Effect of a second-generation motion correction algorithm on image quality and measurement reproducibility of coronary CT angiography in patients with a myocardial bridge and mural coronary artery.

AIM: To determine the effect of second-generation motion correction (MC2) on image quality and measurement reproducibility of cardiac CT images in patients with a myocardial bridge and mural coronary artery (MB-MCA) compared to standard (STD) images without motion correction and with first-generation motion correction (MC1). MATERIALS AND METHODS: A total of 66 patients with MB-MCA in the left anterior descending branch who underwent 256-detector CT with single-heartbeat acquisition were included. Images were reconstructed at 45% and 75% R-R intervals using STD, MC1, and MC2 algorithms. Image quality for MB-MCA was assessed by two observers on a four-point scale (1 = poor and 4 = excellent) and compared among STD, MC1, and MC2. Depth and length of MB, lumen area, and minimal diameter of MCA were measured and compared. RESULTS: At 45% R-R interval, image quality scores were 1.59 ± 0.78, 2.21 ± 0.97, and 3.21 ± 0.62 for MCA, and 2.48 ± 0.79, 2.76 ± 0.75, and 3.58 ± 0.58 for MB with STD, MC1 and MC2, respectively. At 75% R-R interval, these values were 2.26 ± 0.60, 3.03 ± 0.89, and 3.59 ± 0.55 for MCA and 3.00 ± 0.93, 3.17 ± 0.83, and 3.80 ± 0.44 for MB. Although MC1 was superior to STD in displaying MCA, there was no statistical difference between the two algorithms for MB (p>0.05). Compared with STD and MC1, MC2 statistically improved image quality and interpretability for both MCA and MB and had narrower limits in interobserver agreement for measurements at both 45% and 75% R-R intervals. CONCLUSION: MC2 improves CT image quality and measurement reproducibility in patients with MB-MCA compared to STD and MC1.

Chloride Channel-3 (ClC-3) Modifies the Trafficking of Leucine-Rich Repeat-Containing 8A (LRRC8A) Anion Channels.

Chloride channel-3 (ClC-3) Cl-/H+ antiporters and leucine-rich repeat-containing 8 (LRRC8) family anion channels have both been associated with volume-regulated anion currents (VRACs). VRACs are often altered in ClC-3 null cells but are absent in LRRC8A null cells. To explore the relationship between ClC-3, LRRC8A, and VRAC we localized tagged proteins in human epithelial kidney (HEK293) cells using multimodal microscopy. Expression of ClC-3-GFP induced large multivesicular bodies (MVBs) with ClC-3 in the delimiting membrane. LRRC8A-RFP localized to the plasma membrane and to small cytoplasmic vesicles. Co-expression demonstrated co-localization in small, highly mobile cytoplasmic vesicles that associated with the early endosomal marker Rab5A. However, most of the small LRRC8A-positive vesicles were constrained within large MVBs with abundant ClC-3 in the delimiting membrane. Dominant negative (S34A) Rab5A prevented ClC-3 overexpression from creating enlarged MVBs, while constitutively active (Q79L) Rab5A enhanced this phenotype. Thus, ClC-3 and LRRC8A are endocytosed together but independently sorted in Rab5A MVBs. Subsequently, LRRC8A-labeled vesicles were sorted to MVBs labeled by Rab27A and B exosomal compartment markers, but not to Rab11 recycling endosomes. VRAC currents were significantly larger in ClC-3 null HEK293 cells. This work demonstrates dependence of LRRC8A trafficking on ClC-3 which may explain the association between ClC-3 and VRACs.

Exploratory use of romosozumab for osteoporosis in a patient with Hajdu-Cheney syndrome: a case report.

Hajdu-Cheney syndrome (HCS) is an inherited skeletal disorder caused by mutations in the Notch homolog protein 2 gene (NOTCH2). Treatment of this rare disease is challenging because there are no established guidelines worldwide. Previous case reports using bisphosphonates, denosumab, or teriparatide suggested that curative treatment for HCS did not exist yet in terms of preventing the disease progression. Therefore, the efficacy of romosozumab for osteoporosis in patients with HCS needs to be evaluated. Herein, we report the case of a 43-year-old woman who had progressive acro-osteolysis and repeated fractures since the age of 29 years. Next-generation sequencing confirmed HCS with a mutation at nucleotide 6758G>A, leading to Trp2253Ter replacement in NOTCH2. Romosozumab treatment was initiated because she had already received bisphosphonate for more than 10 years at other hospitals. After 1 year of romosozumab treatment, the bone mineral density (BMD) increased by 10.2%, 6.3%, and 1.3%, with Z scores of -2.9, -1.6, and -1.2 at the lumbar spine, femoral neck, and total hip, respectively. In addition, C-telopeptide was suppressed by 26.4% (0.121 to 0.089 ng/mL), and procollagen type I N-terminal propeptide increased by 18.7% (25.2 to 29.9 ng/mL). This was the first report of romosozumab treatment in patient with osteoporosis and HCS in Korea. One year of romosozumab treatment provided substantial gains in BMD with maintaining the last acro-osteolytic status without deteriorating, representing a possible treatment option for HCS.

Oxidant-resistant LRRC8A/C anion channels support superoxide production by NADPH oxidase 1.

KEY POINTS: LRRC8A-containing anion channels associate with NADPH oxidase 1 (Nox1) and regulate superoxide production and tumour necrosis factor-α (TNFα) signalling. Here we show that LRRC8C and 8D also co-immunoprecipitate with Nox1 in vascular smooth muscle cells. LRRC8C knockdown inhibited TNFα-induced O2•- production, receptor endocytosis, nuclear factor-κB (NF-κB) activation and proliferation while LRRC8D knockdown enhanced NF-κB activation. Significant changes in LRRC8 isoform expression in human atherosclerosis and psoriasis suggest compensation for increased inflammation. The oxidant chloramine-T (ChlorT, 1 mM) weakly (∼25%) inhibited LRRC8C currents but potently (∼80%) inhibited LRRC8D currents. Substitution of the extracellular loop (EL1, EL2) domains of 8D into 8C conferred significantly stronger (69%) ChlorT-dependent inhibition. ChlorT exposure impaired subsequent current block by DCPIB, which occurs through interaction with EL1, further implicating external oxidation sites. LRRC8A/C channels most effectively sustain Nox1 activity at the plasma membrane. This may result from their ability to remain active in an oxidized microenvironment. ABSTRACT: Tumour necrosis factor-α (TNFα) activates NADPH oxidase 1 (Nox1) in vascular smooth muscle cells (VSMCs), producing superoxide (O2•- ) required for subsequent signalling. LRRC8 family proteins A-E comprise volume-regulated anion channels (VRACs). The required subunit LRRC8A physically associates with Nox1, and VRAC activity is required for Nox activity and the inflammatory response to TNFα. VRAC currents are modulated by oxidants, suggesting that channel oxidant sensitivity and proximity to Nox1 may play a physiologically relevant role. In VSMCs, LRRC8C knockdown (siRNA) recapitulated the effects of siLRRC8A, inhibiting TNFα-induced extracellular and endosomal O2•- production, receptor endocytosis, nuclear factor-κB (NF-κB) activation and proliferation. In contrast, siLRRC8D potentiated NF-κB activation. Nox1 co-immunoprecipitated with 8C and 8D, and colocalized with 8D at the plasma membrane and in vesicles. We compared VRAC currents mediated by homomeric and heteromeric LRRC8C and LRRC8D channels expressed in HEK293 cells. The oxidant chloramine T (ChlorT, 1 mM) weakly inhibited 8C, but potently inhibited 8D currents. ChlorT exposure also impaired subsequent current block by the VRAC blocker DCPIB, implicating external sites of oxidation. Substitution of the 8D extracellular loop domains (EL1, EL2) into 8C conferred significantly stronger ChlorT-mediated inhibition of 8C currents. Our results suggest that LRRC8A/C channel activity can be effectively maintained in the oxidized microenvironment expected to result from Nox1 activation at the plasma membrane. Increased ratios of 8D:8C expression may potentially depress inflammatory responses to TNFα. LRRC8A/C channel downregulation represents a novel strategy to reduce TNFα-induced inflammation.

Defining an international cut-off of two-legged countermovement jump power for sarcopenia and dysmobility syndrome.

We aimed to establish jump power cut-offs for the composite outcome of either sarcopenia (EWGSOP2) or dysmobility syndrome using Asian and Caucasian cohorts. Estimated cut-offs were sex specific (women: < 19.0 W/kg; men: < 23.8 W/kg) but not ethnicity specific. Jump power has potential to be used in definitions of poor musculoskeletal health. PURPOSE: Weight-corrected jump power measured during a countermovement jump may be a useful tool to identify individuals with poor musculoskeletal health, but no cut-off values exist. We aimed to establish jump power cut-offs for detecting individuals with either sarcopenia or dysmobility syndrome. METHODS: Age- and sex-matched community-dwelling older adults from two cohorts (University of Wisconsin-Madison [UW], Korean Urban Rural Elderly cohort [KURE], 1:2) were analyzed. Jump power cut-offs for the composite outcome of either sarcopenia defined by EWGSOP2 or dysmobility syndrome were determined. RESULTS: The UW (n = 95) and KURE (n = 190) cohorts were similar in age (mean 75 years) and sex distribution (68% women). Jump power was similar between KURE and UW women (19.7 vs. 18.6 W/kg, p = 0.096) and slightly higher in KURE than UW in men (26.9 vs. 24.8 W/kg, p = 0.050). In UW and KURE, the prevalence of sarcopenia (7.4% in both), dysmobility syndrome (31.6% and 27.9%), or composite of either sarcopenia or dysmobility syndrome (32.6% and 28.4%) were comparable. Low jump power cut-offs for the composite outcome differed by sex but not by ethnicity (< 19.0 W/kg in women; < 23.8 W/kg in men). Low jump power was associated with elevated odds of sarcopenia (adjusted odds ratio [aOR] 4.07), dysmobility syndrome (aOR 4.32), or the composite of sarcopenia or dysmobility syndrome (aOR 4.67, p < 0.01 for all) independent of age, sex, height, and ethnicity. CONCLUSION: Sex-specific jump power cut-offs were found to detect the presence of either sarcopenia or dysmobility syndrome in older adults independent of Asian or Caucasian ethnicity.

The diagnostic value of phase angle, an integrative bioelectrical marker, for identifying individuals with dysmobility syndrome: the Korean Urban-Rural Elderly study.

Low phase angle, a non-invasive bioimpedance marker, is associated with elevated odds of dysmobility syndrome and its components. Phase angle (estimated cutoffs: < 4.8° in men; < 4.5° in women) can be used to detect dysmobility syndrome in community-dwelling older adults as a simple, integrative screening tool. INTRODUCTION: Dysmobility syndrome uses a score-based approach to predict fracture risk that incorporates the concepts of osteoporosis, sarcopenia, and obesity. Low phase angle (PhA), a simple, non-invasive bioelectrical impedance marker, was associated with low lean mass, high fat mass, and poor muscle function. We aimed to investigate the association between PhA and dysmobility syndrome, with the exploration of the diagnostic cutoffs. METHODS: In a community-dwelling Korean older adult cohort, dysmobility syndrome was defined as the presence of ≥ 3 of the following components: osteoporosis, low lean mass, falls in the preceding year, low grip strength, high fat mass, and poor timed up and go performance. RESULTS: Among the 1825 participants (mean age 71.6, women 66.7%), subjects were classified into sex-stratified PhA tertiles. The prevalence of dysmobility syndrome increased from the highest PhA tertile group to the lowest (15.50 to 2.45% in men; 33.41 to 12.25% in women, P for trend < 0.001). The mean PhA values decreased as the dysmobility score increased (5.33° to 4.65° in men; 4.76° to 4.39° in women, P for trend < 0.001). Low PhA (cutoff: < 4.8° in men; < 4.5° in women) was associated with twofold elevated odds of dysmobility syndrome after adjusting for age, sex, and conventional risk factors. Low PhA improved the identification of individuals with dysmobility syndrome when added to the conventional risk model (area under the curve, 0.73 to 0.75, P = 0.002). CONCLUSION: Low PhA was associated with dysmobility syndrome and its components, independent of age, sex, body mass index, nutritional status, and inflammation.

Strong exciton-plasmon coupling in dye-doped film on a planar hyperbolic metamaterial.

We experimentally demonstrate the direct strong coupling between the S0→S1 absorption transition of rhodamine 6G (R6G) dye molecules and the surface plasmon polaritons of a hyperbolic metamaterial (HMM) substrate. The surface plasmon mode was excited by a guided mode of the R6G-doped polymer thin film on the HMM. The coupling strengths of the interactions between the surface plasmon and two molecular exciton modes are greater than the average linewidths of the individual modes indicating a strong coupling regime. This is the first, to the best of our knowledge, experimental demonstration of the direct strong coupling between the resonance mode supported by the HMM and the dye molecules on the HMM surface, not embedded in the HMM structure. The study may provide the foundation for the development of novel planar photonic or electronic devices.

A Comparative Study of Biomechanical and Geometrical Attributes of Abdominal Aortic Aneurysms in the Asian and Caucasian Populations.

In this work, we provide a quantitative assessment of the biomechanical and geometric features that characterize abdominal aortic aneurysm (AAA) models generated from 19 Asian and 19 Caucasian diameter-matched AAA patients. 3D patient-specific finite element models were generated and used to compute peak wall stress (PWS), 99th percentile wall stress (99th WS), and spatially averaged wall stress (AWS) for each AAA. In addition, 51 global geometric indices were calculated, which quantify the wall thickness, shape, and curvature of each AAA. The indices were correlated with 99th WS (the only biomechanical metric that exhibited significant association with geometric indices) using Spearman's correlation and subsequently with multivariate linear regression using backward elimination. For the Asian AAA group, 99th WS was highly correlated (R2 = 0.77) with three geometric indices, namely tortuosity, intraluminal thrombus volume, and area-averaged Gaussian curvature. Similarly, 99th WS in the Caucasian AAA group was highly correlated (R2 = 0.87) with six geometric indices, namely maximum AAA diameter, distal neck diameter, diameter-height ratio, minimum wall thickness variance, mode of the wall thickness variance, and area-averaged Gaussian curvature. Significant differences were found between the two groups for ten geometric indices; however, no differences were found for any of their respective biomechanical attributes. Assuming maximum AAA diameter as the most predictive metric for wall stress was found to be imprecise: 24% and 28% accuracy for the Asian and Caucasian groups, respectively. This investigation reveals that geometric indices other than maximum AAA diameter can serve as predictors of wall stress, and potentially for assessment of aneurysm rupture risk, in the Asian and Caucasian AAA populations.

High diversity of Diaporthe species associated with pear shoot canker in China.

Species of Diaporthe (syn. Phomopsis) are important endophytes, saprobes and pathogens, infecting a wide range of plants and resulting in important crop diseases. However, the species occurring on pear remain largely unresolved. In this study, a total of 453 Diaporthe isolates were obtained from branches of Pyrus plants (including P. bretschneideri, P. communis, P. pyrifolia and P. ussuriensis collected from 12 provinces in China) showing shoot canker symptoms. Phylogenetic analyses based on five loci (ITS, TEF, CAL, HIS, and TUB) coupled with morphology of 113 representative isolates revealed that 19 Diaporthe species were isolated, representing 13 known species (including D. caryae, D. cercidis, D. citrichinensis, D. eres, D. fusicola, D. ganjae, D. hongkongensis, D. padina, D. pescicola, D. sojae, D. taoicola, D. unshiuensis and D. velutina) and six new species described here as D. acuta, D. chongqingensis, D. fulvicolor, D. parvae, D. spinosa and D. zaobaisu. Although Koch's postulates confirmed all species to be pathogenic, a high degree of variation in aggressiveness was observed. Moreover, these species have a high diversity, plasticity, and prevalence related to the geographical location and pear species involved.

Population-based study of the impact of small bowel obstruction due to adhesions on short- and medium-term mortality.

BACKGROUND: Small bowel obstruction due to adhesions (aSBO) is a common indication for admission to a surgical unit. Despite the prevalence of this condition, the short- and medium-term survival of this patient population has not been well described. The purpose of this study was to measure the short- and medium-term survival of patients admitted to hospital with aSBO. METHODS: Linked administrative data were used to identify patients admitted to hospital in Ontario, Canada, for aSBO between 2005 and 2011. Patients were divided into two groups: those aged less than 65 years (younger group) and those aged 65 years and older (older group). Thirty-day, 90-day and 1-year mortality rates were estimated. One-year mortality was compared with that in the general population, adjusting for age and sex. The timing of deaths in relation to admission was assessed, as well as the proportion of patients discharged before experiencing short-term mortality. RESULTS: There were 22 197 patients admitted to hospital for aSBO for the first time in the study interval. Mean age was 64·5 years and 52·2 per cent of the patients were women. Overall, the 30-day, 90-day and 1-year mortality rates for the cohort were 5·7 (95 per cent c.i. 5·4 to 6·0), 8·7 (8·3 to 9·0) and 13·9 (13·4 to 14·3) per cent respectively. For both groups, the 1-year risk of death was significantly greater than that of the age-matched general population. The majority of deaths (62·5 per cent) occurred within 90 days of admission, with 36·4 per cent occurring after discharge from the aSBO admission. CONCLUSION: Patients admitted with aSBO have a high short-term mortality rate. Increased monitoring of patients in the early period after admission is advisable.

ANTECEDENTES: La obstrucción del intestino delgado por adherencias (adhesive small bowel obstruction, aSBO) es una indicación frecuente de ingreso en una unidad quirúrgica. A pesar de la prevalencia de esta patología, la supervivencia de estos pacientes a corto y a medio plazo no ha sido bien descrita. El objetivo de este estudio fue determinar la supervivencia a corto y a medio plazo de pacientes con aSBO ingresados en el hospital. MÉTODOS: Utilizando el enlace de datos administrativos se identificaron a los pacientes ingresados por aSBO en Ontario, Canadá, entre 2005-2011. Los pacientes se dividieron en dos subgrupos: los menores de 65 años de edad (subgrupo joven) y los de 65 años o más (subgrupo mayor). Se estimó la mortalidad a los 30 días, 90 días y a 1 año. La mortalidad a 1 año se comparó con la de la población general, ajustando por edad y sexo. Se evaluó el momento del fallecimiento respecto al ingreso, así como la proporción de pacientes que fueron dados de alta antes de fallecer a los 30 días. RESULTADOS: Durante el periodo de estudio se ingresaron en el hospital 22.197 pacientes con aSBO por primera vez. La edad media de los pacientes era de 65 años y un 52% eran mujeres. La mortalidad global de la cohorte a los 30 días, a los 90 días y a 1 año fue del 5,7% (i.c. del 95%: 5,4-6,0%), 8,3% (i.c. del 95%: 8,3-9,0%) y 13% (i.c. del 95%: 12,9-15,0%), respectivamente. Para ambos subgrupos, el riesgo de mortalidad a 1 año fue significativamente mayor que en la población general emparejada por edad. La mayoría de los fallecimientos (59%) ocurrieron durante los 90 días del ingreso, con un 36% tras el alta después del ingreso por aSBO. CONCLUSIÓN: Los pacientes ingresados por aSBO presentan una alta mortalidad a corto plazo. Se recomienda incrementar la vigilancia de estos pacientes en el periodo temprano tras el alta hospitalaria.

Colletotrichum species associated with anthracnose of Pyrus spp. in China.

Colletotrichum species are plant pathogens, saprobes, and endophytes on a range of economically important hosts. However, the species occurring on pear remain largely unresolved. To determine the morphology, phylogeny and biology of Colletotrichum species associated with Pyrus plants, a total of 295 samples were collected from cultivated pear species (including P. pyrifolia, P. bretschneideri, and P. communis) from seven major pear-cultivation provinces in China. The pear leaves and fruits affected by anthracnose were sampled and subjected to fungus isolation, resulting in a total of 488 Colletotrichum isolates. Phylogenetic analyses based on six loci (ACT, TUB2, CAL, CHS-1, GAPDH, and ITS) coupled with morphology of 90 representative isolates revealed that they belong to 10 known Colletotrichum species, including C. aenigma, C. citricola, C. conoides, C. fioriniae, C. fructicola, C. gloeosporioides, C. karstii, C. plurivorum, C. siamense, C. wuxiense, and two novel species, described here as C. jinshuiense and C. pyrifoliae. Of these, C. fructicola was the most dominant, occurring on P. pyrifolia and P. bretschneideri in all surveyed provinces except in Shandong, where C. siamense was dominant. In contrast, only C. siamense and C. fioriniae were isolated from P. communis, with the former being dominant. In order to prove Koch's postulates, pathogenicity tests on pear leaves and fruits revealed a broad diversity in pathogenicity and aggressiveness among the species and isolates, of which C. citricola, C. jinshuiense, C. pyrifoliae, and C. conoides appeared to be organ-specific on either leaves or fruits. This study also represents the first reports of C. citricola, C. conoides, C. karstii, C. plurivorum, C. siamense, and C. wuxiense causing anthracnose on pear.

Teriparatide therapy for severe, refractory osteoradionecrosis of the jaw.

Although osteoradionecrosis (ORN) is a serious complication of craniofacial radiotherapy, the current management methods remain suboptimal. Teriparatide (TPTD), a recombinant human parathyroid hormone (1-34), has shown beneficial effects on osseous regeneration in medication-related osteonecrosis of the jaw or periodontitis. However, TPTD therapy in irradiated bones has not been indicated yet because of the theoretical risk of osteosarcoma seen in rat models. Hence, we first report here two patients with tongue cancer with late-emerging ORN who were successfully treated with TPTD for 4-6 months with serum calcium and vitamin D supplementation. In contrast to the usual progress of ORN, the bone defect regenerated well and bone turnover markers including serum C-terminal telopeptide of type 1 collagen and osteocalcin were restored with TPTD therapy. Our experience might suggest that TPTD therapy with careful monitoring can provide an effective treatment option for patients with ORN in select refractory cases, with the benefits outweighing the potential risks.

Clinical and laboratory features of patients with osteomalacia initially presenting with neurological manifestations.

Patients with osteomalacia often visit the neurology department with conditions mimicking other myopathies. We analyzed clinical features of osteomalacia patients who visited the neurology department. These patients frequently presented with hypocalcemia, hypovitaminosis D, and pain with less severe weakness. Osteomalacia should be considered when patients present with pain and weakness. INTRODUCTION: Osteomalacia is a disease of bone metabolism; however, some patients with osteomalacia initially visit the neurology department. As these patients often complain of weakness and gait disturbance, osteomalacia can be confused with other myopathies. We analyzed the clinical features of patients with osteomalacia who visited the neurology department. METHODS: We retrospectively reviewed the medical records. Osteomalacia was diagnosed based on symptoms, laboratory features, and imaging results. We compared the characteristics of patients with osteomalacia who visited the neurology department with (1) those who did not visit the neurology department and (2) patients with idiopathic inflammatory myopathy. RESULTS: Eighteen patients with osteomalacia visited the neurology department (NR group). The common etiologies in the NR group included tumors or antiepileptic medication, whereas antiviral medication was the most common in patients who did not visit the neurology department (non-NR group). The NR group showed lower serum calcium (p = 0.004) and 25-hydroxyvitamin D (p = 0.006) levels than the non-NR group. When compared with patients with inflammatory myopathy, both groups showed proximal dominant weakness. However, pain was more common in osteomalacia than in myopathy (p = 0.008), and patients with osteomalacia showed brisk deep tendon reflex more often (p = 0.017). Serum calcium (p = 0.003) and phosphate (p < 0.001) levels were lower in osteomalacia than in myopathy. CONCLUSIONS: It was not uncommon for patients with osteomalacia to visit the neurology department. The clinical presentation of these patients can be more complex owing the superimposed neurological disease and accompanying hypocalcemia. Osteomalacia should be considered when patients present with pain and weakness.

Characterization of Causal Agents of a Novel Disease Inducing Brown-Black Spots on Tender Tea Leaves in China.

A novel disease characterized by small brown-black spots (1 to 2 mm in diameter) on tender tea leaves (Camellia sinensis) has been observed in many regions of Hubei Province, China, which severely affects the yield and quality of tea. Tea leaf samples with typical symptoms were collected from three major tea-cultivation regions of Hubei, and were subjected to pathogen isolation for etiological analysis. As a result, 34 Pestalotiopsis isolates were obtained from 20 samples, and they were identified as Pestalotiopsis theae (14 isolates), P. camelliae (12), and P. clavispora (8), determined by morphologies and phylogenetic analysis based on internal transcribed spacer, and partial ß-tubulin and translation elongation factor 1-alpha genes. Pathogenicity tests on detached tea leaves showed that no matter what mycelial discs or conidium suspensions were used, inoculation of the Pestalotiopsis fungi could result in small brown-black spots (1 to 2 mm in diameter) on wounded leaves, similar to those observed in the field in the sizes and colors. It also revealed that only P. theae had pathogenicity on unwounded tea leaves, and P. theae and P. clavispora showed significantly higher virulence than P. camelliae. Inoculation test with conidium suspension on intact tea leaves in the field further confirmed that P. theae as the pathogen of brown-black spots. Reisolation of the pathogens from diseased leaves confirmed that the symptom was caused by the inoculation of Pestalotiopsis fungi. The P. theae isolates responsible for brown-black spots were also compared with those for tea gray blight disease in growth rate, pathogenicity, and molecular characteristics in parallel. To our knowledge, this is the first report that the Pestalotiopsis fungi cause brown-black spot disease on tender tea leaves. The results provide important implications for the prevention and management of this economically important disease.

Budget impact analysis of a breast rapid diagnostic unit.

BACKGROUND: The Odette Cancer Centre's recent implementation of a rapid diagnostic unit (rdu) for breast lesions has significantly decreased wait times to diagnosis. However, the economic impact of the unit remains unknown. This project defined the development and implementation costs and the operational costs of a breast rdu in a tertiary care facility. METHODS: From an institutional perspective, a budget impact analysis identified the direct costs associated with the breast rdu. A base-case model was also used to calculate the cost per patient to achieve a diagnosis. Sensitivity analyses computed costs based on variations in key components. Costs are adjusted to 2015 valuations using health care-specific consumer price indices and are reported in Canadian dollars. RESULTS: Initiation cost for the rdu was $366,243. The annual operational cost for support staff was $111,803. The average per-patient clinical cost for achieving a diagnosis was $770. Sensitivity analyses revealed that, if running at maximal institutional capacity, the total annual clinical cost for achieving a diagnosis could range between $136,080 and $702,675. CONCLUSIONS: Establishment and maintenance of a breast rdu requires significant investment to achieve reductions in time to diagnosis. Expenditures ought to be interpreted in the context of institutional patient volumes and trade-offs in patient-centred outcomes, including lessened patient anxiety and possibly shorter times to definitive treatment. Our study can be used as a resource-planning tool for future rdus in health care systems wishing to improve diagnostic efficiency.

Control of cell proliferation, endoreduplication, cell size, and cell death by the retinoblastoma-related pathway in maize endosperm.

The endosperm of cereal grains is one of the most valuable products of modern agriculture. Cereal endosperm development comprises different phases characterized by mitotic cell proliferation, endoreduplication, the accumulation of storage compounds, and programmed cell death. Although manipulation of these processes could maximize grain yield, how they are regulated and integrated is poorly understood. We show that the Retinoblastoma-related (RBR) pathway controls key aspects of endosperm development in maize. Down-regulation of RBR1 by RNAi resulted in up-regulation of RBR3-type genes, as well as the MINICHROMOSOME MAINTENANCE 2-7 gene family and PROLIFERATING CELL NUCLEAR ANTIGEN, which encode essential DNA replication factors. Both the mitotic and endoreduplication cell cycles were stimulated. Developing transgenic endosperm contained 42-58% more cells and ∼70% more DNA than wild type, whereas there was a reduction in cell and nuclear sizes. In addition, cell death was enhanced. The DNA content of mature endosperm increased 43% upon RBR1 down-regulation, whereas storage protein content and kernel weight were essentially not affected. Down-regulation of both RBR1 and CYCLIN DEPENDENT KINASE A (CDKA);1 indicated that CDKA;1 is epistatic to RBR1 and controls endoreduplication through an RBR1-dependent pathway. However, the repressive activity of RBR1 on downstream targets was independent from CDKA;1, suggesting diversification of RBR1 activities. Furthermore, RBR1 negatively regulated CDK activity, suggesting the presence of a feedback loop. These results indicate that the RBR1 pathway plays a major role in regulation of different processes during maize endosperm development and suggest the presence of tissue/organ-level regulation of endosperm/seed homeostasis.

Characterization of phenotype variations of luminescent and non-luminescent variants of Vibrio harveyi wild type and quorum sensing mutants.

Vibrio harveyi, a luminescent Gram-negative motile marine bacterium, is an important pathogen responsible for causing severe diseases in shrimp, finfish and molluscs leading to severe economic losses. Non-luminescent V. harveyi obtained by culturing luminescent strains under static and dark condition were reported to alter the levels of virulence factors and metalloprotease gene and luxR expression when compared to their luminescent variants. Presently, we conducted an in vitro study aiming at the characterization of virulence-related phenotypic traits of the wild-type V. harveyi BB120 strain and its isogenic quorum sensing mutants before and after switching to the non-luminescent status. We measured the production of caseinase, haemolysin and elastase and examined swimming motility and biofilm formation. Our results showed that switching from the bioluminescent to the non-luminescent state changed the phenotypic physiology or behaviour of V. harveyi resulting in alterations in caseinase and haemolytic activities, swimming motility and biofilm formation. The switching capacity was to a large extent independent from the quorum sensing status, in that quorum sensing mutants were equally capable of making the phenotypic switch.

[Stress distribution and deformation of uterosacral ligament and cardinal ligament under different working conditions simulated by the finite element model].

OBJECTIVE: To establish the finite element model of uterosacral ligament (USL) and cardinal ligament (CL) and analyze the stress distribution and deformation with USL and CL under different working conditions. METHODS: Patients with stage Ⅲ-Ⅳ pelvic organ prolapse (POP) and healthy female volunteers were selected for research subject, and divided into anterior uterus group and posterior uterus group. Two POP patients and two volunteers were selectd into the anterior uterus group and posterior uterine group respectively. Pelvic MRI scan was performed in two groups. Based on the original MRI data sets, the finite element model of USL and CL was constructed by using the software such as the Mimics, and the stress distribution and deformation of USL and CL were simulated. RESULTS: Under the premise of the elastic modulus fixed and three different working conditions such as 60 cmH2O, 99 cmH2O and 168 cmH2O (1 cmH2O=0.098 kPa) with abdominal pressure generated by maximum Valsalva maneuver, according to the present conditions and the simulation, the trend was analyzed: the stress and deformation of the uterus, anterior vaginal wall, USL and CL in two groups were mainly distributed in the middle and lower part of the anterior vaginal wall or the ligament and the cervix-vagina junction, the maximum stress and the maximum displacement were mainly concentrated in the lower region of the anterior vaginal wall. With increasing of abdominal pressure generated by the maximum Valsalva maneuver, the maximum stress values of the POP patient in anterior uterus group under three different working conditions were: 0.027 9, 0.046 0, 0.078 0 MPa, and the maximum displacement values were: 9.145 5, 15.090 0, 25.607 0 mm. The maximum stress values of the volunteer in anterior uterus group under three different working conditions were: 0.012 6, 0.020 8, 0.035 3 MPa, and the maximum displacement values were: 1.816 7, 2.997 5, 5.086 7 mm. The maximum stress values of the POP patient in posterior uterine group under three different conditions were: 0.069 4, 0.114 6, 0.194 5 MPa, and the maximum displacement values were: 11.658 0, 19.236 0, 32.643 0 mm. The maximum stress values of the volunteer in posterior uterus group under three different working conditions were: 0.009 1, 0.015 1, 0.025 6 MPa, and the maximum displacement values were: 2.581 6, 4.259 6, 7.228 4 mm. The maximum stress values and the maximum displacement values were all increased with increasing of abdominal pressure in the two groups. The maximum stress values and the maximum displacement values of the POP patients were greater than those of volunteers. Under different working conditions, the maximum stress values and maximum displacement values of the posterior uterus POP patient were all greater than those of the anterior uterus POP patient. CONCLUSIONS: The finite element model of USL and CL is completely based on the MRI technology and the model is real and reliable. The increase of abdominal pressure will produce a larger stress and deformation of USL and CL, which is one of the reasons causing the injury of the ligament.

Improving patient flow and timeliness in the diagnosis and management of breast abnormalities: the impact of a rapid diagnostic unit.

BACKGROUND: Efforts to streamline the diagnosis and treatment of breast abnormalities are necessary to limit patient anxiety and expedite care. In the present study, we examined the effect of a rapid diagnostic unit (rdu) on wait times to clinical investigations and definitive treatment. METHODS: A retrospective before-after series, each considering a 1-year period, examined consecutive patients with suspicious breast lesions before and after initiation of the rdu. Patient consultations, clinical investigations, and lesion characteristics were captured from time of patient referral to initiation of definitive treatment. Outcomes included time (days) to clinical investigations, to delivery of diagnosis, and to management. Groups were compared using the Fisher exact test or Student t-test. RESULTS: The non-rdu group included 287 patients with 164 invasive breast carcinomas. The rdu group included 260 patients with 154 invasive carcinomas. The rdu patients had more single visits for biopsy (92% rdu vs. 78% non-rdu, p < 0.0001). The rdu group also had a significantly shorter wait time from initial consultation to delivery of diagnosis (mean: 2.1 days vs. 16.7 days, p = 0.0001) and a greater chance of receiving neoadjuvant chemotherapy (37% vs. 24%, p = 0.0106). Overall time from referral to management remained statistically unchanged (mean: 53 days with the rdu vs. 50 days without the rdu, p = 0.3806). CONCLUSIONS: Introduction of a rdu appears to reduce wait times to definitive diagnosis, but not to treatment initiation, suggesting that obstacles to care delivery can occur at several points along the diagnostic trajectory. Multipronged efforts to reduce system-related delays to definitive treatment are needed.