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Purpose: We assessed the structural similarity of the optic disc and peripapillary region between monozygotic (MZ) twin pairs. Through these analyses, we sought to determine whether these structures are more likely to be affected by genetic or environmental factors., Methods: Using fundus photographs of 362 MZ twins, cup-to-disc ratio, tilt ratio of the optic disc, and the angle between the major temporal retinal vessels were measured. We also checked for the presence of peripapillary atrophy (PPA) and, if present, recorded its size and direction. We compared the level of consistency of these parameters and axial length (AL) between the right and left eyes within each individual and also between the corresponding paired eyes of the twins. Subgroup analysis was performed according to age and the difference in the AL between the twin pairs., Results: The mean (SD) age of the twins included in this study was 38.6 years (8.1). The size of the PPA was significantly correlated with the AL, but not with the intraocular pressure. For PPA-related factors, the level of consistency was weaker between corresponding paired eyes of the twins than between the right and left eyes within each individual. The level of consistency of the AL was the strongest in both comparisons. The level of consistency of both PPA-related factors and tilt ratio between the corresponding paired eyes of the twins was weaker in the group with a larger intertwin difference of AL than in the group with a smaller difference. Subgroup analyses by age (older age group, 45.3±6.3 y; younger age group, 32.4±2.7 y) showed that the level of consistency of PPA-related factors was weaker in the older age group than in the younger age group, after adjusting the AL., Conclusions: Unlike AL and cup-to-disc ratio, similarity of PPA between MZ twins decreased with age, suggesting that PPA could be formed as a result of various factors in addition to genetic ones.

Background: We investigated the individual and additive effects of three modifiable maternal metabolic factors, including pre-pregnancy overweight/obesity, gestational weight gain (GWG), and gestational diabetes mellitus (GDM), on early childhood growth trajectories and obesity risk., Methods: A total of 1425 mother-offspring dyads (953 black and 472 white) from a longitudinal birth cohort were included in this study. Latent class growth modeling was performed to identify the trajectories of body mass index (BMI) from birth to 4 years in children. Poisson regression models were used to examine the associations between the maternal metabolic risk factors and child BMI trajectories and obesity risk at 4 years., Results: We identified three discrete BMI trajectory groups, characterized as rising-high-BMI (12.6%), moderate-BMI (61.0%), or low-BMI (26.4%) growth. Both maternal pre-pregnancy obesity (adjusted relative risk [adjRR] = 1.96; 95% confidence interval [CI]: 1.36-2.83) and excessive GWG (adjRR = 1.71, 95% CI: 1.13-2.58) were significantly associated with the rising-high-BMI trajectory, as manifested by rapid weight gain during infancy and a stable but high BMI until 4 years. All three maternal metabolic indices were significantly associated with childhood obesity at age 4 years (adjRR for pre-pregnancy obesity = 2.24, 95% CI: 1.62-3.10; adjRR for excessive GWG = 1.46, 95% CI: 1.01-2.09; and adjRR for GDM = 2.14, 95% = 1.47-3.12). In addition, risk of rising-high BMI trajectory or obesity at age 4 years was stronger among mothers with more than one metabolic risk factor. We did not observe any difference in these associations by race., Conclusion: Maternal pre-pregnancy obesity, excessive GWG, and GDM individually and jointly predict rapid growth and obesity at age 4 years in offspring, regardless of race. Interventions targeting maternal obesity and metabolism may prevent or slow the rate of development of childhood obesity.

Many neuropsychiatric risk genes contribute to epigenetic regulation but little is known about specific chromatin-associated mechanisms governing the formation of neuronal connectivity. Here we show that transcallosal connectivity is critically dependent on C11orf46, a nuclear protein encoded in the chromosome 11p13 WAGR risk locus. C11orf46 haploinsufficiency was associated with hypoplasia of the corpus callosum. C11orf46 knockdown disrupted transcallosal projections and was rescued by wild type C11orf46 but not the C11orf46 R236H mutant associated with intellectual disability. Multiple genes encoding key regulators of axonal development, including Sema6a, were hyperexpressed in C11orf46-knockdown neurons. RNA-guided epigenetic editing of Sema6a gene promoters via a dCas9-SunTag system with C11orf46 binding normalized SEMA6A expression and rescued transcallosal dysconnectivity via repressive chromatin remodeling by the SETDB1 repressor complex. Our study demonstrates that interhemispheric communication is sensitive to locus-specific remodeling of neuronal chromatin, revealing the therapeutic potential for shaping the brain's connectome via gene-targeted designer activators and repressor proteins.

To date, the mechanical loads imposed on isolated cardiac muscle tissue in vitro have been oversimplified. Researchers typically applied loads that are time-invariant, resulting in either isometric and auxotonic contractions, or flat-topped (isotonic shortening) work-loops. These contraction types do not fully capture the dynamic response of contracting tissues adapting to a variable load, such as is experienced by ventricular tissue in vivo. In this study, we have successfully developed a loading system that presents a model-based, time-varying, continuously updated, load to cardiac tissue preparations. We combined a Windkessel model of vascular fluid impedance together with Laplace's Law and encoded it in a real-time hardware-based force-length control system. Experiments were carried out on isolated rat left ventricular trabeculae; we directly compare the work-loops arising from this protocol with those of a typical simplified isotonic shortening work-loop system. We found that, under body conditions, cardiac trabeculae achieved greater mechanical work output against our new loading system, than with the simplified isotonic work-loop protocol. We further tested whether loading the tissue with a mechanical impedance defined by "diseased" Windkessel model parameters had an effect on the performance of healthy trabeculae. We found that trabecula shortening decreased when applying the set of Windkessel parameters describing the hypertensive condition, and increased in the hypotensive state. Our implementation of a real-time model of arterial characteristics provides an improved, physiologically derived, instantly calculated load for use in studying isolated cardiac muscle, and is readily applicable to study various disease conditions., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Purpose: To investigate the outflow characteristics of silicone tubes with intraluminal stents used in membrane-tube (MT) type glaucoma shunt devices., Methods: The silicone tubes used in MicroMT (internal diameter of 100 μm with a 7-0 nylon intraluminal stent) and Finetube MT (internal diameter of 200 μm with a 5-0 nylon intraluminal stent) were connected to a syringe-pump that delivered a continuous flow of distilled water at flow rates of 2, 5, 10, and 25 μL/min. The pressures and resistances of tubes were measured at a steady flow rate with full-length, half-length, and absence of intraluminal stents., Results: The mean outflow resistance of the two types of tubes ranged from 3.0 ± 1.9 to 3.8 ± 1.7 mmHg/μL/min with a full-length intraluminal stent, 1.8 ± 1.1 to 2.2 ± 1.1 mmHg/μL/min with a half-length intraluminal stent, and 0.1 ± 0.0 to 0.2 ± 0.0 mmHg/μL/min without an intraluminal stent. Theoretically, for a physiologic state with a flow rate of 2 μL/min and episcleral venous pressure of 6 mmHg, the mean pressures of tubes were expected to be 13.2 ± 3.0, 10.5 ± 2.4, and 6.4 ± 0.2 mmHg in MicroMT with full-length, half-length, and absence of intraluminal stents, respectively, and 12.5 ± 3.9, 9.6 ± 2.4, and 6.2 ± 0.2 mmHg in Finetube MT with full-length, half-length, and absence of intraluminal stents, respectively. The pressure variance also decreased with intraluminal stent retraction ( p < 0.01)., Conclusions: The small diameter tubes of 100 and 200 μm internal diameters, with 7-0 and 5-0 nylon intraluminal stents, respectively, used in the MT-type glaucoma shunt device showed safe and effective outflow characteristics., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2019 The Korean Ophthalmological Society.)

Purpose: To investigate the topographic relationship among focal lamina cribrosa (LC) defect, microvasculature dropout (MvD) and border tissue morphology in open angle glaucoma (OAG) eyes using spectral-domain (SD) optical coherence tomography (OCT) and OCT angiography., Design: Cross-sectional study., Methods: One hundred twenty-six OAG eyes and 97 normal eyes were included. The maximum externally oblique border tissue (EOBT) length was measured by using enhanced depth imaging SD-OCT as well as focal LC defect size. Circumferential MvD width and height ratio were measured using OCT angiography., Results: Significant correlations were found among the locations of focal LC defect, MvD and maximum EOBT length. The mean absolute locational difference was 29.1° (95% CI, -47.6 to 105.7) between focal LC defect and MvD, 10.0° (95% CI, -79.4 to 99.4) between focal LC defect and maximum EOBT length, and 10.6° (95% CI, -71.1 to 92.3) between MvD and maximum EOBT length. In multivariate logistic regression analysis, a worse VF defect was significantly associated with the presence of focal LC defects and MvDs (P < .002; P = .002, respectively). MvD circumferential width was associated with glaucoma severity (R = -0.66, P < .001), whereas focal LC defect size and MvD height ratio were associated with maximum EOBT length (R = 0.48, P < .001; R = 0.65, P < .001, respectively) and AL (R = 0.53, P < .001; R = 0.52, P < .001, respectively)., Conclusions: There was a topographical correlation among the locations of focal LC defect, MvD and maximum border length. In addition, the presence of focal LC defect and MvD were also strongly associated with glaucoma severity. Thus, it is thought that focal LC defect and MvD may be biomarkers that reflect glaucoma severity especially at the location of maximum border tissue elongation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

An array of amorphous tin oxide (a-SnO x ) nanohelixes (NHs) was fabricated on copper foil as an electrode for Na-ion batteries via the oblique angle deposition method, a solution- and surfactant-free process. The combination of the amorphous phase SnO x with a low oxidation number and its vertically aligned NH geometry with a large surface area and high porosity, which facilitate Na-ion dynamics and accommodate the volume changes, enabled a reversible capacity of up to 915 mA h g -1 after 50 cycles, fast rate capability with 48.1% retention at 2 A g -1 , and high stability, which are superior to those of crystalline nanoparticle-based electrodes.

We studied the energy expenditure of isometric contractions using both right-ventricular (RV) and left-ventricular (LV) trabeculae isolated from the rat heart. The energy expenditure under isometric contraction presents entirely as heat liberation. Preparations were challenged to perform at various rates of energy demand while accounting for their inevitable time-dependent decline of performance. They were electrically stimulated to contract at 37 °C with a frequency order (between 0.1 Hz and 10 Hz) dictated by a fully-balanced Latin-Square experimental design. We measured, simultaneously, their stress production and heat output. As functions of stimulus frequency, active stress and heat were not significantly different between RV and LV trabeculae. However, contraction kinetics, indexed as the maximal rate of rise and fall of twitch, were lower in the LV trabeculae. The ratio of heat to stress was greater in the LV trabeculae, suggesting that the economy of contraction of the LV trabeculae is lower. Their lower economy became more pronounced at high stimulus frequencies. Our results allow us to assess whether slowing of kinetics is a causative mechanism for improvement of economy of contraction.

Purpose: To compare the local distribution of prelaminar and neuroretinal rim (NRR) thickness between eyes with nonarteritic anterior ischemic optic neuropathy (NAION) and normal tension glaucoma (NTG) using enhanced depth imaging spectral-domain optical coherence tomography (OCT)., Methods: This cross-sectional study included pairs of NAION and NTG patients, and controls. We measured the central prelaminar thickness; Bruch's membrane opening (BMO)-horizontal (HRW), minimal (MRW), and vertical rim widths (VRW), and vertical/horizontal thicknesses at knee of curve at rising curvature of the cup wall. HV ratio was calculated as BMO-HRW/BMO-VRW. The six thicknesses and their differences were compared., Results: We had 12 pairs, with comparable visual field loss and retinal nerve fiber layer (RNFL) thickness between NAION and NTG. Within the optic nerve head (ONH), BMO-MRW, BMO-HRW, horizontal width at the knee of curve, and central prelaminar tissue showed significantly larger values in NAION compared to NTG (P < 0.05). The difference of NRR thickness between NAION and NTG increased in a centripetal manner, being maximum at the knee of curve. The mean HV ratio was 1.63 in NAION, 0.83 in NTG, and 1.06 in controls (P < 0.001). OCT showed disproportionately less altered prelaminar tissue in NAION., Conclusions: NAION and NTG showed significantly different distributions of prelaminar and NRR tissue thicknesses despite similar RNFL thicknesses, with the maximal difference being the horizontal cup wall thickness at the knee of curve. Sparing of prelaminar tissue loss characterized the ONH in NAION. OCT might aid in differential diagnosis based on local variation in thinning patterns.

Force enhancement (FE) is a phenomenon that is present in skeletal muscle. It is characterized by progressive forces upon active stretching-distinguished by a linear rise in force-and enhanced isometric force following stretching (residual FE (RFE)). In skeletal muscle, non-cross-bridge (XB) structures may account for this behaviour. So far, it is unknown whether differences between non-XB structures within the heart and skeletal muscle result in deviating contractile behaviour during and after eccentric contractions. Thus, we investigated the force response of intact cardiac trabeculae during and after isokinetic eccentric muscle contractions (10% of maximum shortening velocity) with extensive magnitudes of stretch (25% of optimum muscle length). The different contributions of XB and non-XB structures to the total muscle force were revealed by using an actomyosin inhibitor. For cardiac trabeculae, we found that the force-length dynamics during long stretch were similar to the total isometric force-length relation. This indicates that no (R)FE is present in cardiac muscle while stretching the muscle from 0.75 to 1.0 optimum muscle length. This finding is in contrast with the results obtained for skeletal muscle, in which (R)FE is present. Our data support the hypothesis that titin stiffness does not increase with activation in cardiac muscle.

This is the first study to investigate the impact of a second fibula flap or a soft tissue flap combined with bridging plate for a repeated segmental mandibulectomy reconstruction on flap outcomes in head and neck cancer patients. A retrospective comparative analysis (2007-2016) of 61 patients who underwent a second segmental mandibulectomy was performed. 20 patients underwent a fibula flap reconstruction whereas 41 had a soft tissue flap and plate reconstruction. No significant difference was seen in the operative time, total hospital stay, flap loss, re-exploration rates, plate exposure rate, or recipient site infection rate. On multivariate analysis, patients reconstructed with a soft tissue flap and bridging plate (odds ratio (OR) 3.997; 95% confidence interval (CI), 1.046-15.280, p = 0.043) and complications developed in previous surgery (OR 4.792; 95% CI, 1.120-20.493, p = 0.035) were shown to be independent predictors of a prolonged nasogastric tube dependence. The utilization of a soft tissue flap with plate is associated with comparative results of acute complication rate within 1 week, recipient site infection rate, and plate exposure rate to free fibula flaps alone. Free fibula flaps may result in a decreased risk for prolonged tube dependence compared to free soft tissue flap reconstructions.

When exposed to an abrupt stretch, cardiac muscle exhibits biphasic active force enhancement. The initial, instantaneous, force enhancement is well explained by the Frank-Starling mechanism. However, the cellular mechanisms associated with the second, slower phase remain contentious. This review explores hypotheses regarding this "slow force response" with the intention of clarifying some apparent contradictions in the literature. The review is partitioned into three sections. The first section considers pathways that modify the intracellular calcium handling to address the role of the sarcoplasmic reticulum in the mechanism underlying the slow force response. The second section focuses on extracellular calcium fluxes and explores the identity and contribution of the stretch-activated, non-specific, cation channels as well as signalling cascades associated with G-protein coupled receptors. The final section introduces promising candidates for the mechanosensor(s) responsible for detecting the stretch perturbation., (© 2019 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Rare pain-insensitive individuals offer unique insights into how pain circuits function and have led to the development of new strategies for pain control. We investigated pain sensitivity in humans with WAGR (Wilms tumor, aniridia, genitourinary anomaly, and range of intellectual disabilities) syndrome, who have variably sized heterozygous deletion of the 11p13 region. The deletion region can be inclusive or exclusive of the brain-derived neurotrophic factor (BDNF) gene, a crucial trophic factor for nociceptive afferents. Nociceptive responses assessed by quantitative sensory testing demonstrated reduced pain sensitivity only in the WAGR subjects whose deletion boundaries included the BDNF gene. Corresponding behavioral assessments were made in heterozygous Bdnf knockout rats to examine the specific role of Bdnf. These analogous experiments revealed impairment of Aδ- and C-fiber-mediated heat nociception, determined by acute nociceptive thermal stimuli, and in aversive behaviors evoked when the rats were placed on a hot plate. Similar results were obtained for C-fiber-mediated cold responses and cold avoidance on a cold-plate device. Together, these results suggested a blunted responsiveness to aversive stimuli. Our parallel observations in humans and rats show that hemizygous deletion of the BDNF gene reduces pain sensitivity and establishes BDNF as a determinant of nociceptive sensitivity.

Purpose: Subthreshold binge-eating disorder (BED) symptoms can lead to additive physical and psychological health challenges and may put youth at risk for developing BED during the early adulthood. We examined the implementation of a condensed dialectical behavior therapy (DBT) skills intervention for subthreshold binge-eating behaviors in adolescents., Methods: Fifteen 14-18 years old participated in a 10-week DBT skills group, which experientially introduced mindfulness, distress tolerance, emotion regulation, and interpersonal effectiveness skills in the context of emotionally driven overeating behaviors. Adolescents and caregivers completed measures of emotional eating and binge-eating behaviors at baseline and post-intervention, including the Eating Disorder Examination Questionnaire and Emotional Eating Scale for Children and Adolescents. Eleven participants were retained at 3-month follow-up., Results: Descriptive statistics were compared at all three time points. Results suggested a reduction in emotional eating and binge-eating behaviors based on youth self-report and caregiver report. Acceptability ratings of the treatment were high among participants completing the intervention., Conclusions: Using DBT skills to target emotionally driven overeating behaviors in youth may be useful in the treatment of subthreshold BED behaviors and potentially deter future development of full-criteria BED., Level of Evidence: Level IV, uncontrolled pilot trial.

In the late 19th century, Otto Frank presented a diagram (Frank O. Z Biol 37: 483-526, 1899) showing that cardiac end-systolic pressure-volume relations are dependent on the mode of contraction: one for isovolumic contractions that locate above that for afterloaded ejecting contractions. Conflicting results to Frank's have been subsequently demonstrated in various species, both within and among preparations, ranging from the whole hearts to single myocytes, showing a single pressure-volume or force-length relation that is independent of the mode of contraction. Numerous explanations for these conflicting results have been proposed but are mutually contradictory and hence unsatisfying. The present study aimed to explore how these conflicting findings can be reconciled. We thus explored the cardiac force-length relation across a wide spectrum of both preloads and afterloads, encompassing the physiological working range. Experiments were performed using isolated ventricular trabeculae at physiological temperature and stimulus frequency. The force-length relation obtained from isometric contractions was indeed located above a family of those obtained from shortening contractions. Low preload conditions rendered the relation contraction mode independent. High afterload conditions also showed a comparable effect. Our exploration allowed us to reveal the loading conditions that can explain the apparent single, contraction mode-independent, force-length relation that is in contrast with that presented by Frank. Resolving this century-old cardiac conundrum highlights the caution that must be taken when using the end-systolic force-length relation to illustrate as well as to understand the concepts of the Frank-Starling law of the heart, "potential energy," and cardiac contractility. NEW & NOTEWORTHY Our exploration of the cardiac force-length relation under wide ranges of preload and afterload has allowed us to reconcile conflicting results in the literature regarding its length dependency. We show that the relation is dependent on the mode of contraction but can appear to be otherwise under certain conditions. This finding highlights the need for caution when using the force-length relation to understand key concepts in cardiac physiology.

Adipose‑derived stem cells (ADSCs) and bone marrow‑derived stem cells (BMSCs) are considered to be prospective sources of mesenchymal stromal cells (MSCs), that can be used in cell therapy for atherosclerosis. The present study investigated whether ADSCs co‑cultured with M1 foam macrophages via treatment with oxidized low‑density lipoprotein (ox‑LDL) would lead to similar or improved anti‑inflammatory effects compared with BMSCs. ADSCs, peripheral blood monocytes, BMSCs and ox‑LDL were isolated from ten coronary heart disease (CHD) patients. After three passages, the supernatants of the ADSCs and BMSCs were collected and systematically analysed by liquid chromatography‑quadrupole time‑of‑flight‑mass spectrometry (6530; Agilent Technologies, Inc., Santa Clara, CA, USA). Cis‑9, trans‑11 was deemed to be responsible for the potential differences in the metabolic characteristics of ADSCs and BMSCs. These peripheral blood monocytes were characterized using flow cytometry. Following peripheral blood monocytes differentiation into M1 macrophages, the formation of M1 foam macrophages was achieved through treatment with ox‑LDL. Overall, 2x106 ADSCs, BMSCs or BMSCs+cis‑9, trans‑11 were co‑cultured with M1 foam macrophages. Anti‑inflammatory capability, phagocytic activity, anti‑apoptotic capability and cell viability assays were compared among these groups. It was demonstrated that the accumulation of lipid droplets decreased following ADSCs, BMSCs or BMSCs+cis‑9, trans‑11 treatment in M1 macrophages derived from foam cells. Consistently, ADSCs exhibited great advantageous anti‑inflammatory capabilities, phagocytic activity, anti‑apoptotic capability activity and cell viability over BMSCs or BMSCs+cis‑9, trans‑11. Additionally, BMSCs+cis‑9, trans‑11 also demonstrated marked improvement in anti‑inflammatory capability, phagocytic activity, anti‑apoptotic capability activity and cell viability in comparison with BMSCs. The present results indicated that ADSCs would be more appropriate for transplantation to treat atherosclerosis than BMSCs alone or BMSCs+cis‑9, trans‑11. This may be an important mechanism to regulate macrophage immune function.

Purpose: To evaluate whether optic nerve head (ONH) tilt has relations with the visual field (VF) defect in myopic normal tension glaucoma (NTG)., Materials and Methods: Comparisons of variables were performed between less and more advanced VF defect groups in bilateral myopic NTG. Vertical, horizontal, maximal ONH tilt angles and angular location of maximal ONH tilt were measured using fundus photography and spectral-domain optical coherence tomography. Logistic regression analysis was performed to evaluate variables associated with more advanced VF defect in bilateral myopic NTG., Results: In total, 112 patients who have bilateral myopic NTG were included. Significant correlation was found between horizontal ONH tilt angle and angular location of maximal ONH tilt (R=0.45; P<0.001). In logistic regression analysis, a larger number of medications, greater horizontal ONH tilt, and greater angular location of maximal ONH tilt were associated with more advanced VF defect in myopic NTG (P=0.004, 0.014, 0.037, respectively). The location of VF defect was associated with the horizontal ONH tilt direction and angular location of maximal ONH tilt (κ=0.63, P<0.001; κ=0.48, P<0.001, respectively)., Conclusions: The horizontal ONH tilt and angular location of maximal ONH tilt correlated with the severity and location of VF defects in myopic NTG eyes.

Self-assembled Ni(OH) 2 nanosheet-decorated hierarchical flower-like MnCo 2 O 4.5 nanoneedles were synthesized via a cost-effective and facile hydrothermal strategy, aiming to realize a high-capacity advanced electrode of a battery-supercapacitor hybrid (BSH) device. It is demonstrated that the as-synthesized hierarchical flower-like MnCo 2 O 4.5 @Ni(OH) 2 -nanosheet electrode exhibits a high specific capacity of 318 mAh g -1 at a current density of 3 A g -1 and still maintains a capacity of 263.5 mAh g -1 at a higher current density of 20 A g -1 , with an extremely long cycle lifespan of 87.7% capacity retention after 5000 cycles. Moreover, using the unique core-shell structure as the cathode and hollow Fe 2 O 3 nanoparticles/reduced graphene oxide as the anode, the BSH device delivers a high energy density of 56.53 Wh kg -1 when the power density reaches 1.9 kW kg -1 , and there is an extraordinarily good cycling stability with the capacity retention rate of 90.4% after 3000 cycles. It is believed that the superior properties originate from desirable core-shell structures alleviating the impact of volume changes as well as the existence of two-dimensional Ni(OH) 2 nanosheets with more active sites, thereby improving the cycle stability and achieving ultrahigh capacity. These results will provide more access to the rational material design of diverse nanostructures toward high-performance energy storage devices.

In the arid Hexi Corridor of northwest China, vegetation cover plays a pivotal role in sustaining the unique terrestrial ecosystem. In this paper, vegetation changes during growth season from April to October were investigated through examining the trends in the Normalized Difference Vegetation Index (NDVI) across the Hexi region. Based on the GMMIS NDVI 3g.v1 dataset, NDVI trend and its dependency on elevation and land cover were analyzed for the period 1982-2015 according to multiple statistical tests. Results showed that NDVI exhibited a significantly increasing trend in ∼70% of the vegetated area, in contrast with a negative trend only in 2.85%. The resulting distinct groups with respect to decreasing, increasing and no trends presented significant differences in elevation and land cover composition, and the correlation between elevation, land cover and NDVI trend magnitude was subjected to precipitation and temperature change. The elevation and grassland cover were found to mainly account for variations in NDVI trend, and increase in elevation and various types of land cover excluding impervious and bare land would facilitate the trend magnitude. The dependency of NDVI trend on elevation and land cover was very vulnerable to increasing air temperature, which triggered an improvement in the vegetable activity to adapt to climate change, especially grass and forest. The contribution of crop and shrub to NDVI change was sensitive to precipitation trend change, but the crop was primarily influenced by human activities. The identified patterns of vegetation change would help to gain insights into the adapting mechanism of the fragile ecosystems in arid areas to changing environmental conditions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and Purpose: To investigate small vessel abnormalities in patients with cognitive impairment, we compared retinal microvascular alterations between patients with cognitive impairment related to Alzheimer's disease (ADCI) and those with subcortical vascular cognitive impairment (SVCI)., Methods: We prospectively recruited 29 amyloid-positive ADCI patients, 28 amyloid-negative SVCI patients that were confirmed by 11 C-PiB-PET scan and 34 individuals with normal cognition (NC). The three groups were compared in terms of retinal vascular variables (retinal fractal dimension, vascular caliber, tortuosity and branching angle) by using a semi-automated, computer-assisted analysis of digital fundus photographs. We also investigated the relationship between retinal variables and white matter hyperintensities (WMH) on MRI., Results: Compared to NC individuals, the SVCI patients had smaller total and arteriolar fractal dimensions, whereas there was no significant difference of fractal dimension between ADCI and NC. Other retinal variables did not differ among the three groups. A significant correlation existed between fractal dimension and WMH volume., Conclusions: Retinal microvascular alterations, especially retinal fractal dimension, may be useful markers that reflect cerebral microvascular changes in patients with SVCI as opposed to ADCI, who had no definite difference in retinal variables compared to the NC group., (Copyright © 2018. Published by Elsevier B.V.)

Objective: Maxillofacial fractures with concomitant laryngeal injuries put both the quality and maintenance of life in jeopardy. Because of its low incidence, it is often overlooked in the clinical setting. The purpose of this study is to review the incidence, clinical presentations, managements, and outcomes of these patients., Methods: A retrospective analysis of medical records from 2008 to 2015 was conducted at a single institute. A case series (n = 12, which contributed 22.2% of laryngeal injuries in our institute) of these patients was presented, and propensity score matching was applied for further statistical analysis., Results: When comparing patients who sustained maxillofacial fractures with concomitant laryngeal injuries with patients with only maxillofacial fractures and no laryngeal injuries, subcutaneous emphysema (83.3% vs 4.2%, P < 0.001), neck pain (75.0% vs 6.3%, P < 0.001), dyspnea (75.0% vs 0%, P < 0.001), hoarseness (41.7% vs 0%, P < 0.001), neck swelling (66.7% vs 4.2%, P = 0.012), stridor (16.7% vs 0%, P = 0.037), hemoptysis (16.7% vs 0%, P = 0.037), and thoracic trauma (58.3% vs 10.4%, P = 0.001) all showed significant differences. The length of intensive care unit stay (7.42 days vs 3.21 days, P = 0.008), ventilator use (66.7% vs 18.8%, P = 0.002), and tracheostomy (58.3% vs 0%, P < 0.001) were also significantly different., Conclusions: A significant portion of laryngeal injuries is concurrent with maxillofacial fractures. As a craniofacial surgeon, we should be alert to the signs of laryngeal injury. Diagnosis of laryngeal injuries should be established before definitive surgery for maxillofacial fractures.

Purpose: To evaluate changes in the peripapillary retinal nerve fiber layer (RNFL) thicknesses using spectral-domain optical coherence tomography (SD-OCT) in hydroxychloroquine (HCQ) users., Methods: The medical records of HCQ users were retrospectively reviewed. In these HCQ users, an automated perimetry, fundus autofluorescence photography, and SD-OCT with peripapillary RNFL thickness measurements were performed. The peripapillary RNFL thicknesses were compared between the HCQ users and the control groups. The relationships between the RNFL thicknesses and the duration or cumulative dosage of HCQ use were analyzed., Results: This study included 77 HCQ users and 20 normal controls. The mean duration of HCQ usage was 63.6 ± 38.4 months, and the cumulative dose of HCQ was 528.1 ± 3.44 g. Six patients developed HCQ retinopathy. Global and six sectoral RNFL thicknesses of the HCQ users did not significantly decrease compared to those of the normal controls. No significant correlation was found between the RNFL thickness and the duration of use or cumulative dose. The eyes of those with HCQ retinopathy had temporal peripapillary RNFL thicknesses significantly greater than that of normal controls., Conclusions: The peripapillary RNFL thicknesses did not change in the HCQ users and did not correlate with the duration of HCQ use or cumulative doses of HCQ. RNFL thickness is not a useful biomarker for the early detection of HCQ retinal toxicity., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2018 The Korean Ophthalmological Society.)

Brain-derived neurotrophic factor (BDNF) is a key neuropeptide in the central regulation of energy balance. The Bdnf gene contains nine promoters, each producing specific mRNA transcripts that encode a common protein. We sought to assess the phenotypic outcomes of disrupting BDNF production from individual Bdnf promoters. Mice with an intact coding region but selective disruption of BDNF production from Bdnf promoters I, II, IV, or VI (Bdnf-e1 -/- , -e2 -/- , -e4 -/- , and -e6 -/- ) were created by inserting an enhanced green fluorescent protein-STOP cassette upstream of the targeted promoter splice donor site. Body composition was measured by MRI weekly from age 4 to 22 wk. Energy expenditure was measured by indirect calorimetry at 18 wk. Food intake was measured in Bdnf-e1 -/- and Bdnf-e2 -/- mice, and pair feeding was conducted. Weight gain, lean mass, fat mass, and percent fat of Bdnf-e1 -/- and Bdnf-e2 -/- mice (both sexes) were significantly increased compared with wild-type littermates. For Bdnf-e4 -/- and Bdnf-e6 -/- mice, obesity was not observed with either chow or high-fat diet. Food intake was increased in Bdnf-e1 -/- and Bdnf-e2 -/- mice, and pair feeding prevented obesity. Mutant and wild-type littermates for each strain (both sexes) had similar total energy expenditure after adjustment for body composition. These findings suggest that the obesity phenotype observed in Bdnf-e1 -/- and Bdnf-e2 -/- mice is attributable to hyperphagia and not altered energy expenditure. Our findings show that disruption of BDNF from specific promoters leads to distinct body composition effects, with disruption from promoters I or II, but not IV or VI, inducing obesity.

Background: The current upper limits of normal (ULN) for serum alanine aminotransferase (ALT) are increasingly challenged. We aimed to re-evaluate the ULN for ALT and assess the potential impact on the classification of natural course of chronic hepatitis B virus (HBV) infection in children., Methods: Laboratory data obtained from three hospitals in China were retrospectively analysed. In total, 2054 children with chronic HBV infection and 8149 healthy children at age ≤18 years were included in the study., Results: Age-specific and gender-specific ULNs for ALT, at averages of 30 U/L for boys and 24 U/L for girls, were calculated from the data of healthy children. Using the revised ULNs vs. the current ULNs (40-50 U/L), 31-60% vs. 9-17% of the 2054 HBV-infected children had an abnormal result as seen in their ALT baseline analysis, and the highest abnormality rate was seen in the infants. Data of 516 HBV-infected children were applied for the classification of clinical phase, 28.8% vs. 19.8% of the children were classified into the phases of hepatitis B e antigen (HBeAg-)positive/negative hepatitis. During a median follow-up of 62 months, 39 of 153 children underwent HBeAg seroconversion, whereas 3 of them had persistently "normal" ALT, according to the current ULN., Conclusions: The revision of ULN for ALT in children substantially impacts the classification of the natural course of chronic HBV infection. Mild ALT fluctuation is common during the stage childhood, suggesting a need to rethink the current conceptions of immune tolerance and natural course of chronic HBV infection in the children.

Objective: To explore the value of the intraoperative transesophageal echocardiography during the aortic valve reconstruction. Methods: The echocardiographic features were retrospectively summarized in 19 patients (male: 15 cases; female: 4 cases; age ranged from 12 to 65 years, mean age: 37.7 years) with aortic valve reconstruction at Beijing Anzhen Hospital between October 2014 and October 2016. Results: The findings of the neo-aortic valve on the transesophageal echocardiography included the slightly thickened and hyperechogenicity of the commission, especially the central coaptation point of the neo-valve. Trace aortic regurgitation was noted in 9 cases after operation, mild aortic regurgitation in 1 case and no aortic regurgitation in 9 cases. The velocity of the aortic valve increased significantly in 2 cases. Compared with pre-operation, the diameter of ascending aorta[(32.7±6.1) mm vs (36.4±6.3) mm, P <0.001]and the inner diameter of left ventricle[(48.3±6.1) mm vs (59.1±7.3) mm, P <0.001]decreased significantly after operation, the coaptation length of aortic valve[(6.6±1.3) mm vs (2.2±0.7) mm, P <0.001]significantly increased than that of pre-operation. The mean immediate velocity after operation (175 cm/s) was slightly higher than that (165 cm/s) of 3-month follow-up after surgery, but with no significant difference ( P =0.367). Severe aortic regurgitation was found 15 days after operation in 1 case and 12 months after operation in 2 cases. Conclusion: Intraoperative transesophageal echocardiography is a useful tool to evaluate the result of the aortic valve reconstruction.

Bacillus species are commonly used as probiotics in the poultry feed industry for preventing infectious diseases and improving productivity by altering gastrointestinal microbiota. The growth parameters of Bacillus subtilis for surfactin production in fermentation and the benefits of surfactin on broiler chickens remain unclear. In this study, we examined the growth parameters of B. subtilis in fermentation and evaluated the effects of surfactin from B. subtilis-fermented products on Clostridium perfringens-induced necrotic enteritis and growth performance in broilers. Results showed that the highest viable biomass of B. subtilis was observed at 10% molasses and 2% yeast supplementation during fermentation. The 4- and 6-day fermented B. subtilis products were heat-, acid- and bile-resistant. Furthermore, the 4-day fermented B. subtilis products with the highest surfactin concentration showed the maximal antimicrobial activity against pathogens, including Escherichia coli, Staphylococcus aureus, Salmonella typhimurium and C. perfringens. Dietary B. subtilis-fermented product supplementation in broilers significantly improved intestinal morphology and necrotic lesions under C. perfringens challenge. Bacillus subtilis treatments could enhance broiler productivity, as well as promote bone quality and intestinal morphology. These results together indicate that B. subtilis-fermented products containing surfactin have potential for the development as feed additives and use as possible substitutes for antibiotics to treat C. perfringens in the poultry industry., (© 2018 Blackwell Verlag GmbH.)

Time-restricted feeding (TRF) limits the duration of food availability without altering diet composition and can combat obesity in humans and mice. For this study we evaluated the effect of timing of food access during a TRF protocol on weight gain, adiposity, and inflammation. Young male C57BL/6 mice were placed on a high-fat (HF) diet (45% fat) for 8 weeks. Food access was unrestricted (HF) or restricted to 6 h per day, either for the first half (HF-early) or the second half (HF-late) of the active phase to resemble a window of time for food consumption early or late in the day in a human population. Weight, obesity-associated parameters, and inflammation were measured. TRF reduced weight gain over the 8-week period in mice consuming the same high-fat diet. Consistent with decreased weight gain in the TRF groups, body fat percentage, liver triglycerides, and plasma leptin and cholesterol levels were reduced. Adipose tissue inflammation, measured by CD11b + F4/80 + macrophage infiltration, was reduced in both TRF groups, but systemic tumor necrosis factor-α was increased in all groups consuming the high-fat diet. The HF-late group gained more weight than the HF-early group and had increased insulin resistance, while the HF-early group was protected. Therefore, a TRF protocol is beneficial for weight management when a high-fat diet is consumed, with food consumption earlier in the day showing greater health benefits. However, increased inflammatory markers in the TRF groups suggest that diet components can still increase inflammation even in the absence of overt obesity.

Alström Syndrome is a ciliopathy associated with obesity, insulin resistance/type 2 diabetes mellitus, cardiomyopathy, retinal degeneration, hearing loss, progressive liver and kidney disease, and normal cognitive function. ALMS1, the protein defective in this disorder, localizes to the cytoskeleton, microtubule organizing center, as well as the centrosomes and ciliary basal bodies and plays roles in formation and maintenance of cilia, cell cycle regulation, and endosomal trafficking. Kidney disease in this disorder has not been well characterized. We performed comprehensive multisystem evaluations on 38 patients. Kidney function decreased progressively; eGFR varied inversely with age (p = 0.002). Eighteen percent met the definition for chronic kidney disease (eGFR < 60 mL/min/1.73 m 2 and proteinuria); all were adults with median age of 32.8 (20.6-37.9) years. After adjusting for age, there were no significant associations of kidney dysfunction with type 2 diabetes mellitus, dyslipidemia, hypertension, cardiomyopathy or portal hypertension suggesting that kidney disease in AS is a primary manifestation of the syndrome due to lack of ALMS1 protein. Approximately one-third of patients had hyperechogenicity of the renal parenchyma on imaging. While strict control of type 2 diabetes mellitus may decrease kidney-related morbidity and mortality in Alström syndrome, identification of novel targeted therapies is needed., (Copyright © 2018. Published by Elsevier Inc.)

Purpose: We investigated the relationship between visual field (VF) defect pattern and deep optic nerve head (ONH) morphology in open angle glaucoma (OAG) eyes using spectral-domain optical coherence tomography (SD-OCT)., Methods: Of 278 OAG eyes, 169 with and 55 without externally oblique border tissue (EOBT) were included in the final analysis. Enhance depth imaging SD-OCT was used to measure the deep ONH parameters, such as EOBT length, ONH tilt angle, and optic canal (OC) obliqueness. The extents and locations of the maximum deep ONH parameters were explored according to VF pattern in OAG eyes., Results: OAG eyes with EOBT showed longer axial length (AL; 25.6 vs. 24.4 mm; P < 0.001) and greater superior VF defects (67.5% vs. 49.1%; P = 0.02) compared to OAG eyes without EOBT. Multivariate logistic regression analysis revealed that relatively inferior location of maximum deep ONH parameters was associated with superior hemifield defects dominant in OAG (P < 0.001 in all parameters). In addition, the locations of maximum deep ONH parameters were consistent with dominant VF defect locations in OAG eyes with AL < 24.5 mm. The presence of paracentral scotoma in OAG was associated with worse mean deviation (MD) and relatively inferior location of deep ONH parameters., Conclusions: The locations of maximum deep ONH parameters were associated with the location of dominant VF defects and presence of paracentral scotoma in OAG eyes.

Highly transparent and superhydrophilic sapphire with surface antireflective subwavelength structures were prepared by wet etching using colloidal monolayer silica masks. The film thicknesses of the silica masks were adjusted by the volume concentrations of polystyrene spheres. The evolution of etching morphologies of sapphire was studied, and antireflective concave pyramid nanoarrays on sapphire substrates were designed by calculation and were then prepared. The transmission and wettability of as-obtained patterned sapphire substrates were also investigated. As for sapphire with optimum surface concave micropyramid arrays, average visible transmittance can reach 91.7%, which is apparently higher than that of flat sapphire (85.5%). Moreover, the concave pyramid arrays can significantly increase the surface hydrophilicity of sapphire, exhibiting a water contact angle of 12.6° compared with 62.7° of flat sapphire. The proposed method can be an excellent strategy for preparing antireflective and self-cleaning concave micropyramid subwavelength structures on sapphire without complicated equipment and expensive raw materials.

First principles calculation and Boltzmann transport theory have been used to reveal the effects of trigonal deformation on electronic structure and thermoelectric properties of bulk bismuth. It is found that the semimetal-semiconductor transition would happen at the critical c/a points of 2.41 and 2.51, and that such a transition should be ascribed to the opposite changes of band edges at T and L points during trigonal deformation. Calculations also reveal that trigonal deformation has an important effect on various temperature-dependent thermoelectric properties, and that carrier density plays a decisive role in determining the magnitude of Seebeck coefficient and figure of merit. The semimetal  →  semiconductor transition as a result of trigonal compression with the decrease of c/a fundamentally induces the best performance of the thermoelectric properties of bismuth at the c/a ratio of 2.45. The present results agree well with experimental observations in the literature, and provide a deep understanding of the intrinsic relationship between trigonal deformation, band structure, and thermoelectric properties of bismuth.

Background: The previous study showed that mycophenolic acid (MPA) synergizing with lipopolysaccharide (LPS) promoted interleukin (IL)-1β release, but the mechanism is unclear. This study aimed to investigate the mechanism of MPA synergizing with LPS to induce IL-1β release., Methods: Undiluted human blood cells, THP-1 human myeloid leukemia mononuclear cells (THP-1) cells, or monocytes were stimulated with LPS and treated with or without MPA, and the supernatant IL-1β was detected by enzyme-linked immunosorbent assay. The mRNA levels of IL-1β were detected by real-time quantitative polymerase chain reaction. The intracellular protein levels of nuclear factor kappa B (NF-κB) phospho-p65 (p-p65), precursor interleukin-1β (pro-IL-1β), NOD-like receptor pyrin domain containing-3 (NLRP3), and cysteine aspartic acid-specific protease-1 (caspase-1) p20 in THP-1 cell were measured by Western blot., Results: The MPA alone failed to induce IL-1β, whereas MPA synergized with LPS to increase IL-1β in a dose-dependent manner (685.00 ± 20.00 pg/ml in LPS + 5 μmol/L MPA group, P = 0.035; 742.00 ± 31.58 pg/ml in LPS + 25 μmol/L MPA group, P = 0.017; 1000.00 ± 65.59 pg/ml in LPS + 75 μmol/L MPA group, P = 0.024; versus 408.00 ± 35.50 pg/ml in LPS group). MPA alone has no effect on the IL-1β mRNA expression, LPS induced the expression of IL-1β mRNA 2761 fold, and LPS + MPA increased the IL-1β expression 3018 fold, which had the same effect with LPS group (P = 0.834). MPA did not affect the intracellular NF-κB p-p65 and pro-IL-1β protein levels but activated NLRP3 inflammasome. Ac-YVAD-cmk blocked the activation of caspase-1 and subsequently attenuated IL-1β secretion (181.00 ± 45.24 pg/ml in LPS + MPA + YVAD group vs. 588.00 ± 41.99 pg/ml in LPS + MPA group, P = 0.014)., Conclusions: Taken together, MPA synergized with LPS to induce IL-1β release via the activation of caspase-1, rather than the enhanced production of pro-IL-1β. These findings suggested that patients immunosuppressed with mycophenolate mofetil may have overly activated caspase-1 during infection, which might contribute to a more sensitive host defense response to invading germs., Competing Interests: There are no conflicts of interest

Purpose: We evaluated the applicability of the ISNT rule using Bruch's membrane opening minimum rim width (BMO-MRW) in healthy eyes and eyes with normal tension glaucoma (NTG)., Materials and Methods: In total, 124 healthy eyes and 136 NTG eyes were analyzed. Using 2-dimensional disc photographs, neuroretinal rim (NRR) thickness was measured at the superior, inferior, nasal, and temporal sides of the optic disc. Using spectral domain-optical coherence tomography, BMO-MRW was measured at the same regions. We compared the applicability of the ISNT rule in healthy and NTG eyes between these 2 methods. If the NRR was not clearly distinguished on disc photographs, the eye was classified into the "indistinguishable NRR" group and we only tested applicability of the ISNT rule using BMO-MRW., Results: The specificity of "violation of the ISNT rule" for the diagnosis of glaucoma was higher when BMO-MRW was used (66.3%) than using disc photographs (42.2%), whereas the sensitivity did not show a significant difference between the 2 methods (91.7% vs. 86.5%). Compared with eyes with distinguishable NRR (179 eyes), eyes with indistinguishable NRR (81 eyes) had higher axial length, more negative refractive error, and higher tilt ratio (P<0.001). The diagnostic ability of "violation of ISNT rule" using BMO-MRW was not significantly different between eyes with indistinguishable NRR and those with distinguishable NRR (P>0.05)., Conclusions: Application of the ISNT rule using BMO-MRW shows superiority in distinguishing between healthy and glaucomatous optic discs compared with disc photographs. The ISNT rule can be applied using BMO-MRW even when NRR is indistinguishable on disc photographs, such as in myopic tilted discs.

Background: Alström syndrome (AS), a monogenic form of obesity, is caused by recessive mutations in the centrosome- and basal body-associated gene ALMS1. AS is characterized by retinal dystrophy, sensory hearing loss, cardiomyopathy, childhood obesity, and metabolic derangements., Objective: We sought to characterize the endocrine and metabolic features of AS while accounting for obesity as a confounder by comparing patients with AS to body mass index (BMI)-matched controls., Methods: We evaluated 38 patients with AS (age 2 to 38 years) who were matched with 76 controls (age 2 to 48 years) by age, sex, race, and BMI. Fasting biochemistries, mixed meal test (MMT), indirect calorimetry, dual-energy X-ray absorptiometry, and MRI/magnetic resonance spectroscopy were performed., Results: Frequent abnormalities in AS included 76% obesity, 37% type 2 diabetes mellitus (T2DM), 29% hypothyroidism (one-third central, two-thirds primary), 3% central adrenal insufficiency, 57% adult hypogonadism (one-third central, two-thirds primary), and 25% female hyperandrogenism. Patients with AS and controls had similar BMI z scores, body fat, waist circumference, abdominal visceral fat, muscle fat, resting energy expenditure (adjusted for lean mass), free fatty acids, glucagon, prolactin, ACTH, and cortisol. Compared with controls, patients with AS were shorter and had lower IGF-1 concentrations (Ps ≤ 0.001). Patients with AS had significantly greater fasting and MMT insulin resistance indices, higher MMT glucose, insulin, and C-peptide values, higher HbA1c, and higher prevalence of T2DM (Ps < 0.001). Patients with AS had significantly higher triglycerides, lower high-density lipoprotein cholesterol, and a 10-fold greater prevalence of metabolic syndrome (Ps < 0.001). Patients with AS demonstrated significantly greater liver triglyceride accumulation and higher transaminases (P < 0.001)., Conclusion: Severe insulin resistance and T2DM are the hallmarks of AS. However, patients with AS may present with multiple other endocrinopathies affecting growth and development.

Background: Higher hepatitis B surface antigen (HBsAg) facilitates hepatitis C virus (HCV) clearance in patients with hepatitis B virus (HBV)/HCV co-infection. We investigated the effect of exogenous HBsAg on the inhibition of HCV replication mediated by natural killer (NK) cells., Methods: After isolated from peripheral blood of 42 chronic hepatitis B (CHB) patients and 16 healthy individuals, NK cells were co-cultured with HCV-infected Huh7 cells, respectively, with or without HBsAg. Three days later, the co-cultured supernatants were collected and HCV RNA levels were measured by real-time quantitative PCR. NKG2D, NKp46 and NKG2A expression levels were measured by flow cytometry. NKG2D on NK cells from CHB responsive subgroup was blocked and HCV RNA levels were examined again., Results: HCV RNA levels in the co-cultured system were significantly reduced by NK cells isolated from healthy donors (P < 0.01) but not from CHB patients. However, HCV RNA levels in CHB cultures were significantly decreased following HBsAg addition (P < 0.05), whereas no such effect was seen in control cultures. No significant difference was observed in basic NKG2D expression between the CHB patients and healthy donors. On NK cells from CHB patients, the expression of NKG2D was increased significantly by HBsAg stimulation (P < 0.01), and higher than that from healthy controls (P < 0.05). HCV RNA levels were increased significantly after the blockage of NKG2D on NK cells from responsive CHB patients in the co-cultured system (P < 0.05)., Conclusion: Exogenous HBsAg stimulated NKG2D expression on NK cells from CHB patients which inhibit HCV replication, suggesting that HBsAg may facilitate the clearance of HCV in patients with HBV/HCV co-infection., (Copyright © 2018. Published by Elsevier B.V.)

Purpose: To investigate the relationship between glaucomatous disc hemorrhage (DH) location with respect to the nasal or temporal margin of the retinal nerve fiber layer defect (RNFLD) and the direction of RNFLD widening., Materials and Methods: This is a retrospective, cross-sectional study. Patients with any documented episode of glaucomatous DH throughout the follow-up period, and definite RNFLD widening on retinal nerve fiber layer photographs were analyzed. The location of DH was recorded as either nasal or temporal, and the direction of RNFLD widening was investigated. The laterality of DH location on the RNFLD border and the direction of RNFLD widening were correlated with each other. We also compared clinical parameters between eyes with nasal versus temporal margin DHs., Results: We analyzed 123 eyes from 116 patients with definite widening of the RNFLD and glaucomatous DH at the border between the healthy and damaged retinal nerve fiber layer. The most common diagnosis was normal-tension glaucoma (109, 87.9%). The most frequent location of DH was the temporal margin of an inferotemporal RNFLD (75, 61.0%), and the most frequent pattern of change in RNFLD was temporal widening (89, 72.4%). The absolute congruency was 82.9% and the total congruency was 99.2%. No significant differences were identified between eyes with nasal versus temporal margin DHs., Conclusions: The lateral location of DH on the RNFLD border was highly congruent with the direction of RNFLD widening. This correspondence of laterality between DH development and progression of RNFLD may suggest an intimate structural relationship during the pathogenesis of DH, at the enlarging RNFLD border.

The Healthy Lifestyle Clinic (HLC) is an interdisciplinary weight management clinic conceived to address alarming rates of pediatric obesity and related comorbidities in the midsouth region of the United States. The clinical cohort presented is a subset of the 609 patients evaluated during the first 2 years of the HLC and comprises 380 patients with a minimum of 6 months of follow-up. The primarily non-Hispanic black (67.1%) cohort presented with severe obesity ( M zBMI = 2.52 ± 0.41) and particularly high rates of insulin resistance, among other comorbidities. This article offers insight into the challenges of intervening with a cohort of youth and their families, many with limited resources to support intensive behavioral and lifestyle changes. Our experiences implementing a weight management clinic with a diverse clinical cohort provide guidance for emerging programs and impetus to investigate environmental and cultural factors that contribute to high attrition in the treatment of pediatric obesity.

1α-Hydroxycholecalciferol (1α-OH-D3) is a vitamin D derivative. The objective of this study was to evaluate the effects of 1α-OH-D3 on the growth and the mRNA expression of vitamin D receptor (VDR) in the small intestine and kidney of chickens. A total of 240 males of one-day-old Ross 308 broilers was randomly assigned to 4 treatments with 5 replicates of 12 birds per replicate. Three levels of 1α-OH-D3 (1.25, 2.5, and 5 μg/kg) were added to a basal diet containing 0.50% calcium (Ca), 0.25% non-phytate phosphorus (NPP), and without supplemental cholecalciferol (vitamin D3). The control diet contained 1.00% Ca, 0.45% NPP, and 25 μg/kg cholecalciferol. Dietary 1α-OH-D3 levels linearly improved the average daily feed intake (ADFI), average daily gain (ADG), femur and tibia mineralization, and plasma Ca concentration, and retained Ca and total phosphorus (tP) amounts in broilers from 1 to 21 d of age (P < 0.05). In addition, 1α-OH-D3 also linearly up-regulated the mRNA expression levels of VDR in the duodenum as well as those of VDR and sodium-phosphate cotransporter NaPi-IIa and NaPi-IIc in the kidney of broilers (P < 0.05). However, 1α-OH-D3 did not affect the mRNA levels of 25-hydroxylase in the liver or NaPi-IIb in the duodenum (P > 0.05). No differences were observed in the ADFI, ADG, bone length, plasma mineral concentration, retained tP amount, or the mRNA levels of the above genes (except for VDR in the kidney) between the birds fed the diet with 5 μg/kg 1α-OH-D3 and the birds fed the control diet (P > 0.05). By contrast, the weight, ash weight, ash percentage, and Ca percentage of the bone, retained Ca amount, and the mRNA level of VDR in the kidney were lower in the birds fed the diet with 5 μg/kg 1α-OH-D3 than in the birds fed the control diet (P < 0.05). These data indicate that 1α-OH-D3 up-regulates the gene expression of VDR in the small intestine and kidney at the transcriptional level, thereby improving the growth performance and bone mineralization of broiler chickens from 1 to 21 d of age.

Four experiments were conducted in this study. Experiment 1 was carried out to examine mRNA expressions of nuclear vitamin D receptor (nVDR), membrane vitamin D receptor (mVDR), and type IIb sodium-phosphate cotransporter (NaPi-IIb) in the small intestine of broiler chickens. Experiments 2, 3, and 4 were implemented to evaluate effects of age, non-phytate phosphorus (NPP), and 25-hydroxycholecalciferol (25-OH-D3) on mRNA expressions of nVDR, mVDR, and NaPi-IIb in the duodenum of chickens. Results showed that mRNA expression levels of nVDR and NaPi-IIb were highest in the duodenum of 21-day-old broilers, lower in the jejunum, and lowest in the ileum. By contrast, no differences in mRNA expression levels of mVDR were detected among the duodenum, jejunum, and ileum. Age quadratically affected mRNA expressions of nVDR, mVDR, and NaPi-IIb in the duodenum and 25-hydroxylase in the liver of 7- to 42-day-old broilers, with the highest levels observed at 21 d of age. By contrast, age linearly decreased mRNA expression level of 1α-hydroxylase in kidneys. Dietary NPP levels quadratically affected mRNA expression levels of nVDR and mVDR in the duodenum and 25-hydroxylase in the liver of 21-day-old broilers. The highest mRNA expression levels of nVDR and mVDR and lowest mRNA level of 25-hydroxylase were observed at 0.55% NPP. mRNA expression level of NaPi-IIb linearly declined when dietary NPP levels increased from 0.25 to 0.65%. Addition of 12.5 μg/kg of 25-OH-D3 increased mRNA expression level of 1α-hydroxylase in kidneys and those of nVDR, mVDR, and NaPi-IIb in the duodenum of broilers compared with birds fed the diet without 25-OH-D3. These data indicate that mRNA expressions of nVDR and NaPi-IIb are highest in the duodenum, and the greatest mRNA levels of nVDR, mVDR, and NaPi-IIb are observed at 21 d of age. Dietary NPP levels quadratically increase mRNA expressions of nVDR and mVDR but linearly decrease NaPi-IIb mRNA level. 25-OH-D3 up-regulates the above gene transcription.

Purpose: To determine deep optic nerve head structure changes after transient intraocular pressure elevation during laser in situ keratomileusis (LASIK) for myopia., Methods: Enhanced depth imaging-optical coherence tomography was performed in each myopic eye that underwent LASIK surgery. Enhanced depth imaging-optical coherence tomography images were created at postoperative 1 day, 1 week, 2 weeks, and 1 month. Lamina cribrosa (LC) thickness, LC depth and prelaminar thickness at the superior, middle and inferior portions of the optic nerve head were measured by two investigators., Results: Forty eyes in 40 patients were included in the present study. During follow-up, there were no significant differences in prelaminar thickness or LC depth. The LC demonstrated increased thickness at postoperative 1 day at all three locations (superior, middle, and inferior) (p < 0.001, p < 0.001, p < 0.001, respectively). However, no significant changes were observed at postoperative 1 week, 2 weeks, and 1 month., Conclusions: The LC thickness could increase at 1 day after LASIK surgery. However, the thickness will gradually return to baseline morphology. Temporary intraocular pressure increase during LASIK does not appear to induce irreversible LC thickness changes., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2018 The Korean Ophthalmological Society.)

Key Points: Pulmonary arterial hypertension (PAH) triggers right ventricle (RV) hypertrophy and left ventricle (LV) atrophy, which progressively leads to heart failure. We designed experiments under conditions mimicking those encountered by the heart in vivo that allowed us to investigate whether consequent structural and functional remodelling of the ventricles affects their respective energy efficiencies. We found that peak work output was lower in RV trabeculae from PAH rats due to reduced extent and velocity of shortening. However, their suprabasal enthalpy was unaffected due to increased activation heat, resulting in reduced suprabasal efficiency. There was no effect of PAH on LV suprabasal efficiency. We conclude that the mechanism underlying the reduced energy efficiency of hypertrophied RV tissues is attributable to the increased energy cost of Ca 2+ cycling, whereas atrophied LV tissues still maintain normal mechano-energetic performance., Abstract: Pulmonary arterial hypertension (PAH) greatly increases the afterload on the right ventricle (RV), triggering RV hypertrophy, which progressively leads to RV failure. In contrast, the disease reduces the passive filling pressure of the left ventricle (LV), resulting in LV atrophy. We investigated whether these distinct structural and functional consequences to the ventricles affect their respective energy efficiencies. We studied trabeculae isolated from both ventricles of Wistar rats with monocrotaline-induced PAH and their respective Control groups. Trabeculae were mounted in a calorimeter at 37°C. While contracting at 5 Hz, they were subjected to stress-length work-loops over a wide range of afterloads. They were subsequently required to undergo a series of isometric contractions at various muscle lengths. In both protocols, stress production, length change and suprabasal heat output were simultaneously measured. We found that RV trabeculae from PAH rats generated higher activation heat, but developed normal active stress. Their peak external work output was lower due to reduced extent and velocity of shortening. Despite lower peak work output, suprabasal enthalpy was unaffected, thereby rendering suprabasal efficiency lower. Crossbridge efficiency, however, was unaffected. In contrast, LV trabeculae from PAH rats maintained normal mechano-energetic performance. Pulmonary arterial hypertension reduces the suprabasal energy efficiency of hypertrophied right ventricular tissues as a consequence of the increased energy cost of Ca 2+ cycling., (© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.)

Objective: PAX6 haploinsufficiency ( +/-) can occur due to mutations involving only PAX6 in patients with isolated aniridia or as contiguous gene deletions in patients with Wilms tumor, aniridia, genitourinary anomalies, and range of developmental and intellectual disabilities syndrome. Given the role of PAX6 in pineal development and circadian regulation, adolescents with PAX6+/- may experience sleep-wake disturbances. The purpose of this observational study was to explore sleep-related phenotypes in adolescents with PAX6+/-., Methods: This study compared sleep phenotypes of nine subjects with PAX6+/- (aged 10-19 years) with previously published data on healthy adolescents ( n = 25, aged 10-18 years). Subjects completed the Cleveland Adolescent Sleepiness Questionnaire (CASQ), Patient Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (v. 1.0; 8a), and PROMIS Sleep-Related Impairment (v. 1.0; 8b) Questionnaires and wore actigraphs for seven nights to record sleep patterns., Results: Total CASQ, PROMIS sleep-related impairment, and PROMIS sleep disturbance scores were not statistically different between the groups ( ps > .15). Actigraph data for lights off to sleep-onset time were found to be significantly higher in subjects with PAX6+/- versus the healthy comparison group (adjusted mean [95% confidence interval]: 20.1 min [8.1, 49.8] vs. 6.2 min [3.7, 10.4], respectively, p = .04)., Conclusion: Both adolescents with PAX6+/- and the healthy comparison group on average slept less than 8 hr/night, and overall sleep deprivation in adolescents may have masked differences between groups. This study used rare genetic disorders with biological vulnerability to sleep problems as a genotype-phenotype model. Knowledge of sleep-related phenotypes will assist in designing studies to manage sleep-related symptoms in adolescents.

Compared with conventional anti-reflective film, an anti-reflective sub-wavelength surface structure provides an ideal choice for a sapphire optical window especially in harsh environments. However, it is still a challenge to obtain a sapphire anti-reflective surface microstructure because of its high hardness and chemical inertness. In this paper, combined with optical simulation, we proposed a facile method based on the anodic oxidation of aluminum film and following epitaxial annealing. Al thin film was deposited on a sapphire substrate by magnetron sputtering, and anodic oxidation was then performed to prepare surface pore-like structures on the Al film. Followed by two-step annealing, both the anodic oxidized coating and underlying unoxidized Al film were transformed totally into alumina. The parameters of anodic oxidation were analyzed to obtain the optimal pore-like structures for the antireflection in the mid-infrared and visible spectrum regions, respectively. Finally, the optimized surface sub-wavelength nanostructure on sapphire can increase the transmittance by 7% in the wavelength range of 3000-5000 nm and can increase 13.2% significantly for visible spectrum region, respectively. Meanwhile, the surface wettability can be also manipulated effectively. The preparation of surface pore-like sub-wavelength structure by the annealing of anodic oxidized aluminum film on sapphire is a feasible, economical and convenient approach and can find the applications for various optoelectronic fields.

This study evaluated the effect of temperature on methane production by CO 2 reduction during microbial electrosynthesis (MES) with a mixed-culture biocathode. Reactor performance, in terms of the amount and rate of methane production, current density, and coulombic efficiency, was compared at different temperatures. The microbial properties of the biocathode at each temperature were also analyzed by 16S rRNA gene sequencing. The results showed that the optimum temperature for methane production from CO 2 reduction in MES with a mixed-culture cathode was 50°C, with the highest amount and rate of methane production of 2.06±0.13mmol and 0.094±0.01mmolh -1 , respectively. In the mixed-culture biocathode MES, the coulombic efficiency of methane formation was within a range of 19.15±2.31% to 73.94±2.18% due to by-product formation at the cathode, including volatile fatty acids and hydrogen. Microbial analysis demonstrated that temperature had an impact on the diversity of microbial communities in the biofilm that formed on the MES cathode. Specifically, the hydrogenotrophic methanogen Methanobacterium became the predominant archaea for methane production from CO 2 reduction, while the abundance of the aceticlastic methanogen Methanosaeta decreased with increased temperature., (Copyright © 2017. Published by Elsevier B.V.)

Pulmonary arterial hypertension (PAH) alters the geometries of both ventricles of the heart. While the right ventricle (RV) hypertrophies, the left ventricle (LV) atrophies. Multiple lines of clinical and experimental evidence lead us to hypothesize that the impaired stroke volume and systolic pressure of the LV are a direct consequence of the effect of pressure overload in the RV, and that atrophy in the LV plays only a minor role. In this study, we tested this hypothesis by examining the mechanoenergetic response of the atrophied LV to RV hypertrophy in rats treated with monocrotaline. Experiments were performed across multiple-scales: the whole-heart in vivo and ex vivo , and its trabeculae in vitro . Under the in vivo state where the RV was pressure-overloaded, we measured reduced systemic blood pressure and LV ventricular pressure. In contrast, under both ex vivo and in vitro conditions, where the effect of RV pressure overload was circumvented, we found that LV was capable of developing normal systolic pressure and stress. Nevertheless, LV atrophy played a minor role in that LV stroke volume remained lower, thereby contributing to lower LV mechanical work output. Concomitantly lower oxygen consumption and change of enthalpy were observed, and hence LV energy efficiency was unchanged. Our internally consistent findings between working-heart and trabecula experiments explain the rapid improvement of LV systolic function observed in patients with chronic pulmonary hypertension following surgical relief of RV pressure overload.

Soybean meal is the main vegetable protein source in animal feed. Soybean meal contains several anti-nutritional factors, which directly affect digestion and absorption of soy protein, thereby reducing growth performance and value in animals. Fermented soybean meal is rich in probiotics and functional metabolites, which facilitates soybean protein digestion, absorption and utilization in piglets. However, the mixed solid-state fermentation (SSF) conditions of soybean meal remain to be optimized. In this study, we investigated the optimal parameters for SSF of soybean meal by Lactobacillus species and Clostridium butyricum . The results showed that two days of fermentation was sufficient to increase the viable count of bacteria, lactic acid levels and degradation of soybean protein in fermented soybean meal at the initial moisture content of 50%. The pH value, lowering sugar content and oligosaccharides in fermented soybean meal, was significantly reduced at the initial moisture content of 50% after two days of fermentation. Furthermore, the exogenous proteases used in combination with probiotics supplementation were further able to enhance the viable count of bacteria, degradation of soybean protein and lactic acid level in the fermented soybean meal. In addition, the pH value and sugar content in fermented soybean meal were considerably reduced in the presence of both proteases and probiotics. Furthermore, the fermented soybean meal also showed antibacterial activity against Staphylococcus aureus and Escherichia coli . These results together suggest that supplementation of both proteases and probiotics in SSF improves the nutritional value of fermented soybean meal and this is suitable as a protein source in animal feed., (© 2018 Li-Wen Su et al.)

Background: Sequelae of inadequate orbital reconstruction include enophthalmos, hypoglobus, and diplopia. Accuracy of orbital reconstruction is largely subjective and especially difficult to achieve because of anatomic distortion in secondary or late reconstruction and in extensive injury. We combined computer navigation and endoscopy to perform accurate, aesthetic, and safe minimal-access primary and secondary orbital reconstruction., Methods: From 2013 to 2014, 24 patients underwent unilateral primary and secondary or late minimally invasive orbital reconstruction with mainly Medpor and/or titanium mesh by navigation and endoscopic assistance through transantral, transconjunctival, or upper blepharoplasty approaches. Mean follow-up was 13.8 months (range, 6.2 months to 2.8 years)., Results: All orbital fractures were successfully reduced. Average enophthalmos among patients who underwent early reconstruction, late reconstruction, and multiorbital wall repair improved (p < .001) to 0.2 mm from 1.6, 2.6, and 2.6 mm, respectively. Hypoglobus and diplopia resolved in all. In early reconstruction patients, mean interorbital volume difference improved from 1.72 ± 0.87 to 0.53 ± 0.83 ml (P = .03). For late reconstruction patients, this difference improved from 3.41 ± 1.23 to 0.56 ± 0.96 ml (p < .001). There were no major complications during follow-up, and all were satisfied with their final appearance and function., Conclusion: Navigation sharpens reconstructive accuracy and avoids injury to vital structures. Combined with endoscopic assistance for minimal-access reconstruction of wide-ranging orbital defects from primary to secondary or late cases and to extensive multiwall fractures, navigation facilitates minimal cosmetic incision and synergistic endoscope use and clearly optimizes aesthetic and functional outcomes, all with enhanced safety and unparalleled intraoperative visualization., (Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)