The Symbiotic Relationship Between Drug Discovery and Organic Chemistry.
All pharmaceutical products contain organic molecules; the source may be a natural product or a fully synthetic molecule, or a combination of both. Thus, it follows that organic chemistry underpins both existing and upcoming pharmaceutical products. The reverse relationship has also affected organic synthesis, changing its landscape towards increasingly complex targets. This Review article sets out to give a concise appraisal of this symbiotic relationship between organic chemistry and drug discovery, along with a discussion of the design concepts and highlighting key milestones along the journey. In particular, criteria for a high-quality compound library design enabling efficient virtual navigation of chemical space, as well as rise and fall of concepts for its synthetic exploration (such as combinatorial chemistry; diversity-, biology-, lead-, or fragment-oriented syntheses; and DNA-encoded libraries) are critically surveyed.


Saline-dependent regulation of manganese peroxidase genes in the hypersaline-tolerant white rot fungus Phlebia sp. strain MG-60.
The expression pattern of manganese peroxidases (MnPs) in nitrogen-limited cultures of the saline-tolerant fungus Phlebia sp. strain MG-60 is differentially regulated under hypersaline conditions at the mRNA level. When MG-60 was cultured in nitrogen-limited medium (LNM) containing 3% (wt/vol) sea salts (LN-SSM), higher activity of MnPs was observed than that observed in normal medium (LNM). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis demonstrated that two MnP isoenzymes were de novo synthesized in the culture of LN-SSM. Three MnP-encoding genes (MGmnp1, MGmnp2, and MGmnp3) were isolated by reverse transcription (RT)-PCR and rapid amplification of cDNA ends PCR techniques. The corresponding isozymes were identified by peptide mass fingerprinting analysis. MnP isozymes encoded by MGmnp2 and MGmnp3 were observed mainly in LN-SSM. Real-time RT-PCR analysis revealed high levels of MGmnp2 and MGmnp3 transcripts in LN-SSM 48 h after the addition of 2% NaCl. The induction of MnP production and the accumulation of gene transcripts by saline were well correlated in the presence of Mn(2+). However, in the absence of Mn(2+), there was no clear correlation between mnp transcripts levels and MnP activity, suggesting posttranscriptional regulation by Mn(2+).


Identification and characterization of an aquaporin 1 immunoreactive amacrine-type cell of the mouse retina.
Using immunocytochemistry, a type of amacrine cell that is immunoreactive for aquaporin 1 was identified in the mouse retina. AQP1 immunoreactivity was found in photoreceptor cells of the outer nuclear layer (ONL) and in a distinct type of amacrine cells of the inner nuclear layer (INL). AQP1-immunoreactive (IR) amacrine cell somata were located in the INL and their processes extended through strata 3 and 4 of the inner plexiform layer (IPL) with thin varicosities. The density of the AQP1-IR amacrine cells increased from 100/mm(2) in the peripheral retina to 350/mm(2) in the central retina. The AQP1-IR amacrine cells comprise 0.5% of the total amacrine cells. The AQP1-IR amacrine cell bodies formed a regular mosaic, which suggested that they represent a single type of amacrine cell. Double labeling with AQP1 and glycine, gamma-aminobutyric acid (GABA) or GAD(65) antiserum demonstrated that the AQP1-IR amacrine cells expressed GABA or GAD(65) but not glycine. Their synaptic input was primarily from other amacrine cell processes. They also received synaptic inputs from a few cone bipolar cells. The primary synaptic targets were ganglion cells, followed by other amacrine cells and cone bipolar cells. In addition, gap junctions between an AQP1-IR amacrine process and another amacrine process were rarely observed. In summary, a GABAergic amacrine cell type labeled by an antibody against AQP1 was identified in the mouse retina and was found to play a possible role in transferring a certain type of visual information from other amacrine or a few cone bipolar cells primarily to ganglion cells.


Murine leukaemia virus p30 heterogeneity as revealed by two-dimensional gel electrophoresis is not an artefact of the technique.
We have utilized two-dimensional (2D) gel electrophoresis [the first dimension being a linear pH gradient (5 to 8) and the second and 8 to 15% acrylamide gradient] to characterize the virion protein, p30, from several strains of purified murine leukaemia virus (MuLV). In all cases, we found that there was a predominant (70 to 90%) Coomassie Brilliant Blue-staining p30 spot, as well as several other species which differed in pI. The major p30 spot differed in pI among different MuLV strains and the minor spots varied depending on the host cell used to grow the virus. Specifically, (i) Moloney (M)-MuLV/NIH-3T3 showed two spots, a major one at pI 6.3 and a more acidic one, (ii) AKR/NIH-3T3, AKR/mouse embryo, and Gross/NIH-3T3 showed four spots, with the two basic, minor spots of AKR/NIH-3T3 appearing relatively decreased in intensity, and (iii) Rauscher (R)-MuLV/JLS-V9 (BALB/c) showed two spots, a major one with greater than 90% of the estimated Coomassie Brilliant Blue stain at a pI of 6.5 and a minor, acidic one. The major spots of AKR and M-MuLV viruses also differed in pI. The major spot of the AKR and Gross N-tropic viruses had a pI of 6.7 while that of NB-tropic virus M-MuLV had a pI of 6.3. The possibility that the heterogeneity observed in p30 was an artefact of the 2D gel technique had to be considered since urea was used to denature proteins in the first dimension of the gel. This possibility was made unlikely by our finding that another technique, chromatofocusing, gave the same results. Specifically, M-MuLV/JLS-V9 p30, when separated on chromatofocusing columns under non-denaturing conditions yielded three peaks, each of which directly corresponded to the three spots (pI: 6.1, 6.3, 6.6) observed on 2D gels. Furthermore, tryptic peptide maps of the major (pI 6.3) and one of the minor (pI 6.6) M-MuLV spots, although very similar in peptide composition, showed about five clearly defined differences. These results indicate (i) that the p30s of several N- and NB-tropic viruses are heterogeneous in pI, and (ii) for one particular MuLV, the p30 heterogeneity can be explained by a difference in amino acid composition. These findings of p30 charge heterogeneity may reflect either the presence of several different p30s in each virus particle and/or a heterogeneity in the virus population.


Access to and utilisation of healthcare services by sex workers at truck-stop clinics in South Africa: A case study.
Sex worker-specific health services aim to respond to the challenges that this key population faces in accessing healthcare. These services aim to integrate primary healthcare (PHC) interventions, yet most services tend to focus on prevention of HIV and sexually transmitted infections (STIs). North Star Alliance (North Star) is a public-private partnership providing a healthcare service package in roadside wellness clinics (RWCs) to at-risk populations along transport corridors in sub-Saharan Africa. To inform future service development for sex workers and describe North Star's contribution to healthcare provision to this population in South Africa, we describe services provided to and utilised by sex workers, and their views of these services. Using a mixed-methods approach, we present quantitative analyses of anonymised North Star routine data for sex workers for October 2013 - September 2015, covering nine sites in seven provinces. Clinic visits were disaggregated by type of service accessed. We performed thematic analysis of 25 semi-structured interviews conducted at five clinics. A total of 2 794 sex workers accessed RWCs during the 2 years. Sex workers attending clinics were almost exclusively female (98.2%) and aged <40 years (83.8%). The majority were South African (83.8%), except at Musina, where the majority of clients were Zimbabwean. On average, sex workers visited the clinics 1.5 times per person. However, in most cases only one service was accessed per visit. PHC services other than for HIV and STIs were accessed more commonly than HIV-specific services and STI treatment. There was an increase in the number of services accessed over time, the figure almost doubling from 1 489 during the first year to 2 936 during the second year. Although during recruitment participants reported having had sex in exchange for goods or money during the past 3 months, not all participants self-identified as sex workers during interviews; however, all reported feeling at higher risk of poor health than the general population owing to their involvement in sex work. Participants reported satisfaction with site accessibility, location and operating hours. Sex workers accessing sites described services as being suitable and accessible, with friendly staff. RWCs were highly appreciated by the users, as they are suitable and accessible. The sex workers who used the clinics visited them irregularly, mostly for PHC services other than HIV and STIs. Services other than the one for which the sex worker came to the clinic rarely appeared to be offered. We recommend areas for service expansion.


The relationships between self-compassion, rumination, and depressive symptoms among older adults: the moderating role of gender.
Depression is a significant mental health issue for older adults. Rumination is a key risk factor for depressive symptoms, and self-compassion is a protective factor. The aim of the current study was to test the processes by which self-compassion might act as a protective factor among older adults by investigating a mediation model, and whether the model is conditional on gender. It was hypothesised that self-compassion and its six components (self-kindness, common humanity, mindfulness, self-judgement, isolation, and over-identification) would be indirectly associated with depressive symptoms via rumination. A sample of 135 older Australian women and 106 older Australian men aged between 65 and 89 years completed the Centre for Epidemiologic Studies Depression Scale, the Ruminative Thought Style Questionnaire, and the Self-Compassion Scale. Results supported the mediation models for self-compassion for both men and women, however, support for the models involving the individual components of self-compassion varied according to gender. The mediation effects were stronger for women than men. Interventions aimed at increasing self-compassion might have benefits for older adults. Future research investigating whether tailoring interventions according to gender of participants is efficacious is needed.


Large-Scale Cross-Modality Search via Collective Matrix Factorization Hashing.
By transforming data into binary representation, i.e., Hashing, we can perform high-speed search with low storage cost, and thus, Hashing has collected increasing research interest in the recent years. Recently, how to generate Hashcode for multimodal data (e.g., images with textual tags, documents with photos, and so on) for large-scale cross-modality search (e.g., searching semantically related images in database for a document query) is an important research issue because of the fast growth of multimodal data in the Web. To address this issue, a novel framework for multimodal Hashing is proposed, termed as Collective Matrix Factorization Hashing (CMFH). The key idea of CMFH is to learn unified Hashcodes for different modalities of one multimodal instance in the shared latent semantic space in which different modalities can be effectively connected. Therefore, accurate cross-modality search is supported. Based on the general framework, we extend it in the unsupervised scenario where it tries to preserve the Euclidean structure, and in the supervised scenario where it fully exploits the label information of data. The corresponding theoretical analysis and the optimization algorithms are given. We conducted comprehensive experiments on three benchmark data sets for cross-modality search. The experimental results demonstrate that CMFH can significantly outperform several state-of-the-art cross-modality Hashing methods, which validates the effectiveness of the proposed CMFH.


[Catecholamines in the pathochemical structure of depressive conditions (according to material from a biological study)].
By a combination of biochemical and pharmacodynamical analyses the author conducted a differentiated study of the role of separate neurohormones (adrenalin, noradrenalin, dopamine, serotonine) and their interconnection with other regulating systems (corticosteroids, nucleic acids) in the neurochemical structure of experimental models in depressive behaviour (reserpine depressions, depressions due to inhibitors of dopamine-beta-oxydase). In the aspect of the author's concept concerning reciprocity of relationships between the central and peripheral catecholamine mechanisms on the basis of the obtained experimental data, their comparison with the previous clinico-biochemical investigations and literary data is considered to be the pathochemical basis of depression. This is considered to be a multicomponent structure of pathologically fixed changes of the central noradrenergic activity, relationships in the catecholaminergic system (hypothalamus--medullau substance of the adrenal glands) and processes of reswitching catecholamine influences on the state of other neurochemical regulatory systems.


Membrane mirror and bias electronics.
We have designed and built an electrostatically deformable membrane mirror with simple bias and driver electronics to evaluate its suitability for a curvature-sensing adaptive optics system. It has a 100-mm-diameter aluminized nitrocellulose membrane, with 31 actuators arranged concentrically. The unit operates at atmospheric pressure with a high bias voltage applied to the membrane. The high-voltage electronics are contained within the mirror housing for safety reasons. An entrance window reduces the effects of air-coupled vibration. Details of the device and design rationale are presented. With a proper bias, the unit can provide low-order (including tip-tilt) wave-front correction.


Do patients return to work after total knee arthroplasty?
Although there is extensive literature supporting a high success rate, there are limited data on return to work after total knee arthroplasty (TKA). We sought to determine (1) the percentage of patients who returned to work after TKA; (2) what percentage returned to their original job; (3) whether this varied based on the physical job demand category; and (4) whether there were differences between men and women in terms of the likelihood of returning to work after TKA. A multicenter study was conducted of patients of working age (18-60 years) who underwent TKA 1 to 5 years previously. An independent third-party survey center with expertise in collecting healthcare data for state and federal agencies collected the data. Definitions from the US Department of Labor's Dictionary of Occupational Titles were used to determine physical job demand categories of sedentary, light, medium, heavy, and very heavy. Complete data were collected on 661 patients undergoing TKA (average age 54 years, 61% women). Seventy-five percent (494 of 661) were employed in the 3 months before their TKA and 98% (482 of 494) returned to work after surgery; 89% (440 of 494) returned to the same job. Before surgery, physical demand categories of the patients' jobs were sedentary 12%, light 10%, medium 24%, heavy 24%, and very heavy 30%. The return to work rate for those employed during the 3 months before surgery by physical demand category was sedentary 95%, light 91%, medium 100%, heavy 98%, and very heavy 97%. Men were more likely than women to have worked within the 3 months before TKA but there was no difference between sexes in return to work after TKA. In this group of young patients, most returned to work at their usual occupation after TKA.


Use of in situ extracorporeal shock wave lithotripsy in upper ureteric stone.
This study was done to determine the effectiveness of in situ extracorporeal shock wave lithotripsy (ESWL) in upper ureteric calculi in terms of stone clearance, peroperative & postoperative complications and also to determine some criteria for selection of patients for this procedure. From July, 2003 to July 2004, a total of 67 patients, with excreting kidneys and having stone size less than 2 cm were treated by in situ ESWL using Lithostar plus Lithotriptor. The patient group comprised of 52 men and 15 women, age ranged from 14 years to 65 years. Of the total 67 patients selected for study 44 patients were included in group I, having stone size ?1.5 and visible distal flow of contrast on IVU & 23 patients were included in Group II with stone size>1.5 cm to 2 cm and contrast seen only upto stone. Four (04) patients from Group I and three (03) patients from group II were dropped out during the follow up period so that data of 40 patients in group I and 20 patients in group II were analyzed finally. Number of shock wave was given in 1 to 3 sessions. Finally 95% of group I and 85% of group II achieved complete clearance of calculi at the end of 3 sessions. In situ ESWL is a good option for the treatment of upper ureteric calculi.


Study of the circumoval precipitate in Schistosomiasis japonica by immunofluorescent technic.
The 48-hour circumoval precipitates formed by infected human and rabbit sera on lyophilized Schistosoma japonicum eggs were stained with the corresponding fluorescein-labelled monospecific goat antisera for study under a fluorescent microscope. The three major Ig classes were found to participate in the formation of the precipitate, with major components being IgG and IgM; IgA participated least. IgE and C3 also contributed to the precipitate. The circumoval precipitate on S. japonicum eggs is therefore a complex of different immunoglobulins reactive with antigen(s) from the egg.


Comparison of fatty acid contents of erythrocyte membrane in hemodialysis and peritoneal dialysis patients.
Membrane fatty acid composition plays an important role in the cellular function. Erythrocyte fatty acid composition mirrors that of myocardium and is influenced by diet. Earlier studies have shown significant alterations of membrane fatty acid composition in ethnically mixed patients with end-stage renal disease. Given the impact of ethnic and dietary factors, we sought to examine membrane fatty acid composition in an ethnically homogeneous end-stage renal disease population residing in a coastal region of Korea with high fish consumption. Cross-sectional study. Outpatient facility at Dong-A University Hospital, Busan, Republic of Korea. We recruited 15 stable hemodialysis patients, 14 peritoneal dialysis patients, and 10 age- and gender-matched normal controls. Patients with significant malnutrition, short duration of dialysis, recent infection, malignancy, or liver disease were excluded. Dietary intake and use of omega-3 fatty acid supplements were determined. Erythrocyte membrane fatty acid contents measured by gas chromatography. Palmitoleic acid and alpha-linolenic acid levels were lower, whereas oleic acid, linoleic acid, and arachidonic acid levels were higher in patients with end-stage renal disease compared with the control group. Total monounsaturated fatty acids (palmitoleic acid and oleic acid) were significantly higher in peritoneal dialysis than in hemodialysis patients. Eicosapentaenoic acid and omega-3 docosapentaenoic acid were significantly higher, but total omega-6 fatty acids, omega-6/omega-3, and arachidonic acid/eicosapentaenoic acid ratios were significantly lower in hemodialysis patients consuming omega-3 supplements compared with those who did not. Patients with end-stage renal disease exhibited significant alterations in erythrocyte membrane fatty acids, which were partially modified by the dialysis modality and omega-3 fatty acid supplementation.


The role of fish intake on asthma in children: A meta-analysis of observational studies.
The evidence is mixed on the use of long chain Omega-3 fatty acids in the prevention and management of childhood asthma. We conducted a systematic search and meta-analysis investigating the role of fish intake, the main dietary source of long chain omega-3 fatty acids, on asthma in children. A total of 1119 publications were identified. Twenty-three studies on fish intake in association with childhood asthma were included in the final review. In 15 of 23 studies, early introduction of fish (6-9 months) and regular consumption (at least once a week) improved asthma symptoms and reduced risk in children 0-14 years as compared to no fish consumption; 6 of 23 showed no effect and 2 of 23 studies suggest adverse effects. Meta-analysis revealed an overall "beneficial effect" for "all fish" intake on "current asthma" [OR: 0.75; 95%CI: 0.60-0.95] and "current wheeze" [OR: 0.62; 95%CI: 0.48-0.80] in children up to 4.5 years old. An overall protective effect of "fatty fish" intake as compared to "no fish" intake in children 8-14 years old was also observed [OR: 0.35; 95%CI: 0.18-0.67]. This meta-analysis suggests that introduction of fish early in life (6-9 months) and regular consumption of all fish (at least once a week) reduces asthma and wheeze in children up to 4.5 years old, while fatty fish intake may be beneficial in older children. Future well-designed clinical trials are recommended to confirm the promising findings documented in this literature analysis.


Systematic review and network meta-analysis of the efficacy and safety of tumour necrosis factor inhibitor-methotrexate combination therapy versus triple therapy in rheumatoid arthritis.
Clinical trials have not consistently demonstrated differences between tumour necrosis factor inhibitor (TNFi) plus methotrexate and triple therapy (methotrexate plus hydroxychloroquine plus sulfasalazine) in rheumatoid arthritis (RA). The study objective was to estimate the efficacy, radiographic benefits, safety and patient-reported outcomes of TNFi-methotrexate versus triple therapy in patients with RA. A systematic review and network meta-analysis (NMA) of randomised controlled trials of TNFi-methotrexate or triple therapy as one of the treatment arms in patients with an inadequate response to or who were naive to methotrexate was conducted. American College of Rheumatology 70% response criteria (ACR70) at 6 months was the prespecified primary endpoint to evaluate depth of response. Data from direct and indirect comparisons between TNFi-methotrexate and triple therapy were pooled and quantitatively analysed using fixed-effects and random-effects Bayesian models. We analysed 33 studies in patients with inadequate response to methotrexate and 19 in patients naive to methotrexate. In inadequate responders, triple therapy was associated with lower odds of achieving ACR70 at 6 months compared with TNFi-methotrexate (OR 0.35, 95% credible interval (CrI) 0.19 to 0.64). Most secondary endpoints tended to favour TNFi-methotrexate in terms of OR direction; however, no clear increased likelihood of achieving these endpoints was observed for either therapy. The odds of infection were lower with triple therapy than with TNFi-methotrexate (OR 0.08, 95% CrI 0.00 to 0.57). There were no differences observed between the two regimens in patients naive to methotrexate. In this NMA, triple therapy was associated with 65% lower odds of achieving ACR70 at 6 months compared with TNFi-methotrexate in patients with inadequate response to methotrexate. Although secondary endpoints numerically favoured TNFi-methotrexate, no clear differences were observed. The odds of infection were greater with TNFi-methotrexate. No differences were observed for patients naive to methotrexate. These results may help inform care of patients who fail methotrexate first-line therapy.


Proteus syndrome associated with liver involvement: case report.
We report a patient with proteus syndrome who has epidermal nevus, right-sided asymmetric growth of extremities, pelvis, vertebrae and hemimegalencephaly. This patient also had enlargement of the liver which is not reported before in the proteus syndrome.


Intrinsically radiolabeled multifunctional cerium oxide nanoparticles for in vivo studies.
Cerium oxide nanoparticles (CONPs) have demonstrated protection properties against oxidation in various cells and tissues. The mechanism of this, however, is poorly understood. Monitoring the interaction of CONPs with biological compartments 'in situ' is crucial to understand their biochemical and physiological properties in vivo. In this paper, a multifunctional nanoparticle platform was obtained through an intrinsic radiolabeling strategy and extrinsic surface functionalization to combine dual imaging components (Single Photon Emission Computed Tomography/Optical Imaging, SPECT/OI) in one nanoparticle. The cell viability, cell uptake and overall in vivo biodistribution of CONPs were also manipulated through surface functionalization. The intrinsic radiolabeling strategy is demonstrated by incorporating radionuclides (141Ce, 111In or 65Zn) into CONPs and a radiolabeled CONP (rCONP) was coated with biocompatible polymers including Dextran T10 (DT10), poly(acrylic acid) (PAA), or functionalized DT10 (DT10-NH2, DT10-PEG and DT10-sulfobetaine). Fluorescent CONPs were obtained through conjugation of fluorescein isothiocyanate (FITC) with DT10-NH2 rCONP and used for cell imaging. The DT10 and DT10-NH2 rCONP did not show decreased viability up to 120 μg mL-1 whilst the PAA rCONP showed decreased viability beyond 40 μg mL-1. Variations in blood circulation and renal/hepatic clearance of rCONPs were demonstrated and were dependent on surface coating and the hydrodynamic size of nanoparticles. The ex vivo biodistribution results were reflected in SPECT imaging of 141Ce-rCONPs, showing accumulation in the liver and spleen of a living mouse over a one week period. The intrinsic radiolabeling and extrinsic surface modifications together determine the biophysical properties of CONPs and their potential applications for in vivo studies and biomedical imaging.


Laparoscopic Ovarian Drilling Reduces Testosterone and Luteinizing Hormone/Follicle-Stimulating Hormone Ratio and Improves Clinical Outcome in Women with Polycystic Ovary Syndrome.
Laparoscopic ovarian drilling (LOD) is one of the common modes of treatment for women with polycystic ovary syndrome (PCOS) who are resistant to clomiphene citrate. The data related to the effect of LOD on sex hormones are limited. The objective of the study was to investigate the effect of LOD on hormonal parameters and clinical outcomes in women with PCOS. This study was conducted in a tertiary care hospital. Fifty PCOS patients who were admitted for LOD were enrolled in the study. Serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were estimated in all the patients before and after LOD. Paired t-test was used to assess the differences in hormonal parameters before and after LOD. LOD reduces testosterone (P < 0.001), LH (P < 0.001), and LH/FSH ratio (P < 0.001), increases FSH (P < 0.001) levels, and improves the rate of ovulation (38/50) and clinical pregnancy (21/50) in PCOS. When subgroup analysis was done, LOD significantly reduced testosterone and LH/FSH ratio in ovulatory and conceived groups. Furthermore, the menstrual cycle became regular, and hirsutism and acne were reduced after LOD in women with PCOS. LOD reduces testosterone and LH/FSH ratio and improves clinical outcome in PCOS.


Embryohistiogenesis of Vascular Tufts of Glomeruli: a Possible Hypothesis.
Embryogenesis of the kidney glomeruli, especially its vascular component, has not been well documented. Glomeruli capillary tuft is surrounded and enveloped by visceral epithelial cells, which is a unique portal system that connects afferent with efferent arteriole without interaction with venular circulation. We hypothesized that the portal system embryologically has developed by extension of the intima of afferent arteriole into the stroma of glomerulus. We also hypothesized that juxtaglomeruli apparatus was developed from remnants of smooth muscle cells of the media of afferent arteriole at the anastomosing site with the Bowman capsule entrance. We studied 5 human fetal kidneys by hematoxylin-eosin, periodic acid-Schiff, and immunoperoxidase staining techniques. Hematoxylin-eosin staining of fetal kidney showed presence of erythrocytes in early vesicle form of glomeruli that was confirmed by immunohistochemical staining with CD31, smooth muscle actin, and CD34 markers. These stains showed extension of extraglomerular arterioles to the glomeruli. Periodic acid-Schiff staining showed also the continuity of the basement membrane in extraglomeruli and internal glomerular vascular tufts. This study shows that there is a relationship between the metanephric blast cells and major vessel critical for angiogenesis. When afferent arteriole come in contact with the immature glomeruli, its intima migrates into the glomerular tuft to form intraglomerular capillary system, while its smooth muscle remains at the entrance orifice and develops juxtaglomerular apparatus cells.


Effect of gastrin-releasing peptide on the secretion of mouse islet hormones in vitro.
Collagenase-isolated mouse islets were incubated with gastrin-releasing peptide (GRP). At 5.6 mmol glucose/l. 10 nmol GRP/l increased the release of insulin (by 50%) and glucagon (by twofold), decreased the release of pancreatic polypeptide (by 35%), but did not significantly affect the release of somatostatin. At 16.7 mmol glucose/l, 10 nmol GRP/l increased glucagon release (by fivefold) and decreased pancreatic polypeptide release (by 46%), without significantly altering insulin and somatostatin release. GRP (200 nmol/l) did not affect insulin release by perifused mouse islets at 2.8 mmol glucose/l, but increased both first and second phase insulin release after a square wave increase in the glucose concentration to 11.1 mmol/l. At 5.6 mmol glucose/l, GRP (100 pmol/1-100 nmol/l) increased (by 50-70%) insulin release by the RINm5F clonal cell line. GRP did not affect glucose oxidation or the cyclic adenosine monophosphate content of RINm5F cells. However, the intracellular free Ca2+ concentration of RINm5F cells was rapidly and transiently increased by GRP (maximum increase of 64% about 10 s after exposure to 1 mumol GRP/l). The rise of intracellular free Ca2+ was approximately halved in the absence of extracellular Ca2+. The results suggest that GRP may contribute to the normal regulation of the endocrine pancreas. The insulin-releasing effect of GRP is mediated via increased cytosolic free Ca2+, derived both from an increased net influx of extracellular Ca2+ and from mobilization of intracellular Ca2+ stores.


Dibut-yl{N'-[1-(5-chloro-2-oxidophenyl-κO)ethyl-idene]-3-hy-droxy-2-naphtho-hydrazidato-κN',O}tin(IV).
The five-coordinate Sn(IV) atoms in the two crystallographically independent mol-ecules of the title compound, [Sn(C(4)H(9))(2)(C(19)H(13)ClN(2)O(3))], are in distorted cis-C(2)NO(2)Sn trigonal-bipyramidal coordination environments. The tridentate dianion of the Schiff base, N'-[1-(5-chloro-2-oxidophen-yl)ethyl-idene]-3-hy-droxy-2-naphtho-hydrazide, displays inter-molecular O-H⋯N hydrogen bonding, which stabilizes the overall compound.


Evaluation of sustainable and healthy eating behaviors and adherence to the planetary health diet index in Turkish adults: a cross-sectional study.
The Planetary Health Diet Index (PHDI) is a relatively new index, and studies about its relationship with eating behaviors, nutritional status, and obesity in adults are very limited. For this reason, in this study, sustainable healthy eating behaviors of individuals and compliance of their diets with PHDI were evaluated. This cross-sectional study was conducted with 1,112 adults (70.1% women and 29.9% men with mean age = 28.7 years, SE = 9.47). Study data were obtained with the face-to-face interview method via a questionnaire including sociodemographic characteristics, anthropometric measurements, the Sustainable and Healthy Eating (SHE) Behaviors Scale, and 24-h dietary recall. PHDI was evaluated for adherence to EAT-Lancet Commission recommendations. The average PHDI total score was 41.5 points. Higher SHE Behaviors Scale and PHDI scores were observed in participants with a duration of education above 8 years (p < 0.05). Those with lower SHE Behaviors Scale and PHDI scores were more likely to be obese (p < 0.001). The total PHDI score was positively associated with fiber, vitamin E, potassium, and folate, and negatively associated with pyridoxine and calcium (p < 0.05). The total SHE Behaviors Scale score was positively associated with carbohydrates, fiber, and potassium and negatively associated with pyridoxine, calcium, and energy (p < 0.05). A one-unit increase in SHE Behaviors Scale total score resulted in a 5,530 unit (95%CI: 4.652; 6.407) increase in PHDI total score and a one-unit increase in duration of education (years) resulted in a 0.660 unit (95%CI: 0.403; 0.918) increase in PHDI total score. Furthermore, a one-unit increase in Body Mass Index (BMI) (kg/m2) resulted in a - 0.218 unit (95%CI: -0.424; -0.013) decrease in PHDI total score. The participants' PHDI index scores were low; therefore, the adherence to the EAT-Lancet recommendation was low which might be associated with obesity. Clinical studies evaluating the effects of adherence to sustainable diets on adequate and balanced nutrition and health outcomes are recommended.


Metals content of recycled construction and demolition wood before and after implementation of best management practices.
A limitation to recycling wood from construction and demolition (C&D) waste is contamination of metals from the inadvertent inclusion of preservative treated wood, in particular wood treated with chromated copper arsenate (CCA) and newer copper-based formulations. To minimize contamination many regions have developed best management practices (BMPs) for separating treated from untreated wood. The objective of this study was to evaluate the fraction of preservative treated wood in recycled C&D wood after the implementation of BMPs, using Florida as a case study. Methods involved collecting recycled C&D wood samples from throughout the state, measuring metals concentrations (As, Cu, and Cr) in the samples to compute the fraction of recycled wood treated with waterborne wood preservatives, and comparing measurements with those taken prior to the formalization of BMPs. Metals concentrations were measured using two methods, one based on traditional laboratory digestion methods and another using a more rapid hand-held X-ray Fluorescence (XRF) device in the field. The proportion of waterborne preservative-treated wood in recycled wood products has reduced significantly in the intervening 20 years (from 6% to 2.9%), and the fraction of CCA-treated wood has been reduced even further, to 1.4%. The remaining fraction of waterborne preservative-treated wood is comprised of new formulations of copper-based preservatives. This suggests that restrictions from the wood preservation industry and best management practices implemented at recycling facilities have been effective in reducing heavy metal contamination from pressure treated lumber in recycled wood products.


Downregulation of endothelial transient receptor potential vanilloid type 4 channel underlines impaired endothelial nitric oxide-mediated relaxation in the mesenteric arteries of hypertensive rats.
The endothelium contributes to the maintenance of vasodilator tone by releasing endothelium-derived relaxing factors, including nitric oxide (NO). In hypertension, endothelial nitric oxide synthase (eNOS) produces less NO and could be one of the contributing factors to the increased peripheral vascular resistance. Agonist-induced Ca(2+) entry is essential for the activation of eNOS. The transient receptor potential vanilloid type 4 (TRPV4) channel, a Ca(2+)-permeant cation channel, is expressed in the endothelial cells and involved in the regulation of vascular tone. The present study aimed to investigate the role of TRPV4 channel in endothelium-dependent NO-mediated relaxation of the resistance artery in hypertensive rats. Using a wire myograph, relaxation response to the TRPV4 activator, 4alpha-phorbol-12,13-didecanoate (4alphaPDD) was assessed in mesenteric arteries obtained from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). Compared to WKY, SHR demonstrated a significantly attenuated 4alphaPDD-induced endothelium-dependent NO-mediated relaxation. Immunohistochemical analysis revealed positive staining for TRPV4 in the endothelium of mesenteric artery sections in both WKY and SHR. Furthermore, TRPV4 mRNA and protein expressions in SHR were significantly lower than their expression levels in WKY rats. We conclude that 4alphaPDD-induced endothelium-dependent NO-mediated vasorelaxation is reduced in SHR and downregulation of TRPV4 could be one of the contributing mechanisms.


Hepatic disposition of trimethoprim and sulfamethoxazole.
Hepatic disposition of trimethoprim (TMP) and sulfamethoxazole (SMX) and the liver distributional volumes were investigated in the in situ perfused rat liver preparation. Perfusion experiments were conducted using Krebs-bicarbonate buffer delivered via the portal vein (15 ml/min) in a single-pass mode. Erythrocytes (intravascular marker) and Evans blue (extracellular marker) were used for the estimation of liver distributional volumes, and desiccation and freeze-drying methods were used for the estimation of liver water content. TMP and SMX were administered together as a bolus in the presence (1%) and absence of protein. Although SMX profiles displayed a characteristic sharp peak followed by a slower eluting tail in all cases, TMP profiles were dependent on protein; in the absence of protein, the early sharp peak was replaced by a flatter profile with a later peak. Fractional effluent recovery (F; 0.77 vs. 0.82) and hepatic clearance (CL(H); 3.44 vs. 2.70 ml/min) for TMP were not influenced by albumin; with SMX, F increased (0.32 vs. 0.60) and CL(H) decreased (10.2 vs. 6.0 ml/min) with an increase in the perfusate protein concentration. Hepatic extraction of TMP was low (<0.30), whereas it was intermediate (<0.70) for SMX. In addition, distributional volumes and total water content of the liver were successfully determined.


Protective effect of Quercetin in the Regression of Ethanol-Induced Hepatotoxicity.
This study examined the protective effects of quercetin on chronic ethanol-induced liver injury. Rats were treated with ethanol at a dose of 4 g/100 g/day for 90 days. After ethanol intoxication, levels of serum amino transferases were significantly elevated. Decreased activity of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase was also observed on ethanol administration. Increased amounts of lipid peroxidation products viz. hydroperoxides, conjugated dienes and malodialdehyde were observed on ethanol intoxication. Ethanol administration resulted in significant decrease in liver glutathione content. After 90 days, the control animals were divided into two groups, the control group and the control+quercetin group. Ethanol-treated group was divided into two groups, abstention group and quercetin-supplemented group. After 30 days, the animals were sacrificed and various biochemical parameters were analyzed. The changes in enzyme activities as well as levels of lipid peroxidation products were reversed to a certain extent by quercetin. Quercetin supplementation resulted in increase of glutathione content to a significant level compared to normal abstention group. Quercetin supplemented group showed a faster recovery than abstention group. This shows the protective effect of quercetin against chronic ethanol induced hepatotoxicity. Histopathological study is also in line with these results.


[Adaptation of food ingestion to energy expenditure].
Body energy balance is regulated in adults. The accuracy of the phenomenon is particularly evident in laboratory animals under steady conditions. Moreover, it has been repeatedly demonstrated that this balance is maintained in spite of fluctuations in food intake or energy expenditure. When animals such as rats, dogs or rabbits are presented with a diluted or concentrated version of familiar food, they compensate rapidly by increasing or decreasing their ponderal intake. This is achieved first by a change in meal frequency, then meal size adapts to the new caloric content and meal frequency returns to the original pattern. This adaptation is based on the learning of post-ingestive cues. Hypo or hyperphagia leads to reduced or increased energy expenditure, as the case may be; the basal metabolic rate is modulated by thyroid hormones and diet-induced thermogenesis by the sympathetic system. These variations are partly regulatory. In a cold environment, the increase in energy expenditure caused by increased thermogenesis is rapidly compensated by increased caloric intake. Physical activity activates the sympathetic system responsible for numerous hormonal changes, the most important of which is insulin hyposecretion. In animals or humans, moderate aerobic exercise induces a small weight loss; afterwards, weight gain is normalized and increased caloric intake compensates for energy expenditures such as exercise, increased basal metabolic rate and diet-induced thermogenesis. Extreme changes in body weight and fat are produced by gestation and lactation; they are satisfactorily explained by concomitant hormonal changes. Especially during lactation, food intake is regulated so that it allows body weight to return to pregestation level. Studies on the mechanisms implicated in the regulation of body energy balance are still in progress. Friedman and Ramirez (1985) suggest that the way fatty acids are utilized is important. Kasser et al. (1985) show a striking difference in the cellular metabolism of hypothalamic regions, depending on the metabolic state or the animal, and Woods et al. (1985) strongly suggest a role for the central insulin level. These hypotheses are well-documented and not exclusive of each other.


Comparative study of resection and radiofrequency ablation in the treatment of solitary colorectal liver metastases.
We compared outcomes in patients with solitary colorectal liver metastases treated by either hepatic resection (HR) or radiofrequency ablation (RFA). A retrospective analysis from a prospective database was performed on 67 consecutive patients with solitary colorectal liver metastases treated by either HR or RFA. Forty-two patients underwent HR and 25 patients underwent RFA. The 5-year overall and local recurrence-free survival rates after HR (50.1% and 89.7%, respectively) were higher than after RFA (25.5% and 69.7%, respectively) (P = .0263 and .028, respectively). In small tumors less than 3 cm (n = 38), the 5-year survival rates between HR and RFA were similar, including overall (56.1% vs 55.4%, P = .451) and local recurrence-free (95.7% vs 85.6%, P = .304) survival rates. On multivariate analysis, tumor size, metastases treatment, and primary node status were significant prognostic factors. HR had better outcomes than RFA for recurrence and survival after treatment of solitary colorectal liver metastases. However, in tumors smaller than 3 cm, RFA can be recommended as an alternative treatment to patients who are not candidates for surgery because the liver metastases is poorly located anatomically, the functional hepatic reserve after a resection would be insufficient, the patient's comorbidity inhibits a major surgery, or extrahepatic metastases are present.


Pilot-symbols-aided cycle slip mitigation for DP-16QAM optical communication systems.
A pilot-symbols-aided phase unwrapping (PAPU), which utilizes the time-division multiplexed pilot symbols that are transmitted with data, is proposed to do cycle slip detection and correction with the carrier phase estimation (CPE). Numerical simulations for 10 Gbaud dual-polarization 16-ary quadrature amplitude modulation (DP-16QAM) systems show that the block averaging quadrature phase-shift keying (QPSK) partitioning with PAPU greatly eliminates the performance degradation caused by cycle slips, maintains a low CS probability with less influence of filter length, and achieves a bit-error-rate (BER) performance below soft-decision forward error correction (FEC) limit 2 × 10⁻² at 15 dB optical signal-to-noise ratio with only 1.56% overhead and 6 MHz combined laser linewidth.


Copolymer-controlled homogeneous precipitation for the synthesis of porous microfibers of alumina.
Mesoporous aluminas with a uniform fibrous morphology were synthesized using a copolymer-controlled homogeneous precipitation method under hydrothermal conditions. Scanning electron microscopy, X-ray diffraction, solid-state magic-angle spinning nuclear magnetic resonance, transmission electron microscopy, thermogravimetric analysis, nitrogen adsorption, Fourier transform infrared spectrometry, and elemental analysis techniques were used to characterize the samples. The effect of various synthesis conditions on the morphology and mesoporous structure of the alumina fibers was investigated. Such porous alumina microfibers may find applications in nanotechnology and catalysis. They can also be used as advanced high-temperature composite materials and templates for fabrication of fibrous materials of various compositions, such as carbon, transition-metal oxides, and polymers.


Comparison of the antitumor activity of gemcitabine and ara-C in a panel of human breast, colon, lung and pancreatic xenograft models.
Gemcitabine is a new deoxycytidine analog that exhibits significant cytotoxicity against a variety of cultured murine and human tumor cells. The cytotoxic action of gemcitabine appears to be due to the inhibition of DNA synthesis by inhibition of ribonucleotide reductase and by competition with dCTP for incorporation into DNA. We have previously shown that gemcitabine, but not cytosine arabinoside (ara-C), has a broad spectrum of antitumor activity against 7 different types of murine solid tumors. The activity of gemcitabine was schedule dependent. To further characterize its activity, gemcitabine was tested against 12 human carcinoma xenografts. When given on an every 3 day x 4 schedule, the following percent inhibitions (at maximally tolerated doses [MTD]; MTD/2) in tumor growth were seen: MX-1 mammary (93%; 80%), CX-1 colon (92%; 82%), HC-1 colon (96%; 92%), GC3 colon (98%; 94%), VRC5 colon (99%; 100%), LX-1 lung (76%; 61%), CALU-6 lung (75%; 38%), NCI-H460 lung (45%; 46%), HS766T pancreatic (73%; not tested), PaCa-2 pancreatic (69%; 40%), PANC-1 pancreatic (70%; 60%), and BxPC-3 pancreatic (9%; 19%). In contrast, only the LX-1 lung carcinoma xenograft was responsive to ara-C treatment, which inhibited tumor growth by a marginal 62 percent. Thus, like its activity against murine solid tumors, gemcitabine has excellent antitumor activity against a broad spectrum of human solid tumors.


Eosinophilia-myalgia syndrome: the Cleveland Clinic experience.
Eosinophilia-myalgia syndrome is a recently described clinical syndrome caused by a suspected contaminant of L-tryptophan, an essential amino acid that was manufactured and sold as a nutritional supplement. This study reports the clinical and pathological findings of 22 cases of eosinophilia-myalgia syndrome evaluated at the Cleveland Clinic and includes data for up to 1 year of follow-up (for the epidemic cases). Nineteen of the 22 cases were evaluated and followed prospectively in the time period from November 1989 to November 1990. Two of the 22 represented nonepidemic forms of the syndrome which occurred prior to the 1989 epidemic. During a review of all cases of biopsy-proven diffuse fasciitis with eosinophilia at the Cleveland Clinic since 1978, one of the 22 was retrospectively identified as having an epidemic form of the syndrome, with onset in July 1989. In this study, adverse prognosticating factors in eosinophilia-myalgia syndrome included nerve and muscle involvement, fasciitis, and weight loss. Eosinophilia-myalgia syndrome is striking in its severity and diversity, and its features are similar to those of two other unusual illnesses--toxic oil syndrome and diffuse fasciitis with eosinophilia. With the recent purification of the suspected contaminant, it is hoped that further clues to the etiology of this syndrome and similar syndromes will be uncovered.


A confirmatory factor analysis of an electronic format painDETECT questionnaire for patients with low back pain.
The substantial burden of low back pain on patients and healthcare systems is exacerbated by unclear pathology and ineffective diagnostic methods, hindering effective management. The painDETECT questionnaire (PD-Q) has been used to facilitate the evaluation and categorisation of low back pain. While preliminary validation and translations of the paper-based format of PD-Q into languages such as Spanish and Dutch have been accomplished, the underlying factor model inherent to the electronic format of the PD-Q remains to be established. The objective of this study was to utilise confirmatory factor analysis (CFA) to investigate the factor structure of an electronic format PD-Q among patients with neuropathic low back pain. This cross-sectional study was conducted at a Spinal Clinic in Sydney between November 2020 and October 2022. Eligible participants were adults over 18 with low back pain and no history of lumbar surgery history or systemic co-morbidities. Participants completed the electronic format of the PD-Q, and CFA was employed to assess the validity of the suggested two-factor, nine-item structure. Recommended cut-offs for goodness-of-fit indices were used to evaluate the model fit. Of the 236 patients that visited the clinic during the data collection period, 142 (71, 50% female, mean age 51.26 ± 15.28 years) participated in the study. Median pain severity was 9/10 over four weeks. CFA indicated strong model fit, with goodness-of-fit and comparative fit indices over 0.9, and overall internal consistency was 0.77. Construct validity analysis demonstrated the PD-Q's effectiveness in distinguishing neuropathic, mixed, and nociceptive LBP, aiding neuropathic pain evaluation in low back pain patients. This study confirms the reliability and two-factor structure of the electronic PD-Q for neuropathic pain assessment in low back pain patients. To enhance comprehension of the clinical applicability of the electronic format PD-Q, future research should conduct clinimetric evaluations.


[Survival among patients with prostate cancer after distant radiotherapy and low-intensity near-infrared phototherapy].
The paper discusses the effect of photography with near-infrared photography on survival of patients with prostate cancer (PC) after distant radio- (DRT) and hormonal therapy (January 2000 - June 2007). The control group (n=251) were treated with standard radio- and hormonal therapy alone. Besides, patients of the study group (n=308) received phototherapeutic treatment to prevent radiation-induced injuries of the urinary bladder and rectum. The groups were compared relatively to PC cell differentiation, DRT and hormonal treatment. Survival was evaluated (Caplan-Meyer); log-rank test was used to compare the results. Overall survival in the study group of patients with localized (T1-2N0 M0) and generalized (T1-4N0-1 M1) tumors did not differ from that of controls (p > or = 0.05). In patients with locally advanced tumors (T3-4N0-1 M0, T1-4N1 M0), significant differences in survival between controls and study group were recorded beginning from year 3 of the investigation: 5-year survival rates were 67% and 89%, respectively (p < or = 0.05).


Ribosome exchange revisited: a mechanism for translation-coupled ribosome detachment from the ER membrane.
In current models, ribosome release from the endoplasmic reticulum (ER) is coupled to the termination of protein translation. Thus, coincident with termination, membrane-bound ribosomes dissociate into their component subunits and are released into the cytosol. Here, we review past and current data and propose that the affinity of the ribosome for the ER membrane is decreased during translation, with ribosome release occurring when a membrane-bound ribosome is engaged in the synthesis of a protein lacking a signal sequence. Our model emphasizes a role for the conformation of the large ribosomal subunit in the regulation of membrane affinity and provides a mechanism for translation-coupled ribosome release.


Biochemical differences in the mechanism of macrophage lysosomal exocytosis initiated by zymosan particles and weak bases.
By utilizing compounds with different inhibitory properties, discrete biochemical differences were found in the mechanism of selective lysosomal enzyme secretion by macrophages in response to stimulation with zymosan particles and methylamine. Pretreatment of macrophages with trypsin markedly impaired the capacity of the cells to respond to stimulation with zymosan particles, but had no effect on methylamine-stimulated lysosomal enzyme secretion. Similarly, the addition of phenylmethanesulphonyl fluoride or EDTA to the incubation medium substantially inhibited zymosan-induced lysosomal enzyme secretion, whereas the methylamine-stimulated response was unaffected by these agents. The addition of 2-deoxyglucose to incubation media, however, strongly inhibited both zymosan- and methylamine-stimulated beta-galactosidase secretion. These findings are consistent with a mechanism for lysosomal enzyme secretion by macrophages, based on a receptor-dependent uptake of zymosan particles and a receptor-independent uptake of methylamine.


The resonance frequency shift, pattern formation, and dynamical network reorganization via sub-threshold input.
We describe a novel mechanism that mediates the rapid and selective pattern formation of neuronal network activity in response to changing correlations of sub-threshold level input. The mechanism is based on the classical resonance and experimentally observed phenomena that the resonance frequency of a neuron shifts as a function of membrane depolarization. As the neurons receive varying sub-threshold input, their natural frequency is shifted in and out of its resonance range. In response, the neuron fires a sequence of action potentials, corresponding to the specific values of signal currents, in a highly organized manner. We show that this mechanism provides for the selective activation and phase locking of the cells in the network, underlying input-correlated spatio-temporal pattern formation, and could be the basis for reliable spike-timing dependent plasticity. We compare the selectivity and efficiency of this pattern formation to a supra-threshold network activation and a non-resonating network/neuron model to demonstrate that the resonance mechanism is the most effective. Finally we show that this process might be the basis of the phase precession phenomenon observed during firing of hippocampal place cells, and that it may underlie the active switching of neuronal networks to locking at various frequencies.


Nutritional implications and metabolizable energy value of D-xylose and L-arabinose in chicks.
An experiment was conducted to examine the effects of graded levels (2.5, 5.0, 7.5, 10.0, and 15.0%) of dietary D-xylose or L-arabinose on chick performance. As reference, D-glucose was included in the experiment. A second experiment was performed to determine the AMEn of D-xylose and L-arabinose. Results of Experiment 1 showed a significant linear decrease (P less than .05) in weight gain and efficiency of feed utilization when the dietary level of either D-xylose or L-arabinose was increased. The same was true for daily feed intake of the D-xylose treatments. Water intake was linearly (P less than .05) increased as dietary level of both pentose sugars increased, and, as a result, dry matter content of the droppings decreased. Results of Experiment 2 showed that the AMEn value of either pentose sugar was dose related. The AMEn values for D-xylose at 5 and 10% dietary inclusion were 2,660 and 2,020 kcal/kg, respectively. Those for L-arabinose at these inclusion levels were 2,300 and 1,360 kcal/kg, respectively. Feeding equal dietary levels of either pentose sugar resulted in higher concentrations of xylose than of arabinose in blood plasma. Concentration of glucose in blood was not affected by feeding either D-xylose or L-arabinose. Cecal length and weight were markedly increased by feeding L-arabinose and intermediately by D-xylose.


New Insights into the Morphology of Silica and Carbon Black Based on Their Different Dispersion Behavior.
Precipitated silica in combination with bifunctional organosilanes almost fully replaces currently the commonly used carbon black fillers in modern passenger car tire tread compounds to improve tire properties such as wet traction (safety) and rolling resistance (fuel consumption). However, it is still challenging to reach a sufficient level of abrasion resistance (service life). An optimum macrodispersion quality of the silica is a fundamental precondition for an optimum abrasion resistance. This goal can be reached by the development of new tailor-made highly dispersible silica grades. In order to achieve this, it is essential to be aware of the analytical silica parameters, which affect the dispersion process. One of these parameters known from carbon black is the structure of the filler. To gain deeper insights into the in-rubber dispersibility of the silica, the structure was investigated by two different methods, the DOA measurement and the void volume measurement. The results were correlated to the in-rubber macrodispersion. In contrast to carbon black filled compounds, no sufficient correlation of the structure with the macrodispersion could be found for the silica-filled compounds. Therefore, it was concluded that the morphology of silica differs from that one that is claimed for carbon black. Additional investigations like TEM, FT-IR and X-ray diffraction measurements were carried out. Carbon black shows a more elastic structure, which can withstand the external forces during the mixing process in a better way. Silica contains a much higher void volume in the structure even after exposed to high forces. These new findings will help to understand the macrodispersion process in rubber in a better way.


Purification and partial characterization of the glutathione S-transferases in carp liver, and their interaction with 2,4-dichlorophenoxyacetic acid and 1,4-benzoquinone.
The hepatic glutathione S-transferase (GST) activity in the cytosol of the freshwater fish carp (Cyprinus carpio) was enriched by glutathione affinity chromatography. The anionic (GST A1-A3) and cationic (GST C1-C3) isoenzymes were then separated in two chromatofocusing steps. SDS electrophoresis showed GST C1 to be a heterodimer with subunits of Mr 25,000 and 28,000, and all other isoenzymes to be homodimers with subunits of Mr 25,400. They were partially characterized by different biochemical parameters. The water pollutants 2,4-dichlorophenoxyacetic acid and 1,4-benzoquinone inhibited all carp GST isoenzymes, following the same kinetic inhibition patterns as for rat liver GST. It is concluded that hepatic carp GST can play an important role in the detoxication of aquatic pollutants.


Evidence for coupling of resynthesis to hydrolysis in the phosphoinositide cycle.
Previous data suggest that agonist-induced hydrolysis of phosphatidylinositol bisphosphate is accompanied by resynthesis through phosphatidylinositol such that these metabolic events function in a cyclic manner. However, it is not known whether resynthesis depends on the presence of agonist or is a direct result of agonist-induced breakdown. In the present study we demonstrate that: (1) increasing the intracellular free inositol concentration will not stimulate phosphatidylinositol synthesis, as measured by assessing the amount of [32P]Pi incorporation; (2) regeneration of free inositol is required for resynthesis; however, addition of exogenous inositol can sustain resynthesis under conditions which inhibit the regeneration of endogenous inositol; (3) resynthesis can take place in the absence of agonist provided that cells have been previously incubated under conditions which prevent resynthesis; and (4) the presence of agonist does not increase the rate of resynthesis. Thus the resynthetic phase of the phosphoinositide cycle is a compensatory event triggered either by the decrease in the level of phosphatidylinositol or by an increase in precursor substrates. The agonist itself appears to have no direct effect on the resynthesis process.


Ventricular tachycardia catheter ablation in arrhythmogenic right ventricular dysplasia: a 16-year experience.
Arrhythmogenic right ventricular dysplasia (ARVD) is a structural heart disease affecting young adults that leads to cardiac rhythm disorders including supraventricular and mostly ventricular arrhythmias. Sudden death may be the first presentation of the disease. Ablation techniques have been used for the treatment of ventricular tachycardia in cases resistant to drug therapy. Radiofrequency is appropriate as a first approach for ventricular tachycardia ablation in ARVD; however, its effectiveness is less than 40% at the first session. Fulguration is effective for ventricular tachy-cardia ablation and should be used in the same session after ineffective radiofrequency ablation. However, fulguration requires expertise, general anesthesia, and more than one session in half of all patients. Radiofrequency and fulguration plus other common forms of treatment including pacemakers and automatic implantable cardioverter defibrillators provides a clinical success rate of 81% to 93% in a series of 50 consecutive patients studied during 16 years. Earlier poor reputation of fulguration was the result of poorly understood technical problems concerning the physics and biophysics of the procedure under control with presently available methods. This in-depth study of a large population over a long time period demonstrates that fulguration should be rehabilitated.


Cell autonomous and microenvironmental regulation of tumor progression in precursor states of multiple myeloma.
Multiple myeloma is a plasma cell malignancy evolving in the bone marrow and leading to end organ damage such as bone lesions, cytopenias, and kidney failure. This review delineates recent advances in the molecular mechanisms leading to tumor progression in multiple myeloma. Two different aspects enable tumor expansion: cell autonomous through genomic alterations in the tumor clone and noncell autonomous deregulations in the bone marrow tumor microenvironment. These alterations provide the framework for the continuous progression of multiple myeloma from early precursor conditions such as monoclonal gammopathy of undetermined significance and smoldering multiple myeloma to overt multiple myeloma. In this review, we discuss recent findings in the genomic alterations that occur in the tumor clone such as somatic genomic mutations, copy number variation and chromosomal translocation, and delineate noncell autonomous deregulations in which tumor cells take advantage of a permissive microenvironment to further proliferate. The latter compartment includes interaction with bone marrow stromal cells, osteoblasts, osteoclasts, and immune escape. Understanding the mechanisms that lead tumor progression from early stages to overt multiple myeloma could guide to more effective therapies and therefore prevent disease progression.


Fish and egg specific immunoglobin e in multiple sclerosis patients.
The effect of nutrition in the course of multiple sclerosis (MS) is a topic of great interest. The present study was aimed to evaluate the immunoglobin E (IgE) against egg and fish in MS patients compared to healthy controls. Between March 2012 and July 2012, 48 MS patients were selected and compared with 48 healthy subjects to assess the frequency of IgE against egg and fish in MS patients compared to healthy control. Fish and Egg specific IgE was determined by Immuno CAP. Sex and the frequency of specific IgE were compared between study groups by Chi-square test. Total of 96 subjects was assessed (22% male and 78% female). The mean age of the study subjects was 30.8 ± 6.6 years. Mean age of case and control groups was 30.7 (±6.9) versus 30.9 ± 6.3, respectively (P = 0.83). There were no detection of egg and fish specific IgE in serum of MS patients and healthy subjects. IgE allergy against fish and egg may be very unlikely to affect MS course.


[Nutrition integrators in sports].
The use or abuse of many preparations, available in the gymnasium or as top-bench drugs, used as nutritive integrators, determines both toxicological and deontological and especially sport medicine problems, because these products are also involved in the antidoping control. Therefore, this article cover the needs for providing a consultation and information manual for all sport operators in the delicate phase of drug-food integration of the athlete, not only to prevent and restrict the doping phenomenon, but also for health-preservation of the athlete.


Tobacco Screening Practices and Perceived Barriers to Offering Tobacco Cessation Services among Texas Health Care Centers Providing Behavioral Health Treatment.
Tobacco use, and thus tobacco-related morbidity, is elevated amongst patients with behavioral health treatment needs. Consequently, it is important that centers providing health care to this group mandate providers' use of tobacco screenings to inform the need for tobacco use disorder intervention. This study examined the prevalence of mandated tobacco screenings in 80 centers providing health care to Texans with behavioral health needs, examined key factors that could enhance screening conduct, and delineated providers' perceived barriers to tobacco use intervention provision. The results indicated that 80% of surveyed centers mandated tobacco use screenings; those that did were significantly more likely than those that did not to have a hard stop for tobacco use status in health records and were marginally more likely to make training on tobacco screening available to providers. The most widespread barriers to tobacco use disorder care provision were relative perceived importance of competing diagnoses, lack of community resources to refer patients, perceived lack of time, lack of provider knowledge or confidence, and belief that patients do not comply with cessation treatment. Overall, the results suggest that there are opportunities for centers providing care to Texans with behavioral health needs to bolster their tobacco screening and intervention capacity to better address tobacco-related health disparities in this group. Health care centers can support their providers to intervene in tobacco use by mandating screenings, streamlining clinical workflows with hard stops in patient records, and educating providers about the importance of treating tobacco with brief evidence-based intervention strategies while providing accurate information about patients' interest in quitting and providers' potential impacts on a successful quit attempt.


A Comprehensive Analysis of the Association Between Gleason Score at a Positive Surgical Margin and the Risk of Biochemical Recurrence After Radical Prostatectomy.
Our objective was to identify the best of the existing definitions of Gleason score (GS) at a positive surgical margin (PSM) by validating them in our radical prostatectomy cohort. We analyzed 251 patients who had mixed (3+4, 3+5, 4+3 or 5+3) pathologic GS and PSM. We used 5 definitions to record GS at a PSM. Univariate and multivariate analyses were used to study the association between each definition and the risk of biochemical recurrence (BCR). We also tested the prognostic value of multivariate models including established predictors and each of the studied definitions of GS at a PSM. GS 3+3 was seen at a PSM in 57.4% of the cases and was more common in patients with lower overall GS. Over a median follow-up of 4.0 years 89 patients (35.5%) developed BCR. All of the definitions of GS at a PSM were independent predictors of the BCR-free survival. Most of them also improved the prognostic value of the multivariate models when added to the established parameters. The degree of improvement was similar for the most complex definition (full GS at a PSM) and the easiest to record binary definition (presence of Gleason 4/5 pattern at a PSM). We conclude that compared with the other possible options of reporting GS at a PSM, the presence of Gleason 4/5 pattern may be the most practical definition. It is at least as predictive as other definitions, may be the easiest to record and is the best studied of the existing alternatives.


Complex chiral modulations in FeGe close to magnetic ordering.
We report on detailed polarized small-angle neutron scattering on cubic FeGe in magnetic fields applied either along (transverse) the scattering vector or parallel (longitudinal) to the neutron beam. The (H, T) phase diagrams for all principal axes contain a segmented A-phase region just below the onset of magnetic order. Hexagonal Bragg-spot patterns were observed across the entire A-phase region for the longitudinal geometry. Scattering intensity was observed in parts of the A phase for both scattering configurations. Only in a distinct pocket (A(1)) was vanishing scattering intensity found in the transverse geometry.


Challenges in the quality of herbal medicinal products with a specific focus on contaminants.
The complex regulatory framework for the quality of herbal medicinal products, in particular with regard to potential contaminants, consists of legal provisions including Pharmacopoeia requirements, relating to limits as well as in most cases to methods for determination. This review intends to provide an overview on the legal requirements for testing potential contaminants in herbal drugs used for the production of herbal medicinal products. The following issues are described and discussed: For the assessment of pesticide residues, Chapter 2.8.13 of the European Pharmacopoeia and Regulation (EC) 396/2005 applies, for heavy metals the general Pharmacopoeia monograph as well as the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q3D guideline on elemental impurities. The Pharmacopoeia also includes limits and acceptance criteria for microbiological purity and aflatoxins, respectively. Polycyclic aromatic hydrocarbons are mentioned in Regulation (EC) 1881/2006 for food as well as in a Reflection Paper on herbal medicinal products. For several years, a potential contamination with pyrrolizidine alkaloids was discussed which led to measures being imposed on industry and health authorities. Various examples demonstrate that the evaluation of data from daily analytical practice is extremely useful to gain an overview on the occurrence of residues and/or contaminants in herbal drugs and herbal preparations. Such evaluations might assist manufacturers in their individual risk assessment and the definition of their testing strategies and contribute to guarantee the quality and safety of the marketed products. Annual data evaluations demonstrate that a remarkable decrease of the pyrrolizidine alkaloid content burden in herbal drugs and extracts used for the production of herbal medicinal products has been achieved over the past few years. However, it has also become clear that this issue cannot be completely solved in the near future.


Esophageal motility disorders: current concepts of pathogenesis and treatment.
Current concepts of esophageal motility disorders are summarized. Primary data sources were located via MEDLINE or cross-citation. No attempt was made to be comprehensive or inclusive of the literature because fewer than 10% of citations are discussed. Instead, emphasis was placed on new developments in diagnosis, therapeutics and practice patterns. Controlled therapeutic trials and pathophysiological observations are emphasized. Achalasia is a rare disease of failed lower sphincter relaxation and aperistalsis. Diffuse esophageal spasm (DES), an equally rare disease, is defined by nonpropagated esophageal contractions. Nonspecific motility disorders, including nutcracker esophagus and hypertensive lower esophageal sphincter, are identified only by manometry and are 10 times as prevalent. Neuromuscular pathology is evident only with achalasia (myenteric plexus neuron destruction). Pharmacological therapies have limited efficacy with achalasia, more limited efficacy with DES and no efficacy with the nonspecific motility disorders. More efficacious therapies for the nonspecific disorders are directed at associated reflux disease or psychiatric disorders. Pneumatic dilation is effective therapy for achalasia in 72% of instances but frequently requires repeat dilation and is complicated by a 3% perforation rate. Surgical myotomy is effective in 88% of patients with achalasia; morbidity from thoracotomy has been the major limitation but has been sharply reduced with a laparoscopic approach. In conclusion, although it has been suggested that esophageal motility disorders are distinct clinical entities, critical review of the literature supports this only in the case of achalasia, a disease of well defined pathophysiology, functional disturbance and therapies. This clarity diminishes progressively for DES and nonspecific esophageal motility disorders.


[From Axial Spondyloarthritis to Osteoporosis - Spectrum of Skeletal Involvement in Inflammatory Bowel Diseases].
From Axial Spondyloarthritis to Osteoporosis - Spectrum of Skeletal Involvement in Inflammatory Bowel Diseases Abstract. Inflammatory bowel diseases (IBD) are frequently accompanied by non-inflammatory joint pain and inflammatory spondyloarthritides. Spondyloarthritides can restrict joint function and typically manifest with inflammatory back pain with nightly pain and morning stiffness that improves upon exercising. In other patients, small or large peripheral joints are predominantly involved. Treatment comprises pain medication including COX-II selective non-steroidal anti-inflammatory drugs (NSAID), since non-selective NSAID can aggravate IBD. For axial manifestations, physiotherapy and tumor necrosis factor (TNF) inhibitors are effective, while for peripheral manifestations steroid injections, sulfasalazine and TNF inhibitors are useful. Osteopenia and osteoporosis may result from inflammation, malabsorption and/or steroids. Long-lasting disease activity or steroid treatment should prompt osteoporosis screening. Adequate calcium and vitamin D intake must be ensured and treatment with bisphosphonates evaluated.


Environmental conditions, diel period, and fish size influence the horizontal and vertical movements of red snapper.
Most demersal fishes are difficult to observe and track due to methodological and analytical constraints. We used an acoustic positioning system to elucidate the horizontal and vertical movements of 44 red snapper (Lutjanus campechanus) off North Carolina, USA, in 2019. Mean movement rate and distance off bottom varied by individual, with larger red snapper generally moving faster and spending more time farther off the bottom than smaller individuals. We used generalized additive mixed models that accounted for temporal autocorrelation in the data to show that mean hourly red snapper movement rate was lower during the day than at night and was negatively related to bottom water temperature. Moreover, red snapper spent more time off the bottom during the day than at night, and vertical movements were mostly related to bottom upwelling events that sporadically occurred in May-July. Our results and previous observations suggest that red snapper feed primarily on benthic organisms at night, and display diel vertical migration (i.e., thermotaxis) up to warmer waters (when present) during the day to aid digestive efficiency. Movement is a central organizing feature in ecology, and the sustainable management of fish will benefit from a better understanding of the timing and causes of fish movement.


Expression of a bacterial bi-functional chorismate mutase/prephenate dehydratase modulates primary and secondary metabolism associated with aromatic amino acids in Arabidopsis.
Plants can synthesize the aromatic amino acid Phe via arogenate, but it is still not known whether they also use an alternative route for Phe biosynthesis via phenylpyruvate, like many micro-organisms. To examine this possibility, we expressed a bacterial bi-functional PheA (chorismate mutase/prephenate dehydratase) gene in Arabidopsis thaliana that converts chorismate via prephenate into phenylpyruvate. The PheA-expressing plants showed a large increase in the level of Phe, implying that they can convert phenylpyruvate into Phe. In addition, PheA expression rendered the plants more sensitive than wild-type plants to the Trp biosynthesis inhibitor 5-methyl-Trp, implying that Phe biosynthesis competes with Trp biosynthesis from their common precursor chorismate. Surprisingly, GC-MS, LC-MS and microarray analyses showed that this increase in Phe accumulation only had a very minor effect on the levels of other primary metabolites as well as on the transcriptome profile, implying little regulatory cross-interaction between the aromatic amino acid biosynthesis network and the bulk of the Arabidopsis transcriptome and primary metabolism. However, the levels of a number of secondary metabolites derived from all three aromatic amino acids (Phe, Trp and Tyr) were altered in the PheA plants, implying regulatory cross-interactions between the flux of aromatic amino acid biosynthesis from chorismate and their further metabolism into various secondary metabolites. Taken together, our results provide insights into the regulatory mechanisms of aromatic amino acid biosynthesis and their interaction with central primary metabolism, as well as the regulatory interface between primary and secondary metabolism.


Fas/Fas ligand interaction in human colorectal hepatic metastases: A mechanism of hepatocyte destruction to facilitate local tumor invasion.
This study demonstrates a novel role for the Fas pathway in the promotion of local tumor growth by inducing apoptotic cell death in normal hepatocytes at the tumor margin in colorectal hepatic metastases. Our results show that >85% of lymphocytes infiltrating colorectal liver cancer express high levels of Fas-ligand (Fas-L) by flow cytometry. Using immunohistochemistry of tumor tissue we showed strong Fas expression in noninvolved hepatocytes, whereas Fas-L expression was restricted to tumor cells and infiltrating lymphocytes at the tumor margin. Apoptosis was observed in 45 +/- 13% of the Fas(high) hepatocytes at the tumor margin whereas only 7 +/- 3% tumor cells were apoptotic (n = 10). In vitro, primary human hepatocytes expressed Fas receptor and crosslinking with anti-Fas antibody induced apoptosis in 44 +/- 5% of the cells compared with 4. 6 +/- 1.0% in untreated controls (P = 0.004). Both tumor-infiltrating lymphocytes (TIL) and human metastatic colon cancer cells cells are able to induce Fas-mediated apoptosis of primary human hepatocytes in coculture cytotoxic assays. TIL induced apoptosis in 47 +/- 9% hepatocytes compared with control 4.3 +/- 1. 0% (P = 0.009) and this effect was reduced by anti-human Fas-L mAb (18.7 +/- 1.3%, P = 0.009). SW620 cells induced apoptosis in 26 +/- 2% hepatocytes compared with control 5.6 +/- 1.7% (P = 0.004) and this was reduced to 11.2 +/- 1.8% (P = 0.004) in the presence of anti-human Fas-L mAb. These data suggest that the inflammatory response at the margin of colorectal liver metastases induces Fas expression in surrounding hepatocytes, allowing them to be killed by Fas-L-bearing TIL or tumor cells and facilitating the invasion of the tumor into surrounding liver tissue.


The novel metastasis promoter Merm1/Wbscr22 enhances tumor cell survival in the vasculature by suppressing Zac1/p53-dependent apoptosis.
Understanding metastasis is integral to curative cancer treatments. Using a mouse genetic screening model, we identified Merm1/Wbscr22 as a novel metastasis promoter that includes a methyltransferase fold in its structure. Merm1 showed high levels of expression in invasive breast cancer. Ectopic expression of Merm1 in nonmetastatic cells enhanced metastasis formation without affecting cell growth and motility. The intact methyltransferase fold of Merm1 was required for metastasis formation. Interestingly, Merm1 expression promoted cell survival after entrapment in the lung microvasculature. Consistent with these results, knockdown of endogenous Merm1 in tumor cells reduced lung retention and metastasis formation. On the basis of comparative transcriptome analysis, Merm1 expression was negatively correlated with the expression of tumor suppressor Zac1. We confirmed that Merm1 suppressed Zac1 expression with histone H3 methylation at Lys(9) in the Zac1 promoter region. Zac1 can induce apoptosis through its ability to transcriptionally coactivate p53, which regulates apoptosis in the vasculature and is often downregulated in metastasis. We found that Zac1 knockdown reduced the p53-dependent apoptosis that was enhanced by Merm1 knockdown, thereby increasing lung retention of metastatic cells. Our findings show that Merm1 enhances cancer cell survival in the vasculature by suppressing Zac1/p53-dependent apoptosis, thereby enhancing metastasis.


Hyperlayer separation in hollow fiber flow field-flow fractionation: effect of membrane materials on resolution and selectivity.
Hollow fiber flow FFF (HF FlFFF) has recently shown its capability to separate and characterize the size of submicrometer particles and has demonstrated the potential to be developed into a disposable flow FFF channel. In this work, HF FIFFF was used for the hyperlayer separation of micron-sized particles and the separation capability was examined by using various hollow fiber membrane materials (Polysulfones, cPVC, and PAN). From the experiments, PAN (polyacrylonitriles) showed an outstanding performance in particle separation compared to the other membranes. By orienting the fiber module in an upright direction, the upstream flow migration reduced band broadening of eluted peaks. When the efficiency of the PAN hollow fiber system was tested by varying the ratio of outflow-rate to radial flow-rate, it was found that optimum separation in hyperlayer HF FlFFF can be obtained at the ratio of about 6-7. From the examination of retention at or around steric inversion diameter, it was observed that experiments showed a good agreement with predictions by semi-empirical calculation. In hyperlayer HF FlFFF the diameter based selectivity values were shown to be 1.2-1.7 depending on the type of membranes and the field strength (the radial flow-rate) conditions.


Research Progress on the Etiology and Treatment of Premature Ovarian Insufficiency.
Menopause in women marks the knot of reproductive life, and menopause is defined as the last menstrual period in a woman, but this is caused by the failure of the ovarian reserve. The average age of natural menopause in the general population of women has remained around 50-52 years. Premature ovarian insufficiency (POI) is a debilitating clinical syndrome that manifests as a decline in ovarian function in women under 40. This condition is a prominent cause of female infertility. POI is a debilitating condition that not only wreaks havoc on patients' physical and mental well-being but also imposes substantial mental, psychological, and economic burdens, particularly on women. In addition to diminished fertility, individuals afflicted with POI face an elevated risk of developing debilitating conditions such as osteoporosis and cardiovascular disease. The etiologies of POI are highly heterogeneous, and it can be caused by spontaneous genetic defects or induced by autoimmune diseases, infections, and iatrogenic or environmental factors. Alarmingly, idiopathic POI, a subtype characterized by an unknown etiology, accounts for more than half of all POI cases. Currently, clinical interventions for POI primarily consist of hormone replacement therapy. Fertility preservation methods are cryopreservation of embryos, oocytes, and ovarian tissue. Immunological interventions, gene editing techniques, and stem cell-based therapies are being explored to unravel the diverse etiologies and underlying mechanisms of POI, thereby enabling the identification of optimal therapeutic interventions. These innovative approaches offer unprecedented opportunities to advance the field of reproductive medicine. The main aim of this paper was to offer a succinct summary of the latest research breakthroughs concerning the elucidation of the mechanisms governing the origin and management of POI.


Strengthening Grapevine Resistance by Pseudomonas fluorescens PTA-CT2 Relies on Distinct Defense Pathways in Susceptible and Partially Resistant Genotypes to Downy Mildew and Gray Mold Diseases.
Downy mildew caused by the oomycete Plasmopara viticola and gray mold caused by the fungus Botrytis cinerea are among the highly threatening diseases in vineyards. The current strategy to control these diseases relies totally on the application of fungicides. The use of beneficial microbes is arising as a sustainable strategy in controlling various diseases. This can be achieved through the activation of the plants' own immune system, known as induced systemic resistance (ISR). We previously showed that bacteria-mediated ISR in grapevine involves activation of both immune response and priming state upon B. cinerea challenge. However, the effectiveness of beneficial bacteria against the oomycete P. viticola remains unknown, and mechanisms underpinning ISR against pathogens with different lifestyles need to be deciphered. In this study, we focused on the capacity of Pseudomonas fluorescens PTA-CT2 to induce ISR in grapevine against P. viticola and B. cinerea by using two grafted cultivars differing in their susceptibility to downy mildew, Pinot noir as susceptible and Solaris as partially resistant. On the basis of their contrasting phenotypes, we explored mechanisms underlying ISR before and upon pathogen infection. Our results provide evidence that in the absence of pathogen infection, PTA-CT2 does not elicit any consistent change of basal defenses, while it affects hormonal status and enhances photosynthetic efficiency in both genotypes. PTA-CT2 also induces ISR against P. viticola and B. cinerea by priming common and distinct defensive pathways. After P. viticola challenge, PTA-CT2 primes salicylic acid (SA)- and hypersensitive response (HR)-related genes in Solaris, but SA and abscisic acid (ABA) accumulation in Pinot noir. However, ISR against B. cinerea was associated with potentiated ethylene signaling in Pinot noir, but with primed expression of jasmonic acid (JA)- and SA-responsive genes in Solaris, together with downregulation of HR-related gene and accumulation of ABA and phytoalexins.


Aerosol-jet-printed, 1 volt H-bridge drive circuit on plastic with integrated electrochromic pixel.
In this report, we demonstrate a printed, flexible, and low-voltage circuit that successfully drives a polymer electrochromic (EC) pixel as large as 4 mm(2) that is printed on the same substrate. All of the key components of the drive circuitry, namely, resistors, capacitors, and transistors, were aerosol-jet-printed onto a plastic foil; metallic electrodes and interconnects were the only components prepatterned on the plastic by conventional photolithography. The large milliampere drive currents necessary to switch a 4 mm(2) EC pixel were controlled by printed electrolyte-gated transistors (EGTs) that incorporate printable ion gels for the gate insulator layers and poly(3-hexylthiophene) for the semiconductor channels. Upon application of a 1 V input pulse, the circuit switches the printed EC pixel ON (red) and OFF (blue) two times in approximately 4 s. The performance of the circuit and the behavior of the individual resistors, capacitors, EGTs, and the EC pixel are analyzed as functions of the printing parameters and operating conditions.


Clustering analyses in peptidomics revealed that peptide profiles of infant formulae are descriptive.
Prompted by the accumulating evidence on bioactive moieties of milk-derived peptides, novel methods were applied to compare the peptide composition among commercially available hydrolysate formulations and to determine batch-to-batch variations of protein hydrolysate products. Despite the availability of general methods to measure, for example, the degree of hydrolysis and peptide mass distribution at a high level, the objective of this study was to more qualitatively compare peptide sequences and composition. By a comprehensive approach combining peptidomics technologies and multivariate clustering analyses, the peptide profiles of different hydrolyzed milk protein formulations were compared. Moreover, peptide profiles of various hydrolysate batches that had been produced over a period of 5 years were included. Coupling of identified peptide sequences to the position in their corresponding milk proteins produced numerical datasets that subsequently were utilized for multivariate data analyses. These analyses revealed that batch-to-batch variation in the peptide profiles of a specific extensively hydrolyzed casein preparation was low. Moreover, extensive multivariate evaluations revealed that the peptide profiles of different commercially available hydrolyzed milk protein formulations provided a descriptive and distinct signature. Overall, the described methodology may contribute to the field of peptide research as observed dissimilarities in peptide profiles of similar products may be related to differences in their overall functionality.


Clinical practice guidelines in idiopathic facial paralysis: systematic review using the appraisal of guidelines for research and evaluation (AGREE II) instrument.
Bell's palsy, or idiopathic facial paralysis, is a peripheral facial palsy of unknown cause that presents as sudden, unilateral weakness of the muscles of the face. Prompt treatment of Bell's palsy is critical in order for patients to achieve complete recovery of facial function. Delays in diagnosis and management can result in permanent facial defects. A number of clinical practice guidelines (CPG) exist to guide clinical decision-making in patients presenting with idiopathic facial paralysis. However, to date, there has been no comprehensive review of the methodological rigor and quality of these CPGs. Thus, the objective of the authors is to appraise the existing CPGs to ensure safe and effective practices. A total of eight guidelines met the inclusion criteria and were appraised. Only two CPGs achieved an overall rating of 'High', having five or more quality domains scoring > 60%. Across the CPGs, the domains of rigor of development, stakeholder involvement, and applicability has the lowest overall scores with 48.1%, 43.9%, and 43.1%, respectively. Based on the AGREE II instrument, the methodological rigor and quality of CPGs for Bell's palsy is low to average. In particular, future guidelines for Bell's palsy should look to the quality domains of rigor of development, stakeholder involvement, and applicability as the greatest opportunities for improvement.


The secreted peptide BATSP1 promotes thermogenesis in adipocytes.
Although brown adipose tissue (BAT) has historically been viewed as a major site for energy dissipation through thermogenesis, its endocrine function has been increasingly recognized. However, the circulating factors in BAT that play a key role in controlling systemic energy homeostasis remain largely unexplored. Here, we performed a peptidomic analysis to profile the extracellular peptides released from human brown adipocytes upon exposure to thermogenic stimuli. Specifically, we identified a secreted peptide that modulates adipocyte thermogenesis in a cell-autonomous manner, and we named it BATSP1. BATSP1 promoted BAT thermogenesis and induced browning of white adipose tissue in vivo, leading to increased energy expenditure under cold stress. BATSP1 treatment in mice prevented high-fat diet-induced obesity and improved glucose tolerance and insulin resistance. Mechanistically, BATSP1 facilitated the nucleocytoplasmic shuttling of forkhead transcription factor 1 (FOXO1) and released its transcriptional inhibition of uncoupling protein 1 (UCP1). Overall, we provide a comprehensive analysis of the human brown adipocyte extracellular peptidome following acute forskolin (FSK) stimulation and identify BATSP1 as a novel regulator of thermogenesis that may offer a potential approach for obesity treatment.


Postoperative ketorolac does not predispose to pseudoarthrosis following posterior spinal fusion and instrumentation for adolescent idiopathic scoliosis.
A retrospective review comparing patients who had postoperative ketorolac and those who did not following posterior spinal fusion and instrumentation (PSFI) for adolescent idiopathic scoliosis (AIS). To analyze the effect of postoperative ketorolac on the incidence of pseudoarthrosis in postoperative AIS patients. Ketorolac (Toradol, Roche Laboratories, Nutley, NJ) is a nonsteroidal antiinflammatory drug that is an effective adjunct to manage postoperative pain. It has been previously demonstrated to inhibit spinal fusion in adult patients undergoing a L4 to sacral fusion. To our knowledge, there are no large studies analyzing this effect following PSFI for AIS. An IRB-approved retrospective medical record review was performed from 1994 to 2000 of patients undergoing a PSFI for AIS at a single institution. Segmental spinal instrumentation (Texas Scottish Rite Hospital) and iliac crest bone graft were used in both groups. Demographic and operative data were recorded. Patients were divided into those who had postoperative ketorolac (K group) and those who did not (NK group). Patients who had a surgically confirmed pseudoarthrosis were identified and the K group and NK group were statistically compared. There were 161 patients in the NK group and 158 in the K group. There were no differences with respect to age (14.4 vs. 14.2 years), gender (83.9% vs. 84.8% females), levels fused (9.8 vs. 9.7), or preoperative curve magnitude (57.9 degrees vs. 58.9 degrees ). In the K group, the number of doses of ketorolac administered was 6.7 for an average of 26.7 mg for a duration of 46 hours after surgery. Patients in the K group were more likely to have Motrin (average 5.8 doses) compared with the NK group (average 0.7 doses) (P < 0.01). No patient in the K group had a history of cigarette smoking compared with 2 patients in the NK group, both of whom went on to solid arthrodesis. The overall incidence of pseudoarthrosis was 2.5% for all patients. There was no difference in the incidence of pseudoarthrosis comparing the K (1.9%) and the NK group (3.1%)(P = 0.7). When the single rod posterior implants were excluded, there was no difference between the K (0.7%) and NK groups (1.8%) (P = 0.58). Ketorolac does not increase the incidence of developing a pseudoarthrosis when used as an adjunct for postoperative analgesia following a PSFI for AIS using segmental spinal instrumentation and iliac crest bone graft. The differences seen here compared with adults may be due to the greater healing potential in these young patients. We recommend utilization of ketorolac after surgery to supplement pain management when necessary.


Stigma of mental illnesses as perceived by north korean defectors living in South Korea.
This study aims to provide the information of the stigmas of mental illness such as psychosis, alcoholism, attempt suicide, and depression among North Korean defectors. We examined stigma for the mental illnesses of 639 North Korean defectors aged 19 to 65 years who live in the Settlement Support Center for North Korean Refugees. The stigmas of mental illnesses were assessed using the Perceived Devaluation-Discrimination Scale We directly compared the stigma level between North Korean defectors and the general population of South Korea. North Korean defectors had higher perceived stigmas of psychosis and alcoholism and lower perceived stigmas of depression than South Koreans. Perceived stigma associated with attempted suicide was similar for North Korean defectors and South Koreans. Only marital status in sociodemographic variables had associations with higher perceived stigma of psychosis, alcoholism, and depression in the North Korean defectors. North Korean defectors, who spent more than one year in transit country, had associations with lower perceived stigma of psychosis and alcoholism. North Korean defectors, who had the experience of compulsory repatriation to North Korea or North Korean family in South Korea, had an association with higher perceived stigma of depression. North Korean defectors had higher perceived stigmas of psychosis and alcoholism and lower perceived stigmas of depression than South Koreans. Further studies are needed to document serial changes in stigmas for mental illnesses associated with the receipt of education at the Settlement Support Center for North Korean defectors.


Effect of culture PO2 on macrophage (RAW 264.7) nitric oxide production.
Macrophages are commonly cultured at a PO2 of 149 Torr, but tissue macrophages in vivo live in an environment of much lower oxygen tension. Despite the many potential mechanisms for changes in oxygen tension to influence nitric oxide (NO) synthesis, there have been few reports investigating the effect of PO2 on macrophage NO production. With the use of a culture chamber designed to rigorously control oxygen tension, we investigated the effects of culture PO2 on macrophage NO production, inducible nitric oxide synthase (iNOS) activity, iNOS protein, and tumor necrosis factor production. NO production and iNOS activity were linearly related in the range of 39.4 to 677 Torr, but not in the range of 1.03 to 39.4 Torr. Therefore, results obtained in vitro for the high oxygen tensions commonly used in cell culture were quantitatively and qualitatively different from results obtained in cells cultured at the lower oxygen tensions that more accurately reflect the in vivo environment. The influence of oxygen tension on NO production has implications for cell culture methodology and for the relationship between microcirculatory dysfunction and inflammatory responses in rodent models of sepsis.