Dearomative [2 + 1] Spiroannulation of Bromophenols with Electron-Deficient Alkenes.

A base-assisted dearomative [2 + 1] spiroannulation of p/o-bromophenols with activated olefins (methylenemalonates) to construct various cyclopropyl spirocyclohexadienone skeletons is reported. Furthermore, several other halophenols (X = Cl, I) were also tolerated in this process. Control experiments reveal a dearomative Michael addition of phenols at their halogenated positions to methylenemalonates, followed by intramolecular radical-based SRN1 dehalogenative cyclopropanation. However, according to the density functional theory (DFT) calculations, an SN2 dehalogenative cyclopropanation with the same low activation energy barrier should not be excluded. The utility of this method is showcased by gram-scale syntheses and transformations of the dearomatized products.

Abnormal expression of miR-3653-3p, caspase 1, IL-1ß in peripheral blood of schizophrenia.

Schizophrenia (SCZ) is a chronic, highly relapsing, severe mental disorder with an unclear etiology. Cytokine-mediated neuroimmune abnormalities have been repeatedly revealed. IL-1ß was reported to play a vital role in expanding the inflammatory response. However, the underlying molecular mechanism is poorly understood. In this study, we found that miR-3653-3p with the NLRP3 binding site in Targetscan was differentially expressed in miRNA high-throughput sequencing in schizophrenia (SCZ), and indeed, its downregulation in SCZ peripheral blood was also verified by RT-qPCR (P-value = 0.015). Furthermore, we found that the mRNAs of caspase 1 and IL-1ß are elevated in people who suffer from SCZ (P = 0.044 and P = 0.001, respectively). Moreover, the interaction of NLRP3, Caspase1, and IL-1ß was found in the peripheral blood of patients with SCZ. The expression level of miR-3653-3p was negatively correlated with NLRP3 and IL-1ß mRNA contents (r = 0.487, P = 0.04 and r = 0.508, P = 0.037, respectively). NLRP3 mRNA was positively correlated with caspase1 mRNA. Meanwhile, the expression of miR-3653-3p was also negatively correlated with negative symptom subscores of PANSS (r = 0.450, P = 0.046). IL-1ß mRNA is positively correlated with the total scores of PANSS (r = 0.690, P = 0.002) and the sub-scores of general psychopathology of PANSS (r = 0.583, P = 0.014). Additionally, a significant positive relationship exists between IL-1ß and the total duration (r = 0.638, P = 0.006). We found that the combination of miR-3653-3p, caspase 1, and IL-1ß have better diagnostic values. The results indicate that miR-3653-3p, caspase 1, and IL-1ß can potentially be biomarkers of SCZ, identifying negative symptoms or a chronic course. A further understanding of the involvement of IL-1ß in SCZ may be a crucial molecular effector for the chronic course to intervene.

Peripheral Blood Leukocyte RNA-Seq Identifies a Set of Genes Related to Abnormal Psychomotor Behavior Characteristics in Patients with Schizophrenia.

BACKGROUND Schizophrenia is a multigene disease with a complex etiology and different clinical manifestations. It is of great significance to understand the etiology and pathogenesis of schizophrenia patients from different clinical dimensions and to interpret the potential molecular changes of schizophrenia patients from different clinical dimensions. MATERIAL AND METHODS RNA-Seq was performed on peripheral blood leukocytes of 50 patients with schizophrenia and 50 healthy controls. Phenotypic information of patients with schizophrenia was collected during blood sampling. Differentially expressed genes (DEGs) were screened by the edgeR package of R software. To better analyze the correlation between DEG expression values, explore the potential association between differential genes and clinical dimensions of schizophrenia, and identify hub genes, we constructed a DEG co-expression network using weighted gene co-expression network analysis (WGCNA). RESULTS We provide the transcription profiles of peripheral blood leukocytes in patients with schizophrenia and found a gene module (including 89 genes) closely related to the clinical dimension of abnormal psychomotor behavior in schizophrenia. CONCLUSIONS The findings enhance our understanding of the biological processes of schizophrenia, enabling us to identify specific clinical dimensions of genes for diagnosis and prognostic markers and possibly for targeted therapy.

Prolactin and Thyroid Stimulating Hormone (TSH) Levels and Sexual Dysfunction in Patients with Schizophrenia Treated with Conventional Antipsychotic Medication: A Cross-Sectional Study.

BACKGROUND This study aimed to investigate the relationship between serum profiles of prolactin and thyroid stimulating hormone (TSH) and sexual dysfunction in patients with schizophrenia treated with conventional antipsychotic medication. MATERIAL AND METHODS A hospital-based cross-sectional study included 118 patients, age range 18-57 years (55 men, 63 women), with a confirmed diagnosis of schizophrenia. All patients were stable after antipsychotic treatment. Serum levels of hormones, including prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone, testosterone, thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3) and free thyroxine (FT4), were detected in venous blood. The Positive and Negative Syndrome Scale (PANSS) score was used to measure symptom severity of patients with schizophrenia. The Mandarin Chinese version of the Arizona Sexual Experience Scale (ASEX), a 5-item scale, was used to measure sexual function. RESULTS There were 66 patients (55.9%) who had hyperprolactinemia, the prevalence of hyperprolactinemia was markedly higher in the sexual dysfunction group than the non-sexual dysfunction group (91.8% vs. 17.5%) (P<0.001). Mean prolactin levels were significantly increased in patients with sexual dysfunction compared with the patients without sexual dysfunction (P<0.001), with a higher incidence in female patients. Subclinical hypothyroidism and hyperprolactinemia were found to be independently associated with sexual dysfunction, and an increased PANSS negative score was an independent risk factor for the development of sexual dysfunction. CONCLUSIONS The incidence of sexual dysfunction was significantly increased in patients with schizophrenia. Hyperprolactinemia and subclinical hypothyroidism were associated with sexual dysfunction, especially in female patients.

Effect of Early Inhibition of Toll-Like Receptor 4 on Hippocampal Plasticity in a Neonatal Rat Model of Hypoxic-Ischemic Brain Damage.

Hippocampal plasticity is closely related to physiological brain functions such as learning and memory. However, the effect of toll-like receptor 4 (TLR4) activation on hippocampal plasticity after neonatal hypoxic-ischaemic brain damage (HIBD) remains unclear. In our study, seven-day-old rat pups were randomly categorised into three groups: control, hypoxic-ischemia (HI), and HI + TAK-242 (TAK-242). The pups were ligated in the left common carotid artery and then subjected to hypoxia to establish the neonatal HIBD model.The expression of the TLR4 in the left hippocampus of the HI group was increased compared to the control group, while TAK-242 reduced the expression level at 3 days after HIBD. Additionally, TAK-242 reversed the increased Zea-Longa score, increased the left/right hippocampal weight ratio, and increased the number of Nissl-positive neurons in the hippocampal CA1 region compared to HI group at 3 days after HIBD. Pre-injection of TAK-242 alleviated the decrease in PSD95, Aggrecan and NR1, BDNF, CREB, and pCREB expression in the hippocampus at 24 h after HIBD. It also alleviated the decrease in PSD95, BDNF, and NR2A/NR1 expression in the hippocampus at 7 days after HIBD. Furthermore, Pre-injection of TAK-242 alleviated the decrease in NR2A/NR1 expression at 21 days after HIBD. Finally,TAK-242 increased the percentage of third-grade dendritic mushroom spines processes in the basal and apical segments of neurons in the hippocampal CA1 region at 21 days after HIBD.Therefore, we conclude that preinhibition of TLR4 prior to neonatal HIBD improved the plasticity of the hippocampus.

Association between a changeable lifestyle, sedentary behavior, and suicide risk: A systematic review and meta-analysis.

BACKGROUND: Suicide and self-injury have become increasingly serious public health crises. Yet current evidence about the association between sedentary behavior (SB) and suicide is inconclusive. We explore the relationship between SB and suicide behavior to provide intervention measures to change the risk factors of the latter. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science from database inception to September 10, 2023. Adjusted odds ratios (ORs) with 95 % confidence intervals (CIs) were used as effect measures. Subgroup analysis was conducted based on gender, regions and countries, age, and study type. RESULTS: A total of 13 studies were included. According to the meta-analysis of suicide type, compared with individuals without sedentary behavior, individuals with sedentary behavior have a higher risk of suicide attempt (OR = 1.23, 95%CI: 1.15-1.37, p < 0.001), suicide ideation (OR = 1.47, 95%CI:1.28-1.68, p < 0.001) and suicide plan (OR = 1.30, 95%CI:1.16-1.44, p < 0.001). We conducted multiple subgroup analyses for different suicidal behaviors. The analysis found that SB can increase the risk of suicide attempt in different subgroups of different genders, different research centers, Africa, and adolescents; SB can increase the risk of suicide ideation in the subgroups of different genders and ages, different research centers, Asia and Africa; SB can increase the risk of suicide plan in the subgroups of different genders, multi-center study, Africa, and adolescents. LIMITATIONS: Future research should focus on objective SB measurement and explore its dose-response relation and time limit. CONCLUSION: A sedentary lifestyle is associated with suicide behavior risk, with varying effects across age groups and regions, as evidenced in both single-center and multi-center studies.

Modifiable Lifestyle, Sedentary Behaviors and the Risk of Frailty: A Univariate and Multivariate Mendelian Randomization Study.

This research conducted a two-sample univariate and multivariate Mendelian Randomization (MR) analysis to explore the causal link between different types of leisure sedentary behavior (LSB) and frailty. Independent instrumental variables significantly associated with sedentary behaviors (p < 5 × 10-8) are obtained from a genome-wide association study (GWAS) of 422,218 individuals, and Frailty Index (FI) are derived from the latest GWAS dataset of 175,226 individuals. MR analysis is conducted using inverse variance weighting, MR-Egger, weighted median, simple mode, and weighted mode, supplemented by MRAPSS. Univariate MR revealed that sedentary behaviors such as watching television increased the risk of frailty (OR, 1.271; 95% CI: 1.202-1.345; p = 6.952 × 10-17), as sedentary driving behaviors are done (OR, 1.436; 95% CI: 1.026-2.011; p = 0.035). Further validation through APSS, taking into account cryptic relatedness, stratification, and sample overlap, maintained the association between television viewing and increased frailty risk (OR, 1.394; 95% CI: 1.266-1.534; p = 1.143 × 10-11), while the association with driving dissipated. In multivariate inverse variance weighted (IVW) analysis, after adjusting for C-reactive protein (CRP) levels, television Sedentary behavior (SB) inversely affected frailty (OR, 0.782; 95% CI: 0.724-0.845; p = 4.820 × 10-10). This study indicates that televisio SB significantly increases the risk of frailty, suggesting potential biological heterogeneity behind specific sedentary activities. This process may interact with inflammation, influencing the development of frailty.

Exploring the association of addiction-related genetic factors with non-suicidal self-injury in adolescents.

Background: Non-suicidal self-injury (NSSI) is self-injurious behavior without suicidal intent commonly seen in the adolescent population and poses a serious threat to the life safety of adolescents. Related researches suggest a possible correlation between addiction and the occurrence of NSSI. This study aimed to explore the correlation between addiction and NSSI from a molecular biological perspective by analyzing the differential expression of addiction-related genes in NSSI patients. Methods: (1) The association between addiction and non-suicidal self-injury in a Chinese adolescent population was verified with the help of questionnaires on substance and non-substance addictions and non-suicidal self-injury among 1,329 adolescents in China, (2) Screening for key genes associated with addiction by bioinformatics analysis, and (3) RT-qPCR experiment was performed to validate key genes and Receiver Operating Characteristic curves were plotted for target genes. Results: (1) Substance and non-substance addictions were all significantly correlated with non-suicidal self-injury, (2) Four target genes: SERPINA3, SLC14A1, RPS6 and RPS3A were screened by bioinformatics technique, and (3) Relative quantitative analysis by RT-qPCR revealed that the expression levels of SLC14A1 (p < 0.01), RPS6 (p < 0.05) and RPS3A (p < 0.01) were significantly higher in NSSI patients than in healthy controls. Conclusion: (1) The significant association between addiction and NSSI exists in the Chinese adolescent population and (2) Addiction-related genes SLC14A1, RPS6, and RPS3A are differentially expressed in adolescents with NSSI. The genes have the potential to become biological markers for the diagnosis of NSSI.

Self-esteem and professional identity among male nurses and male nursing students: mediating roles of perceived prejudice and psychological distress.

Introduction: There are not enough nurses around the world, and there are even fewer male nurses. It has not been easy for men to become nurses because of stereotypes about the roles of men and women in the workplace, which lead to prejudice and discrimination. This study explored how the self-esteem of male nurses and male nursing students affects their professional identity in an environment where stereotypes and social prejudice exist. This study also examined the differences of relevant variables in different sociodemographic characteristics of the research subjects in a Chinese social context. Methods: By purposive and snowball sampling, 464 male nurses and male nursing students were surveyed through questionnaires from November 2021 to January 2022. Data analysis was performed using SPSS 25.0 and PROCESS Macro 3.3. Results: Self-esteem could indirectly affect professional identity through perceived prejudice and psychological distress. Nonetheless, self-esteem still had a significant direct effect on professional identity. The total mediating effect accounted for 32.816% of the total effect, and the direct effect accounted for 67.184% of the total effect. Also of note was that 81.7% of participants reported experiencing psychological distress. Discussion: To improve the professional identity of male nurses and male nursing students, nursing educators and administrators should do the following: protect and improve their self-esteem; take steps to reduce social prejudice against them; value their mental health and alleviate their psychological distress.

Whole transcriptome analysis reveals dysregulation of molecular networks in schizophrenia.

To characterize the regulatory relationships between different types of transcripts and the altered molecular networks in schizophrenia (SCZ), we performed a whole transcriptome study by quantifying mRNAs, long noncoding RNAs (lncRNAs), miRNAs, and circular RNAs (circRNAs) in the same individuals simultaneously. A total of 807 dysregulated genes showed differential expression in SCZ cases compared with controls. Network-based analysis revealed dysregulation of molecular networks in SCZ. Finally, integration of the transcriptome data with published data identified promising SCZ candidate genes. Our study reveals that dysregulated molecular networks and regulatory relationships between different types of transcript may have a role in SCZ.

Brain Imaging Study on the Pathogenesis of Depression & Therapeutic Effect of Selective Serotonin Reuptake Inhibitors.

OBJECTIVE: Predefining the most effective treatment for patients with depressive disorders remains a problem. We will examine the differential brain regions of gray matter (GM) in major depressive disorder (MDD) patients and the relationship between changes in their volume and the efficacy of early antidepressant treatment using magnetic resonance imaging (MRI). METHODS: 159 never-medicated patients with first-episode MDD and 53 normal control subjects (NCs) were enrolled. The brains were scanned by MRI and measured with the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and after 2 weeks of treatment with selective serotonin reuptake inhibitor (SSRI)s, and the non-responder group and responder group were obtained. The patients were analyzed by voxel-based morphological (VBM) and SPSS software. Receiver operator characteristics (ROC) analysis was performed for the difference between the responder group and the non-responder group in the differential brain regions, and Pearson correlations were computed between volume size and HAMD score reduction rate. RESULTS: Smaller GM volume of the right superior temporal gyrus (STG), and the orbital parts of the right medial frontal gyrus and right inferior frontal gyrus were observed in MDD versus the NCs. The non-responder group demonstrated a significant volume reduction at the right STG compared with the responders, but no corresponding change in orbital part of right medial frontal gyrus and right inferior frontal gyrus. ROC analysis showed that Accuracy=71.2%. There was a positive correlation between the STG gray matter volume and the HAMD-17 score reduction rate (r=0.347, p=0.002). CONCLUSION: The study results confirmed the local changes in brain structure in MDD and may initially predict the early treatment response produced by SSRIs as antidepressants.

Effects of risperidone on blood levels of interleukin-6 in schizophrenia: A meta-analysis.

BACKGROUND: To evaluate the association between risperidone use and interleukin-6 (IL-6) levels by conducting a meta-analysis of controlled before-and-after studies. METHODS: Studies were identified through a systematic search of PubMed and Embase. The mean and standardized differences were extracted to calculate the standardized mean differences. IL-6 levels were compared in patients with schizophrenia before and after risperidone treatment. RESULTS: Ten studies were included in the final meta-analysis. The primary findings from our study suggest that there was a significant decrease in serum IL-6 levels after risperidone treatment (P = .021). A subgroup analysis revealed the sources of heterogeneity. The sensitivity analysis indicated that the results were stable, and no publication bias was observed. CONCLUSIONS: The present meta-analysis provides evidence that risperidone can significantly reduce IL-6 levels in schizophrenia. IL-6 is a potential biomarker of the pathophysiology and clinical processes of schizophrenia.

Does single gene expression omnibus data mining analysis apply for only tumors and not mental illness? A preliminary study on bipolar disorder based on bioinformatics methodology.

BACKGROUND: Bipolar disorder (BD), a common kind of mood disorder with frequent recurrence, high rates of additional comorbid conditions and poor compliance, has an unclear pathogenesis. The Gene Expression Omnibus (GEO) database is a gene expression database created and maintained by the National Center for Biotechnology Information. Researchers can download expression data online for bioinformatics analysis, especially for cancer research. However, there is little research on the use of such bioinformatics analysis methodologies for mental illness by downloading differential expression data from the GEO database. METHODS: Publicly available data were downloaded from the GEO database (GSE12649, GSE5388 and GSE5389), and differentially expressed genes (DEGs) were extracted by using the online tool GEO2R. A Venn diagram was used to screen out common DEGs between postmortem brain tissues and normal tissues. Functional annotation and pathway enrichment analysis of DEGs were performed by using Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses, respectively. Furthermore, a protein-protein interaction network was constructed to identify hub genes. RESULTS: A total of 289 DEGs were found, among which 5 of 10 hub genes [HSP90AA1, HSP90AB 1, UBE2N, UBE3A, and CUL1] were identified as susceptibility genes whose expression was downregulated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that variations in these 5 hub genes were obviously enriched in protein folding, protein polyubiquitination, apoptotic process, protein binding, the ubiquitin-mediated proteolysis pathway, and protein processing in the endoplasmic reticulum pathway. These findings strongly suggested that HSP90AA1, UBE3A, and CUL 1, which had large areas under the curve in receiver operator curves (P < .05), were potential diagnostic markers for BD. CONCLUSION: Although there are 3 hub genes [HSP90AA1, UBE3A, and CUL 1] that are tightly correlated with the occurrence of BD, mainly based on routine bioinformatics methods for cancer-related disease, the feasibility of applying this single GEO bioinformatics approach for mental illness is questionable, given the significant differences between mental illness and cancer-related diseases.

Mental Health Status of Healthcare Workers in China for COVID-19 Epidemic.

Background: COVID-19 first appeared in China in December 2019, with a high rate of infectivity and morbidity, which brought tremendous psychological pressure to healthcare workers. Purpose: To understand the psychological health status of healthcare workers during the COVID-19 outbreak and decline, and to provide a theoretical reference for the future establishment of a psychological crisis intervention system. Methods: Healthcare workers were recruited using convenience sampling and snowball sampling methods, and the electronic version of the SCL-90 scale and a sociodemographic questionnaire were administered. In the pretest, a total of 5018 responses were collected; after six weeks, random sampling was performed. The SCL-90 and measures of other epidemic-related problems were administered, with 1570 responses received; then, the final data analysis was performed. Results: After six weeks, the post-test GSI score; SCL-90 total score; and PST, PSDI, O-C, I-S, DEP, ANX, PHOB, PAR, PSY, and HOS scores were significantly lower than the corresponding pretest scores (p < 0.05). The results by occupational category showed that the scores of nursing staff decreased significantly for 12 indexes and that the scores of the doctors and other hospital staff also significantly decreased. There was a significant difference between the pretest (50.78 ± 28.18) and post-test (45.00 ± 28.49) scores for the degree of worry about the epidemic. Healthcare workers believed that the top three aspects of life affected by the epidemic were economic problems (816 people), interpersonal communication problems (731 people), and mental health (728 people). Conclusion: Over the course of the epidemic, the item scores generally declined significantly. Therefore, during an outbreak period, attention should be paid to psychological crisis interventions for healthcare workers; problems caused by psychological pressure, and even other psychological conditions, can be significantly alleviated to reduce the probability of subsequent health problems.

Investigating aberrantly expressed microRNAs in peripheral blood mononuclear cells from patients with treatment­resistant schizophrenia using miRNA sequencing and integrated bioinformatics.

Treatment­resistant schizophrenia (TRS) is a common phenotype of schizophrenia that places a considerable burden on patients as well as on society. TRS is known for its tendency to relapse and uncontrollable nature, with a poor response to antipsychotics other than clozapine. Therefore, it is urgent to identify objective biological markers, so as to guide its treatment and associated clinical work. In the present study, the peripheral blood mononuclear cells (PBMCs) of patients with TRS and a healthy control group, which were gender­, age­ and ethnicity­matched, were subjected to microRNA (miRNA/miR) sequencing to screen out the top three miRNAs with the highest fold change values. These were then validated in the TRS (n=34) and healthy control (n=31) groups by reverse transcription­quantitative PCR. For two of the top three miRNAs, the PCR results were in accordance with the sequencing result (P<0.01), while the third miRNA exhibited the opposite trend (P<0.01). To elucidate the functions of these two miRNAs, Homo sapiens (hsa)­miR­218­5p and hsa­miR­1262 and their regulatory network, target gene prediction was first performed using online TargetScan and Diana­micro T software. Bioinformatics analysis was then performed using functional enrichment analysis to determine the Gene Ontology terms in the category biological process and the Kyoto Encyclopedia of Genes and Genomes pathways. It was revealed that these target genes were markedly associated with the nervous system and brain function, and it was obvious that the differentially expressed miRNAs most likely participated in the pathogenesis of TRS. A receiver operating characteristic curve was generated to confirm the distinct diagnostic value of these two miRNAs. It was concluded that aberrantly expressed miRNAs in PMBCs may be implicated in the pathogenesis of TRS and may serve as specific peripheral blood­based biomarkers for the early diagnosis of TRS.

An epidemiological cross-sectional study of prevalence of mental disorders in Dulong nationality of Southwest China.

The Dulong nationality is one of the 5 smallest ethnic minorities in China. The suicide rate among people of the Dulong nationality is very serious. To address this issue, we conducted cross-sectional epidemiological studies on the prevalence of mental disorders in ethnic groups. Studying the unique situation of ethnic minorities can help us better understand their mental state and improve their quality of life.We conducted a cross-sectional epidemiological survey on a minority group in Southwest China. We used the cluster sampling method, and 2129 people were included in the study.The highest 1-month disorder prevalence was for alcohol dependence/abuse (4.16%), and the prevalence of lifelong mood disorders was 9.82%. The results of multivariate analysis showed that women faced a higher risk of mood disorders and anxiety disorders.This epidemiological survey of the prevalence of mental disorders in ethnic minorities in Southwest China provides a significant reference for mental health interventions for other ethnic minorities around the world.

Posterior reversible encephalopathy syndrome with essential thrombocythemia: A case report.

RATIONALE: Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disease of the posterior subcortical white matter that manifests as headache, seizures, visual impairment, disturbance of consciousness, and changes in mental state. While PRES is associated with specific imaging findings involving the posterior circulation area of the brain. In the present study, we report the first case of PRES associated with essential thrombocythemia (ET). PATIENT CONCERNS: A 49-year-old man suddenly experienced headache, followed by the gradual appearance of consciousness disorders and mental behavior abnormalities. Neurological tests showed that the patient had a Glasgow Coma Scale score of 12, normal muscle strength and tension of the limbs, and was negative for meningeal irritation. DIAGNOSIS: Magnetic resonance imaging of the brain showed extensive vasogenic edema in the deep white matter of the right cerebellum and the left occipital and temporal lobes and a diagnosis of PRES was considered. Routine blood test showed that his platelet count was markedly increased, and the JAK2 V617F mutation analysis with allele-specific real-time polymerase chain reaction was positive. The bone marrow biopsy indicated an increasing number of megakaryocytes. These findings indicated ET. INTERVENTIONS: PRES was treated with a dehydrating agent and supportive and symptomatic treatments. Aspirin tablets were prescribed to address the patient's ET. OUTCOME: After treatment, the abnormal findings on head imaging were completely reversed. His neurological symptoms were completely relieved. LESSONS: PRES may be correlated with ET; specifically, ET may trigger PRES and be a risk factor for the acute onset of neurological deficits.

Early TLR4 inhibition reduces hippocampal injury at puberty in a rat model of neonatal hypoxic-ischemic brain damage via regulation of neuroimmunity and synaptic plasticity.

Neonatal hypoxic-ischemic brain damage (HIBD) survivors present with long-term neurological disorders affecting their quality of life, and there remains a lack of effective treatment. Toll-like receptor 4 (TLR4) is widely distributed in nerve cells and its inhibition has a neuroprotective effect against brain injury. The present study aimed to evaluate the long-term neuroprotective effects of early inhibition of TLR4 during HIBD. Seven-day-old rat pups were subjected to left carotid artery ligation followed by 2 h of hypoxia (8.0% O2). A single dose of TAK-242 (0.5 mg/kg), a TLR4-specific antagonist, was intraperitoneally injected half an hour prior to hypoxic ischemia (HI). The long-term effects of TAK-242 inhibition on the induced hippocampal injury were investigated by assessing behaviour at P28, and then using a variety of methods to exploring the mechanism, including immunofluorescence, Golgi silver staining, Western blotting and real-time polymerase chain reaction (RT-PCR). TAK-242 treatment significantly reduced the expression levels of TLR4 and its downstream signalling molecules in the ipsilateral lesion of the hippocampus 24 h after HIBD. The Morris water maze (MWM) test demonstrated that TAK-242 treatment reduced the loss of HI-induced learning and memory functions. Immunofluorescence experiments showed that TAK-242 administration attenuated HI-induced loss of neurons, prevented the activation of microglia and astrocytes, and increased the expression of the glutamate receptor subtype, N-methyl d-aspartate 2A (NR2A) in the ipsilateral hippocampus region. Golgi silver staining revealed that TAK-242 prevented an HI-induced decline in spine density in the ipsilateral hippocampus. Western blot and RT-PCR results indicated that the expression of NR2A protein and mRNA in the ipsilateral hippocampi of adolescent rats decreased after neonatal HIBD; early TAK-242 administration may reverse these effects. In conclusion, our findings indicate that early inhibition of TLR4 signalling may improve the long-term prognosis of neonatal HIBD. The mechanisms contributing to this improvement involve reductions in neuronal loss, a decrease in glial cell activation, and an improvement in synaptic plasticity.

Enumeration of thermophilic Bacillus species in composts and identification with a Random Amplification Polymorphic DNA (RAPD) protocol.

The thermophilic microbial flora of general garden and domestic wastes composts, derived from thermogenic, post-thermogenic and maturation phases, was analysed using spore and total plate counts in combination with an optimised RAPD protocol. A total of 459 isolates were recovered obtained at 55 degrees C, and another 56 at 70 degrees C using tryptic soy-starch agar plates, with near-equal numbers being derived from total plate counts or spore preparations. The isolates were obtained from 11 compost samples and were assigned to eighteen different RAPD fingerprint types, with 76.1% of these ultimately being positively assigned by their RAPD profiles to just 2 species including Bacillus thermodenitrificans and B. licheniformis. Viable cell numbers ranged from 1.4 to 150 x 10(6) colony forming units per gram compost (wet weight), with the highest two counts being from 2 week and 4 week old compost samples with temperatures of 70 degrees C and 55 degrees C, respectively. B. thermodenitrificans was a dominant isolate (representing more than 50% of isolates from total plate counts) in 7 of the 11 individual compost total plate count samples between 30 degrees C to 73 degrees C, and accounted for 68.9% of all isolates overall. Another relatively common Bacillus species that was identified with RAPDs in significant numbers included B. licheniformis (7.2% of all isolates and dominant isolate in 1 sample). Three other relatively common RAPD profiles could not be identified by comparison with known species in a RAPD profile database but were tentatively identified using 16S rDNA sequence comparisons. These were B. sporothermodurans (4.9% of all isolates and dominant in 1 sample), B. thermosphaericus (7.4% and dominant in 1 sample) and Terrabacter tumescens (5.0%). Overall, based on the vegetative and spore count results and the subsequent RAPD-based identification, the data strongly support a significant role for B. thermodenitrificans in the composting process, and casts doubt on the notion that B. stearothermophilus sensu strictu (DSMZ 22) is a prominent member within compost ecology.