Degradation and metabolite formation of 17ß-estradiol-3-glucuronide and 17ß-estradiol-3-sulphate in river water and sediment.
Laboratory degradation tests with two model estrogen conjugates, 17ß-estradiol-3-glucuronide (E2-3G) and 17ß-estradiol-3-sulphate (E2-3S), using river water and sediment as inoculum under aerobic conditions were investigated. Throughout the 14-day incubation, degradation of E2-3G in river water, at environmentally-relevant level (25 ng/L), obeyed first-order kinetics with the formation of 17-ß estradiol and estrone; in contrast, E2-3S was slowly converted to estrone-3-sulphate stoichiometrically. Degradation of the two conjugates across the spiking concentrations (0.01-1 μg/g) was much faster in sediment than in river water where 25 ng/L of conjugate standards were spiked, possibly due to relatively high population densities of microorganisms in sediment. De-conjugation of the thio-ester bond at C-3 position and oxidation at C-17 position were the predominant degradation mechanisms for E2-3G and E2-3S, respectively, with negligible presence of metabolites estrone-3-glucuronide for E2-3G and 17ß-estradiol for E2-3S. In addition, delta-9(11)-dehydroestrone and 6-ketoestrone were determined as new metabolites of the two conjugates. Also, a lactone compound, hydroxylated estrone and a few sulfate conjugates were tentatively identified. With the observation of new metabolites, biodegradation pathways of E2-3G and E2-3S were proposed. The formation of new metabolites may pose unknown risks to aquatic biota.


Role of mitochondrial DNA damage in the development of diabetic retinopathy, and the metabolic memory phenomenon associated with its progression.
Diabetic retinopathy does not halt after hyperglycemia is terminated; the retina continues to experience increased oxidative stress, suggesting a memory phenomenon. Mitochondrial DNA (mtDNA) is highly sensitive to oxidative damage. The goal is to investigate the role of mtDNA damage in the development of diabetic retinopathy, and in the metabolic memory. mtDNA damage and its functional consequences on electron transport chain (ETC) were analyzed in the retina from streptozotocin-diabetic rats maintained in poor control (PC, glycated hemoglobin >11%) for 12 months or PC for 6 months followed by good control (GC, GHb < 6.5%) for 6 months. Diabetes damaged retinal mtDNA and elevated DNA repair enzymes (glycosylase). ETC proteins that were encoded by the mitochondrial genome and the glycosylases were compromised in the mitochondria. Re-institution of GC after 6 months of PC failed to protect mtDNA damage, and ETC proteins remained subnormal. Thus, mtDNA continues to be damaged even after PC is terminated. Although the retina tries to overcome mtDNA damage by inducing glycosylase, they remain deficient in the mitochondria with a compromised ETC system. The process is further exacerbated by subsequent increased mtDNA damage providing no relief to the retina from a continuous cycle of damage, and termination of hyperglycemia fails to arrest the progression of retinopathy.


Structural characterization of mouse neutrophil serine proteases and identification of their substrate specificities: relevance to mouse models of human inflammatory diseases.
It is widely accepted that neutrophil serine proteases (NSPs) play a critical role in neutrophil-associated lung inflammatory and tissue-destructive diseases. To investigate NSP pathogenic role(s), various mouse experimental models have been developed that mimic acutely or chronically injured human lungs. We and others are using mouse exposure to cigarette smoke as a model for chronic obstructive pulmonary disease with or without exacerbation. However, the relative contribution of NSPs to lung disease processes as well as their underlying mechanisms remains still poorly understood. And the lack of purified mouse NSPs and their specific substrates have hampered advances in these studies. In this work, we compared mouse and human NSPs and generated three-dimensional models of murine NSPs based on three-dimensional structures of their human homologs. Analyses of these models provided compelling evidence that peptide substrate specificities of human and mouse NSPs are different despite their conserved cleft and close structural resemblance. These studies allowed us to synthesize for the first time novel sensitive fluorescence resonance energy transfer substrates for individual mouse NSPs. Our findings and the newly identified substrates should better our understanding about the role of NSPs in the pathogenesis of cigarette-associated chronic obstructive pulmonary disease as well as other neutrophils-associated inflammatory diseases.


The effect of ketoconazole on sebum secretion in patients suffering from acne and seborrhoea.
Ketoconazole, an imidazolic antimycotic derivative, has proved to have an antiandrogenous effect, which may be observed to inhibit the adrenal and gonadal steroid synthesis. The authors wished to verify this effect of the drug in men and women suffering from acne and seborrhoea, conditions believed to indicate a heightened androgenous effect in the sebaceous gland. They aimed to do this by studying the cutaneous sebum, which is considered a reliable indirect indicator of androgenous activity. They found a statistically significant decrease in the rate of sebum production in all patients administered with a single daily oral dose of ketoconazole (200 mg). Moreover no untoward side-effects were reported. The anti-androgenous property of ketoconazole would therefore suggest that the drug could be proposed as a useful alternative in the treatment of acne and seborrhoea.


[Different aspects of the cognitive activities of patients with schizophrenia. IV. Imbalance between assertions and negations].
Not being able to equilibrate affirmations and negations, the schizophrenic patient accedes only exceptionally to the majoring equilibrations of the second and third levels. In the logico-mathematic field, he does not approach the constructive synthetizing generalisations of reasoning. Lacking reflective abstraction, he cannot balance his logico-mathematic reasoning and differentiate what is structurally possible from what is materially possible, thus explaining his inaccessibility to perceive logic necessities, contrasting with the certainties of his delirium. In the logico-experimental domain, he reaches only rarely clause reasoning generalisation, and relapses regularly to the level of inappropriate generalisations of the extended inductive type. It is useless to try to find the "primum movens" of his difficulties, either in his imbalance assimilation/accommodation, or in his impossibility to see his contradictions, or even in his incapacity to equilibrate affirmations and negations. The majoring equilibrations, of which he is unable, are the functional expression of structures which do not follow the linear causality of Laplace's determinism but the circular causality characteristic of teleonomic processes. After a month of neuroleptic treatment, the decompensated schizophrenic's balance between assimilation and accommodation is partially restored.


CD137 enhancement of HPV positive head and neck squamous cell carcinoma tumor clearance.
Standard-of-care cisplatin and radiation therapy (CRT) provides significant tumor control of human papillomavirus (HPV)-mediated head and neck squamous cell carcinomas (HNSCCs); this effectiveness depends on CRT-mediated activation of the patient's own immune system. However, despite good survival, patients suffer significant morbidity necessitating on-going studies to define novel therapies that alleviate this burden. Given the role of the immune system in tumor clearance, immune modulation may further potentiate the CRT-activated response while potentially decreasing morbidity. CD137, an inducible cell surface receptor found on activated T cells, is involved in differentiation and survival signaling in T cells upon binding of its natural partner (CD137L). A number of studies have shown the effectiveness of targeting this immune-stimulatory pathway in regards to tumor clearance. Here we test its role in HPV+ HNSCC tumor clearance using a previously characterized mouse model. We show that amplification of this stimulatory pathway synergizes with CRT for enhanced tumor clearance. Interestingly, tumor clearance is further potentiated by local tumor cell expression of CD137L.


[Autosomal recessive cerebellar ataxias with oculomotor apraxia].
Autosomal recessive cerebellar ataxias (ARCA) comprise a phenotypically and genetically heterogeneous group of diseases. Recently, a subgroup of ARCA associated with oculomotor apraxia has been delineated. The ataxias with oculomotor apraxia (AOA) include four distinct genetic entities at least: ataxia-telangiectasia, ataxia telangiectasia-like disorder, ataxia with oculomotor apraxia type 1 (AOA1) and type 2 (AOA2). The responsible genes, ATM, MRE11, APTX and SETX respectively, are implicated in DNA-break repair mechanisms. We describe the phenotypic and genetic characteristics of these ataxias, based on a review of the literature and a personal study of AOA1 and AOA2 patients.


Effect of Bacteria Content in Wheat Flour on Storage Stability of Fresh Wet Noodles.
The effect of bacteria content in wheat flour on shelf life and storage stability of fresh wet noodles (FWNs) was evaluated in this study. Nine kinds of wheat flour with different bacterial contents were selected to make FWNs. With the increase in total plate count (TPC) from 120 CFU/g to 5500 CFU/g in flour, the shelf life of FWNs decreased from 23 d to 9 d at 4 °C. During storage, the acidity increased, which was significantly correlated with the change of TPC (p < 0.05), and the pH value and L* value of FWNs decreased significantly (p < 0.05). Changes in viscosity characteristics of starch components were also detected, the higher the TPC in flour, the more obvious the viscosity decreased. Moreover, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed that with the deterioration of FWNs, some low molecular weight protein subunits increased; texture analysis showed that the hardness of noodles increased firstly and then decreased, the adhesiveness increased and the springiness decreased during storage. In summary, choosing flour with low TPC to prepare FWNs can extend the shelf life and slow down the quality deterioration of FWNs during storage at 4 °C.


Quantitative cerebral blood flow measurements in the rat using a beta-probe and H2 15O.
Beta-probes are a relatively new tool for tracer kinetic studies in animals. They are highly suited to evaluate new positron emission tomography tracers or measure physiologic parameters at rest and after some kind of stimulation or intervention. In many of these experiments, the knowledge of CBF is highly important. Thus, the purpose of this study was to evaluate the method of CBF measurements using a beta-probe and H2 15O. CBF was measured in the barrel cortex of eight rats at baseline and after acetazolamide challenge. Trigeminal nerve stimulation was additionally performed in five animals. In each category, three injections of 250 to 300 MBq H2 15O were performed at 10-minute intervals. Data were analyzed using a standard one-tissue compartment model (K1 = CBF, k2 = CBF/p, where p is the partition coefficient). Values for K1 were 0.35 +/- 0.09, 0.58 +/- 0.16, and 0.49 +/- 0.03 mL x min(-1) x mL(-1) at rest, after acetazolamide challenge, and during trigeminal nerve stimulation, respectively. The corresponding values for k2 were 0.55 +/- 0.12, 0.94 +/- 0.16, and 0.85 +/- 0.12 min(-7), and for p were 0.64 +/- 0.05, 0.61 +/- 0.07, and 0.59 +/- 0.06. The standard deviation of the difference between two successive experiments, a measure for the reproducibility of the method, was 10.1%, 13.0%, and 5.7% for K1, k2, and p, respectively. In summary, beta-probes in conjunction with H2 15O allow the reproducible quantitative measurement of CBF, although some systematic underestimation seems to occur, probably because of partial volume effects.


Visible-Light Photoinitiation of (Meth)acrylate Polymerization with Autonomous Post-conversion.
Conversion plateaus rapidly in radical photopolymerizations (RPPs) following discontinuation of irradiation due to rapid termination of reactive radicals, which restricts the wider use of RPPs in applications that involve nonuniform light access including those with attenuated light transmission or irregular surfaces. Based on our recent report of a radical dark-curing photoinitiator (DCPI) that continues polymerization beyond the cessation of irradiation by enabling latent redox initiation with photo-released amine in the presence of a suitable oxidant, we developed a new DCPI with an absorption spectrum that extends well into the visible range. Our design process involved a series of computational investigations of candidate molecules, including a systematic study of substituents and their position-dependent effects on absorption characteristics, electronic transitions, and the photochemical mechanism and its associated energetics. Our quantum chemical computations identified the target compound 5,7-dimethoxy-6-bromo-3-aroylcoumarin-DMPT/BPh4 and predicted that it would facilitate the dark-curing mechanism by concurrent photo-radical generation and photo-induced release of an efficient redox reductant under visible irradiation. This reductant-tethered chromophore was then synthesized and optically characterized with UV-vis spectroscopy that revealed its strong visible-light absorption with a molar absorptivity of 5710 M-1 cm-1 at 405 nm and 50 M-1 cm-1 at 455 nm. We then demonstrated extensive dark-curing of >35% additional conversion over 25 min following brief activation of the shelf-stable one-part system by irradiation with a 455 nm LED that was ceased at 20% conversion. In contrast, shuttering irradiation of the control formulation at that same point resulted in immediate cessation of conversion, which plateaued at 20%. We determined a remarkable initiator efficiency of 2.82 that results from the additional redox-generated radicals with a 77% photo-reductant generation quantum yield. The combination of superior photo- and dark-curing efficiencies of this new visible DCPI is expected to open new application opportunities in RPP, especially those involving resins that are highly light attenuating, surfaces that possess irregular features that produce uneven irradiance, and production lines where continued dark-curing downstream of the light activation step enhances line efficiencies.


Ductal carcinoma in situ of the breast -- among factors predicting for recurrence, distance from the nipple is important.
To assess local and systemic recurrence rates and factors predicting for recurrence in patients treated for ductal carcinoma of the breast (DCIS). Patients with DCIS treated between January 1986 and January 1997 were identified. All pathology specimens were reviewed. DCIS type, lesion size, nuclear grade and margin clearance were assessed. Mammograms were reviewed and mammographic patterns, size, type of lesion and distance from the nipple were measured. Treatments and subsequent outcomes were established by case note review. Factors predicting for recurrence were analysed by both univariant and multivariant analysis. Of the 220 patients, 153 (70%) had breast-conserving surgery. Sixty-seven (30%) had a mastectomy. Ninety-seven patients had adjuvant therapy of which 22 had radiotherapy alone, 54 had tamoxifen alone and 21 had radiotherapy and tamoxifen. Following mastectomy, two patients developed axillary recurrences. Following breast-conserving surgery 20 (13%) patients developed local recurrences, of which one developed systemic disease and died from breast cancer. Mammographic nipple to lesion distance of <40 mm and high/intermediate nuclear grade were the only factors found to increase the likelihood of recurrence.


Female sterilisation: National Women's Hospital 1988-9.
To determine the failure rate of all female sterilisation procedures performed at National Women's Hospital in order to identify ways of improving the service. A review was made of all sterilisation procedures performed at National Women's Hospital in 1988 and 1989. All patient notes and theatre records were examined. A consumer questionnaire was mailed to all patients monthly for 3 months. If there was no response efforts were made to contact these women via their last known general practitioner. Epsom Day Hospital where 95% of all terminations of pregnancy in Auckland are performed also examined their records. 1094 procedures were performed at National Women's Hospital in Auckland during 1988 and 1989. Failures were classified into two groups: those pregnant at the time of surgical procedure (administrative failures) and those pregnant after the procedure (surgical failure). There were 15 surgical failures (1.4%). Laparoscopy using Filshie clips was the most common method used and had a 1.2% surgical failure rate. Registrars had a 1.3% failure rate, consultants 1.9% and when both a consultant and registrar performed the procedure a failure rate of 0.7% was recorded. Eighty-six percent (6/7) of women who had a subsequent laparotomy after a failed sterilisation were found to have surgical misapplication of the occlusive device. There were 7 (0.6%) women who were pregnant at the time of the procedure. There were no patient or procedure-related factors which were associated with failures. Sterilisation is associated with a significant failure rate. Contraception counselling at the time of booking for the procedure needs to be improved. Preoperative pregnancy testing should be introduced to avoid sterilisation procedures in early pregnancy. Surgical misapplication of devices was a common cause of failure, not recanalisation as found elsewhere. From this review it would appear that the involvement of two surgeons lowers the failure rate.


Granular cell tumour.
A 5½-years-old boy presented with multiple skin coloured subcutaneous nodules on scrotum and penoscrotal regions. Oldest lesion started 8 months back and new lesion was one month old. Biopsy report revealed the tumour to be granular cell tumour.


Physical activity patterns defined by continuous heart rate monitoring.
To investigate the physical activity patterns of British primary schoolchildren (mean (SD) 10.7 (0.3) years) the minute by minute heart rates of 67 boys and 65 girls were monitored continuously for three 12 hour periods during normal schooldays. In addition 39 children had their heart rates monitored during a 12 hour period on a Saturday. Few children experienced the volume (frequency, intensity, and duration) of physical activity associated with an improvement in cardiopulmonary fitness. Shorter (five minute) periods of the required intensity were, however, quite common. No difference between moderate amounts of activity was detected between boys and girls, but the boys had more five minute sessions of intense activity than the girls. These findings suggest that more research into the effects of short periods of intense physical activity on the cardiopulmonary systems of young children is required and that the determinants of habitual physical activity require further investigation especially in the context of sex differences at such an early age.


Predictors of life satisfaction among Asian American adolescents- analysis of add health data.
Life satisfaction correlates with adolescent risk taking behavior and their outcomes in adulthood. Despite the fast rise in numbers of Asian adolescents in the U.S., the predictors of their life satisfaction are not well understood. This study examined the relationship between several demographic and contextual factors and global life satisfaction among this population. Data were derived from the National Longitudinal Study of Adolescent Health (Add Health), a nationally representative probability sample of US adolescents. Bivariate and multivariable logistic regression was conducted to evaluate hypothesized predictors of global life satisfaction of Asian American adolescents. All analyses were conducted using STATA version 11. After exclusion of cases with missing values, 1021 Asian American adolescents were studied. Self- rated health, self-esteem, perceived neighborhood quality, parental support and peer support were significantly and positively related to better global life satisfaction. However, after controlling for other factors, only self-esteem (adjusted odds ratio [aOR]: 4.76; 95% confidence interval [CI]: 2.86-8.33) and perceived peer support (aOR: 2.76; 95% CI: 1.33-5.76) significantly predicted higher life satisfaction. Peer support and adolescents' self-concept are strongly correlated with Asian American adolescents' subjective well-being. To promote the wellness of this population, culturally sensitive strategies in developing peer relationship and healthy self-concept may be effective. More studies are needed for subgroup comparison of various ethnicities among Asian American adolescents.


Alpha-particle emissivity of the moon: an observed upper limit.
Measurements made by the moon-orbiting spacecraft Explorer 35 during 1967-1968 show that it is unlikely that the alpha-particle emissivity of the moon is greater than 0.064 per square centimeter per second per steradian and exceedingly unlikely that it is greater than 0.128, these values being respectively 0.1 and 0.2 of the provisional estimates made by Kraner et al. in 1966. This result implies that the abundance of uranium-238 in the outer crust (approximately a few meters thick) of the moon is much less than that typical of the earth's lithosphere, though it is consistent with the abundance of uranium-238 in terrestrial basalt or in chondritic meteorites.


13Check_RNA: a tool to evaluate 13C chemical shift assignments of RNA.
Chemical shifts (CS) are an important source of structural information of macromolecules such as RNA. In addition to the scarce availability of CS for RNA, the observed values are prone to errors due to a wrong re-calibration or miss assignments. Different groups have dedicated their efforts to correct CS systematic errors on RNA. Despite this, there are not automated and freely available algorithms for evaluating the referencing of RNA 13 C CS before their deposition to the BMRB or re-reference already deposited CS with systematic errors. Based on an existent method we have implemented an open source python module to correct 13 C CS (from here on 13Cexp) systematic errors of RNAs and then return the results in 3 formats including the nmrstar one. This software is available on GitHub at https://github.com/BIOS-IMASL/13Check_RNA under a MIT license. Supplementary data are available at Bioinformatics online.


Mechanism of YLTZ on glycolipid metabolism based on UPLC/TOF/MS metabolomics.
Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by dysfunction of glycolipid metabolism. YLTZ is used to treat hyperlipidemia, yet its hypolipidemic and hypoglycemic mechanism on T2DM are unknown. Thus, UPLC/TOF/MS was applied in this study to identify the potential bio-markers, and deduce the possible metabolic pathways. According to bio-indexes, the increased blood lipid levels, including TC, TG, LDL and FA, and the decreased HDL, the elevated glucose, reduced insulin level and impaired OGTT were observed in diabetic rat model. While YLTZ can decrease the lipid levels and glucose content, as well as increased insulin standards and improve OGTT. After data from UPLC/TOF/MS processed, 17 metabolites were obtained, including phospholipids (LPCs, PCs and PGP (18:1)), beta-oxidation production (HAA, VAG and CNE) and precursors (THA), bile acid (CA, CDCA and IDCA), hydrolysate of TG (MG (22:4)), glycometabolism (G6P), cholesterol-driven synthetics (ADO) and production of arachidonate acid (THETA). As a result, YLTZ was able to reduce LPCs, PCs, PGP (18:1), HAA, VAG, CNE, CA, ADO and THETA, as well as enhance MG (22:4) and G6P. After analyzing results, several metabolic pathways were deduced, which containing, cholesterol synthesis and elimination, FA beta-oxidation, TG hydrolysis, phospholipids synthesis, glycolysis, gluconeogenesis and inflammation. Consequently, YLTZ performed to prohibit the FA beta-oxidation, synthesis of cholesterol and phospholipids, gluconeogenesis and inflammation level, as well as promote TG hydrolysis, glycolysis and blood circulation. Hence, applying metabonomics in TCM research can uncover its pharmacological edges, elucidating comprehensively that YLTZ has capacity of hypolipidemic, hypoglycemic and promoting blood circulation, matching the effect of removing blood stasis, eliminating phlegm and dampness.


Metabolomics reveals the sex-specific effects of the SORT1 low-density lipoprotein cholesterol locus in healthy young adults.
Metabolite profiles of individuals possessing either the cardiovascular risk or protective variants of the low-density lipoprotein cholesterol (LDL-C) associated 1p13.3 locus of the SORT1 gene (rs646776) were analyzed. Serum metabolites and lipids were assessed using LC-MS-based metabolomics in a healthy young population (n = 138: 95 males, 43 females). Although no significant differences were observed in the combined cohort, divergent sex effects were identified. Females carrying the protective allele showed increased phosphatidylcholines, very long chain fatty acids (>C20), and unsaturated fatty acids. Unsaturated fatty acids are considered to be protective against cardiovascular disease. In contrast, males carrying the protective allele exhibited decreased long-chain fatty acids (≤C20) and sphingomyelins, which is similarly considered to decrease cardiovascular disease risk. No significant changes in clinically assessed lipids such as LDL-C, high-density lipoprotein (HDL-C), total cholesterol, or triglycerides were observed in females, whereas only LDL-C was significantly changed in males. This indicates that, apart from reducing LDL-C, other mechanisms may contribute to the protective effect of the SORT1 locus. Thus, the analysis of metabolic biomarkers might reveal early disease development that may be overlooked by relying on standard clinical parameters.


[Plasma temperature of white-eye hexagonal pattern in dielectric barrier discharge].
By using the water-electrode discharge experimental setup, the white-eye hexagonal pattern is firstly observed and investigated in the dielectric barrier discharge with the mixture of argon and air whose content can be varied whenever necessary, and the study shows that the white-eye cell is an interleaving of three different hexagonal sub-structures: the spot, the ring, and the halo. The white-eye hexagonal pattern has the excellent discharge stability and sustainability during the experiment. Pictures recorded by ordinary camera with long exposure time in the same argon content condition show that the spot, the ring, and the halo of the white-eye hexagonal pattern have different brightness, which may prove that their plasma states are different. And, it is worth noting that there are obvious differences not only on the brightness but also on the color of the white-eye cell in conditions of different argon content, which shows that its plasma state also changed with the variation of the argon content. The white-eye hexagonal pattern is observed at a lower applied voltage so that the temperature of the water electrodes almost keeps unchanged during the whole experiment, which is advantageous for the long term stable measurement. The plasma state will not be affected by the temperature of the electrodes during the continuous discharge. Based on the above phenomena, plasma temperatures of the spot, the ring, and the halo in white-eye hexagonal pattern including molecule vibrational temperature and variations of electron density at different argon content are investigated by means of optical emission spectroscopy (OES). The emission spectra of the N2 second positive band(C3Πu-->B3Πg)are measured, and the molecule vibrational temperature of the spot, the ring, and the halo of the white-eye hexagonal pattern are calculated by the emission intensities. Furthermore, emission spectra of Ar I (2P2-->1S5)is collected and the changes of its width with different argon content are used to estimate the variations of electron density of the spot, the ring, and the halo of the white-eye hexagonal pattern. In the same argon content condition, the molecule vibrational temperatures of halo, ring, and spot in the white-eye hexagonal pattern are in descending order, while the electron densities of halo, ring, and spot are in ascending order. With argon content increasing from 70% to 90%, both the molecule vibrational temperature and the electron density of the spot increase, while both of them of the halo decrease. And the molecule vibrational temperature of the ring keeps constant, while its electron density decreases. The experimental results indicate that the plasma state of the spot, the halo and the ring in a white-eye cell of the white-eye hexagonal pattern is different. These results are of great importance to the investigation of the multilayer structure of the patterns in dielectric barrier discharge and applications in industry.


NetCooperate: a network-based tool for inferring host-microbe and microbe-microbe cooperation.
Host-microbe and microbe-microbe interactions are often governed by the complex exchange of metabolites. Such interactions play a key role in determining the way pathogenic and commensal species impact their host and in the assembly of complex microbial communities. Recently, several studies have demonstrated how such interactions are reflected in the organization of the metabolic networks of the interacting species, and introduced various graph theory-based methods to predict host-microbe and microbe-microbe interactions directly from network topology. Using these methods, such studies have revealed evolutionary and ecological processes that shape species interactions and community assembly, highlighting the potential of this reverse-ecology research paradigm. NetCooperate is a web-based tool and a software package for determining host-microbe and microbe-microbe cooperative potential. It specifically calculates two previously developed and validated metrics for species interaction: the Biosynthetic Support Score which quantifies the ability of a host species to supply the nutritional requirements of a parasitic or a commensal species, and the Metabolic Complementarity Index which quantifies the complementarity of a pair of microbial organisms' niches. NetCooperate takes as input a pair of metabolic networks, and returns the pairwise metrics as well as a list of potential syntrophic metabolic compounds. The Biosynthetic Support Score and Metabolic Complementarity Index provide insight into host-microbe and microbe-microbe metabolic interactions. NetCooperate determines these interaction indices from metabolic network topology, and can be used for small- or large-scale analyses. NetCooperate is provided as both a web-based tool and an open-source Python module; both are freely available online at http://elbo.gs.washington.edu/software_netcooperate.html.


[Patient reported process and outcome indicators for clinical audit in short-stay surgery].
Based on patient-reported process and outcome indicators of care, a system for quality improvement in short-stay surgery was developed for hernia repair and cholecystectomy. The study aimed to test the feasibility and validity of the system. In two centres for short-stay surgery all patients referred for hernia repair or cholecystectomy were surveyed between August 1999 and January 2002 (T0: preoperative, T1: 14 days post-OP, T2: 6 months post-OP). At T0 and T1 survey instruments were given to patients in the participating centres, at T2 the survey instruments were mailed. Of 342 hernia patients and 250 cholecystolithiasis patients at T0, responses from only 54.1% (hernia) and 63.4% (cholecystolithiasis) were available at T2. Non-response predominantly occurred between T0 and T1. Patients reported on satisfaction with care (FKKP), health-related quality of life (HRQL; SF-36), disease-specific symptoms (symptom checklists), treatment satisfaction and other indicators. Satisfaction with care was quite high. The process indicator of the lowest satisfaction was the provision of competencies to deal with problems at home after discharge at home. At T2 21.1% (hernia) and 66.2% (cholecystolithiasis) reported no complications. Both symptom checklists reflect the positive postoperative course (effect size T0-T2: 1.16 and 0.75). From a T0 level lower than the German reference population (six of the eight SF-36 subscales) HRQL reaches or exceeds the population norms at T2. In general, both the proposed proceedings and the instrument were applicable and feasible. Patient-oriented quality indicators contain additional information on processes and outcomes of care. However, the participating centres were not fully prepared to spend the extra effort necessary to organise such a longitudinal survey. To decrease non-response between T0 and T1, survey instruments should be mailed at T1 (instead of handing them over to patients during their postoperative visit).


Baetis (Baetis) cypronyx sp. n., a new species of the Baetis alpinus species-group (Insecta, Ephemeroptera, Baetidae) from Cyprus, with annotated checklist of Baetidae in the Mediterranean islands.
A detailed description of the larvae of Baetis (Baetis) cypronyx sp. n., a representative of the Baetis alpinus species-group within the mayfly family Baetidae, is provided, including a differential diagnosis with regard to closely related species of the group, especially Baetis melanonyx (Pictet, 1843) and Baetis baroukianus Thomas & Dia, 1984. The new species is mainly distinguished by mouthparts (i.e. the shape and setation of labrum, maxillary and labial palps, details of paraglossae and mandibular incisors), setation of legs and abdominal terga, and length of paracercus. All available data on the biology of this putative endemic species of Cyprus are summarized. Annotated distributional data of the 33 species of Baetidae so far recorded from the Mediterranean islands are given, including new records and also including first data from Malta.


Susceptibility patterns and cross-resistance of antibiotics against Pseudomonas aeruginosa isolated from burn patients in the South of Iran.
Pseudomonas aeruginosa plays a prominent role in serious infections in burn patients. Rapid acquisition of multi-drug resistance leads to high morbidity and mortality, especially in burn centers. Ten antibiotics, which were widely used in our burn patients were selected. MICs for imipenem, mropenem, cefepime, ceftazidime, cafoparazone/sulbactam, ticarcillin/clavulanate, piperacillin/tazobactam, ciprofloxacin, tobramycin and amikacin to 70 strains of P. aeruginosa, which were isolated from burn patients were determined by the E-test method (AB Biodisk, Sweden). Extended-spectrum beta-lactamase, group I inducible beta-lactamases and metallo-beta-lactamase activities were also determined. Imipenem and meropenum were the most active in vitro antibacterial agents followed by ciprofloxacin (p<0.05), whereas, ticarcillin/clavulanate was the least active. Almost all (98-100%) of the resistant isolates also showed cross-resistance to cefepime. The majority of imipenem and meropenem resistant isolates (85-100% and 76-100%) demonstrated cross-resistance to all the other antibiotics. ESBLs were detected in only three (4.3%) isolates, whereas, inducible beta-lactamase was observed in eight (11.4%) isolates. Metallo-beta-lactamase was detected in none of the isolates. Almost all of the antibiotic resistant isolates also showed cross-resistance to the majority of penicillins and cephalosporins with or without beta-lactamase inhibitors, from which ticarcillin/clavulanate demonstrated this phenomenon at the highest level.


Fluctuating Hemiparesis Secondary to Moyamoya Phenomenon in a Child with Down Syndrome: a case report.
Moyamoya phenomenon is a term used to describe extensive collateralization of the circle of Willis arteries associated with severe unilateral or bilateral internal carotid artery stenosis or occlusion in the presence of certain conditions. Down syndrome is among these conditions. A case is reported of a young girl with Down syndrome who presented with fluctuating right-sided weakness and facial droop found to have cerebral ischemia. Subsequent investigations disclosed characteristic "puff of smoke" patterns on angiographic studies consistent with moyamoya phenomenon. The patient was initially treated with aspirin and eventually underwent an encephalomyosynangiosis. This young patient with Down syndrome and moyamoya phenomenon serves as a reminder of the association between these two conditions.


Lycopene counteracts the hepatic response to 7,12-dimethylbenz[a]anthracene by altering the expression of Bax, Bcl-2, caspases, and oxidative stress biomarkers.
Lycopene is a carotenoid found in tomato, watermelon, pink grapefruit, and guava in high concentration. Dietary intake of lycopene has been proposed to inversely correlate with the risk of cancer. It has also been reported to provide protection against cellular damage caused by reactive oxygen species, which makes it worthwhile to study the effect of lycopene on liver damage in rat model. In this study, we report the effect of lycopene on 7,12-dimethylbenz[a]-anthracene (DMBA)-induced expression of Bax, Bcl-2, caspases, and oxidative stres biomarkers in the liver. Lycopene was administered orally at 20 mg/kg body weight for 20 weeks followed by the intraperitoneal injection of DMBA (50 mg/kg body weight) on day 1 and day 30 of the experiment. Control rats received vehicle (olive oil) or DMBA alone. Rats were sacrificed after completion of the treatment. We observed that the levels of Bax, caspase-3, and caspase-9 decreased to 44, 67, and 43%, respectively, and Bcl-2 increased by 80% in DMBA-treated rats. Lycopene reversed the changes in the respective groups, and decreased the level of Bcl-2 to 25%, while increasing the Bax to 42% when compared to DMBA control. Lycopene increased the expression of caspase-3 (82.09%) and caspase-9 (58.96%), and attenuated the level of hepatic malondialdehyde (41%) and 8-isoprostane (40%) when compared to the respective controls. Glutathione (GSH) decreased significantly in DMBA group (15.89%), but reached the normal level in lycopene-treated animals. Hepatic lycopene concentration in treated rats was 8.2 nmol/g tissue. The study reports that lycopene counteracts the hepatic response to DMBA by altering the expression of Bax, Bcl-2, caspases, and oxidative stress biomarkers in animal model.


[Hypoglycemic sulfonylurea metabolites: clinical interest. Experiences with glibenclamide in the rat].
Glibenclamide, a hypoglycemic sulfonylurea, is extensively metabolized by the body and eliminated primarily in the form of its hydroxylated derivatives. The major metabolite, 4-trans-hydroxy-glibenclamide, is usually cleared rapidly from the bloodstream, but in certain pathological states (e.g. renal failure) blood levels of this product may increase. A protocol therefore was designed to test the hypoglycemic potency of this important metabolite in rats. Various quantities were injected intraperitoneally, and alterations in blood glucose concentrations were measured during a 5-hour period and compared to those in animals similarly treated with glibenclamide and in saline-injected controls. Using the dose capable of decreasing blood glucose levels by 30% (ED30) as a comparative index, it was observed that the metabolic has a marked hypoglycemic activity; though 6--7 times less potent than the parent drug, 4-trans-hydroxy-glibenclamide is nevertheless more potent than tolbutamide. Thus, while the glibenclamide metabolite probably has little influence on blood glucose when its clearance is normal, this product may exert marked effects if allowed to accumulate in the blood, as for example in renal failure. Finally, the role of such sulfonylurea metabolites should be taken into account when attempting to explain the occasional excessive and sustained hypoglycemia which occurs in some diabetic patients treated with these drugs.


Highly Thermal Conductive Graphite Films Derived from the Graphitization of Chemically Imidized Polyimide Films.
With the large-scale application and high-speed operation of electronic equipment, the thermal diffusion problem presents an increasing requirement for effective heat dissipation materials. Herein, high thermal conductive graphite films were fabricated via the graphitization of polyimide (PI) films with different amounts of chemical catalytic reagent. The results showed that chemically imidized PI (CIPI) films exhibit a higher tensile strength, thermal stability, and imidization degree than that of purely thermally imidized PI (TIPI) films. The graphite films derived from CIPI films present a more complete crystal orientation and ordered arrangement. With only 0.72% chemical catalytic reagent, the graphitized CIPI film achieved a high thermal conductivity of 1767 W·m-1·K-1, which is much higher than that of graphited TIPI film (1331 W·m-1·K-1), with an increase of 32.8%. The high thermal conductivity is attributed to the large in-plane crystallite size and high crystal integrity. It is believed that the chemical imidization method prioritizes the preparation of high-quality PI films and helps graphite films achieve an excellent performance.


Time-reversal symmetry adaptation in relativistic density matrix renormalization group algorithm.
In the nonrelativistic Schrödinger equation, the total spin S and spin projection M are good quantum numbers. In contrast, spin symmetry is lost in the presence of spin-dependent interactions, such as spin-orbit couplings in relativistic Hamiltonians. Therefore, the relativistic density matrix renormalization group algorithm (R-DMRG) only employing particle number symmetry is much more expensive than nonrelativistic DMRG. In addition, artificial breaking of Kramers degeneracy can happen in the treatment of systems with an odd number of electrons. To overcome these issues, we propose time-reversal symmetry adaptation for R-DMRG. Since the time-reversal operator is antiunitary, this cannot be simply achieved in the usual way. We introduce a time-reversal symmetry-adapted renormalized basis and present strategies to maintain the structure of basis functions during the sweep optimization. With time-reversal symmetry adaptation, only half of the renormalized operators are needed, and the computational costs of Hamiltonian-wavefunction multiplication and renormalization are reduced by half. The present construction of the time-reversal symmetry-adapted basis also directly applies to other tensor network states without loops.


Review of the genus Hechinoschema Thomson, 1857 (Coleoptera: Cerambycidae: Lamiinae: Monochamini), with description of a new genus and two new species.
A taxonomic review of the genus Hechinoschema is presented. A new genus, Propedicellus gen. nov., is described, and two new species Propedicellus guoliangi sp. nov. and Propedicellus qiului sp. nov. are described from China. A new combination Propedicellus vitalisi (Pic, 1925) comb. nov. is proposed. A key to species of Propedicellus is presented.


PreSPI: a domain combination based prediction system for protein-protein interaction.
With the accumulation of protein and its related data on the Internet, many domain-based computational techniques to predict protein interactions have been developed. However, most techniques still have many limitations when used in real fields. They usually suffer from low accuracy in prediction and do not provide any interaction possibility ranking method for multiple protein pairs. In this paper, we propose a probabilistic framework to predict the interaction probability of proteins and develop an interaction possibility ranking method for multiple protein pairs. Using the ranking method, one can discern the protein pairs that are more likely to interact with each other in multiple protein pairs. The validity of the prediction model was evaluated using an interacting set of protein pairs in yeast and an artificially generated non-interacting set of protein pairs. When 80% of the set of interacting protein pairs in the DIP (Database of Interacting Proteins) was used as a learning set of interacting protein pairs, high sensitivity (77%) and specificity (95%) were achieved for the test groups containing common domains with the learning set of proteins within our framework. The stability of the prediction model was also evident when tested over DIP CORE, HMS-PCI and TAP data. In the validation of the ranking method, we reveal that some correlations exist between the interacting probability and the accuracy of the prediction.


Reliability and validity evidence of the Assessment of Language Use in Social Contexts for Adults (ALUSCA).
Background: The appropriate use of language in context depends on the speaker's pragmatic language competencies. A coding system was used to develop a specific and adult-focused self-administered questionnaire to adults who stutter and adults who do not stutter, The Assessment of Language Use in Social Contexts for Adults, with three categories: precursors, basic exchanges, and extended literal/non-literal discourse. This paper presents the content validity, item analysis, reliability coefficients and evidences of construct validity of the instrument. Methods: Content validity analysis was based on a two-stage process: first, 11 pragmatic questionnaires were assessed to identify items that probe each pragmatic competency and to create the first version of the instrument; second, items were assessed qualitatively by an expert panel composed by adults who stutter and controls, and quantitatively and qualitatively by an expert panel composed by clinicians. A pilot study was conducted with five adults who stutter and five controls to analyse items and calculate reliability. Construct validity evidences were obtained using the hypothesized relationships method and factor analysis with 28 adults who stutter and 28 controls. Results: Concerning content validity, the questionnaires assessed up to 13 pragmatic competencies. Qualitative and quantitative analysis revealed ambiguities in items construction. Disagreement between experts was solved through item modification. The pilot study showed that the instrument presented internal consistency and temporal stability. Significant differences between adults who stutter and controls and different response profiles revealed the instrument's underlying construct. Conclusion: The instrument is reliable and presented evidences of construct validity.


Mortality attributable to nosocomial infections in the ICU.
Although a direct relationship between nosocomial infection and mortality in intensive care unit (ICU) patients has not always been demonstrated formally, it is possible to conclude that nosocomial infections increase the risk of death in critically ill patients. A more precise analysis indicates that: 1) this effect is highly probable for pneumonia, doubtful for bacteremia, and uncertain for urinary tract infection; 2) risk increases with duration of stay in the ICU; 3) bacterial etiology modifies the risk; and 4) this effect is stronger in less severely ill patients, probably because the severity of underlying disease remains the most significant factor.


[A survey of infection control among community home care service providers].
This study aimed to explore the current situation of infection control by community home care providers. We investigated an area managed by one of 6 municipal social welfare offices in Fukushima. Two questionnaires were sent to all home care agencies providing home help services, visiting bathing care and visit-nursing: one to the 82 chiefs of the agencies (response rate of 90.2%) and the other to 1024 health care workers working for them (57.2%). The questionnaire covered health checkups of employees, maintenance and management of devices, infection control education and manuals, and hand hygiene. 1. Medical checkups were organized once a year or more at 94.6% of the agencies and employee participation of once a year or more was 87.6%. 2. Regarding the management of health care devices, personnel were assigned and a registration system was introduced at 43.2% and 20.8% of the agencies, respectively. Most agencies (94.6%) provided disposable gloves and 82.6% of the employees used them when handling body fluids or excretions. However, not many agencies provided hand-washing equipment (43.2%) and paper towels (39.2%). 3. Infection control educational programs were organized at 40.3% of the agencies and attended by 30.2% of the employees. Among the agencies without such programs, 76.2% gave employees' time constraint as a reason for not giving training. On the other hand, 78.5% of non-attendants of the program answered that they were not given a chance to participate. 4. Infection control manuals were available at 68.9% of the agencies, but only 69.4% of their employees were aware of them and only 44.3% utilized them. Agencies were aware of the situation and only 42.9% answered that their manuals were fully utilized. Among the agencies currently without manuals, 47.8% are developing manuals. 5. When and how to wash hands and how to use towels in home care settings were specified in 73.0%, 78.4% and 35.1% of the agencies, respectively. As high as 92.0% of employees washed their hands after caring for clients and 74.6% after handling body fluids or excretions, but 52.2% did so before caring. It was noted that although 82.7% of the employees washed their hands with water and soap (and antiseptic agents), only 7.5% used paper towels to dry their hands. The chiefs of home care providers should be required to develop and implement better infection control strategies with the support of local governmental agencies.


Alternative Medicine in North America: A Christian Pastoral Response.
Complementary and Alternative Medicine is popular among North Americans. However, there are many areas of concern, both scientific and spiritual, about its appropriate use. Those involved in pastoral care may be consulted for advice and therefore should be knowledgeable about Complementary and Alternative Medicine. This paper reviews and evaluates it from a Christian perspective, and offers suggestions for a pastoral response.


Expression of thermophilic two-domain laccase from Catenuloplanes japonicus in Escherichia coli and its activity against triarylmethane and azo dyes.
Two-domain laccases are copper-containing oxidases found in bacteria in the beginning of 2000ths. Two-domain laccases are known for their thermal stability, wide substrate specificity and, the most important of all, their resistance to so-called «strong inhibitors» of classical fungal laccases (azides, fluorides). Low redox potential was found to be specific for all the two-domain laccases, due to which these enzymes lost the researchers' interest as potentially applicable for various biotechnological purposes, such as bioremediation. Searching, obtaining and studying the properties of novel two-domain laccases will help to obtain an enzyme with high redox-potential allowing its practical application. A gene encoding two-domain laccase was identified in Catenuloplanes japonicus genome, cloned and expressed in an Echerichia coli strain. The protein was purified to homogeneity by immobilized metal ion affinity chromatography. Its molecular properties were studied using electrophoresis in native and denaturing conditions. Physico-chemical properties, kinetic characteristics, substrate specificity and decolorization ability of laccase towards triphenylmethane dyes were measured spectrophotometrically. A novel two-domain recombinant laccase CjSL appeared to be a multimer with a subunit molecular mass of 37 kDa. It oxidized a wide range of phenolic substrates (ferulic acid, caffeic acid, hydroquinone, catechol, etc.) at alkaline pH, while oxidizing of non phenolic substrates (K4[Fe(CN)6], ABTS) was optimal at acidic pH. The UV-visible absorption spectrum of the purified enzyme was specific for all two-domain laccases with peak of absorption at 600 nm and shoulder at 340 nm. The pH optima of CjSL for oxidation of ABTS and 2, 6-DMP substrates were 3.6 and 9.2 respectively. The temperature optimum was 70 °C. The enzyme was most stable in neutral-alkaline conditions. CjSL retained 53% activity after pre-incubation at 90 °C for 60 min. The enzyme retained 26% activity even after 60 min of boiling. The effects of NaF, NaN3, NaCl, EDTA and 1,10-phenanthroline on enzymatic activity were investigated. Only 1,10-phenanthroline reduced laccase activity under both acidic and alkaline conditions. Laccase was able to decolorize triphenylmethane dyes and azo-dyes. ABTS and syringaldehyde were effective mediators for decolorization. The efficacy of dye decolorization depended on pH of the reaction medium.


IncRNA XIST Promotes Cardiac Fibrosis in Mice with Diabetic Nephropathy via Sponging miR-106a-5p to Target RUNX1.
Diabetic nephropathy (DN) accompanied by cardiac fibrosis (CF) increases the mortality rate among people with diabetes. This study sought to explore the molecular mechanism of long non-coding RNA X inactive specific transcript (lncRNA XIST) in CF in DN mice. The animal model of DN was established by streptozocin (STZ). The levels of lncRNA XIST, microRNA (miR)-106a-5p, and RUNX family transcription factor 1 (RUNX1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR), followed by biochemical analysis, hematoxylin & eosin and Masson staining, echocardiography, and quantification of collagen I, collagen III, α-smooth muscle actin (α-SMA), and transforming growth factor-β1 (TGF-β1) levels through qRT-PCR and Western blot assay. The subcellular localization of lncRNA XIST was analyzed by nuclear/cytoplasmic fractionation assay and the bindings of miR-106a-5p to lncRNA XIST and RUNX1 were confirmed by RNA immunoprecipitation and dual-luciferase assays. Functional rescue experiments were performed to validate the role of miR-106a-5p/RUNX1 in CF in DN mice. lncRNA XIST and RUNX1 were elevated while miR-106a-5p was decreased in STZ mice. lncRNA XIST inhibition reduced myocardial injury and collagen deposition, along with decreased levels of fasting blood glucose, serum creatinine, blood urea nitrogen, and urinary microalbumin, collagen I, collagen III, α-SMA, and TGF-β1. lncRNA XIST competitively bound to miR-106a-5p to promote RUNX1 transcription. miR-106a-5p downregulation or RUXN1 upregulation reversed the protective role of lncRNA XIST inhibition in STZ mice. lncRNA XIST competitively bound to miR-106a-5p to promote RUNX1 transcription, thereby aggravating renal dysfunction and CF in DN mice.


Mucocutaneous disorders in Hiv positive patients.
Twenty eight HIV positive patients were included in this study. They were evaluated for their mucocutaneous disorders, sexually transmitted diseases and other systemic disorders between 1994-95 in the department of Dermatology and STD Dr R M L Hospital of New Delhi. The heterosexual contact with commercial sex workers (CSWs) was the most common route of HIV transmission. Chancroid, syphilis and genital warts were common STDs found in HIV positive patients. Oral thrush (67.9%) was the commonest mucocutaneous disorder found in these patients followed by herpes zoster (25%) and seborrhoeic dermatitis (21.4%). There was no unusual clinical presentation seen in mucocutaneous disorders and STDs.


Polygonal Fracture and Fold Systems in the Salt Crust, Great Salt Lake Desert, Utah.
Small folds and fractures (thrusts) up to 50 feet apart that have produced polygonal patterns in the Bonneville salt crust, western Utah, are believed to be caused by the annual expansion of the salt crust due to the growth of salt crystals within the salt layer plus the effect of increased summer temperature. It is suggested that these strain systems are caused by positive (compressional) isotropic planar stresses developed within the salt layers of the salt crust.


A Call for Epidemiological Research on Myeloid-Derived Suppressor Cells in Ovarian Cancer: A Review of the Existing Immunological Evidence and Suggestions for Moving Forward.
Recently, there have been encouraging findings suggesting that myeloid-derived suppressor cells (MDSCs) may be a good target for studying immune suppression in ovarian cancer. MDSCs are an abundance of immature myeloid cells that have demonstrated the ability to decrease tumor-infiltrating immune cells, increase the accrual of tumor-associated macrophages and regulatory T cells, as well as secrete various pro-inflammatory mediators and growth stimulating cytokines. Most studies on this topic utilized murine models, but there are limited reports in human subjects which have important limitations. With the majority of ovarian cancer patients presenting with distant metastases and a corresponding 5-year relative survival rate of < 30%, continued efforts are obligatory toward identifying potential prognostic factors. Given the difficulty of studying exposures in this patient population, as well as the existing immunologic characteristics of this cancer, there is growing interest in further identifying genetic and immunologic associations with patient survival. Furthermore, prognostic factors that may necessitate therapeutic intervention may significantly alter disease outlook. In this review paper, we address the current literature on MDSCs and their immunosuppressive behavior in ovarian cancer patients. While the previous studies on these cells in ovarian cancer have demonstrated some potential prognostic significance, there are many limitations to such studies including small sample sizes, inconsistent staging and histology, as well as inconsistent surface markers for the identification of MDSCs. Additionally, such studies include minimal patient characteristics involved with the clinical course of ovarian cancer. Here, we have proposed improving on studies analyzing MDSCs as a potential prognostic factor in ovarian cancer patients, as well as further identifying the potential of this novel prognostic factor in future care, through the use of a comprehensive epidemiologic model.


GhCalS5 is involved in cotton response to aphid attack through mediating callose formation.
Callose synthase plays an essential role in plant growth and development and in response to all sorts of stresses through regulating callose formation. However, few research about the function and mechanism of the insect resistance of callose synthase genes have been reported in cotton. In this study, a cotton callose synthase gene GhCalS5 was cloned, and its function and mechanism of resistance to cotton aphids were analyzed. The expression of GhCalS5 was significantly upregulated in both, leaves and stems of cotton plants at 48 h after cotton aphid infestation and in the leaves of cotton plants at 24 h after salicylic acid treatment. The overexpression of GhCalS5 enhanced cotton resistance to cotton aphids. Expectedly silencing of GhCalS5 reduced cotton resistance to cotton aphids. Overexpression of GhCalS5 enhanced callose formation in cotton leaves. Our results suggest that GhCalS5 is involved in cotton resistance against cotton aphids by influencing callose formation.


Age-related increases in motivation among children with mental retardation and MA- and CA-matched controls.
Child positive affect and task orientation in response to a series of cognitively demanding puzzle tasks were assessed at two time points separated by a 12-month interval in children with mild mental retardation and MA- and CA-matched controls (age range 1 to 5 years). At the first assessment, children with mild mental retardation exhibited mastery behavior appropriate for MA but not CA. At the second assessment, the goal-directed behavior of children with mild mental retardation was no different from that of both the MA and CA controls. Correlates of motivation were similar for children with mild mental retardation and typically developing children. Implications for the developmental study of children with mild mental retardation are discussed.


Negative correlation between ACE2 gene expression levels and loss of taste in a cohort of COVID-19 hospitalized patients: New clues to long-term cognitive disorders.
In early 2020, one of the most prevalent symptoms of SARS-CoV-2 infection was the loss of smell (anosmia), found in 60-70% of all cases. Anosmia used to occur early, concomitantly with other symptoms, and often persisted after recovery for an extended period, sometimes for months. In addition to smell disturbance, COVID-19 has also been associated with loss of taste (ageusia). The latest research suggests that SARS-CoV-2 could spread from the respiratory system to the brain through receptors in sustentacular cells localized to the olfactory epithelium. The virus invades human cells via the obligatory receptor, angiotensin-converting enzyme II (ACE2), and a priming protease, TMPRSS2, facilitating viral penetration. There is an abundant expression of both ACE2 and TMPRSS2 in sustentacular cells. In this study, we evaluated 102 COVID-19 hospitalized patients, of which 17.60% presented anosmia and 9.80% ageusia. ACE1, ACE2, and TMPRSS2 gene expression levels in nasopharyngeal tissue were obtained by RT-qPCR and measured using ΔCT analysis. ACE1 Alu287bp association was also evaluated. Logistic regression models were generated to estimate the effects of variables on ageusia and anosmia Association of ACE2 expression levels with ageusia. was observed (OR: 1.35; 95% CI: 1.098-1.775); however, no association was observed between TMPRSS2 and ACE1 expression levels and ageusia. No association was observed among the three genes and anosmia, and the Alu287bp polymorphism was not associated with any of the outcomes. Lastly, we discuss whetherthere is a bridge linking these initial symptoms, including molecular factors, to long-term COVID-19 health consequences such as cognitive dysfunctions.


Effects of resveratrol on laminar shear stress-induced mitochondrial biogenesis in human vascular endothelial cells.
The purpose of the study was to determine the combined effects of resveratrol supplementation with high-flow LSS on mitochondrial biogenesis in human vascular endothelial cells. Cultured human umbilical vein endothelial cells were treated with 20 μM of RSV. For the shear experiments, cells grown to a >90% confluence were exposed to physiological levels of LSS (5 to 20 dyne/cm2) for 12 to 36 hours using a cone and plate shear apparatus. Gene expressions were analyzed by western blotting. Depletion of mitochondrial integrity was directly associated with increase in endothelial activation/dysfunction. The expressions of mitochondrial biogenesis regulator genes, such as SIRT1, PGC-1α, and TFAM, and the mitochondrial contents were significantly increased after treatment with both resveratrol and high-flow LSS for 12 hours. However, supplementation of resveratrol to high-flow LSS for a prolonged duration had no synergistic effect on the levels of mitochondrial biogenesis regulator gene expressions and mitochondrial content compared to the LSS treatment alone. The present study demonstrated that the supplementation of resveratrol to high-flow LSS has no synergistic effects on enhancing mitochondrial integrity in human vascular endothelial cells.


Serum calcium metabolism in acute experimental pancreatitis.
Serum calcium changes in severe pancreatitis were studied in 23 dogs. Twelve dogs underwent duodenotomy and served as controls. Pancreatitis was induced in the other 11 by autologous bile injection (1 ml/kg) into the pancreatic duct. Serum amylase, total calcium, ionized calcium, albumin, magnesium, chloride, phosphorous, parathyroid hormone (PTH), and calcitonin were measured at 0, 1/2, 1, 3, 6, 24, 48, and 72 hours after duodenotomy or bile injection. Serum amylase levels became significantly elevated in all dogs with pancreatitis at 30 minutes (p less than 0.01) and remained so throughout the entire experiment. Total calcium levels dropped significantly 30 minutes after pancreatitis was induced from 10.0 +/- 0.3 mg/dl compared with 8.8 +/- 0.4 mg/dl in control dogs (p less than 0.05) and remained statistically lower for as long as 1 hour. Ionized calcium levels were significantly lower than were those of control dogs at 1/2, 1, 3, and 6 hours (p less than 0.05). Serum magnesium and chloride levels showed no significant changes between both groups. The only significant difference in phosphorus values was at 6 hours when they were higher in dogs with pancreatitis than in controls (6.2 +/- 0.3 mg/dl versus 4.8 +/- 0.4 mg/dl; p less than 0.05). Serum albumin levels remained unchanged throughout the study except for 48 hours when they were significantly lower in animals with pancreatitis (p less than 0.02). PTH levels were significantly greater in dogs with pancreatitis than in controls at 1, 3, 6, and 24 hours (p less than 0.05). There was no significant difference in calcitonin levels between both groups. Ionized calcium is a more reliable indicator of calcium fluxes in acute experimental pancreatitis since it remains depressed longer than total serum calcium. The time course of PTH elevation indicates a reaction to hypocalcemia, and failure of PTH secretion is not the cause of hypocalcemia in pancreatitis. This study does not support elevation of calcitonin as a cause of hypocalcemia in acute pancreatitis.


Underrecognition of preexisting cognitive impairment by physicians in older ICU patients.
Cognitive impairment increases with age, as do many serious illnesses requiring intensive care. Little is known, however, about physician recognition of preexisting cognitive impairment in the ICU and which patient factors may play a role in physician recognition. Cross-sectional comparative study. Urban university teaching hospital. A total of 165 patients aged > or =65 years who were admitted to the medical ICU. Two previously validated proxy measures of cognitive impairment, the modified Blessed dementia rating scale and the informant questionnaire on cognitive decline in the elderly. Physician interviews and medical record abstraction were used to evaluate the recognition of cognitive impairment. The prevalence of preexisting cognitive impairment in the ICU was 37%. Attending physicians were unaware of the preexisting cognitive impairment in 53% of cases, and intern physicians were unaware in 59% of cases. The recognition of preexisting cognitive impairment increased as the severity of the cognitive impairment increased. Two independent risk factors were identified that were significantly associated with the increased recognition of preexisting cognitive impairment (ie, impairment in activities of daily living or being admitted to the ICU from a nursing home). If both were present, preexisting cognitive impairment was 13 times more likely to be recognized. A substantial number of older ICU patients have preexisting cognitive impairment on admission to the ICU, and ICU physicians caring for these patients are unaware of this cognitive impairment in the majority of cases. Future research is needed to identify outcomes related to preexisting cognitive impairment and to improve its recognition.


Systematic Review and Meta-Analysis of Cardiovascular Medications in Neonatal Hypotension.
Comparative studies among the various cardiovascular medications used for the treatment of neonatal hypotension are lacking. This systematic review and pairwise meta-analysis of the anti-hypotensive treatments in preterm and term infants was conducted to evaluate efficacy and impact on outcome. Electronic databases were searched up to February 2021 for relevant articles. As an extension of the current approach for study selection, a machine learning technique was used. Only randomized controlled trials (RCTs) of inotropes, pressors, volume therapy, and corticosteroids were included. Response to treatment was the primary outcome while secondary outcomes included mortality and common morbidities. Nineteen RCTs involving 758 preterm and term neonates were found, and 8 treatments were evaluated. Most studies involved subjects with early hypotension associated with prematurity. Pairwise meta-analysis among treatments showed that dopamine was more effective than dobutamine regarding the response to treatment (restoration of normotension or normalization of blood pressure) (7 trials, 286 neonates, odds ratio, 3.06 [95% CI = 1.06-8.87]; I2 = 49%, very low quality of the evidence per GRADE). Comparisons of other treatments were not significant. No differences were found among regimens regarding survival and other secondary outcomes. In this systematic review and pairwise meta-analysis, only the comparison of dopamine versus dobutamine provided evidence for efficacy of treatment and favored dopamine. No safe conclusions could be reached in regard to other treatments. Data regarding the management of arterial hypotension in conditions other than transition after birth in preterm newborns are sparse both in preterm and term infants.


Genetically engineered avidins and streptavidins.
Chicken avidin and bacterial streptavidin, (strept)avidin, are proteins widely utilized in a number of applications in life science, ranging from purification and labeling techniques to diagnostics, and from targeted drug delivery to nanotechnology. (Strept)avidin-biotin technology relies on the extremely tight and specific affinity between (strept)avidin and biotin (dissociation constant, K(d) approximately 10(-14)-10(-16) M). (Strept)avidins are also exceptionally stable proteins. To study their ligand binding and stability characteristics, the two proteins have been extensively modified both chemically and genetically. There are excellent accounts of this technology and chemically modified (strept)avidins, but no comprehensive reviews exist concerning genetically engineered (strept)avidins. To fill this gap, we here go through the genetically engineered (strept)avidins, summarizing how these constructs were designed and how they have improved our understanding of the structural and functional characteristics of these proteins, and the benefits they have provided for (strept)avidin-biotin technology.


[Osteomyelitis. A rare and serious complication of inguinal hernia surgery].
We report two cases of osteomyelitis following herniotomy ad modum Lichtenstein with implantation of a polypropylene mesh. With the new prosthetic materials, the hernia recurrence rate and sick leave are reduced. In the case of persistent wound infection serious complications might occur.


The incidence of sexually related conditions in asymptomatic versus symptomatic patients.
We studied, retrospectively, 400 consecutive case-notes (200 for each sex) for patients who presented with or without complaints of urethral or vaginal discharge. The incidence of sexually related conditions was identified for each of the four patients subgroups to objectively inform the process of triage. In all, 60% of asymptomatic female and 40% of asymptomatic male patients in the study had a condition of genitourinary (GU) medicine significance. Two-thirds of female patients had a condition of GU medicine significance whether they were symptomatic or asymptomatic. Some 16% of asymptomatic males would have had a delay in treatment of chlamydia, with a 19% loss of identifying non-specific urethritis, if they were triaged on the basis of lack of symptoms, and microscopy tests were abandoned for this group of patients.


Nanostructural change of human melanocytes stimulated with α-melanocyte stimulating hormone observed by atomic force microscopy.
It is well known that α-melanocyte stimulating hormone (α-MSH) induces melanization, but structural changes of melanocytes after α-MSH exposure are not well known. This study investigated the serial morphologic changes of human cultured melanocytes after stimulation with α-MSH using atomic force microscopy (AFM). Cultured human melanocytes were treated with α-MSH for 7 days. Contact mode AFM images were obtained using a NANOstation II and fixed melanocytes were scanned in PBS solution at a resolution of 512 × 512 pixels, at a scan speed of 0.4 line/s. The surface roughness and pore-like structures of the melanocytes were measured from topographic images using the Scanning Probe Imaging Processor. The surface roughness of cell body did not change significantly over time. All three roughness parameters (Sa, Sq, Sz) inside the pore-like structures on the dendrites increased significantly. The number of pore-like structures increased and the length and the breadth of pore-like structures also increased gradually. Pore-like structures changed statistically significantly in response to α-MSH stimulation. Further study will be needed to clarify whether the nature of pore-like structures is related to movement of melanosomes.


Mitochondrial sequence data clarify species concepts in the Cyclocephala mafaffa species complex (Coleoptera: Scarabaeidae: Dynastinae: Cyclocephalini).
The speciose genus Cyclocephala Dejean (Coleoptera: Scarabaeidae: Dynastinae: Cyclocephalini) has attracted research attention due to their diversity, agroeconomic importance, and floral visitation habits. Uniquely among Cyclocephala species, C. mafaffa Burmeister and C. deceptor (Casey), two nearly identical species, are diagnosed by a pronotal character: beaded or not beaded basal pronotal margin. We evaluated these morphological species hypotheses with a phylogenetic analysis of 12S and COI, neighbor-joining analysis, and several single-locus species delimitation procedures (automatic barcode gap analysis and three Poisson tree processes analyses). Together, these analyses supported the species concepts for C. deceptor and C. mafaffa. Delimitation procedures supported several distinct molecular operational taxonomic units among these taxa. We consider the separation of C. deceptor and C. mafaffa to be valid. We conservatively synonymize the West Indian subspecies C. mafaffa grandis Burmeister under C. mafaffa and offer a discussion on subspecific concepts in Cyclocephalini. We designate the lectotype of Stigmalia deficiens Casey. Implications of this study for other geographically widespread cyclocephalines or species with variable pronotal morphology are discussed.


Structural analysis of the 17q22-23 amplicon identifies several independent targets of amplification in breast cancer cell lines and tumors.
A novel region of amplification in breast tumors has recently been identified on chromosome 17q22-23. In an effort to identify the oncogenes in the region that are targeted by the amplification process, we determined the structure of the amplicon in breast cancer cell lines and tumors. Physical and transcription maps of the approximately 3.5-Mb region were established and used as the basis for copy number analysis within the region by Southern blot and fluorescence in situ hybridization. Seven specific and independent amplification maxima were identified in breast cancer cell lines and breast tumors. We present correlative amplification and overexpression studies for the FLJ21316 and Hs.6649 genes suggesting a role for these candidates as amplification-dependent oncogenes.


Challenges of Diabetes Care in Older People With Type 2 Diabetes and the Role of Basal Insulin.
IN BRIEF The use of long-acting basal insulin analogs is a recommended strategy in older people with diabetes because of their lower risk of hypoglycemia compared to intermediate-acting insulins. In this article, we review the results from recent clinical trials of second-generation basal insulin preparations. We conclude that, although these preparations have improved the management of insulin-requiring older people with type 2 diabetes, there is a need for additional and more specific studies to address the complexities of hyperglycemia management in this population.


Bimanual coupling is associated with left frontocentral network activity in a task-specific way.
When performing bimanual tasks, hands are typically not controlled individually but rather as a coupled system to achieve high spatiotemporal coordination. On a brain level, intrahemispheric and interhemispheric networks that control the left and right hand are necessary to exchange information between hemispheres and to couple movements. Behaviourally, coupling is, however, highly task-specific requiring, for example, to maintain a specific relative phase in cyclic tasks (e.g., inphase or antiphase) or to perform a role differentiated task where one hand is modulating and the other hands is stabilizing and needs to be kept as still as possible (e.g., holding a notepad and writing on it). In this study, we used electroencephalography to investigate functional brain network characteristics (task-related activation and connectivity) in bimanual force-control tasks with different coordination modes: inphase, antiphase and role-differentiated with the left- or right-hand stabilizing and the other hand manipulating. We aimed to examine (1) how network characteristics differ with respect to the coordination mode and (2) how they are related to the performance. Results revealed task-related differences in the overall activation and connectivity with role-differentiated tasks leading to higher desynchronization as compared to inphase and antiphase tasks. In addition, we showed that the strength of bimanual coupling is modulated task specifically through left-hemispheric networks including C3, FC3 and F3 electrodes. Results highlight the importance of the left frontocentral regions for bimanual coordination.


Descriptive epidemiology of chronic childhood adversity in Mexican adolescents.
To estimate the prevalence of adversity (neglect and abuse, parental loss, parental psychopathology, economic adversity, and serious physical illness), the interrelatedness of adversities, and their socio-demographic correlates. This is a multistage probability survey of 3005 adolescents aged 12-17 years residing in Mexico City. Youth were administered the computer-assisted adolescent version of the World Mental Health Composite International Diagnostic Interview in their homes. The childhood and posttraumatic stress disorder sections provided information regarding adversity. Descriptive and logistic regression analyses were performed considering the multistage and weighted sample design. A total of 68% of adolescents have experienced at least one type of chronic childhood adversity, whereas almost 7% have experienced four of more. The most frequent adversity is economic adversity followed by witnessing domestic violence. Boys experience more neglect than girls, and girls experience more sexual abuse than boys. Family dysfunction adversities tend to clump together such that youth exposed to abuse of any form also report witnessing domestic violence and parental mental pathology. Youth whose parents have divorced are likely to experience economic adversity. Parental death is independent of experiencing other childhood adversities. Older adolescents, school drop-outs, those with young mothers, those with more siblings, and those whose parents have less education are more likely to experience adversity. Although most adolescents have experienced some adversity, a small group is exposed to many adversities. Understanding the distribution of adversities may help us to identify at-risk youth and to better interpret the findings from studies on the role of adversity in diverse health outcomes.


Molecular modeling of the minor histocompatibility antigen HA-1 peptides binding to HLA-A alleles.
Mismatch of the minor histocompatibility antigen HA-1 has been shown to correlate with graft-versus-host disease in HLA-matched sibling marrow transplants. The HA-1H peptide (VLHDDLLEA) that generates this response is known to be presented by HLA-A*0201. In order to understand the interaction of HA-1 peptides with other HLA-A alleles, we have used the LOOK interface to construct molecular models of both HA-1H peptide (VLHDDLLEA) and HA-1R peptide (VLRDDLLEA) binding with 103 HLA-A alleles. The results show that in addition to A*0201, 21/103 other HLA-A alleles should be able to bind HA-1H peptide but not HA-1R peptide. Based on the modeled predictions, HLA alleles can be categorised into 4 groups with respect to their interaction with HA-1 peptides: Group 1 - bind HA-1H peptide but not HA-1R peptide; Group 2 - bind HA-1R peptide but not HA-1H peptide; Group 3 - bind both HA-1H and HA-1R peptides; Group 4 - bind neither peptide. These predicted binding patterns of HA-1 peptides will be useful as an aid for defining a wider pool of HLA-A alleles in which HA-1 disparities among donor-recipient pairs can be investigated.


Fabrication of X-ray Gratings for Interferometric Imaging by Conformal Seedless Gold Electroplating.
We present a method to produce small pitch gratings for X-ray interferometric imaging applications, allowing the phase sensitivity to be increased and/or the length of the laboratory setup to be minimized. The method is based on fabrication of high aspect ratio silicon microstructures using deep reactive ion etching (Bosch technique) of dense grating arrays and followed by conformal electroplating of Au. We demonstrated that low resistivity Si substrates (<0.01 Ohm·cm) enable the metal seeding layer deposition step to be avoided, which is normally required to initiate the electroplating process. Etching conditions were optimized to realize Si recess structures with a slight bottom tapering, which ensured the void-free Au filling of the trenches. Vapor HF was used to remove the native oxide layer from the Si grating surface prior to electroplating in the cyanide-based Au electrolyte. Fabrication of Au gratings with pitch in the range 1.2-3.0 µm was successfully realized. A substantial improved aspect ratio of 45:1 for a pitch size of 1.2 µm was achieved with respect to the prior art on 4-inch wafer-based technology. The fabricated Au gratings were tested with X-ray interferometers in Talbot-Laue configuration with measured visibility of 13% at an X-ray design energy of 26 keV.


Antigen-presenting cells from calves persistently infected with bovine viral diarrhoea virus, a member of the Flaviviridae, are not compromised in their ability to present viral antigen.
The aim of this study was to assess whether the infection of antigen-presenting cells (APC) in vivo, evident in calves persistently infected (PI) with bovine viral diarrhoea virus (BVDV), compromised their ability to stimulate virus-specific T cell responses. Major histocompatibility complex (MHC) molecule-identical cattle were identified from the inbred family at the Institute for Animal Health. One was PI and immunotolerant to BVDV. Virus was not isolated from the remaining calves, which were classified as BVDV-immune or BVDV-naïve depending on the presence or absence of BVDV-specific antibodies in sera. Two-colour flow-cytometric analysis of PBMC from the PI calf showed that 40% of CD14(+) monocytes were infected in vivo. Monocytes from the PI calf (PI monocytes) were used as naturally infected ex vivo APC with CD4(+) or CD8(+) T cells isolated from the BVDV-naïve or BVDV-immune animals. PI monocytes stimulated proliferative responses with CD4(+) and CD8(+) T cells from BVDV-immune animals, but not from BVDV-naïve calves. This provided evidence for the presence of virus-specific CD4(+) and CD8(+) memory T cells after acute infection and indicated that ex vivo monocytes from PI, immunotolerant calves stimulated both MHC class I- and MHC class II-restricted T cell responses to BVDV. Additionally, naturally infected ex vivo monocytes cultured in vitro for 3 days stimulated effective T cell responses to the virus with which they were infected.


Pulsed ultrasound enhances nanoparticle penetration into breast cancer spheroids.
Effective treatment of solid tumors requires homogeneous distribution of anticancer drugs within the entire tumor volume to deliver lethal concentrations to resistant cancer cells and tumor-initiating cancer stem cells. However, penetration of small molecular weight chemotherapeutic agents and drug-loaded polymeric and lipid particles into the hypoxic and necrotic regions of solid tumors remains a significant challenge. This article reports the results of pulsed ultrasound enhanced penetration of nanosized fluorescent particles into MCF-7 breast cancer spheroids (300-350 μm diameter) as a function of particle size and charge. With pulsed ultrasound application in the presence of microbubbles, small (20 nm) particles achieve 6-20-fold higher penetration and concentration in the spheroid's core compared to those not exposed to ultrasound. Increase in particle size to 40 and 100 nm results in their effective penetration into the spheroid's core to 9- and 3-fold, respectively. In addition, anionic carboxylate particles achieved higher penetration (2.3-, 3.7-, and 4.7-fold) into the core of MCF-7 breast cancer spheroids compared to neutral (2.2-, 1.9-, and 2.4-fold) and cationic particles (1.5-, 1.4-, and 1.9-fold) upon US exposure for 30, 60, and 90 s under the same experimental conditions. These results demonstrate the feasibility of utilizing pulsed ultrasound to increase the penetration of nanosized particles into MCF-7 spheroids mimicking tumor tissue. The effects of particle properties on the penetration enhancement were also illustrated.


A prospective study of C-reactive protein in patients with obesity during IVF.
This prospective cohort pilot study investigated the physiology of C-reactive protein (CRP) during in vitro fertilization (IVF) cycles and its effect on outcomes in women with and without obesity. The study was conducted from April to August 2014, in the IVF Unit of a university-affiliated hospital. Women aged 18-42 years were enrolled. Those with chronic inflammatory diseases or acute illness were excluded. A total of 31 patients were included: 17 with BMI < 30 kg/m2 and 14 with BMI ≥ 30 kg/m2. Serum CRP levels were measured: (i) before starting ovarian stimulation; (ii) on the day of β-HCG administration; and (iii) on day of ovum pick-up (OPU), in both serum and follicular fluid. Serum CRP levels were significantly higher in women with obesity at all time points. For the entire cohort, a positive correlation was found between basal oestradiol (E2) and basal CRP (r = 0.71, p < 0.05). A specific pattern of CRP levels was not detected during the IVF cycle. High serum CRP levels on OPU day had a negative effect on embryo quality (p = 0.056). CRP ≥ 0.5 mg/dL was associated with lower quality embryos (2.6 ± 0.3 vs. 3.3 ± 0.3; p = 0.04). High serum CRP level on OPU day negatively affects embryo quality.


ADAMTS13 and von Willebrand factor concentrations in patients with diabetes mellitus.
The von Willebrand factor (VWF) is elevated in patients with diabetes mellitus and degraded by a metalloprotease, ADAMTS13. We hypothesized that this elevation is due to a decreased function of ADAMTS13. Thus, we investigated ADAMTS13 in patients with diabetes mellitus without and with peripheral artery occlusive disease (PAOD). When treating the latter group with dalteparin, VWF is reported to increase significantly, and we therefore measured ADAMTS13 also in these patients. VWF antigen and ADAMTS13 antigen and activity concentrations were measured in patients with diabetes mellitus but without PAOD (diabetes mellitus; n = 23) and with diabetes mellitus and PAOD (diabetes mellitus + PAOD; n = 65) before and after treatment with dalteparin or placebo. In the diabetes mellitus group, concentration of VWF antigen was significantly higher, whereas that of ADAMTS13 activity was significantly lower than in the healthy controls. In the diabetes mellitus along with PAOD group, VWF antigen was significantly higher, but ADAMTS13 antigen or activity did not differ significantly from those of healthy controls. The ADAMTS13 activity/antigen ratio was lower than in controls only in the diabetes mellitus patient group. VWF antigen increased significantly during dalteraprin treatment, whereas ADAMTS13 activity and antigen remained unchanged. Only patients with diabetes mellitus had significantly lower concentrations of ADAMTS13 activity in plasma than controls, although the diabetes mellitus along with PAOD had a more pronounced VWF antigen elevation than diabetes mellitus patients, illustrating a possible link between ADAMTS13 and microangiopathy in diabetes mellitus patients. The increase in VWF antigen concentration during treatment with dalteparin does not seem to be due to changes in ADAMTS13.


High-dose naproxen aggravates pancreatic fibrosis in a rat model of chronic pancreatitis.
: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for the treatment of pain in chronic pancreatitis (CP). This study aimed to investigate the effect of NSAIDs on the inflammation and fibrosis progression in trinitrobenzene sulfonic acid-induced CP rats. Chronic pancreatitis was induced by trinitrobenzene sulfonic acid infusion into rat pancreatic ducts. Naproxen treatment (20 and 40 mg/kg per os [PO] and intraperitoneally) started 2 weeks after the induction of CP for 3 weeks. Histological analysis of the pancreas, Van Gieson staining, and contents of hydroxyproline were used to evaluate pancreatic damage and fibrosis. Furthermore, the effect of naproxen on nociceptive reflective behaviors and serum tumor necrosis factor alpha concentration were studied, and immunohistochemical analysis of alpha-smooth muscle actin in the pancreas was performed. Pancreatic collagen content and alpha-smooth muscle actin expression were higher in the CP group treated with high-dose (40 mg/kg PO) naproxen (P < 0.05). High-dose naproxen administered orally aggravated pancreatic fibrosis and inflammation (P < 0.05). Instead of playing an analgesic role, high-dose naproxen decreased the thermal withdrawal latencies in CP rats (P < 0.05). High-dose naproxen treatment (40 mg/kg PO) aggravated pancreatic fibrosis in CP rats and played an algogenic role that suggests the potential risk of long-term use of NSAIDs as analgesic in clinical practice with CP.


Material Dimensionality Effects on Electron Transfer Rates Between CsPbBr3 and CdSe Nanoparticles.
Films containing mixtures of zero- or two-dimensional nanostructures (quantum dots or nanoplatelets) were prepared in order to investigate the impacts of dimensionality on electronic interactions. Electron transfer from CsPbBr3 to CdSe was observed in all of the mixtures, regardless of particle dimensionality, and characterized via both static and transient absorption and photoluminescence spectroscopies. We find that mixtures containing nanoplatelets as the electron acceptor (CdSe) undergo charge transfer more rapidly than those containing quantum dots. We believe the faster charge transfer observed with nanoplatelets may arise from the extended spatial area of the CdSe nanoplatelets and/or the continuous density of acceptor states that are present in nanoplatelets. These results bolster the use of one- or two-dimensional nanomaterials in the place of zero-dimensional quantum dots in the design of related optoelectronic devices such as solar cells, light-emitting diodes, and photocatalysts and further offer the prospect of fewer required hopping events to transport carriers due to the larger spatial extent of the particles.


Ventilation/Perfusion SPECT lung scintigraphy and computed tomography pulmonary angiography in patients with clinical suspicion of pulmonary embolism.
The aim was to compare ventilation/perfusion SPECT lung scintigraphy (V/Q-SPECT) and computed tomography pulmonary angiography (CTPA) in patients with suspicion of pulmonary embolism (PE). This prospectively designed study included 53 patients with intermediate or high clinical probability of PE. A V/Q-SPECT and CTPA was performed on all patients. The V/Q-SPECT was interpreted according to the European Association of Nuclear Medicine and Molecular Imaging (EANMMI) guidelines. CTPA was reported as positive, negative, or indeterminate. CTPA was positive in 22 cases, negative in 28, and indeterminate in 3. V/Q-SPECT was positive in 27 cases, negative in 24, and non-diagnostic in 2. In the 22 with positive CTPA, V/Q-SPECT was positive in 18, negative in 3, and non-diagnostic in 1. In the 28 with negative CTPA, V/Q-SPECT was positive in 8, negative in 19, and non-diagnostic in 1. In the 3 with indeterminate CTPA, V/Q-SPECT was positive in 1 and negative in 2. In the 2 non-diagnostic cases V/Q-SPECT, CTPA was positive in 1 and negative in one. In the 10 high clinical probabilities, CTPA and V/Q-SPECT were positive in 7, negative in 2, and in 1, CTPA was positive and V/Q-SPECT negative. In the 38 intermediate probability group, CTPA and V/Q-SPECT were positive in 11, negative in 17, with CTPA negative and V/Q-SPECT positive in 8, and in 2 CTPA was positive and V/Q-SPECT negative. The results show that V/Q-SPECT detected PE in 5 patients more than CTPA. Our results show a 77% concordance of both techniques. Overall V/Q-SPECT detected PE in 18% more patients than CTPA in the intermediate group. Both techniques have a complementary role when a diagnosis cannot be made with one of them.


Phosphorus-doped ordered mesoporous carbons with different lengths as efficient metal-free electrocatalysts for oxygen reduction reaction in alkaline media.
Phosphorus-doped ordered mesoporous carbons (POMCs) with different lengths were synthesized using a metal-free nanocasting method of SBA-15 mesoporous silica with different sizes as template and triphenylphosphine and phenol as phosphorus and carbon sources, respectively. The resultant POMC with a small amount of P doping is demonstrated as a metal-free electrode with excellent electrocatalytic activity for oxygen reduction reaction (ORR), coupled with much enhanced stability and alcohol tolerance compared to those of platinum via four-electron pathway in alkaline medium. Interestingly, the POMC with short channel length is found to have superior electrochemical performances compared to those with longer sizes.


When hearing aids go bad: an FM success story.
Both clinical and research findings support the effectiveness of frequency-modulated (FM) technology among individuals who continue to encounter significant communication problems despite the use of conventional hearing instruments. The use rate of FM devices throughout the nation, however, remains disappointingly low. The authors present a case of a longtime hearing aid user whose hearing aids provided decreasing benefit as his hearing impairment increased to the extent that cochlear implantation was considered. Through the establishment of patient-specific treatment goals, the provision of appropriate FM technology as verified through real-ear measurements, and careful and deliberate counseling and follow-up, this patient was able to realize significant communication benefits as reported through several self-assessment measures. The cost-benefit implications of FM technology versus cochlear implantation are discussed.


Demand characteristics and self-report measures of imaginary audience sensitivity: implications for interpreting age differences in adolescent egocentrism.
Self-consciousness during early adolescence has been explained as an outcome of adolescent egocentrism, in which adolescents create an imaginary audience (IA) of attentive, critical peers. The possibility that such self-consciousness might result from contact with peers who are more attentive and critical than those encountered during childhood or adulthood has not been considered. Study 1 tested whether young adults, who are not theoretically susceptible to IA, could be made to receive high scores on IA and self-consciousness measures by having them complete a procedure in 1 of 3 laboratory conditions-a critical audience, a noncritical audience, or no audience. However, participants in the critical-audience condition received significantly lower IA and self-consciousness scores than participants in the no-audience condition did. Study 2 tested whether the directions given to Study 1 participants might have been responsible for the unexpected findings. Results indicated that participants instructed to give mature-sounding responses received lower IA/self-consciousness scores than did those asked to report their honest opinions. Together, the results of Studies 1 and 2 indicated that survey measures of IA are subject to demand characteristics and highlighted the need to interpret with caution age differences in IA as traditionally assessed.


Homocysteine and nitric oxide in patients undergoing diagnostic coronary angiography.
We evaluated the plasma homocysteine (tHcy) and nitric oxide metabolites (nitrite plus nitrate; NOx) data of consecutive patients undergoing diagnostic coronary angiography (n=79) with respect to the presence and severity of coronary artery disease (CAD), the presence of acute coronary syndromes (ACS), and the risk status of patients. Hyperhomocysteinemia (>15 micromol/L) was detected in 11% of the controls (n=19) and 37% of CAD patients (n=60) (p=0.03). Plasma tHcy in CAD patients was not significantly different from controls, but those with 3-vessel disease had a significantly higher tHcy concentrations than did controls (p=0.049). The patients with 3-vessel disease and ACS had the highest concentrations of tHcy (16.9 +- 4.4 micromol/L), and the difference from the ACS patients with 1- and 2-vessel involvement was significant (p=0.03). In patients with 1-vessel involvement, tHcy was correlated with NOx (r=0.62, p=0.005); in patients with 2- and 3-vessel disease this correlation could not be observed. The high-risk patients (n=51) had a higher mean number of vessel involvement and tHcy (p<0.001, p<0.05, respectively) but lower NOx (p<0.05) when compared to the low-risk patients (n=28). It appears that in the early stages of atherosclerosis hyperhomocysteinemia causes an increase in NOx production, but with progression of the disease this compensatory increase disappears.


Synthesis of alpha-ketoglutaric acid by Yarrowia lipolytica yeast grown on ethanol.
The ability of yeast to synthesize alpha-ketoglutaric acid (KGA) from ethanol has been studied. Thiamine-auxotrophic yeasts of different genera and species may be able to produce KGA; the main condition of synthesis is growth limitation by thiamine. Using a model culture, mutant Yarrowia lipolytica N 1, the principal conditions affecting KGA oversynthesis were identified. These were: thiamine concentration in medium and in cells, nitrogen and oxygen concentration in medium, and pH level. A KGA concentration of 49 g/l and a yield from ethanol consumed of 42% were achieved. Based on the results of the analysis of the activities of the key enzymes participating in ethanol metabolism and KGA synthesis, a concept of the mechanism of KGA biosynthesis by Y. lipolytica yeast is suggested and discussed.