C-Type LECTIN receptor-like kinase 1 and ACTIN DEPOLYMERIZING FACTOR 3 are key components of plasmodesmata callose modulation.

Plasmodesmata (PDs) are intercellular organelles carrying multiple membranous nanochannels that allow the trafficking of cellular signalling molecules. The channel regulation of PDs occurs dynamically and is required in various developmental and physiological processes. It is well known that callose is a critical component in regulating PD permeability or symplasmic connectivity, but the understanding of the signalling pathways and mechanisms of its regulation is limited. Here, we used the reverse genetic approach to investigate the role of C-type lectin receptor-like kinase 1 (CLRLK1) in the aspect of PD callose-modulated symplasmic continuity. Here, we found that loss-of-function mutations in CLRLK1 resulted in excessive PD callose deposits and reduced symplasmic continuity, resulting in an accelerated gravitropic response. The protein interactome study also found that CLRLK1 interacted with actin depolymerizing factor 3 (ADF3) in vitro and in plants. Moreover, mutations in ADF3 result in elevated PD callose deposits and faster gravitropic response. Our results indicate that CLRLK1 and ADF3 negatively regulate PD callose accumulation, contributing to fine-tuning symplasmic opening apertures. Overall, our studies identified two key components involved in the deposits of PD callose and provided new insights into how symplasmic connectivity is maintained by the control of PD callose homoeostasis.

Chrysosplenol-C Increases Contraction by Augmentation of Sarcoplasmic Reticulum Ca2+ Loading and Release via Protein Kinase C in Rat Ventricular Myocytes.

Naturally found chrysosplenol-C (4',5,6-trihydroxy-3,3',7-trimethoxyflavone) increases the contractility of cardiac myocytes independent of ß-adrenergic signaling. We investigated the cellular mechanism for chrysosplenol-C-induced positive inotropy. Global and local Ca2+ signals, L-type Ca2+ current (ICa), and contraction were measured from adult rat ventricular myocytes using two-dimensional confocal Ca2+ imaging, the whole-cell patch-clamp technique, and video-edge detection, respectively. Application of chrysosplenol-C reversibly increased Ca2+ transient magnitude with a maximal increase of ∼55% within 2- to 3-minute exposures (EC50 ≅ 21 µM). This chemical did not alter ICa and slightly increased diastolic Ca2+ level. The frequency and size of resting Ca2+ sparks were increased by chrysosplenol-C. Chrysosplenol-C significantly increased sarcoplasmic reticulum (SR) Ca2+ content but not fractional release. Pretreatment of protein kinase C (PKC) inhibitor but not Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor abolished the stimulatory effects of chrysosplenol-C on Ca2+ transients and Ca2+ sparks. Chrysosplenol-C-induced positive inotropy was removed by the inhibition of PKC but not CaMKII or phospholipase C. Western blotting assessment revealed that PKC-δ protein level in the membrane fractions significantly increase within 2 minutes after chrysosplenol-C exposure with a delayed (5-minute) increase in PKC-α levels in insoluble membrane. These results suggest that chrysosplenol-C enhances contractility via PKC (most likely PKC-δ)-dependent enhancement of SR Ca2+ releases in ventricular myocytes. SIGNIFICANCE STATEMENT: Study shows that chrysosplenol-C, a natural flavone showing a positive inotropic effect, increases SR Ca2+ releases on depolarizations and Ca2+ sparks with an increase of SR Ca2+ loading but not L-type Ca2+ current in ventricular myocytes. Chrysosplenol-C-induced enhancement in contraction is eliminated by PKC inhibition, and it is associated with redistributions of PKC to the membrane. These indicate that chrysosplenol-C enhances contraction via PKC-dependent augmentations of SR Ca2+ release and Ca2+ loading during action potentials.

Hong Kong Geriatrics Society and Hong Kong Urological Association consensus on personalised management of male lower urinary tract symptoms in the era of multiple co-morbidities and polypharmacy.

Lower urinary tract symptoms (LUTS) are common complaints of adult men. Benign prostatic hyperplasia (BPH) represents the most common underlying cause. As the incidence of BPH increases with age, and pharmacological treatment is a major part of the disease's management, the majority of patients with LUTS are managed by primary care practitioners. There are circumstances in which specialist care by urologists or geriatricians is required, such as failure of medical treatment, adverse effects from medical treatment, or complications from BPH. Referral choices can be confusing to patients and even practitioners in different specialties under such circumstances. There is currently no local consensus about the diagnosis, medical management, or referral mechanism of patients with BPH. A workgroup was formed by members of The Hong Kong Geriatrics Society (HKGS) and the Hong Kong Urological Association (HKUA) to review evidence for the diagnosis and medical treatment of LUTS. A consensus was reached by HKGS and HKUA on an algorithm for the flow of male LUTS care and the use of uroselective alpha blockers, antimuscarinics, beta-3 adrenoceptor agonists, and 5α-reductase inhibitors in the primary care setting. This consensus by HKGS and HKUA provides a new management paradigm of male LUTS.

Predictors of Bowel Resection During Nonelective Ladd Procedure for Pediatric Malrotation.

BACKGROUND: The objective of this study was to identify risk factors for bowel resection in a modern cohort of patients undergoing nonelective Ladd procedures. MATERIALS AND METHODS: Retrospective descriptive analysis of patients with Ladd procedure (CPT 44055) in the National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database (2012-2015). Exclusion criteria were elective case, duodenal atresia, or other known congenital anomaly (except cardiac, structural central nervous system, or airway anomaly) and open wounds from prior surgery or drains. Independent variables included all preoperative variables within NSQIP-P. The primary outcome variable was bowel resection as a concurrent procedure. Multivariate analysis was performed by incorporating all independent variables into a stepwise forward logistic regression model to identify independent risk factors for bowel resection. RESULTS: Of 267,289 patients in NSQIP-P, 1284 had a Ladd procedure. Of these, 292 were performed urgently or emergently in children with no known atresias, congenital anomalies, or open wounds. Twenty-nine (10%) had a bowel resection. On univariate analysis, bowel resection rates did not differ by age, weight, prematurity, ventilator dependence, asthma, chronic lung disease, tracheostomy, esophageal or gastrointestinal disease, hepatobiliary or pancreatic disease, cerebral palsy, central nervous system abnormality, neuromuscular disorder, intraventricular hemorrhage, steroid use, hematologic disorder, malignancy, sepsis, inotropic support, or CPR (P = nonsignificant). Higher rates of bowel resection were observed in patients with cardiac risk factors, white blood count (WBC) >15K, oxygen support, nutritional support, and developmental delay (P < 0.05). Only cardiac risk factors and WBC >15K were significant on multivariate analysis. CONCLUSIONS: Bowel resections (10% in this cohort of nonelective Ladd procedures) were independently associated with cardiac risk factors and WBC >15K. LEVEL OF EVIDENCE: III.

Nanoscale heat transport through the hetero-interface of SrRuO3 thin films.

A SrRuO3 thin film has been widely used as a metal electrode in electronic devices based on transition metal oxides, and hence it is important to understand its thermal transport properties to minimize a thermal degradation problem during the device operation. Using the time-domain thermoreflectance measurement technique, we investigate the cross-plane thermal conductivity of the SrRuO3 thin films with a thickness variation from 1 µm to 8 nm. We find that the thermal conductivity is reduced from about 6 W m-1 K-1 for the 1 µm thick film to about 1.2 W m-1 K-1 for the 8 nm thick film, and attribute this behavior to the boundary scattering of thermal carriers which originally have the mean free path of about 20 nm in a bulk state. Also, we observe a clear dip behavior of the thermal conductivity in the intermediate thickness around 30 nm which suggests an existence of a strong scattering source other than the film boundary. We explain this result by considering an additional interfacial scattering at the tetragonal-orthorhombic phase boundary which is formed during the strain relaxation with an increase of the film thickness.

Strategies in the transfer of varying grades of vitrified-warmed blastocysts in women aged over 35 years: A propensity-matched analysis.

AIM: For in vitro fertilization, the optimal number of blastocysts to transfer according to blastocyst grade has not been well established, especially with respect to vitrified-warmed blastocyst transfer (VBT) in women aged over 35 years. This study aimed to compare the pregnancy and neonatal outcomes for three different VBT methods with variable numbers and qualities of blastocysts in women aged over 35 years. METHODS: All VBT cycles were categorized into three groups according to blastocyst grade: GG (two good-quality blastocysts transferred), GP (one good-quality blastocyst transferred with one of poor quality) and GS (one good-quality blastocyst transferred). Blastocysts graded greater than or equal to 3BB were considered good quality. We conducted three 1:1 propensity score-matched analyses (GG vs GS, GP vs GS and GG vs GP) to compare the clinical pregnancy rate (CPR), live birth rate (LBR), multiple pregnancy rate (MPR), preterm birth rate and low birthweight rate. RESULTS: Compared to GS, GG had higher CPR and LBR; however, MPR was also higher with GG. There were no significant differences, except implantation rate and MPR between GP and GS. Although implantation rate and CPR with GG were higher than those with GP, there were no significant differences in LBR and MPR. CONCLUSION: To reduce high MPR after double blastocyst transfer methods, single good-quality blastocyst transfers are recommended in the VBT of women aged over 35 years. Transferring a good blastocyst with a poor one should be avoided because it confers no advantage.

Factors associated with HIV/AIDS-related stigma and discrimination by medical professionals in Korea: A survey of infectious disease specialists in Korea.

OBJECTIVES: This study sought to identify factors associated with this discrimination by medical professionals in Korea. SUBJECTS AND METHODS: This study was a cross-sectional survey. We conducted web-based surveys against infectious disease specialists and infectious disease nurse. We evaluated the frequency of human immunodeficiency virus (HIV)/AIDS-related discrimination by medical professionals by health service type on the 5-point scale. We identified the association between several factors and HIV/AIDS-related stigma and discrimination by medical professionals on the 5-point scale. RESULTS: A total of 81 experts, 57 infectious disease specialists (approximately 27% of all infectious disease specialists in Korea) and 24 infectious disease nurse practitioners, participated in this study. The frequency of stigma and discrimination increased significantly when invasive treatment included both outpatient and inpatient services (both P < 0.05). Medical professional's preconceptions, fear of infection, and lack of knowledge have an association with HIV/AIDS-related stigma and discrimination by medical professionals. CONCLUSION: HIV/AIDS-related stigma and discrimination by medical professionals in Korea might be associated with factors related to the fear of medical professionals.

Proliferative leukoplakia: Proposed new clinical diagnostic criteria.

OBJECTIVE: We aimed to characterize proliferative verrucous leukoplakia (PVL) from a clinical and histopathological standpoint and suggest an updated classification. SUBJECTS AND METHODS: Records of patients seen at three oral medicine centers with a clinical diagnosis of PVL were reviewed for clinical and histopathological features and malignant transformation (MT). RESULTS: There were 42 patients (median age: 69 years [range: 36-88]; 35 females). 12.2% were current smokers. Family history of cancer was present in 43.7% of patients. Partial demarcation of lesion margins was present in 31.3% of lesions, followed by verrucous (27.5%), smooth (22.7%) erythematous (22.3%), and fissured (18.3%) appearance. Large and contiguous and multisite and non-contiguous lesions comprised 57.1% (24/42) and 35.7% (15/42) of PVL cases, respectively. 19.1% had prominent erythema (erythroleukoplakia). The most common histopathological diagnosis at first visit was hyperkeratosis without dysplasia (22/42; 56.4%). MT occurred in 71.4% patients after a median of 37 months [range: 1-210] from initial visit; erythroleukoplakia exhibited MT in 100% of cases. CONCLUSION: The generic term "proliferative leukoplakia (PL)" may be more appropriate than PVL because 18.3% were fissured and 22.7% erythematous. We also propose the term proliferative erythroleukoplakia to more accurately describe the subset of PL with prominent erythema, which had the highest MT rate.

Immunohistopathological characterization and the impact of topical immunomodulatory therapy in oral chronic graft-versus-host disease: A pilot study.

OBJECTIVE: To characterize the immunohistopathological features of oral chronic graft-versus-host disease (cGVHD), and the impact of topical immunomodulatory therapy on the infiltrating cells. MATERIAL AND METHODS: Paired oral cGVHD biopsies obtained before (n = 12) and 1 month after treatment (n = 12) with topical dexamethasone (n = 8) or tacrolimus (n = 4) were characterized by immunohistochemistry using a panel of CD1a, CD3, CD4, CD8, CD20, CD31, CD62E, CD103, CD163, c-kit, and FoxP3. Controls included acute GVHD (aGVHD; n = 3), oral lichen planus (OLP; n = 5), and normal tissues (n = 5). RESULTS: Oral cGVHD specimens prior to treatment were mainly characterized by basal cell squamatization, lichenoid inflammation, sclerosis, apoptosis, and lymphocytic exocytosis. The infiltrating cells in oral cGVHD primarily consisted of CD3+ , CD4+ , CD8+ , CD103+ , CD163+ , and FoxP3+ cells, which were higher than in normal tissues. Topical dexamethasone or tacrolimus reduced neutrophilic exocytosis, basal cell squamatization, and lichenoid inflammation in oral cGVHD, and dexamethasone reduced the number of CD4+ and CD103+ cells. CONCLUSION: The high expression of CD3, CD4, CD8, CD103, CD163, and FoxP3 confirms that oral cGVHD is largely T-cell-driven with macrophage participation. The impact of topical immunomodulatory therapy was variable, reducing histological inflammatory features, but with a weak clinicopathological correlation. Topical dexamethasone reduced the expression of CD4 and CD103, which may offer novel therapeutic targets.

The accuracies of abdominal computed tomography and the neutrophil-to-lymphocyte ratio used to predict the development of clinically severe acute cholecystitis in elderly patients visiting an emergency department.

BACKGROUND: Mortality in patients with severe acute cholecystitis (AC) remains high, and the prognosis for elderly patients tends to be poor. A comparative analysis of clinical, laboratory, and abdominal computed tomography (CT) parameters was conducted in this study to investigate the effectiveness of each index for predicting clinically severe AC in elderly patients in the emergency department (ED). METHODS: This was a single-center, retrospective study that included 156 patients (≥65 years of age) with AC who were admitted in the ED between January 2012 and December 2014. Parameters including age, gender, initial clinical findings, laboratory findings, and CT findings in the ED were examined for their ability to predict severity. RESULTS: Forty-five patients were diagnosed with clinically severe AC. The white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, erythrocyte sedimentation rate, protein, albumin, and prothrombin time/International Normalized Ratio values were significantly higher in the severe group than in the nonsevere group (P < 0.05). In addition, the CT parameters of increased pericholecystic fat stranding and pericholecystic fluid collection were significantly higher in the severe group than in the nonsevere group (P < 0.001, P < 0.001). Increased pericholecystic fat stranding (odds ratio [OR], 8.17; 95% confidence interval [CI], 2.29-29.22; P = 0.001), pericholecystic fluid collection (OR, 6.55; 95% CI, 1.39-30.92; P = 0.018), and an NLR cutoff value of 9.9 (OR, 4.20; 95% CI, 1.01-17.53; P = 0.049) were independent predictors of severe AC in elderly patients. CONCLUSIONS: The CT parameters of increased pericholecystic fat stranding and pericholecystic fluid collection with an NLR cutoff of 9.9 were useful for predicting the severity of AC in elderly patients in the ED.

Recent Results of In Situ Abdominal Aortic Reconstruction with Cryopreserved Arterial Allograft.

OBJECTIVE: To evaluate treatment outcomes of in situ abdominal aortic reconstruction with cryopreserved arterial allograft (CAA) for patients with abdominal aortic infection. MATERIALS AND METHODS: A retrospective review of prospectively collected data was conducted of patients who underwent in situ aortic reconstruction using CAA for primary, secondary, or prosthetic infection of the abdominal aorta between May 2006 and July 2015, at a single institution. Clinical presentation, indications for treatment, procedural details, early post-operative mortality and morbidity, late death, and graft related complications during the follow up period were investigated. Patient survival and event free survival (any death or re-operation) were calculated using the Kaplan-Meier method. RESULTS: Twenty-five patients (male, n = 20, 80%; mean age, 70.2 ± 8.7 years) underwent in situ abdominal aortic reconstruction (48% aortic, 52% aorto-bi-iliac) with vessel size and ABO matched CAA for treatment of abdominal aortic infection caused by infected abdominal aortic aneurysm (n = 15), aortic prosthesis infection (n = 7), aortic reconstruction with concomitant colon resection (n = 2), and primary suppurative aortitis (n = 1). The median follow up was 19.1 months (range 1-73 months). There were seven post-operative deaths including two (8%) early (<30 days) and five (20%) late deaths There were three (12%) graft related complications including thrombotic occlusion of the CAA, aneurysmal dilatation, and aorto-enteric fistula. Three years after CAA implantation, patient survival was 74% and the event free survival was 58%. CONCLUSIONS: It is believed that in situ abdominal aortic reconstruction with CAA is a useful option for treating primary, secondary, or prosthetic infection of the abdominal aorta.

Metastatic Patterns of Solitary Fibrous Tumors: A Single-Institution Experience.

OBJECTIVE: The objective of our study was to evaluate the metastatic patterns and imaging features of solitary fibrous tumors (SFTs). MATERIALS AND METHODS: This retrospective study included 139 patients with pathologically proven SFT, 49 of whom developed metastases. Electronic medical records and all available images were reviewed to record the pattern and imaging appearances of metastatic disease, and comparisons of thoracic SFTs and extrathoracic SFTs were also performed. Associations of metastatic spread were studied using univariate and multivariate Cox regression analyses. RESULTS: A total of 49 (35%) patients developed metastases at a median of 124 months (interquartile range [IQR], 66-195 months) after SFT diagnosis; 11 patients (8%) had metastases at presentation. Of these 49 patients, 40 patients died at a mean of 183 months after diagnosis. The associations with metastatic disease on univariate analysis were tumor size ≥ 10 cm (p = 0.01) and malignant pathology or mitotic count ≥ 4 per 10 high-power fields (HPF) (p < 0.001). Malignant pathology and a mitotic count of ≥ 4 per 10 HPF were also associated with metastatic disease on multivariate analysis (p = 0.01; hazard ratio, 0.22; 95% CI, 0.05-0.73). The most common sites of metastasis were the lungs (30/49, 61%) followed by the pleura (24/49, 49%) and then the liver (20/49, 41%), bones (20/49, 41%), and peritoneum (20/49, 41%). A significantly higher proportion of patients with extrathoracic SFT had metastatic disease (37/139, 27%) compared with those with thoracic SFT (12/139, 9%) (p = 0.003). The overall metastasis-free survival was a median of 117 months (IQR, 33-169 months) in patients with extrathoracic SFT and a median of 120 months (IQR, 82-169 months) in patients with thoracic SFT (p = 0.01). CONCLUSION: A mitotic count of ≥ 4 per 10 HPF or malignant pathology was significantly associated with metastatic disease on both univariate and multivariate analyses. The sites of metastatic disease differed depending on the site of the primary SFT but were most commonly the lung and pleura. Patients with extrathoracic SFT were statistically more likely to develop metastatic disease than those with thoracic SFT.

Oral mucous membrane pemphigoid and pemphigus vulgaris-a retrospective two-center cohort study.

OBJECTIVES: Few studies have compared oral mucous membrane pemphigoid (MMP) and pemphigus vulgaris (PV). Descriptive analysis of oral features, extent of extra-oral involvement, and management outcomes were performed. SUBJECTS AND METHODS: Patients with PV and MMP, the latter with exclusive oral involvement at first presentation, were included. RESULTS: There were 26 MMP (46%) and 31 PV (54%) patients. Desquamative gingivitis was evident in 84% of MMP cases compared to 28% of PV cases (P < 0.05). Non-gingival lesions were noted in 6% of MMP cases compared to 55% of PV cases (P < 0.01). Management of MMP consisted of only topical corticosteroids in 88% of cases while 12% of cases required concomitant systemic therapy. All PV cases (100%) required systemic therapy. No patients with MMP developed scarring or ocular lesions, and one patient (4%) developed cutaneous lesions. Five PV cases (16%) had oral cavity involvement only with three (60%) developing pharyngeal involvement and two (40%) developing cutaneous lesions on follow-up. CONCLUSION: Oral MMP presents primarily as desquamative gingivitis, infrequently involving extragingival sites, and is highly amenable to topical therapy, while PV is a systemic mucocutaneous disease with extensive non-gingival oral lesions that almost always requires systemic therapy.

Simvastatin inhibits the expression of inflammatory cytokines and cell adhesion molecules induced by LPS in human dental pulp cells.

AIM: To investigate the effect of simvastatin on lipopolysaccharide (LPS)-stimulated inflammatory cytokines, cell adhesion molecules and nuclear factor-κB (NF-κB) transcription factors in human dental pulp cells (HDPCs). METHODOLOGY: The effect of LPS and simvastatin on human dental pulp cell (HDPCs) viability was measured using a 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide (MTT) assay. The expression of inflammatory cytokines and cell adhesion molecules was evaluated by reverse-transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. NF-κB transcription factors were evaluated by Western blot analysis. Statistical analysis was performed with analysis of variance (anova). RESULTS: The viability of cells exposed to different concentrations of E. coli LPS, P. gingivalis LPS and simvastatin was not significantly different compared with that of control cells (P > 0.05). LPS significantly increased interleukin (IL)-1ß (P < 0.05) and IL-6 mRNA expression (P < 0.05) and vascular cell adhesion molecule-1 (VCAM-1) (P < 0.05) and intercellular adhesion molecule-1 (ICAM-1) protein expression (P < 0.05) in HDPCs. Treatment with simvastatin significantly attenuated LPS-stimulated production of IL-1ß, IL-6, VCAM-1 and ICAM-1 (P < 0.05). Treatment with simvastatin decreased LPS-induced expression of p65 and phosphorylation of IκB and also significantly decreased the phosphorylation of p65 and IκB in the cytoplasm and the level of p65 in the nucleus (P < 0.05). CONCLUSIONS: Simvastatin has a suppressing effect on LPS-induced inflammatory cytokine, cell adhesion molecules and NF-κB transcription factors in HDPCs. Therefore, simvastatin might be a useful candidate as a pulp-capping agent in vital pulp therapy.

Scoring systems for Oral Lichen Planus used by differently experienced raters.

BACKGROUND: Scoring systems have been widely used to evaluate the severity and activity of oral lichen planus (OLP). The aim of the present study was to compare two existing (one modified) scoring systems in the evaluation of OLP severity and correlation with pain. Three differently experienced raters were involved. MATERIALS AND METHODS: Consecutive patients with OLP were assessed for pain using the Visual Analogue Scale and examined at 10 intraoral sites before starting (T0) and three weeks after (T1) steroid therapy (Clobetasol). Three differently experienced raters evaluated photographs using two scoring systems designated White-Erosive-Atrophic (WEA) modified from an older WEA system (WEA-MOD) and Reticular-erythematous-Ulcerative (REU) systems. WEA-MOD Kendall's W and interclass correlation coefficient were calculated and correlation between REU/WEA-MOD and pain was calculated using Spearman coefficient. RESULTS: Most patients showed lesions on buccal mucosa (85-93,5%) and maxillary/mandibular gingivae (31,8-31,2%), predominantly reticular. At T0, Kendall-W coefficients of 0.89 and 0.74 were obtained for the REU and WEA respectively. At T1, Kendall-W coefficients of 0.83 and 0.58 were obtained for the REU and WEA respectively. Interclass correlation coefficient ranged from 0.87 to 0.90 for REU and from 0.58 to 0.87 for WEA. REU and WEA scores significantly decreased after therapy (p<0.000) as well as VAS (p<0.05). REU score showed correlation with VAS. CONCLUSION: All the raters achieved comparable measures using REU whereas WEA and WEA-MOD seem less reproducible. REU seems to correlate to disease activity and pain.

Iliacus abscess with radiculopathy mimicking herniated nucleus pulposus: Additional diagnostic value of magnetic resonance imaging.

An iliacus abscess is an extremely rare cause of low back pain. With an iliacus abscess, the classical signs seen with a psoas abscess are frequently absent. Therefore, a timely diagnosis at the initial visit is difficult and inadequate treatment usually results in high mortality. Here, we report the case of 19-year-old man who presented with acute low back pain with radiculopathy and was ultimately diagnosed with an iliacus muscle abscess.

Updated prostate imaging reporting and data system (PIRADS v2) recommendations for the detection of clinically significant prostate cancer using multiparametric MRI: critical evaluation using whole-mount pathology as standard of reference.

OBJECTIVES: To evaluate the recommendations for multiparametric prostate MRI (mp-MRI) interpretation introduced in the recently updated Prostate Imaging Reporting and Data System version 2 (PI-RADSv2), and investigate the impact of pathologic tumour volume on prostate cancer (PCa) detectability on mpMRI. METHODS: This was an institutional review board (IRB)-approved, retrospective study of 150 PCa patients who underwent mp-MRI before prostatectomy; 169 tumours ≥0.5-mL (any Gleason Score [GS]) and 37 tumours <0.5-mL (GS ≥4+3) identified on whole-mount pathology maps were located on mp-MRI consisting of T2-weighted imaging (T2WI), diffusion-weighted (DW)-MRI, and dynamic contrast-enhanced (DCE)-MRI. Corresponding PI-RADSv2 scores were assigned on each sequence and combined as recommended by PI-RADSv2. We calculated the proportion of PCa foci on whole-mount pathology correctly identified with PI-RADSv2 (dichotomized scores 1-3 vs. 4-5), stratified by pathologic tumour volume. RESULTS: PI-RADSv2 allowed correct identification of 118/125 (94 %; 95 %CI: 90-99 %) peripheral zone (PZ) and 42/44 (95 %; 95 %CI: 89-100 %) transition zone (TZ) tumours ≥0.5 mL, but only 7/27 (26 %; 95 %CI: 10-42 %) PZ and 2/10 (20 %; 95 %CI: 0-52 %) TZ tumours with a GS ≥4+3, but <0.5 mL. DCE-MRI aided detection of 4/125 PZ tumours ≥0.5 mL and 0/27 PZ tumours <0.5 mL. CONCLUSIONS: PI-RADSv2 correctly identified 94-95 % of PCa foci ≥0.5 mL, but was limited for the assessment of GS ≥4+3 tumours ≤0.5 mL. DCE-MRI offered limited added value to T2WI+DW-MRI. KEY POINTS: • PI-RADSv2 correctly identified 95 % of PCa foci ≥0.5 mL • PI-RADSv2 was limited for the assessment of GS ≥4+3 tumours ≤0.5 mL • DCE-MRI offered limited added value to T2WI+DW-MRI.

The Kaiser Permanente Northern California research program on genes, environment, and health (RPGEH) pregnancy cohort: study design, methodology and baseline characteristics.

BACKGROUND: Exposures during the prenatal period may have lasting effects on maternal and child health outcomes. To better understand the effects of the in utero environment on children's short- and long-term health, large representative pregnancy cohorts with comprehensive information on a broad range of environmental influences (including biological and behavioral) and the ability to link to prenatal, child and maternal health outcomes are needed. The Research Program on Genes, Environment and Health (RPGEH) pregnancy cohort at Kaiser Permanente Northern California (KPNC) was established to create a resource for conducting research to better understand factors influencing women's and children's health. Recruitment is integrated into routine clinical prenatal care at KPNC, an integrated health care delivery system. We detail the study design, data collection, and methodologies for establishing this cohort. We also describe the baseline characteristics and the cohort's representativeness of the underlying pregnant population in KPNC. METHODS: While recruitment is ongoing, as of October 2014, the RPGEH pregnancy cohort included 16,977 pregnancies (53 % from racial and ethnic minorities). RPGEH pregnancy cohort participants consented to have blood samples obtained in the first trimester (mean gestational age 9.1 weeks ± 4.2 SD) and second trimester (mean gestational age 18.1 weeks ± 5.5 SD) to be stored for future use. Women were invited to complete a questionnaire on health history and lifestyle. Information on women's clinical and health assessments before, during and after pregnancy and women and children's health outcomes are available in the health system's electronic health records, which also allows long-term follow-up. DISCUSSION: This large, racially- and ethnically-diverse cohort of pregnancies with prenatal biospecimens and clinical data is a valuable resource for future studies on in utero environmental exposures and maternal and child perinatal and long term health outcomes. The baseline characteristics of RPGEH Pregnancy Cohort demonstrate that it is highly representative of the underlying population living in the broader community in Northern California.

Three-Dimensional Quantum Confinement of Charge Carriers in Self-Organized AlGaN Nanowires: A Viable Route to Electrically Injected Deep Ultraviolet Lasers.

We report on the molecular beam epitaxial growth and structural characterization of self-organized AlGaN nanowire arrays on Si substrate with high luminescence efficiency emission in the deep ultraviolet (UV) wavelength range. It is found that, with increasing Al concentration, atomic-scale compositional modulations can be realized, leading to three-dimensional quantum confinement of charge carriers. By further exploiting the Anderson localization of light, we have demonstrated, for the first time, electrically injected AlGaN lasers in the deep UV band operating at room temperature. The laser operates at ∼289 nm and exhibits a threshold of 300 A/cm(2), which is significantly smaller compared to the previously reported electrically injected AlGaN multiple quantum well lasers.