A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes. Investigating these genes' functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health lifestyle. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausible nature of distinct influences of both sleep duration extremes in cardiovascular health. Several of our loci are specific towards a particular population background or sex, emphasizing the importance of addressing heterogeneity entangled in gene-environment interactions, when considering precision medicine design approaches for blood pressure management.

A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausibility of distinct influences of both sleep duration extremes in cardiovascular health. With several of our loci reflecting specificity towards population background or sex, our discovery sheds light on the importance of embracing granularity when addressing heterogeneity entangled in gene-environment interactions, and in therapeutic design approaches for blood pressure management.

Comparison of COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease shock syndrome: case reports and literature review.

Multisystem inflammatory syndrome in children (MIS-C) is a serious post-infectious complication of COVID-19 characterized by hyperinflammation and multi-organ dysfunction including shock. Shock is also seen in a severe form of Kawasaki disease (KD) called KD shock syndrome (KDSS). Here, we present one MIS-C and one KDSS case and compare similarities and differences between them. Both MIS-C (case 1) and KDSS (case 2) showed hyperinflammation, KD-related features, gastrointestinal problems, hypotension, and coagulopathy. The extent of systemic inflammation and organ dysfunction was more severe in KDSS than in MIS-C. Case 1 was diagnosed as MIS-C because SARS-CoV-2 was confirmed, and case 2 was diagnosed as KDSS because no pathogen was identified in microbiological studies. We believe that the most important difference between MIS-C and KDSS was whether SARS-CoV-2 was identified as an infectious trigger. Organ dysfunction is a hallmark of MIS-C and KDSS, but not KD, so MIS-C shares more clinical phenotypes with KDSS than with KD. Comparison of MIS-C and KDSS will be an interesting and important topic in the field of KD-like hyperinflammatory disease research.

Utilization and Availability of Advanced Imaging in Patients With Acute Ischemic Stroke.

BACKGROUND: Recent clinical trials have established the efficacy of endovascular stroke therapy and intravenous thrombolysis using advanced imaging, particularly computed tomography perfusion (CTP). The availability and utilization of CTP for patients and hospitals that treat acute ischemic stroke (AIS), however, is uncertain. METHODS: We performed a retrospective cross-sectional analysis using 2 complementary Medicare datasets, full sample Texas and 5% national fee-for-service data from 2014 to 2017. AIS cases were identified using International Classification of Diseases, NinthRevision and International Classification of Diseases, Tenth Revision coding criteria. Imaging utilization performed in the initial evaluation of patients with AIS was derived using Current Procedural Terminology codes from professional claims. Primary outcomes were utilization of imaging in AIS cases and the change in utilization over time. Hospitals were defined as imaging modality-performing if they submitted at least 1 claim for that modality per calendar year. The National Medicare dataset was used to validate state-level findings, and a local hospital-level cohort was used to validate the claims-based approach. RESULTS: Among 50 797 AIS cases in the Texas Medicare fee-for-service cohort, 64% were evaluated with noncontrast head CT, 17% with CT angiography, 3% with CTP, and 33% with magnetic resonance imaging. CTP utilization was greater in patients treated with endovascular stroke therapy (17%) and intravenous thrombolysis (9%). CT angiography (4%/y) and CTP (1%/y) utilization increased over the study period. These findings were validated in the National dataset. Among hospitals in the Texas cohort, 100% were noncontrast head CT-performing, 77% CT angiography-performing, and 14% CTP-performing in 2017. Most AIS cases (69%) were evaluated at non-CTP-performing hospitals. CTP-performing hospitals were clustered in urban areas, whereas large regions of the state lacked immediate access. CONCLUSIONS: In state-wide and national Medicare fee-for-service cohorts, CTP utilization in patients with AIS was low, and most patients were evaluated at non-CTP-performing hospitals. These findings support the need for alternative means of screening for AIS recanalization therapies.

Risk of intracranial hemorrhage associated with pregnancy in women with cerebral arteriovenous malformations.

BACKGROUND: Prior studies on rupture risk of brain arteriovenous malformations (AVMs) in women undergoing pregnancy and delivery have reported conflicting findings, but also have not accounted for AVM morphology and heterogeneity. Here, we assess the association between pregnancy and the risk of intracranial hemorrhage (ICH) in women with AVMs using a cohort-crossover design in which each woman serves as her own control. METHODS: Women who underwent pregnancy and delivery were identified using DRG codes from the Healthcare Cost and Utilization Project State Inpatient Databases for California (2005-2011), Florida (2005-2014), and New York (2005-2014). The presence of AVM and ICH was determined using ICD 9 codes. Pregnancy was defined as the 40 weeks prior to delivery, and postpartum as 12 weeks after. We defined a non-exposure control period as a 52-week period prior to pregnancy. The relative risks of ICH during pregnancy were compared against the non-exposure period using conditional Poisson regression. RESULTS: Among 4 022 811 women identified with an eligible delivery hospitalization (median age, 28 years; 7.3% with gestational diabetes; 4.5% with preeclampsia/eclampsia), 568 (0.014%) had an AVM. The rates of ICH during pregnancy and puerperium were 6355.4 (95% CI 4279.4 to 8431.5) and 14.4 (95% CI 13.3 to 15.6) per 100 000 person-years for women with and without AVM, respectively. In cohort-crossover analysis, in women with AVMs the risk of ICH increased 3.27-fold (RR, 95% CI 1.67 to 6.43) during pregnancy and puerperium compared with a non-pregnant period. CONCLUSIONS: Among women with AVM, pregnancy and puerperium were associated with a greater than 3-fold risk of ICH.

Growth differentiation factor-11 supplementation improves survival and promotes recovery after ischemic stroke in aged mice.

Growth differentiation factor (GDF) 11 levels decline with aging. The age-related loss of GDF 11 has been implicated in the pathogenesis of a variety of age-related diseases. GDF11 supplementation reversed cardiac hypertrophy, bone loss, and pulmonary dysfunction in old mice, suggesting that GDF11 has a rejuvenating effect. Less is known about the potential of GDF11 to improve recovery after an acute injury, such as stroke, in aged mice. GDF11/8 levels were assessed in young and aged male mice and in postmortem human brain samples. Aged mice were subjected to a transient middle cerebral artery occlusion (MCAo). Five days after MCAo, mice received and bromodeoxyuridine / 5-Bromo-2'-deoxyuridine (BrdU) and either recombinant GDF11 or vehicle for five days and were assessed for recovery for one month following stroke. MRI was used to determine cerebrospinal fluid (CSF) volume, corpus callosum (CC) area, and brain atrophy at 30 days post-stroke. Immunohistochemistry was used to assess gliosis, neurogenesis, angiogenesis and synaptic density. Lower GDF11/8 levels were found with age in both mice and humans (p<0.05). GDF11 supplementation reduced mortality and improved sensorimotor deficits after stroke. Treatment also reduced brain atrophy and gliosis, increased angiogenesis, improved white matter integrity, and reduced inflammation after stroke. GDF11 may have a role in brain repair after ischemic injury.

Increased Risk of Subsequent Meningioma Among Women with Malignant Breast Cancer.

OBJECTIVE: Despite the increasing evidence of the association between breast cancer and meningioma in women, the relationship between these tumors remains improperly examined. In this study, we aim to identify the sociodemographic and clinicopathologic features of women with breast cancer associated with a higher risk of developing a meningioma. METHODS: The SEER (Surveillance Epidemiology and End Results) database (18 registries) was used to identify women with breast cancer as their first neoplasm. The risk of subsequent meningioma was reported as the standardized incidence ratio (SIR) and was analyzed by sociodemographic and clinicopathologic subgroups. Results are given as SIR (95% confidence interval [CI]). RESULTS: A total of 564,516 women diagnosed with breast cancer between 2004 and 2016 were included for analysis. A 26% increased risk of meningioma development (SIR, 1.26; 95% CI, 1.19-1.33; P < 0.05) was found in the cohort compared with the general population. Patients aged between 18 and 49 years (SIR, 2.16; 95% CI, 1.78-2.61; P < 0.05) and those with a more advanced tumor stage (stage IV; SIR, 2.39; 95% CI, 1.71-3.25; P < 0.05) were at a higher risk. Hormone receptor expression and treatment modality subgroups were at a similar risk compared with the general population. CONCLUSIONS: Our study corroborated the known association between these tumors and found a 26% risk of meningioma development in women with breast cancer, with younger patients and those with a more aggressive disease having a higher than expected risk.

Plasma Lipid Profiling Identifies Biomarkers of Cerebral Microvascular Disease.

Brain-specific sphingolipids (SLs) may serve as effective biomarkers of white matter hyperintensities (WMH). Here, we investigate the efficacy of SLs as a novel fluid-based biomarker to identify WMH reflective of chronic ischemia. Patients presenting to our stroke center for evaluation of acute neurological deficits were enrolled in the Advanced Serum Profiling in Recent Stroke (ASPIRE) study. From this cohort of 202 individuals, 58 patients who underwent an MRI and did not have a clinical stroke event were included in this study. Plasma samples were collected at the time of MRI, and targeted SL profiling was performed by HPLC/tandem mass spectrometry. T2 FLAIR imaging was evaluated for WMH and scored according to the Fazekas scoring (FS) method and manually quantified. Twenty two SLs were definitively identified, consisting of ceramide (Cer) and sphingomyelin (SM) species. Of these, two sphingolipids, SM 38:1 and Cer 34:1, significantly correlated with high FS (r = 0.287, p = 0.029, and r = 0.356, p = 0.006, respectively) and were used in subsequent analysis. SM 38:1 (OR 1.129, 95% CI 1.032, 1.236, p = 0.008) and Cer 34:1 (OR 1.118, 95% CI 1.031, 1.212, p = 0.007), accurately differentiated between FS 0-2 vs. 2.5-6 in regression analysis. A combined lipid score demonstrated fair discrimination in ROC analysis (AUC = 0.729, p = 0.003) and was cross-validated using leave-one-out analysis. Plasma levels of brain-specific SLs may serve as effective biomarkers of subacute white matter disease.

Machine Learning-Enabled Automated Determination of Acute Ischemic Core From Computed Tomography Angiography.

Background and Purpose- The availability of and expertise to interpret advanced neuroimaging recommended in the guideline-based endovascular stroke therapy (EST) evaluation are limited. Here, we develop and validate an automated machine learning-based method that evaluates for large vessel occlusion (LVO) and ischemic core volume in patients using a widely available modality, computed tomography angiogram (CTA). Methods- From our prospectively maintained stroke registry and electronic medical record, we identified patients with acute ischemic stroke and stroke mimics with contemporaneous CTA and computed tomography perfusion (CTP) with RAPID (IschemaView) post-processing as a part of the emergent stroke workup. A novel convolutional neural network named DeepSymNet was created and trained to identify LVO as well as infarct core from CTA source images, against CTP-RAPID definitions. Model performance was measured using 10-fold cross validation and receiver-operative curve area under the curve (AUC) statistics. Results- Among the 297 included patients, 224 (75%) had acute ischemic stroke of which 179 (60%) had LVO. Mean CTP-RAPID ischemic core volume was 23±42 mL. LVO locations included internal carotid artery (13%), M1 (44%), and M2 (21%). The DeepSymNet algorithm autonomously learned to identify the intracerebral vasculature on CTA and detected LVO with AUC 0.88. The method was also able to determine infarct core as defined by CTP-RAPID from the CTA source images with AUC 0.88 and 0.90 (ischemic core ≤30 mL and ≤50 mL). These findings were maintained in patients presenting in early (0-6 hours) and late (6-24 hours) time windows (AUCs 0.90 and 0.91, ischemic core ≤50 mL). DeepSymNet probabilities from CTA images corresponded with CTP-RAPID ischemic core volumes as a continuous variable with r=0.7 (Pearson correlation, P<0.001). Conclusions- These results demonstrate that the information needed to perform the neuroimaging evaluation for endovascular therapy with comparable accuracy to advanced imaging modalities may be present in CTA, and the ability of machine learning to automate the analysis.

Sex Differences in Outcome After Endovascular Stroke Therapy for Acute Ischemic Stroke.

Background and Purpose- We determined the effect of sex on outcome after endovascular stroke thrombectomy in acute ischemic stroke, including lifelong disability outcomes. Methods- We analyzed patients treated with the Solitaire stent retriever in the combined SWIFT (Solitaire FR With the Intention for Thrombectomy), STAR (Solitaire FR Thrombectomy for Acute Revascularization), and SWIFT PRIME (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment) cohorts. Ordinal and logistic regression were used to examine known factors influencing outcome after endovascular stroke thrombectomy and study the effect of sex on the association between these factors and outcomes, including age and time to reperfusion. Years of optimal life after thrombectomy were defined as disability-adjusted life years and calculated by projecting disability through adjusted poststroke life expectancy by sex. Results- Among 389 patients treated with endovascular stroke thrombectomy, 55% were females, and median National Institutes of Health Stroke Scale was 17 (interquartile range, 8-28). There were no differences between females versus males in presenting deficit severity (National Institutes of Health Stroke Scale score, 17 versus 17, P=0.21), occlusion location (69% versus 64% M1, P=0.62), presenting infarct extent (Alberta Stroke Program Early CT Score 8 versus 8, P=0.24), rate of substantial reperfusion (Thrombolysis in Cerebral Infarction 2b/3, 87% versus 83%, P=0.37), onset to reperfusion time (294 versus 302 minutes, P=0.46). Despite older ages (69 versus 64, P<0.001) and higher rate of atrial fibrillation (45% versus 30%, P=0.002) for females compared with males, adjusted rates of functional independence at 90 days were similar (odds ratio, 1.0; 95% CI, 0.6-1.6). After adjusting for age at presentation and stroke severity, females had more years of optimal life (disability-adjusted life year) after endovascular stroke thrombectomy, 10.6 versus 8.5 years (P<0.001). Conclusions- Despite greater age and higher rate of atrial fibrillation, females experienced comparable functional outcomes and greater years of optimal life after intervention compared with males.

14th International Symposium on Thrombolysis, Thrombectomy and Acute Stroke Therapy: Proceedings and summary of discussions.

The 14th International Symposium on Thrombolysis, Thrombectomy and Acute Stroke Therapy (TTST) took place in Houston, Texas on 21-22 October 2018. Attended by 150+ invited global experts, the objectives of TTST 2018 were to explore the changing landscape of acute ischemic stroke therapy and to address current controversies in thrombolysis and thrombectomy, including expanding access and systems of care with global relevance. This article summarizes the proceedings of TTST 2018. The key points of each session are listed below, the full text of presentations and discussion are available in the online supplement, and the full list of contributing authors appear in the Appendix at the end of this article.

Accuracy of "At Risk" Tissue Predictions Using CT Perfusion in Acute Large Vessel Occlusions.

BACKGROUND AND PURPOSE: The validity of CT perfusion (CTP) predictions of expected infarction volume ("at risk" tissue) without rapid recanalization remains poorly characterized. METHODS: From the MR CLEAN trial, we included patients who underwent CTP without successful recanalization. "At risk" volume was defined as Tmax > 6 seconds and ischemic core as relative CBF < 30 (Olea Sphere). Coprimary outcomes were follow-up infarct volume (FIV) on CT at 1-5 days and 90-day mRS. Data are presented as median [IQR] or OR [95% CI] unless otherwise specified. RESULTS: Among 37 patients who met criteria, 14 (38%) were women, median age was 61 years [52-69], NIHSS was 19 [15-21], ASPECTS was 8 [7-9], and onset to imaging was 160 minutes [39-200]. Occlusion location was M1 for 22 (59%), ICA-T in 10 (27%), and M2 in 4 (11%). In univariable analysis, "at risk" volume correlated poorly with FIV (r = .06, P = .77). Among patients with predicted "at risk" volume < 100 mL, 36% had FIV > 200 mL. In adjusted linear regression, NIHSS but not "at risk" volume was associated with FIV (Coef 12, P = .045; Coef -.15, P = .8). In adjusted logistic regression, NIHSS but not "at risk" volume was associated with mRS 0-2 at 90 days (OR .7 [.5-.99]; OR 1.0 [.99-1.04]). CONCLUSION: Predictions of "at-risk" tissue using CTP may underestimate the natural history of infarction from acute large vessel occlusions. NIHSS may perform better as a predictor of clinical outcomes in patients without rapid recanalization.

Screening Molecular Chaperones Similar to Small Heat Shock Proteins in Schizosaccharomyces pombe.

To screen molecular chaperones similar to small heat shock proteins (sHsps), but without α-crystalline domain, heat-stable proteins from Schizosaccharomyces pombe were analyzed by 2-dimensional electrophoresis and matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Sixteen proteins were identified, and four recombinant proteins, including cofilin, NTF2, pyridoxin biosynthesis protein (Snz1) and Wos2 that has an α-crystalline domain, were purified. Among these proteins, only Snz1 showed the anti-aggregation activity against thermal denaturation of citrate synthase. However, pre-heating of NTF2 and Wos2 at 70℃ for 30 min, efficiently prevented thermal aggregation of citrate synthase. These results indicate that Snz1 and NTF2 possess molecular chaperone activity similar to sHsps, even though there is no α-crystalline domain in their sequences.

Development of job standards for clinical nutrition therapy for dyslipidemia patients.

Dyslipidemia has significantly contributed to the increase of death and morbidity rates related to cardiovascular diseases. Clinical nutrition service provided by dietitians has been reported to have a positive effect on relief of medical symptoms or reducing the further medical costs. However, there is a lack of researches to identify key competencies and job standard for clinical dietitians to care patients with dyslipidemia. Therefore, the purpose of this study was to analyze the job components of clinical dietitian and develop the standard for professional practice to provide effective nutrition management for dyslipidemia patients. The current status of clinical nutrition therapy for dyslipidemia patients in hospitals with 300 or more beds was studied. After duty tasks and task elements of nutrition care process for dyslipidemia clinical dietitians were developed by developing a curriculum (DACUM) analysis method. The developed job standards were pretested in order to evaluate job performance, difficulty, and job standards. As a result, the job standard included four jobs, 18 tasks, and 53 task elements, and specific job description includes 73 basic services and 26 recommended services. When clinical dietitians managing dyslipidemia patients performed their practice according to this job standard for 30 patients the job performance rate was 68.3%. Therefore, the job standards of clinical dietitians for clinical nutrition service for dyslipidemia patients proposed in this study can be effectively used by hospitals.

Distinct functional roles of peroxiredoxin isozymes and glutathione peroxidase from fission yeast, Schizosaccharomyces pombe.

To investigate the differences in the functional roles of peroxiredoxins (Prxs) and glutathione peroxidase (GPx) of Schizosaccharomyces pombe, we examined the peroxidase and molecular chaperone properties of the recombinant proteins. TPx (thioredoxin peroxidase) exhibited a capacity for peroxide reduction with the thioredoxin system. GPx also showed thioreoxin-dependent peroxidase activity rather than GPx activity. The peroxidase activity of BCP (bacterioferritin comigratory protein) was similar to that of TPx. However, peroxidase activity was not observed for PMP20 (peroxisomal membrane protein 20). TPx, PMP20, and GPx inhibited thermal aggregation of citrate synthase at 43(o)C, but BCP failed to inhibit the aggregation. The chaperone activities of PMP20 and GPx were weaker than that of TPx. The peroxidase and chaperone properties of TPx, BCP, and GPx of the fission yeast are similar to those of Saccharomyces cerevisiae. The fission yeast PMP20 without thioredoxin-dependent peroxidase activity may act as a molecular chaperone.

Potent anti-inflammatory effects of two quinolinedione compounds, OQ1 and OQ21, mediated by dual inhibition of inducible NO synthase and cyclooxygenase-2.

BACKGROUND AND PURPOSE: Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) have been suggested as key components in various inflammatory diseases. Here we examined the effects of new quinolinedione derivatives, 6-(4-fluorophenyl)-amino-5,8-quinolinedione (OQ1) and 6-(2,3,4-trifluorophenyl)-amino-5,8-quinolinedione (OQ21) on activity and expression of iNOS and COX-2 to explore their anti-inflammatory properties. EXPERIMENTAL APPROACH: The effects of OQ1 and OQ21 were assessed on lipopolysaccharide (LPS)-induced iNOS and COX-2 in murine macrophage cell line (RAW264.7), along with isolated enzyme assays to measure enzyme inhibition. Nuclear factor-kappaB (NFkappaB) activation pathways were investigated to elucidate mechanisms underlying OQ-mediated suppression of the expression of iNOS and COX-2. In vivo anti-inflammatory activities of OQ compounds were evaluated in mouse ear oedema, induced by topical 12-O-tetradecanoylphorbol-13-acetate (TPA). KEY RESULTS: LPS-induced NO production in RAW264.7 cells was inhibited by OQ1 and OQ21 through the attenuation of iNOS expression as well as iNOS activity. Down-regulation of iNOS followed blocking of NFkappaB activation, as assessed by inhibitory kappaB degradation and electrophoretic mobility shift assay for NFkappaB. Synthesis and accumulation of prostaglandin E(2) were also suppressed by OQ1 and OQ21. LPS-induced COX-2 expression and cellular COX-2 activities were attenuated by OQ1 and OQ21. Consistent with these results, OQ1 showed potent anti-inflammatory effects in mouse ear oedema induced by TPA. CONCLUSIONS AND IMPLICATIONS: The novel quinolinedione derivatives, OQ1 and OQ21, showed potent anti-inflammatory activity through dual inhibitory effects on iNOS and COX-2, suggesting that OQ derivatives might provide a new therapeutic modality for chronic inflammatory diseases, refractory to conventional drug therapies.

Aspartyl aminopeptidase of Schizosaccharomyces pombe has a molecular chaperone function.

To screen chaperone proteins from Schizosaccharomyce pombe (S. pombe), we prepared recombinant citrate synthase of the fission yeast as a substrate of anti-aggregation assay. Purified recombinant citrate synthase showed citrate synthase activity and was suitable for the substrate of chaperone assay. Several heat stable proteins including aspartyl aminopeptidase (AAP) for candidates of chaperone were screened from the supernatant fraction of heat-treated crude extract of S. pombe. The purified AAP migrated as a single band of 47 kDa on SDS-polyacrylamide gel electrophoresis. The native size of AAP was estimated as 200 kDa by a HPLC gel permeation chromatography. This enzyme can remove the aspartyl residue at N-terminus of angiotensin I. In addition, AAP showed the heat stability and protected the aggregation of citrate synthase caused by thermal denaturation. This study showed that S. pombe AAP is a moonlight protein that has aspartyl aminopeptidase and chaperone activities.

Hepatitis C virus E2 links soluble human CD81 and SR-B1 protein.

Limited information is available regarding hepatitis C virus (HCV) entry events. Viral attachment and infection studies have been performed using HCV envelope glycoprotein (E2) and HCV pseudo-particle (HCVpp) models to obtain general information about the early entry events. However, the details involved in each step of viral entry into human cells are still obscure. This study provides molecular clue for the formation of a heteromultimeric complex as a possible post-attachment step. Among several putative receptors, human CD81 and scavenger receptor class B type 1 (SR-B1) have been demonstrated as considerable determinants in infectious outcome as well as attachment. In this study, we provide molecular evidence demonstrating that HCV E2 links soluble CD81 and SR-B1 protein together. This physical neighboring might explain why both CD81 and SR-B1 are indispensable factors for HCVpp infection. These data further elucidate our understanding of HCV entry and provide new insight into directing future studies identifying novel liver-specific fusion receptor(s).

Nosocomial infection of malnourished patients in an intensive care unit.

Malnutrition is one of the most important factors for the development of nosocomial infection (NI). We performed a study of the correlation between abnormal nutritional factors and NI risk by investigating the patients who stayed longer than 3 days in the intensive care unit (ICU) of our university hospital. The patients were classified into three groups based on serum albumin levels and total lymphocyte counts (TLC). The criteria of Group I (well nourished group) were serum albumin level of 3.5 g/dl or higher and TLC of 1,400/mm3 or higher. The criteria of Group III (severely malnourished group) were serum albumin of less than 2.8 g/dl and TLC of less than 1,000/mm3. The other patients were classified as Group II (moderately malnourished group). The occurrences of NI were monitored during the study period and the APACHE III Score was calculated. The probability of first NI infection in Group III was 2.4 times higher than that in Groups I and II. The mortality rate of 20.5% was more significantly correlated with APACHE III Score than nutritional status. Nineteen (53%) of the total 36 NI patients were infected within 10 days after ICU admission and they all belonged to Group III. When we compared the gap period between infections, the time to first infection was significant.

Regulation of thioredoxin peroxidase activity by C-terminal truncation.

Thioredoxin peroxidase is a member of peroxiredoxin (Prx) family, which uses a thioredoxin (Trx) as an immediate electron donor for the reduction of peroxide. We have identified C-terminal truncated TPx from Schizosaccharomyces pombe and also have found the truncated form is significantly tenacious against the inactivation of H2O2 than the intact form. Peroxidase assay of a series of recombinant C-terminal truncation mutants (Delta192, Delta191, Delta188, Delta184, Delta176, and Delta165) revealed that TPx could be inactivated (Delta192), reactivated (Delta191-Delta176) and reinactivated (Delta165) by serial truncation from C-terminus. We did not find any significant kinetic difference among reactivated forms; however, distinctive loss of affinity to H2O2 (K(m) = 5 microM) than that of the intact form (<<5 microM, undeterminable) was monitored. Characterization of a series of Lys(191) point mutants manifested that the loss of affinity caused by a deprivation of positive charge born in Lys(191) and the loss of affinity resulted in the resistibility to H2O2. Disk inhibition assay with S. pombe cells overexpressing wild-type, Delta192 and Delta191 mutants evidenced that the truncated forms functioning in vitro as well as in vivo.