Dynamic secretion changes in the salt glands of the mangrove tree species Avicennia officinalis in response to a changing saline environment.
The specialized salt glands on the epidermis of halophytic plants secrete excess salts from tissues by a mechanism that is poorly understood. We examined the salt glands as putative salt and water bi-regulatory units that can respond swiftly to altering environmental cues. The tropical mangrove tree species (Avicennia officinalis) is able to grow under fluctuating salinities (0.7-50.0 dS m(-1)) at intertidal zones, and its salt glands offer an excellent platform to investigate their dynamic responses under rapidly changing salinities. Utilizing a novel epidermal peel system, secretion profiles of hundreds of individual salt glands examined revealed that these glands could secrete when exposed to varying salinities. Notably, rhythmic fluctuations observed in secretion rates were reversibly inhibited by water channel (aquaporin) blocker, and two aquaporin genes (PIP and TIP) preferentially expressed in the salt gland cells were rapidly induced in response to increasing salt concentration. We propose that aquaporins are involved and contribute to the re-absorption of water during salt removal in Avicennia officinalis salt glands. This constitutes an adaptive feature that contributes to salt balance of trees growing in saline environments where freshwater availability is limited.


Gastric hepatoid adenocarcinoma and familial investigation: does it always produce alpha-fetoprotein?
We present the case of a 68-year-old Caucasian man with gastric hepatoid adenocarcinoma without increased levels of alpha-fetoprotein (AFP) in the serum. The patient had a strong history of gastric cancer in his family, affecting seven members, including a brother and a sister. The patient underwent subtotal gastrectomy, but 4 months later presented hepatic metastases, and 6 months after the initial diagnosis he succumbed to the disease. Immunohistochemical tests showed that the tumour was positive for AFP, hepatocyte paraffin 1, and neuron-specific enolase, but negative for synaptophysin and chromogranin. Previously reported cases of hepatoid gastric tumours showed that they produce large amounts of AFP and that they have a poor prognosis.


Comprehensive assessment of human pharmacokinetic prediction based on in vivo animal pharmacokinetic data, part 1: volume of distribution at steady state.
The authors present a comprehensive analysis on the estimation of volume of distribution at steady state (VD(ss) ) in human based on rat, dog, and monkey data on nearly 400 compounds for which there are also associated human data. This data set, to the authors- knowledge, is the largest publicly available, has been carefully compiled from literature reports, and was expanded with some in-house determinations such as plasma protein binding data. This work offers a good statistical basis for the evaluation of applicable prediction methods, their accuracy, and some methods-dependent diagnostic tools. The authors also grouped the compounds according to their charge classes and show the applicability of each method considered to each class, offering further insight into the probability of a successful prediction. Furthermore, they found that the use of fraction unbound in plasma, to obtain unbound volume of distribution, is generally detrimental to accuracy of several methods, and they discuss possible reasons. Overall, the approach using dog and monkey data in the íie-Tozer equation offers the highest probability of success, with an intrinsic diagnostic tool based on aberrant values (<0 or >1) for the calculated fraction unbound in tissue. Alternatively, methods based on dog data (single-species scaling) and rat and dog data (íie-Tozer equation with 2 species or multiple regression methods) may be considered reasonable approaches while not requiring data in nonhuman primates.


Endoplasmic Reticulum Stress-Related Four-Biomarker Risk Classifier for Survival Evaluation in Esophageal Cancer.
Esophageal cancer (EC) is a lethal digestive tumor worldwide with a dismal clinical outcome. Endoplasmic reticulum (ER) stress poses essential implications for a variety of tumor malignant behaviors. Here, we set up an ER stress-based risk classifier for assessing patient outcome and exploiting robust targets for medical decision-making of EC cases. 340 EC cases with transcriptome and survival data from two independent public datasets (TCGA and GEO) were recruited for this project. Cox regression analyses were employed to create a risk classifier based on ER stress-related genes (ERGs) which were strongly linked to EC cases' outcomes. Then, we detected and confirmed the predictive ability of our proposed classifier via a host of statistical methods, including survival analysis and ROC method. In addition, immune-associated algorithm was implemented to analyze the immune activity of EC samples. Four EGRs (BCAP31, HSPD1, PDHA1, and UBE2D1) were selected to build an EGR-related classifier (ERC). This classifier could distinguish the patients into different risky subgroups. The remarkable differences in patient outcome between the two groups were observed, and similar results were also confirmed in GEO cohort. In terms of the immune analysis, the ERC could forecast the infiltration level of immunocytes, such as Tregs and NK cells. We created a four-ERG risk classifier which displays the powerful capability of survival evaluation for EC cases.


Cathodoluminescence visualisation of local thickness variations of GaAs/AlGaAs quantum-well tubes on nanowires.
We present spatially and spectrally resolved emission from nanowires with a thin radial layer of GaAs embedded in AlGaAs barriers, grown radially around taper-free GaAs cores. The GaAs layers are thin enough to show quantization, and are quantum wells. Due to their shape, they are referred to as quantum well tubes (QWTs). We have investigated three different nominal QWT thicknesses: 1.5, 2.0, and 6.0 nm. They all show average emission spectra from the QWT with an energy spread corresponding to a thickness variation of ±30%. We observe no thickness gradient along the length of the nanowires. Individual NWs show a number of peaks, corresponding to different QW thicknesses. Apart from the thinnest QWT, the integrated emission from the QWTs shows homogeneous emission intensity along the NW. The thinnest QWTs show patchy emission patterns due to the incomplete coverage of the QWT. We observe a few NWs with larger diameters. The QWTs in these NWs show spatially resolved variations across the NW. An increase in the local thickness of the QWT at the corners blocks the diffusion of carriers from facet to facet, thereby enabling us to visualise the thickness variations of the radial quantum wells.


[The expression of receptor activator nuclear factor-kappaB ligand and osteoprotegerin in cholesteatoma].
To observe the expression of receptor activator nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) in cholesteatoma and to determine their roles in the destruction of bone. To observe the role of osteoclasts in bone destruction. Immunohistochemical technique and computer image analysis were used to examine the expression of RANKL and OPG in 27 cholesteatoma and 11 normal tissue respectively. RANKL was expressed mainly in promatrix cells, including fibroblasts and foam cells. OPG was expressed both in epithelium and promatrix cells. The results of the computer image quantitative analysis showed that the mean optical density of RANKL and the ratio of RANKL/OPG in cholesteatoma were higher than that in normal skin epithelial tissue (P<0.05). There was no significant difference between the mean optical density of OPG in cholesteatoma and that in normal skin epithelial tissue (P>0.05). The overexpression of RANKL and the increased ratio of RANKL/OPG in cholesteatoma are associated with the destruction of bone. Osteoclasts is possible mediator of osteolysis.


Administrative reinstatement interlock programs: Florida, a 10-year study.
Interlocks reduce driving-under-the-influence (DUI) recidivism by 64%, but offenders resist installing them, preferring to risk driving while their driver's licenses are revoked. One method of motivating offenders to install an interlock is require it for reinstatement of their driver's license. This report updates an earlier evaluation of the administrative reinstatement interlock program (ARIP) procedure implemented in Florida in 2002. Driver records and interlock program records covering 120,000 DUI offenders were followed over 10 years. The flow through the sanction system--conviction, reinstatement, interlock program, and postinterlock period--is described. Logistical regression was used to identify the characteristics of offenders who installed interlocks, and survival analysis was used to evaluate the recidivism of offenders in the various stages in the ARIP. At any given time, approximately one-third of the convicted offenders were serving their license-revocation periods. Half of the offenders who completed their revocation periods remain unqualified for reinstatement because they do not fulfill other requirements. ARIP offenders who do qualify for reinstatement and install interlocks have lower recidivism rates while the devices are on their vehicles. After 10 years, Florida's ARIP is a mature system that succeeds in forcing all offenders in the program who qualify for reinstatement to install an interlock for at least 6 months. However, half of all offenders who complete their mandatory revocation period are either unable to or choose not to qualify for reinstatement.


Functional analysis of the Brassica napus L. phytoene synthase (PSY) gene family.
Phytoene synthase (PSY) has been shown to catalyze the first committed and rate-limiting step of carotenogenesis in several crop species, including Brassica napus L. Due to its pivotal role, PSY has been a prime target for breeding and metabolic engineering the carotenoid content of seeds, tubers, fruits and flowers. In Arabidopsis thaliana, PSY is encoded by a single copy gene but small PSY gene families have been described in monocot and dicotyledonous species. We have recently shown that PSY genes have been retained in a triplicated state in the A- and C-Brassica genomes, with each paralogue mapping to syntenic locations in each of the three "Arabidopsis-like" subgenomes. Most importantly, we have shown that in B. napus all six members are expressed, exhibiting overlapping redundancy and signs of subfunctionalization among photosynthetic and non photosynthetic tissues. The question of whether this large PSY family actually encodes six functional enzymes remained to be answered. Therefore, the objectives of this study were to: (i) isolate, characterize and compare the complete protein coding sequences (CDS) of the six B. napus PSY genes; (ii) model their predicted tridimensional enzyme structures; (iii) test their phytoene synthase activity in a heterologous complementation system and (iv) evaluate their individual expression patterns during seed development. This study further confirmed that the six B. napus PSY genes encode proteins with high sequence identity, which have evolved under functional constraint. Structural modeling demonstrated that they share similar tridimensional protein structures with a putative PSY active site. Significantly, all six B. napus PSY enzymes were found to be functional. Taking into account the specific patterns of expression exhibited by these PSY genes during seed development and recent knowledge of PSY suborganellar localization, the selection of transgene candidates for metabolic engineering the carotenoid content of oilseeds is discussed.


Role and importance of biochemical markers in clinical cardiology.
This paper reviews the current contribution of the biochemical marker determination to clinical cardiology and discusses some important developments in this field. Biochemical markers play a pivotal role in the diagnosis and management of patients with acute coronary syndrome (ACS), as witnessed by the incorporation of cardiac troponins into new international guidelines for patients with ACS and in the re-definition of myocardial infarction. Despite the success of cardiac troponins, there is still a need for the development of early markers that can reliably rule out ACS from the emergency room at presentation and also detect myocardial ischaemia in the absence of irreversible myocyte injury. Under investigation are two classes of indicators: markers of early injury/ischaemia and markers of inflammation and coronary plaque instability and disruption. Finally, with the characterisation of the cardiac natriuretic peptides, Laboratory Medicine is also assuming a role in the assessment of cardiac function.


Dipeptidyl peptidase-IV in synovial fluid and in synovial fluid mononuclear cells of patients with rheumatoid arthritis.
Dipeptidyl peptidase-IV (DPP-IV) enzymatic activity controls biological halftime of multiple local mediators. Its deregulation is associated with pathogenesis of several autoimmune diseases, including rheumatoid arthritis (RA). Although DPP-IV is the canonical representative of the group, a number of other proteins have been shown to have similar enzymatic activity. This study was aimed to identify the molecular source of DPP-IV activity in synovial fluid (SF) and fluid mononuclear cells (FMNC) in patients with RA and osteoarthritis (OA). In addition, the association of DPP-IV and the concentration of stromal cell-derived factor-1alpha (SDF), DPP-IV substrate, were evaluated. DPP-IV activity was measured by the kinetic fluorimetric method. The expression of studied molecules in FMNC and their concentrations in SF were assayed using flow cytometry and ELISA respectively. DPP-IV activity in SF, dominantly derived from the canonical DPP-IV, does not significantly differ between RA and OA. However, a significantly lower DPP-IV activity and expression in FMNC was found in RA as opposed to OA patients. Negative correlation between SDF concentration in SF and the relative amount of CD3+CD26+ cells was observed. We report decreased presence of DPP-IV/CD26 in CD3+ FMNC in RA, which also may participate on impaired balance of SDF concentration in SF.


Comparative Morphometry of the Sacrum and Its Clinical Implications: A Retrospective Study of Osteometry in Dry Bones and CT Scan Images in Patients Presenting With Lumbosacral Pathologies.
Background Morphometric measurement of the sacrum is crucial due to its active involvement in the instrumentation for lumbar pathologies. From screw placement to stabilization procedures for the spine, the sacrum remains a site of surgical importance. Thus, the purpose of this study was to generate baseline data by comparing two techniques, namely, osteometry in dry bones and CT scan imaging. Methodology In this study, 30 dry, fully ossified, disarticulated sacra were studied for osteometry, and 60 CT scan reports of patients with lumbar pathologies were retrospectively evaluated. In both cases, similar parameters were measured. The mean values were determined, the two methods were compared, and statistical analysis was performed. Results Among the 30 dry bone samples, 33.3% (10 out of 30) were males, while 55% of the CT scan group were males. Correlation between the different measurements in the CT scan group suggested that the vertebral body maximum width of S1 had a significant positive correlation with the vertebral body height of S1, sacral height, sacral breadth, transverse diameter of auricular surface, and vertical diameter of auricular surface. Statistically significant higher values (P < 0.001) were observed for the vertebral body mid diameter of S1, vertebral body height of S1, pedicle width, and pedicle depth measurements in the dry bone group compared to the CT scan group. Conclusions The efficiency of anaesthetic blocks can be increased if the parameters are evaluated beforehand. Moreover, sexual dimorphism of the bone can account for the varied results of the parameters, indicating the necessity to conduct gender-based studies in a wider population.


Drug interaction between rifampicin and cotrimoxazole in patients with tuberculosis.
1. Patients (n = 15) who were admitted with complications of tuberculosis, were given antitubercular therapy (ATT) with rifampicin (RIF), for a minimum period of 15 d, and cotrimoxazole (CTZ), concurrently, for 5-10 d. 2. The serum RIF levels were measured before the start of CTZ treatment and at the end of its administration. 3. The plasma half-life (t1/2) of RIF increased significantly from 1.92 +/- 0.57 h to 2.31 +/- 0.134 h after CTZ treatment. 4. The mean serum levels of RIF increased significantly at 4 and 6 h after CTZ administration.


Iatrogenic bile duct injury: a population-based study of 152 776 cholecystectomies in the Swedish Inpatient Registry.
Older age, male sex, and low yearly hospital volume of cholecystectomy may increase the risk of bile duct injury (BDI), whereas the use of intraoperative cholangiography may decrease the risk. The incidence of BDI at cholecystectomy may have increased after the introduction of laparoscopic cholecystectomy. Nationwide population-based study of all cholecystectomies registered in the Swedish Inpatient Registry from 1987 through 2001. All hospitals performing inpatient cholecystectomies in Sweden. Cholecystectomies were identified using International Classification of Diseases, Ninth and 10th Revisions surgical procedure codes. After exclusion of patients with hepatobiliary and pancreatic malignancies, patients with codes indicating reconstructive bile duct operations within 1 year after cholecystectomy were considered BDI cases. Risk factors for BDI were analyzed using multivariate logistic regression. The incidence proportion of BDI was calculated by dividing the number of cases by the number of cholecystectomies. Relative risks were estimated using odds ratios with 95% confidence intervals, and incidence proportion was used to describe incidence. Among 152 776 cholecystectomies, 613 reconstructed BDIs (0.40%) were identified. Older age and male sex were positively associated with BDI, whereas intraoperative cholangiography was negatively associated with BDI. The incidence proportion of BDI was 0.40% from 1987 to 1990, decreased to 0.32% from 1991 to 1995, and increased to 0.47% from 1996 to 2001. The mean yearly hospital volume did not affect the risk of BDI. Older age and male sex increased the risk of BDI, whereas intraoperative cholangiography was protective. There was a small to moderate long-term increase in the risk of BDI after the introduction of laparoscopic cholecystectomy compared with the pre-laparoscopic era.


Lycium barbarum polysaccharide improves traumatic cognition via reversing imbalance of apoptosis/regeneration in hippocampal neurons after stress.
Previous studies in our laboratory have demonstrated the increased neuronal apoptosis in the hippocampus and abnormal hippocampal morphology after severe stress, which directly correlates to the pathogenesis of post-traumatic stress disorder (PTSD). This study aims to investigate the effects of Lycium barbarum polysaccharide (LBP) on intrusive memory of posttraumatic stress in rats, and to analyze the mechanism of regeneration/apoptosis balance in the hippocampal neurons. The experimental rats received 20 inescapable electric foot shocks in an enclosed box for six times in three days. The rats were treated by intragastric administration of LBP (20mg/kg/day) for 3 days before stress in the stress plus prophylactic group, and for 28 days after stress in the stress plus therapeutic group. The emotion, intrusive memory-related behavior (freezing, open field, pain latency, spatial cognition), hippocampus cell morphology, and relation of neurogenesis and apoptosis in dental gyrus of the hippocampus were observed. The hippocampus volume was evaluated by stereology. Meanwhile, the neurogenesis and apoptosis were analyzed with 5-bromo-2'-deoxyuridine and terminal deoxylnucleotidyl transferase mediated-dUTP nick end labeling (TUNEL) method. The treatment of LBP in pre-stress and post-stress had obvious beneficial effect on the behaviors and neurogenesis. The stressed rats showed improvement of intrusive memory related cognition defect, alleviation of the apoptosis in the hippocampus and recovery for the neurogenesis, which was related to the hippocampus volume after LBP treatment. LBP treatment might effectively improve the traumatic cognition defect induced by severe stress and be useful for the intrusive memory-related cognition recovery.


Safety observations from the pilot phase of the randomized r-Hirudin for Improvement of Thrombolysis (HIT-III) study. A study of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte (ALKK)
Adjunctive therapy for thrombolysis in acute myocardial infarction consists of platelet inhibition with aspirin and thrombin inhibition with heparin. Thrombin inhibition may be improved by the use of hirudin as indicated by experimental and phase II clinical studies. The randomized, double-blind phase III r-Hirudin for Improvement of Thrombolysis study (HIT III) compared a recombinant hirudin (HBW 023) with heparin. The primary end point was the incidence of death or reinfarction. Seven thousand patients with acute myocardial infarction and a duration of symptoms of less than 6 hours were to be randomized to receive intravenous heparin (70 IU/kg body wt bolus and 15 IU.kg-1.h-1) or hirudin (0.4 mg/kg body wt bolus and 0.15 mg.kg-1.h-1) infused over 48 to 72 hours and adjusted to an activated partial thromboplastin time of 2 to 3.5 times baseline values. In a pilot phase, 1000 patients receiving front-loaded alteplase for thrombolysis were to be recruited by 93 German centers. After enrollment of 302 patients, the trial was stopped after an increased rate of intracranial bleeding was observed in the hirudin group (5 of 148, 3.4%) compared with the heparin group (0 of 154). The overall stroke rate was 3.4% in the hirudin group and 1.3% in the heparin group. Other major bleeding occurred in five versus three patients and ventricular rupture occurred in three versus one patient in the hirudin and heparin groups, respectively. There were 19 in-hospital deaths, with 13 of them from the hirudin group. Although the number of patients was too small for a definite benefit-risk assessment, at the dosage tested, hirudin in combination with front-loaded alteplase and aspirin may be associated with an increased rate of intracranial hemorrhage. Our findings are consistent with the observations of the GUSTO-II and TIMI-9 trials, where higher doses of another recombinant hirudin were used. Therefore, the therapeutic range of hirudin as an adjunct to thrombolysis may be smaller than previously thought, and reappraisal of dose finding should be considered.


Mechanisms of multistep carcinogenesis and carcinogen risk assessment.
Many different types of chemical exposures can increase the incidence of tumors in animals and humans, but usually a long period of time is required before the carcinogenic risk of an exposure is manifested. Both of these observations can be explained by a multistep/multigene model of carcinogenesis. In this model, a normal cell evolves into a cancer cell as the result of heritable changes in multiple, independent genes. The two-stage model of initiation and promotion for chemical carcinogenesis has provided a paradigm by which chemicals can act by qualitatively different mechanisms, but the process of carcinogenesis is now recognized as more complex than simply initiation and promotion. Even a three-stage model of initiation, promotion, and progression, which can be operationally defined, is not adequate to describe the carcinogenic process. The number of genes altered in a cancer cell compared to a normal cell is not known; recent evidence suggests that 3-10 genetic events are involved in common adult malignancies in humans. Two distinct classes of genes, protooncogenes and tumor-suppressor genes, are involved in the cancer process. Multiple oncogenes may be activated in a tumor, while multiple tumor-suppressor genes may be inactivated. Identification of the genes involved in carcinogenesis and elucidation of the mechanisms of their activation or inactivation allows a better understanding of how chemical carcinogens influence the process of neoplastic evolution. The findings of multiple genetic changes (including point mutations, chromosomal translocations, deletions, gene amplification, and numerical chromosome changes) in activated protooncogenes and inactivated tumor-suppressor genes provide experimental support for Boveri's somatic mutation theory of carcinogenesis. In addition to mutagenic mechanisms, chemicals may heritably alter cells by epigenetic mechanisms and enhance the clonal expansion of altered cells. Most chemical carcinogens operate via a combination of mechanisms, and even their primary mechanism of action may vary depending on the target tissues. The classification of chemicals by mechanism of action or by nongenotoxic or genotoxic activity has certain inherent difficulties because no classification of chemicals is exhaustive or definitive.


Pharmaceutical Cocrystals: New Solid Phase Modification Approaches for the Formulation of APIs.
Cocrystals can be used as an alternative approach based on crystal engineering to enhance specific physicochemical and biopharmaceutical properties of active pharmaceutical ingredients (APIs) when the approaches to salt or polymorph formation do not meet the expected targets. In this article, an overview of pharmaceutical cocrystals will be presented, with an emphasis on the intermolecular interactions in cocrystals and the methods for their preparation. Furthermore, cocrystals of direct pharmaceutical interest, along with their in vitro properties and available in vivo data and characterization techniques are discussed, highlighting the potential of cocrystals as an attractive route for drug development.


Quality of water in hemodialysis centers in Baghdad, Iraq.
Dialysis water quality is one of the important parameters all over the world because of its direct influence on the health of kidney patients. In Iraq, there are more than 20 dialysis centers; most of them contain identical units for the production of dialysis water. In this work, the quality of water used for dialysis in six dialysis centers located within Baghdad hospitals was evaluated. Samples of product water from each of the six dialysis centers were examined for total heterotrophic bacteria, endotoxin, and chemical contaminants. Endotoxin was measured on-site using a portable instrument. Bacteriological and chemical examinations were done in the laboratory after collecting samples from each dialysis center. The results showed a fluctuation in the produced water quality that makes the produced water unaccepted when compared with international standards. Bacterial counts for 60% of the analyzed samples were above the action level (50 colony-forming units[CFU]/mL), while five out of the six dialysis centers showed values higher than the maximum value (100 CFU/mL). Chemical analysis showed that the dialysis water quality suffers from elevated aluminum concentration for all dialysis centers. All hemodialysis centers need thorough monitoring and preventive maintenance to ensure good water quality. In addition, it is important to revise the design of the water treatment units according to the feed and product water quality.


Physiological effects of TGF(alpha)-PE40 expression in recombinant Escherichia coli JM109.
Physiological effects of isopropyl-thiogalactopyranoside (IPTG) induction were examined in Escherichia coli strain JM109 expressing a fusion protein composed of transforming growth factor alpha and a 40-kD portion of Pseudomonas aeruginosa exotoxin A (TGF(alpha)-PE40) under control of the tac promoter. Fermentations at the 15-L scale in complex medium compared growth and metabolite profiles of the untransformed JM109 host strain, the strain transformed with the vector lacking the TGF(alpha)-PE40 open reading frame (JM109[pKK2.7]), and the strain with the complete plasmid for TGF(alpha)-PE40 expression (JM109[pTAC-TGF57-PE40]). Metabolite and growth profiles of JM109 (pTAC-TGF57-PE40) cultures changed significantly in IPTG-induced versus uninduced cultures. Prior to induction, glucose was metabolized to acetate or completely oxidized to CO(2). Following induction, pyruvate was also excreted in addition to acetate. In the absence of inducer, pyruvate was excreted by JM109 (pTAC-TGF57-PE40) only when dissolved oxygen levels fell to less than 10% of saturation (microaerobic rather than anaerobic conditions). The untransformed JM109 host strain or JM109 (pKK2.7) did not excrete pyruvate in the presence or absence of inducer, although JM109 (pKK2.7) exhibited a pattern of growth following addition of IPTG that closely resembled JM109 (pTAC-TFG57-PE40). Fermentations of JM109 (pTAC-TFG57-PE40) in a synthetic medium supported lower expression levels, but resulted in similar alterations in metabolite profiles. Induction in synthetic medium resulted in pyruvate excretion without further acetate accumulation. Taken together, these data suggest that one consequence of TGF(alpha)-PE40 expression in JM109 is altered patterns of pyruvate oxidation.


[Preparation and characterization of specific monoclonal antibodies against hexon of HAdV 3].
To obtain the monoclonal antibody against hexon protein of human adenovirus. BALB/c mice were immunized with purified recombinant hexon protein, and the spleen cells of the mice were isolated and fused with myloma cells. Four hybridoma cell strains were screened by indirect ELISA and cultured, and the sensitivity, specificity and virus neutralizing activity were analyzed with ELISA, Western blotting and neutralizing test. The mouse ascites produced by these hybridoma cells contained specific monoclonal antibodies against hexon protein of human adenovirus as identified by ELISA and Western blot, and the antibody generated by 4C6 strain showed human adenovirus type 3-neutralizing activity. The monoclonal antibodies against hexon protein with high specificity have been successfully obtained, and these antibodies can be useful in developing assays for early diagnosis of HAdV3 infection and also in study of therapeutic drugs of the infection.


Cerebral Blood Flow Measured by Phase-Contrast Magnetic Resonance Angiography in Preterm and Term Neonates.
Preterm infants show a decreased tortuosity in all proximal segments of the cerebral vasculature at term-equivalent age (TEA). Recently MRI techniques were developed to measure cerebral blood flow (CBF) based on phase-contrast images. We hypothesized that arterial CBF corrected for brain size differs between full-term and preterm infants at TEA. 344 infants without major brain abnormalities had a cranial MRI for clinical reasons including phase-contrast magnetic resonance angiography (PC-MRA) around TEA (mean 41.1 ± SD 1.2 weeks). This cohort consisted of 172 preterm infants (gestational age at birth 24.1-31.9 weeks) and 172 term-born infants (gestational age at birth 37.0-42.6 weeks). The total CBF in milliliters/minute was calculated by adding the blood flow of the carotid and basilar arteries, and compared to age at scan, body weight, and several parameters of estimated brain size. After logarithmic transformation, total CBF was associated with body weight, estimated brain weight, head circumference, and 2D brain surface measurements at TEA. Total CBF was significantly (9-12%) higher in term compared to preterm infants after correction for 2D brain surface measurements, head circumference or postmenstrual age at MRI (p < 0.05). Total CBF as measured by PC-MRA was associated with body and (estimated) brain weight and 2D brain surface measurements and was higher in term compared to preterm born infants.


1-Propanol probing methodology: two-dimensional characterization of the effect of solute on H2O.
The wording "hydrophobicity/hydrophilicity" has been used in a loose manner based on human experiences. We have devised a more quantitative way to redefine "hydrophobes" and "hydrophiles" in terms of the mole fraction dependence pattern of one of the third derivative quantities, the enthalpic interaction between solute molecules. We then devised a thermodynamic methodology to characterize the effect of a solute on H2O in terms of its hydrophobicity and/or hydrophilicity. We use a thermodynamic signature, the enthalpic interaction of 1-propanol, H, to monitor how the test solute modifies H2O. By this method, characterization is facilitated by two indices; one pertaining to its hydrophobicity and the other its hydrophilicity. Hence differences among amphiphiles are quantified in a two-dimensional manner. Furthermore, an individual ion can be characterized independent of a counter ion. By using this methodology, we have studied the effects on H2O of a number of solutes, and gained some important new insights. For example, such commonly used examples of hydrophobes in the literature as tetramethyl urea, trimethylamine-N-oxide, and tetramethylammonium salts are in fact surprisingly hydrophilic. Hence the conclusions about "hydrophobes" using these samples ought to be interpreted with caution. The effects of anions on H2O found by this methodology are in the same sequence of the Hofmeister ranking, which will no doubt aid a further investigation into this enigma in biochemistry. Thus, it is likely that this methodology could play an important role in the characterization of the effects of solutes in H2O, and a perspective view may be useful. Here, we describe the basis on which the methodology is developed and the methodology itself in m.ore detail than given in individual papers. We then summarize the results in two dimensional hydrophobicity/hydrophilicity maps.


A novel self-sensing technique for tapping-mode atomic force microscopy.
This work proposes a novel self-sensing tapping-mode atomic force microscopy operation utilizing charge measurement. A microcantilever coated with a single piezoelectric layer is simultaneously used for actuation and deflection sensing. The cantilever can be batch fabricated with existing micro electro mechanical system processes. The setup enables the omission of the optical beam deflection technique which is commonly used to measure the cantilever oscillation amplitude. Due to the high amount of capacitive feedthrough in the measured charge signal, a feedforward control technique is employed to increase the dynamic range from less than 1 dB to approximately 35 dB. Experiments show that the conditioned charge signal achieves excellent signal-to-noise ratio and can therefore be used as a feedback signal for atomic force microscopy imaging.


Prognostic value of heart rate variability in post-infarction patients.
Depressed heart rate variability (HRV) indicating autonomic disequilibrium and propensity to ventricular ectopy can be useful for risk stratification in patients following acute myocardial infarction (AIM). The aim of the study was to assess heart rate variability as a predictor of all-cause mortality in post-infarction patients. We analyzed the 24-hour electrocardiographic (ECG) recordings of 100 patients (80 males) during hospitalization for The mean age of patients was 56.99 + 11.03 years. Time domain heart rate variability analysis was obtained from 8 to 13 days after index infarction by mean of a 24-hour ECG recording, and the calculated parameters were: standard deviation of all normal to normal RR intervals (SDNN), RRmax-RRmin (difference between the longest RR interval and the shortest RR interval), mean RR interval. We also analyzed ventricular premature complexes from the ECG data. The patients underwent clinical evaluation, laboratory tests and echocardiography. Within a one-year follow-up period 11 patients experienced death, 10 of them because of cardiac reason and one because of stroke. There were significantly lower values of SDNN (60.55 ± 12.84 ms vs 98.38 ± 28.21 ms), RRmax-RRmin (454.36 ± 111.00 ms vs 600.99 ± 168.72 ms) and mean RR interval (695.82 ± 65.87 ms vs 840.07 ± 93.97 ms) in deceased patients than in the survivors, respectively (p < 0.01). The deceased patients were of higher mean age, with lower left ventricular ejection fraction (0.46 ± 0.05 vs 0.56 ± 0.06 in survivors), and more frequent clinical signs of heart failure and ventricular ectopic activity (> 10VPCs/h; p < 0.01). Multivariate Cox analysis showed that SDNN was a significant, independent predictor of all-cause mortality in post-infarction patients. The other independent predictors were clinical signs of heart failure--Killip class II and III and ventricular ectopic activity. Depressed HRV is an independent predictor of mortality in post-infarction patients and may provide useful additional prognostic information in non-invasive risk stratification of these patients.


Proteomic analysis of hair shafts from monozygotic twins: Expression profiles and genetically variant peptides.
Forensic association of hair shaft evidence with individuals is currently assessed by comparing mitochondrial DNA haplotypes of reference and casework samples, primarily for exclusionary purposes. Present work tests and validates more recent proteomic approaches to extract quantitative transcriptional and genetic information from hair samples of monozygotic twin pairs, which would be predicted to partition away from unrelated individuals if the datasets contain identifying information. Protein expression profiles and polymorphic, genetically variant hair peptides were generated from ten pairs of monozygotic twins. Profiling using the protein tryptic digests revealed that samples from identical twins had typically an order of magnitude fewer protein expression differences than unrelated individuals. The data did not indicate that the degree of difference within twin pairs increased with age. In parallel, data from the digests were used to detect genetically variant peptides that result from common nonsynonymous single nucleotide polymorphisms in genes expressed in the hair follicle. Compilation of the variants permitted sorting of the samples by hierarchical clustering, permitting accurate matching of twin pairs. The results demonstrate that genetic differences are detectable by proteomic methods and provide a framework for developing quantitative statistical estimates of personal identification that increase the value of hair shaft evidence.


Photosynthetic pigment-protein complexes as highly connected networks: implications for robust energy transport.
Photosynthetic pigment-protein complexes (PPCs) are a vital component of the light-harvesting machinery of all plants and photosynthesizing bacteria, enabling efficient transport of the energy of absorbed light towards the reaction centre, where chemical energy storage is initiated. PPCs comprise a set of chromophore molecules, typically bacteriochlorophyll species, held in a well-defined arrangement by a protein scaffold; this relatively rigid distribution leads to a viewpoint in which the chromophore subsystem is treated as a network, where chromophores represent vertices and inter-chromophore electronic couplings represent edges. This graph-based view can then be used as a framework within which to interrogate the role of structural and electronic organization in PPCs. Here, we use this network-based viewpoint to compare excitation energy transfer (EET) dynamics in the light-harvesting complex II (LHC-II) system commonly found in higher plants and the Fenna-Matthews-Olson (FMO) complex found in green sulfur bacteria. The results of our simple network-based investigations clearly demonstrate the role of network connectivity and multiple EET pathways on the efficient and robust EET dynamics in these PPCs, and highlight a role for such considerations in the development of new artificial light-harvesting systems.


Profiling of Campylobacter jejuni Proteome in Exponential and Stationary Phase of Growth.
Campylobacter jejuni has been reported as a major cause of bacterial food-borne enteritides in developed countries during the last decade. Despite its fastidious growth requirements, including low level of oxygen and high level of CO2, this pathogen is able to persist in the environment without permanent loss of its viability and virulence. As C. jejuni is not able to multiply outside a host, the cells spend significant amount of time in stationary phase of growth. The entry into the stationary phase is often correlated to resistance to various stresses in bacteria. The switching between exponential and stationary phases is frequently mediated by the regulator sigma S (RpoS). However, this factor is absent in C. jejuni and molecular mechanisms responsible for transition of cells to the stationary phase remain elusive. In this work, proteomic profiles of cells from exponential and stationary phases were compared using 2-D electrophoresis (2DE) fingerprinting combined with mass spectrometry analysis and qRT-PCR. The identified proteins, whose expression differed between the two phases, are mostly involved in protein biosynthesis, carbon metabolism, stress response and motility. Altered expression was observed also in the pleiotropic regulator CosR that was over-expressed during stationary phase. A shift between transcript and protein level evolution of CosR throughout the growth of C. jejuni was observed using qRT-PCR and (2DE). From these data, we hypothesized that CosR could undergo a negative autoregulation in stationary phase. A consensus sequence resulting from promoter sequence alignment of genes potentially regulated by CosR, including its own upstream region, among C. jejuni strains is proposed. To verify experimentally the potential autoregulation of CosR at the DNA level, electrophoretic mobility shift assay was performed with DNA fragments of CosR promoter region and rCosR. Different migration pattern of the promoter fragments indicates the binding capacity of CosR, suggesting its auto-regulation potential.


The Role of Microglia in Retinal Neurodegeneration: Alzheimer's Disease, Parkinson, and Glaucoma.
Microglia, the immunocompetent cells of the central nervous system (CNS), act as neuropathology sensors and are neuroprotective under physiological conditions. Microglia react to injury and degeneration with immune-phenotypic and morphological changes, proliferation, migration, and inflammatory cytokine production. An uncontrolled microglial response secondary to sustained CNS damage can put neuronal survival at risk due to excessive inflammation. A neuroinflammatory response is considered among the etiological factors of the major aged-related neurodegenerative diseases of the CNS, and microglial cells are key players in these neurodegenerative lesions. The retina is an extension of the brain and therefore the inflammatory response in the brain can occur in the retina. The brain and retina are affected in several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and glaucoma. AD is an age-related neurodegeneration of the CNS characterized by neuronal and synaptic loss in the cerebral cortex, resulting in cognitive deficit and dementia. The extracellular deposits of beta-amyloid (Aβ) and intraneuronal accumulations of hyperphosphorylated tau protein (pTau) are the hallmarks of this disease. These deposits are also found in the retina and optic nerve. PD is a neurodegenerative locomotor disorder with the progressive loss of dopaminergic neurons in the substantia nigra. This is accompanied by Lewy body inclusion composed of α-synuclein (α-syn) aggregates. PD also involves retinal dopaminergic cell degeneration. Glaucoma is a multifactorial neurodegenerative disease of the optic nerve, characterized by retinal ganglion cell loss. In this pathology, deposition of Aβ, synuclein, and pTau has also been detected in retina. These neurodegenerative diseases share a common pathogenic mechanism, the neuroinflammation, in which microglia play an important role. Microglial activation has been reported in AD, PD, and glaucoma in relation to protein aggregates and degenerated neurons. The activated microglia can release pro-inflammatory cytokines which can aggravate and propagate neuroinflammation, thereby degenerating neurons and impairing brain as well as retinal function. The aim of the present review is to describe the contribution in retina to microglial-mediated neuroinflammation in AD, PD, and glaucomatous neurodegeneration.


Effects of simulated digests of Biota orientalis and a dietary nutraceutical on interleukin-1- induced inflammatory responses in cartilage explants.
To test the hypothesis that simulated digests of Biota orientalis (BO) and a dietary nutraceutical (DN; composed of mussel, shark cartilage, abalone, and BO seed lipid extract) inhibit prostaglandin E2 (PGE2), nitric oxide (NO), and glycosaminoglycan (GAG) production in interleukin (IL)-1-stimulated cartilage explants. Cartilage tissue from 12 pigs. Articular cartilage explants were conditioned with a simulated digest of BO (BOsim) or DN (DNsim) at concentrations of 0, 0.06, or 0.18 mg/mL or indomethacin (INDOsim; 0 or 0.02 mg/mL) for 72 hours. Control explants received digest vehicle only. Explants were or were not stimulated with recombinant human-IL-1beta (10 or 0 ng/mL) during the final 48 hours of culture. Concentrations of PGE2, GAG, and NO in media samples (mPGE2,mGAG, and mNO concentrations, respectively) were analyzed, and explant tissue was stained fluorochromatically to determine chondrocyte viability. Treatment effects during the final 48-hour culture period were analyzed. IL-1 increased mPGE2, mGAG, and mNO concentrations in control explants without adversely affecting cell viability. Treatment with INDOsim blocked PGE2 production and increased mNO concentration in IL-1-stimulated and unstimulated explants and increased mGAG concentration in unstimulated explants. Treatment with DNsim (0.06 and 0.18 mg/mL) reduced mPGE2 concentration in IL-1-stimulated and unstimulated explants, reduced mNO concentration in IL-1-stimulated explants, and increased mNO concentration in unstimulated explants. Treatment with 0.18 mg of DNsim/mL increased cell viability in the presence of IL-1. In IL-1-stimulated explants, BOsim (0.06 and 0.18 mg/mL) reduced mPGE2 concentration, but 0.18 mg of BOsim/mL increased cell viability. Effects of IL-1 on cartilage explants in vitro were modulated by DNsim and BOsim.


Enhancement of synthetic Trichoderma-based enzyme mixtures for biomass conversion with an alternative family 5 glycosyl hydrolase from Sporotrichum thermophile.
Enzymatic conversion of lignocellulosic materials to fermentable sugars is a limiting step in the production of biofuels from biomass. We show here that combining enzymes from different microbial sources is one way to identify superior enzymes. Extracts of the thermophilic fungus Sporotrichum thermophile (synonym Myceliophthora thermophila) gave synergistic release of glucose (Glc) and xylose (Xyl) from pretreated corn stover when combined with an 8-component synthetic cocktail of enzymes from Trichoderma reesei. The S. thermophile extracts were fractionated and an enhancing factor identified as endo-β1,4-glucanase (StCel5A or EG2) of subfamily 5 of Glycosyl Hydrolase family 5 (GH5_5). In multi-component optimization experiments using a standard set of enzymes and either StCel5A or the ortholog from T. reesei (TrCel5A), reactions containing StCel5A yielded more Glc and Xyl. In a five-component optimization experiment (i.e., varying four core enzymes and the source of Cel5A), the optimal proportions for TrCel5A vs. StCel5A were similar for Glc yields, but markedly different for Xyl yields. Both enzymes were active on lichenan, glucomannan, and oat β-glucan; however, StCel5A but not TrCel5A was also active on β1,4-mannan, two types of galactomannan, and β1,4-xylan. Phylogenetically, fungal enzymes in GH5_5 sorted into two clades, with StCel5A and TrCel5A belonging to different clades. Structural differences with the potential to account for the differences in performance were deduced based on the known structure of TrCel5A and a homology-based model of StCel5A, including a loop near the active site of TrCel5A and the presence of four additional Trp residues in the active cleft of StCel5A. The results indicate that superior biomass-degrading enzymes can be identified by exploring taxonomic diversity combined with assays in the context of realistic enzyme combinations and realistic substrates. Substrate range may be a key factor contributing to superior performance within GH5_5.


Image analysis techniques for automatic evaluation of two-dimensional electrophoresis.
Techniques for automatic analysis of two-dimensional electrophoresis gels by computer-aided image analysis are described. Original gels or photographic films are scanned using a laser scanner and the files are transferred to a microcomputer. The program package first performs a compression and preevaluation of the files. Spot identification and quantification is performed by the chain code algorithm after appropriate zooming and cutting. Labeling facilitates spot identification and quantification in numerical and graphical (pseudocolor) representation on peripheral devices for camera ready output. Interpolation between measured basepoints is performed by cubic spline algorithms which are automatically switched on and off, depending on the need by the program. High speed analysis and graphic representation is achieved using fast Assembler language routines rather than high level languages. One-dimensional gels can be analyzed using the same software. Spot matching between parallel two-dimensional gels has not yet been implemented.


Comparison of Two Different Doses of Nalbuphine With Isobaric Ropivacaine in Patients Undergoing Lower Segment Cesarean Section Under Subarachnoid Block: A Randomized Controlled Trial.
Obstetric analgesia and anesthesia is a challenge in itself. It requires an understanding of the physiological changes during pregnancy and labor and the effect of anesthetic agents on the fetus and newborn. Because neuraxial techniques provide superior analgesia and materno-fetal benefits, their use have increased significantly over the past three decades or so. A combination of local anesthetics like ropivacaine with opioids like nalbuphine has been shown to have additive beneficial effects in subarachnoid block (SAB) in lower segment cesarean section (LSCS). However, the optimal dose combination of ropivacaine and nalbuphine to maximize their benefits and minimize side effects remains to be established. Our study has compared the clinical efficacy and safety of 0.75% isobaric ropivacaine (15 mg) with two different doses of nalbuphine (0.4 mg and 0.6 mg) when given intrathecally for LSCS in terms of quality of sensory and motor blocks, hemodynamic parameters, duration of effective analgesia, Apgar score in newborn, and associated side effects. In this prospective, randomized, double-blind study, a total of 69 parturients between the age of 20-45 years, belonging to American Society of Anesthesiologists (ASA) grade I and II, undergoing cesarean section under SAB were evaluated. Patients were randomly allocated into three groups of 23 each by using the draw-of-lots technique. The patient and the observer were kept blinded as to which dose of drug (intrathecal) was being given to the patient. Patients in Group A received 0.75% isobaric ropivacaine 15 mg (2 ml) + 0.3 ml normal saline; patients in Group B received 0.75% isobaric ropivacaine 15 mg (2 ml) + 0.4 mg of nalbuphine (0.2 ml) + 0.1 ml normal saline; patients in Group C received 0.75% isobaric ropivacaine 15 mg (2 ml) + 0.6 mg of nalbuphine (0.3 ml). The total volume of drug solution in all three groups was 2.3 ml. We found that the time to onset of sensory block was shortest in Group A (5.87±1.290 minutes) followed by Group C (6.00±1.087 minutes) and Group B (6.17±1.696 minutes); time to two-segment regression of sensory block was longest in Group C (101.74±8.996 minutes) followed by Group B (85.87±15.348 minutes) and Group A (65.00±7.071 minutes); duration of effective analgesia was longest in Group C (206.09±18.766 minutes) followed by Group B (183.91±15.880 minutes) and Group A (121.74±11.833 minutes); and time from SAB to complete regression of motor block was longest in Group C (216.52±15.553 minutes) followed by Group B (203.48±20.138 minutes) and Group A (174.78±14.731 minutes). Side effects were comparable among all three groups. The optimal dose combination in SAB for cesarean section was 15 mg of 0.75% isobaric ropivacaine + 0.6 mg nalbuphine, with minimal side effects.


SMO-CRISPR-mediated apoptosis in CD133-targeted cancer stem cells and tumor growth inhibition.
Cancer stem cells (CSCs) possess the ability to indefinitely proliferate and resist therapy, leading to cancer relapse and metastasis. To address this, we aimed to develop a CSC-inclusive therapy that targets both CSCs and non-CSC glioblastoma (GBM) cells. We accomplished this by using a smoothened (SMO) CRISPR/Cas9 plasmid to suppress the hedgehog pathway in CSCs, in combination with inhibiting the serine hydroxymethyl transferase 1 (SHMT1)-driven thymidylate biosynthesis pathway in non-CSC GBM cells using SHMT1 siRNA (siSHMT1). We targeted CSCs using a CD133 peptide attached to an osmotically active vitamin B6-coupled polydixylitol vector (VPX-CD133) by a photoactivatable heterobifunctional linker. VPX-CD133 nanocomplexes in comparison to VPX complexes remarkably targeted and transfected CSCs both in vitro and in subcutaneous tumor. The VPX-CD133-mediated targeted delivery of SMO CRISPR in CSCs led to SMO suppression that negatively affected its growth. Next, we performed comprehensive therapy in xenograft mice using VPX-CD133, which delivered SMO-CRISPR to CSCs, and VPX, which delivered siSHMT1 to non-CSC GBM cells. The combined treatment induced apoptosis in a large number of cells, reduced tumor volume by up to 81%, and improved the health of treated mice significantly. By eliminating CSCs together with the non-CSC GBM cells, the combined study paves the way for developing CSC-inclusive therapies for GBM.


[Genetic differentiation and phylogenetic relationships among Palearctic mice (Rodentia, Muridae)].
Genetic differentiation of 18 Palearctic mouse species (genera Sylvaemus, Mus, Apodemus, Micromys, and Rattus) with respect to 31 biochemical loci was estimated to define the taxonomic status of these genera. On the basis of genetic data, two independent centers of origin of species belonging to the family Muridae were identified. The first is the Indo-African center, from which the modern Sylvaemus species and Palearctic representatives of Mus originated in the Pleistocene (1.0-2.0 million years ago). Genera Micromys and Apodemus, which diverged in early Pliocene (about 7 million years ago), trace their origin to the same center. From the second center, located in Southeast Asia, Rattus species radiated. The genetic divergence of taxa issuing from these two centers attains the level characteristic of differentiation between families and dates back to the late Miocene (over 10 million years ago). Species were compared pairwise to determine the percent of fixed gene differences (Pfd) between them. Analysis of Pfd distribution confirmed distinct periodicity of speciation in mice and revealed two speciation peaks. The first, at the level of genera, occurred in the Pliocene, and the second, at the species level, in the Pleistocene.


Diabetes mellitus is a recurrence-independent risk factor in patients with hepatitis B virus-related hepatocellular carcinoma undergoing resection.
The prognostic impact of diabetes mellitus and its association with virological factors on patients with hepatocellular carcinoma (HCC) are unclear. This study aimed to investigate the outcome in HCC patients undergoing resection with and without diabetes mellitus and the interaction with hepatitis B virus (HBV) and hepatitis C virus (HCV). A total of 239 HCC patients were included. Survival and tumour recurrence were analysed according to the status of diabetes mellitus and viral hepatitis. Diabetic patients tended to have an overall decreased survival compared with non-diabetic patients in 32 +/- 19 months of follow-up. A total of 113 (47%) patients developed tumour recurrence during the follow-up period. No significant difference of tumour recurrence between diabetic and non-diabetic patients, or between patients seropositive and seronegative for HBV surface antigen (HBsAg), was noted. Stratified analysis showed that diabetic patients with HBV but not with HCV infection had a poor long-term outcome. In the HBV group, the one-, three- and five-year survival rates were 83%, 51% and 41% versus 90%, 78% and 73% in diabetic and non-diabetic patients, respectively, compared with 90%, 83% and 42% versus 91%, 73% and 73% in the HCV group with and without diabetes mellitus, respectively. Cox multivariate analysis disclosed that diabetic patients seropositive for HBsAg had a significantly poor survival. Diabetes mellitus does not affect the long-term survival in HCV-related HCC but is a recurrence-independent poor prognostic factor for HBV-related HCC.


A new structural transition of serum albumin dependent on the state of Cys34. Detection by 1H-NMR spectroscopy.
1. Reactions of fatty-acid-free bovine serum albumin and recombinant human albumin with a range of antiarthritic gold(I) complexes [auranofin, deacetylated auranofin, triethylphosphinegold(I) chloride] and related thiols (thioglucose, tetraacetylthioglucose, glutathione, dithiothreitol) have been investigated using 1H-NMR spectroscopy. 2. In reactions of albumin with auranofin, tetraacetylthioglucose and dithiothreitol, release of cystine was detected, whereas for deacetylated auranofin, thioglucose and glutathione, mixed disulphides with cysteine were produced. It has been previously proposed that Cys34 of human and bovine serum albumins is partly blocked by disulphide formation with cysteine and glutathione. The above reactions lead to deblocking by thiol-disulphide interchange reactions. No release of glutathione from albumin was detected. 3. Changes in the His H epsilon 1 regions of the 1H-NMR spectra show that albumin exists in two structural forms dependent on whether the side-chain of Cys34 is a free thiolate, or blocked by gold(I)triethylphosphine, by disulphide formation with cysteine or by another form of oxidation. We propose that Cys34 is either in a buried or in an exposed environment; the possible molecular basis of the structural change is discussed. 4. The relationship between reactions at Cys34, cysteine release, and the observed structural transition are discussed in terms of chrysotherapy, albumin metabolism and the use of gold(I) as a heavy atom derivative in X-ray crystallographic studies of albumins.


H pylori status and angiogenesis factors in human gastric carcinoma.
To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density (MVD), thymidine phosphorylase (TP), vascular endothelial growth factor receptor-1 (VEGF-R1), p53 and circulating VEGF levels. Angiogenic markers were analyzed immunohistochemically in 56 primary gastric cancers. H pylori cytotoxin (vacA) and the cytotoxin-associated gene (cagA) amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELISA, respectively. A total of 69% of patients were positive for circulating IgG antibodies against H pylori. cagA-positive H pylori strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was significantly associated with cagA (P = 0.0001). MVD was significantly correlated with both tumor VEGF expression (r = 0.361, P = 0.009) and serum VEGF levels (r = -0.347, P = 0.041). Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level (P = 0.026). H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic characteristics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical disease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent.


Quantitative Analysis of Synthetic Cell Lineage Tracing Using Nuclease Barcoding.
Lineage tracing by the determination and mapping of progeny arising from single cells is an important approach enabling the elucidation of mechanisms underlying diverse biological processes ranging from development to disease. We developed a dynamic sequence-based barcode system for synthetic lineage tracing and have demonstrated its performance in C. elegans, a model organism whose lineage tree is well established. The strategy we use creates lineage trees based upon the introduction of synthetically controlled mutations into cells and the propagation of these mutations to daughter cells at each cell division. We analyzed this experimental proof of concept along with a corresponding simulation and analytical model to gain a deeper understanding of the coding capacity of the system. Our results provide specific bounds on the fidelity of lineage tracing using such approaches.


Jail administrators' perceptions of the use of psychiatric advance directives in jails.
Individuals with serious mental illnesses are at high risk of incarceration. Jails are often unable to obtain information needed to provide appropriate care. Psychiatric advance directives may be useful tools to communicate treatment information to jails. This study explored their use as a novel intervention for individuals with mental illnesses in jails. Eighty jail administrators in North Carolina were surveyed to determine their support for psychiatric advance directives in jails. Relationships between respondents' job type (jail administrator or medical administrator) or jail census and support for the directives were examined by using chi square tests. Open-ended responses were analyzed using qualitative methods. Seventy-three percent of respondents indicated they supported psychiatric advance directives. Respondents from jails at or below a median census of 120 were significantly more likely to support psychiatric advance directives than those from larger jails. Psychiatric advance directives' informational function may prove valuable in jail settings. Additional research assessing directives as interventions for individuals with mental illnesses at risk of incarceration is needed.


Alliance Between Therapist and Multi-stressed Families During the COVID-19 Pandemic: The Effect of Family-Based Videoconferencing.
A strong therapeutic alliance or working relationship is essential for effective face-to-face family-based psychotherapy. However, little is known about the use of VC on alliance in family-based therapy. The recent COVID-19 pandemic led to a national lockdown during which most family-based therapy transferred to VC. The current study analyzed the development and strength of alliance prior and during lockdown for multi-stressed families participating in Multisystemic Therapy (MST). Alliance with the therapist was reported monthly by 846 caregivers (81% female). Using latent growth curve models (longitudinal approach), the development of alliance was estimated for families participating in MST prior to the lockdown, transferring to VC early in treatment or late in treatment. Using regression analyses (cross-sectional approach), lockdown (yes/no) was included as predictor of alliance. In these analyses, type of family (regular; intellectual disability; concerns regarding child abuse or neglect) and gender of caregiver were included as moderators. Both analytical approaches showed that alliance was not affected by VC, except for families with concerns of child abuse, who reported lower alliances during lockdown. However, these results where no longer significant when controlling for multiple testing. Strong alliances can be developed and maintained during family-based VC sessions with multi-stressed families. However, for some subgroups, such as families with concerns of child abuse, VC might not be suitable or sufficient. Future research needs to investigate the potential and limitations of using VC with families.


Transport properties of merodiploids covering the dagA locus in Escherichia coli K-12.
A membrane componenet of the dag transport system which serves for glycine, D-alanine, and D-serine is coded for by the dagA gene at minute 83 of the Escherichia coli chromosome. Merodiploid strains (dagA+/dagA+) show two to three times the transport activity for only those amino acids that are substrates of the dag transport system. The increased transport activity is a result of a two-to threefold increase in Vmax for amino acid uptake with little or no change in the Km value. The two- to threefold gene dose effect of the merodiploid strains is maintained even during carbon starvation, eliminating the possibility that a greater energy supply for transport activity may account for the effect. Since merodiploids which carry more than one copy of the dagA allele show a gene dose response for transport activity, we conclude that the membrane componenet of the dag transport system which is coded for by the dagA allele is present in limiting amounts.


[Effects of rosiglitazone on inflammatory reaction and insulin resistance in obese patients with newly diagnosed type 2 diabetes].
To study the effect of rosiglitazone on serum high-sensitivity C-reactive protein (hs-CRP), interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor-alpha (TNF-alpha) and insulin resistance in obese patients with newly diagnosed type 2 diabetes. This study involved 118 patients with newly diagnosed type 2 diabetes and obesity, who were randomly assigned into two groups for a 12-week treatment with rosiglitazone (4 mg/day, group A) or sulfonylureas (group B). Serum hs-CRP, IL-1beta, IL-6, TNF-alpha, fasting plasma glucose (FPG) and fasting insulin (FINS) were measured before and after the treatment. Insulin resistance index was calculated according to the HOMA Model. In group A, rosiglitazone treatment resulted in significantly reduced serum hs-CRP, IL-1beta, IL-6, TNF-alpha, FPG and insulin resistance index (P<0.01). No difference in FPG was found between the two groups after the treatment (P>0.05), but serum hs-CRP, IL-1beta, IL-6, TNF-alpha and insulin resistance index were significantly lower in group A than in group B (P<0.05). Rosiglitazone can decrease FPG, reduce the inflammation reaction and improve insulin resistance in obese patients with type 2 diabetes.


Possible mechanism for medial smooth muscle cell injury in diabetic nephropathy: glycoxidation-mediated local complement activation.
Although recent studies have emphasized the pathogenic role of intrarenal muscular arteries in patients with diabetic nephropathy, notice has not been taken of their pathological characteristics. We focused on medial smooth muscle cell (SMC) injury and the involvement of glycoxidation and complement activation. Renal samples were obtained at autopsy from patients with diabetes mellitus (DM), patients with hypertension without renal involvement (n = 9), patients with benign nephrosclerosis (n = 7), and age-matched control subjects (n = 12). Patients with DM had glomerulosclerosis classified as severe (n = 9; DM-sev), moderate (n = 11; DM-mod), and minimal (n = 7). Renal samples were immunohistochemically determined. Activation of plasma complement from healthy subjects using advanced glycation end products (AGEs) also was performed. A marked SMC loss was noted in the media of patients with DM-sev and DM-mod. A membrane attack complex (MAC) observed in the area with SMC loss correlated well with the loss. Considerable carboxymethyllysine (CML), an oxidatively modified AGE, was deposited in the area with SMC loss in patients with DM-mod and DM-sev. Degrees of MAC deposition, SMC loss, and CML deposition were greater in the DM-sev group than the non-DM groups. Another oxidative product, acrolein, colocalized with CML. Plasma complements were not activated by AGE-modified bovine serum albumin in our in vitro assays, which included a complement hemolytic activity assay and determination of complement fragments, including C4d, C3bB, iC3b, and MAC. It is strongly suggested that medial SMC injury in intrarenal arteries is caused by interaction between glycoxidation and complement activation and contributes to the progression of diabetic nephropathy.


A new genus and five new species of Anostostomatidae from the Lesser Antilles (Orthoptera: Ensifera).
Most high volcanic islands of Lesser Antilles harbor one single genus of Anostostomatidae: Rhumosa n. gen: Rhumosa bolognei n. gen. n. sp. in Guadeloupe, Rhumosa macoucheriei n. gen. n. sp. in Dominica, Rhumosa depazei n. gen. n. sp. in Martinique, Rhumosa admiralrodneyei n. gen. n. sp. in Saint Lucia, Rhumosa captainblighei n. gen. n. sp., in Saint Vincent. These species are restricted to well preserved rainforests; species from northern islands apparently occurring at higher elevation than species of southern islands. The distribution and generic position of Rhumosa n. gen. species is discussed, as well as the generic position of Lutosa cubaensis (Haan, 1843).


Method for controlling boundary condition effects on the measurement of acoustic properties of small samples in tubes.
As standard ASTM E2611 reveals, the normal incidence sound transmission loss measured on a small sample in an acoustic tube is not only a property of the material but also strongly dependent on boundary conditions (generally unknown) and on the way the material is mounted. This article proposes an experimental method to control the effects of the lateral boundary conditions in an acoustic tube. The main objective is to deduce the properties of a "client element" (material sample) from the measured global acoustic properties of a patchwork composed by the "client material" and a known "host support." Three patchwork configurations have to be distinguished: patchworks with and without an impervious and rigid interface between the elements and patchworks composed by elements that cannot be identified as equivalent fluids. For each of these configurations, the use of a specific method based on the Mixing Rule Method (MRM) or on the Parallel Transfer Matrix Methods (P-TMM or dP-TMM) used in reverse way is proposed. Numerical and experimental validations are proposed in acoustic tubes on a convenient configuration: a material sample surrounded by an air ring. This configuration allows reducing the material elastic-frame behavior to leave a limp-frame behavior. The proposed methods allow removing the effect of the lateral air ring host surrounding the material. For homogeneous materials, the two methods based on MRM and dP-TMM give similar good results. For non-homogeneous materials or for materials that cannot be modeled as equivalent fluids, only the method based on dP-TMM gives good results.


The effects of necrotic enteritis, aflatoxin B1, and virginiamycin on growth performance, necrotic enteritis lesion scores, and mortality in young broilers.
The effects of increasing aflatoxin B1 concentration (0, 0.75, 1.5 mg/kg) on broilers with or without necrotic enteritis or virginiamycin were determined. In the 23-d study, 22 male Cobb 500 chicks per pen were allotted to 12 treatments (3 × 2 × 2 factorial arrangement) with 8 replications. Intestines of 5 birds per pen were examined for lesions on d 21. Birds were allowed to consume feed and water ad libitum. Aflatoxin was included in the diets from d 0. All birds received a 10× dose of coccidiosis vaccine on d 10. Pens of birds where necrotic enteritis was being induced were on Clostridium perfringens pathogen (CPP) contaminated litter from d 0. Aflatoxin decreased gain and feed intake and resulted in poorer feed:gain, increased mortality, and higher lesion scores. Inducing necrotic enteritis increased lesion scores and decreased feed intake and gain. Adding virginiamycin to the diets improved gain, feed intake, feed conversion, and decreased mortality. There was a 3-way interaction (aflatoxin × virginiamycin × CPP) on gain; increasing aflatoxin decreased gain and the effects of CPP and virginiamycin were dependent on aflatoxin concentration. In the absence of aflatoxin virginiamycin increased gain but was unable to prevent the growth suppression caused by CPP. At 0.75 mg/kg of aflatoxin virginiamycin no longer increased growth in non-CPP challenged birds but was able to increase growth in CPP-challenged birds. At the 1.5 mg/kg of aflatoxin concentration, virginiamycin increased gain in non-CPP-challenged birds but challenging birds with CPP had no effect on gain. Virginiamycin improved overall feed conversion with the greatest improvement at 1.5 mg/kg (aflatoxin × virginiamycin, P < 0.05). Aflatoxin increased lesion scores in unchallenged birds but not in challenged birds (aflatoxin × CPP, P < 0.001). Aflatoxin and necrotic enteritis decrease broiler performance and interact to decrease weight gain, virginiamycin helps improve gain in challenged birds at 0.75 mg/kg of aflatoxin, but not at 1.5 mg/kg of aflatoxin.


Clonal analysis of deletions on chromosome 20q and JAK2-V617F in MPD suggests that del20q acts independently and is not one of the predisposing mutations for JAK2-V617F.
We developed a real-time copy number polymerase chain reaction assay for deletions on chromosome 20q (del20q), screened peripheral blood granulocytes from 664 patients with myeloproliferative disorders, and identified 19 patients with del20q (2.9%), of which 14 (74%) were also positive for JAK2-V617F. To examine the temporal relationship between the occurrence of del20q and JAK2-V617F, we performed colony assays in methylcellulose, picked individual burst-forming units-erythroid (BFU-E) and colony-forming units-granulocyte (CFU-G) colonies, and genotyped each colony individually for del20q and JAK2-V617F. In 2 of 9 patients, we found that some colonies with del20q carried only wild-type JAK2, whereas other del20q colonies were JAK2-V617F positive, indicating that del20q occurred before the acquisition of JAK2-V617F. However, in colonies from 3 of 9 patients, we observed the opposite order of events. The lack of a strict temporal order of occurrence makes it doubtful that del20q represents a predisposing event for JAK2-V617F. In 2 patients with JAK2-V617F and 1 patient with MPL-W515L, microsatellite analysis revealed that del20q affected chromosomes of different parental origin and/or 9pLOH occurred at least twice. The fact that rare somatic events, such as del20q or 9pLOH, occurred more than once in subclones from the same patients suggests that the myeloproliferative disorder clone carries a predisposition to acquiring such genetic alterations.


Augmented TME O-GlcNAcylation Promotes Tumor Proliferation through the Inhibition of p38 MAPK.
O-GlcNAcylation is a dynamic O-linked glycosylation event that plays a crucial role in regulating cellular signaling. Recent studies indicate that increased O-GlcNAcylation is a general feature in cancer and contributes to various cancer phenotypes, including cell proliferation, survival, invasion, metastasis, and energy metabolism. However, the role of O-GlcNAcylation in the tumor microenvironment (TME) is not fully elucidated. Here, B16 melanoma cells were subcutaneously transplanted into O-GlcNAc transferase transgenic (Ogt-Tg) mice exhibiting elevated O-GlcNAcylation to examine the effect of O-GlcNAcylation in the TME on tumor progression. In this model system, B16 tumor growth was significantly higher in Ogt-Tg/+ mice compared with wild-type (WT) mice. The tumors grown in Ogt-Tg/+ mice showed significant downregulation of p38 MAPK activity and upregulation of the ERK1/2 signaling pathway. In addition, proinflammatory cytokine production was significantly lower in the tumor tissues from Ogt-Tg/+ mice than in those from WT mice. Activation of NF-κB, a key regulator in the cytokine production, was downregulated in the macrophages of the tumor tissues grown in Ogt-Tg/+ mice. These data reveal that elevated O-GlcNAcylation in the TME reduces the production of inflammatory cytokines and promotes cancer progression through downregulation of p38 MAPK activity and subsequent upregulation of the ERK1/2 signaling pathway.Implications: The reduced production of inflammatory cytokines by augmented O-GlcNAcylation in the TME, mainly macrophages, promotes tumor proliferation through the inhibition of p38 MAPK and suggests a possible cause of increased morbidity and mortality rates for various cancers in diabetic patients. Mol Cancer Res; 15(9); 1287-98. ©2017 AACR.


Do not treat the numbers: lithium toxicity.
We describe the case of a 62-year-old man with a history of bipolar disorder, previously stable on lithium for over 20 years, who presented with a manic relapse and signs of lithium toxicity in the form of a coarse tremor. Serum lithium levels were in the normal range, and the patient had stage 3 chronic kidney disease. He was admitted for treatment under Section 2 of the Mental Health Act, and after stopping lithium was started on olanzapine. Signs of lithium toxicity improved after withdrawal of lithium. This case highlights the need to treat normal serum lithium levels with caution in patients showing signs of clinical lithium toxicity.


Topical amitriptyline and ketamine for the treatment of neuropathic pain.
A neuropathy is a disturbance of function or pathological change in nerves. In some cases, peripheral neuropathic pain may occur due to a lesion or disease of the peripheral somatosensory nervous system. Efficacy of different agents for peripheral neuropathic pain conditions is less than optimal. The administration of topical analgesics might be an option, due to the potential of reduced adverse effects and increased patient compliance. There is major interest in compounding topical analgesics for peripheral neuropathic pain, but several challenges remain for this approach. Topical analgesics have the potential to be a valuable additional approach for the management of peripheral neuropathic pain. Topical amitriptyline-ketamine combination (AK) is a promising agent for peripheral neuropathic pain conditions. Some studies have shown its efficacy in neuropathic pain conditions. However, this data was not uniformely obtained and its role remains still controversial. Efficacy may depend on many factors, including the choice of the vehicle, the concentration, the pain site, and specific diseases. More studies are necessary to support the use of AK in clinical practice.


[Change of the cell immunity indexes in patients with multiple gastroduodenal ulcers under the influence of surgical treatment].
There were followed up 62 patients with multiple gastroduodenal ulcers. Before the operation in them distinct changes of the cell chain of immunity were established: T-lymphopenia, the T-lymphocytes subpopulations dysbalance, predominantly with reduction of the circulating T-helpers/inductors (CD4+) quantity with preservation on nearly normal and moderately subnormal level of T-suppressors/killers (CD8+), the immunoregulatory index (CD4/CD8) lowering. The quantity of B-lymphocytes (CD22+) was in normal limits or moderately reduced. Essential lowering of index of the lymphocytes blasttransformation reaction was noted, witnessing inhibition of the T-lymphocytes functional activity occurrence. Overall the data obtained have had witnessed the secondary immunodeficiency state presence, which deepened after operative intervention performance and was not removed as a result of the conventional treatment conduction.


Establishment of a Novel Method for Screening Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance Mutations in Lung Cancer.
Drug resistance to targeted therapies occurs in lung cancer, and resistance mechanisms related to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are continuously being discovered. We aimed to establish a novel method for highly parallel multiplexed detection of genetic mutations related to EGFR TKI-resistant lung cancer using Agena iPLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on the MassARRAY mass spectrometry platform. A review of the literature revealed 60 mutation hotspots in seven target genes (EGFR, KRAS, PIK3CA, BRAF, ERBB2, NRAS, and BIM) that are closely related to EGFR TKI resistance to lung cancer. A total of 183 primers comprised 61 paired forward and reverse amplification primers, and 61 matched extension primers were designed using Assay Design Software. The detection method was established by analyzing nine cell lines, and by comparison with LungCarta™ kit in ten lung cancer specimens. EGFR, KRAS, and BIM genes in all cell lines and clinical samples were subjected to Sanger sequencing for confirming reproducibility. Our data showed that designed panel was a high-throughput and robust tool, allowing genotyping for sixty hotspots in the same run. Moreover, it made efficient use of patient diagnostic samples for a more accurate EGFR TKIs resistance analysis. The proposed method could accurately detect mutations in lung cancer cell lines and clinical specimens, consistent with those obtained by the LungCarta™ kit and Sanger sequencing. We also established a method for detection of large-fragment deletions based on single-base extension technology of MassARRAY platform. We established an effective method for high-throughput detection of genetic mutations related to EGFR TKI resistance based on the MassARRAY platform, which could provide more accurate information for overcoming cancers with de novo or acquired resistance to EGFR-targeted therapies.


Upregulation of CFTR expression but not SLC26A3 and SLC9A3 in ulcerative colitis.
In inflamed colonic mucosa, the equilibrium between absorptive and secretory functions for electrolyte and salt transport is disturbed. We compared the expression of three major mediators of the intestinal salt transport between healthy and inflamed colonic mucosa to understand the pathophysiology of diarrhea in inflammatory bowel disease. Expression levels of the cystic fibrosis transmembrane regulator (CFTR) (Cl- channel), SLC26A3 (Cl-/HCO exchanger) and SLC9A3 (Na+/H+ exchanger) mRNAs were measured by real-time quantitative RT-PCR in peroperative colonic samples from controls (n = 4) and patients with ulcerative colitis (n = 10). Several samples were obtained from each individual. Tissue samples were divided into three subgroups according to their histological degree of inflammation. Expression of CFTR and SLC26A3 proteins were determined by immunohistochemistry and Western blotting from the same samples, respectively. Increased expression of CFTR mRNA was observed in all three groups of affected tissue samples, most pronounced in mildly inflamed colonic mucosa (5-fold increase in expression; P < 0.001). The expression of the CFTR protein was detected from health and inflamed colon tissue. Although the expression of the SLC26A3 mRNA was significantly decreased in severe ulcerative colitis (P < 0.05), the SLC26A3 protein levels remained unchanged in all groups. The expression of SLC9A3 mRNA was significantly changed between the mild and severe groups. Intestinal inflammation modulates the expression of three major mediators of intestinal salt transport and may contribute to diarrhea in ulcerative colitis both by increasing transepithelial Cl- secretion and by inhibiting the epithelial NaCl absorption.


Comparative Effectiveness of Various Radiofrequency Ablation Catheters in the Ablation of Typical Atrial Flutter.
Although ablation of typical atrial flutter (AFL) can be easily achieved with radiofrequency energy (RF), no studies compare the effectiveness of different ablation catheters. Our study aimed to compare the efficacy of various types of ablation catheters in treating typical AFL. We analyzed patients with AFL who underwent RF ablation by a single operator at our institution. Successful ablation was evidenced by a bidirectional conduction block (trans-isthmus conduction time ≥ 130 ms or double potentials ≥ 90 ms). Logistic regression was used to compare success rate and linear regression to compare lesion time. Out of 222 patients, only six did not meet the success criteria (2.7%). The catheters used were non-irrigated, large-tip, internally irrigated (Chili II Boston Scientific), and externally irrigated (non-force-sensing) catheters (Cool Path, Abbott). An externally irrigated force-sensing catheter (TactiCath, Abbott) was used with > 10 gm of force and (LPLD) setting (30 W- 45 °C- 60 s), and high-power short-duration (HPSD) setting (50 W- 43 °C - 12 s). No complications were encountered. The catheter type had no statistically significant association with ablation success. With the use of externally irrigated catheter with contract force-sensing and HPSD settings, statistically significantly shortening of lesion time was achieved 758.3 s, [CI - 1128.29, - 388.35 s] followed by LPLD by 419.0 s [CI - 808.49, - 29.47 s]. The typical atrial flutter radiofrequency ablation procedure had a high success rate, which was not influenced by the type of ablation catheter. Contact force ablation catheter and HPSD are associated with shorter total lesion time.


Role of Multidetector Computed Tomography in the Evaluation of Maxillofacial Trauma.
Maxillofacial fractures are among the commonest injuries occurring in trauma patients. Multislice computed tomography (CT) is a widely used radiological investigation that accurately reveals the number, location, and extent of the fractures as well as concomitant soft tissue injuries and has been found to be superior in the diagnosis of maxillofacial fractures owing to high sensitivity and specificity. This study was performed to assess the efficacy of axial, coronal, sagittal, and three-dimensional (3D) reformatted images in the detection of fractures in maxillofacial trauma. This was a cross-sectional descriptive study conducted on 49 adult patients with maxillofacial injuries undergoing multislice CT using a multidetector SiemensSOMATOM Emotion eco 16 slice CT scanner (Siemens AG, Munich, Germany). CT protocol consisted of non-contrast axial 16-slice helical series beam collimation ~ 3 mm, pitch ~ 0.8 - 1, tube current ~ 270 mAs, voltage ~ 130 kV, Total exposure time ~ 18 seconds, total radiation ~ 200 mGy. Along with the axial, coronal and sagittal images were reconstructed with 0.5 mm increment. 3D volume-rendering images were also obtained. 3D images were compared with axial images, coronal and sagittal plane images. The maximum number of cases was in the age group of 21-30 years with the male: female ratio being 5.12:1. The most common cause of injury was road traffic accidents (RTA). Mandible fractures were found to be the most common (20 patients, 40.8%) followed by fractures of nasal bone (18 patients, 36.7%). The incidence of frontal bone fractures was found to be the least (six patients, 12.24%). Our study found that 3D images are superior to axial in assessing the extent and degree of displacement of maxillofacial fractures in general. The maxillary sinus was found to be the most commonly fractured sinus (19 patients, 38.7%). Sphenoid sinus fractures were the least common (seen in two patients, 4.08%). CT findings correlated with the operative findings in most types of fractures. Multidetector CT with multiplanar and 3D reformation is highly accurate in the identification of fractures and assessing the extent and degree of displacement of fractures; hence, it is the imaging modality of choice in maxillofacial trauma. 3D images are much better for the detection of maxillofacial fractures compared to axial, coronal, or sagittal views, especially in maxilla and mandibular bone fractures. It is also found to be better at providing information on the patterns of the fracture lines and the displacement of the fracture fragments. Another added advantage of multidetector CT is that it is a non-invasive technique with good accuracy and a short scan time.


Global Increases in Individualism.
Individualism appears to have increased over the past several decades, yet most research documenting this shift has been limited to the study of a handful of highly developed countries. Is the world becoming more individualist as a whole? If so, why? To answer these questions, we examined 51 years of data on individualist practices and values across 78 countries. Our findings suggest that individualism is indeed rising in most of the societies we tested. Despite dramatic shifts toward greater individualism around the world, however, cultural differences remain sizable. Moreover, cultural differences are primarily linked to changes in socioeconomic development, and to a lesser extent to shifts in pathogen prevalence and disaster frequency.


Immunohistochemical changes in the mouse striatum induced by the pyrethroid insecticide permethrin.
Epidemiological studies have linked insecticide exposure and Parkinson's disease. In addition, some insecticides produce damage or physiological disruption within the dopaminergic nigrostriatal pathway of non-humans. This study employed immunohistochemical analysis in striatum of the C57BL/6 mouse to clarify tissue changes suggested by previous pharmacological studies of the pyrethroid insecticide permethrin. Dopamine transporter, tyrosine hydroxylase, and glial fibrillary acidic protein immunoreactivities were examined in caudate-putamen to distinguish changes in amount of dopamine transporter immunoreactive protein from degeneration or other damage to dopaminergic neuropil. Weight-matched pairs of pesticide-treated and vehicle-control mice were dosed and sacrificed on the same days. Permethrin at 0.8, 1.5 and 3.0 mg/kg were the low doses and at 200 mg/kg the high dose. Brains from matched pairs of mice were processed on the same slides using the avidin-biotin technique. Four fields were morphometrically located in each of the serial sections of caudate-putamen, digitally photographed, and immunopositive image pixels were counted and compared between members of matched pairs of permethrin-treated and vehicle-control mice. For low doses, only 3.0 mg/kg produced a significant decrease in dopamine transporter immunostaining. The high dose of permethrin did not produce a significant change in dopamine transporter or tyrosine hydroxylase immunostaining, but resulted in a significant increase in glial fibrillary acidic protein immunostaining. These data suggest that a low dose of permethrin can reduce the amount of dopamine transporter immunoreactive protein in the caudate-putamen. They also suggest that previously reported reductions in dopamine uptake of striatal synaptosomes of high-dose mice may be due to nondegenerative tissue damage within this region as opposed to reductions of dopamine transporter protein or death of nigrostriatal terminals. These data provide further evidence that insecticides can affect the primary neurodegenerative substrate of Parkinson's disease.


Relationship of CSF shunting and IQ in children with myelomeningocele: a retrospective analysis.
This paper reviews 75 infants with myelomeningocele treated either at birth or from an early age at Rainbow Babies and Children's Hospital, for whom complete records and psychometric testing (IQ) are available (including complete summaries from referring hospitals). Three groups are compared: (1) infants without complications who were shunted for hydrocephalus (n = 41); (2) infants with complications who were shunted (n = 16), and (3) infants who were not shunted (n = 18). Complications were defined as ventriculitis (positive CSF cultures with elevated protein, depressed glucose and inflammatory cells), anoxia, poorly controlled hydrocephalus or other CNS anomalies such as porencephaly. The mean IQ of infants who were not shunted was 104, of those shunted without complications it was 91, and of those shunted who had complications it was 70. These IQ differences were significant at p less than 0.01, and were not explained by differences in spinal lesion levels.


Development of a high efficient "Dual Bt-Plus" insecticide using a primary form of an entomopathogenic bacterium, Xenorhabdus nematophila.
A phase variation has been reported in an entomopathogenic bacterium, Xenorhabdus nematophila. Compared with a wild-type primary form, a secondary form usually loses several physiological and biochemical characters. This study showed that the phase variation of X. nematophila caused a significant alteration in its immunosuppressive activity and subsequent entomopathogenicity. A secondary form of X. nematophila was detected in laboratory colonies and exhibited significant differences in dye absorption and entomopathogenicity. In addition, the secondary form was different in its production of eicosanoid-biosynthesis inhibitors (EBIs) compared with the primary form of X. nematophila. Production of oxindole and phydroxypropionic acid was significantly reduced in the culture broth of the secondary form of X. nematophila. The reduced EBI production resulted in significant suppression in the inhibitory effects on cellular nodule formation and phenoloxidase activity. Culture broth of the primary form of X. nematophila enhanced the pathogenicity of Bacillus thuringiensis ( Bt) significantly more than the culture broth of the secondary form. Furthermore, this study developed a highly efficient "Dual Bt-Plus" to control both lepidopteran insect pests Plutella xylostella and Spodoptera exigua, by mixing two effective Bt strains along with the addition of potent bacterial metabolites or 100-fold concentrated X. nematophila culture broth.


Investigating the adequacy of the Competence-Turnover Intention Model: how does nursing competence affect nurses' turnover intention?
The aim of this study was to test the adequacy of the Competence-Turnover Intention Model, which was developed to identify how nursing competence could affect nurses' turnover intention (nurses' intention to voluntarily leave an organisation). Recent studies have suggested that the level of nursing competence is negatively related to nurses' intention to leave their jobs, suggesting that a lack of competence threatens both the quality and quantity of the nursing workforce. However, the mechanism of how nursing competence affects nurses' turnover intention has not been explored previously. A cross-sectional survey design was used. Surveys were distributed to 1337 Japanese registered nurses/midwives in October, 2013. The adequacy of the model was analysed using structural equation modelling. In total, 766 questionnaires were returned, with a return rate of 57%. The model fitted well with the data. The results showed that the level of nursing competence was related positively to the quantity of organisational rewards they felt they had received, and negatively related to the level of exhaustion they experienced. Moreover, the perceived organisational rewards and exhaustion were correlated with nurses' turnover intention through affective commitment. The Competence-Turnover Intention Model is useful for explaining how nursing competence impacts on their turnover intention. Clinical implications derived from the findings are that: promoting nursing competence is key to improving not only the quality of care provided by nurses, but also to retaining the nursing workforce, and the model can be used to develop strategies that would mitigate their turnover intention.


Gene therapy for cancer.
Recent advances in our understanding of the molecular basis of neoplasia and of the mechanics underlying activation of the immune system provide us with exciting new possibilities for the treatment of cancer. This article reviews several of the recent developments that may enter widespread clinical use by the start of the next century. Indeed, the twenty-first century may well become for medicine, the era of gene therapy and molecular pharmacology.