Association between genotype and phenotype in uromodulin-associated kidney disease.
Uromodulin-associated kidney disease (UAKD) is an autosomal dominant disease caused by uromodulin (UMOD) gene mutations. This study explored genotype-phenotype correlations by examining the relationship between the type of UMOD mutation and the age at onset of ESRD. Extensive bibliographic research was used to ascertain patient-level data of all patients with UAKD published up to October 2011. Data included sex; ages at onset of hyperuricemia, gout, and ESRD; and UMOD genotype. Kaplan-Meier analysis and Cox proportional hazards models fitted with shared gamma frailty terms to adjust for within-family correlations were used to model time to event. Thirty-one peer-reviewed publications reporting on 202 patients from 74 families with 59 different UMOD mutations were included. Median ages at onset of hyperuricemia, gout, and ESRD were 24, 40, and 56 years, respectively. Men developed gout and ESRD significantly earlier than did women (age at ESRD was 50 years for men and 60 for women; P=0.04, shared frailty model). Median ages at ESRD development were lowest with Cys77Tyr (37.5 years) and highest with Gln316Pro (65.5 years) UMOD mutations. Onset of ESRD was significantly earlier with UMOD mutations located within the epidermal growth factor domains 2 and 3 (range, 45-52 years; P<0.01 and 0.04, respectively) compared with the cysteine-rich domains (range, 60-65 years; by shared frailty model). The UMOD genotype is related to the clinical phenotype of UAKD. This finding may assist in counseling of patients.


The effects of food quality on the life history parameters of the terrestrial isopod (Armadillidium vulgare (Latreille)).
Growth, reproduction, and survivorship of Armadillidium vulgare have been observed when laboratory populations were fed experimental diets consisting of leaves from different species of plant in different states of decay.Growth and fecundity were highest when the foods consisted of standing dead dicotyledonous plant leaves. Feeding on monocotyledonous material caused increased mortality as well as reducing both growth rates and reproductive output to very low levels. When the dicotyledonous material was extensively decayed before feeding, growth rates and survivorship decreased but this treatment did not significantly alter the results for monocotyledonous foods.Growth and survivorship rates were not significantly correlated with the total nitrogen content of the food but appeared to be related to the extent to which it could be digested and absorbed across the gut wall.Some of the implications of these results for the dynamics of field populations of terrestrial isopods are discussed.


Prognostic value of CA20, a score based on centrosome amplification-associated genes, in breast tumors.
Centrosome amplification (CA) is a hallmark of cancer, observable in ≥75% of breast tumors. CA drives aggressive cellular phenotypes such as chromosomal instability (CIN) and invasiveness. Thus, assessment of CA may offer insights into the prognosis of breast cancer and identify patients who might benefit from centrosome declustering agents. However, it remains unclear whether CA is correlated with clinical outcomes after adjusting for confounding factors. To gain insights, we developed a signature, "CA20", comprising centrosome structural genes and genes whose dysregulation is implicated in inducing CA. We found that CA20 was a significant independent predictor of worse survival in two large independent datasets after adjusting for potentially confounding factors. In multivariable analyses including both CA20 and CIN25 (a gene expression-based score that correlates with aneuploidy and has prognostic value in many types of cancer), only CA20 was significant, suggesting CA20 captures the risk-predictive information of CIN25 and offers information beyond it. CA20 correlated strongly with CIN25, so a high CA20 score may reflect tumors with high CIN and potentially other aggressive features that may require more aggressive treatment. Finally, we identified processes and pathways differing between CA20-low and high groups that may be valuable therapeutic targets.


The teaching content of Shanghai style furniture design for Chinese art design speciality.
Shanghai style furniture (SSF) was the classic case of Chinese furniture culture, we have researched on the teaching content of SSF design for the furniture design course in Chinese art design speciality, and carried out the teaching practice of SSF design for some students. According to this teaching practice, the students' design attitude towards SSF was summarized, which will provide a basis for inheriting SSF design and developing SSF design teaching. In our teaching practice, 132 students had learned the design experiences of SSF, carried on the design practice of SSF, and summarized their SSF design. In the process of students' redesign of SSF, generally speaking, the SSF style was characterized by the combination of China and the European and modern simplicity. Modern elements were added to the SSF design, and fine works were refined in the traditional Chinese modeling, so as to make SSF more in line with the trend of modern design and better carry forward the concept of design service life. After studying this course, these students had basically mastered the design method of SSF. Excavating the practical value of SSF culture and designing new SSF, which are not to copy traditional art style, but the recreation and redesign basing on modern cultures.


NT-proBNP and changes in cognition and global brain structure: The Rotterdam Study.
To investigate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and changes in cognition and global brain structure. In the Rotterdam Study, baseline NT-proBNP was assessed at baseline from 1997 to 2008. Between 1997 and 2016, participants without dementia or stroke at baseline (n = 9566) had repeated cognitive tests (every 3-6 years) for global cognitive function, executive cognitive function, fine manual dexterity, and memory. Magnetic resonance imaging of the brain was performed repeatedly at re-examination visits between 2005 and 2015 for 2607 participants to obtain brain volumes, focal brain lesions, and white matter microstructural integrity as measures of brain structure. Among 9566 participants (mean age 65.1 ± 9.8 years), 5444 (56.9%) were women, and repeated measures of cognition were performed during a median follow-up time of 5.5 (range 1.1-17.9) years, of whom 2607 participants completed at least one brain imaging scan. Higher levels of NT-proBNP were associated with a faster decline of scores in the global cognitive function (p value = 0.003) and the Word-Fluency test (p value = 0.003) but were not related to a steeper deterioration in brain volumes, global fractional anisotropy, and mean diffusivity, as indicators of white matter microstructural integrity, or focal brain lesions. Higher baseline NT-proBNP levels were associated with a faster decline in cognition; however, no association with global brain structure was found.


HIV testing behaviors among undocumented Central American immigrant women in Houston, Texas.
This paper describes HIV testing behaviors among undocumented Central American immigrant women living in Houston, Texas, USA. Respondent driven sampling was used to recruit participants for an HIV behavioral survey. HIV testing items included lifetime history of testing, date and location of the most recent test, and reason for testing. Multivariate logistic regression was used to assess the demographic, behavioral, and structural characteristics associated with testing. The lifetime prevalence of HIV testing was 67%. Half of those who tested did so within the past 2 years and almost 80% received their most recent test in a healthcare setting. The primary reason for testing was pregnancy. Lifetime testing was associated with being from Honduras, having over a sixth grade education, having a regular healthcare provider, and having knowledge of available healthcare resources. Our results suggest that expanding access to healthcare services may increase the prevalence of HIV testing in this population.


Surgical approach to anterior scalenectomy.
Anterior scalenectomy can be accomplished with a low complication rate following the steps in the surgical technique described. In the author's experience, when using this technique in addition to brachial plexus neurolysis, patient satisfaction and improvement rate are extremely high. The incidence of complications is low and the vast majority of patients are discharged within 24 hours of the procedure.


Primary alterations during the development of hidradenitis suppurativa.
Hidradenitis suppurativa (HS) is a chronic, inflammatory disease of the apocrine gland-rich (AGR) skin region. The initial steps of disease development are not fully understood, despite intense investigations into immune alterations in lesional HS skin. We aimed to systematically investigate the inflammatory molecules involved in three stages of HS pathogenesis, including healthy AGR, non-lesional HS and lesional HS skin, with the parallel application of multiple mRNA and protein-based methods. Immune cell counts (T cells, dendritic cells, macrophages), Th1/Th17-related molecules (IL-12B, TBX21, IFNG, TNFA, IL-17, IL10, IL-23A, TGFB1, RORC, CCL20), keratinocyte-related sensors (TLR2,4), mediators (S100A7, S100A8, S100A9, DEFB4B, LCN2, CAMP, CCL2) and pro-inflammatory molecules (IL1B, IL6, TNFA, IL-23A) were investigated in the three groups by RNASeq, RT-qPCR, immunohistochemistry and immunofluorescence. Epidermal changes were already detectable in non-lesional HS skin; the epidermal occurrence of antimicrobial peptides (AMPs), IL-1β, TNF-α and IL-23 was highly upregulated compared with healthy AGR skin. In lesional HS epidermis, TNF-α and IL-1β expression remained at high levels while AMPs and IL-23 increased even more compared with non-lesional skin. In the dermis of non-lesional HS skin, signs of inflammation were barely detectable (vs. AGR), while in the lesional dermis, the number of inflammatory cells and Th1/Th17-related mediators were significantly elevated. Our findings that non-lesional HS epidermal keratinocytes produce not only AMPs and IL-1β but also high levels of TNF-α and IL-23 confirm the driver role of keratinocytes in HS pathogenesis and highlight the possible role of keratinocytes in the transformation of non-inflammatory Th17 cells (of healthy AGR skin) into inflammatory cells (of HS) via the production of these mediators. The fact that epidermal TNF-α and IL-23 appear also in non-lesional HS seems to prove these cytokines as excellent therapeutic targets.


Plasma Metabolic Profiling Analysis of Gout Party on Acute Gout Arthritis Rats Based on UHPLC-Q-TOF/MS Combined with Multivariate Statistical Analysis.
Gout Party is a Chinese medicine prescription composed of Aconiti Lateralis Radix Praeparaia, Aconiti Radix Cocta, Cremastrae Pseudobulbus Pleiones Pseudobulbus, Smilacis Glabrae Rhizoma, Rehmanniae Radix, and Glycyrrhizae Radix et Rhizoma, which can relieve joint pain caused by gouty arthritis (GA) and rheumatoid, and has a therapeutic effect on acute gouty arthritis (AGA). However, little information is available on the molecular biological basis and therapeutic mechanism of Gout Party for the treatment of AGA. AGA model was established by injecting sodium urate, and colchicine served as a positive control drug. We established a metabolomic method based on ultra-high-performance liquid chromatography-tandem quadrupole/time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to analyze the plasma samples of model group rats and blank group rats. Multiple statistical analyses, including principal component analysis (PCA) and partial least square discrimination analysis (PLS-DA), were used to examine metabolite profile changes in plasma samples. Finally, we identified 2-ketobutyric acid, 3-hexenedioic acid, but-2-enoic acid, and so on; 22 endogenous metabolites associated with AGA. After successful molding, we found that 2-ketobutyric acid, 3-hexenedioic acid, but-2-enoic acid, argininic acid, galactonic acid, lactic acid, equol 4'-O-glucuronide, deoxycholic acid glycine conjugate, glycocholic acid, sphinganine 1-phosphate, LPE (0:0/20:3), LPE (0:0/16:0), LPC (15:0) decreased significantly (p < 0.05 or p < 0.01), alanine, erythrulose, 3-dehydrocarnitine, m-methylhippuric acid, 3-hydroxyoctanoic acid, p-cresol sulfate, estriol 3-sulfate 16-glucuronide, 10-hydroxy-9-(phosphonooxy)octadecenoate, docosahexaenoic acid increased significantly (p < 0.05 or p < 0.01). After Gout Party treatment, 14 biomarkers had a tendency to normal conditions. These above biomarkers were mainly involved in fatty acid metabolism, bile acid metabolism, amino acid metabolism, and energy metabolism pathways. These results suggested that Gout Party exerted therapeutic effects of treating AGA by improving energy metabolism disorder and amino acid metabolism dysfunction, and attenuating fatty acid metabolism abnormal and inflammation. The results of this experiment provided a reference for revealing the metabolic mechanism produced by Gout Party in the treatment of AGA, but the subsequent studies need to be further improved and supported by relevant cell experiments and clinical experiments.


DFT calculation of the electronic properties of fluorene-1,3,4-thiadiazole oligomers.
Thiadiazole derivatives have been widely employed in the areas of pharmaceutical, agricultural, industrial, and polymer chemistry. The electronic and molecular structures of thiadiazoles are of interest because they have an equal number of valence electrons and similar molecular structures to thiophenes, which are currently used in the construction of organic solar cells due to their relatively high hole mobilities and good light-harvesting properties. For this reason, the electronic properties of fluorene-1,3,4-thiadiazole oligomers warrant investigation. In the present work, the structure of fluorene-1,3,4-thiadiazole with one thiadiazole unit in the structure was analyzed. This molecule was then expanded until there were 10 thiadiazole units in the structure. The band gap, HOMO and LUMO distributions, and absorption spectrum were analyzed for each molecule. All calculations were performed by applying the B3LYP/6-31G(d) chemical model in the Gaussian 03W and GaussView software packages. The electronic properties were observed to significantly enhance as the number of monomeric units increased, which also caused the gap energy to decrease from 3.51 eV in the oligomer with just one thiadiazole ring to 2.33 eV in the oligomer with 10 units. The HOMO and LUMO regions were well defined and separated for oligomers with at least 5 monomer units of thiadiazole.


Effect of ureteral stent length and implantation position on migration after implantation.
Ureteral obstruction is a urinary system disease that causes urinary retention, renal injury, renal colic, and infection. Ureteral stents are often used for conservative treatment in clinics, and their migration usually results in ureteral stent failure. The migrations include proximal migration to the kidney side and distal migration to the bladder side, but the biomechanism of stent migration is still unknown. Finite element models of stents with lengths from 6-30 cm were developed. The stents were implanted into the middle of the ureter to analyze the effect of stent length on its migration, and the effect of stent implantation position on 6-cm-long stent migration was also observed. The stents' maximum axial displacement was used to assess the ease of stent migration. A time-varying pressure was applied to the ureter outer wall to simulate peristalsis. The stent and ureter adopted friction contact conditions. The two ends of the ureter were fixed. The radial displacement of the ureter was used to evaluate the effect of the stent on peristalsis. The maximum migration occurs in the positive direction for a 6-cm-long stent implanted at the proximal ureter (CD and DE), but in the negative direction at the distal ureter (FG and GH). The 6-cm-long stent demonstrated almost no effect on ureteral peristalsis. The 12-cm-long stent diminished the radial displacement of the ureter from 3-5 s. The 18-cm stent diminished the radial displacement of the ureter from 0-8 s, and the radial displacement within 2-6 s was weaker than other time. The 24-cm stent diminished the radial displacement of the ureter from 0-8 s, and the radial displacement within 1-7 s was weaker than other time. The biomechanism of stent migration and ureteral peristalsis weakening after stent implantation was explored. Shorter stents were more likely to migrate. The implantation position had less influence on ureteral peristalsis compared with the stent length, which provided a reference for stent design aimed at reducing stent migration. Stent length was the main factor affecting ureteral peristalsis. This study provides a reference for the study of ureteral peristalsis.


Co-Fermentation of Cheese Whey and Crude Glycerol in EGSB Reactor as a Strategy to Enhance Continuous Hydrogen and Propionic Acid Production.
This study evaluated the production of hydrogen and propionic acid in an expanded granular sludge bed (EGSB) reactor by co-fermentation of cheese whey (CW) and crude glycerol (CG). The reactor was operated at hydraulic retention time (HRT) of 8 h by changing the CW/CG ratio from 5:1 to 5:2, 5:3, 5:4, and 5:5. At the ratio of 5:5, HRT was reduced from 8 to 0.5 h. The maximum hydrogen yield of 0.120 mmol H2 g COD-1 was observed at the CW/CG ratio of 5:1. Increasing the CG concentration repressed hydrogen production in favor of propionic acid, with a maximum yield of 6.19 mmol HPr g COD-1 at the CW/CG ratio of 5:3. Moreover, by reducing HRT of 8 to 0.5 h, the hydrogen production rate was increased to a maximum value of 42.5 mL H2 h-1 L-1at HRT of 0.5 h. The major metabolites were propionate, 1,3-propanediol, acetate, butyrate, and lactate.


Effects of cyclosporine A on cyclic AMP generation and GTP-binding proteins in isolated islets.
The role of cyclosporine A (CsA) in cAMP generation and its relationship with guanine nucleotide-binding proteins (G-proteins) was investigated in isolated islets. cAMP accumulation in response to glucose, 3-isobutyl-1-methyl-xanthine (a phosphodiesterase inhibitor) and the calcium ionophore A23187 increased significantly (P less than 0.05) in the presence of 0.5 microgram/mL CsA. CsA (0.5 microgram/mL) was unable to affect the 2.1-fold increase in cAMP formation induced by 30 microM forskolin (an adenylate cyclase complex activator). The pertussis toxin-induced cAMP generation in the presence of 20 mM glucose was suppressed by CsA by 34%. On the other hand, CsA enhanced cAMP levels in cholera toxin-treated islets. CsA caused a non-competitive inhibition of phosphodiesterase activity with half-maximal inhibition at 5 micrograms/mL CsA. CsA blocked the pertussis toxin ADP-ribosylation of a 41-kDa and a 21-kDa islet protein, but not the cholera toxin ADP-ribosylation of a 45-kDa and a 21-kDa islet protein. These data indicate that CsA increases cAMP content by a non-competitive inhibition of phosphodiesterase activity and by acting through G-proteins involved in the modulation of adenylate cyclase activity. An inhibitory effect of CsA on a 21-kDa pertussis toxin-sensitive G-protein was also observed.


Spontaneous cholesteatoma of the external auditory canal: the utility of CT.
Spontaneous external auditory canal (EAC) cholesteatoma is a rare disease. The symptoms are nonspecific. It is diagnosed by clinical examination and radiological investigation. The clinical examination alone is often insufficient for accurately assessing spread of the cholesteatoma into the temporal bone, meaning cross-sectional imaging modalities are required, and specifically computed tomography. We report three cases of spontaneous cholesteatoma of the external auditory canal. All of our patients underwent surgery. In two cases, the cholesteatoma was restricted to the external auditory canal, while in one case, it was complicated by a fistula with the lateral semicircular canal. Good anatomical and functional results were obtained in all three cases, with the external auditory canal patent and a good calibre on completion.


CtsR, the Gram-positive master regulator of protein quality control, feels the heat.
Protein quality networks are required for the maintenance of proper protein homeostasis and essential for viability and growth of all living organisms. Hence, regulation and coordination of these networks are critical for survival during stress as well as for virulence of pathogenic species. In low GC, Gram-positive bacteria central protein quality networks are under the control of the global repressor CtsR. Here, we provide evidence that CtsR activity during heat stress is mediated by intrinsic heat sensing through a glycine-rich loop, probably in all Gram-positive species. Moreover, a function for the recently identified arginine kinase McsB is confirmed, however, not for initial inactivation and dissociation of CtsR from the DNA, but for heat-dependent auto-activation of McsB as an adaptor for ClpCP-mediated degradation of CtsR.


Antioxidant Properties of Bioactive Compounds in Fruit and Vegetable Waste.
In recent years, great interest has arisen in the study of compounds with antioxidant activity present in agri-food residues [...].


Examining unsupervised ensemble learning using spectroscopy data of organic compounds.
One solution to the challenge of choosing an appropriate clustering algorithm is to combine different clusterings into a single consensus clustering result, known as cluster ensemble (CE). This ensemble learning strategy can provide more robust and stable solutions across different domains and datasets. Unfortunately, not all clusterings in the ensemble contribute to the final data partition. Cluster ensemble selection (CES) aims at selecting a subset from a large library of clustering solutions to form a smaller cluster ensemble that performs as well as or better than the set of all available clustering solutions. In this paper, we investigate four CES methods for the categorization of structurally distinct organic compounds using high-dimensional IR and Raman spectroscopy data. Single quality selection (SQI) forms a subset of the ensemble by selecting the highest quality ensemble members. The Single Quality Selection (SQI) method is used with various quality indices to select subsets by including the highest quality ensemble members. The Bagging method, usually applied in supervised learning, ranks ensemble members by calculating the normalized mutual information (NMI) between ensemble members and consensus solutions generated from a randomly sampled subset of the full ensemble. The hierarchical cluster and select method (HCAS-SQI) uses the diversity matrix of ensemble members to select a diverse set of ensemble members with the highest quality. Furthermore, a combining strategy can be used to combine subsets selected using multiple quality indices (HCAS-MQI) for the refinement of clustering solutions in the ensemble. The IR + Raman hybrid ensemble library is created by merging two complementary "views" of the organic compounds. This inherently more diverse library gives the best full ensemble consensus results. Overall, the Bagging method is recommended because it provides the most robust results that are better than or comparable to the full ensemble consensus solutions.


Sildenafil citrate (Viagra) impairs fertilization and early embryo development in mice.
To determine the effects of sildenafil citrate, a cyclic monophosphate-specific type 5 phosphodiesterase inhibitor known to affect sperm function, on fertilization and early embryo cleavage. This acute mammal study included male and female mice assigned randomly, the females sacrificed after mating and their oocytes/embryos evaluated at four time periods after treatment. Academic research environment. Male and female CBAB(6) mice. Female mice were injected intraperitoneally with 5 IU gonadotropin (hCG) to stimulate follicular growth and induce ovulation. They were each caged with a male that had been gavaged with sildenafil citrate (0.06 mg/0.05 mL) and allowed to mate. After 12, 36, 60, and 84 h, females were killed, their oviducts were dissected out, and retrieved embryos were assessed for blastomere number and quality. Fertilization rates and numbers of embryos were evaluated after treatment. Fertilization rates (day 1) were markedly reduced (-33%) in matings where the male had taken sildenafil citrate. Over days 2-4, the numbers of embryos developing in the treated group were significantly fewer than in the control group. There was also a trend for impaired cleavage rates within those embryos, although this did not reach significance. The impairments to fertility caused by sildenafil citrate have important implications for infertility centers and for couples who are using this drug precoitally while attempting to conceive.


An observational study of the use of beclomethasone dipropionate suppositories in the treatment of lower urinary tract inflammation in men.
Nonbacterial prostatitis, together with chronic pelvic pain syndrome, accounts for 90-95 % of prostatitis cases. Anti-inflammatory medications are commonly used to reduce storage/inflammatory symptoms that can deteriorate quality of life. The purpose of this study was to observe the efficacy and safety of beclomethasone dipropionate rectal suppositories (Topster®) in inflammations of the lower urinary tract in men. Patients underwent diagnostic and therapeutic protocols according to current evidence-based practice. Efficacy assessments: voiding parameters, perineal pain, International Prostate Symptom Score (IPSS), digital rectal examination (DRE). Adverse events and patient compliance were recorded throughout the study. One hundred eighty patients were enrolled, mean age 52 ± 14.97. Most frequent diagnosis: nonbacterial prostatitis (85 %). All patients completed visits 1 and 2. All patients were treated with beclomethasone dipropionate (BDP) suppositories, 136/180 also with Serenoa repens (SR) extract. Antibiotics were rarely required. 162/180 patients presented clinically significant improvements and terminated treatment. Mean change vs. baseline in voiding frequency: -3.55 ± 2.70 n/day in patients taking only BDP and -3.68 ± 2.81 n/day in those taking both BDP and SR (P<.0001 in both groups). Uroflowmetry improved significantly; change from baseline 3.26 ± 5.35 ml/s in BDP only group and 5.61 ± 7.32 ml/s in BDP + SR group (P = 0.0002 for BDP, P<.0001 for BDP + SR). Urine stream normal in 35 % of patients at visit 1 and 57.22 % of patients at visit 2. Mean change in perineal pain, on 0-10 VAS, -0.66 ± 2.24 for BDP only group (P = 0.0699) and -1.37 ± 2.40 for BDP + SR group (P<.0001). IPSS increased at visit 2. No adverse events were reported. For all parameters, none of the comparisons between groups was found to be statistically significant. This study confirmed the drug's good safety profile. We also observed an improvement in the main storage symptoms and clinical findings associated with lower urinary tract inflammation in patients treated with beclomethasone dipropionate suppositories.


Divergent signaling mechanisms for venous versus arterial contraction as revealed by endothelin-1.
Venous function is underappreciated in its role in blood pressure determination, a physiologic parameter normally ascribed to changes in arterial function. Significant evidence points to the hormone endothelin-1 (ET-1) as being important to venous contributions to blood pressure. We hypothesized that the artery and vein should similarly depend on the signaling pathways stimulated by ET-1, specifically phospholipase C (PLC) activation. This produces two functional arms of signaling: diacylglycerol (DAG; protein kinase C [PKC] activation) and inositol trisphosphate (IP3) production (intracellular calcium release). The model was the male Sprague-Dawley rat. Isolated tissue baths were used to measure isometric contraction. Western blot and immunocytochemical analyses measured the magnitude of expression and site of expression, respectively, of IP3 receptors in smooth muscle/tissue. Pharmacologic methods were used to modify PLC activity and signaling elements downstream of PLC (IP3 receptors, PKC). ET-1-induced contraction was PLC dependent in both tissues as the PLC inhibitor U-73122 significantly reduced contraction in aorta (86% ± 4% of control; P < .05) and vena cava (49% ± 11% of control; P < .05). However, ET-1-induced contraction was not significantly inhibited by the IP3 receptor inhibitor 2-aminoethoxydiphenylborane (100 μM) in vena cava (82% ± 8% of control; P = .23) but was in the aorta (55% ± 4% of control; P < .05). All three IP3 receptor isoforms were located in venous smooth muscle. IP3 receptors were functional in both tissues as the novel membrane-permeable IP3 analogue (Bt-IP3; 10 μM) contracted aorta and vena cava. Similarly, whereas the PKC inhibitor chelerythrine (10 μM) attenuated ET-1-induced contraction in vena cava and aorta (5% ± 2% and 50% ± 5% of control, respectively; P < .05), only the vena cava contracted to the DAG analogue 1-oleoyl-2-acetyl-sn-glycerol. These findings suggest that ET-1 activates PLC in aorta and vena cava, but vena cava contraction to ET-1 may be largely IP3 independent. Rather, DAG—not IP3—may contribute to contraction to ET-1 in vena cava, in part by activation of PKC. These studies outline a fundamental difference between venous and arterial smooth muscle and further reinforce a heterogeneity of vascular smooth muscle function that could be taken advantage of for therapeutic development.


Acetone powder from dormant seeds of Ricinus communis L: lipase activity and presence of toxic and allergenic compounds.
The influence of several factors on the hydrolytic activity of lipase, present in the acetone powder from dormant castor seeds (Ricinus communis) was evaluated. The enzyme showed a marked specificity for short-chain substrates. The best reaction conditions were an acid medium, Triton X-100 as the emulsifying agent and a temperature of 30 degrees C. The lipase activity of the acetone powder of different castor oil genotypes showed great variability and storage stability of up to 90%. The toxicology analysis of the acetone powder from genotype Nordestina BRS 149 showed a higher ricin (toxic component) content, a lower 2S albumin (allergenic compound) content, and similar allergenic potential compared with untreated seeds.


Biological influence of infant death on fertility.
This study examines the biological influence of infant death on subsequent fertility in three Asian countries--Indonesia, Nepal and Sri Lanka, comparing the birth interval between two consecutive births up to the sixth birth by survival status of the preceding infant among breast-feeding women not using contraception. There is consistent evidence of biological influence in each of the three countries. Infant death shortens birth intervals by up to 30%, though its influence varies between the countries.


Transaortic division of the mitral subvalvar apparatus.
Adequate exposure of the mitral valve can be difficult to obtain through a median sternotomy. A variety of techniques have been described to facilitate exposure in this situation. This report describes the use of trans-aortic technique which allows easy and accurate division of the mitral subvalvar apparatus. The mitral valve can then be approached through a left atriotomy, everted and the excision completed.


Anterior deflected urinary stream.
We present a case of anterior deflected urinary stream (ADUS) secondary to meatal shelf with no dysfunctional voiding symptoms (DV). The video illustrates the presentation, operative management and literature review. Meatal deformity in girls has been described in association with DV. Hoebeke et al. highlighted the strong correlation between meatal abnormality and non-neurogenic bladder dysfunction in girls. They demonstrated that girls with ADUS had more severe dysfunction on urodynamics. Klijn et al. prospectively evaluated the effect of surgical meatal correction in girls with ADUS. They found that 39% of female patients with DV had ADUS, 50% of them were free of symptoms following surgical correction. This is the first reported case of an isolated ADUS without DV. Early correction of the anomaly is advocated to limit social distress, and potentially prevent development of DV.


Feeding ecology and life history variation of the blue tit in Mediterranean deciduous and sclerophyllous habitats.
High variation in laying date and clutch size of the blue tit between a Mediterranean mixed habitat on the mainland, southern France, and a sclerophyllous habitat on the island of Corsica is hypothesized to be related to differences in the food supply. The diet of the nestlings and feeding frequencies were studied using camera nestboxes and electronic chronographs. Food items brought to the nestlings were much more diverse on Corsica than on the mainland, including many fewer caterpillars and a wider range of taxa. However, when expressed as a volume index, prey items were on average larger on Corsica than on the mainland. Feeding frequencies were significantly lower on Corsica. A good correlation was found in both habitats between laying date and the caterpillar peak date, although both the leafing development of oaks and the peak of abundance of caterpillars occurred 3 weeks later in the Corsican sclerophyllous trees than in the mainland deciduous ones. Differences in the feeding ecology of tits between the two habitats are discussed in the light of the evergreen habit, which means that only 30% of leaves are available for phyllophagous insects instead of 100% in deciduous trees. the combination of a late and low food supply in evergreen trees is the best explanation for the differences in breeding traits betwen the two populations.


Microcantilever-integrated photonic circuits for broadband laser beam scanning.
Laser beam scanning is central to many applications, including displays, microscopy, three-dimensional mapping, and quantum information. Reducing the scanners to microchip form factors has spurred the development of very-large-scale photonic integrated circuits of optical phased arrays and focal plane switched arrays. An outstanding challenge remains to simultaneously achieve a compact footprint, broad wavelength operation, and low power consumption. Here, we introduce a laser beam scanner that meets these requirements. Using microcantilevers embedded with silicon nitride nanophotonic circuitry, we demonstrate broadband, one- and two-dimensional steering of light with wavelengths from 410 nm to 700 nm. The microcantilevers have ultracompact ~0.1 mm2 areas, consume ~31 to 46 mW of power, are simple to control, and emit a single light beam. The microcantilevers are monolithically integrated in an active photonic platform on 200-mm silicon wafers. The microcantilever-integrated photonic circuits miniaturize and simplify light projectors to enable versatile, power-efficient, and broadband laser scanner microchips.


Pain in Children and Adolescents With Sickle Cell Disease: Multidimensional Assessment.
Patients with sickle cell disease (SCD) suffer from recurrent painful vaso-occlusive episodes with a significant impact on their quality of life. The aim of this study was to perform a multidimensional assessment of pain in Portuguese children and adolescents with SCD. Subjects were children and adolescents and their parents recruited from the outpatient pediatric hematology clinic in a Portuguese Hospital. Pain frequency and a broader multidimensional evaluation was performed using the Pediatric Pain Questionnaire (PedsQL) (that includes Visual Analog Scales, color indicators, qualitative descriptors of pain [open question] and body diagram) and a structured questionnaire (PQ2), that included a term list of the Adolescent Pediatric Pain Tool, among other questions. Included 60 children and adolescents (36 boys and 24 girls) with a mean age of 11±4.0 years (range, 5 to 18). The majority of children (83.1%) reported no present pain and 57.6% reported pain last month, with several degrees of pain intensity. Abdomen, thorax, and limbs were the most frequent localizations. Red was the color most chosen to describe "severe pain," whereas blue and green were more used to describe "no pain." The number of pain descriptors is different using an open-ended question (2.1±1.5) than a given list of terms (15.3±8.1). The most frequent terms used in the open question were "strong/very strong," "hurts a lot," "makes cry," and "horrible." Parents used similar pain descriptors. "Makes cry," "horrible," "tiring," "unbearable," and "uncomfortable" were the most frequent terms chosen in the PQ2. Pain interfered variably with daily activities for most of the patients. Pain experienced in SCD has a broad range of intensity levels, localization, and frequency. There are a number of pain descriptors and socio-emotional factors related to the pain experience. A comprehensive multidimensional assessment that includes both child's and parents' perspective seem to be the most adequate strategy to assess pain.


Measurement of human erythrocyte C4d to erythrocyte complement receptor 1 ratio in cardiac transplant recipients with acute symptomatic allograft failure.
Complement activation has been recognized as a contributing factor to cardiac allograft dysfunction. Combined measurement of erythrocyte C4d (E-C4d) and complement receptor 1 (E-CR1) are potential biomarkers to monitor complement activity in patients with autoimmune diseases. We conducted a prospective study using CR1-2B11 monoclonal antibody to detect the E-C4d to E-CR1 ratio among our cardiac transplant recipients with acute symptomatic allograft failure. Eight recipients with acute cardiac allograft failure and 72 healthy controls were included in this study. Levels of E-C4d and E-CR1 were measured by indirect immunofluorescence and flow cytometry. The results were utilized to determine the association between patient C4d staining, histological features, and clinical outcomes. Eight patients with nine episodes of sudden onset of graft failure and suspected antibody-mediated rejection (AMR) were included in this study. One patient who received emergent mechanical circulatory support was treated with plasmapheresis for his unstable hemodynamic status. The mean pretreatment left ventricular ejection fraction was 30.3%. No histological study demonstrated cellular rejection or AMR in any patient. There were two patients with positive C4d immunostaining. Three patients had four episodes of acute rejection with sudden death at home. The mean E-C4d/E-CR1 ratio in the study group (n = 9) was 0.22 +/- 0.07, and 0.12 +/- 0.10 in the control group (n = 72). As comparing both groups, we found the ratios were significant higher in the study group (P = .0003). Measurement of the E-C4d/E-CR1 ratio may be a noninvasive method for detecting acute rejection after cardiac transplantation.


From blood donation to kidney sales: the gift relationship and transplant commercialism.
In The Gift Relationship, Richard Titmuss argued that the practice of altruistic blood donation fosters social solidarity while markets in blood erode it. This paper considers the implications of this line of argument for the organ market debate. I defend Titmuss' arguments against a number of criticisms and respond to claims that Titmuss' work is not relevant to the context of live donor organ transplantation. I conclude that Titmuss' arguments are more resilient than many advocates of organ markets suggest, and more relevant to the debate than is commonly appreciated.


[Cervical cancer in Bas-Rhin: trend and prediction of the incidence in 2014].
In the world, the cervix cancer is the second commonest cancer in women. Its incidence is decreasing but it is still too frequent. The aim of this study was to predict the incidence of cervix cancer among women in the Department of Bas-Rhin. Incidence data were provided by the Bas-Rhin Tumor Registry. The incidence of in situ tumors and invasive cancers was predicted in 2010-2014 by using an age - period - cohort model and a Bayesian approach. The incidence rates predicted by the model, standardized to the European population, were 99.7 per 10(5)population in 2000-2004 (CI 95%: [82.7-118.5]) and 177.1 per 10(5) population in 2010-2014 (CI 95%: [103.7-288.5]) for in situ and 13.0 per 10(5) population (CI 95%: [9.5-17.2]) in 2000-2004 and 11.1 per 10(5)population (CI 95%: [4.5-22.7]) in 2010-2014 for invasive tumors. The decrease of invasive tumors is due to screening. The improvement of the quality of the screening and treatment of in situ tumors would allow the number of incident cases of cervix cancer to decrease.


The impact of AIDS on gay male sexual behavior patterns in New York City.
A sample of 745 gay men, ages 20 to 65, were interviewed in 1985 as part of an effort to determine the impact of the AIDS (acquired immunodeficiency syndrome) epidemic on the non-ill but at-risk community. Measured in terms of the number of different sexual partners, sexual activity was reported to have declined by 78 per cent since hearing about AIDS. The frequency of sexual episodes involving the exchange of body fluids and mucous membrane contact declined by 70 per cent, and condom use during anal intercourse increased from 1.5 to 20 per cent. Abstinence from gay sex did not change over time.


[The electrocardiogram of the long-lived. Observations gathered from a study of 190 subjects over 80].
The Authors have examined the ECG of 190 older than 80 patients. The 5,78% have resulted "normal" and the 12,10% "border-line"; the disturbances of the excitability (67,36%) have been more than those of the conduction (31,04%) among which the Left Anterior Emi-block have been important (12,10%). The myocardial infarction has been infrequent (7,89%) where the Left Ventricular Hypertrophia has been the 20%; the left deviation of the ventricular complexes has represented the 61,57%, the synusal rhythm the 85,26%, the normal rate has been present in 79,47% of the cases.


Factors affecting prevalence and abundance of A.perfoliata infections in horses from south-eastern Poland.
Equine Anoplocephalosis constitute a significant problem in horses worldwide. The aim of this study was to analyse intrinsic (host age and sex) and extrinsic (management type, pasture type and moisture) factors that influence the prevalence and FEC of A. perfoliata infections. Faecal samples were collected from 994 horses managed in studs or individually between 2012 and 2014. The Sedimentation-flotation method was applied for coproscopic analysis, and faecal egg counts were calculated. The overall prevalence was 25.1% (21.4-29.0) with the highest prevalence (36.1% [28.1-44.8]) found in horses 10-20 years old. The individuals kept in studs showed three times higher A. perfoliata prevalence compared to the ones managed individually. The prevalence significantly differed between pasture types, with individuals kept in studs (37.6% [34.3-40.9]) showing four times higher prevalence than horses kept individually (9.2% [4.8-16.5]). More horses kept on watery (42.0% [36.6-47.6]) and semi-watery (35.9% [31.3-40.7]) pastures were infected than those on dry (6.6% [4.6-9.2]) pastures. The overall A. perfoliata FEC in all examined individual was 2.67 and differed within sex, with mares showing 4.3 - times higher FEC of infection than stallions. Horses bred in studs (3.65±0.289) showed higher FEC than these bred individually (1.28±0.198). There was the effect of pasture type on A. perfoliata FEC, with horses kept on joint pastures (4.06±0.29) showing higher FEC than individuals kept individually (0.88±0.23). Pasture moisture significantly affected A. perfoliata FEC with the highest FECs in horses from watery pastures. Horses bred on dry pastures showed 16 times lower FEC than horses bred on watery pastures. Host age also significantly affected A. perfoliata FEC, with the oldest individuals showing the highest mean FEC. The presented analysis of intrinsic and extrinsic factors may help to overcome A. perfoliata infections in horses in different breeding systems. Understanding the role of management and pasture type risk factors that influence this parasitosis may benefit both breeders and veterinary surgeons.


Fabrication of device with poly(N-isopropylacrylamide)-b-ssDNA copolymer brush for resistivity study.
In this study, we grafted bromo-terminated poly(N-isopropylacrylamide) (PNIPAAm) brushes onto thin gold films deposited on silicon, and then reacted with NaN3 to produce azido-terminated PNIPAAm brushes. A probe sequence of single-stranded DNA (ssDNA) with a 4-pentynoic acid succinimidyl ester unit was grafted onto the azido-terminated PNIPAAm brushes through a click reaction, resulting in the formation of block copolymer brushes. The PNIPAAm-b-ssDNA copolymer brushes formed supramolecular complexes stabilized by bio-multiple hydrogen bonds (BMHBs), which enhanced the proton transfer and thereby decreased the resistivity of the structures. In addition, the optimal operation window for DNA detection ranges from 0 to 0.2 M of NaCl concentration. Therefore, the specimens were prepared in the PBS solution at 150 mM NaCl concentration for target hybridization. The supramolecular complex state of the PNIPAAm-b-ssDNA copolymer brushes transformed into the phase-separated state after the hybridization with 0.5 ng/µL of its target DNA sequence owing to the competition between BMHBs and complementary hydrogen bonds. This phase transformation of the PNIPAAm and probe segments inhibited the proton transfer and significantly increased the resistivity at 25 °C. Moreover, there were no significant changes in the resistivity of the copolymer brushes after hybridization with the target sequence at 45 °C. These results indicated that the phase-separated state of the PNIPAAm-b-ssDNA copolymer brushes, which was generally occurred above the LCST, can be substantially generated after hybridization with its target DNA sequence. By performing the controlled experiments, in the same manner, using another sequence with lengths similar to that of the target sequence without complementarity. In addition, the sequences featuring various degrees of complementarity were exploited to verify the phase separation behavior inside the PNIPAAm-b-ssDNA copolymer thin film.


Untangling the effects of the Belt and Road Initiative on carbon dioxide emissions.
The Belt and Road Initiative (BRI), which was first put forward by China in late 2013, has made a significant contribution to international economic activities and inevitably reshaped the pattern of carbon dioxide (CO2) emissions. Considering the spatial spillover effects of CO2 emissions among countries, this paper employs spatial difference-in-differences models in order to investigate the BRI's effects on total CO2 emissions (TCE), per capita CO2 emissions (PCE), and CO2 emissions intensity (CEI), respectively. The results of global Moran's I index prove the existence of spatial correlations of CO2 emissions. The BRI's effect on TCE is significantly positive, while the effects on PCE and CEI are significantly negative, suggesting the BRI has aggravated the amount of CO2 emissions in the partner countries, but has promoted green development by decreasing PCE and CEI. Besides, the spatial effects of control variables on CO2 emissions are also evaluated. Some tests, including placebo test and employing alternative weight matrices, are further conducted to verify the robustness of the model. The findings indicate the BRI has facilitated green economic growth, by eventually achieving emission reduction targets in the partner countries.


Pre-selection of monitoring stations for marine water quality using affinity propagation: A case study of Xincun Lagoon, hainan, China.
The development, protection, and restoration of bays require works in scientific research and applications, and the success of which depends on a well deployment of monitoring stations for marine water quality. However, for bays without historical data, it is difficult to carry out related research on deployment of the monitoring stations, resulting in very few research works. This paper has introduced the affinity propagation (AP) clustering algorithm and achieved good results by correcting the preferences. The results show that under the given preference, that is, when the value of M is -6800, the number of monitoring stations in the Xincun lagoon area is 24. Simultaneous the sensitivity analysis of preferences shows that the number of exemplars decreases with lower preferences, that is, when M decreased from -4000 to -12000, the number also decreased from 70 to 36. However, some exemplars remain unchanged or being changed to adjacent positioning. This shows the stability of computation results and the rationality of AP. The research results can be well applied to other bays, even open waters.


[Computed tomography findings in bilateral blindness (author's transl)].
The use of computed tomography (CT) simplifies neuroradiological investigations. A CT helped to confirm the diagnosis of an occipital vascular leasion in two cases of bilateral blindness.


Modification of certain medical standards and procedures and duration of certain medical certificates. Final rule.
This rule extends the duration of first- and third-class medical certificates for certain individuals. A first-class medical certificate is required when exercising airline transport pilot privileges and at least a third-class medical certificate when exercising private pilot privileges. Certain conforming amendments to medical certification procedures and some general editorial amendments are also adopted. The intent of this action is to improve the efficiency of the medical certification program and service provided to medical certificate applicants.


High glucose uptake unexpectedly is accompanied by high levels of the mitochondrial ß-F1-ATPase subunit in head and neck squamous cell carcinoma.
A hallmark of solid tumors is the consumption of large amounts of glucose and production of lactate, also known as Warburg-like metabolism. This metabolic phenotype is typical for aggressive tumor growth, and can be visualized by 18F-fluorodeoxyglucose (18F-FDG) uptake detected by positron emission tomography (PET). High 18F-FDG uptake inversely correlates with survival and goes along with reduced expression of the catalytic beta-subunit of the H+-ATP synthase (ß-F1-ATPase) in several tumor entities analyzed so far.For this study we characterized a series of 15 head and neck squamous cell carcinoma (HNSCC) by (i) determining 18F-FDG-uptake; (ii) quantitative expression analysis of ß-F1-ATPase (Complex V), NDUF-S1 (Complex I) and COX1 (Complex IV) of the mitochondrial electron transport chain (ETC), as well as Hsp60 (mitochondrial mass) and GAPDH (glycolysis) in tumor cells; (iii) sequencing of the mtDNA of representative tumor samples.Whereas high 18F-FDG-uptake also correlates with poor prognosis in HNSCC, it surprisingly is accompanied by high levels of ß-F1-ATPase, but not by any of the other analyzed proteins.In conclusion, we here describe a completely new phenotype of metabolic adaptation possibly enabling those tumors with highest levels of ß-F1-ATPase to rapidly proliferate even in hypoxic zones, which are typical for HNSCC.


Nemopilema nomurai jellyfish venom attenuates phenotypic modulation of PDGF BB-induced vascular smooth muscle cells and κ-carrageenan-induced rat tail thrombosis.
Jellyfish venoms have long been recognized as a potentially rich source of natural bioactive compounds with pharmacological potential for the creation of innovative drugs. Our previous study demonstrated that Nemopilema nomurai jellyfish venom (NnV) has a chymotrypsin-like serine protease with fibrinolytic activity in vitro. Therefore, the present study aims to investigate the potential effect of NnV on cell migration, proliferation, and differentiation of vascular smooth muscle cells (VSMC; A7r5 cells) involved in the probable mechanism pathways. We also determined its anti-thrombotic effect through κ-carrageenan-induced Sprague-Dawley (SD) rat tail thrombus model. NnV inhibits on Platelet-derived growth factor (PDGF)-BB-stimulated A7r5 cells migration and proliferation by decreasing matrix metalloproteinase 2 (MMP-2) level and phosphorylation of ERK and Akt in a dose-dependent manner, but not p38. Furthermore, NnV regulates the phenotype transition of differentiation in PDGF-BB-stimulated A7r5 cells via ɑ-SMA and calponin in a dose-dependent manner. In an in vivo study, NnV treatment demonstrated clear anti-thrombotic activity in a dose-dependent manner, which was associated with decreased thrombus formation and length in κ-carrageenan-induced SD rat tail. These findings suggested that NnV has a novel fibrinolytic enzyme that can be used to prevent and/or treat thrombosis-related cardiovascular disorders.


Evaluation of swallowing function in patients with oropharyngeal secretions.
Several studies have reported a strong association between the presence of oropharyngeal secretions in the laryngeal vestibule and the likelihood of aspiration of food or liquid. However, no previous studies have evaluated the accumulation of saliva and swallowing dynamics. The objective of this study was to examine the factors related to decreased function that result in saliva accumulation based on images from videofluoroscopic examination of swallowing (VF) performed on the same day as videoendoscopic examination of swallowing (VE). This retrospective study investigated 47 patients with dysphagia who underwent VF and VE on the same day. Saliva accumulation in the pharynx was assessed on VE and classified by the Murray secretion scale. Pharyngeal residue was assessed on VF. In addition, displacement of the hyoid bone and larynx on swallowing and the opening size of the esophageal orifice were measured, and contact between the base of the tongue and the posterior pharyngeal wall was examined on VF. Moderate correlations were found between saliva accumulation and perpendicular displacement of the larynx and upper esophageal sphincter opening. The percentage of patients showing contact between the base of the tongue and the posterior pharyngeal wall was significantly greater in those with a saliva accumulation score of 0 or 1. Less laryngeal elevation and upper esophageal sphincter opening and absence of contact between the base of the tongue and the posterior pharyngeal wall when swallowing tended to result in accumulation of saliva in the pharynx.


Patient Evaluation and Preparation in Vascular and Interventional Radiology: What Every Interventional Radiologist Should Know (Part 2: Patient Preparation and Medications).
Performing an interventional procedure imposes a commitment on interventional radiologists to conduct the initial patient assessment, determine the best course of therapy, and provide long-term care. Patient care before and after an interventional procedure, identification, and management of early and delayed complications of various procedures are equal in importance to the procedure itself. In this second part, we complete the comprehensive, methodical review of pre-procedural care and patient preparation before vascular and interventional radiology procedures.


Perinatal choline supplementation attenuates behavioral alterations associated with neonatal alcohol exposure in rats.
Children exposed to alcohol prenatally suffer from a variety of behavioral alterations, including hyperactivity and learning deficits. Given that women continue to drink alcohol during pregnancy, it is critical that effective interventions and treatments be identified. Previously, we reported that early postnatal choline supplementation can reduce the severity of learning deficits in rats exposed to alcohol prenatally. The present study examined whether choline supplementation can reduce the severity of behavioral alterations associated with alcohol exposure during the third trimester equivalent brain growth spurt. Male neonatal rats were assigned to one of three treatment groups. One group was exposed to alcohol (6.6 g/kg/day) from postnatal days (PD) 4-9 via an artificial rearing procedure. Artificially reared and normally reared control groups were included. One half of subjects from each treatment received daily subcutaneous injections of a choline chloride solution from PD 4-30, whereas the other half received saline vehicle injections. On PD 31-34, after choline treatment was complete, activity level was monitored and, on PD 40-42, subjects were tested on a serial spatial discrimination reversal learning task. Subjects exposed to alcohol were significantly hyperactive compared to controls. The severity of ethanol-induced hyperactivity was attenuated with choline treatment. In addition, subjects exposed to ethanol during the neonatal period committed a significantly greater number of perseverative-type errors on the reversal learning task compared to controls. Exposure to choline significantly reduced the number of ethanol-related errors. Importantly, these behavioral changes were not due to the acute effects of choline, but were related to long-lasting organizational effects of early choline supplementation. These data suggest that early dietary interventions may reduce the severity of fetal alcohol effects.


Bsd2 binds the ubiquitin ligase Rsp5 and mediates the ubiquitination of transmembrane proteins.
Membrane proteins destined for the vacuolar or lysosomal lumen are typically ubiquitinated, the ubiquitin serving as a targeting signal for the multivesicular body pathway. The RING-domain ubiquitin ligase Tul1 is an integral membrane protein that modifies the yeast vacuolar enzyme carboxypeptidase S (Cps1), the polyphosphatase Ppn1/Phm5 and other proteins containing exposed hydrophilic residues within their transmembrane domains (TMDs). Here we show that Bsd2 provides an alternative ubiquitination mechanism for Cps1, Phm5 and other proteins. Bsd2 is a three-TMD protein with a PPXY motif that binds the HECT domain ubiquitin ligase Rsp5. It can thus act as a specific adaptor linking Rsp5 to its substrates. Like Tul1, the Bsd2 system recognises polar TMDs. Bsd2 also controls the vacuolar targeting of a manganese transporter and a mutant plasma membrane ATPase, and together with the ER retrieval receptor Rer1, it protects cells from stress. We suggest that Bsd2 has a wide role in the quality control of membrane proteins. Bsd2 is the yeast homologue of human NEDD4 binding protein N4WBP5, which may therefore have similar functions.


A meta-analysis of translumbar embolization versus transarterial embolization for type II endoleak after endovascular repair of abdominal aortic aneurysm.
This systematic review and meta-analysis aimed to compare the clinical outcomes between transarterial and translumbar (direct aneurysm sac puncture) approaches for persistent type II endoleak after endovascular repair of abdominal aortic aneurysm. We searched multiple electronic databases (up to October 31, 2018) for eligible trials in patients with type II endoleaks after endovascular abdominal aortic aneurysm repairs that evaluated the outcomes of translumbar embolization vs transarterial embolization. The primary outcome was clinical success (absence of the endoleak on the last examination); the secondary outcomes were technical success and complication rate. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. Among the 904 studies screened, 9 studies with 354 participants were included in this review. None of the studies reported rupture or mortality. The translumbar group had a relatively higher clinical success rate than the transarterial group, but this difference was not statistically significant (OR, 2.29; 95% CI, 1.00-5.25; P = .05; I2 = 52%). The technical success rate was significantly higher in the translumbar group than in the transarterial group (OR, 13.32; 95% CI, 3.41-52.07; P = .0002; I2 = 0%). No significant difference was found in the complication rate of the two groups (OR, 1.15; 95% CI, 0.26-4.96; P = .85; I2 = 0%). We also included five studies that reported the clinical outcomes of open repair. All patients were technically treated by open repair, and 58 of 60 patients owned clinical success during the follow-up period. The translumbar route was more successful in obliterating the endoleak on follow-up imaging. When repeated endovascular embolizations fail, a laparotomy should follow.


Ultrastructural and biochemical studies of lipolysis by lipolysosomes in chick hepatocytes.
Lipolysosomes in chick hepatocytes were studied by biochemical and electron-microscopic techniques. Their lipolysis was investigated in vitro using the floating lipid fraction isolated from chick liver homogenates. Many lipid droplets were noted to be enveloped by a unit membrane with a partially thickened electron-dense layer containing some myelin-like structures, electron-dense material or electron-lucent droplets, close to the inner leaflet of the membrane. Cytochemically, the dense layer showed acid phosphatase activity, and thus the lipid droplets were identified as lipolysosomes. The lipolysosomes isolated in a floating lipid fraction retained the characteristic dense layer and the surrounding membrane, and the fraction showed little contamination by other organelles. Free fatty acids were released in the fraction after incubation at 37 degrees C, but not at 0 degree C. The reaction was completely inhibited by HgCl2, p-chloromercuribenzoate and esterastin, a potent inhibitor of acid lipase. These results suggest an involvement of acid lipase in lipolysis of the lipolysosomes.


Peroxisome proliferator-activated receptor-α activation facilitates contextual fear extinction and modulates intrinsic excitability of dentate gyrus neurons.
The dentate gyrus (DG) of the hippocampus encodes contextual information associated with fear, and cell activity in the DG is required for acquisition and extinction of contextual fear. However, the underlying molecular mechanisms are not fully understood. Here we show that mice deficient for peroxisome proliferator-activated receptor-α (PPARα) exhibited a slower rate of contextual fear extinction. Furthermore, selective deletion of PPARα in the DG attenuated, while activation of PPARα in the DG by local infusion of aspirin facilitated extinction of contextual fear. The intrinsic excitability of DG granule neurons was reduced by PPARα deficiency but increased by activation of PPARα with aspirin. Using RNA-Seq transcriptome we found that the transcription level of neuropeptide S receptor 1 (Npsr1) was tightly correlated with PPARα activation. Our results provide evidence that PPARα plays an important role in regulating DG neuronal excitability and contextual fear extinction.


Mechanism of glial differentiation of neural progenitor cells by amyloid precursor protein.
We found that human neural progenitor cells (HNPCs) exposed to high concentrations of amyloid precursor protein (APP) or transplanted into APP transgenic mice (APP23) primarily differentiated into astrocytes, suggesting that pathological alterations of APP processing in Alzheimer's disease (AD) may prevent neuronal differentiation of HNPCs. To investigate the mechanism of APP-induced glial differentiation of HNPCs. We treat HNPCs with APP and analyze the expression and phosphorylation of signaling molecules using PCR and Western blots. To confirm the involvement of the factors, RNA interference of the signaling molecule is conducted. APP treatment caused inductions of CNTF, gp130 and JAK1 gene expressions, and STAT3 phosphorylation, while silencing of these genes by RNA interference suppressed the glial differentiation of the cells, indicating involvement of the IL-6/gp130 pathway. APP also increased the generation of notch intracellular domain and gene expression of Hes1, indicating that glial differentiation of HNPCs may be mediated by the notch signaling. These results indicate that APP may regulate HNPC differentiation through activation of both the IL-6/gp130 and notch signaling pathway. Although the importance of adult neurogenesis is not clear, glial differentiation of HNPCs may cause problems in maintaining normal brain function and may contribute to the AD pathology.


Intestinal permeability to polyethyleneglycol 600 in Crohn's disease. Peroperative determination in a defined segment of the small intestine.
Ileal permeability to different sized polyethyleneglycols (590-942 dalton PEG) was investigated peroperatively in 11 patients with Crohn's disease and seven with colonic carcinoma. A 15 cm ileal segment was converted into a tied loop, in which the PEG's were deposited. Absorption from the ileal segment was then measured as six-hour urinary recovery of the PEg dose. Polyethyleneglycol absorption in Crohn's disease was greater than in cancer patients and similar throughout the weight range, but in the cancer patients it was inversely proportional to molecular weight. Thus there was significantly greater absorption of the higher weights (greater than or equal to 678 dalton) in the Crohn's, than in the cancer patients. The apparently increased permeability of the small intestine in Crohn's disease may be an important factor in its pathogenesis.


Improved PVC/ZnO Nanocomposite Insulation for High Voltage and High Temperature Applications.
Nanosized inorganic oxides have the trends to improve many characteristics of solid polymer insulation. In this work, the characteristics of improved poly (vinyl chloride) (PVC)/ZnO are evaluated using 0, 2, 4 and 6 phr of ZnO nanoparticles dispersed in polymer matrix using internal mixer and finally compressed into circular disk with 80 mm diameter using compression molding technique. Dispersion properties are studied by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), and optical microscopy (OM). The effect of filler on the electrical, optical, thermal, and dielectric properties of the PVC are also analyzed. Hydrophobicity of nano-composites is evaluated by measuring contact angle and recording hydrophobicity class using Swedish transmission research institute (STRI) classification method. Hydrophobic behavior decreases with the increase in filler content; contact angle increases up to 86°, and STRI class of HC3 for PZ4 is observed. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) are employed to evaluate the thermal properties of the samples. Also, continuous decrease of optical band gap energy from 4.04 eV for PZ0 to 2.57 eV for PZ6 is observed. In the meantime, an enhancement in the melting temperature, Tm, is observed from 172 to 215 °C. To check the stability of materials against hydrothermal stresses, all the fabricated materials are then subjected to a hydrothermal aging process for 1000 h and their structural stability is analyzed using optical microscopy and FTIR analyses.


Pathogenic changes in group 2 innate lymphoid cells (ILC2s) in a steroid-insensitive asthma model of mice.
A certain population of asthma patients is resistant to steroid therapy, whereas the mechanisms remain unclear. One of characteristic features of steroid-resistant asthma patients is severe airway eosinophilia based on type-2 inflammation. Aims of this study were: 1) to develop a murine model of steroid-resistant asthma, 2) to elucidate that predominant cellular source of a type-2 cytokine, IL-5 was group 2 innate lymphoid cells (ILC2s), 3) to analyze pathogenic alteration of ILC2s in the severe asthma, and 4) to evaluate therapeutic potential of anti-IL-5 monoclonal antibody (mAb) on the steroid-resistant asthma. Ovalbumin (OVA)-sensitized BALB/c mice were intratracheally challenged with OVA at 5 or 500 μg/animal 4 times. Development of airway eosinophilia and remodeling in 5-μg OVA model were significantly suppressed by 1 mg/kg dexamethasone, whereas those in 500-μg OVA model were relatively insensitive to the dose of dexamethasone. ILC2s isolated from the lung of the steroid-insensitive model (500-μg OVA) produced significantly larger amounts of IL-5 in response to IL-33/TSLP than ILC2s from the steroid-sensitive model (5-μg OVA). Interestingly, TSLP receptor expression on ILC2s was up-regulated in the steroid-insensitive model. Treatment with anti-IL-5 mAb in combination with dexamethasone significantly suppressed the airway remodeling of the steroid-insensitive model. In conclusion, multiple intratracheal administration of a high dose of antigen induced steroid-insensitive asthma in sensitized mice. IL-5 was mainly produced from ILC2s, phenotype of which had been pathogenically altered probably through the up-regulation of TSLP receptors. IL-5 blockage could be a useful therapeutic strategy for steroid-resistant asthma.


Respiratory viral infections during the first 28 days after transplantation in pediatric hematopoietic stem cell transplant recipients.
Respiratory viruses (RVs) are a known cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). In this retrospective study, we focused on the first 28 d after transplantation in pediatric HSCT recipients and showed that a multiplex PCR assay significantly increased RV detection compared with a viral culture method. Among 176 pediatric HSCT recipients, 84 with respiratory symptoms within one yr after HSCT were tested by viral culture or multiplex PCR. Within 28 d after HSCT, nine patients were infected with RVs; the incidence of a first episode of RV infection within 28 d after HSCT was 5.1%. Eight patients recovered without complications. However, one patient died of adenovirus (AdV) pneumonia with pulmonary hemorrhage; the mortality rate of RV infection within 28 d after HSCT was 0.57%. In the nine patients with RV infection, five different types of RV were identified, either alone or with another RV. These were corona virus (CoV), rhinovirus (RhV) and respiratory syncytial virus combined with CoV; AdV combined with RhV; and parainfluenza virus. Viral culture detected only one case of RV infection, while multiplex PCR detected eight, suggesting that screening of respiratory infections using multiplex PCR is better than the conventional culture method.


Dyslipidemia and atherogenic indexes in children with transfusion-dependent thalassemia.
This study endeavored to assess the lipid profile and atherogenic lipid indexes in children with transfusion-dependent thalassemia (TDT) and to compare them with matched healthy children. The study group consisted of a total of 72 TDT patients aged 3 to14 years, while the control group had 83 age- and sex-matched healthy children. The fasting lipid profile and lipid indexes were estimated and the atherogenic index of plasma (AIP), Castelli's risk indexes I and II, atherogenic coefficient were calculated and compared between the two groups. Compared to the control group, the mean LDL, HDL and cholesterol levels were significantly lower among the case group (p-value < 0.001). The mean VLDL and triglycerides were significantly higher in the case group (p-value < 0.001). Lipid indexes, including the atherogenic index of plasma (AIP), Castelli's risk indexes I and II and atherogenic coefficients were significantly higher in TDT children. Dyslipidemia and increased risk of atherosclerosis were found in TDT children, as they had elevated atherogenic lipid indexes. Our study underlines the importance of the routine use of these indexes in TDT children. Future studies should focus on lipid indexes in this high-lipid group of children so that preventive strategies can be planned accordingly.


Prevalence and Angiographic Characteristics of Coronary Artery Ectasia among Patients with Coronary Artery Disease: A Retrospective Analysis between 2014 and 2022.
Coronary artery ectasia (CAE) is defined as segmental dilatation with a diameter of 1.5-fold greater than that of an adjacent normal segment. Whether CAE is a unique clinical finding or results from other clinical entities remains to be determined. The purpose of the study was to investigate the prevalence, and clinical and angiographic characteristics of CAE in patients with coronary artery disease (CAD). Among the 8,845 coronary angiograms reviewed between the years 2014 and 2022, 142 patients had CAE yielding a detection rate of 4.9% among 2,870 CAD angiograms, and 28 patients had isolated CAE showing a detection rate of 0.32% (28/8,845) among total coronary angiography procedures. Overall, the incidence of CAE was 1.92% (170/8,845). The most commonly affected coronary artery by ectasia was the right coronary artery (RCA) (46.28%) among CAE coexisting with CAD cohort. The proportion of obesity, family history of CAD, and the proportion of hyperlipidemia in CAD patients who had ectasia were significantly higher than that in CAD patients who did not have ectasia (P < 0.05). In conclusion, CAE is an uncommon finding in coronary angiography, most commonly affecting the RCA. The obesity, family history of CAD, and the coexistence of hyperlipidemia were independent variables associated with CAE in CAD patients.


Essential norm of some extensions of the generalized composition operators between kth weighted-type spaces.
We calculate the essential norm of some extensions of the generalized composition operators between kth weighted-type spaces on the unit disk in the complex plane, considerably extending some results in the literature.


Temperament and coping: advantages of an individual differences perspective.
This paper examines the advantages that arise from an individual differences approach to children's coping and vulnerabilities. It suggests that the basic motivational and attentional systems involved in temperament constitute relatively primitive coping mechanisms. With development, these primitive coping skills are aided by representational and other cortical functions, allowing the coping process to begin before a stressful event and thereby increasing the child's capacity to plan an effective coping option and to enhance self-control. Such an emphasis on motivational and attentional differences allows us to take advantage of children's diverse personalities as "experiments of nature" and to better understand the temperamental patterns that contribute to adaptive and maladaptive outcomes.


An examination of the correlation between nurses' organizational trust and burnout levels.
Decrease in the organizational trust level of nurses, leads to increase turnover rate of nurses, causes an increase in workload, causes a decrease in motivation and quality of patient care. The results caused by the lack of organizational trust is important for both individuals and organizations. To investigate the relationship between nurses' organizational trust and burnout level. This descriptive and relational study is carried out at an university hospital with 155 nurses who were agreed to participate. Data were collected with Identifying Information Form, Organizational Trust Inventory and Maslach Burnout Inventory. Data were analyzed with numbers, percentage, mean standard deviation, spearman correlation analysis and multiple linear regression. A negative, very weak and statistically significant relationship was found between emotional exhaustion level and trust in employer level (r = 0.304, p < 0.01) and trust in institution level (r = 0.335, p < 0.01); a negative, very weak and statistically significant relationship was found between emotional exhaustion level and trust in colleagues level (r = 0.240, p < 0.01); between depersonalization level and trust in employer level (r = 0.315, p < 0.01); between depersonalization level and trust in colleagues level (r = 0.282, p < 0.01); between reduced personal accomplishment level and trust in employer level (r = 0.238, p < 0.01). It was concluded that there was a statistically significant relationship between the nurses' organizational trust level and burnout level. In addition, organizational trust was a significant predictor of emotional exhaustion, depersonalization and reduced personal accomplishment level.


Neonatal electroencephalography shows low sensitivity to anesthesia.
This study examined EEG under clinical anesthesia in neonates and infants, to clarify how growth affects EEG during anesthesia. Subjects comprised 62 neonates and infants. Patients were divided into four groups according to age: Group 1 (neonates), <1 month; Group 2, 1-2 months; Group 3, 3-5 months; and Group 4, 6 months to 2 years. Anesthesia was maintained with sevoflurane and fentanyl and/or caudal block. At four points of sevoflurane concentration (0.5%, 1%, 1.5%, and 2%), 90% spectral edge frequency (SEF90), burst suppression ratio (BSR), relative beta ratio (RBR) and approximate entropy (ApEn) were analyzed. In Group 4, SEF90, BSR, RBR and ApEn changes were dependent on the concentration of anesthesia, along with changes in sevoflurane concentration from 0.5% to 2% (from 14.3 (2.7) [mean (SD)] Hz to 8.2 (3.8) Hz, from 0.0 to 0.32 (0.36), from -1.58 (0.14) to -1.10 (0.15), and from 0.56 (0.25) to 0.24 (0.25) respectively; p<0.05 each). Conversely, these processed EEG parameters in Group 1 showed little anesthesia-dependent change under sevoflurane concentrations between 0.5% and 2% (SEF90: 7.3 (1.2) Hz vs. 7.7 (2.1) Hz; BSR: 0.51 (0.20) vs. 0.62 (0.29); RBR: -1.00 (0.17) vs. -1.03 (0.27); ApEn: 0.32 (0.18) vs. 0.25 (0.14), respectively). The unique EEG features of neonates during anesthesia rapidly change to the usual anesthesia-dependent patterns seen in older children, with a boundary of 3-5 months old. In infants younger than 6 months old, neural network regulation reflected in EEG by anesthesia is weak.


Acellular bovine pericardium as a biological dressing for treatment of cutaneous wounds of the distal limb in donkeys (Equus Asinus).
This research was performed to determine the impact of repeated topical dressing with acellular bovine pericardium (ABP) on healing distal limb wounds in donkeys. Twelve male clinically healthy donkeys were subjected to general anesthesia, and full-thickness wounds of six cm2 (2 × 3 cm) were created on the middle dorsolateral surface of the metacarpi. Two defects were made on each donkey's forelimbs; the right limb was considered a control wound, and the left one was considered a treated wound. Moreover, the control wounds were irrigated with saline every three days postoperatively and bandaged with a standard dressing. The treated wounds were covered with ABP dressings. The ABP dressing was reapplied thrice at 7-, 14- and 21-days post-wound induction. In addition, the wound healing process was monitored clinically, histopathologically, and immunohistochemically of tissue as growth factor-β1, epidermal growth factor receptor, and vascular endothelial growth factor. Besides, the gene expression profile of angiogenic and myofibroblastic genes was applied as vascular endothelial growth factor-A, collagen type 3α1, fibroblast growth factor 7, and the transforming growth factor-β1.The results revealed that the wounds treated with ABP healed more quickly than the control wounds. Additionally, the mean days required for healing were significantly shorter in the ABP-treated wounds (p < 0.05; 69.5 ± 1.6) compared to control wounds (86.3 ± 3). Furthermore, immunohistochemical and gene expression analyses were significantly improved in ABP wounds than in control wounds. In conclusion, ABP is considered a natural biomaterial and promotes the healing of distal limb wounds in donkeys if applied weekly during the first three-week post-wound induction.


The role of miRNA-26a-5p and target gene socs1a in flutolanil induced hepatotoxicity of zebrafish at environmental relevant levels.
Flutolanil has been detected worldwide in aquatic environment and fish, which has become an undeniable stressor on ecosystem and human health. Flutolanil has been reported to be toxic to aquatic organisms. However, the pathophysiological and molecular mechanism behind the detrimental effects remains obscure. Here we reported hepatotoxicity induced by flutolanil in HepG2 cells and zebrafish, as revealed by toxicokinetic, HE staining, miRNAs-mRNAs sequencing, molecular dynamic simulations and dual luciferase reporter assays. Collectively, our results indicated that flutolanil could be absorbed by and accumulated in the liver of zebrafish, causing hepatic vacuolar degeneration, steatosis and nuclear condensation and abnormal liver function, where its exposure at environmental levels disrupted the expressions of miRNA-26a-5p and its target gene socs1a by mediating JAK-STAT signaling pathway, which was partially responsible for hepatotoxicity, correlated with oxidative stress, cell apoptosis, inflammation, cell cycle disorder and mitochondrial dysfunction. These findings suggest that miRNA-26a-5p/socs1a can serve as potential biomarkers of hepatotoxicity in zebrafish following exposure to flutolanil. This uncovered route will provide a new tool for the risk assessment of flutolanil and a guide to proper use of flutolanil and environmental remedy, and open up a new horizon for liver disease assessment.


Methotrexate inhibits proliferation and regulation of the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by cultured human umbilical vein endothelial cells.
The mechanism by which a low dose of methotrexate (MTX) works to treat psoriasis is not clear. The overexpression of cell adhesion molecules on dermal vessels is important in the pathogenesis of psoriasis and is probably induced by upregulation of tumour necrosis factor (TNF)-alpha. To determine the effects of MTX at concentrations comparable with in vivo levels after the administration of low-dose MTX to human umbilical vein endothelial cells (HUVEC) on the growth and expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Cell proliferation assay, immunostaining, immunoblotting, cell enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) were performed to examine the effects of MTX on HUVEC. MTX inhibited the proliferation of HUVEC at 10-7 mol L-1 and 10-6 mol L-1 without showing cytotoxic effects. It also inhibited TNF-alpha-induced ICAM-1 and VCAM-1 expression by HUVEC at 10-6 mol L-1. The inhibitory effect of MTX was more pronounced on ICAM-1 expression than on VCAM-1 expression. RT-PCR analysis revealed that TNF-alpha-induced ICAM-1 gene expression was strongly downregulated by MTX. Low-dose MTX may act on psoriasis by suppressing the TNF-alpha-induced expression of ICAM-1 and VCAM-1 by vascular endothelial cells. Inhibition of neovascularization may be another mechanism of action of MTX.


The effect of aging on epidermal mass in Balb/c female mice.
Epidermal mass of the skin of Balb/c female mice of 2, 6, 12, and 20 months of age was determined by measuring epidermal wet weight, RNA, DNA, and protein per unit area (100 cm2) of skin. Epidermal wet weight is significantly decreased in 20-month-old mice compared to 2-month-old mice. This represents a real decrease in epidermal mass, because associated with the decrease in epidermal wet weight there is a significant decrease in protein and RNA per 100 cm2 of epidermis. DNA per 100 cm2 of epidermis is not significantly reduced, and the total number of epidermal nuclei per mm of interfollicular epidermis is only slightly reduced, the latter due entirely to a decrease in the number of basal cells per mm of interfollicular epidermis. It appears that aging results in a decrease in epidermal mass in Balb/c female mice, and that this decrease is probably primarily due to a decrease in epidermal cell size.


Longitudinal Associations between Ambient Air Pollution and Angiogenic Biomarkers among Pregnant Women in the LIFECODES Study, 2006-2008.
Exposures to ambient air pollution during pregnancy have been linked to adverse pregnancy outcomes such as preeclampsia and fetal growth restriction. Although evidence has shown that women with preeclampsia have higher ratio of soluble fms-like tyrosine kinase 1 to placental growth factor (sFlt-1/PlGF ratio), the potential impact of air pollution on markers of placental growth and function has not been well studied. We aimed to examine longitudinal associations between ambient air pollution exposure and angiogenic factors among pregnant women in LIFECODES, a prospective birth cohort and biorepository in Massachusetts in the United States. PlGF and sFlt-1 were measured among pregnant women using plasma samples collected around 10, 18, 26, and 35 wk' gestation. Women's exposures to ozone (O3), fine particulate matter with aerodynamic diameter ≤2.5μm (PM2.5), and nitrogen dioxide (NO2) within 1, 2, 4, and 8 wk prior to each plasma sample collection were estimated based on geocoded residential addresses, and mixed effect linear regression models were fitted to assess their associations with sFlt-1/PlGF ratio, sFlt-1 (ng/mL), and PlGF (pg/mL). Percent changes in outcomes associated with each interquartile range increase in exposures were reported, along with their 95% confidence intervals. A total of 1,066 pregnant women were included. In the multipollutant models, significant associations were observed for increased sFlt-1/PlGF ratio (PM2.5 3-8 wk' gestation, NO2: 35-39 wk' gestation), elevated sFlt-1 (O3: 26-34 wk' gestation, PM2.5: 3-8 wk' gestation), decreased sFlt-1 (NO2: 4-8 wk' gestation), and decreased PlGF (NO2: 34-39 wk' gestation) after adjusting for sociodemographic status, smoking, drinking, body mass index, parity, history of chronic hypertension, and conception time. Exposures to PM2.5 during early pregnancy and exposures to O3 and NO2 during late pregnancy were associated with increased sFlt-1/PlGF ratio, elevated sFlt-1 and with decreased PlGF, which may be a potential mechanism underlying ambient air pollution's impacts on adverse pregnancy and birth outcomes. https://doi.org/10.1289/EHP11909.


Toilet training in individuals with Angelman syndrome: a case series.
To assess if adapted versions of the response restriction toilet training protocol, based on the behavioral phenotype of Angelman syndrome (AS), were successful in fostering urinary continence in seven individuals with AS. Data were collected in AB-designs during baseline, training, generalization and follow-up. The response restriction protocol was adapted: individuals were trained in their natural environment, were prompted to void and along with improving continence, the interval between voids was prolonged and time-on-toilet decreased. During generalization five individuals had less than two accidents and one to six correct voids per day; during baseline more accidents and/or less correct voids occurred. In two participants correct voids increased, but several accidents still occurred. Three participants maintained positive results after 3-18 months. Despite their intellectual and behavioral challenges, urinary continence can be acquired in AS. Several indications of voiding dysfunctions were found; further research is indicated.


Executive function relates to surface area of frontal and temporal cortex in very-low-birth-weight late teenagers.
Being born with very low birth weight (VLBW; birth weight (BW) ≤1500 g) is associated with increased risk of maldevelopment of the immature brain which may affect neurological functioning. Deficits in attention and executive function problems have been reported in VLBW survivors compared with healthy subjects. The aim of this study was to evaluate attention and executive functions and to relate the clinical test results to cortical morphometry findings in VLBW young adults compared with term-born controls. Prospective follow-up study of three year cohorts of VLBW and control children from birth to adulthood. A comprehensive neuropsychological test battery was administered to 55 VLBW subjects born preterm (mean BW: 1217 g) and 81 term-born controls (mean BW: 3707 g) at age 19-20. Cerebral MRI was successfully obtained in 46 VLBW subjects and 61 controls. The FreeSurfer software package was applied for the cortical analyses based on T1-weighted MRI images. The VLBW group obtained inferior scores on 15 of the 29 neuropsychological measures assessing attention and executive function and on both the attention and executive function domain scores. We found positive correlations between the executive function domain score and cortical surface area, especially in the antero-medial frontal and the temporal lobes of the brain in the VLBW group. Young adults born with VLBW show deficits in attention and executive function compared with controls. The executive problems were related to smaller cortical surface area in brain regions known to be involved in higher order cognitive functioning.


Assessment of Image Quality of Repeated Limited Transthoracic Echocardiography After Cardiac Surgery.
The use of limited transthoracic echocardiography (TTE) has been restricted in patients after cardiac surgery due to reported poor image quality. The authors hypothesized that the hemodynamic state could be evaluated in a high proportion of patients at repeated intervals after cardiac surgery. Prospective observational study. Tertiary university hospital. The study comprised 51 patients aged 18 years or older presenting for cardiac surgery. Patients underwent TTE before surgery and at 3 time points after cardiac surgery. Images were assessed offline using an image quality scoring system by 2 expert observers. Hemodynamic state was assessed using the iHeartScan protocol, and the primary endpoint was the proportion of limited TTE studies in which the hemodynamic state was interpretable at each of the 3 postoperative time points. Hemodynamic state interpretability varied over time and was highest before surgery (90%) and lowest on the first postoperative day (49%) (p<0.01). This variation in interpretability over time was reflected in all 3 transthoracic windows, ranging from 43% to 80% before surgery and from 2% to 35% on the first postoperative day (p<0.01). Image quality scores were highest with the apical window, ranging from 53% to 77% across time points, and lowest with the subcostal window, ranging from 4% to 70% across time points (p< 0.01). Hemodynamic state can be determined with TTE in a high proportion of cardiac surgery patients after extubation and removal of surgical drains.


Thioxanthenes, chlorprothixene and flupentixol inhibit proton currents in BV2 microglial cells.
The thioxanthene antipsychotic drugs chlorprothixene and flupentixol have anti-inflammatory and antioxidant properties. The reactive oxygen species produced by NADPH oxidase during microglia-mediated inflammatory responses cause neuronal damage, thereby contributing to various neurodegenerative diseases. Voltage-gated proton channels sustain the NADPH oxidase activity, and inhibition of the channels' activity reduces the production of reactive oxygen species. Herein, the effects of chlorprothixene and flupentixol on proton currents were investigated in BV2 microglial cells using the whole-cell patch-clamp method. Both drugs inhibited the proton currents in a concentration-dependent manner (IC50=1.7μM and 6.6μM, respectively). Chlorprothixene at 3μM slightly shifted the activation voltage toward depolarization. Both the activation and the deactivation kinetics of the proton currents were slowed by chlorprothixene 1.2- and 3.5-fold, respectively. Thus, the inhibition of proton currents may be partly responsible for the antioxidant effects of thioxanthene antipsychotic drugs.


[Aortic origin of the left pulmonary artery in an infant with Fallot's tetralogy].
We report the case of a male neonate who had a prenatal diagnosis of Fallot's tetralogy. He presented with respiratory distress during the second week of life. Chest x-ray showed an enlarged right ventricle and pulmonary edema. Echocardiography demonstrated characteristic features of Fallot's tetralogy. However, cardiac catheterization disclosed that, in this case of Fallot's tetralogy, the left pulmonary artery had an anomalous origin in the ascending aorta. At 23 days of age, the patient underwent total surgical correction of the defects, during which a direct anastomosis was employed without conduit placement. 10 days later, he was discharged. We present the results of a literature review of the epidemiological, physiopathological, clinical, diagnostic, and surgical characteristics of this rare condition.


Clinical potential of aldose reductase inhibitors in diabetic neuropathy.
A number of aldose reductase inhibitors (ARIs) have been developed over the past few decades with the expectation of therapeutic effects for diabetic complications. Neuropathy is the complication that has been most intensively studied as a potential target for ARIs. Most ARIs have shown satisfactory effects in animal models. However, the clinical potential of ARIs in diabetic patients has been controversial due to the lack of conclusive evidence. The safety of this category of drugs is also uncertain. This article summarizes the results of clinical trials of ARIs for patients with diabetic neuropathy that have been performed to date. The efficacy and toxicity of each ARI will be briefly assessed by the clinical data. The theoretical background along with major issues in the evaluation of drug efficacy will also be discussed. Overall the observed efficacy varied among the compounds. A few ARIs showed favorable effects in multiple endpoints in the majority of trials, while the results from many ARIs seemed ambivalent. One drug barely exhibited positive effects on any endpoint. This discrepancy may be attributable at least in part to the different degree of inhibition of the polyol pathway in nerve tissues, which is determined not only by the pharmacokinetic properties of the drug but also by its penetration into nerve tissues. In addition to the uncertain potential of each ARI, the issues of design and analytical methods used for clinical trials may underlie the ambivalent outcomes. The power of analysis and the duration of trials were apparently inadequate in a large number of the studies. Various indices selected as endpoints are not necessarily sensitive or reproducible. Studies of longer duration, large-scale trials, better methods to assess neuropathy, and the selection of patients with a homogenous background would provide more conclusive evidence. The risk of serious adverse reactions, for example, hypersensitivity reactions and hepatic damage, has led to some ARIs being withdrawn from the market or from further development. These adverse effects, however, do not appear to result from the inhibition of aldose reductase activity per se but from specific reactions to each compound. In conclusion, sufficient inhibition of the nerve aldose reductase activity seems likely to prevent or ameliorate diabetic neuropathy, and further development of more potent and safe ARIs is necessary before extensive clinical application.


Cardiovascular safety assessments in the cynomolgus monkey: Unmasking potential background arrhythmias in general toxicity studies.
We describe experience with an unexpectedly high background incidence of atrioventricular block (AVB) observed in Mauritian cynomolgus monkeys (MCM) during preclinical safety assessment for bitopertin, a glycine-transporter-1 inhibitor. Preclinical ECGs were reviewed to assess potential effects on cardiac conductivity, specifically AVB. Bitopertin administration in Chinese/Vietnamese monkeys (CVM; n=46) or MCM (n=64, from all relevant studies) revealed dose-dependent hypoactivity with a lack of expected increases in heart rate in response to chair-restraint during ECG recordings. Instances of 2° AVB were detected post-dose in two repeat-dose studies in MCM. AVB was generally restricted to animals showing a lower than expected increase in heart rate during restraint compared to placebo conditions (111-161 to 220-250bpm). A subsequent study in MCM prescreened for AVB found pre-existing 2° AVB in 15.4% of animals. After exclusion of these animals, no incidences of AVB were identified over 36weeks of bitopertin treatment. No evidence of AVB was observed in CVM in a 14-day study with continuous ECG recordings or in any clinical studies to date. Bitopertin-treatment was not associated with a direct effect on AV conduction in AVB naive MCM. Pre-test detection of AVB in MCM was likely due to the unmasking of pre-existing AVB through a slowed heart rate. The background incidence of AVB in the current MCM cohort was much higher than has been previously reported. These data suggest that ECG prescreening of unrestrained, nonstressed animals is recommended for the accurate assessment of possible treatment-related increases in AVB, especially in MCM.


Epidural clonidine treatment for refractory reflex sympathetic dystrophy.
Intraspinally administered alpha 2-adrenergic agonists may relieve pain in sympathetically maintained pain (SMP) syndromes, such as reflex sympathetically dystrophy (RSD), by spinal, peripheral, and central nervous system actions. This study examined analgesic efficacy and side effects of epidurally administered clonidine in patients with severe, refractory RSD. Twenty-six patients with severe chronic pain consistent with RSD were studied in a randomized, blinded, placebo-controlled design. Cervical or lumbar epidural catheters were inserted for patients with upper or lower extremity RSD, respectively, and patients received, in random order on three consecutive days, epidural injection of clonidine, 300 or 700 micrograms, or placebo. Pain (by visual analog score (VAS) and McGill Pain Questionnaire), sedation, blood pressure, and heart rate were monitored at specified intervals for 6 h after injection. Patients who responded to clonidine, but not placebo, then entered a trial of open-label, continuous epidural infusion of clonidine (10-50 micrograms/h). Clonidine, but not placebo, caused pain relief, sedation, and decreased blood pressure and heart rate after bolus epidural injection. The smaller clonidine dose (300 micrograms), produced pain relief and decreases in blood pressure and heart rate similar to those of the 700 micrograms dose, but with less sedation. Epidural clonidine was infused for a mean of 43 days in 19 patients at a mean rate of 32 micrograms/h for sustained analgesia. Transdermal clonidine has been demonstrated to produce analgesia in the area surrounding its application site in patients with SMP. The current study indicates that extensive analgesia may be obtained by epidural administration. Sedation and hypotension may limit bolus epidural clonidine administration for RSD. The role for chronic epidural infusion of clonidine has not yet been established.