Aneurysmal subarachnoid hemorrhage occurring during sleep: Clinical characteristics and risk factors.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is known to be triggered by several specific human activities. Sleep, by contrast, has not been considered a triggering activity for aSAH, and clinical characteristics of patients who sustain aSAH during sleep have rarely been reported in the literature. METHODS: This is a retrospective analysis on the data acquired through a multicenter aSAH registry. Between January 2019 and December 2021, a total of 732 aSAH patients had been registered into our database. After excluding 109 patients whose activities at aSAH onset had been unidentifiable, the remaining 623 aSAH patients were dichotomized to 59 patients who sustained aSAH during sleep (Sleep group) and 564 patients who sustained aSAH during daytime activities (Awake group). Two-group comparison of demographic variables and multivariate logistic regression analysis were performed to clarify their clinical characteristics and identify potential risk factors. RESULTS: The Sleep group exhibited significantly higher frequencies of diabetes (15.5 % vs. 6.4 %, p = 0.01) and antiplatelet use (13.8 % vs. 4.6 %, p=0.004) than the Awake group. Furthermore, multivariate logistic regression analysis showed that diabetes (OR, 3.051; 95 % CI, 1.281-7.268; p = 0.012) and antiplatelet use (OR, 3.640; 95 % CI, 1.422-9.316; p = 0.007) were correlated with aSAH occurring during sleep. There were no significant inter-group differences in the patient outcomes evaluated at discharge. CONCLUSION: The current results indicate that risk factors may exist for aSAH occurring during sleep. Further investigations on how comorbidities such as diabetes, antiplatelet use and sleep apnea affect human hemodynamic and hemostatic parameters during sleep is warranted to better understand those relationships.

Characteristics of Pediatric Nasal Foreign Body Cases That Required Multiple Removal Procedures: A Single Tertiary Medical Center Cross-Sectional Study.

OBJECTIVES: Removal of nasal foreign bodies in children should be completed as few numbers of times as possible to reduce the burden on the child. This study aimed to reveal the characteristics of pediatric nasal foreign body cases that required multiple removal procedure and to investigate the appropriate removal method for each shape of foreign body. METHODS: We retrospectively reviewed patients who visited a pediatric emergency department because of nasal foreign body from November 1, 2018, to October 31, 2020. We compared the characteristics of patients, foreign bodies, and treatment between the success and failure groups in the first removal procedure. Moreover, we described the detail of patients in the failure group. We also showed final successful removal methods according to the shape of the foreign bodies. RESULTS: We included 104 children in our analysis. Between the success and failure groups in the first removal procedure, there was no statistically significant difference in the characteristics of patients and foreign bodies but a significant difference in the removal method ( P < 0.001). In the failure groups, the most frequent number of times required for removal is 2 and the most common methods in the first removal procedure was the parent's kiss, most of which were performed on spherical foreign bodies in younger children, Finally, only 7 cases (6.7%) failed to remove the foreign body. According to the shape of the foreign bodies, the percentage of forceps and clamps used for successful removal was high in every shape. CONCLUSIONS: There was a significant difference in the removal method between the success and failure groups in the first removal procedure, but finally, most foreign bodies were removed by emergency physicians. Therefore, further research is needed to determine the appropriate removal method for each patient and foreign body.

Prediction of genetic subgroups in adult supra tentorial gliomas by pre- and intraoperative parameters.

Recent progress in neuro-oncology has validated the significance of genetic diagnosis in gliomas. We previously investigated IDH1/2 and TP53 mutations via Sanger sequencing for adult supratentorial gliomas and reported that PCR-based sequence analysis classified gliomas into three genetic subgroups that have a strong association with patient prognosis: IDH mutant gliomas without TP53 mutations, IDH and TP53 mutant gliomas, and IDH wild-type gliomas. Furthermore, this analysis had a strong association with patient prognosis. To predict genetic subgroups prior to initial surgery, we retrospectively investigated preoperative radiological data using CT and MRI, including MR spectroscopy (MRS), and evaluated positive 5-aminolevulinic acid (5-ALA) fluorescence as an intraoperative factor. We subsequently compared these factors to differentiate each genetic subgroup. Multiple factors such as age at diagnosis, tumor location, gadolinium enhancement, 5-ALA fluorescence, and several tumor metabolites according to MRS, such as myo-inositol (myo-inositol/total choline) or lipid20, were statistically significant factors for differentiating IDH mutant and wild-type, suggesting that these two subtypes have totally distinct characteristics. In contrast, only calcification, laterality, and lipid13 (lipid13/total Choline) were statistically significant parameters for differentiating TP53 wild-type and mutant in IDH mutant gliomas. In this study, we detected several pre- and intraoperative factors that enabled us to predict genetic subgroups for adult supratentorial gliomas and clarified that lipid13 quantified by MRS is the key tumor metabolite that differentiates TP53 wild-type and mutant in IDH mutant gliomas. These results suggested that each genetic subtype in gliomas selects the distinct lipid synthesis pathways in the process of tumorigenesis.

World Health Organization grade II-III astrocytomas consist of genetically distinct tumor lineages.

Recent investigations revealed genetic analysis provides important information in management of gliomas, and we previously reported grade II-III gliomas could be classified into clinically relevant subgroups based on the DNA copy number aberrations (CNAs). To develop more precise genetic subgrouping, we investigated the correlation between CNAs and mutational status of the gene encoding isocitrate dehydrogenase (IDH) of those tumors. We analyzed the IDH status and CNAs of 174 adult supratentorial gliomas of astrocytic or oligodendroglial origin by PCR-based direct sequencing and comparative genomic hybridization, respectively. We analyzed the relationship between genetic subclassification and clinical features. We found the most frequent aberrations in IDH mutant tumors were the combined whole arm-loss of 1p and 19q (1p/19q codeletion) followed by gain on chromosome arm 7q (+7q). The gain of whole chromosome 7 (+7) and loss of 10q (-10q) were detected in IDH wild-type tumors. Kaplan-Meier estimates for progression-free survival showed that the tumors with mutant IDH, -1p/19q, or +7q (in the absence of +7p) survived longer than tumors with wild-type IDH, +7, or -10q. As tumors with +7 (IDH wild-type) showed a more aggressive clinical nature, they are probably not a subtype that developed from the slowly progressive tumors with +7q (IDH mutant). Thus, tumors with a gain on chromosome 7 (mostly astrocytic) comprise multiple lineages, and such differences in their biological nature should be taken into consideration during their clinical management.

Neuroepithelial cyst of the fourth ventricle.

PURPOSE: Neuroepithelial cyst is considered an unusual differential diagnosis for cysts in the posterior fossa. Here, we present a paediatric case with such a pathology and review the pertinent literature. METHODS: A 12-year old girl with headache, vertigo and disturbed gait was diagnosed with a cystic lesion in the fourth ventricle after brain MRI study. She was operated with the pre-operative diagnosis of arachnoid cyst. RESULTS: A transparent, colourless cyst was observed intra-operatively. As frozen sections were consistent with endodermal cyst, total removal of the cyst was attempted. Definite histopathological studies and immunohistochemistry stains were in favour of neuroepithelial cyst. No regrowth of the cyst or recurrence of the symptoms was observed in her 2-year follow-up. CONCLUSIONS: As neuroepithelial cyst is rarely encountered in the posterior fossa, the clinical, radiological and pathological characteristics of our case along with similar cases in the literature were reviewed and discussed.

Cardiac wall motion abnormality after bleeding from vertebral artery aneurysms.

OBJECTIVE: Lesions in the medulla oblongata may be causally associated with cardiac wall motion abnormality (WMA). Although subarachnoid hemorrhage (SAH) patients occasionally develop WMA, the relationship between aneurysmal locations and the frequency of WMA has rarely been investigated. The objective of this study was to evaluate whether the frequency of WMA was higher after the rupture of vertebral artery (VA) aneurysms than that of non-VA aneurysms. METHODS: We performed a retrospective chart analysis of 244 SAH patients who underwent transthoracic echocardiography and plasma catecholamine measurements. The frequencies of WMA and electrocardiographic (ECG) abnormalities were compared among patients classified by the location of aneurysms. Multivariate regression analysis was conducted to identify variables correlated with WMA. Furthermore, the relationship between plasma catecholamine levels and aneurysmal locations was evaluated. RESULTS: The frequency of WMA was significantly higher in patients with VA aneurysms than in those with non-VA aneurysms (45 vs. 22 %, p = 0.01). However, there was no significant difference in the frequency of ECG abnormalities. Multivariate regression analysis showed that VA aneurysms (OR, 3.317; 95 % CI, 1.129-9.745), poor-grade SAH (OR, 2.733; 95 % CI, 1.320-5.658) and concomitant hydrocephalus (OR, 3.658; 95 % CI, 1.690-7.917) correlated with WMA. There were no significant intergroup differences in plasma catecholamine levels. CONCLUSION: VA aneurysms are close to several medullary nuclei that integrate autonomic inputs. A transient deformation and ischemia of the medulla oblongata caused by the mechanical stress related to the rupture of a VA aneurysm and/or a concomitant hydrocephalus may be responsible for the disproportionately high frequency of WMA.

Hemispheric differences in the surgical outcomes of patients with traumatic acute subdural hematoma.

BACKGROUND: Our assumption that prognosis of patients with traumatic acute subdural hematoma (ASDH) does not differ significantly according to the hemispheric laterality has never been verified. METHODS: A review of the charts/radiographic images of 61 adult traumatic ASDH patients (33 left/28 right) was conducted. Intergroup comparison was made on the demographics, autonomic/laboratory data, and outcomes (90-day mortality rate). Based on the presence of concomitant brain contusion, patients were further quadrichotomized as: left ASDH with contusion (n = 14), right ASDH with contusion (n = 16), left ASDH without contusion (n = 19), and right ASDH without contusion (n = 12). Comparisons were made on demographic and outcome variables between the left ASDH with contusion and right ASDH with contusion, and between the left ASDH without contusion and right ASDH without contusion. Multivariate regression analysis was conducted to identify clinical variables correlated with fatality. RESULTS: There were no significant differences in the demographic, autonomic, and laboratory data between the left and right ASDH patients. However, 90-day mortality rate was significantly higher in the left ASDH patients when concomitant contusion was present (79% vs. 25%, p = 0.009). However, there were no significant hemispheric differences in the mortality rate among those without contusion (32% vs. 33%, p = 0.77). Multivariate regression analysis showed that left ASDH was correlated with fatality among those with contusion (OR: 6.620; 95% CI: 1.219-46.249). CONCLUSIONS: This study is probably the first to report that the left ASDH patients fared substantially worse than the right-sided counterparts. Future trials on traumatic ASDHs may benefit from considering hemispheric differences in the outcomes.

The Cdk inhibitor flavopiridol enhances temozolomide-induced cytotoxicity in human glioma cells.

The recent progress in chemotherapy for malignant gliomas is attributable to the introduction of the DNA-methylating agent temozolomide (TMZ); however, drug resistance remains a major issue. Previous studies have shown that TMZ induces prolonged arrest of human glioma cells in the G2/M phase of the cell cycle followed by a senescence-like phenomenon or mitotic catastrophe. These findings suggest that the G2 checkpoint is linked to DNA repair mechanisms. We investigated the effect of a cyclin-dependent kinase (Cdk) inhibitor flavopiridol (FP) that inhibits the action of Cdc2, a key protein in the G2 checkpoint pathway, on TMZ-treated glioma cells. Colony formation efficiency revealed that FP potentiated the cytotoxicity of TMZ in glioma cells in a p53-independent manner. This effect was clearly associated with the suppression of key proteins at the G2-M transition, accumulation of the cells exclusively at the G2 phase, and increase in a double-stranded DNA break marker (seen on performing immunoblotting). TMZ-resistant clones showed activation of the G2 checkpoint in response to TMZ, while FP treatment resensitized these clones to TMZ. FP also enhanced the cytotoxicity of TMZ in U87MG-AktER cells. Moreover, administration of TMZ and/or FP to nude mice with xenografted U87MG cells revealed that FP sensitized xenografted U87MG cells to TMZ in these mice. Our findings suggest that TMZ resistance could be promoted by enhanced DNA repair activity in the G2-M transition and that a Cdk inhibitor could suppress this activity, leading to potentiation of TMZ action on glioma cells.

Surgical navigation-assisted endoscopic biopsy is feasible for safe and reliable diagnosis of unresectable solid brain tumors.

Stereotactic biopsy has been validated for tissue sampling of deep-seated lesions that cannot be easily resected via open craniotomy. However, some inherent problems including the inability to directly observe the lesion and difficulty in confirming hemostasis limit its usefulness. To overcome these issues, we used the endoscope in brain tumor biopsy, for not only intraventricular tumors but also intraparenchymal tumors. The rigid scope was used in association with a surgical navigation system for intraparenchymal lesions via a transcortical route. There were no useful anatomical landmarks when the trajectory to the lesions was decided; therefore, surgical navigation system was required for the transcortical procedures. The endoscopic procedure described here was attempted in 21 cases of intraparenchymal lesions between January 2007 and February 2012. A definitive diagnosis was obtained in all cases, and genetic analysis was performed when required. Serious postsurgical hemorrhage or neurological deficits were not observed in any cases. Endoscopic surgery provides a clear view of the target and makes it easier to differentiate tumor tissue from normal brain tissue. Moreover, the endoscope helped to confirm hemostasis during the procedure. Thus, endoscopic biopsy has the potential to contribute toward safe and reliable diagnosis of brain tumors.

Early seizures after clipping of unruptured aneurysms of the anterior circulation: analysis on consecutive 1,000 cases.

Seizures occurring after clipping of unruptured cerebral aneurysms have rarely been documented in the literature. The objective of this retrospective study is to clarify whether the frequency of early seizures, i.e., seizures occurring within 14 days of surgery, is influenced by patient- or aneurysm-specific characteristics. Data on 1,000 consecutive patients who underwent clipping of unruptured anterior circulation aneurysms were reviewed. They consisted of 387 men and 613 women with mean age of 59.8 ± 9.7 years. Fifty-one patients (5.1 %) developed early seizures. Interestingly, the frequency was similar to that occurring after clipping of unruptured posterior circulation aneurysms (n = 20, 5.0 %). Multivariate regression analysis revealed that younger age was correlated with early seizures (odds ratio (OR) 0.902; 95 % confidence interval (CI) 0.891-0.989). However, other variables, including aneurysm size and operation length, were not correlated. Although patients with history of epilepsy exhibited relatively high frequency of early seizures, the difference was not statistically significant. The frequency was unaffected by location or multiplicity of aneurysms. Thirty-one patients (61 %) developed seizures within 24 h of clipping. Regarding seizure types, 34 (67 %) developed generalized seizures and the other 17 (33 %) experienced partial seizures. Patients with generalized seizures were significantly more likely to harbor an iatrogenic brain lesion than those with partial seizures (47 vs. 18 %; OR 4.148; 95 % CI 1.005-17.113). Among 40 patients with follow-up period >12 months, seizures were temporary without recurrence in 38 (95 %). Although early seizures are mostly benign, a small possibility of them becoming a permanent morbidity needs to be explained to patients undergoing elective clipping.

Early CT signs of hypoxia in patients with subarachnoid hemorrhage presenting with cardiac arrest: early CT signs in SAH patients presenting with CA.

BACKGROUND: For cardiac arrest (CA) victims, brain computed tomography (CT) may serve as a prognosticator. Loss of gray-white matter discrimination (GWMD) and sulcal edema/effacement are reliable CT signs of hypoxia, and a time window may exist for development of these signs. Most data are derived from CA victims of cardiac etiology, however, and CT signs have rarely been evaluated in victims of CA secondary to subarachnoid hemorrhage (SAH). METHODS: A retrospective study was conducted to clarify the incidence, temporal profile, and prognostic significance of early CT signs in resuscitated SAH-CA patients. RESULTS: During a 6-year period, 35 SAH-CA patients were identified. CT signs were observed in 94 %: loss of GWMD was observed in 94 %, whereas sulcal edema/effacement was observed in 77 %. In 29 patients, the interval between CA and the return of spontaneous circulation (ROSC) was estimated. CT signs developed almost invariably when the CA-ROSC interval exceeded 10 min. Loss of GWMD always preceded sulcal edema/effacement. None of the 35 patients achieved long-term survival, regardless of the presence of the CT signs. CONCLUSION: CT signs may develop earlier in patients with SAH-CA than CA of cardiac origin. Because of a poor prognosis, early CT signs are not useful prognosticators in that population.

Decompressive hemicraniectomy for malignant hemispheric stroke in the elderly: comparison of outcomes between individuals 61-70 and >70 years of age.

BACKGROUND: Malignant hemispheric infarction is a life-threatening condition with a high mortality rate. Decompressive hemicraniectomy (DHC) is frequently a life-saving procedure that has shown the highest grade of evidence for patients 18 to 60 years of age. However, the efficacy of DHC in patients>60 years of age has rarely been investigated. METHODS: A retrospective study was conducted in a single academic institution. Surrogates of patients with clinical signs of impending brain herniation despite standard medical therapy were offered the option of DHC regardless of age or the side of the lesion. The clinical data from 18 patients>60 years of age who underwent DHC for malignant hemispheric infarction in our institution were analyzed. Patients were classified into the following 2 groups: 61-70 and >70 years of age, and their demographics and surgical outcomes were compared. The variables compared included the male:female ratio, side of the lesion, type of stroke, site of vascular occlusion, use of thrombolytic therapy, National Institutes of Health Stroke Scale score, stroke onset-to-DHC interval, duration of hospital stay, infectious complications, and 90-day mortality rate. RESULTS: There were no significant intergroup differences in any of the demographic variables evaluated. However, the 30-day mortality rate was significantly higher in the group that was >70 years of age (0% v 60%; P=.01) than in the group that was 61 to 70 years of age. CONCLUSIONS: We suggest that the efficacy of DHC in malignant hemispheric stroke patients between 61 and 70 years of age be further investigated in future randomized trials. By contrast, it appears unlikely that patients>70 years of age would benefit from DHC.

Annual patterns in the outcomes and post-arrest care for pediatric out-of-hospital cardiac arrest: A nationwide multicenter prospective registry in Japan.

AIM: Out-of-hospital cardiac arrest (OHCA) has a poor prognosis in children; however, the annual patterns of prognosis and treatment have not been fully investigated. METHODS: From the Japanese Association for Acute Medicine OHCA registry, a multicenter prospective observational registry in Japan, we identified pediatric patients (zero to 17 years old) between June 2014 and December 2019. The primary outcome was one-month survival. We investigated the annual patterns in patient characteristics, treatment, and one-month prognosis. RESULTS: During the study period, 1188 patients were eligible for analysis. For all years, the zero-year-old group accounted for a large percentage of the total population (between 30% and 40%). There were significant increases in the rates of bystander-initiated cardiopulmonary resuscitation (CPR; from 50.6% to 62.3%, p = 0.003), dispatcher instructions (from 44.7% to 65.7%, p = 0.001), and adrenaline administration (from 2.4% to 6.9%, p = 0.014) over time, whereas the rate of advanced airway management decreased significantly (from 17.7% to 8.8%, p = 0.003). The odds ratios for one-month survival adjusted for potential resuscitation factors also did not change significantly (from 7.1% to 10.3%, adjusted odds ratio for one-year increment = 0.98, confidence interval: 0.86-1.11). CONCLUSION: Despite an increase in the rate of bystander-initiated CPR and pre-hospital adrenaline administration, there was no significant change in one-month survival.

The role of catecholamines in the pathogenesis of neurogenic pulmonary edema associated with subarachnoid hemorrhage.

BACKGROUND: Neurogenic pulmonary edema (NPE) occurs frequently after aneurysmal subarachnoid hemorrhage (SAH), and excessive release of catecholamines (epinephrine/norepinephrine) has been suggested as its principal cause. The objective of this retrospective study is to evaluate the relative contribution of each catecholamine in the pathogenesis of NPE associated with SAH. METHODS: Records of 63 SAH patients (20 men/43 women) whose plasma catecholamine levels were measured within 48 h of SAH onset were reviewed, and the clinical characteristics and laboratory data of those who developed early-onset NPE were analyzed thoroughly. RESULTS: Seven patients (11 %) were diagnosed with NPE on admission. Demographic comparison revealed that the NPE+ group sustained more severe SAH than the NPE- group. Cardiac dysfunction was also significantly more profound in the former, and the great majority of the NPE+ group sustained concomitant cardiac wall motion abnormality. There was no significant difference in the plasma epinephrine levels between NPE+ and NPE- group (324.6 ± 172.8 vs 163.1 ± 257.2 pg/ml, p = 0.11). By contrast, plasma norepinephrine levels were significantly higher in the NPE+ group (2977.6 ± 2034.5 vs 847.9 ± 535.6 pg/ml, p < 0.001). Multivariate regression analysis revealed that increased norepinephrine levels were associated with NPE (OR, 1.003; 95 % CI, 1.002-1.007). Plasma epinephrine and norepinephrine levels were positively correlated (R = 0.48, p < 0.001). According to receiver operating characteristic curve analysis, the threshold value for plasma norepinephrine predictive of NPE was 2,000 pg/ml, with an area under the curve value of 0.85. CONCLUSIONS: Elevated plasma norepinephrine may have more active role in the pathogenesis of SAH-induced NPE compared with epinephrine, although both catecholamines may be involved via multiple signaling pathways.

Cerebral venous sinus thrombosis in an adult patient presenting as headache and acute subdural hematoma.

We report a 55-year-old man with cerebral venous sinus thrombosis presenting as acute subdural hematoma. He was treated with an intravenous infusion of heparin sodium and the occluded superior sagittal sinus was recanalized. According to our literature review, acute subdural hematoma caused by cerebral venous sinus thrombosis is relatively rare, and only a single case has reported thus far. We speculate that dehydration was the reason for cerebral venous sinus thrombosis in the present case, and the sudden rise in intracranial pressure in addition to hemodynamic stress caused by cerebral venous sinus thrombosis resulted in the collapse of a bridging vein and caused an acute subdural hematoma.

Target Temperature Management and Survival with Favorable Neurological Outcome After Out-of-Hospital Cardiac Arrest in Children: A Nationwide Multicenter Prospective Study in Japan.

To assess whether target temperature management (TTM) is effective for 1-month survival with favorable neurological outcome among pediatric patients who achieved return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA). The Japanese Association for Acute Medicine-out-of-hospital cardiac arrest (JAAM-OHCA) Registry, a multicenter prospective observational registry in Japan, included OHCA patients aged ≤17 years who achieved ROSC between June 2014 and December 2017. The primary outcome was 1-month survival with favorable neurological outcomes, defined as pediatric cerebral performance category 1 or 2. We conducted a propensity score analysis with inverse-probability-of-treatment weighting (IPTW) and evaluated the effect of TTM using logistic regression models with IPTW. A total of 167 patients [120 in the non-TTM group (71.9%) and 47 in the TTM group (28.1%)] were eligible for our analysis. The proportion of patients demonstrating 1-month survival with favorable neurological outcomes was 25.5% (12/47) in the TTM group and 16.7% (20/120) in the non-TTM group; there were no significant differences in favorable neurological outcomes (odds ratio, 1.36; 95% confidence interval, 0.55-3.35) between the non-TTM and TTM groups after performing adjustments with IPTW. In our study population composed of pediatric patients who achieved ROSC after OHCA, we did not find a positive association between TTM implementation and 1-month survival with favorable neurological outcomes.

Dimer structure and conformational variability in the N-terminal region of an archaeal small heat shock protein, StHsp14.0.

Small heat shock proteins (sHsps), which are categorized into a class of molecular chaperones, bind and stabilize denatured proteins to prevent aggregation. The sHsps undergo transition between different oligomeric states to control their hydrophobicity. So far, only the structures of sHsps in large oligomeric states have been reported. Here we report the structure of StHsp14.0 from Sulfolobus tokodaii in the dimeric state, which is formed by means of a mutation at the C-terminal IXI/V motif. The dimer is the sole building block in two crystal forms, and the dimeric mode is the same as that in the large oligomers. The N-terminal helix has variety in its conformation. Furthermore, spectroscopic and biochemical experiments were performed to investigate the conformational variability at the N-terminus. The structural, dynamical and oligomeric properties suggest that chaperone activity of StHsp14.0 is mediated by partially dissolved oligomers.

Human amniotic epithelial cells express melatonin receptor MT1, but not melatonin receptor MT2: a new perspective to neuroprotection.

Recent studies have demonstrated that the human placenta is a novel source of adult stem cells. We have provided laboratory evidence that transplantation of these human placenta-derived cells in vitro and in vivo stroke models promotes functional recovery. However, the mechanisms underlying these observed therapeutic benefits of human placenta-derived cells unfortunately remain poorly understood. Here, we examined the expression of two discrete types of melatonin receptors and their roles in proliferation and differentiation of cultured human amniotic epithelial cells (AECs). Cultured AECs express melatonin receptor type 1A (MT1), but not melatonin receptor type 1B (MT2). The proliferation of cultured AECs was increased in the melatonin-treated group in a dose-dependent manner, and the viability of cultured AECs could be further enhanced by melatonin. Moreover, the viability of AECs significantly decreased with H(2) O(2) exposure, which was reversed by pretreatment with melatonin, resulting in increased cell survival rate and cell proliferation. Immunocytochemically, administration of melatonin significantly suppressed nestin proliferation, but enhanced TUJ1 differentiation of MT1-expressing AECs. Additional experiments incorporating antibody blocking and synergistic AEC-melatonin treatments further showed AEC therapeutic benefits via MT1 modulation. Finally, analysis of trophic factors revealed cultured AECs secreted VEGF in the presence of melatonin. These data indicate that melatonin by stimulating MT1 increased cell proliferation and survival rate while enhancing neuronal differentiation of cultured AECs, which together with VEGF upregulation, rendered neuroprotection against experimental in vitro models of ischemic and oxidative stress injury.

Current management for foreign body and toxic agent ingestion in a paediatric primary emergency centre.

OBJECTIVES: Accidental foreign body ingestion (FBI) and toxic agent ingestion (TAI) are commonly encountered among children in primary emergency settings. Early detection and appropriate medical intervention are crucial to improve outcomes. Although many reports from tertiary institutions have shown improvements in therapy, data are still lacking from primary emergency facilities. METHODS: We performed a retrospective analysis based on medical records of FBI/TAI over 4 years at the Kobe Children's Primary Emergency Medical Center. We collected patient information, including age, sex, time between FBI/TAI occurrence and centre visit, provision of first aid, symptoms, type of FBI/TAI, examinations, treatments, and outcomes. RESULTS: A total of 580 children were enrolled. The median age was 1.3 years, and patients under 2 years old accounted for 70% of total cases. Cigarettes (17.5%) were the most common ingested foreign body, followed by medicines (15.3%), detergents (8.1%), in TAI, plastics (14.1%), metal (13.4%), batteries (9.0%) in FBI, and others (22.6%). A total of 42 patients were transferred to advanced hospitals; among these, 22 patients were hospitalised but the foreign body was removed in only 3 (0.9%) patients. Transferred patients were significantly older (P<0.05) in FBI and had a higher rate of any of symptoms (P<0.05) in FBI/TAI. CONCLUSIONS: This large-scale retrospective study of accidental FBI/TAI conducted at a primary emergency facility clarified current management, including treatment at a primary facility. Very few cases of FBI/TAI were treated, even when they were transferred to an advanced treatment hospital. Unified protocols should be established, to improve the management of FBI/TAI.

Crystallization and heavy-atom derivatization of StHsp14.0, a small heat-shock protein from Sulfolobus tokodaii.

Small heat-shock proteins (sHsps) bind and stabilize proteins denatured by heat or other stresses in order to prevent unfavourable protein aggregation. StHsp14.0 is an sHsp found in the acidothermophilic archaeon Sulfolobus tokodaii. A variant of StHsp14.0 was crystallized by the sitting-drop vapour-diffusion method. The crystals diffracted X-rays to 1.85 A resolution and belonged to space group P2(1)2(1)2, with unit-cell parameters a = 40.4, b = 61.1, c = 96.1 A. The V(M) value was estimated to be 2.1 A(3) Da(-1), assuming the presence of two molecules in the asymmetric unit. Heavy-atom derivative crystals were prepared successfully by the cocrystallization method and are isomorphic to native crystals.