Effectiveness of next-generation sequencing for patients with advanced non-small-cell lung cancer: a population-based registry study.

BACKGROUND: Despite the growing use of next-generation sequencing (NGS) in the management of advanced non-small-cell lung cancer (NSCLC), there is little evidence that its use leads to improved clinical outcomes. This study aimed to compare the effectiveness of NGS with that of single-gene testing (SGT) alone in patients with advanced NSCLC. MATERIALS AND METHODS: This was a retrospective cohort study conducted on patients diagnosed with advanced lung adenocarcinoma between 2017 and 2018 from a nationwide, population-based database. We identified patients who had SGT exclusively (SGT group) or underwent upfront NGS or NGS following SGT as an initial evaluation (NGS group). Patients were followed up until death or the end of the study (31 December 2019). The adjusted hazard ratio (aHR) for death was estimated using the Cox proportional hazards model. The factors affecting the adoption of NGS were identified. RESULTS: Of 8566 patients diagnosed with advanced lung adenocarcinoma, 402 and 6932 patients were assigned to the NGS and SGT groups, respectively. More NGS was carried out in younger patients, those with higher incomes, and those living in urban areas. After balancing these confounders through matching, no difference was observed in the median overall survival and risk of death between the NGS and SGT groups [18.5 versus 19.7 months, log-rank P = 0.783; aHR 0.98, 95% confidence interval (CI) 0.84-1.14, respectively]. Only in a subgroup for whom epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) inhibitors were not indicated, NGS was associated with better survival outcomes (14.1 versus 9.0 months, log-rank P = 0.006; aHR 0.82, 95% CI 0.69-0.97). CONCLUSIONS: In the real world, NGS for all-comers in patients with advanced NSCLC did not increase survival outcomes. When health care resources to support equal access to NGS are limited, upfront SGT followed by NGS may be a more efficient strategy.

Association of Left Vertebral Artery Hypoplasia with Posterior Circulation Stroke and the Functional Outcome of Patients with Atrial Fibrillation-Related Cardioembolic Stroke.

BACKGROUND AND PURPOSE: A cardiogenic embolus could reach the posterior circulation through the right vertebral artery because of a relatively larger diameter in cases of left vertebral artery hypoplasia. Hence, we investigated whether left vertebral artery hypoplasia is associated with cardiac embolisms with atrial fibrillation in the posterior circulation and its functional outcomes. MATERIALS AND METHODS: In this monocentric retrospective study, patients with acute cardioembolic stroke with atrial fibrillation were enrolled and underwent CT or neck MRA, which visualized the aortic arch and subclavian arteries. The laterality and size of vertebral artery hypoplasia were recorded. Posterior circulation stroke, basilar artery occlusion, and the functional outcomes after 3 months were investigated. RESULTS: This study included 407 patients; the patients with left vertebral artery hypoplasia experienced a higher rate of posterior circulation stroke (19 versus 73; 42.2% versus 20.2%; P = .001) and basilar artery occlusion (5 versus 10; 11.1% versus 2.8%; P = .005) than the patients without left vertebral artery hypoplasia. Multivariate analysis revealed that left vertebral artery hypoplasia showed an association with lower odds of achieving a good functional outcome 3 months after the stroke (OR = 0.4; 95% CI, 0.2-0.9; P = .027). CONCLUSIONS: Patients with cardioembolic stroke and left vertebral artery hypoplasia had posterior circulation stroke, basilar artery occlusion, and poor functional outcomes after 3 months.

Improved Sleep Quality Is Associated with Reduced Insulin Resistance in Cancer Survivors Undertaking Circuit, Interval-Based Exercise.

PURPOSE: Cancer patients often experience poor sleep quality, typically induced by cancer-related treatments, a sedentary lifestyle, and psychological distress, leading to an increased risk of metabolic dysregulation such as obesity and insulin resistance. In this novel 16-week pilot study, we examined the effect of a circuit-based aerobic and resistance exercise intervention on self-reported sleep quality in breast, prostate, and colorectal cancer survivors and explored the association between changes in sleep quality and insulin resistance. METHODS: Survivors of breast, prostate or colorectal cancers who were sedentary, overweight or obese (BMI>25.0 kg/m2) were randomized to exercise (n=60) or usual care (n=30). The 16-week intervention included supervised moderate-vigorous aerobic (65-85% of VO2max) and resistance (65-85% of 1-repetition maximum) exercise performed in a circuit, interval fashion three times per week. Patient-reported sleep quality and insulin resistance were assessed at baseline and post-intervention using Pittsburgh Sleep Quality Index (PSQI) and Homeostasis Model of Assessment (HOMA-IR), respectively. Mean changes in PSQI score that are negative demonstrate improvements in sleep. Between-group differences were determined using repeated-measures analysis of variance. Associations between changes in PSQI and insulin resistance were computed using Pearson correlations. RESULTS: Participants were 63.2±10.8 years old, obese (87%), female (55%), and completed chemotherapy + radiation therapy (75%). Adherence to the intervention was 92% and the retention rate was 100%. Post-intervention, the PSQI global score improved significantly in the exercise group when compared to usual care (mean between-group difference, -2.7; 95% CI, -4.2 to -0.6). Change in PSQI was inversely associated with change in HOMA-IR (r=-0.91; p<0.01) among the exercise group. CONCLUSIONS: A circuit, interval-based aerobic and resistance exercise intervention improved patient-reported sleep quality in breast, prostate, and colorectal cancer survivors. Additionally, this exercise-induced improvement in sleep-quality may result in reduced insulin resistance.

Comparison of High-Resolution MR Imaging and Digital Subtraction Angiography for the Characterization and Diagnosis of Intracranial Artery Disease.

BACKGROUND AND PURPOSE: High-resolution MR imaging has recently been introduced as a promising diagnostic modality in intracranial artery disease. Our aim was to compare high-resolution MR imaging with digital subtraction angiography for the characterization and diagnosis of various intracranial artery diseases. MATERIALS AND METHODS: Thirty-seven patients who had undergone both high-resolution MR imaging and DSA for intracranial artery disease were enrolled in our study (August 2011 to April 2014). The time interval between the high-resolution MR imaging and DSA was within 1 month. The degree of stenosis and the minimal luminal diameter were independently measured by 2 observers in both DSA and high-resolution MR imaging, and the results were compared. Two observers independently diagnosed intracranial artery diseases on DSA and high-resolution MR imaging. The time interval between the diagnoses on DSA and high-resolution MR imaging was 2 weeks. Interobserver diagnostic agreement for each technique and intermodality diagnostic agreement for each observer were acquired. RESULTS: High-resolution MR imaging showed moderate-to-excellent agreement (interclass correlation coefficient = 0.892-0.949; κ = 0.548-0.614) and significant correlations (R = 0.766-892) with DSA on the degree of stenosis and minimal luminal diameter. The interobserver diagnostic agreement was good for DSA (κ = 0.643) and excellent for high-resolution MR imaging (κ = 0.818). The intermodality diagnostic agreement was good (κ = 0.704) for observer 1 and moderate (κ = 0.579) for observer 2, respectively. CONCLUSIONS: High-resolution MR imaging may be an imaging method comparable with DSA for the characterization and diagnosis of various intracranial artery diseases.

First Report of Alternaria Leaf Spot Caused by Alternaria sp. on Highbush Blueberry (Vaccinium corymbosum) in South Korea.

In South Korea, the culture, production, and consumption of blueberry (Vaccinium corymbosum) have increased rapidly over the past 10 years. In June and July 2012, blueberry plants with leaf spots (~10% of disease incidence) were sampled from a blueberry orchard in Jinju, South Korea. Leaf symptoms included small (1 to 5 mm in diameter) brown spots that were circular to irregular in shape. The spots expanded and fused into irregularly shaped, large lesions with distinct dark, brownish-red borders. The leaves with severe infection dropped early. A fungus was recovered consistently from sections of surface-disinfested (1% NaOCl) symptomatic leaf tissue after transfer onto water agar and sub-culture on PDA at 25°C. Fungal colonies were dark olive and produced loose, aerial hyphae on the culture surfaces. Conidia, which had 3 to 6 transverse septa, 1 to 2 longitudinal septa, and sometimes also a few oblique septa, were pale brown to golden brown, ellipsoid to ovoid, obclavate to obpyriform, and 16 to 42 × 7 to 16 µm (n = 50). Conidiophores were pale to mid-brown, solitary or fasciculate, and 28 to 116 × 3 to 5 µm (n = 50). The species was placed in the Alternaria alternata group (1). To confirm the identity of the fungus, the complete internal transcribed spacer (ITS) rDNA region of a representative isolate, AAVC-01, was amplified using ITS1 and ITS4 primers (2). The DNA products were cloned into the pGEM-T Easy vector (Promega, Madison, WI) and the resulting pOR13 plasmid was sequenced using universal primers. The resulting 570-bp sequence was deposited in GenBank (Accession No. KJ636460). Comparison of ITS rDNA sequences with other Alternaria spp. using ClustalX showed ≥99% similarity with the sequences of A. alternata causing blight on Jatropha curcas (JQ660842) from Mexico and Cajannus cajan (JQ074093) from India, citrus black rot (AF404664) from South Africa, and other Alternaria species, including A. tenuissima (WAC13639) (3), A. lini (Y17071), and A. longipes (AF267137). Two base substitutions, C to T at positions 345 and 426, were found in the 570-bp amplicon. Phylogenetic analysis revealed that the present Alternaria sp. infecting blueberry grouped separately from A. tenuissima and A. alternata reported from other hosts. A representative isolate of the pathogen was used to inoculate V. corymbosum Northland leaves for pathogenicity testing. A conidial suspension (2 × 104 conidia/ml) from a single spore culture and 0.025% Tween was spot inoculated onto 30 leaves, ranging from recently emerged to oldest, of 2-year-old V. corymbosum Northland plants. Ten leaves were treated with sterilized distilled water and 0.025% Tween as a control. The plants were kept in a moist chamber with >90% relative humidity at 25°C for 48 h and then moved to a greenhouse. After 15 days, leaf spot symptoms similar to those observed in the field developed on the inoculated leaves, whereas the control plants remained asymptomatic. The causal fungus was re-isolated from the lesions of the inoculated plants to fulfill Koch's postulates. To our knowledge, this is the first report of Alternaria sp. on V. corymbosum in South Korea. References: (1) E. G. Simmons. Page 1797 in: Alternaria: An Identification Manual. CBS Fungal Biodiversity Centre, Utrecht, The Netherlands, 2007. (2) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, 1990. (3) M. P. You et al. Plant Dis. 98:423, 2014.

First Report of Sclerotium Rot Caused by Sclerotium rolfsii on Yacón in South Korea.

Yacón, or ground apple (Smallanthus sonchifolius), is a perennial plant grown in the northern and central Andes from Colombia to northern Argentina for its crisp, sweet, and tuberous roots. In 2012, yacóns cultivated in the research field of the Gyeongsangnam-do Agriculture and Extension Services, Jinju, South Korea, suddenly died. The characteristic symptoms consisted of rotting, wilting, and blighting. Initial symptoms included water-soaked lesions on lower stem tissue near the soil line. Infected plants gradually withered, and white mycelial mats and sclerotia appeared on the surface of roots and stems at the soil line. The sclerotia were collected and disinfested by immersion in 1% sodium hypochlorite solution for 30 s and in sterilized distilled water for 1 min. Then, the sclerotia were placed on potato dextrose agar (PDA) and incubated at 30°C. Numerous globoid sclerotia were formed on PDA after 18 days of growth. The sclerotia (1 to 3 mm in diameter) were white at first and then gradually turned dark brown. Aerial mycelia usually formed many narrow hyphal strands 4 to 9 µm wide. The white mycelium formed a typical clamp connection after 5 days of growth. To fulfill Koch's postulates, 50-day-old healthy seedlings were transplanted individually into pots (10 × 10 × 9 cm) containing autoclaved soil. After 7 days, five seedlings were inoculated with colonized agar discs (6 mm in diameter) directly on the base of the plant, and five yacón seedlings were inoculated similarly with PDA discs as the control treatment. The inoculated and non-inoculated plants were incubated in a humid growth chamber at 28°C for 24 h and then maintained in a greenhouse. Eight days after inoculation, the yacón seedlings inoculated with the fungus died, whereas those treated with PDA discs were symptomless. The fungus was re-isolated from the artificially inoculated plants. To confirm the identity of the causal fungus, the complete internal transcribed spacer (ITS) rDNA region of the fungus was amplified using the primers ITS1 (5'-TCCGTAGGTGAACCTGCGG-3') and ITS4 (5'-TCCTCCGCTTATTGATATGC-3') (2), and the PCR amplicons were cloned into the pGEM-T Easy vector. The resulting plasmid (pOR119) was sequenced in both directions with the primers M13F and M13R. The resulting 684 bp of ITS rDNA sequence was deposited in GenBank (Accession No. KJ944395). A DNA analysis revealed that it was 100% identical to Sclerotium rolfsii (HM355751). Cultures of S. rolfsii have been deposited with the Korean Agricultural Culture Collection (KACC 47750), National Academy of Agricultural Science, Suwon, South Korea. On the basis of symptoms, fungal colonies, the ITS sequence, and pathogenicity to the host, this fungus was identified as S. rolfsii Saccardo (1). This is the first report of sclerotium rot on yacón caused by S. rolfsii in South Korea. References: (1) J. E. M. Mordue. CMI Descriptions of Pathogenic Fungi and Bacteria, No. 410, 1974. (2) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, San Diego, 1990.

High resolution MRI difference between moyamoya disease and intracranial atherosclerosis.

BACKGROUND AND PURPOSE: Along with intracranial atherosclerotic disease (ICAD), moyamoya disease (MMD) is the most common cause of middle cerebral artery (MCA) occlusion in Asians. Although they have differing vascular wall pathologies, conventional angiographic evaluation methods cannot easily differentiate MMD from ICAD in certain situations, such as in young patients with atherosclerotic risk factors. High resolution magnetic resonance imaging (HR-MRI) findings for the diseased segments of MCAs in MMD and symptomatic ICAD were compared to further elucidate differences in arterial wall changes. METHODS: Angiographically confirmed patients, 12 MMD and 20 ICAD, who suffered a stroke due to MCA occlusion were recruited and underwent HR-MRI. The size of the outer diameter and other stenotic vessel wall characteristics revealed by HR-MRI, including enhancement, eccentricity and other lesion patterns, were analyzed by two independent reviewers in a blind fashion. RESULTS: MMD patients were younger than ICAD patients (32.92 ± 11.08 years vs. 51.85 ± 11.97 years; mean ± SD) and displayed a smaller outer diameter in the stenotic portion (1.61 ± 0.43 mm for MMD vs. 3.03 ± 0.53 mm for ICAD, P < 0.0001). Eccentric lesions (three of 12 in MMD vs. 19 of 20 in ICAD, P < 0.0001) and focal enhancements in diseased areas (two of seven in MMD vs. 13 of 17 in ICAD, P = 0.061) were less common in MMD cases. CONCLUSIONS: Our HR-MRI findings show that MMD is associated with smaller, concentric occlusive lesions which are rarely enhanced compared with symptomatic ICAD, consistent with the results of previous pathological reports. HR-MRI may therefore have utility in differentiating MMD from ICAD.

Stroke recurrence patterns are predicted by the subtypes and mechanisms of the past, non-cardiogenic stroke.

BACKGROUND AND PURPOSE: The association between past stroke subtypes and recurrent stroke subtypes in non-cardiogenic stroke remains unknown. METHODS: Patients with ischaemic stroke who had a past history of large-artery disease (LAD) or small-artery disease (SAD) subtypes were assessed. LAD was subdivided into intracranial atherosclerosis (ICAS) and extracranial atherosclerosis (ECAS). LAD stroke mechanisms were categorized as artery-to-artery embolism, in situ thrombotic occlusion and local branch occlusion, while SAD was subdivided into lacunar infarction (LI) and branch atheromatous disease (BAD) on the basis of magnetic resonance imaging findings. The relationship between past and current strokes was analyzed. RESULTS: Among the 202 patients enrolled, the LAD group (n = 111) had 64 and 47 patients with ICAS and ECAS, and the SAD group (n = 91) had 63 and 28 patients with LI and BAD, respectively, at the time of past stroke. Patients with LAD developed LAD-associated strokes most often (n = 99, 89.2%), and patients with SAD developed SAD most often (n = 69, 75.8%; P < 0.001). Patients with ICAS were more likely to develop ICAS later (n = 46, 79.3%), whereas those with ECAS developed ECAS more often (n = 31, 75.6%; P < 0.001). Patients with ICAS presenting with artery-to-artery embolism more often developed artery-to-artery embolism later (n = 26, 72.2%), whereas those with local branch occlusion developed recurrent local branch occlusion most often (n = 10, 66.7%, P = 0.005). In the SAD group, patients with BAD developed LAD more frequently than the LI group (n = 11, 39.3% vs. n = 9, 14.3%, P = 0.022). CONCLUSIONS: The subtypes and mechanisms of recurrent stroke are significantly influenced by those of the past stroke.

Porcine model to evaluate local tissue tolerability associated with subcutaneous delivery of protein.

INTRODUCTION: The conversion from intravenous (IV) to subcutaneous (SC) delivery of biotherapeutics has increased in recent years. Some of the reasons for this shift in route of delivery are due to patient convenience, reduced adverse systemic effects, lack of a need for vascular access, and reduced cost of patient care, which ultimately lead to improved patient quality of life. One caveat to SC delivery is the limited volumes that can be administered at a single site and the associated local tolerability. To characterize factors that affect subcutaneous delivery of large volumes of therapeutic proteins, a porcine model was developed. Model endpoints included measurement of interstitial pressure, assessment of local skin visco-elasticity, and the qualitative assessment of local infusion sites. METHODS: Immunoglobulin G (IgG) was subcutaneously infused into the abdominal region of Yucatan miniature swine. Changes in interstitial pressure were measured, using an in-line pressure transducer, during and after infusions. Additionally, pre- and post-infusion changes in local skin visco-elasticity were measured using a Cutometer®. Lastly, infusion sites were assessed for post-infusion local skin reactions such as erythema and swelling. Similar assessments were made following SC IgG delivery with the permeation enhancer recombinant human hyaluronidase PH20 (rHuPH20). RESULTS: Subcutaneous infusions of IgG, in the presence of rHuPH20, significantly reduced average interstitial pressures by 55% during the infusion period and by 67% during the post-infusion period, compared to the control. Infusions in the presence of rHuPH20 also maintained better local skin elasticity as seen by a 42% increase in local skin pliability compared to the control. Finally, infusions with rHuPH20 resulted in an 80% reduction in swelling area compared to the control. DISCUSSION: A large animal model was developed that incorporates both quantitative and qualitative assessment methods to aid in understanding SC delivery of proteins.

Rebamipide abolishes Helicobacter pylori CagA-induced phospholipase D1 expression via inhibition of NFκB and suppresses invasion of gastric cancer cells.

Infection with cagA-positive Helicobacter pylori is a risk factor for the development of severe gastritis and gastric cancer (GC). CagA protein is injected into gastric epithelial cells and deregulates a variety of cellular signaling molecules. Phospholipase D (PLD) is elevated in many different types of human cancers and has been implicated as a critical factor in inflammation and carcinogenesis. In this study, we show that infection with cagA-positive H. pylori in GC cells significantly induces PLD1 expression via CagA-dependent activation of nuclear factor κB (NFκB). Interestingly, the level of PLD1 protein and IκBα phosphorylation is aberrantly upregulated in H. pylori-infected human GC tissues. Infection with cagA-positive H. pylori and expression of CagA enhanced the binding of NFκB to the PLD1 promoter, and two functional NFκB-binding sites were identified within the PLD1 promoter. Rebamipide, a mucosal-protective antiulcer agent, abolished H. pylori cagA-induced PLD1 expression via inhibition of binding of NFκB to the PLD1 promoter, and also inhibited PLD activity. Moreover, rebamipide suppressed H. pylori-induced matrix metalloproteinase-9, interleukin-8 and activation-induced cytidine deaminase expression as well as invasion of GC cells through downregulation of PLD1. Our data suggest that H. pylori cagA targets PLD1 for invasion of GC cells, and rebamipide might contribute to the antitumorigenic effect of GC cells via inhibition of the H. pylori cagA-NFκB-PLD1 signaling pathway.

Blood-brain barrier disruption after cardiac surgery.

BACKGROUND AND PURPOSE: CNS complications are often seen after heart surgery, and postsurgical disruption of the BBB may play an etiologic role. The objective of this study was to determine the prevalence of MR imaging-detected BBB disruption (HARM) and DWI lesions after cardiac surgery. MATERIALS AND METHODS: All patients had an MRI after cardiac surgery. For half the patients (group 1), we administered gadolinium 24 hours after surgery and obtained high-resolution DWI and FLAIR images 24-48 hours later. We administered gadolinium to the other half (group 2) at the time of the postoperative scan, 2-4 days after surgery. Two stroke neurologists evaluated the images. RESULTS: Of the 19 patients we studied, none had clinical evidence of a stroke or delirium at the time of the gadolinium administration or the scan, but 9 patients (47%) had HARM (67% in group 1; 30% in group 2; P = .18) and 14 patients (74%) had DWI lesions (70% in group 1; 78% in group 2; P = 1.0). Not all patients with DWI lesions had HARM, and not all patients with HARM had DWI lesions (P = .56). CONCLUSIONS: Almost half the patients undergoing cardiac surgery have evidence of HARM, and three-quarters have acute lesions on DWI after surgery. BBB disruption is more prevalent in the first 24 hours after surgery. These findings suggest that MR imaging can be used as an imaging biomarker to assess therapies that may protect the BBB in patients undergoing heart surgery.

Sclerotium rolfsii Causes White Rot on Taro in Korea.

Taro (Colocasia esculenta L.) is grown throughout the world primarily for its tubers, which become edible after cooking. Taro stems are often used in a traditional soup in South Korea. In September 2012, a suspected white rot of taro occurred in a farmer's fields in Jinju, South Korea. Infected plants gradually withered, a white mycelial mat appeared, and numerous sclerotia developed on the surface of petioles near the soil line. The heavily infected petioles rotted and the entire plant eventually died. The freshly isolated pathogenic fungus was grown on potato dextrose agar (PDA) and examined microscopically. Aerial mycelia usually formed many narrow hyphal strands 4 to 8 µm wide. The white mycelia formed a typical clamp connection structure after 6 days growth at 25°C. The sclerotia were white at first, gradually turned dark brown, and were 1 to 3 mm in diameter. Small globoid sclerotia formed abundantly on PDA after 18 days of growth. Ten 2-month-old potted taro plants were inoculated with S. rolfsii-colonized agar discs directly at the base of each plant and kept at 25°C in a greenhouse to test pathogenicity. Three taro plants were inoculated similarly with uncolonized agar discs as controls. Eight days after inoculation, blight symptoms were observed, and S. rolfsii was reisolated from the artificially inoculated plants. The control taro plants remained healthy. We amplified and sequenced an internal transcribed spacer (ITS) rDNA region of the isolate using the ITS1 (5'-TCCGTAGGTGAACCTGCGG-3') and ITS4 (5'-TCCTCCGCTTATTGATATGC-3') primers to confirm the identity of the fungus (2). The resulting 684-bp sequence was deposited in GenBank (Accession No. KC491876). A comparison with other sequences available in the GenBank database revealed that the ITS sequence shared 100% similarity with Sclerotium rolfsii sequences (HQ420816 and JN017199). Based on the symptoms, mycological characteristics, ITS sequence analysis, and host plant pathogenicity, this fungus was identified as S. rolfsii Saccardo (1). To our knowledge, this is the first report of white rot in taro caused by S. rolfsii in Korea. References: (1) J. E. Mordue. CMI Descriptions of Pathogenic Fungi and Bacteria. No. 410, 1974. (2) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, New York, 1990.

Age- and weight-adjusted warfarin initiation nomogram for ischaemic stroke patients.

OBJECTIVES: Specific guidelines for initial dosing of warfarin in ischaemic stroke patients have not been developed. Therefore, we have developed an age- and weight-adjusted warfarin initiation nomogram (AW-WIN) for ischaemic stroke patients and then evaluated the efficacy and safety of AW-WIN compared with physician-determined warfarin dosing (PDWD). METHODS: The age- and weight-adjusted warfarin initiation nomogram was administered to 104 acute ischaemic stroke patients between January 2008 and February 2009. A historical control group (PDWD) of 96 patients was selected from comparable patients who were discharged with warfarin during the previous year. Time-to-therapeutic international normalized ratios (INRs) and the incidence of excessive anticoagulation were compared in the AW-WIN and PDWD groups. RESULTS: The general characteristics, risk factors, and stroke mechanism of the AW-WIN and PDWD groups did not differ significantly. The mean time to INR ≥ 2.0 was significantly shorter in the AW-WIN than in the PDWD group (4.9 ± 0.7 vs. 6.2 ± 0.8 days, P = 0.0008). After adjustment for potential confounding variables, the AW-WIN group reached target INR faster than the PDWD group (hazard ratio, 1.76; 95% confidence interval, 1.26-2.45; P = 0.001). The time-to-therapeutic INR ≥1.7 was shorter (P = 0.0002), the proportion of patients with therapeutic INR (2-3) at 5 days was higher (P = 0.002), and the rate of excessive anticoagulation of ≥3.5 INR during hospitalization was lower (P = 0.024) in the AW-WIN than in the PDWD group. CONCLUSIONS: AW-WIN reduces the time to target INR and the risk of excessive anticoagulation. AW-WIN may be an efficient and safe method of anticoagulation during the acute phase of ischaemic stroke.

Poststroke depression and emotional incontinence: factors related to acute and subacute stages.

OBJECTIVES: To investigate the characteristics and prevalence of poststroke depression (PSD) and poststroke emotional incontinence (PSEI) and the factors related to these conditions at admission and 3 months after stroke. METHODS: We evaluated 508 consecutive patients with acute ischemic stroke for PSD and PSEI at admission and 3 months later. PSD was evaluated using the Beck Depression Inventory, and PSEI was evaluated using Kim's criteria. Blood samples were collected and genotyped for the promoter region of the serotonin transporter protein (5-HTTLPR) and the number of tandem repeats within intron 2 (STin2 VNTR). Perceived social support (the ENRICHD Social Support Inventory) was also measured. RESULTS: PSD and PSEI were present in 13.7% and 9.4% of patients, respectively, at admission and in 17.7% and 11.7%, respectively, at 3 months after stroke. Multivariate analyses showed that PSD at admission was associated with the NIH Stroke Scale score at admission (p < 0.001), whereas PSD at 3 months was associated with the presence of microbleeds (p < 0.01) and perceived low social support (p < 0.001). In contrast, only lesion location (p = 0.022) was associated with PSEI at admission, whereas modified Rankin Scale score (p = 0.019), STin2 VNTR (p = 0.040), and low social support (p = 0.042) were related to PSEI 3 months after stroke. CONCLUSIONS: Diverse factors such as neurologic dysfunction, lesion location, microbleeds, genetic traits, and social support are differently related to acute and subacute emotional disturbances. Strategies to prevent or manage these problems should consider these differences.

Isolated lateral thalamic infarction: the role of posterior cerebral artery disease.

BACKGROUND AND PURPOSE: Lateral thalamic infarction (LTI) is usually caused by small vessel disease (SVD), i.e., occlusion of the deep perforator. However, focal atherosclerotic posterior cerebral artery disease (PCAD) may produce LTI via thrombotic occlusion of the perforator. We aimed to investigate the prevalence of PCAD in LTI and differences in clinical and imaging findings between LTIs associated with PCAD and SVD. METHODS: We retrospectively evaluated 58 consecutive patients with isolated LTI who underwent diffusion-weighted imaging (DWI) and MR angiography (MRA) within 7 days after stroke onset. Patients were divided into two groups: those with PCAD and those with SVD. Clinical syndromes were divided into pure sensory stroke (PSS) and sensory stroke plus (SS-plus), i.e., the concomitant presence of motor dysfunction or ataxia. Clinical and imaging findings were compared between these two groups. RESULTS: Of the 58 patients, 13 (22.4%) had PCAD. PSS was more frequently associated with SVD than with PCAD (57.8% vs. 23.1%, P=0.032). Initial DWI lesion volume (cm³) was significantly larger in PCAD than in patients with SVD (0.38±0.13 vs. 0.33±0.22, P=0.025). Among the 23 patients (39.7%) who underwent follow-up DWI, patients with PCAD showed a significantly greater increase in subacute lesion volume than those with SVD (P=0.019). Although National Institutes of Health Stroke Scale scores did not differ at admission (P=0.185), they were significantly higher at discharge in PCAD than in patients with SVD (P=0.012). CONCLUSIONS: Our data suggest that PCAD is an important cause of LTI, being related to SS-plus, larger lesion volume, and worse clinical outcomes.

An Outbreak of Leaf Spot Caused by Corynespora cassiicola on Korean Raspberry in Korea.

In September and October 2010, leaf spots were observed on Korean raspberry (Rubus crataegifolius Bunge) plants in farmers' fields in Hapcheon, Gyeongnam Province, South Korea. Disease incidence ranged from 50 to 80% among fields. Circular- to irregular-shaped spots surrounded by yellow halos occurred frequently on the leaves of Korean raspberry plants. Brown spots became dark with wavy borders and ranged from 20 to 300 mm in diameter. Infected leaves became chlorotic, blighted, and eventually died. Fungal hyphae covered the lesions with abundant conidia and conidiophores. Fresh leaf specimens were collected from infected plants and the putative causal pathogen was isolated onto potato dextrose agar (PDA). A total of 30 isolates of the fungus were collected from diseased plants collected in the field. Fungal colonies were gray to brown on PDA. Colonies formed conidia, 38 to 210 × 8 to 20 µm, which were solitary or catenary, obclavate to cylindrical, smooth, straight or curved, and subhyaline to pale brown or brown. Conidiophores, 98 to 840 × 4 to 12 µm, were slightly or conspicuously swollen at apex, single, simple, straight or slightly flexuous, pale to midbrown, smooth, septate, thick, monotretic, and determinate or in tufts. Morphological characteristics of the fungal specimens were similar to descriptions of Corynespora cassiicola (1). A representative isolate of the pathogen was used to inoculate leaves of Korean raspberry plants for pathogenicity testing. Five leaves of a 3-month-old potted plant were sprayed with a suspension of conidia in water. Conidia were harvested from PDA cultures and adjusted to 2 × 104 conidia/ml with a hemocytometer. Five leaves sprayed with sterile distilled water served as controls. Inoculated plants were placed in a humid chamber with 100% relative humidity at 30°C for 24 h and then moved to a greenhouse. Symptoms similar to those observed in the farmers' fields developed on the inoculated leaves within 12 days, whereas the controls remained asymptomatic. The causal fungus was reisolated from the lesions of inoculated plants to satisfy Koch's postulates. To confirm the identity of the fungus, the complete internal transcribed spacer (ITS) rDNA region was amplified and sequenced (3). Amplification of the ITS region generated a 559-bp sequence (GenBank Accession No. JQ340026) with 100% similarity to sequences of C. cassiicola in GenBank (Accession No. GU138988) causing leaf spot on cassava (2). Based on the symptoms, morphological characteristics, pathogenicity, and molecular identification, this fungus was identified as C. cassiicola (1). To our knowledge, this is the first report of leaf spot caused by C. cassiicola on Korean raspberry. The recent occurrence of leaf spot on Korean raspberry suggests that C. cassiicola is spreading widely and posing a serious threat to these plants in Korea. References: (1) M. B. Ellis et al. No. 303 in: CMI Descriptions of Pathogenic Fungi and Bacteria. Surrey, Kew, UK, 1971. (2) X.-B. Liu et al. Plant Dis. 94:916, 2010. (3) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, Inc., New York, 1990.

Bacille Calmette Guérin (BCG) can induce Kawasaki disease-like features in programmed death-1 (PD-1) gene knockout mice.

OBJECTIVES: Various genetic variants of inhibitory immune signals have been suspected as feasible causes of Kawasaki disease (KD). We investigated the associative role of programmed death-1 (PD-1) gene in the pathogenesis of KD by injecting bacilli Calmette Guérin (BCG) to PD-1 gene knockout (PD-1KO) mice. METHODS: In order to induce KD-like clinical manifestations in young PD-1KO mice, intradermal injection of the bacilli Calmette Guérin (BCG) was performed twice on the abdominal skin with a 4-week interval. For defining the role of BCG, heat shock protein (HSP) 65 was challenged. In addition, Staphylococcus aureus was adopted as a microorganism that does not contain HSP65 structure. One month after the second injection, heart, liver, and kidneys were removed and examined. RESULTS: PD-1KO mice showed KD-like features including prolonged fever for more than 5 days, erythematous swelling on soles, tail skin desquamation, and gallbladder (GB) hydrops. Inflammatory cell aggregation and intimal proliferation in at least more than one coronary artery was found in all PD-1KO mice whereas scanty coronary lesion was found in wild type (WT) mice. When the PD-1KO mice were injected twice with HSP65, coronary arterial lesions similar to those seen after BCG injection were observed. Inflammatory reactions in other organs including hepatic arteries, renal arteries, and biliary arteries were also observed in PD-1KO mice. CONCLUSIONS: Our data suggest that PD-1 gene may be one of the genetic predispositions of KD and antigens containing HSP65 structure could be a triggering factor of KD by our animal model of KD.

Anaerobic digestion and co-digestion processes of vegetable and fruit residues: process and microbial ecology.

This study evaluated the feasibility of methane production from fruit and vegetable waste (FVW) obtained from the central food distribution market in Mexico City using an anaerobic digestion (AD) process. Batch systems showed that pH control and nitrogen addition had significant effects on biogas production, methane yield, and volatile solids (VS) removal from the FVW (0.42 m(biogas)(3)/kg VS, 50%, and 80%, respectively). Co-digestion of the FVW with meat residues (MR) enhanced the process performance and was also evaluated in a 30 L AD system. When the system reached stable operation, its methane yield was 0.25 (m(3)/kg TS), and the removal of the organic matter measured as the total chemical demand (tCOD) was 65%. The microbial population (general Bacteria and Archaea) in the 30 L system was also determined and characterized and was closely correlated with its potential function in the AD system.

The arcuate NPY, POMC, and CART expressions responding to food deprivation are exaggerated in young female rats that experienced neonatal maternal separation.

This study was conducted to examine the effect of neonatal maternal separation on the hypothalamic feeding peptides expression in young female offspring. Sprague-Dawley pups were separated from dam for 3h daily during PND 1-14 (MS), or left undisturbed except routine cage cleaning (NH). Weanling female pups were housed in group and the arcuate mRNA levels of neuropeptide Y (NPY), proopiomelanocortin (POMC), and cocaine-amphetamine regulated transcript (CART) were examined at two months of age with or without food deprivation. The basal arcuate expression levels of these peptides did not differ between NH and MS group. However, a 48 h of food deprivation significantly increased NPY mRNA level, and decreased POMC and CART, in the arcuate nucleus of MS females, but not in NH females. Fasting-induced elevation of the plasma corticosterone tended to be greater in MS group than in NH, but the basal levels did not differ between the groups. Plasma leptin levels were decreased in MS females compared with NH, and food deprivation significantly suppressed the leptin levels both in NH and MS groups. Results suggest that MS experience may increase stress vulnerability in female rats and exaggerate the feeding peptides expression in the arcuate nucleus responding to metabolic stress food deprivation.

Comparison of 90-day case-fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis.

BACKGROUND: It has not been clarified whether the disparity in ischemic stroke outcome between populations is caused by ethnic and geographic differences or by variations in case mix. Propensity score matching (PSM) analysis can overcome some analytical problems but is rarely used in stroke outcome research. This study was to compare the ischemic stroke case-fatality between two PSM cohorts of Sweden and Korea. METHODS: Prognostic variables related to baseline characteristics and stroke care were included in our PSM model. Then, we selected 7675 Swedish and 1220 Korean patients with ischemic stroke from each stroke registers and performed one-to-one matching based on propensity scores of each patient. RESULTS: After PSM, all measured variables were well balanced in 1163 matched subjects, and the 90-day case-fatality was identical 6.2% (HR 0.997, 95%CI 0.905-1.099) in Sweden and Korea. CONCLUSIONS: No difference is found in the 90-day case-fatality in propensity score-matched Swedish and Korean patients with ischemic stroke.