Asymmetric Hydrogenation of Tetrasubstituted Cyclic Enones to Chiral Cycloalkanols with Three Contiguous Stereocenters.
A highly efficient iridium-catalyzed asymmetric hydrogenation of tetrasubstituted cyclic enones has been developed for the enantioselective synthesis of chiral cycloalkanols with three contiguous stereocenters. The C═O and C═C bonds of the enone substrates were hydrogenated sequentially in one pot with excellent enantioselectivity (92 to >99% ee) and diastereoselectivity (dr 95:5 to >99:1). The reaction provided a practical approach to all of the stereoisomers of the antiulcer drug rosaprostol.


From Meso to Macro: Controlling Hierarchical Porosity in Supraparticle Powders.
A drying droplet containing colloidal particles can consolidate into a spherical assembly called a supraparticle. Such supraparticles are inherently porous due to the spaces between the constituent primary particles. Here, the emergent, hierarchical porosity in spray-dried supraparticles is tailored via three distinct strategies acting at different length scales. First, mesopores (<10 nm) are introduced via the primary particles. Second, the interstitial pores are tuned from the meso- (35 nm) to the macro scale (250 nm) by controlling the primary particle size. Third, defined macropores (>100 nm) are introduced via templating polymer particles, which can be selectively removed by calcination. Combining all three strategies creates hierarchical supraparticles with fully tailored pore size distributions. Moreover, another level of the hierarchy is added by fabricating supra-supraparticles, using the supraparticles themselves as building blocks, which provide additional pores with micrometer dimensions. The interconnectivity of the pore networks within all supraparticle types is investigated via detailed textural and tomographic analysis. This work provides a versatile toolbox for designing porous materials with precisely tunable, hierarchical porosity from the meso- (3 nm) to the macroscale (≈10 µm) that can be utilized for applications in catalysis, chromatography, or adsorption.


Immunochemical studies of the mannans of Saccharomyces cerevisiae X2180-1A-5 and Saccharomyces cerevisiae 4484-24D-1 mutant strains, with special reference to their phosphate content.
The mannans from Saccharomyces cerevisiae mutant strains X2180-1A-5 and 4484-24D-1, both of which were shown to contain small amounts of phosphate (less than 0.2%), were fractionated on a column of diethylaminoethyl-Sephadex into five subfractions designated as fractions I to V. These subfractions contain different amounts of phosphate, ranging from 0.03 to 0.09 (strain X2180-1A-5) and from 0.01 to 0.17% (strain 4484-24D-1). Fractions I to IV from strain X2180-1A-5 showed nearly identical precipitin activities against the homologous anti-whole cell serum, whereas fraction V, containing the largest amount of phosphate and protein among this mannan subfraction series, showed unexpectedly weaker precipitin activity than those of the other fractions. A synthetic mannan consisting or consecutive alpha-1 leads to 6-linked D-mannopyranosyl residues was found to be cross-reactive with all the mannan subfractions of strain X2180-1A-5 against anti-X2180-1A-5 serum. On the other hand, antibody-precipitating activities of the mannan subfractions of the latter strain were proportional to their phosphate content, although the increments of precipitated antibody nitrogen among the subfractions were quite small. However, fraction V of this mannan subfraction series, containing the largest amounts of phosphate and protein, showed lower precipitin activity than did the other four fractions. These findings indicate that mannans containing no phosphate or relatively small amounts of phosphate, such as those investigated in the present study, are less heterogeneous in the densities of the branching moieties than are highly phosphorylated mannans. These findings suggest that the transfer step of mannosyl-1-phosphate into the precursor(s) of the wild-type strain mannans during the biosynthetic process corresponds to the key reaction responsible for the anionic heterogeneity due to the density heterogeneity of the antigenic determinants.


Isolation and characterization of a developmentally regulated homeobox sequence in the Mexican axolotl Ambystoma mexicanum.
A homeobox-containing genomic DNA fragment was isolated from the Mexican axolotl. This clone was obtained from a partial genomic library enriched for sequences that cross-hybridized with the Drosophila Antp homeobox under low stringency hybridization conditions. DNA sequence analysis revealed that this sequence (Ahox1) was 66% homologous to the Antp homeobox sequence and was most closely related to the mouse Hox-1.6 (84% identity) and Drosophila lab (79% identity) homeobox sequences. Several cross-hybridizing fragments to Ahox1 were detected in both mouse and axolotl genomic DNA. This sequence was also shown to be conserved in other Ambystoma species. Northern blot analysis revealed that genes containing this sequence are developmentally regulated. Transcripts hybridizing to the Ahox1 homeobox probe were detected during the neurula and tail bud stages of development.


Ultra-processed foods and the limits of product reformulation.
The nutritional reformulation of processed food and beverage products has been promoted as an important means of addressing the nutritional imbalances in contemporary dietary patterns. The focus of most reformulation policies is the reduction in quantities of nutrients-to-limit - Na, free sugars, SFA, trans-fatty acids and total energy. The present commentary examines the limitations of what we refer to as 'nutrients-to-limit reformulation' policies and practices, particularly when applied to ultra-processed foods and drink products. Beyond these nutrients-to-limit, there are a range of other potentially harmful processed and industrially produced ingredients used in the production of ultra-processed products that are not usually removed during reformulation. The sources of nutrients-to-limit in these products may be replaced with other highly processed ingredients and additives, rather than with whole or minimally processed foods. Reformulation policies may also legitimise current levels of consumption of ultra-processed products in high-income countries and increased levels of consumption in emerging markets in the global South.


HIV in Singapore--past, present, and future.
The first case of HIV infection in Singapore was reported in 1985. Between 1991 and 1998, the number of reported cases of HIV and AIDS increased rapidly before stabilizing from 1999. The epidemiology of the AIDS epidemic in Singapore is characterized by a predominance of male cases (seven to one) and heterosexual transmission. A multipronged control program comprising public education and education of high-risk groups, legislation, protection of the national blood supply, management of cases, and epidemiological surveillance has been put in place. The promotion of condom use among local sex workers has been fairly successful, with very low rates of HIV and other sexually transmitted infections (STIs). However, freelance and potential indirect sex workers such as masseuses and lounge hostesses are a concern in view of their higher prevalence of HIV and STIs. Another concern is the high proportion of cases who are diagnosed only when they develop AIDS. A better understanding of sexual networks among men who have sex with men will enable more effective intervention programs for this group. Fresh innovative approaches are needed to encourage safe sex practices and early screening.


Impact of nutritional status on peritonitis in CAPD patients.
To determine the impact of nutritional status on peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) in a developing country. 56 patients with end-stage renal disease on CAPD were randomly selected for this study. These patients were assessed for nutritional status and peritonitis episodes. Nutritional parameters were assessed by anthropometry, diet, body mass index (BMI), Nutritional Risk Index (NRI), serum albumin level, and Subjective Global Assessment (SGA). Based on SGA, patients were categorized into either group 1 (malnutrition, n = 31) or group 2 (normal nutritional status, n = 25). Peritonitis was considered the primary outcome and was compared between the two groups. Demographic profiles, Kt/V, creatinine clearance, and mean follow-up of the two groups were similar. Number of peritonitis episodes was significantly higher in patients with malnutrition (25/31) compared to patients with normal nutritional status (4/25) (p = 0.001). Mean peritonitis rate per patient per year was also significantly higher in patients with malnutrition (0.99 +/- 1.07) compared to patients with normal nutritional status (0.18 +/- 0.42) (p = 0.007). On univariate analysis, malnutrition based on SGA (p = 0.009), NRI (p = 0.02), serum albumin level (p = 0.005), and calorie intake (p = 0.006) was a significant predictor of peritonitis. On multivariate Cox regression analysis, only SGA (p = 0.001, odds ratio 0.08, 95% confidence interval 0.02-0.36) was found to be a significant predictor of peritonitis. On general linear model, the observed power of prediction of peritonitis was 0.96 based on SGA. On Kaplan-Meier survival analysis, peritonitis-free survival in patients with normal nutrition (42 months) was significantly higher compared to patients with malnutrition (21 months) based on SGA (log rank p = 0.003). We conclude that peritonitis rate is high in patients with malnutrition and that malnutrition indices, especially SGA, can predict the peritonitis rate in CAPD patients.


Cerebrospinal fluid cytology in histiocytic proliferative disorders.
Morphologically atypical histiocytes were observed in the cerebrospinal fluid (CSF) of five patients with histiocytic proliferative disorders, including one each classified as Letterer-Siwe disease and Hand-Schüller-Christian disease and three as malignant histiocytosis. In all of these patients except the one with Letterer-Siwe disease, neurologic examination, CSF leukocyte count and protein and glucose concentrations were normal. Necropsy studies in the three fatal cases (one patient with Letterer-Siwe disease and two with malignant histiocytosis) demonstrated leptomeningeal involvement by atypical histiocytes in all three and brain involvement in the patient with Letterer-Siwe disease. These observations suggest that cytologic examination of CSF is warranted in patients with histiocytic proliferative disorders and may be reliable in documenting central nervous system, particularly leptomeningeal, involvement. The atypicality of the histiocytes in the CSF, however, was not indicative of the classification of the histiocytic proliferative disorder. Because the patient with Hand-Schüller-Christian disease continues to have a normal neurologic examination seven years after abnormal histiocytes were initially detected in his CSF, we believe that the clinical condition of the patient and classification of the histiocytic proliferative disorder are of primary importance for initiating aggressive therapy directed at the central nervous system.


Pancreatic procarboxypeptidases: oligomeric structures and activation processes revisited.
The activation peptides of procarboxypeptidases of the A1 type act in a post-activation mechanism of control, limiting the expression of activity immediately after the limited proteolysis has occurred. This effect is due to structural complementarity between the enzymatic moiety and the released fragments, and is further enhanced by the occurrence of procarboxypeptidase A1 in oligomeric complexes of different type depending on the species studied. In those complexes, the activation segment has an important role in the stabilisation of the quaternary structure. The relationship between oligomeric structure and activation is reviewed here for two of the most extensively studied systems.


The effectiveness of spinal and systemic morphine on rat dorsal horn neuronal responses in the spinal nerve ligation model of neuropathic pain.
The treatment of pain arising from nerve injury can be difficult and the opioid sensitivity of neuropathic pain remains debatable. Clinical and animal studies report a wide range in the effectiveness of morphine, ranging from inadequate to potent analgesia. In this electrophysiological study we compare the effectiveness of spinal versus systemic administration of morphine on the natural and electrically evoked responses of spinal neurones of rats with a selective spinal nerve (L5/6) ligation. Recordings were made 1 week and/or 2 weeks after ligation. We have also compared the effects of morphine, by the two routes, on normal and sham operated animals. In spinal nerve ligated rats, morphine (0.1-5 microg) administered via the intrathecal route produced greater dose-dependent inhibitions of the neuronal responses compared with those produced by the systemic route (1-6 mg/kg). The dose response curves for intrathecal morphine on the C-fibre evoked and noxious natural stimuli evoked neuronal responses (mechanical and thermal) of spinal nerve ligated rats were to the left of those of sham operated and normal rats, suggesting an enhanced potency of intrathecal morphine after nerve injury. This was clearest for the lower doses of the opioid. The effects of spinal morphine on the responses to low intensity stimuli were similar in all groups of rats. In contrast to the spinal route, systemic morphine was less effective in inhibiting the evoked neuronal responses of spinal nerve ligated rats. This was especially clear for the C-fibre evoked and noxious natural stimuli evoked responses (mechanical and thermal) of spine nerve ligated rats. Our results suggest that the effectiveness of morphine may be partly related to the timing of the treatment relative to the duration of the neuropathy, the route of administration and also the neuropathic symptom. Spinal opioids may be a useful approach to pain control in neuropathic pain states where systemic routes produce inadequate analgesia.


Low-loss plasmonic supermodes in graphene multilayers.
We investigate the supermodes in arbitrary layers of graphene sheets, which are collective guided modes formed by coupling of surface plasmon polaritons (SPPs) in each graphene sheet. In terms of the dispersion relation, we analyse the effective indexes and mode profiles of the supermodes. Numerical simulations reveal that the supermodes can be well approximated by linear superposition of SPPs in individual graphene sheets. Among all the possible supermodes, there is an interesting one possessing both lowest propagation loss and shortest mode wavelength. The loss of the supermode decreases as the number of layers increases and saturates at about 5 layers. The graphene multilayers may find potential applications in low-loss plasmonic waveguides and so constructed optical devices.


A convenient reagent for the conversion of aldoximes into nitriles and isonitriles.
For the dehydroxylation of aldoximes with 4-nitro-1-((trifluoromethyl)sulfonyl)-imidazole (NTSI), slight modifications of reaction conditions resulted in significantly different reaction paths to provide either nitriles or isonitriles. The challenging conversion of aldoximes into isonitriles was achieved under mild conditions.


Evaluation of common elbow pathologies: a focus on physical examination.
Elbow tendinopathy accounts for the majority of elbow pathology in patients presenting to upper extremity and sports medicine surgeons. With increased participation in overhead sports in an aging population, the incidence of elbow injuries has risen. A comprehensive knowledge of elbow anatomy and biomechanical function of the elbow complex is prerequisite in the assessment of patients with elbow injuries; however, a thorough understanding of alternative and confounding pathologies is essential for accurate diagnosis. Because tendinopathy, tendonitis, and tendon tears have an anatomic basis for their pathology, a targeted history and meticulous physical examination often yields an accurate clinical diagnosis. The importance of physical examination and provocative examination maneuvers must be stressed in a technologically advanced era where clinical diagnosis is too commonly attained solely by advanced imaging modalities. A revived dedication to the physical examination may enhance our ability to correctly diagnose various pathologies about the elbow. Early and accurate clinical diagnosis is the first step in the proper initiation of treatment modalities and improvement in overall patient outcome.


Australian Aboriginal people and Torres Strait Islanders have an atherogenic lipid profile that is characterised by low HDL-cholesterol level and small LDL particles.
To characterise lipid profiles for Australian Aboriginal people and Torres Strait Islanders. Community-based, cross-sectional surveys in 1995-1997 including: 407 female and 322 male Australian Aboriginal people and 207 female and 186 male Torres Strait Islanders over 15 years old. A comparator of 78 female (44 with diabetes) and 148 male (73 with diabetes) non-indigenous participants recruited to clinical epidemiological studies was used. Lipids were determined by standard assays and LDL diameter by gradient gel electrophoresis. Diabetes prevalence was 14.8% and 22.6% among Aboriginal people and Torres Strait Islanders, respectively. LDL size (mean [95% CI (confidence interval)]) was smaller (P<0.05) in non-diabetic Aboriginal (26.02 [25.96-26.07] nm) and Torres Strait Islander women (26.01 [25.92-26.09] nm) than in non-diabetic non-indigenous women (26.29 [26.13-26.44] nm). LDL size correlated (P<0.0005) inversely with triglyceride, WHR, and fasting insulin and positively with HDL-cholesterol. HDL-cholesterol (mean [95% CI] mmol/L) was lower (P<0.0005) in indigenous Australians than in non-indigenous subjects, independent of age, sex, diabetes, WHR, insulin, triglyceride, and LDL size: Aboriginal (non-diabetic women, 0.86 [0.84-0.88]; diabetic women, 0.76 [0.72-0.80]; non-diabetic men, 0.79 [0.76-0.81]; diabetic men, 0.76 [0.71-0.82]); Torres Strait Islander (non-diabetic women, 1.00 [0.95-1.04]; diabetic women, 0.89 [0.83-0.96]; non-diabetic men, 1.00 [0.95-1.04]; diabetic men, 0.87 [0.79-0.96]); non-indigenous (non-diabetic women, 1.49 [1.33-1.67]; diabetic women, 1.12 [1.03-1.21]; non-diabetic men, 1.18 [1.11-1.25]; diabetic men, 1.05 [0.98-1.12]). Indigenous Australians have a dyslipidaemia which includes small LDL and very low HDL-cholesterol levels. The dyslipidaemia was equally severe in both genders. Strategies aimed at increasing HDL-cholesterol and LDL size may reduce high CVD risk for indigenous populations.


Vitreous floaters.
Floaters are a common presenting ophthalmic symptom that may accompany sight-threatening disorders. In most cases, they are often secondary to benign, degenerative changes in the vitreous. In this review, we briefly examine the anatomy of the vitreous and describe how degenerative vitreous change contributes to the development of floaters. The causality of floaters in the presence and absence of a posterior vitreous detachment is reviewed, as is the clinical significance of these symptoms and signs in relation to their predictive value for determining the presence of sight-threatening retinal tears and/or detachment. Finally, a brief review of management options for debilitating floaters is presented.


[Ossification of the posterior longitudinal ligament (OPLL) and the ligamentum flavum (OLF)].
The adult population is frequently sustained with ossification of the posterior longitudinal ligament (OPLL) and/or the ligamentum flavum (OLF) of the spine and the diseases may subsequently result is serious spinal cord insult with profound paralysis of the extremities. These pathologies are genetically denoted metaplasia of the elastic fibers of the ligament with consequent ectopic ossification process. The spinal cord is chronically compressed and will result in profound motor paralysis with sensory deficit. Both diseases are well imaged on CT and MRI, showing a various magnitude of spinal cord compression.


Concomitant upregulation of nuclear factor-kB activity, proinflammatory cytokines and ICAM-1 in the injured brain after cortical contusion trauma in a rat model.
Nuclear factor kappa B (NF-kB), proinflammatory cytokines and intercellular adhesion molecule 1 (ICAM-1) are frequently upregulated in the injured brain after traumatic brain injury (TBI). However, the temporal pattern of upregulation is not well defined. The current study was undertaken to investigate the temporal profile of the expression of NF-kB, proinflammatory cytokines and ICAM-1 in the injured brain after cortical contusion trauma of the rat brain. A rat model of cortical contusion was produced by a free-falling weight on the exposed dura of right parietal lobe. The rats were randomly divided into control group and TBI groups at hours 3, 12, 24 and 72, and on day 7. NF-kB binding activity in the surrounding brain of injured area was studied by electrophoretic mobility shift assay (EMSA). The levels of TNF-alpha and IL-6 were detected using ELISA and ICAM-1 expression studied by immunohistochemistry. The data were analyzed by one-way ANOVA followed by Student-Newman-Keuls post hoc test. Relation between variables was analyzed using bivariate correlation with two-tailed test. Compared with that of control group, NF-kB binding activity in the injured brain was significantly increased through 12 h and 7 days postinjury, with the maximum at 72 h. The concentrations of TNF-alpha and IL-6 in the injured brain were significantly increased from 3 h to 7 days and maximal at 24 h postinjury. The number of ICAM-1 immunostained microvessels was significantly increased in the injured brain from 24 h to 7 days postinjury, with its peak at 72 h. Concomitant upregulation of TNF-alpha, IL-6, ICAM-1 and the cytokine mediators NF-kB in the injured brain was observed in the injured brain after cortical contusion, and there was a highly positive relation among these variables. Cortical contusion trauma could induce a concomitant and persistent upregulation of NF-kB binding activity, TNF-alpha, IL-6 and ICAM-1 in the injured rat brain which might play a central role in the injury-induced immune response of brain.


[Description and evaluation of diagnostic measures in German-language clinical journals].
A literature study was performed in four German-language medical journals of 1985 and 1986 on the methodology of published diagnostic studies. A total of 93 papers was investigated. The results showed that fundamental requirements for the evaluation of diagnostic tests, such as blindness of judgement, were met only in 5% of the papers. In more than half of the publications the use of test parameters (sensitivity, specificity) was insufficient and the relationship between pretest and posttest probability was considered only in isolated cases. It is concluded that the methodologic criteria for the evaluation of diagnostic tests do not seem to be widely known and that a significant improvement is desirable.


Gene expression dynamics during bone healing and osseointegration.
Understanding the molecular features of bone repair and osseointegration may aid in the development of therapeutics to improve implant outcomes. The purpose of this investigation is to determine the gene expression dynamics during alveolar bone repair and implant osseointegration. An implant osseointegration preclinical animal model was used whereby maxillary defects were created at the time of oral implant placement, while a tooth extraction socket healing model was established on the contralateral side of each animal. The surrounding tissues in the zone of the healing defects were harvested during regeneration for temporal evaluation using histology, immunohistochemistry, laser capture microdissection, and quantitative reverse transcription-polymerase chain reaction for the identification of a panel of 17 putative genes associated with wound repair. In both models, three distinct expression patterns were displayed: 1) genes that are slowly increased during the healing process, such as bone morphogenetic protein 4, runt-related transcription factor 2, and osteocalcin; 2) genes that are upregulated at the early stage of healing and then downregulated at later stages, such as interleukin and chemokine (C-X-C motif) ligands 2 and 5; and 3) genes that are constitutively expressed over time, such as scleraxis. Although some similarities between osseointegration and tooth extraction socket were seen, distinct features developed and triggered a characteristic coordinated expression and orchestration of transcription factors, growth factors, extracellular matrix molecules, and chemokines. Characterization of these events contributes to a better understanding of cooperative molecular dynamics in alveolar bone healing, and highlights potential pathways that could be further explored for the enhancement of osseous regenerative strategies.


Dominant Salmonella Serovars in Australian Broiler Breeder Flocks and Hatcheries: a Longitudinal Study.
A longitudinal study was conducted to determine the dominance and prevalence of Salmonella enterica subsp in Australian broiler breeder flocks and hatcheries. Twenty-two flocks (n = 3339 samples) were sampled over 6 time points beginning at placement until week 40. Hatcheries (n = 274 samples) were sampled following removal of chicks hatched from eggs originating from the 22 donor parent flocks. The percent of positive flocks (36%) and frequency of positive samples (15.6%) were highest during rearing at week 7. The frequency of positive samples decreased over the 40 weeks; however, the number of positive flocks remained relatively consistent. Geographical location had a greater influence on Salmonella detection frequency than company sample origin, despite differing management and vaccination protocols within and between companies. Twelve serovars were detected in total. The predominant serovars during rearing were Salmonella Mbandaka (32%), S. Saintpaul (27%), and S. Liverpool (18%). The predominant serovars detected during production were S. Cubana (27%), S. Saintpaul (24%), and S. Havana (13%). Salmonella Typhimurium, S. Ohio, and S. Hessarek were detected in the hatcheries. Of the serovars detected, only S. Typhimurium and S. Ohio were found in both broiler breeder flocks and hatcheries. However, detection did not correspond to the status of the flock eggs feeding into the hatchery. This study provides an up-to-date capture of the current Salmonella serovars circulating in the broiler breeder industry. Continued surveillance within the Australian Chicken Meat industry is imperative to mitigate and reduce the risk of salmonellosis in the community related to chicken meat. IMPORTANCE This study identified prevalent and dominant Salmonella enterica subsp in Australian Broiler Breeder flocks, as well as in hatcheries post chick hatch and removal, from eggs originating from these donor parent flocks. The captured Salmonella data was further compared to the most common Salmonella serovars isolated from broilers, as well as human salmonellosis notification data, which is useful for consideration of the circulating serovars within the chicken meat industry and their significance in public health. As there are multiple entry points for Salmonella during the entire chicken meat production chain that can lead to carcass contamination, it is important to distinguish serovars present between the different stages of vertical integration to implement and enable Salmonella control strategies.


The ENTPD1 promoter polymorphism -860 A > G (rs3814159) is associated with increased gene transcription, protein expression, CD39/NTPDase1 enzymatic activity, and thromboembolism risk.
Ectonucleoside triphosphate diphosphohydrolase 1 (NTPDase1) degrades the purines ATP and ADP that are key regulators of inflammation and clotting. We hypothesized that NTPDase1 polymorphisms exist and that they regulate this pathway. We sequenced the ENTPD1 gene (encoding NTPDase1) in 216 subjects then assessed genotypes in 2 cohorts comprising 2213 humans to identify ENTPD1 polymorphisms associated with venous thromboembolism (VTE). The G allele of the intron 1 polymorphism rs3176891 was more common in VTE vs. controls (odds ratio 1.26-1.9); it did not affect RNA splicing, but it was in strong linkage disequilibrium with the G allele of the promoter polymorphism rs3814159, which increased transcriptional activity by 8-fold. Oligonucleotides containing the G allele of this promoter region bound nuclear extracts more avidly. Carriers of rs3176891 G had endothelial cells with increased NTPDase1 activity and protein expression, and had platelets with enhanced aggregation. Thus, the G allele of rs3176891 marks a haplotype associated with increased clotting and platelet aggregation attributable to a promoter variant associated with increased transcription, expression, and activity of NTPDase1. We term this gain-of-function phenotype observed with rs3814159 G "CD39 Denver."-Maloney, J. P., Branchford, B. R., Brodsky, G. L., Cosmic, M. S., Calabrese, D. W., Aquilante, C. L., Maloney, K. W., Gonzalez, J. R., Zhang, W., Moreau, K. L., Wiggins, K. L., Smith, N. L., Broeckel, U., Di Paola, J. The ENTPD1 promoter polymorphism -860 A > G (rs3814159) is associated with increased gene transcription, protein expression, CD39/NTPDase1 enzymatic activity, and thromboembolism risk.


Elevated serum levels of pancreatic secretory proteins in cigarette smokers after secretin stimulation.
The secretory pancreatic proteins in serum were analyzed in a group of cigarette smokers and a control group of nonsmokers before and after intravenous secretin stimulation. None of these persons had any signs of pancreatic disease. In the control group, serum total amylase activity, pancreatic isoamylase, cationic trypsinogen, and pancreatic secretory trypsin inhibitor concentrations varied within the normal range before and after secretin injection. In contrast, the concentrations of these pancreatic proteins in all the cigarette smokers elevated from normal to abnormally high serum concentrations after secretin stimulation. The results indicate a probable toxic effect of cigarette smoking on the exocrine pancreas.


Evaluation of the nutritional characteristics of a finger millet based complementary food.
Finger millet (Eleusine coracana), kidney beans (Phaseolus vulgaris), peanuts (Arachis hypogoea), and mango (Mangifera indica) were processed separately and then combined, on the basis of their amino acid scores and energy content, into a complementary food for children of weaning age. The finger millet and kidney beans were processed by germination, autoclaving, and lactic acid fermentation. A mixture containing, on a dry matter basis, 65.2, 19.1, 8.0, and 7.7% of the processed finger millet, kidney beans, peanuts, and mango, respectively, gave a composite protein with an in vitro protein digestibility of 90.2% and an amino acid chemical score of 0.84. This mixture had an energy density of 16.3 kJ.g(-1) of dry matter and a decreased antinutrient content and showed a measurable improvement in the in vitro extractability for calcium, iron, and zinc. A 33% (w/v) pap made from a mix of the processed ingredients had an energy density of 5.4 kJ.g(-1) of pap, which is sufficient to meet the energy requirements of well-nourished children of 6-24 months of age at three servings a day and at the FAO average breast-feeding frequency.


Effective factors on brace compliance in idiopathic scoliosis: a literature review.
Objectives: Compliance plays a major role in the success of brace treatment and is influenced by factors such as the kind of brace, measurements method, regimen for brace wear, pattern wearing at night/day or full/part time and another factor is also psychological condition of the wearer. The objective of this review is to assess affecting factors on compliance of spinal braces in idiopathic scoliosis.Materials and methods: The guideline of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) was used for conducting review and assessing the quality of evidence. The search in Pubmed databases had 175 results of which 17 articles met the inclusion criteria. Effective factors on compliance were extracted and categorized into six groups based on type of brace, measurement method, age, day/night time pattern wearing, full/part time wearing and psychological aspect that can improve the result of spinal brace treatment in idiopathic scoliosis.Results: The results demonstrated that the type of braces determines structure and appearance and affects compliance. Psychological aspects, age, brace wear pattern (daytime or nighttime or part-time versus fulltime) and the assessment method (using temperature versus pressure sensors) can affect recorded compliance.Conclusions: Compliance can be augmented by considering factors in the design and delivery of the brace. Superior appearance and comfortable within the brace can improve psychological acceptance and improve the compliance. Lower age, involving the patient in treatment procedure, considering the child habits, and improved family awareness of the treatment plan of idiopathic scoliosis can also improve overall compliance of the brace.Implications for rehabilitationThis article reviews factors that affect compliance with orthotic treatment in idiopathic scoiliosis.


Therapy of calcium oxalate urolithiasis in a rhesus macaque (Macaca mulatta).
A rhesus macaque (Macaca mulatta) was presented for anuria. Examination revealed calcium oxalate concrements in the bladder. A cystotomy was performed, and a therapy with alfuzosin was conducted. Over 1 year after the treatment, the rhesus macaque had not shown any more signs of stranguria. This is the first case reporting the successful treatment of urolithiasis in a rhesus macaque.


The genetic basis of pectoralis major myopathies in modern broiler chicken lines.
This is the first report providing estimates of the genetic basis of breast muscle myopathies (BMM) and their relationship with growth and yield in broiler chickens. In addition, this paper addresses the hypothesis that genetic selection for increase breast yield has contributed to the onset of BMM. Data were analyzed from ongoing recording of BMM within the Aviagen breeding program. This study focused on three BMM: deep pectoral myopathy (DPM; binary trait), white striping (WS; 4 categories) and wooden breast (WB; 3 categories). Data from two purebred commercial broiler lines (A and B) were utilized providing greater than 40,000 meat quality records per line. The difference in selection history between these two lines has resulted in contrasting breast yield (BY): 29% for Line A and 21% for Line B. Data were analyzed to estimate genetic parameters using a multivariate animal model including six traits: body weight (BW), processing body weight (PW), BY, DPM, WB, and WS, in addition to the appropriate fixed effects and permanent environmental effect of the dam. Results indicate similar patterns of heritability and genetic correlations for the two lines. Heritabilities (h2) of BW, PW and BY ranged from 0.271-0.418; for DPM and WB h2<0.1; and for WS h2≤0.338. Genetic correlations between the BMM and BW, PW, or BY were ≤0.132 in Line A and ≤0.248 in Line B. This paper demonstrates the polygenic nature of these traits and the low genetic relationships with BW, PW, and BY, which facilitates genetic improvement across all traits in a balanced breeding program. It also highlights the importance of understanding the environmental and/or management factors that contribute greater than 65% of the variance in the incidence of white striping of breast muscle and more than 90% of the variance of the incidence of wooden breast and deep pectoral myopathy in broiler chickens.


Patients' perspective of a group intervention for perfectionism in anorexia nervosa: A qualitative study.
This study aimed to explore the experiences of adults with anorexia nervosa who took part in a perfectionism group intervention in an inpatient setting. Thematic analysis was used to explore patient feedback collected in focus groups. Patient feedback was generally positive and centred around three main themes: perceived benefits of the group, the content of the group and suggested improvements. The findings suggest that a brief perfectionism group intervention is an acceptable treatment with a range of perceived benefits for patients with severe anorexia nervosa. Understanding patients' experiences of the intervention can provide further important information to maximise therapeutic impact of the group in inpatient settings.


Graphene quantum-dot-doped polypyrrole counter electrode for high-performance dye-sensitized solar cells.
Herein graphene quantum dot (GQD), a graphene material with lateral dimension less than 100 nm, is explored to dope PPy on F-doped tin oxide glass as an efficient counter electrode for high-performance dye-sensitized solar cells (DSSCs). The GQDs-doped PPy film has a porous structure in comparison to the densely structured plain PPy, and displays higher catalytic current density and lower charge transfer resistance than the latter toward I3(-)/I(-) redox reaction. The highest power conversion efficiency (5.27%) for DSSCs is achieved with PPy doped with10% GQDs, which is comparable to that of Pt counter electrode-based DSSCs. This work provides an inexpensive alternative to replace platinum for DSSCs.


Albuminuria-Related Genetic Biomarkers: Replication and Predictive Evaluation in Individuals with and without Diabetes from the UK Biobank.
Increased albuminuria indicates underlying glomerular pathology and is associated with worse renal disease outcomes, especially in diabetic kidney disease. Many single nucleotide polymorphisms (SNPs), associated with albuminuria, could be potentially useful to construct polygenic risk scores (PRSs) for kidney disease. We investigated the diagnostic accuracy of SNPs, previously associated with albuminuria-related traits, on albuminuria and renal injury in the UK Biobank population, with a particular interest in diabetes. Multivariable logistic regression was used to evaluate the influence of 91 SNPs on urine albumin-to-creatinine ratio (UACR)-related traits and kidney damage (any pathology indicating renal injury), stratifying by diabetes. Weighted PRSs for microalbuminuria and UACR from previous studies were used to calculate the area under the receiver operating characteristic curve (AUROC). CUBN-rs1801239 and DDR1-rs116772905 were associated with all the UACR-derived phenotypes, in both the overall and non-diabetic cohorts, but not with kidney damage. Several SNPs demonstrated different effects in individuals with diabetes compared to those without. SNPs did not improve the AUROC over currently used clinical variables. Many SNPs are associated with UACR or renal injury, suggesting a role in kidney dysfunction, dependent on the presence of diabetes in some cases. However, individual SNPs or PRSs did not improve the diagnostic accuracy for albuminuria or renal injury compared to standard clinical variables.


Dynamic analysis of the light scattered by the non-equilibrium fluctuations of a ternary mixture of polystyrene-toluene-n-hexane.
Dynamic analysis of the light scattered by non-equilibrium fluctuations in a thermodiffusion experiment has been performed on a sample of polystyrene-toluene-n -hexane, at 0.9-49.55-49.55% mass fraction. Time decays of the non-equilibrium fluctuations have been obtained revealing the accurate detectability of three modes. The slowest mode has been attributed to the mass diffusion of the polymer into the binary solvent; the intermediate one to mass diffusion of the two molecular components of the solvent; finally, the fastest one has been attributed to the thermal diffusivity of the overall mixture. The two eigenvalues of the mass diffusion matrix have been evaluated with accuracy in the order of 1%. Neglecting cross-diffusion effects we obtain a simplified expression for the relative amplitude of the two mass diffusion modes, allowing a parameterized determination of polystyrene and toluene Soret coefficients in the ternary mixture. We suggest that a two wavelength shadowgraph experiment is needed for a complete determination of all the coefficients.


Role of mTOR signalling in the control of translation initiation and elongation by nutrients.
Protein synthesis requires nutrients both as precursors (amino acids) and as a source of energy, since this process consumes a high proportion of cellular metabolic energy. Recent work has shown that both types of nutrients directly influence the activities of components of the translational machinery in mammalian cells. Amino acids positively regulate signalling through the mammalian target of the rapamycin (mTOR) pathway, although the degree of dependency on external amino acids varies between cell types. mTOR signalling modulates several key components involved in mRNA translation, in particular (via repressor proteins) the cap-binding initiation factor eIF4E, the ribosomal protein S6 kinases, and elongation factor eEF2. The branched-chain amino acid leucine is the most effective one in most cell types. It is currently unclear how mammalian cells sense prevailing amino acid levels, although this may involve intracellular amino acids. Cellular ATP levels can also influence mTOR activity. The activities of some translation factors are modulated by mTOR-independent mechanisms. Examples include the regulation of eEF2 by cellular energy levels, which may be controlled via the AMP-activated protein kinase, and the activity of the guanine nucleotide-exchange factor eIF2B, which is modulated by amino acids and metabolic fuels.


Immunohistochemical analysis of effects of cyclosporin A on gingival epithelium.
Cyclosporin A (CSA)-induced gingival overgrowth was immunohistochemically compared with that phenytoin-induced and nonspecific inflammatory gingiva, and CSA concentration was determined for dental plaque. Leu-6+ epithelial dendric cells (EDC) were found to significantly decrease in number in CSA-induced gingival overgrowth, while the ratio of HLA-DR+ EDC to Leu-6+ EDC did not change significantly. The expression of class II major histocompatibility complex antigens, such as HLA-DR, -DP and -DQ on keratinocytes did not change by CSA-treatment. Leu-4+ mononuclear cells in CSA-induced gingival overgrowth were located primarily in the connective tissue far outside the epithelium. CSA concentration was much higher in dental plaque than in blood and other tissues. Immune response thus appears to be suppressed in the epithelial layer of CSA-induced gingival overgrowth through decrease in Leu-6+ HLA-DR+ EDC and T cell infiltration, both due to CSA in dental plaque. DNA polymerase alpha was detected in much fewer basal keratinocytes of CSA- and phenytoin-induced gingival overgrowth. Epithelial hyperplasia may thus be not due to increased keratinocyte proliferation, but rather to enhanced keratinocyte life span.


Effects of a vildagliptin/metformin combination on markers of atherosclerosis, thrombosis, and inflammation in diabetic patients with coronary artery disease.
Diabetic patients present with an accelerated atherosclerotic process and an increased risk for future cardiovascular events. In addition to the risk imposed by the disease itself, pharmacological treatment adds also a sizable risk, especially if certain classes of antidiabetic drugs are employed. Animal evidence indicates that dipeptidyl peptidase-4 inhibitors have anti-atherosclerotic effects, yet clinical data are scarcely available. We plan to prospectively investigate the effects of dipeptidyl peptidase-4 inhibition with vildagliptin on a number of atherothrombotic markers and adipokines in patients with proven atherosclerosis and type 2 diabetes. The selected markers are: interleukin-6, high sensitivity C reactive protein, interleukin 1-beta, total adiponectin levels, matrix metallo-proteinase 9 and platelet reactivity testing. Sixty eligible patients will be randomized in a 2:1 ratio to vildagliptin/metformin or metformin only treatment, for a 3-month duration treatment. Blood sampling for the proposed investigations will be taken at enrollment and immediately after completion of the study period. Demonstrating antiatherothrombotic properties of dipeptidyl peptidase-4 inhibitors on proven markers is of substantial clinical significance. Coupled with their proven good safety profile these findings could translate into a significant clinical benefit.


Herbal Compound "Songyou Yin" Renders Hepatocellular Carcinoma Sensitive to Oxaliplatin through Inhibition of Stemness.
We investigated the effect of Chinese herbal compound Song-you Yin on HCC stemness. MHCC97H and Hep3B cell lines were pretreated with SYY for 4 weeks, and their chemosensitivity to oxaliplatin was evaluated. The expression of CSC-related markers, cell invasion and migration, and colony formation were also examined. SYY-treated orthotopic nude mouse models of human HCC were developed to explore the effect of oxaliplatin on tumor growth, metastasis, and survival. The CSC-related molecular changes in vivo were also evaluated. The result showed that MHCC97H and Hep3B cells pretreated with SYY showed significantly increased chemosensitivity to oxaliplatin and the downregulation of CSC-related markers CD90, CD24, and EPCAM. SYY also attenuated cell motility, invasion, and colony formation in MHCC97H and Hep3B cell lines. The reduced tumorigenicity and pulmonary metastasis were observed in SYY-pretreated cell lines. Combination treatment with oxaliplatin and SYY significantly reduced tumor volume and pulmonary metastasis and prolonged survival compared with oxaliplatin treatment alone. Immunohistochemical analysis showed reduced expression of CD90, ABCG2, ALDH, CD44, EPCAM, vimentin, and MMP-9 and increased the expression of E-cadherin, in HCC cells following combination treatment. These data clearly demonstrate that SYY renders hepatocellular carcinoma sensitive to oxaliplatin through the inhibition of stemness.


The 677C>T (rs1801133) polymorphism in the MTHFR gene contributes to colorectal cancer risk: a meta-analysis based on 71 research studies.
The 677C>T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene is considered to have a significant effect on colorectal cancer susceptibility, but the results are inconsistent. In order to investigate the association between the MTHFR 677C>T polymorphism and the risk of colorectal cancer, a meta-analysis was held based on 71 published studies. Eligible studies were identified through searching the MEDLINE, EMBASE, PubMed, Web of Science, Chinese Biomedical Literature database (CBM) and CNKI database. Odds ratios (OR) and 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with x(2)-based Q-test. Begg's and Egger's test were also carried out to evaluate publication bias. Sensitive and subgroup analysis were also held in this meta-analysis. Overall, 71 publications including 31,572 cases and 44,066 controls were identified. The MTHFR 677 C>T variant genotypes are significantly associated with increased risk of colorectal cancer. In the stratified analysis by ethnicity, significantly increased risks were also found among Caucasians for CC vs TT (OR=1.076; 95%CI= 1.008-1.150; I(2) =52.3%), CT vs TT (OR=1.102; 95%CI=1.032-1.177; I(2) =51.4%) and dominant model (OR=1.086; 95%CI=1.021-1.156; I(2) =53.6%). Asians for CC vs TT (OR =1.226; 95%CI =1.116-1.346; I(2) =55.3%), CT vs TT (OR =1.180; 95%CI =1.079-1.291; I(2) =36.2%), recessive (OR =1.069; 95%CI =1.003-1.140; I(2) =30.9%) and dominant model (OR =1.198; 95%CI =1.101-1.303; I(2) =52.4%), and Mixed populations for CT vs TT (OR =1.142; 95%CI =1.005-1.296; I(2) =0.0%). However, no associations were found in Africans for all genetic models. This meta-analysis suggests that the MTHFR 677C>T polymorphism increases the risk for developing colorectal cancer, while there is no association among Africans found in subgroup analysis by ethnicity.


Mixture Modeling of 2-D Gel Electrophoresis Spots Enhances the Performance of Spot Detection.
2-D gel electrophoresis is the most commonly used method in biomedicine to separate even thousands of proteins in a complex sample on a single gel. Even though the technique is quite known, there is still a need to find an efficient and reliable method for detection of protein spots on gel image. In this paper, a three-step algorithm based on mixture of 2-D normal distribution functions is introduced to improve the efficiency of spot detection performed by the existing algorithms, namely Pinnacle software and watershed segmentation method. Comparison of methods is based on using simulated and real data sets with known true spot positions and different number of spots. Fitting a mixture of components to gel image allows for achieving higher sensitivity in detecting spots, regardless the method used to find initial conditions for the model parameters, and it leads to better overall performance of spot detection. By using mixture model, location of spot centers can be estimated with higher accuracy than using the Pinnacle method. An application of spot shape modeling gives higher sensitivity of obtaining low-intensity spots than the watershed method, which is crucial in the discovery of novel biomarkers.


Gradient Nanostructured Tantalum by Thermal-Mechanical Ultrasonic Impact Energy.
Microstructural evolution and wear performance of Tantalum (Ta) treated by ultrasonic nanocrystalline surface modification (UNSM) at 25 and 1000 °C were reported. The UNSM treatment modified a surface along with subsurface layer with a thickness in the range of 20 to 150 µm, which depends on the UNSM treatment temperature, via the surface severe plastic deformation (S²PD) method. The cross-sectional microstructure of the specimens was observed by electron backscattered diffraction (EBSD) in order to confirm the microstructural alteration in terms of effective depth and refined grain size. The surface hardness measurement results, including depth profile, revealed that the hardness of the UNSM-treated specimens at both temperatures was increased in comparison with those of the untreated ones. The increase in UNSM treatment temperature led to a further increase in hardness. Moreover, both the UNSM-treated specimens with an increased hardness resulted in a higher resistance to wear in comparison with those of the untreated ones under dry conditions. The increase in hardness and induced compressive residual stress that depend on the formation of severe plastically deformed layer with the refined nano-grains are responsible for the enhancement in wear resistance. The findings of this study may be implemented in response to various industries that are related to strength improvement and wear enhancement issues of Ta.


Restrictive bare stent prevents distal stent graft-induced new entry in endovascular repair of type B aortic dissection.
Distal stent graft-induced new entry (SINE) can occur after thoracic endovascular aortic repair (TEVAR) of type B aortic dissection. This study investigated the mechanism of distal SINE and its prevention using a restrictive bare stent (RBS) technique. From January 2013 to December 2014, 68 consecutive type B aortic dissection patients received endovascular repair at our center. The RBS technique was used with distal oversizing (between the diameter of the thoracic stent graft and the descending aorta true lumen diameter at the level of the intended distal edge of the thoracic stent graft) >20%. Twenty-three patients received TEVAR with a single thoracic stent graft (TEVAR group, n = 23); the rest received TEVAR combined with the RBS technique (TEVAR + RBS group, n = 45). Four distal SINEs occurred in the TEVAR group. Distal oversizing (69.7% ± 35.5% vs 31.2% ± 24.5%; P = .005) and expansion mismatch ratio (132.2% ± 16.9% vs 106.5% ± 11.6%; P < .05) were significantly higher in the SINE patients. Compared with standard TEVAR, TEVAR + RBS was associated with significantly lower distal oversizing (TEVAR vs TEVAR + RBS group, 59.8% ± 24.7% vs 16.7% ± 7.6%; P < .05), lower expansion mismatch ratio (113.8% ± 14.6% vs 103.8% ± 11.7%; P = .012), and lower distal SINE rate (4/23 [17.4%] vs 0/45 [0%]; P = .011). Compared with the TEVAR group, the false lumen was reduced significantly at the level of the RBS distal edge (P = .029). Excessive distal oversizing and distal expansion mismatch ratio may contribute to the occurrence of distal SINE. The RBS technique reduced the incidence of distal SINE. Based on our midterm and long-term observations, implantation of an RBS may improve aortic remodeling.


Transcriptional responses of Medicago truncatula upon sulfur deficiency stress and arbuscular mycorrhizal symbiosis.
Sulfur plays an essential role in plants' growth and development and in their response to various abiotic and biotic stresses despite its leachability and its very low abundance in the only form that plant roots can uptake (sulfate). It is part of amino acids, glutathione (GSH), thiols of proteins and peptides, membrane sulfolipids, cell walls and secondary products, so reduced availability can drastically alter plant growth and development. The nutritional benefits of symbiotic interactions can help the plant in case of S deficiency. In particular the arbuscular mycorrhizal (AM) interaction improves N, P, and S plant nutrition, but the mechanisms behind these exchanges are not fully known yet. Although the transcriptional changes in the leguminous model plant Medicago truncatula have been already assessed in several biotic and/or abiotic conditions, S deficiency has not been considered so far. The aim of this work is to get a first overview on S-deficiency responses in the leaf and root tissues of plants interacting with the AM fungus Rhizophagus irregularis. Several hundred genes displayed significantly different transcript accumulation levels. Annotation and GO ID association were used to identify biological processes and molecular functions affected by sulfur starvation. Beside the beneficial effects of AM interaction, plants were greatly affected by the nutritional status, showing various differences in their transcriptomic footprints. Several pathways in which S plays an important role appeared to be differentially affected according to mycorrhizal status, with a generally reduced responsiveness to S deficiency in mycorrhized plants.


Content-specific network analysis of peer-to-peer communication in an online community for smoking cessation.
Analysis of user interactions in online communities could improve our understanding of health-related behaviors and inform the design of technological solutions that support behavior change. However, to achieve this we would need methods that provide granular perspective, yet are scalable. In this paper, we present a methodology for high-throughput semantic and network analysis of large social media datasets, combining semi-automated text categorization with social network analytics. We apply this method to derive content-specific network visualizations of 16,492 user interactions in an online community for smoking cessation. Performance of the categorization system was reasonable (average F-measure of 0.74, with system-rater reliability approaching rater-rater reliability). The resulting semantically specific network analysis of user interactions reveals content- and behavior-specific network topologies. Implications for socio-behavioral health and wellness platforms are also discussed.


Pretreatment levels of serum alkaline phosphatase are associated with the prognosis of patients with non‑small cell lung cancer receiving immune checkpoint inhibitors.
Immune checkpoint inhibitors (ICIs) have been an encouraging treatment method in non-small cell lung cancer (NSCLC). However, bone and liver metastases are considered to restrain immunotherapy efficacy. Since serum alkaline phosphatase (ALP) is associated with bone and liver metastases, it was investigated whether serum ALP could be a novel biomarker to predict the efficacy of ICIs treatment. In the present study, 143 patients with NSCLC receiving ICIs treatment were retrospectively analyzed. The objective response rate (ORR) was compared between the ALP high and low groups, bone metastasis and non-bone metastasis groups, and liver metastasis or non-liver metastasis groups. The associations between clinical characteristics, including ALP level, bone or liver metastasis and median progression-free survival (mPFS) time were analyzed by univariate and multivariate Cox regression analysis. It was found that bone metastasis was associated with a lower ORR (24 vs. 43%; P<0.05) and shorter mPFS (10.2 vs. 17.3 months; P=0.010) in patients with NSCLC receiving ICIs. Liver metastasis was associated with lower ORR (22 vs. 38%; P<0.05), but not with mPFS (P=0.119). The ALP level was higher in patients with bone or liver metastasis than in those without (119.6 or 103.6 vs. 83.3 U/l, respectively; P<0.05). Higher ALP levels were also associated with bone or liver metastasis, lower ORR (20 vs. 39%; P<0.05) and shorter mPFS (8.5 vs. 15.4 months; P=0.009). Cox regression analysis demonstrated that ALP was an independent prognostic indicator of mPFS (hazard ratio, 1.856; 95% confidence interval, 1.030-3.343; P=0.040). In conclusion, pretreatment levels of serum ALP might be a predictive indicator of clinical outcome in patients with NSCLC after ICIs treatment.


Physiological and psychological responses to 100 km cross-country skiing during 2 days.
Physical exercise can have beneficial as well as detrimental effects on body tissues. The purpose of this study was to examine how the body responds to a 2-day 100 km ski event. Two-day follow-up, field trial to measure changes in body mass, postural response of heart rate, pain perception, range of joint movement, muscle circumferences, vertical jump, creatine kinase (CK) and profile of mood state to repeated long distance cross-country skiing during 2 days. 10 physically active men (34.8+/-9.7 y, 1.82+/-0.05 m, 76.1+/-6.6 kg, BMI: 23.0+/-1.5. kgxm-2) participating in the Finlandia Ski Race, covering a total distance of 100 km during 2 days. Cardiorespiratory loading was high (over 85% of the maximal heart rate). However, leg measurements showed no signs of edema or a decline in flexibility or functional strength. SUBJECTS with excellent aerobic fitness are able to ski at high intensity a total of 100 km over 2 successive days without any major adverse effects on the musculoskeletal system or mood state.


Cardiovascular responses to progressive cycle exercise in healthy children and adults.
The aim of this study was to compare resting, relative submaximal (at the same percentage of maximal oxygen uptake) and maximal cardiovascular responses to progressive cycle exercise in pre-pubertal children and young adults with similar aerobic aptitude. Fourteen healthy children (7 girls and 7 boys) with a mean age of 10.8 yr and 16 healthy young adults (8 women and 8 men) with a mean age of 22.4 yr underwent a progressive cycle test until exhaustion with estimation of stroke volume and cardiac output by Doppler echocardiography. Submaximal responses were evaluated at similar exercise intensities (around 40, 60 and 80 % of maximal oxygen uptake). Mean submaximal and maximal oxygen uptake were not significantly different between the children and the adults. As expected, the adults demonstrated larger absolute values of stroke volume and cardiac output at all levels of intensity but when related to body surface area, the differences disappeared. The relationships between cardiac output and oxygen uptake calculated from comparable submaximal intensities were similar (slopes and intercepts) in the children and the adults. According to these results, it seems that the lower cardiovascular responses to exercise in children may be attributed to their smaller heart size.


Antiapoptotic cytokine IL-3 + SCF + FLT3L influence on proliferation of gamma-irradiated AC133+/CD34+ progenitor cells.
Recovery from radiation-induced bone marrow aplasia depends on appropriate cytokine support. The aim of our work was to find a cytokine combination allowing in vitro gamma-irradiated (2.5 Gy) CD34+/AC133+ haematopoietic stem cells to evade radiation-induced apoptosis and to enhance damage reparation, which should enable proliferation and ex vivo expansion of cells. Cells were isolated using separation in a Cobe separator followed by immunomagnetic selection by antibody against the AC133 antigen. Thus isolated cells were 80% AC133+/CD34+ and 10% of them expressed the CD33+ antigen. Ten thousand of AC133+ cells formed 1146 CFU-GM and 304 BFU-E. We proved a high expansion efficiency of cytokine combination SCF + IL-3 + FLT3L in comparison with the combination SCF + IL-3 + IL-11 in both, non-irradiated cells and cells irradiated with a dose of 2.5 Gy. The D0 value for AC133+ cells was determined by the clonogeneity test. The D0 value for CFU-GM was estimated to be 1.08 Gy and for BFU-E 0.95 Gy. The results of DNA analysis showed that the majority of isolated AC133+ cells were in G0/G1 phase of the cell cycle. We proved that the dose of 2.5 Gy induced massive apoptosis (80%) of these cells without progression through the cell cycle, which indicates interphase cell death. Under the influence of cytokine combination (SCF + IL-3 + FLT3L), the surviving 20% of cells entered the cell cycle and, similarly to non-irradiated control cells, on 7th day 35% of cells were in S phase.


Mutation site specificity of N-nitroso-N-methyl-N-alpha-acetoxybenzylamine: a model derivative of an esophageal carcinogen.
A total of 171 mutations induced by N-nitroso-N-methyl-N-alpha-acetoxybenzylamine within the first 180 base pairs of the lacI gene of Escherichia coli were characterized at the DNA sequence level. Consistent with the methylating ability of this compound and the predicted mutagenic specificity of the O6-methylguanine lesion, all but two of these mutations were G:C----A:T transitions. An analysis of neighboring sequences revealed the same 5' flanking sequence influence on mutability reported for other SN1-type direct-acting alkylating agents. G:C----A:T transitions were found to be six times more likely to occur at G:C base pairs at which the guanine residues were flanked (5') by a purine than at those preceded by a pyrimidine. This mutagenic and site specificity appeared to be independent of the dose and likely reflects the behaviour of the activated parent carcinogen, N-nitroso-N-methyl-N-benzylamine in the esophagus.


Supernumerary derivative 22 chromosome resulting from novel constitutional non-Robertsonian translocation: t(20;22)-Case Report.
Maternal non-Robertsonian translocation-t(20;22)(q13;q11.2) between chromosomes 20 and 22resulting in an additional complex small supernumerary marker chromosome as derivative (22)inherited to the proband is not been reported yet. A 4 years old boy with a history of developmental delay, low set ears, and facial dysmorphism was presented to the genetic clinic. Periauricular pit, downward slanting eyes, medially flared eyebrows, downturned mouth corners, and micrognathia were observed. He had congenital heart defect with atrial septal defect (ASD), ventricular septal defect (VSD), and central nervous system (CNS) anomalies with the gross cranium. Karyotype analysis, Fluorescent in-situ hybridization analysis (FISH), and Chromosomal microarray analysis (CMA) were used to determine the chromosomal origin and segmental composition of the derivative 22 chromosome. Karyotype and FISH analyses were performed to confirm the presence of a supernumerary chromosome, and Microarray analysis was performed to rule out copy number variations in the proband's 22q11.2q12 band point. The probands' karyotype revealed the inherited der(22)t(20;22)(q13;q11.2)dmat. Parental karyotype confirmed the mother as the carrier, with balanced non-Robertsonian translocation-46,XX,t(20;22)(q13;q11.2). The mother had a non-Robertsonian translocation t(20;22)(q13;q11.2) between chromosomes 20 and 22, which resulted in Emanuel syndrome in the proband. The most plausible explanation is 3:1 meiotic malsegregation, which results in the child inheriting derivative chromosome. The parental karyotype study aided in identifying the carrier of the supernumerary der(22), allowing future pregnancies with abnormal offspring to be avoided.


Hyperactive children: a study of the content analysis of their speech.
A group of hyperactive boys with attention deficit disorder (DSM-III) (n = 13) was compared to a group of normative, nonhyperactive boys (n = 16) with respect to Gottschalk-Gleser scores derived from 5-min speech samples they produced in response to standardized and purposely ambiguous instructions. The hyperactive boys had significantly higher mean scores than the normative boys for cognitive impairment, social alienation-personal disorganization, and total depression. Of the eight depression subscales, the hyperactive boys had significantly elevated scores on hopelessness, self-accusation (a cluster composed of shame, guilt, and hostility inwards), and psychomotor retardation. Problems with the classification of the hyperactive syndrome, which is equated with the attention deficit disorder, are briefly discussed. The present study gives some support to the concept, as adjudged from the content analysis of verbal behavior, that hyperactivity, at least in boys, may be associated with cognitive impairment, increased general psychiatric morbidity, and depression. Whether single or multiple etiological factors are involved in this disorder cannot be ascertained from this study.


Comprehensive functional analysis of large lists of genes and proteins.
The interpretation of high dimensional datasets resulting from genomic and proteomic experiments in a timely and efficient manner is challenging. ClueGO software is a Cytoscape App that extracts representative functional biological information for large lists of genes or proteins. The functional enrichment analysis is based on the latest publicly available data from multiple annotation and ontology resources that can be automatically accessed through ClueGO. Predefined settings for the selection of the terms are provided to facilitate the analysis. Results are visualized as networks in which Gene Ontology (GO) terms and pathways are grouped based on their biological role. Many species are now supported by ClueGO and additional organisms are added on demand. ClueGO can be used together with the CluePedia App to enable the visualization of protein-protein interactions within or between pathways.


Biomonitoring of mercury and persistent organic pollutants in Michigan urban anglers and association with fish consumption.
The 32-mile Detroit River and surrounding tributaries have been designated as a Great Lakes Area of Concern due to pollution from decades of municipal and industrial discharges, sewer overflows and urban development. Key pollutants in fish samples from the Detroit River include mercury, polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), dioxins and furans. A biomonitoring study was conducted to assess exposures to these persistent toxic substances in Detroit urban shoreline anglers who may be at high exposure risk due to consumption of locally caught fish. Using a modified venue-based sampling approach, 287 adult shoreline anglers along the Detroit River were recruited and participated in the program. Study participants provided blood and urine specimens and completed a questionnaire following informed consent. We examined percentile estimates for total blood mercury, PCBs, DDE, and dioxin-like total toxic equivalency (TEQ) concentrations among study participants. Multiple linear regression was used to identify important predictors of contaminant concentrations. Participants consumed a median of 64 Detroit River caught fish meals in the past year. The Detroit urban anglers' median total blood mercury concentrations was 3.2 times higher than that for the general adult U.S. population. PCB concentrations among the Detroit anglers aged 18-39 years were higher than the U.S. population of the same race/ethnicity. Elevated levels of DDE and total TEQ concentrations were not observed in the cohort. Eating more locally caught fish was associated with higher total blood mercury and serum PCB concentrations. The biomonitoring data served to inform public health officials and help guide environmental public health actions to reduce harmful exposures.


Photostriction of CH3 NH3 PbBr3 Perovskite Crystals.
Organic-inorganic hybrid perovskite materials exhibit a variety of physical properties. Pronounced coupling between phonon, organic cations, and the inorganic framework suggest that these materials exhibit strong light-matter interactions. The photoinduced strain of CH3 NH3 PbBr3 is investigated using high-resolution and contactless in situ Raman spectroscopy. Under illumination, the material exhibits large blue shifts in its Raman spectra that indicate significant structural deformations (i.e., photostriction). From these shifts, the photostrictive coefficient of CH3 NH3 PbBr3 is calculated as 2.08 × 10-8 m2 W-1 at room temperature under visible light illumination. The significant photostriction of CH3 NH3 PbBr3 is attributed to a combination of the photovoltaic effect and translational symmetry loss of the molecular configuration via strong translation-rotation coupling. Unlike CH3 NH3 PbI3 , it is noted that the photostriction of CH3 NH3 PbBr3 is extremely stable, demonstrating no signs of optical decay for at least 30 d. These results suggest the potential of CH3 NH3 PbBr3 for applications in next-generation optical micro-electromechanical devices.


Scanning electron microscopy of the air bladder in the spotted gar, Lepisosteus occulatus.
The surface of the gar respiratory epithelium was examined by scanning electron microscopy. Nonciliated and ciliated cells constitute the epithelium. Puffs appear to be an unusual feature of the ciliated cells as well as nonciliated cells. There appears to be a transition from nonciliated to puff ciliated cells through a puff stage. The role of the cell types as related to oxygen available in the air bladder is discussed.


Catalyst- and Additive-free, Regioselective 1,6-Hydroarylation of para-Quinone Methides with Anilines in HFIP.
A simple and efficient method for the synthesis of diarylmethyl-functionalized anilines through the hexafluoroisopropanol (HFIP)-mediated regioselective 1,6-hydroarylation reaction of para-quinone methides (p-QMs) with anilines under catalyst- and additive-free conditions is reported. Various kinds of p-QMs and amines (e. g. primary, secondary and tertiary amines) are well tolerated in this transformation without the pre-protection of amino group, and the corresponding products could be generated with good to excellent yields and satisfactory regioselectivity under the optimized reaction conditions. In addition to adaptable amine compounds, indoles and their derivatives are also compatible with this reaction system. This transformation can be easily extended to a gram scale-synthesis level to synthesize the target product. Furthermore, it is worth noting that some complex small aniline molecules with biological activity can be selectively modified using this method. The possible reaction mechanism is proposed through the step-by-step control experiments and DFT calculations, showing that the key process for achieving the regioselective 1,6-hydroarylation of p-QMs is the hydrogen bonding effect of HFIP to substrates.


Mid-trimester ultrasound parameters for predicting birth weight in low risk pregnancies vs high-risk pregnancies complicated with pre-gestational diabetes mellitus.
The aim of the study was to assess the utility of mid-trimester ultrasound parameters in predicting birth weight in low-risk pregnancy and high-risk pregnancy complicated with pregestational diabetes mellitus. A study group comprised 97 healthy women and 160 women with pregestational diabetes (PGDM, type 1), all in singleton pregnancy. Ultrasound examination was performed between weeks 11 and 14, and in weeks 20 and 30 of gestation, based on recommendations of the Polish Society of Gynecologists and Obstetricians, Ultrasonography Division. We also checked uterine artery blood flow parameters. There is a correlation between the birth weight and ultrasound-ascertained parameters, including those characterising uterine artery blood flow and foetal biometry [abdominal circumference (AC), femoral length (FL), biparietal dimension (BPD)].The biparietal dimension (BPD), head circumference (HC) abdominal circumference (AC) and pre-existing diabetes are the ultrasound predictors of LGA. The presence of an early-diastolic uterine artery blood flow waveform notching, as well as the uterine artery pulsatility index (UAPI), femoral length (FL) and hypertension in pregnancy are the ultrasound predictors of SGA. In the subset of women with pre-gestational diabetes (PGDM), there is a negative correlation between the birth weight and the uterine artery pulsatility index and early-diastolic uterine artery blood flow waveform notching. In women with pre-gestational diabetes mellitus (PGDM), femoral length (FL) is a significant predictor of LGA and in case of SGA significant predictors are uterine artery pulsatility index, artery blood flow waveform notching and femoral length (FL). Midtrimester ultrasound parameters with confirmed usefulness in the prediction of birth weight in low-risk pregnancy and high-risk pregnancy complicated with pregestational diabetes mellitus include: uterine artery PI, early-diastolic uterine artery blood flow waveform notching and foetal biometry.


Health-Care Workers' Perspectives on Preparedness of Health-Care Facilities for Outbreak of Communicable Diseases in Nigeria: A Qualitative Study.
A high probability of another outbreak of communicable disease exists in sub-Saharan African countries, after the Ebola virus disease outbreak of 2014. Thus, health-care facility (HCF) preparedness for a prompt and effective response to disease outbreaks needs to be ascertained. In this study, Nigerian health-care workers' (HCWs) knowledge of preparedness, perception of the level of preparedness existing in these HCFs, militating factors, and possible ways to improve, were evaluated through qualitative data collection, using focus group discussion and in-depth interview. Among the 193 HCWs which participated in the study, the perception of 190 (98.4%) was that their HCFs were insufficiently equipped to respond to disease outbreaks. None of the facilities had an emergency operation unit (EOU). Most HCWs perceived preparedness as observation of universal precautions. Other aspects of preparedness, such as training, routine emergency drills, disease surveillance, waste management, and design and location of HCFs were minimally mentioned. None of the participants had undergone any form of emergency drill training. Among the suggestions of how to improve on preparedness were immunization of staff, improved inter-departmental communication within the HCF, and routine training. The overall poor level of preparedness which exists in the HCFs means that they cannot prevent or contain a communicable disease outbreak. There is a need to improve universal precautions, communication within the HCFs, and routine interpretation of surveillance data by epidemiologists. There is also a need for the establishment of EOU in every HCF, a system that responds to, and manages emergency response to disease outbreaks, which also must be functional during non-outbreak periods.


Revealing the mammalian lignan precursor secoisolariciresinol diglucoside in flax seed by ionspray mass spectrometry.
Ionspray mass spectrometry allowed the rapid detection and unambiguous identification of secoisolariciresinol diglucoside, an important mammalian lignan precursor occurring in flax seed. It was observed that this compound is embedded in a complex form, probably a complex glucoside of still undisclosed structure, among the polar solvent extractables of flax seed from which it could not be released as such without the intervention of alkaline methanolysis. Comparison of ionspray mass spectra of untreated and methanolysed flax-seed extracts confirmed methanolysis as the crucial step in setting up any further analytical or preparative procedure concerned with secoisolariciresinol diglucoside.


Release of biologically active fragments from human plasma-fibronectin by murine T cell-specific proteinase 1 (TSP-1).
We have studied the proteolytic activity of TSP-1, a tissue-specific serine proteinase expressed by activated murine T cells, on human plasma fibronectin and have investigated by affinity chromatography the biological activity of the polypeptides released after limited proteolysis. A Mr approximately 2.9 x 10(4) peptide bound to denatured collagen (gelatine) but not to heparin, a Mr approximately 3.0 x 10(4) fragment contained heparin-binding but not collagen-binding sites and a third Mr approximately 3.5 x 10(4) peptide did not express either of the two activities. All larger fragments - an array of five to six polypeptides with relative molecular masses between 15 x 10(4) and 19 x 10(4) - were bound to heparin-Sepharose but not to gelatine-Sepharose and could be eluted with high salt concentration. These data confirm recent results suggesting multiple, proteinase-resistant domains with discrete biological functions within fibronectins. The release of small, biologically active fibronectin fragments by TSP-1, an enzyme specifically released by activated T cells upon contact with antigen, suggests a role for this enzyme in the numerous cellular functions elicited by T lymphocytes in vivo.


Thoughts on an integrative approach to teach wellness within the context of a traditional science/bioengineering curriculum.
Engineers and scientists are valuable resources to society and might be referred to as human capital. Faculties are charged with protecting society's investment in human capital by developing competency-based curricula. These curricula primarily focus on technical skills to assure society that the trainees are competent to perform their job but frequently neglect to teach the competency of self-awareness. Lack of self-awareness contributes to poor stress management, increased incidence of job burnout, high health care costs associated with stress-related chronic diseases, and a loss of valuable human capital. In this paper Guiding Principles are presented for incorporating the concepts of self-awareness, stress management and wellness into existing curricula. The guiding principles aim to provide an evidence-based approach to wellness by including opportunities for self-assessments of physiological parameters such as posturography, heart rate variability, and immune stress markers.


[Psychotic disorders: special aspects in general practice].
In emergency situations the general practitioner is often the first professional contact psychotic patients have. The following article conveys basic knowledge about psychotic disorders and their clinical features typically seen in general practice.


Laparoscopic Roux-en-Y hepaticojejunostomy in children with long common pancreaticobiliary channel: surgical technique and functional outcome.
In patients with maljunction of pancreatic and common bile duct (CBD)-defined as a long common pancreaticobiliary channel (LCPC)-a resection of the CBD and a hepaticojejunostomy is recommended. To date, this operation is usually performed through an open approach. In this article, we report on our experience with minimally invasive surgery (MIS) for LCPC in children. From 2004 to 2008, 7 children underwent MIS for LCPC. Mean age at operation was 46 months. Two patients had a choledochal cyst (Todani type IV) additionally. Diagnosis was made preoperatively by magnetic resonance cholangiopancreaticography, in 5 children confirmed by endoscopic retrograde cholangio-pancreaticography. A four-trocar technique was used for the laparoscopic approach. Follow-up examinations included laboratory tests, ultrasound, and scintigraphy. A Roux-en-Y hepaticojejunostomy was performed in all patients-in 6 children completely by laparoscopy. In 1 child, the operation was converted to open after CBD diversion due to a large, vulnerable liver. In 2 children with extended choledochal cyst, additionally, a reconstruction of the separated hepatic ducts was performed. Reresection of a CBD stump was carried out by laparoscopy in another patient. A leakage of the anastomosis occurred in 1 child. The laparoscopic approach for pathology of pancreaticobiliary ducts might be a new alternative for surgical treatment in infants and children. It can also be performed in cases with choledochal cyst involving the hepatic ducts and for reresection of remnants of CBD.


A method for the preparation of cerebral blood vessels.
Elements of the cerebral vascular system of the rat have been prepared by simultaneous perfusion with fibrinogen and thrombin. The resulting fibrin fills and serves to support the vessels which can then easily be excised from the brain and prepared for light and electron microscopy. The structure and ultrastructure of cerebral blood vessels is well preserved by this technique.


Development of a Comprehensive Quality Evaluation System for Foxtail Millet from Different Ecological Regions.
Foxtail millet (Setaria italica L.) is a critical grain with high nutritional value and the potential for increased production in arid and semiarid regions. The foxtail millet value chain can be upgraded only by ensuring its comprehensive quality. Thus, samples were collected from different production areas in Shanxi province, China, and compared in terms of quality traits. We established a quality evaluation system utilizing multivariate statistical analysis. The results showed that the appearance, nutritional content, and culinary value of foxtail millet produced in different ecological regions varied substantially. Different values of amino acids (DVAACs), alkali digestion values (ADVs), and total flavone content (TFC) had the highest coefficients of variation (CVs) of 50.30%, 39.75%, and 35.39%, respectively. Based on this, a comprehensive quality evaluation system for foxtail millet was established, and the quality of foxtail millet produced in the five production areas was ranked in order from highest to lowest: Dingxiang > Zezhou > Qinxian > Xingxian > Yuci. In conclusion, the ecological conditions of Xinding Basin are favorable for ensuring the comprehensive quality of foxtail millet. .


A randomized, double-blind, three-arm, parallel group, single-dose phase I study to evaluate the pharmacokinetic similarity between SB12 (a proposed eculizumab biosimilar) and eculizumab (Soliris) in healthy subjects.
To compare the pharmacokinetics (PK), pharmacodynamics (PD), safety, and immunogenicity between SB12 (a proposed eculizumab biosimilar) and the reference product (RP) eculizumab (i.e., European Union (EU)-sourced Soliris and United States (US)-sourced Soliris). In this phase I study, healthy adult subjects were randomized to receive a 300-mg dose of SB12 or RP eculizumab via intravenous infusion. The PK endpoints were area under the serum concentration-time curve from time zero to infinity and to the last quantifiable concentration, and maximum serum concentration. Bioequivalence for the PK endpoints was determined if the 90% confidence intervals (CIs) for the ratio of geometric least squared means (Lsmeans) were within the pre-defined bioequivalence margins of 80.00 - 125.00%. PD, safety, and immunogenicity were also investigated. The 90% CIs of the geometric Lsmeans ratios of the PK endpoints were fully contained within the pre-defined bioequivalence margin. PD profiles and incidence of treatment-emergent adverse events across treatment groups were comparable. Incidence of anti-drug antibodies was also comparable between all groups, and a positive result for neutralizing antibodies was not detected. This study demonstrated PK bioequivalence and similar PD, safety, and immunogenicity profiles of SB12 to both reference eculizumab products.


TLR4 is the signaling but not the lipopolysaccharide uptake receptor.
TLR4 is the primary recognition molecule for inflammatory responses initiated by bacterial LPS (endotoxin). Internalization of endotoxin by various cell types is an important step for its removal and detoxification. Because of its role as an LPS-signaling receptor, TLR4 has been suggested to be involved in cellular LPS uptake as well. LPS uptake was investigated in primary monocytes and endothelial cells derived from TLR4 and CD14 knockout C57BL/6 mice using tritiated and fluorescein-labeled LPS. Intracellular LPS distribution was investigated by deconvolution confocal microscopy. We could not observe any difference in LPS uptake and intracellular LPS distribution in either monocytes or endothelial cells between TLR4(-/-) and wild-type cells. As expected, CD14(-/-) monocytes showed a highly impaired LPS uptake, confirming CD14-dependent uptake in monocytes. Upon longer incubation periods, the CD14-deficient monocytes mimicked the LPS uptake pattern of endothelial cells. Endothelial cell LPS uptake is slower than monocyte uptake, LBP rather than CD14 dependent, and sensitive to polyanionic polymers, which have been shown to block scavenger receptor-dependent uptake mechanisms. We conclude that TLR4 is not involved in cellular LPS uptake mechanisms. In membrane CD14-positive cells, LPS is predominantly taken up via CD14-mediated pathways, whereas in the CD14-negative endothelial cells, there is a role for scavenger receptor-dependent pathways.


Prostate cancer gene therapy and the role of radiation.
Even though prostate cancer is detected earlier than in the pre-PSA era, prostate cancer is the second leading cause of cancer mortality in the American male. Prostate cancer therapy is not ideal, especially for high-risk localized and metastatic cancer; therefore, investigators have sought new therapeutic modalities such as angiogenesis inhibitors, inhibitors of the cell signaling pathway, vaccines, and gene therapy. Gene therapy has emerged as potential therapy for both localized and systemic prostate cancer. Gene therapy has been shown to work supra-additively with radiation in controlling prostate cancer in vivo. With further technological advances in radiation therapy, gene therapy, and the understanding of prostate cancer biology, gene therapy will potentially have an important role in prostate cancer therapy.


Solvation forces on biomolecular structures: a comparison of explicit solvent and Poisson-Boltzmann models.
Continuum electrostatics methods have become increasingly popular due to their ability to provide approximate descriptions of solvation energies and forces without expensive sampling required by explicit solvent models. In particular, the Poisson-Boltzmann equation (PBE) provides electrostatic potentials, solvation energies, and forces by modeling the solvent as a featureless, dielectric material, and the mobile ions as a continuous distribution of charge. Polar solvation forces and energies obtained from the PBE are often supplemented with simple solvent-accessible surface area (SASA) models of nonpolar solvation. Given the recent development of methods that enable the use of PBE and SASA forces in molecular dynamics simulations, it is important to determine the ability of these implicit solvent models to accurately reproduce the solvation forces of more detailed explicit solvent simulations. In this article, we compare PBE and SASA solvation forces with explicit solvent forces for several snapshots from eight trajectories of static conformations of intestinal fatty acid binding protein. The results from this comparison show that current implementations of the PBE are capable of generating polar solvation forces that correlate well with explicit solvent forces but systematically overestimate the magnitude of the interaction. However, SASA-based nonpolar forces are found to have no significant correlation with nonpolar explicit solvent forces. Nevertheless, due to the small magnitude of the nonpolar forces in the current system, a good correlation is still obtained for total solvation forces. The good correlation of implicit solvent forces with more detailed explicit solvent models is encouraging and implies that the systematic errors identified in these models could be corrected by appropriate parameterization of the force fields.


Corticomedullary procollagen alpha1(IV) mRNA levels and localization after subtotal nephrectomy.
The relationships between tubular hypertrophy/hyperplasia, procollagen alpha1(IV) mRNA levels, and the development of tubular basement membrane thickening were studied in male Sprague-Dawley rats subjected to subtotal renal ablation and sacrificed 2 or 15 days later. Tubular hypertrophy and hyperplasia were demonstrable at 2 days, however no increment in procollagen alpha1 (IV) mRNA levels was discerned at that time, demonstrating a dissociation between mRNA levels for classical type IV collagen and tubular enlargement. At 15 days, tubular procollagen alpha1(IV) mRNA levels did increase approximately 2-fold (p < 0.002), localizing predominantly in proximal tubules in the deep cortex and outer medullary stripe. At this time point, there was still no significant correlation to tubular enlargement, but there was a significant correlation to tubular basement membrane thickening (r = 0.89, p < 0.01). These studies demonstrated that an increase in mRNA for classical type IV collagen is not required for the development of hypertrophy, and that the increment is a better marker for matrix expansion than it is for hypertrophy.


Movement of Tribolium castaneum (Coleoptera: Tenebrionidae) adults in response to temperature gradients in vertical and horizontal wheat and corn columns.
The movement and redistribution of adult Tribolium castaneum (Herbst) in stored grain provide important information for detection of insect pests and for simulations of their distribution in grain bins. Movement and redistribution of T. castaneum adults in 1 or 6 d and in wheat or corn were determined in a 100 by 100 by 1000-mm acrylic box with a 10 degrees C/m temperature gradient (from 20 to 30 degrees C) or at a uniform temperature (20, 25, and 30 degrees C). In a vertical corn column with a uniform temperature, approximately 15 and 25% of adults moved to the top or bottom section in 6 d, respectively; and < 30% of adults were recovered in 1-d movement in the middle two sections where insects were initially introduced. In a horizontal or vertical wheat column, > 90% of the adults were recovered in the two middle sections where insects were introduced after 6 d. Adults responded to the temperature gradient and preferred the warmer areas in both wheat and corn. The slower movement in wheat is probably caused by the small granular space in bulk wheat than in bulk corn.


Soundscapes and deep learning enable tracking biodiversity recovery in tropical forests.
Tropical forest recovery is fundamental to addressing the intertwined climate and biodiversity loss crises. While regenerating trees sequester carbon relatively quickly, the pace of biodiversity recovery remains contentious. Here, we use bioacoustics and metabarcoding to measure forest recovery post-agriculture in a global biodiversity hotspot in Ecuador. We show that the community composition, and not species richness, of vocalizing vertebrates identified by experts reflects the restoration gradient. Two automated measures - an acoustic index model and a bird community composition derived from an independently developed Convolutional Neural Network - correlated well with restoration (adj-R² = 0.62 and 0.69, respectively). Importantly, both measures reflected composition of non-vocalizing nocturnal insects identified via metabarcoding. We show that such automated monitoring tools, based on new technologies, can effectively monitor the success of forest recovery, using robust and reproducible data.


Patient-reported goal achievement after antimuscarinic treatment in patients with overactive bladder symptoms.
Standardised traditional outcome measures may fail to address factors that are important to patients and address irrelevant factors. Aim of this study was to assess patient-reported goals and goal achievement (GA) in the antimuscarinic treatment for overactive bladder (OAB) patients. Men and women aged ≥ 18 years with OAB symptoms were eligible for the study. Treatment began with a dose of 10 mg oxybutynin, to be increased if necessary to 30 mg. Before treatment, each patient's primary treatment goal was identified. After 12-week treatment, patients reported GA using a Likert scale from 0 (no achievement) to 5 (complete achievement). Successful achievement was defined as a score of 4 or 5. Traditional outcome measures including voiding diaries, the OAB questionnaire short form, patient perception of bladder condition, and treatment benefit and satisfaction were assessed. Baseline characteristics affecting GA and the correlation between GA and traditional outcome measures were evaluated. A total of 303 goals were identified from 303 patients (51 men, 252 women). Of those, 72.3% addressed symptom relief and frequency as the most common target symptom. Other goals addressed were improving quality of life (13.5%) and eliminating coping behaviours (14.2%). After treatment, 42% had a successful GA with a median score of 3 (interquartile range; 2-4). Age had a negative effect on GA. Goal achievement was the outcome measure most correlated with treatment benefit and satisfaction. Goal achievement can be a valuable outcome measure in OAB patients, addressing individual treatment goals and reflecting treatment benefit and patient satisfaction.


[Usefulness and safety of dobutamine stress thallium myocardial scintigraphy].
Pharmaceutical stress test is performed for diagnosis of coronary artery disease in patients who can not perform exercise test. We studied whether high dose dobutamine stress test is useful and safe. Subjects consisted of 133 patients (pts) in doubutamine stress test and 45 pts in exercise test. Dobutamine stress test was initiated by 10 micrograms/kg/min, followed by 10 micrograms/kg/min increment every 3 minutes. Maximal doubutamine dose was 40 micrograms/kg/min for 3 minutes. Endpoints of dobutamine stress were as follows: ST depression equal to or more than (> or =) 0.2 mV: 30 pts, > or = 75% predictive maximum heart rate: 20 pts, > or = 20 mmHg systolic blood pressure fallen: 10 pts, 40 micrograms/kg/min for 3 minutes: 10 pts, chest pain: 7 pts, pressure rate product (PRP) > or = 25,000: 1 patient. Side effects of dobutamine stress test were as follows: palpitation: 52%, arrhythmia: 13%, angina and dyspnea: 7%, headache: 6%. These symptoms were disappeared within 2 minutes. One patient, who performed dobutamine test 2 day after PTCA, had myocardial infarction. At peak of dobutamine stress test, systolic blood pressure, heart rate and PRP were increased similar to exercise test. However, diastolic blood pressure was not changed. The concentration at peak of dobutamine was 25.5 +/- 7.8 micrograms/kg/min. The duration of dobutamine stress test was 7.3 +/- 2.3 minutes. The 65 patients (49%) need more than 20 micrograms/kg/min of dobutamine which was maximal loading dose in previous reports. For diagnosis of coronary artery disease, sensitivity was 91% (31/34) and specificity was 70% (7/10). From these data, high dose dobutamine stress test is useful and relatively safe stress method for diagnosis of coronary disease. This stress test would be performed in patients who can not perform exercise test.


Connecting carbon nanotubes using Sn.
Process of Sn coating on mutiwalled carbon nanotubes (MWCNT) and formation of interconnections among nanotubes are studied using high resolution transmission electron microscopy (HRTEM) and energy dispersive X-ray spectroscopy (EDX). Surface oxidation of nanotubes during heating with HNO3 prior to the SnCl2 treatment and the bonding between functional groups and Sn are found to be responsible for the coating and its stability. Open nanotubes are filled as well as coated during tin chloride treatment. Coating and filling are converted into the coatings on the inner as well as outer walls of the nanotubes during reduction with H2/N2. EDX studies show the formation of intermetallic compounds e.g., Cu6Sn5 and Cu3Sn at the joints between nanotubes. Formation of intermetallic compounds is supposed to be responsible for providing the required strength for bending and twisting of nanotubes joining of nanotubes. Paper presents a detailed mechanism of coating and filling processes, and interconnections among nanotubes.


Variations in the Quality of Care at Large Public Hospitals in Beijing, China: A Condition-Based Outcome Approach.
Public hospitals deliver over ninety percent of all outpatient and inpatient services in China. Their quality is graded into three levels (A, B, and C) largely based on structural resources, but empirical evidence on the quality of process and outcome of care is extremely scarce. As expectations for quality care rise with higher living standards and cost of care, such evidence is urgently needed and vital to improve care and to inform future health reforms. We compiled and analyzed a multicenter database of over 4 million inpatient discharge summary records to provide a comprehensive assessment of the level and variations in clinical outcomes of hospitalization at 39 tertiary hospitals in Beijing. We assessed six outcome measures of clinical quality: in-hospital mortality rates (RSMR) for AMI, stroke, pneumonia and CABG, post-procedural complication rate (RS-CR), and failure-to-rescue rate (RS-FTR). The measures were adjusted for pre-admission patient case-mix using indirect standardization method with hierarchical linear mixed models. We found good overall quality with large variations by hospital and condition (mean/range, in %): RSMR-AMI: 6.23 (2.37-14.48), RSMR-stroke: 4.18 (3.58-4.44), RSMR-pneumonia: 7.78 (7.20-8.59), RSMR-CABG: 1.93 (1.55-2.23), RS-CR: 11.38 (9.9-12.88), and RS-FTR: 6.41 (5.17-7.58). Hospital grade was not significantly associated with any risk-adjusted outcome measures. Going to a higher grade public hospital does not always lead to better patient outcome because hospital grade only contains information about hospital structural resources. A hospital report card with some outcome measures of quality would provide valuable information to patients in choosing providers, and for regulators to identify gaps in health care quality. Reducing the variations in clinical practice and patient outcome should be a focus for policy makers in the next round of health sector reforms in China.