A rare waterborne outbreak of Bacillus paranthracis in Shandong province, China, 2020: epidemiologic survey, genomic insights, and virulence characteristics.

Bacillus paranthracis, a Gram-positive conditional pathogen of Bacillus cereus group species, is capable of causing foodborne and waterborne illnesses, leading to intestinal diseases in humans characterized by diarrhoea and vomiting. However, documented cases of B. paranthracis infection outbreaks are rare in the world, and the genomic background of outbreak strains is seldom characterized. This study retrospectively analyzed strains obtained from an outbreak in schools, as well as from water systems in peri-urban areas, China, in 2020. In total, 28 B. cereus group isolates were retrieved, comprising 6 from stool samples and 22 from water samples. Epidemiological and phylogenetic investigations indicated that the B. paranthracis isolate from drinking water as the causative agent of the outbreak. The genomic comparison revealed a high degree of consistency among 8 outbreak-related strains in terms of antimicrobial resistance gene profiles, virulence gene profiles, genomic content, and multilocus sequence typing (MLST). The strains related to the outbreak show highly similar genomic ring diagrams and close phylogenetic relationships. Additionally, this study shed light on the pathogenic potential and complexity of B. cereus group through its diversity in virulence genes and mice infection model. The findings highlight the usefulness of B. paranthracis genomes in understanding genetic diversity within specific environments and in tracing the source of pathogens during outbreak situations, thereby enabling targeted infection control interventions.

Intestinal colonization with ESBL-producing Klebsiella pneumoniae in healthy rural villager: A genomic surveillance study in China, 2015-2017.

Background: The worldwide emergence and diffusion of extended-spectrum ß-lactamase-K. pneumoniae (ESBL-KP) is of particular concern. Although ESBL-KP can inhabit the human gut asymptomatically, colonization with ESBL-KP is associated with an increased risk of ESBL-KP infection and mortality. In this study, we investigated the prevalence and characteristics of ESBL-KP in fecal samples from healthy persons in 12 villages in Shandong Province, China. Methods: Screening for ESBL-KP in fecal samples was performed by selective cultivation. The bacterial species were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rDNA sequence analysis. Minimum inhibitory concentrations (MICs) of 16 antibiotics were determined by the agar dilution method. Plasmid replicons, antimicrobial resistance genes and Sequence types (STs) of the isolates were determined by whole-genome sequencing (WGS). Genetic relatedness of ESBL-KP isolates was determined by the single nucleotide polymorphisms (SNP). The S1 nuclease-pulsed-field gel electrophoresis (S1-PFGE) was used to characterize the plasmids carried by ESBL-KP isolates. Conjugation assays was used to verify the transferability of bla CTX - M. Results: ESBL-KP prevalence rates increased from 12.0% in 2015 to 27.5% in 2017. The experimental results showed that 97% of isolates had multi-drug resistance. Multiple ESBL resistance genotypes were commonly detected in the isolates. STs among the ESBL-KP isolates were diverse. All 69 bla CTX-M-3-positive isolates were located on plasmids, and these genes could be transferred with plasmids between different strains. Phylogenetic analysis showed the possibility of transmission among some isolates. Conclusion: This study obtained the drug resistance patterns, the drug resistance phenotype and molecular characteristics of fecal-derived ESBL-KP in rural communities in Shandong Province, China. We report a rapid increase in occurrence of ESBL-KP among fecal samples collected from healthy rural residents of Shandong Province from 2015 to 2017. The carriage rate of multidrug-resistant bacteria in healthy residents is increasing. Thus, a need for further monitoring and possible interventions of ESBL-KP in this region is warranted.

Personality profile of the primary blepharospasm (BSP): An investigation using the Minnesota Multiphasic Personality Inventory.

OBJECTIVE: To explore whether patients with blepharospasm (BSP) have abnormal personality traits by the Minnesota Multiphasic Personality Inventory (MMPI) questionnaire. METHOD: The personality profiles of patients with BSP and its relationship with clinical characteristics were assessed in this research. 46 patients with BSP and 33 age-and-gender matched healthy controls were assessed using the MMPI questionnaire. The scores of three validity scales and ten clinical scales were calculated and compared. Then the relationship between those scales and clinical characteristics of patients with BSP was analyzed in the BSP group. RESULTS: It was found that patients with BSP scored significantly higher than healthy controls on the D, Hy, Pt clinical scales. The peak values of profiles were Hy, D, Hs scale scores. However, there was no statistical relationship between the clinical scales of MMPI and the clinical characteristics of BSP after Bonferroni Correction. CONCLUSION: The findings indicated that MMPI could be a useful psychometric tool to characterize a specific pattern of the personality of BSP patients and BSP patients may have avoidant and somatization personality characteristics.

Characterization of a novel panel of plasma microRNAs that discriminates between Mycobacterium tuberculosis infection and healthy individuals.

Cavities are important in clinical diagnosis of pulmonary tuberculosis (TB) infected by Mycobacterium tuberculosis. Although microRNAs (miRNAs) play a vital role in the regulation of inflammation, the relation between plasma miRNA and pulmonary tuberculosis with cavity remains unknown. In this study, plasma samples were derived from 89 cavitary pulmonary tuberculosis (CP-TB) patients, 89 non-cavitary pulmonary tuberculosis (NCP-TB) patients and 95 healthy controls. Groups were matched for age and gender. In the screening phase, Illumina high-throughput sequencing technology was employed to analyze miRNA profiles in plasma samples pooled from CP-TB patients, NCP-TB patients and healthy controls. During the training and verification phases, quantitative RT-PCR (qRT-PCR) was conducted to verify the differential expression of selected miRNAs among groups. Illumina high-throughput sequencing identified 29 differentially expressed plasma miRNAs in TB patients when compared to healthy controls. Furthermore, qRT-PCR analysis validated miR-769-5p, miR-320a and miR-22-3p as miRNAs that were differently present between TB patients and healthy controls. ROC curve analysis revealed that the potential of these 3 miRNAs to distinguish TB patients from healthy controls was high, with the area under the ROC curve (AUC) ranged from 0.692 to 0.970. Moreover, miR-320a levels were decreased in drug-resistant TB patients than pan-susceptible TB patients (AUC = 0.882). In conclusion, we identified miR-769-5p, miR-320a and miR-22-3p as potential blood-based biomarkers for TB. In addition, miR-320a may represent a biomarker for drug-resistant TB.

Reduced prefrontal activation during verbal fluency task in chronic insomnia disorder: a multichannel near-infrared spectroscopy study.

PURPOSE: Daytime complaints such as memory and attention deficits and failure to accomplish daily tasks are common in insomnia patients. However, objective psychological tests to detect cognitive impairment are equivocal. Neural function associated with cognitive performance may explain the discrepancy. The aim of this study was to investigate the hemodynamic response patterns of patients with chronic insomnia disorder (CID) using the noninvasive and low-cost functional neuroimaging technique of multichannel near-infrared spectroscopy (NIRS) in order to identify changes of neural function associated with cognitive performance. PATIENTS AND METHODS: Twenty-four CID patients and twenty-five healthy controls matched for age, right-hand dominance, educational level, and gender were examined during verbal fluency tasks (VFT) using NIRS. A covariance analysis was conducted to analyze differences of oxygenated hemoglobin (oxy-Hb) changes in prefrontal cortex (PFC) between the two groups and reduce the influence of the severity of depression. Pearson correlation coeffcients were calculated to examine the relationship between the oxy-Hb changes, with the severity of insomnia and depressive symptoms assessed by the Pittsburgh Sleep Quality Index (PSQI) and the Hamilton Rating Scale for Depression (HAMD). RESULTS: The number of words generated during the VFT in CID groups showed no statistical differences with healthy controls. CID patients showed hypoactivation in the PFC during the cognitive task. In addition, we found that the function of left orbitofrontal cortex (OFC) during the VFT was significantly negatively correlated with the PSQI scores and the function of right dorsolateral PFC (DLPFC) was significantly negatively correlated with the HAMD scores. CONCLUSION: The present study detected dysfunctions in PFC in spite of intact performance which indicates the role of PFC in the neurophysiological underpinnings. Left OFC function is associated with insomnia symptoms and right DLPFC function is associated with depressive symptoms.

Decreased prefrontal brain activation during verbal fluency task in patients with somatoform pain disorder: An exploratory multi-channel near-infrared spectroscopy study.

BACKGROUND: Pain is a common phenomenon. Patients with somatoform pain disorder (SPD) suffer from lasting chronic pain which may cause cognitive impairment. The dysfunction of prefrontal cortex (PFC) may be involved in pain-induced cognition impairment, which is the most important part in regulating of cognitive function. Multi-channel near-infrared spectroscopy (NIRS) is a noninvasive and low-cost functional neuroimaging technique being used to detect the prefrontal cortex activation during cognitive tasks to demonstrate the relationship between PFC dysfunction and cognition impairment in SPD patients. METHODS: 24 patients with SPD and 24 age-, gender- and education level-matched healthy controls were examined by NIRS of the relative concentration of oxygenated hemoglobin (oxy-Hb) in PFC during verbal fluency task (VFT). All data analysis procedures were accomplished under MATLAB, SPM and SPM-fNIRS which is an SPM12-based software for fNIRS analysis. RESULTS: 1. The number of words generated during the VFT tasks in SPD patients were fewer than healthy controls. 2. The activated areas in SPD patients were smaller than healthy controls. 3. The average activation strength of [oxy-Hb] in SPD patients was much lower than healthy controls. 4. The difference of activation areas between left and right lobe were particularly obvious in SPD patients. CONCLUSION: There are evidences suggested that the markedly dysfunction in PFC especially bilateral dorsolateral prefrontal cortex (DLPFC) areas may be involved in the cognitive deficiency in patients with SPD.

Improvement of Orbitofrontal Cortex Function Associated with Blephrospasm Symptom Remission.

OBJECTIVE: To determine whether orbitofrontal cortex (OFC) function improves with blepharospasm (BSP) symptom remission using a verbal fluency task and near-infrared spectroscopy (NIRS). METHODS: Nineteen BSP patients and 9 healthy controls (HCs) matched by gender and education were examined using NIRS. The BSP patients were divided into 2 groups based on the onset or remission of BSP symptoms. A covariance analysis was conducted to analyze the differences among the 3 groups to avoid the influence of different ages. The least significant difference was used to process the post hoc test. RESULTS: The hemoglobin concentration and cerebral blood flow of the bilateral orbitofrontal area (channels 27, 31, 34, 37, and 39) were not significantly different between the BSP remission and HC groups (p > 0.05); however, both groups were significantly increased compared with the BSP onset group (BSP remission group vs. BSP onset group: p = 0.003, p = 0.018, p = 0.013, p = 0.001, and p = 0.011, respectively; BSP remission group vs. BSP onset group: p = 0.037, p = 0.044, p = 0.023, p = 0.016, and p = 0.025, respectively). CONCLUSION: This is the first investigation to control for symptom stages in BSP patients examined via NIRS. Cognitive ability and OFC function improve with BSP symptom remission. Thus, the OFC may be inter-connected with motor and cognitive symptoms in BSP.

Near-Infrared Spectroscopy Reveals Abnormal Hemodynamics in the Left Dorsolateral Prefrontal Cortex of Menopausal Depression Patients.

Background/Objective. Menopausal depression (MD) is characterized by depressive symptoms along with hormonal fluctuations. We investigate brain function alteration between major depressive disorder (MDD) and MD. Methods. The difference in oxygenated hemoglobin (Oxy-Hb) for the prefrontal cortex (PFC) was compared retrospectively among 90 females presented with 30 MDD, 30 MD, and 30 healthy controls (HCs) using verbal fluency task (VFT) with near-infrared spectroscopy (NIRS). Results. We observed a significant difference in Oxy-Hb alteration in the left dorsolateral PFC (DLPFC) using VFT with NIRS (channel 18, P = 0.007) between the MD and MDD groups. A significant difference in Oxy-Hb levels was observed among the three groups in the bilateral DLPFC (channels 18, 27, 33, 39, 41, and 45; P < 0.05). Compared to the HCs, the MD group presented lower Oxy-Hb activation in the right DLPFC (channel 41; P = 0.048) and the left DLPFC (channels 18, 39, and 45; P < 0.05), and the MDD group presented lower Oxy-Hb activation in the right DLPFC (channels 27, 33, and 41; P < 0.05) and the left DLPFC (channels 39 and 45; P < 0.05). Conclusion. Abnormal hemodynamics of the left DLPFC can differentiate MD from MDD by NIRS.

Prefrontal Hemodynamic Functions during a Verbal Fluency Task in Blepharospasm Using Multi-Channel NIRS.

Blepharospasm (BSP) has a morbidity of 16 to 133 per million and is characterized by orbicularis oculi spasms. BSP can severely impact daily life. However, to date, its pathophysiology has not been clearly demonstrated. Near-infrared spectroscopy (NIRS) is a portable, non-invasive, and high time resolution apparatus used to measure cerebral blood flow. This study aimed to investigate the hemodynamic response patterns of BSP patients and determine whether BSP alone can be an attributional factor to influence the function of the prefrontal area using a verbal fluency task (VFT) and NIRS. Twenty-three BSP patients (10 males and 13 females) and 13 healthy controls (HC; five males and eight females) matched by gender and education were examined using NIRS. BSP patients were divided into two groups based on the presence or absence of depression and anxiety symptoms. A covariance analysis was conducted to analyze differences between the three groups and reduce the influence of different ages and educational levels. Bonferroni was used to process the post hoc test. The bilateral orbitofrontal area (ch36, 39, and 41; P<0.01) exhibited a lower activation in BSP patients without psychiatric symptoms compared with HC. This study is the first report to identify the prefrontal function in BSP using NIRS. Our findings indicate that BSP alone may cause a hypoactive hemodynamic performance in the prefrontal cortex in the absence of psychiatric symptoms. These findings provide evidence to support novel pathophysiological mechanisms of BSP.

Dominant modern sublineages and a new modern sublineage of Mycobacterium tuberculosis Beijing family clinical isolates in Heilongjiang Province, China.

Mycobacterium tuberculosis Beijing family includes a variety of sublineages. Knowledge of the distribution of a certain sublineage of the Beijing family may help to understand the mechanisms of its rapid spread and to establish an association between a certain genotype and the disease outcome. We have previously found that M. tuberculosis Beijing family clinical isolates represent approximately 90% of the clinical isolates from Heilongjiang Province, China. To clarify the distribution of M. tuberculosis Beijing family sublineages in Heilongjiang Province, China and to investigate the regularity rule for their evolution, we examined single nucleotide polymorphisms (SNPs) of 250 M. tuberculosis Beijing family clinical isolates using 10 SNP loci that have been identified as appropriate for defining Beijing sublineages. After determining the sequence type (ST) of each isolate, the sublineages of all M. tuberculosis Beijing family isolates were determined, and phylogenetic analysis was performed. We found that 9 out of the 10 SNP loci displayed polymorphisms, but locus 1548149 did not. In total, 92.8% of the isolates in Heilongjiang Province are modern sublineages. ST10 is the most prevalent sublineage (ST10 and ST22 accounted for 63.2% and 23.6% of all the Beijing family isolates, respectively). A new ST, accounting for 4% of the Beijing family isolates in this area, was found for the first time. Each new ST isolate showed a unique VNTR pattern, and none were clustered. The present findings suggest that controlling the spread of these modern sublineages is important in Heilongjiang Province and in China.

Relationship between the prefrontal function and the severity of the emotional symptoms during a verbal fluency task in patients with major depressive disorder: a multi-channel NIRS study.

Multi-channel near-infrared spectroscopy (NIRS) is a noninvasive and low-cost functional neuroimaging technique in psychiatric research, and it has been wildly used for detecting the spatiotemporal characteristics of brain activity. In order to evaluate the clinical value of NIRS data in the assistant diagnosis of major depressive disorder (MDD), prefrontal cortex (PFC) hemoglobin concentration exchange of 30 MDD patients combined with anxious and obsessive-compulsive symptom was detected by NIRS under voice fluency task (VFT), then the relationship between the severity of depressive, anxious and obsessive-compulsive symptom assessed by Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Rating Scale (HAMA) and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) with NIRS data in PFC was analyzed. Hypoactivation in lateral and lower PFC of MDD patients was confirmed in this study. Furthermore, Spearman correlation found that oxy-hemoglobin concentration ([oxy-Hb]) exchange in right-lateral PFC was associated with the severity of anxiety, while bilateral PFC and antero-medial PFC were associated with severity of depression. Meanwhile, no statistical correlation was observed on the severity of obsessive-compulsive symptom. The results prompted that MDD patients with anxiety and obsession-compulsion symptom showed a PFC hypoactivation state in NIRS. Furthermore, the function of right-lateral PFC was associated with anxiety symptom, while bilateral PFC and antero-medial PFC were associated with depression symptom. Different from depression and anxiety, obsession-compulsion may have a different biological character in PFC function.

Converging evidence implicates the dopamine D3 receptor gene in vulnerability to schizophrenia.

The dopamine D3 receptor has been implicated in the pathophysiology of schizophrenia (SZ). A glycine-to-serine polymorphism at codon 9 of the dopamine D3 receptor gene (DRD3), rs6280, has been widely studied for its association with SZ, but with conflicting results. Altered levels of DRD3 mRNA have also been reported in SZ compared with normal controls. Moreover, it has been suggested that DRD3 is subject to recent positive selection in European populations. To explore the potential role of DRD3 in SZ from these various aspects, we conducted a threefold study. First, we tested the genetic association of rs6280 with SZ in 685 SZ patients and 768 normal controls. Second, we examined DRD3 mRNA levels in peripheral leukocytes in a subset of 37 patients and 37 controls. Finally, we investigated the possible recent positive selection on DRD3 in an East Asian population. Consequently, we observed that the genotypic distribution of rs6280 was nominally associated with SZ (P = 0.045), with the ancestral CC genotype being significantly over-represented in SZ patients. DRD3 mRNA levels were significantly lower in patients than in controls (P = 5.91E-5). The derived C-allele of rs6280 might have been subject to recent positive selection (P < 0.001) in the East Asian population. Taken together, our results suggest that DRD3, a gene possibly under natural selection, might be involved in vulnerability to SZ in the Han Chinese population. These findings may further add to the body of data implicating DRD3 as a schizophrenia risk gene.

An association study of DRD2 gene polymorphisms with schizophrenia in a Chinese Han population.

Dopamine signaling is strongly implicated in the etiology of schizophrenia (SZ). Because of the essential role dopamine D2 receptor (DRD2) in dopamine signaling, DRD2 gene has been regarded as one of the top candidate genes for SZ. However, the findings from linkage and association analyses on this gene are mixed and largely inconsistent across various studies. The aim of this study is to investigate the correlation of DRD2 gene variation and the risk for SZ in a Chinese Han population. Three SNPs (rs1801028, rs6275 and rs6277) of DRD2 gene were genotyped in a patient-control sample involving 421 SZ patients and 404 healthy controls. Our data indicated a nominally significant association of rs6277 with SZ, with T-allele being the risk allele (OR=1.58, 95%CI=1.03-2.43, P=0.034). This study suggests that rs6277 T-allele may play a role in the genetic vulnerability for SZ, supporting the involvement of DRD2 gene in SZ pathogenesis.

Association analyses of the interaction between the ADSS and ATM genes with schizophrenia in a Chinese population.

BACKGROUND: The blood-derived RNA levels of the adenylosuccinate synthase (ADSS) and ataxia telangiectasia mutated (ATM) genes were found to be down- and up-regulated, respectively, in schizophrenics compared with controls, and ADSS and ATM were among eight biomarker genes to discriminate schizophrenics from normal controls. ADSS catalyzes the first committed step of AMP synthesis, while ATM kinase serves as a key signal transducer in the DNA double-strand breaks response pathway. It remains unclear whether these changes result from mutations or polymorphisms in the two genes. METHODS: Six SNPs in the ADSS gene and three SNPs in the ATM gene in a Chinese population of 488 schizophrenics and 516 controls were genotyped to examine their association with schizophrenia (SZ). Genotyping was performed using the Sequenom platform. RESULTS: There was no significant difference in the genotype, allele, or haplotype distributions of the nine SNPs between cases and controls. Using the Multifactor Dimensionality Reduction (MDR) method, we found that the interactions among rs3102460 in the ADSS gene and rs227061 and rs664143 in the ATM gene revealed a significant association with SZ. This model held a maximum testing accuracy of 60.4% and a maximum cross-validation consistency of 10 out of 10. CONCLUSION: These findings suggest that the combined effects of the polymorphisms in the ADSS and ATM genes may confer susceptibility to the development of SZ in a Chinese population.