HUFA synthesis pathways in salmon.


Monoclonal radioimmunoassays for hepatitis B surface antigen: demonstration of hepatitis B virus DNA or related sequences in serum and viral epitopes in immune complexes.
High-affinity monoclonal IgM and IgG antibodies (anti-HBs) to hepatitis B surface antigen (HBsAg) have recently been developed and used by us in the construction of highly sensitive radioimmunoassays for the detection of HBsAg-associated determinants in serum. We now report that selected serum samples demonstrating monoclonal immunoreactive material also contain nucleic acid sequences complementary to hepatitis B virus (HBV) DNA by molecular hybridization analysis. In addition, monoclonal radioimmunoassays can detect viral determinants in HBsAg-anti-HBs immune complexes formed in anti-HBs excess; such determinants are undetectable by commercial radioimmunoassay. These and our previous studies suggest that there are HBV or "HBV-related" agents present in human serum that are detected by monoclonal antibodies but are not identified by conventional polyvalent antibodies.


Detection of nitric oxide production in lipopolysaccharide-treated rats by ESR using carbon monoxide hemoglobin.
Release of nitric oxide (NO), from macrophages activated with E. coli lipopolysaccharide (LPS) and endothelial cells, has been proposed using chemiluminescence and spectrophotometry. However these methods can not distinguish NO from NO2-. The present study was aimed to prove in vivo production of NO, by ESR using CO-hemoglobin (HbCO) as a trapping agent of NO in the peritoneal cavity of rats treated with LPS. We detected a broad signal in the recovered HbCO solution. Inositol hexaphosphate induced a three-line hyperfine structure, characteristic of NO-hemoglobin (HbNO). In the arterial blood, ESR signal of HbNO with faint hyperfine structure was detected. NG-Monomethyl-L-arginine inhibited the formation of HbNO. HbNO was not detected in the peritoneal cavity of the LPS-untreated rat given i.p. both NO2- and HbCO. HbNO was, therefore, derived from NO, not from NO2-. These results show that free NO is produced in vivo by the stimulation of LPS.


Outcome of 23-gauge sutureless transconjunctival vitrectomy for endophthalmitis.
To review the outcomes of 23-gauge transconjunctival vitrectomy in patients with postoperative endophthalmitis. Non-randomized, interventional case series of patients with postoperative endophthalmitis over a 1-year period. 23-gauge transconjunctival vitrectomy was performed on 6 patients with a mean age of 67.7 years without intraoperative or postoperative complications. There were no cases of postoperative hypotony or wound leak. The mean change in IOP was -4.2 mmHg compared to the preoperative IOP (P=0.239). Final VA improved significantly compared to preoperative VA (P=0.062), with VA of at least 20/40 in 5 of 6 patients (83.3%). 23-gauge transconjunctival vitrectomy is a useful technique for treating postoperative endophthalmitis.


Submental flap as an alternative to microsurgical flap in intraoral post-oncological reconstruction in the elderly.
Oral and oropharyngeal squamous cell carcinoma (Scc) occur most commonly in middle-aged and elderly individuals. Free flaps are commonly used for reconstruction of extensive tumor resection defects in the oral cavity. Age alone is not an independent variable for increased risk in microvascular reconstruction; however operative time and ASA risk score correlated with medical complications but not with surgical complications. The submental island flap has proven to be a reliable alternative in reconstruction of composite oral cavity defects for its thinness, pliability and versatility in design, shared by the radial forearm free flap, and its advantageous donor site. The submental flap can be easily raised and involves shorter operative time and hospital stay compared to the free-flap procedure. It can be an excellent choice in patients with a high ASA risk score, moreover in elderly patients, where the potential complications linked to microsurgical procedures are avoided.


Facial mimicry and metacognitive judgments in emotion recognition are distinctly modulated by social anxiety and autistic traits.
Facial mimicry as well as the accurate assessment of one's performance when judging others' emotional expressions have been suggested to inform successful emotion recognition. Differences in the integration of these two information sources might explain alterations in the perception of others' emotions in individuals with Social Anxiety Disorder and individuals on the autism spectrum. Using a non-clinical sample (N = 57), we examined the role of social anxiety and autistic traits in the link between facial mimicry, or confidence in one's performance, and emotion recognition. While participants were presented with videos of spontaneous emotional facial expressions, we measured their facial muscle activity, asked them to label the expressions and indicate their confidence in accurately labelling the expressions. Our results showed that confidence in emotion recognition was lower with higher social anxiety traits even though actual recognition was not related to social anxiety traits. Higher autistic traits, in contrast, were associated with worse recognition, and a weakened link between facial mimicry and performance. Consequently, high social anxiety traits might not affect emotion recognition itself, but the top-down evaluation of own abilities in emotion recognition contexts. High autistic traits, in contrast, may be related to lower integration of sensorimotor simulations, which promote emotion recognition.


[Influence of freezing and storage on food value of berries of the red currant].
The red currant is perspective culture for use in industry functional pectin foodstuff. Freezing use as an effective way of conservation, allows to keep as much as possible vitamin properties of raw materials within all year and to expand assortment of fruit production.


N-Desmethylclozapine, a major clozapine metabolite, acts as a selective and efficacious delta-opioid agonist at recombinant and native receptors.
The present study examined the effects of N-desmethylclozapine (NDMC), a biologically active metabolite of the atypical antipsychotic clozapine, at cloned human opioid receptors stably expressed in Chinese hamster ovary (CHO) cells and at native opioid receptors present in NG108-15 cells and rat brain. In CHO cells expressing the delta-opioid receptor (CHO/DOR), NDMC behaved as a full agonist both in stimulating [(35)S]GTPgammaS binding (pEC(50)=7.24) and in inhibiting cyclic AMP formation (pEC(50)=6.40). NDMC inhibited [(3)H]naltrindole binding to CHO/DOR membranes with competition curves that were modulated by guanine nucleotides in an agonist-like manner. Determination of intrinsic efficacies by taking into consideration both the maximal [(35)S]GTPgammaS binding stimulation and the extent of receptor occupancy at which half-maximal effect occurred indicated that NDMC had an efficacy value equal to 82% of that of the full delta-opioid receptor agonist DPDPE, whereas clozapine and the other clozapine metabolite clozapine N-oxide displayed much lower levels of agonist efficacy. NDMC exhibited poor agonist activity and lower affinity at the kappa-opioid receptor and was inactive at mu-opioid and NOP receptors. In NG108-15 cells, NDMC inhibited cyclic AMP formation and stimulated the phosphorylation of extracellular signal-regulated kinase 1/2 by activating the endogenously expressed delta-opioid receptor. Moreover, in membranes of different brain regions, NDMC stimulated [(35)S]GTPgammaS binding and regulated adenylyl cyclase activity and the effects were potently antagonized by naltrindole. These data demonstrate for the first time that NDMC acts as a selective and efficacious delta-opioid receptor agonist and suggest that this unique property may contribute, at least in part, to the clinical actions of the atypical antipsychotic clozapine.


A triple-blind randomized clinical trial of different associations between dexamethasone and non-steroids anti-inflammatories for preemptive action in third molar extractions.
The aim of this study is to evaluate the preemptive analgesic effects of dexamethasone (DEX) alone or combined with non-steroidal anti-inflammatory drugs (NSAIDs) in third molar surgeries. The subjects were divided into five groups (n = 20 teeth/group); subjects received only 8 mg of dexamethasone 1 h before the surgical procedure (DEX group), or in combination with etodolac (DEX + ETO), ketorolac (DEX + KET), ibuprofen (DEX + IBU), loxoprofen (DEX + LOX). Paracetamol 750 mg was provided as the number of rescue analgesics (NRA). Salivary PGE2 expression was measured preoperatively and at 48 h. Edema and Maximum mouth opening (MMO) were measured postoperatively at 48 h and 7 days. A visual analog scale (VAS) was performed postoperatively at 6, 12, 24, 48, 72 h, and 7 days. Salivary expression of PGE2 showed a decrease only for the DEX group. Edema and MMO and NRA consumption showed no significant differences among the groups (P > 0.05). The VAS showed a significantly lower pain perception at 6 h after the surgery for the DEX + ETO and DEX + KET groups (P < 0.05). The combination of DEX and NSAIDS should be considered for preemptive acute postsurgical pain management in third molar surgery. In some drug associations such as dexamethasone 8 mg + NSAIDS (ETO and KET) in the pre-operative time, only a few rescue analgesics are necessary.


Wolff-Parkinson-White Syndrome in Third Trimester of Pregnancy.
Wolff-Parkinson-White (WPW) syndrome is rare and is characterized by an accessory pathway that predisposes patients to tachyarrhythmias and sudden cardiac death. Early recognition is important and should be evaluated by a multidisciplinary team for adequate management and treatment. We present a pregnant woman that presented to the emergency department and discuss her diagnosis, treatment, and outcome.


A key factor analysis of a sparrowhawk population.
During 1972-86, the Sparrowhawk breeding population in Eskdale, southern Scotland, remained fairly stable, with nest numbers fluctuating between 29 and 39 in different years. The annual production of young varied rather more, between 44 and 86 in different years. In a key factor analysis, the 'overwinter loss' operating in the period between the fledging of young and subsequent recruitment to the breeding population, emerged as the 'key factor', explaining 77% of the variance in total annual loss, and largely accounting for the pattern of change in breeding numbers. Overwinter loss in each new cohort was also the only form of loss which was density dependent. In a simulation model this loss was found to be capable, on its own, of stabilising the nesting population at the mean level observed. Losses during the breeding season were inversely correlated with losses over the ensuing winter. Thus, good breeding seasons, when many young were produced, were followed by high losses over winter, while poor breeding seasons were followed by reduced losses over winter. No density dependence was detected at any stage of breeding, or in the annual mortality of established breeders.


Evaluation of a preschool nutrition education program based on the theory of multiple intelligences.
This report describes the evaluation of a preschool nutrition education program based on the theory of multiple intelligences. Forty-six nutrition educators provided a series of 12 lessons to 6102 preschool-age children. The program was evaluated using a pretest/post-test design to assess differences in fruit and vegetable identification, healthy snack choices, willingness to taste foods, and eating behaviors. Subjects showed significant improvement in food identification and recognition, healthy snack identification, willingness to taste foods, and frequency of fruit, vegetable, meat, and dairy consumption. The evaluation indicates that the program was an effective approach for educating preschool children about nutrition.


Increased Langerhans cells and related cells in mesenteric lymph nodes of DNCB-sensitive mice.
We used electron microscopy to study mesenteric lymph nodes (LNs) of 2,4-dinitro-1-chlorobenzene(DNCB)-sensitive mice. It was found that Langerhans cells (LCs) and cells containing Birbeck-granule-like structures (BgSs) increased in number only after challenge with DNCB. This increase reached a peak 4 h after challenge. LCs and BgS cells were only found in the paracortical area of LNs. There were no appreciable differences in the morphology of LCs, BgS cells, and interdigitating reticulum cells (IDCs), except for the presence or absence of Bgs or BgSs. No LCs, BgS cells, or IDCs were found in the marginal sinus of mesenteric LNs or in the surroundings of afferent blood vessels. These findings were in complete agreement with those obtained in our previous study of cutaneous LNs. From our findings and the results of previously published studies, we propose the following conclusions: first, LCs and BgS cells observed in mesenteric LNs are the product of the differentiation and maturation of precursor cells pre-existing in the paracortical area of LNs caused by DNCB stimulation. Second, the activated T lymphocyte to DNCB pre-exists in the paracortical area; thus, the DNCB used for challenge stimulates this T lymphocyte to release lymphokine, which then causes some precursor cells to differentiation into LCs and/or BgS cells. Finally, morphological findings suggest that precursor cells of LCs and BgS cells are probably IDCs.


Elevated pyruvate kinase activity in patients with hemolytic anemia due to red cell pyruvate kinase "deficiency".
Two patients with non-spherocytic hemolytic anemia were found to have elevated red blood cell pyruvate kinase activities commensurate with the decreased mean red cell age, but the residual pyruvate kinase had marked kinetic abnormalities. Accumulation of metabolic intermediates before pyruvate kinase and reduced levels of activity of the red blood cells of the parents of both patients supported the diagnosis of an inherited abnormal pyruvate kinase causing hemolytic anemia. Although it was observed in two unrelated persons, review of enzyme assays performed on the red blood cells of 651 patients with hereditary non-spherocytic hemolytic anemia suggests that this occurrence is rare.


The novel anticonvulsant BIA 2-093 inhibits transmitter release during opening of voltage-gated sodium channels: a comparison with carbamazepine and oxcarbazepine.
(S)-(-)-10-acetoxy-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide (BIA 2-093) is endowed with high anticonvulsant activity and shares with carbamazepine (CBZ) and oxcarbazepine (OXC) the capability to inhibit voltage-gated sodium channels (VGSC). The present study was aimed to compare the effects of BIA 2-093, CBZ and OXC on the release of glutamate, aspartate, gamma-aminobutyric acid (GABA) and dopamine from striatal slices induced by the VGSC opener veratrine. The release of glutamate, aspartate, GABA and aspartate by veratrine from rat striatal slices was a concentration and time dependent process. All the three dibenzazepine carboxamide derivatives, BIA 2-093, CBZ and OXC inhibited in a concentration dependent manner (from 30 to 300 microM) the veratrine-induced release of glutamate, aspartate, GABA and dopamine. CBZ, OXC and BIA 2-093 were endowed with similar potencies in inhibiting veratrine-induced transmitter release. It is concluded that BIA 2-093, CBZ and OXC inhibit veratrine-induced transmitter release, which is in agreement with their capability to block VGSC. This property may be of importance for the anticonvulsant effects of BIA 2-093.


Comparison of cognitive functional therapy and movement system impairment treatment in chronic low back pain patients: a randomized controlled trial.
This study aimed to compare the effects of cognitive functional therapy (CFT) and movement system impairment (MSI)-based treatment on pain intensity, disability, Kinesiophobia, and gait kinetics in patients with chronic non-specific low back pain (CNSLBP). In a single-blind randomized clinical trial, we randomly assigned 91 patients with CNSLBP into CFT (n = 45) and MSI-based treatment (n = 46) groups. An 8-week training intervention was given to both groups. The researchers measured the primary outcome, which was pain intensity (Numeric rating scale), and the secondary outcomes, including disability (Oswestry disability index), Kinesiophobia (Tampa Kinesiophobia Scale), and vertical ground reaction force (VGRF) parameters at self-selected and faster speed (Force distributor treadmill). We evaluated patients at baseline, at the end of the 8-week intervention (post-treatment), and six months after the first treatment. We used mixed-model ANOVA to evaluate the effects of the interaction between time (baseline vs. post-treatment vs. six-month follow-up) and group (CFT vs. MSI-based treatment) on each measure. CFT showed superiority over MSI-based treatment in reducing pain intensity (P < 0.001, Effect size (ES) = 2.41), ODI (P < 0.001, ES = 2.15), and Kinesiophobia (P < 0.001, ES = 2.47) at eight weeks. The CFT also produced greater improvement in VGRF parameters, at both self-selected (FPF[P < 0.001, ES = 3], SPF[P < 0.001, ES = 0.5], MSF[P < 0.001, ES = 0.67], WAR[P < 0.001, ES = 1.53], POR[P < 0.001, ES = 0.8]), and faster speed, FPF(P < 0.001, ES = 1.33, MSF(P < 0.001, ES = 0.57), WAR(P < 0.001, ES = 0.67), POR(P < 0.001, ES = 2.91)] than the MSI, except SPF(P < 0.001, ES = 0.0) at eight weeks. This study suggests that the CFT is associated with better results in clinical and cognitive characteristics than the MSI-based treatment for CNSLBP, and the researchers maintained the treatment effects at six-month follow-up. Also, This study achieved better improvements in gait kinetics in CFT. CTF seems to be an appropriate and applicable treatment in clinical setting. The researchers retrospectively registered the trial 10/11/2022, at https://www.umin.ac.jp/ with identifier number (UMIN000047455).


Free drug provision for tuberculosis increases patient follow-ups and successful treatment outcomes in the Indian private sector: a quasi experimental study using propensity score matching.
The private sector is an important yet underregulated component of the TB treatment infrastructure in India. The Joint Effort for Elimination of Tuberculosis (Project JEET) aims to link private sector TB care with the constellation of social support mechanisms available through the Indian National TB Elimination Programme (NTEP), including the provision of free fixed-dose combination (FDCs) drugs to patients. This quasi-experimental study analysed routinely collected data to determine the impact of free drugs on patient follow-ups and treatment outcomes. We used data for private sector patients enrolled with Project JEET who were diagnosed with pulmonary and extrapulmonary TB between 1 and 2019 and 31 March 2020, and completed treatment by 31 December 2021. Propensity score matching was used to create a dataset to compare the number of follow-ups and proportion of successful treatment outcomes for patients on free drugs to a control group who paid out-of-pocket. 11,621 matched pairs were included in the analysis. Logistic regression and ordinary least squares regression models were used to estimate the impact of free drugs on number of follow-ups and treatment success, where latter is defined as treatment completion or cure. After controlling for potential confounders, patients on free drugs received on average 2.522 (95% C.I.: 2.325 to 2.719) additional follow-ups compared to patients who paid out of pocket. This equates to a 25% mean and 32% median increase in follow-ups for patients availing free drugs. For treatment success, patients receiving free drugs had 45% higher odds of a successful treatment (Odds Ratio: 1.452, 95% C.I.: 1.288 to 1.637). Patients receiving free drugs were found to follow up with their treatment coordinator more frequently, in part likely to enable drug refilling, compared to patients who were paying out of pocket. These additional contacts would have offered opportunities to address concerns regarding side effects, provide additional treatment information, and connect with social support services, all of which subsequently contributed to patients' continual engagement with their treatment. This potentially represents the unmeasured effect of free drugs on continual social support, which translates into a higher odds of treatment success for patients.


Factors associated with intensification of oral diabetes medications in primary care provider-patient dyads: a cohort study.
Although suboptimal glycemic control is known to be common in diabetic adults, few studies have evaluated factors at the level of the physician-patient encounter. Our objective was to identify novel visit-based factors associated with intensification of oral diabetes medications in diabetic adults. We conducted a nonconcurrent prospective cohort study of 121 patients with type 2 diabetes and hyperglycemia (A1C > or =8%) enrolled in an academically affiliated managed-care program. Over a 24-month interval (1999-2001), we identified 574 hyperglycemic visits. We measured treatment intensification and factors associated with intensification at each visit. Provider-patient dyads intensified oral diabetes treatment in only 128 (22%) of 574 hyperglycemic visits. As expected, worse glycemia was an important predictor of intensification. Treatment was more likely to be intensified for patients with visits that were "routine" (odds ratio [OR] 2.55 [95% CI 1.49-4.38]), for patients taking two or more oral diabetes drugs (2.82 [1.74-4.56]), or for patients with longer intervals between visits (OR per 30 days 1.05 [1.00-1.10]). In contrast, patients with less recent A1C measurements (OR >30 days before the visit 0.53 [0.34-0.85]), patients with a higher number of prior visits (OR per prior visit 0.94 [0.88-1.00]), and African American patients (0.59 [0.35-1.00]) were less likely to have treatment intensified. Failure to intensify oral diabetes treatment is common in diabetes care. Quality improvement measures in type 2 diabetes should focus on overcoming inertia, improving continuity of care, and reducing racial disparities.


Spectrophotometric and conductometric study of complexation of salophen and some transition metal ions in nonaqueous polar solvents.
The complexation reaction between Cu2+, Co2+ and Ni2+ metal cations with N,N'-bis(salicylidene)-1,2-phenylenediamine (salophen), in three nonaqueous polar solvents such as: acetonitrile (AN), dimethyl sulfoxide (DMSO), methanol (MeOH) and two binary mixtures of AN:DMSO and AN:MeOH at 25 degrees C were studied by spectrophotometric and conductometric methods. All investigated metal ions form 1:1 ML complex which their stability constants were determined and increase as Irving-Williams stability order of Co2+ < Ni2+ < Cu2+ in all solvent systems except in the pure MeOH and binary mixture of AN:MeOH 20:80; in which, Ni2+ < Co2+ < Cu2+ was observed. The values of the thermodynamic parameters (DeltaH degrees , DeltaS degrees and DeltaG degrees ) for complexation reactions obtained from the temperature dependence of the stability constants and the results show that for all metal ion complexes, the value of DeltaH degrees , DeltaS degrees and DeltaG degrees are solvent dependent.


Green roof systems: a study of public attitudes and preferences in southern Spain.
This study investigates people's preconceptions of green roofs and their visual preference for different green roof design alternatives in relation to behavioral, social and demographical variables. The investigation was performed as a visual preference study using digital images created to represent eight different alternatives: gravel roof, extensive green roof with Sedums not in flower, extensive green roof with sedums in bloom, semi-intensive green roof with sedums and ornamental grasses, semi-intensive green roof with shrubs, intensive green roof planted with a lawn, intensive green roof with succulent and trees and intensive green roof with shrubs and trees. Using a Likert-type scale, 450 respondents were asked to indicate their preference for each digital image. Results indicated that respondents' sociodemographic characteristics and childhood environmental background influenced their preferences toward different green roof types. Results also showed that green roofs with a more careful design, greater variety of vegetation structure, and more variety of colors were preferred over alternatives.


A physical interpretation of the Haicheng earthquake prediction.
A possible explanation for the successful prediction of the 1975 Haicheng earthquake is that the earthquake was triggered by a deformation front that propagated 1,000 km through NE China at a velocity of about 110 km yr(-1). The various phenomena that were used to predict the earthquake can be explained by the deformation front.


Parenting with a Life-Limiting Illness.
Parents with life-threatening illness face unique challenges in their dual roles as patients and parents. They are at risk for depression, parenting stress, and impaired family functioning, and their children are at risk for adjustment difficulties. In addition to treatment of depression and other mental health issues, patients may also benefit from evidence-informed guidance addressing the challenges of parenting while ill. Consultations should be tailored to each family, with consideration of children's developmental stage and temperament. Clinical recommendations for communication about a parent's anticipated death, helping children spend meaningful time with an ill parent, and legacy leaving are provided.


Marginalised social groups differentials in nutritional status (BMI) among reproductive-aged women in West Bengal.
SCs and STs, historically marginalized communities in India, have been subjected to social and economic discrimination for centuries. Despite affirmative action policies, these communities face systemic discrimination and exclusion in various aspects of their lives. Poor health conditions among SC and ST women are caused by insufficient consumption of nutritious food, leading to undernutrition and related health issues. To address gaps in the literature regarding the nutritional status of these women, this study aims to compare the BMI of SC and ST women in West Bengal and investigate the factors affecting their BMI. The study's findings can inform targeted interventions to improve the nutritional status of SC and ST women in West Bengal and reduce disparities in their health outcomes. This study analyzed data from the National Family Health Survey (NFHS-5) to examine the distribution of underweight and non-underweight SC and ST women in West Bengal. The sample included 5,961 non-pregnant reproductive-aged SC women and 1,496 non-pregnant reproductive-aged ST women. A binary logistic regression model was used to determine how background characteristics affect the nutritional status (BMI) of respondents, while a multivariate decomposition analysis was conducted to identify the covariates contributing to the nutritional status difference between SC and ST women. QGIS 2.18.25 software was utilized to map the spatial distribution of underweight and non-underweight SC and ST reproductive-aged women. This study examines the nutritional status and differential background characteristics among SC and ST women in West Bengal, India. Results show that undernutrition affects the ST population more than the SC population, with age, marital status, religion, place of residence, educational status, and wealth quintile being significant factors affecting nutritional status. Food and dietary habits also impact nutritional status, with milk or curd, pulses or beans, dark green leafy vegetables, eggs, and fish being associated with lower rates of underweight. Binary logistic regression analysis reveals significant associations between socio-demographic factors and underweight status among SC and ST women. Socio-demographic factors were found to be the major contributors to the gap between SC and ST women, followed by food and dietary factors. The study highlights the need for targeted interventions to improve the nutritional status of marginalized communities like SC and ST women in West Bengal. The study highlights a significant population suffering from underweight in West Bengal, with socio-economic factors and dietary habits significantly contributing to the nutritional gap between SC and ST reproductive-aged women. Policy implications suggest targeted interventions to improve access to education and employment opportunities and promote a healthy and balanced diet to reduce the gap. Future studies could explore vulnerability risks of these domains.


dECM based dusal-responsive vascular graft with enzyme-controlled adenine release for long-term patency.
Rapid occlusion is the culprit leading to implantation failure of biological blood vessels. Although adenosine is a clinical-proven drug to overcome the problem, its short half-life and turbulent burst-release limit its direct application. Thus, a pH/temperature dual-responsive blood vessel possessed controllable long-term adenosine secretion was constructed based on acellular matrix via compact crosslinking by oxidized chondroitin sulfate (OCSA) and functionalized with apyrase and acid phosphatase. These enzymes, as adenosine micro-generators, controlled the adenosine release amount by "real-time-responding" to acidity and temperature of vascular inflammation sites. Additionally, the macrophage phenotype was switched from M1 to M2, and related factors expression proved that adenosine release was effectively regulated with the severity of inflammation. What's more, the ultra-structure for degradation resisting and endothelialization accelerating was also preserved by their "double-crosslinking". Therefore, this work suggested a new feasible strategy providing a bright future of long-term patency for transplanted blood vessels.


Wnt-5a is involved in TGF-beta3-stimulated chondrogenic differentiation of chick wing bud mesenchymal cells.
In this study we investigated whether signalling by TGF-beta3 and Wnt-5a cross-talk during chondrogenic differentiation of chick wing mesenchyme. Using differential display polymerase chain reaction screening, we found the expression of Wnt-5a to be significantly increased during transforming growth factor-beta3 (TGF-beta3)-induced precartilage condensation in mesenchyme micromass cultures. Transfection of cells with a Wnt-5a expression construct promoted precartilage condensation and chondrogenesis in micromass cultures, similar to that observed when chondrogenic-competent cells were exposed to TGF-beta3. Overexpression of Wnt-5a or treatment with TGF-beta3 stimulated the activation of protein kinase C-alpha (PKC-alpha) and p38 mitogen-activated protein kinase (MAPK), both positive regulators of chondrogenic differentiation. Inactivation of PKC-alpha and p38 MAPK by specific inhibitors abrogated chondrogenesis stimulated by both TGF-beta3 and Wnt-5a. Similarly, partial reduction in TGF-beta3-induced Wnt-5a expression by small interfering RNA resulted in decreased activities of PKC-alpha and p38 MAPK, and abolished the chondro-stimulatory effect of TGF-beta3. Collectively, these findings indicate that Wnt-5a, a non-canonical Wnt, can mediate the chondro-stimulatory effect of TGF-beta3 through upregulation of PKC-alpha and p38MAPK signaling.


Initiation of ER Body Formation and Indole Glucosinolate Metabolism by the Plastidial Retrograde Signaling Metabolite, MEcPP.
Plants have evolved tightly regulated signaling networks to respond and adapt to environmental perturbations, but the nature of the signaling hub(s) involved have remained an enigma. We have previously established that methylerythritol cyclodiphosphate (MEcPP), a precursor of plastidial isoprenoids and a stress-specific retrograde signaling metabolite, enables cellular readjustments for high-order adaptive functions. Here, we specifically show that MEcPP promotes two Brassicaceae-specific traits, namely endoplasmic reticulum (ER) body formation and induction of indole glucosinolate (IGs) metabolism selectively, via transcriptional regulation of key regulators NAI1 for ER body formation and MYB51/122 for IGs biosynthesis). The specificity of MEcPP is further confirmed by the lack of induction of wound-inducible ER body genes as well as IGs by other altered methylerythritol phosphate pathway enzymes. Genetic analyses revealed MEcPP-mediated COI1-dependent induction of these traits. Moreover, MEcPP signaling integrates the biosynthesis and hydrolysis of IGs through induction of nitrile-specifier protein1 and reduction of the suppressor, ESM1, and production of simple nitriles as the bioactive end product. The findings position the plastidial metabolite, MEcPP, as the initiation hub, transducing signals to adjust the activity of hard-wired gene circuitry to expand phytochemical diversity and alter the associated subcellular structure required for functionality of the secondary metabolites, thereby tailoring plant stress responses.


Twenty years of endophthalmitis: Incidence, aetiology and clinical outcome.
To review the incidence, aetiology and outcomes of endophthalmitis during a 20-year period in a Norwegian university hospital. Single-centre retrospective review. Medical records of all patients admitted to Stavanger University Hospital with suspected endophthalmitis between January 1999 and December 2018 were reviewed. We identified 84 eyes of 81 patients. Postoperative endophthalmitis (PE) was seen in 64 eyes (76%), endogenous endophthalmitis in thirteen eyes (15%), trauma in four eyes (5%) and three eyes (4%) had keratitis-associated endophthalmitis. Administration of intravitreal injections (IVI) was the most common cause (30%), followed by cataract surgery (CS) (21%). Of 40238 IVI, 23 PE cases were identified (incidence, 0.057%; 95% confidence interval [CI] 0.036-0.086%). Of 39697 CS, 12 PE cases were identified (incidence, 0.030%; 95%CI 0.016-0.053%). After introduction of intracameral cefuroxime PE incidence after CS decreased from 0.10% in 1999-2003 to 0.015% in 2004-2018 (p = 0.003). Eighty-four per cent of organisms were Gram-positive. Coagulase-negative staphylococci accounted for 54% of culture-proven cases, and 89% of post-IVI culture-proven cases. Thirty eyes (36%) either regained their previous vision or lost ≤1 Early Treatment Diabetic Retinopathy Study line. One third of endophthalmitis cases had a favourable visual outcome of logMAR 0.2 or better. PE after IVI occurred in 1 in 1750 procedures, and was the most common cause of PE. The incidence of PE after CS has decreased >sixfold since 2003, to 1 in 6700 surgeries. A high proportion of low-virulence bacterial species may have contributed to the favourable visual outcome.


Alzheimer's disease, enzyme targets and drug discovery struggles: from natural products to drug prototypes.
Alzheimer's disease (AD) is an incapacitating neurodegenerative disease that slowly destroys brain cells. This disease progressively compromises both memory and cognition, culminating in a state of full dependence and dementia. Currently, AD is the main cause of dementia in the elderly and its prevalence in the developed world is increasing rapidly. Classic drugs, such as acetylcholinesterase inhibitors (AChEIs), fail to decline disease progression and display several side effects that reduce patient's adhesion to pharmacotherapy. The past decade has witnessed an increasing focus on the search for novel AChEIs and new putative enzymatic targets for AD, like β- and γ-secretases, sirtuins, caspase proteins and glycogen synthase kinase-3 (GSK-3). In addition, new mechanistic rationales for drug discovery in AD that include autophagy and synaptogenesis have been discovered. Herein, we describe the state-of-the-art of the development of recent enzymatic inhibitors and enhancers with therapeutic potential on the treatment of AD.


Electrical and memory properties of Si3N4 MIS structures with embedded Si nanocrystals.
Memory structures with an embedded sheet of separated Si nanocrystals were prepared by low pressure chemical vapour deposition using a Si3N4 control layer and different Si2O2 or Si3N4 tunnel layers. It was obtained that Si nanocrystals improve the charging behaviour of the MNOS structures. Memory window width of 1.3 V and 2.0 V were obtained for pulse amplitudes of +/-9 V and +/-10 V, 100 ms, respectively. The extrapolated memory window after 10 years is about 15% of its initial value.


Apelin inhibits an endothelium-derived hyperpolarizing factor-like pathway in rat cerebral arteries.
Apelin has complex vasomotor actions inasmuch as the peptide may cause either vasodilation or vasoconstriction depending on the vascular bed and experimental conditions. In cerebral arteries, apelin inhibits endothelium-dependent relaxations mediated by nitric oxide (NO); however, its effects on relaxation to other endothelium-derived substances (e.g. prostacyclin, endothelium-derived hyperpolarizing factors(s) (EDHF)) are unknown. The present study was designed to determine effects of apelin on endothelium-dependent relaxations that are independent of NO in rat cerebral arteries. In arterial rings contracted with 5-HT, A23187 caused endothelium-dependent relaxation that was unaffected by inhibitors of eNOS, guanylyl cyclase or cyclooxygenase, but was attenuated by MS-PPOH, a selective inhibitor of cytochrome P450 catalyzed synthesis of epoxyeicosatrienoic acids (EETs) and by 14,15-EE(Z)E, an EET-receptor antagonist. Apelin inhibited A23187-induced relaxation, as well as relaxations evoked by exogenous 11,12- and 14,15-EET. These effects of apelin were mimicked by the selective BKCa channel blocker, iberiotoxin. The APJ receptor antagonist, F13A abolished the effects of apelin on A23187-induced relaxations. Both 11,12- and 14,15-EET also increased BKCa channel current density in isolated cerebral artery smooth muscle cells, effects that were inhibited in a similar manner by apelin and iberiotoxin. These findings provide evidence that apelin impairs endothelium-dependent relaxation of cerebral arteries by inhibiting an NO-independent pathway (i.e. "EDHF-like") involving activation of smooth muscle cell BKCa channels by endothelium-derived EETs. Inhibition of such pathway may create an environment favoring vasoconstriction in cerebral arteries.


Molecular mechanism of SSR128129E, an extracellularly acting, small-molecule, allosteric inhibitor of FGF receptor signaling.
The fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) signaling network plays an important role in cell growth, survival, differentiation, and angiogenesis. Deregulation of FGFR signaling can lead to cancer development. Here, we report an FGFR inhibitor, SSR128129E (SSR), that binds to the extracellular part of the receptor. SSR does not compete with FGF for binding to FGFR but inhibits FGF-induced signaling linked to FGFR internalization in an allosteric manner, as shown by crystallography studies, nuclear magnetic resonance, Fourier transform infrared spectroscopy, molecular dynamics simulations, free energy calculations, structure-activity relationship analysis, and FGFR mutagenesis. Overall, SSR is a small molecule allosteric inhibitor of FGF/FGFR signaling, acting via binding to the extracellular part of the FGFR.


Association of physical fitness with cognitive function in the community-dwelling older adults.
Cognitive function generally declines with the aging process. Although the association of physical fitness with cognitive function has been proved, how many and how well the physical fitness components are linked to cognitive function is not clear. This study aimed to examine the association of physical fitness with cognitive function, and find out which aspects of physical fitness components are the most closely related to cognitive function in community-dwelling older adults. This cross-sectional study was conducted from March to July 2019. The sample consisted of 107 older people in the community with a mean age of 71.7 ± 5.0 years. The cognitive function of the participants was measured by a Chinese version of the Mini-Mental State Examination (MMSE). Several physical fitness items including grip strength, 5-repetition sit-to-stand, timed up and go, sit and reach, one-leg balance with the eye open, and 6-min walk were measured to reflect muscle strength, muscle endurance, agility, flexibility, balance, and cardiopulmonary endurance, respectively. The correlation analysis showed that the grip strength and the 6-min walk were positively related to cognitive function (r = 0.42 and 0.35, P < 0.05), while the 5-repetition sit-to-stand was negatively associated with cognitive function (r = -0.43, P < 0.01) adjusting for sex, age and years of education. It was also found that the mean values of physical fitness items including grip strength and 6-min walk were significantly lower, and 5-repetition sit-to-stand and timed up and go were significantly greater in the older adults with cognitive impairment (MMSE score < 27) than those in the normal older adults (MMSE score ≥ 27) (P < 0.05). Stepwise regression analysis revealed that age, together with physical fitness items including grip strength and 6-min walk can explain the cognitive function in older adults. The findings suggest that there is an association between physical fitness and cognitive function, and the grip strength and 6-min walk can help explain the cognitive function in community-dwelling older adults. More attention needs to be paid to the increase in physical fitness for preventing or improving the cognitive dysfunction of older persons in the community, and further longitudinal study is warranted.


High-fat diet negatively affects brain markers, cognitive behaviors, and noncognitive behaviors in the rTg4510 tau mouse model.
Alzheimer's disease (AD) drastically impacts cognitive and noncognitive behaviors in both humans and animal models. Two hallmark proteins in AD, amyloid-β plaques and tau neurofibrillary tangles, accumulate in regions of the brain critical for learning and memory, including the hippocampus. Poor dietary choices have been shown to exacerbate cognitive deficits seen in AD. In this study, we assessed the effects of a high-fat diet (HFD - 60 kcal% fat) on cognitive & noncognitive behaviors as well as on brain markers in the rTg4510 tau mouse model. While all mice learned the Morris Water Maze (MWM) task, it was noted that on the last day of acquisition female tau mice had a significantly higher latency to find the platform than male tau mice (p < 0.01). Mice given the HFD spent significantly less time in the target quadrant than those given a control diet (CD) (p < 0.05). Tau mice showed impaired burrowing (p < 0.05) and nesting behaviors (p < 0.001) compared to WT mice and HFD administration worsened burrowing in tau mice. Tau mice exhibited greater levels of glial fibrillary acidic protein (GFAP) (p < 0.05) and significantly less hippocampal cell density than WT mice (p < 0.001). We observed trends of HFD mice having greater levels of GFAP and greater average tangle size than CD mice. These results highlight the importance of dietary choices, especially in older populations more susceptible to AD and its effects.


Particle exposure and inhaled dose while commuting in Lisbon.
While commuting, individuals are exposed to high concentrations of urban air pollutants that can lead to adverse health effects. This study aims to assess commuters' exposure to particulate matter (PM) when travelling by car, bicycle, metro and bus in Lisbon. Mass concentrations of PM2.5 and PM10 were higher in the metro. On the other hand, the highest BC and PN0.01-1 average concentrations were found in car and bus mode, respectively. In cars, the outdoor concentrations and the type of ventilation appeared to affect the indoor concentrations. In fact, the use of ventilation led to a decrease of PM2.5 and PM10 concentrations and to an increase of BC concentrations. The highest inhaled doses were mostly observed in bicycle journeys, due to the longest travel periods combined with enhanced physical activity and, consequently, highest inhalation rates.


Detection, visualization and animation of abnormal anatomic structure with a deformable probabilistic brain atlas based on random vector field transformations.
This paper describes the design, implementation and preliminary results of a technique for creating a comprehensive probabilistic atlas of the human brain based on high-dimensional vector field transformations. The goal of the atlas is to detect and quantify distributed patterns of deviation from normal anatomy, in a 3-D brain image from any given subject. The algorithm analyzes a reference population of normal scans and automatically generates color-coded probability maps of the anatomy of new subjects. Given a 3-D brain image of a new subject, the algorithm calculates a set of high-dimensional volumetric maps (with typically 384(2) x 256 x 3 approximately 10(8) degrees of freedom) elastically deforming this scan into structural correspondence with other scans, selected one by one from an anatomic image database. The family of volumetric warps thus constructed encodes statistical properties and directional biases of local anatomical variation throughout the architecture of the brain. A probability space of random transformations, based on the theory of anisotropic Gaussian random fields, is then developed to reflect the observed variability in stereotaxic space of the points whose correspondences are found by the warping algorithm. A complete system of 384(2) x 256 probability density functions is computed, yielding confidence limits in stereotaxic space for the location of every point represented in the 3-D image lattice of the new subject's brain. Color-coded probability maps are generated, densely defined throughout the anatomy of the new subject. These indicate locally the probability of each anatomic point being unusually situated, given the distributions of corresponding points in the scans of normal subjects. 3-D MRI and high-resolution cryosection volumes are analyzed from subjects with metastatic tumors and Alzheimer's disease. Gradual variations and continuous deformations of the underlying anatomy are simulated and their dynamic effects on regional probability maps are animated in video format (on the accompanying CD-ROM). Applications of the deformable probabilistic atlas include the transfer of multi-subject 3-D functional, vascular and histologic maps onto a single anatomic template, the mapping of 3-D atlases onto the scans of new subjects, and the rapid detection, quantification and mapping of local shape changes in 3-D medical images in disease and during normal or abnormal growth and development.


Clinical predictors of descending necrotizing mediastinitis after deep neck infections.
To identify the clinical predictors of descending necrotizing mediastinitis (DNM) secondary to deep neck infections (DNIs) before treatment. Retrospective case series. We reviewed 73 patients with DNIs who had been treated with external drainage at our institute between April 2009 and March 2019. We divided these patients into either a DNI group without mediastinitis (n = 55) or a DNM group secondary to DNI (n = 18). We collected clinical data and compared them between the groups, conducting univariate and multiple logistic regression analysis to identify the predictors of DNM. We identified age, C-reactive protein (CRP), neutrophil percentage, lymphocyte percentage, neutrophil to lymphocyte ratio (NLR), presence of comorbidities, presence of gas, and abscess extension below the hyoid bone as statistically significant by univariate analysis. Moreover, multiple logistic regression analysis showed that age ≥55 years, NLR ≥13, and CRP ≥30 mg/dL were statistically significant. We identified age ≥55, NLR ≥13, and CRP ≥30 before DNI treatment as clinical predictors of a DNM complication. 4 Laryngoscope, 130:E567-E572, 2020.


If you are good you can have a cookie: How memories of childhood food rules link to adult eating behaviors.
The aim of this study was to determine whether memories of parental rules about food during childhood are linked to adult eating behaviors. An adult community sample (N=122) (56% female, 44% male) with a mean age of 44.6 years completed self-report measures of weight and dieting history, current eating patterns, and recollection of different types of rules about food from their parents. Three types of food rules were assessed: (a) rules which restrict intake of certain foods, (b) rules which encourage food intake, and (c) rules where food is used to reward or punish behavior. Binge eating and dietary restraint in adulthood are significantly related to participants' recollection of their parents using food to control their behavior in childhood. These results held true regardless of body mass index (BMI), ethnicity, age, or childhood weight status. This study suggests that some childhood food rules may have a long-lasting impact on eating behaviors. Further research on the impact of using food to reward and punish children's behavior is needed to inform recommendations to parents regarding the use of food for behavioral control.


Name or hum that tune: feeling of knowing for music.
This is the first reported research that explores the feeling of knowing (FOK) for musical stimuli. Subjects attempted to recall melodies and titles of musical pieces, made FOK ratings when recall failed, and then had a recognition test. With instrumental music (Experiment 1), more titles were recalled when melodies were given as cues than vice versa. With songs whose lyrics were not presented (Experiment 2), however, more melodies were recalled than were titles. For nonrecalled items, although the overall levels of recognition did not differ, FOK ratings were higher for titles than for melodies in Experiment 1, and the opposite pattern occurred in Experiment 2. In both experiments, the FOK ratings predicted melody recognition more accurately than they did title recognition.


Current-voltage relationship of the basolateral membrane of a tight epithelium.
The polyene antibiotic nystatin is used to reduce selectively to zero the apical membrane resistance of the rabbit descending colon, allowing the measurement of the current-voltage curve of the basolateral membrane. The I--V relationship is described by the Goldman-Hodgkin-Katz equations allowing calculation of PNa/PK, PCl/PK and PK for the basolateral membrane. Cs+ is found to block inward current (serosa to mucosa) in a manner similar to that found in excitable membranes.


Characterization and cytotoxicity studies of DPPC:M(2+) novel delivery system for cisplatin thermosensitivity liposome with improving loading efficiency.
A novel, metal ion-assisted drug-loading model, in which the metal ion was used to modify the microstructure of DPPC bilayers, has been developed to improve the drug-loading efficiency of cisplatin thermosensitivity liposomes. The reactions of dipalmitoyl phosphatidylcholine (DPPC) with diverse metal ions (Zn(2+), Cu(2+), Mn(2+) and Mg(2+)) yield four typical liposomes, which have been characterized by FT-IR, Raman and fluorescence techniques; the mechanism for higher drug encapsulation efficiency has also been investigated. In these prepared liposomes, the conformation of DPPC is changed due to the electrostatic interaction between the metal ions and phospholipid acyl group, leading to a closer arrangement of the lipid hydrocarbon chains and higher Tm of DPPC. As a result, the encapsulation efficiency of metal ion-assisted loading liposome is significantly higher than that of metal ion-free state. While for the release time, all four metal ion-assisted liposomes could be released within 10min at 42±0.5°C, which approach to the phase transition temperature, indicating that the introduction of metal ions into the DPPC bilayer membranes has no influence on the thermosensitivity of the liposome. Furthermore, the higher cytotoxicity of metal ion-bounded liposomes than that of free cisplatin solution suggests that high encapsulation efficiency can cause cytotoxicity increase. Hence, this work highlighted that metal ion-assisted loading model increased the encapsulation efficiency and cell cytotoxicity of cisplatin in thermosensitive liposomes with no obvious effects on sustained and temperature-dependent drug release.


Assessment of health-related quality of life in individuals with depressive symptoms: validity and responsiveness of the EQ-5D-3L and the SF-6D.
The EQ-5D and the SF-6D are examples of commonly used generic preference-based instruments for assessing health-related quality of life (HRQoL). However, their suitability for mental disorders has been repeatedly questioned. To assess the responsiveness and convergent validity of the EQ-5D-3L and SF-6D in patients with depressive symptoms. The data analyzed were from cardiac patients with depressive symptoms and were collected as part of the SPIRR-CAD (Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease) trial. The EQ-5D-3L and SF-6D were compared with the HADS (Hospital Anxiety and Depression Scale) and PHQ-9 (Patient Health Questionnaire) as disease-specific instruments. Convergent validity was assessed using Spearman's rank correlation. Effect sizes were calculated and ROC analysis was performed to determine responsiveness. Data from 566 patients were analysed. The SF-6D correlated considerably better with the disease-specific instruments (|rs|= 0.63-0.68) than the EQ-5D-3L (|rs|= 0.51-0.56). The internal responsiveness of the SF-6D was in the upper range of a small effect (ES: - 0.44 and - 0.47), while no effect could be determined for the EQ-5D-3L. Neither the SF-6D nor the EQ-5D-3L showed acceptable external responsiveness for classifying patients' depressive symptoms as improved or not improved. The ability to detect patients whose condition has deteriorated was only acceptable for the EQ-5D-3L. Overall, both the convergent validity and responsiveness of the SF-6D are better than those of the EQ-5D-3L in patients with depressive symptoms. The SF-6D appears, therefore, more recommendable for use in studies to evaluate interventions for this population.


Nitrogen-containing polyhydroxylated aromatics as HIV-1 integrase inhibitors: synthesis, structure-activity relationship analysis, and biological activity.
Four series of forty-five nitrogen-containing polyhydroxylated aromatics based on caffeic acid phenethyl ester were designed and synthesized as HIV-1 integrase (IN) inhibitors. Most of these compounds inhibited IN catalytic activities in low micromolar range. Among these new analogues, compounds 9e and 9f were the most potent IN inhibitors with IC(50) value of 0.7 μM against strand transfer reaction. Their key structure-activity relationships were also discussed.


A systematic review on the use of virtual patient and computer-based simulation for experiential pharmacy education.
Simulation use is rapidly expanding, with technologies like virtual patients (VPs) and computer-based simulation (CBS) allowing for educators to equip pharmacy students with the necessary skills that are aligned with the demands and expectations of a practicing pharmacy professional. These technologies enable pharmacy students to be exposed to challenging or infrequent patient case scenarios in an authentic pharmacy setting. This allows for the reinforcing of care processes and for techniques and crucial skills to be applied. To consolidate the existing evidence regarding the utilization of VPs and CBS in preparing and supporting students in pharmacy experiential education and evaluate the effectiveness of these approaches in enhancing student pharmacists' learning outcomes, including knowledge, skills, confidence, enjoyment, and engagement. Five electronic databases were searched using combined keyword and indexing terms (when available) with Boolean operators for the literature search. Studies that reported or investigated the use of VPs and CBS in pharmacy experiential education were included. Data on study design, demographics of participants, information on the interventions, course/skills, primary and secondary outcomes, and qualitative findings were extracted. A total of 911 unique articles were initially identified and filtered down to 19 articles fitting within the inclusion criteria. The selected 19 articles involved student pharmacists (Y1-Y5) and pre-registered pharmacists from ten countries. Simulation tools were used in various pharmacy courses, including Advanced Pharmacy Practice Experience (APPE), Advanced Pharmaceutical Care II, and Medication Management. Implementing these tools in pharmacy experiential education demonstrated a statistically significant improvement in student knowledge (p < 0.05). Most students agreed/strongly agreed that practicing with virtual patient cases enhanced their clinical reasoning, counseling skills, confidence in communication, and attitudes toward the courses. This systematic review supports the use of VPs and CBS in pharmacy experiential education and provides practical recommendations for educators including selecting suitable tools, implementing them strategically within courses, integrating them with existing activities, and considering financial and IT support.


Conserved pattern of OTP-positive cells in the paraventricular nucleus and other hypothalamic sites of tetrapods.
The paraventricular nucleus complex (Pa) is a component of central neural circuitry that regulates several homeostatic variables. The paraventricular nucleus is composed of magnocellular neurons that project to the posterior pituitary and parvicellular neurons that project to numerous sites in the central nervous system. According to the revised prosomeric model, the paraventricular nucleus is located caudal to the eye stalk along the rostrocaudal dimension of the dorsal hypothalamic alar plate. Caudally, the paraventricular nucleus abuts the prethalamus (prosomere 3), and the entire complex is flanked ventrally and dorsally by Dlx5-expressing domains of the alar plate. The homeodomain transcription factor Orthopedia (Otp) is expressed in several separate hypothalamic sites: the paraventricular nucleus, perimammillary region and arcuate nucleus. In this study, we compared Otp expression in the hypothalamus of mouse (Mus musculus), chick (Gallus gallus), frog (Rana perezi) and axolotol (Ambystoma mexicanum), using immunohistochemical and in situ hybridization techniques. In all cases, Otp-positive cells in the paraventricular nucleus were excluded from Dlx5-expressing adjacent domains. Other positive neuronal populations were observed in the arcuate nucleus and oblique perimammillary band. Expression in the medial amygdala appears to be continuous with the Otp-expressing paraventricular nucleus complex. This area is relatively unevaginated in the amphibian brains, barely evaginated in the chick, and fully evaginated in the mouse. These data led us to conclude that the expression pattern of Otp is topologically highly conserved in tetrapods and is plesiomorphic among chordates.


Chronic inflammatory rheumatism associated with Takayasu disease.
Takayasu disease is rarely associated with other autoimmune diseases. Therefore, the cases discussued herein are uncommon because we are reporting Takayasu disease associated with rheumatoid polyarthritis and spondylarthropathy. The first case concerns a 40-year-old woman presenting with Takayasu disease 11 years after the diagnosis of erosive and seronegative rheumatoid polyarthritis. The upper limb arteries and 1 lower limb artery were affected. The second 41-year-old case presented with ankylosing spondylitis that had been evolving for 10 years. Human leukocyte antigen-B27 typing was negative. Takayasu disease was revealed by severe high blood pressure. In both cases, radiologic examination revealed a typical aspect of the aorta and its main collaterals. Rarely in the literature have these associations been reported, and the pathology remains unknown.


RF atomic magnetometer array with over 40 dB interference suppression using electron spin resonance.
An unshielded array of 87Rb atomic magnetometers, operating close to 1 MHz, is used to attenuate interference by 42-48 dB. A sensitivity of 15 fT/Hz to a local source of signal is retained. In addition, a 2D spectroscopic technique, in which the magnetometers are repeatedly pumped and data acquired between pump times, enables a synchronously generated signal to be distinguished from an interfering signal very close in frequency; the timing and signal mimics what would be observed in a magnetic resonance echo train. Combining the interference rejection and the 2D spectroscopy techniques, a 100 fT local signal is differentiated from a 20 pT interference signal operating only 1 Hz away. A phase-encoded reference signal is used to calibrate the magnetometers in real time in the presence of interference. Key to the strong interference rejection is the accurate calibration of the reference signal across the array, obtained through electron spin resonance measurements. This calibration is found to be sensitive to atomic polarization, RF pulse duration, and direction of the excitation. The experimental parameters required for an accurate and robust calibration are discussed.


Motion-robust, blood-suppressed, reduced-distortion diffusion MRI of the liver.
To evaluate feasibility and reproducibility of liver diffusion-weighted (DW) MRI using cardiac-motion-robust, blood-suppressed, reduced-distortion techniques. DW-MRI data were acquired at 3T in an anatomically accurate liver phantom including controlled pulsatile motion, in eight healthy volunteers and four patients with known or suspected liver metastases. Standard monopolar and motion-robust (M1-nulled, and M1-optimized) DW gradient waveforms were each acquired with single-shot echo-planar imaging (ssEPI) and multishot EPI (msEPI). In the motion phantom, apparent diffusion coefficient (ADC) was measured in the motion-affected volume. In healthy volunteers, ADC was measured in the left and right liver lobes separately to evaluate ADC reproducibility between the two lobes. Image distortions were quantified using the normalized cross-correlation coefficient, with an undistorted T2-weighted reference. In the motion phantom, ADC mean and SD in motion-affected volumes substantially increased with increasing motion for monopolar waveforms. ADC remained stable in the presence of increasing motion when using motion-robust waveforms. M1-optimized waveforms suppressed slow flow signal present with M1-nulled waveforms. In healthy volunteers, monopolar waveforms generated significantly different ADC measurements between left and right liver lobes ( p = 0 . 0078 $$ p=0.0078 $$ , reproducibility coefficients (RPC) = 470 × 1 0 - 6 $$ 470\times 1{0}^{-6} $$ mm 2 $$ {}^2 $$ /s for monopolar-msEPI), while M1-optimized waveforms showed more reproducible ADC values ( p = 0 . 29 $$ p=0.29 $$ , RPC = 220 × 1 0 - 6 $$ \mathrm{RPC}=220\times 1{0}^{-6} $$ mm 2 $$ {}^2 $$ /s for M1-optimized-msEPI). In phantom and healthy volunteer studies, motion-robust acquisitions with msEPI showed significantly reduced image distortion ( p < 0 . 001 $$ p<0.001 $$ ) compared to ssEPI. Patient scans showed reduction of wormhole artifacts when combining M1-optimized waveforms with msEPI. Synergistic effects of combined M1-optimized diffusion waveforms and msEPI acquisitions enable reproducible liver DWI with motion robustness, blood signal suppression, and reduced distortion.


[A case of orbital apex syndrome due to aspergillus infection that avoided loss of visual acuity by optic canal decompression].
A 71-year-old woman was admitted to our hospital complaining of left orbital pain, headache, diplopia and left-sided ptosis, which she had suffered for two months. On examination, the patient had loss of visual acuity, left-sided ptosis, lateral gaze disturbance, and was diagnosed as having left orbital apex syndrome. An abnormal signal to the left orbital cone was detected on MRI. Serum β-D-glucan was increased, and serum Aspergillus antigen and antibody were both positive. Although antifungal drugs (voriconazole and liposomal amphotericin B) were administered, the symptoms deteriorated. The patient then underwent optic nerve decompression surgery and was treated with intravenous methylprednisolone, which gradually improved the patient's symptoms, Aspergillus hyphae were confirmed by pathological examination. To obtain good prognosis for patients with orbital apex syndrome associated with Aspergillus infection, optic nerve decompression surgery should be considered.


Ophthalmic manifestations of acute leukaemias: the ophthalmologist's role.
With evolving diagnostic and therapeutic advances, the survival of patients with acute leukaemia has considerably improved. This has led to an increase in the variability of ocular presentations in the form of side effects of the treatment and the ways leukaemic relapses are being first identified as an ocular presentation. Leukaemia may involve many ocular tissues either by direct infiltration, haemorrhage, ischaemia, or toxicity due to various chemotherapeutic agents. Ocular involvement may also be seen in graft-versus-host reaction in patients undergoing allogeneic bone marrow transplantation, or simply as increased susceptibility to infections as a result of immunosuppression that these patients undergo. This can range from simple bacterial conjunctivitis to an endophthalmitis. Leukaemia can present as pathology in the adnexae, conjunctiva, sclera, cornea, anterior chamber, iris, lens, vitreous, retina, choroid, and optic nerve. Recognition of the varied ocular presentations is also important in assessing the course and prognosis of leukaemia. We have presented a systematic approach taking each part of the eye in turn and outlining how leukaemia has been shown to affect it.


Pharmacological therapy for the prevention of cardiovascular events in patients with myocardial infarction with non-obstructed coronary arteries (MINOCA): Insights from a multicentre national registry.
To assess the effect of pharmacological therapy on long-term prognosis of patients with MINOCA. In this retrospective multicentre cohort study involving 9 Hub Hospitals across Italy we enrolled consecutive patients 18 years and older with diagnosis of MINOCA discharged from 1st March 2012 to 31st March 2018. Data on baseline characteristics and pharmacological therapy at discharge (ACEI/ARB, angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists; ASA, acetylsalicylic acid; beta-blockers; CCB, calcium-channel blockers; DAPT, dual anti-platelet therapy; statins), were collected systematically. The primary endpoint (PE) of the study was a composite of all cause death or acute myocardial infarction or acute coronary syndrome or heart failure leading to hospitalization or stroke. A total of 621 patients were included (mean [SD] age 65.1 [13.9] years; 344 [55.4%] female), of whom 106 (17.1%) experienced PE, including 27 patients (4.3%) who died. Multivariable analysis, after correction for all baseline differences, showed a significant association between pharmacological therapy at discharge and an increased risk of PE for aspirin (HR[95%CI] = 2.47[1.05-5.78], adjusted p = 0.04), whereas beta-blockers were associated with a significant benefit (HR[95%CI] = 0.49 [0.31-0.79], adjusted p = 0.02). The use of beta-blockers was significantly associated to a less frequent occurrence of adverse outcomes at long-term follow-up among patients with MINOCA, whereas ASA displayed a potentially harmful impact on prognosis. The findings in the study may be relevant for the design of future studies which should take into account possible heterogeneity among MINOCA patients.


Alcohol dependence in a community sample of Aboriginal and Torres Strait Islander Australians: harms, getting help and awareness of local treatments.
Few studies have examined links between current alcohol dependence and specific harms among Indigenous Australians. We investigated these associations as well as help seeking for drinking, awareness of local treatments and recommendations to help family or friends cut down or stop drinking in two Indigenous communities. A representative sample of Indigenous Australians was surveyed in one urban and one remote community in South Australia. Data were collected via the Grog Survey App. Participants were dependent if they reported two or more symptoms of alcohol dependence (ICD-11). Pearson chi-square tests were used to describe relationships between employment by gender, and dependence by awareness of medicines and local treatment options. Multivariate logistic regressions were used to predict the odds of dependent drinkers experiencing harms and getting help for drinking, controlling for age, gender, schooling and income. A total of 775 Indigenous Australians took part in the study. After controlling for confounders, dependent drinkers were nearly eight times more likely to report a harm and nearly three times more likely to get help for their drinking-compared with non-dependent drinkers. Participants recommended accessing local support from an Aboriginal alcohol and other drugs worker, or a detoxification/ rehabilitation service. More support and funding is needed for Indigenous Australians to ensure local treatment options for dependent drinkers are readily available, appropriate and accessible. Involvement of local Aboriginal or Torres Strait Islander health professionals in delivery of care can help ensure that it is appropriate to an individual's culture and context.


Effort/reward imbalance and sedentary lifestyle: an observational study in a large occupational cohort.
To investigate the association between effort/reward imbalance (ERI) at work and sedentary lifestyle. Cross sectional data from the ongoing Finnish Public Sector Study related to 30,433 women and 7718 men aged 17-64 were used (n = 35,918 after exclusion of participants with missing values in covariates). From the responses to a questionnaire, an aggregated mean score for ERI in a work unit was assigned to each participant. The outcome was sedentary lifestyle defined as <2.00 metabolic equivalent task (MET) hours/day. Logistic regression with generalised estimating equations was used as an analysis method to include both individual and work unit level predictors in the models. Adjustments were made for age, marital status, occupational status, job contract, smoking, and heavy drinking. Twenty five per cent of women and 27% of men had a sedentary lifestyle. High individual level ERI was associated with a higher likelihood of sedentary lifestyle both among women (odds ratio (OR) = 1.08, 95% CI 1.01 to 1.16) and men (OR = 1.17, 95% CI 1.02 to 1.33). These associations were not explained by relevant confounders and they were also independent of work unit level job strain measured as a ratio of job demands and control. A mismatch between high occupational effort spent and low reward received in turn seems to be associated with an increased risk of sedentary lifestyle, although this association is relatively weak.


An evaluation of the efficacy of monensin against Fasciola hepatica in the albino rat.
The in vivo efficacy of monensin against Fasciola hepatica was determined in the albino rat. The results were variable, with monensin generally showing greater activity against juvenile (two-week-old) than adult (12-week-old) flukes. Significant (p less than 0.005) reductions in worm burdens were obtained only following treatment of adult flukes with 2 X 10 mg/kg monensin (52.9% efficacy), and of juvenile flukes with 1 X 10 mg/kg (42.4% efficacy) and 2 X 10 mg/kg (56.23% efficacy). Monensin administered in the diet (200 ppm) had a negligible effect on juvenile and adult fluke burdens. Prophylactic treatment of rats with monensin (100 ppm) produced a 45.5% efficacy, but this was not statistically significant. At doses of 1 X 5 mg/kg and 2 X 2.5 mg/kg, monensin had little effect on egg output by F. hepatica. No clear relationship was established between egg output and worm burden, and so faecal egg counting was not a reliable indicator of fluke burdens in the rat.


Modeling Complex Neurological Diseases with Stem Cells: A Study of Bipolar Disorder.
The pathogenesis of bipolar disorder (BPD) is unknown. Using human-induced pluripotent stem cells (hiPSCs) to unravel pathological mechanisms in polygenic diseases is challenging, with few successful studies to date. However, hiPSCs from BPD patients responsive to lithium have offered unique opportunities to discern lithium's mechanism of action and hence gain insight into BPD pathology. By profiling the proteomics of BPD-hiPSC-derived neurons, we found that lithium alters the phosphorylation state of collapsin response mediator protein-2 (CRMP2). The "set point" for the ratio of pCRMP2:CRMP2 is elevated uniquely in hiPSC-derived neurons from lithium responsive (Li-R) BPD patients, but not other psychiatric and neurological disorders. Utilizing neurons differentiated from human patient stem cells as an in vitro platform, we were able to elucidate the mechanism driving the pathogenesis and pathophysiology of lithium-responsive BPD, heretofore unknown. Importantly, the findings in culture were validated in human postmortem material as well as in animal models of BPD behavior. These data suggest that the "lithium response pathway" in BPD governs CRMP2's phosphorylation, which regulates cytoskeletal organization, particularly in dendritic spines, leading to modulated neural networks that may underlie Li-R BPD pathogenesis. This chapter reviews the methodology of leveraging a functional agent, lithium, to identify unknown pathophysiological pathways with hiPSCs and how to translate this disease modeling approach to other neurological disorders.


Determinants of gender in Jack-in-the-pulpit: the influence of plant size and reproductive history.
Jack-in-the-pulpit, Arisaema triphyllum, is a perennial forest herb with the ability to change sex. At two sites in upstate New York, plant sex was correlated with plant size: males were smaller than females, nonflowering plants were smaller than males. Changes in plant size were accompanied by changes in sex. Sex change occurred quite frequently; at one site, 8% of nonflowering plants, 64% of males, and 63% of females changed their sex from one season to the next. The probability that a plant will change size and sex between years was altered by artificial defoliation and by the production of seeds, but was not affected by supplementing plants with nutrient fertilizer. Discriminant analysis indicated that several historical factors significantly affected plant sex: a model including the variables of current plant size, previous year's plant size, and previous year's sex was significantly better at predicting the current sex of individuals than was a model containing only current plant size. However, even the consideration of these three variables left up to a third of the plants misclassified with respect to gender. This analysis explains in part why plants at the two sites changed sex at different sizes, but it is likely that other factors-e.g. genetic differences-are involved.


Fetal blood sampling.
We sought to review indications, technical aspects, risks, and recommendations for fetal blood sampling (FBS). A systematic review was performed using MEDLINE, PubMed, EMBASE, and Cochrane Library using the terms "fetal blood sampling," "percutaneous umbilical blood sampling," and "cordocentesis." The search was restricted to English-language articles published from 1966 through July 2012. Priority was given to articles reporting original research, in particular randomized controlled trials, although review articles and commentaries also were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document. Evidence reports and guidelines published by organizations or institutions such as the National Institutes of Health, Agency for Health Research and Quality, American Congress of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine were also reviewed, and additional studies were located by reviewing bibliographies of identified articles. Grade (Grading of Recommendations Assessment, Development, and Evaluation) methodology was employed for defining strength of recommendations and rating quality of evidence. Consistent with US Preventive Task Force guidelines, references were evaluated for quality based on the highest level of evidence. Ultrasound-guided FBS is the only procedure that provides direct access to the fetal circulation. When invasive testing is planned for suspected severe fetal anemia or thrombocytopenia, we recommend FBS as the procedure of choice, with availability of immediate transfusion if confirmed. We recommend against the use of FBS for indications in which other less invasive, and therefore lower risk, alternatives are available. The overall success rate of FBS is high, and blood samples can be obtained in >98% of patients. We suggest that counseling for FBS include discussion about the potential risk of FBS that may include, but may not be limited to: bleeding from puncture site (20-30%); fetal bradycardia (5-10%); pregnancy loss (≥1.3%, depending on indication, gestational age, and placental penetration); and vertical transmission of hepatitis or human immunodeficiency virus. We recommend that FBS be performed by experienced operators at centers with expertise in invasive fetal procedures when feasible.


Cooperative Chloride Hydrogel Electrolytes Enabling Ultralow-Temperature Aqueous Zinc Ion Batteries by the Hofmeister Effect.
Aqueous zinc ion batteries have high potential applicability for energy storage due to their reliable safety, environmental friendliness, and low cost. However, the freezing of aqueous electrolytes limits the normal operation of batteries at low temperatures. Herein, a series of high-performance and low-cost chloride hydrogel electrolytes with high concentrations and low freezing points are developed. The electrochemical windows of the chloride hydrogel electrolytes are enlarged by > 1 V under cryogenic conditions due to the obvious evolution of hydrogen bonds, which highly facilitates the operation of electrolytes at ultralow temperatures, as evidenced by the low-temperature Raman spectroscopy and linear scanning voltammetry. Based on the Hofmeister effect, the hydrogen-bond network of the cooperative chloride hydrogel electrolyte comprising 3 M ZnCl2 and 6 M LiCl can be strongly interrupted, thus exhibiting a sufficient ionic conductivity of 1.14 mS cm-1 and a low activation energy of 0.21 eV at -50 °C. This superior electrolyte endows a polyaniline/Zn battery with a remarkable discharge specific capacity of 96.5 mAh g-1 at -50 °C, while the capacity retention remains ~ 100% after 2000 cycles. These results will broaden the basic understanding of chloride hydrogel electrolytes and provide new insights into the development of ultralow-temperature aqueous batteries.