Search

Objectives: To assess the safety, tolerability, and key pharmacodynamic effects of subcutaneous batoclimab, a fully human anti‐neonatal Fc receptor monoclonal antibody, in patients with generalized myasthenia gravis and anti‐acetylcholine receptor antibodies. Methods: A Phase 2a, proof‐of‐concept, randomized, double‐blind, placebo‐controlled trial is described. Eligible patients were randomized (1:1:1) to receive once‐weekly subcutaneous injections of batoclimab 340 mg, batoclimab 680 mg, or matching placebo for 6 weeks. Subsequently, all patients could enter an open‐label extension study where they received batoclimab 340 mg once every 2 weeks for 6 weeks. Primary endpoints were safety, tolerability, and change from baseline in total immunoglobulin G, immunoglobulin G subclasses, and anti‐acetylcholine receptor antibodies at 6 weeks post‐baseline. Secondary endpoints included changes from baseline to 6 weeks post‐baseline for Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, Myasthenia Gravis Composite, and revised 15‐item Myasthenia Gravis Quality of Life scores. Results: Seventeen patients were randomized to batoclimab 680 mg (n = 6), batoclimab 340 mg (n = 5), or placebo (n = 6). Batoclimab was associated with significantly greater reductions in total immunoglobulin G and anti‐acetylcholine receptor antibodies from baseline to 6 weeks post‐baseline than placebo. Reductions in immunoglobulin G subclasses were generally consistent with total immunoglobulin G. While clinical measures showed directionally favorable improvements over time, the study was not powered to draw conclusions about therapeutic efficacy. No safety issues were identified. Interpretation: The safety profile, pharmacodynamics, and preliminary clinical benefits observed in this study support further investigation of subcutaneous batoclimab injections as a potential patient‐administered therapy for seropositive generalized myasthenia gravis. [ABSTRACT FROM AUTHOR]

As one of the major abiotic stresses restricting the development of global agriculture, saline–alkali stress causes osmotic stress, ion poisoning, ROS damage and high pH damage, which seriously restrict sustainable development of fruit industry. Therefore, it is essential to develop and cultivate saline–alkali‐resistant apple rootstocks to improve the yield and quality of apples in China.Based on transcriptome data, MhANR (LOC114827797), which is significantly induced by saline–alkali stress, was cloned from Malus halliana. The physicochemical properties, evolutionary relationships and cis‐acting elements were analysed. Subsequently, the tolerance of MhANR overexpression in Arabidopsis thaliana, tobacco, and apple calli to saline–alkali stress was verified through genetic transformation.Transgenic plants contained less Chl a, Chl b and proline, SOD, POD and CAT activity, and higher relative electrical conductivity (REC) compared to WT plants under saline–alkali stress. In addition, expression of saline–alkali stress‐related genes in overexpressed apple calli were also lower than in WT calli, including the antioxidant genes (MhSOD and MhCAT^), the Na+ transporter genes (MhCAX5, MhCAX5, MhSOS1, MhALT1), and the H+‐ATPase genes (MhAHA2 and MhAHA8), while expression of the K+ transporter genes (MhSKOR and MhNHX4) were higher.Expression of MhANR reduced tolerance of A. thaliana, tobacco, and apple calli to saline–alkali stress by regulating osmoregulatory substances, chlorophyll content, antioxidant enzyme activity, and expression of saline–alkali stress‐related genes. This research provides a theoretical basis for cultivating apple rootstocks with effective saline–alkali stress tolerance. [ABSTRACT FROM AUTHOR]

The Chinese Meteorology Administration chemistry model Chinese Unified Atmospheric Chemistry Environment (CUACE) is online integrated into the mesoscale operational numerical weather prediction (NWP) model (GRAPES_Meso5.1) and aerosol‐cloud‐radiation interaction is achieved to establish the first version (V1) of chemistry‐weather (CW) interacted model GRAPES‐Meso5.1/CUACE CW V1. The most polluted winter 2016–2017 is selected to study the meteorology impacts on haze/fog prediction, the impact of aerosol‐radiation, aerosol‐cloud and CW interaction (ARI, ACI, CWI) on haze/fog prediction and NWP. Single way model without CWI displays reasonable PM2.5 and visibility prediction in general. However, modeled PM2.5 peaks are underestimated and visibility valleys are overestimated during haze/fog pollution, the underestimation of relative humidity (RH) contributes major to this misestimation; CWI model cut the negative bias of PM2.5 peaks and the positive bias of visibility valleys. The improvement of 5 and 3 km low visibility by CWI during severe haze/fog period is more obvious than that of 10 km, which just compensates for the largest deficiency in low visibility prediction related with severe haze/fog by single way model; The NWP including sea level pressures, RH, temperature, wind speed are also improved by CWI from surface to upper troposphere; ARI contributes larger to the predicted PM2.5,visibility and NWP improvement than that of ACI, their relative contributions varies with model vertical height and the overlapping condition of cloud and aerosols. Due to the joint contribution of RH and PM2.5, CWI's improving on visibility is larger than PM2.5. This study illustrates the importance of including CWI in air quality prediction model. Plain Language Summary: Double way atmospheric chemistry model considering complete aerosol‐radiation‐cloud interaction is the hot and difficult issue in climate, weather and air quality (AQ) modeling. Focusing on better prediction of haze/fog pollution in China, the first version (V1) of chemistry‐weather (CW) interacted model GRAPES‐Meso5.1/CUACE CW V1 is established by online coupling the Chinese Meteorology Administration CUACE chemistry model with the updated operational mesoscale weather model GRAPES_Meso5.1 and the further completion of aerosol‐cloud‐radiation interaction in it. The meteorology impacts on haze/fog prediction including PM2.5 and visibility is discussed. The impacts of aerosol‐cloud interaction (ACI), aerosol radiation interaction (ARI) and the both (CWI) on haze/fog prediction and mesoscale NWP is further studied. The study results shows that the important impacts of relative humidity on high PM2.5 and low visibility and the improving of PM2.5, low visibility prediction and NWP by ARI, ACI and CWI during haze/fog episode, indicating the importance of CW model in better AQ prediction and NWP in polluted region. Key Points: An online chemistry‐weather (CW) interacted GRAPES_Meso5.1/Chinese Unified Atmospheric Chemistry Environment CW V1.0 model with aerosol‐radiation‐cloud interaction is establishedSingle way model shows basic reasonable haze/fog prediction including visibility and PM2.5 in most polluted subregions in ChinaCW Interaction improves PM2.5, visibility and numerical weather prediction from surface to upper troposphere to varying degree [ABSTRACT FROM AUTHOR]

The lentivirus containing dox-induced ITK targeting shRNA or ITK overexpression plasmid were used to mediate conditional ITK knockdown or stable overexpression of ITK. To further validate this therapeutic effect, NKTCL cells were treated with ITK inhibitors for 24h, 48h and 72h in vitro, The ITK inhibitors repressed the viability of these NKTCL cells in a concentration and time-dependent manner. Furthermore, ITK inhibitors treatment abolished the colony formation of NKTCL cells, which indicated the ITK might represent the potential therapeutic target for NKT cell lymphoma. [Extracted from the article]

Objective: The US risdiplam expanded access program (EAP; NCT04256265) was opened to provide individuals with Type 1 or 2 spinal muscular atrophy (SMA) who had no satisfactory treatment options access to risdiplam prior to commercial availability. The program was designed to collect safety data during risdiplam treatment. Methods: Patients were enrolled from 23 non‐preselected sites across 17 states and treated with risdiplam orally once daily. Eligible patients had a 5q autosomal recessive Type 1 or 2 SMA diagnosis, were aged ≥2 months at enrollment, and were ineligible for available and approved SMA treatments or could not continue treatment due to a medical condition, lack/loss of efficacy, or the COVID‐19 pandemic. Results: Overall, 155 patients with Type 1 (n = 73; 47.1%) or 2 SMA (n = 82; 52.9%) were enrolled and 149 patients (96.1%) completed the EAP (defined as obtaining access to commercial risdiplam, if desired). The median treatment duration was 4.8 months (range, 0.3–9.2 months). The median patient age was 11 years (range, 0–50 years), and most patients (n = 121; 78%) were previously treated with a disease‐modifying therapy. The most frequently reported adverse events were diarrhea (n = 10; 6.5%), pyrexia (n = 7; 4.5%), and upper respiratory tract infection (n = 5; 3.2%). The most frequently reported serious adverse event was pneumonia (n = 3; 1.9%). No deaths were reported. Interpretation: In the EAP, the safety profile of risdiplam was similar to what was reported in pivotal risdiplam clinical trials. These safety data provide further support for the use of risdiplam in the treatment of adult and pediatric patients with SMA. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the accuracy of an automated three-dimensional (3D) ultrasound technique for fetal intracranial measurements compared with manual acquisition.Methods: This was a prospective observational study of patients presenting for routine anatomical survey between 18 + 0 and 22 + 6 weeks' gestation. After providing informed consent, each patient underwent two consecutive ultrasound examinations of the fetal head, one by a sonographer and one by a physician. Each operator obtained manual measurements of the biparietal diameter (BPD), head circumference (HC), transcerebellar diameter (TCD), cisterna magna (CM) and posterior horn of the lateral ventricle (Vp), followed by automated measurements of these structures using an artificial intelligence-based tool, SonoCNS® Fetal Brain. Both operators repeated the automated approach until all five measurements were obtained in a single sweep, up to a maximum of three attempts. The accuracy of automated measurements was compared with that of manual measurements using intraclass correlation coefficients (ICC) by operator type, accounting for patient and ultrasound characteristics.Results: One hundred and forty-three women were enrolled in the study. Median body mass index was 24.0 kg/m2 (interquartile range (IQR), 22.5-26.8 kg/m2 ) and median subcutaneous thickness was 1.6 cm (IQR, 1.3-2.0 cm). Fifteen (10%) patients had at least one prior Cesarean delivery, 17 (12%) had other abdominal surgery and 78 (55%) had an anterior placenta. Successful acquisition of the automated measurements was achieved on the first, second and third attempts in 70%, 22% and 3% of patients, respectively, by sonographers and in 76%, 16% and 3% of cases, respectively, by physicians. The automated algorithm was not able to identify and measure all five structures correctly in six (4%) and seven (5%) patients scanned by the sonographers and physicians, respectively. The ICCs reflected good reliability (0.80-0.88) of the automated compared with the manual approach for BPD and HC and poor to moderate reliability (0.23-0.50) for TCD, CM and Vp. Fetal lie, head position, placental location, maternal subcutaneous thickness and prior Cesarean section were not associated with the success or accuracy of the automated technique.Conclusions: Automated 3D ultrasound imaging of the fetal head using SonoCNS reliably identified and measured BPD and HC but was less consistent in accurately identifying and measuring TCD, CM and Vp. While these results are encouraging, further optimization of the automated technology is necessary prior to incorporation of the technique into routine sonographic protocols. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Pre‐eclampsia (PE) is a pregnancy‐associated condition initiated by placental factors. We have demonstrated that placental extracellular vesicles (pcEVs) cause hypertension and proteinuria in pregnant and non‐pregnant mice. Study design: An observational study with both case‐control and longitudinal designs. Setting: A single centre at the Department of Obstetrics and Gynaecology, Tianjin Medical University. Population: We collected blood samples and clinical information from 54 PE patients, 33 normally pregnant women at 30–36 gestational weeks and on postpartum days 1 and 4 for the cross‐sectional study, and at 22–31, 32–35 and 36–40 weeks for the longitudinal study. Non‐pregnant women were also recruited. Methods: Blood samples were analysed using flow cytometry, coagulation tests and ELISA. Main outcome measures: The primary outcome was plasma pcEV and other extracellular vesicles (EVs), and their expressions of anionic phospholipids and von Willebrand factor (VWF). Secondary variables included coagulation, ADAMTS‐13 and the anionic phospholipid‐binding proteins. Results: Plasma pcEVs progressively increased from pregnant women during non‐menstrual period (NW) to PE patients (interquartile range [IQR] for NW: 206/microlitre [116–255], normal pregnancy [NP]: 1108/microlitre [789–1969] and PE: 8487/microlitre [4991–16 752]) and predicted PE. EVs from endothelial cells, platelets and erythrocytes accounted for <10% of pcEVs. VWF became hyper‐adhesive in PE patients and contributed to the pregnancy‐associated hypercoagulability. Conclusion: Placental, platelet‐ and endothelial cell‐derived EVs were significantly elevated in PE patients, but only pcEVs predicted PE. These EVs played a causal role in the pregnancy‐induced hypercoagulability. Placenta‐derived extracellular vesicles predict pre‐eclampsia and the associated hypercoagulability. Placenta‐derived extracellular vesicles predict pre‐eclampsia and the associated hypercoagulability. [ABSTRACT FROM AUTHOR]

Background: Quantifying associations between genetic mutations and loss of ambulation (LoA) among males diagnosed with childhood‐onset dystrophinopathy is important for understanding variation in disease progression and may be useful in clinical trial design. Methods: Genetic and clinical data from the Muscular Dystrophy Surveillance, Tracking, and Research Network for 358 males born and diagnosed from 1982 to 2011 were analyzed. LoA was defined as the age at which independent ambulation ceased. Genetic mutations were defined by overall type (deletion/duplication/point mutation) and among deletions, those amenable to exon‐skipping therapy (exons 8, 20, 44–46, 51–53) and another group. Cox proportional hazards regression modeling was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Mutation type did not predict time to LoA. Controlling for corticosteroids, Exons 8 (HR = 0.22; 95% CI = 0.08, 0.63) and 44 (HR = 0.30; 95% CI = 0.12, 0.78) were associated with delayed LoA compared to other exon deletions. Conclusions: Delayed LoA in males with mutations amenable to exon‐skipping therapy is consistent with previous studies. These findings suggest that clinical trials including exon 8 and 44 skippable males should consider mutation information prior to randomization. [ABSTRACT FROM AUTHOR]

Consumers in emerging markets are known to have strong preferences for well‐known foreign brands. Drawing on schema and categorization theories, this study empirically investigates how accessible two components of brand foreignness – globalness and country of brand origin – are in consumer perceptions of brand quality in emerging markets. In addition, we argue that brand globalness can be shaped by inferential reasoning and test how consumer perceptions of brand globalness are affected by both a brand's country of origin and its perceived quality. Two different studies were conducted with young‐adult consumers in China. The study found that in their evaluations of foreign brands consumers are more influenced by country of origin than by brand globalness. It also found that consumers tend to perceive a high level of globalness in high‐quality brands and brands from a favorable country‐of‐origin. Further, this tendency was found to differ between well‐known and lesser‐known brands. These findings confirm the predictive validity of country of origin, but contrast with extant literature on the role of brand globalness as a principal quality cue for foreign brands among consumers in emerging markets. Our findings also imply brand globalness can be an inferred attribute of perceived brand quality and country‐of‐origin image. Keywords: brand foreignness, brand globalness, country‐of‐origin effect, emerging markets. [ABSTRACT FROM AUTHOR]

To analyze the impact of participation in sports with different cardiorespiratory fitness (CRF) demands on changes in metabolic and cardiovascular markers in adolescents. Longitudinal study with 12 months of follow‐up (Analysis of Behaviors of Children During Growth [ABCD Growth Study]). Overall, 184 adolescents (age 15.6 ± 2.1) were classified according to sports participation: non‐sport (control), low CRF sports, and high CRF sports. Metabolic outcomes were total cholesterol (TC) and its fractions, triacylglycerol (TG), glucose, insulin levels, and the insulin resistance index. Cardiovascular outcomes were arterial thickness (carotid and femoral [ultrasound]), blood pressure, and resting heart rate. Adolescents engaged in sports classified as high CRF demand presented a significant increase in HDL‐c (1.2 mg/dL [95%CI: −0.5 to 3.0]) when compared to the non‐sport group (−2.4 mg/dL [95%CI: −4.4 to −0.5]). Regular engagement in high CRF sports was significantly related to changes in TC (β = −0.027 [95%CI: −0.048 to −0.005]), HDL‐c (β = 0.009 [95%CI: 0.001 to 0.019]), LDL‐c (β = −0.032 [95%CI: −0.049 to −0.016]), and glucose (β = −0.017 [95%CI: −0.025 to −0.008]), while engagement in low CRF sports was related to changes in TG (β = −0.065 [95%CI: −0.112 to −0.019]). No significant relationships for cardiovascular parameters were observed in the low CRF group, but one significant relationship was found between high CRF sports and changes in SBP (β = −0.063 [95%CI: −0.117 to −0.009]). In conclusion, engagement in sports seems to be beneficial for improvements in metabolic and cardiovascular parameters in adolescents, mainly sports with higher CRF demand. [ABSTRACT FROM AUTHOR]

Objective: The NLRP3 inflammasome is closely linked to the pathophysiology of a wide range of inflammatory diseases. This study was undertaken to identify small molecules that directly bind to NLRP3 in order to develop pharmacologic interventions for NLRP3‐related diseases. Methods: A structure‐based virtual screening analysis was performed with ~62,800 compounds to select efficient NLRP3 inhibitors. The production of caspase 1‐p10 and interleukin‐1β (IL‐1β) was measured by immunoblotting and enzyme‐linked immunosorbent assay to examine NLRP3 inflammasome activation. Two gouty arthritis models and an air pouch inflammation model induced by monosodium urate monohydrate (MSU) crystal injection were used for in vivo experiments. Primary synovial fluid cells from gout patients were used to determine the relevance of NLRP3 inflammasome inhibition in human gout. Results: Beta‐carotene (provitamin A) suppressed the NLRP3 inflammasome activation induced by various activators, including MSU crystals, in mouse bone marrow–derived primary macrophages (P < 0.05). Surface plasmon resonance analysis demonstrated the direct binding of β‐carotene to the pyrin domain (PYD) of NLRP3 (KD = 3.41 × 10−6). Molecular modeling and mutation assays revealed the interaction mode between β‐carotene and the NLRP3 PYD. Inflammatory symptoms induced by MSU crystals were attenuated by oral administration of β‐carotene in gouty arthritis mouse models (P < 0.05), correlating with its suppressive effects on the NLRP3 inflammasome in inflamed tissues. Furthermore, β‐carotene reduced IL‐1β secretion from human synovial fluid cells isolated from gout patients (P < 0.05), showing its inhibitory efficacy in human gout. Conclusion: Our results present β‐carotene as a selective and direct inhibitor of NLRP3, and the binding of β‐carotene to NLRP3 PYD as a novel pharmacologic strategy to combat NLRP3 inflammasome–driven diseases, including gouty arthritis. [ABSTRACT FROM AUTHOR]

Introduction: Rest-activity disruption is an important feature of Duchenne muscular dystrophy (DMD). We sought to describe sleep impairment and its relationship to quality of life (QOL) and to evaluate associations between rest-activity, sleep quality, and 6-minute walk test (6MWT) in DMD.Methods: Sleep impairment and its relationship to QOL was assessed by questionnaire in 54 children (33 ambulatory, 21 nonambulatory) with DMD. Rest-activity characteristics were calculated for 23 of these children (14 ambulatory, nine nonambulatory) by actigraphy.Results: Pathologic sleep was reported in 11 (20%) participants and correlated with lower QOL but not with ambulatory status. In ambulatory participants who completed actigraphy, rest-activity rhythm fragmentation was associated with subjective sleep impairment. Habitual daytime activity level was associated with 6MWT performance.Discussion: Children with DMD experience substantial sleep impairment that is related to QOL. Wrist actigraphy may be a parsimonious tool for monitoring both sleep and motor impairment in ambulatory children with DMD. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of positive allergen reactions in intradermal and IgE serological tests in dogs presenting to a dermatology referral centre in South Australia and the clinical efficacy of subsequent allergen‐specific immunotherapy. Design: Retrospective study. Methods: Results from 108 intradermal allergy tests, 25 IgE serological assays and immunotherapy outcomes in 37 dogs were retrospectively analysed. Immunotherapy outcomes were determined as excellent, good, modest or failure using a global assessment of efficacy matrix which incorporated pruritus scores, lesion severity, medication requirements, and owner and clinician opinion. Results: The most common positive reactions in intradermal allergy tests were Red clover (59%), Dermatophagoides farinae (29%), Tyrophagus putrescentiae (28%), Yellow dock (25%) and Malassezia pachydermatis (24%). In the IgE serological tests, Yorkshire fog grass (40%), Yellow dock (36%), Kentucky bluegrass (36%) and T. putrescentiae (36%) were the most commonly reported positive results. The outcome of allergen‐specific immunotherapy was judged to be excellent in 20% of dogs, good in 15%, modest in 18% and a failure in 47%. Conclusion: As has been reported in other geographical areas, environmental mites and plant pollens frequently gave positive reactions in allergy tests in South Australia. However, the prevalence of individual allergen reactions differed between intradermal and IgE serological tests, with M. pachydermatis being identified as a common cause of hypersensitivity in intradermal tests but not in IgE serological assays. Immunotherapy was judged to be a beneficial treatment in 35% of dogs but was essentially unsuccessful in 65%. [ABSTRACT FROM AUTHOR]

Renal cancer is a common urogenital system malignance. Novel biomarkers could provide more and more critical information on tumor features and patients' prognosis. Here, we performed an integrated analysis on the discovery set and established a three‐gene signature to predict the prognosis for clear cell renal cell carcinoma (ccRCC). By constructing a LASSO Cox regression model, a 3‐messenger RNA (3‐mRNA) signature was identified. Based on the 3‐mRNA signature, we divided patients into high‐ and low‐risk groups, and validated this by using three other data sets. In the discovery set, this signature could successfully distinguish between the high‐ and low‐risk patients (hazard ratio (HR), 2.152; 95% confidence interval (CI),1.509–3.069; p < 0.0001). Analysis of internal and two external validation sets yielded consistent results (internal: HR, 2.824; 95% CI, 1.601–4.98; p < 0.001; GSE29609: HR, 3.002; 95% CI, 1.113–8.094; p = 0.031; E‐MTAB‐3267: HR, 2.357; 95% CI, 1.243–4.468; p = 0.006). Time‐dependent receiver operating characteristic (ROC) analysis indicated that the area under the ROC curve at 5 years was 0.66 both in the discovery and internal validation set, while the two external validation sets also suggested good performance of the 3‐mRNA signature. Besides that, a nomogram was built and the calibration plots and decision curve analysis indicated the good performance and clinical utility of the nomogram. In conclusion, this 3‐mRNA classifier proved to be a useful tool for prognostic evaluation and could facilitate personalized management of ccRCC patients. The 3‐mRNA classifier proved be a useful tool for prognostic evaluation and could facilitate personalized management of ccRCC patients. [ABSTRACT FROM AUTHOR]

Background: Anxiety and depression are clinically significant comorbidities associated with psoriasis. Improvements in psoriasis are known to decrease anxiety and depression. Guselkumab, an anti‐interleukin‐23 monoclonal antibody, has demonstrated efficacy and safety for the treatment of moderate‐to‐severe psoriasis. Objective: Assess improvements in anxiety and depression with guselkumab vs. placebo and adalimumab using the Hospital Anxiety and Depression Scale (HADS). Methods: In VOYAGE 2, a Phase 3, randomized, double‐blind, placebo‐ and adalimumab‐controlled study, patients received placebo (through week 16 followed by crossover to guselkumab), guselkumab, or adalimumab through week 24. HADS consists of two subscales measuring anxiety (HADS‐A) and depression (HADS‐D), with scores ranging from 0 to 21 and higher scores indicating more severe symptoms. Scores ≥8 indicate instrument‐defined anxiety or depression. Severity of psoriasis was assessed using the Psoriasis Area and Severity Index (PASI). Results: Among 989 patients randomized (with baseline HADS measurements), mean HADS‐A and HADS‐D scores were 6.8 ± 4.2 and 5.3 ± 4.2, respectively; 38.6% of patients reported HADS‐A ≥8 and 27.7% HADS‐D ≥8 at baseline. At week 16, a significantly greater proportion of guselkumab patients with baseline HADS‐A or HADS‐D ≥8 reported HADS‐A <8 (51.4% vs. 25.9%; P < 0.001) or HADS‐D <8 (59.2% vs. 27.0%; P < 0.001) vs. placebo patients. At week 24, a greater proportion of guselkumab patients with baseline HADS‐A or HADS‐D ≥8 reported HADS‐A <8 (58.4% vs. 42.9%; P = 0.028) or HADS‐D <8 (59.8% vs. 46.4%; P = 0.079) vs. adalimumab patients. PASI improvements correlated with improvement in anxiety (r = 0.27; P < 0.0001) and depression (r = 0.25; P < 0.0001) scores in patients with baseline HADS‐A or HADS‐D ≥8. Greater improvements in HADS were also observed at week 16 in guselkumab‐treated patients vs. placebo using a more stringent cut‐off of HADS ≥11. Conclusion: Guselkumab treatment was associated with greater improvements in symptoms of anxiety and depression scores in patients with psoriasis compared with placebo and adalimumab. [ABSTRACT FROM AUTHOR]

The authors propose a dual-energy approach to reduce cone-beam artefacts in a circular orbit cone-beam computed tomography (CT) system. When there exist multiple dense structures within a large cone angle, two-pass algorithm is ineffective for reducing cone-beam artefacts because high-density materials are incorrectly segmented with simple thresholding. The proposed algorithm utilises projection data obtained with dual-energy X-ray spectra to estimate projections of the high-density materials from multi-density anatomical structures. Using bone and water as two of basis functions, the projection data of bone materials can be precisely estimated via dual-energy scans. Then, bone-only images are reconstructed by a constrained total-variation minimisation-based iterative algorithm. The reconstructed bone images are used to generate cone-beam artefacts and the final corrected images are acquired by subtracting the generated cone-beam artefacts from the original Feldkamp, Davis, and Kress images. The proposed method was validated using an extended cardiac-torso phantom with complex vertebral anatomy and compared with the two-pass algorithm. The results show that the proposed method restores distorted bony structures and intensity values, especially in regions with large cone angles. A qualitative evaluation of the mean-squared errors and structural similarities demonstrates the effectiveness of the proposed method compared to the two-pass algorithm. [ABSTRACT FROM AUTHOR]

Abstract: Background: How patients experience the symptoms/signs of psoriasis is highly relevant for assessing treatment response. Objectives: Compare outcomes with guselkumab, placebo and adalimumab utilizing the novel, validated Psoriasis Symptoms and Signs Diary (PSSD). Methods: VOYAGE 1 is an ongoing, phase III, double‐blinded, controlled trial of patients with moderate‐to‐severe psoriasis. Patients were randomized to guselkumab 100 mg every 8 weeks; placebo‐to‐guselkumab 100 mg every 8 weeks; or adalimumab 40 mg every 2 weeks. The PSSD was self‐administered to assess symptoms (i.e. itch, skin tightness, burning, stinging and pain) and signs (i.e. dryness, cracking, scaling, shedding/flaking, redness and bleeding) of psoriasis (0–10 [absent‐to‐worst‐imaginable]) every 24 h. Symptom and sign summary scores were derived (0–100) based on average scores of the individual symptoms and signs. Proportions of patients with clinically meaningful improvements and symptom‐ and sign‐free scores of 0 were evaluated across treatment groups at weeks 16, 24 and 48. Results: At baseline, 652 of 837 randomized patients had PSSD scores. The proportion of patients achieving clinically meaningful improvements in PSSD summary scores was significantly higher in the guselkumab group compared with the placebo group at week 16 (P < 0.001) and compared with the adalimumab group at weeks 24 (P = 0.002) and 48 (P < 0.001). The proportions of patients achieving PSSD symptom and sign summary scores of 0 (i.e. symptom‐ and sign‐free) were significantly higher for guselkumab vs. placebo at week 16 and vs. adalimumab at weeks 24 and 48 (all P < 0.001). Conclusions: Based on PSSD scores, greater improvements in symptoms and signs of psoriasis were reported by patients treated with guselkumab compared with placebo at week 16 or adalimumab through 48 weeks. [ABSTRACT FROM AUTHOR]

Abstract: Oestrogen‐related receptor (ERR) is involved in oestrogen receptor (ER) signalling pathways owing to its similarity to ER in terms of domain structure and co‐activator and response elements. Although insects lack ER, they harbour an ERR gene that is thought to modulate metabolism and energy conversion via an unknown mechanism. The present study investigated the function of ERR in insects using female silkworm (Bombyx mori, Bm). We found that the expression of B. mori vitellogenin (BmVg) and B. mori ERR (BmERR) in the fat bodies of female silkworms at different stages of development exhibited alternating patterns, and RNA interference of BmERR in females induced BmVg transcription, resulting in an increase in egg weight relative to the control. Furthermore, BmERR was found to be involved in regulating the transcription of BmVg through an oestrogen‐related receptor response element (ERRE) in the promoter of the BmVg gene, as demonstrated by electrophoretic mobility shift assay, cell transfection assay and chromatin immunoprecipitation. In summary, our results indicate that BmERR bound to the ERRE motif in the BmVg promoter reducing the expression of BmVg in the fat body of the female silkworm. To our surprise, the ERRE also showed the ability to bind the ecdysone receptor (BmEcR) and ultraspiracle complex. Thus, we surmise that ERR participates in steroid hormone signalling by engaging in crosstalk with the ER pathway in vertebrates and with the EcR pathway in insects. [ABSTRACT FROM AUTHOR]

The purpose of this study is to analyze the effects of surface defects (eg, notches) and external environment conditions (eg, operating temperature, the number of re-weldings) on the static strength and fatigue of C1220T-O copper tubes used in the heat exchangers of air conditioners. Instead of using standardized specimens, as is done in general rotary bending fatigue tests, special specimens were fabricated in this study by inserting metal plugs on both ends of the copper tubes to perform fatigue tests on the actual tube product, and then the fatigue characteristics were evaluated using stress-life (S-N) curves. Regarding the welding conditions (maximum 1000°C and 10 seconds), the grain size grew (grain size number decreased), and the hardness decreased as the number of re-weldings increased. The effects of the operating temperatures on the fatigue life were examined at a room temperature of 25°C and a heat exchanger operating temperature of 125°C, resulting in the same fatigue limit (70.21 MPa) at both room and operating temperatures. However, the fatigue limit of 37.46 MPa measured in the notched specimens (radius of 3 mm, depth of 0.2 mm) was lower than that obtained from those without notches. The material constant (1.07) used in the Peterson equation was then computed from the fatigue notch factor (1.87 = 70.21/37.46), and the stress concentration factor (2.18) of the notched tube specimens was obtained from the structural analysis. This material constant can be used to predict a decrease in the fatigue limit over varying notch sizes in copper tubes (C1220T-O). [ABSTRACT FROM AUTHOR]

Abstract: Background: Symmetrical acral keratoderma (SAK) is a rare skin disorder and its pathogenesis and inheritability are unknown. Objectives: To investigate the inheritance and pathogenesis of SAK. Methods: Four SAK cases occurred in a four‐generation Chinese family. Exome sequencing identified SNPs with potential SAK‐related mutations, and a potentially responsible gene transcription factor 4 (TCF4) was identified. TCF4 was then sequenced in all 11 family members, and pedigree analysis was performed. Histopathology and immunohistochemistry evaluated TCF4 expression in skin lesions. The gene mutation was investigated in human keratinocytes for keratin‐related protein expression. Results: A novel heterozygous missense mutation, c.85C>A (p.Pro29Thr) was found in TCF4. The mutation showed autosomal dominant inheritance and perfectly cosegregated with the SAK phenotype in all family members. In skin lesions, TCF4 was present in the cytoplasm and membranes of the basal layer, the stratum spinosum and the stratum granulosum of the epidermis. The mutant TCF4 induced overexpression of differentiation markers including KRT1, KRT14, loricrin and involucrin. Conclusions: A SAK‐related gene mutation in TCF4 may function through transcriptional regulation of keratin. [ABSTRACT FROM AUTHOR]

Summary: Plant protoplasts are useful for assessing the efficiency of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9) mutagenesis. We improved the process of protoplast isolation and transfection of several plant species. We also developed a method to isolate and regenerate single mutagenized Nicotianna tabacum protoplasts into mature plants. Following transfection of protoplasts with constructs encoding Cas9 and sgRNAs, target gene DNA could be amplified for further analysis to determine mutagenesis efficiency. We investigated N. tabacum protoplasts and derived regenerated plants for targeted mutagenesis of the phytoene desaturase (NtPDS) gene. Genotyping of albino regenerants indicated that all four NtPDS alleles were mutated in amphidiploid tobacco, and no Cas9 DNA could be detected in most regenerated plants. [ABSTRACT FROM AUTHOR]

Abstract: Cryospheric changes have great effects on alpine hydrology, but these effects are still unclear owing to rare observations and suitable models in the western cold regions of China. Based on long‐term field observations in the western cold regions of China, a cryospheric basin hydrological model was proposed to evaluate the cryospheric effects on streamflow in the upper Hei River basin (UHR), and the relationship between the cryosphere and streamflow was further discussed with measured data. The Norwegian Earth System Model outputs were chosen to project future streamflow under scenarios Representative Concentration Pathways (RCP)2.6, RCP4.5, and RCP8.5. The cryospheric basin hydrological model results were well validated by the measured precipitation, streamflow, evapotranspiration, soil temperature, glacier and snow cover area, and the water balance of land cover in the UHR. The moraine‐talus region contributed most of the runoff (60%), even though it made up only about 20% of the area. On average, glacier and snow cover, respectively, contributed 3.5% and 25.4% of the fresh water to the streamflow in the UHR between 1960 and 2013. Because of the increased air temperature (2.9°C/54a) and precipitation (69.2 mm/54a) over the past 54 years, glacial and snowmelt runoff increased by 9.8% and 12.1%, respectively. The increase in air temperature brought forward the snowmelt flood peak and increased the winter flow due to permafrost degradation. Glaciers may disappear in the near future because of their small size, but snowmelt would increase due to increases in snowfall in the higher mountainous areas, and the basin runoff would increase slightly in the future. [ABSTRACT FROM AUTHOR]

Summary: Quercetin, a polyphenolic flavonoid with diverse biological activities including anti‐inflammatory and antiviral, inhibits lipid peroxidation, prevents oxidative injury and cell death. The purpose of the research was to investigate the effect of quercetin on productive performance, reproductive organs, hormones and apoptotic genes in laying hens between 37 and 45 weeks of age, because of the structure and oestrogenic activities similar to 17β‐oestradiol. The trial was conducted using 240 Hessian laying hens (37 weeks old), housed in wire cages with two hens in each cage. These hens were randomly allotted to four treatments with six replicates, 10 hens in each replicate and fed with diets containing quercetin as 0, 0.2, 0.4 and 0.6 g/kg feed for 8 weeks. The results showed that dietary quercetin significantly increased (p < .05) the laying rate and was higher in group supplemented with 0.4 g/kg, and feed‐egg ratio was decreased (p < .05) by quercetin. Dietary quercetin has no effect (p > .05) on average egg weight and average daily feed intake. Compared with control, secretion of hormones, oestradiol (E2), progesterone (P4), follicle‐stimulating hormone (FSH), luteinizing hormone (LH), insulin‐like growth factors‐1 (IGF‐1) and growth hormone (GH), was found to be significantly higher (p < .05) in quercetin‐supplemented groups. Also ovary index, uterus index and oviduct index were not significantly influenced (p > .05) by quercetin, whereas magnum index, isthmus index, magnum length, isthmus length and follicle numbers were significantly increased (p < .05) with quercetin supplementation. Additionally, expression of apoptotic genes was significantly (p < .05) up‐regulated or down‐regulated by quercetin. These results indicated that quercetin improved productive performance, and its mechanism may be due to the oestrogen‐like activities of quercetin. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study is to empirically investigate the country‐level antecedents of cross‐country differences in consumer cosmopolitanism and consumer ethnocentrism (CET) using samples from 21 nations. Country‐level antecedents have not been examined extensively in the past, in spite of their importance in understanding consumer behavior across countries. Specifically, we perform a multilevel analysis with various country‐level cultural and economic antecedents as between‐country factors and individual‐level demographics as within‐country covariates. Our findings show that the level of consumer cosmopolitanism in a country is related to several country‐level factors. It was found to be high in more individualistic, less masculine, and high‐uncertainty‐avoidance cultures; developing countries; and countries with trade surpluses. On the other hand, CET had a high level in economically open countries. In addition, CET was higher among older consumers across countries. [ABSTRACT FROM AUTHOR]

In the formation of goose fatty liver induced by a high-carbohydrate diet, it is characterized by the quick cell growth of liver. The carbohydrate is mostly digested and absorbed in the small intestine by the form of glucose. Recent studies have suggested a crucial role for PI3K-Akt- mTOR pathway in regulating cell proliferation, and then we speculate that PI3K-Akt- mTOR pathway may mediate glucose-induced liver cell proliferation. Goose primary hepatocytes were isolated and incubated in either no addition as a control or glucose or PI3K-Akt- mTOR pathway inhibitors or cotreatment with glucose and PI3K-Akt- mTOR pathway inhibitors. The results firstly showed that 35 mmol/l glucose stimulated the mRNA level and protein content of factors involved in PI3K-Akt- mTOR signal pathway in goose primary hepatocytes. Secondly, 35 mmol/l glucose evidently changed the cell cycle PI index and protein expression of cyclin D1. Meanwhile, the upregulation of 35 mmol/l glucose on the DNA synthesis rate, cell cycle PI index, the mRNA expression, protein content and protein expression of factors involved in the cell proliferation was decreased significantly by the inhibitors of PI3K-Akt- mTOR pathway, LY294002, rapamycin or NVP- BEZ235. In summary, glucose could stimulate the cell proliferation, and the PI3K-Akt- mTOR pathway inhibitors could dismiss glucose-induced the upregulation of cell proliferation in goose primary hepatocyte. [ABSTRACT FROM AUTHOR]

Vitellogenin (Vg) is a source of nutrition for embryo development. Our previous study showed that the silkworm ( Bombyx mori) transcription factor broad complex isoform 2 (BmBrC-Z2) regulates gene expression of the Vg gene ( BmVg) by induction with 20-hydroxyecdysone (20E). However, the mechanism by which 20E regulates BmVg expression was not clarified. In this study, cell transfection experiments showed that the BmVg promoter containing the POU homeodomain transcription factor POUM2 (POUM2) and BrC-Z2 cis-response elements (CREs) showed a more significant response to 20E than that harbouring only the BrC-Z2 or POUM2 CRE. An electrophoretic mobility shift assay and chromatin immunoprecipitation assay showed that BmPOUM2 could bind to the POUM2 CRE of the BmVg promoter. Over-expression of BmPOUM2 and BmBrC-Z2 in B. mori embryo-derived cell line (BmE) could enhance the activity of the BmVg promoter carrying both the POUM2 and BrC-Z2 CREs following 20E induction. Quantitative PCR and immunofluorescence histochemistry showed that the expression pattern and tissue localization of BmPOUM2 correspond to those of BmVg. Glutathione S-transferase pull-down and co-immunoprecipitation assays confirmed that BmPOUM2 interacts only with BmBrC-Z2 to regulate BmVg expression. Down-regulation of BmPOUM2 in female silkworm by RNA interference significantly reduced BmVg expression, leading to abnormal egg formation. In summary, these results indicate that BmPOUM2 binds only to BmBrC-Z2 to collaboratively regulate BmVg expression by 20E induction to control vitellogenesis and egg formation in the silkworm. Moreover, these findings suggest that homeodomain protein POUM2 plays a novel role in regulating insect vitellogenesis. [ABSTRACT FROM AUTHOR]

Halogenated analogues of the neurotoxic alkaloid muscimol were prepared with fluorine, iodine or trifluoromethyl at the 4 position of the isoxazole ring system. These compounds were investigated as agonists for GABAA receptors. Only the C-4 fluorine-containing analogue proved to be an active compound in these assays. The fluoro analogue was less active than muscimol, however it showed differential activity between synaptic (α1β2γ2) and extrasynaptic (α4β2γ) GABAA receptors, having a similar potency to the neurotransmitter GABA for the extrasynaptic (α4β2γ) receptor. [ABSTRACT FROM AUTHOR]

Copyright of International Journal of Cosmetic Science is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The chloroplast NAD(P)H dehydrogenase-like ( NDH) complex consists of about 30 subunits from both the nuclear and chloroplast genomes and is ubiquitous across most land plants. In some orchids, such as Phalaenopsis equestris, Dendrobium officinale and Dendrobium catenatum, most of the 11 chloroplast genome-encoded ndh genes (cp- ndh) have been lost. Here we investigated whether functional cp- ndh genes have been completely lost in these orchids or whether they have been transferred and retained in the nuclear genome. Further, we assessed whether both cp- ndh genes and nucleus-encoded NDH-related genes can be lost, resulting in the absence of the NDH complex. Comparative analyses of the genome of Apostasia odorata, an orchid species with a complete complement of cp- ndh genes which represents the sister lineage to all other orchids, and three published orchid genome sequences for P. equestris, D. officinale and D. catenatum, which are all missing cp- ndh genes, indicated that copies of cp- ndh genes are not present in any of these four nuclear genomes. This observation suggests that the NDH complex is not necessary for some plants. Comparative genomic/transcriptomic analyses of currently available plastid genome sequences and nuclear transcriptome data showed that 47 out of 660 photoautotrophic plants and all the heterotrophic plants are missing plastid-encoded cp- ndh genes and exhibit no evidence for maintenance of a functional NDH complex. Our data indicate that the NDH complex can be lost in photoautotrophic plant species. Further, the loss of the NDH complex may increase the probability of transition from a photoautotrophic to a heterotrophic life history. [ABSTRACT FROM AUTHOR]

The H ∞ framework provides an efficient and systemic method for the design of controllers for both linear and nonlinear systems. In the nonlinear controller synthesis, however, the limitation of this method is usually associated with the existence of a solution to the Hamilton-Jacobi-Isaac (HJI) equation. In this paper, an innovative energy compensation-based approach to the solution of the HJI equations is presented and compared with the existing methods relying on Taylor series expansion. This new approach provides an efficient methodology that ensures the existence of a solution to the HJI equation. Numerical application to spacecraft attitude control is presented to validate the developments. [ABSTRACT FROM AUTHOR]

Background Irritable bowel syndrome ( IBS) is a heterogeneous condition with a number of pathophysiological mechanisms that appear to contribute to symptom chronicity. One of these is altered pain sensitivity. Methods Women between ages 18-45 were recruited the community. Of those enrolled, 56 had IBS and 36 were healthy control ( HC) women. Participants completed questionnaires, kept a 4-week symptom diary and had a 12-h Holter placed to assess nighttime heart rate variability including high frequency power ( HF), low frequency power ( LF), and total power ( TP). At mid-follicular phase approximately 80% of women completed a thermal pain sensitivity test with conditioned pain modulation and visceral pain sensitivity using a water load symptom provocation ( WLSP) test. Key Results As expected, daily abdominal pain was significantly higher in the IBS compared to HC group. There were no differences between the bowel pattern subgroups ( IBS-diarrhea [ IBS-D], IBS-constipation plus mixed [ IBS- CM]). Thermal pain sensitivity did not differ between the IBS and the HC groups, but was significantly higher in the IBS- CM group than the IBS-D group. In the WLSP test, the IBS group experienced significantly more symptom distress than HCs and the IBS- CM group was higher than the IBS-D group. Heart rate variability indicators did not differ between the groups or IBS subgroups. Daily abdominal pain was positively correlated with LF and TP in the IBS group. Conclusions & Inferences Despite similar levels of abdominal pain in IBS, the IBS- CM group demonstrated greater sensitivity to both thermal and visceral testing procedures. [ABSTRACT FROM AUTHOR]

Background: We hypothesize that pain and brain responses are affected by changes in the presentation sequence of noxious stimuli that are, overall, identical in intensity and duration.Methods: During functional magnetic resonance imaging (fMRI) scanning, 21 participants experienced three patterns of noxious stimulation: Up-type (step-up noxious stimulation, 15 s), Down-type (step-down noxious stimulation, 15 s), and Down-up-type (decreasing and increasing pattern of noxious stimulation, 15 s). The total intensity and duration of the three noxious stimulation patterns were identical, but the stimulation sequences were different.Results: Pain and unpleasantness ratings in the Down- and Down-up-type noxious stimulations were lower than in the Up-type noxious stimulation. The left prefrontal cortex [(PFC, BA (Brodmann area) 10, (-45, 50, 1)] was more highly activated in the Down- and Down-up-type noxious stimulations than in the Up-type noxious stimulation. The S1, S2, insula, bilateral PFC (BA 46), and midcingulate cortex were more highly activated in the Up-type noxious stimulation than in the Down-type noxious stimulation. PFC BA 10 was located at an inferior level compared to the bilateral PFC BA 46 (Z axis = 1 for BA 10, compared to 22 and 25 for the right and left BA 46, respectively). When cortisol level was increased, the left hippocampal cortex, along with the left parahippocampal cortex, was greatly activated for the Up-type noxious stimulation.Conclusion: When pain cannot be avoided in clinical practice, noxious stimuli should be applied to patients in a step-down pattern that delivers the most intense pain first and the least intense pain last. [ABSTRACT FROM AUTHOR]

The Sergyemla Mountains have unique timberline patterns. Abies georgei var. smithii (Viguie & Gaussen) and Juniperus saltuaria (Rehder & E. H. Wilson) dominate the north-facing and south-facing slopes of a U-shaped valley, respectively. Although these two timberlines represent the world's highest natural tree lines, little is known about the structure of their soil bacterial communities and the factors that control them. To characterize and compare the soil bacterial communities of two timberline ecotones with different spatial orientations, we investigated their structures by terminal restriction fragment length polymorphism analysis and sequencing methods. We found that the structures of the soil bacterial communities differed significantly between the two opposite slopes, and the difference between the bacterial communities correlated primarily with soil carbon:nitrogen ratios. This probably relates to differences in the microclimate (mean soil temperature) between the two aspects in the world's highest timberline ecotones. In addition, the structures of soil bacterial communities also differed significantly with soil depth, and total nitrogen content had the greatest effect on the bacterial communities. In this region, soil temperature rather than mean annual precipitation has a major effect on the structures of soil bacterial communities. Microclimate differences (mainly differences in soil temperature) between the two opposite slopes might indicate that an amplitude increase of 2°C in soil temperature could change the structures of soil bacterial communities by changing the status of soil carbon and nitrogen in these timberline ecotones. [ABSTRACT FROM AUTHOR]

This Letter proposes a new two‐sample excess loop delay compensation in continuous‐time delta‐sigma modulators using time‐shifted differentiated digital‐to‐analogue converter (DAC). This is done by using the information inherently available but ignored in the conventional methods, and therefore no additional hardware is required. Simulation results and mathematical analysis are provided to verify the effectiveness of the proposed structure. [ABSTRACT FROM AUTHOR]

Contents Early follicular development is closely related to oocyte-granulosa cells-ovarian stromal cells/theca cells. The aim of the present study was to investigate the effects of ovarian cortical, medullary stromal and theca cells on oestradiol and progesterone biosynthesis, proliferation and apoptosis of goat ovary granulosa cells in vitro. Using Transwell coculture system, we evaluated steroidogenesis, cell proliferation and apoptosis, and some molecular expressions regarding steroidogenic enzyme, luteinizing hormone receptor and apoptosis-related genes in granulosa cells. The results indicated that ovarian stromal/theca cells were able to stimulate oestradiol and progesterone production, promote cell proliferation and inhibit apoptosis of granulosa cells. Among all the three kinds of cells, theca cells affected strongly on granulosa cell function, and ovarian medullary stromal cells had the weakest effect on granulosa cells. These findings would provide an important knowledge of cell interaction among follicular cells during follicular development. [ABSTRACT FROM AUTHOR]

In this article, the authors focus on the experience of 17 surgeons related to the simulation testing potassium-titanyl-phosphate laser (KTP laser) protective eyewear for improving visualisation of blood and endoscopic images. They inform that differentiation blood from mucosa has been impaired by using laser protective eyewear, which has been improved by adjusting the colour palate of the image. They mention that images have been manipulated using Adobe Photoshop CS2.

Objective: Because the number of elderly is increasing worldwide, cognitive dysfunction becomes important health care issue. This study investigated the association between cognitive dysfunction and mortality in the elderly. Method: Data were analyzed from a longitudinal mortality follow-up study of 2712 Korean elderly aged 60 and over, examined in 2002 with complete data followed an average 6.03 years. Measurements included socio-demographic and clinical factors and Mini-Mental State Examination (MMSE). MMSE was categorized into groups with no, mild, or moderate cognitive dysfunction, and the subscores of MMSE domains were categorized into no dysfunction or dysfunction. The Cox proportional hazards models were conducted to examine the association between MMSE score and mortality, after adjusting for age, gender, education and other socio-demographic factors. Results: Death during follow-up occurred in 318 subjects. The mortality risk was significantly associated with the elderly with mild cognitive dysfunction [hazard ratio (HR) = 1.93] and with moderate cognitive dysfunction (HR = 2.66). 'Orientation-to-time' (HR = 1.39) and 'Attention' (HR = 1.48) domains of MMSE were independently associated with mortality. Conclusion: This study showed that cognitive dysfunction independently predicted mortality in the elderly. Cognitive dysfunction should be considered part of identifying the elderly at high risk for mortality. [ABSTRACT FROM AUTHOR]

Kim YS, Kang SJ, Kim JW, Cho HR, Moon SB, Kim KY, Lee HS, Han CH, Ku SK, Lee YJ. Effects of Polycan, a β-glucan, on experimental periodontitis and alveolar bone loss in Sprague-Dawley rats. J Periodont Res 2012; 47: 800-810. © 2012 John Wiley & Sons A/S Background and Objective: Polycan is a promising candidate for the treatment of periodontal disease. This study was undertaken to examine whether Polycan, a type of β-glucan, has a protective effect on ligature-induced experimental periodontitis and related alveolar bone loss in Sprague-Dawley rats. Material and Methods: Polycan was orally administered, daily, for 10 d, at 21.25, 42.5 or 85 mg/kg, beginning 1 d after ligation. Changes in body weight and alveolar bone loss were monitored, and the anti-inflammatory effects of Polycan were determined by measuring the levels of myeloperoxidase (MPO), interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in gingival tissue. We also evaluated inducible nitric oxide synthase (iNOS) activity and malondialdehyde (MDA) concentrations as a measure of the antioxidant effect. Results: Ligature placement led to a marked decrease in body weight, increased alveolar bone loss and increased concentrations of MPO, IL-1β, TNF-α and MDA, as well as increased iNOS activity and inflammatory cell infiltration and decreased collagen-fiber content. Histological examination revealed increases in the number and activity of osteoclast cells, decreases in alveolar bone volume and elevated percentages of osteclasts on the alveolar bone surface. Daily oral treatment with 42.5 or 85 mg/kg of Polycan for 10 d led to significant, dose-dependent inhibition of the effect of ligature placement. Conclusion: Taken together, these results suggest that 10 d of oral treatment with Polycan effectively inhibits ligature placement-induced periodontitis and related alveolar bone loss via an antioxidant effect. [ABSTRACT FROM AUTHOR]

In this study, we have synthesized and characterized Li4Ti5O12 (LTO)-coated meso-carbon micro beads (MCMB) as an anode material for Li-batteries. The surface of MCMB powders was uniformly coated by the LTO nanoparticles to form a core-shell structure via a sol-gel process, followed by calcination. The average size of MCMB core was 15 μm while the thickness of LTO shell was 80 to 120 nm. We found that LTO-coated MCMB had better rate-capability and cycle life, compared with the pristine MCMB. Electrochemical impedance spectroscopy (EIS) results showed that after 40 cycles, the cell resistance of the LTO-coated MCMB electrode increased slightly, while that of the pristine MCMB electrode increased significantly. The enhanced performance of the LTO-coated MCMB electrode is attributed to the LTO coating, which suppresses the increase in the charge-transfer resistance during prolonged cycle. [ABSTRACT FROM AUTHOR]

Objective To determine whether prenatal myelomeningocele repair is a cost-effective strategy compared to postnatal repair. Methods Decision-analysis modeling was used to calculate the cumulative costs, effects and incremental cost-effectiveness ratio of prenatal myelomeningocele repair compared with postnatal repair in singleton gestations with a normal karyotype that were identified with myelomeningocele between T1 and S1. The model accounted for costs and quality-adjusted life years (QALYs) in three populations: (1) myelomeningocele patients; (2) mothers carrying myelomeningocele patients; and (3) possible future siblings of these patients. Sensitivity analysis was performed using one-way, two-way and Monte Carlo simulations. Results Prenatal myelomeningocele repair saves $ 2 066 778 per 100 cases repaired. Additionally, prenatal surgery results in 98 QALYs gained per 100 repairs with 42 fewer neonates requiring shunts and 21 fewer neonates requiring long-term medical care per 100 repairs. However, these benefits are coupled to 26 additional cases of uterine rupture or dehiscence and one additional case of neurologic deficits in future offspring per 100 repairs. Results were robust in sensitivity analysis. Conclusion Prenatal myelomeningocele repair is cost effective and frequently cost saving compared with postnatal myelomeningocele repair despite the increased likelihood of maternal and future pregnancy complications associated with prenatal surgery. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Small nerve fiber neuropathy (SFN) often occurs without apparent cause, but no systematic genetic studies have been performed in patients with idiopathic SFN (I-SFN). We sought to identify a genetic basis for I-SFN by screening patients with biopsy-confirmed idiopathic SFN for mutations in the SCN9A gene, encoding voltage-gated sodium channel Na(V) 1.7, which is preferentially expressed in small diameter peripheral axons. METHODS: Patients referred with possible I-SFN, who met the criteria of >=2 SFN-related symptoms, normal strength, tendon reflexes, vibration sense, and nerve conduction studies, and reduced intraepidermal nerve fiber density (IENFD) plus abnormal quantitative sensory testing (QST) and no underlying etiology for SFN, were assessed clinically and by screening of SCN9A for mutations and functional analyses. RESULTS: Twenty-eight patients who met stringent criteria for I-SFN including abnormal IENFD and QST underwent SCN9A gene analyses. Of these 28 patients with biopsy-confirmed I-SFN, 8 were found to carry novel mutations in SCN9A. Functional analysis revealed multiple gain of function changes in the mutant channels; each of the mutations rendered dorsal root ganglion neurons hyperexcitable. INTERPRETATION: We show for the first time that gain of function mutations in sodium channel Na(V) 1.7, which render dorsal root ganglion neurons hyperexcitable, are present in a substantial proportion (28.6%; 8 of 28) of patients meeting strict criteria for I-SFN. These results point to a broader role of Na(V) 1.7 mutations in neurological disease than previously considered from studies on rare genetic syndromes, and suggest an etiological basis for I-SFN, whereby expression of gain of function mutant sodium channels in small diameter peripheral axons may cause these fibers to degenerate. ANN NEUROL 2012;71:26-39. [ABSTRACT FROM AUTHOR]

Summary This study was designed to investigate the effects of dietary lipid levels on growth performance, lipid deposition and activities of lipid metabolic enzymes in hybrid tilapia ( Oreochromis niloticus × O. aureus). Four isonitrogenous (300 g/kg crude protein) experimental diets containing graded levels of lipid (25, 55, 85 and 115 g/kg) were randomly assigned to triplicate groups of 180 juvenile fish. Fish were fed twice daily for 8 weeks. At the end of the experiment, the growth performance and proximate composition of fish were determined. The activities and gene expression of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) were assessed as well. Fish fed the diets with 55 and 85 g/kg lipid had a significantly (p < 0.05) higher body weight gain than those fed the diets with 25 and 115 g/kg lipid. The whole-body and liver lipid contents were significantly (p < 0.05) elevated with increasing dietary lipid levels. Moreover, the activities and mRNA abundances of LPL and HSL in the liver, dorsal muscle and fat tissues were markedly altered by dietary lipid levels. Our data demonstrate a profound influence of dietary lipid levels on the growth and lipid deposition in hybrid tilapia, which is likely associated with the regulation of lipid metabolic enzymes including LPL and HSL. [ABSTRACT FROM AUTHOR]

Numerous lenses of eclogite occur in a belt of augen orthogneisses in the Gubaoquan area in the southern Beishan orogen, an eastern extension of the Tianshan orogen. With detailed petrological data and phase relations, modelled in the system NCFMASHTO with thermocalc, a quantitative P-T path was estimated and defined a clockwise P-T path that showed a near isothermal decompression from eclogite facies (>15.5 kbar, 700-800 °C, omphacite + garnet) to high-pressure granulite facies (12-14 kbar, 700-750 °C, clinopyroxene + sodic plagioclase symplectitic intergrowths around omphacite), low-pressure granulite facies (8-9.5 kbar, ∼700 °C, orthopyroxene + clinopyroxene + plagioclase symplectites and coronas surrounding garnet) and amphibolite facies (5-7 kbar, 600-700 °C, hornblende + plagioclase symplectites). The major and trace elements and Sm-Nd isotopic data suggest that most of the Beishan eclogite samples had a protolith of oceanic crust with geochemical characteristics of an enriched or normal mid-ocean ridge basalt. The U-Pb dating of the Beishan eclogites indicates an Ordovician age of c. 467 Ma for the eclogite facies metamorphism. An 39Ar/40Ar age of c. 430 Ma for biotite from the augen gneiss corresponds to the time of retrograde metamorphism. The combined data from geological setting, bulk composition, clockwise P-T path and geochronology support a model in which the Beishan eclogites started as oceanic crust in the Palaeoasian Ocean, which was subducted to eclogite depths in the Ordovician and exhumed in the Silurian. The eclogite-bearing gneiss belt marks the position of a high-pressure Ordovician suture zone, and the calculated clockwise P-T path defines the progression from subduction to exhumation. [ABSTRACT FROM AUTHOR]

Objective To determine whether routine measurement of second-trimester transvaginal cervical length by ultrasound in low-risk singleton pregnancies is a cost-effective strategy. Methods We developed a decision analysis model to compare the cost-effectiveness of two strategies for identifying pregnancies at risk for preterm birth: (1) no routine cervical length screening and (2) a single routine transvaginal cervical length measurement at 18-24 weeks' gestation. In our model, women identified as being at increased risk (cervical length < 1.5 cm) for preterm birth would be offered daily vaginal progesterone supplementation. We assumed that vaginal progesterone reduces preterm birth at < 34 weeks' gestation by 45%. We also assumed that a decreased cervical length could result in additional costs (ultrasound scans, inpatient admission) without significantly improved neonatal outcomes. The main outcome measure was incremental cost-effectiveness ratio. Results Our model predicts that routine cervical-length screening is a dominant strategy when compared to routine care. For every 100 000 women screened, $ 12 119 947 can be potentially saved (in 2010 US dollars) and 423.9 quality-adjusted life-years could be gained. Additionally, we estimate that 22 cases of neonatal death or long-term neurologic deficits could be prevented per 100 000 women screened. Screening remained cost-effective but was no longer the dominant strategy when cervical-length ultrasound measurement costs exceeded $ 187 or when vaginal progesterone reduced delivery risk at < 34 weeks by less than 20%. Conclusion In low-risk pregnancies, universal transvaginal cervical length ultrasound screening appears to be a cost-effective strategy under a wide range of clinical circumstances (varied preterm birth rates, predictive values of a shortened cervix and costs). Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Ustekinumab, a human anti-interleukin-12/23 monoclonal antibody, has been shown to effectively treat moderate-to-severe psoriasis which significantly affects health-related quality of life (HRQoL), including patients' sexual lives. The aim of this study was to determine if sexual difficulties associated with psoriasis are related to disease severity and whether sexual difficulties improve with skin disease during ustekinumab treatment. In phase III PHOENIX 1 and 2 trials, psoriasis patients were randomized to ustekinumab ( n = 1334) at weeks 0 and 4 and q12 weeks thereafter or placebo ( n = 662) at weeks 0 and 4 with crossover to ustekinumab at week 12. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) were used to assess psoriasis severity and patient-reported HRQoL respectively. Based on DLQI Question #9, impaired sexual function was defined as 'very much' or 'a lot' of sexual difficulties. At baseline, mean DLQI was 12.0, indicating a very large negative effect on patients' lives. Impaired sexual function was reported by 22.6% (women = 27.1%; men = 20.8%) and was significantly associated with increased psoriasis severity. At week 12, ustekinumab-treated patients had a greater mean improvement in DLQI (−9.13 vs. −0.53 with placebo, P < 0.001) and the proportion of patients with impaired sexual function decreased from 22.4% to 2.7% compared with no change with placebo ( P < 0.001). Patients with greater PASI improvement experienced a greater reduction of sexual difficulties due to psoriasis. A similar pattern of improved sexual function was observed at weeks 24-28 in placebo crossover patients. Ustekinumab treatment is associated with significant improvement in HRQoL and sexual difficulties due to psoriasis. [ABSTRACT FROM AUTHOR]

Aim Advanced glycation end products play an important role in the pathophysiology of several chronic and age-related diseases, especially diabetes mellitus. Skin auto fluorescence is a non-invasive method for assessing levels of tissue advanced glycation end products. This study aims to establish the normal reference value of advanced glycation end products accumulated in tissue measured by the advanced glycation end product reader-skin auto fluorescence-and discusses some factors influencing it. Methods The values of auto fluorescence in healthy individuals in China were determined by the advanced glycation end product reader; age, gender, skin reflectance, smoking habits and alcohol consumption of the subjects were also recorded. Results Themean reference values of auto fluorescence in healthy Chinese subjects are (95% confidence interval) 20-29 years: 1.54-1.62 arbitrary units; 30-39 years: 1.66-1.75; 40-49 years: 1.78-1.89; 50-59 years: 1.87-2.03; 60-69 years: 1.86-2.09; 70-79 years: 1.97-2.31. The value of auto fluorescence is strongly related to age, but no significant difference between males and female swere found (allP > 0.05).Autofluorescence was higher in smokers than in non-smokers (P < 0.05). In persons with low skin reflectance (< 10%), skin auto fluorescence was dependent on skin colour, but was still related to age. Conclusions The mean reference values of auto fluorescence we established could be used for a Chinese population in a clinical setting and are agreement with those in a Caucasian population. Future developments are needed to make the advanced glycation end product reader reliable for lower skin reflections as well, independently of the skin colour. [ABSTRACT FROM AUTHOR]

Background Dexlansoprazole MR is a Dual Delayed Release formulation of dexlansoprazole, an enantiomer of lansoprazole, designed to extend the duration of acid suppression. Aim To assess the 12-month safety of dexlansoprazole MR in patients with symptomatic gastro-oesophageal reflux disease (GERD). Methods In this randomised open-label study, patients received dexlansoprazole MR 60 or 90 mg once-daily for 12 months. Safety was evaluated at months 1, 3, 6, 9 and 12/final visit through physical examinations, laboratory evaluations, endoscopies, gastric biopsies, fasting serum gastrin values and adverse events (AEs). Results Of 591 patients receiving dexlansoprazole MR 60 and 90 mg, 71% and 65%, respectively, experienced ≥1 treatment-emergent AE; the most frequent AE was upper respiratory infection (14% and 13% in the 60- and 90-mg groups). Thirty patients experienced ≥1 serious AE; a majority of serious AEs were unrelated to study drug. No clinically meaningful change in any clinical laboratory parameters was noted. As expected, serum gastrin values rose with dexlansoprazole therapy; increases were not dose related. No clinically concerning trends were identified in gastric pathology results; no endocrine cell hyperplasia, adenocarcinoma, or lymphoma were observed. Conclusions Twelve-month treatment with dexlansoprazole MR 60 and 90 mg was well tolerated by GERD patients in this study (Clinicaltrials.gov identifier NCT00255190). [ABSTRACT FROM AUTHOR]