Veno-venous extracorporeal membrane oxygenation for perioperative management of infective endocarditis after COVID-19 with acute respiratory distress syndrome: a case report.

BACKGROUND: Infective endocarditis (IE) is a rare cardiovascular complication in patients with coronavirus disease 2019 (COVID-19). IE after COVID-19 can also be complicated by acute respiratory distress syndrome (ARDS); however, the guidelines for the treatment of such cases are not clear. Here, we report a case of perioperative management of post-COVID-19 IE with ARDS using veno-venous extracorporeal membrane oxygenation (V-V ECMO). CASE PRESENTATION: The patient was a 40-year-old woman who was admitted on day 18 of COVID-19 onset and was administered oxygen therapy, remdesivir, and dexamethasone. The patient's condition improved; however, on day 24 of hospitalization, the patient developed hypoxemia and was admitted to the intensive care unit (ICU) due to respiratory failure. Blood culture revealed Corynebacterium striatum, and transesophageal echocardiography revealed vegetation on the aortic and mitral valves. Valve destruction was mild, and the cause of respiratory failure was thought to be ARDS. Despite continued antimicrobial therapy, ARDS did not improve the patient's condition, and valve destruction progressed; therefore, surgical treatment was scheduled on day 13 of ICU admission. After preoperative consultation with the team, a decision was made to initiate V-V ECMO after the patient was weaned from CPB, with concerns about further worsening of her respiratory status after surgery. The patient returned to the ICU with transition to V-V ECMO, and her circulation remained stable. The patient was weaned off V-V ECMO on postoperative day 33 and discharged from the ICU on postoperative day 47. CONCLUSIONS: ARDS may occur in patients with IE after COVID-19. Owing to concerns about further exacerbation of pulmonary damage, the timing of surgery should be comprehensively considered. Preoperatively, clinicians should discuss perioperative ECMO introduction and configuration.

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS).

Background: Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is increasingly recognized as a clinicoradiological syndrome. Its etiology is diverse, encompassing a variety of triggers, including infections and metabolic abnormalities. Uniquely, MERS may present with psychiatric symptoms, such as delirium, visual hallucinations, and catatonia, posing diagnostic challenges. The variability of these neuropsychiatric symptoms necessitates early diagnosis through magnetic resonance imaging (MRI) to avoid prolonged antipsychotic treatment. Case Presentation: This report details a case of MERS in a 39-year-old male. The patient initially presented with headache, sore throat, and abnormal laboratory results: leukocytosis, neutrophilia with a left shift, elevated C-reactive protein (CRP) levels, and hyponatremia. On the fourth day of admission, he developed severe anxiety and restlessness, exhibited thoughts of death, and reported experiencing vivid hallucinations upon closing his eyes. MRI revealed a hyperintense lesion in the corpus callosum. A lumbar puncture showed no increase in cell count or protein. The patient showed a positive response to treatment with antibiotics and olanzapine, demonstrating rapid symptomatic improvement. A follow-up MRI on the 11th day showed complete resolution of the brain lesions. Six months later, no neurological or psychiatric sequelae were noted. The patient's clinical progression and imaging findings led to a definitive diagnosis of MERS. Conclusion: The early presentation of symptoms such as restlessness, hallucinations, and death ideation played a critical role in diagnosing MERS, with early MRI examination being instrumental in both diagnosis and preventing prolonged antipsychotic medication use.

Arterial oxygen pressure during veno-venous extracorporeal membrane oxygenation may be increased by advancing the tip of the drainage cannula into the superior vena cava: a case report.

A simple and robust method for veno-venous extracorporeal membrane oxygenation (V-V ECMO) involves a drainage cannula into the inferior vena cava via the femoral vein (FV) and a reinfusion cannula into the right atrium (RA) via the internal jugular vein (IJV) (F-J configuration). However, with this method, the arterial oxygen (PaO2) is said to remain below 100 mmHg.Since recently, in our ICU, to prevent drainage failure, we apply a modification from the commonly practiced F-J configuration by advancing the tip of the drainage cannula inserted via the FV into the superior vena cava (SVC) and crossing the reinfusion cannula inserted via the IJV in the RA (F(SVC)-J(RA) configuration). We experienced that this modification can be associated with unexpectedly high PaO2 values, which here we investigated in detail.Veno-arteriovenous ECMO was induced in a 65-year-old male patient who suffered from repeated cardiac arrest due to acute respiratory distress syndrome. His chest X-ray images showed white-out after lung rest setting, consistent with near-absence of self-lung ventilation. Cardiac function recovered and the system was converted to F(SVC)-J(RA) configuration, after which both PaO2 and partial pressure of pulmonary arterial oxygen values remained high above 200 mmHg. Transesophageal echocardiography could not detect right-to-left shunt, and more efficient drainage of the native venous return flow compared to common F-J configuration may explain the increased PaO2.Although the F(SVC)-J(RA) configuration is a small modification of the F-J configuration, it seems to provide a revolutionary improvement in the ECMO field by combining robustness/simplicity with high PaO2 values.

Association of circulating histone H3 and high mobility group box 1 levels with postoperative prognostic indicators in intensive care unit patients: a single-center observational study.

Objectives: Damage associated molecular patterns (DAMPs) levels are associated with sepsis severity and prognosis. Histone and high mobility group box 1 (HMGB1) levels are also potential indicators of prognosis. We investigated the relationship between serum histone H3 and HMGB1 levels and the illness severity score and prognosis in postoperative patients. Methods: Postoperative serum histone H3 and HMGB1 levels in 39 intensive care unit (ICU) patients treated at our institution were measured. The correlation between peak histone H3 and HMGB1 levels in each patient and clinical data (age, sex, surgical time, length of ICU stay, and survival after ICU discharge), which also included the patients' illness severity score, was examined. Results: Histone H3 but not HMGB1 levels were positively correlated with surgical time, the Sequential Organ Failure Assessment score, the Japanese Association for Acute Medicine acute phase disseminated intravascular coagulation diagnosis score, and the length of ICU stay. Both histone H3 and HMGB1 levels were negatively correlated with age. However, survival post-ICU discharge was not correlated with histone H3 or HMGB1 levels. Conclusions: Histone H3 levels are correlated with severity scores and the length of ICU stay. Serum histone H3 and HMGB1 levels are elevated postoperatively. These DAMPs, however, are not prognostic indicators in postoperative ICU patients.

Long-chain alkenes and alkadienes of eight lichen species collected in Japan.

The hydrocarbons of eight lichen species isolated in Japan were analyzed, and diverse mono-, di-, and tri-unsaturated alkenes were detected. The positions of the double bonds of C17 alkadienes (heptadecadiene) and C17-C20 alkenes were determined by mass spectrometry of their dimethyl disulfide adducts. We found that the six lichens containing green algal photobionts were distinguished by the presence of 1,8-heptadecadiene, 6,9-heptadecadiene, and 8- and 7-heptadecenes. On the other hand, 1-octadecene, 4-octadecene, and 5-nonadecene were the major alkene components of the two lichens with cyanobacterial photobionts. These alkadienes and alkenes were present in large quantities in the lichen samples. In particular, 1,8-heptadecadiene accounted for more than 90% of the total alkenes in all four lichens containing it. Our results provide new insights into the origin of C17 alkadienes and C17-C20 alkenes in environmental and geological samples, and these alkenes can potentially be applied as lichen biomarkers.

Structural variation in the glycogen synthase kinase 3ß and brain-derived neurotrophic factor genes in Japanese patients with bipolar disorders.

BACKGROUND: Lithium is the first-line drug for the treatment of bipolar disorders (BDs); however, not all patients responded. Glycogen synthase kinase (GSK) 3ß and brain-derived neurotrophic factor (BDNF) play a role in the therapeutic action of lithium. Since structural variations were reported in these genes, it is possible that these genomic variations may be involved in the therapeutic responses to lithium. METHOD: Fifty patients with BDs and 50 healthy subjects (mean age 55.0 ± 15.0 years; M/F 19/31) participated. We examined structural variation of the GSK3ß and BDNF genes by real-time PCR. We examined the influence of structural variation of these genes on the therapeutic responses to lithium and the occurrence of antidepressant-emergent affective switch (AEAS). The efficacy of lithium was assessed using the Alda scale, and AEAS was evaluated using Young Mania Rating Scale. RESULTS: Although we examined structural variations within intron II and VII of the GSK3® gene and from the end of exon IV to intron IV and within exon IX of the BDNF gene, no structural variation was found in BDs. Whereas 5 of 50 patients exhibited three copies of the genomic region within exon IV of the BDNF gene, all healthy subjects had two copies. No difference in the therapeutic efficacy of lithium was found between patients with three and two copies. No difference in the occurrence of AEAS was found between the two groups. CONCLUSION: The amplification of the BDNF gene influenced neither the therapeutic responses to lithium nor the occurrence of AEAS.

The synaptic pathology of cognitive life
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Prospective, community-based studies allow evaluation of associations between cognitive functioning and synaptic measures, controlled for age-related pathologies. Findings from >400 community-based participants are reviewed. Levels of two presynaptic proteins, complexin-I (inhibitory terminals), and complexin-II (excitatory terminals) contributed to cognitive variation from normal to dementia. Adding the amount of protein-protein interaction between two others, synaptosome-associated protein-25 and syntaxin, explained 6% of overall variance. The presynaptic protein Munc18-1 long variant was localized to inhibitory terminals, and like complexin-I, was positively associated with cognition. Associations depended on Braak stage, with the level of complexin-I contributing nearly 15% to cognitive variation in stages 0-II, while complexin-II contributed 7% in stages V-VI. Non-denaturing gels identified multiple soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein-protein (SNARE) complexes in frontal and in temporal lobes, making specific contributions to cognitive functions. Multiple mechanisms of presynaptic plasticity contribute to cognitive function during aging.
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Los estudios prospectivos realizados en la comunidad permiten evaluar las asociaciones entre el funcionamiento cognitivo y las mediciones sinápticas, controladas por patologías relacionadas con la edad. Se revisan los hallazgos de más de 400 participantes de la comunidad. Los niveles de dos proteínas presinápticas, complexina-I (terminales inhibitorios) y complexina-II (terminales excitatorios) contribuyeron a la variación cognitiva entre la situación normal y la demencia. Al agregar la interacción proteína-proteína entre la proteína 25 asociada al sinaptosoma y la sintaxina, se explicó el 6% de la varianza general. La variante larga de la proteína presináptica Munc 18-1 se localizó en terminales inhibitorios y, al igual que la complexina I, se asoció positivamente con la cognición. Las asociaciones dependían de la etapa de Braak, siendo el nivel de complexina-I responsable de casi el 15% de la variación cognitiva para las etapas 0-II, mientras que la complexina-II contribuyó con el 7% en las etapas V-VI. Los geles no desnaturalizantes identificaron múltiples complejos de proteína-proteína del receptor de proteína de unión al factor sensible a N-etilmaleimida soluble (SNARE) en los lóbulos frontales y temporales, los cuales contribuyen de manera específica a las funciones cognitivas. Durante el envejecimiento participan múltiples mecanismos de plasticidad presináptica en la función cognitiva.

Des études prospectives communautaires permettent d'évaluer des associations entre le fonctionnement cognitif et des mesures synaptiques, contrôlées pour des pathologies liées à l'âge. Des résultats issus de plus de 400 participants communautaires sont analysés. Les taux de complexine-I (terminaisons inhibitrices) et de complexine-II (terminaisons excitatrices), deux protéines présynaptiques, contribuent aux variations cognitives de la normalité à la démence. S'y ajoute l'interaction protéine-protéine entre la protéine SNAP25 (protéine 25 associée au synaptosome) et la syntaxine, expliquant 6 % de la variance totale. Le variant long de la protéine pré-synaptique Munc18-1 est localisé sur les terminaisons inhibitrices et associé positivement à la cognition, comme la complexine-I. Les associations dépendent du stade Braak, le taux de complexine-I étant responsable de presque 15 % de la variation cognitive pour les stades 0-II alors que la complexine-II contribue pour 7 % aux stades V-VI. Des gels non dénaturants identifient des complexes multiples protéine-protéine SNARE (Soluble N-ethylmaleimide-sensitive factor Attachment protein REceptor) dans les lobes frontaux et temporaux, contribuant spécifiquement aux fonctions cognitives. Au cours du vieillissement, de nombreux mécanismes de plasticité présynaptique participent à la fonction cognitive.

Complexin 2 regulates secretion of immunoglobulin in antibody-secreting cells.

INTRODUCTION: Complexins (CPLXs), initially identified in neuronal presynaptic terminals, are cytoplasmic proteins that interact with the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) complex to regulate the fusion of vesicles to the plasma membrane. Although much is known about CPLX function in neuronal synaptic vesicle exocytosis, their distribution and role in immune cells are still unclear. In this study, we investigated CPLX2 knockout (KO) mice to reveal the role of CPLXs in exocytosis of lymphocytes. METHODS: We examined the expression of CPLXs and SNAREs in lymphocytes. To study the effect of CPLXs on the immune system in vivo, we analyzed the immune phenotype of CPLX2 KO mice. Furthermore, antibodies secretion from the peritoneal cavity, spleen, and bone marrow cells of wild-type (WT) and CPLX2 KO mice were determined. RESULTS: CPLX2 was detected in B cells but not in T cells, while other CPLXs and SNAREs were expressed at a similar level in both B and T cells. To clarify the function of CPLX2 in B lymphocytes, serum concentrations of immunoglobulin G (IgG), IgA, IgM, and IgE were measured in WT and CPLX2 KO mice using enzyme-linked immunosorbent assay. The level of IgM, which mainly consists of natural antibodies, was higher in KO mice than that in WT mice, while the levels of other antibodies were similar in both types of mice. Additionally, we found that spontaneous secretion of IgM and IgG1 was enhanced from the splenic antibody-secreting cells (ASCs) of CPLX2 KO mice. CONCLUSION: Our data suggest that CPLX2 inhibits spontaneous secretion of IgM and IgG1 from splenic ASCs. This study provides new insight into the mechanism of antibody secretion of ASCs.

Enhancement of the Olfactory Response by Lipocalin Cp-Lip1 in Newt Olfactory Receptor Cells: An Electrophysiological Study.

Previously, we have detected the expression of 2 lipocalin genes (lp1 and lp2) in the olfactory epithelium of the Japanese newt Cynops pyrrhogaster. Recombinant proteins of these genes (Cp-Lip1 and Cp-Lip2, respectively) exhibited high affinities to various odorants, suggesting that they work like the odorant-binding proteins (OBPs). However, the physiological functions of OBP generally remain inconclusive. Here, we examined the effect of Cp-Lip1 on the electrophysiological responses of newt olfactory receptor cells. We observed that the electro-olfactogram induced by the vapor of an odorant with high affinity to Cp-Lip1 appeared to increase in amplitude when a tiny drop of Cp-Lip1 solution was dispersed over the olfactory epithelium. However, the analysis was difficult because of possible interference by intrinsic components in the nasal mucus. We subsequently adopted a mucus-free condition by using suction electrode recordings from isolated olfactory cells, in which impulses were generated by puffs of odorant solution. When various concentration (0-5 µM) of Cp-Lip1 was mixed with the stimulus solution of odorants highly affinitive to Cp-Lip1, the impulse frequency increased in a concentration-dependent manner. The increase by Cp-Lip1 was seen more evidently at lower concentration ranges of stimulus odorants. These results strongly suggest that Cp-Lip1 broadens the sensitivity of the olfactory cells toward the lower concentration of odorants, by which animals can detect very low concentration of odorants.

Musical disability in children with autism spectrum disorder.

Although enhanced musical ability is reported in individuals with autism spectrum disorders (ASD), this observation may be uncommon, and reports of auditory processing deficits suggest musical ability may be impaired. We hypothesized that musical ability would be impaired in children with ASD, that the severity of impairment would correlate with cognitive dysfunction, and with clinical features of illness. We evaluated 26 children with ASD and 27 typically developing (TD) children using the Montreal Battery of Evaluation of Amusia short version (MBEA-s) as well as cognitive tests and clinical evaluations of ASD symptomatology. Mean scores on the MBEA-s were significantly lower in children with ASD. MBEA-s scores did not correlate with cognitive test results in either ASD or TD children, and did not correlate with symptom severity in ASD children. For the ASD children only, the combination of hyperactivity/inattention and working memory resulted in a significant contribution to the variance in the MBEA-s score. The findings indicate that musical ability appears to be impaired in children with ASD, and assessment of musical ability may complement cognitive tests and measures of symptomatology in characterizing the shared neural substrates for these dysfunctions in ASD.

Lithium levels in tap water and psychotic experiences in a general population of adolescents.

Recently, several epidemiologic studies have reported that lithium in drinking water may be associated with lower rates of suicide mortality, lower incidence of dementia, and lower levels of adolescents' depression and aggression at the population level. However, to our knowledge, no study has investigated lithium level in tap water in relation to psychotic experiences in a general population of adolescents. This is the first study to investigate this using a large dataset. Information on psychotic experiences, distress associated with these experiences, and depressive symptoms were collected in 24 public junior high schools in Kochi Prefecture in Japan. Samples were collected from sources that supplied drinking water to schools, and lithium levels were measured using atomic absorption spectrophotometry. The association of lithium levels with psychotic experiences, considering distress as a degree of severity, was examined using an ordinal logistic regression model with schools and depressive symptoms as random effects. In total, 3040 students responded to the self-reporting questionnaire (response rate: 91.8%). Lithium levels in tap water were inversely associated with psychotic experiences (p = 0.021). We concluded that lithium level in tap water was inversely associated with psychotic experiences among a general population of adolescents and may have a preventive effect for such experiences and distress.

Frontotemporal dysregulation of the SNARE protein interactome is associated with faster cognitive decline in old age.

The molecular underpinnings associated with cognitive reserve remain poorly understood. Because animal models fail to fully recapitulate the complexity of human brain aging, postmortem studies from well-designed cohorts are crucial to unmask mechanisms conferring cognitive resistance against cumulative neuropathologies. We tested the hypothesis that functionality of the SNARE protein interactome might be an important resilience factor preserving cognitive abilities in old age. Cognition was assessed annually in participants from the Rush "Memory and Aging Project" (MAP), a community-dwelling cohort representative of the overall aging population. Associations between cognition and postmortem neurochemical data were evaluated in functional assays quantifying various species of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) machinery in samples from the inferior temporal (IT, n = 154) and middle-frontal (MF, n = 174) gyri. Using blue-native gel electrophoresis, we isolated and quantified several types of complexes containing the three SNARE proteins (syntaxin-1, SNAP25, VAMP), as well as the GABAergic/glutamatergic selectively expressed complexins-I/II (CPLX1/2), in brain tissue homogenates and reconstitution assays with recombinant proteins. Multivariate analyses revealed significant associations between IT and MF neurochemical data (SNARE proteins and/or complexes), and multiple age-related neuropathologies, as well as with multiple cognitive domains of MAP participants. Controlling for demographic variables, neuropathologic indices and total synapse density, we found that temporal 150-kDa SNARE species (representative of pan-synaptic functionality) and frontal CPLX1/CPLX2 ratio of 500-kDa heteromeric species (representative of inhibitory/excitatory input functionality) were, among all the immunocharacterized complexes, the strongest predictors of cognitive function nearest death. Interestingly, these two neurochemical variables were associated with different cognitive domains. In addition, linear mixed effect models of global cognitive decline estimated that both 150-kDa SNARE levels and CPLX1/CPLX2 ratio were associated with better cognition and less decline over time. The results are consistent with previous studies reporting that synapse dysfunction (i.e. dysplasticity) may be initiated early, and relatively independent of neuropathology-driven synapse loss. Frontotemporal dysregulation of the GABAergic/glutamatergic stimuli might be a target for future drug development.

Musical deficits and cortical thickness in people with schizophrenia.

Investigation of acquired amusia caused by brain damage suggested that cortical lesions of the right hemisphere contributed to musical deficits. We previously reported reduced musical ability in schizophrenia; these deficits were correlated with clinical manifestations such as cognitive dysfunction and negative symptoms. However, the neural substrate underlying the musical disability in schizophrenia remains unclear. We investigated the relationship between musical deficits and cortical thickness in patients with schizophrenia using structural MRI. We recruited 24 patients (13 males; age mean=45.9years old), and 22 controls (14 males, age mean=43.5years old). Musical ability was assessed with the Montreal Battery for Evaluation of Amusia (MBEA), cognitive function with the Brief Assessment of Cognition in Schizophrenia (BACS) and clinical features of illness with the Positive and Negative Syndrome Scale (PANSS). MRI Images were acquired and processed using FreeSurfer. Surface-based analysis showed that thinner cortex in left temporal and inferior frontal region was associated with lower musical ability in schizophrenia. In contrast, in controls thicker cortex in the left supramarginal region was correlated with lower musical ability. These results shed light on the clinical pathology underlying the associations of musical ability, cognitive dysfunction and negative symptoms in patients with schizophrenia.

Cold-induced metabolic conversion of haptophyte di- to tri-unsaturated C37 alkenones used as palaeothermometer molecules.

The cosmopolitan marine haptophyte alga Emiliania huxleyi accumulates very long-chain (C37-C40) alkyl ketones with two to four trans-type carbon-carbon double bonds (alkenones). These compounds are used as biomarkers of haptophytes and as palaeothermometers for estimating sea-surface temperatures in biogeochemistry. However, the biosynthetic pathway of alkenones in algal cells remains enigmatic, although it is well known that the C37 tri-unsaturated alkenone (K37:3) becomes dominant at low temperatures, either by desaturation of K37:2 or by a separate pathway involving the elongation of tri-unsaturated alkenone precursors. Here, we present experimental evidence regarding K37:3 synthesis. Using the well-known cosmopolitan alkenone producer E. huxleyi, we labelled K37:2 with 13C by incubating cells with 13C-bicarbonate in the light at 25 °C under conditions of little if any K37:3 production. After stabilisation of the 13C-K37:2 level by depleting 13C-bicarbonate from the medium, the temperature was suddenly reduced to 15 °C. The 13C-K37:2 level rapidly decreased, and the 13C-K37:3 level increased, whereas the total 13C-K37 level-namely [K37:2 + K37:3]-remained constant. These 13C-pulse-chase-like experimental results indicate that 13C-K37:2 is converted directly to 13C-K37:3 by a desaturation reaction that is promoted by a cold signal. This clear-cut experimental evidence is indicative of the existence of a cold-signal-triggered desaturation reaction in alkenone biosynthesis.

Lithium Levels in Tap Water and the Mental Health Problems of Adolescents: An Individual-Level Cross-Sectional Survey.

OBJECTIVE: We investigated the association between lithium level in tap water and mental health problems, including depressive symptoms, anxiety, and aggressive and suicidal behaviors, in a general population of adolescents using a large individual-level dataset. METHODS: A school-based, cross-sectional survey was conducted in Kochi Prefecture in Japan between 2008 and 2009. Students in 24 public junior high schools were asked to anonymously complete a self-report questionnaire. The main outcome measures were mental health problems, including those on the 12-item General Health Questionnaire, interpersonal violence, bullying, destructive behavior, self-harm, and suicidal ideation. Samples were collected from sources that supplied drinking water to schools, and lithium levels were measured using atomic absorption spectrophotometry. The associations of lithium levels with mental health problems were examined using a generalized linear mixed model with schools as the fixed effect. Potential confounding factors were also added into the model. RESULTS: A total of 3,040 students among 3,311 students responded to the self-report questionnaire (response rate, 91.8%). The mean lithium concentration in tap water was 0.48 µg/L (SD = 0.52; range, 0.01 to 2.10; skewness = 2.01; kurtosis = 4.04), and it was relatively low compared with previous studies. In multivariable regression analysis, lithium level in tap water had an inverse association with depressive symptoms (P = .02) and interpersonal violence (P = .02) but not with suicidal behaviors (suicidal ideation, P = .82; self-harm, P = .46). CONCLUSIONS: Lithium level in tap water was inversely associated with depressive symptoms and interpersonal violence among a general population of adolescents and may have antidepressive and antiaggressive effects.

Presynaptic proteins complexin-I and complexin-II differentially influence cognitive function in early and late stages of Alzheimer's disease.

Progressive accumulation of Alzheimer's disease-related pathology is associated with cognitive dysfunction. Differences in cognitive reserve may contribute to individual differences in cognitive function in the presence of comparable neuropathology. The protective effects of cognitive reserve could contribute differentially in early versus late stages of the disease. We investigated presynaptic proteins as measures of brain reserve (a subset of total cognitive reserve), and used Braak staging to estimate the progression of Alzheimer's disease. Antemortem evaluations of cognitive function, postmortem assessments of pathologic indices, and presynaptic protein analyses, including the complexins I and II as respective measures of inhibitory and excitatory terminal function, were assayed in multiple key brain regions in 418 deceased participants from a community study. After covarying for demographic variables, pathologic indices, and overall synapse density, lower brain complexin-I and -II levels contributed to cognitive dysfunction (P < 0.01). Each complexin appeared to be dysregulated at a different Braak stage. Inhibitory complexin-I explained 14.4% of the variance in global cognition in Braak 0-II, while excitatory complexin-II explained 7.3% of the variance in Braak V-VI. Unlike other presynaptic proteins, complexins did not colocalize with pathologic tau within neuritic plaques, suggesting that these functional components of the synaptic machinery are cleared early from dystrophic neurites. Moreover, complexin levels showed distinct patterns of change related to memory challenges in a rat model, supporting the functional specificity of these proteins. The present results suggest that disruption of inhibitory synaptic terminals may trigger early cognitive impairment, while excitatory terminal disruption may contribute relatively more to later cognitive impairment.

Impacts of nicorandil on infarct myocardium in comparison with nitrate: assessed by cardiac magnetic resonance imaging.

In this pilot study, we compared the infarct and edema size in acute myocardial infarction (MI) patients treated by nicorandil with those treated by nitrate, using cardiac magnetic resonance (CMR) imaging. Fifty-two acute MI patients who underwent emergency percutaneous coronary intervention (PCI) were enrolled, and were assigned to receive nicorandil or nitrate at random just before reperfusion. For the assessment of infarct and edema areas, short-axis delayed enhancement (DE) and T2-weight (T2w) CMR images were acquired 6.1 ± 2.4 days after the onset of MI. A significant correlation was observed between the peak creatinine kinase (CK) level and the infarct size on DE CMR (r = 0.62, p < 0.05), as well as the edema size on T2w CMR (r = 0.70, p < 0.05) in patients treated by nicorandil (28 patients). A similar correlation was seen between the peak CK level and the infarct size on DE CMR (r = 0.84, p < 0.05), as well as the edema size on T2w CMR (r = 0.84, p < 0.05) in patients treated by nitrate (24 patients). The maximum CK level was significantly lower in patients treated by nicorandil rather than nitrate (1991 ± 1402, 2785 ± 2121 IU/L, respectively, p = 0.03). Both the edema size on T2w CMR and the infarct size on DE CMR were significantly smaller in patients treated by nicorandil rather than nitrate (17.7 ± 9.9, 21.9 ± 13.7 %; p = 0.03, 10.3 ± 6.0, 12.7 ± 6.9 %, p = 0.03, respectively). The presence and amount of microvascular obstruction were significantly smaller in patients treated by nicorandil rather than nitrate (39.2, 64.7 %; p = 0.03; 2.2 ± 1.3, 3.4 ± 1.5 cm(2); p = 0.02, respectively). Using CMR imaging, we demonstrated that the complementary use of intravenously and intracoronary administered nicorandil during PCI favorably acts more on the damaged myocardium after MI than nitrate. We need a further powered prospective study on the use of nicorandil.

Whole-Genome Sequence of Aquamicrobium sp. Strain SK-2, a Polychlorinated Biphenyl-Utilizing Bacterium Isolated from Sewage Sludge.

Here, we report the whole-genome sequence of Aquamicrobium sp. strain SK-2, a bacterium which can use 2,2',4,4',5,5'-hexachlorobiphenyl as the sole carbon source for its growth. An approximately 9.23-Mb genome sequence of SK-2 will greatly facilitate research efforts regarding the study of the polychlorinated biphenyl (PCB) degradation mechanism.

Hippocampal subfield volumes in first episode and chronic schizophrenia.

BACKGROUND: Reduced hippocampal volume in schizophrenia is a well-replicated finding. New imaging techniques allow delineation of hippocampal subfield volumes. Studies including predominantly chronic patients demonstrate differences between subfields in sensitivity to illness, and in associations with clinical features. We carried out a cross-sectional and longitudinal study of first episode, sub-chronic, and chronic patients, using an imaging strategy that allows for the assessment of multiple hippocampal subfields. METHODS: Hippocampal subfield volumes were measured in 34 patients with schizophrenia (19 first episode, 6 sub-chronic, 9 chronic) and 15 healthy comparison participants. A subset of 10 first episode and 12 healthy participants were rescanned after six months. RESULTS: Total left hippocampal volume was smaller in sub-chronic (p = 0.04, effect size 1.12) and chronic (p = 0.009, effect size 1.42) patients compared with healthy volunteers. The CA2-3 subfield volume of chronic patients was significantly decreased (p = 0.009, effect size 1.42) compared to healthy volunteers. The CA4-DG volume was significantly reduced in all three patient groups compared to healthy group (all p < 0.005). The two affected subfield volumes were inversely correlated with severity of negative symptoms (p < 0.05). There was a small, but statistically significant decline in left CA4-DG volume over the first six months of illness (p = 0.01). CONCLUSIONS: Imaging strategies defining the subfields of the hippocampus may be informative in linking symptoms and structural abnormalities, and in understanding more about progression during the early phases of illness in schizophrenia.

n-Nonacosadienes from the marine haptophytes Emiliania huxleyi and Gephyrocapsa oceanica.

The hydrocarbons in cultures of marine haptophytes Emiliania huxleyi NIES837 and Gephyrocapsa oceanica NIES1315 were analyzed, and nonacosadienes and hentriacontadienes were detected as the major compounds in both strains. C29 and C31 monoenes and di-, tri- and tetra-unsaturated C33 alkenes were also detected as minor compounds but not C37 and C38 alkenes. The positions of the double bonds in the C29 and C31 alkenes were determined by mass spectrometry of their dimethyl disulfide (DMDS) adducts. Among the four C29 alkenes identified, the most abundant isomer was 2,20-nonacosadiene, and the other three compounds were 1,20-nonacosadiene, 3,20-nonacosadiene and 9-nonacosene, respectively. Hitherto, 2,20-nonacosadiene and 3,20-nonacosadiene were unknown to be natural products. The double bond at the n-9 (ω9) position in these C29 alkenes is hypothesized to be derived from precursors of unsaturated fatty acids possessing an n-9 double bond, such as (9Z)-9-octadecenoic acid. Nonacosadienes have the potential for being used as distinct haptophyte biomarkers.