Water-Tolerant Superbase Polyoxometalate [H2(Nb6O19)]6- for Homogeneous Catalysis.

Here, doubly protonated Lindqvist-type niobium oxide cluster [H2(Nb6O19)]6-, fabricated by microwave-assisted hydrothermal synthesis, exhibited superbase catalysis for Knoevenagel and crossed aldol condensation reactions accompanied by activating C-H bond with pKa >26 and proton abstraction from a base indicator with pKa=26.5. Surprisingly, [H2(Nb6O19)]6- exhibited water-tolerant superbase properties for Knoevenagel and crossed aldol condensation reactions in the presence of water, although it is well known that the strong basicity of metal oxides and organic superbase is typically lost by the adsorption of water. Density functional theory calculation revealed that the basic surface oxygens that share the corner of NbO6 units in [H2(Nb6O19)]8- maintained the negative charges even after proton adsorption. This proton capacity and the presence of un-protonated basic sites led to the water tolerance of the superbase catalysis.

Thermal stability of crown-motif [Au9(PPh3)8]3+ and [MAu8(PPh3)8]2+ (M = Pd, Pt) clusters: Effects of gas composition, single-atom doping, and counter anions.

The thermal behaviors of ligand-protected metal clusters, [Au9(PPh3)8]3+ and [MAu8(PPh3)8]2+ (M = Pd, Pt) with a crown-motif structure, were investigated to determine the effects of the gas composition, single-atom doping, and counter anions on the thermal stability of these clusters. We successfully synthesized crown-motif [PdAu8(PPh3)8][HPMo12O40] (PdAu8-PMo12) and [PtAu8(PPh3)8][HPMo12O40] (PtAu8-PMo12) salts with a cesium-chloride-type structure, which is the same as the [Au9(PPh3)8][PMo12O40] (Au9-PMo12) structure. Thermogravimetry-differential thermal analysis/mass spectrometry analysis revealed that the crown-motif structure of Au9-PMo12 was decomposed at ∼475 K without weight loss to form Au nanoparticles. After structural decomposition, the ligands were desorbed from the sample. The ligand desorption temperature of Au9-PMo12 increased under 20% O2 conditions because of the formation of Au nanoparticles and stronger interaction of the formed O=PPh3 than PPh3. The Pd and Pt single-atom doping improved the thermal stability of the clusters. This improvement was due to the formation of a large bonding index of M-Au and a change in Au-PPh3 bonding energy by heteroatom doping. Moreover, we found that the ligand desorption temperatures were also affected by the type of counter anions, whose charge and size influence the localized Coulomb interaction and cluster packing between the cationic ligand-protected metal clusters and counter anions.

Creation of High-Performance Heterogeneous Photocatalysts by Controlling Ligand Desorption and Particle Size of Gold Nanocluster.

Recently, the creation of new heterogeneous catalysts using the unique electronic/geometric structures of small metal nanoclusters (NCs) has received considerable attention. However, to achieve this, it is extremely important to establish methods to remove the ligands from ligand-protected metal NCs while preventing the aggregation of metal NCs. In this study, the ligand-desorption process during calcination was followed for metal-oxide-supported 2-phenylethanethiolate-protected gold (Au) 25-atom metal NCs using five experimental techniques. The results clearly demonstrate that the ligand-desorption process consists of ligand dissociation on the surface of the metal NCs, adsorption of the generated compounds on the support and desorption of the compounds from the support, and the temperatures at which these processes occurred were elucidated. Based on the obtained knowledge, we established a method to form a metal-oxide layer on the surface of Au NCs while preventing their aggregation, thereby succeeding in creating a water-splitting photocatalyst with high activity and stability.

Age-Related Differences in the Time Course of Coagulation and Fibrinolytic Parameters in Patients with Traumatic Brain Injury.

Coagulopathy and older age are common and well-recognized risk factors for poorer outcomes in traumatic brain injury (TBI) patients; however, the relationships between coagulopathy and age remain unclear. We hypothesized that coagulation/fibrinolytic abnormalities are more pronounced in older patients and may be a factor in poorer outcomes. We retrospectively evaluated severe TBI cases in which fibrinogen and D-dimer were measured on arrival and 3-6 h after injury. Propensity score-matched analyses were performed to adjust baseline characteristics between older patients (the "elderly group," aged ≥75 y) and younger patients (the "non-elderly group," aged 16-74 y). A total of 1294 cases (elderly group: 395, non-elderly group: 899) were assessed, and propensity score matching created a matched cohort of 324 pairs. Fibrinogen on admission, the degree of reduction in fibrinogen between admission and 3-6 h post-injury, and D-dimer levels between admission and 3-6 h post-injury were significantly more abnormal in the elderly group than in the non-elderly group. On multivariate logistic regression analysis, independent risk factors for poor prognosis included low fibrinogen and high D-dimer levels on admission. Posttraumatic coagulation and fibrinolytic abnormalities are more severe in older patients, and fibrinogen and D-dimer abnormalities are negative predictive factors.

A retrospective study of the effect of fibrinogen levels during fresh frozen plasma transfusion in patients with traumatic brain injury.

BACKGROUND: The association between traumatic brain injury (TBI) and coagulopathy is well established. While coagulopathy prophylaxis in TBI involves replenishing coagulation factors with fresh frozen plasma (FFP), its effectiveness is controversial. We investigated the relationship between plasma fibrinogen concentration 3 h after initiating FFP transfusion and outcomes and evaluated the correlation with D-dimer levels at admission. METHODS: We retrospectively examined data from 380 patients with severe isolated TBI with blood samples collected a maximum of 1 h following injury. Plasma fibrinogen and D-dimer concentrations were obtained at admission, and plasma fibrinogen concentration was again assessed 3-4 h following injury. The patients were divided into two groups based on whether or not they received FFP transfusion. Patients were also divided into subgroups according their fibrinogen level: ≥ 150 mg/dL (high-fibrinogen subgroup) or < 150 mg/dL (low-fibrinogen subgroup) 3 h after injury. Demographic, clinical, radiological and laboratory data were compared between these subgroups. RESULTS: Glasgow Outcome Scale (GOS) scores at discharge and 3 months after injury were significantly lower in the FFP transfusion group than in the FFP non-transfusion group. Among patients who received FFP, GOS scores at discharge and 3 months after injury were significantly higher in the high-fibrinogen subgroup than in the low-fibrinogen subgroup. Elevated admission D-dimer predicted subsequent fibrinogen decrease. CONCLUSIONS: In FFP transfusion, fibrinogen level ≥ 150 mg/dL 3 h after injury was associated with better outcomes in TBI patients. Assessing the admission D-dimer and tracking the fibrinogen are crucial for optimal coagulopathy prophylaxis in TBI patients.

Efficacy of Thyrotropin-Releasing Hormone Analog for Protracted Disturbance of Consciousness due to Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: The efficacy of thyrotropin-releasing hormone tartrate (TRH-T) for treating prolonged disturbance of consciousness due to aneurysmal subarachnoid hemorrhage (SAH) remains unclear. The purpose of the present study was to determine whether TRH-T was really effective, and what was the recovery factor when it was valid. This was a retrospective study of a single facility. METHODS: We treated 208 patients with aneurysmal SAH at our hospital between 2011 and 2017. Among them, we investigated 97 cases in which TRH-T was administered to prolonged disturbance of consciousness. Thirty one patients with Hasegawa dementia rating scale-revised (HDS-R) score less than 20 were included. Patients' HDS-R scores were evaluated 7 days after clipping the aneurysm and 2 days after completing a course of TRH-T treatment. HDS-R score increases of greater than or over equal to 8 and less than 8 were defined as good and poor outcomes, respectively. Outcomes were compared to 11 patients who did not receive TRH-T treatment. RESULTS: Average initial and post-treatment HDS-R scores were 9 ± 6.6 and 19 ± 9.5, respectively. The good outcome group included 19 patients. Statistically significant differences in HDS-R score changes were observed between the group with initial HDS-R scores of 0-4 and the other groups. Poor outcomes were significantly correlated with age of greater than 60 years and initial HDS-R scores less than oroverequal to 4 points. The improvement in HDS-R score was significantly greater in the TRH-T administration group than the control group. CONCLUSIONS: TRH-T was effective for treating prolonged disturbance of consciousness due to aneurysmal SAH, especially in young patients with HDS-R scores between 5 and 20.

Serum Glucose and Potassium Ratio as Risk Factors for Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Cerebral vasospasm is associated with poor prognosis in patients with aneurysmal subarachnoid hemorrhage (SAH), and biomarkers for predicting poor prognosis have not yet been established. We attempted to clarify the relationship between serum glucose/potassium ratio and cerebral vasospasm in patients with aneurysmal SAH. METHODS: We studied 333 of 535 aneurysmal SAH patients treated between 2006 and 2016 (123 males, 210 females; mean age 59.7 years; range 24-93). We retrospectively analyzed the relationship between cerebral vasospasm grade and clinical risk factors, including serum glucose/potassium ratio. RESULTS: Postoperative angiography revealed cerebral vasospasm in 112 patients (33.6%). Significant correlations existed between the ischemic complication due to cerebral vasospasm and glucose/potassium ratio (P < .0001), glucose (P = .016), and potassium (P = .0017). Serum glucose/potassium ratio was elevated in the cerebral vasospasm grade dependent manner (Spearman's r = 0.1207, P = .0279). According to the Glasgow Outcome Scale (GOS) score at discharge, 185 patients (55.5%) had a poor outcome (GOS scores 1-3). Serum glucose/potassium ratio was significantly correlated between poor outcome (GOS scores 1-3) and age (P < .0001), serum glucose/potassium ratio (P < .0001), glucose (P < .0001), potassium (P = .0004), white blood cell count (P = .0012), and cerebral infarction due to cerebral vasospasm (P < .0001). Multivariate logistic regression analyzes showed significant correlations between cerebral infarction due to cerebral vasospasm and serum glucose/potassium ratio (P = .018), glucose (P = .027), and potassium (P = .052). CONCLUSIONS: Serum glucose/potassium ratio in cases of aneurysmal SAH was significantly associated with cerebral infarction due to cerebral vasospasm and GOS at discharge. Therefore, this factor was useful to predict prognosis in patients with cerebral vasospasm and aneurysmal SAH.

Retrograde suction decompression of a large internal carotid aneurysm using a balloon guide catheter combined with a blood-returning circuit and STA-MCA bypass: a technical note.

It is difficult to treat large internal carotid aneurysms with simple surgical clipping. Here, we present a retrograde suction decompression (RSD) procedure for large internal carotid aneurysms using a balloon guide catheter combined with a blood-returning circuit and a superficial temporal artery to middle cerebral artery (STA-MCA) bypass.All patients underwent an STA-MCA bypass before the temporary occlusion of the internal carotid artery (ICA). A 6-French sheath was inserted into the common carotid artery (CCA), and a 6-French Patrive balloon catheter was placed into the ICA 5 cm past the bifurcation. Aneurysm exposure was obtained; temporary clips were placed on the proximal M1, A1, and posterior communicating (Pcom) segments; and an extension tube was then connected to the balloon catheter. A three-way stopcock was placed, and aspiration was performed through the device to collapse the aneurysm. The aspirated blood was returned to a venous line with an added heparin to prevent anemia after aspiration. During the decompression, the blood flow to the cortical area was supplied through the STA-MCA bypass. After the aneurysm collapse, the surgeon carefully dissected the perforating artery from the aneurysm dome or neck, and permanent clips were then placed on the aneurysm neck. Our procedure has several advantages, such as STA-MCA bypass without external carotid artery occlusion for preventing ischemic complications of the cortical area, anemia may be avoided because of the return of the aspirated blood, and a hybrid operation room is not required to perform this method.

Counteranion-induced structural isomerization of phosphine-protected PdAu8 and PtAu8 clusters.

Controlling the geometric structures of metal clusters through structural isomerization allows for tuning of their electronic state. In this study, we successfully synthesized butterfly-motif [PdAu8(PPh3)8]2+ (PdAu8-B, B means butterfly-motif) and [PtAu8(PPh3)8]2+ (PtAu8-B) by the structural isomerization from crown-motif [PdAu8(PPh3)8]2+ (PdAu8-C, C means crown-motif) and [PtAu8(PPh3)8]2+ (PtAu8-C), induced by association with anionic polyoxometalate, [Mo6O19]2- (Mo6) respectively, whereas their structural isomerization was suppressed by the use of [NO3]- and [PMo12O40]3- as counter anions. DR-UV-vis-NIR and XAFS analyses and density functional theory calculations revealed that the synthesized [PdAu8(PPh3)8][Mo6O19] (PdAu8-Mo6) and [PtAu8(PPh3)8][Mo6O19] (PtAu8-Mo6) had PdAu8-B and PtAu8-B respectively because PdAu8-Mo6 and PtAu8-Mo6 had bands in optical absorption at the longer wavelength region and different structural parameters characteristic of the butterfly-motif structure obtained by XAFS analysis. Single-crystal and powder X-ray diffraction analyses revealed that PdAu8-B and PtAu8-B were surrounded by six Mo6 with rock salt-type packing, which stabilizes the semi-stable butterfly-motif structure to overcome high activation energy for structural isomerization.

Gender-related differences in the coagulofibrinolytic responses and long-term outcomes in patients with isolated traumatic brain injury: A 2-center retrospective study.

Coagulation function differs by gender, with women being characterized as more hypercoagulable. Even in the early stages of trauma, women have been shown to be hypercoagulable. Several studies have also examined the relationship between gender and the prognosis of trauma patients, but no certain conclusions have been reached. Patients with isolated traumatic brain injury (iTBI) are known to have coagulopathy, but no previous studies have examined the gender differences in detail. This is a retrospective analysis of a prospective registry conducted at 2 centers. The study included adult patients with iTBI enrolled from April 2018 to March 2021. Coagulofibrinolytic markers were measured in each patient at 1 hour, 24 hours, 3 days, and 7 days after injury, and neurological outcomes were assessed with the Glasgow Outcome Scale Extended at 6 months. Subgroup analysis was also performed by categorizing patients into groups according to neurological prognosis or age at 50 years. Males (n = 31) and females (n = 21) were included in the analysis. In males, there was a significant difference in the levels of activated partial thromboplastin time (P = .007), fibrin/fibrinogen degradation products (P = .025), D-dimer (P = .034), α2-plasmin inhibitor (P = .030), plasmin-α2-plasmin inhibitor complex (P = .004) at 1 hour after injury between favorable and unfavorable long-term neurological outcome groups, while in females there was no significant difference in these markers between 2 groups. In the age group under 50 years, there were significant gender differences in fibrinogen (day 3: P = .018), fibrin/fibrinogen degradation products (1 hour: P = .037, day 3: P = .009, day 7: P = .037), D-dimer (day 3: P = .005, day 7: P = .010), plasminogen (day 3: P = .032, day 7: P = .032), and plasmin-α2-plasmin inhibitor complex (day 3: P = .001, day 7: P = .001), and these differences were not evident in the age group over 50 years. There were differences in coagulofibrinolytic markers depending on gender in patients with iTBI. In male patients, aggravation of coagulofibrinolytic markers immediately after traumatic brain injury may be associated with poor neurologic outcome 6 months after injury.

Direct Air Capture of CO2 Using a Liquid Amine-Solid Carbamic Acid Phase-Separation System Using Diamines Bearing an Aminocyclohexyl Group.

The phase separation between a liquid amine and the solid carbamic acid exhibited >99% CO2 removal efficiency under a 400 ppm CO2 flow system using diamines bearing an aminocyclohexyl group. Among them, isophorone diamine [IPDA; 3-(aminomethyl)-3,5,5-trimethylcyclohexylamine] exhibited the highest CO2 removal efficiency. IPDA reacted with CO2 in a CO2/IPDA molar ratio of ≥1 even in H2O as a solvent. The captured CO2 was completely desorbed at 333 K because the dissolved carbamate ion releases CO2 at low temperatures. The reusability of IPDA under CO2 adsorption-and-desorption cycles without degradation, the >99% efficiency kept for 100 h under direct air capture conditions, and the high CO2 capture rate (201 mmol/h for 1 mol of amine) suggest that the phase separation system using IPDA is robust and durable for practical use.

Antithrombin activity levels for predicting long-term outcomes in the early phase of isolated traumatic brain injury.

Coagulopathy management is an important strategy for preventing secondary brain damage in patients with traumatic brain injury (TBI). Antithrombin (AT) is a natural anticoagulant that controls coagulation and inflammation pathways. However, the significance of AT activity levels for outcomes in patients with trauma remains unclear. This study aimed to investigate the relationship between AT activity levels and long-term outcomes in patients with TBI; this was a sub-analysis of a prior study that collected blood samples of trauma patients prospectively in a tertiary care center in Kawaguchi City, Japan. We included patients with isolated TBI (iTBI) aged ≥16 years admitted directly to our hospital within 1 h after injury between April 2018 and March 2021. General coagulofibrinolytic and specific molecular biomarkers, including AT, were measured at 1, 3, 6, 12, and 24 h after injury. We analyzed changes in the AT activity levels during the study period and the impact of the AT activity levels on long-term outcomes, the Glasgow Outcome Scale-Extended (GOSE), 6 months after injury. 49 patients were included in this study; 24 had good neurological outcomes (GOSE 6-8), and 25 had poor neurological outcomes (GOSE 1-5). Low AT activity levels were shown within 1 h after injury in patients in the poor GOSE group; this was associated with poor outcomes. Furthermore, AT activity levels 1 h after injury had a strong predictive value for long-term outcomes (area under the receiver operating characteristic curve of 0.871; 95% CI: 0.747-0.994). Multivariate logistic regression analysis with various biomarkers showed that AT was an independent factor of long-term outcome (adjusted odds ratio: 0.873; 95% CI: 0.765-0.996; p=0.043). Another multivariate analysis with severity scores showed that low AT activity levels were associated with poor outcomes (adjusted odds ratio: 0.909; 95% CI: 0.822-1.010; p=0.063). We demonstrated that the AT activity level soon after injury could be a predictor of long-term neurological prognosis in patients with iTBI.

Hyperfibrinolysis and fibrinolysis shutdown in patients with traumatic brain injury.

Traumatic brain injury (TBI) is associated with coagulation/fibrinolysis disorders. We retrospectively evaluated 61 TBI cases transported to hospital within 1 h post-injury. Levels of thrombin-antithrombin III complex (TAT), D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were measured on arrival and 3 h, 6 h, 12 h, 1 day, 3 days and 7 days after injury. Multivariate logistic regression analysis was performed to identify prognostic factors for coagulation and fibrinolysis. Plasma TAT levels peaked at admission and decreased until 1 day after injury. Plasma D-dimer levels increased, peaking up to 3 h after injury, and decreasing up to 3 days after injury. Plasma PAI-1 levels increased up to 3 h after injury, the upward trend continuing until 6 h after injury, followed by a decrease until 3 days after injury. TAT, D-dimer, and PAI-1 were elevated in the acute phase of TBI in cases with poor outcome. Multivariate logistic regression analysis showed that D-dimer elevation from admission to 3 h after injury and PAI-1 elevation from 6 h to 1 day after injury were significant negative prognostic indicators. Post-TBI hypercoagulation, fibrinolysis, and fibrinolysis shutdown were activated consecutively. Hyperfibrinolysis immediately after injury and subsequent fibrinolysis shutdown were associated with poor outcome.

Neurointensive Care of Traumatic Brain Injury Patients Based on Coagulation and Fibrinolytic Parameter Monitoring.

Coagulopathy, a common complication of traumatic brain injury (TBI), is characterized by a hypercoagulable state developing immediately after injury, with hyperfibrinolysis and bleeding tendency peaking 3 h after injury, followed by fibrinolysis shutdown. Reflecting this timeframe, the coagulation factor fibrinogen is first consumed and then degraded after TBI, its concentration rapidly decreasing by 3 h post-TBI. The fibrinolytic marker D-dimer reaches its maximum concentration at the same time. Hyperfibrinolysis in the acute phase of TBI is associated with poor prognosis via hematoma expansion. In the acute phase, the coagulation and fibrinolysis parameters must be monitored to determine the treatment strategy. The combination of D-dimer plasma level at admission and the level of consciousness upon arrival at the hospital can be used to predict the patients who will "talk and deteriorate." Fibrinogen and D-dimer levels should determine case selection and the amount of fresh frozen plasma required for transfusion. Surgery around 3 h after injury, when fibrinolysis and bleeding diathesis peak, should be avoided if possible. In recent years, attempts have been made to estimate the time of injury from the time course of coagulation and fibrinolysis parameter levels, which has been particularly useful in some cases of pediatric abusive head trauma patients.

Serum Glucose-To-Potassium Ratio as a Prognostic Predictor for Severe Traumatic Brain Injury.

BACKGROUND: Initial management of severe traumatic brain injury is important and includes treatment decision-making and prediction of prognosis. We examined whether biomarkers at admission could be useful prognostic predictors. We focused on electrolytes and blood glucose, which can be measured easily at any facility and for which results can be obtained promptly, before those of other biomarkers, such as D-dimer. METHODS: All trauma patients with head injuries treated at Chiba Hokusoh Hospital between 2014 and 2017 were investigated. Cases of multiple trauma accompanied by fatal trauma, hemorrhagic shock, or cardiopulmonary arrest, and pediatric cases, were excluded from this study. Blood gas data at the initial hospital visit were reviewed retrospectively. A poor outcome was defined as death during hospitalization or a vegetative state due to head injury. Factors related to poor outcomes were analyzed. RESULTS: Of the 185 male and 79 female patients studied, 34 had poor outcomes. Poor outcome was significantly correlated with potassium (P = 0.003), glucose (P < 0.001), and glucose-to-potassium ratio (P < 0.001) at arrival. The odds ratio was 4.079 for a glucose-to-potassium ratio of ≥50. CONCLUSIONS: We evaluated blood gas data at the initial hospital visit, as these results can be obtained more quickly than those of other biomarkers assessed previously. Serum glucose-to-potassium ratio at admission may be a potential predictor of prognosis for severe traumatic brain injury.

Time course of coagulation and fibrinolytic parameters in pediatric traumatic brain injury.

OBJECTIVE: Coagulopathy is a well-recognized risk factor for poor outcomes in patients with traumatic brain injury (TBI). Differences in the time courses of coagulation and fibrinolytic parameters between pediatric and adult patients with TBI have not been defined. METHODS: Patients with TBI and an Abbreviated Injury Scale of the head score ≥ 3, in whom the prothrombin time (PT)-international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen concentration, and plasma D-dimer levels were measured on arrival and at 3, 6, and 12 hours after injury, were retrospectively analyzed. Propensity score-matched analyses were performed to adjust baseline characteristics between pediatric patients (aged < 16 years) and adult patients (aged ≥ 16 years). RESULTS: A total of 468 patients (46 children and 422 adults) were included. Propensity score matching resulted in a matched cohort of 46 pairs. Higher PT-INR and APTT values at 1 to 12 hours after injury and lower fibrinogen concentrations at 1 to 6 hours after injury were observed in the pediatric group compared with the adult group. Plasma levels of D-dimer were elevated in both groups at 1 to 12 hours after injury, but no significant differences were seen between the groups. Multivariate logistic regression analysis of the initial coagulation and fibrinolytic parameters in the pediatric group revealed no prognostic significance of the coagulation parameter values, but elevation of the fibrinolytic parameter D-dimer was an independent negative prognostic factor. CONCLUSIONS: In the acute phase of TBI, pediatric patients were characterized by prolongation of PT-INR and APTT and lower fibrinogen concentrations compared with adult patients, but these did not correlate with outcome. D-dimer was an independent prognostic outcome factor in terms of the Glasgow Outcome Scale in pediatric patients with TBI.

Treatment of Geriatric Traumatic Brain Injury: A Nationwide Cohort Study.

BACKGROUND: Because of the aging of the Japanese population, traumatic brain injuries (TBI) have increased in elderly adults. However, the effectiveness and prognosis of intensive treatment for geriatric TBI have not yet been determined. Thus, we used nationwide data from the Japan Neurotrauma Data Bank (JNTDB) projects to analyze prognostic factors for intensive and aggressive treatments. METHODS: We analyzed 1,879 geriatric TBI cases (age ≥65 years) registered in four JNTDB projects: Project 1998 (P1998) to Project 2015 (P2015). Clinical features, use of aggressive treatment, and 6-month outcomes on the Glasgow Outcome Scale (GOS) were compared among study projects. Logistic regression was used to identify prognostic factors in aggressively treated patients. RESULTS: The percentage of geriatric TBI cases significantly increased with time-P1998: 30.1%; Project 2004 (P2004): 34.6%; Project 2009 (P2009): 43.9%; P2015: 53.6%, p<0.0001). Use of aggressive treatment also significantly increased, from 67.0% in P1998 to 69.3% in P2015 (p<0.0001). Less invasive methods, such as trepanation and normothermic targeted temperature management, were more often chosen for geriatric patients. These efforts resulted in a significant decrease in the 6-month mortality rate, from 76.2% in P1998 to 63.1% in P2015 (p=0.0003), although the percentage of severely disabled patients increased, from 8.9% in P1998 to 11.1% in P2015 (p=0.0003). Intraventricular hemorrhage was the factor most strongly associated with unfavorable 6-month outcomes (OR 3.79, 95% CI 1.78-8.06, p<0.0001). CONCLUSIONS: Less invasive treatments reduced mortality in geriatric TBI but did not improve functional outcomes. Patient age was not the strongest prognostic factor; thus, physicians should consider characteristics other than age.

Paternal valproic acid exposure in mice triggers behavioral alterations in offspring.

Sodium valproate (VPA) is the most widely used antiepileptic drug and is increasingly also being used for several non-epileptic indications including migraines and bipolar disorder. It is known that maternal VPA exposure during pregnancy increases the risk of autism spectrum disorder (ASD) in children. Animal model studies have shown that maternal treatment with VPA in rodents conveys an increased risk for ASD-like phenotypes at the molecular, cellular, and behavioral levels. In contrast, the effect of paternal VPA exposure on behaviors in offspring is unknown. This study seeks to investigate whether paternal VPA exposure in rodents triggers behavioral and epigenetic alterations in offspring. The results show that paternal VPA exposure impairs object cognitive memory, suppresses the hyperactivity evoked by an NMDA receptor antagonist in male and female offspring, and disturbs sensorimotor gating in only females. In addition, since VPA is well known as an inhibitor of histone deacetylases, we examined the levels of acetylated histone H3 in the frontal cortex and hippocampus in the offspring of VPA-exposed sires. Interestingly, paternal VPA exposure down-regulates the levels of acetylated histone H3 in the brain in offspring even though VPA exposure increased acetylated histone H3 levels in the testes of sires. Collectively, these findings suggest that paternal VPA exposure may disturb the histone acetylation balance in the brain of offspring through changes in the germline epigenome, leading to behavioral alterations in offspring.

Serum glucose/potassium ratio as a clinical risk factor for aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (SAH) can result in poor outcomes, and biomarkers for predicting poor prognosis have not yet been established. The aim of this study was to clarify the significance of the serum glucose/potassium ratio for predicting the prognosis of aneurysmal SAH. METHODS: The authors retrospectively reviewed the records of 565 patients with aneurysmal SAH between 2006 and 2016. The patient group comprised 208 men and 357 women (mean age 61.5 years, range 10-95 years). A statistical analysis was conducted of the clinical and laboratory risk factors of poor outcome, including the serum glucose/potassium ratio. RESULTS: On estimation of the initial assessment using Hunt and Kosnik (H-K) grading, 233 patients (41.2%) were classified as the severe SAH group (H-K Grade IV or V). There were significant correlations between the severe SAH group and serum glucose/potassium ratio (p < 0.0001). Serum glucose/potassium ratio was elevated in an H-K grade-dependent manner (Spearman's r = 0.5374, p < 0.0001). With the estimation of the Glasgow Outcome Scale (GOS) score at discharge, 355 patients (62.8%) were classified as poor outcome (GOS score 1-3). The serum glucose/potassium ratio was elevated in a GOS score at discharge-dependent manner (Spearman's r = 0.4006, p < 0.0001), and was significantly elevated in the poor outcome group compared with the good outcome group (GOS score 4 or 5; p = 0.0245). There were significant correlations between poor outcome and serum glucose/potassium ratio (p < 0.0001), age (p < 0.0001), brain natriuretic peptide levels (p = 0.011), cerebral infarction due to vasospasm (p < 0.0001), and H-K grade (p < 0.0001). Multivariate logistic regression analyses showed significant correlations between poor outcome and serum glucose/potassium ratio (p = 0.009). CONCLUSIONS: In this study, the serum glucose/potassium ratio of patients with aneurysmal SAH at admission was significantly correlated with H-K grade and GOS score at discharge. Therefore, this ratio was useful for predicting prognosis of aneurysmal SAH, especially in severe cases.