The Design of Individual Orthopedic Insoles for the Patients with Diabetic Foot Using Integral Curves to Describe the Plantar Over-Pressure Areas.
Identification of over-pressure areas in the plantar side of the foot in patients with diabetic foot and reduction of plantar pressure play a major role in clinical practice. The use of individual orthopedic insoles is essential to reduce the over-pressure. The aim of the present study is to mark the over-pressure areas of the plantar part of the foot on a pedogram and describe them with high accuracy using a mathematical research method. The locally over-pressured areas with calluses formed due to repeated injuries were identified on the patients' pedograms. The geometric shapes of the over-pressure areas were described by means of the integral curves of the solutions to Dirichlet singular boundary differential equations. Based on the mathematical algorithm describing those curves, the computer programs were developed. The individual orthopedic insoles were produced on a computer numerical control milling machine considering the locally over-pressured areas. The ethylene vinyl acetate polymers of different degrees of hardness were used to produce the individual orthopedic insoles. For the over-pressure areas, a soft material with a hardness of 20 Shore A was used, which reduces the pressure on the plantar side of the foot and increases the contact area. A relatively hard material with a hardness of 40 Shore A was used as the main frame, which imparts the stability of shape to the insole and increases its wear life. The individual orthopedic insoles produced by means of such technology effectively reduce the pressure on the plantar side of the foot and protect the foot from mechanical damage, which is important for the treatment of the diabetic foot.


Immunomodulatory effects of polysaccharide compounds in macrophages revealed by high resolution AFM.
Polysaccharide compounds (PCs), which composed of different kinds of polysaccharides always isolated from different kinds of traditional Chinese medicine, are now attracting more and more attentions due to their strong immunomodulatory activities beyond the corresponding one-component polysaccharides. In this study, we demonstrated for the first time that PCs-1 and PCs-2 had strong immunomodulatory effects on macrophages both in in vitro and in vivo models by atomic force microscopy (AFM). By high resolution AFM imaging, PCs-1 and PCs-2 were found to inhibit LPS induced cell surface particle size and roughness increase in RAW264.7 macrophages, demonstrating the anti-inflammatory effects of PCs-1 and PCs-2 on macrophages. PCs-1 and PCs-2 were also proved to increase the particle size and roughness of resting RAW264.7 macrophages, which suggested that PCs could activate resting RAW264.7 macrophages. And additionally, PCs-1 and PCs-2 were also found to reverse the surface particle size and roughness decrease of peritoneal macrophages isolated from cyclophosphamide induced immunosuppressive mice, suggesting the activation effects of PCs-1 and PCs-2 on immunosuppressive macrophages. These results further enhanced our understanding of macrophage activations by direct imaging of cell surface ultrastructure and also highlighted AFM as a novel nanotool for macrophage detections. And most importantly, these results also indicated the outstanding immunomodulatory effects of PCs on macrophages, which therefore suggested that PCs could be served as a kind of novel immunomodulatory agents that would benefit human health. SCANNING 38:792-801, 2016. © 2016 Wiley Periodicals, Inc.


Roflumilast treatment inhibits lung carcinogenesis in benzo(a)pyrene-induced murine lung cancer model.
Roflumilast, a potent and selective inhibitor of phosphodiesterase-4 (PDE4), has been used in treatment of COPD. PDE4 inhibitor is associated with inhibition of chronic airway inflammation, oxidative stress, and mesenchymal markers in B(a)P-induced lung tumors. The aim of this study was to assess whether roflumilast alone or added to inhaled budesonide might have dose-dependent inhibition on lung carcinogenesis induced by carcinogen B(a)P in mice. Female A/J mice were given a single dose of benzo(a)pyrene. Administration of roflumilast (1mg/kg or 5mg/kg) via oral gavage and aerosolized budesonide (2.25mg/ml) began 2 weeks post-carcinogen treatment and continued for 26 weeks. Tumor load was determined by averaging the total tumor volume in each group. Benzo(a)pyrene induced an average tumor size of 9.38 ± 1.75 tumors per mouse, with an average tumor load of 19.53 ± 3.81mm3. Roflumilast 5mg/kg treatment decreased (P < 0.05) tumor load per mouse compared to the B(a)P group. Roflumilast 5mg/kg treatment significantly increased the levels of cAMP in tumors with adjacent lung tissues (P < 0.05). The expression level of PDE4D gene was decreased by roflumilast 5mg/kg treatment, significantly (P < 0.05). Compared to the B(a)P exposure group, expression levels of HIF-1α and VEGFA were attenuated by roflumilast 5mg/kg treatment (P < 0.05). High-dose roflumilast can attenuate lung carcinogenesis in B(a)P-induced murine lung cancer model. The chemopreventive effect of roflumilast might be associated with inhibition of increased cAMP-mediated inflammatory process and markers of angiogenesis in tumor tissues.


Cholecystokinin (pancreozymin). Synthesis and properties of the N alpha-acetyl-derivative of cholecystokinin 27-33.
The acetyl-derivative of the biologically active C-terminal 7-peptide portion of cholecystokinin (CCK), N-acetyl-O-sulfate-L-tyrosyl-L-methionyl-glycyl-L-tryptophyl-L-methionyl-L-aspartyl-L-phenylalanine amide was prepared by the condensation of 2-peptide segments with 1-isobutyloxycarbonyl-2-isobutyloxy-1,2-dihydroquinoline as coupling reagent. The N-terminal residue, tyrosine was incorporated by the active ester method. The same 7-peptide was prepared also by stepwise chain-lengthening, starting with the C-terminal residue. The 9-fluorenylmethyloxycarbonyl group was applied for the protection of alpha-amino functions. In the release of amylase from acinar cells of the pancreas of guinea pigs, the acetyl-7-peptide amide was about 3 times more potent than CCK 27-33 and equal in potency to CCK 26-33. The new derivative strongly stimulated the contraction of the in situ guinea pig gall bladder.


Drastic fluorine effect: complete reversal of the selectivity in the Au-catalyzed hydroalkoxylation reaction of fluorinated haloalkynes.
The gold-catalyzed hydration reaction of haloalkynes is highly regioselective producing 2-halomethylketones as the sole products. Herein, we document a drastic fluorine effect where the reaction of 1-halo-3,3-difluoroalkynes as substrates leads to a complete reversal of selectivity and produces 3,3-difluoroesters as the unique products.


Personality of males charged with outrage of modesty.
Outrage of modesty (OOM) is considered a serious crime in Singapore and offenders are often charged with a period of imprisonment with or without a fine and caning. Previous studies have indicated that non-violent sexual offenders tend to have a socially inhibited personality. No published study has yet been conducted to investigate the personality of OOM offenders. The purpose of the current study was to assess the personality of males charged with outrage of modesty and compare them to a group of males charged with theft using the 16 Personality Factors questionnaire (16PF; Cattell, Eber, and Tatsuoka, 1970). Participants were selected over a two-year study period from a cohort of prisoners serving sentence at Changi Prison. A total of 30 OOM and 22 theft offenders completed the 16PF. All OOM subjects had been charged for molesting an adult female. Unexpectedly, planned comparisons revealed that OOM subjects had marginally higher scores on Factor H (boldness) compared to theft subjects. Exploratory analyses revealed no other significant differences between OOM and theft subjects. Implications of findings and limitations of the study are discussed.


Tyrosine hydroxylase-like immunoreactive neurons in the olfactory bulb of the snake, Elaphe quadrivirgata, with special reference to the colocalization of tyrosine hydroxylase- and GABA-like immunoreactivities.
The distribution and structural features of tyrosine hydroxylase-like immunoreactive (TH-LI) neurons were studied in the olfactory bulb of a snake, Elaphe quadrivirgata, by using pre- and post-embedding immunocytochemistry at the light microscopic level. In contrast to rodent olfactory bulbs previously reported, many TH-LI neurons were seen not only in the main olfactory bulb (MOB) but also in the accessory olfactory bulb (AOB). With regard to the TH-like immunoreactivity, there appeared no appreciable differences between MOB and AOB. As in mammalian MOB, the majority of TH-LI neurons were clustered in the periglomerular region and appeared to send their dendritic branches into glomeruli, which as a whole make an intense TH-LI band in the glomerular layer (GML). In the external plexiform/mitral cell layer (EPL/ML) of MOB and AOB as well as in the outer sublamina of the internal plexiform layer (OSL) of AOB, an appreciable number of TH-LI neurons were scattered, extending dendritic processes which appeared to make a loose meshwork. TH-LI neurons in EPL/ML (including OSL) appeared to consist of at least two morphologically different types. The first had a small perikaryon and one or two smooth dendrites which usually extended to GML and were frequently confirmed to enter into glomeruli. The second had a larger perikaryon and 2-3 dendrites which branched into several varicose processes extending in EPL/ML/OSL but appeared not to enter into glomeruli. The TH-like immunoreactivity was rarely seen in the internal plexiform layer and internal granule cell layer. The colocalization of GABA-like and TH-like immunoreactivities was further studied. Almost all TH-LI neurons in both EPL/ML/OSL and GML contained GABA-like immunoreactivity irrespectively of the type of TH-LI cells.


Negative pressure effects on mechanically opposing pharyngeal muscles in awake and sleeping goats.
Our aim was to investigate the effects of the negative pressure reflex on mechanically opposing pharyngeal muscles during wakefulness, slow-wave sleep (SWS), and rapid eye movement (REM) sleep. In four goats with isolated upper airways, we measured tracheal airflow and electrical activity of the thyropharyngeus (TP; constricting), the stylopharyngeus (SP; dilating), and the diaphragm (Dia). In the wakefulness state in response to negative pressure tests, TP decreased (65%), SP increased (198%), and tidal volume (VT) (66%) and rate of rise of Dia (Dia(slope), 69%) decreased (P < 0.02). Similarly, during SWS, the negative pressure response of TP (31%), VT (61%), and Dia(slope) (60%) decreased, whereas SP (113%) increased, relative to SWS control (P < 0.02). In REM sleep, the negative pressure response by TP and SP were small, whereas both VT (38%) and Dia(slope) (24%) were greatly decreased (P < 0.02) compared with REM control. Inspiratory duration remained unchanged in response to negative pressure tests in all states. These data provide evidence that mechanically opposing inspiratory and expiratory pharyngeal muscles are reciprocally controlled and their response to negative pressure are state dependent.


An investigation into the role of initial K(L)a on the growth and alkaloid accumulation by cultures of Catharanthus roseus.
The effect of initial K(L)a on the batch culture of Catharanthus roseus ID1 in a 12.5-L bioreactor has been examined. Optimum K(L)a values were found for both growth and alkaloid accumulation. Different sparger designs were used to alter the K(L)a values. High K(L)a values caused increased aggregation of the cultures, depressed biomass yields, and altered patterns of alkaloid accumulation.


A divide and conquer real-space approach for all-electron molecular electrostatic potentials and interaction energies.
A computational scheme to perform accurate numerical calculations of electrostatic potentials and interaction energies for molecular systems has been developed and implemented. Molecular electron and energy densities are divided into overlapping atom-centered atomic contributions and a three-dimensional molecular remainder. The steep nuclear cusps are included in the atom-centered functions making the three-dimensional remainder smooth enough to be accurately represented with a tractable amount of grid points. The one-dimensional radial functions of the atom-centered contributions as well as the three-dimensional remainder are expanded using finite element functions. The electrostatic potential is calculated by integrating the Coulomb potential for each separate density contribution, using our tensorial finite element method for the three-dimensional remainder. We also provide algorithms to compute accurate electron-electron and electron-nuclear interactions numerically using the proposed partitioning. The methods have been tested on all-electron densities of 18 reasonable large molecules containing elements up to Zn. The accuracy of the calculated Coulomb interaction energies is in the range of 10(-3) to 10(-6) E(h) when using an equidistant grid with a step length of 0.05 a(0).


Volume therapy with hypertonic saline hydroxyethyl starch solution in cardiac surgery.
The ideal solution for volume therapy remains controversial. In cardiac surgery, haemodynamic efficacy as well as the influence of extracorporeal oxygenation are of major interest when administering volume. The present study examines the effects of a new hypertonic saline hydroxyethyl starch solution in comparison to a 6% hydroxyethyl starch solution on haemodynamics and laboratory variables. Patients scheduled for elective aortocoronary bypass grafting received hypertonic saline hydroxyethyl starch (n = 10) or hydroxyethyl starch (n = 10) after induction of anaesthesia in order to double baseline pulmonary capillary wedge pressure. Ten patients without volume therapy served as a control group. Significantly less hypertonic solution than standard solution was effective in doubling pulmonary capillary wedge pressure. Fluid requirements in the patients who received the hypertonic solution were significantly less during, as well as after, cardiopulmonary bypas in comparison to those in the other groups. Cardiac index increased most in the patients who received the hypertonic solution (+34.8%), as did right ventricular end-diastolic volume. Patients in that group showed the highest decrease in total systemic resistance (-29.8%), whereas arterial pressure and right ventricular ejection fraction remained almost unchanged in all groups. No negative alteration in coagulation or organ function was demonstrated within the investigation period. It can be concluded that hypertonic saline hydroxyethyl starch solution seems to be a valuable alternative to conventional volume therapy in cardiac surgery.


Intrahepatic cholangiocarcinoma associated with central calcification and arterio-portal shunt.
Although several diagnostic imaging modalities have been significantly improved in the recent years, the definitive diagnosis of intrahepatic cholangiocarcinoma (IHC) is still sometimes difficult because of the versatile features of IHC with each imaging. A 68-year-old Japanese man with alcoholic liver cirrhosis developed an intrahepatic tumor. Several imaging modalities demonstrated various features, such as central calcification and arterio-portal (A-P) shunt. Since we could not reach a final diagnosis and the tumor size gradually increased, partial hepatectomy was done after obtaining written informed consent from the patient. The postoperative histopathological examination revealed a cholangiocarcinoma. Herein, we report this case of IHC that was very difficult to diagnose due to the simultaneous association with central calcification and A-P shunt.


Peptides and small molecules of the plant-pathogen apoplastic arena.
Plants reside within an environment rich in potential pathogens. Survival in the presence of such threats requires both effective perception of, and appropriate responses to, pathogenic attack. While plants lack an adaptive immune system, they have a highly developed and responsive innate immune system able to detect and inhibit the growth of the vast majority of potential pathogens. Many of the critical interactions that characterize the relationship between plants and pathogens are played out in the intercellular apoplastic space. The initial perception of pathogen invasion is often achieved through specific plant receptor-like kinases that recognize conserved molecular patterns presented by the pathogen or respond to the molecular debris caused by cellular damage. The perception of either microbial or damage signals by these receptors initiates a response that includes the production of peptides and small molecules to enhance cellular integrity and inhibit pathogen growth. In this review, we discuss the roles of apoplastic peptides and small molecules in modulating plant-pathogen interactions.


Synthesis and site selective C-H functionalization of imidazo-[1,2-a]pyridines.
Imidazo[1,2-a]pyridine has attracted much interest in drug development because of its potent medicinal properties, therefore the discovery of novel methods for its synthesis and functionalization continues to be an exciting area of research. Although transition metal catalysis has fuelled the most significant developments, extremely beneficial metal-free approaches have also been identified. Even though pertinent reviews focused on imidazo[1,2-a]pyridine synthesis, properties (physicochemical and medicinal), and functionalization at the C3 position have been published, none of these reviews has focused on the outcomes obtained in the field of global ring functionalization. We wish here to describe a brief synthesis and an overview of all the functionalization reactions at each carbon atom, viz, C2, C3, C5, C6, C7 and C8 of this scaffold, divided into sections based on site-selectivity and the type of functionalization methods used.


Changes in muscle fibre size and physical performance in patients with rheumatoid arthritis after short-term physical training.
Ten patients with rheumatoid arthritis of moderate severity were given 6 weeks' intense physical training. During the investigation period the patients improved their physical performance capacity as well as their rate of perceived exertion. There was an increase in the muscle fibre size, of type I and type II, most pronounced in the latter fibre group. No 'flare-up' of the arthritis could be seen during the training period. Comments are made as to which patients might benefit by a short-term physical training.


Effects of upregulation of Hsp27 expression on oocyte development and maturation derived from polycystic ovary syndrome.
Heat shock protein 27 (Hsp27) is a heat shock protein family member which can inhibit apoptosis. Our previous studies reported down-regulated Hsp27 in ovarian tissue derived from women with polycystic ovary syndrome (PCOS) however, the exact effect of Hsp27 on oocyte maturation and developmental competence in PCOS is unclear. The effect of Hsp27 over-expression was studied in vitro using oocytes derived from PCOS patients. An artificial GFP-plasmid was injected into human oocyte to increase Hsp27 protein level. Oocyte maturation was evaluated by morphological observation. Mature oocytes were fertilized by intracytoplasmic sperm injection (ICSI) and embryonic developmental competence was evaluated. Critical apoptotic factors and cytokines were measured at both the mRNA and protein level. Our results revealed that Overexpression of HSP27 lowered the maturation rate of oocytes derived from PCOS patients. Meanwhile, fertilization rate and high quality embryo rate were similar between the Hsp27 overexpressing group and controls; however, the blastocyst formation rate in this group was significantly higher than control. Expression analysis revealed that the oocyte-secreted factors, BMP15 and GDF9, and the apoptotic-related regulators, Caspase 3, 8 and 9, were all significantly decreased in Hsp27 overexpressing oocytes. In conclusion, upregulation of Hsp27 inhibits oocyte maturation from PCOS patients, but improves embryonic developmental potential.


DDX3X mutations in two girls with a phenotype overlapping Toriello-Carey syndrome.
Recently, de novo heterozygous variants in DDX3X have been reported in about 1.5% of 2659 females with previously unexplained intellectual disability (ID). We report on the identification of DDX3X variants in two unrelated girls with clinical features of Toriello-Carey Syndrome (T-CS). In patient 1, the recurrent variant c.1703C>T; p.(P568L) was identified when reconsidering X-linked de novo heterozygous variants in exome sequencing data. In patient 2, the DDX3X variant c.1600C>G; p.(R534G) was also detected by exome sequencing. Based on these data, de novo heterozygous DDX3X variants should be considered not only in females with unexplained ID, but also in individuals with a clinical diagnosis of T-CS.


Tongue sole creatine kinases function as DAMP and activate antimicrobial immunity via TLR2.
Creatine kinase (CK) is an enzyme that regulates adenosine triphosphate (ATP) metabolism to maintain energy homeostasis. Although CK has been reported to be involved in pathogen infection, the immune function of CK remains elusive. In this study, we identified two muscle-type CK from the teleost tongue sole Cynoglossus semilaevis (designated CsCKM-1 and CsCKM-2). Bacterial infection modulated CsCKM-1/2 expression in tongue sole tissues and induced the release of CsCKM-1/2 into serum. Recombinant CsCKM-1/2 (rCsCKM-1/2) exhibited robust kinase activity and bound to bacterial pathogens and pathogen-associated molecular patterns. rCsCKM-1/2 also bound to tongue sole peripheral blood leukocytes (PBLs) and promoted PBLs to uptake bacterial pathogens, inhibit bacterial proliferation, and express proinflammatory cytokines. When co-expressed in HEK293T cells, CsCKM-1/2 were found to interact with the leucine rich domain of toll-like receptor 2 (TLR2). The presence of TLR2 antagonist significantly reduced CsCKM-1/2-induced immune response and antibacterial effect. Taken together, these results indicated that tongue sole creatine kinases function as damage-associated molecular pattern (DAMP) molecules and play an important role in antimicrobial immunity via TLR2.


Novel heterozygous mutations in the PGAM2 gene with negative exercise testing.
Pathogenic variants in the PGAM2 gene are associated with glycogen storage disease type X (GSDX) and is characterized by exercise induced muscle cramping, weakness, myoglobinuria, and often tubular aggregates in skeletal muscle. We report here a patient diagnosed with GSDX at 52 years of age with a normal increase in post-exercise lactate with both anaerobic and aerobic exercise. Genetic testing found two novel PGAM2 variants (c.426C > A, p.Tyr142Ter and c.533delG, p.Gly178Alafs*31).


Neurokinin-induced salivation in the anesthetized rat: a three receptor hypothesis.
Substance P (3 micrograms/kg), neurokinin A (20 micrograms/kg), neurokinin B (6 micrograms/kg) and acetylcholine (875 micrograms/kg) all produced salivation upon i.v. infusion in the anesthetized rat. Against single equivalent agonist doses, atropine (135 micrograms/kg i.v.) blocked both acetylcholine- and neurokinin B-, but not substance P- or neurokinin A-induced salivation. [D-Pro2,D-Trp7,9]-substance P (1 mg/kg i.v.), a putative substance P antagonist, reduced responses to mammalian neurokinins but caused a 2-fold potentiation of acetylcholine-induced salivation. [D-Pro2,D-Trp6,8,Nle10]-Neurokinin B (1 mg/kg i.v.), a novel putative neurokinin B antagonist, significantly reduced substance P- and neurokinin B- but not acetylcholine- or neurokinin A-induced salivation. The three agonists (at doses that produced salivation) and [D-Pro2,D-Trp6,8,Nle10]-neurokinin B (1 mg/kg i.v.) lowered blood pressure in anesthetized rats by 35 to 40%. [D-Pro2,D-Trp7,9]-Substance P (1 mg/kg i.v.) had no significant effect on blood pressure. Hydralazine at 0.60 mg/kg (i.v.), a dose which lowered blood pressure by 47%, did not reduce substance P-induced salivation. Thus, blockade of neurokinin-induced salivation by [D-Pro2,D-Trp6,8,Nle10]-neurokinin B was probably not due to hypotension. Based on the differential effects of the three antagonists on neurokinin- and acetylcholine-induced salivation, we hypothesize the existence of three distinct neurokinin receptors in rat salivary gland, and suggest that neurokinin B receptors reside presynaptically.


A clinical retrospective evaluation of FA/HA coated (Biocomp) dental implants. Results after 1 year.
In this retrospective clinical evaluation, the performance of loaded titanium implants with a bilayer bioactive surface coating of the relatively reactive hydroxylapatite (HA, outer layer) and the more stable fluorapatite (FA, inner layer) was evaluated. 98 consecutive patients were included in the study for a total of 354 implants, loaded by overdentures, fixed partial dentures and single tooth replacements. Statistical analyses revealed a cumulative probability of implant survival on a per patient basis of 94.5% (s.e. 2.7%), one year after implant installation. On implants that were lost parts of the bilayer FA/HA coating had vanished as a result of primary or secondary infection and subsequently epithelial down growth. Most complications were associated with implants placed in the maxilla. Periotest values (PTV) were generally high, indicating adequate osseointegration. The PTV's were statistically significantly less favorable in implants placed in the maxilla. The most favorable PTV's and gingival index scores were found around implants servicing overdentures. Marginal bone loss averaged approximately 2mm during the observation period. The amount of marginal bone loss corresponded with the distance from the neck of the implant to the first thread of the implant's cervical screw-section. It is concluded that, during the relatively short observation period, the FA/HA coated implants function adequately. However, in the absence of a direct implant-to-bone contact preceding implant loss, part of the FA/HA coating on the titanium implants generally dissolves.


Approach to palpitations.
Palpitations are one of the most common presentations to general practice. While they are usually benign, they may be associated with an adverse prognosis. This article presents a systematic approach to the patient with palpitations and addresses considerations of aetiology, history and examination; appropriate diagnostic work-up; cardiology/electrophysiology referral and management strategies. Not all palpitations are due to arrhythmia, and because of the transitory nature of palpitations, the work-up will usually be performed between episodes. Direction from history, examination and 12-lead electrocardiography will guide further investigations and will often include an echocardiogram and ambulatory electrocardiographic monitoring. The intensity of ambulatory electrocardiographic monitoring and diagnostic work-up will be dictated by the frequency, nature and severity of symptoms, and will sometimes require incorporation of new technologies and electrophysiology referral. Ultimately, management must be tailored on a case-by-case basis depending on the cause of palpitations and symptom severity.


[Clinical efficacy of adalimumab for a postoperative marginal ulcer in gastrointestinal Behçet disease].
A 63-year-old woman with Behçet disease presented with epigastric pain due to refractory gastric ulcers. Examinations indicated that these ulcers were caused by gastrointestinal Behçet disease. Steroid therapy proved ineffective, so we gave 5mg/kg of infliximab. However, since the patient responded poorly to the treatment the infliximab was discontinued and a total gastrectomy was performed. After surgery, a marginal ulcer developed and infliximab was again administered. Although this brought about improvement in the conditions of the marginal ulcer, infusion-related hypersensitivities in the patient caused polyarthralgia. We therefore discontinued the infliximab treatment and began 40 mg of adalimumab every other week. After 3 months of the new treatment, the patient's marginal ulcer completely healed and her epigastric pain disappeared. This case suggests that adalimumab may be as useful as infliximab for treating refractory gastrointestinal Behçet disease.


Structural characterization and anti-HSV-1 and HSV-2 activity of glycolipids from the marine algae Osmundaria obtusiloba isolated from Southeastern Brazilian coast.
Glycolipids were extracted from the red alga Osmundaria obtusiloba from Southeastern Brazilian coast. The acetone insoluble material was extracted with chloroform/methanol and the lipids, enriched in glycolipids, were fractionated on a silica gel column eluted with chloroform, acetone and then methanol. Three major orcinol-positive bands were found in the acetone and methanol fractions, being detected by thin layer chromatography. The structures of the corresponding glycolipids were elucidated by ESI-MS and (1)H/(13)C NMR analysis, on the basis of their tandem-MS behavior and HSQC, TOCSY fingerprints. For the first time, the structure of sulfoquinovosyldiacylglycerol from the red alga Osmundaria obtusiloba was characterized. This molecule exhibited potent antiviral activity against HSV-1 and HSV-2 with EC(50) values of 42 µg/mL to HSV-1 and 12 µg/mL to HSV-2, respectively. Two other glycolipids, mono- and digalactosyldiacylglycerol, were also found in the alga, being characterized by ESI-MS/MS. The structural elucidation of algae glycolipids is a first step for a better understanding of the relation between these structures and their biological activities.


Anthracene-terpyridine metal complexes as new G-quadruplex DNA binders.
The formation of quadruple-stranded DNA induced by planar metal complexes has particular interest in the development of novel anticancer drugs. This is especially relevant for the inhibition of telomerase, which plays an essential role in cancer cell immortalization and is overexpressed in ca. 85-90% of cancer cells. Moreover, G-quadruplexes also exist in other locations in the human genome, namely oncogene promoter regions, and it has been hypothesized that they play a regulatory role in gene transcription. Herein we report a series of new anthracene-containing terpyridine ligands and the corresponding Cu(II) and Pt(II) complexes, with different linkers between the anthracenyl moiety and the terpyridine chelating unit. The interaction of these ligands and metal complexes with different topologies of DNA was studied by several biophysical techniques. The Pt(II) and Cu(II) complexes tested showed affinity for quadruplex-forming sequences with a good selectivity over duplex DNA. Importantly, the free ligands do not have significant affinity for any of the DNA sequences used, which shows that the presence of the metal is essential for high affinity (and selectivity). This effect is more evident in the case of the Pt(II) complexes. Moreover, the presence of a longer linker between the chelating terpyridine unit and the anthracene moiety enhances the interaction with G-quadruplex-forming sequences. We further evaluated the ability of the Cu(II) complexes to interact with, and stabilize G-quadruplex containing regions in oncogene promoters via a polymerase stop assay. These studies indicated that the metal complexes are able to induce G-quadruplex formation and stop polymerase activity.


Kikuchi-Fujimoto Disease in an Old Italian Woman: Case Report and Review of the Literature.
Kikuchi-Fujimoto disease (KFD) is a rare, benign, generally self-limiting disease that has higher prevalence in Asian people with a few cases reported in European countries. It generally affects young subjects under 40 years of age and is characterized by regional lymphadenopathy. Here, we present a case of a 66-year-old Italian woman who was extensively examined for right unilateral laterocervical lymph nodes associated with fever, night sweats, fatigue, and weight loss. She was diagnosed as having the KFD only after an excision biopsy of the largest laterocervical lymph node and was then managed symptomatically with NSAIDs. We also made a review of the literature for better awareness of the disease among physicians especially in those countries, like Italy, where the disease is not prevalent and may be frequently misdiagnosed. In fact, to our best knowledge, only seven Italian cases of KFD have been published in the last 15 years with patients being younger than 40 years. We finally highlight that it is noteworthy to consider KFD as differential diagnosis of lymphadenopathy even in old patients, and, since a misdiagnosis of lymphoma is actually feasible, an early biopsy has to be taken into account for confirming diagnosis and helping in the timely and appropriate management.


Effects of low density lipoprotein on type IV collagen production by cultured rat mesangial cells.
Hyperlipidemia, especially hypercholesterolemia, may contribute to glomerulosclerosis as it does to atherosclerosis. Low density lipoprotein (LDL) stimulates the production of extracellular matrix by mesangial cells in culture as well as the proliferation of mesangial cells. This study was carried out to examine the effects of LDL on the type IV collagen (CIV) production by cultured rat mesangial cells (CRMC). Subconfluent CRMC monolayers which were grown in RPMI with 20% lipid-free fetal calf serum for 48 h were challenged with LDL (0, 50, 100, 150 and 200 micrograms/ml) for another 48 h. LDL was prepared from normal human plasma. Mesangial cell proliferation was examined by [3H]-thymidine uptake. Production of CIV was evaluated as the expression of CIV on the cell surface by flow-cytometric analysis. The collagen synthesis was measured by the [3H]-proline uptake. Total RNA was extracted from CRMC at 6 and 24 h of incubation with 150 micrograms/ml LDL, and Northern blotting and hybridization was performed with cDNAs for alpha 1-CIV, for 72-kD collagenase and for tissue inhibitor of metalloproteinase (TIMP)-2. The amount of total mRNA was corrected with beta-actin mRNA. Mesangial cell proliferation increased in all concentrations studied and had a peak value of 221% with 150 micrograms/ml of LDL. Expression of CIV increased by 30-60% in 100-200 micrograms/ml of LDL. Collagen synthesis also increased by 50-70% in 150-200 micrograms/ml of LDL. The mRNA ratio (procollagen alpha 1(IV)/beta-actin) increased to 133% at 24 h. The mRNA ratio (TIMP-2/beta-actin) increased to 137% at 24 h. mRNA ratios at 6 h showed no change.(ABSTRACT TRUNCATED AT 250 WORDS)


Potential role of sulfur-containing antioxidant systems in highly oxidative environments.
All forms of life maintain a reducing environment (homeostasis) within their cells. Perturbations in the normal redox state can lead to an oxidative environment which has deleterious effects, especially in health. In biological systems, metabolic activities are dependent mainly on mitochondrial oxidative phosphorylation, a metabolic pathway that uses energy released by the oxidation of nutrients to produce ATP. In the process of oxidative phosphorylation, electrons are transferred from electron donors to electron acceptors such as oxygen in redox reactions and often results to the generation of reactive species. Reactive oxygen species consist of a class of radical and non-radical oxygen derivatives. The imbalance between the reactive oxygen species and antioxidant defence systems leads to oxidative burden and hence, damage biological molecules. Antioxidants help to prevent or fix the deleterious effects of reactive species. Sulfur is an important element in biological systems. This atom is usually integrated into proteins as the redox-active cysteine residue and in molecules such as glutathione, thioredoxin and glutaredoxin which are vital antioxidant molecules and are therefore essential for life. This review covers the role of sulfur containing antioxidant systems in oxidative environments.


Antiepileptic effect of high-frequency stimulation of the subthalamic nucleus (corpus luysi) in a case of medically intractable epilepsy caused by focal dysplasia: a 30-month follow-up: technical case report.
Currently, some forms of epilepsy are resistant to both pharmacological and surgical interventions. As a result, there is a need for new therapeutic strategies. Because the nigral system modulates neuronal excitability in animal models of epilepsy, we considered therapeutic high-frequency stimulation of the subthalamic nucleus (STN). We were encouraged by the known relationship between the STN and the nigral system, as well as by our experience with high-frequency stimulation of the STN in Parkinsonian patients. A 5-year-old girl with pharmacologically resistant, inoperable epilepsy caused by focal centroparietal dysplasia underwent implantation with a permanent electrode in the left STN and was chronically stimulated. To date, we have followed up this patient for 30 months postoperatively. High-frequency stimulation of the STN induced a significant voltage-dependent reduction (by 80%) in the number and severity of seizures. In addition, consistent improvement in both motor and cognitive functions was noted as a result of reduced postictal states. The effect was more prominent for seizures occurring in clusters (89% reduction) and during the day (88% reduction) than for those that occurred during sleep (53% reduction). This is the first report of epilepsy control using chronic high-frequency stimulation of the STN. Preliminary observations in three other operated patients (at 2, 12, and 18 mo) confirm these data. We think that high-frequency stimulation of the STN may hold significant future potential as a treatment for epilepsy, similar to its established role in the treatment of Parkinson's disease. This finding opens completely new experimental and therapeutic avenues for the treatment of surgically and medically intractable epilepsy.


Synchronization between two hele-shaw cells.
Complete synchronization between two Hele-Shaw cells is examined. The two dynamical systems are chaotic in time and spatially extended in two dimensions. It is shown that a large number of connectors are needed to achieve synchronization. In particular, we have studied how the number of connectors influences the dynamical regime that is set inside the Hele-Shaw cells.


Rapid effectiveness of certolizumab pegol in non-radiographic axial spondyloarthritis.
In axial spondyloarthritis (SpA), the efficacy of certolizumab pegol (CZP), a novel pegylated anti-tumor necrosis factor alpha drug has not been investigated. We report that CZP showed a rapid effectiveness, assessed clinically and by magnetic resonance imaging, in a patient with a non-radiographic axial SpA, classified according to Assessment in SpondyloArthritis International Society (ASAS) criteria. This case suggests that CZP could be considered an useful treatment in non-radiographic axial SpA, supporting that an earlier therapeutic approach could play a relevant role in the management of the disease.


Obstructive sleep apnea in the Rubinstein-Taybi syndrome.
The Rubinstein-Taybi syndrome is characterized by a pattern of malformations including broad thumbs and big toes, microcephaly, facial dysmorphism, small stature, and mental retardation. Obstructive sleep apnea (OSA), has been described in several facial or skeletal malformations, but never in the Rubinstein-Taybi syndrome. We studied a 9-year-old boy, previously diagnosed as having the Rubinstein-Taybi syndrome and affected by severe OSA, as documented by polysomnography. He manifested the habitual and heavy snoring with breathing difficulties at night, and excessive daytime sleepiness. Short neck and obesity were important factors for the severity of the syndrome. Continuous positive airway pressure was not tolerated and weight loss was the only possible treatment, as upper airway surgery was not indicated by cephalometric, otolaryngologic or clinical results.


Molecular evidence for ten species and Oligo-Miocene vicariance within a nominal Australian gecko species (Crenadactylus ocellatus, Diplodactylidae).
Molecular studies have revealed that many putative 'species' are actually complexes of multiple morphologically conservative, but genetically divergent 'cryptic species'. In extreme cases processes such as non-adaptive diversification (speciation without divergent selection) could mask the existence of ancient lineages as divergent as ecologically and morphologically diverse radiations recognised as genera or even families in related groups. The identification of such ancient, but cryptic, lineages has important ramifications for conservation, biogeography and evolutionary biology. Herein, we use an integrated multilocus genetic dataset (allozymes, mtDNA and nuclear DNA) to test whether disjunct populations of the widespread nominal Australian gecko species Crenadactylus ocellatus include distinct evolutionary lineages (species), and to examine the timing of diversification among these populations. We identify at least 10 deeply divergent lineages within the single recognised species Crenadactylus ocellatus, including a radiation of five endemic to the Kimberley region of north-west Australia, and at least four known from areas of less than 100 km2. Lineages restricted to geographically isolated ranges and semi-arid areas across central and western Australia are estimated to have began to diversify in the late Oligocene/early Miocence (~20-30 mya), concurrent with, or even pre-dating, radiations of many iconic, broadly sympatric and much more species-rich Australian vertebrate families (e.g. venomous snakes, dragon lizards and kangaroos). Instead of a single species, Crenadactylus is a surprisingly speciose and ancient vertebrate radiation. Based on their deep divergence and no evidence of recent gene flow, we recognise each of the 10 main lineages as candidate species. Molecular dating indicates that the genus includes some of the oldest vertebrate lineages confounded within a single species yet identified by molecular assessments of diversity. Highly divergent allopatric lineages are restricted to putative refugia across arid and semi-arid Australia, and provide important evidence towards understanding the history and spread of the Australian arid zone, suggesting at a minimum that semi-arid conditions were present by the early Miocene, and that severe aridity was widespread by the mid to late Miocene. In addition to documenting a remarkable instance of underestimation of vertebrate species diversity in a developed country, these results suggest that increasing integration of molecular dating techniques into cryptic species delimitation will reveal further instances where taxonomic conservatism has led to profound underestimation of not only species numbers, but also highly significant phylogenetic diversity and evolutionary history.


Protective effect of choline theophyllinate on histamine, acetylcholine, and propranolol-induced airflow obstruction.
The protective effect of choline theophyllinate, 600 mg orally, was studied by examining the effects on inhaled histamine, acetylcholine, and propranolol in 19 asthmatic patients. Only 9 of them showed a propranolol threshold. This bronchodilator significantly increased the threshold values of histamine and acetylcholine, but showed no protective effect on propranolol thresholds. The histamine threshold changed from 2(2.5 +/- (SD)1.2) to 2(3.8 +/- 1.0) mg/ml (p less than 0.001). With acetylcholine an initial value of 2(4.2 +/- 1.4 mg/ml was determined, which changed to 2(5.5 +/- 1.1 mg/ml (p less than 0.01). The propranolol threshold changed from 1.17% +/- 0.40 to 1.36% +/- 0.40 indicating that theophylline has no statistically significant protective effect on propranolol inhalation. The reproducibility of the challenges was assessed in 8 control patients. A placebo did not significantly change the initial airway reactivity to the three agents. The protective effect of choline theophyllinate on histamine and acetylcholine correlated with the initial degree of reactivity on both agents (r = -0.60; p less than 0.01 and r = -0.84; p less than 0.001, respectively), whereas no significant correlation with the degree of bronchodilation was observed. The latter observation indicates that the protective effect of theophylline does not depend on its bronchodilating activity.


Prostaglandin FP agonists alter metalloproteinase gene expression in sclera.
The present study was undertaken to determine whether exposure of the sclera to prostaglandin (PG)F(2alpha) or to the PGF(2alpha) analogue latanoprost acid alters mRNA for matrix metalloproteinases. Fifteen human eye bank eyes were studied. Circular pieces of sclera were either immediately preserved in a stabilization reagent or cultured in low-serum DMEM/F-12 medium. The cultures were treated for 24 hours with medium supplemented with PGF(2a), latanoprost acid, or vehicle. Total RNA was then isolated, and the expression of mRNA for matrix metalloproteinase (MMP)-1, -2, -3, -8, -9, -10, and -12 were determined by real-time PCR. All results were normalized according to the GAPDH mRNA in each sample. Altered mRNA expression after PG treatments also was evaluated with microarrays containing 19 MMP genes and 4 tissue inhibitor of matrix metalloproteinase (TIMP) genes. Real-time PCR results showed that 24 hours of exposure to 100 nM PGF(2alpha) significantly increased mRNA for MMP-1 and -9 (P < 0.06 Wilcoxon test) and that exposure to 100 nM latanoprost acid significantly increased mRNA for MMP-9 (P < 0.06 Wilcoxon test). Array analysis demonstrated increases of MMP-3 and -10 mRNA after exposure to 100 nM latanoprost and further increases after exposure to 200 nM latanoprost. The array results also showed that latanoprost induced dose-dependent increases in the expression of TIMP-1, -2, and -3 mRNA in the scleral cultures. PGF(2alpha) and latanoprost acid induce coordinated alterations of MMP gene transcription in scleral organ cultures. These results indicate that PGs can directly trigger MMP gene transcription changes within the sclera. These changes support a role for increased MMPs in the enhancement of uveoscleral outflow that occurs after topical treatment with latanoprost.


Effect of long-distance transportation on serum metabolic profiles of steer calves.
Long-distance transportation is sometimes inevitable in the beef industry because of the geographic separation of major breeding and fattening areas. Long-distance transportation negatively impacts production and health of cattle, which may, at least partly, result from the disturbance of metabolism during and after transportation. However, alteration of metabolism remains elusive in transported cattle. We investigated the effects of transportation on the metabolomic profiles of Holstein steer calves. Non-targeted analysis of serum concentrations of low molecular weight metabolites was performed by gas chromatography mass spectrometry. Transportation affected 38 metabolites in the serum. A pathway analysis suggested that 26, 10, and 10 pathways were affected immediately after transportation, and 3 and 7 days after transportation, respectively. Some pathways were disturbed only immediately after transportation, likely because of feed and water withdrawal during transit. Nicotinate and nicotinamide metabolism, and citric acid cycle were affected for 3 days after transportation, whereas propionate metabolism, phenylalanine and tyrosine metabolism were affected throughout the experiment. Four pathways were not affected immediately after transportation, but were altered thereafter. These results suggested that many metabolic pathways had marked perturbations during transportation. Metabolites such as citric acid, propionate, tyrosine and niacin can be candidate supplements for mitigating transportation-induced adverse effects.


Changes in the expression of drug-metabolising enzymes and drug transporters in mice with collagen antibody-induced arthritis.
1. We investigated the changes in the expression of drug-metabolising enzymes and drug transporters in the liver, small intestine and kidney of mice with collagen antibody-induced arthritis (CAIA) to determine whether changes in these expressions affect pharmacokinetics of drugs in patients with rheumatoid arthritis.2. mRNA expression levels of cytochrome P450 (Cyp) 2b10, Cyp2c29 and Cyp3a11 were observed to be lower in the liver and small intestine of CAIA mice than in control mice. Compared with control mice, mRNA expression levels of multidrug resistance 1 b, peptide transporter 2 and organic anion transporter (Oat) 2 were high in the liver of CAIA mice. Changes in these expression levels were different among organs. However, elevated expression of Oat2 mRNA was not associated with an increase in protein expression and transport activity evaluated using [3H]cGMP as a substrate.3. These results suggest that arthritis can change the expression of pharmacokinetics-related genes, but the changes may not necessarily be linked to the pharmacokinetics in patients with rheumatoid arthritis. On the other hand, we found Oat2 mRNA expression level was positively correlated with plasma interleukin-6 level, indicating that transcriptional activation of Oat2 may occur in inflammatory state.


Impact of alpha-amylase and maltodextrin on physicochemical, functional and antioxidant capacity of spray-dried purple sweet potato flour.
Purple sweet potato flour could be used to enhance food products through colour, flavour and nutrients. Purple sweet potato flour has not yet been prepared with maltodextrin and amylase treatment using spray drying. Thus, the investigation was to evaluate the effect of various levels of maltodextrin (30 and 50 g kg(-1) w/v), amylase (3 and 7 g kg(-1) puree) and combined with maltodextrin and amylase on the physicochemical, functional and antioxidant capacity of spray dried purple sweet potato flours. Amylase and amylase with maltodextrin-treated flours had a higher anthocyanin and total phenolic content than the control and maltodextrin-treated flours. However, the antioxidant capacity was higher in the control and maltodextrin-treated flours compared to the amylase and amylase with maltodextrin-treated flours. The control had a higher water absorption index and lower water solubility index compared to the maltodextrin and combined with amylase and maltodextrin-treated flours. On the other hand, maltodextrin increased whereas alpha-amylase decreased the glass transition temperature. With respect to morphology, the particles of amylase-treated flours were smaller than the control and maltodextrin-treated flours. The results showed that good quality flour could be prepared by combining 30 g kg(-1) maltodextrin and 7 g kg(-1) amylase treatment.


Shape change and obesity prevalence among male UK offshore workers after 30 years: New insight from a 3D scanning study.
In 1984, male UK offshore workers had greater overweight and obesity prevalence and fat content than the general population. Since then, body weight has increased by 19%, but, without accompanying anthropometric measures, their size increase, current obesity, and fatness prevalence remain unknown. This study therefore aimed to acquire contemporary anthropometric data, profile changes since the original survey, and assess current obesity prevalence in the male offshore workforce. A total of 588 men, recruited via quota sampling to match the workforce weight profile, underwent stature, weight, and 3D photonic scanning measurements from which anatomical girths were extracted, enabling computation of body mass index (BMI), total fat, and visceral adipose tissue (VAT). On average, UK male offshore workers are now 8.1 y older, 3.1 cm taller, 13.9 kg heavier, and have greater girths than in 1984, which are >97% attributable to increased weight, and <3% to age difference. Mean BMI increased significantly from 24.9 to 28.1 kg/m2 and of the contemporary sample, 18% have healthy weight, 52% are overweight, and 30% obese, representing an increase in overweight and obesity prevalence by 6% and 24%, respectively. Waist cutoffs identify 39% of the contemporary sample as healthy, 27% at increased health risk, and 34% at high risk. UK offshore workers today have higher BMI than Scottish men, although some muscular individuals may be misclassified by BMI. Girth data, particularly at the waist, where dimensional increase was greatest, together with predictions of total and visceral fatness, suggest less favorable health status in others.


Comparative genomic analysis of Campylobacter hepaticus genomes associated with spotty liver disease, Georgia, United States.
Campylobacter hepaticus has re-emerged as an important cause of disease in egg laying birds worldwide, resulting in morbidity, mortality, and significant losses in eggs for the breeding and table egg laying industries. Although birds may appear asymptomatic, the disease is characterized by spots on the liver of birds and histopathological analysis reveals multifocal fibrogranulocytic necrotizing hepatitis microscopically. The re-emergence of C. hepaticus may be linked with housing practices as the disease appears more prevalent in pasture raised birds with outside exposure. Here we describe, the whole genome sequences and comparative analysis of four C. hepaticus genomes associated with an outbreak on pasture raised breeders from a farm in Georgia, United States. All four genomes were relatively similar in size and virulence genes harbored. Using these genomes, comparison with current C. hepaticus genomes available in NCBI and other databases and other members of the Campylobacter species was carried out. Using current tools available, virulence gene factor content was compared, and it was found that different tools lead to different numbers of factors identified. The four genomes from this study were relatively similar to C. hepaticus HV10 the type strain from Australia but differed from the other sequenced US strains from Iowa and Florida. C. hepaticus was found to have an overall lower gene content for genes associated with virulence and iron acquisition compared to other Campylobacter genomes and appears to cluster differently than UK genomes on phylogenetic analysis, suggesting the emergence of two lineages of C. hepaticus. This analysis provides valuable insight into the emerging pathogen C. hepaticus, its virulence factors and traits associated with disease in poultry production in the US, potentially providing insight into targets for its control and treatment for laying birds. Our analysis also confirms genes associated with iron acquisition are limited and the presence of the multidrug efflux pump CmeABC in C. hepaticus which may promote survival and persistence in the host niche - the chicken liver/bile. One unique aspect of this study was the finding of a close genetic relationship between C. hepaticus and Campylobacter fetus species and evidence of genome reduction in relation to host niche specificity.


Enteroaggregative Escherichia coli Adherence Fimbriae Drive Inflammatory Cell Recruitment via Interactions with Epithelial MUC1.
Enteroaggregative Escherichia coli (EAEC) causes diarrhea and intestinal inflammation worldwide. EAEC strains are characterized by the presence of aggregative adherence fimbriae (AAF), which play a key role in pathogenesis by mediating attachment to the intestinal mucosa and by triggering host inflammatory responses. Here, we identify the epithelial transmembrane mucin MUC1 as an intestinal host cell receptor for EAEC, demonstrating that AAF-mediated interactions between EAEC and MUC1 facilitate enhanced bacterial adhesion. We further demonstrate that EAEC infection also causes elevated expression of MUC1 in inflamed human intestinal tissues. Moreover, we find that MUC1 facilitates AAF-dependent migration of neutrophils across the epithelium in response to EAEC infection. Thus, we show for the first time a proinflammatory role for MUC1 in the host response to an intestinal pathogen.IMPORTANCE EAEC is a clinically important intestinal pathogen that triggers intestinal inflammation and diarrheal illness via mechanisms that are not yet fully understood. Our findings provide new insight into how EAEC triggers host inflammation and underscores the pivotal role of AAFs-the principal adhesins of EAEC-in driving EAEC-associated disease. Most importantly, our findings add a new dimension to the signaling properties of the transmembrane mucin MUC1. Mostly studied for its role in various forms of cancer, MUC1 is widely regarded as playing an anti-inflammatory role in response to infection with bacterial pathogens in various tissues. However, the role of MUC1 during intestinal infections has not been previously explored, and our results describe the first report of MUC1 as a proinflammatory factor following intestinal infection.


Infectious diarrhea in human immunodeficiency virus infection.
Gastrointestinal symptoms, particularly diarrhea, are common in patients with AIDS. Recent evidence indicates that enteric pathogens can be identified in most of these cases. Appreciating the clinical features caused by protozoal, fungal, bacterial, and viral pathogens will assist the clinician in effectively evaluating the gastrointestinal symptoms. Antimicrobial agents now are available for many of these pathogens.


The fiber orientation in the coronary arterial wall at physiological loading evaluated with a two-fiber constitutive model.
A patient-specific mechanical description of the coronary arterial wall is indispensable for individualized diagnosis and treatment of coronary artery disease. A way to determine the artery's mechanical properties is to fit the parameters of a constitutive model to patient-specific experimental data. Clinical data, however, essentially lack information about the stress-free geometry of an artery, which is necessary for constitutive modeling. In previous research, it has been shown that a way to circumvent this problem is to impose extra modeling constraints on the parameter estimation procedure. In this study, we propose a new modeling constraint concerning the in-situ fiber orientation (β (phys)). β (phys), which is a major contributor to the arterial stress-strain behavior, was determined for porcine and human coronary arteries using a mixed numerical-experimental method. The in-situ situation was mimicked using in-vitro experiments at a physiological axial pre-stretch, in which pressure-radius and pressure-axial force were measured. A single-layered, hyperelastic, thick-walled, two-fiber material model was accurately fitted to the experimental data, enabling the computation of stress, strain, and fiber orientation. β (phys) was found to be almost equal for all vessels measured (36.4 ± 0.3)°, which theoretically can be explained using netting analysis. In further research, this finding can be used as an extra modeling constraint in parameter estimation from clinical data.


Simultaneous deblurring and iterative reconstruction of CBCT for image guided brain radiosurgery.
One of the limiting factors in cone-beam CT (CBCT) image quality is system blur, caused by detector response, x-ray source focal spot size, azimuthal blurring, and reconstruction algorithm. In this work, we develop a novel iterative reconstruction algorithm that improves spatial resolution by explicitly accounting for image unsharpness caused by different factors in the reconstruction formulation. While the model-based iterative reconstruction techniques use prior information about the detector response and x-ray source, our proposed technique uses a simple measurable blurring model. In our reconstruction algorithm, denoted as simultaneous deblurring and iterative reconstruction (SDIR), the blur kernel can be estimated using the modulation transfer function (MTF) slice of the CatPhan phantom or any other MTF phantom, such as wire phantoms. The proposed image reconstruction formulation includes two regularization terms: (1) total variation (TV) and (2) nonlocal regularization, solved with a split Bregman augmented Lagrangian iterative method. The SDIR formulation preserves edges, eases the parameter adjustments to achieve both high spatial resolution and low noise variances, and reduces the staircase effect caused by regular TV-penalized iterative algorithms. The proposed algorithm is optimized for a point-of-care head CBCT unit for image-guided radiosurgery and is tested with CatPhan phantom, an anthropomorphic head phantom, and 6 clinical brain stereotactic radiosurgery cases. Our experiments indicate that SDIR outperforms the conventional filtered back projection and TV penalized simultaneous algebraic reconstruction technique methods (represented by adaptive steepest-descent POCS algorithm, ASD-POCS) in terms of MTF and line pair resolution, and retains the favorable properties of the standard TV-based iterative reconstruction algorithms in improving the contrast and reducing the reconstruction artifacts. It improves the visibility of the high contrast details in bony areas and the brain soft-tissue. For example, the results show the ventricles and some brain folds become visible in SDIR reconstructed images and the contrast of the visible lesions is effectively improved. The line-pair resolution was improved from 12 line-pair/cm in FBP to 14 line-pair/cm in SDIR. Adjusting the parameters of the ASD-POCS to achieve 14 line-pair/cm caused the noise variance to be higher than the SDIR. Using these parameters for ASD-POCS, the MTF of FBP and ASD-POCS were very close and equal to 0.7 mm-1 which was increased to 1.2 mm-1 by SDIR, at half maximum.


Increased return of spontaneous circulation at the expense of neurologic outcomes: Is prehospital epinephrine for out-of-hospital cardiac arrest really worth it?
Current guidelines for the management of out-of-hospital cardiac arrest (OHCA) recommend the use of prehospital epinephrine by initial responders. This recommendation was initially based on data from animal models of cardiac arrest and minimal human data, but since its inception, more human data regarding prehospital epinephrine in this setting are now available. Although out-of-hospital return of spontaneous circulation (ROSC) may be higher with the use of epinephrine, worse neurologic outcomes may be associated with its use. A systematic review of the literature was conducted by search of databases including PubMed, Embase, and OVID to identify studies comparing patients with OHCA who had received epinephrine before arrival to the hospital with those who had not. Studies were assessed for quality and bias, and data were abstracted from studies deemed appropriate for inclusion. A meta-analysis was conducted using a Mantel-Haenszel model for dichotomous outcomes. Outcomes studied were prehospital ROSC, survival at 1 month, survival to discharge, and positive neurologic outcome. A total of 14 studies with 655853 patients were included for the meta-analysis. The use of epinephrine for OHCA before arrival to the hospital was associated with a significant increase in ROSC (odds ratio, 2.86; P<.001) and a significant increase in the risk of poor neurologic outcome at the time of discharge (odds ratio 0.51, P=.008). There was no significant difference in survival at 1 month or survival to discharge. Use of epinephrine before arrival to the hospital for OHCA does not increase survival to discharge but does make it more likely for those who are discharged to have poor neurologic outcome. There is a need for additional randomized controlled trials.


Collision complexes in dissociative single electron transfer between Ne2+ and N2.
Experiments involving the coincident detection of the two monocationic products (Ne+ and N+) from the dissociative electron transfer reaction between Ne2+ and N2 at 7.8 eV collision energy allow the nascent velocity vectors of the ionic and neutral (N) products to be determined. Examination of the correlations between these vectors shows that one pathway to the products involves the dissociation of a transitory collision complex (N2Ne2+).


Comparison of subtotal vertebral resection with reconstruction and percutaneous vertebroplasty for treatment of metastasis in the lumbar spine.
Purpose: Tumor metastasis in the spine can cause pain and fractures, leading to deformities, and deficits in movement, sensation, and bowel/bladder function. Percutaneous vertebroplasty (PVP) and subtotal vertebral resection with reconstruction (SVR) are suitable treatments, but their relative clinical efficacy is uncertain. The purpose of this retrospective cohort study was to compare the management and clinical effect of SVR for lumbar metastatic tumor with PVP.Methods: Sixty-seven patients (mean age: 58.6 years) with metastases in the lumbar spine received SVR or PVP at our institution between 2010 and 2013. Thirty-three patients received SVR via a posterior approach, in which vertebrae were resected, with the anterior and lateral walls retained using polymethylmethacrylate (PMMA), followed by reconstruction and pedicle screw fixation. Thirty-four patients received PVP via the vertebral pedicle. Patients were followed for 3-26 months.Results: None of the patients experienced serious complications after surgery, and all patients experienced significant amelioration of pain. Twelve patients (8 in the PVP group and 4 in the SVR group) died during the follow-up, and the survival time was significantly longer in the SVR group. Two patients in the SVR group and 7 patients in the PVP groups experienced recurrence during follow-up, but the groups had no significant difference in local recurrence. Both treatments significantly reduced scores for pain on a visual analog scale (pain-VAS) and disability (Oswestry Disability Index [ODI]), and increased performance status (Karnofsky Performance Status [KPS]). Compared with the PVP group, the SVR group had better ODI score at 1 month and 3 months after surgery and a higher KPS score at 1 month after surgery. The two groups had no significant difference in pain-VAS scores during follow-up.Conclusions: SVR is a reliable treatment for lumbar metastatic tumor and provides good survival rate and satisfying follow-up results.


[Concept and clinical characteristics of diabetes mellitus in the elderly].
Both decreased insulin secretion and insulin resistance are two major factors of impaired glucose tolerance (IGT) in the elderly. Up to now, decreased lean body mass and relatively increased fat mass, so-called sarcopenia or sarcopenic obesity, contribute to insulin resistance in the elderly. However, recent reports indicate that muscle mitochondrial function is reduced in aging, and this age-associated decline in mitochondrial function contributes to insulin resistance in the elderly. In addition, exercise intervention to IGT in the elderly is more effective to reduce in the incidence of type 2 diabetes than in younger people. Exercise seems to improve insulin resistance through mitochondrial function by activating AMP-activated protein kinase(AMPK) and PPARgamma coactivator-1alpha (PGC-1alpha). Because cognitive impairment is a most crucial factor plunging into frailty in diabetic elderly, diabetic control would be very important in preventing cognitive decline as well as vascular events. However, comprehensive management of diabetes, including dyslipidemia and hypertension, might contribute to the prevention of declines in cognitive function in older diabetic patients.


Machine learning-based diffusion model for prediction of coronavirus-19 outbreak.
The coronavirus pandemic has been globally impacting the health and prosperity of people. A persistent increase in the number of positive cases has boost the stress among governments across the globe. There is a need of approach which gives more accurate predictions of outbreak. This paper presents a novel approach called diffusion prediction model for prediction of number of coronavirus cases in four countries: India, France, China and Nepal. Diffusion prediction model works on the diffusion process of the human contact. Model considers two forms of spread: when the spread takes time after infecting one person and when the spread is immediate after infecting one person. It makes the proposed model different over other state-of-the art models. It is giving more accurate results than other state-of-the art models. The proposed diffusion prediction model forecasts the number of new cases expected to occur in next 4 weeks. The model has predicted the number of confirmed cases, recovered cases, deaths and active cases. The model can facilitate government to be well prepared for any abrupt rise in this pandemic. The performance is evaluated in terms of accuracy and error rate and compared with the prediction results of support vector machine, logistic regression model and convolution neural network. The results prove the efficiency of the proposed model.


Utilization of inulin-containing waste in industrial fermentations to produce biofuels and bio-based chemicals.
Inulins are polysaccharides that belong to an important class of carbohydrates known as fructans and are used by many plants as a means of storing energy. Inulins contain 20 to several thousand fructose units joined by β-2,1 glycosidic bonds, typically with a terminal glucose unit. Plants with high concentrations of inulin include: agave, asparagus, coffee, chicory, dahlia, dandelion, garlic, globe artichoke, Jerusalem artichoke, jicama, onion, wild yam, and yacón. To utilize inulin as its carbon and energy source directly, a microorganism requires an extracellular inulinase to hydrolyze the glycosidic bonds to release fermentable monosaccharides. Inulinase is produced by many microorganisms, including species of Aspergillus, Kluyveromyces, Penicillium, and Pseudomonas. We review various inulinase-producing microorganisms and inulin feedstocks with potential for industrial application as well as biotechnological efforts underway to develop sustainable practices for the disposal of residues from processing inulin-containing crops. A multi-stage biorefinery concept is proposed to convert cellulosic and inulin-containing waste produced at crop processing operations to valuable biofuels and bioproducts using Kluyveromyces marxianus, Yarrowia lipolytica, Rhodotorula glutinis, and Saccharomyces cerevisiae as well as thermochemical treatments.


Mental health service and provider preference among American Indians with type 2 diabetes.
In this study, we investigated mental health service and provider preferences of American Indian adults with type 2 diabetes from two tribes in the northern Midwest. Preferences were determined and compared by participant characteristics. After controlling for other factors, living on reservation lands was associated with increased odds of Native provider preference, and decreased odds of biomedical service preference. Anxiety also was associated with decreased odds of biomedical service preference. Spiritual activity engagement and past health care discrimination were associated with increased odds of traditional service preference. We discuss implications for the types of mental health services offered and characteristics of providers who are recruited for tribal communities.


Cellular and Circuitry Bases of Autism: Lessons Learned from the Temporospatial Manipulation of Autism Genes in the Brain.
Transgenic mice carrying mutations that cause Autism Spectrum Disorders (ASDs) continue to be valuable for determining the molecular underpinnings of the disorders. Recently, researchers have taken advantage of such models combined with Cre-loxP and similar systems to manipulate gene expression over space and time. Thus, a clearer picture is starting to emerge of the cell types, circuits, brain regions, and developmental time periods underlying ASDs. ASD-causing mutations have been restricted to or rescued specifically in excitatory or inhibitory neurons, different neurotransmitter systems, and cells specific to the forebrain or cerebellum. In addition, mutations have been induced or corrected in adult mice, providing some evidence for the plasticity and reversibility of core ASD symptoms. The limited availability of Cre lines that are highly specific to certain cell types or time periods provides a challenge to determining the cellular and circuitry bases of autism, but other technological advances may eventually overcome this obstacle.


Additive and antagonistic antinociceptive interactions between magnesium sulfate and ketamine in the rat formalin test.
Because ketamine and magnesium block NMDA receptor activation by distinct mechanisms of action, we hypothesized that in a model of inflammatory pain in rats the combination of ketamine and magnesium might be more effective than ketamine alone. Antinociceptive activity was assessed by the formalin test in male Wistar rats (200-250 g). Animals were injected with 100 μL of 2.5% formalin to the plantar surface of the right hind paw. Data were recorded as the total time spent in pain-related behavior after the injection of formalin or vehicle (0.9% NaCl). Ketamine and magnesium sulfate given separately reduced nocifensive behavior in the second phase of the formalin test in rats. When ketamine was applied after magnesium sulfate, the log dose-response curves for the effects of ketamine and the magnesium sulfate-ketamine combination revealed antagonistic interaction, and about 1.6 (CL 1.2-2.4) fold increment in ketamine dosage. A low dose of magnesium sulfate (5 mg/kg, subcutaneously) administered after ketamine increased the antinociceptive effect of ketamine by a factor of only 1.2 (CL 0.95-1.38), indicating an additive interaction. There was a 1.8-fold reduction in dosage of ketamine when ketamine was administered before rather than after the magnesium sulfate. The present study revealed that both ketamine and magnesium reduced pain-related behavior in the second phase of the formalin test in rats. Ketamine, when administered before or after the magnesium, provided additive or antagonistic antinociceptive interactions, respectively. Whether there will be an additive or antagonistic antinociceptive interaction between ketamine and magnesium depends on the order of drug administration.


Monitoring of Vibrio harveyi quorum sensing activity in real time during infection of brine shrimp larvae.
Quorum sensing, bacterial cell-to-cell communication, has been linked to the virulence of pathogenic bacteria. Indeed, in vitro experiments have shown that many bacterial pathogens regulate the expression of virulence genes by this cell-to-cell communication process. Moreover, signal molecules have been detected in samples retrieved from infected hosts and quorum sensing disruption has been reported to result in reduced virulence in different host-pathogen systems. However, data on in vivo quorum sensing activity of pathogens during infection of a host are currently lacking. We previously reported that quorum sensing regulates the virulence of Vibrio harveyi in a standardised model system with gnotobiotic brine shrimp (Artemia franciscana) larvae. Here, we monitored quorum sensing activity in Vibrio harveyi during infection of the shrimp, using bioluminescence as a read-out. We found that wild-type Vibrio harveyi shows a strong increase in quorum sensing activity early during infection. In this respect, the bacteria behave remarkably similar in different larvae, despite the fact that only half of them survive the infection. Interestingly, when expressed per bacterial cell, Vibrio harveyi showed around 200-fold higher maximal quorum sensing-regulated bioluminescence when associated with larvae than in the culture water. Finally, the in vivo quorum sensing activity of mutants defective in the production of one of the three signal molecules is consistent with their virulence, with no detectable in vivo quorum sensing activity in AI-2- and CAI-1-deficient mutants. These results indicate that AI-2 and CAI-1 are the dominant signals during infection of brine shrimp.


The integration of multiple signaling pathways provides for bidirectional control of CRHR1 gene transcription in rat pituitary cell during hypoxia.
Hypoxia upregulates hypothalamic corticotrophin releasing hormone (CRH) and its receptor type-1 (CRHR1) expression and activates the HPA axis and induces hypoxic sickness and behavioral change. The transcriptional mechanism by which hypoxia differently regulates CRHR1 expression remains unclear. Here we report hypoxia time-dependently induced biphasic expression of CRHR1mRNA in rat pituitary during different physiological status. Short exposure of gestational dams to hypoxia reduced CRHR1mRNA in the pituitary of P1-P14 male rat offspring. A short- and prolonged-hypoxia evoked biphasic response of CRHR1mRNA characterized initially by decreases and subsequently by persistent increases, mediated by a rapid negative feedback via CRHR1 signaling and positive transcriptional control via NF-κB, respectively. Further analysis of CRHR1 promoter in cultured primary anterior pituitary and AtT20 cells showed that c-Jun/AP-1 delivered negative while HIF-1α and NF-κB delivered positive control of transcription at CRHR1 promoter. The negative and positive inputs are integrated by hypoxic initiation and duration in CRHR1 transcription.


3,5-Bis{4-[(benzimidazol-1-yl)methyl]phenyl}-4H-1,2,4-triazol-4-amine and its one-dimensional polymeric complex with HgCl2.
The molecule of 3,5-bis{4-[(benzimidazol-1-yl)methyl]phenyl}-4H-1,2,4-triazol-4-amine (L), C(30)H(24)N(8), has an antiperiplanar conformation of the two terminal benzimidazole groups and forms two-dimensional networks along the crystallographic b axis via two types of intermolecular hydrogen bonds. However, in catena-poly[[[dichloridomercury(II)]-μ-3,5-bis{4-[(benzimidazol-1-yl)methyl]phenyl}-4H-1,2,4-triazol-4-amine] dichloromethane hemisolvate], {[HgCl(2)(C(30)H(24)N(8))]·0.5CH(2)Cl(2)}(n), synthesized by the combination of L with HgCl(2), the L ligand adopts a synperiplanar conformation. The Hg(II) cation lies in a distorted tetrahedral environment, which is defined by two N atoms and two Cl atoms to form a one-dimensional zigzag chain. These zigzag chains stack via hydrogen bonds which expand the dimensionality of the structure from one to two.


Potential Involvement of Platelet-Derived Microparticles and Microparticles Forming Immune Complexes during Monocyte Activation in Patients with Systemic Lupus Erythematosus.
Microparticles (MPs) are vesicles derived from the plasma membrane of different cells, are considered a source of circulating autoantigens, and can form immune complexes (MPs-ICs). The number of MPs and MPs-ICs increases in patients with systemic lupus erythematosus (SLE). MPs activate myeloid cells by inducing IL-6 and TNF-α in both SLE and other diseases. Therefore, we propose that the recognition of MPs-ICs by monocytes rather that MPs may define their phenotype and contribute to the inflammatory process in patients with SLE. Thus, the aims of this study were to evaluate the association among circulating MPs-ICs from different cell sources, alterations observed in monocyte subsets, and disease activity in patients with SLE and to establish whether monocytes bind and respond to MPs-ICs in vitro. Circulating MPs and monocyte subsets were characterized in 60 patients with SLE and 60 healthy controls (HCs) using multiparametric flow cytometry. Patients had higher MP counts and frequencies of MPs-CD41a + (platelet-derived) compared with HCs, regardless of disease activity. MPs from patients with SLE were C1q + and formed ICs with IgM and IgG. MPs-IgG + were positively correlated with active SLE (aSLE), whereas MPs-IgM + were negatively correlated. Most of the circulating total ICs-IgG + were located on MPs. The proportion and number of non-classical monocytes were significantly decreased in patients with SLE compared with HCs and in patients with aSLE compared with patients with the inactive disease. Non-classical monocytes obtained from patients with SLE exhibited increased levels of CD64 associated with MPs-IgG +, MPs-C1q +, total circulating ICs-IgG +, and disease activity. The direct effects of MPs and MPs-IgG + on monocytes were evaluated in cell culture. Monocytes from both HCs and patients bound to and internalized MPs and MPs-IgG + independent of CD64. These vesicles derived from platelets (PMPs), mainly PMPs-IgG +, activated monocytes in vitro and increased the expression of CD69, CD64, and pro-inflammatory cytokines such as IL-1β, TNF-α, and IFN-α. Therefore, MPs are one of the most representative sources of the total amount of circulating ICs-IgG + in patients with SLE. MPs-IgG + are associated with SLE activity, and PMPs-IgG + stimulate monocytes, changing their phenotype and promoting pro-inflammatory responses related to disease activity.


[Interrelations in the immune system of Staphylococcus aureus carriers].
The immune status of 60 S. aureus carriers and 60 donors without carrier state was studied with respect to the interrelations of their antistaphylococcal immunity characteristics and natural resistance factors with the levels of different parameters. In contrast to the donors without carrier state, new interrelations between specific and nonspecific humoral immunity factors were shown to appear in S. aureus carriers, their blood sera having the elevated levels of bactericidal activity and the increased titers of staphylococcal antibodies. The phagocytic activity of the blood in the carriers proved to be below the normal level. The S. aureus carriers were found to have disturbances in the interrelations of their phagocytic activity and specific humoral immunity. The immune status of the carriers as characterized by the interrelations of its parameters is compared with the immune status of normal persons.


Statistical mechanics and thermodynamic limit of self-gravitating fermions in D dimensions.
We discuss the statistical mechanics of a system of self-gravitating fermions in a space of dimension D. We plot the caloric curves of the self-gravitating Fermi gas giving the temperature as a function of energy and investigate the nature of phase transitions as a function of the dimension of space. We consider stable states (global entropy maxima) as well as metastable states (local entropy maxima). We show that for D> or =4, there exists a critical temperature (for sufficiently large systems) and a critical energy below which the system cannot be found in statistical equilibrium. Therefore, for D> or =4, quantum mechanics cannot stabilize matter against gravitational collapse. This is similar to a result found by Ehrenfest (1917) at the atomic level for Coulomb forces. This makes the dimension D=3 of our Universe very particular with possible implications regarding the anthropic principle. Our study joins a long tradition of scientific and philosophical papers that examined how the dimension of space affects the laws of physics.


Duration of periventricular densities in preterm infants and neurological outcome at 6 years of age.
Parenchymal echogenicities that break down into extensive cystic lesions are generally followed by severe motor deficit. However, the effect of echodensities in the periventricular white matter, so called 'flares', on later development is less well documented. The aim of the present study was to investigate the impact of neonatal flares in preterm infants on neurological status and motor competence at 6 years of age and to see to what extent outcome was related to duration of flares. Forty four children with flares, subdivided into three groups according to the duration of flares, and 62 children with normal scans were assessed on Touwen's neurological examination, the Movement ABC, and the British Ability Scales. No differences in cognitive abilities were found between the groups. The results of the motor assessments showed that performance decreased significantly with increasing duration of flares. In addition, there was a suggestion that this trend was stronger in measures assessing lower limb function than those of upper limb. Teachers were also able to identify differences between the groups of children on the basis of their motor performance in school.


Differences in Physicians' and Nurses' Recent Suicide Attempts: An Exploratory Study.
The aim of this study was to examine the characteristics of physicians' and nurses' suicide attempts (SA). A retrospective review of 493 medical records of physicians and nurses admitted to an inpatient unit for health professionals; 36 patients had a recent SA. Depression, cluster B and C personality disorders, and a history of previous SA were more prevalent in patients with a recent SA compared to those without it. Both professional groups preferred drug overdose as a suicide method. Physicians made more lethal attempts and had a history of more previous stressors than nurses. Depression, cluster B and C personality disorders, and previous SA should be appropriately screened and treated in order to prevent SA amongst physicians and nurses.


Super-SILAC: current trends and future perspectives.
Stable isotope labeling with amino acids in cell culture (SILAC) has risen as a powerful quantification technique in mass spectrometry (MS)-based proteomics in classical and modified forms. Previously, SILAC was limited to cultured cells because of the requirement of active protein synthesis; however, in recent years, it was expanded to model organisms and tissue samples. Specifically, the super-SILAC technique uses a mixture of SILAC-labeled cells as a spike-in standard for accurate quantification of unlabeled samples, thereby enabling quantification of human tissue samples. Here, we highlight the recent developments in super-SILAC and its application to the study of clinical samples, secretomes, post-translational modifications and organelle proteomes. Finally, we propose super-SILAC as a robust and accurate method that can be commercialized and applied to basic and clinical research.


Crystalloid preload versus rapid crystalloid administration after induction of spinal anaesthesia (coload) for elective caesarean section.
Current methods of crystalloid preload administration prior to spinal anaesthesia for elective caesarean section are relatively ineffective in preventing hypotension. This study examined the relevance of the timing of the fluid administered. Fifty women were randomly allocated to receive either 20 ml x kg(-1) of crystalloid solution during 20 minutes prior to induction of spinal anaesthesia (preload), or an equivalent volume by rapid infusion immediately after induction (coload). Significantly more patients in the coload group did not require vasopressor therapy pre-delivery (P=0.047). The coload group required a lower median dose (P=0.03) and a lower median number (P=0.04) of ephedrine doses for the treatment of maternal hypotension pre-delivery. There was no between-group difference in either the total cumulative dose, or in the total number of doses of ephedrine. Neonatal outcomes among the two groups were similar. Rapid crystalloid administration after, rather than over 20 minutes before the induction of spinal anaesthesia for elective caesarean section, may be advantageous in terms of managing maternal blood pressure prior to delivery.


Bacterial proteomics and identification of potential vaccine targets.
Currently, the greatest causes of human morbidity and mortality are infectious diseases. Vaccination remains the most effective measure to lessen this burden on the human population. Many vaccines presently in use were developed using techniques first proposed by Louis Pasteur, which involved the use of inactivated, attenuated live forms, or extracts of pathogenic organisms to immunize the host and provide protection from the disease. The advent of the genomic era has recently led to a new generation of rationally designed vaccines developed using a process termed reverse vaccinology. This approach uses genomic data in silico to identify proteins encoded by the pathogen as potential vaccine candidates. Proteomic technologies serve as an important complement to the reverse vaccinology approach to antigen discovery. Proteomic techniques are able to identify proteins that are expressed by the pathogen during infection of a host and the subset of proteins that reside on the surface of the pathogen. These two traits should be considered central factors to vaccine antigen selection as they assure that the host will be able to mount an effective immune response that leads to lasting protection from the pathogen.


Psychological impact of the physician-patient relationship on compliance: a case study and clinical strategies.
This article presents a case of a heart transplant recipient's noncompliance. A patient's probable medical compliance is among the primary psychosocial criteria in determining his or her eligibility for a heart transplant. The ability to predict and facilitate patient compliance remains a challenge to physicians in all areas of medicine and surgery. The accuracy of the compliance prediction is often contingent upon information generated by patient interviews, other medical personnel, and the patient's family members. All too often, this vital information is based on subjective data, creating difficulty for physicians in appraising patient compliance behavior. Such an amorphous data gathering process may leave physicians at a loss to explain the nature and extent of their patients' behaviors. Research has yet to provide consistent objective measures for compliance prediction. Patient compliance affects all corridors of medical practice and is responsible for an innumerable loss of human life, and financial resources each year.


Reforming the Uniformity of Solid Electrolyte Interphase by Nanoscale Structure Regulation for Stable Lithium Metal Batteries.
The stability of high-energy-density lithium metal batteries depends on the uniformity of solid electrolyte interphase (SEI) on lithium metal anodes. Rationally improving SEI uniformity is hindered by poorly understanding the effect of structure and components of SEI on its uniformity. Herein, a bilayer structure of SEI formed by isosorbide dinitrate (ISDN) additives in localized high-concentration electrolytes was demonstrated to improve SEI uniformity. In the bilayer SEI, LiNx Oy generated by ISDN occupies top layer and LiF dominates bottom layer next to anode. The uniformity of lithium deposition is remarkably improved with the bilayer SEI, mitigating the consumption rate of active lithium and electrolytes. The cycle life of lithium metal batteries with bilayer SEI is three times as that with common anion-derived SEI under practical conditions. A prototype lithium metal pouch cell of 430 Wh kg-1 undergoes 173 cycles. This work demonstrates the effect of a reasonable structure of SEI on reforming SEI uniformity.


Effect of Alfalfa Cultivars and Ages on the Occurrence of Verticillium Wilt Caused by Verticillium alfalfae.
In August 2019, Verticillium wilt was observed in commercial alfalfa fields in Jinta County, Jiuquan, located to the west of Gansu, China, where Verticillium wilt of alfalfa was first observed in this region. This study was conducted to evaluate the effect of alfalfa cultivars (Galaxie Max, Liangmu No. 2, and Danon VNS, planted in 2017) and ages (cultivar Adrenalin, planted in 2014, 2015, and 2016) on the occurrence of Verticillium wilt caused by Verticillium alfalfae. The results showed that V. alfalfae was successfully isolated from both symptomatic and asymptomatic plants. The percentage of V. alfalfae colonization ranged from 22 to 83% in symptomatic plants and 19 to 31% in asymptomatic plants. Among the three cultivars tested, the lowest incidence of disease symptoms was observed in the plants of cultivar Galaxie Max, In addition, the plants of Galaxie Max had a lower rate of infection with V. alfalfae in the field than the cultivar Danon VNS. Moreover, the diseased plants of Galaxie Max had a higher shoot dry weight and levels of nitrogen (N), phosphorus (P), starch, sucrose, and chlorophyll than the diseased plants of Liangmu No. 2 and Danon VNS. This demonstrated that Galaxie Max has higher resistance/tolerance to Verticillium wilt than Danon VNS. An examination of the different ages of Adrenalin indicated that the plants in 2014 had a higher incidence of disease and rate of infection in the field than the plants in 2016. In addition, the diseased plants in 2016 had a higher shoot dry weight and contents of N, P, sucrose, and starch than the diseased plants in 2014 and 2015. This result indicated that an increase in the age of alfalfa plants contributes to the occurrence and development of Verticillium wilt. The infection of V. alfalfae significantly decreased the shoot dry weights and the contents of chlorophyll, N, P, and starch of alfalfa plants. These results provide a better understanding of the physiological mechanisms of the response of alfalfa plants to Verticillium wilt caused by V. alfalfae.


Malignant tumors of the salivary glands.
The incidence of malignant salivary gland tumors is influenced by geographic and racial factors. Some etiological aspects and diagnostic pitfalls are discussed. The treatment of salivary gland malignancies is primarily surgical but the extent of the surgery should be dependent on the availability and application of routine postoperative high or supervoltage radiotherapy on a "regional" basis of invasive low-grade and all high-grade malignant tumors.


Identification of Glypican-3 as a potential metastasis suppressor gene in gastric cancer.
Gastric cancer is a prevalent tumor that is usually detected at an advanced metastatic stage. Currently, standard therapies are mostly ineffective. Here, we report that Glypican-3 (GPC3) is absent in invasive tumors and metastatic lymph nodes, in particular in aggressive and highly disseminated signet ring cell carcinomas. We demonstrate that loss of GPC3 correlates with poor overall survival in patients. Moreover, we show that absence of GPC3 causes up-regulation of MAPK/FoxM1 signaling and that blockade of this pathway alters cellular invasion. An inverse correlation between GPC3 and FoxM1 is also shown in patient samples. These data identify GPC3 as a potential metastasis suppressor gene and suggest its value as a prognostic marker in gastric cancer. Development of therapies targeting signaling downstream of GPC3 are warranted.


Evolving pathologic concepts of serrated lesions of the colorectum.
Here, we provide an up-to-date review of the histopathology and molecular pathology of serrated colorectal lesions. First, we introduce the updated contents of the 2019 World Health Organization classification for serrated lesions. The sessile serrated lesion (SSL) is a new diagnostic terminology that replaces sessile serrated adenoma and sessile serrated polyp. The diagnostic criteria for SSL were revised to require only one unequivocal distorted serrated crypt, which is sufficient for diagnosis. Unclassified serrated adenomas have been included as a new category of serrated lesions. Second, we review ongoing issues concerning the morphology of serrated lesions. Minor morphologic variants with distinct molecular features were recently defined, including serrated tubulovillous adenoma, mucin-rich variant of traditional serrated adenoma (TSA), and superficially serrated adenoma. In addition to intestinal dysplasia and serrated dysplasia, minimal deviation dysplasia and not otherwise specified dysplasia were newly suggested as dysplasia subtypes of SSLs. Third, we summarize the molecular features of serrated lesions. The critical determinant of CpG island methylation development in SSLs is patient age. Interestingly, there may be ethnic differences in BRAF/KRAS mutation frequencies in SSLs. The molecular pathogenesis of TSAs is divided into KRAS and BRAF mutation pathways. SSLs with MLH1 methylation can progress into favorable prognostic microsatellite instability-positive (MSI+)/CpG island methylator phenotype-positive (CIMP+) carcinomas, whereas MLH1-unmethylated SSLs and BRAF-mutated TSAs can be precursors of poor-prognostic MSI-/CIMP+ carcinomas. Finally, based on our recent data, we propose an algorithm for stratifying risk subgroups of non-dysplastic SSLs.


New drug developments in the Netherlands. "Tetracyclic" psychotropic drugs.
Based on qualitative and quantitative EEG findings, the psychotropic properties of GB-94, GC-46, and GC-94 were predicted. According to the EEG model, GB-94 was predicted to be similar to amitriptyline and GC-46 t( imipramine. GC-94 was found to be much less effective on the CNS than GB-94 and GC-46 and was predicted to have "stimulatory" clinical effects similar to desipramine. The clinical trials demonstrated that GB-94 is indeed an antidepressive psychotropic compound similar to amitriptyline. GB-94 in lower dosages was also found to be effective in anxiety syndromes. In some schizophrenics GB-94 showed some therapeutic effects, while in others it obviously exacerbrated the psychotic symptomatology. GC-94 was not found to be significantly effective in a heterogenous psychiatric population. Only slight improvement in some schizophrenic patients was observed However, a noticeable worsening in the symptomatology of manic and hypomanic patients was seen. The study demonstarted that GC-94 indeed has a central stimulatory effect, but no minor or major tranquilizer properties or sedative antidepressive qualities were observed. GC-46 was tried in only three subjects. Based on this pilot trial, no conclusion can be made about the psychotropic properties of this compound. Our quantitative pharmaco-EEG and clinical trials clearly demonstrated the significant value of quantitative EEG in early screening of psychoactive drugs in order to predict their clinical values and effective dosage ranges.


Actinomycin D in the treatment of Paget's disease of bone.
Fifteen patients with Paget's disease of bone were treated with actinomycin D for periods of up to 15 months. It was found that actinomycin D is effective in reducing the pain but not the neurological effects of Paget's disease. Careful adjustment of dose according to weight and initial response is necessary to prevent gastrointestinal side effects. If this is done, the risk of hepatic, renal, or haematological side effects is negligible.