The necessity of lumbar puncture in adult emergency patients with fever-associated seizures.

OBJECTIVE: Central nervous system (CNS) infections are often suspected in adult patients with fever-associated seizures. However, it is unclear whether lumbar puncture (LP) is routinely required in patients with fever-associated seizures. This study aimed to examine the prevalence of meningitis and encephalitis in adult patients with fever-associated seizures and to evaluate whether LP is routinely required. METHODS: We retrospectively studied patients aged ≥16 years who presented to the emergency department with complaints of seizures and fever above 37.5 °C who were admitted to the hospital between January 2017 and December 2019. LP was performed when the emergency physician suspected meningitis or encephalitis. Neurologists assessed patients with normal cerebrospinal fluid (CSF) findings and those admitted without LP after hospitalization. A neurologist confirmed the diagnoses of meningitis and encephalitis. RESULTS: The study included 148 patients. Ninety-seven patients (65.5%) were male, and the median age was 60 years. LP was performed in 105 patients (70.9%), and 14 (13.4%) had CSF pleocytosis. Meningitis and encephalitis were diagnosed in nine patients (6.1%), of whom four (2.8%) had CNS infections. Patients diagnosed with meningitis and encephalitis were more likely to have Glasgow Coma Scale <13 (P = 0.03) and less likely to have a history of seizures or epilepsy (P = 0.04) and had higher C-reactive protein levels than the other patients (P = 0.02). CONCLUSION: The prevalence of meningitis or encephalitis is relatively low in adult patients with fever-associated seizures. Lumbar puncture is considered unnecessary to be performed routinely, but its indication should be carefully considered with reference to the clinical course, comorbidities, and blood tests. Further validation studies with larger sample sizes are needed to confirm the findings of this study.

Head CT findings and deterioration risk in children with head injuries and Glasgow Coma Scales of 15.

OBJECTIVE: Head injuries are an important problem in pediatric emergency care. The majority of head injuries are mild. Even when abnormalities are noted on computed tomography (CT), most patients have good outcomes. We aimed to evaluate the clinical course of pediatric patients who had head injuries and Glasgow Coma Scale (GCS) scores of 15, in whom abnormal findings were noted on head CT, to determine the impact of radiographic features on the need for hospitalization and clinical progression. METHODS: We retrospectively examined patients under 15 years of age with isolated mild head injuries, GCS scores of 15, and abnormal CT findings, and visited the emergency department between September 2011 and March 2019. RESULTS: Ninety-nine patients were included in the study. The median age was 2 years (0-15 years), and 61 (62%) patients were male. Eighty-six (87%) patients were hospitalized, and the median hospital stay was 1 day (1-10 days). Sixty-eight (69%) patients underwent repeat CT, and 12 (18%) patients showed signs of radiographic progression. These 12 patients had subdural or epidural hematomas, and surgical intervention was required for two patients (2%). In patients with isolated skull fracture or subarachnoid hemorrhage alone, no deterioration was noted radiographically or clinically. CONCLUSION: Pediatric head injuries with GCS scores of 15 may rarely require surgical intervention, even when CT shows abnormalities. In particular, patients diagnosed with isolated skull fracture or subarachnoid hemorrhage on CT may not require routine hospitalization. A validation study is needed to confirm the findings of this study.

High fever or hypotension predicts non-hypoglycemia in patients with impaired consciousness in prehospital settings.

AIM: To evaluate whether vital signs can predict whether hypoglycemia can be eliminated as the cause of impaired consciousness in prehospital settings. METHODS: We extracted the data of patients who underwent blood glucose measurements by paramedics in Kobe City, Japan from April 2015 to March 2019. We used receiver operating characteristic curves and calculated the area under the curve (AUC) to evaluate the validity of the vital signs in distinguishing hypoglycemia. We also calculated stratum-specific likelihood ratios to examine the threshold at which hypoglycemia becomes less likely for each vital sign. RESULTS: Of the 1,791 patients, 1,242 were eligible for analysis. Hypoglycemia was observed in 324 patients (26.1%). Significant differences in each vital sign were noted between the hypoglycemic and non-hypoglycemic groups. Body temperature was moderately accurate in differentiating between the two groups (AUC, 0.71; 95% confidence interval, 0.68-0.74). Furthermore, in patients with systolic blood pressure <100 mmHg and body temperature ≥38°C, it was unlikely that hypoglycemia caused impaired consciousness (stratum-specific likelihood ratios 0.12 and 0.15; 95% confidence intervals, 0.05-0.25 and 0.06-0.35, respectively). CONCLUSION: In the prehospital assessment of patients with impaired consciousness, high fever or hypotension was helpful in differentiating between hypoglycemia and non-hypoglycemia. In particular, body temperature ≥38°C or systolic blood pressure <100 mmHg indicated a low likelihood of hypoglycemia. A validation study is needed to confirm the findings in this study.

Progesterone increases blood glucose via hepatic progesterone receptor membrane component 1 under limited or impaired action of insulin.

Hepatic gluconeogenesis is the main pathway for blood glucose maintenance activated during fasting. Retardation of insulin action, such as in diabetes mellitus, activates gluconeogenesis during the fed state. While the role of progesterone (P4) in diabetes is controversial, the P4 receptor, progesterone receptor membrane component 1 (PGRMC1), is known to stimulate pancreatic insulin secretion. We investigated the role of P4, via hepatic PGRMC1, during gluconeogenesis. The PGRMC1 binding chemical, AG-205, induced PGRMC1 monomer (25 kDa) abundance, and increased PEPCK expression and glucose production in parallel with cyclic AMP (cAMP) induction in Hep3B cells. PGRMC1-mediated cyclic AMP was inhibited by an adenylate cyclase inhibitor (MDL-12,330A). PEPCK suppression in Pgrmc1 KO hepatocyte was not observed after treatment of MDL-12,330A. PGRMC1 knockdown or overexpression systems in Hep3B cells confirmed that PGRMC1 mediates PEPCK expression via phosphorylation of cAMP-response element binding protein (CREB). CREB phosphorylation and PEPCK expression in primary hepatocytes were greater than that in PGRMC1 knock-out hepatocytes. Progesterone increased PGRMC1 expression, which induced cAMP and PEPCK induction and glucose production. In vivo, P4 suppressed gluconeogenesis following plasma insulin induction under normal conditions in a mouse model. However, P4 increased blood glucose via gluconeogenesis in parallel with increases in PGRMC1 and PEPCK expression in mice in both insulin-deficient and insulin-resistant conditions. We conclude that P4 increases hepatic glucose production via PGRMC1, which may exacerbate hyperglycaemia in diabetes where insulin action is limited.

Synthesis of quercetin-3-O-glucoside from rutin by Penicillium decumbens naringinase.

UNLABELLED: Enzymatic bioconversion of rutin to quercetin-3-O-glucoside (Q-3-G) by Penicillium decumbens naringinase was increased with reaction pH increased approximately to pH 6.0. It resulted in greater than 92% production of Q-3-G due to the removal of the terminal rhamnose at the controlled pH 6.0. The enzymatic bioconversion of rutin to Q-3-G was repetitively performed, yielding 84% after 5 batches with little quercetin formation. Interestingly, the water solubility of Q-3-G was enhanced 69- and 328-fold over those of rutin and quercetin, which may make Q-3-G more bioavailable in food. Q-3-G was approximately 6- and 1.4-fold more potent than rutin as an inhibitor of human intestinal maltase and human DL-3-hydroxy-3-methylglutalyl coenzyme A reductase. Q-3-G was less potent (16- and 1.3-fold, respectively) than quercetin as an inhibitor of these enzymes. However, the results suggest that Q-3-G may be confirmed more effective and bioavailable food component than rutin and even quercetin because of its enhanced solubility and inhibitory properties. PRACTICAL APPLICATION: Bioconverted intermediate, quercetin-3-O-glucoside (Q-3-G), was found and confirmed to be largely more soluble than rutin and quercetin in water solution, which might make it more bioavailable as food ingredient. In addition, Q-3-G inhibited mildly the intestinal maltase, which might act as antidiabetic substance by modulating the adsorption of glucose in the intestine.

Enzymatic bioconversion of citrus hesperidin by Aspergillus sojae naringinase: enhanced solubility of hesperetin-7-O-glucoside with in vitro inhibition of human intestinal maltase, HMG-CoA reductase, and growth of Helicobacter pylori.

Hesperetin-7-O-glucoside (Hes-7-G) was produced by the enzymatic conversion of hesperidin by Aspergillus sojae naringinase due to the removal of the terminal rhamnose. Extracts from orange juice and peel containing the hesperidin were so treated by this enzyme that the hesperidin could also be converted to Hes-7-G. The solubility of Hes-7-G in 10% ethanol was enhanced 55- and 88-fold over those of hesperidin and hesperetin, respectively, which may make Hes-7-G more bioavailable. Hes-7-G was 1.7- and 2.4-fold better than hesperidin and hesperetin, respectively, in the inhibition of human intestinal maltase. Hes-7-G was more potent by 2- and 4-fold than hesperidin in the inhibition of human HMG-CoA reductase. Additionally, Hes-7-G exhibited more effective inhibition of the growth of Helicobacter pylori than hesperetin, while its effectiveness was similar to that of hesperidin. Therefore, the results suggest that bioconverted Hes-7-G is more effective and bioavailable than hesperidin, as it has enhanced inhibitory and solubility properties.

miR-206 regulates brain-derived neurotrophic factor in Alzheimer disease model.

OBJECTIVE: Alzheimer disease (AD) brains are deficient in brain-derived neurotrophic factor (BDNF), which regulates synaptic plasticity and memory. MicroRNAs (miRNAs) are ∼22-nucleotide small noncoding RNAs that control a variety of physiological and disease processes. Here, we show that miR-206 regulates BDNF and memory function in AD mice. METHODS: Expression of miRNAs was analyzed in Tg2576 AD transgenic mice and human AD brain samples. Regulation of BDNF by a selected miRNA was validated by in silico prediction, target gene luciferase assay, and dendritic spine responses in neurons. AM206, a neutralizing inhibitor of miR-206 (antagomir), was injected into the third ventricle of Tg2576 mice, after which memory function, synaptogenesis, neurogenesis, and target gene expression were assessed. For noninvasive delivery, antagomirs were administered intranasally. RESULTS: The brains of Tg2576 mice and the temporal cortex of human AD brains had increased levels of miR-206. This miRNA targeted BDNF transcripts, and AM206 prevented the detrimental effects of amyloid-ß42 on BDNF and dendritic spine degeneration in Tg2576 neurons. Injection of AM206 into the cerebral ventricles of AD mice increased the brain levels of BDNF and improved their memory function. In parallel, AM206 enhanced the hippocampal synaptic density and neurogenesis. Furthermore, intranasally administered AM206 also reached the brain and increased BDNF levels and memory function in AD mice. INTERPRETATION: Our findings demonstrate a novel miRNA-dependent regulation of BDNF in AD and suggest possible therapeutic approaches, such as noninvasive intranasal delivery of AM206.

Quantitative assessment of nanoparticle single crystallinity: palladium-catalyzed splitting of polycrystalline metal oxide nanoparticles.

Crystal gazing: A simple Pd-catalyzed site-specific nanoetching method was developed to visualize the polycrystalline nature of Fe(3)O(4) (see picture), Fe(2)O(3), MnFe(2)O(4), CoFe(2)O(4), and MnO nanoparticle systems. The technique relies on the very fast etching speed of the grain interface within bi- or polycrystalline nanocrystals.

Selective enrichment of cysteine-containing peptides using SPDP-functionalized superparamagnetic Fe(3)O(4)@SiO(2) nanoparticles: application to comprehensive proteomic profiling.

Superparamagnetic Fe(3)O(4)@SiO(2) core-shell nanoparticles (ca. 30 nm diameter), which are surface-modified with a thiol-specific functional group, exhibit superb capturing efficiency toward cysteinyl peptides without contamination from nonspecifically interacting peptides, as clearly evidenced through LC/MS/MS analysis.