Epigenetic regulation of resistance to emotional stress: possible involvement of 5-HT1A receptor-mediated histone acetylation.
The ability to resist stress is an important defensive function of a living body. Thus, elucidation of the mechanisms by which the brain resists stress could help to pave the way for new therapeutic strategies for stress-related psychiatric disorders including depression. The present review focuses on the roles of brain 5-HT1A receptor-mediated epigenetic mechanisms in the development of resistance to emotional stress. Behavioral pharmacological studies have demonstrated that treatment with a 5-HT1A receptor agonist 24 h before testing suppressed the decrease in emotional behaviors induced by acute restraint stress. Studies with DNA microarray technology have revealed that histone deacetylase genes were decreased in the hippocampus of mice that had been pretreated with a 5-HT1A receptor agonist 24 h beforehand. This preliminary finding was supported by data that hippocampal acetylated histone H3 was increased in mice that had developed emotional resistance to acute restraint stress by 5-HT1A receptor agonist. Furthermore, the histone deacetylase inhibitor trichostatin A also protected against the emotional changes induced by acute restraint stress, accompanied by the induction of histone H3 acetylation. These findings suggest that epigenetic mechanisms that are functionally coupled with 5-HT1A receptors may play a key role in the development of resistance to emotional stress.


Cosmology Meets Functional QCD: First-Order Cosmic QCD Transition Induced by Large Lepton Asymmetries.
The lepton flavor asymmetries of the Universe are observationally almost unconstrained before the onset of neutrino oscillations. We calculate the cosmic trajectory during the cosmic QCD epoch in the presence of large lepton flavor asymmetries. By including QCD thermodynamic quantities derived from functional QCD methods in our calculation, our work reveals for the first time the possibility of a first-order cosmic QCD transition. We specify the required values of the lepton flavor asymmetries for which a first-order transition occurs for a number of different benchmark scenarios.


[Metastatic neoplasms of the heart].
Two cases are presented of metastatic neoplasm of the heart easy for echocardiographic diagnosis. One infiltrated the pericardium with encapsulated fluid (visible also on X-ray), and the other was associated with filling of the right atrial lumen.


The Exploitation Index: an early warning indicator of boundary violations in psychotherapy.
Exploitive behavior by therapists is highly disruptive in psychotherapy because it violates the sense of trust derived from a coherent treatment boundary. Such behavior may be difficult to detect because it is often associated with self-deception. The compensatory need to feel "special," a state of mind often associated with exploitiveness, suggests that narcissistic mechanisms play a significant role. The authors present an "Exploitation Index" (EI), a self-assessment questionnaire for therapists that is designed to serve as an early warning indicator of boundary violations.


Protein kinase stimulation of steroidogenesis in rat luteal cell mitochondria.
The regulatory role of cAMP-dependent protein kinase in steroidogenesis was examined in luteal cell mitochondria prepared from heavily luteinized prepubertal rat ovaries. The cAMP-dependent protein kinase, localized in luteal mitochondria, comprised 5.5% of the total cellular protein kinase activity (cAMP-dependent). Intact mitochondria supported by a suitable electron-donor substrate and inhibited by isoxazole converted cholesterol to a single steroid product, pregnenolone. Neither (Bu)2 cAMP nor a crude preparation of cytosolic protein kinase stimulated pregnenolone production from cholesterol when added to intact luteal cell mitochondria; however, mitochondria treated with 10 mM CaCl2 became responsive to both (Bu)2 cAMP and protein kinase by showing increased pregnenolone production. Likewise, the addition of cytosol protein kinase to incubations of cholesterol and crude cholesterol sidechain cleavage enzyme (cytochrome P-450cscc) isolated from luteal mitochondria, also stimulated pregnenolone production. Cholesterol-poor mitochondria, depleted of endogenous sterol by prolonged preincubation, when subsequently incubated with Ca+2 plus (Bu)2 cAMP and protein kinase showed significantly increased pregnenolone production. Conversely, mitochondria with greatly increased intramitochondrial cholesterol after preincubation with 200 microM cholesterol and a cytochrome P-450cscc inhibitor (aminoglutethimide) synthesized pregnenolone in significantly higher amounts than either normal or cholesterol-poor mitochondria after removal of the aminoglutethimide block. However, addition of (Bu)2cAMP or protein kinase to Ca+2-treated cholesterol-rich mitochondria failed to additionally stimulate pregnenolone synthesis. We conclude from these observations that the mitochondrial membrane normally excludes protein kinase and (Bu)2cAMP from any stimulatory action on cholesterol side-chain cleavage. Disruption of the mitochondrial membrane by high Ca+2 concentrations eliminates this barrier and permits (Bu)2cAMP and protein kinase stimulation of the CSCC enzyme system. The mechanism of stimulation is not clear. It could involve direct action on the CSCC enzyme. Alternatively, an increase in either intramitochondrial transport or binding of cholesterol substrate to the CSCC enzyme could be facilitated by protein kinase action. Direct stimulation of the enzyme by protein kinase seems less likely, since increased enzyme activity was not observed in the presence of high concentrations of intramitochondrial cholesterol substrate.


[The legitimacy of representation in forums with social participation: the case of the Bahia State Health Council, Brazil].
The electoral representation model is insufficient and inadequate for new participatory roles such as those played by members of health councils. This article analyzes representation and representativeness in the Bahia State Health Council, Brazil. The study included interviews with 20 current or former members of the State Health Council, analysis of the council minutes and bylaws, and observation of plenary meetings. Discourse analysis technique was used to analyze interventions by members. The article discusses the results in four analytical lines: the process by which various organizations name representatives to the Council; the relationship between Council members and their constituencies; interest representation in the Council; and criteria used by the plenary to take positions. The study reveals various problems with the representativeness of the Bahia State Health Council and discusses the peculiarities of representation in social participation forums and the characteristics that give legitimacy to representatives.


Emotion among women with psychopathy during picture perception.
Emotional reactions in women with psychopathy were examined in a mixed-picture paradigm using psychophysiological measures. Startle probes were presented at 2.0 or 4.5 s following onset of a 6-s picture presentation. At 2.0 s, nonpsychopaths exhibited the typical pattern of eyeblink reflex magnitude: unpleasant > neutral > pleasant. Psychopaths with high general levels of anxiety also exhibited this pattern. Psychopaths with lower anxiety exhibited attenuated reflex magnitudes during unpleasant pictures. Similarly, when focusing on psychopathy components, only individuals expressing high antisocial behavior and high emotional detachment exhibited smaller reflex magnitudes during unpleasant pictures. At 4.5 s, all groups exhibited normal, potentiated reflex magnitudes during unpleasant pictures. Group differences were not observed for other measures.


An ethno-botanical study of indigenous medicinal plants and their usage in rural valleys of Swabi and Hazara region of Pakistan.
An ethnobotanical study was conducted to document indigenous medicinal plants and their usage from knowledgeable and elderly persons in Razzar and Gadoon valley of Swabi and Allai and Tanawal valley of Hazara region of Pakistan during 2016-2019. Several systematic field visits and questionnaire surveys were carried out in selected sites of the study area to gather relevant information from the local community. Rapid assessment method was adopted for data collection by interviewing the local people having enough knowledge of medicinal plants use for treatment of different ailments. UV (UV) formula was applied to calculate the relative importance of medicinal plant species in each site of the study area. In the present study, 221 medicinal plants belonging to 105 families have been reported through 580 respondents (385 males, 138 females and 57 local health healer) from the Swabi and Hazara region. The main sources of herbal medicines were leaves (21%) followed by fruits (21%), seeds (17%), whole plants (14%), roots (9%), bark (9%), flowers (7%) and gum (2%). Mentha spicata L. and Berberis lycium Royle were reported with highest UV (UV) i.e. 0.92 and 0.68 in Razzar tehsil and Gadoon valley of Swabi, whereas Mentha longifolia L and Geranium wallichianum D were reported with highest UV i.e. (0.65) and (0.88) in Allai and Tanawal valley of Hazara region, respectively. It was concluded that Swabi and Hazara region is rich in medicinal plants species and associated traditional knowledge. Moreover, ethno-medicines have played significant role in the indigenous healthcare system of the study area. However, uprooting the entire plant for ethno-medicine is a big threat to conservation of medicinal plants diversity in the study area.


Pulsed Vacuum Drying of Pepper (Capsicum annuum L.): Effect of High-Humidity Hot Air Impingement Blanching Pretreatment on Drying Kinetics and Quality Attributes.
With a high moisture content, fresh peppers are perishable and rot easily. Drying is essential for shelf-life extension. The natural thin wax layer on the pepper surface hinders moisture transfer. Traditionally, chemical dipping or mechanical pricking is used to remove this wax layer. However, in chemical dipping, chemical residues can trigger food-safety issues, while the low efficiency of mechanical pricking hinders its industrial application. Feasible pretreatment methods are advantageous for industrial use. Here, an emerging pretreatment technique (high-humidity hot-air impingement blanching, HHAIB) was used for peppers before drying and its effects on drying characteristics, microstructure, and polyphenol oxidase (PPO) activity were explored. The impact of drying temperature on color parameters and red pigment content of pulsed-vacuum-dried peppers was also evaluated. PPO activity was reduced to less than 20% after blanching at 110 °C for 60 s. HHAIB reduced drying time and PPO activity and promoted chemical-substance release. Effective water diffusivity was highest (5.01 × 10-10 m2/s) after blanching at 110 °C for 90 s, and the brightness value and red pigment content were highest (9.94 g/kg) at 70 °C. HHAIB and pulsed vacuum drying are promising pretreatment and drying methods for enhancing the drying rate and quality of red peppers.


[Effectiveness of the "Internet Plus-based AIDS Comprehensive Prevention Service System" among MSM in Guangzhou].
Objective: To evaluate the effectiveness of the "Internet Plus-based AIDS Comprehensive Prevention Service System" among men who have sex with men in Guangzhou. Methods: Data through case-reporting and follow-up programs on MSM HIV/AIDS in Guangzhou was collected from the China Information System for Disease Control and Prevention, which including those from the referral and follow-up treatment compliance programs in 2008-2014 (pre-treatment) and 2017-2018 (post-treatment). According to the types of care services, three groups were set as: with "Internet Plus" service, with 'HIV counseling/testing service' or with 'routine medical service'. General Estimating Equation (GEE) was used to analyze the follow up situation of HIV/AIDS cases, annually. Cox proportional hazard regression model was used to analyze the proportions of treatment referral, within the 30 days of diagnosis. Results: Before the implementation of immediate treatment after HIV diagnosis, 90.6% (707/780) of the HIV/AIDS cases received the first follow up program including the CD(4)(+) T cells counts (CD(4)) test service within 90 days of diagnosis, in the "Internet Plus-based HIV/AIDS care service" group presented 1.19 times (95%CI: 1.14-1.25) of the routine medical service group. The implementation of immediate treatment after HIV diagnosis, compared with the routine medical service group, the "Internet Plus" service group presented 1.71 times (95%CI: 1.03- 2.83) more treatment referrals within the 30 days of diagnosis, when the first testing CD(4) was ≤200 cells/μl. Compared with the routine medical service group, the HIV counseling and testing service group showed 1.37 times (95%CI: 1.20-1.56) more of the treatment referrals within the 30 days of HIV diagnosis, after the first testing CD(4) counts as >200 cells/μl. Conclusion: Standardized care and follow-up service should be promoted as soon as the referral and treatment programs were set after the diagnosis was made, under the "Internet Plus-based AIDS Comprehensive Prevention Service System" for the MSM population, in Guangzhou.


Monitoring the Micro-Structural Evolution Mechanism of Next-Generation Ultra-High-Energy All-Nitrogen Materials: A Molecular Dynamic Study.
Micro-structural evolution mechanisms of next-generation ultra-high-energy all-nitrogen materials under the extreme conditions of high temperature coupled with high pressure were revealed by state-of-the-art ab initio molecular dynamics studies based on highest-nitrogen-content energetic material 2,2'-azobis(5-azidotetrazole). The results indicate that there are three primary initial uni-molecular decomposition pathways, namely, tetrazole ring opening, azido group elimination, and the breaking of the N-N bond between the azo group and azidotetrazole. In complicated global decomposition reactions, there exists the formation of nitrogen-rich clusters and all-nitrogen species. Lowering the temperature or increasing the pressure is conducive to increasing the N content in the nitrogen-rich cluster and widening the time distribution for the cluster. Abundant all-nitrogen species N4, N5, N6, N7, N8, N9, N10, and N13 were formed, and their detailed evolutionary process and construction mechanisms were enunciated. We innovatively constructed a series of next-generation ultra-high-energy all-nitrogen materials, which are expected to realize the controllable construction of next-generation ultra-high-energy all-nitrogen materials under extreme conditions.


Easy and convenient millimole-scale synthesis of new, potential biomarkers for gamma-hydroxybutyric acid (GHB) intake: Feasible for analytical laboratories.
New biomarkers indicating the abuse of drugs and alcohol are still of major interest for clinical and forensic sciences. The endogenous neurotransmitter and approved drug, gamma-hydroxybutyric acid (GHB), is often illegally used for drug-facilitated crimes by spiking GHB into alcoholic beverages. Analytical detection windows of only 6 h in blood and 12 h in urine are often too short to provide reliable proof of GHB ingestion. Therefore, new biomarkers are needed to prove exogenous GHB administration. Previously, amino acid GHB conjugates were discovered in an untargeted metabolomics screening and fatty acid esters with GHB were recently discussed as promising biomarkers to enlarge the analytical detection time windows. However, the development of analytical methods is still slowed down since reference compounds for targeted screenings are still missing. In this paper, we describe simple procedures for the rapid synthesis and purification of amino acid GHB conjugates as well as fatty acid esters, which can be adopted in analytical and clinical/forensic laboratories. Structural characterization data, together with IR, 1 H-nuclear magnetic resonance (NMR), 13 C-NMR, high-resolution mass spectra (MS), and MS/MS spectra in positive and negative ionization mode are reported for all obtained GHB conjugates and GHB conjugate precursors.


Laproscopic management of wandering biliary ascariasis.
Ascariasis is one of the most common helminthic diseases in humans, occurring mostly in countries with low standards of public health and hygiene, thereby making ascariasis highly endemic in developing countries. In endemic areas, 30% of adults and 60-70% of children harbour the adult worm. Biliary ascariasis is a rare cause of obstructive jaundice. Conventional management involves endoscopic extraction of worm. We are reporting a rare case of ascaris which induced extrahepatic biliary obstruction in a young male who presented with acute cholangitis. The ascaris was removed by laparoscopic exploration of the common bile duct. Postoperative period was uneventful.


Fingerprinting Cardiolipin in Leukocytes by Mass Spectrometry for a Rapid Diagnosis of Barth Syndrome.
Cardiolipin (CL), a dimeric phospholipid carrying four fatty acid chains in its structure, is the lipid marker of mitochondria, wherein it plays a crucial role in the functioning of the inner membrane. Its metabolite monolysocardiolipin (MLCL) is physiologically nearly absent in the lipid extract of animal cells and its appearance is the hallmark of the Barth syndrome (BTHS), a rare and often misdiagnosed genetic disease that causes severe cardiomyopathy in infancy. The method described here generates a "cardiolipin fingerprint" and allows a simple assay of the relative levels of CL and MLCL species in cellular lipid profiles. In the case of leukocytes, only 1 mL of blood is required to measure the MLCL/CL ratio via matrix-assisted laser desorption ionization - time-of-flight/mass spectrometry (MALDI-TOF/MS) just within 2 h from blood withdrawal. The assay is straightforward and can be easily integrated into the routine work of a clinical biochemistry laboratory to screen for BTHS. The test shows 100% sensitivity and specificity for BTHS, making it a suitable diagnostic test.


An emerging role for calcineurin Aalpha in the development and function of the kidney.
For many years, calcineurin has been a familiar molecule as a target of the immunosuppressive agents cyclosporin A and FK-506. Calcineurin inhibition interferes with T cell signaling by preventing activation of the transcription factor NFATc. However, calcineurin is expressed in most tissues in the body, and calcineurin inhibition undoubtedly alters many other cellular processes. As a result, serious side effects of calcineurin inhibitors regularly occur, including hypertension and renal dysfunction. Because nephrotoxicity is often a barrier to continued clinical use of calcineurin inhibitors, understanding the role of calcineurin in the kidney is of particular importance. Recent work has demonstrated that the two main isoforms of the catalytic subunit of calcineurin, Aalpha and Abeta, may have distinct functions, particularly in the kidney. Calcineurin isoforms may be differentially expressed, and/or the activity of each may be differentially regulated, leading to tissue-specific functions. Differences between the action of the two isoforms are most evident in knockout mice lacking each isoform. Mice lacking the beta-isoform are characterized principally by altered development and function of immune cells. alpha-Knockout mice, in contrast, can still be immune suppressed by cyclosporin A but display pervasive developmental defects, including renal dysfunction. Therefore, it is intriguing to consider that while the beta-isoform may be responsible for calcineurin action in T cells, the alpha-isoform may be the predominant catalytic isoform in the kidney. This conclusion, if correct, may have substantial clinical implication for novel strategies to selectively target calcineurin action in T cells without associated nephrotoxicity.


Assessing the equality of means of healthcare costs.
The main analytic problems for assessing the equality of means of healthcare costs are the skewed and heteroscedastic nature of the distribution of healthcare costs and the occurrence of persons with zero cost values. Without taking these special features into consideration, any statistical method may lead to the wrong conclusion. The available analytic methods that are appropriate for handling these features of healthcare costs are reviewed.


Clinical and Imaging Findings of Neonatal Seizures Presenting as Diffuse Cerebral White Matter Abnormality on Diffusion-Weighted Imaging without any Structural or Metabolic Etiology.
Some patients with neonatal seizures show diffuse, symmetric diffusion-restricted lesions in the cerebral white matter. The aim of this study was to describe clinical and imaging findings of patients with neonatal seizures who had diffuse, symmetric diffusion-restricted lesions without any structural or metabolic etiology. A total of 56 neonates aged less than 1 week underwent brain magnetic resonance imaging (MRI) for evaluation of seizures from November 2008 to February 2017. After excluding 43 patients, 13 patients showed diffuse white matter abnormality on diffusion-weighted imaging. Initial and follow-up clinical and MRI findings were analyzed retrospectively. All 13 patients were born at full term. Among the ten patients who underwent a stool test for viruses, six were positive for rotavirus and one for astrovirus. MRI revealed diffuse, symmetric diffusion-restricted lesions distributed along the cerebral white matter, thalami, and midbrain variably. Diffuse, symmetric diffusion-restricted lesions involving the cerebral white matter can be seen in patients with neonatal seizures without any structural or metabolic etiology. Rotavirus is commonly but not exclusively detected in these patients. Nevertheless, viral infection-associated encephalopathy should be considered for patients with characteristic clinical and MRI findings.


eHealth promotion: the use of the Internet for health promotion.
The use of the Internet for health promotion is explored in this edition including growth trends, general applicability, and evaluation strategies for online interventions. This article examines the range of preliminary studies of eHealth Promotion interventions and their summary results, and reviews potential evaluation tools and their use in online programming. Also assessed is their utility in population-based programming and review-selected implications for the field.


An online ordering system for therapy beds and mattresses.
Within this article, the authors have put forward a solution to keep track of pressure-relieving devices using internet-based secure online systems. In partnership with a therapy bed company they set up a system that was able to manage and monitor the requirements of their trust and ensure that products are used for patients who most need them. In using these systems they were also able to gather real-time data on usage and costs as well as time-dependent analysis. The system has also allowed a means of gathering outcome measurement of all products in use. Over a 6-month period the authors have shown how a forecasted 18% budget deficit has been turned into a 10% under spend of the overall budget. It is suggested that these systems could be one way of managing the pressure-relieving needs of hospital trusts ensuring both clinical effectiveness and cost-benefit.


Site of mitomycin-C application during trabeculectomy.
The outcome and postoperative complications after trabeculectomies with mitomycin-C application before flap dissection (episcleral) or after flap dissection (scleral bed) were analyzed retrospectively in 82 patients (82 eyes). Thirty-six eyes (43.9%) had an episcleral mitomycin-C application, and 46 (56.1%) had scleral-bed mitomycin-C administration. After a mean follow-up of 10.1 +/- 3.8 months and 9.9 +/- 4.3 months for the episcleral and scleral-bed groups, respectively, complete success (intraocular pressure </=21 mm Hg without medications) was achieved in 18 eyes (50%) in the episcleral group and in 43 eyes (93.5%) in the scleral-bed group. Qualified success (intraocular pressure </=21 mm Hg with glaucoma medications) was achieved in 10 eyes (27.8%) in the episcleral group and in 8 eyes (17.4%) in the scleral-bed group. Rates of cumulative survival and time of trabeculectomy survival were statistically higher in the scleral bed group (p = 0.002 and 0.0004, respectively). There was a statistically significant difference in the success rates between groups (p = 0.03). The final intraocular pressure was significantly lower in the scleral-bed group (p = 0.015). There were no differences in duration of postoperative follow-up or frequency of complications. Mitomycin-C application after the scleral flap dissection appears to be associated with higher success rates than mitomycin-C application before scleral flap dissection.


Imipramine treatment increases the number of hippocampal synapses and neurons in a genetic animal model of depression.
The aim was to investigate treatment effects of the antidepressant imipramine on the markers of neuronal plasticity. We investigated changes in neuron and synapse numbers in a rat strain that displays a genetic susceptibility to depressive behavior, the Flinders Sensitive and Resistant Lines (FSL/FRL). All rats were treated with imipramine (15 mg/kg) or saline (i.p) once daily for 25 days. The volume, neuron and synapse numbers in the hippocampus were estimated using design-based stereological methods. Under untreated conditions, the volume and the number of neurons and synapses were significantly smaller in the FSL saline group (untreated "depressed" rats) compared with the FRL saline group (normal rats), showing correlation to the observed decreased immobility in the forced swim test. Imipramine treatment significantly increased the number of neurons in the granule cell layer (GCL) and spine synapses in the CA1 in the FSL imipramine group (treated "depressed" rats) compared with the FSL saline group. The neuron numbers in the GCL and Hilus showed no differences in the FSL imipramine group compared to the FRL saline group. In conclusion, baseline levels of the volume and the number of neurons and spine synapses in hippocampus were significantly smaller in the untreated FSL rats. Our findings indicate that chronic imipramine treatment reverses the suppression of neurogenesis and synaptogenesis in the hippocampus of the "depressed" FSL rats, and this occurs in correlation with behavioral effects. Our results support the neuronal plasticity hypothesis that depressive disorders may be related to impairments of structural plasticity and neuronal viability in hippocampus, furthermore, antidepressant treatment counteracts the structural impairments.


Effect of chronic home care on admission to institutions providing long-term care.
Home care programs are operating throughout Ontario. In October 1975 pilot-test chronic home care (CHC) programs were added in three areas. Whether the Kingston CHC program prevented or delayed admission to an institution providing long-term care was studied in the 218 patients admitted to the program up to mid-March 1976. Forms were completed for all 218 patients admitted, for the 109 still in the program 6 months later, and for the 131 who had left the program by August 1976. Of the 218 patients 20% had applied for admission to an institution providing long-term care before applying for CHC, and another 22% had seriously considered applying to such an institution. The CHC staff judged that 61% would have needed institutional care without CHC. Only 12% of the 218 patients left the CHC program to enter an institution, only 1 of the 48 patients discharged to self-care at home was considering a move to an institution, and only 2 receiving CHC for 6 months applied to an institution during that time. CHC therefore seems to delay greatly admission to an institution providing long-term care for a substantial group of patients.


[Urological emergencies in paediatric surgery: a survey of 40 cases].
The objective of this study is to report our experience on the epidemiology of urological emergencies in pediatric surgery, and to analyze the diagnosis and therapeutic process. It was a prospective survey which was carried out between January 2010 and June 2011 in the pediatric service of Aristide Le Dantec Hospital (HALD). All the children who came for a urological emergency consultation were included in the study. the urological emergencies accounted for forty cases which represented 2.57% of pediatric surgery emergencies. The average age of our patients was 4.5 years with extremes of 10 days and 15 years of age. 29 cases of severe big bursae were observed and among them there were strangulated hernia and ten cases of suspicious spermatic cord torsion. The other admission motives consisted of three cases of urine retention, two pyelonephritis cases, two cases of post circumcision glans sections, two paraphimosis cases, one tight phimosis case, one case of penis traumatism provoked by a game incident. The scrotum ultrasound performed on six patients helped find out a specificity of 66.6%. 60% of strangulated hernia have been reduced through under sedation taxis. In case of confirmed torsion, a detorsion followed by an orchidopexy were performed. Two orchidectomy were performed for a testicular necrosis. the painful big bursa is the number one cause for a urology pediatric consultation. It implies a fast and adequate diagnosis and treatment so as not to miss a digestive or testicular pain.


Strategies for the construction and use of peptide and antibody libraries displayed on phages.
Combinatorial chemistry and biology have become popular methods for the identification of bio-active molecules in drug discovery. A widely used technique in combinatorial biology is "phage display", by which peptides, antibody fragments and enzymes are displayed on the surface of bacteriophages, and can be selected by simple procedures of biopanning. The construction of phage libraries of peptides or antibody fragments provides a huge source of ligands and bio-active molecules that can be isolated from the library without laborious studies on antigen characteristics and prediction of ligand structure. This "irrational" approach for the construction of new drugs is extremely rapid and is now used by thousands of laboratories world-wide. The bottleneck in this procedure is the availability of large reliable libraries that can be used repeatedly over the years without loss of ligand expression and diversity. Construction of personalized libraries is therefore important for public and private laboratories engaged in the isolation of specific molecules for therapeutic or diagnostic use. Here we report the general strategies for constructing large phage peptide and antibody libraries, based on the experience of researchers who built the world's most widely used libraries. Particular attention is paid to advanced strategies for the construction, preservation and panning.


[Retroperitoneal extravasation as the primary symptom of a pancreatic carcinoma].
Adenocarcinoma of the pancreas has a low 5-year survival rate of approximately 5%. Early diagnostics of pancreatic carcinoma during early tumor stages is made difficult by the lack of symptoms. In particular, individuals suffering from carcinomas located within the pancreatic tail are at high risk of a missed diagnosis. The early symptoms are usually nonspecific (e.g., nonspecific upper abdominal complaints, decrease in weight, loss of appetite, and impaired performance) and are characteristic only in carcinomas of the pancreatic head with painless icterus. If the patient complains of low back pain, a severe infiltration with no chance of a complete surgical resection is found in most cases. An adenocarcinoma of the pancreatic tail was diagnosed in this case report based on a large retroperitoneal extravasation missing further symptoms. The extravasation found represented a primary infiltration of the left ureter which was not diagnosed in primary computed tomography.


Results of femoral intramedullary nailing in patients who are obese versus those who are not obese: a prospective multicenter comparison study.
Antegrade femoral nailing through a piriformis fossa starting point in patients who are obese has been demonstrated to be problematic. Retrograde femoral nailing therefore has been advocated in this patient population, but little data exist to support such a recommendation. The purpose of this study was to evaluate and compare antegrade and retrograde femoral nailing technique in both patients who are and are not obese. Prospective, multicenter, nonrandomized, internal review board (IRB)-approved study. Four Level 1 trauma centers. Patients (151) with a femoral shaft fracture (OTA 32) treated with intramedullary nailing were studied. Thirty-two with a body mass index (BMI) of >or=30 comprised the obese group (OG), and 119 with a BMI of <30 comprised the nonobese group (NOG). Antegrade nailing was performed in 15 patients from the OG and 84 from the NOG. Retrograde nailing was performed in 17 patients from the OG and 35 from the NOG. Reamed intramedullary nailing of a femoral shaft fracture. Patient and fracture characteristics, operative time, fluoroscopy time, healing, complications, and functional outcome based on the lower extremity measure (LEM) were evaluated. Antegrade technique in the OG was associated with a 52% greater average operative time (94 minutes) compared with antegrade nailing in the NOG (62 minutes; P < 0.003). For retrograde nailing technique, there was no difference in the average operative time between the OG (67 minutes) and NOG (62 minutes; P = 0.51). Antegrade technique in the OG was associated with a 79% greater average radiation exposure time (247 seconds) compared with antegrade nailing in the NOG (135 seconds; P < 0.03). For retrograde nailing technique, average fluoroscopy time was similar between the OG (76 seconds) and the NOG (63 seconds; P = 0.44). Within the OG, antegrade nailing required 40% greater average operative time (94 minutes versus 67 minutes, P < 0.02) and more than 3 times more average fluoroscopy time (242 seconds versus 76 seconds, P < 0.002) than retrograde nailing. Thirty-eight patients from the original cohort were not available for follow-up. Of the 113 patients followed (average 9 months, range: 4 to 25 months), healing complications occurred similarly between the 2 groups, with 1 nonunion and 2 delayed unions in the OG (12%), and 3 nonunions and 9 delayed unions in the NOG (14%). This study provides evidence, in the form of decreased operative and radiation exposure times, to support the use of retrograde nailing technique for the treatment of femoral shaft fractures in patients who are obese. Also, antegrade nailing was found to require significantly more operative and radiation exposure time in the patient who is obese as opposed to the patients who is not obese. Although having similar baseline functional scores, patients who are obese recovered at a slower rate and more incompletely than patients who are not obese.


Ground-state computation of Bose-Einstein condensates by an imaginary-time quantum lattice Boltzmann scheme.
The multidimensional formulation of the quantum lattice Boltzmann (qLB) scheme is extended to the case of nonlinear quantum wave equations. More specifically, imaginary-time formulations of the qLB scheme are developed and applied to the numerical computation of the ground state of the Gross-Pitaevskii equation in one and two spatial dimensions. The calculation is validated through detailed comparison with other numerical methods, as well as with analytical results based on the Thomas-Fermi approximation. The linear scaling of the time-step size with the spatial mesh spacing, a distinctive feature of the present quantum kinetic approach, is also numerically demonstrated.


A Data Model and Task Space for Data of Interest (DOI) Eye-Tracking Analyses.
Eye-tracking data is traditionally analyzed by looking at where on a visual stimulus subjects fixate, or, to facilitate more advanced analyses, by using area-of-interests (AOI) defined onto visual stimuli. Recently, there is increasing interest in methods that capture what users are looking at rather than where they are looking. By instrumenting visualization code that transforms a data model into visual content, gaze coordinates reported by an eye-tracker can be mapped directly to granular data shown on the screen, producing temporal sequences of data objects that subjects viewed in an experiment. Such data collection, which is called gaze to object mapping (GTOM) or data-of-interest analysis (DOI), can be done reliably with limited overhead and can facilitate research workflows not previously possible. Our paper contributes to establishing a foundation of DOI analyses by defining a DOI data model and highlighting its differences to AOI data in structure and scale; by defining and exemplifying a space of DOI enabled tasks; by describing three concrete examples of DOI experimentation in three different domains; and by discussing immediate research challenges in creating a framework of visual support for DOI experimentation and analysis.


Gamma-glutamyl transpeptidase in synovial fluid, serum, and urine of patients with rheumatoid arthritis.
The changes in the levels of GGT activity in various body fluids, ESR, SF-protein concentration, and SF-WBC count were determined in 59 RA patients and 18 control subjects. The SF-GGT and UGGT were markedly elevated in all RA patients investigated. The increase of SF-GGT is more pronounced than UGGT. The observation of comparable levels of SGGT in RA patients and control subjects indicates that SGGT does not gain entry into synovial fluid or urine. No differences were noticed in SF-protein concentration whereas ESR levels and SF-WBC counts were significantly higher in RA patients than in control subjects. Statistically significant correlations were observed between SF-GGT versus UGGT, SF-WBC, and ESR in females, and between SF-GGT and SF-protein and SGGT in male RA patients. The correlation coefficient values between UGGT versus SF-protein, SF-WBC, and ESR were found to be significant in male RA patients. UGGT levels correlated strongly with SGGT in all RA patients. These findings suggest that the measurement of SF-GGT and UGGT might be useful in understanding the pathogenesis of rheumatoid arthritis.


Desensitization of animals to the inflammatory effects of ultraviolet radiation is mediated through mechanisms which are distinct from those responsible for endotoxin tolerance.
The studies presented in this report indicate that the mechanisms responsible for both ultraviolet radiation (UVR)- and lipopolysaccharide (LPS)-induced desensitization are different from one another and appear to be regulated at the site(s) of administration of the inflammatory agent. Furthermore, desensitization to either UVR or LPS is not due to the inability of interleukin 1 (IL 1)-sensitive target cells within these animals to respond to this endogenous mediator of inflammation. These conclusions were based on the demonstrated ability of UVR-desensitized mice to undergo an acute-phase response after exposure to a systemically administered inflammatory agent (LPS). In a reciprocal manner, LPS-desensitized mice were found to elicit a normal acute-phase response after a single UVR exposure. In addition, both UVR- and LPS-desensitized mice were found to respond normally to the systemic administration of an exogenous source of semi-purified IL 1. Desensitization to the inflammatory properties of either UVR or LPS appears to be controlled at the site of interaction between the tissues capable of producing epidermal-derived thymocyte-activating factor (ETAF)/IL 1 (epidermal keratinocytes or reticuloendothelial cells, respectively) and the exogenous inflammatory stimulus. Peritoneal macrophages obtained from LPS-desensitized mice were found to have a markedly reduced capacity to secrete ETAF/IL 1 in vitro when compared to peritoneal exudate cells (PEC) obtained from normal mice. In parallel with this decreased secretory potential by PEC was the appearance of membrane-associated forms of this mediator. Membrane-associated IL 1 was not found to be present on PEC obtained from normal mice. Keratinocytes obtained from the skin of normal mice or keratinocytes isolated from the irradiated skin site of UVR-desensitized mice were both found to secrete high levels of ETAF/IL 1 constitutively in vitro. Furthermore, both sources of keratinocytes also expressed membrane-associated forms of ETAF/IL 1 constitutively. Therefore, unlike LPS desensitization, the phenomenon of UVR desensitization does not appear to induce changes in the ability of keratinocytes to secrete soluble forms or to express membrane forms of ETAF/IL 1. UVR desensitization may be a result of the inability of ETAF/IL 1 generated within the skin to reach the various IL 1-responsive target cells throughout the body, or may result from the impaired ability of UVR to stimulate ETAF/IL 1 production due to changes in the structure of the skin of chronically UVR-exposed animals.


Biochar catalyzed dechlorination - Which biochar properties matter?
Bone char catalyzed dechlorination of trichloroethylene (TCE) by green rust (iron(II)-iron(III) hydroxide, GR) has introduced a promising new reaction platform for degradation of chlorinated solvents. This study aimed to reveal whether a broader class of biochars are catalytically active for the dechlorination reaction and to identify which biochar properties are the most important for the catalytic activity. Biochars produced by pyrolysis of animal, plant, and sewage waste substrates at 950 °C were prepared for catalytic dechlorination of TCE by GR tested in batch experiments with 0.15 g L-1 biochar, 3.2 g L-1 GR, and ~ 20 µM TCE. The results showed that the biochar substrate significantly affects its catalytic activity, with the highest TCE reduction rate observed for bone and shrimp-based biochars (k ≥ 0.18 h-1), whereas no reactivity was seen for graphite and activated carbon references. Multivariate regression indicated that the biochar catalytic activity is controlled by multiple biochar properties - biochar surface area, TCE sorption, abundance of C-O groups, and pore size are the properties that impact the catalytic activity most. Derivation of biochar reactivity relationship for a broad spectrum of biochars provides a new approach for identifying proper biochar catalysts for pollutant degradation.


QTL mapping and KASP marker development for seed vigor related traits in common wheat.
Seed vigor is an important parameter of seed quality, and identification of seed vigor related genes can provide an important basis for highly efficient molecular breeding in wheat. In the present study, a doubled haploid (DH) population with 174 lines derived from a cross between Yangmai16 and Zhongmai 895 was used to evaluate 10 seed vigor related traits in Luoyang during the 2018-2019 cropping season and in Mengjin and Luoning Counties during 2019-2020 cropping season for three environments. Quantitative trait locus (QTL) mapping of 10 seed vigor related traits in the DH population resulted in the discovery/identification of 28 QTLs on chromosomes 2B, 3D, 4B, 4D, 5A, 5B, 6A, 6B, 6D, 7A and 7D, explaining 3.6-23.7% of the phenotypic variances. Among them, one QTL cluster for shoot length, root length and vigor index was mapped between AX-89421921 and Rht-D1_SNP on chromosome 4D in the physical intervals of 18.78-19.29 Mb (0.51 Mb), explaining 9.2-20.5% of the phenotypic variances. Another QTL for these traits was identified at the physical position 185.74 Mb on chromosome 5B, which was flanked by AX-111465230 and AX-109519938 and accounted for 8.0-13.3% of the phenotypic variances. Two QTLs for shoot length, shoot fresh weight and shoot dry weight were identified in the marker intervals of AX-109384026-AX-111120402 and AX-111651800-AX-94443918 on chromosomes 6A and 6B, explaining 8.2-11.7% and 3.6-10.3% of the phenotypic variance, respectively; both alleles for increasing phenotypic values were derived from Yangmai 16. We also developed the KASP markers for the QTL cluster QVI.haust-4D.1/QSL.haust-4D/QRL.haust-4D, and validated in an international panel of 135 wheat accessions. The germplasm, genes and KASP markers were developed for breeders to improve wheat varieties with seed vigor related traits.


Dural fistulas of the cavernous sinus. A report of 5 cases.
Five cases of dural fistulas of the cavernous sinus are reported. The clinical aspect of this lesion is often misleading in the absence of subjective or objective bruits. The diagnosis is made at angiography which should systematically include the internal and external carotid arteries bilaterally. The goal of this study was to elucidate the great variability of the venous drainage and to correlate it with the clinical symptoms and course. The main problem is to know when and how these fistulas should be treated. Vascular ligatures should not be performed. Therapeutic angiography is the treatment of choice, but should be limited to the following indications: poorly tolerated bruits, severe ophthalmic damage (elevated ocular tension, diminished visual acuity, or oculomotor paralysis), angiographically demonstrated massive arteriovenous shunting, and a high degree of cortical venous reflux. Whatever the indication, the course after embolisation is rarely predictable and in particular the risk of extensive venous thrombosis or recurrence is great.


In silico characterization of microbial electrosynthesis for metabolic engineering of biochemicals.
A critical concern in metabolic engineering is the need to balance the demand and supply of redox intermediates such as NADH. Bioelectrochemical techniques offer a novel and promising method to alleviate redox imbalances during the synthesis of biochemicals and biofuels. Broadly, these techniques reduce intracellular NAD+ to NADH and therefore manipulate the cell's redox balance. The cellular response to such redox changes and the additional reducing power available to the cell can be harnessed to produce desired metabolites. In the context of microbial fermentation, these bioelectrochemical techniques can be used to improve product yields and/or productivity. We have developed a method to characterize the role of bioelectrosynthesis in chemical production using the genome-scale metabolic model of E. coli. The results in this paper elucidate the role of bioelectrosynthesis and its impact on biomass growth, cellular ATP yields and biochemical production. The results also suggest that strain design strategies can change for fermentation processes that employ microbial electrosynthesis and suggest that dynamic operating strategies lead to maximizing productivity. The results in this paper provide a systematic understanding of the benefits and limitations of bioelectrochemical techniques for biochemical production and highlight how electrical enhancement can impact cellular metabolism and biochemical production.


Bayesian mapping of pulmonary tuberculosis in Antananarivo, Madagascar.
Tuberculosis (TB), an infectious disease caused by the Mycobacterium tuberculosis is endemic in Madagascar. The capital, Antananarivo is the most seriously affected area. TB had a non-random spatial distribution in this setting, with clustering in the poorer areas. The aim of this study was to explore this pattern further by a Bayesian approach, and to measure the associations between the spatial variation of TB risk and national control program indicators for all neighbourhoods. Combination of a Bayesian approach and a generalized linear mixed model (GLMM) was developed to produce smooth risk maps of TB and to model relationships between TB new cases and national TB control program indicators. The TB new cases were collected from records of the 16 Tuberculosis Diagnostic and Treatment Centres (DTC) of the city from 2004 to 2006. And five TB indicators were considered in the analysis: number of cases undergoing retreatment, number of patients with treatment failure and those suffering relapse after the completion of treatment, number of households with more than one case, number of patients lost to follow-up, and proximity to a DTC. In Antananarivo, 43.23% of the neighbourhoods had a standardized incidence ratio (SIR) above 1, of which 19.28% with a TB risk significantly higher than the average. Identified high TB risk areas were clustered and the distribution of TB was found to be associated mainly with the number of patients lost to follow-up (SIR: 1.10, CI 95%: 1.02-1.19) and the number of households with more than one case (SIR: 1.13, CI 95%: 1.03-1.24). The spatial pattern of TB in Antananarivo and the contribution of national control program indicators to this pattern highlight the importance of the data recorded in the TB registry and the use of spatial approaches for assessing the epidemiological situation for TB. Including these variables into the model increases the reproducibility, as these data are already available for individual DTCs. These findings may also be useful for guiding decisions related to disease control strategies.


Leukemia and other cancers following radiation treatment of pelvic disease.
Follow-up studies of patients treated for cancer of the cervix with radiotherapy have shown such women to be at little or no increased risk of leukemia subsequent to the radiation exposure. However, women exposed to lower doses of radiation in the pelvic area, in the induction of an artificial menopause, appear to show increased risks of both leukemia and cancers of those sites directly in the radiation field. The studies of these two types of radiation exposure are reviewed. The findings may possibly be reconciled with each other on the basis of the distribution of radiation dose to the bone marrow. Irradiation for cancer of the cervix delivers radiation doses to a small portion of the marrow which are probably lethal for most marrow cells. The mean dose to cells distant from the cervix may be too small to produce a detectable increase in leukaemia incidence. The lower and more uniformly distributed radiation dose used to induce an artificial menopause will be less lethal for marrow cells and may consequently deliver a higher "effective" marrow dose to surviving--cells, resulting in an increased leukemia risk.


Dysfunctional brain dopamine systems induced by psychotomimetic NMDA-receptor antagonists and the effects of antipsychotic drugs.
Clinical studies utilizing imaging techniques demonstrate that classical antipsychotic drugs, such as haloperidol, in clinically effective doses display around 75% dopamine (DA)-D(2) receptor occupancy in the brain. In contrast, the atypical antipsychotic drug clozapine is even more effective at only about 45% D(2)-receptor occupancy. Yet at this D(2)-receptor occupancy classical antipsychotics are not effective, raising the question of which other receptors may be involved in mediating the atypical antipsychotic profile of clozapine and other atypical antipsychotics. The present paper describes experimental work aimed at elucidating this critical question, utilizing the phencyclidine (PCP) model of schizophrenia in combination with studies of typical and atypical antipsychotics as well as various specific receptor blocking agents. Both electrophysiological methods, i.e. single cell recording from DA neurons in the ventral tegmental area (VTA), and biochemical analysis of biogenic amines such as DA following microdialysis in difference DA terminal areas in the brain, were used. In addition, behavioural measurements using the conditioned avoidance response (CAR) paradigm and assessments of locomotor activity were utilized. Experiments with functional inactivation of the medial frontal cortex (mPFC) in the rat as well as with MK-801 and other antagonists at central NMDA-receptors revealed that following systemic administration of schizophrenomimetic NMDA-receptor antagonists a profound dysregulation of the mesocorticolimbic DA system occurs, severely impairing the dynamic physiological response range of the neurons. Specifically, DA neurons which largely project to the mPFC showed a profound loss of burst firing, whereas VTA-DA neurons, which mainly project subcortically, showed an increased monotonous high-frequency firing with increased DA output from nerve terminals and concomitant behavioural activation. Significantly, drugs with a prominent 5-HT(2A)-receptor blocking action could effectively restore the burst firing mode, i.e. phasic responsivity, in mesocortically projecting DA neurons, and also potentiate the CAR suppressant effect of the selective D(2)/D(3)-receptor antagonist raclopride without increasing catalepsy scores. The selective alpha(1)-adrenoreceptor antagonist prazosin effectively suppressed both the stereotyped, high-frequency firing of subcortically projecting DA neurons following systemic MK-801 and the concomitant behavioural, i.e. locomotor, activation. In addition, the MK-801 evoked DA release in the nucleus accumbens was suppressed. A similar effect was seen also with AMPA-receptor antagonists when applied locally into the VTA and, in addition, systemic administration of chemically different AMPA-receptor antagonists caused a CAR-suppressant effect similar to both classical and atypical antipsychotic drugs. These results and other data showing a clearcut difference between typical and atypical antipsychotic drugs on DA output in the shell and core, respectively, of the nucleus accumbens, suggest that both the 5-HT(2A)- and the alpha(1)-adrenoreceptor blocking effects of a number of atypical antipsychotic drugs in all probability contribute to their antipsychotic effect. Moreover, our results indicate that AMPA-receptor antagonists may possess an atypical antipsychotic profile.


Ablation of left ventricular tachycardia via transeptal approach and crossing of a mechanical mitral valve prosthesis.
This report describes the clinical course of a patient with left ventricular assist device (LVAD) and refractory ventricular tachycardia (VT) who underwent successful left ventricular (LV) mapping and ablation complicated by the presence of a bioprosthetic aortic and a mechanical mitral valve. LV catheterization was achieved by crossing the mechanical valve. The patient remained hemodynamically stable during the procedure most likely as a result of LVAD support. There were no complications. A recurrence of monomorphic VT 2 months later required a second VT ablation procedure using the same transseptal-transmitral approach. The patient has since been free of implantable cardioverter defibrillator shocks for 2 months since the second procedure.


New nanocrystalline materials: a previously unknown simple cubic phase in the SnS binary system.
We report a new phase in the binary SnS system, obtained as highly symmetric nanotetrahedra. Due to the nanoscale size and minute amounts of these particles in the synthesis yield, the structure was exclusively solved using electron diffraction methods. The atomic model of the new phase (a = 11.7 Å, P2(1)3) was deduced and found to be associated with the rocksalt-type structure. Kramers-Kronig analysis predicted different optical and electronic properties for the new phase, as compared to α-SnS.


Mapping parents' journey following prenatal diagnosis of CHD: a qualitative study.
To better understand parents' accounts of their prenatal and postnatal experience after prenatal diagnosis of CHD - particularly emotional processing and coping mechanisms - to identify strategies to improve support. This single-centre, longitudinal qualitative study included pregnant mothers and their support persons seen in Fetal Cardiology Clinic at Vanderbilt Children's Hospital from May through August 2019 for probable complex CHD. Twenty-seven individuals from 17 families participated in 62 phone interviews during pregnancy and postpartum: 27 conducted after the initial prenatal cardiology consultation, 15 after a follow-up prenatal visit, and 20 after birth. Applied thematic analysis approach was used to code and analyse transcribed interviews. Coding and codebook revisions occurred iteratively; intercoder reliability was >80%. Patients included mothers (16 [59%]), fathers (8 [30%]), and other support persons (3 [11%]). Initial fetal diagnoses included a range of moderate to severe CHD. Prenatally, parents sought to maintain hope while understanding the diagnosis; planning for the future rather than focusing on day-to-day was more common if prognoses were better. Postnatally, with confirmation of prenatal diagnoses, parents' sense of control expanded, and they desired more active engagement in clinical decision making. To enhance effective communication and support, understanding how parents conceptualise hope in relation to diagnosis and how that may evolve over time is critical. Expectant parents whose child has a significant risk of mortality may demonstrate hope by focusing on positivity. As prognostic uncertainty diminishes postpartum, the parental role on the team may shift, requiring clinicians to provide different support.


Determination and pharmacokinetic study of two triterpenoid saponins in rat plasma after oral administration of the extract of Aralia elata leaves by UHPLC-ESI-MS/MS.
Aralia elata (Miq.) Seems (A. elata) grow in Northeast China and the total saponins of A. elata is used to auxiliary treatment for the acute hepatitis, chronic hepatitis and the transaminase on the high side. Aralia-saponinV and Aralia-saponinVI are the major bioactive saponins in A. elata leaves. A selective and sensitive UHPLC-MS/MS method was developed and validated for the determination and pharmacokinetic study of Aralia-saponinV and Aralia-saponinVI indwelling the extract in rat plasma in this article. The sample pretreatment involved a one-step extraction of 0.2mL plasma with methanol. Shengmaxinside C was used as internal standard (I.S.). The separation was carried out on an Agilent SB-C18 column (1.8μm, 50mm×2.1mm) at 30°C with a mobile phase of acetonitrile-5mM ammonium acetate (90:10, v/v) at a flow rate of 0.2mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source operating in the negative ionization mode. The optimized mass transition ion-pairs (m/z) monitored for Aralia-saponinV, Aralia-saponinVI and I.S. were 1103.2/941.2, 1119.2/957.0 and 707.0/647.1, respectively. The current UHPLC-MS/MS assay method was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability, and it was suitable for the pharmacokinetic studies of the two saponins after oral administration of extract of A. elata leaves. The lower limits of quantification were 5.70ng/mL for Aralia-saponinV and 6.15ng/mL for Aralia-saponinVI. Intra-day and inter-day precisions were less than 7.4% and the accuracy range was from 1.19% to 8.60%. The mean extraction recoveries of analytes and I.S. from rat plasma were all more than 89.5%. This paper described a simple, sensitive and validated UHPLC-MS/MS method for simultaneous determination of Aralia-saponinV and Aralia-saponinVI in rat plasma after oral administration of the extract of A. elata leaves, and investigated on their pharmacokinetic studies as well.


Saccade launch site as a predictor of fixation durations in reading: comments on Hand, Miellet, O'Donnell, and Sereno (2010).
An important question in research on eye movements in reading is whether word frequency and word predictability have additive or interactive effects on fixation durations. A fair number of studies have reported only additive effects of the frequency and predictability of a target word on reading times on that word, failing to show significant interactions. Recently, however, Hand, Miellet, O'Donnell, and Sereno (see record 2010-19099-001) reported interactive effects in a study that included the distance of the prior fixation from the target word (launch site). They reported that when the saccade into the target word was launched from very near to the word (within 3 characters), the predictability effect was larger for low frequency words, but when the saccade was launched from a medium distance (4-6 characters from the word) the predictability effect was larger for high frequency words. Hand et al. argued for the importance of including launch site in analyses of target word fixation durations. Here we describe several problems with Hand et al.'s use of analyses of variance in which launch site is divided into distinct ordinal levels. We describe a more appropriate way to analyze such data-linear mixed-effect models-and we use this method to show that launch site does not modulate the interaction between frequency and predictability in two other data sets.


Subclinical vestibular dysfunction in migraineurs without vertigo: A Clinical study.
This observational study aimed to investigate the presence of potential vestibular system subclinical dysfunction among migraineurs without a history of vertigo and dizziness compared with healthy controls. Patients diagnosed with episodic migraine with and without aura were enrolled. All patients and healthy controls underwent vestibular examination using the following conventional tests: sitting position, Pagnini-McClure's, Dix-Hallpike's, head hanging, video head impulse, subjective visual vertical, Romberg, Fukuda, and caloric vestibular stimulation by Fitzgerald-Hallpike's tests. Nystagmus and angular velocity of the slow phase during culmination phase was analyzed by video-nystagmography. Overall, 33 patients (76% female, 7 with aura and 26 without aura; mean age (mean ± SD): 29.1 ± 4.3 years) and 22 controls (33% female, mean age: 30.8 ± 9.4 years) were enrolled. There were no statistically significant differences in demographic features between patients and controls. Caloric vestibular stimulation test results were found to differ among patients and controls. In particular, right and left angular velocity (AV) were highly correlated one another (r = 0.88, P < .001). Right AV (53.0 ± 6.7 vs 44.0 ± 9.6) and left AV (54.3 ± 5.3 vs 43.3 ± 9.0) were statistically higher in migraineurs as compared to controls (P < .001). Also right V-HIT (1.1 ± 0.1 vs 0.8 ± 0.4) and left V-HIT (1.1 ± 0.1 vs 0.7 ± 0.2) were statistically higher in migraineurs compared to controls (P < .001). Our findings suggest a subclinical alteration of vestibular pathway in migraineurs who have never complained vertigo or postural imbalance. This finding supports the hypothesis of a vestibular-cerebellar dysfunction in migraineurs, particularly among those with aura.


Effect of root agglutinin on microbial activities in the rhizosphere.
A total of 220 bacterial isolates were obtained from pea rhizosphere and nonrhizosphere samples. Of these samples, 100 isolates were chosen randomly to test for their agglutinative reaction against pea root exudate. The percentage of positive agglutination of bacteria isolated from the nonrhizosphere sample was significantly lower than that of bacteria isolated from the rhizosphere sample. Moreover, this agglutinative reaction could not be blocked either by treating the bacterial cells or root exudate with different carbohydrates before they were mixed or by boiling the root exudate first. Bacteria that could be agglutinated by pea root exudate followed the downward growth of the pea root through the soil profile. The greater abilities of such bacteria to colonize the pea rhizosphere were indicated by their higher rhizosphere-colonizing (rhizosphere/nonrhizosphere) ratios, whether the bacteria were added alone or together with nonagglutinating bacteria. However, bacteria did show different agglutinative reactions toward root exudates obtained from different plants.


[Bile excretion of hepatocytes cultured in vitro].
To regain bile excretory function of hepatocytes cultured in vitro. Sandwich configuration was used to culture hepatocytes and the structure of bile canaliculi as well as the function of bile excretion was observed by immunocytochemistry and the test of FDA metabolism with a single collagen configuration as a control. First, the formation of bile canaliculi was observed by immunocytochemistry. In sandwiched hepatocytes, the gradual development of bile canaliculi-like structures into an anastomotic network was observed. At 24 h after cell culture, the formation of bile canaliculi was observed. With time progressed, the bile canaliculi became more clear and the network was established at 120 h. In contrast, hepatocytes in single collagen configuration showed almost no network of bile canaliculi. Second, the ability for hepatocytes to internalize, metabolize and excrete compounds into bile was indicated by FDA metabolized in the hepatocytes. In sandwiched hepatocytes, the bile excretory function was shown at 96 h, but in single collagen system, no bile excretion was observed. Cultured hepatocytes are able to regain bile excretion in a given certain condition. Sandwich-cultured hepatocytes can reestablish bile canalicular structure and regain bile excretory function.


Fibrinogen interaction with the red blood cell membrane.
A brief review of the fibrinogen molecule composition and structure is presented like as an introduction to the effects of this plasma protein on the red blood cell hemorheoplogical properties namely erythrocyte aggregation tendency and deformability ability. The protein membrane RBC target for fibrinogen is also highlight as well as the erythrocyte signal transduction pathway associated with nitric oxide mobilization resulting from its binding.


Development of an HPLC assay for Staphylococcus aureus sortase: evidence for the formation of the kinetically competent acyl enzyme intermediate.
Many bacterial surface proteins containing an LPXTG motif are anchored to the cell wall peptidoglycan by catalysis with the thiol transpeptidase sortase. The transpeptidation and hydrolysis reactions of sortase have been proposed to proceed through a common acyl enzyme intermediate. The reactions of Staphylococcus aureus sortase with fluorogenic substrate Abz-LPETG-Dnp in the presence or absence of triglycine were characterized in this study to gain additional insight into the kinetic mechanism of sortase. We report here the development of a reverse-phase HPLC assay to identify and characterize sortase reaction intermediates. The HPLC results provide for the first time clear evidence for the formation of a kinetically competent acyl enzyme intermediate during the overall transpeptidation reaction. The results also suggest that sortase undergoes an unexpected intramolecular acyl transfer reaction in the absence of a nucleophile. The significance of this type of HPLC assay as a tool to study enzyme mechanism is discussed.


Axillary artery rupture caused by shoulder dislocation.
A case of axillary artery disruption following an anterior shoulder dislocation is reported, the eleventh such case in the past 25 years. As an alternative to dividing the pectoralis major tendon, two incisions, infraclavicular and transaxillary incisions, were used to repair the artery with an interposition Dacron graft. An absent radial pulse following a shoulder dislocation suggests the possibility of axillary artery injury, usually a dissected intimal flap but occasionally a ruptured vessel. Early arterial repair is indicated, preceded by arteriography, if available. Brachial plexus injury frequently accompanies arterial damage and is not affected by arterial repair. Permanent, partial motor dysfunction is common, especially involving the extensors of the hand.


Harris criterion on hierarchical lattices: rigorous inequalities and counterexamples in Ising systems.
Random bond Ising systems on a general hierarchical lattice are considered. The inequality between the specific heat exponent of the pure system, alpha(p), and the crossover exponent straight phi, alpha(p)</= phi, gives rise to the possibility of a negative alpha(p) along with a positive phi, leading to random criticality in disagreement with the Harris criterion. An explicit example where this really happens for an Ising system is presented and discussed. In addition to that, it is shown that in the presence of full long-range correlations the crossover exponent is larger than in the uncorrelated case.


Asymmetric Total Synthesis of (+)-Epiibogamine Enabled by Three-Component Domino Michael/Michael/Mannich Annulation of N-Sulfinyl Metallosilylenamines.
The iboga alkaloids are promising antiaddictive and neuroregeneration candidates for medical treatment. There is a lack of studies for C20-epi iboga alkaloids due to the synthetic difficulties. Herein we report the shortest total synthesis of (+)-epiibogamine in seven steps from trimethyl orthobutyrate. The novel N-sulfinyl silylenamine reagent enabled the key step, with three-component domino Michael/Michael/Mannich annulation providing the 1-amino-2,4-diester scaffold with four new chiral centers, and access to the isoquinuclidine in high yield (84%) and diastereoselectivity (>95:5 dr).


Helical scanning CT for hepatocellular carcinoma.
To evaluate the clinical usefulness of helical scanning CT for hepatocellular carcinoma, 39 patients were examined using a Toshiba CT system, the Xforce. Helical scanning CT data were acquired using up to 20 continuous 1.5-sec rotations, with contrast medium bolus injection of 100-150 ml at a rate of 1.5-3 ml/sec, and during a single breath-hold. Scanning was begun 35 to 50 sec after the start of injection. Helical scanning CT permits axial images to be reconstructed at any desired position within the scanned area, and provides images without interslice gaps caused by respiratory movement. Contrast enhanced helical scanning CT permits blood vessels to be clearly displayed following the bolus injection of contrast medium using an automatic injector. Furthermore, the shorter scanning time makes it possible to scan the target area in the desired vascular phase. In all 39 patients who were examined using contrast enhanced helical scanning CT, high-quality three-dimensional images were obtained. Such images were particularly useful for assessing the three-dimensional relationships among high density tumors and vascular structures. In conclusion, helical scanning CT was considered to be useful for hepatocellular carcinoma.


[Ultrasound screening of the infant hip].
The sonographic screening of the hip has led to a marked decrease in treatment of children with developmental dysplasia of the hip (ddh) as inpatients. The prognosis for this disorder has greatly improved in the past few years due to early diagnosis and correspondingly early beginning of therapy, in many cases by using simple therapeutic methods. This undisputed success has been achieved with a high treatment rate in comparison with international practice (6.4%). The expectancy of reducing the number of checks, and thus costs, by deciding on the 4th to 6th week of life as the time for screening has not been met.


[Mechanism of Buyang Huanwu Decoction glycosides against atherosclerotic inflammation through NF-κB signaling pathway].
This study aims to explore the effect of Buyang Huanwu Decoction glycosides on the inflammatory response of apolipoprotein E~(-/-)(ApoE~(-/-)) mice and RAW264.7 cells through nuclear factor kappa-B(NF-κB) signaling pathway. In the in vivo experiment, ApoE~(-/-) mice were fed with high-fat diets for 12 weeks to induce the animal model of atherosclerosis, and 75 μg·mL~(-1) oxidized low-density lipoprotein(Ox-LDL) incubated RAW264.7 cells for 24 h to establish the atherosclerosis cell model. Automatic biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay(ELISA), Western blot, and droplet digital polymerase chain reaction(PCR) were used to determine the blood lipid levels, aortic intimal thickness, inflammatory factor content, NF-κB pathway-related proteins, and mRNA expression levels, and evaluate arterial atherosclerotic lesions and anti-atherosclerotic mechanisms of the drug. The model of atherosclerosis was successfully established in ApoE~(-/-) mice after 12 weeks of feeding with high-fat diets. In the model group, the plasma levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-C) were increased(P<0.01), the intima of the blood vessels was thickened, the levels of inflammatory factors tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were increased, and the protein and mRNA expressions of NF-κB and inhibitor of NF-κB(IκBα) were significantly increased as compared with the control group. Compared with the model group, the high-dose Buyang Huanwu Decoction glycoside group decreased the plasma levels of TC, TG, and LDL-C, reduced the plaque area and thickness and the content of inflammatory factor TNF-α, and inhibited the protein and mRNA expressions of NF-κB and IκBα, with the effect same as Buyang Huanwu Decoction. In the in vivo experiment, 75 μg·mL~(-1) Ox-LDL stimulated RAW264.7 cells for 24 h to successfully establish a foam cell model. As compared with the control group, the nuclear amount of NF-κB and the protein and mRNA expressions of IκBα in the model group increased. Compared with the model group, the middle-dose and high-dose Buyang Huanwu Decoction glycoside groups decreased the nuclear amount of NF-κB and the protein and mRNA expressions of IκBα. The above results show that the glycosides are the main effective substances of Buyang Huanwu Decoction against atherosclerosis, which inhibit the NF-κB pathway and reduce the inflammatory response, thus playing the role against atherosclerotic inflammation same as Buyang Huanwu Decoction.


Pulmonary Hypertension Secondary to COPD.
The development of pulmonary hypertension in COPD adversely affects survival and exercise capacity and is associated with an increased risk of severe acute exacerbations. Unfortunately not all patients with COPD who meet criteria for long term oxygen therapy benefit from it. Even in those who benefit from long term oxygen therapy, such therapy may reverse the elevated pulmonary artery pressure but cannot normalize it. Moreover, the recent discovery of the key roles of endothelial dysfunction and inflammation in the pathogenesis of PH provides the rationale for considering specific pulmonary vasodilators that also possess antiproliferative properties and statins.


A randomized trial to assess the pharmacodynamics and pharmacokinetics of a single dose of an extended-release aspirin formulation.
Low-dose acetylsalicylic acid (ASA; aspirin) for secondary prevention reduces cardiovascular disease mortality risk. ASA acetylates cyclooxygenase in the portal circulation and is rapidly (half-life, 20 min) hydrolyzed. Certain patients with cardiovascular disease may exhibit high on-therapy platelet reactivity as a result of high platelet turnover, a process whereby platelets are produced and are active beyond the duration of antiplatelet coverage provided by once-daily immediate-release (IR) ASA. A once-daily, extended-release (ER) ASA formulation using ER microcapsule technology was developed to release ASA over the 24-h dosing interval and reduce maximal plasma concentrations to spare peripheral endogenous endothelial prostacyclin production. Healthy adults (n = 50) were randomized in a crossover study to receive two different ER-ASA single doses (up to 325 mg) and two different IR-ASA single doses (up to 81 mg) in four periods, each separated by ≥14 days. Pharmacodynamics was assessed by measuring serum thromboxane B2 (TXB2), urine 11-dehydro-TXB2, and arachidonic acid-induced platelet aggregation. Pharmacokinetics was determined for ASA and salicylic acid (SA). Both formulations produced dose-dependent inhibition on all pharmacodynamic parameters. Marked inhibition of TXB2 and 11-dehydro-TXB2 was maintained over the 24-h dosing interval after a dose of ≥81 mg ER-ASA or ≥40 mg IR-ASA. The dose required to achieve 50% of maximum TXB2 inhibition with ER-ASA was 49.9 mg versus 29.6 mg for IR-ASA, for a similar maximum pharmacodynamic effect (98.9% TXB2 inhibition). This suggests that an approximately twofold greater ER-ASA dose (162.5 mg) is necessary to obtain the same response as that of IR-ASA 81 mg. Peak ASA concentrations were lower and Tmax was longer with ER-ASA versus IR-ASA. Administration of IR-ASA resulted in a dose-normalized mean Cmax of ASA that was approximately sixfold higher than that for ER-ASA and a Cmax of SA approximately two- to threefold higher than that for ER-ASA. Both ASA formulations showed dose-dependent antiplatelet activity. Compared with the IR-ASA, ER-ASA released active drug more slowly, resulting in prolonged absorption and lower systemic drug concentrations, which is expected for an ER (24-h) formulation.


Evaluation of the French version of the Orientation Towards Chocolate Questionnaire: chocolate-related guilt and ambivalence are associated with overweight and disordered eating.
The aims of this study were firstly to evaluate the psychometric properties of the French version of the Orientation towards Chocolate Questionnaire (OCQ), secondly to examine differences in chocolate craving as a function of weight status, and thirdly to examine the OCQ craving dimensions as predictors of body dissatisfaction and disordered eating. Participants included 247 female students from the University of Toulouse, France, who completed measures of chocolate craving, body dissatisfaction, bulimia, drive for thinness, and emotional eating, and for whom body mass index (BMI) was available. Confirmatory factor analysis supported the three-factor model of the OCQ, with guilt, approach, and avoidance subscales. Patterns of endorsement of chocolate craving dimensions differed according to weight status, with ambivalence present only amongst overweight participants. Guilt and approach were positively associated with disordered eating, whereas avoidance was negatively associated with bulimia. These results confirm the validity and reliability of the French version of the OCQ and highlight strong associations between chocolate craving dimensions and disordered eating patterns.


From humans to hydra: patterns of cancer across the tree of life.
Cancer is a disease of multicellularity; it originates when cells become dysregulated due to mutations and grow out of control, invading other tissues and provoking discomfort, disability, and eventually death. Human life expectancy has greatly increased in the last two centuries, and consequently so has the incidence of cancer. However, how cancer patterns in humans compare to those of other species remains largely unknown. In this review, we search for clues about cancer and its evolutionary underpinnings across the tree of life. We discuss data from a wide range of species, drawing comparisons with humans when adequate, and interpret our findings from an evolutionary perspective. We conclude that certain cancers are uniquely common in humans, such as lung, prostate, and testicular cancer; while others are common across many species. Lymphomas appear in almost every animal analysed, including in young animals, which may be related to pathogens imposing selection on the immune system. Cancers unique to humans may be due to our modern environment or may be evolutionary accidents: random events in the evolution of our species. Finally, we find that cancer-resistant animals such as whales and mole-rats have evolved cellular mechanisms that help them avoid neoplasia, and we argue that there are multiple natural routes to cancer resistance.


[Biological and health effects on electric and magnetic fields at extremely low frequencies].
While the enormous benefits of using electricity in everyday life and health care are unquestioned, during the past 20 years the general public has become increasingly concerned about potential adverse health effects of exposure to electric and magnetic fields at extremely low frequencies (ELF). Such exposures arise mainly from the transmission and use of electrical energy at the power frequencies of 50/60 Hz. The international scientific community is addressing the associated health issues through in vitro, in vivo and epidemiological studies, although present research results are often contradictory. The purpose of this paper is to provide information about the possible impacts of exposure to electric and magnetic field at ELF frequencies on health within the community and the workplace. Information comes from recent research studies on this subject and from epidemiological pooled studies recently reviewed by eminent authorities.


Biomimetic synthesis of hyperolactones.
Through a biomimetic pathway, hyperolactone D, 4-hydroxyhyperolactone D, and hyperolactone C were synthesized from methyl acetoacetate via Weiler's dianion method, asymmetric allylic alkylation, biomimetic lactonization, oxidation, and cyclization. The stereochemistry of the quaternary carbon was controlled efficiently by Palladium-catalyzed asymmetric allylic alkylation. This strategy was also used for the synthesis of hyperolactone B.


Liver cirrhosis on the colonic anastomotic healing in rats.
To investigate the effects of cirrhosis on colonic anastomosis healing in rats. Fifty five Wistar male rats were used (23 in the control group and 32 in the cirrhosis group). On the first day of the procedure, the rats in the cirrhosis group underwent double ligation and folding of the common bile duct to induce liver cirrhosis, and the control rats underwent a laparotomy and intestinal manipulation. On the fourteenth and thirty-fifth days, all of the animals were biochemically assessed for serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, bilirubin, total protein, and albumin and for liver histopathology. On the thirty-fifth day, cirrhosis was confirmed. On the twenty-eighth day, all of the animals were subjected to left colon transection and anastomosis. On the seventh day after the colonic anastomosis, the rats were sacrificed and macroscopically evaluated for dehiscence. The region of the colonic anastomosis was removed and subjected to hydroxyproline content measurement, conventional histology, and the immunohistochemical determination of vascular endothelial growth factor (VEGF) and matrix metalloproteinase type 1 (MMP 1). The biochemical and histopathological examinations confirmed cirrhosis in all of the animals in the cirrhosis group. More deaths occurred after anastomosis in the cirrhosis group (5/25) than in the control group (0/21), and anastomotic dehiscence was more frequent in the cirrhosis group (8/25) than in the control group (0/21). The average hydroxyproline concentration was lower in the cirrhosis group than in the control group. The immunohistochemical studies showed that the average VEGF expression in the cirrhosis group was lower than in the control group, and the average MMP1 expression was higher in the cirrhosis group. Hepatic cirrhosis leads to increased mortality and colonic anastomotic dehiscence, an increased distance between the mucosal edges of the anastomosis area, and a lower hydroxyproline concentration in the colonic anastomosis; therefore, these conditions are deleterious to healing.


Agent-based modeling in ecological economics.
Interconnected social and environmental systems are the domain of ecological economics, and models can be used to explore feedbacks and adaptations inherent in these systems. Agent-based modeling (ABM) represents autonomous entities, each with dynamic behavior and heterogeneous characteristics. Agents interact with each other and their environment, resulting in emergent outcomes at the macroscale that can be used to quantitatively analyze complex systems. ABM is contributing to research questions in ecological economics in the areas of natural resource management and land-use change, urban systems modeling, market dynamics, changes in consumer attitudes, innovation, and diffusion of technology and management practices, commons dilemmas and self-governance, and psychological aspects to human decision making and behavior change. Frontiers for ABM research in ecological economics involve advancing the empirical calibration and validation of models through mixed methods, including surveys, interviews, participatory modeling, and, notably, experimental economics to test specific decision-making hypotheses. Linking ABM with other modeling techniques at the level of emergent properties will further advance efforts to understand dynamics of social-environmental systems.


Chemoenzymatic synthesis of sacranosides a and B.
Direct beta-glucosidation between (-)-myrtenol and nerol and D-glucose (3) using the immobilized beta-glucosidase from almonds with the synthetic prepolymer ENTP-4000 gave myrtenyl O-beta-D-glucoside (4) and neryl O-beta-D-glucoside (10), respectively. The coupling of the myrtenyl or neryl O-beta-D-glucopyranoside congeners (7 or 13) and 2,3,4-tri-O-benzoyl-beta-L-arabinopyranosyl bromide (8) afforded the coupled products (9 or 14), respectively. Deprotection of the coupled products (9 or 14) afforded the synthetic myrtenyl 6-O-alpha-L-arabinopyranosyl-beta-D-glucopyranoside (Sacranoside A, 1) or neryl 6-O-alpha-L-arabinopyranosyl-beta-D-glucopyranoside (Sacranoside B, 2), respectively.


Recent advances in optical coherence tomography for anterior segment imaging in small animals and their clinical implications.
Anterior segment optical coherence tomography (AS-OCT) is a rapidly evolving area of OCT imaging, providing high-resolution and non-invasive volumetric imaging of the anterior segment. This review focuses on recent advances in AS-OCT imaging in small animals, which we categorize into ultrahigh-resolution, spectroscopic, magnetomotive, polarization-sensitive, and angiographic AS-OCTs. We summarize their technical foundations, review their applications to small animal imaging, and briefly discuss their current and future clinical applications.


Deflux® Endoscopic Treatment of Vesicoureteral Reflux (VUR) in Japan.
The aim of this study is to present the results of a multi-institutional outcome analysis conducted to determine the extent of endoscopic Deflux® injection for treating primary vesicoureteral reflux in Japan. A 22-question survey was distributed to 174 certified pediatric urologists (Ninteii in Japanese) and councilors of the Japanese Society of Pediatric Urology working at 140 centers to determine the usage and clinical efficacy of Deflux® for treating primary vesicoureteral reflux in Japan. Forty-three of 140 (30.7%) centers participated, which exceeded participation rates of 27.9 and 18.0% for similar surveys conducted in America in 2006 and 2014, respectively. Deflux® was administered at 43 centers using subureteral transurethral injection (n = 19; 44.2%), hydrodistention implantation (n = 5; 11.6%), or double hydrodistention implantation (n = 19; 44.2%) and was the first-line treatment for primary vesicoureteral reflux at 39 (90.7%) centers. Overall, 1,563 ureters were treated in 1,076 patients. The male:female ratio was 527:549; mean follow-up was 5.1 years (range: 3.2-8 years); mean age at diagnosis of primary vesicoureteral reflux was 4.2 years, and mean age at first Deflux® treatment was 6.2 years. Overall cure rates were 65.3% after one Deflux® treatment, 75.3% after two, and 77.3% after three. To the best of our knowledge, this is the first multi-institutional outcome analysis of Deflux® usage for primary vesicoureteral reflux in Japan.


Embedded system design for classification of COPD and pneumonia patients by lung sound analysis.
Chronic obstructive pulmonary disease (COPD) and pneumonia are lethal pulmonary illnesses with equivocal nature of abnormal pulmonic acoustics. Using lung sound signals, the classification of pulmonary abnormalities is a difficult task. A standalone system was conceived for screening COPD and Pneumonia patients through signal processing and machine learning methodologies. The proposed system will assist practitioners and pulmonologists in the accurate classification of disease. In this research work, ICBHI's and self-collected lung sound (LS) databases are used to investigate COPD and pneumonia patient. In this scheme, empirical mode decomposition (EMD), discrete wavelet transform (DWT), and analysis of variance (ANOVA) techniques are employed for segmentation, noise elimination, and feature selection, respectively. To overcome the inherent limitation of ICBHI's LS database, the adaptive synthetic (ADASYN) sampling technique is used to eradicate class imbalance. Lung sound features are used to train fine Gaussian support vector machine (FG-SVM) for classification of COPD, pneumonia, and heathy healthy subjects. This machine learning scheme is implemented on low cost and portable Raspberry pi 3 model B+ (Cortex-A53 (ARMv8) 64-bit SoC @ 1.4 GHz through hardware-supported language. Resultant hardware is capable of screening COPD and pneumonia patients accurately and assist health professionals.


Transcriptome profiling of the Plutella xylostella (Lepidoptera: Plutellidae) ovary reveals genes involved in oogenesis.
As a specialized organ, the insect ovary performs valuable functions by ensuring fecundity and population survival. Oogenesis is the complex physiological process resulting in the production of mature eggs, which are involved in epigenetic programming, germ cell behavior, cell cycle regulation, etc. Identification of the genes involved in ovary development and oogenesis is critical to better understand the reproductive biology and screening for the potential molecular targets in Plutella xylostella, a worldwide destructive pest of economically major crops. Based on transcriptome sequencing, a total of 7.88Gb clean nucleotides was obtained, with 19,934 genes and 1861 new transcripts being identified. Expression profiling indicated that 61.7% of the genes were expressed (FPKM≥1) in the P. xylostella ovary. GO annotation showed that the pathways of multicellular organism reproduction and multicellular organism reproduction process, as well as gamete generation and chorion were significantly enriched. Processes that were most likely relevant to reproduction included the spliceosome, ubiquitin mediated proteolysis, endocytosis, PI3K-Akt signaling pathway, insulin signaling pathway, cAMP signaling pathway, and focal adhesion were identified in the top 20 'highly represented' KEGG pathways. Functional genes involved in oogenesis were further analyzed and validated by qRT-PCR to show their potential predominant roles in P. xylostella reproduction. Our newly developed P. xylostella ovary transcriptome provides an overview of the gene expression profiling in this specialized tissue and the functional gene network closely related to the ovary development and oogenesis. This is the first genome-wide transcriptome dataset of P. xylostella ovary that includes a subset of functionally activated genes. This global approach will be the basis for further studies on molecular mechanisms of P. xylostella reproduction aimed at screening potential molecular targets for integrated pest management.


[Effect of Uremic Clearance Granules on improvement of chronic kidney disease in rats based on microbiome-metabolomics and its mechanism].
This research aimed to study the effect of Uremic Clearance Granules on chronic kidney disease in SD rats by using the methods of microbial functional genomics combined with metabolomics, and to preliminarily explore its mechanism. The SD rat model of chronic kidney disease was established by the adenine-induced method. After the model was successfully induced, the animals were randomly divided into a negative control group, a Uremic Clearance Granule treatment group, and a normal control group, with 8 rats in each group. After 4 weeks of administration, animal feces and serum were collected, and 16S rDNA sequencing technology was used to analyze the abundance, diversity, and function prediction of intestinal microorganisms. Liquid chromatography-mass spectrometry(LC-MS) technology was used to perform high-throughput sequencing to detect animal serum metabolites. The MetPA database was used to screen out potential biomarkers of chronic kidney disease in rats and conduct the enrichment analysis of metabolic pathways. Spearman's method was used to analyze the correlation between the two omics. The results showed that Uremic Clearance Granules effectively improved the body weight loss and renal function-related biochemical and appearance indicators in rats with chronic kidney disease. The results of 16S rDNA sequencing showed that Uremic Clearance Granules regulated the diversity and composition of the intestinal flora in rats with chronic kidney disease. The changes in the intestinal flora affected functional metabolic pathways such as amino acid biosynthesis and metabolism, lipid metabolism, and carbohydrate metabolism. The results of LC-MS showed that as compared with the negative control group, 15 metabolites were reversed in the Uremic Clearance Granule treatment group, among which 11 potential marker metabolites were significantly up-regulated and 4 potential marker metabolites were significantly down-regulated. Five amino acid metabolic pathways were mainly involved, which were significantly correlated with changes in the intestinal flora. Therefore, Uremic Clearance Granules can improve the renal function of rats with chronic kidney disease, and the mechanism may be related to its effect on the amino acid metabolism pathway by regulating the intestinal flora.


Predicted vs. observed radiographic progression in early rheumatoid arthritis (POPeRA): results from a randomized trial.
The aim of this study was to apply a previously published method for evaluating radiographic progression, namely, predicted vs. observed radiographic progression in early rheumatoid arthritis (POPeRA), to the Swedish pharmacotherapy (SWEFOT) trial. In SWEFOT, 487 patients with eRA were given methotrexate (MTX), and non-responders were randomized to group A [triple therapy: MTX+sulfasalazine (SSZ)+hydroxychloroquine (HCQ)] and group B [anti-tumour necrosis factor (anti-TNF) therapy: MTX+infliximab]. Responders continued on MTX. Predicted progression for 343 eligible patients was calculated based on the baseline total Sharp/van der Heijde score (SHS) divided by symptom duration, compared to observed progression at 12 and 24 months. Observed radiographic progression was reduced from predicted by a mean of 50.1% (A), 72.3% (B), and 73.9% (MTX) at 12 months and by 87.2, 89.8, and 87.8% at 24 months, respectively. Among completers, reductions of 56.7% (A) and 76.5% (B) at 12 months and of 91.0% and 96.0% at 24 months, respectively, were observed. At 12 months, there were no significant between-group differences. At 24 months, progression was reduced more in group B than in group A (first quartile difference 8.5% favouring group B) and in MTX [n=316, 89.8% (sd±32.0) vs. 87.2% (±32.2), p=0.021; vs. 87.8% (±27.8), p=0.013, respectively]. The POPeRA method confirms the original SWEFOT finding in that anti-TNF therapy was statistically marginally superior (2.6%) to triple therapy in preventing radiographic progression at 24 months among initial MTX non-responders. The simulation provided through POPeRA may facilitate comparisons of the relative efficacy of various treatments in preventing radiographic progression.


Creating Individual Surgeon Performance Assessments in a Statewide Hospital Surgical Quality Improvement Collaborative.
Surgeon performance profiling is of great interest to surgeons, hospitals, health plans, and the public, yet efforts to date have been contested, with stakeholders at odds over the selection, reliability, and validity of metrics used. We sought to create surgeon-level comparative assessments within the Illinois Surgical Quality Improvement Collaborative. American College of Surgeons NSQIP data were obtained for 51 Illinois hospitals covering a 30-month period from 2014 to 2016. Surgeon-level, risk-adjusted outcomes rates were estimated from 3-level crossed random effects logistic regression models and classified as low, as expected, or high for each of 7 postoperative outcomes. Model intra-class correlations and provider-specific reliability statistics were calculated. A total of 123,141 cases were analyzed for 2,724 surgeons. Median provider case volume was 17 (interquartile range 4 to 54). Overall crude complication rates ranged from 0.62% to 7.14% across the 7 outcomes investigated. Surgeon-level variance estimates were low (intra-class correlation coefficients between 0.007 and 0.074). No performance outliers were detected for 3 of the outcomes measures, while a small number of outliers were identified for any morbidity (11 surgeons), surgical site infection (10 surgeons), death or serious morbidity (8 surgeons), and reoperation (1 surgeon). Among all physicians, median reliability was below 0.1 for each outcome. Few individual surgeon performance outliers could be detected in NSQIP clinical registry data for a statewide hospital collaborative over a 30-month period using postoperative patient outcomes. Low surgeon-specific case volumes and minimal variance between surgeons may limit the utility of American College of Surgeons NSQIP outcomes measures for individual profiling. Alternative metrics, such as process measures, patient experience, composite measures, or technical skill assessments should be explored for surgeon-level measurement.