Is the use of Tenofovir Dipivoxil fumarate effective and safe in preventing vertical transmission in pregnant women with chronic HBV with high viral load?
In our country, transmission from mother to baby is the most common form of transmission of viral hepatitis B. A high viral load in the mother and HBeAg positivity pose the greatest risk of transmission from mother to baby. The best way to prevent this is to try to eliminate the viral load in the mother by using a strong antiviral such as prenatal TDF in mothers with a high viral load during pregnancy. This study aimed to evaluate the efficacy and safety of TDF in pregnant women with high viral load. Seventy patients with hepatitis B e-antigen positive and negative were included in the retrospective study conducted in our clinic. In 35 cases, pregnant women with HBeAg (+) positive chronic HBV and HBV-DNA levels of 107 copies/mL were between 18 and 27 weeks of pregnancy. The pregnant women took 300 mg of TDF per day. There were 35 untreated HBeAg-negative, chronic HBV patients in the control group. Babies born to HBeAg-positive and HBeAg-negative mothers are given an initial dose of 200 IU of hepatitis B immune globulin (HBIG) and 20 g of recombinant hepatitis B vaccine in the first 12 hours after birth, followed by 4, 8, and 24 weeks. HBsAg and HBV-DNA findings were examined in newborn serum 28 weeks after birth. Postpartum 28 weeks, none of the babies born to HBeAg-positive mothers treated with TDF had HBsAg positivity, while 3.5% of babies born to HBeAg-negative mothers and not treated with TDF had HBsAg positivity and immunoprophylaxis failure. There was no statistically significant difference between the treatment and control groups regarding maternal height, weight, gestational age, or congenital malformations (p<0.05). There was no significant difference between the side effects seen in mothers. In the examination performed at the 28th week postpartum, a statistically significant decrease in HBV-DNA levels was observed in mothers who received TDF treatment compared to those who did not (88.5%) (p<0.05). In 31 of the 35 patients receiving TDF treatment, ALT was reported to be normalized in 25 of the 35 patients who did not receive TDF treatment (p<0.05). It has been observed that the use of TDF, which has a strong efficacy and high barrier, in the second and/or third trimester of pregnancy reduces transmission rates without causing side effects in both the mother and the newborn, thereby preventing vertical transmission of viral hepatitis B from the mother to child.


Occupational lead poisoning, animal deaths, and environmental contamination at a scrap smelter.
Occupational lead poisoning and environmental contamination were evaluated at a lead scrap smelter. Thirty of 37 employees (81 per cent) has blood lead levels of greater than or equal to 80 mug/100 ml, indicating unacceptable absorption, and 35 had free erythrocyte protoporphyrin (FEP) levels greater than 60mug/100ml rbc, indicating toxicity of lead on heme metabolism in red blood cells; eight current and previous employees had been hospitalized with lead colic, and another with encephalopathy. Levels of lead in surface soil (1,800 ppm) and vegetation (20,000 ppm) at the smelter were high and decreased with distance. Animals on nearby pasture had died, and lead levels in the blood, milk, and hair of large and small animals were elevated. Adults living within 100 meters of the smelter had higher blood and hair lead levels than controls, who lived at greater distances, but there was no evidence in them of lead toxicity.


Boron Oxygen Pair Effect in p+ Emitter and Nanosized Boron Rich Layer by Fold Coordination Analysis for Crystalline Silicon Solar Cell Applications.
N-type substrates possess better material characteristics than p-type substrates for high efficiency mass producible Si solar cells with HIT, IBC structures. The major drawbacks of these structures are a complicated fabrication process and an expensive unit cost. In this paper, the boron emitter doping profile of a nanosized boron rich layer (BRL), for which the boron and oxygen concentrations are correlated, is optimized to fabricate high efficiency solar cells on an n-type substrate. Boron doping was carried out using a BBr3 furnace with varying oxygen gas ratios and the surface was treated with acid etching. The effect of the oxygen on the nanosized BRL was analyzed using both FTIR spectroscopy and XPS, where by conductivity and the Si-B bond were observed for the three-fold and four-fold coordinated borons, respectively. The results showed that the oxygen quantities in the boron doped emitter and the nanosized BRL affected the characteristics of the solar cell. Regarding the solar cells that were fabricated using the boron emitter and shallow emitter (90 ohm/sq) processes, the open-circuit voltage increased by 54 mV and the short circuit current (J(sc)) increased by 3.7 mA/cm2. The J(sc) increase was due to an increased quantum efficiency in the short wavelength range. The shallow emitter etch back process minimized the boron-oxygen defects in the doping profile.


Spinodal-assisted nucleation in the two-dimensional q-state Potts model with short-to-long-range interactions.
We study homogeneous nucleation in the two-dimensional q-state Potts model for q=3,5,10,20 and ferromagnetic couplings J_{ij}∝Θ(R-|i-j|) by means of Monte Carlo simulations employing heat bath dynamics. Metastability is induced in the low-temperature phase through an instantaneous quench of the magnetic field coupled to one of the q spin states. The quench depth is adjusted, depending on the value of temperature T, interaction range R, and number of states q, in such a way that a constant nucleation time is always obtained. In this setup, we analyze the crossover between the classical compact droplet regime occurring in the presence of short-range interactions R∼1 and the long-range regime R≫1 where the properties of nucleation are influenced by the presence of a mean-field spinodal singularity. We evaluate the metastable susceptibility of the order parameter as well as various critical droplet properties, which along with the evolution of the quench depth as a function of q,T and R are then compared with the field theoretical predictions valid in the large R limit to find the onset of spinodal-assisted nucleation. We find that, with a mild dependence of the values of q and T considered, spinodal scaling holds for interaction ranges R≳8-10 and that signatures of the presence of a pseudospinodal are already visible for remarkably small interaction ranges R∼4-5. The influence of spinodal singularities on the occurrence of multistep nucleation is also discussed.


Autophagy Protects Advanced Glycation End Product-Induced Apoptosis and Expression of MMP-3 and MMP-13 in Rat Chondrocytes.
Aging is one of the most prominent risk factors for the pathological progression of osteoarthritis (OA). One feature of age-related changes in OA is advanced glycation end products (AGEs) accumulation in articular cartilage. Autophagy plays a cellular housekeeping role by removing dysfunctional cellular organelles and proteins. However, the relationship between autophagy and AGE-associated OA is unknown. The aim of this study is to determine whether autophagy participates in the pathology of AGE-treated chondrocytes and to investigate the exact role of autophagy in AGE-induced cell apoptosis and expression of matrix metalloproteinase- (MMP-) 3 and MMP-13. AGEs induced notable apoptosis that was detected by Annexin V/PI double-staining, and the upregulation of MMP-3 and MMP-13 was confirmed by Western blotting. Autophagy-related proteins were also determined by Western blotting, and chondrocytes were transfected with mCherry-GFP-LC3B-adenovirus to monitor autophagic flux. As a result, autophagy significantly increased in chondrocytes and peaked at 6 h. Furthermore, rapamycin (RA) attenuated AGE-induced apoptosis and expression of MMP-3 and MMP-13 by autophagy activation. In contrast, pretreatment with autophagy inhibitor 3-methyladenine (3-MA) enhanced the abovementioned effects of AGEs. We therefore demonstrated that autophagy is linked with AGE-related pathology in rat chondrocytes and plays a protective role in AGE-induced apoptosis and expression of MMP-3 and MMP-13.


[Cardio-respiratory arrest. New concepts and physiopathological consequences].
In the past few years, many studies have been devoted to cardiac arrest (CA) resuscitation. The "Chain of Survival" concept is considered as the best comprehensive approach of CA prognostic improvement. It includes 4 links: early access (recognition of early signs of CA and activation of the emergency medical system), early cardiopulmonary resuscitation, early defibrillation of ventricular fibrillations and early advanced cardiac life support (intubation, intravenous medication). Non withstanding all the recent progress en physiology or therapeutics, the early management is still the basis of the prognosis. That is why prehospital care organization is the main determinant of CA survival.


Is the NHS Winning the Great Paper Chase?
A paper-free health service is a worthy ambition but achieving it has proved easier said than done - so what might a more realistic plan look like, asks Matthew Shelley.


[Particularities of splanchnic innervation of the upper abdomen organs - clinical experience].
Due to pain because of supramesocolic malignancies of the upper abdomen organs in 50 patients at nonoperative stage, we have performed 18 right sided, 11 left sided and 21 bilateral TSS interventions. Video recordings of all operations have been examined postoperatively and have been registered the anatomical variations of the splanchnic nerves formation. There have been made conclusions concerning the intraoperative behavior and tactics for surgical pain control in pancreatic, distal esophageal, gastric, extrahepatic bile ducts and liver neoplasms in nonoperative stage.


Rural telemedicine: lessons from Alaska for developing regions.
Alaska shares many characteristics with other rural and remote regions of the Asia-Pacific, including a small population spread over a large area, lack of roads linking villages to hospitals, a significant indigenous population, and a shortage of doctors in rural areas. Communication with village health aides was originally by high frequency (HF) radio. Satellites brought reliable voice communication in the 1970s. Alaska has now introduced the first permanent upgrade to the voice satellite system, known as the Alaska Federal Health Care Access Network (AFHCAN). This satellite-based system is now the world's most extensive telemedicine network, linking 248 sites, including 158 village health centers. This paper examines the approach used to design the network, and includes preliminary findings on utilization of the network and associated cost-savings. It also discusses the U.S. Universal Service Fund subsidy for rural health care facilities. It concludes with lessons learned that could be applicable for other remote and isolated areas and developing regions.


Adrenal versus nonadrenal sympathetic preganglionic neurones in the lower thoracic intermediolateral nucleus of the cat: effects of serotonin, substance P, and thyrotropin-releasing hormone.
Adrenal and nonadrenal sympathetic preganglionic neurones (SPNs) in the intermediolateral nucleus of spinal segments T8-T10 in the cat were compared according to their responses to iontophoretic application of serotonin, substance P, and thyrotropin-releasing hormone (TRH). Responses of both types of SPN to iontophoretic application of serotonin were characterized by an increase in the rate of discharge that was slow in onset (mean +/- SD = 36 +/- 21 s) and prolonged in afterdischarge (115 +/- 70 s) following termination of application. Depression was never observed and responses were similar whether using serotonin at a pH of 3.3 or 4.5, suggesting that the absence of a depressant effect cannot be accounted for by pH, as has been reported with cortical neurones. Iontophoretic application of methysergide resulted in a decrease in the rate of discharge of both types of SPN and blocked the excitatory responses to serotonin. Adrenal and nonadrenal SPNs were excited by iontophoretic application of substance P. Responses of both types of SPN were similar and were characterized by a gradual increase in the rate of discharge that was slow in onset (42 +/- 27 s) and prolonged in afterdischarge (96 +/- 42 s). Finally, adrenal and nonadrenal SPNs were also weakly excited by iontophoretic application of TRH. These responses were slow in onset (48 +/- 27 s) and prolonged in afterdischarge (78 +/- 35 s). These data indicate that serotonin, substance P, and TRH exert excitatory effects on functionally dissimilar sympathetic preganglionic neurones and support the possibility that they may be chemical mediators of synaptic transmission in the intermediolateral nucleus. In addition, these data may be interpreted to support the notion that serotonin, substance P, and TRH are involved in global activation of the sympathetic nervous system.


Esophageal manometry in oculopharyngeal dystrophy.
Four cases of oculopharyngeal dystrophy (OPD) seen within five years are presented. The cardinal features of OPD are dysphagia and ptosis. The manometric abnormalities in OPD are similar to those seen in other myopathies; low pharyngeal pressures, abnormalities in relaxation and coordination of the pharyngoesophageal sphincter and weak aperistaltic swallows in the proximal esophagus. In addition, weak aperistaltic swallows frequently occur in the distal esophagus and may exacerbate dysphagia. Although there is no specific therapy for ODP, one patient showed marked improvement following cricopharyngeal myotomy.


Inhibition of transglutaminase by hypoglycaemic sulphonylureas in pancreatic islets and its possible relevance to insulin release.
Pancreatic islet homogenates display calcium-sensitive transglutaminase activity, but the role of this enzyme in the process of insulin release remains to be elucidated. Tolbutamide, gliclazide, glisoxepide, glipizide and glibenclamide inhibited transglutaminase activity in islet homogenates. When the cationic response of islet cells to hypoglycaemic sulphonylureas was suppressed by exposing intact islets to quinine, tolbutamide, gliclazide and glibenclamide caused a rapid, sustained, reversible and dose-related inhibition of insulin release. The relative efficiency of distinct hypoglycaemic sulphonylureas as inhibitor of transglutaminase activity was in mirror image of their relative potency as insulin secretagogue. However, the dose-action relationship for the inhibitory action of these agents upon insulin release from quinine-treated islets was similar in response to either tolbutamide, gliclazide or glibenclamide. These results indicate that hypoglycaemic sulphonylureas may exert an inhibitory action upon insulin release, but suggest that such an effect is not tightly related to inhibition of transglutaminase.


An association between body mass index and high-sensitivity C-reactive protein concentrations is influenced by age in community-dwelling persons.
High sensitivity C-reactive protein (hsCRP) is an acute phase reactant and a sensitive marker of inflammation. Age and adiposity can potentially promote the production of C-reactive protein (CRP). However, only a few studies have investigated any interaction between age and adiposity on hsCRP concentrations. We recruited 822 men (mean age, 61 ± 14 years) and 1097 women (63 ± 12 years) during their annual health examination from a single community. We cross-sectionally examined whether age, body mass index (BMI), and the interaction are significantly associated with hsCRP concentrations, independent of confounding factors. Multiple linear regression analyses for hsCRP showed that in men, age (β = 0.169, P < 0.001) and BMI (β = 0.114, P = 0.004) as well as smoking status, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), uric acid, and gamma-glutamyl transferase (GGT) were significantly associated with hsCRP; and in women, age (β = 0.203, P < 0.001) and BMI (β = 0.225, P < 0.001) as well as HDL-C, fasting plasma glucose (FPG), uric acid, GGT and high-molecular weight adiponectin were significantly associated with hsCRP. In addition to their direct associations, the interaction between age and BMI was also a significant and independent determinant for hsCRP in both men (F = 4.407, P = 0.036) and women (F = 5.487, P = 0.019). In participants aged < 75 years, overweight (BMI ≥ 25.0 kg/m(2)) persons were more likely to have a prevalence of elevated hsCRP concentrations (≥ 1.00 mg/L) compared with the normal-weight (BMI <22.0 kg/m(2)), but such an association was not observed in those aged ≥ 75 years. Adiposity promotes low-grade systemic inflammation in community-dwelling persons aged <75 years.


Molecular cloning of Clostridium difficile toxin A gene fragment in lambda gt11.
Toxin A of Clostridium difficile has been purified and monospecific antiserum produced. A reliable procedure for isolation and restriction of C. difficile chromosomal DNA was developed which allowed for the construction of a genomic library in lambda gt11. Approx. 35,000 plaques were screened using anti-toxin A which resulted in the identification of one stable positive clone, lambda cd19. Verification of the immunological identity of the isolated toxin A gene fragment in lambda cd19 was determined by affinity purifying toxin A antibodies specific for lambda cd19 gene product, and using these selected antibodies to probe a Western blot of purified toxin A. The insert in lambda cd19 was demonstrated to be a 0.3 kb fragment by restriction digestion, and by hybridization of the clone to a chromosomal digest of C. difficile. The peptide coded for by the toxin A gene fragment in lambda cd19 was not cytotoxic for 3T3 mammalian tissue culture cells.


Genome-wide transcriptional profiling analysis of adaptation of Bacillus subtilis to high salinity.
The gram-positive soil bacterium Bacillus subtilis often faces increases in the salinity in its natural habitats. A transcriptional profiling approach was utilized to investigate both the initial reaction to a sudden increase in salinity elicited by the addition of 0.4 M NaCl and the cellular adaptation reactions to prolonged growth at high salinity (1.2 M NaCl). Following salt shock, a sigB mutant displayed immediate and transient induction and repression of 75 and 51 genes, respectively. Continuous propagation of this strain in the presence of 1.2 M NaCl triggered the induction of 123 genes and led to the repression of 101 genes. In summary, our studies revealed (i) an immediate and transient induction of the SigW regulon following salt shock, (ii) a role of the DegS/DegU two-component system in sensing high salinity, (iii) a high-salinity-mediated iron limitation, and (iv) a repression of chemotaxis and motility genes by high salinity, causing severe impairment of the swarming capability of B. subtilis cells. Initial adaptation to salt shock and continuous growth at high salinity share only a limited set of induced and repressed genes. This finding strongly suggests that these two phases of adaptation require distinctively different physiological adaptation reactions by the B. subtilis cell. The large portion of genes with unassigned functions among the high-salinity-induced or -repressed genes demonstrates that major aspects of the cellular adaptation of B. subtilis to high salinity are unexplored so far.


Non-common path aberration correction in an adaptive optics scanning ophthalmoscope.
The correction of non-common path aberrations (NCPAs) between the imaging and wavefront sensing channel in a confocal scanning adaptive optics ophthalmoscope is demonstrated. NCPA correction is achieved by maximizing an image sharpness metric while the confocal detection aperture is temporarily removed, effectively minimizing the monochromatic aberrations in the illumination path of the imaging channel. Comparison of NCPA estimated using zonal and modal orthogonal wavefront corrector bases provided wavefronts that differ by ~λ/20 in root-mean-squared (~λ/30 standard deviation). Sequential insertion of a cylindrical lens in the illumination and light collection paths of the imaging channel was used to compare image resolution after changing the wavefront correction to maximize image sharpness and intensity metrics. Finally, the NCPA correction was incorporated into the closed-loop adaptive optics control by biasing the wavefront sensor signals without reducing its bandwidth.


Modern Warfare: Video Game Playing and Posttraumatic Symptoms in Veterans.
Many of the current generation of veterans grew up with video games, including military first-person shooter (MFPS) video games. In MFPS games, players take the role of soldiers engaged in combat in environments modeled on real-life warzones. Exposure to trauma-congruent game content may either serve to exacerbate or to ameliorate posttraumatic symptoms. The current study examined the relationship between MFPS and other shooter video game playing and posttraumatic stress disorder (PTSD) symptoms among current and former members of the military (N = 111). Results indicated that video game play was very common, and 41.4% of participants reported playing MFPS or other shooter games (shooter players group). The shooter players group reported higher levels of PTSD symptoms than participants who did not play any video or shooter games (nonshooter/nonplayers group; d = 0.44); however, playing shooter games was not predictive of PTSD symptoms after accounting for personality, combat exposure, and social support variables. This may indicate that the same psychosocial factors predict both PTSD and shooter video game play. Although veterans may benefit from the development and use of clinical applications of video games in PTSD treatment, clinical attention should continue to focus on established psychosocial predictors of PTSD symptoms.


Efficacy of cognitive-behavioral interventions targeting personality risk factors for youth alcohol misuse.
Sensation seeking, anxiety sensitivity, and hopelessness are personality risk factors for alcohol use disorders, each associated with specific risky drinking motives in adolescents. We developed a set of interventions and manuals that were designed to intervene at the level of personality risk and associated maladaptive coping strategies, including alcohol misuse. Manuals contained psychoeducational information on the target personality risk factor and how it is associated with maladaptive coping, as well as exercises targeting maladaptive cognitions and behaviors specific to each personality type. We tested the efficacy of these novel interventions on reducing drinking behavior by randomly assigning 297 Canadian high school students (56% girls, mean age 16, mean grade 11) to personality-targeted interventions (group format; 2 sessions) or to a no-treatment control group. Intent-to-treat analyses indicated beneficial effects of the intervention and Intervention x Personality interactions on drinking rates, drinking quantity, binge drinking, and problem drinking symptoms at 4-month follow-up.


Synthesis of Nonalternating Polyketones Using Cationic Diphosphazane Monoxide-Palladium Complexes.
Copolymerization of olefin with carbon monoxide has received considerable interest from both academia and industry, and the introduction of polar carbonyl group renders the resultant polyketones with excellent mechanical strength, crystallinity, photodegradability, hydrophilicity, surface, and barrier properties. However, most of the reported polyketones are difficult to be processed because of limited solubility in common solvents and high melting temperature (Tm ∼ 260 °C) resulting from the strictly alternative structure. Nonalternating copolymerization of ethylene with CO is a very promising method to circumvent the problem of processability of traditional perfectly alternating polyketone. In the contribution, the palladium coordinated diphosphazane monoxide substituted by strong electron-donating groups is discovered to be highly reactive for producing nonalternating polyketones, and up to 24.2% extra ethylene incorporation has lowered Tm values to 147 and 165 °C and further improved thermal stability (Td ∼ 339 °C) of the resultant materials. Our data demonstrates that cationic palladium complexes can also exhibit excellent reactivity and an unprecedented nonalternating degree in this copolymerization.


Familial third-fourth pharyngeal pouch syndrome with apparent autosomal dominant transmission.
A family is presented in which both siblings and their father had evidence of third-fourth pharyngeal pouch syndrome (DiGeorge syndrome). All three individuals had hypocalcemia and unusual facies. Both infants had truncus arteriosus. One infant had evidence of impaired cell-mediated immunity; the father had a relatively decreased number of T-lymphocytes. The syndrome is uncommon, most cases being isolated, and familial presentations are even rarer. Two recent reports described several affected individuals who also had partial deletions of chromosome 22. Chromosome banding studies in our family were normal. Thus our family demonstrates an autosomal dominant pattern of inheritance, although it cannot be proved that this is a single gene defect. We propose that inasmuch as the presentation of the syndrome is quite varied, thorough family investigation including high-resolution cytogenetic analysis is necessary. Familial cases may be more common and require genetic counseling.


Enhanced neurobehavioral effects of cocaine with chronic neuroleptic exposure in rats.
Individuals with schizophrenia are often treated with medications that block dopamine (DA) neurotransmission. Chronic administration of many DA antagonists alters dopaminergic function, causing a supersensitivity to DA agonists. Because the DA agonist properties of cocaine seem to be involved in its behavioral effects, chronic DA antagonist treatments may enhance these effects of cocaine. This article presents evidence to support this hypothesis, as well as its implications for treating schizophrenia patients who abuse cocaine and suggestions for future research.


Corticotropin-releasing factor (CRF) and the urocortins differentially regulate catecholamine secretion in human and rat adrenals, in a CRF receptor type-specific manner.
Corticotropin-releasing factor (CRF) affects catecholamine production both centrally and peripherally. The aim of the present work was to examine the presence of CRF, its related peptides, and their receptors in the medulla of human and rat adrenals and their direct effect on catecholamine synthesis and secretion. CRF, urocortin I (UCN1), urocortin II (UCN2), and CRF receptor type 1 (CRF1) and 2 (CRF2) were present in human and rat adrenal medulla as well as the PC12 pheochromocytoma cells by immunocytochemistry, immunofluorescence, and RT-PCR. Exposure of dispersed human and rat adrenal chromaffin cells to CRF1 receptor agonists induced catecholamine secretion in a dose-dependent manner, an effect peaking at 30 min, whereas CRF2 receptor agonists suppressed catecholamine secretion. The respective effects were blocked by CRF1 and CRF2 antagonists. CRF peptides affected catecholamine secretion via changes of subplasmaliminal actin filament polymerization. CRF peptides also affected catecholamine synthesis. In rat chromaffin and PC12 cells, CRF1 and CRF2 agonists induced catecholamine synthesis via tyrosine hydroxylase. However, in human chromaffin cells, activation of CRF1 receptors induced tyrosine hydroxylase, whereas activation of CRF2 suppressed it. In conclusion, it appears that a complex intraadrenal CRF-UCN/CRF-receptor system exists in both human and rat adrenals controlling catecholamine secretion and synthesis.


Bleeding risk and outcomes of Bivalirudin versus Glycoprotein IIb/IIIa inhibitors with targeted low-dose unfractionated Heparin in patients having percutaneous coronary intervention for either stable or unstable angina pectoris.
For patients undergoing elective percutaneous coronary intervention (PCI), procedural anticoagulation with bivalirudin was previously shown to significantly reduce bleeding complications at the cost of a modest increase in ischemic events compared with unfractionated heparin (UFH) and glycoprotein IIb/IIIa inhibitors (GPIs). However, the excess bleeding in patients treated with UFH and GPIs may have been caused by excessively high UFH doses and increased activated clotting times. This study sought to determine the bleeding risk of targeted low-dose UFH with GPIs compared with bivalirudin in patients undergoing elective PCI. Of 1,205 patients undergoing elective PCI, 602 underwent PCI with adjunctive UFH and GPIs with the UFH dose targeted to an activated clotting time of approximately 250 seconds, and 603 patients matched for baseline characteristics underwent PCI with bivalirudin. Outcomes were analyzed for major bleeding (hematocrit decrease >15%, gastrointestinal bleed, or major hematoma) and 6-month major adverse cardiac events (death, myocardial infarction, and target-lesion revascularization). The maximum activated clotting time achieved was 261.7 +/- 61.6 seconds in the UFH/GPI group and 355.4 +/- 66.6 in the bivalirudin group (p <0.001). In-hospital major bleeding rates were similar between groups (1.8% UFH/GPI vs 1.7% bivalirudin; p = 0.83), as were transfusion requirements (1.2% UFH/GPI vs 0.5% bivalirudin; p = 0.61). The 6-month major adverse cardiac event rate was also similar between groups (9.5% UFH/GPI vs 9.0% bivalirudin; p = 0.81). In conclusion, there were no significant differences in major bleeding and 6-month major adverse cardiac events for patients undergoing elective PCI treated with targeted low-dose UFH and GPIs compared with those treated with bivalirudin.


Absence of myocardial 123I-BMIPP uptake in the presence of a normal coronary angiogram and normokinetics on a left ventriculogram.
We present the case of a 44-year-old man with abnormal myocardial fatty acid metabolism who exhibited no myocardial uptake of 123I-beta-methyl- iodophenyl pentadecanoic acid (123I-BMIPP). This patient presented to our hospital with an ECG abnormality detected during a medical check-up. He felt no chest discomfort, but a 12-lead ECG at rest showed flat T-waves in leads I, V5, and V6 with no marked ischemic changes during exercise. A left ventriculogram and coronary angiograms were normal. Thallium-201 single photon emission computed tomography imaging revealed a normal myocardial uptake, but 123I-BMIPP imaging showed no such uptake. However, 18F-labelled fluorodeoxyglucose positron emission tomography imaging after an overnight fast showed a marked increase in myocardial uptake. It appears that myocardial uptake of 123I-BMIPP was totally lacking and that energy production by the myocardium during fasting depended on the metabolism of glucose rather than of fatty acids.


Efficacy of recombinant N- and C-terminal derivative of EmIMP1 against E. maxima infection in chickens.
1. Immune mapped protein-1 (IMP1) of E. maxima has been identified as a vaccine antigen candidate for E. maxima infection. 2. In the current study, the N- and C-terminal derivative of EmIMP1 were expressed in E. coli and administered to chickens. The antibody response, cell-mediated immune (CMI) response and the protective efficacy of the protein vaccines against E. maxima challenge were evaluated. 3. The results showed that C-terminal derivative of EmIMP1 vaccination could increase weight gain, reduce enteric lesions, and decrease faecal oocysts shedding. Moreover, the C-terminal derivative of EmIMP1 caused reasonable improvement in serum antibodies and the numbers of IFN-γ producing peripheral blood mononuclear cells (PBMC), as compared to the control group. 4. This study demonstrated that the C-terminal derivative of EmIMP1 could be used as a potent immunogenic candidate in the development of subunit vaccines against E. maxima infection.


Bovine and porcine transscleral solute transport: influence of lipophilicity and the Choroid-Bruch's layer.
To determine the influence of the choroid-Bruch's layer and solute lipophilicity on in vitro transscleral drug permeability in bovine and porcine eyes. The in vitro permeability of two VEGF inhibitory drugs, budesonide and celecoxib, which are lipophilic and neutral at physiologic pH, and of three marker solutes, 3H-mannitol (hydrophilic, neutral), sodium fluorescein (hydrophilic, anionic), and rhodamine 6G (lipophilic, cationic), were determined across freshly excised scleras, with or without the underlying choroid-Bruch's layer. Select studies were performed using porcine sclera with and without choroid-Bruch's layer. Neural retina was removed by exposure of the eyecup to isotonic buffer and wherever required, the retinal pigment epithelial (RPE) layer of the preparation was disrupted and removed by exposure to hypertonic buffer. Because of the poor solubility of celecoxib and budesonide, permeability studies were conducted with 5% wt/vol of hydroxypropyl-beta-cyclodextrin (HPbetaCD). For other solutes, permeability studies were conducted, with and without HPbetaCD. Partitioning of the solutes into bovine sclera and choroid-Bruch's layer was also determined. The calculated log (distribution coefficient) values were -2.89, -0.68, 2.18, 3.12, and 4.02 for mannitol, sodium fluorescein, budesonide, celecoxib, and rhodamine 6G, respectively. Removal of RPE was confirmed by transmission electron microscopy and differences in the transport of mannitol. The order of the permeability coefficients (Papp) across sclera and sclera-choroid-Bruch's layers in bovine and porcine models was 3H-mannitol > fluorescein > budesonide > celecoxib > rhodamine 6G, with HPbetaCD, and 3H-mannitol > fluorescein > rhodamine 6G, without HPbetaCD. The presence of choroid-Bruch's layer reduced the bovine scleral permeability by 2-, 8-, 16-, 36-, and 50-fold and porcine tissue permeability by 2-, 7-, 15-, 33-, and 40-fold, respectively, for mannitol, sodium fluorescein, budesonide, celecoxib, and rhodamine 6G. The partition coefficients measured in bovine tissues correlated positively with the log (distribution coefficient) and exhibited a trend opposite that of transport. The partition coefficient ratio of bovine choroid-Bruch's layer to sclera was approximately 1, 1.5, 1.7, 2, and 3.5, respectively, for the solutes, as listed earlier. The choroid-Bruch's layer is a more significant barrier to drug transport than is sclera. It hinders the transport of lipophilic solutes, especially a cationic solute, more than hydrophilic solutes and in a more dramatic way than does sclera. The reduction in transport across this layer directly correlates with solute binding to the tissue. Understanding the permeability properties of sclera and underlying layers would be beneficial in designing better drugs for transscleral delivery.


The Protein Data Bank.
The Protein Data Bank [PDB; Berman, Westbrook et al. (2000), Nucleic Acids Res. 28, 235-242; http://www.pdb.org/] is the single worldwide archive of primary structural data of biological macromolecules. Many secondary sources of information are derived from PDB data. It is the starting point for studies in structural bioinformatics. This article describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information and plans for the future development of the resource. The reader should come away with an understanding of the scope of the PDB and what is provided by the resource.


Outcome of nasopharyngeal carcinoma in Finland: A nationwide study.
Nasopharyngeal carcinoma (NPC) is uncommon in western countries and data on the outcome and histological presentation are scarce in nonendemic areas. We report here the outcome on all patients with NPC treated in Finland between 1990 and 2009. The Finnish Cancer Registry database was used to identify the patients. Histopathological specimens and clinical records were reviewed to confirm the histological subtypes, prognostic factors, treatment techniques and outcome across different stage groups. Primary NPC was identified in 207 patients and 42 (20%) had keratinizing squamous cell carcinoma (SCC). The stage distribution was: I, 11%; II, 25%; III, 39%; IV, 25%. Of 191 patients treated with curative intent 85 (44%) received radiotherapy and 106 (56%) chemoradiotherapy. The five-year overall survival for all patients was 57% and for stages I-IV 87%, 69%, 55% and 31%, respectively. The five-year disease-specific and overall survival of all patients treated between 1990 and 1999 were 58% and 49%, and those between 2000 and 2009 66% and 63%, respectively. While survival rates are improving and comparable to other western countries they remain inferior to those of endemic countries. This may reflect the different biology of NPC in nonendemic areas, where keratinizing SCC is common.


Characterization of retinaldehyde dehydrogenase 3.
RALDH3 (retinal dehydrogenase 3) was characterized by kinetic and binding studies, protein engineering, homology modelling, ligand docking and electrostatic-potential calculations. The major recognition determinant of an RALDH3 substrate was shown to be an eight-carbon chain bonded to the aldehyde group whose kinetic influence (kcat/Km at pH 8.5) decreases when shortened or lengthened. Surprisingly, the b-ionone ring of all-trans-retinal is not a major recognition site. The dissociation constants (Kd) of the complexes of RALDH3 with octanal, NAD+ and NADH were determined by intrinsic tryptophan fluorescence. The similarity of the Kd values for the complexes with NAD+ and with octanal suggests a random kinetic mechanism for RALDH3, in contrast with the ordered sequential mechanism often associated with aldehyde dehydrogenase enzymes. Inhibition of RALDH3 by tri-iodothyronine binding in competition with NAD+, predicted by the modelling, was established kinetically and by immunoprecipitation. Mechanistic implications of the kinetically influential ionizations with macroscopic pKa values of 5.0 and 7.5 revealed by the pH-dependence of kcat are discussed. Analogies with data for non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase from Streptococcus mutans, together with the present modelled structure of the thioacyl RALDH3, suggest (a) that kcat characterizes deacylation of this intermediate for specific substrates and (b) the assignment of the pKa of the major ionization (approximating to 7.5) to the perturbed carboxy group of Glu280 whose conjugate base is envisaged as supplying general base catalysis to attack of a water molecule. The macroscopic pKa of the minor ionization (5.0) is considered to approximate to that of the carboxy group of Glu488.


Biomechanical contribution of transverse connectors to segmental stability following long segment instrumentation with thoracic pedicle screws.
An in vitro biomechanical cadaver study of long segment thoracic pedicle screw constructs with transverse connectors (TC). To determine the resultant degree of motion of the instrumented thoracic spine after segmental pedicle screw instrumentation with and without TC. SUMMARY OF BACKGROUND DATA.: TC are generally not thought to be necessary with thoracic pedicle screw constructs, yet to date no study has reported the effect of TCs after all pedicle screw long thoracic fusions. Eight human cadaveric spines were potted and then instrumented from T4-T10 with bilateral 5.5 mm multiaxial titanium (Ti) pedicle screws and 5.5 mm contoured Ti rods. Specimens were tested with a six-degree-of-freedom spine stimulator in the intact condition, after instrumentation, after placement of 1 TC (3 different locations) and after placement of both TCs. Data were analyzed by loading modality (axial rotation, flexion-extension, and lateral bending) using one-way analysis of variance with an alpha of 0.05. Paired t tests were used for post hoc analysis with correction for multiple comparisons. There was no difference with the addition of 1 or 2 TCs in terms of flexion-extension or lateral bending when compared to the instrumented condition (P > 0.05). Biomechanical testing of the long-segment thoracic constructs in axial rotation (torsion) loading modes generated the most significant findings of this study. After instrumentation with thoracic pedicle screws, T4-T10 full ROM was significantly reduced from the intact condition (P < 0.05). On average, TPS alone resulted in a 65% decrease in ROM. However, the addition of a transverse connector at 1 of the 3 positions tested yielded another 20% improvement in axial segmental stability as represented by further ROM reduction. These differences were significant from the TPS only group (no TCs), regardless of the TC position (P < 0.05). Furthermore, 2 TCs placed at the proximal and distal ends of the construct provided the greatest biomechanical axial stability to the instrumented specimens (P < 0.05). This was highlighted by an average of 35% ROM reduction from the stability level achieved with the TPS only constructs (P < 0.05), or an additional 15% improvement in axial stability over a single TC. For long thoracic pedicle screw constructs, the addition of 1 or 2 TCs significantly decreases construct axial rotation, which is the primary plane of motion for the thoracic spinal region. A single TC contributed to a significant reduction of T4-T10 ROM (an additional 20%) relative to TPS fixation alone (P < 0.05), while the location of the TC within the construct was irrelevant. A second TC had an additive effect (an additional 15% reduction) on axial stability. (P < 0.05) Flexion-extension and lateral bending are not affected. Single TC significantly improves axial rotation stability in long thoracic pedicle screw constructs. Two crosslinks, however, are better than one.


[Recent findings on the external oculomotor nucleus: the center for horizontal ocular movement].
Various neurobiological methods allowing the analysis of electrophysiological and morphological properties of a cell population within the central nervous system will be illustrated in the study of the abducens nucleus. Intracellular recordings provided the functional identification of the different types of cells within the abducens nucleus. Antidromic excitation, refractoriness, conduction velocity and frequency of discharges indicated the properties of the abducens motoneurones. Various types of afferent stimulations were applied to study the synaptic responses of the neurones. A dye was then electrophoretically injected and the labelled neurone observed with a light microscope. Full reconstruction of dendritic arborization and of axon trajectory was performed. The morphological study has shown the heterogeneity of the population of the motor nucleus, and the ultrastructural features indicated a complex synaptic organisation. The origin of some afferent terminals was determined.


Recurrent breast relapses in a patient with acute lymphoblastic leukaemia following allogeneic bone marrow transplantation.
Isolated extramedullary relapse is very rare after allogeneic bone marrow transplantation (BMT) in acute lymphoblastic leukaemia (ALL) and continues to be a therapeutic problem. We report recurrent breast relapses in a patient with ALL after allogeneic BMT. On both occasions, bone marrow cells were shown to be of donor origin and masses disappeared after systemic chemotherapy. Treatment of the isolated extramedullary relapse after allogeneic BMT is discussed.


The first total synthesis of anemarchalconyn and anemarcoumarin A.
Anemarchalconyn (1) and anemarcoumarin A (2), the natural bioactive compounds isolated from the rhizomes of Anemarrhena asphodeloides Bunge (Liliaceae), were first totally synthesized using easily available materials in short, convenient routes with overall yields of 32 and 48%.


[Effects of acclimation temperature on the growth of Perna viridis (Bivalvia: Mytilidae), using the RNA/DNA ratio].
Temperature affects growth rate in aquatic organisms. This can be evaluated in short term using biochemical indexes (RNA/DNA and Protein/DNA). The effect of acclimatization temperature on the instantaneous growth and physiological condition of Perna viridis was studied in organisms collected in La Esmeralda, Sucre State (Venezuela) and taken to the laboratory, where groups of 100 organisms (size 3.0 - 3.5 cm, anteroposterior measurement) were acclimatized at 15, 20, 26 or 28 degrees C during four weeks. Later they were kept in a 60 liters aquarium for another six weeks under the same conditions. Each week, ten organisms per group were extracted to measure concentrations of RNA, DNA (by a fluorometric method with ethidium bromide) and proteins (by a colorimetric method), in tissues (digestive gland, adductor muscle and gills). Protein concentration was greater and highly significant at 15 degrees C for all studied tissues. The opposite was obtained with the RNA/DNA and Protein/DNA ratios: the greatest increase was observed at the highest temperature (28 degrees C) for all tissues. At the lowest temperature there was a tendency to reduce both indexes with time. Greater instantaneous growth can be expected at higher temperatures and 28 degrees C was optimal for growth in these specimens.


Trichinella isolates from polar bears in Svalbard. Freeze resistance and infectivity in rats and swine.
The author isolated Trichinella strains from five polar bears in Svalbard (the high arctic region of Norway). Based on infectivity experiments with white mice (BOM:NMR), the freeze resistance limits of the Trichinella strains are outlined. Further experiments showed that white rats (MOL:WIST) and pigs (sus scrofa domestica) are almost refractory to these Trichinella strains. The infectivity of Svalbard isolates in the above mentioned test animals was compared, in parallel experiments, with that of T. spiralis (Owen). The latter showed a very high infectivity to the same species of test animals. It is thus probable that the arctic Trichinella found in the polar bear is biologically distinct from both T. spinalis (Owen) and T. nativa ( Britov and Boev ).


Use of conserved key amino acid positions to morph protein folds.
By using three-dimensional (3D) structure alignments and a previously published method to determine Conserved Key Amino Acid Positions (CKAAPs) we propose a theoretical method to design mutations that can be used to morph the protein folds. The original Paracelsus challenge, met by several groups, called for the engineering of a stable but different structure by modifying less than 50% of the amino acid residues. We have used the sequences from the Protein Data Bank (PDB) identifiers 1ROP, and 2CRO, which were previously used in the Paracelsus challenge by those groups, and suggest mutation to CKAAPs to morph the protein fold. The total number of mutations suggested is less than 40% of the starting sequence theoretically improving the challenge results. From secondary structure prediction experiments of the proposed mutant sequence structures, we observe that each of the suggested mutant protein sequences likely folds to a different, non-native potentially stable target structure. These results are an early indicator that analyses using structure alignments leading to CKAAPs of a given structure are of value in protein engineering experiments.


Characterization of the T cell response to the major hazelnut allergen, Cor a 1.04: evidence for a relevant T cell epitope not cross-reactive with homologous pollen allergens.
IgE antibodies specific for the major birch-pollen allergen, Bet v 1, cross-react with homologous allergens in particular foods, e.g. apples, carrots and hazelnuts. In a high number of tree pollen-allergic individuals, this cross-reactivity causes clinical symptoms, commonly known as the 'birch-fruit-syndrome'. To characterize the T cell response to the Bet v 1-related major allergen in hazelnuts, Cor a 1.04, and its cellular cross-reactivity with Bet v 1 and the homologous hazel pollen allergen, Cor a 1. Using recombinant Cor a 1.04, T cell lines (TCL) and T cell clones (TCC) were established from peripheral blood mononuclear cells of tree pollen-allergic patients with associated food allergy. T cell epitopes were determined using overlapping synthetic peptides in Cor a 1.04-reactive TCL and TCC. In parallel, reactivity to Bet v 1 and Cor a 1 was tested. In total, 20 distinct T cell epitopes on the hazelnut allergen were identified. Several Cor a 1.04-specific TCL and TCC reacted with pollen allergens albeit less pronounced than with the hazelnut allergen. Several Cor a 1.04-specific TCC did not react with pollen allergens. Interestingly, these clones were found to react with the Bet v 1-related major allergen in carrots, Dau c 1. The cellular cross-reactivity between both food allergens could be associated with the most frequently recognized T cell epitope of Cor a 1.04, Cor a 1.04(142-153). The major hazelnut allergen cross-reacts with the major allergens of birch and hazel pollen but apparently contains a relevant T cell epitope not shared with pollen allergens. Our finding may have important implications for the specific immunotherapy of tree pollen-allergic patients suffering from concomitant hazelnut allergy.


Invited Commentary: The Enduring Role of "Place" in Health-A Historic Perspective.
In public health, it has long been observed that "place"-specifically, where one lives-affects individual health, with the main research question distinguishing between the effects of "context" (defined as area characteristics) and "composition" (the characteristics of inhabitants) on health outcomes. There have been many studies in which the spatial patterning of disease has been explored, but they were often ecological in design, used broad census geographic levels, lacked individual-level data, or when available, did not simultaneously analyze community- and individual-level risk factors using appropriate modeling techniques. The paper by Diez-Roux et al. (Am J Epidemiol. 1997;146(1):48-63) represents an important expansion of the literature in terms of analytic methods used and level of geography studied. The authors demonstrated that both neighborhood- and individual-level measures of socioeconomic status work together to play an important role in shaping disease risk. Analyses incorporating both levels of data have the potential to provide epidemiologists with a deeper understanding of the divergent pathways via which neighborhood affects health.


Effect of meal-feeding on the daily variations of insulin, glucose, and NADP-linked dehydrogenases in rats.
Normal and adrenalectomized rats were either ad libitum fed or meal-fed a 66.5% glucose diet for 1 to 3 weeks. Ad libitum-fed rats exhibited synchronized daily rhythms in the levels of immunoreactive insulin, glucose, hepatic glucose-6-phosphate dehydrogenase, and malic enzyme activities. These rhythms were shifted late-morning 2-hour feeding period. The rhythms of adrenalectomized ad libitum-fed rats were different from those for nonadrenalectomized rats. These results indicate that differences between ad libitum- and meal-fed animals may be attributable to the timing of food intake with respect to the timing of observation rather than to meal-feeding alone. It is further concluded that the adrenals play a role in the maintenance of these rhythms.


The informationist: a prospective uncontrolled study.
To determine whether doctors in an Australian tertiary hospital would use an informationist service, and to identify how the service would influence care. A prospective uncontrolled pilot study July 2002-January 2003. A teaching hospital in South Australia. Fourteen doctors working in the selected units. An informationist attended specified medical in-patient ward rounds and clinical meetings in the Respiratory Medicine, Sleep Disorders, and Rheumatology units. Main outcomes measures. Clinician self-assessed impact of information on a range of outcomes relating to clinical decision-making, clinician education, and avoidance of adverse events. In 23 weeks, 52 questions were generated by nine of 14 eligible doctors. Forty-eight of 52 (92%) feedback forms were completed, indicating an average of 5.7 impacted outcomes per response. Twenty-five of 48 (52%) provided new information to doctors, and 24/48 (50%) provided at least some information that could be used immediately. Most common contributions of the service to patient care were revision of treatment plan (21/48, 44%) and confirmation of proposed therapy (18/48, 38%). Thirteen of 48 (27%) contributed to avoiding adverse events, and 10/48 (21%) contributed to avoiding additional tests and procedures. Eleven of 11 (100%) doctors who used the service assessed that it contributed or probably contributed to their professional development, with 8/10 (80%) indicating a similar impact on improving clinical outcomes. Medical staff will use an informationist service, which contributes substantially to a multiplicity of outcomes relating to medical decision-making, clinician education, and clinical outcomes.


[Plasma assay of methadone enantiomers with high performance liquid chromatography].
6-Dimethylamino-4,4-diphenylheptane-3-one (methadone) is a synthetic opioid. Presence of an assymetrical carbon in its structure explains existence of two enantiomers. Levogyral enantiomer or R-methadone exhibits an 25 fold superior analgesic activity to the dextrogyral enantiomer S-methadone. In order to run separately a plasma assay of these two enantiomers, a chromatographic chiral separation method coupled with an ultraviolet detection has been performed. It allows selective assay of each enantiomer. This method, although an analytical interference with d-propoxyphene, is sensitive, reproductible, specific and shows a convenient resolution for the analysis of both the stereospecific and racemic forms. This method can be applied for pharmacokinetic study of the drug in patients treated by methadone.


Roles of respirologists in lung transplantation in Japan: narrative review.
Lung transplantation (LTx) in Japan has taken steps toward increasing the number of donors and recipients and is at the maturity stage of development, at which point pulmonologists (hereinafter referred to as "respirologists") become involved in transplant practice. Because of severe donor shortage and limited number of LTx surgeries, most of transplant process from candidacy evaluation to post-operative management has been handled only by thoracic surgeons, which takes away opportunities from respirologists to manage LTx recipients. Given the growth of both LTx and the number of patients with complex problems, cooperation with respirologists in transplant practice is urgently needed to achieve transplant success in Japan. Authors summarized current transplant circumstance in Japan from the transplant physician's standpoint. A systematic search through PubMed database and Google Scholar was performed by terms of "respirologists", "pulmonologist", "lung transplant" or "Japan" from 2000 and 2022. Thoracic surgeons working at each transplant center were asked to complete a questionnaire on physicians' intervention to LTx. The roles of respirologists in LTx differ with facility size and function, depending on whether they are working at a non-transplant center with other respirologists or at a transplant center with transplant physicians. LTx centers are currently devoted to educating respirologists who work at non-transplant or low-volume transplant centers in order for them to deal with patients before and after transplantation. Joint efforts and training of outstanding personnel who can take care of recipients are required, this being the greatest issue for the success of transplantation in Japan.


Exploration of "over kill effect" of high-LET Ar- and Fe-ions by evaluating the fraction of non-hit cell and interphase death.
The reason why RBE for cell killing fell to less than unity (1.0) with very high-LET heavy-ions ((40)Ar: 1,640 keV/microm; (56)Fe: 780, 1,200, 2,000 keV/microm) was explored by evaluating the fraction of non-hit cell (time-lapse observation) and cells undergoing interphase death (calculation based on our previous data). CHO cells were exposed to 4 Gy (30% survival dose) of Ar (1,640 keV/microm) or Fe-ions (2,000 keV/microm). About 20% of all cells were judged to be non-hit, and about 10% cells survived radiation damage. About 70% cells died after dividing at least once (reproductive death) or without dividing (interphase death). RBE for reproductive (RBE[R]) and interphase (RBE[I]) death showed a similar LET dependence with maximum around 200 keV/microm. In this LET region, at 30% survival level, about 10% non-survivors underwent interphase death. The corresponding value for very high-LET Fe-ions (2,000 keV/microm) was not particularly high (approximately 15%), whereas that for X-rays was less than 3%. However, reproductive death (67%) predominated over interphase death (33%) even in regard to rather severely damaged cells (1% survival level) after exposure to Fe-ions (2,000 keV/microm). These indicate that interphase death is a type of cell death characteristic for the cells exposed to high-LET radiation and is not caused by "cellular over kill effect". Both NHF37 (non-hit fraction at 37% survival) and inactivation cross-section for reproductive death (sigma[R]) began to increase when LET exceeded 100 keV/microm. The exclusion of non-hit fraction in the calculation of surviving fraction partially prevented the fall of RBE[R] when LET exceeded 200 keV/microm. On the other hand, the mean number of lethal damage per unit dose (NLD/Gy) showed the same LET-dependent pattern as RBE[R]. These suggest that the increase in non-hit fraction and sigma[R] with an increasing LET is caused by enhanced clustering of ionization and DNA damage which lowers the energy efficiency for producing damage and RBE.


Total Synthesis of Antibacterial Macrolide Sorangiolide A.
A convergent route for the asymmetric total synthesis of antibacterial macrolide sorangiolide A has been developed for the first time. The key feature of this synthesis includes Krische iridium-catalyzed anti-diastereoselective carbonyl crotylation, Crimmins acetate aldol, Yamaguchi esterification, Julia-Kocienski olefination, Horner-Wadsworth-Emmons olefination, and ring-closing metathesis. The origin of the low intensity of the 13C{1H} NMR signals of the C1 and C2 centers of the natural product has been investigated, disclosing possible forms of existence for the natural product in the solution phase.


The mechanism of action of bufalin in inhibition of lipid droplet accumulation in mouse macrophages.
A cardiotonic glycoside, bufalin, originally isolated from the dried white venom of Chinese toad Bufo gargarizans, was found to inhibit lipid droplet accumulation in mouse macrophages. Bufalin selectively inhibited synthesis of [C]cholesteryl ester (CE), a main component of lipid droplet, from [C]oleic acid and [C]cholesterol with IC values of 8.6 µM and 10 µM, respectively. The postlysosomal metabolism of cholesterol to CE in macrophages was also inhibited by the compound with a similar IC value of 13.2 µM. However, the compound exhibited almost no effect on acyl-CoA : cholesterol acyltransferase, a key enzyme in CE synthesis localized in the endoplasmic reticulum (ER). From the fluorescent microscopic observation of cellular lipids, bufalin-treated macrophages increased the accumulation of free cholesterol in lysosomes and caused to enlarge the shape and volume of lysosomes as well as pregnenolone-treated macrophages. These findings suggest that bufalin inhibited the postlysosomal metabolism of cholesterol, leading to a reduction of lipid droplets in mouse macrophages without cytotoxicity.


Effects of dietary crude protein on protein and fat deposition in milk-fed veal calves.
Research on veal calf production has focused on maximizing lean tissue growth. Nevertheless, limited attention has been paid to the evolution of digestive and metabolic utilization of N and energy as calves get older, whereas age at slaughter increases. The objective of this study was to determine the effects of 4 concentrations of dietary crude protein (CP) content on protein and fat deposition and energy utilization in milk-fed calves at 3 stages of fattening using the balance technique combined with heat production measurements in a respiration chamber. At each stage, 16 Prim'Holstein male calves (mean body weight at each stage: 72, 136, and 212 kg) received 4 isocaloric diets with CP contents of 76, 88, 100, and 112% of a reference CP content fixed at 20% during the first stage and 19% during the 2 later stages. After 2 wk of adaptation to their respective diets and housing conditions, the calves were placed for 1 wk in an open-circuit respiration chamber for N and energy balance measurements (first 6 d) and measurement of the fasting heat production (last day). Measurements for a stage were performed over 2 periods of 4 successive weeks. There was no effect of dietary CP on digestibility during the 2 later stages, but the low-protein diet resulted in lower digestibility coefficients for dry matter, organic matter, gross energy, CP, and crude fat during the first stage. Endogenous fecal N was estimated as 2.5 g/kg of dry matter intake irrespective of stage, and metabolic urinary N was estimated at 0.07 g/kg of body weight(0.85) per day. Maximum N retention was 32.8, 40.5, and 44.0 g/d at stages 1, 2, and 3, respectively. The effect of protein intake on protein deposition was dependent on age of the calves, because the marginal efficiency of digestible protein utilization decreased from 64 to 18% as animals got older. Fat deposition decreased with increasing dietary CP content irrespective of stage. Total energy retention was not modified by dietary CP content. The composition of body weight gain was affected differently for each stage, because the protein content of body weight gain increased with increasing dietary CP content during the first stage, whereas it remained constant during the other 2 stages. Fat and energy content in body weight gain decreased with increasing dietary CP irrespective of stage. These results provide a basis for estimating protein requirement of veal calves according to a factorial approach.


"Spice" and "K2" herbal highs: a case series and systematic review of the clinical effects and biopsychosocial implications of synthetic cannabinoid use in humans.
Cannabis, the most commonly used illicit substance, exerts its primary psychoactive effect via delta-9 tetrahydrocannabinol (Δ(9) -THC) agonism of cannabinoid receptor type 1 (CB1). Some users develop a cannabis use disorder and physical dependence manifested by withdrawal symptoms during abstinence. Hence, there is growing public health concern about increasing use of a new generation of synthetic cannabinoid (SC) agonists (eg, JWH-018, CP 47,497) marketed as natural herbal incense mixtures under brand names such as "Spice" and "K2." Anecdotal reports suggest overlapping effects with marijuana when the mixtures are smoked, however, systematic evaluation of SC-related psychoactive properties and adverse effects is lacking. We conducted a systematic review of published reports on SC clinical effects in humans. Most highlight potential toxicity such as acute anxiety and psychosis. In addition, we carefully document three cases in which experienced marijuana users meeting criteria for cannabis dependence with physiologic dependence smoked SC products regularly. The SC mixture effects were reportedly similar to marijuana and well tolerated. The individuals all reported that SC product use effectively alleviated cannabis withdrawal. Biopsychosocial factors associated with SC initiation and usage by the cases help to shed light on psychopharmacologic, clinical, and public health aspects of SC product consumption.


Optimizing the Management of Disabling Spasticity Following Spinal Cord Damage: The Ability Network-An International Initiative.
Optimizing the treatment of disabling spasticity in persons with spinal cord damage is hampered by a lack of consensus regarding the use of acceptable definitions of spasticity and disabling spasticity, and the relative absence of decision tools such as clinical guidelines and concise algorithms to support decision-making within the broader clinical community. Many people with spinal cord damage are managed outside specialist centers, and variations in practice result in unequal access to best practice despite equal need. In order to address these issues, the Ability Network-an international panel of clinical experts-was initiated to develop management algorithms to guide and standardize the assessment, treatment, and evaluation of outcomes of persons with spinal cord damage and disabling spasticity. To achieve this, consensus was sought on common definitions through facilitated, in-person meetings. To guide patient selection, an in-depth review of the available tools was performed and expert consensus sought to develop an appropriate instrument. Literature reviews are guiding the selection and development of tools to evaluate treatment outcomes (body functions, activity, participation, quality of life) as perceived by people with spinal cord damage and disabling spasticity, and their caregivers and clinicians. Using this approach, the Ability Network aims to facilitate treatment decisions that take into account the following: the impact of disabling spasticity on health status, patient preferences, treatment goals, tolerance for adverse events, and in cases of totally dependent persons, caregiver burden.


Associations of Self-Esteem With Attachment to Parents: A Meta-Analysis.
The main objective of the present meta-analysis was to analyze associations between security of attachment to parents and self-esteem. Studies were included if they assessed bivariate associations between self-esteem and attachment security with mothers and/or fathers, or with both parents in general. A systematic search in the electronic databases PSYCINFO, Web of Science, Google Scholar, and PSYNDEX identified 202 studies with 81,485 participants that were included in this multilevel meta-analysis. Criteria from the Mixed Methods Appraisal Tool were used for assessing the quality of the individual studies. Most studies assessed security with verbal measures (190 studies), and the mean age of participants was 16.5 years. We found a moderate positive concurrent correlation of attachment security to parents with self-esteem (r = .34; 95% confidence interval [CI], .33-.36), with associations being stronger when assessing attachment to parents in general (r = .37; CI, .35 to .40) rather than to mothers (r = .33; CI, .31 to .35) or fathers (r = .32; CI, .30 to .34) in particular. Cross-lagged effects indicate that higher initial attachment security predicts an increase in self-esteem over time (r = .19; CI, .09 to .28), while initial self-esteem predicts change in security (r = .08; CI, .02 to .14). Correlations of attachment security with self-esteem were weaker in older participants and stronger in studies with validated attachment measures. As most of the included studies have been conducted with adolescents and young adults, knowledge about associations of secure attachment to parents and self-esteem in the first years of life is still limited. Nonetheless, it is concluded that the available results support suggestions of attachment theory on the role of secure attachment for self-esteem, although causal effects could only be tested in experimental studies.


Lead removal from aqueous solutions by raw sawdust and magnesium pretreated biochar: Experimental investigations and numerical modelling.
Lead removal from aqueous solutions by raw cypress (Cupressus sempervirens L.) sawdust (RCS) and its derivative magnesium pretreated biochar (Mg-B) was investigated under static and dynamic conditions through batch and column assays. The Hydrus-1D model was used to estimate the transport parameters of the lead measured breakthrough curves. The batch experiments results showed that Mg-B was very efficient in removing lead compared to RCS and several other previously tested natural and modified materials. The column experiments results indicated that for both RCS and Mg-B, lead breakthrough curves and the related removal efficiencies were mainly dependent on the used initial concentration and the adsorbents bed height. The use of Hydrus-1D showed that the two-site chemical non-equilibrium model describes better the experimental lead breakthrough curves for both RCS and Mg-B as the equilibrium model.


[Complex analysis of the physical metabolic and genetic state in children of mothers with type 1 diabetes].
Complex assessment of the development, clinical and immunological state of children born by mothers with type 1 diabetes, in the years 1998-2000. Material examined were 30 newborns, and subsequently 25 in the first, 30 children at 5-6 years of life. In newborns and in the 5-6 years the antibodies: IA-2A, IAA, ICA, anti GAD, insulin (IRI), peptide C were determined. In the first year HbA(1c), TSH, antigens HLA DQA1 and DQB1 were determined, in the 5th-6th years of life, the level of antibodies anti endomizium. Developmental anomalies in newborns were found in 6, in 3 in first and in the 5th-6th years in 4 children. Systemic infections were found in 6, hypoxia and prematurity in 12 newborns. A positive titer of anti GAD in 15, ICA in 18, IA-2A in 8, IAA in 18 newborns. In the first year of life, anti GAD in 2, in the 5-6th years in 4 children. In one child anti GAD was found during three examinations. In the case of this positive titer of antibodies, the allele DQB1*0302 was present. Allel DQB1*0302 was present in 28% of children, allele DQA1*0301 was absent. Mean levels of IRI afterbirth and in the first year of life were: 23.6 and 9.7 uIU/ml and peptide C 1.25 and 0.92 ng/ml. Mean levels of HbA(1c) in the first and 5th yrs of life were: x 6.2%, TSH 2.45 uIU/ml and 3.4 uIU/ml. Pathological values of antibodies anti endomizium were found in 4 children, biopsy of the small intestine confirmed coeliac disease. A normal body mass was seen in 9 newborns in 16 in the first, and 14 children 5-6 years of age. Deficiency in body mass was found in 2 newborns and 3 children in the first and 5-6th yrs. Macrosomia was found in 8 newborns in group I and 3 in group II. Overweight was found in 5 children in the first year and 9 in 5-6th yrs of life. None of the children have developed diabetes. 1. Children of mothers with type 1 diabetes should be monitored by an outpatient clinic for diabetic patients. 2. Children of mothers with diabetes should have determined regularly immunological markers for diabetes and other autoimmunological disease.


ARE THE FACTORS AFFECTING ADVERSE PREGNANCY OUTCOMES DIFFERENT IN OBESE GESTATIONAL DIABETES PREGNANT WOMEN RECEIVING DIET OR INSULIN TREATMENT?
We aimed to examine the factors affecting adverse gestational outcome in gestational diabetes (GDM) patients, who were grouped as obese and normal- weight, having only-diet, or insulin treatments. The study included 373 patients, treated with diet or insulin. These patients were sub-grouped as obese and non-obese, and examined retrospectively. The variables affecting adverse gestational outcome in obese GDM patients having dietary and/ or insulin treatments were detected with multiple regression analysis. The weight gained during pregnancy in the GDM group having insulin treatment was more than the one in only-diet treated GDM group (p=0.004). Pre-pregnancy body mass index, the weight gained during pregnancy, hemoglobin A1C levels in the second and third trimesters, caesarian rates were higher in the insulin-treated obese patients than in the other groups (p<0.001). The odds ratio for fasting blood glucose level in insulin-treated obese GDM group was 1.081 (95% CI =1.004 - 1.163) (p=0.039); and it was 0.982 (95% CI =0.924 - 1.002) (p=0.048) for the weight gained during pregnancy, in only-diet treated obese GDM patients. The control of weight gained during pregnancy, and of fasting blood glucose levels in obese patients having GDM, is important to decrease adverse gestational outcome.


Reconstructing the regulatory circuit of cell fate determination in yeast mating response.
Massive technological advances enabled high-throughput measurements of proteomic changes in biological processes. However, retrieving biological insights from large-scale protein dynamics data remains a challenging task. Here we used the mating differentiation in yeast Saccharomyces cerevisiae as a model and developed integrated experimental and computational approaches to analyze the proteomic dynamics during the process of cell fate determination. When exposed to a high dose of mating pheromone, the yeast cell undergoes growth arrest and forms a shmoo-like morphology; however, at intermediate doses, chemotropic elongated growth is initialized. To understand the gene regulatory networks that control this differentiation switch, we employed a high-throughput microfluidic imaging system that allows real-time and simultaneous measurements of cell growth and protein expression. Using kinetic modeling of protein dynamics, we classified the stimulus-dependent changes in protein abundance into two sources: global changes due to physiological alterations and gene-specific changes. A quantitative framework was proposed to decouple gene-specific regulatory modes from the growth-dependent global modulation of protein abundance. Based on the temporal patterns of gene-specific regulation, we established the network architectures underlying distinct cell fates using a reverse engineering method and uncovered the dose-dependent rewiring of gene regulatory network during mating differentiation. Furthermore, our results suggested a potential crosstalk between the pheromone response pathway and the target of rapamycin (TOR)-regulated ribosomal biogenesis pathway, which might underlie a cell differentiation switch in yeast mating response. In summary, our modeling approach addresses the distinct impacts of the global and gene-specific regulation on the control of protein dynamics and provides new insights into the mechanisms of cell fate determination. We anticipate that our integrated experimental and modeling strategies could be widely applicable to other biological systems.


MR angiography of the aortoiliac and femoropopliteal vessels.
The variety of MR angiography strategies can be applied to the evaluation of vascular disease in the aortoiliac and femoropopliteal vessels. When used appropriately, a combination of these strategies can be offered to patients with peripheral vascular disease as a safe and effective alternative to conventional angiography for planning treatment options. This article presents the clinical issues, MR techniques, and the results of relevant studies in a detailed manner pertinent to accomplishing diagnostic MR angiography in the aortoiliac and femoropopliteal segments.


Silver coated anionic cellulose nanofiber composites for an efficient antimicrobial activity.
Herein, we report a comparative study of silver coated anionic cellulose nanocomposite before (CMC-Ag) and after (AgNPs/CMC) chemical reduction for antibacterial activity. Cellulose nanofibers were prepared by deacetylation of electrospun cellulose acetate nanofibers, which were then treated with sodium chloroacetate to prepare anionic cellulose nanofibers (CMC). Aqueous AgNO3 solution with different concentrations was employed to produce nanofiber composites. To obtain AgNPs/CMC, the resultant Ag/CMC nanofibers were chemically reduced with NaBH4. The nanocomposites were characterized by FE-SEM, FTIR, XPS and SEM-EDS. Antimicrobiality tests were conducted using S. aureus and Escherichia coli bacteria following standard test method JIS L1902, 2008. The EDS results confirmed higher silver content in CMC-Ag nanofibers than AgNPs/CMC nanofibers. The antimicrobial test and EDS results demonstrated higher silver release (larger halo width) by the former in comparison to later which confers better antimicrobiality by CMC-Ag nanofibers.


Phantom vibration and phantom ringing among mobile phone users: A systematic review of literature.
The last decade has witnessed considerable interest in pathological conditions stemming from misuse or overuse of technology, a condition commonly referred to as technopathology. Of the several complaints reported, phantom vibration or phantom ringing is one that has not yet been widely explored. The objective of conducting a systematic review is to provide an understanding of the phenomena and summarize the research conducted so far. Major databases were searched and articles that matched the inclusion criteria were selected for final analysis. According to findings obtained, phantom vibration or phantom ringing was commonly experienced by mobile phone users; however, few found it bothersome and hence took no steps to eliminate it. As of now, literature in the area is limited and many aspects of the phenomena such as its prevalence across populations, causal factors, consequences, and treatment plans are yet to be studied. Also, a clinical criterion for identification of the condition needs to be formulated. With increase in the number of individuals reporting mobile phone-related problem behavior, phantom vibration, or phantom ringing may be expected to become a cause of concern for mental health professionals within some years. Finally, the need for further research is emphasized while presenting directions for future investigations.


DBD atmospheric plasma-modified, electrospun, layer-by-layer polymeric scaffolds for L929 fibroblast cell cultivation.
This paper reported a study related to atmospheric pressure dielectric barrier discharge (DBD) Ar + O2 and Ar + N2 plasma modifications to alter surface properties of 3D PCL/Chitosan/PCL layer-by-layer hybrid scaffolds and to improve mouse fibroblast (L929 ATCC CCL-1) cell attachment, proliferation, and growth. The scaffolds were fabricated using electrospinning technique and each layer was electrospun sequentially on top of the other. The surface modifications were performed with an atmospheric pressure DBD plasma under different gas flow rates (50, 60, 70, 80, 90, and 100 sccm) and for different modification times (0.5-7 min), and then the chemical and topographical characterizations of the modified samples were done by contact angle (CA) measurements, scanning electron microscopy (SEM), atomic force microscopy, and X-ray photoelectron spectroscopy. The samples modified with Ar + O2 plasma for 1 min under 70 cm(3)/min O2 flow rate (71.077° ± 3.578) showed a 18.83% decrease compare to unmodified samples' CA value (84.463° ± 3.864). Comparing with unmodified samples, the average fiber diameter values for plasma-modified samples by Ar + O2 (1 min 70 sccm) and Ar + N2 (40 s 70 sccm) increased 40.756 and 54.295%, respectively. Additionally, the average inter-fiber pore size values exhibited decrease of 37.699 and 48.463% for the same Ar + O2 and Ar + N2 plasma-modified samples, respectively, compare to unmodified samples. Biocompatibility performance was determined with MTT assay, fluorescence, Giemsa, and confocal imaging as well as SEM. The results showed that Ar + O2-based plasma modification increased the hydrophilicity and oxygen functionality of the surface, thus affecting the cell viability and proliferation on/within scaffolds.


P-RnaPredict--a parallel evolutionary algorithm for RNA folding: effects of pseudorandom number quality.
This paper presents a fully parallel version of RnaPredict, a genetic algorithm (GA) for RNA secondary structure prediction. The research presented here builds on previous work and examines the impact of three different pseudorandom number generators (PRNGs) on the GA's performance. The three generators tested are the C standard library PRNG RAND, a parallelized multiplicative congruential generator (MCG), and a parallelized Mersenne Twister (MT). A fully parallel version of RnaPredict using the Message Passing Interface (MPI) was implemented on a 128-node Beowulf cluster. The PRNG comparison tests were performed with known structures whose sequences are 118, 122, 468, 543, and 556 nucleotides in length. The effects of the PRNGs are investigated and the predicted structures are compared to known structures. Results indicate that P-RnaPredict demonstrated good prediction accuracy, particularly so for shorter sequences.


Rapid Progression After 177Lu-DOTATATE in Patients With Neuroendocrine Tumors.
Peptide receptor radionuclide therapy (PRRT) is a treatment option for somatostatin receptor-positive, unresectable or metastatic neuroendocrine tumors (NETs). Despite high disease control rates seen with PRRT, a subset of the NET population seems to have a short progression-free interval. We hypothesize that patients with NETs with rapid progression post-PRRT may have mixed low- and high-grade cell populations, and PRRT treats the lower-grade component, allowing the more aggressive high-grade component to progress.We report 7 patients with biopsy-proven NET who received PRRT with 177Lu-DOTATATE at the Stanford Cancer Center who had evidence of progressive disease (PD) on or within 6 months of therapy.All patients had primary pancreatic, metastatic, well-differentiated NET on diagnosis and were heavily pretreated before receiving PRRT. Two patients had PD while on PRRT; 5 had PD within 6 months of completing PRRT. The median time from the last cycle to PD was 3.2 months (range, 1.1-4.6 months). The median progression-free survival was 7.7 months (95% confidence interval, 5.7-9.8 months). Three patients had a repeat biopsy post-PRRT, 2 of which demonstrated higher disease grade compared with their initial pathology. Further evaluation in larger patient cohorts is warranted to elucidate predictive factors of PRRT response/nonresponse to enable better patient selection.


[Thermogenesis from the breakdown of a ketogenic diet in an experimental model using swine].
A respiration calorimetry experiment with 10 matures sows was conducted to study the effect of a ketogenic diet on heat production and energy utilization. The ketogenic diet contained no carbohydrates and 85% of its energy as fat. The control diet was a mixed diet with most of its energy as carbohydrates. Both diets provided the same daily protein intake, which was slightly below the calculated protein requirement. The level of energy intake was adjusted to a moderate positive energy balance. Both diets were allocated to the same animal for three weeks each according to a crossover design. Seven-day collection periods and 48-hours measurements of the gaseous exchange (carbon-nitrogen balance method) were conducted on individual sows per diet. The ketogenic diet substantially increased the energy losses in faeces, which resulted in a energy digestibility of 75% compared to 93% with the mixed diet. The methane production was also significantly depressed. In contrast, the urine energy excretion was not influenced by the extremely high fat diet. The nitrogen balance showed lower faecal nitrogen losses and a higher urine nitrogen excretion in the animals with the high fat diet. Because of this compensative response no difference in nitrogen retention was observed between the two dietary treatments. The ketogenic diet caused no detrimental effects on thermogenesis or energy utilization. The results of both criteria could be fully explained by the well accepted ideas of the efficiency of utilization of the energy from fat under balanced nutrition conditions. Overall the results demonstrate that a high fat diet has no regulatory effect on the usually diet-induced thermogenesis.


Vanillic Acid Alleviates Acute Myocardial Hypoxia/Reoxygenation Injury by Inhibiting Oxidative Stress.
Oxidative stress is an important factor of myocardial hypoxia/reoxygenation (H/R) injury. Our research focuses on how to reduce the cardiac toxicity caused by oxidative stress through natural plant extracts. Vanillic acid (VA) is a phenolic compound found in edible plants and rich in the roots of Angelica sinensis. Experimental studies have provided evidence for this compound's effectiveness in cardiovascular diseases; however, its mechanism is still unclear. In this study, molecular mechanisms related to the protective effects of VA were investigated in H9c2 cells in the context of H/R injury. The results showed that pretreatment with VA significantly increased cell viability and decreased the percentage of apoptotic cells, as well as lactate dehydrogenase and creatine phosphokinase activity, in the supernatant, accompanied by reduced levels of reactive oxygen species and reduced caspase-3 activity. VA pretreatment also restored mitochondrial membrane potentials. Moreover, preincubation with VA significantly attenuated mitochondrial permeability transition pore activity. VA administration upregulated adenosine monophosphate-activated protein kinase α2 (AMPKα2) protein expression, and interestingly, pretreatment with AMPKα2-siRNA lentivirus effectively attenuated the cardioprotective effects of VA in response to H/R injury.


Vitamin E: A potential preventive approach against dental erosion-an in vitro short-term erosive study.
This study evaluated the in vitro effect of different components of palm oil on enamel in a short-term erosive challenge. The acquired enamel pellicle (AEP) was previously formed in situ for 2 h. Subsequently, the bovine enamel blocks were treated in vitro according to following solutions: G1-palm oil; G2-85% tocotrienol solution; G3-oily vitamin E; G4-oily vitamin A; G5-deionized water (negative control); G6-stannous-containing solution (Elmex® Erosion Protection Dental Rinse) (positive control). After application of the treatment solutions (500 µl, 30 s), the blocks were immersed in 0.5% citric acid (pH 2.4) during 30 s (initial erosion). The response variable was the percentage of surface hardness loss. Data were analyzed by one-way ANOVA and Fisher's Test (p < 0.05). The positive control (G6), palm oil (G1) and oily vitamin E (G3) groups presented the lowest percentage of surface hardness loss, and were statistically different from the negative group (G5) (p < 0.05), and no differences were found between these three groups. The 85% tocotrienol solution (G2) and oily vitamin A groups (G4) were not different to the negative control group. Stannous-containing positive control (Elmex® Erosion Protection), palm oil and oily Vitamin E were able to protect enamel against the erosive challenge performed in this in vitro study. In addition, vitamin E is probably the key ingredient of palm oil responsible for preventing enamel erosion. Vitamin E presented similar preventive effect to a commercial mouthwash stannous-containing solution (Elmex® Erosion Protection) against initial erosion and, it can be considered as a promising natural alternative for the formulations of solutions aiming to prevent erosive tooth wear.


A systematic approach to analyze the social determinants of cardiovascular disease.
Cardiovascular diseases are the leading cause of human mortality worldwide. Among the many factors associated with the etiology, incidence, and evolution of such diseases; social and environmental issues constitute an important and often overlooked component. Understanding to a greater extent the scope to which such social determinants of cardiovascular diseases (SDCVD) occur as well as the connections among them would be useful for public health policy making. Here, we will explore the historical trends and associations among the main SDCVD in the published literature. Our aim will be finding meaningful relations among those that will help us to have an integrated view on this complex phenomenon by providing historical context and a relational framework. To uncover such relations, we used a data mining approach to the current literature, followed by network analysis of the interrelationships discovered. To this end, we systematically mined the PubMed/MEDLINE database for references of published studies on the subject, as outlined by the World Health Organization's framework on social determinants of health. The analyzed structured corpus consisted in circa 1190 articles categorized by means of the Medical Subheadings (MeSH) content-descriptor. The use of data analytics techniques allowed us to find a number of non-trivial connections among SDCVDs. Such relations may be relevant to get a deeper understanding of the social and environmental issues associated with cardiovascular disease and are often overlooked by traditional literature survey approaches, such as systematic reviews and meta-analyses.


[Biochemical mechanisms of neurotoxic lead activity].
This article presents the latest study results on lead (Pb2+) neurotoxicity, in order to draw attention of the Polish public to the issue and initiate a nation-wide programme eliminating lead contamination effects, especially in children. We discuss the after-effect of exposure to lead in concentrations lower than presently accepted as 'safe'. The pathway of lead transport to the brain, and the effects of lead accumulation in neurons, oligodendroglia and astroglia, are examined. We also present the impairing influence of lead on the cognitive brain functions and learning abilities as a result of affecting three main neurotransmission systems: dopaminergic, cholinergic and glutaminergic. The present knowledge on the influence of lead on receptors, neutransmitter release and synaptic proteins.


Integrative Analysis of lncRNA-mRNA Profile Reveals Potential Predictors for SAPHO Syndrome.
Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is known as a rare disease characterized by inflammatory lesions on bones and skin. Polymorphism of clinical manifestation and lack of molecular biomarkers have both limited its diagnosis. Our study performed RNA sequencing (RNA-seq) and integrative bioinformatics analysis of long noncoding RNA (lncRNA)-messenger RNA (mRNA) profile in patients with SAPHO syndrome and healthy controls. A total of 4,419 differentially expressed (DE) mRNAs and 2,713 lncRNAs were identified (p < 0.05, fold change > 2) and a coexpression network was constructed to further investigate their regulatory interactions. The DE lncRNAs were predicted to interact with mRNAs in both cis and trans manners. Functional prediction found that the lncRNA-targeted genes may function in SAPHO syndrome by participating in biological process such as adipocytokine signaling pathway, ErbB signaling pathway, FoxO signaling pathway, as well as production and function of miRNAs. The expression levels of three pairs of coexpressed lncRNA-mRNAs were validated by qRT-PCR, and their relative expression levels were consistent with the RNA-seq data. The deregulated RNAs GAS7 and lnc-CLLU1.1-1:2 may serve as potential diagnostic biomarkers, and the combined receiver operating characteristic (ROC) curve of the two showed more reliable diagnostic ability with an AUC value of 0.871 in distinguishing SAPHO patients from healthy controls. In conclusion, this study provides a first insight into long noncoding RNA transcriptome profile changes associated with SAPHO syndrome and inspiration for further investigation on clinical biomarkers and molecular regulators of this inadequately understood clinical entity.


A 3-day delay in synovial fluid crystal identification did not hinder the reliable detection of monosodium urate and calcium pyrophosphate crystals.
Arthrocentesis is an essential emergency step in managing patients with acute arthritis. To identify a bacterial infection, Gram staining is performed promptly. However, crystal analysis may not be immediately performed in many facilities. Being considered not to be stable over time, synovial fluid (SF) is sometimes discarded instead of being stored for crystal identification. The aim of this study was to assess the detectability of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in SF over a period of 3 days. Consecutive SF samples from 75 joints were analyzed for MSU, CPP crystals, and pH. Two independent observers evaluated the samples by regular light and polarization microscopy immediately after arthrocentesis and after 1, 2, and 3 days at room temperature or at 4°C. Of 75 samples, 27 contained crystals (16 MSU, 6 CPP, 5 both); semiquantitative counts of both MSU and CPP crystals did not change significantly after 3 days. There was no new formation of crystals in any of the crystal-negative samples, which was independent of the storage temperature. Synovial fluid pH was not predictive of crystals and did not change over time. Although immediate workup for microbiology, including Gram stain and culture, is indispensable and well established, crystal analysis may at times not be immediately performed. Our study suggests that when crystal identification cannot be done immediately, it can be safely performed up to 3 days after arthrocentesis when SF is stored at 4°C or even at stable room temperature (20°C).


Paralytic peptide: an insect cytokine that mediates innate immunity.
Host animals combat invading pathogens by activating various immune responses. Modulation of the immune pathways by cytokines is critical for efficient pathogen elimination. Insects and mammals possess common innate immune systems, and individual immune pathways have been intensively studied over the last two decades. Relatively less attention, however, has been focused on the functions of cytokines in insect innate immunity. Here, we summarize our recent findings from studies of the insect cytokine, paralytic peptide, in the silkworm Bombyx mori. The content of this report was presented at the First Asian Invertebrate Immunity Symposium. Acute activation of paralytic peptide occurs via proteolysis after stimulation with the cell wall components of pathogens, leading to the induction of a wide range of cellular and humoral immune responses. The pathogenic bacterium Serratia marcescens suppresses paralytic peptide-dependent immune activation, which impairs host resistance. Studies of insect cytokines will broaden our understanding of the basic mechanisms underlying the interaction between host innate immunity and pathogenic agents.


The assessment of clinically significant change using the Life Skills Profile.
In the context of the need to develop practical outcome measures, the present study aimed to assess the sensitivity of the Life Skills Profile (LSP) in terms of differences between hospital-based and community-based clients, and to assess the sensitivity of the LSP to changes over time. In this way, criteria could be established whereby the LSP could be used to determine appropriate changes in locus of care, both in terms of the "cut-off' for hospital-based and community-based tenure, and the level of "clinically significant change' in functioning. The LSP was administered at 3-monthly intervals to 200 clients of an area public mental health service with serious mental illness over a 21-month period. Locus of care (hospital or community) was noted at each administration. Clients in the community scored significantly better than those in hospital, however there was a great deal of overlap. Using hospital or community tenure as the variable of interest, a measure of reliable and clinically significant change over a 3-month period based on the LSP was developed. A total LSP score of 116.5 or above best discriminated clients in the community from those in hospital, and a difference of 18 points or more in two LSP obtained 3 months apart was unlikely to have arisen by chance. A simple, two-part criterion of significant change based on these results showed 89% accuracy in matching transition (or lack of transition) between hospital and community with changes in LSP scores. The results need to be understood within the methodological limitations of the present study. The findings provide users of the LSP with guidelines for the interpretation of repeat assessments. This may encourage more services to use formal reassessment methods to monitor the progress of their clients.


Strain paint: noncontact strain measurement using single-walled carbon nanotube composite coatings.
Composite coatings have been developed that reveal strains in underlying structural elements through noncontact optical measurement. Dilute individualized single-walled carbon nanotubes are embedded in a polymeric host and applied to form a thin coating. Strain in the substrate is transmitted through the polymer to the nanotubes, causing systematic and predictable spectral shifts of the nanotube near-infrared fluorescence peaks. This new method allows quick and precise strain measurements at any position and along any direction of the substrate.


Age-associated loss of heterozygosity of tumor suppressor genes in the gastric mucosa of humans.
The current study is based on the hypothesis that aging predisposes gastric mucosa to carcinogenesis through altered expression and/or mutations of genes involved in cell growth. To test this hypothesis, we investigated the age-associated changes in mutation of adenomatous polyposis coli (APC), deleted in colorectal cancer (DCC), p53, and K-ras genes in the gastric mucosa of 19 healthy subjects of varying ages (25-91 yr). Specifically, we studied the loss of heterozygosity (LOH) of these genes in cardia, body, and antrum of the stomach. We observed that 3 of 19 subjects (16%) over 60 yr of age show LOH of at least one of the tumor suppressor genes. Among the subjects over 60 yr of age, the incidence of LOH is 38% (3/8). Two of three subjects had mutations in more than one tumor suppressor gene. In all three affected subjects, mutation in APC, DCC, or p53 was located mainly in the body of the stomach, suggesting increased susceptibility of this region to neoplastic changes. However, no LOH of K-ras was observed in these subjects. Our observation that subjects over 60 yr of age show mutation in one or more of the tumor suppressor genes suggests an age-related increase in predisposition of the stomach to neoplasia.