Clinical spectrum of late symptomatic neurosyphilis in China: an 11-year retrospective study.

OBJECTIVES: This study aimed to describe the clinical features of neurosyphilis in Chinese patients in an attempt to find clinical features that are helpful for the early identification of neurosyphilis. METHODS: This retrospective study included people with syphilis who visited Shanghai Skin Disease Hospital between January 2010 and December 2020. Lumbar puncture was performed on those who met the inclusion and exclusion criteria. The diagnosis of neurosyphilis was based on clinical and laboratory findings. The parameters were analysed statistically. RESULTS: Of the 3524 patients with neurosyphilis, 2111 (59.9%) and 1413 (40.1%) were asymptomatic and symptomatic neurosyphilis, respectively. General paresis was the most common type of symptomatic neurosyphilis (46.8%). The clinical manifestations of symptomatic neurosyphilis include psychiatric and neurotic symptoms, among which general paresis predominantly presented as psychiatric symptoms such as affective (66.7%) and memory disorder (72.9%). Tabes dorsalis is often presented as neurotic symptoms. One hundred fifty patients (10.6%) with symptomatic neurosyphilis presented candy signs, a rare and specific neurosyphilis symptom that is common in general paresis. Girdle sensation was presented in 13 patients, mainly with tabes dorsalis, which had not been reported in previous studies. CONCLUSIONS: Notably, the candy sign is identified as a specific symptom of general paresis, while girdle sensations are highlighted as a particular symptom of tabes dorsalis. This is the largest study describing the clinical spectrum of neurosyphilis since the onset of the penicillin era and could help doctors learn more about the disease. A comprehensive description of the possible clinical manifestations of late symptomatic neurosyphilis, particularly highlighting rare symptoms, can identify suspicious patients and prevent diagnostic delays.

Clinical parameter-based prediction model for neurosyphilis risk stratification.

Accurately predicting neurosyphilis prior to a lumbar puncture (LP) is critical for the prompt management of neurosyphilis. However, a valid and reliable model for this purpose is still lacking. This study aimed to develop a nomogram for the accurate identification of neurosyphilis in patients with syphilis. The training cohort included 9,504 syphilis patients who underwent initial neurosyphilis evaluation between 2009 and 2020, while the validation cohort comprised 526 patients whose data were prospectively collected from January 2021 to September 2021. Neurosyphilis was observed in 35.8% (3,400/9,504) of the training cohort and 37.6% (198/526) of the validation cohort. The nomogram incorporated factors such as age, male gender, neurological and psychiatric symptoms, serum RPR, a mucous plaque of the larynx and nose, a history of other STD infections, and co-diabetes. The model exhibited good performance with concordance indexes of 0.84 (95% CI, 0.83-0.85) and 0.82 (95% CI, 0.78-0.86) in the training and validation cohorts, respectively, along with well-fitted calibration curves. This study developed a precise nomogram to predict neurosyphilis risk in syphilis patients, with potential implications for early detection prior to an LP.

A New Specimen for Syphilis Diagnosis: Evidence by High Loads of Treponema pallidum DNA in Saliva.

BACKGROUND: DNA from many pathogens can be detected in saliva. However, the presence and quantity of Treponema pallidum DNA in patients with syphilis in saliva is unknown. METHODS: 234 patients with syphilis with different stages and 30 volunteers were enrolled. Paired saliva and plasma samples were collected from all participants. Consecutive saliva samples from 9 patients were collected every 4 hours following treatment. Treponema pallidum DNA in samples was determined by nested polymerase chain reaction (PCR) and droplet digital PCR targeting polA and Tpp47. RESULTS: Treponema pallidum DNA detection rates in saliva and plasma were 31.0% (9/29) and 51.7% (15/29) in primary syphilis (P = .11), 87.5% (63/72) and 61.1% (44/72) in secondary syphilis (P < .001), 25.6% (21/82) and 8.5% (7/82) in latent syphilis (P = .004), and 21.6% (11/51) and 5.9% (3/51) in symptomatic neurosyphilis (P = .021), respectively. Median (range) loads of Tpp47 and polA in saliva were 627 (0-101 200) and 726 (0-117 260) copies/mL, respectively, for patients with syphilis. In plasma, however, loads of Tpp47 and polA were low: medians (range) of 0 (0-149.6) and 0 (0-176) copies/mL, respectively. Loads of T. pallidum DNA in saliva during treatment fluctuated downward; the clearance time was positively correlated with the loads of T. pallidum DNA before treatment. CONCLUSIONS: Collection of saliva is noninvasive and convenient. The high loads of T. pallidum DNA in saliva and reduction after treatment indicated that saliva can be not only a diagnostic fluid for syphilis but also an indicator of therapeutic effectiveness.

Internal Migration and Leprosy in Shanghai from 2000 to 2019: an Epidemiological Study of New Cases.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Massive internal migration from rural to urban areas poses new challenges for leprosy control in Shanghai, China. This retrospective epidemiological study examined new cases of leprosy diagnosed in Shanghai from 2000 to 2019, with emphasis on internal migration cases. There were 145 cases of leprosy in the study period; the majority of cases (89.0%) were internal migrants. Migrant cases had a mean of 25.4 months lag time from onset of symptoms to diagnosis, which was significantly longer than that of resident cases (mean 10.8 months, p < 0.001). Greater lag time from the first visit to diagnosis was observed in migrant cases (mean 23.2 months) compared with resident cases (mean 9.4 months, p < 0.001). A large majority of cases (91.0%) had been misdiagnosed. Internal migrant cases were responsible for most incidences of leprosy in Shanghai. They often did not receive timely diagnosis and treatment, which may have an adverse impact on the prevention of epidemic leprosy.

Glycopeptidolipid Genotype Correlates With the Severity of Mycobacterium abscessus Lung Disease.

BACKGROUND: Smooth and rough colony morphotypes of Mycobacterium abscessus are associated with virulence, but some isolates form both smooth and rough colonies, impeding successful morphotype identification. Reportedly, smooth/rough morphotypes are also related to the glycopeptidolipid (GPL) genotype. However, the accuracy of GPL genotyping to discriminate morphotypes and the relationship between GPL genotype and clinical characteristics of M abscessus lung disease have not been verified. METHODS: A retrospective analysis of colony morphology, GPL genotype, and clinical data from 182 patients with M abscessus lung disease was conducted. RESULTS: Of 194 clinical isolates, 126 (65.0%), 15 (7.7%), and 53 (27.3%) exhibited rough, smooth, and mixed colony morphotypes, respectively. Glycopeptidolipid genotyping indicated that 86.7% (13 of 15) of smooth isolates belonged to the GPL-wild type (WT) group, whereas 98.4% (124 of 126) of rough isolates belonged to the GPL-mutant type (MUT) group. Therefore, GPL genotyping accurately distinguished between smooth and rough morphotypes. Mixed colony morphotypes were also divided into GPL-WT (18.9%) and GPL-MUT (81.1%) groups. Further analysis revealed that patients infected with the GPL-MUT group presented with significantly worse baseline clinical characteristics and exacerbated episodes of lung disease. CONCLUSIONS: Glycopeptidolipid genotyping accurately distinguishes smooth and rough colony morphotypes. Patients infected with the GPL-MUT genotype exhibit worse clinical characteristics and are at a higher risk of exacerbated lung disease.

Molecular Analysis of Linezolid-Resistant Clinical Isolates of Mycobacterium abscessus.

A total of 194 Mycobacterium abscessus isolates were collected from patients, and the whole genomes were sequenced. Eighty-five (43.8%) isolates showed linezolid (LZD) resistance. Only 8.2% of resistant isolates harbored 23S rRNA mutations. Quantitative real-time PCR (qRT-PCR) revealed higher transcriptional levels of efflux pumps lmrS and mmpL9 in LZD-resistant isolates. Genome comparative analysis identified several new LZD resistance-associated genes. This study highlights the role of efflux pumps in LZD-resistant M. abscessus and proposes potential target genes for further studies.

The Clarithromycin Susceptibility Genotype Affects the Treatment Outcome of Patients with Mycobacterium abscessus Lung Disease.

Mycobacterium abscessus accounts for a large proportion of lung disease cases caused by rapidly growing mycobacteria. The association between clarithromycin sensitivity and treatment outcome is clear. However, M. abscessus culture and antibiotic susceptibility testing are time-consuming. Clarithromycin susceptibility genotyping offers an alternate, rapid approach to predicting the efficacy of clarithromycin-based antibiotic therapy. M. abscessus lung disease patients were divided into two groups based upon the clarithromycin susceptibility genotype of the organism isolated. A retrospective analysis was conducted to compare the clinical features, microbiological characteristics, and treatment outcomes of the two groups. Several other potential predictors of the response to treatment were also assessed. Sixty-nine patients were enrolled in the clarithromycin-resistant genotype group, which included 5 infected with rrl 2058-2059 mutants and 64 infected with erm(41)T28-type M. abscessus; 31 were in the clarithromycin-sensitive group, i.e., 6 and 25 patients infected with genotypes erm(41)C28 and erm(41) M type, respectively. The results showed that lung disease patients infected with clarithromycin-sensitive and -resistant M. abscessus genotypes differed significantly in clarithromycin-based combination treatment outcomes. Patients infected with the clarithromycin-sensitive genotype exhibited higher initial and final sputum-negative conversion and radiological improvement rates and better therapeutic outcomes. Multivariate analysis demonstrated that genotyping was a reliable and, more importantly, rapid means of predicting the efficacy of clarithromycin-based antibiotic treatment for M. abscessus lung disease.

Determination of MIC Distribution and Mechanisms of Decreased Susceptibility to Bedaquiline among Clinical Isolates of Mycobacterium abscessus.

Chemotherapeutic options against Mycobacterium abscessus infections are very limited. Bedaquiline, a new antituberculosis (anti-TB) drug, is effective for the treatment of multidrug-resistant TB. However, few data are available on bedaquiline for treatment of M. abscessus infections. In this study, we determined the profile for in vitro susceptibility of M. abscessus clinical isolates to bedaquiline and investigated the potential molecular mechanisms of decreased susceptibility. A total of 197 M. abscessus clinical isolates were collected from sputum and bronchoalveolar fluid of patients with lung infections. Standard broth microdilution test revealed that bedaquiline exhibited high in vitro killing activity against M. abscessus isolates, with a MIC50 of 0.062 and a MIC90 of 0.125 mg/liter. Whole-genome sequencing data showed that no nonsynonymous mutation occurred in atpE, the gene encoding the bedaquiline-targeted protein. However, of 6 strains with decreased susceptibility of bedaquiline (MIC = 0.5 to 1 mg/liter), 3 strains had nonsynonymous mutations in mab_4384, the gene encoding the repressor of efflux pump MmpS5/MmpL5. Quantitative reverse transcription-PCR (qRT-PCR) analysis showed that the expression of MmpS5/MmpL5 in the group with decreased susceptibility to bedaquiline was significantly higher than in those with medium MICs (MIC = 0.125 to 0.5 mg/liter) or in the low-MIC group (MIC ≤ 0.062 mg/liter). Two isolates with increased MICs did not show overexpression of MmpS5/MmpL5, which could not be explained by known molecular mechanisms. This is the first report showing the association of MmpS5/MmpL5 with decreased bedaquiline susceptibility in M. abscessus clinical isolates and suggesting the presence of other, yet-to-be identified mechanisms for decreased bedaquiline susceptibility in M. abscessus.

High ceftazidime hydrolysis activity and porin OmpK35 deficiency contribute to the decreased susceptibility to ceftazidime/avibactam in KPC-producing Klebsiella pneumoniae.

Objectives: To investigate mechanisms for the decreased susceptibility to ceftazidime/avibactam in KPC-producing Klebsiella pneumoniae (KPC-KP). Methods: A total of 24 isolates, 8 each with ceftazidime/avibactam MICs of 4-8, 1-2 and ≤0.5 mg/L, were randomly selected from 214 clinical isolates of KPC-KP, and the ß-lactamase hydrolysis activity and porin expression profiles were determined. Plasmid profile and relative expression and copy number of the bla KPC gene were also analysed. Results: Ceftazidime/avibactam MIC 50 and MIC 90 were 2 and 4 mg/L, respectively, for the 214 KPC-KP isolates. The hydrolysis activities of nitrocefin and ceftazidime in both of the ceftazidime/avibactam MIC 4-8 and 1-2 mg/L groups were significantly higher than those of the MIC ≤0.5 mg/L group, while the hydrolysis activities were 4-4.6-fold higher in the MIC 4-8 mg/L group than in the other two groups when 4 mg/L avibactam was added. The relative expression and copy number of the bla KPC gene in the MIC 4-8 mg/L group were 4.2-4.8-fold higher than in the other two groups. Meanwhile, SDS-PAGE showed that all isolates in the two groups with MIC ≥1 mg/L lacked OmpK35, which had either an early frameshift with a premature stop codon ( n = 15, ST11) or overexpression of the negative regulation genes, micF and ompR ( n = 1, ST15), whereas OmpK35 and OmpK36 could both be observed in all isolates with MIC ≤0.5 mg/L. Conclusions: Decreased ceftazidime/avibactam susceptibility in KPC-KP clinical isolates is caused by high ceftazidime hydrolysis activity and OmpK35 porin deficiency and the majority of isolates belong to ST11.

HtrA, a Temperature- and Stationary Phase-Activated Protease Involved in Maturation of a Key Microbial Virulence Determinant, Facilitates Borrelia burgdorferi Infection in Mammalian Hosts.

High-temperature requirement protease A (HtrA) represents a family of serine proteases that play important roles in microbial biology. Unlike the genomes of most organisms, that of Borrelia burgdorferi notably encodes a single HtrA gene product, termed BbHtrA. Previous studies identified a few substrates of BbHtrA; however, their physiological relevance could not be ascertained, as targeted deletion of the gene has not been successful. Here we show that BbhtrA transcripts are induced during spirochete growth either in the stationary phase or at elevated temperature. Successful generation of a BbhtrA deletion mutant and restoration by genetic complementation suggest a nonessential role for this protease in microbial viability; however, its remarkable growth, morphological, and structural defects during cultivation at 37°C confirm a high-temperature requirement for protease activation and function. The BbhtrA-deficient spirochetes were unable to establish infection of mice, as evidenced by assessment of culture, PCR, and serology. We show that transcript abundance as well as proteolytic processing of a borrelial protein required for cell fission and infectivity, BB0323, is impaired in BbhtrA mutants grown at 37°C, which likely contributed to their inability to survive in a mammalian host. Together, these results demonstrate the physiological relevance of a unique temperature-regulated borrelial protease, BbHtrA, which further enlightens our knowledge of intriguing aspects of spirochete biology and infectivity.

Multifocal musculoskeletal tuberculosis mimicking multiple bone metastases: a case report.

BACKGROUND: The occurrence of non-contiguous, multiple, and remote involvement tuberculous spondylitis is rare. The clinical presentation in patients with multifocal musculoskeletal tuberculosis may closely mimic that in patients with multiple bone metastases, which makes the accurate clinical diagnosis challenging. Herein, we report a multifocal musculoskeletal tuberculosis case that was misdiagnosed for 8 months as multiple bone metastases. CASE PRESENTATION: A 63-year-old male farmer of Chinese Han ethnicity presented to us with pain in left side of the neck, right side of the chest and the back for 10 months without typical tuberculosis symptoms. His past medical history, the CT and fluoroscopy-guided biopsy were negative for tuberculosis. Interferon gamma by T-SPOT was also negative. Radiological findings including CT, MRI and PET-CT suggested that the patient had multiple metastases. Accordingly, the patient was misdiagnosed as having musculoskeletal tumors until a swelling under the right nipple ulcerated. The smear test for acid-fast bacilli and the PCR test for TB-DNA of the pus from the swollen area were both positive, leading to the final correct diagnosis of musculoskeletal tuberculosis. CONCLUSION: The proper diagnosis of musculoskeletal tuberculosis is clinically challenging due to Mycobacterium tuberculosis variants involved and atypical presentations, especially when the lesions are multiple. Our findings indicate that multiple tuberculous spondylitis must be considered in the differential diagnosis of multiple musculoskeletal lesions.

Cyclic Di-GMP receptor PlzA controls virulence gene expression through RpoS in Borrelia burgdorferi.

As an obligate pathogen, the Lyme disease spirochete Borrelia burgdorferi has a streamlined genome that encodes only two two-component signal transduction systems, Hk1-Rrp1 and Hk2-Rrp2 (in addition to CheA-CheY systems). The output of Hk1-Rrp1 is the production of the second messenger cyclic di-GMP (c-di-GMP), which is indispensable for B. burgdorferi to survive in the tick vector. The output of Hk2-Rrp2 is the transcriptional activation of the global regulator RpoS, which is essential for the pathogen to accomplish its tick-mouse transmission and to establish mammalian infection. Although evidence indicates that these two systems communicate with each other, how they are connected is not fully understood. In this study, we showed that the c-di-GMP-binding protein PlzA, a downstream effector of Rrp1, positively modulates the production of RpoS, a global regulator and downstream target of Rrp2. Thus, PlzA functions as a connector that links Hk1-Rrp1 with Hk2-Rrp2. We further showed that PlzA regulates rpoS expression through modulation of another regulator, BosR, at both the transcriptional and the posttranscriptional levels. In addition, PlzA was also capable of regulating rpoS expression independently of Rrp1, suggesting that besides being a c-di-GMP-binding protein, PlzA has other functions. Along with the previous finding of PlzA controlling motility, these studies demonstrate that PlzA is a multifunctional protein. These findings further reinforce the notion that B. burgdorferi utilizes its limited signaling systems and regulators to govern multiple cellular processes during its complex enzootic cycle between ticks and mammals.

DhhP, a cyclic di-AMP phosphodiesterase of Borrelia burgdorferi, is essential for cell growth and virulence.

Cyclic di-AMP (c-di-AMP) is a recently discovered second messenger in bacteria. Most of work on c-di-AMP signaling has been done in Gram-positive bacteria, firmicutes, and actinobacteria, where c-di-AMP signaling pathways affect potassium transport, cell wall structure, and antibiotic resistance. Little is known about c-di-AMP signaling in other bacteria. Borrelia burgdorferi, the causative agent of Lyme disease, is a spirochete that has a Gram-negative dual membrane. In this study, we demonstrated that B. burgdorferi BB0619, a DHH-DHHA1 domain protein (herein designated DhhP), functions as c-di-AMP phosphodiesterase. Recombinant DhhP hydrolyzed c-di-AMP to pApA in a Mn(2+)- or Mg(2+)-dependent manner. In contrast to c-di-AMP phosphodiesterases reported thus far, DhhP appears to be essential for B. burgdorferi growth both in vitro and in the mammalian host. Inactivation of the chromosomal dhhP gene could be achieved only in the presence of a plasmid-encoded inducible dhhP gene. The conditional dhhP mutant had a dramatic increase in intracellular c-di-AMP level in comparison to the isogenic wild-type strain. Unlike what has been observed in Gram-positive bacteria, elevated cellular c-di-AMP in B. burgdorferi did not result in an increased resistance to ß-lactamase antibiotics, suggesting that c-di-AMP's functions in spirochetes differ from those in Gram-positive bacteria. In addition, the dhhP mutant was defective in induction of the σ(S) factor, RpoS, and the RpoS-dependent outer membrane virulence factor OspC, which uncovers an important role of c-di-AMP in B. burgdorferi virulence.

Review of tracer kinetic models in evaluation of gliomas using dynamic contrast-enhanced imaging.

Glioma is the most common type of primary malignant tumor of the central nervous system (CNS), and is characterized by high malignancy, high recurrence rate and poor survival. Conventional imaging techniques only provide information regarding the anatomical location, morphological characteristics, and enhancement patterns. In contrast, advanced imaging techniques such as dynamic contrast-enhanced (DCE) MRI or DCE CT can reflect tissue microcirculation, including tumor vascular hyperplasia and vessel permeability. Although several studies have used DCE imaging to evaluate gliomas, the results of data analysis using conventional tracer kinetic models (TKMs) such as Tofts or extended-Tofts model (ETM) have been ambiguous. More advanced models such as Brix's conventional two-compartment model (Brix), tissue homogeneity model (TH) and distributed parameter (DP) model have been developed, but their application in clinical trials has been limited. This review attempts to appraise issues on glioma studies using conventional TKMs, such as Tofts or ETM model, highlight advancement of DCE imaging techniques and provides insights on the clinical value of glioma management using more advanced TKMs.

Emergence of Neisseria gonorrhoeae Clone with Reduced Susceptibility to Sitafloxacin in China: An In Vitro and Genomic Study.

Drug-resistant Neisseria gonorrhoeae poses an urgent threat to public health. Recently, sitafloxacin, a new-generation fluoroquinolone, has shown high in vitro activity against drug-resistant N. gonorrhoeae. However, data on its effectiveness in clinical isolates remains limited. In this study, we collected 507 N. gonorrhoeae isolates from 21 hospitals in Shanghai, China, during 2020 and 2021. Antimicrobial susceptibility testing revealed that sitafloxacin minimum inhibitory concentrations (MICs) exhibited a bimodal distribution, ranging from <0.004 to 2 mg/L. The MIC50 and MIC90 for sitafloxacin were 0.125 mg/L and 0.5 mg/L, respectively, which are 32 and 16 times lower than those for ciprofloxacin (4 mg/L and 8 mg/L, respectively). Sitafloxacin demonstrated high in vitro activity against isolates resistant to either ceftriaxone, azithromycin, or both. Notably, among the isolates with reduced sitafloxacin susceptibility (MIC ≥ MIC90), 83.7% (36/43) were identified as sequence type (ST) 8123. Further phylogenetic analysis showed that ST8123 has evolved into two subclades, designated as subclade-I and subclade-II. A majority of the isolates (80%, 36/45) within subclade-I exhibited reduced susceptibility to sitafloxacin. In contrast, all isolates from subclade-II were found to be susceptible to sitafloxacin. Subsequent genomic investigations revealed that the GyrA-S91F, D95Y, and ParC-S87N mutations, which were exclusively found in ST8123 subclade-I, might be linked to reduced sitafloxacin susceptibility. Our study reveals that sitafloxacin is a promising antibiotic for combating drug-resistant N. gonorrhoeae. However, caution is advised in the clinical application of sitafloxacin for treating N. gonorrhoeae infections due to the emergence of a clone exhibiting reduced susceptibility.

Quantitative and Qualitative Parameters of DCE-MRI Predict CDKN2A/B Homozygous Deletion in Gliomas.

RATIONALE AND OBJECTIVES: Homozygous deletion (HD) of CDKN2A/B holds important prognostic value in gliomas. This study aimed to explore the predictive potential of conventional MRI characteristics combined with dynamic contrast-enhanced MRI parameters in predicting CDKN2A/B HD status in gliomas. MATERIALS AND METHODS: Preoperative MRI data of 105 patients (69 without CDKN2A/B HD, and 36 with CDKN2A/B homozygous deletion) with gliomas were retrospectively collected. Conventional MRI features and dynamic contrast-enhanced-MRI qualitative parameter time-intensity curve type, quantitative parameters Ktrans, Kep, Ve, Vp, and iAUC were obtained. Logistic regression models for prediction of CDKN2A/B HD status were constructed in all types of gliomas and both subtypes of IDH-mutant and IDH-wild gliomas. RESULTS: Multivariate analysis for all patients demonstrated that age (OR=1.103, p = 0.002) and Ktrans (OR=1.051, p < 0.001) independently predicted CDKN2A/B HD. In IDH-mutant subgroup, multivariate analysis results indicated that Ktrans (OR=1.098, p = 0.031) emerged as autonomous predictors of CDKN2A/B HD. In IDH-wild subgroup, age (OR=1.111, p = 0.002) and Ktrans (OR=1.032, p = 0.001) were independent predictors of CDKN2A/B HD according to the multivariate analysis. The areas under the receiver operating characteristic curve of the corresponding models were 0.90, 0.95 and 0.84, respectively. CONCLUSION: Ktrans can serve as valuable predictive parameters for identifying CDKN2A/B HD status in all types of gliomas and both subtypes of IDH-mutant and IDH-wild gliomas. These findings provide a foundation for precise preoperative non-invasive diagnosis and personalized treatment approaches for glioma patients.

Manganese and zinc regulate virulence determinants in Borrelia burgdorferi.

Borrelia burgdorferi, the causative agent of Lyme disease, must adapt to two diverse niches, an arthropod vector and a mammalian host. RpoS, an alternative sigma factor, plays a central role in spirochetal adaptation to the mammalian host by governing expression of many genes important for mammalian infection. B. burgdorferi is known to be unique in metal utilization, and little is known of the role of biologically available metals in B. burgdorferi. Here, we identified two transition metal ions, manganese (Mn(2+)) and zinc (Zn(2+)), that influenced regulation of RpoS. The intracellular Mn(2+) level fluctuated approximately 20-fold under different conditions and inversely correlated with levels of RpoS and the major virulence factor OspC. Furthermore, an increase in intracellular Mn(2+) repressed temperature-dependent induction of RpoS and OspC; this repression was overcome by an excess of Zn(2+). Conversely, a decrease of intracellular Mn(2+) by deletion of the Mn(2+) transporter gene, bmtA, resulted in elevated levels of RpoS and OspC. Mn(2+) affected RpoS through BosR, a Fur family homolog that is required for rpoS expression: elevated intracellular Mn(2+) levels greatly reduced the level of BosR protein but not the level of bosR mRNA. Thus, Mn(2+) and Zn(2+) appeared to be important in modulation of the RpoS pathway that is essential to the life cycle of the Lyme disease spirochete. This finding supports the emerging notion that transition metals such as Mn(2+) and Zn(2+) play a critical role in regulation of virulence in bacteria.

Predicting MGMT Promoter Methylation in Diffuse Gliomas Using Deep Learning with Radiomics.

This study aimed to investigate the feasibility of predicting oxygen 6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in diffuse gliomas by developing a deep learning approach using MRI radiomics. A total of 111 patients with diffuse gliomas participated in the retrospective study (56 patients with MGMT promoter methylation and 55 patients with MGMT promoter unmethylation). The radiomics features of the two regions of interest (ROI) (the whole tumor area and the tumor core area) for four sequences, including T1 weighted image (T1WI), T2 weighted image (T2WI), apparent diffusion coefficient (ADC) maps, and T1 contrast-enhanced (T1CE) MR images were extracted and jointly fed into the residual network. Then the deep learning method was developed and evaluated with a five-fold cross-validation, where in each fold, the dataset was randomly divided into training (80%) and validation (20%) cohorts. We compared the performance of all models using area under the curve (AUC) and average accuracy of validation cohorts and calculated the 10 most important features of the best model via a class activation map. Based on the ROI of the whole tumor, the predictive capacity of the T1CE and ADC model achieved the highest AUC value of 0.85. Based on the ROI of the tumor core, the T1CE and ADC model achieved the highest AUC value of 0.90. After comparison, the T1CE combined with the ADC model based on the ROI of the tumor core exhibited the best performance, with the highest average accuracy (0.91) and AUC (0.90) among all models. The deep learning method using MRI radiomics has excellent diagnostic performance with a high accuracy in predicting MGMT promoter methylation in diffuse gliomas.

Gut Microbiota Alternation in Disease Progression of Neurosyphilis.

Background: The gut microbiota plays an important role in the development of neurological disorders such as Parkinson's disease and Alzheimer's disease. However, studies on the gut microbiota of patients with neurosyphilis (NS) were rarely reported. Methods: In this study, we collected fecal samples from 62 syphilis patients, including 39 with NS and 23 with non-NS. Among the NS patients, 18 were general paresis (GP). The white blood cell counts, protein concentrations, and Venereal Disease Research Laboratory test positive rates of cerebrospinal fluid from patients in NS or GP group were significantly higher than those from patients in non-NS group. 16S ribosomal RNA sequencing results revealed that the alpha and beta diversities of the gut microbiota were similar between NS and non-NS patients or GP and non-NS patients. Results: Linear discriminant analysis with effect size (LEfSe) analysis showed that some taxa, such as Coprobacter, were increased in both NS group and GP group, compared with non-NS group. Besides, the clade of Akkermansia was also overrepresented in GP Patients. Meanwhile, some taxa such as Clostridia_UCG-014 and SC-I-84 were underrepresented in NS patients. The abundances of class Bacilli and genus Alloprevotella were decreased in GP patients. Among them, the abundances of some taxa such as Coprobacter and Akkermansia have been reported to be associated with other neuropsychiatric disorders. Conclusion: Our findings suggest that the alternation of the gut microbiota in NS patients may contribute to the course of NS, which will deepen our understanding of NS.