Relationship between prognostic nutritional index and post-stroke cognitive impairment.

BACKGROUND: The Prognostic Nutritional Index (PNI) has been described as a useful screening tool for patient prognosis in several diseases. As a potential diagnostic index, it has attracted the interest of many physicians. However, the correlation between the PNI and post-stroke cognitive impairment (PSCI) remains unclear. METHODS: A total of 285 patients with acute ischemic stroke were included. PNI was assessed as serum albumin (g/L) + 5× lymphocyte count (109/L) and was dichotomized according to the prespecified cut-off points 48.43 for the high and low groups. PSCI was defined as Mini-Mental State Examination (MMSE) < 27 at the 6-10 months follow-up. Multiple logistic regression and linear regression analyses were performed to examine the association between PNI and cognitive outcomes. RESULTS: A low PNI was independently associated with PSCI after adjusting for age, sex, education, National Institutes of Health Stroke Scale (NIHSS), deep white matter hyperintensity (DWMH), and stroke history (odds ratio [OR]: 2.158; 95% confidence interval [CI]: 1.205-3.863). The PNI scores were significantly associated with MMSE and attention domain (ß = 0.113, p = 0.006; ß = 0.109, p = 0.041, respectively). The PNI improved the model's discrimination when added to the model with other clinical risk factors. CONCLUSIONS: A low PNI was independently associated with the occurrence of PSCI and the PNI scores were specifically associated with the scores of global cognition and attention domain. It can be a promising and straightforward screening indicator to identify the person with impaired immune-nutritional status at higher risk of PSCI.

Association between the circulating very long-chain saturated fatty acid and cognitive function in older adults: findings from the NHANES.

BACKGROUND: Age-related cognitive decline has a significant impact on the health and longevity of older adults. Circulating very long-chain saturated fatty acids (VLSFAs) may actively contribute to the improvement of cognitive function. The objective of this study was to investigate the associations between arachidic acid (20:0), docosanoic acid (22:0), tricosanoic acid (23:0), and lignoceric acid (24:0) with cognitive function in older adults. METHODS: This study used a dataset derived from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). A total of 806 adults (≥ 60 years) were included who underwent comprehensive cognitive testing and plasma fatty acid measurements. Multivariable linear regression, restricted cubic spline (RCS), and interaction analyses were used to assess associations between VLSFAs and cognitive function. Partial Spearman' s correlation analysis was used to examine the correlations between VLSFAs and palmitic acid (16:0), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides, systemic inflammatory markers, and dietary nutrients. RESULTS: Multivariable linear regression analysis, adjusting for sociodemographic, clinical conditions, and lifestyle factors, showed that 22:0 and 24:0 levels were positively associated with better global cognitive function (ß = 0.37, 95% confidence interval [CI] = 0.01, 0.73; ß = 0.73, 95% CI = 0.29, 1.2, respectively) as well as better CEARD-DR Z-score (ß = 0.82, 95% CI = 0.36, 1.3 and ß = 1.2, 95% CI = 0.63, 1.8, respectively). RCS analysis showed linear associations between higher 22:0 and 24:0 levels and better cognitive performance in both global cognitive function and CERAD-DR tests. CONCLUSIONS: The study suggests that higher levels of 22:0 and 24:0 are associated with better global cognitive function in older adults. 22:0 and 24:0 may be important biomarkers for recognizing cognitive impairment, and supplementation with specific VLSFAs (22:0 and 24:0) may be an important intervention to improve cognitive function. Further studies are needed to elucidate the underlying biological mechanisms between VLSFAs and cognitive function.

One case report of epilepsy and rapidly progressive cognitive impairment after levofloxacin treatment.

OBJECTIVE: To report a case of seizure and rapidly progressive cognitive impairment 20 min after intravenous administration of levofloxacin. A 56-year-old woman was admitted to hospital with episodic unconsciousness and unresponsiveness. About 4 days ago, she experienced a loss of consciousness, fell to the floor, and yelled for 2 min, 20 min before the first intravenous dose of levofloxacin. The patient developed symptoms of cognitive impairment after the seizure. Levofloxacin is a synthetic third generation fluoroquinolone used to treat various infectious diseases. Upon admission, the patient was conscious and unresponsive. After 11 days of symptomatic and supportive treatment, the patient was discharged from the hospital with cognition restored to baseline level and no recurrence of seizures 10 months after discharge. DISCUSSION: Epilepsy is a rare adverse reaction to levofloxacin treatment. The patient in this case had infection-related signs before the onset of the disease, and the disease progressed rapidly with fluctuating changes. After ruling out degenerative, infectious, toxic, and autoimmune causes, the patient's symptoms may be attributed to levofloxacin, and this is the first case of seizure and rapidly progressive cognitive impairment after levofloxacin injection reported in the literature. Clinicians should be aware that unexplained, rapidly progressing cognitive impairment with infection-related signs before onset may be a rare side effect of antibiotics.

Genetic attenuation of alkaloids and nicotine content in tobacco (Nicotiana tabacum).

MAIN CONCLUSION: The role of six alkaloid biosynthesis genes in the process of nicotine accumulation in tobacco was investigated. Downregulation of ornithine decarboxylase, arginine decarboxylase, and aspartate oxidase resulted in viable plants with a significantly lower nicotine content. Attenuation of nicotine accumulation in Nicotiana tabacum was addressed upon the application of RNAi technologies. The approach entailed a downregulation in the expression of six different alkaloid biosynthesis genes encoding upstream enzymes that are thought to function in the pathway of alkaloid and nicotine biosynthesis. Nine different RNAi constructs were designed to lower the expression level of the genes that encode the enzymes arginine decarboxylase, agmatine deiminase, aspartate oxidase, arginase, ornithine decarboxylase, and SAM synthase. Agrobacterium-based transformation of tobacco leaves was applied, and upon kanamycin selection, T0 and subsequently T1 generation seeds were produced. Mature T1 plants in the greenhouse were topped to prevent flowering and leaf nos. 3 and 4 below the topping point were tested for transcript levels and product accumulation. Down-regulation in arginine decarboxylase, aspartate oxidase, and ornithine decarboxylase consistently resulted in lower levels of nicotine in the leaves of the corresponding plants. Transformants with the aspartate oxidase RNAi construct showed the lowest nicotine level in the leaves, which varied from below the limit of quantification (20 µg per g dry leaf weight) to 1.3 mg per g dry leaf weight. The amount of putrescine, the main polyamine related to nicotine biosynthesis, showed a qualitative correlation with the nicotine content in the arginine decarboxylase and ornithine decarboxylase RNAi-expressing transformants. A putative early senescence phenotype and lower viability of the older leaves was observed in some of the transformant lines. The results are discussed in terms of the role of the above-mentioned genes in the alkaloid biosynthetic pathway and may serve to guide efforts to attenuate nicotine content in tobacco leaves.

Hyperglycemia Induces Osteoclastogenesis and Bone Destruction Through the Activation of Ca2+/Calmodulin-Dependent Protein Kinase II.

Hyperglycemia induces osteoclastogenesis and bone resorption through complicated, undefined mechanisms. Ca2+/calmodulin-dependent protein kinase II (CaMKII) promotes osteoclastogenesis, and could be activated by hyperglycemia. Here, we investigated whether CaMKII is involved in hyperglycemia-induced osteoclastogenesis and subsequent bone resorption. Osteoclast formation, bone resorption, CaMKII expression and phosphorylation were measured under high glucose in vitro and in streptozotocin-induced hyperglycemia rats with or without CaMKII inhibitor KN93. The results showed that 25 mmol/L high glucose in vitro promoted cathepsin K and tartrate-resistant acid phosphatase expression (p < 0.05) and osteoclast formation (p < 0.01) associated with enhancing ß isoform expression (p < 0.05) and CaMKII phosphorylation (p < 0.001). Hyperglycemia promoted the formation of osteoclasts and resorption of trabecular and alveolar bone, and inhibited sizes of femur and mandible associated with enhanced CaMKII phosphorylation (p < 0.001) in rats. All these changes could be alleviated by KN93. These findings imply that CaMKII participates not only in hyperglycemia-induced osteoclastogenesis and subsequent bone resorption, but also in the hyperglycemia-induced developmental inhibition of bone.

Downregulation of the CpSRP43 gene expression confers a truncated light-harvesting antenna (TLA) and enhances biomass and leaf-to-stem ratio in Nicotiana tabacum canopies.

MAIN CONCLUSION: Downregulation in the expression of the signal recognition particle 43 (SRP43) gene in tobacco conferred a truncated photosynthetic light-harvesting antenna (TLA property), and resulted in plants with a greater leaf-to-stem ratio, improved photosynthetic productivity and canopy biomass accumulation under high-density cultivation conditions. Evolution of sizable arrays of light-harvesting antennae in all photosynthetic systems confers a survival advantage for the organism in the wild, where sunlight is often the growth-limiting factor. In crop monocultures, however, this property is strongly counterproductive, when growth takes place under direct and excess sunlight. The large arrays of light-harvesting antennae in crop plants cause the surface of the canopies to over-absorb solar irradiance, far in excess of what is needed to saturate photosynthesis and forcing them to engage in wasteful dissipation of the excess energy. Evidence in this work showed that downregulation by RNA-interference approaches of the Nicotiana tabacum signal recognition particle 43 (SRP43), a nuclear gene encoding a chloroplast-localized component of the photosynthetic light-harvesting assembly pathway, caused a decrease in the light-harvesting antenna size of the photosystems, a corresponding increase in the photosynthetic productivity of chlorophyll in the leaves, and improved tobacco plant canopy biomass accumulation under high-density cultivation conditions. Importantly, the resulting TLA transgenic plants had a substantially greater leaf-to-stem biomass ratio, compared to those of the wild type, grown under identical agronomic conditions. The results are discussed in terms of the potential benefit that could accrue to agriculture upon application of the TLA-technology to crop plants, entailing higher density planting with plants having a greater biomass and leaf-to-stem ratio, translating into greater crop yields per plant with canopies in a novel agronomic configuration.

Mechanical Properties and Deformation Mechanisms of Nanocrystalline U-10Mo Alloys by Molecular Dynamics Simulation.

U-Mo alloys were considered to be the most promising candidates for high-density nuclear fuel. The uniaxial tensile behavior of nanocrystalline U-10Mo alloys with average grain sizes of 8-23 nm was systematically studied by molecular dynamics (MD) simulation, mainly focusing on the influence of average grain size on the mechanical properties and deformation mechanisms. The results show that Young's modulus, yield strength and ultimate tensile strength follow as average grain size increases. During the deformation process, localized phase transitions were observed in samples. Grain boundary sliding and grain rotation, as well as twinning, dominated the deformation in the smaller and larger grain sizes samples, respectively. Increased grain size led to greater localized shear deformation, resulting in greater stress drop. Additionally, we elucidated the effects of temperature and strain rate on tensile behavior and found that lower temperatures and higher strain rates not only facilitated the twinning tendency but also favored the occurrence of phase transitions in samples. Results from this research could provide guidance for the design and optimization of U-10Mo alloys materials.

High neutrophil percentage and neutrophil-lymphocyte ratio in acute phase of ischemic stroke predict cognitive impairment: A single-center retrospective study in China.

Background and aims: Recently, various hemocyte and blood cell ratios have garnered researchers' attention, as a low-cost, widely prevalent, and easy-to-measure index for diagnosing and predicting disease. Therefore, we sought to investigate the effect and predictive value of the peripheral blood neutrophil percentage and neutrophil-lymphocyte ratio (NLR) in the acute phase of ischemic stroke (AIS) in post-stroke cognitive impairment (PSCI). Methods: We selected 454 patients with mild AIS and acquired general clinical data. The patients were divided into PSCI and post-stroke no cognitive impairment (PSNCI) groups according to their Montreal Cognitive Assessment (MOCA) scores. We assessed whether there were differences in clinical data, peripheral blood neutrophil percentage, and NLR values between the different groups. We also analyzed the independent influences on the occurrence of PSCI using a binary logistic regression. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of the above inflammatory indicators and models containing different inflammatory indicators for PSCI. Results: In total, 454 patients were included, of whom 253 (55.7%) patients were in the PSCI group, with a mean age of 62.15 ± 7.34 years and median neutrophil percentage and NLR of 0.64 (0.32-0.95) and 2.39 (0.71-54.46), respectively. Both neutrophil percentage (adjusted OR = 1.025; 95% confidence interval: 1.005-1.406) and NLR as a categorical variable (Q5, adjusted OR = 2.167; 95% CI: 1.127-4.166) were independent risk factors for PSCI, and the Q5 group (NLR ≥ 4.05) had significantly worse overall cognition and executive function. Conclusions: Neutrophil percentage and NLR in the acute phase of AIS were independently associated with PSCI, and a high NLR was strongly associated with executive function. In addition, neutrophil percentage and NLR have diagnostic values for PSCI.

Hashimoto's encephalopathy with cerebellar ataxia as the main symptom: A case report and literature review.

Hashimoto's encephalopathy (HE), also known as steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT), has a variety of clinical manifestations, with various neuropsychiatric characteristics, including tremors, transient aphasia, seizures, altered consciousness, myoclonus, cognitive impairment, and psychiatric manifestations. The hallmark presenting feature is a non-specific encephalopathy characterized by alteration of mental status and consciousness ranging from confusion to coma and impaired cognitive function, while those with cerebellar ataxia as the main manifestation is rare. We reported a case of Hashimoto's encephalopathy with cerebellar ataxia as the main manifestation, elevated anti-thyroid antibodies (anti-TPO/TG), and normal thyroid function. The symptoms of cerebellar ataxia improved after steroid treatment. Meanwhile, we reviewed the clinical features of 20 representative cases of HE with cerebellar ataxia as the core symptoms. In conclusion, based on our case findings and literature review, the diagnosis of HE should be suspected in cases of encephalopathy without an obvious cause, to quickly start an effective treatment.

Urinary dysfunction in patients with vascular cognitive impairment.

Vascular cognitive impairment (VCI) is caused by vascular pathologies, with the spectrum of cognitive disorders ranging from subjective cognitive dysfunction to dementia. Particularly among older adults, cognitive impairment is often complicated with urinary dysfunction (UD); some patients may present with UD before cognitive impairment owing to stroke or even when there are white matter hyperintensities on imaging studies. Patients with cognitive impairment often have both language and movement dysfunction, and thus, UD in patients with VCI can often be underdiagnosed and remain untreated. UD has an impact on the quality of life of patients and caregivers, often leading to poor outcomes. Medical history is an important aspect and should be taken from both patients and their caregivers. Clinical assessment including urinalysis, voiding diary, scales on UD and cognitive impairment, post-void residual volume measurement, uroflowmetry, and (video-) urodynamics should be performed according to indication. Although studies on UD with VCI are few, most of them show that an overactive bladder (OAB) is the most common UD type, and urinary incontinence is the most common symptom. Normal urine storage and micturition in a specific environment are complex processes that require a sophisticated neural network. Although there are many studies on the brain-urinary circuit, the specific circuit involving VCI and UD remains unclear. Currently, there is no disease-modifying pharmacological treatment for cognitive impairment, and anti-acetylcholine drugs, which are commonly used to treat OAB, may cause cognitive impairment, leading to a vicious circle. Therefore, it is important to understand the complex interaction between UD and VCI and formulate individualized treatment plans. This review provides an overview of research advances in clinical features, imaging and pathological characteristics, and treatment options of UD in patients with VCI to increase subject awareness, facilitate research, and improve diagnosis and treatment rates.

The Potential Role of Ferroptosis in Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent cause of dementia, accounting for approximately 60%-80%of all cases. Although much effort has been made over the years, the precise mechanism of AD has not been completely elucidated. Recently, great attention has shifted to the roles of iron metabolism, lipid peroxidation, and oxidative stress in AD pathogenesis. We also note that these pathological events are the vital regulators of a novel regulatory cell death, termed ferroptosis-an iron-dependent, oxidative, non-apoptotic cell death. Ferroptosis differs from apoptosis, necrosis, and autophagy with respect to morphology, biochemistry, and genetics. Mounting evidence suggests that ferroptosis may be involved in neurological disorders, including AD. Here, we review the underlying mechanisms of ferroptosis; discuss the potential interaction between AD and ferroptosis in terms of iron metabolism, lipid peroxidation, and the glutathione/glutathione peroxidase 4 axis; and describe some associated studies that have explored the implication of ferroptosis in AD.

Impact of nicotine pathway downregulation on polyamine biosynthesis and leaf ripening in tobacco.

Traditional breeding and molecular approaches have been used to develop tobacco varieties with reduced nicotine and secondary alkaloid levels. However, available low-alkaloid tobacco varieties have impaired leaf quality likely due to the metabolic consequences of nicotine biosynthesis downregulation. Recently, we found evidence that the unbalanced crosstalk between nicotine and polyamine pathways is involved in impaired leaf ripening of a low-alkaloid (LA) Burley 21 line having a mutation at the Nic1 and Nic2 loci, key biosynthetic regulators of nicotine biosynthesis. Since the Nic1 and Nic2 loci are comprised of several genes, all phenotypic changes seen in LA Burley 21 could be due to a mixture of genetics-based responses. Here, we investigated the commercial burley variety TN90 LC and its transgenic versions with only one downregulated gene, either putrescine methyl transferase (PMT-RNAi) or PR50-protein (PR50-RNAi). Nicotine levels of cured lamina of TN90 LC, TN90 PMT-RNAi and TN90 PR50-RNAi, were 70.5 ± 3.8, 2.4 ± 0.5, and 6.0 ± 1.1 mg/g dry weight, respectively. Low-alkaloid transgenic lines showed delayed leaf maturation and impaired leaf quality. We analyzed polyamine contents and ripening markers in wild-type TN90 control plants (WT) and the two transgenic lines. The ripening markers revealed that the PMT-RNAi line showed the most pronounced impaired leaf maturation phenotype at harvest, characterized by higher chlorophyll (19%) and glucose (173%) contents and more leaf mesophyll cells per area (25%), while the ripening markers revealed that maturation of PR50-RNAi plants was intermediate between PMT-RNAi and WT lines. Comparative polyamine analyses showed an increase in free and conjugated polyamines in roots of both transgenic lines, this being most pronounced in the PMT-RNAi plants. For PMT-RNAi plants, there were further perturbations of polyamine content in the leaves, which mirrored the general phenotype, as PR50-RNAi transgenic plants looked more similar to the WT than PMT-RNAi transgenic plants. Activity of ornithine decarboxylase, the enzyme that catalyzes the committing step of polyamine biosynthesis, was significantly higher in roots and mature leaves of PMT-RNAi plants in comparison to WT, while there was no increase observed for arginine decarboxylase. Treatment of both transgenic lines with polyamine biosynthesis inhibitors decreased the polyamine content and ameliorated the phenotype, confirming the intricate interplay of polyamine and nicotine biosynthesis in tobacco and the influence of this interplay on leaf ripening.

High-performance aqueous sodium-ion battery using a hybrid electrolyte with a wide electrochemical stability window.

The practical application of aqueous sodium-ion batteries (ASIBs) is limited by the electrolysis of water, which results in a low working voltage and energy density of ASIBs. Here, a NaClO4-based acetonitrile/water hybrid electrolyte (NaClO4(H2O)2AN2.4) is applied to ASIBs for the first time, which effectively extends the electrochemical stability window (ESW) to 3.0 V and reduces the internal resistance of the battery. Based on this hybrid electrolyte, an ASIB full cell using carbon coated Na2.85K0.15V2(PO4)3 and NaTi2(PO4)3 as the cathode and anode materials, respectively, can afford a discharge capacity and energy density of 52 mA h g-1 and 51 W h kg-1, respectively, at a current density of 1 A g-1. The energy density of this battery exceeds almost all reported traditional ASIBs.

Multifocal occurrence of intraoral isolated MS in a patient without leukemic presentation: A case report and literature review.

Myeloid sarcoma (MS), also referred to as chloroma or granulocytic sarcoma, is a rare extramedullary malignant tumor composed of immature myeloid cells. MS usually occurs with acute myelocytic leukemia, myeloproliferative neoplasm, or myelodysplastic syndrome or as a recurrence of acute myelocytic leukemia; however, MS may occasionally present as isolated, without current or previous peripheral blood or bone marrow involvement. Oral and maxillofacial MS, especially isolated, is extremely rare, and the clinical manifestations are diverse and usually nonspecific. Here, we report a rare case of isolated nonleukemic MS involving the gingivae, the mucosa of the left maxillary edentulous region, and the adjacent hard palate. The pertinent literature was also reviewed to provide additional clarification on the clinicopathologic characteristics, differential diagnosis, treatment regimens, and prognosis of oral and maxillofacial isolated MS.

miR-34a and miR-125b are upregulated in peripheral blood mononuclear cells from patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a leading cause of blindness, non-traumatic amputation and end-stage renal disease, as well as a major cardiovascular risk factor. To determine whether miR-125b and miR-34a serve an important role in the development of T2DM, the current study investigated the expression profile of two microRNAs (miR-34a and miR-125b) and their relative genes in peripheral blood mononuclear cells from 73 patients with T2DM and 52 healthy donors by reverse transcription-quantitative polymerase chain reaction In addition, the association between miR-34a, miR-125b and their relevant genes expression profile were analyzed with respect to the pathogenesis of T2DM. The present study demonstrated that the expression levels of miR-125b and miR-34a were elevated in peripheral blood mononuclear cell samples from patients with T2DM. Furthermore, miR-34a and miR-125b were positively correlated with low-density lipoprotein/high-density lipoprotein (HDL) and Foxp3 and negatively related to triglyceride/HDL. However, no correlation among miR-34a, miR-125b and the value of homeostasis model assessment of insulin resistance, homeostasis model assessment of ß-cell function and the genes of B lymphocyte-induced maturation protein-1, interferon regulatory factor-4, P53 and retinoid-related orphan receptor γt were observed. These results indicate that the alteration of miR-34a and miR-125b exists in patients with T2DM, which may be involved in the pathogenesis of T2DM, and could be a potential novel biomarker of T2DM.

Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease.

Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.