Vascular risk factors for idiopathic normal pressure hydrocephalus: a systematic review and meta-analysis.

Objective: Idiopathic normal-pressure hydrocephalus (iNPH) is a treatable cause of dementia; however, its etiology and pathogenesis remain poorly understood. The objective of this study was to investigate the prevalence and impact of vascular risk factors in patients with iNPH compared to a control cohort to better understand the potential mechanisms and preventive measures. Methods: We systematically searched PubMed, Web of Science, Embase, and the Cochrane Library (from inception to December 20, 2022) for studies reporting vascular risk factors for the development of iNPH. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects models. Results: After screening 1,462 articles, 11 case-control studies comprising 1,048 patients with iNPH and 79,668 cognitively unimpaired controls were included in the meta-analysis. Our data showed that hypertension (N = 991, OR = 2.30, 95% CI 1.64 to 3.23, I2= 64.0%), diabetes mellitus (DM) (N = 985, OR = 3.12, 95% CI 2.29 to 4.27, I2= 44.0%), coronary heart disease (CHD; N = 880, OR = 2.34, 95% CI 1.33 to 4.12, I2= 83.1%), and peripheral vascular disease (N = 172, OR = 2.77, 95% CI 1.50 to 5.13, I2= 0.0%) increased the risk for iNPH, while overweight was a possible factor (N = 225, OR = 2.01, 95% CI 1.34 to 3.04, I2= 0.0%) based on the sensitivity analysis. Smoking and alcohol consumption were not associated with iNPH. Conclusions: Our study suggested that hypertension, DM, CHD, peripheral vascular disease, and overweight were associated with iNPH. These factors might be involved in the pathophysiological mechanisms promoting iNPH. These findings require further investigation in future studies. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, CRD42022383004.

Nitrous oxide-induced neurotoxicity: Clinical characteristics and impacts on overall neurological impairments.

Objective: The reports of the recreational use of nitrous oxide (N2O) and its related neuropathy are increasing. However, it is unclear whether specific clinical characteristics are associated with the overall neurological impairments among these individuals. Methods: We retrospectively included 20 hospitalized patients with N2O-related neurological complaints between January 2016 and March 2021 at the West China Hospital of Sichuan University. Detailed demographic, clinical features, lab tests, and imaging data were collected. A functional disability rating score (FDRS) was calculated to determine the degree of neurological impairment. The relationships between the aforementioned factors and the FDRS sum score were explored. Results: These individuals were aged between 16 and 30 years (mean ± SD: 21.90 ± 4.06). At admission, unsteady gait (95%, nineteen of twenty), weakness (95%, nineteen of twenty), and limb paresthesia (70%, fourteen of twenty) were the most common symptoms; decreased deep tendon reflexes (100%, nineteen of nineteen), reduced muscle strength (95%, nineteen of twenty), and impaired coordination (95%, nineteen of twenty) were frequently found. The FDRS sum scores ranged from 3 to 12. Among all the factors, admission from the emergency room (p = 0.033), decreased hemoglobin (p = 0.004) (without previous VitB12 supplements), decreased red blood cell (RBC) count (p = 0.004) (without previous VitB12 supplements), and increased mean corpuscular volume (p = 0.036) (with previous VitB12 supplements) positively correlated with the FDRS sum score. Conclusion: Nitrous oxide (N2O) could lead to severe neurological impairments among users. Abnormal RBC indicators at admission may be associated with a worse clinical presentation and need further attention. Population education about the consequences of N2O consumption and control measures concerning access to N2O should be further emphasized.

Radiological biomarkers of idiopathic normal pressure hydrocephalus: new approaches for detecting concomitant Alzheimer's disease and predicting prognosis.

Idiopathic normal pressure hydrocephalus (iNPH) is a clinical syndrome characterized by cognitive decline, gait disturbance, and urinary incontinence. As iNPH often occurs in elderly individuals prone to many types of comorbidity, a differential diagnosis with other neurodegenerative diseases is crucial, especially Alzheimer's disease (AD). A growing body of published work provides evidence of radiological methods, including multimodal magnetic resonance imaging and positron emission tomography, which may help noninvasively differentiate iNPH from AD or reveal concurrent AD pathology in vivo. Imaging methods detecting morphological changes, white matter microstructural changes, cerebrospinal fluid circulation, and molecular imaging have been widely applied in iNPH patients. Here, we review radiological biomarkers using different methods in evaluating iNPH pathophysiology and differentiating or detecting concomitant AD, to noninvasively predict the possible outcome postshunt and select candidates for shunt surgery.

Development of an artificial zinc finger - Luciferase fusion protein for the rapid detection of Salmonella typhimurium.

A novel artificial Zinc finger - luciferase fusion protein was successfully developed for rapid detection of Salmonella typhimurium, a worldwide-distributed foodborne pathogen. The designed Zinc finger (ZF) protein bound specifically to a 12 bp region of the Salmonella spp invasion gene invA. While the luciferase from Gaussia princeps called Gaussia luciferase (Gluc) was for the first time fused with the artificial ZF domain to improve the detection sensitivity. The fusion protein successfully recognized and bound to the synthesized invA dsDNA with high specificity and sensitivity. The detection limit was as low as 10 fmol of dsNDA. Then, the bacteria PCR products were subsequently used to assess the zinc finger - luciferase fusion protein. The final results indicated that the ZF-Gluc fusion protein system could detect S. typhimurium as low as 1 CFU/mL in 2 h after the PCR. Therefore, this study provided us with a novel artificial zinc finger fusion protein and an efficient method to accomplish the rapid detection of the major foodborne pathogen S. typhimurium. In addition, the specific artificial ZF proteins that bund to particular dsDNA sequences could be easily designed, the ZF-Gluc might has broad application prospects in the field of rapid pathogenic bacteria detection.

Negative Regulation of Ectoine Uptake and Catabolism in Sinorhizobium meliloti: Characterization of the EhuR Gene.

Ectoine has osmoprotective effects on Sinorhizobium meliloti that differ from its effects in other bacteria. Ectoine does not accumulate in S. meliloti cells; instead, it is degraded. The products of the ehuABCD-eutABCDE operon were previously discovered to be responsible for the uptake and catabolism of ectoine in S. meliloti However, the mechanism by which ectoine is involved in the regulation of the ehuABCD-eutABCDE operon remains unclear. The ehuR gene, which is upstream of and oriented in the same direction as the ehuABCD-eutABCDE operon, encodes a member of the MocR/GntR family of transcriptional regulators. Quantitative reverse transcription-PCR and promoter-lacZ reporter fusion experiments revealed that EhuR represses transcription of the ehuABCD-eutABCDE operon, but this repression is inhibited in the presence of ectoine. Electrophoretic mobility shift assays and DNase I footprinting assays revealed that EhuR bound specifically to the DNA regions overlapping the -35 region of the ehuA promoter and the +1 region of the ehuR promoter. Surface plasmon resonance assays further demonstrated direct interactions between EhuR and the two promoters, although EhuR was found to have higher affinity for the ehuA promoter than for the ehuR promoter. In vitro, DNA binding by EhuR could be directly inhibited by a degradation product of ectoine. Our work demonstrates that EhuR is an important negative transcriptional regulator involved in the regulation of ectoine uptake and catabolism and is likely regulated by one or more end products of ectoine catabolism. IMPORTANCE: Sinorhizobium meliloti is an important soil bacterium that displays symbiotic interactions with legume hosts. Ectoine serves as a key osmoprotectant for S. meliloti However, ectoine does not accumulate in the cells; rather, it is degraded. In this study, we characterized the transcriptional regulation of the operon responsible for ectoine uptake and catabolism in S. meliloti We identified and characterized the transcription repressor EhuR, which is the first MocR/GntR family member found to be involved in the regulation of compatible solute uptake and catabolism. More importantly, we demonstrated for the first time that an ectoine catabolic end product could modulate EhuR DNA-binding activity. Therefore, this work provides new insights into the unique mechanism of ectoine-induced osmoprotection in S. meliloti.