Rapidly progressive cerebral atrophy following a posterior cranial fossa stroke: Assessment with semiautomatic CT volumetry.

BACKGROUND: The effect of posterior cranial fossa stroke on changes in cerebral volume is not known. We assessed cerebral volume changes in patients with acute posterior fossa stroke using CT scans, and looked for risk factors for cerebral atrophy. METHODS: Patients with cerebellar or brainstem hemorrhage/infarction admitted to the ICU, and who underwent at least two subsequent inpatient head CT scans during hospitalization were included (n = 60). The cerebral volume was estimated using an automatic segmentation method. Patients with cerebral volume reduction > 0% from the first to the last scan were defined as the "cerebral atrophy group (n = 47)," and those with ≤ 0% were defined as the "no cerebral atrophy group (n = 13)." RESULTS: The cerebral atrophy group showed a significant decrease in cerebral volume (first CT scan: 0.974 ± 0.109 L vs. last CT scan: 0.927 ± 0.104 L, P < 0.001). The mean percentage change in cerebral volume between CT scans in the cerebral atrophy group was -4.7%, equivalent to a cerebral volume of 46.8 cm3, over a median of 17 days. The proportions of cases with a history of hypertension, diabetes mellitus, and median time on mechanical ventilation were significantly higher in the cerebral atrophy group than in the no cerebral atrophy group. CONCLUSIONS: Many ICU patients with posterior cranial fossa stroke showed signs of cerebral atrophy. Those with rapidly progressive cerebral atrophy were more likely to have a history of hypertension or diabetes mellitus and required prolonged ventilation.

Evolutionary diversification of Japanese Stomaphis aphids (Aphididae, Lachninae) in relation to their host plant use and ant association.

Phytophagous insects are among the most diverse of the earth's organisms, and their diversification patterns and the driving forces behind these have attracted considerable research interest. Host shifting to closely related plant species is thought to play an important role in phytophagous insect diversification, but the extent to which other interactions such as mutualistic associations affect diversification is not yet known. In this study, we reconstructed the molecular phylogeny of Japanese Stomaphis aphids and determined whether host shifting or mutualistic association with different ant species could explain diversification in this aphid genus. We analyzed 12 species of Stomaphis and grouped them into ten well-supported DNA lineages. Species in each lineage used a single or a few host plant species, but were mutualistically associated with many ant species of the genus Lasius. This result suggests that Stomaphis evolutionarily diversified primarily through host plant shifts. Interestingly, the reconstructed phylogeny suggests that Stomaphis host shifts occasionally occurred between very distantly related host plant taxa (spanning up to five plant orders). The dependence of Stomaphis on long-lasting Lasius ant colonies situated in temperate deciduous forests where Lasius is the dominant ant genus may have led the aphids to shift to distantly related but spatially adjacent host tree species.

High HMGA2 expression without gene rearrangement in meningiomas.

High mobility group AT-hook 2 (HMGA2) is a non-histone transcriptional regulator protein. Aberrant expression of the HMGA2 gene (HMGA2) and structural rearrangement at the chromosomal region 12q14 with HMGA2 involvement have been reported in several mesenchymal tumors. We analyzed truncated and full-length HMGA2 expression in 55 cases of meningioma, the most common brain tumor of mesenchymal origin. Fluorescence in situ hybridization and 3'-rapid amplification of cDNA ends were used to investigate the possibility of gene rearrangements. Moreover, the relationship between HMGA2 expression and clinicopathological features was assessed. Compared with normal brain tissues, 95% of the meningioma tissues exhibited increased HMGA2 expression. In 14 cases, the expression of truncated HMGA2 was more than two-fold higher than that of paired full-length HMGA2. Chromosomal translocation involving the chromosomal region 12q14 was undetectable. No significant correlation was found between the Ki-67 labeling index and HMGA2 expression and between the HMGA2 expression and the clinicopathological features. The majority of the meningioma cases displayed increased HMGA2 expression, which was not attributed to the chromosomal rearrangement at the corresponding region. Similar to that in the other mesenchymal tumors, increased HMGA2 expression was not associated with tumor cell proliferation in meningiomas.

[Spontaneous Retroclival Subdural Hematoma Diagnosed Using Magnetic Resonance Imaging in an Adult Patient:A Case Report].

Spontaneous retroclival subdural hematoma is rare among adults. To the best of our knowledge, only six cases have been reported. A 73-year-old man presented with sudden severe headache, diplopia, and dysarthria, with no history of trauma. Head CT revealed a retrociliary hematoma. No obvious causes of bleeding, such as cerebral aneurysms or malformations, were detected. Conservative treatment was provided to the patient. MRI showed an intraventricular hemorrhage and a space between the basilar artery and hematoma three days after onset. The hematoma almost disappeared on day 7. MRI, particularly T2-weighted sagittal MRI, is effective in localizing hematomas and confirming intraventricular hemorrhages.

Clinical impact of insulin resistance on pulmonary vein isolation outcome in patients with paroxysmal atrial fibrillation.

INTRODUCTION: The relationship between insulin resistance and atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) remains unclear. METHODS: Drug-refractory 114 paroxysmal AF patients (89 males, 62 ± 8 years) who underwent successful PVI were enrolled. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated and a value of ≥2.5 was defined as insulin resistant. The left atrial volume index (LAVI) was measured using echocardiography before and 1 year after PVI. Tumor necrosis factor-α (TNF-α) and TGF-ß1 serum levels were measured before PVI, and the left atrium (LA) conduction velocity was calculated. The patients were divided into two groups (group 1: HOMA-IR < 2.5, n = 81; group 2: HOMA-IR ≥ 2.5, n = 33). RESULTS: The LAVI between the two groups before PVI did not significantly differ (P > 0.05), nor did TNF-α (7.7 ± 2.0 vs 7.5 ± 1.0 pg/mL; P = 0.149) or TGF-ß1 (28.4 ± 12.0 vs 27.6 ± 10.3 ng/mL; P = 0.757). LAVI before and 1 year after PVI in each group did not change. The conduction velocity of group 2 was slower than that of group 1 (0.7 ± 0.1 vs 1.1 ± 0.3 m/s, P < 0.001). Kaplan-Meier analysis showed significantly higher AF recurrence in group 2 than that in group 1 ( P = 0.019). Cox multivariable analysis revealed that insulin resistance was an independent predictor of recurrence (hazard ratio 1.287, P = 0.004). CONCLUSION: Our results suggest that insulin resistance promotes LA electrical remodeling and might be related to AF recurrence after PVI.

Glucocorticoids attenuate the sensitivity of glucocorticoid-resistant lymphoid cells to doxorubicin via reduction in OCTN2.

Glucocorticoid (GC) resistance is associated with poor response to the following chemotherapy in lymphoid malignancies, such as lymphoma and leukemia. However, it remains unclear whether GCs interfere with the cytotoxic effects of anti-cancer drugs on GC-resistant cells. In this study, we examined whether GCs affected the sensitivities to vincristine (VCR)/doxorubicin (DOX) and the expression of drug transporters in GC-resistant cells. The dexamethasone (DEX)/prednisolone (PSL)-resistant lymphoid and non-lymphoid cell lines Raji and HL60 were cultured with DEX for 7 days and then treated with VCR or DOX for 3 days. Seven days of DEX treatment increased the IC50s of both VCR and DOX in Raji cells but not in HL60 cells. The mRNA and protein expression levels of organic cation/carnitine transporter (OCTN) 2, one of the drug uptake transporters expressed in both cell lines, were decreased only in Raji cells. When Raji cells were cultured with PSL, the IC50 of DOX but not VCR increased as the expression of OCTN2 decreased. No significant increases in efflux transporter expression were induced by DEX or PSL. When siRNA against OCTN2 was introduced into Raji cells, the IC50 of DOX but not VCR increased significantly. These data suggested that both DEX and PSL decreased the sensitivity of the DEX/PSL-resistant Raji cells to DOX, a change that was at least partially due to reductions in OCTN2. Thus, the continuous usage of GCs may interfere with the effects of chemotherapy on GC-resistant lymphoid cells.

Generation of sub-two-cycle CEP-stable optical pulses at 3.5 µm from a KTA-based optical parametric amplifier with multiple-plate compression.

We demonstrate the generation of 21 fs (1.8 optical cycle), 45-µJ, carrier-envelope phase (CEP)-stable optical pulses with an octave-spanning spectrum from 2.2 to 4.9 µm. Multi-cycle output pulses (120 fs, 149 µJ, 3.5 µm, and 300 Hz) from a KTA-based optical parametric amplifier are compressed down to the sub-two-cycle regime using YAG and Si plates. The single-shot CEP stability of the compressed pulses is measured to be 283 mrad for 500 s. This robust and compact scheme realizes a field strength of 282 MV/cm with f/11 focusing, opening a new regime of attosecond strong-field physics in solids.

Anatomical predisposing factors of transmural thermal injury after pulmonary vein isolation.

Aims: Transmural thermal injury (TTI), such as oesophageal erosion/ulcer and perioesophageal nerve injury leading to gastric hypomotility, is an important complication associated with pulmonary vein isolation (PVI). However, a predictor of TTI concerning anatomical structures surrounding the oesophagus has not yet been fully elucidated. Therefore, we sought to identify the predisposing factors of TTI after PVI. Methods and results: Consecutive 110 patients, who underwent PVI for atrial fibrillation, received oesophagogastroduodenoscopy 2 days later, were investigated. The relationships between TTI and clinical and anatomical parameters were examined. Based on the computed tomography data, we measured the angle of the left atrial (LA) posterior wall to the descending aorta (Ao) (LA-Ao angle), the branching angle of the left inferior pulmonary vein (LIPV) to the coronal plane (LIPV angle), and the minimum distance between the LA posterior wall and descending Ao enclosing the oesophagus (LA-Ao distance). Transmural thermal injuries occurred in 21 patients (oesophageal erosion in 5 and gastric hypomotility in 16). Age, gender, body mass index, LA diameter, and LA volume index in echocardiography were not associated with TTI. However, the LIPV angle was larger and the LA-Ao distance was shorter in the TTI (+) group compared to the TTI (-) group. With multivariate logistic regression analysis, the LIPV angle [odds ratio (OR): 2.144, P = 0.0031] and LA-Ao distance (OR: 0.392, P = 0.0229) were independent predictors of TTI. Conclusion: The anatomical proximities of the LA posterior wall, LIPV, and descending Ao surrounding the oesophagus are strongly associated with the prevalence of TTI.

Association between Serum Uric Acid Level and Ventricular Tachyarrhythmia in Heart Failure Patients with Implantable Cardioverter-Defibrillator.

OBJECTIVES: The uric acid (UA) level is related to cardiac events and mortality, but little is known about the clinical significance of serum UA with regard to the ventricular tachyarrhythmia (VT) risk in patients with heart failure. METHODS: The present study enrolled 56 patients with ischemic and nonischemic cardiomyopathy (37 males, mean age 64.7 ± 11.1 years) who received prophylactic implantable cardioverter-defibrillator (ICD) implantation. Based on a median serum UA value, study subjects were divided into two groups: serum UA < 6.1 mg/dL (group L, n = 29) and ≥6.1 mg/dL (group H, n = 27). Echo- and electrocardiograms (QRS duration and QTc intervals) were examined in each group. RESULTS: During the follow-up period (30 ± 8 months), 22 (39%) patients had appropriate ICD therapies for sustained VT. There was no significant difference in the electro- and echocardiographic data between both groups. However, appropriate ICD therapies were significantly higher in group H than in group L (p = 0.02). In multivariate analysis, UA was an independent predictor of appropriate ICD therapies (hazard ratio 1.826, 95% confidence interval 1.248-2.671, p = 0.002). CONCLUSIONS: Serum UA levels might be a predictor of VT, providing new aspects regarding the decision to adapt ICD implantation in patients with heart failure.

Uncontrolled blood pressure affects atrial remodeling and adverse clinical outcome in paroxysmal atrial fibrillation.

BACKGROUND: To investigate the impact of uncontrolled blood pressure (BP) on left atrial (LA) remodeling and clinical outcome after pulmonary vein isolation (PVI) in paroxysmal atrial fibrillation (AF). METHODS: One hundred and one symptomatic paroxysmal AF patients (85 males, 62.2 ± 8.4-year-old) who underwent successful PVI were classified as follows: group 1 (n = 46), no hypertension (HTN); group 2 (n = 36), HTN with controlled BP; and group 3 (n = 19), HTN with uncontrolled BP. Uncontrolled BP was defined as BP > 140/90 mm Hg. LA dimension was measured by echocardiography before and 6 months after PVI. LA wall thickness along the ablation line was measured using computed tomography prior to PVI. Cox regression analysis was performed for the prediction of recurrence. RESULTS: LA wall thickness in groups 2 and 3 was greater than that of group 1, except for the anterior right superior pulmonary vein (PV) and posterior left inferior PV. Kaplan-Meier analysis revealed a significantly higher recurrence in group 3 (52.6%). LA dimension only increased in group 3 (38.2 ± 5.6 mm to 41.3 ± 6.2 mm, P = 0.022). At the second procedure, all group 3 recurrent patients showed substrate degradation (low voltage area and/or dense scar formation) and required substrate modification. Uncontrolled BP was an independent risk factor for recurrence (hazard ratio: 2.350, P = 0.033). CONCLUSIONS: HTN induced heterogeneous LA hypertrophy regardless of whether HTN was controlled. Uncontrolled BP promoted atrial remodeling, and is therefore a strong predictor for recurrence of AF after PVI.

Change of Exhaled Acetone Concentration in a Diabetic Patient with Acute Decompensated Heart Failure.

In heart failure patients, exhaled acetone concentration, a noninvasive biomarker, is increased according to heart failure severity. Moreover, exhaled acetone concentration is also known to be affected by diabetes mellitus. However, there have been no reports on exhaled acetone concentration in heart failure patients with diabetes mellitus. A 77-year old man was admitted to our hospital with acute decompensated heart failure and atrioventricular block. He had controlled diabetes mellitus under insulin treatment with hemoglobin A1c of 6.5%. He underwent treatment of diuretics and permanent pacemaker implantation. His condition improved and he was discharged at Day 12. Due to the heart failure improvement, his levels of exhaled acetone concentration decreased from 1.623 ppm at admission to 0.664 ppm at discharge. This is the first report to reveal a change of exhaled acetone concentration in a diabetic patient with acute decompensated heart failure.

Crystal structure of a complex of human chymase with its benzimidazole derived inhibitor.

The crystal structure of human chymase complexed with a novel benzimidazole inhibitor, TJK002, was determined at 2.8 Å resolution. The X-ray crystallographic study shows that the benzimidazole inhibitor forms a non-covalent interaction with the catalytic domain of human chymase. The hydrophobic fragment of the inhibitor occupies the S1 pocket. The carboxylic acid group of the inhibitor forms hydrogen bonds with the imidazole N(ℇ) atom of His57 and/or the O(γ) atom of Ser195 which are members of the catalytic triad. This imidazole ring of His57 induces π-π stacking to the benzene ring of the benzimidazole scaffold as P2 moiety. Fragment molecular orbital calculation of the atomic coordinates by X-ray crystallography shows that this imidazole ring of His57 could be protonated with the carboxyl group of Asp102 or hydroxyl group of Ser195 and the stacking interaction is stabilized. A new drug design strategy is proposed where the stacking to the protonated imidazole of the drug target protein with the benzimidazole scaffold inhibitor causes unpredicted potent inhibitory activity for some enzymes.

Structure of the ß-form of human MK2 in complex with the non-selective kinase inhibitor TEI-L03090.

Mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAP-K2), a serine/threonine kinase from the p38 mitogen-activated protein kinase signalling pathway, plays an important role in the production of TNF-α and other cytokines. In a previous report, it was shown that MK2 in complex with the selective inhibitor TEI-I01800 adopts an α-helical glycine-rich loop that is induced by the stable nonplanar conformer of TEI-I01800. To understand the mechanism of the structural change, the structure of MK2 bound to TEI-L03090, which lacks the key substituent found in TEI-I01800, was determined. MK2-TEI-L03090 has a ß-sheet glycine-rich loop in common with other kinases, as predicted. This result suggests that a small compound can induce a drastic conformational change in the target protein structure and can be used to design potent and selective inhibitors.

A Case of Ruptured Carotid Traumatic Blood Blister-like Aneurysm.

Ruptured cerebral aneurysms that occur in the anterior wall of the internal carotid artery (ICA) are known as blood blister-like aneurysms (BBAs); they have been reported to account for 0.3% to 1% of all ruptured ICA aneurysms. In this report, we describe the treatment of an unusual traumatic BBA (tBBA) with high-flow bypass using a radial artery graft, which resulted in a favorable outcome. A 59-year-old female suffered from an acute epidural hematoma, traumatic subarachnoid hemorrhage, and traumatic carotid-cavernous sinus fistula (tCCF) after being involved in a motor vehicle accident. Her angiography results showed tCCF and a tBBA on the anterior wall of the right ICA. On the fourth day after injury, we found rebleeding from the tBBA and performed an emergency high-flow bypass using a radial artery graft with lesion trapping as a curative procedure for the tCCF and tBBA. Postoperatively, right abducens nerve palsy appeared, but no other neurological symptoms were noted; the patient was thereafter transferred to a rehabilitation hospital 49 days after injury. Traumatic ICA aneurysms commonly occur close to the anterior clinoid process, form within 1 to 2 weeks of injury, and often rupture around 2 weeks after trauma. This case was considered rare as the ICA was likely injured and bleeding at the time of injury, resulting in a form of tBBA; this allowed early detection and appropriate treatment that resulted in a good 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.

Kinematic evaluation of the adjacent segments after lumbar instrumented surgery: a comparison between rigid fusion and dynamic non-fusion stabilization.

The aim of the current study was to evaluate changes in lumbar kinematics after lumbar monosegmental instrumented surgery with rigid fusion and dynamic non-fusion stabilization. A total of 77 lumbar spinal stenosis patients with L4 degenerative spondylolisthesis underwent L4-5 monosegmental posterior instrumented surgery. Of these, 36 patients were treated with rigid fusion (transforaminal lumbar interbody fusion) and 41 with dynamic stabilization [segmental spinal correction system (SSCS)]. Lumbar kinematics was evaluated with functional radiographs preoperatively and at final follow-up postoperatively. We defined the contribution of each segmental mobility to the total lumbar mobility as the percent segmental mobility [(sagittal angular motion of each segment in degrees)/(total sagittal angular motion in degrees) × 100]. Magnetic resonance imaging was performed on all patients preoperatively and at final follow-up postoperatively. The discs were classified into five grades based on the previously reported system. We defined the progress of disc degeneration as (grade at final follow-up) - (grade at preoperatively). No significant kinematical differences were shown at any of the lumbar segments preoperatively; however, significant differences were observed at the L2-3, L4-5, and L5-S1 segments postoperatively between the groups. At final follow-up, all of the lumbar segments with rigid fusion demonstrated significantly greater disc degeneration than those with dynamic stabilization. Our results suggest that the SSCS preserved 14% of the kinematical operations at the instrumented segment. The SSCS may prevent excessive effects on adjacent segmental kinematics and may prevent the incidence of adjacent segment disorder.

[Emotional display rules of Japanese and Koreans].

Hypothetical stories designed to arouse feelings of happiness, sadness, or anger were presented to Japanese (n = 310) and Koreans (n = 286) university students. They were asked to rate the intensity of the emotion experienced, and to select the corresponding facial expression to display in an individual situation and in a social situation. Analyses of covariance were conducted on the rating scores of facial expression using the intensities of emotion as the covariance, except for happiness where the within-class regression coefficients were not homogeneous. The results showed that Japanese and Koreans shared the emotional display rules about the expressions of emotions in individual situations more than in social situations. Japanese thought that they should suppress emotions more than Koreans did. Moreover, the differences in facial expressions between Japanese and Koreans were greater in the individual situations than in the social situations.

Target Coil Embolization Using the Combined Transarterial and Transvenous Balloon-assisted Technique for Traumatic Direct Carotid Cavernous Fistula.

Herein, we describe a case of traumatic direct carotid cavernous fistula (DCCF) treated with target coil embolization using the combined transarterial and transvenous balloon-assisted technique. The patient was a 59-year-old woman who had been involved in a vehicular accident. She was admitted to the hospital due to chemosis and exophthalmos. Cerebral angiography revealed a shunt from the internal carotid artery (ICA) to the cavernous sinus (CS), which indicated DCCF. Thus, target coil embolization using the combined transarterial and transvenous balloon-assisted technique was performed. Angiography was performed 1 week after surgery to confirm the disappearance of DCCF. No recurrence was observed during the 1-year follow-up after treatment. Thus, target coil embolization using the combined transarterial and transvenous balloon-assisted technique is safe and effective for the treatment of traumatic DCCF.

Temperature drop in thawing phase reflects sufficient ice formation and better outcome of pulmonary vein isolation using second-generation cryoballoon.

BACKGROUND: Few reports exist regarding the details of ice formation on second-generation cryoballoon (CB) surface during pulmonary vein isolation (PVI). We propose a new parameter "temperature drop" in thawing phase for predicting sufficient ice formation and CB-PVI outcome. METHODS: Consecutive 106 patients who underwent successful CB-PVI for atrial fibrillation (AF) were analyzed. We defined "temperature drop" as a temperature drop of more than 3 °C just after CB catheter bending. We compared the previously known parameters predicting durable PVI between PVs with or without temperature drop. Then, we compared the PVI outcome among three groups: group 1 with temperature drop in all PVs, group 2 with temperature drop in 1-3 PVs, and group 3 without temperature drop in any PV. RESULTS: Temperature drop was present in 206 out of 424 isolated PVs. In those, PV occlusion score was significantly higher (3.7 ± 0.5 vs. 3.5 ± 0.6, P <0.001), and thawing time was significantly longer (55 ± 20 vs. 46 ± 21 s, P < 0.001) in PVs with temperature drop than those without. With a mean follow up period of 376 ± 217 days, Kaplan-Meier survival analysis revealed that no patients in group 1 experienced AF recurrence, 14 out of 86 patients (16%) experienced AF recurrence in group 2, and 5 out of 10 (50%) patients experienced AF recurrence in group 3 (Log-Rank P = 0.003). CONCLUSION: The temperature drop in thawing phase might reflect the state of ice formation and can be used to predict clinical outcome after CB-PVI.