Conformational changes in the oligonucleotide duplex d(GCGTTGCG) x d(CGCAACGC) induced by formation of a cis-syn thymine dimer. A two-dimensional NMR study.
In order to obtain insight into the repair mechanism of DNA containing thymine photo-dimer, the conformation of the duplex d(GCGTTGCG) x d(CGCAACGC) with a thymine dimer incorporated has been studied by proton NMR and the results are compared with NMR data of the parent octamer. Two-dimensional nuclear Overhauser enhancement (2D NOE) spectroscopy and two-dimensional homonuclear Hartmann-Hahn spectroscopy have been applied to assign all the non-exchangeable base protons and most of the deoxyribose protons of both duplexes. From these experiments it is clear that indeed a cis-syn cyclobutane-type thymine photodimer is formed by the irradiation of this oligonucleotide with ultraviolet light. Comparison of 2D NOE spectra and the 1H chemical shifts of the damaged and the intact DNA duplexes reveals that formation of a thymine dimer induces small distortions of the B-DNA structure, the main conformational change occurring at the site of the thymine dimer.


Solution landscapes of the diblock copolymer-homopolymer model under two-dimensional confinement.
We investigate the solution landscapes of the confined diblock copolymer and homopolymer in two-dimensional domain by using the extended Ohta-Kawasaki model. The projection saddle dynamics method is developed to compute the saddle points with mass conservation and construct the solution landscape by coupling with downward and upward search algorithms. A variety of stationary solutions are identified and classified in the solution landscape, including Flower class, Mosaic class, Core-shell class, and Tai-chi class. The relationships between different stable states are shown by either transition pathways connected by index-1 saddle points or dynamical pathways connected by a high-index saddle point. The solution landscapes also demonstrate the symmetry-breaking phenomena, in which more solutions with high symmetry are found when the domain size increases.


Sterility and the disinfection potential of Indian contact lens solutions.
Ocular infection associated with microbial contamination of contact lens care products is a major problem in contact lens wearers. The sterility and the antimicrobial activity of contact lens care systems reflect their suitability for disinfection of contact lenses. These factors remain to be evaluated for the various newer contact lens care products manufactured in India. In this study, 35 bottles of contact lens solutions marketed by different manufacturing units in India were tested for sterility. Seven solutions were tested for antimicrobial effectiveness employing the D value method of analysis. The D value is defined as the time required to reduce a population of organisms by 90% (one log unit). A standard inoculum of the ocular isolates of Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Aspergillus fumigatus, Fusarium solani, and Acanthamoeba castellanii were used as challenge organisms. Bacterial contamination was detected in 20 (57.1%) solution bottles and none yielded fungus or Acanthamoeba. Pseudomonas species were the most commonly encountered contaminant (11/20; 55%). Only sterile solutions were analyzed for antimicrobial activity. D values ranging between 12 and 20 minutes were demonstrated by six of the seven solutions against bacterial challenge. Good antifungal activity was noticed in five solutions against Fusarium solani though results varied with Aspergillus flavus and Candida albicans. All solutions were adequately effective against Acanthamoeba.


CMCTS stabilized Fe3O4 particles with extremely low toxicity as highly efficient near-infrared photothermal agents for in vivo tumor ablation.
With the potential uses of photothermal therapy (PTT) in cancer treatment with excellent efficacy, and the growing concerns about the nanotoxicity of hyperthermia agents such as carbon nanotubes and gold-based nanomaterials, the importance of searching for a biocompatible hyperthermia agent cannot be emphasized too much. In this work, a novel promising hyperthermia agent employing magnetic Fe3O4 particles with fairly low toxicity was proposed. This hyperthermia agent showed rapid heat generation under NIR irradiation. After modification with carboxymethyl chitosan (CMCTS), the obtained Fe3O4@CMCTS particles could disperse stably in PBS and serum without any aggregation. The modification of CMCTS could decrease the adsorption of bovine serum albumin (BSA) and improve the cellular uptake. In a comparative study with hollow gold nanospheres (HAuNS), Fe3O4@CMCTS particles exhibited a comparable photothermal effect and fairly low cytotoxicity. The in vivo magnetic resonance (MR) images of mice revealed that by attaching a magnet to the tumor, Fe3O4@CMCTS particles accumulated in the tumor after intravenous injection and showed a low distribution in the liver. After being exposed to a 808 nm laser for 5 min at a low power density of 1.5 W cm(-2), the tumors on Fe3O4@CMCTS-injected mice reached a temperature of ~52 °C and were completely destroyed. Thus, a kind of multifunctional magnetic nanoparticle with extremely low toxicity and a simple structure for simultaneous MR imaging, targeted drug delivery and photothermal therapy can be easily fabricated.


Twenty-year follow-up of the facial phenotype of Brazilian patients with Sotos syndrome.
Sotos syndrome is characterized by overgrowth starting before birth through childhood with intellectual disability and craniofacial anomalies. The majority of patients are large for gestational age with developmental delay or intellectual disability. The majority of cases are caused by pathogenic variants in NSD1. The most consistent physical features in this disorder are facial dysmorphisms including prominent forehead, downslanted palpebral fissures, prognathism with a pointed chin, and a long and narrow face. We present a follow-up to a cohort of 11 individuals found to harbor heterozygous, pathogenic, or likely pathogenic variants in NSD1. We analyzed the facial dysmorphisms and the condition using retrospective over 20 years. Among these patients, followed in our medical genetics outpatient clinic for variable periods of time, all had a phenotype compatible with the characteristic Sotos syndrome facial features, which evolved with time and became superimposed with natural aging modifications. We present here a long-term follow-up of facial features of Brazilian patients with molecularly confirmed Sotos syndrome. In this largest Brazilian cohort of molecularly confirmed patients with Sotos syndrome to date, we provide a careful description of the facial phenotype, which becomes less pronounced with aging and possibly more difficult to recognize in adults. These results may have broad clinical implications for diagnosis and add to the global clinical delineation of this condition.


Tension plate for treatment of olecranon fractures: new surgical technique and case series study.
Our aim was to determine the effectiveness of a new surgical technique for olecranon fractures using a tension plate (TP) designed by the operating surgeon. We included patients with olecranon fractures treated between September 2010 and August 2013 in our study. Treatment involved a new implant and operative technique, which combined the most favourable characteristics of 2 frequently used methods, tension band wiring and plate osteosynthesis, while eliminating their shortcomings. The new method was based on the newly constructed implant. Twenty patients participated in our study. We obtained the following functional results with our TP: median flexion 147.5° (interquartile range [IQR] 130°- 155°), median extension 135°/deficit 10° (IQR 135°-145°), median pronation 90° (IQR 81.3°-90°), median supination 90° (IQR 80°-90°). Implant-related complications were noted in 1 patient, and implants were removed in 3 patients. The mean functional Mayo elbow performance score was 94.8 (range 65-100). The removal of the implant was considerably less frequent in patients operated using the new method and implant than in patients operated using conventional methods at our institution (p < 0.001). Mean duration of follow-up was 8 months. Our TP for the treatment of olecranon fractures is safe and effective. Functional results are very good, with significantly decreased postoperative inconveniences and need to remove the implant. Less osteosynthetic material was used for TP construction, but stability was preserved.


Activation of PTEN/P13K/AKT Signaling Pathway by miRNA-124-3p-Loaded Nanoparticles to Regulate Oxidative Stress Attenuates Cardiomyocyte Regulation and Myocardial Injury.
As a common cardiovascular disease, acute myocardial infarction seriously affects the health and life of patients. miRNAs play an important role in acute myocardial infarction. Based on miRNA obtained from the previous sequencing, this study investigated whether miRNA (miR)-124-3p-loaded nanoparticles (NPs) affect the phenotype of the acute myocardial infarction (AMI) rat. Nano-miR-124-3p decreased the myocardial infarction area, improved the myocardial tissue structure, and increased the degree of fibrosis. Nano-miR-124-3p decreased apoptosis and the expression of cleaved caspase 3, indicating its role in protecting and repairing the myocardium. To further verify the action mechanism of miRNA, a potential target gene of miR-124-3p, PTEN was identified by STARBASE and further confirmed using double luciferase assays. Following cotransfection of nano-miR-124-3p and PTEN, the areas of tissue structure damage, myocardial infarction, and fibrosis were substantially elevated. The expression of cleaved caspase 3 and the apoptosis rate in the nano-miR-124-3p and PTEN cotransfection group was also significantly increased. Bioinformatics analysis revealed that miRNA-124-3 may regulate oxidative stress injury by targeting PTEN. Taken together, miR-124-3p could protect and repair myocardial tissues through targeting PTEN.


Search for shortcuts on the critical path to market: US FDA perspectives from the diagnostic side.
The US FDA has been regulating medical devices (including laboratory tests) since 1976. Premarket review is well defined and may include requirements for both analytical and clinical information. In 2004, the US FDA initiated the Critical Path initiative to help foster development of new medical products. Biomarkers were seen as an important part of this new program for both traditional diagnostic purposes and to aid in drug development. The US FDA has created programs to foster use of biomarkers both for routine diagnostic and for drug development purposes. There is growing methodology to serve as road maps for efficient and scientifically sound development in this area. The US FDA has a flexible regulatory tool box to apply to biomarker development, and has the clear aim of working as a partner to bring these important medical devices quickly to the medical marketplace.


[The protective effect of pigment epithelial-derived factor modified human umbilical cord mesenchymal stem cells on rats with diabetic retinopathy].
Objective: To investigate the effect of pigment epithelial-derived factor (PEDF) gene-modified human umbilical cord mesenchymal stem cells (MSC) on rats with diabetic retinopathy (DR). Methods: Experimental study. Human umbilical cord MSC were transfected by lentivirus packaging PEDF-MSC-green fluorescent protein (GFP) and GFP-MSC plasmid vectors, and the expression of PEDF and vascular endothelial growth factor (VEGF) was measured in the cell culture medium. Fifty adult male Sprague-Dawley rats were randomly divided into five groups: normal control group (group A), DR control group (group B), phosphate-buffered saline (PBS) treated group (group C), GFP-MSC treated group (group D) and PEDF-MSC-GFP treated group (group E), with 10 rats in each group. Streptozotocin was intraperitoneally injected to make early DR models. After four-month intervention, groups D and E were given intravitreal injection of GFP-MSC and PEDF-MSC-GFP; group C was given intravitreal injection of phosphate-buffered saline; groups A and B did not receive special treatment. The changes of retina in different groups were detected by hematoxylin and eosin staining, and the thickness of inner plexiform layer, inner nuclear layer and outer nuclear layer was measured by computer-based image analytical system. Immunohistochemistry was applied to observe PEDF and VEGF. Real-time quantitative polymerase chain reaction was used to detect the expression of PEDF and VEGF mRNA. Results: The expression of CD105, CD73 and CD90 was positive, while the expression of CD34, CD45, CD11b, CD19 and HLA-DR was negative. ELISA results showed that after transfection PEDF protein expression in the supernatant of PEDF-MSC (84.09±7.07) μg/L was higher than the control group (9.03±0.14) μg/L (P<0.05). At 2 weeks after intravitreal injection, green fluorescence was observed in the rat vitreous of groups D and E under a fluorescence microscope; no obvious green fluorescence was found in the retina. After 2 months of intravitreal injection, the thickness of inner plexiform layer in group E was significantly decreased; the thickness of inner nuclear layer and outer nuclear layer was higher (P<0.05). Immunohistochemical staining showed that 2 months after intravitreal treatment, the average optical density values of PEDF were improved, but the average optical density values of VEGF were decreased in group E (P<0.05). Real-time polymerase chain reaction showed that 2 months after treatment, the expression level of PEDF mRNA in group E was improved, but the expression level of VEGF mRNA was decreased (P<0.05). Conclusions: Intravitreal injection of PEDF-MSC could up-regulate the expression of PEDF and down-regulate the expression of VEGF in diabetic rats and may represent a novel candidate resource for cell therapy of DR nerve damage. (Chin J Ophthalmol, 2017, 53, 540-547).


[Regulation effects of electroacupuncture with different acupoint combinations on blood lipid in rats with hyperlipemia].
To observe the regulatory effects of electroacupuncture with different acupoints combinations on blood lipid and atherosclerosis index (AI) in rats with hyperlipemia, so as to make a preliminary screening for the optimal acupoints combination for hyperlipemia. One hundred and five clean-grade SD male rats were randomly divided into 9 groups, including a normal group, a model group, a Quchi group, a Zhongwan group, a Fenglong group, a Quchi+Zhongwan group, a Quchi+Fenglong group, a Zhongwan+Fenglong group and a Quchi+Zhongwan+Fenglong group (three acupoints group), 17 rats in the normal group and 11 rats in the rest groups. The normal group was fed with normal diet, while the rest groups were fed with high-fat diet for 3 weeks to prepare the hyperlipemia model. All the rats were given unlimited water. After the establishment of model, the normal group was fed freely without any treatment; the model group was bundled and immobilized everyday; the rest groups were bundled, immobilized and treated with electroacupuncture at corresponding acupoints with disperse-dense wave, 20 min per time, once a day. After 4 weeks, the blood examples were collected from abdominal aorta to measure the total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C), and analyzed the AI in each group. After the treatment, TC, TG, HDL-C, LDL-C and AI in each acupuncture group were all lower than those in the model group (P<0.05, P<0.01). Compared with single acupoint group and the Quchi+Zhongwan group, the content of TC in the three acupoints group was lower (P<0.01). The differences of content of TG among each acupuncture group were not significant (all P>0.05). Compared with the rest 6 acupuncture groups, the content of HDL-C and AI in the three acupoints group were significantly different (all P<0.05). The content of LDL-C in the three acupoints group was decreased as compared with the Quchi group and the Zhong-wan group. The electroacupuncture at "Quchi" (LI 11), "Zhongwan" (CV 12) and "Fenglong" (ST 40) has more advantages on regulating the content of HDL-C and LDL-C as well as improving AI in hyperlipemia rats, and it has superior effects on blood lipid metabolism.


Postpartum psychoses: prognosis, risk factors, and treatment.
Puerperal psychoses do not represent a nosological entity, but rather a selection of puerperally triggered "ordinary" functional psychoses with cycloid psychoses predominating and schizophrenias occurring very rarely. The prognosis is basically favorable concerning symptom remission and social and occupational functioning. However, there is a considerable frequency of relapses and an increased suicide rate. The most important risk factors for an episode of a puerperal psychosis are being primiparous and having suffered a previous episode of a psychosis, particularly a cycloid psychosis. Controlled treatment studies up to now are absent. Case studies suggest in acute episodes the efficacy of a symptom-oriented pharmacologic treatment where ablactation is recommended. With respect to prophylactic treatment some authors propose to apply lithium in late pregnancy or immediately after delivery. Because of its possible teratogenic effects and the altogether rather sparse data, the authors however cannot recommend the use of lithium during pregnancy. Applying estradiol after delivery may be beneficial and safe, but further studies are necessary to clarify these issues.


Minimization of skin incisions at stripping by Mayo of large-diameter veins.
The aim of the present study was to analyze the possibility to minimize of the skin incisions up to a puncture size at stripping by Mayo with the use of the stripper with an oval-ring head for large-diameter veins. The problem is solved due to the geometrical changing of the stripper head from a round to an oval one. The laboratory experiment showed that with a vein diameter of 10-20 mm the total cross-sectional area of its walls constituted 13.61 mm2, with a diameter of more than 20 mm it was 19.98 mm2. There were designed three types of the external dimensions for the stripper: 3.0×6.0 mm; 3.5×7.0 mm and 4.0×8.0 mm. From 1997 to 2017, the stripper with an oval-ring head was used in 1274 patients (421 males, 853 females) to treat 1832 lower limbs. Average age was 46.4±12.3 years (range, 29 to 73). GSV and SSV stripping was performed in 1165 and 137 cases, respectively, in patients with the trunk diameter of more than 10 mm, severe vein tortuosity, for a vein located immediately under the skin, as well as for patients with the history of thrombophlebitis. The pain level in the first evening after the operation was 1.59, on day 7, it decreased to 0.12 according to VAS-10. The motion activity level in the first evening after the operation was 7.24; on day 7, it decreased to 9.96 according to VAS-10. All patients had primary wound healing. Hematomas along the location of the eliminated veins were of a moderate nature and resolved, on average, within 17 days. With the GSV diameter of 10-20 mm the skin scars were of 2.93 mm (95% CI: 3.09-4.47 mm), with the GSV diameter of more than 20 mm the skin scars were of 4.10 mm (95% CI: 4.01-5.07 mm). After 3 months, 1102 patients (86.5%) were very satisfied and 172 (13.5%) were just satisfied with the performed operation. The use of the proposed stripper with an oval-ring head in patients with large-diameter subcutaneous trunks leads to the minimization of the skin incisions up to the punctures and, in general, makes the surgery significantly less traumatic, providing a quick recovery and minimization of the skin scars.


Recent advances and future perspectives of CAR-T cell therapy in head and neck cancer.
Head and neck cancer (HNC) ranks as the sixth most prevalent type of cancer globally and accounts for about 4% of all types of cancer. Among all HNC, most are head and neck squamous cell carcinoma (HNSCC) with clinical therapies that include surgery, radiation therapy, chemotherapy, immunotherapy, targeted therapy, and multimodal treatments. In recent years, chimeric antigen receptor (CAR)-T cell immunotherapy has significantly transformed the therapeutic approaches for leukemia and lymphoma and has garnered increased attention as a potential treatment for a wide range of cancers. However, CAR-T immunotherapy in solid tumors, especially HNSCCs, lags significantly behind due to the paucity of tumor-specific antigens, high levels of tumor heterogeneity, immunosuppressive tumor microenvironment, the risk of treatment-related toxicities and off-target adverse events in HNSCCs. The objective of this review is to explore the advancement of CAR-T cell therapy in the treatment of HNSCCs. We aim to outline the targeted antigens in HNSCCs, highlight the challenges and potential solutions, and discuss the relevant combination therapies. Our review presents a comprehensive overview of the recent developments in CAR-T cell therapy for HNSCCs, and provides valuable insights into future research avenues.


Ifosfamide, epirubicin and etoposide rituximab in refractory or relapsed B-cell lymphoma: analysis of remission induction and stem cell mobilization.
Chemotherapy with ifosfamide, epirubicin and etoposide (IEV) is an effective treatment regimen for refractory/relapsed non-Hodgkin lymphoma (NHL). Rituximab has been shown to improve response rates, progression-free survival and overall survival in B-cell NHL. This study included 85 patients who were treated with IEV or rituximab-IEV (R-IEV) for refractory/relapsed B-cell NHL. The overall response rate was 40.7% (IEV) versus 68.8% (R-IEV). Fever occurred after 23.4% of IEV and 19.4% of R-IEV cycles. 94.9% of patients mobilized sufficient numbers of CD34+ cells (IEV) versus 93.8% (R-IEV). Fifty-five patients (64.7%) proceeded to high-dose therapy after IEV+/-rituximab. The median survival time was 60.0 months (IEV) and 19.5 months (R-IEV), and has not been reached for patients who received high-dose therapy. The addition of rituximab to IEV salvage chemotherapy increases the response rates in B-cell NHL without affecting stem cell mobilization, but overall survival for patients proceeding to high-dose chemotherapy is not improved.


Is there a role for thioguanine therapy in IBD in 2017 and beyond?
Conventional thiopurines are effective for the maintenance of remission of Crohn's disease and ulcerative colitis, however, up to half of patients are intolerant or unresponsive to these medications. Thioguanine is an alternative thiopurine that has shown efficacy in inflammatory bowel disease, and is particularly useful to circumvent certain side effects associated with conventional thiopurines, for example, pancreatitis. Its association with nodular regenerative hyperplasia of the liver has hindered its widespread use. Areas covered: We aim to outline the rational use of thioguanine, including safety monitoring, with particular regard to hepatotoxicity. A literature search was performed: PubMed was searched for full papers and abstracts published in English since January 2000 using the following terms, alone and in combination: 'azathioprine', 'thiopurine', 'Crohn's disease', 'inflammatory bowel disease', 'nodular regenerative hyperplasia', 'mercaptopurine', 'thioguanine', 'ulcerative colitis'. Further relevant papers were identified from the reference lists of selected papers. Expert commentary: Despite optimisation strategies such as metabolite measurements and the use of allopurinol, a significant proportion of patients will remain intolerant to thiopurines, especially those with allergic reactions, including pancreatitis. For this subgroup of patients we suggest that low dose thioguanine is an alternative to other therapies that are either parenteral or expensive.


Spatial W-plasty full-thickness skin graft for neovaginal reconstruction.
Although neovaginal reconstruction has achieved satisfactory results, there is still room for refinement and improvement. Despite its popularity, McIndoe's inlay split-thickness skin graft method still has several significant drawbacks. Here a new approach to neovaginal reconstruction by using a full-thickness skin graft displayed in the fashion of spatial W-plasty is described. Our idea combines the advantages of a full-thickness skin graft and Z-plasty principle in clinical practice. Four patients who had been reconstructed with this method had satisfactory results with minimal secondary contracture and unilateral linear groin scar. Three of them have married and enjoy sexual life without difficulties. The fourth patient has not married but shows no contracture in follow-up examinations. Since the result is encouraging, this method deserves wider clinical application.


Brolucizumab for recalcitrant macular neovascularization in age-related macular degeneration with pigment epithelial detachment.
To analyze anatomic and functional response to intravitreal brolucizumab in age-related macular degeneration recalcitrant to previous intravitreal anti-VEGF therapies. In this monocentric, one arm, retrospective study, eyes affected by neovascular age-related macular degeneration (nAMD) resistant to other intravitreally injected anti-vascular endothelial growth factor inhibitors were switched to intravitreal brolucizumab. All patients underwent ophthalmological examinations at baseline and in regular follow-up intervals. Best registered visual acuity (BRVA), Goldmann tonometry, intraocular pressure (IOP), central retinal thickness (CRT) and pigment epithelial detachment (PED) characteristics were analyzed at initiation of anti-VEGF treatment, at treatment switch, and at the end of brolucizumab loading phase. The study included 20 eyes of 18 consecutively treated patients (age: 77 ± 6 years). All eyes had macular neovascularization with PED. Previous treatments included intravitreal aflibercept, bevacizumab, and ranibizumab and had not resulted in a significant improvement in BRVA (0.5 ± 0.5 logMAR vs 0.5 ± 0.6 logMAR) or mean CRT (320 ± 60 µm vs 313 ± 83 µm) up to treatment switch to brolucizumab. At the end of the brolucizumab loading phase, there was significant improvement for both BRVA (0.3 ± 0.2 logMAR, P < 0.05) and CRT (264 ± 55 µm, P < 0.05). Under previous anti-VEGF therapy, there was a significant increase/deterioration in both PED area (2.68 mm2 to 5.18 mm2, P < 0.05) and PED volume (0.39 mm3 to 1.07 mm3, P < 0.05); however, both parameters improved after switching to brolucizumab (3.81 mm2 and 0.37 mm3, P < 0.05). Our results suggest a favourable anatomical and visual response after treatment switch to brolucizumab in patients with nAMD refractory to previous anti-VEGF agents.


Poly(ionic liquid)s as phase splitting promoters in aqueous biphasic systems.
Aqueous biphasic systems (ABSs) provide a sustainable and efficient alternative to conventional liquid-liquid extraction techniques with volatile organic solvents, and can be used for the extraction, recovery, and purification of diverse solutes. In this work, and for the first time, ABSs composed of poly(ionic liquid)s (PILs) and inorganic salts were measured at 25 °C and atmospheric pressure. New PILs having pyrrolidinium polycations combined with different counter-anions, namely acetate [Ac](-), trifluoroacetate [TFAc](-), hexanoate [Hex](-), adipate [Adi](-), and citrate [Cit](-) were synthesized, by a simple and environmentally-friendly procedure, and characterized. The effect of the PIL features, namely molecular weight and anionic character, and other experimental variables, such as temperature, on the phase splitting ability was researched. The aptitude of the studied ABS to be implemented as separation technologies was also evaluated through the use of a model biomolecule, tryptophan.


Noradrenergic influences in the basolateral amygdala on inhibitory avoidance memory are mediated by an action on α2-adrenoceptors.
The role of norepinephrine (NE) in the consolidation of inhibitory avoidance learning (IA) in rats is known to involve α1- and β-adrenoceptor systems in the basolateral nucleus of the amygdala (BLA). However, the amygdala also contains α2-adrenoceptor subtypes, and local microinfusions of the selective α2-adrenoceptor antagonist idazoxan and agonist UK 14,304 respectively into the BLA enhance and inhibit IA performances when administered before acquisition. The present study investigated whether the effects of idazoxan and UK 14,304 on IA were associated with changes in NE release within the BLA before and after one-trial inhibitory avoidance training. Male Sprague-Dawley rats were unilaterally implanted with a microdialysis probe in the BLA and were administered idazoxan (0.1mM) or UK 14,304 (10 μM) by retrodialysis infusion 15 min before the acquisition of IA. Dialysates were collected every 15 min for analysis of NE. Retrodialysis of idazoxan potentiated the release of NE induced by footshock application, whereas UK 14,304 decreased NE release to the extent that the footshock failed to induce any measurable effect on NE levels. Idazoxan infusion enhanced IA retention tested 24h later and this effect was directly related to the level of NE release in the BLA measured during IA acquisition. In contrast, the infusion of UK 14,304 did not modify IA performances in comparison to control animals, possibly due to compensatory activity of the contralateral BLA. These results are consistent with previous evidence that amygdala NE is involved in modulating memory consolidation, and provide evidence for an involvement of presynaptic α2-autoceptors in the BLA in this process.


Use of 13C labeling to assess carbon partitioning in transgenic and nontransgenic (parental) rice and their rhizosphere soil microbial communities.
Photosynthetic assimilation of CO2 is a primary source of carbon in soil and root exudates and can influence the community dynamics of rhizosphere organisms. Thus, if carbon partitioning is affected in transgenic crops, rhizosphere microbial communities may also be affected. In this study, the temporal effects of gene transformation on carbon partitioning in rice and rhizosphere microbial communities were investigated under greenhouse conditions using the 13C pulse-chase labeling method and phospholipid fatty acid (PLFA) analysis. The 13C contents in leaves of transgenic (Bt) and nontransgenic (Ck) rice were significantly different at the seedling, booting and heading stages. There were no detectable differences in 13C distribution in rice roots and rhizosphere microorganisms at any point during rice development. Although a significantly lower amount of Gram-positive bacterial PLFAs and a higher amount of Gram-negative bacterial PLFAs were observed in Bt rice rhizosphere as compared with Ck at all plant development stages, there were no significant differences in the amount of individual 13C-PLFA between Bt and Ck rhizospheres at any growing stage. These findings indicate that the insertion of cry1Ab and marker genes into rice had no persistent or adverse effect on the photosynthate distribution in rice or the microbial community composition in its rhizosphere.


Pharmacological Activation of Autophagy Restores Cellular Homeostasis in Ultraviolet-(B)-Induced Skin Photodamage.
Ultraviolet (UV) exposure to the skin causes photo-damage and acts as the primary etiological agent in photo-carcinogenesis. UV-B exposure induces cellular damage and is the major factor challenging skin homeostasis. Autophagy allows the fundamental adaptation of cells to metabolic and oxidative stress. Cellular dysfunction has been observed in aged tissues and in toxic insults to cells undergoing stress. Conversely, promising anti-aging strategies aimed at inhibiting the mTOR pathway have been found to significantly improve the aging-related disorders. Recently, autophagy has been found to positively regulate skin homeostasis by enhancing DNA damage recognition. Here, we investigated the geno-protective roles of autophagy in UV-B-exposed primary human dermal fibroblasts (HDFs). We found that UV-B irradiation to HDFs impairs the autophagy response in a time- and intensity-independent manner. However, improving autophagy levels in HDFs with pharmacological activators regulates the UV-B-induced cellular stress by decreasing the induction of DNA photo-adducts, promoting the DNA repair process, alleviating oxidative and ER stress responses, and regulating the expression levels of key cell cycle regulatory proteins. Autophagy also prevents HDFs from UV-B-induced nuclear damage as is evident in TUNEL assay and Acridine Orange/Ethidium Bromide co-staining. Salubrinal (an eIF2α phosphatase inhibitor) relieves ER stress response in cells and also significantly alleviates DNA damage and promotes the repair process in UV-B-exposed HDFs. P62-silenced HDFs show enhanced DNA damage response and also disturb the tumor suppressor PTEN/pAKT signaling axis in UV-B-exposed HDFs whereas Atg7-silenced HDFs reveal an unexpected consequence by decreasing the UV-B-induced DNA damage. Taken together, these results suggest that interventional autophagy offers significant protection against UV-B radiation-induced photo-damage and holds great promise in devising it as a suitable therapeutic strategy against skin pathological disorders.


The Cervical Spine Study Group anterior cervical plate nomenclature.
The authors review historical and biomechanical aspects of anterior cervical plate (ACP) systems. They propose a novel classification system for ACPs based on the biomechanical and graft-loading properties of these systems. A retrospective review of the literature comprising both clinical and laboratory investigations regarding the ACP system was undertaken. Comparison of each system is considered in the context of the biomechanical attributes and graft-loading properties of each type of plate. Salient characteristics reviewed include restriction of screw backout, screw-angle variability, and mobility at the screw-plate interface. A new classification system for ACPs is proposed that primarily considers the ability of the construct to restrict screw backout, as well as the properties of the plate-screw interface--that is, the capacity for rotational or translational movement. A new classification system is presented that provides unified, biomechanically descriptive nomenclature. Using this nomenclature, the ACP devices currently available and those developed in the future can be uniformly categorized.


Presumed localized tuberculous inflammation after periocular procedures.
To report 4 rare cases of periocular presumed tuberculosis that developed after eyelid and lacrimal drainage surgery. Retrospective, interventional case series. Review of clinical, laboratory, photographic, and radiologic records of patients with presumed tuberculous inflammation after periocular procedures. Four patients had periocular presumed tuberculosis after blepharoplasty, dacryocystorhinostomy, and intracanalicular lacrimal plug insertion. Diagnosis was made by characteristic histopathologic findings, acid-fast bacilli staining, polymerase chain reaction results, or response to therapeutic trial. All of the patients underwent antituberculosis chemotherapy for a minimum of 9 months and all recovered. Ectropion and eyelid retraction complicated 2 cases. Unresponsiveness of chronic inflammation to conventional treatment after periocular procedures should arouse the clinical suspicion of localized tuberculosis, particularly in endemic areas or in patients who have a tuberculosis history or recent exposure. For presumed eyelid tuberculosis without evidence of Mycobacterium tuberculosis, the clinical diagnosis and therapeutic trials could be considered cautiously especially in countries with an intermediate or high tuberculosis burden. Early diagnosis and appropriate treatment can prevent the sequelae of tuberculosis infection.


Polyclonal and monoclonal antibodies in renal transplant: an update.
There are several monoclonal and polyclonal antibodies used in renal transplantation today, this article will discuss several agents, their updates and newer agents. Antithymocyte globulin and interleukin-2 (IL-2) receptor blocker continue to be used as induction agents. The risk of acute rejection was higher in IL-2 receptor blockers mainly in the first year, but graft survivals were similar in both groups long term. Belatacept is the only approved intravenous maintenance immunosuppressive therapy which provides the benefit of glomerular filtration rate preservation, but it was associated with a higher risk of acute rejection and post-transplant lymphoproliferative disorder. Bortezomib may help decrease donor-specific antibody levels, but there are limited data to support its use for desensitization or rejection. Eculizumab may help in antibody-mediated rejection in some cases but has not shown promising long-term effects in high-risk individuals. Newer agents have been continuously tested for improved efficacy and safety. Transplantation is the standard of care for end-stage renal disease patients, but we still have a long way to go, as we need to improve long-term outcomes. The manipulation of the immune system is a delicate undertaking, with risks of adverse events; therefore, risk versus benefit needs to be carefully evaluated and treatment needs to be individualized.


Selective attention and the acquisition of new phonetic categories.
A class of selective attention models often applied to speech perception is used to study effects of training on the perception of an unfamiliar phonetic contrast. Attention-to-dimension (A2D) models of perceptual learning assume that the dimensions that structure listeners' perceptual space are constant and that learning involves only the reweighting of existing dimensions to emphasize or de-emphasize different sensory dimensions. Multidimensional scaling is used to identify the acoustic-phonetic dimensions listeners use before and after training to recognize the 3 classes of Korean stop consonants. Results suggest that A2D models can account for some observed restructuring of listeners' perceptual space, but listeners also show evidence of directing attention to a previously unattended dimension of phonetic contrast.


Differences in mRNA expression, protein content, and enzyme activity of superoxide dismutases in type II pneumocytes of acute and chronic lung injury.
The lung is protected against oxidative stress by a variety of antioxidants and type II pneumocytes seem to play an important role in antioxidant defense. Previous studies have shown that inhalation of NO2 results in acute and chronic lung injury. How the expression and enzyme activity of antioxidant enzymes are influenced in type II cells of different inflammatory stages has yet not been studied. To elucidate this question, we exposed rats to 10 ppm NO2 for 3 or 20 days to induce acute or chronic lung injury. From these and air-breathing rats, type II pneumocytes were isolated. The mRNA expression and protein content of CuZnSOD and MnSOD as well as total SOD-specific enzyme activity were determined. For the acute lung injury (3 d NO2), the expression of CuZnSOD mRNA was significantly increased, while MnSOD expression was significantly reduced after 3 days of NO2 exposure. For the chronic lung injury (20 d NO2), CuZnSOD expression was still enhanced, while MnSOD expression was comparable to control. In parallel to CuZnSOD mRNA expression, the protein amount was significantly increased in acute and chronic lung injury however MnSOD protein content exhibited no intergroup differences. Total SOD enzyme activity showed a significant decrease after 3 days of NO2 exposure and was similar to control after 20 days. We conclude that during acute and chronic lung injury in type II pneumocytes expression and protein synthesis of CuZnSOD and MnSOD are regulated differently.


Extracellular Glutamate in the Nucleus Accumbens Is Nanomolar in Both Synaptic and Non-synaptic Compartments.
In the CNS, glutamate is both phasically and tonically released into the extracellular space and must be removed by excitatory amino acid transporters (EAATs) to prevent excitotoxic accumulation. There remains uncertainty, however, regarding the functional steady-state concentration, with estimates ranging from tens of nanomolar to tens of micromolar. Efforts to reconcile these disparate values have led to a hypothesis that the extracellular space comprises distinct compartments in which basal glutamate concentrations are maintained independently. We used electrophysiology and two-photon Ca2+ imaging to test this hypothesis in the nucleus accumbens (NAc), where it has been proposed that micromolar extracellular glutamate is necessary for normal function. We found that the average concentration of synaptic glutamate is nanomolar, in agreement with previous electrophysiological estimates. Furthermore, this held true when glutamate uptake was inhibited, indicating that extracellular glutamate is not compartmentalized by EAATs.


Anti-inflammatory coatings of hernia repair meshes: A pilot study.
The current prevalence of postoperative chronic pain from hernioplasty procedures employing polymer mesh is close to 30%. Most of the researchers agree that oxidative stress, resulting from the release of oxidants and enzymes during acute inflammatory response, is a key factor in the development of posthernioplasty complications. This results in both the decrease of the biomechanical properties and stiffening of the polymer fibers of the mesh, leading to chronic pain. Moreover, enhanced activity of inflammatory cells can lead to an excessive deposition of connective tissue around the implant. In this study polypropylene hernia repair meshes coated with vitamin E (α-tocopherol), a known antioxidant, were prepared and characterized. The absorption isotherm of vitamin E on the mesh was characterized and a release profile study yielded a promising results, showing sustained release of the drug over a 10-day period. An animal study was conducted, and histological analysis five weeks after implantation exhibited a reduced host tissue response for a modified mesh as compared to a plain mesh, as evidenced by a higher mature collagen to immature collagen ratio, as well as lower level of fatty infiltrates, neovascularization and fibrosis in the case of modified mesh. These results support the use of α-tocopherol as a potential coating in attempt to reduce the extent of postoperative inflammation, and thereby improve long-term outcomes of hernioplasty. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 589-597, 2018.


Solution structure of the human immunodeficiency virus type 1 p6 protein.
The human immunodeficiency virus type 1 p6 protein represents a docking site for several cellular and viral binding factors and fulfills major roles in the formation of infectious viruses. To date, however, the structure of this 52-amino acid protein, by far the smallest lentiviral protein known, either in its mature form as free p6 or as the C-terminal part of the Pr55 Gag polyprotein has not been unraveled. We have explored the high resolution structure and folding of p6 by CD and NMR spectroscopy. Under membranous solution conditions, p6 can adopt a helix-flexible helix structure; a short helix-1 (amino acids 14-18) is connected to a pronounced helix-2 (amino acids 33-44) by a flexible hinge region. Thus, p6 can be subdivided into two distinct structural and functional domains; helix-2 perfectly defines the region that binds to the virus budding factor AIP-1/ALIX, indicating that this structure is required for interaction with the endosomal sorting complex required for transport. The PTAP motif at the N terminus, comprising the primary late assembly domain, which is crucial for interaction with another cellular budding factor, Tsg101, does not exhibit secondary structure. However, the adjacent helix-1 may play an indirect role in the specific complex formation between p6 and the binding groove in Tsg101. Moreover, binding studies by NMR demonstrate that helix-2, which also comprises the LXXLF motif required for incorporation of the human immunodeficiency virus type 1 accessory protein Vpr into budding virions, specifically interacts with the Vpr binding region, indicating that under the specific solution conditions used for structure analysis, p6 adopted a functional conformation.


cis-Diaquabis(trans-cinnamato-O,O')zinc(II).
The title complex, [Zn(C(9)H(7)O(2))(2)(H(2)O)(2)], shows a distorted octahedral coordination and has a crystallographic twofold rotation axis. Intermolecular O-H.O hydrogen bonding forms a two-dimensional network in the ab plane.


Bilateral accessory soleus: a report on four patients with partial fasciectomy.
Four young adults (average age 24 years) presented with complaints of posterior ankle pain after running. Bilateral accessory soleus muscles were diagnosed using magnetic resonance imaging or CT scan. Symptoms were present an average of 3 years before diagnosis. Two patients had previous surgery (ankle arthroscopy, tarsal tunnel release, and leg compartment release) before diagnosis and treatment. Obliteration of Kager's triangle (posterior ankle fat pad) was present on six out of eight lateral ankle radiographs. Posteromedial prominence was present on four out of eight ankles. Operative exploration confirmed the presence of five muscles and fasciectomy was performed. Follow-up (17 to 29 months) showed good relief of symptoms in all patients and return to long-distance running for three patients. Dissection of 47 preserved cadavers revealed three accessory soleus muscles in the 94 extremities (two muscles were bilateral in one cadaver).


Does metformin increase paraoxonase activity in patients with the metabolic syndrome? Additional data from the MEFISTO study.
In a subanalysis on the metformin, arterial function, intima-media thickness, and nitroxidation in the metabolic syndrome (MEFISTO)(8) (an open-label fashion, with 1 year of 850 mg daily of metformin) subjects' samples, we measured the paraoxonase 1 (PON1) activity in 39 patients that finished the study and relate values with high density lipoprotein (HDL). The comparative PON1 activities at the beginning and at the end of the study were 5.528 ± 0.588 and 4.743 ± 0.619 nmol/mg protein/min (NS) for control group and 3.229 ± 0.403 and 5.135 ± 0.585 nmol/mg protein/min (p < 0.02) for the metformin group. Our data showed an enhance of PON1 activity in patients with metabolic syndrome treated with metformin, although in them, the raise of HDL concentration was less than control patients, suggesting that the increase in quality (measured here as PON1 activity) could be at least as important as an increase in its concentration. Our results point out that there is a relationship among PON1 activity and the reduction of carotideal intima-media thickness.


Increased efficacy of dual proinflammatory cytokine blockade on acute GVHD while maintaining GVT effects.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a potential curative option for treating a variety of hematologic diseases, but acute and chronic graft-versus-host disease (GVHD) remain major barriers limiting efficacy. Acute gut GVHD occurs with marked increases in proinflammatory cytokines (including TNF and IL-6), which we recently demonstrated was exacerbated in obesity resulting in severe gastrointestinal pathology. Given the pleiotropic and overlapping effects of these 2 cytokines, we assessed the impact of dual TNF and IL-6R blockade on GVHD as well as graft-versus tumor (GVT) effects in different mouse GVHD models. Early administration of combined blockade resulted in greater protection and survival from acute gut GVHD compared with single blockade regimens and even development of later chronic skin GVHD. Importantly, double cytokine blockade preserved GVT effects reinforcing that GVT and GVHD can be delineated and may result in greater efficacy in allo-HSCT.


Diversification of antisense research and development: review of the Ringberg meeting, April 1994. Mechanisms of antisense-mediated gene silencing.
Antisense technology has established itself as a new and vibrant entrant into the discipline of molecular biology. As such, it has contributed to basic research by providing tools for the molecular dissection of diverse experimental systems. In applied research, antisense approaches have contributed to development of agricultural products (D. Grierson) now coming to market and to the design of a number of oligonucleotide drugs, now in clinical trials. However, few activities to date have focused on the study of antisense per se. Further, few conceptual perspectives have regarded antisense as an integral part of cellular function and genetic regulation. The Ringberg conference showcased a number of systems that would seem unrelated if we regard antisense as a superficial tool to be imposed on nature. On the other hand, if we want to begin to regard antisense as a field of its own with deeper biological and genetic rationales, the Ringberg meeting provided much tantalizing evidence to do so.


Congenital penile curvature: update and management.
Congenital penile curvature results from disproportionate development of the tunica albuginea of the corporal bodies and is not associated with urethral malformation. Patients usually present after reaching puberty as the curvature becomes more apparent with erections, and severe curvature can make intercourse difficult or impossible, at which point surgical repair is recommended. Excellent outcomes can be expected with surgical intervention. The three most commonly used repair techniques are the original Nesbit procedure, modified Nesbit procedure, and plication. Nesbit and modified Nesbit techniques require that an incision is made in the tunica albuginea while plication techniques utilize plicating sutures without an incision. While Nesbit and modified Nesbit techniques are more complex operations, these generally result in less recurrences and more satisfactory outcomes as opposed to the quicker and simpler plication technique.


The work horse of skull base surgery: orbitozygomatic approach. Technique, modifications, and applications.
The aim of this study was to describe the microsurgical anatomy of the orbitozygomatic craniotomy and its modifications, and detail the stepwise dissection of the temporalis fascia and muscle and explain the craniotomy techniques involved in these approaches. Nine cadaveric embalmed heads injected with colored silicone were used to demonstrate a stepwise dissection of the 3 variations of orbitozygomatic craniotomy. The craniotomies and dissections were performed with standard surgical instruments, and the microsurgical anatomy was studied under microscopic magnification and illumination. The authors performed 2-piece, 1-piece, and supraorbital orbitozygomatic craniotomies in 3 cadaveric heads each. Stepwise dissection of the temporalis fascia and muscle, and osteotomy cuts were shown and the relevant microsurgical anatomy of the anterior and middle fossae was demonstrated in cadaveric heads. Surgical case examples were also presented to demonstrate the application of and indications for the orbitozygomatic approach. The orbitozygomatic approach provides access to the anterior and middle cranial fossae as well as the deep sellar and basilar apex regions. Increased bone removal from the skull base obviates the need for vigorous brain retraction and offers an improved multiangled trajectory and shallower operative field. Modifications to the orbitozygomatic approach provide alternatives that can be tailored to particular lesions, enabling the surgeon to use the best technique in each individual case rather than a "one size fits all" approach.


A prospective randomised study of total laparoscopic hysterectomy, laparoscopically assisted vaginal hysterectomy and non-descent vaginal hysterectomy for the treatment of benign diseases of the uterus.
To compare the three techniques of hysterectomy-total laparoscopic hysterectomy (TLH), laparoscopic assisted vaginal hysterectomy (LAVH) and non-descent vaginal hysterectomy (NDVH). Ninety women with benign disease of uterus with failed medical management or not amenable to medical management were randomised into three groups for either technique of hysterectomy, thirty in each group, by the same surgeon. For each patient, intra-operative parameters including total duration of surgery, blood loss, surgical difficulty and intra-operative complications were recorded. Total hospital stay, adverse events, satisfaction rate and recuperation time was analysed and compared. Statistical analysis was done using SPSS15 software. Non-descent vaginal hysterectomy (NDVH) took least operative time and significantly lesser blood loss (p = 0.02) compared to TLH and LAVH. There was no significant difference between adverse events, recuperation time and postoperative pain between the three techniques. Non-descent vaginal hysterectomy may be a preferred technique over laparoscopic hysterectomy for benign diseases of uterus where extensive pelvic dissection is not required.


Intelligent infusion controller with a physiological information feedback function.
In hospitals, some problems still exist, such as transfusion reaction that cannot be dealt with in time, medical staff cannot observe the physiological information of the infusion patients in real time, and the infusion speed cannot be controlled smartly. To address these problems, we propose a method for intelligent monitoring and designed a controller for dripping speed regulation. A photoelectric sensor was used to obtain the heart rate (HR) information, and a PID parameter self-tuning controller based on the fuzzy control principle was developed to establish a multi-stage adaptive control method based on HR feedback. By controlling the rotation of the motor to drive the cam to control the drip rate smartly. Also, the infusion and physiological information are transmitted to the nurse station to monitor the possible transfusion reaction. The experiments show that the intelligent infusion controller can achieve HR signal detection with an average accuracy of over 94%, dripping speed detection and adjustment with an average accuracy of above 98% and adjustment time within 35 seconds. Our study proved that the intelligent infusion controller can control the infusion process intelligently and effectively, and has excellent reliability, small steady-state error and high practical value.


Effects of visual biofeedback training for fall prevention in the elderly.
[Purpose] The purpose of this study was to investigate the effects of six weeks of visual biofeedback training for prevention of falling in the elderly. The Tetrax system was used for visual biofeedback training. [Subjects and Methods] Thirty elderly persons (experimental group=15, control group=15) who were above 70 and under 80 years of age participated in biofeedback training. They were trained for 15 minutes a day, three times per week. We measured the weight distribution index, stability index, and fall index in the subjects using the Tetrax system, and paired t-tests were used to evaluate the changes before and after intervention. The difference between the groups was compared using an independent t-test. [Results] The experimental group showed significant differences in weight distribution index, stability index, and fall index. The control group showed no significant differences. According to the comparison of training effects between the two groups, the variables of stability index and fall index revealed a statistically significant difference. [Conclusion] The method of visual biofeedback training used in this study should be considered a therapeutic method for the elderly to improve weight distribution, stability, and effectiveness in preventing falls.


Nodular fasciitis of the parotid gland: A challenging diagnosis on FNA.
Nodular fasciitis (NF) is a clonal, self-limited proliferation that has only rarely been described in the parotid gland. Because of its potential to mimic benign and malignant parotid neoplasms clinically, radiographically, and cytomorphologically, NF is often managed with unnecessary surgery, which is associated with a risk for significant surgical complications. The purpose of this study is to present the clinical and cytomorphologic findings for NF of the parotid gland by fine-needle aspiration (FNA). The pathology archives of the authors' respective institutions were searched for salivary gland FNA cytology specimens with a confirmed diagnosis of NF. The clinical history, pathologic diagnosis, cytomorphologic findings, and immunocytochemical results were recorded. A total of 15 cases were identified; the average age was 37 years, and 10 patients (66.7%) were female. Five cases (33.3%), all treated surgically, showed recurrence within an average timeframe of 1.6 months. Only 3 cases (20.0%) were classified as definitive, probable, or suggestive of NF. On average, smears were composed of predominantly single (69.2%), spindled cells (100.0%) with short unipolar (76.9%) and/or bipolar processes (38.5%), round (61.5%) or elongated (84.6%) nuclei, and inconspicuous nucleoli (53.8%). In 69.2%, a tissue-culture appearance was shown, and 76.9% contained myxoid stroma. In 46.2%, a minimal amount of cytologic atypia was shown. Keeping NF in the differential for any bland, single, spindled cell proliferation with elongated cytoplasmic processes and bland nuclei may prompt the clinician to consider more conservative management in the correct clinical context.


Numerical Modeling of Sub-Wavelength Anti-Reflective Structures for Solar Module Applications.
This paper reviews the current progress in mathematical modeling of anti-reflective subwavelength structures. Methods covered include effective medium theory (EMT), finite-difference time-domain (FDTD), transfer matrix method (TMM), the Fourier modal method (FMM)/rigorous coupled-wave analysis (RCWA) and the finite element method (FEM). Time-based solutions to Maxwell's equations, such as FDTD, have the benefits of calculating reflectance for multiple wavelengths of light per simulation, but are computationally intensive. Space-discretized methods such as FDTD and FEM output field strength results over the whole geometry and are capable of modeling arbitrary shapes. Frequency-based solutions such as RCWA/FMM and FEM model one wavelength per simulation and are thus able to handle dispersion for regular geometries. Analytical approaches such as TMM are appropriate for very simple thin films. Initial disadvantages such as neglect of dispersion (FDTD), inaccuracy in TM polarization (RCWA), inability to model aperiodic gratings (RCWA), and inaccuracy with metallic materials (FDTD) have been overcome by most modern software. All rigorous numerical methods have accurately predicted the broadband reflection of ideal, graded-index anti-reflective subwavelength structures; ideal structures are tapered nanostructures with periods smaller than the wavelengths of light of interest and lengths that are at least a large portion of the wavelengths considered.


NADPH-dependent formation of polar and nonpolar estrogen metabolites following incubations of 17 beta-estradiol with human liver microsomes.
By using a versatile high-pressure liquid chromatography method (total elution time approximately 135 min) developed in the present study, we detected the formation of some 20 nonpolar radioactive metabolite peaks (designated as M1 through M20), in addition to a large number of polar hydroxylated or keto metabolites, following incubations of [(3)H]17beta-estradiol with human liver microsomes or cytochrome P450 3A4 in the presence of NADPH as a cofactor. The formation of most of the nonpolar estrogen metabolite peaks (except M9) was dependent on the presence of human liver microsomal proteins, and could be selectively inhibited by the presence of carbon monoxide. Among the four cofactors (NAD, NADH, NADP, NADPH) tested, NADPH was the optimum cofactor for the metabolic formation of polar and nonpolar estrogen metabolites in vitro, although NADH also had a weak ability to support the reactions. These observations suggest that the formation of most of the nonpolar estrogen metabolite peaks requires the presence of liver microsomal enzymes and NADPH. Chromatographic analyses showed that these nonpolar estrogen metabolites were not the monomethyl ethers of catechol estrogens or the fatty acid esters of 17beta-estradiol. Analyses using liquid chromatography/mass spectrometry and NMR showed that M15 and M16, two representative major nonpolar estrogen metabolites, are diaryl ether dimers of 17beta-estradiol. The data of our present study suggest a new metabolic pathway for the NADPH-dependent, microsomal enzyme-mediated formation of estrogen diaryl ether dimers, along with other nonpolar estrogen metabolites.


Influencing Factors of Quality of Life and Prediction Model Building in Patients with Primary Nephrotic Syndrome: A Single-Centre Retrospective Study.
This study aimed to explore the influencing factors of quality of life (QOL) and establish a prediction model in patients with primary nephrotic syndrome (PNS). A single-centre retrospective study was conducted on 245 patients with PNS admitted to Zibo Central Hospital from August 2020 to August 2022. According to the 36-Item Short-Form Health Survey (SF-36) for QOL evaluation, the patients were divided into the good QOL group (the total score ≥50 points) and poor QOL group (the total score <50 points). Univariate analysis was conducted by collecting clinical data from patients, and multiple logistic regression analysis was carried out on single factors with statistically significant differences to construct a clinical prediction model. The diagnostic efficacy of the prediction model was evaluated using the receiver operating characteristic (ROC) curve. A total of 245 questionnaires were distributed, and 243 valid questionnaires were recovered, in which 143 cases had good QOL, with an average score of (71.86 ± 10.83) points, and 100 cases had poor QOL, with an average score of (40.03 ± 5.95) points. Statistical differences were observed in age, education level, monthly family average income, payment methods of medical expenses, albumin, 24-hour urinary protein quantification (24 h UPro) and serum uric acid (SUA) in both groups (p < 0.05), whereas no statistical difference was found in gender, body mass index (BMI) and marital status (p > 0.05). The multiple logistic regression analysis showed that age (X1), monthly family average income (X2), payment methods of medical expenses (X3), albumin (X4), 24 h UPro (X5) and SUA (X6) were risk factors for the QOL of patients with PNS, with Y = -12.105 + 0.130X1 + 0.457X2 + 0.448X3 + -0.161X4 + 0.823X5 + 0.025X6 as the regression prediction model. The results of ROC curve showed that the area under the curve (AUC) was 0.987 with standard error of 0.005 (p < 0.001), and 95% CI was 0.976-0.998. Age, monthly family average income, payment methods of medical expenses, albumin, 24 h UPro and SUA are risk factors that affect the QOL of patients with PNS, and the construction of prediction model has good evaluation value and can provide a reference for clinical practice.


The influence of laterally inhomogeneous corrosion on electrical and optical calcium moisture barrier characterization.
The reaction of calcium thin films with water - monitored optically or electrically - is widely used for evaluating ultrahigh barrier foils for the encapsulation of organic electronic devices. We studied the common optical and the electrical method and compared them with in situ atomic force microscope topography scans. All three methods were applied at the same sample in parallel in a typical test design containing a gas volume for water distribution next to the calcium layer of 60 and 1000 nm thickness, respectively. The common assumption for the interpretation of such measurement data is laterally homogeneous calcium consumption of the layer from top to bottom. In contrast, we observed a significant ratio of laterally inhomogeneous corrosion of the calcium on the micro-scale for both thicknesses. Some areas were strongly or completely corroded through the whole layer while others exhibited less or no corrosion. Furthermore, those corroded spots grew in lateral direction. As a consequence of lateral inhomogeneous calcium corrosion the electrical calcium measurement method underestimates the amount of calcium left; according to our results this does not affect the water vapor transmission rate (WVTR). Optical data evaluated by Lambert-Beer law underestimate the amount of calcium left as well and also underestimate the WVTR. If the data are evaluated, using a linear relationship between transmission and amount of calcium left, the both values are more precise. The scope of this study is to call attention to the existence of lateral inhomogeneity in calcium corrosion and its impact on the calcium permeation measurements. While more investigations would be needed to quantify the effect of this inhomogeneity on the electrical and optical method in general, the discussion sheds light on the way, calcium test data are influenced by lateral inhomogeneous calcium corrosion. Our observations highlight the need for careful interpretation of calcium test results, but also demonstrate its capabilities for precise ultrahigh barrier measurements.


[5-FU, FT-207 and uracil concentrations in the serum and tissues of patients with cervical cancer after UFT oral administration].
The concentrations of 5-FU, FT-207 and uracil were estimated in blood serum, cancer tissue and normal tissue of patients with uterine cervical cancer. A daily dose of 600 mg of UFT was administrated for 7 days to cervical cancer patients, and they received radical hysterectomy and pelvic lymphadenectomy. After single administration of UFT, the serum concentration of 5-FU was highest at 60 minutes (0.094 micrograms/ml) and became reduced with time. On the other hand, when UFT was administered for 7 consecutive days, the serum concentration of 5-FU was found to reach a plateau between 60 minutes (0.215 micrograms/ml) and 120 minutes (0.222 micrograms/ml) with gradual decline thereafter. Significantly higher levels of 5-FU were achieved at 60 min. and 120 min. and apparent accumulation of 5-FU in serum was observed following continuous administration of UFT. Similar results were observed regarding the change of serum concentration of uracil, while FT-207 was observed to remain in serum for a longer time than 5-FU. In the uterine cervix, the concentration of 5-FU cancer tissue was 0.087 micrograms/ml, approximately 3 times that of normal tissue, and approximately 5.1 times that of the preoperative serum concentration of 5-FU, indicating a tendency to accumulate in cancer tissue. Although a higher concentration of 5-FU was detected in pelvic lymph nodes and ovaries, no significant differences were recognized between metastatic nodes and metastasis-free nodes.


Endothelial glycocalyx in retina, hyperglycemia, and diabetic retinopathy.
The endothelial glycocalyx (EG) is a meshlike network present on the apical surface of the endothelium. Membrane-bound proteoglycans, the major backbone molecules of the EG, consist of glycosaminoglycans attached to core proteins. In addition to maintaining the integrity of the endothelial barrier, the EG regulates inflammation and perfusion and acts as a mechanosensor. The loss of the EG can cause endothelial dysfunction and drive the progression of vascular diseases including diabetic retinopathy. Therefore, the EG presents a novel therapeutic target for treatment of vascular complications. In this review article, we provide an overview of the structure and function of the EG in the retina. Our particular focus is on hyperglycemia-induced perturbations in the glycocalyx structure in the retina, potential underlying mechanisms, and clinical trials studying protective treatments against degradation of the EG.


The economic advantages of measured change in health care: an example from obstetrics.
To evaluate the economic effects of an increased oxytocin dosage for labor stimulation at a large urban hospital, a cost analysis of a before and after cohort, analytic clinical trial was performed. Delivery outcomes for two different oxytocin dosages were evaluated from the perspective of provider and consumer costs attributable to the oxytocin regimen. The high-dose oxytocin regimen resulted in an estimated provider and consumer cost savings of approximately $350,000 per year. We conclude that a small change in health care, such as an increased infusion rate of a single drug, can have economic advantages.


DNA polymerase alpha associated protein P1, a murine homolog of yeast MCM3, changes its intranuclear distribution during the DNA synthetic period.
We isolated a murine gene for the DNA polymerase alpha associated protein P1, which shares high homology with the budding yeast MCM3 protein, which is a member of a protein family involved in the early event of DNA replication having a putative DNA-dependent ATPase motif. Using a polyclonal anti-P1 antibody raised against a beta-galactosidase-P1 fusion protein, we identified at least two forms of P1 protein in the nucleus of a mouse cell line, an underphosphorylated form that was associated with a particular nuclear structure and a hyperphosphorylated form loosely bound to the nucleus. During progression through S phase, P1 disappeared, first from the euchromatic region, then from the heterochromatic region, apparently in parallel with temporally ordered DNA replication. Thus, it is likely that the underphosphorylated P1 is dissociated from the nuclear structure after DNA replication by cell cycle-dependent phosphorylation. This is the first direct observation of a protein whose behavior is consistent with that of a hypothetical factor which restricts the chromatin to replicate once per cell cycle in higher eukaryotes.


Data-defined naïve Bayes (DNB) based decision scheme for the nonlinear mitigation for OAM mode division multiplexed optical fiber communication.
In this manuscript, a data-defined naïve Bayes (DNB)-based decision scheme for nonlinear mitigation is presented for an orbital angular momentum (OAM) mode-division multiplexed optical fiber communication system. Due to the inherent nonlinearity characteristic of opto-electronic devices, the strong nonlinear impairments are deemed inevitable in OAM mode-division multiplexed transmission, leading to severely nonlinear effects. A DNB algorithm based on the prior probability distribution is adopted to mitigate the strong device nonlinearity of the OAM communication system, which is hard to solve using the conventional approaches due to the complex theoretical model of opto-electronic devices. An experiment using eight-mode OAM with a 32GBaud Nyquist QPSK signal optical fiber communication system is carried out with ring core fiber (RCF) transmission over 10 km to verify the effectiveness of the proposed scheme. The experimental results demonstrate that the nonlinear effects on OAM transmission can be effectively mitigated using a DNB-based decision with a bit error rate (BER) reduction of at most 66%. Moreover, compared with other nonlinear decision algorithms based on machine learning, such as support vector machine (SVM) or k-nearest neighbors (KNN), the digital signal processing complexity of the DNB algorithm is significantly reduced.


Use of laser light to treat certain lesions in standardbreds.
The final and last-quarter race times and racing classes for a group of Standardbreds were analyzed before and after infrared laser light treatment. These horses had either check ligament injuries, plantar desmitis or pharyngeal lymphoid hyperplasia. A 904-nm infrared laser was used to treat check ligaments at 146 Hz for 26 sec/cm2 of affected area, acute plantar desmitis at 73 Hz and chronic plantar desmitis at 292 Hz for 26 sec/cm2 of affected area, and pharyngeal lymphoid hyperplasia at 146 Hz for 5 minutes. Of 35 horses treated for check ligament injuries, 80% had similar or faster final race times, 68.6% had similar or faster last-quarter times, and 68.6% raced in similar or higher classes after treatment. Of 8 horses treated for plantar desmitis, 87.5% had similar or faster final and last-quarter times, and raced in similar or higher classes after treatment. Of 30 horses treated for pharyngeal lymphoid hyperplasia, 80% had similar or faster final race times, 90% had similar or faster last-quarter times, and 70% raced in similar or higher classes after treatment.


The enzymatic mechanism of the otospongiotic disease and NaF action on the enzymatic balance.
Extensive research on enzymes led to the discovery of the innermost mechanism of the otospongiotic disease. The authors present the results of multiple correlations made from February 1976 to September 1980 on 648 samples of perilymph taken during stapedectomies performed on otosclerotic patients. We studied microdosages of three selected enzymes--trypsin, alpha 1 antitrypsin, and alpha 2 macroglobulin--in each of the samples and their relationship with cochlear deterioration expressed in dBs of bone conduction decrease in pure-tone audiometry testing. This study allowed us a better knowledge of the enzymatic mechanism of the otospongiotic disease, based on the previously reported trypsin-alpha 1 antitrypsin balance, but in which alpha 2 macroglobulin appears to play a role as essential as that of alpha 1 antitrypsin. This enzymatic mechanism explains NaF efficiency, which is due in fact to a double action: not only direct trypsin inhibition, but also an overall reduction in enzymatic values in the perilymph of otospongiotic/otosclerotic patients. Current studies could lead to the possibility of future NaF replacement by proteinase inhibitors either of microbial origin, under study by Japanese researchers, or even of synthetic origin, which should be investigated. In fact, the role of NaF therapy could already be taken over by diphosphonates currently under study.


Toward an applied technology for quality measurement in health care.
Cost containment, financial incentives to conserve resources, the growth of for-profit hospitals, an aggressive malpractice environment, and demands from purchasers are among the forces today increasing the need for improved methods that measure quality in health care. At the same time, increasingly sophisticated databases and the existence of managed care systems yield new opportunities to observe and correct quality problems. Research on targets of measurement (structure, process, and outcome) and methods of measurement (implicit, explicit, and sentinel methods) has not yet produced managerially useful applied technology for quality measurement in real-world settings. Such an applied technology would have to be cheaper, faster, more flexible, better reported, and more multidimensional than the majority of current research on quality assurance. In developing a new applied technology for the measurement of health care quality, quantitative disciplines have much to offer, such as decision support systems, criteria based on rigorous decision analyses, utility theory, tools for functional status measurement, and advances in operations research.


Mycorrhization and phosphorus nutrition affect water relations and CAM induction by drought in seedlings of Clusia minor.
Crassulacean acid metabolism (CAM) is currently viewed as an adaptation to water deficit. In plants of Clusia minor, which grow mostly on acidic, P-deficient soils, CAM is induced by water deficit. The symbiosis between plants and mycorrhizal fungi alleviates the symptoms of P deficiency and may influence drought resistance. Therefore, the effect of P supply, modified by three different experimental treatments, on the induction of CAM by drought in C. minor was investigated to test the hypothesis that P deficiency will produce greater CAM activity and, in addition, that treatment will modify drought tolerance. Seedlings were grown in forest soil sterilized and inoculated with Scutellospora fulgida (SF treatment), sterilized and supplemented with P (Ph treatment) or non-sterilized and containing native mycorrhizae (Nat treatment). Leaf turgor potential (psi(T)) was determined psychrometrically, and CAM activity as nocturnal acid accumulation (DeltaH(+)) by titration of dawn and dusk leaf sap. Plant mass and P content were higher in SF and Ph than in Nat seedlings. After 21 d of water deficit, psi(T) increased in SF, decreased in Ph and remained unchanged in Nat, and, after 7 and 14 d of water deficit, DeltaH(+) in Nat was three times higher than at the beginning of drought, whereas in SF and Ph DeltaH(+) was lower than on day 0. P deficiency in Nat seedlings was ameliorated by inoculation or P addition. The SF and Nat seedlings showed greater tolerance of drought than Ph. P deficiency promoted the induction of CAM by drought in Nat seedlings, whereas P fertilization and mycorrhization did not. Nocturnal acid accumulation was highly and negatively correlated with plant P and N contents, indicating that P and N deficiencies are promoters of CAM in droughted plants of C. minor.


Facile microfluidic synthesis of monodispersed size-controllable quantum dot (QD) microbeads using custom developed QD photoresist.
Fluorescent microbeads (MBs) are widely used as next-generation biosensors for the detection of target chemicals at highly sensitive concentrations, and for imaging and tracking in vitro and in vivo. However, most known methods for producing fluorescent MBs require complicated multistep processes that result in low production rates. In this study, we report a method for fabricating micrometer-sized quantum dot microbeads (QD-MBs) using a microfluidic chip and specially designed QD photoresist (QD-PR). This on-demand lab-on-a-chip method yielded monodispersed QD-MBs ranging from 1.89 to 33 μm with a coefficient of variation of less than 10%. The size distribution of the fabricated QD-MBs was Gaussian with a peak around the mean diameter and a spread of sizes around the peak. Compared with nanoscale QDs, the fabricated QD-MBs showed no emission loss. The full-width at half-maximum of the emission peak of the QD-MBs was smaller than that of the colloidal QDs, indicating a more uniform distribution and a higher density of QDs within the MB structure. In addition, we investigated the microfluidic flow regime that yielded the most uniform and controllable QD-MB. The MBs in the dripping regime were spherical and monodisperse, with an excellent particle size distribution. In this study, we present a simple and effective strategy for producing QD-MBs with controllable sizes, which can be crucial in diverse fields such as biosensing, drug delivery, and imaging.


Methadone dose, take home status, and hospital admission among methadone maintenance patients.
Among patients receiving methadone maintenance treatment (MMT) for opioid dependence, receipt of unobserved dosing privileges (take homes) and adequate doses (ie, ≥ 80 mg) are each associated with improved addiction treatment outcomes, but the association with acute care hospitalization is unknown. We studied whether take-home dosing and adequate doses (ie, ≥80 mg) were associated with decreased hospital admission among patients in an MMT. We reviewed daily electronic medical records of patients enrolled in one MMT program to determine receipt of take-home doses, methadone dose 80 mg or more, and hospital admission date. Nonlinear mixed-effects logistic regression models were used to evaluate whether take-home doses or dose 80 mg or more on a given day were associated with hospital admission on the subsequent day. Covariates in adjusted models included age, sex, race/ethnicity, human immunodeficiency virus status, medical illness, mental illness, and polysubstance use at program admission. Subjects (n = 138) had the following characteristics: mean age 43 years; 52% female; 17% human immunodeficiency virus-infected; 32% medical illness; 40% mental illness; and 52% polysubstance use. During a mean follow-up of 20 months, 42 patients (30%) accounted for 80 hospitalizations. Receipt of take homes was associated with significantly lower odds of a hospital admission (adjusted odds ratio [AOR] = 0.26; 95% confidence interval [CI], 0.11-0.62), whereas methadone dose 80 mg or more was not (AOR = 1.01; 95% CI, 0.56-1.83). Among MMT patients, receipt of take homes, but not dose of methadone, was associated with decreased hospital admission. Take-home status may reflect not only patients' improved addiction outcomes but also reduced health care utilization.


He said what? Physiological and cognitive responses to imagining and witnessing outgroup racism.
Responses to outgroup racism can have serious implications for the perpetuation of bias, yet research examining this process is rare. The present research investigated self-reported, physiological, and cognitive responses among "experiencers" who witnessed and "forecasters" who imagined a racist comment targeting an outgroup member. Although previous research indicates that experiencers self-reported less distress and chose a racist partner more often than forecasters, the present results explored the possibility that experiencers may actually be distressed in such situation but regulate their initial affective reactions. The results from Experiment 1 demonstrated that participants in both roles showed (a) no activation of the hypothalamic pituitary adrenal stress axis (decreased cortisol) and (b) activation of the sympathetic autonomic nervous system (increased skin conductance). However, experiencers but not forecasters displayed a physiological profile indicative of an orienting response (decreased heart rate and increased skin conductance) rather than a defensive response (increased heart rate and increased skin conductance). Furthermore, the results from Experiment 2 provided additional evidence that experiencers are not distressed or regulating their emotional responses. In particular, experiencers showed less cognitive impairment on a Stroop task than forecasters. Together these findings indicate that when people actually encounter outgroup bias, they respond with apathy and do not censure the racist. (PsycINFO Database Record


Safety and immunogenicity of one versus two doses of Takeda's tetravalent dengue vaccine in children in Asia and Latin America: interim results from a phase 2, randomised, placebo-controlled study.
Dengue is the most common mosquito-borne viral disease in human beings, and vector control has not halted its spread worldwide. A dengue vaccine for individuals aged 9 years and older has been licensed, but there remains urgent medical need for a vaccine that is safe and effective against all four dengue virus serotypes (DENV-1-4) in recipients of all ages. Here, we present the preplanned interim analyses at 6 months of a tetravalent dengue vaccine candidate (TDV), which is comprised of an attenuated DENV-2 virus strain (TDV-2) and three chimeric viruses containing the premembrane and envelope protein genes of DENV-1, DENV-3, and DENV-4 genetically engineered into the attenuated TDV-2 genome backbone (TDV-1, TDV-3, and TDV-4). An ongoing phase 2, randomised, double-blind, placebo-controlled trial of a TDV is being done at three sites in dengue-endemic countries (Dominican Republic, Panama, and the Philippines) to determine its safety and immunogenicity over 48 months in healthy participants aged 2-17 years who were randomly assigned (1:2:5:1) using an interactive web response system (stratified by age) to subcutaneous TDV injection (one 0·5 mL dose containing 2·5 × 104 plaque-forming units [PFU] of TDV-1; 6·3 × 103 PFU of TDV-2; 3·2 × 104 PFU of TDV-3; and 4·0 × 105 PFU of TDV-4) in different dose schedules (two-dose regimen at 0 and 3 months, one dose at 0 months, or one dose at 0 months and a booster at 12 months) or placebo. The primary endpoint of this 6 month interim analysis was geometric mean titres (GMTs) of neutralising antibodies against DENV-1-4 in the per-protocol immunogenicity subset at 1 month, 3 months, and 6 months after the first injection. Safety was assessed as a secondary outcome as percentage of participants with serious adverse events in all participants who were injected (safety set), and solicited and unsolicited adverse events (immunogenicity subset). This trial is registered with ClinicalTrials.gov, number NCT02302066. 1800 participants were enrolled between Dec 5, 2014, and Feb 13, 2015. 1794 participants were given study injection as follows: 200 participants were given two-dose regimen at 0 and 3 months (group 1), 398 were given one dose at 0 months (group 2), 998 were given one dose at 0 months and will be given (trial ongoing) a booster at 12 months (group 3), and 198 were given placebo (group 4). These 1794 participants were included in the safety set; 562 participants were randomly assigned to the immunogenicity subset, of which 503 were included in the per-protocol set. TDV elicited neutralising antibodies against all DENV serotypes, which peaked at 1 month and remained elevated above baseline at 6 months. At 6 months, GMTs of neutralising antibodies against DENV-1 were 489 (95% CI 321-746) for group 1, 434 (306-615) for group 2, 532 (384-738) for group 3, and 62 (32-120) for group 4; GMTs of neutralising antibodies against DENV-2 were 1565 (1145-2140) for group 1, 1639 (1286-2088) for group 2, 1288 (1031-1610) for group 3, and 86 (44-169) for group 4; GMTs of neutralising antibodies against DENV-3 were 160 (104-248) for group 1, 151 (106-214) for group 2, 173 (124-240) for group 3, and 40 (23-71) for group 4; and GMTs of neutralising antibodies against DENV-4 were 117 (79-175) for group 1, 110 (80-149) for group 2, 93 (69-125) for group 3, and 24 (15-38) for group 4. No vaccine-related serious adverse events occurred; 15 (3%) of 562 participants in the immunogenicity subset reported vaccine-related unsolicited adverse events. The reactogenicity profile of TDV was acceptable, and similar to previous findings with TDV. TDV is safe and immunogenic in individuals aged 2-17 years, irrespective of previous dengue exposure. A second TDV dose induced enhanced immunogenicity against DENV-3 and DENV-4 in children who were seronegative before vaccination. These data supported the initiation of phase 3 evaluation of the efficacy and safety of TDV given in a two-dose schedule 3 months apart, with analyses that take into account baseline age and dengue serostatus. Takeda Vaccines.


Personality and dementia caring: a review and commentary.
Carers of people with dementia are at increased risk of experiencing psychological distress. This article reviews recent findings on the role of personality traits for psychological outcomes for carers of people with dementia. Several studies have now established that personality influences the caregiving experience, carer well-being and outcomes such as coping ability, burden and caregiving style. Several moderators of these associations have also been identified such as the effect of kinship and type of dementia. There is consistent evidence that carer personality characteristics influence the progression of the disease such as cognitive decline and severity. Most of the recent studies identified in this review are cross-sectional. Taken together, these results indicate that personality is an important psychological resource for carers. Recent findings indicate that personality traits are associated with and influence both carer and patient outcomes. Future research is necessary to guide interventions and to expand further on our understanding of how personality factors shape adjustment to the caregiving role and how these impact on the progression of the disease.


Three-dimensional MOF-type architectures with tetravalent uranium hexanuclear motifs (U6O8).
Four metal-organic frameworks (MOF) with tetravalent uranium have been solvothermally synthesized by treating UCl4 with rigid dicarboxylate linkers in N,N-dimethylfomamide (DMF). The use of the ditopic ligands 4,4'-biphenyldicarboxylate (1), 2,6-naphthalenedicarboxylate (2), terephthalate (3), and fumarate (4) resulted in the formation of three-dimensional networks based on the hexanuclear uranium-centered motif [U6O4(OH)4(H2O)6]. This motif corresponds to an octahedral configuration of uranium nodes and is also known for thorium in crystalline solids. The atomic arrangement of this specific building unit with organic linkers is similar to that found in the zirconium-based porous compounds of the UiO-66/67 series. The structure of [U6O4(OH)4(H2O)6(L)6]⋅X (L = dicarboxylate ligand; X = DMF) shows the inorganic hexamers connected in a face-centered cubic manner through the ditopic linkers to build up a three-dimensional framework that delimits octahedral (from 5.4 Å for 4 up to 14.0 Å for 1) and tetrahedral cavities. The four compounds have been characterized by using single-crystal X-ray diffraction analysis (or powder diffraction analysis for 4). The tetravalent state of uranium has been examined by using XPS and solid-state UV/Vis analyses. The measurement of the Brunauer-Emmett-Teller surface area indicated very low values (Langmuir <300 m(2) g(-1) for 1, <7 m(2) g(-1) for 2-4) and showed that the structures are quite unstable upon removal of the encapsulated DMF solvent.


Efficacy of Periconceptional High-Dose Folic Acid in Isolated Orofacial Cleft Prevention: A Systematic Review.
Background The effectiveness of folic acid in prevention of neural tube defects has been well established. Periconceptional supplementation of folic acid in low doses has been shown to be effective in some studies on its efficacy in prevention of occurrence of clefts. There are few studies on high-dose folic acid for prevention of occurrence and recurrence of clefts in high risk cases and the overall consensus based on these is not available. Objectives The aim of this review is to assess whether high-dose folic acid supplementation during the periconceptional period reduces the risk of occurrence of nonsyndromic clefts and recurrence in high-risk cases. Search Methods Search was conducted in the various databases and trial registers. There were no restrictions in the search with regards to language, study setting, or date of publication. Results The search yielded four studies-one randomized control trial, two prospective control trials, and a case-control surveillance on screening 401 articles. The three case-control studies were specifically on recurrence of clefts in high risk cases. The heterogeneity of the studies prevented conduction of a meta-analysis. But results of the studies demonstrate a strong association between high-dose folic acid and isolated nonsyndromic cleft lip with or without cleft palate (CL±CP). But such an effect is weak with regards to isolated cleft palate (CP). Conclusions With the limited evidence available, our conclusion is that high-dose folic acid probably has a role in prevention of recurrence of isolated CL±CP in high-risk individuals, but not CP.


The role of self-compassion in mediating the effect of perfectionism on personal growth initiative in dental hygienists.
This study explored perfectionism, self-compassion and personal growth initiative in clinical dental hygienists. Cross-sectional survey research was conducted with a non-probability sample of clinical dental hygienists (n = 877). The survey had 55 items and consisted of three validated instruments: Frost's Multidimensional Perfectionism Scale-Brief (including evaluative concerns and perfectionistic striving subscales), Neff's Self-Compassion Scale and Robitschek's Personal Growth Initiative Scale. Descriptive, correlation, t-test, ANOVA and logistic regression analyses were used to evaluate the relationships among variables. Mediation analysis was conducted to determine the presence of a mediated moderation effect of self-compassion on perfectionism and personal growth initiative. The completion rate for the survey was 89% (n = 788). Evaluative concerns (M = 11.83) and perfectionistic strivings (M = 15.44) among dental hygienists were high, levels of self-compassion (SC) were moderate (M = 2.87) and levels of personal growth initiative (PGI) were low (M = 38.07) compared to others not in the dental field. The mediation analysis found that SC mediates the relationship between perfectionistic evaluative concerns and PGI. It was also determined that SC mediates the relationship between perfectionistic strivings and PGI. Dental hygienists have high levels of perfectionism and may lack necessary levels of self-compassion to counteract those perfectionistic tendencies resulting in a decrease in taking the initiative to engage in opportunities for growth. This suggests the importance of dental hygienists developing a more adaptive perfectionism to balance self-criticism along with not having unrealistic expectations for perfection while engaging in self-compassion that includes self-kindness and mindfulness to support their continued growth.


Relationship Between Service Utilization and Runaway Youths' Alcohol and Other Drug Use.
Runaway youths represent a vulnerable, high-risk population that has received little societal attention. Studies show that youths at greatest need are the least likely to access mental health, medical, and other social services. This study evaluated service utilization, including medical visits, psychological, alcohol and drug counseling and 12-step attendance, and substance use. Runaway youths (n = 51) between the ages of 12 and 17 with a diagnosis of alcohol abuse or dependence were recruited from two southwestern runaway shelters. Results showed that psychological counseling and medical visits were associated with less alcohol use while 12-step attendance was associated with more alcohol use at pretreatment. Service utilization was not associated with illicit drug use. The findings suggest that alcohol and other drug use are affected differently by service utilization in this sample of youths. More research is required to evaluate and develop treatments which can effectively intervene with this high-risk group.


[Debrisorb therapy of severe hand infections].
Treatment with DEBRISORB, a new topical agent formed by three dimensional network of dextran polymers in porous hydrophilic beads, was used in 26 cases of infected wounds in the hand. These were of traumatic and postoperative origin, often with remaining necrotic areas and in a few cases with a considerable oedema. The special effect of DEBRISORB was in absorbing the exudate and in reducing the inflammation and swelling of the discharging wounds. Within a few days secretion was diminished and healthy granulation tissue appeared. For covering the defects we employed local transposition flaps, direct flaps and split-skin grafts without complications. Local treatment with DEBRISORB is an effective method to clean infected wounds, to reduce inflammation and oedema, and is useful as treatment before grafting.


The existence of solutions for fractional differential equations with p-Laplacian at resonance.
By giving proper transformation, selecting suitable Banach spaces and operators, and using Mawhin's coincident theory, we investigate the existence of solutions for fractional differential equations with p-Laplacian at resonance under two kinds of boundary conditions, respectively. Examples are given to illustrate our main results.


Polarized type-1 dendritic cells (DC1) producing high levels of IL-12 family members rescue patient TH1-type antimelanoma CD4+ T cell responses in vitro.
Deficiencies in TH1-type immunity in patients with cancer may facilitate tumor progression and limit the effectiveness of current immunotherapy approaches. We hypothesized that Type-1 polarized dendritic cells (DC1) might be able to recondition patient antitumor CD4+ T cell responses toward the TH1-type in vitro. Although DC1 have been previously demonstrated to prime TH1 responses from naive CD4+ T cells, their impact on antigen-experienced TH responses remains unknown. We confirmed our own earlier observations that patient CD4+ T cell reactivity against melanoma-associated antigens (MAA) was weaker and less Type-1-polarized than their corresponding antiviral responses. Stimulation of patient CD4 T cells with peptide-pulsed DC1 (producing multiple IL-12 family member cytokines, including IL-12p70, IL-23, and IL-27) promoted robust TH1-type, epitope-specific T cell responses. Addition of exogenous IL-12 family member cytokines alone, or in combination, to nonpolarized DC was insufficient to equate to the benefits associated with DC1-based stimulation; however, IL-27 and IL-12p70 blockade neutralized the ability of DC1 cells to enhance TH1-type antitumor immunity in vitro. Notably, DC1-based stimulation seemed capable of "revitalizing" defective TH1-type responses within the CD45RO+ subset of antigen-experienced CD4+ T cells in melanoma patients. In addition to promoting elevated levels of IFN-gamma from responder CD4+ T cells, DC1-based stimulation also led to increased levels of IL-12Rbeta2 and t-bet expression by TH cells. These results suggest that preexisting CD4+ T cell immunity to cancer is not relegated to Type-1 insufficiency and may be corrected via the application of DC1-based vaccination protocols.


Higher-order factors of the big five and basic values: empirical and theoretical relations.
The Big Five Model of personality and Schwartz's theory of basic values are two prominent taxonomies that offer a convenient way to organize the major individual differences in, respectively, personality traits and personal values. Both taxonomies provide a hierarchical framework, whose components can be traced back to a smaller number of broader dimensions. The current study investigated the relationship between the two superordinate factors of personality encompassing the Big Five dimensions (alpha and beta) and the four higher-level value types from Schwartz's theory (Self-transcendence, Self-enhancement, Conservation, and Openness to change). To examine the relations between higher-order traits and values, we relied on factor analysis and multidimensional scaling. Results indicated that alpha and beta were differently related to the Conservation versus Openness to change dimension. Alpha was positively related to values that emphasize protecting stability and respecting norms and traditions, and negatively related to values emphasizing receptiveness to change and independence of thought, feeling, and action. The opposite pattern of relations was found for beta.