Association of Firearm Access, Use, and Victimization During Adolescence With Firearm Perpetration During Adulthood in a 16-Year Longitudinal Study of Youth Involved in the Juvenile Justice System.
Preventing firearm violence requires understanding its antecedents. Yet no comprehensive longitudinal study has examined how involvement with firearms during adolescence-use, access, and victimization (defined as threatened with a weapon or gunshot injury)-is associated with the perpetration of firearm violence in adulthood. To examine the association between firearm involvement during adolescence and subsequent firearm perpetration and ownership in adulthood among youth involved in the juvenile justice system. This cohort study analyzed interview responses of 1829 randomly selected participants as part of the Northwestern Juvenile Project, a longitudinal study of health needs and outcomes of youth sampled from a temporary juvenile detention center in a large US city. Youth aged 10 to 18 years were interviewed in detention from November 1995 through June 1998. Participants were reinterviewed up to 13 times over 16 years through February 2015, for a total of 17 776 interviews. The sample was stratified by sex, race/ethnicity, age, and legal status (juvenile or adult court). Data were analyzed from April 2017, when data preparation began, through November 2020. Firearm involvement during adolescence: use (ie, threaten, shoot), access (ownership, ease of access, firearm in household, membership in gang that carries firearms), and victimization (gunshot injury, threatened with a weapon). Firearm involvement during adulthood: perpetration of firearm violence (ie, threatening with or using a firearm) and firearm ownership. Among the 1829 participants, 1388 had a 16-year follow-up interview: 860 males, 528 females; 809 were African American, 203 were non-Hispanic White; 374 were Hispanic; and 2 were other race/ethnicity; median (interquartile range) age of 32 (30-32) years. Eighty-five percent of males and 63.2% of females were involved with firearms as adolescents. Compared with females, males had significantly higher odds of every type of involvement except having a firearm in the home. In adulthood, 41.3% of males and 10.5% of females perpetrated firearm violence. Adolescents who had been threatened with a weapon or injured by firearms had 3.1 (95% CI, 2.0-4.9) and 2.4 (95% CI, 1.2-4.9) times the odds of perpetrating violence during adulthood. Similar associations were found for firearm ownership. Involvement with firearms during adolescence-including victimization-is a significant risk factor for firearm perpetration and ownership during adulthood.


Tetra-aqua-bis-(3,5-dinitro-benzoato-κO (1))magnesium tetra-hydrate.
In the structure of the title compound, [Mg(C7H3N2O6)2(H2O)4]·4H2O, the slightly distorted octa-hedral MgO6 coord-in-ation polyhedron comprises two trans-related carboxyl-ate O-atom donors from mononodentate 3,5-dinitro-benzoate ligands, and four water mol-ecules. The coordinating water mol-ecules and the four water mol-ecules of solvation give both intra- and inter-unit O-H⋯O hydrogen-bonding inter-actions with carboxyl-ate, water and nitro O-atom acceptors, forming a three-dimensional structure.


Identification of Target Genes Involved in the Antiproliferative Effect of Enzyme-Modified Ginseng Extract in HepG2 Hepatocarcinoma Cell.
Ginsenosides are ginseng saponins, which are the major biologically active components of Panax ginseng, often metabolized by intestinal bacteria into more effective forms. In this study, we found that the antiproliferative activity of ginseng increased after enzymatic processing of ginseng saponin (50% inhibitory concentration [IC50], >30 μ g/mL), which may be the result of the accumulation of minor saponins, such as Rh1, Rg3, compound K, and PPT constituents in ginseng saponin. Using the Agilent PrimeView Human Gene Expression Array, we found that the expression of several genes involved in apoptosis (caspase-4, Annexin A2, HSPA9, AIFM1, UQCRC2, and caspase-7) were increased in HepG2 human hepatocarcinoma cells after their treatment with enzyme-modified ginseng extract (EMGE). Furthermore, several genes implicated in cell cycle progression (CDCA3, CDCA8, CABLES2, CDC25B, CNNM3, and CCNK) showed decreased expression in HepG2 cells treated with EMGE. Finally, from flow cytometric analysis, we found that EMGE-treated HepG2 cells showed increased apoptotic sub-G1 population (24%), compared with that observed in DMSO-treated control cells (1.6%). Taken together, our results suggest that EMGE induces anticancer activity through the induction of apoptosis-related genes and cell cycle arrest via decreased expression of cell cycle regulatory genes.


High level manpower movements in Northwest Europe and the role of careers: an explanatory framework.
"This article works towards a theoretical explanatory framework for analyzing the geographical patterns of labor flows between the industrial countries of Western Europe. The framework proposed is based on the disaggregated nature of the modern labor market, in which specialist skills and training result in a workforce segmented into self-contained noncompeting groups. It is applied to the migration within Northwest Europe of high level manpower, especially those moving within multinational organizations."


Colonization of hospitalized patients by Staphylococcus aureus, Staphylococcus epidermidis and enterococci.
Patients admitted to a medical intensive care unit (29), a surgical intensive care unit (29) and a general medical ward (34) were studied to determine the frequency of colonization by Staphylococcus aureus, Staph. epidermidis and enterococci. Cultures of anterior nares, pharynx, axilla, periurethral tissues, and rectum were done within 24 h of admission and every 48-72 h thereafter for the duration of hospitalization. We found Staph. aureus colonization of pharynx, axilla, periurethral tissues and rectum to be equally frequent in patients with and without nasal colonization. Staphylococcus epidermidis was commonly recovered from all sites except the pharynx. The 49 strains of this organism acquired in the hospital were significantly more often resistant to nafcillin, cephalothin, chloramphenicol, trimethoprim-sulfamethoxazole and gentamicin than were 199 isolates recovered from patients at the time of admission. Enterococci were commonly isolated from rectal swabs and, less often, from other sites. Acquisition of enterococcal colonization during hospitalization was correlated significantly with antibiotic administration.


A pediatric protocol for management of extravasation injuries.
The administration of bioactive agents through IV can lead to serious complications, including partial-or full-thickness skin loss, infection, nerve and tendon damage, or loss of limb. Children's Hospital of The King's Daughters (CHKD) implemented a protocol to uniformity identify and treat infiltrates in order to avoid these serious potential complications.


[Diastolic changes in isolated stenosis of the pulmonary artery after correction of valvular defect].
Intracardiac hemodynamics and myocardial function were studied in 20 patients surgically treated for a valve defect. All the patients developed isolated stenosis of the pulmonary artery. It is emphasized that an early postoperative period in relevant correction proceeds with diastolic impairments. Some factors affecting the degree of the diastolic filling of the right ventricle upon the defect correction are determined. Adequate therapy of the disorders in proposed.


Prospective multivariate analysis of factors predictive of complete regression of Barrett's esophagus.
Demographic, endoscopic, and histological features of Barrett's esophagus at initial diagnosis were examined for their ability to predict complete endoscopic and histological regression of Barrett's during long-term follow-up. Barrett's patients who have been followed up for a minimum of 2 yr and who have had at least two follow-up surveillance examinations were included in the analysis. Complete regression of Barrett's was defined as total disappearance of all tongues and patches of Barrett's epithelium at endoscopy (confirmed with Lugol's iodine) in conjunction with only squamous epithelium on biopsy. Chi2 and stepwise logistic regression analyses were performed on the following clinical, endoscopic, and histological variables with regards to their ability to predict complete Barrett's regression: patient age in years (<65 or > or =65), length in cm of Barrett's (< or =2, >2<6, and > or =6), presence of a hiatal hernia (yes or no), presence of dysplasia at diagnosis (yes or no), and type of long-term medical treatment (histamine antagonists, proton pump inhibitor [PPI], or PPI and cisapride). Ninety-nine patients, all men with a mean age +/- SD in years of 61.6+/-13.1 have been followed prospectively for 24-106 months (mean +/- SD, 48.0+/-19.8). Seven patients have had complete regression of Barrett's. Univariate analysis showed that complete regression of Barrett's was associated only with absence of a hiatal hernia (p = 0.012). Stepwise logistic regression analysis revealed that complete regression was significantly and independently associated again only with absence of a hiatal hernia (p = 0.025). Stepwise logistic regression analysis utilizing only hiatal hernia (yes vs no) and length of Barrett's (<6 cm vs > or =6 cm) as variables revealed that absence of a hiatal hernia (p = 0.0447) and shorter lengths (<6 cm) of Barrett's (p = 0.0418) were significantly and independently predictive of complete Barrett's regression. The absence of a hiatal hernia was noted to be the most important factor associated with Barrett's regression. Complete regression of Barrett's esophagus occurs in a minority of patients, primarily in those with no hiatal hernia and shorter lengths of Barrett's epithelium.


Using social robot PLEO to enhance the well-being of hospitalised children.
Hospitalisation is stressful for children. Play material is often offered for distraction and comfort. We explored how contact with social robot PLEO could positively affect a child's well-being. To this end, we performed a multiple case study on the paediatric ward of two hospitals. Child life specialists offered PLEO as a therapeutic activity to children in a personalised way for a well-being related purpose in three to five play like activity sessions during hospital visits/stay. Robot-child interaction was observed; care professionals, children and parents were interviewed. Applying direct content analysis revealed six categories of interest: interaction with PLEO, role of the adults, preferences for PLEO, PLEO as buddy, attainment of predetermined goal(s) and deployment of PLEO. Four girls and five boys, aged 4-13, had PLEO offered as a relief from stress or boredom or for physical stimulation. All but one started interacting with PLEO and showed behaviours like hugging, caring or technical exploration, promoting relaxation, activation and/or making contact. Interaction with PLEO contributed to achieving the well-being related purpose for six of them. PLEO was perceived as attractive to elicit play. Although data are limited, promising results emerge that the well-being of hospitalised children might be fostered by a personalised PLEO offer.


Summary of institutional actions affecting breastfeeding.
It seems appropriate for the lactation consultant to be the advocate for infants and children. We must act ourselves if we want change to occur. When individuals cause even small changes to be made, the cumulative effect can be profound.


Methadone and buprenorphine pharmacokinetics and pharmacodynamics when coadministered with fostemsavir to opioid-dependent, human immunodeficiency virus seronegative participants.
Regional human immunodeficiency virus (HIV) prevalence rates are high in people with history of injection drug use, including those managed with maintenance opioids. Fostemsavir (FTR) is an oral prodrug of temsavir, a first-in-class attachment inhibitor that binds HIV-1 gp120, preventing initial HIV attachment and entry into host immune cells. Here we determine the impact of FTR on the pharmacokinetics of opioids methadone (MET: R-, S- and total) or buprenorphine and norbuprenorphine (BUP and norBUP) when coadministered. Study 206216 (NCT02666001) was a Phase I, open-label study, assessing the effect of FTR 600 mg (extended-release formulation) twice daily on pharmacokinetics of MET or BUP and norBUP, in non-HIV-infected participants on stable maintenance therapy with MET (40-120 mg; n = 16) or BUP plus naloxone (8-24 mg plus 2-6 mg; n = 16); pharmacodynamic response was assessed using standard opioid rating scales. Following coadministration with FTR, dose-normalized MET (R-, S- and total) exposures (maximum concentration in plasma, area under the plasma concentration-time curve over the dosing interval and concentration in plasma at 24 hours) increased 9-15% and BUP and norBUP exposures increased 24-39%. The 90% confidence interval ranges for MET (1.01-1.21) and BUP and norBUP (1.03-1.69) were within respective no-effect ranges (0.7-1.43 and 0.5-2.0). Opioid pharmacodynamic scores were similar with and without MET/BUP with no symptoms of withdrawal/overdose; no new safety signal for FTR when combined with a stable opioid regimen. FTR did not impact MET and had no clinically significant impact on BUP pharmacokinetics. Standardized assessments of opioid pharmacodynamics were unchanged throughout FTR administration with MET or BUP. FTR can be administered with MET or BUP without dose adjustment.


Familial progressive aphasia: its relationship to other forms of lobar atrophy.
Two brothers presented with slowly progressive aphasia. One brother, who became behaviourally disturbed only at the end of his illness, was found at necropsy to have predominant left frontotemporal atrophy. The other brother developed severe behavioural disturbances shortly after the onset of language impairment. His brain revealed bilateral frontotemporal atrophy. In both there was non-Alzheimer's disease pathology with the histological features of loss of large cortical nerve cells, spongiform change and mild gliosis. The differential anatomical atrophy supports the view that clinical manifestations of lobar atrophy are dictated by the topographical distribution of a common underlying pathology, linking the syndromes of progressive aphasia to dementia of frontal lobe type (DFT) and DFT with motor neuron disease.


Origin of the oscillator strength of the triplet state of a trion in a magnetic field.
The dynamics of the spin-triplet trion state, under high magnetic field in a GaAs/AlGaAs quantum well, are studied using time resolved spectroscopy. The oscillator strength of the triplet transition is shown to rise with increasing electron density, in good agreement with a theoretical model where the trion interacts with excess electrons in the quantum well. This analysis suggests that the spin-triplet trion state, which is expected to be an optically "dark" state, is experimentally observable due to the interactions with the excess electrons, demonstrating that X- cannot be regarded as an isolated three particle complex.


[HIV vaccines].
The devastation caused by the HIV pandemic will probably not be quelled until a safe and effective vaccine has been developed that is also affordable and available in the developing countries where the impact of this virus is most severe. Considerable progress has been made over the past several years in the search for a vaccine against HIV: roughly 30 different types are currently being investigated in phase I/II clinical trials. Major scientific challenges nonetheless still remain. An ideal vaccine would elicit both neutralizing antibodies and cytotoxic T lymphocytes (CTL) and, perhaps, mucosal immune response. The precise correlates of immunity have not been defined. Recombinant live vector-based vaccines, lipopeptides, and plasmid DNA have all been shown to induce CTL. The different forms of prime-boost vaccine strategies currently being tested in numerous clinical trials provide reasons for hope.


[Effectiveness and difficulty of education on nosocomial infection control for pre-clinical practice in the clinic, so-called inclusive clinical practice phase I, for students in the Faculty of Dentistry, Tokyo Medical and Dental University].
It has been planned to give pre-clinical practice in the clinic, so-called inclusive clinical practice phase I, for fifth-grade students in the School of Dentistry, Faculty of Dentistry, Tokyo Medical and Dental University, to give them the clinical training needed to perform dental practice and clinical practicum for comprehensive patient care, namely inclusive clinical practice phase II. This study analyzed the educative efficiency of the class on nosocomial infection control (NIC) by comparing achievements pre- and post-test, and discussed appropriate education planning on the NIC for dental students. Sixty-two fifth-grade students in the 2007 academic year sat the pre- and post-tests; the mean score and standard deviation of these tests were 5.30 +/- 1.26 (n = 56) and 8.59 +/- 1.18 (n = 59), respectively. There was a statistically significant difference between them (paired t-test, p < 0.01). Another finding was that students with high scores in the post-test did not necessarily achieve high ratings in the pre-test. It is suggested that the introduction of pre- and post-tests and the clarification of main points in the class as a theme of NIC could be a useful tool for increasing the comprehension of students on the theme. Since students at lower grades will attend clinical practice in the university hospital, it is thought that students should be given NIC training early in the clinical course, and the current curriculum should be improved to increase the opportunity for students to study this important issue.


Vaccination for respiratory immunity: latest developments.
Advances over the last 20 years in immunology and molecular biology have provided many new tools for identifying the important antigens and new ways to achieve the appropriate immune responses to these antigens. These provide many more options to achieve the best immune response from deletion mutations, subunit antigens, vectors or DNA immunization. These tools are being adopted to screen, discover and produce the appropriate antigens and to deliver them by the optimal method and with novel adjuvants to achieve the appropriate immune response. These developments will result in vaccines for respiratory disease that are safer and more efficacious, and provide greater flexibility for use and administration.


Income level and chronic ambulatory care sensitive conditions in adults: a multicity population-based study in Italy.
A relationship between quality of primary health care and preventable hospitalizations has been described in the US, especially among the elderly. In Europe, there has been a recent increase in the evaluation of Ambulatory Care Sensitive Conditions (ACSC) as an indicator of health care quality, but evidence is still limited. The aim of this study was to determine whether income level is associated with higher hospitalization rates for ACSC in adults in a country with universal health care coverage. From the hospital registries in four Italian cities (Turin, Milan, Bologna, Rome), we identified 9384 hospital admissions for six chronic conditions (diabetes, hypertension, congestive heart failure, angina pectoris, chronic obstructive pulmonary disease, and asthma) among 20-64 year-olds in 2000. Case definition was based on the ICD-9-CM coding algorithm suggested by the Agency for Health Research and Quality - Prevention Quality Indicators. An area-based (census block) income index was used for each individual. All hospitalization rates were directly standardised for gender and age using the Italian population. Poisson regression analysis was performed to assess the relationship between income level (quintiles) and hospitalization rates (RR, 95% CI) separately for the selected conditions controlling for age, gender and city of residence. Overall, the ACSC age-standardized rate was 26.1 per 10.000 inhabitants. All conditions showed a statistically significant socioeconomic gradient, with low income people being more likely to be hospitalized than their well off counterparts. The association was particularly strong for chronic obstructive pulmonary disease (level V low income vs. level I high income RR = 4.23 95%CI 3.37-5.31) and for congestive heart failure (RR = 3.78, 95% CI = 3.09-4.62). With the exception of asthma, males were more vulnerable to ACSC hospitalizations than females. The risks were higher among 45-64 year olds than in younger people. The socioeconomic gradient in ACSC hospitalization rates confirms the gap in health status between social groups in our country. Insufficient or ineffective primary care is suggested as a plausible additional factor aggravating inequality. This finding highlights the need for improving outpatient care programmes to reduce the excess of unnecessary hospitalizations among poor people.


Relaxin stimulates glycodelin mRNA and protein concentrations in human endometrial glandular epithelial cells.
Human endometrium is the major organ that produces glycodelin A (GdA). The production of endometrial GdA causes a fluctuation of the peripheral glycodelin concentrations in women during the menstrual cycle and pregnancy. It has recently been reported that the rise of plasma concentrations of glycodelin is correlated with relaxin during the late luteal phase and early pregnancy. In addition, administration of relaxin increases glycodelin plasma concentrations, suggesting that relaxin induces GdA production in endometrium. To investigate whether relaxin regulates the GdA synthesis, human endometrial glandular epithelial cells were isolated and cultured with or without relaxin for up to 4 days. Western blot showed that GdA synthesized and secreted from epithelial glands had a major molecular weight of 28 kDa, i.e. the same as the GdA isolated from amniotic fluid. Cells incubated with relaxin consistently increased in GdA production rate (2-6-fold). The GdA mRNA concentrations increased 2-11-fold in cells incubated with relaxin for 2-4 days, as determined by solution hybridization/ribonuclease protection assay. The increase of the mRNA concentration indicates that relaxin activates GdA transcription.


Energetic conditions promoting top-down control of prey by predators.
Humans remove large amounts of biomass from natural ecosystems, and large bodied high trophic level animals are especially sensitive and vulnerable to exploitation. The effects of removing top-predators on food webs are often difficult to predict because of limited information on species interaction strengths. Here we used a three species predator-prey model to explore relationships between energetic properties of trophodynamic linkages and interaction strengths to provide heuristic rules that indicate observable energetic conditions that are most likely to lead to stable and strong top-down control of prey by predator species. We found that strong top-down interaction strengths resulted from low levels of energy flow from prey to predators. Strong interactions are more stable when they are a consequence of low per capita predation and when predators are subsidized by recruitment. Diet composition also affects stability, but the relationship depends on the form of the functional response. Our results imply that for generalist satiating predators, strong top-down control on prey is most likely for prey items that occupy a small portion of the diet and when density dependent recruitment is moderately high.


Fracture healing: a consensus report from the International Osteoporosis Foundation Fracture Working Group.
We used the RAND UCLA appropriateness method to decide appropriateness of use of osteoporosis medication after incident fracture and potential for fracture healing and make suggestions for trial design for clinical and preclinical research. To develop appropriateness criteria to assist in the use and study of osteoporosis medications in patients with recent fracture and in the potential use of osteoporosis medications to enhance delayed fracture healing. To promote further research by suggesting preclinical and clinical trial design for studies where fracture healing is the endpoint. RAND/UCLA appropriateness method (RUAM). A panel of experts, both members and non-members of the International Osteoporosis Foundation Fracture Working Group, were identified consisting of geriatricians, rheumatologists, orthopedists, endocrinologists, and internists. This resulted in a round 1 panel of 15 panelists, round 2 panel of 15 members, and a round 3 panel of 14 members. Agreement on statements and scenarios using RUAM. Three rounds of voting by panelists took place. Agreement in a third round was reached for 111 statements and scenarios, measured by median panel ratings and the amount of dispersion of panel ratings, based on the interpercentile range. An expert panel validated a set of statements and scenarios about the use of osteoporosis medications after incident fracture and use of these medications to enhance delayed fracture healing and made recommendations for study designs to investigate the effect of osteoporosis medications on fracture healing. The result of this exercise is intended to assist in improving patient care by identifying the appropriateness of use of osteoporosis medications after fracture and in fracture healing and to make suggestions for further preclinical and clinical research.


Time lapse in vivo visualization of developmental stabilization of synaptic receptors at neuromuscular junctions.
The lifetime of nicotinic acetylcholine receptors (AChRs) in neuromuscular junctions (NMJs) is increased from <1 day to >1 week during early postnatal development. However, the exact timing of AChR stabilization is not known, and its correlation to the concurrent embryonic to adult AChR channel conversion, NMJ remodeling, and neuromuscular diseases is unclear. Using a novel time lapse in vivo imaging technology we show that replacement of the entire receptor population of an individual NMJ occurs end plate-specifically within hours. This makes it possible to follow directly in live animals changing stabilities of end plate receptors. In three different, genetically modified mouse models we demonstrate that the metabolic half-life values of synaptic AChRs increase from a few hours to several days after postnatal day 6. Developmental stabilization is independent of receptor subtype and apparently regulated by an intrinsic muscle-specific maturation program. Myosin Va, an F-actin-dependent motor protein, is also accumulated synaptically during postnatal development and thus could mediate the stabilization of end plate AChR.


Mutagenic analysis of functional domains of the mos proto-oncogene and identification of the sites important for MAPK activation and DNA binding.
We constructed in-frame deletion/replacement mutations in the Xenopus mos proto-oncogene that lie within conserved Mos-specific codons, but outside of the regions that are conserved among the src kinase family of genes. All gene products were assayed in vitro for kinase activity and in vivo for their ability to induce oocyte maturation, embryonic cleavage arrest and cellular transformation. Most mutations in Mos eliminated both kinase and biological activity. However, a mutation in Mos that removed two basic amino acid residues (R94 and K97) downstream from the lysine at the ATP binding site (K90) markedly enhanced autophosphorylation activity. Moreover, this mutant displayed markedly reduced biological activity, lacked transforming activity, and failed to activate mitogen activated protein kinase (MAPK). A second mutant Mos product, lacking amino acids R45-A54, displayed a five-fold increase in cellular transforming activity. This Mos mutant specifically localized to the cytoplasm; in contrast to wild-type (wt) Mos that localized to both the nucleus and the cytoplasm. These data indicate that Mos transforming activity is mediated via signalling exerted in the cytoplasm, presumably through MAPK, and that nuclear localization of the oncogene product interferes with transforming activity. We also show that amino acids R45-A54 are important for Mos DNA binding activity.


Islet cell transplantation.
Islet cell transplantation is an attractive alternative therapy to conventional insulin treatment or vascularized whole pancreas transplantation for type 1 diabetic patients. It represents a successful example of somatic cell therapy in humans based on complex procedures for islet isolation from whole pancreas. The islets, that are only 1% of the total pancreas tissue, are isolated by two steps method starting with collagenase digestion that operates a rapid dissociation of the stromal component of the gland, while preserving islet anatomical integrity. After digestion, islets are then separated from exocrine tissue by centrifugation in density gradients. Transplantation consists of a simple injection of few milliliter-purified tissue in the portal vein through a percutaneous trans-hepatic approach performed in local anesthesia. Several studies have now demonstrated that islet transplant can replace pancreatic endocrine function without major side effects and with liver viability preservation in selected patients affected by long-term type 1 diabetes. It can restore endogenous insulin secretion, achieve insulin independence in more than 80% of patients, and recover the metabolism of glucose, protein and lipids. Improved control of glycated HbA1c, reduced risk of recurrent hypoglycemia and of diabetic complications are also seen as important benefits of islet cell transplantation, irrespective of the status of insulin independence. Many protocols are now on going for reduction of immunosuppression therapy in recipients, induction of tolerance, and prolongation of graft function.


The Bacterial Cell Wall: From Lipid II Flipping to Polymerization.
The peptidoglycan (PG) cell wall is an extra-cytoplasmic glycopeptide polymeric structure that protects bacteria from osmotic lysis and determines cellular shape. Since the cell wall surrounds the cytoplasmic membrane, bacteria must add new material to the PG matrix during cell elongation and division. The lipid-linked precursor for PG biogenesis, Lipid II, is synthesized in the inner leaflet of the cytoplasmic membrane and is subsequently translocated across the bilayer so that the PG building block can be polymerized and cross-linked by complex multiprotein machines. This review focuses on major discoveries that have significantly changed our understanding of PG biogenesis in the past decade. In particular, we highlight progress made toward understanding the translocation of Lipid II across the cytoplasmic membrane by the MurJ flippase, as well as the recent discovery of a novel class of PG polymerases, the SEDS (shape, elongation, division, and sporulation) glycosyltransferases RodA and FtsW. Since PG biogenesis is an effective target of antibiotics, these recent developments may lead to the discovery of much-needed new classes of antibiotics to fight bacterial resistance.


Primary hyperoxaluria: a rare but important cause of nephrolithiasis.
We report on a middle-aged man with end-stage renal failure apparently secondary to recurrent renal stones. He developed systemic oxalosis soon after commencing dialysis. The diagnosis of primary hyperoxaluria type 1 was supported by the finding of high dialysate glycolate excretion. The patient subsequently received an isolated cadaveric renal transplant, but the outcome was a rapid recurrence of oxalosis and early graft failure. Although isolated liver or renal transplantation in addition to various adjuvant measures may be considered in the early stage, combined liver-kidney transplantation remains the only definitive therapy for a patient with end-stage renal failure and systemic oxalosis due to hyperoxaluria type 1. This case illustrates the possible late presentation of primary hyperoxaluria type 1 and the poor outcome with isolated renal transplantation after the development of systemic oxalosis. One should thus have a high index of suspicion in patients with recurrent renal stones of this rare, but nevertheless important, entity.


Positive and negative curvatures nested in an antiresonant hollow-core fiber.
We propose a negative curvature hollow-core fiber that has a nested elliptical element in the antiresonant tubes. The additional elliptical element effectively adds two curvatures, namely, a positive and a negative curvature. Our numerical study shows that it enhances the confinement of the light in the core. Moreover, the nested elements provided an extra degree of freedom that can be exploited to suppress higher-order modes through the change of the ellipticity. The resulting low confinement loss and single-mode guidance properties of the proposed fiber make it a suitable candidate for applications in ultrashort pulse delivery and gas-based nonlinear systems.


Helical conformation at the carboxy-terminal portion of human C3a is required for full activity.
Human C3a, a 77-residue fragment released during complement activation, is a potent spasmogen that contracts smooth muscle, enhances vascular permeability, and suppresses humoral immune responses. Studies with synthetic peptides have shown that the active site of this anaphylatoxin resides in the COOH-terminal portion of C3a; the minimal peptide structure capable of expressing activity contains residues 73-77, Leu-Gly-Leu-Ala-Arg (C3a-73-77). Longer synthetic C3a analogue peptides, e.g., C3a-57-77 containing the 21 COOH-terminal amino acids, exhibit activity nearly equivalent to that of intact C3a. Circular dichroism spectra of peptide C3a-57-77 in aqueous buffer containing 25% (v/v) trifluoroethanol indicated helical structure (41% helix), and analysis of the sequence suggested an amphipathic surface. We have synthesized several 21-residue peptide analogues of the natural C3a sequence containing residues 57-77 that were designed to enhance helix and to accentuate amphipathy. Syntheses were designed to include strategic placement of the helix-promoting residues 2-aminobutyric acid (beta-methylalanine) and 2-aminoisobutyric acid (alpha-methylalanine). Two 21-residue C3a analogue peptides that were designed to enhance helical content were shown to exhibit greater biological activity than either the native factor C3a or C3a-57-77. Moreover, activity was abrogated by the appropriate placement of helix-breaking residues, e.g., proline, suggesting that a conformational requirement for activity is genuine. These observations suggest that a helical conformation is requisite for optimal C3a activity and that in intact C3a the NH2-terminal portion (residues 1-21) and the disulfide-linked core (residues 22-57) function primarily to stabilize ordered conformation at the COOH-terminal region of the molecule.


ICH E9 guideline 'Statistical principles for clinical trials': a case study.
The International Conference on Harmonization (ICH) E9 guideline 'Statistical principles for clinical trials' was adopted by the Committee for Proprietary Medicinal Products in March 1998, and consequently is operational in Europe. It has also been adopted in the U.S.A. and Japan. The aim of this paper is to relate the problems encountered during a recent regulatory submission to those discussed in the ICH E9 guideline. Statistical principles discussed in the guideline, but not comprehensively addressed when the clinical development programme was initiated in the mid-1990s, will be reviewed. The impact of each issue on the approvability of the dossier will be discussed, together with recommendations on how to avoid such problems with other ongoing clinical development programmes.


Necrotizing soft tissue infection in two patients with multiple myeloma.
Necrotizing soft tissue infection (NSTI) remains associated with substantial morbidity and risk of death, especially in immunocompromised patients, such as those with multiple myeloma. Early diagnosis and treatment is crucial, yet particularly complicated in patients with atypical presentations and impaired host defenses. A report of two cases of multiple myeloma and NSTI at a single institution. Review of pertinent international literature. Necrotizing soft tissue infections are rare in patients with multiple myeloma. However, when they occur, the presentation may be atypical, and morbidity is high. Anti-tumor chemotherapy must be suspended, worsening an already-guarded prognosis. A high index of suspicion for NSTI is necessary for immunocompromised patients, such as those with multiple myeloma, in view of the possibility of atypical presentation. Diagnosis may therefore be challenging, and a protracted course is possible because of host immunosuppression.


Colorectal cancer surgery of octogenarians in Hong Kong: who will survive?
OBJECTIVE. To assess the accuracy of the Association of Coloproctology of Great Britain and Ireland scoring system in predicting the 30-day mortality after surgery for colorectal cancer in Hong Kong elderly (aged 80 years or more) patients. DESIGN. Early mortality outcome audit in a historical cohort. SETTING. Queen Elizabeth Hospital, Hong Kong. PATIENTS. All Chinese patients (aged 80 years or more) who underwent elective or emergency surgery for colorectal cancer in the Department of Surgery between January 2005 and December 2009. MAIN OUTCOME MEASURES. Receiver operating characteristic curve analyses were used to estimate the predictive ability of the score. RESULTS. In all, 180 patients with colorectal cancer were included in this review. The overall 30-day and hospital mortality rates were 29/180 (16%) and 31/180 (17%), respectively. The Association of Coloproctology of Great Britain and Ireland score was significantly higher among patients who died within 30 days (4.2 vs 3.1, P=0.0001), and was the only independent predictor for 30-day mortality by logistic regression (P=0.009; odds ratio=2.555; 95% confidence interval, 1.277-4.932). The mean score of this study population was 3.22 (median, 3.10), giving a predicted 30-day mortality rate of 16.0 to 17.4%, which corresponded with an observed 30-day mortality of 16.1% encountered in this study. The score had a significantly larger area under the curve for the 30-day mortality rates (odds ratio=0.811; 95% confidence interval, 0.722-0.849) as compared to the American Society of Anesthesiologists score (0.664; 0.589-0.735) [P=0.0001]. CONCLUSION. The Association of Coloproctology of Great Britain and Ireland scoring system can accurately predict the 30-day mortality rate of elderly Hong Kong Chinese patients (aged 80 years or more) operated on for colorectal cancer.


Detection and sizing of small particles in an open cavity gas laser.
The open cavity of a He-Ne gas laser oscillating at 632.8 microm was used to detect and size aerosol particles. This was done for two transverse modes of the laser, the TEM(oo) and TEM(o1) *. Plots of particle extinction loss vs laser power are shown to agree with the theory for an inhomogeneously broadened line under the condition of small saturated gain per pass. The TEM(ol)*, doughnut, mode is shown to be preferable for use in an operational instrument. Extrapolation of the measurement to particles smaller than the wavelength of the laser radiation is discussed.


The effect of hyperoxia on submaximal exercise with the self-contained breathing apparatus.
The effects of hyperoxia on submaximal exercise with the self-contained breathing apparatus (SCBA) were studied in 25 males. Each participant completed a graded exercise test for the determination of ventilatory threshold (VT) and then a submaximal practice trial with a normoxic gas mixture. The normoxic (20.93 +/- 0.22% O(2); SUB(21)) and hyperoxic (40.18 +/- 0.73% O(2); SUB(40)) submaximal trials were then administered in a random order. All exercise tests were completed on separate days while wearing firefighting gear and the SCBA. Compared with SUB(21), hyperoxia significantly reduced minute ventilation (V(E)), mask pressure (P(mask)), heart rate, blood lactate concentration, perceived exertion, and perceived breathing distress. As expected, hemoglobin saturation remained higher (p < 0.05) during SUB(40). The reductions in both V(E) and P(mask) with hyperoxia imply a reduction in the work of breathing during exercise. Total gas consumption was 10.3 +/- 8.1% lower during SUB(40) when compared to SUB(21), another finding that has significant practical implications for occupational safety.


Allergenic relevance of Cupressus arizonica pollen extract and biological characterization of the allergoid.
Cupressaceae (cypress) pollens can cause pollinosis in winter. However, the lack of specific commercial extracts combined with the early pollination period of cypress trees make a precise diagnosis difficult. The need for a reliable and effective cypress extract for diagnostic and therapeutic purposes is increasingly felt. Mixed or single Cupressus arizonica, lusitanica and sempervirens pollen extracts precipitated with ammonium sulfate (PPT) were compared by direct RAST, RAST inhibition and SDS-PAGE techniques. The major allergen of C. arizonica (Cup a 1), purified by anion exchange chromatography, was checked by immunoblotting experiments before chemical modification, in parallel with a C. arizonica extract, with potassium cyanate (KCNO) to obtain a monomeric allergoid. The allergoid extract was characterized for its biological, chemico-physical and immunological features by RAST inhibition, SDS-PAGE and ELISA assays. Direct RAST, RAST inhibition, and SDS-PAGE data indicated that the PPT C. arizonica pollen extract showed the most allergenic potential, and it can be considered representative of the Cupressus spp. Immunoblotting data confirmed Cup a 1 as a major allergen. RAST inhibition and ELISA showed that modified PPT C. arizonica extract had less IgE reactivity than the native, non-modified extract, while preserving the immunogenic capacity typical for an allergoid. Finally, the SDS-PAGE profile of Cup a 1 allergoid was similar to native Cup a 1 allergen, suggesting the modified C. arizonica extract shows the characteristics of a monomeric allergoid. The PPT C. arizonica pollen extract shows good in vitro diagnostic potential and its chemically modified form offers the features of a monomeric allergoid. It might therefore lend itself to the development of a product to be administered by the sublingual or oromucosal route for immunotherapy of individuals with cypress pollinosis.


Brucellosis control in small ruminants in the Republic of Macedonia.
To present the main goals and activities of the strategy for control of brucellosis caused by B. melitensis in sheep and goats in the Republic of Macedonia. Relevant documents and reports from the Veterinary Directorate were used to present the approaches for control of the disease in small ruminants in R. Macedonia. The new strategy for control and eradication of brucellosis started its implementation in 2008 with combination of measures for test and slaughter of the sero-positive sheep and goats, mass vaccination and vaccination of young replacements. In 2008, a total of 596,213 animals have been tested in 5,820 flocks out of which 16,853 (2.8%) had Brucella positive results in 636 (10.9%) flocks. In 2009, a total of 543,011 sheep and goats had been tested in 5,507 flocks out of which 9,606 (1.8%) animals showed positive results in 666 (12.1%) flocks. While the number of positive flocks does not indicate great improvement, the individual number of Brucella-positive animals has decreased dramatically. The number of human cases in 2008 and 2009 were 490 and 287 respectively. Direct savings only from compensation to farmers for slaughtered animals for 2008 and 2009 are estimated to be more than 100,000,000 denars (~1.6 million Euro). RESULTS from 2009 have been evaluated and foreseen amendments will allow that the country will be systematically divided in a more detailed epidemiological fashion, i.e. division of the country into epidemiological units based on the disease status and accepted risk and implementation of appropriate measures therein.


Imaging findings of disseminated cysticercosis with unusual involvement of spleen and pancreas.
In this study, we present a case of disseminated cysticercosis involving the brain, orbit, myocardium, muscle, subcutaneous tissues, pancreas, and spleen. Imaging studies are described with emphasis on pancreatic and splenic involvement which is a rare manifestation of a rather common disease and has been radiologically demonstrated only once previously. Although the involvement of the pancreas by parasites leading to pancreatitis has been described previously, in our case there was no clinical or biochemical evidence of pancreatitis due to infection by cysticerci.


Amorphous Co2B Grown on CoSe2 Nanosheets as a Hybrid Catalyst for Efficient Overall Water Splitting in Alkaline Medium.
In this work, we synthesized a novel hybrid catalyst (Co2B/CoSe2) by growing amorphous Co2B on the surface of CoSe2 nanosheets. Benefiting from the prominent coupled effects between Co2B and CoSe2 nanosheets, an efficient oxygen evolution reaction catalyst Co2B/CoSe2 exhibits a very low overpotential of 320 mV @ 10 mA cm-2 with a Tafel slope of 56.0 mV dec-1 in alkaline medium. An overpotential of 300 mV can also be achieved by Co2B/CoSe2 at the same condition for hydrogen evolution reaction. Notably, at the applied potential of 1.73 V, the electrocatalyst Co2B/CoSe2 demonstrates a current density of 10 mA cm-2 for overall water splitting and displays an outstanding long-term stability. The faradaic efficiencies of Co2B/CoSe2 for both hydrogen and oxygen evolution are close to 100%.


Different Respiratory Rates during Resuscitation in a Pediatric Animal Model of Asphyxial Cardiac Arrest.
Actual resuscitation guidelines recommend 10 respirations per minute (rpm) for advanced pediatric life support. This respiratory rate (RR) is much lower than what is physiological for children. The aim of this study is to compare changes in ventilation, oxygenation, haemodynamics and return of spontaneous circulation (ROSC) rates with three RR. An experimental model of asphyxial cardiac arrest (CA) in 46 piglets (around 9.5 kg) was performed. Resuscitation with three different RR (10, 20 and 30 rpm) was carried out. Haemodynamics and gasometrical data were obtained at 3, 9, 18 and 24 minutes after beginning of resuscitation. Measurements were compared between the three groups. No statistical differences were found in ROSC rate between the three RR (37.5%, 46.6% and 60% in the 10, 20 and 30 rpm group respectively P = 0.51). 20 and 30 rpm groups had lower PaCO2 values than 10 rpm group at 3 minutes (58 and 55 mmHg vs 75 mmHg P = 0.08). 30 rpm group had higher PaO2 (61 mmHg) at 3 minutes than 20 and 10 rpm groups (53 and 45 mmHg P = 0.05). No significant differences were found in haemodynamics or tissue perfusion between hyperventilated (PaCO2 <30 mmHg), normoventilated (30-50 mmHg) and hypoventilated (>50 mmHg) animals. PaO2 was significantly higher in hyperventilated (PaO2 153 mmHg) than in normoventilated (79 mmHg) and hypoventilated (47 mmHg) piglets (P<0.001). Our study confirms the hypothesis that higher RR achieves better oxygenation and ventilation without affecting haemodynamics. A higher RR is associated but not significantly with better ROSC rates.


Double-blind, placebo-controlled, multicenter trial of a vasopressin V2-receptor antagonist in patients with schizophrenia and hyponatremia.
Hyponatremia (serum sodium [Na+] concentration <136 mmol/L) is a prevalent and potentially life-threatening medical comorbidity for schizophrenic patients. No definitive pharmacological treatments have been established. Tolvaptan (OPC-41061), an oral non-peptide V2-receptor antagonist, was recently shown to correct hyponatremia in a diverse population of 448 hyponatremic patients. Efficacy in a sub-set of 19 schizophrenic patients with idiopathic hyponatremia included in that sample is specifically examined. Nineteen subjects were randomly assigned to receive placebo (n = 12) or tolvaptan (n = 7) once daily for 30 days. Dosage adjustment was based on serum Na+ changes, initially 15 mg, titratable to 30 or 60 mg. The average daily area under the curve (AUC) changes in serum Na+ from baseline to Day 4 and Day 30 were co-primary end points. Increases in serum Na+ concentrations were significantly greater with tolvaptan than placebo at Day 4 (p = .0055) and at Day 30 (p < .0001). Two subjects receiving tolvaptan (28.6%) became dehydrated and experienced hypotension, and five subjects receiving placebo (41.7%) experienced symptoms associated with dilutional hyponatremia. These results suggest that tolvaptan effectively normalizes idiopathic hyponatremia in schizophrenic patients. Clinicians are advised to carefully monitor fluid status especially at the beginning of treatment to prevent dehydration.


Multiportal robotic access to the anterior cranial fossa: a surgical and engineering feasibility study.
Integration of robotic surgical technology into skull base surgery is limited due to minimum angle requirements between robotic tools (narrow funnel effect), steep angle of approach, and instrumentation size. The objectives of this study were to systematically analyze surgical approach portals using a computer model, determine optimal approaches, and assess feasibility of the derived approaches on robotic surgical systems. Computer analysis on 10 computed tomography scans was performed to determine approach trajectories, angles between robotic tools, and distances to specified skull base target locations for transorbital and transnasal surgical approach portals. Dry laboratory and cadaver laboratory. The optimal combinations were tested on the da Vinci and Raven robotic systems. Multiportal analyses showed the angles between 2 robotic tools were 14.7, 28.3, and 52.0 degrees in the cases of 2 transnasal portals, combined transnasal and medial orbit portals, and bilateral superior orbit portals, respectively, approaching a prechiasmatic target. The addition of medial and superior transorbital portals improved the skull base trajectory angles 21 and 27 degrees, respectively. Two robotic tools required an angle of at least 20 degrees between them to function effectively at skull base targets. Technical feasibility of robotic transorbital and transnasal approaches to access sella and parasellar target locations was demonstrated. This technique addresses the 2 major drawbacks of (1) the narrow funnel effect generated from portals in close proximity and (2) the steep angle of approach to the skull base, as observed in previous studies analyzing transoral, transcervical, transmaxillary, and transhyoid portals.


Suppression effect of recombinant adenovirus vector containing hIL-24 on Hep-2 laryngeal carcinoma cells.
The melanoma differentiation-associated gene-7 [MDA-7; renamed interleukin (IL)-24] was isolated from human melanoma cells induced to terminally differentiate by treatment with interferon and mezerein. MDA-7/IL-24 functions as a multimodality anticancer agent, possessing proapoptotic, antiangiogenic and immunostimulatory properties. All these attributes make MDA-7/IL-24 an ideal candidate for cancer gene therapy. In the present study, the human MDA-7/IL-24 gene was transfected into the human laryngeal cancer Hep-2 cell line and human umbilical vein endothelial cells (HUVECs) with a replication-incompetent adenovirus vector. Reverse transcription polymerase chain reaction and western blot analysis confirmed that the Ad-hIL-24 was expressed in the two cells. The expression of the antiapoptotic gene, Bcl-2, was significantly decreased and the IL-24 receptor was markedly expressed in Hep-2 cells following infection with Ad-hIL-24, but not in HUVECs. In addition, the expression of the proapoptotic gene, Bax, was induced and the expression of caspase-3 was increased in the Hep-2 cells and HUVECs. Methyl thiazolyl tetrazolium assay indicated that Ad-hIL-24 may induce growth suppression in Hep-2 cells but not in HUVECs. In conclusion, Ad-hIL-24 selectively inhibits proliferation and induces apoptosis in Hep-2 cells. No visible damage was found in HUVECs. Therefore, the results of the current study indicated that Ad-hIL-24 may have a potent suppressive effect on human laryngeal carcinoma cell lines, but is safe for healthy cells.


Bacterial colitis.
Bacterial colitis results in an inflammatory-type diarrhea that is characterized by bloody, purulent, and mucoid stool. These diseases have been designated as bacterial hemorrhagic enterocolitis. Associated symptoms include fever, tenesmus, and severe abdominal pain. The pathologic changes range from superficial exudative enterocolitis to a transmural enterocolitis with ulceration. Common pathologic bacteria causing bacterial colitis include Campylobacter, Salmonella, Shigella, Escherichia, and Yersinia species. The primary source of transmission is fecal-oral spread and ingestion of contaminated food and water. Although detailed history and identification of specific risk factors assist in the diagnosis, definitive diagnosis requires bacterial identification. Therefore, the physician must be familiar with the disease pathophysiology, epidemiology, and specific diagnostic modalities for clinical diagnosis and management. Specific tests are used to detect enteric pathogens and include stool and rectal swab culture, histology, and identification of specific bacterial toxins. Although many of these bacterial colitis infections are self-limiting, antibiotics should be used for high-risk patients and patients with complicated disease.


Vitamin B12: the forgotten micronutrient for critical care.
To analyse the anti-inflammatory and antioxidant properties of vitamin B12 and evaluate current evidence on vitamin B12 status in the critically ill with systemic inflammation. Data on vitamin B12 status of intensive care unit patients are scarce. Cobalamins could potentially be useful agents for inhibiting nitric oxide synthase and nitric oxide production, controlling nuclear factor-kappa B activation, and restoring optimal bacteriostasis and phagocytosis in which transcobalamins play a proven role. The antioxidant properties of vitamin B12, with a glutathione-sparing effect, are secondary to stimulation of methionine synthase activity and reaction with free oxygen or nitrogen radicals. Large parenteral doses are routinely administered for cyanide poisoning, with only mild, reversible side-effects. Current evidence suggests that high-dose parenteral vitamin B12 may prove an innovative approach to treat critically ill systemic inflammatory response syndrome patients, especially those with severe sepsis/septic shock. In this setting, vitamin B12 and transcobalamins could modulate systemic inflammation contributing to the anti-inflammatory cascade and potentially improve outcome. Despite evidence from animal studies, so far there are no clinical intervention trials that have studied vitamin B12 as a pharmaconutrient strategy for critical care. Well designed animal and clinical studies are required to clarify several outstanding questions on the optimal posology, safety, and efficacy of high-dose vitamin B12 in the critically ill.


AI protein structure prediction-based modeling and mutagenesis of a protostome receptor and peptide ligands reveal key residues for their interaction.
The protostome leucokinin (LK) signaling system, including LK peptides and their G protein-coupled receptors, has been characterized in several species. Despite the progress, molecular mechanisms governing LK peptide-receptor interactions remain to be elucidated. Previously, we identified a precursor protein for Aplysia leucokinin-like peptides (ALKs) that contains the greatest number of amidated peptides among LK precursors in all species identified so far. Here, we identified the first ALK receptor from Aplysia, ALKR. We used cell-based IP1 activation assays to demonstrate that two ALK peptides with the most copies, ALK1 and ALK2, activated ALKR with high potencies. Other endogenous ALK-derived peptides bearing the FXXWX-amide motif also activated ALKR to various degrees. Our examination of cross-species activity of ALKs with the Anopheles LK receptor was consistent with a critical role for the FXXWX-amide motif in receptor activity. Furthermore, we showed, through alanine substitution of ALK1, the highly conserved phenylalanine (F), tryptophan (W), and C-terminal amidation were each essential for receptor activation. Finally, we used an artificial intelligence-based protein structure prediction server (Robetta) and Autodock Vina to predict the ligand-bound conformation of ALKR. Our model predicted several interactions (i.e., hydrophobic interactions, hydrogen bonds, and amide-pi stacking) between ALK peptides and ALKR, and several of our substitution and mutagenesis experiments were consistent with the predicted model. In conclusion, our results provide important information defining possible interactions between ALK peptides and their receptors. The workflow utilized here may be useful for studying other ligand-receptor interactions for a neuropeptide signaling system, particularly in protostomes.


What is the best biomarker to assess arsenic exposure via drinking water?
Arsenic (As) is a ubiquitous element. The current WHO guideline for As in drinking water is 10 μg/L. Furthermore, about 130 million people have only access to drinking water containing more than 10 g As/L. Although numerous studies have shown the related adverse effects of As, sensitive appropriate biomarkers are still required for studies of environmental epidemiology. A review of the literature has shown that various biomarkers are used for such research. Their limits and advantages are highlighted in this paper: (i) the detection of As or its derivatives in the blood is an indication of the dose ingested but it is not evidence of chronic intoxication. (ii) The detection of As in urine is an indispensible procedure because it is a good marker for internal dose. It has been demonstrated to correlate well for a number of chronic effects related to As levels in drinking water. However confounding factors must be taken into account to avoid misinterpretation and this may require As speciation. (iii) As in the hair and nails reflects the level of long term exposure but it is difficult to relate the level with the dose ingested. (iv) Some studies showed a correlation between urinary As and urinary and blood porphyrins. However, it is difficult to use only porphyrins as a biomarker in a population survey carried out without doing further studies. (v) Genotoxic effects are based on the characterization of these potential effects. Most studies have detected increases in DNA damage, sister chromatid exchange, micronuclei or chromosomal aberrations in populations exposed to As in drinking water. Micronuclei assay is the technique of choice to follow these populations, because it is sensitive and easy to use. To conclude, whatever epidemiological studies are, the urinary and toenail biomarkers are useful to provide indications of internal dose. Moreover, micronuclei assay can be complementary use as biomarker of early effects.


Microneedle-mediated delivery of viral vectored vaccines.
Microneedle array platforms are a promising technology for vaccine delivery, due to their ease of administration with no sharp waste generated, small size, possibility of targeted delivery to the specified skin depth and efficacious delivery of different vaccine formulations, including viral vectors. Areas covered: Attributes and challenges of the most promising viral vector candidates that have advanced to the clinic and that have been leveraged for skin delivery by microneedles; The importance of understanding the immunobiology of antigen-presenting cells in the skin, in particular dendritic cells, in order to generate further improved skin vaccination strategies; recent studies where viral vectors expressing various antigens have been coupled with microneedle technology to examine their potential for improved vaccination. Expert opinion: Simple, economic and efficacious vaccine delivery methods are needed to improve health outcomes and manage possible outbreaks of new emerging viruses. Understanding what innate/inflammatory signals are required to induce both immediate and long-term responses remains a major hurdle in the development of the effective vaccines. One approach to meet these needs is microneedle-mediated viral vector vaccination. In order for this technology to fulfil this potential the industry must invest significantly to further develop its design, production, biosafety, delivery and large-scale manufacturing.


Generation of infectious cDNA clones of a Korean strain of tomato aspermy virus.
Infectious full-length cDNA clones of the Korean strain of tomato aspermy cucumovirus (KC-TAV) were constructed using a long-template reverse transcription-polymerase chain reaction. The in vitro RNA transcripts, which were produced using T7 RNA polymerase from full-length cDNAs, could systemically infect the Nicotiana tabacum cv. Xanti-nc plants and induce systemic symptoms on the upper leaves that are similar to the wildtype KC-TAV. The complete nucleotide sequences of genomic RNAs of KC-TAV were determined from the infectious full-length cDNA clones. RNA1 and RNA2 of KC-TAV contain 3412 nucleotides and 3074 nucleotides, respectively. RNA3 of KC-TAV, 2222 nucleotides long, encodes the 3a protein and coat protein (CP) that are separated by 295 nucleotides intergenic region. The overall sequence analysis of the whole genome of KC-TAV revealed a strong homology (99%) to the genome of the V-TAV strain, the only strain whose entire genomic nucleotide sequence was available in the database, and an overall 60% homology to those of other cucumber mosaic virus and peanut stunt virus strains. A sequence comparison analysis of the deduced amino acid sequences of cDNAs of KC-TAV RNA 1, 2, and 3 indicates that there is no genetic diversity in the TAV population, although the virus exists in different geographical distributions.


Synchronization affector of autonomous short-period-sustained oscillation of Saccharomyces cerevisiae.
When the yeast Saccharomyces cerevisiae was grown under aerobic continuous culture, an autonomous short-period-sustained oscillation appeared. This oscillation was observed in concentrations of various extracellular and intracellular parameters, such as ethanol, acetate, glycogen, dissolved oxygen and intracellular pH. In this work the synchronization affecter of this oscillation was investigated. Ethanol was found not to be the synchronizer of the oscillation because a pulse of ethanol did not affect the phase or period of the oscillation. The oscillation was dependent on the aeration rate, i.e., the oscillation occurred only between 150 and 600 ml min-1. However, the oxygen concentration did not influence synchronization as an upward shift in the oxygen concentration of the gas flow did not affect the sustainability of the oscillation. On the other hand, synchronization was stopped by an enhanced gas flow rate, keeping dissolved oxygen tension at the oscillatory condition, suggesting that synchronization was caused by a volatile compound in the culture. A stepwise increase in carbon dioxide concentration of the gas flow rate ceased synchronization, yet the oscillation seem to continue in each individual cell. Oscillatory behaviour of intracellular pH and carbon dioxide evolution rate showed a phase difference of 90 degrees. Based on these facts it is postulated that carbon dioxide, through the influence of its dissociation on intracellular pH, could be the synchronization affector of the autonomous short-period-sustained oscillation of S. cerevisiae.


Effect of potassium channel and cytochrome P450 inhibition on transient hypotension and survival during lipopolysaccharide-induced endotoxic shock in the rat.
The purpose of this study was to determine whether inhibition of potassium channels or cytochrome P450 attenuates the transient phase of hypotension during endotoxic shock in vivo, and to determine whether these interventions improve the rate of survival. Male Sprague-Dawley rats were pretreated with saline (0.2 ml, i.v.), tetraethylammonium chloride (TEA 30 mg/kg; 0.2 ml, i.v.), proadifen (SKF-525 A; 50 mg/kg, i.p.) or ketoconazole (50 mg/kg, i.p.) and challenged with lipopolysaccharide (LPS; 20 mg/kg, i.p.). Changes in heart rate, mean (MAP), systolic (SP) and diastolic (DP) arterial pressures as well as survival rate were then monitored for 45 min. Potassium channel inhibition with TEA had no effect on LPS-induced hypotension at any time point compared with saline (maximal fall in MAP of 79 +/- 18 and 80 +/- 13 mm Hg, respectively). Pretreatment with proadifen or ketoconazole, inhibitors of cytochrome P450, significantly attenuated LPS-induced hypotension compared with saline (maximal fall in MAP of 34, 26 and 63% below baseline, respectively). This effect was evident in all arterial pressures measured, MAP, SP and DP. At 45 min, the survival rate in the saline group was 66%. Pretreatment with TEA significantly reduced survival rate to 50% and pretreatment with proadifen or ketoconazole improved survival to 100% (p < 0.05). These results suggest that an arachidonic acid metabolite produced by a cytochrome P450-catalyzed reaction may contribute to the transient phase of LPS-induced hypotension. However, these effects do not appear to be mediated through potassium channel activation.


Alpha-melanocyte stimulating hormone-induced pigmentation is blocked by depletion of protein kinase C.
We have explored the role of protein kinase C (PKC) in pigmentation induced by alpha-melanocyte stimulating hormone (alpha-MSH). Using the well-studied S91 Cloudman mouse melanoma model system in which 10(-7) M alpha-MSH is known to produce a time-dependent increase in pigmentation, we found an increase in the activity of tyrosinase, the key enzyme in pigmentation, between Days 2 and 6 accompanied by an increase in mRNA and protein levels of tyrosinase, as well as an increase in the level of specifically the beta isoform of PKC. When S91 cells were treated with phorbol dibutyrate, 95% of PKC activity was lost within 48 h and the alpha-MSH-induced melanogenesis was completely blocked, as was the induction of tyrosinase mRNA and protein. Serially passaged S91 cells no longer capable of responding to alpha-MSH had an undetectable level of PKC-beta, although the tyrosinase protein level was identical to that of alpha-MSH-responsive cells. Furthermore, in these S91 cells alpha-MSH also did not increase the level of tyrosinase mRNA. Thus, induction of murine melanogenesis by alpha-MSH involves up-regulation of tyrosinase mRNA and protein mediated in part by the PKC-dependent pathway, associated with an up-regulation of the beta isoform previously demonstrated to specifically activate tyrosinase in human melanocytes.


[Determination of trace mercury in different sorts of Chinese herbs by atomic fluorescence spectrometry with microwave digestion].
A method for the determination of trace mercury in different sorts of Chinese herbs using hydride generation atomic fluorescence spectrometry under different microwave digestion conditions was developed. Under the optimized experimental conditions, the linear equation was I(F) = 809.1 x -3.327 5, the correlation coefficient was 0.999 998,and the linear range for mercury was 0-80 ng x mL(-1). The detection limit of mercury was 0.014 ng x mL(-1) (n = 11) and the relative standard deviation was 2.03%. The recoveries for these samples were 96.8%-102.80% (n = 6) while the detection limit of the method was 1.17 ng x g(-1). The method's accuracy and precision for different sorts of Chinese herbs using the standard reference standard substance of rice (GBW08508), poplar leaf (GBW07601), and mytilus edulis (GBW08571) was checked, and the results were found to be basically consistent with the reference values. This method has been proved to be sensitive, simple and rapid with satisfactory results.


Spatially resolved x-ray spectroscopy investigation of femtosecond laser irradiated Ar clusters.
High temperature plasmas have been created by irradiating Ar clusters with high intensity 60-fs laser pulses. Detailed spectroscopic analysis of spatially resolved, high resolution x-ray data near the He(alpha) line of Ar is consistent with a two-temperature collisional-radiative model incorporating the effects of highly energetic electrons. The results of the spectral analysis are compared with a theoretical hydrodynamic model of cluster production, as well as interferometric data. The plasma parameters are notably uniform over one Rayleigh length (600 microm).


Managing Patient Falls in Psychiatric Inpatient Units: Part 2.
Patient falls in the hospital psychiatric inpatient units are more frequent than in the medical-surgical units. The purpose of this study was to explore psychiatric unit directors' perceptions of the factors that contribute to patient falls in the State of Michigan. A quantitative online questionnaire was sent to the directors of psychiatric units in Michigan. Two research questions (RQs) guided the study: (a) What are psychiatric unit directors' perceptions of the possible intrinsic factors that contribute to patient falls in the psychiatric inpatient units, and (b) what are psychiatric unit directors' perceptions of the possible extrinsic factors that contribute to patient falls in the psychiatric inpatient units? In comparing the results, 6 of the 7 factors with the highest mean levels of agreement were intrinsic factors. In the current study, patient gait (mean, 4.65) ranked first, history of falls (mean, 4.52) second, and multiple medications (mean, 4.50) third as fall-risk factors. The need for the involvement of the team members (mean, 4.55) in preventing falls was the most highly rated factor among the extrinsic factors. Educating unit team members in assisting with fall prevention is a critical consideration for leaders.


PKCβ inhibition with ruboxistaurin reduces oxidative stress and attenuates left ventricular hypertrophy and dysfunction in rats with streptozotocin-induced diabetes.
Oxidative stress plays critical roles in the development of diabetic cardiovascular complications, including myocardial hypertrophy. The β isoform of PKC (protein kinase C) is preferentially overexpressed in the myocardium of diabetic subjects accompanied with increased activation of the pro-oxidant enzyme NADPH oxidase, which may exacerbate oxidative stress. We hypothesized that myocardial PKCβ is a major upstream mediator of oxidative stress in diabetes and that PKCβ inhibition can attenuate myocardial hypertrophy and dysfunction. Control or streptozotocin-induced diabetic rats were treated with the selective PKCβ inhibitor RBX (ruboxistaurin; 1 mg/kg of body weight per day) or the antioxidant NAC (N-acetylcysteine) for 4 weeks. LV (left ventricular) dimensions and functions were detected by echocardiography. 15-F2t-isoprostane (a specific index of oxidative stress) and myocardial activities of superoxide dismutase as well as protein levels of NADPH oxidase were assessed by immunoassay or Western blotting. Echocardiography revealed that the LV mass/body weight ratio was significantly increased in diabetic rats (P<0.01 compared with the control group) in parallel with the impaired LV relaxation. A significant increase in cardiomyocyte cross-sectional area was observed in diabetic rats accompanied by an increased production of O2- (superoxide anion) and 15-F2t-isoprostane (all P<0.05 compared with the control group). RBX normalized these changes with concomitant inhibition of PKCβ2 activation and prevention of NADPH oxidase subunit p67phox membrane translocation and p22phox overexpression. The effects of RBX were comparable with that of NAC, except that NAC was inferior to RBX in attenuating cardiac dysfunction. It is concluded that RBX can ameliorate myocardial hypertrophy and dysfunction in diabetes, which may represent a novel therapy in the prevention of diabetic cardiovascular complications.


Does the combination of resveratrol with Al (III) and Zn (II) improve its antioxidant activity?
This communication describes the in situ combination of Al(III) and Zn(II) with resveratrol, and evaluation of the antioxidant power of the novel species via DPPH* assay. The formation of the complexes in aqueous medium was verified by Job's method, using fluorescence spectroscopy. The metal/ligand stoichiometry for the Zn(II)/resveratrol complex was found to be 1:2 and, for the Al(III)/resveratrol complex two preferential species were formed with 1:1 and 3:1 stoichiometries. The compounds were also studied by 1H and 13C NMR spectroscopy. Their antioxidant activity, evaluated by a scavenging assay using DPPH* (1,1-diphenyl-2-picrylhydrazyl), demonstrated that the combined species are more effective free radical scavengers than free resveratrol. The electrochemical behavior of the complexes revealed the occurrence of irreversible oxidation processes, which take place at a lower potential than that observed with free resveratrol. These results indicate that metallic complexes of this natural product have a higher antioxidant power than resveratrol alone.


Hypokalemic rhabdomyolysis: an unusual presentation of Sjogren's syndrome.
Hypokalaemic rhabdomyolysis represents a medical emergency requiring rapid diagnosis and appropriate aetiological treatment. Renal tubular acidosis is a common cause of hypokalemia which can be idiopathic or secondary to systemic disorders such as Sjogren's syndrome. It can remain asymptomatic or manifest with metabolic abnormalities including hypokalemia paralysis, hypocalcaemia and hyperchloremic metabolic acidosis. Rhabdomyolysis presenting with severe hypokalemia as the first manifestation of Sjogren's syndrome is rare. We report a case of a 59-year-old woman who presented to our department with severe weakness of all limbs. Laboratory examination demonstrated hypokalemic rhabdomyolysis caused by distal renal tubular acidosis. Investigations revealed Sjogren's syndrome as the underlying cause of the metabolic disorders.


Management of viral retinitis.
Cytomegalovirus, herpes simplex, and herpes zoster are responsible for the majority of cases of viral retinitis. Herpes zoster also has been strongly incriminated as a causal agent in acute retinal necrosis. Effective chemotherapy exists for retinitis caused by herpes simplex and herpes zoster, along with acute retinal necrosis. Conventional antiviral therapy and immunomodulators are ineffective in the treatment of cytomegalovirus retinitis in patients with acquired immune deficiency disorder. Ganciclovir, a new antiviral agent, has significantly reduced visual morbidity in these patients. Recurrence of the infection is not uncommon while patients are on the drug or when the agent is discontinued, because ganciclovir is virostatic and does not stop viral replication in the retina. The inability to control this viral retinitis using presently available chemotherapy indicates a need to examine other therapeutic modalities.


The Reliability and Validity of a Novel Ankle Isometric Plantar Flexion Strength Test.
Strengthening of ankle plantar flexor muscles is one of the important components in the rehabilitation of many lower limb injuries and disorders. However, there are few simple methods to evaluate ankle plantar flexor strength in clinical situations without using equipment. The purpose of this study was to verify the intraexaminer and interexaminer reliability and the concurrent validity of a novel ankle isometric plantar flexion (PF) strength test (PF break test [PFBT]). Case-control study. The intraexaminer and interexaminer reliabilities of the PFBT were evaluated in 57 orthopedic patients and 30 healthy adults. The range of motion of the ankle joint and the number of heel raises were compared between positive and negative PFBT cases. Then, isometric ankle PF torque (ankle PF of 0°, 15°, and 30°) was compared in knee extension and in the 50° flexion position between positive and negative PFBT cases in 30 healthy adults. The intraexaminer reliability (κ) of the PFBT was .81 to .94, and the interexaminer reliability (κ) was .37 to .74. The PFBT positive group had a significantly smaller range of motion in the ankle joint (P < .05) and a significantly lower number of heel raises (P < .001) than the PFBT negative group in orthopedic patients, but no significant differences in healthy adults. The PFBT positive group had less ankle PF torque than the PFBT negative group at all ankle PF angles (P < .01). The isometric PF torque in the end range of ankle PF in knee extension could predict the results of the PFBT and correctly classified 90.0% of cases (P < .001). The PFBT is considered a simple and valid method to evaluate isometric ankle PF strength in the clinical setting.


[Outcomes of traumatic dental injuries in children].
The aim of the study was to review literature data on incidence and outcomes of traumatic dental injuries (TDI) in pediatric population. A systematic search was conducted using Elibray, Pubmed/Medline, Scopus databases in October 2018. Reference lists were also hand-searched to identify additional literature. The most prevalent complication of TDI is pulp necrosis (PN) which triggers inflammatory root resorption (IRR). PN and IRR are however much more specific for mature permanent teeth. In immature teeth pulp revascularization may occur even after avulsion. Pulpectomy timing is well defined for mature teeth only. It is accepted that pulp extirpation should be performed in the first 10 days after trauma. In immature teeth no criteria exist with pulp electrosensitivity having very low negative prognostic value as drop of pulp sensitivity because of trauma not necessary indicate PN. Follow-up protocol for immature teeth with various TDI would be useful for proper timing of pulpectomy and prevention of IRR.


Correlation of thrombophilia and hypofibrinolysis with pulmonary embolism following total hip arthroplasty: an analysis of genetic factors.
The increased thromboembolic risk associated with total hip arthroplasty is multifactorial. We assessed whether the prevalence of abnormalities shown by newer genetic screening tests for thrombophilia and hypofibrinolysis was higher in patients in whom pulmonary embolism had developed after total hip arthroplasty than it was in matched control patients. Fourteen patients with documented pulmonary embolism after total hip arthroplasty and fourteen matched control patients who had undergone total hip arthroplasty without any clinical indication of thromboembolism were evaluated for risks of thrombophilia and hypofibrinolysis. Functional tests of hemostasis included evaluations of prothrombin time; activated partial thromboplastin time; levels of fibrinogen, serum homocysteine, protein C and S, and antithrombin III; activated protein-C resistance; and dilute Russell viper venom time. Molecular genetic testing was performed for factor-V Leiden, prothrombin promoter G20210A, methylenetetrahydrofolate reductase C677T, plasminogen activator inhibitor-1 4G/4G, and platelet glycoprotein IIb/IIIa A1/A2 or A2/A2 mutations. The total number of genetic thrombophilic abnormalities identified was higher in the pulmonary embolism group (twenty-four abnormalities) than in the control group (fifteen abnormalities). Only patients with pulmonary embolism were found to have heterozygosity or homozygosity for the prothrombin G20210A mutation (four of fourteen patients; p = 0.05 compared with the control group) and a decreased antithrombin-III level (three of thirteen patients; p = 0.10 compared with the control group). Patients with pulmonary embolism were much more likely than control patients to have at least one thrombophilic abnormality: seven of fourteen patients with pulmonary embolism had a low antithrombin-III level or the prothrombin G20210A gene mutation compared with none of the fourteen in the control group (Fisher exact test, p < 0.01). The presence of the prothrombin G20210A gene mutation was significantly correlated with pulmonary embolism (r = 0.41, p = 0.03), as was the presence of least one abnormality (a low antithrombin-III level or the presence of the prothrombin G20210A gene mutation) (r = 0.58, p = 0.001). Genetic thrombophilia and hypofibrinolysis were more frequent in patients who had had pulmonary embolism after total hip arthroplasty than in those who had not. The presence of multiple genetic thrombophilic polymorphisms, particularly prothrombin G20210A and antithrombin III, rather than any single genetic prothrombotic abnormality, appears to signal an increased thromboembolic risk in patients undergoing total hip arthroplasty. Future refinements and availability of these tests will likely allow preoperative identification of patients with an increased genetic predisposition for thromboembolism.


Mechanical effects of electrodes on the vibrations of quartz crystal plates.
A system of approximate first-order equations is extracted from an infinite system of 2-D equations for piezoelectric crystal plates with thickness-graded material properties, which is deduced from the 3-D equations of linear piezoelectricity. These equations are used to study mechanical effects on the thickness-shear (TS), flexural (F), and face-shear (FS) vibrations of an AT-cut quartz plated with two identical electrodes. Dispersion curves are calculated from the present 2-D equations as well as the 3-D equations. The comparison of these curves shows that the agreement is very close for all three frequency branches of TS, F, and FS modes in a range up to the 1.5 times the fundamental TS frequency and for gold and aluminum electrodes with R, the ratio of the mass of the electrodes to that of the plate, equal to 0.05. without introducing any correction factors. In order to assess electrode effects, spectra of omega vs. a/bq (length-to-thickness ratio of the quartz) are computed for plates with gold and aluminum electrodes and different R ratios. And the spectrum of omega vs. R is computed for plates with aluminum electrodes and a given a/bq ratio. For a plate with gold electrodes, the frequencies of predominant TS, F, and FS modes are decreasing as R increases, but the amount of frequency changes for the TS mode is much greater than those for the other two modes. However, for a plate with aluminum electrodes, the frequencies of the TS and FS modes are decreasing, but those of the F modes are increasing as R increases.


The role of coaching in creating cultures of engagement.
This article examines "just in time learning" from a coaching perspective. It explores the organizational and managerial skills that are necessary requirements for coaching to succeed. It considers the benefits of coaching for organizations that are committed to deeply engaging their employees to produce sustainable, high-quality results while increasing their personal and professional satisfaction on the job.


K(3)(Sc(0.875)Nb(0.125))Nb(2)O(9)H(1.75): a new scandium niobate with a unique cage structure.
Potassium scandium niobate hydroxide, K(3)(Sc(0.875)Nb(0.125))Nb(2)O(9)H(1.75), is a new scandium niobate with a unique cage structure. The structure contains two non-equivalent K(+) sites (3m and 6m2 site symmetry), one disordered Sc(3+)/Nb(5+) site (3m site symmetry), one Nb(5+) site (3m site symmetry), two O(2-) sites (m and mm2 site symmetry) and one H(+) site (m site symmetry). Both scandium and niobium have octahedral environments, which combine to form cages around potassium. One K atom lies in a cube-like cage built of seven octahedra, while the other K atom is encapsulated by an eight-membered trigonal face-bicapped prism. The cages form sheets that extend along the ab plane.


Manipulating membrane Fatty Acid compositions of whole plants with tween-Fatty Acid esters.
This paper describes a method for manipulating plant membrane fatty acid compositions without altering growth temperature or other conditions. Tween-fatty acid esters carrying specific fatty acids were synthesized and applied to various organs of plants growing axenically in glass jars. Treated plants incorporated large amounts of exogenous fatty acids into all acylated membrane lipids detected. Fatty acids were taken up by both roots and leaves. Fatty acids applied to roots were found in leaves, while fatty acids applied to leaves appeared in both leaves higher on the plant and in roots, indicating translocation (probably in the phloem). Foliar application was most effective; up to 20% of membrane fatty acids of leaves above the treated leaf and up to 40% of root membrane fatty acids were exogenously derived. Plants which took up exogenous fatty acids changed their patterns of fatty acid synthesis such that ratios of saturated to unsaturated fatty acids remained essentially unaltered. Fatty acid uptake was most extensively studied in soybean (Glycine max [L.] Merr.), but was also observed in other species, including maize (Zea mays L.), mung beans (Vigna radiata L.), peas (Pisum sativum L.), petunia (Petunia hybrida L.) and tomato (Lycopersicon esculentum Mill.). Potential applications of this system include studying internal transport of fatty acids, regulation of fatty acid and membrane synthesis, and influences of membrane fatty acid composition on plant physiology.


Phospholipids in the developing soybean seed.
The distribution of phospholipids in developing soybean seeds [Glycine max (L.) Merr., var. "Chippewa 64," "Harosoy 63," "Wayne," and "Clark 63"] was followed. From 30 to 60 days after flowering expressed as mole per cent of phospholipid phosphorus phosphatidic acid decreased from 14.8 to 9.1; phosphatidylinositol increased from 0 to 9.1; phosphatidylcholine increased from 8.2 to 9.8; phosphatidylethanolamine increased from 5.3 to 8.6; phosphatidylglycerol increased from 3.2 to 4.8; diphosphatidylglycerol increased from 2.7 to 4.1; and N-acylphosphatidylethanolamine decreased from 65.8 to 54.6. However, from 60 days after flowering to maturity, phosphatidic acid decreased to 0; phosphatidylinositol increased roughly 2-fold; phosphatidylcholine increased roughly 4.7-fold; phosphatidylethanolamine increased 3-fold; N-acylphosphatidylethanolamine decreased 11-fold; whereas phosphatidylglycerol and diphosphatidylglycerol remained essentially constant. Percentages of individual phospholipid species were not statistically different between any two varieties at a given time period.Immature soybean cotyledons incubated with (14)C-acetate or -pyruvate demonstrated rapid incorporation into the phospholipid fraction. N-acylphosphatidylethanolamine was found to account for nearly 70% of the total radioactivity incorporated by the total polar lipid fraction and greater than 30% of the total radioactivity added.


Electrochemical studies and differential pulse polarographic analysis of lansoprazole in pharmaceuticals.
The electrochemical reduction of lansoprazole was investigated by cyclic voltammetry and direct current and differential pulse polarography. The reduction potential was -1.32 V vs. Ag/AgCl with a dropping mercury electrode in a supporting electrolyte consisting of phosphate buffer (pH 9.0)-tetramethylammonium iodide (4 + 1). The reversibility of the electrode reaction and the type of limiting current were studied. The temperature coefficient and the diffusion constant were determined. A mechanism for the electrode reaction was proposed. A new simple and sensitive differential pulse polarographic method was also developed for the quantification of lansoprazole. A linear calibration graph was obtained in the range 0.04-11.35 micrograms ml-1. The limit of detection was 0.03 microgram ml-1 and the intra- and inter-day precisions were 0.84-2.32 and 0.72-3.09%, respectively. The developed method was applied to six different commercial pharmaceutical capsule preparations containing enteric-coated granules. The relative standard deviations ranged from 1.36 to 2.85%. Recovery studies for the accuracy of the method were performed by adding a synthetic mixture to known amounts of lansoprazole and the mean recovery was 100.45%. The data obtained from commercial preparations were compared with those from a published spectrophotometric method. No difference was found statistically.


Human fetal and adult bone marrow-derived mesenchymal stem cells use different signaling pathways for the initiation of chondrogenesis.
Cartilage injuries and osteoarthritis are leading causes of disability in developed countries. The regeneration of damaged articular cartilage using cell transplantation or tissue engineering holds much promise but requires the identification of an appropriate cell source with a high proliferative propensity and consistent chondrogenic capacity. Human fetal mesenchymal stem cells (MSCs) have been isolated from a range of perinatal tissues, including first-trimester bone marrow, and have demonstrated enhanced expansion and differentiation potential. However, their ability to form mature chondrocytes for use in cartilage tissue engineering has not been clearly established. Here, we compare the chondrogenic potential of human MSCs isolated from fetal and adult bone marrow and show distinct differences in their responsiveness to specific growth factors. Transforming growth factor beta 3 (TGFβ3) induced chondrogenesis in adult but not fetal MSCs. In contrast, bone morphogenetic protein 2 (BMP2) induced chondrogenesis in fetal but not adult MSCs. When fetal MSCs co-stimulated with BMP2 and TGFβ3 were used for cartilage tissue engineering, they generated tissue with type II collagen and proteoglycan content comparable to adult MSCs treated with TGFβ3 alone. Investigation of the TGFβ/BMP signaling pathway showed that TGFβ3 induced phosphorylation of SMAD3 in adult but not fetal MSCs. These findings demonstrate that the initiation of chondrogenesis is modulated by distinct signaling mechanisms in fetal and adult MSCs. This study establishes the feasibility of using fetal MSCs in cartilage repair applications and proposes their potential as an in vitro system for modeling chondrogenic differentiation and skeletal development studies.


Design of withdrawal-weighted SAW filters.
This paper presents a new design algorithm for a withdrawal-weighted surface acoustic wave (SAW) transversal filter. The proposed algorithm is based on the effective transmission loss theory and a delta function model of a SAW transversal filter. The design process consists of three steps, which eventually determine eight geometrical design parameters for the filter in order to satisfy given performance specifications. First, the number of fingers in the input and output interdigital transducers (IDTs), plus their geometrical sizes is determined using the insertion loss specification. Second, the number and positions of the polarity reverses in the output IDT are determined using the bandwidth and ripple specifications. Third, the number and position for withdrawing and switching specific fingers in the output IDT and attached electrode area are determined to achieve the desired sidelobe level. The efficiency of the technique is illustrated using a sample design of an IF filter consisting of a uniform input IDT and withdrawal-weighted output IDT. The proposed algorithm is distinct from conventional techniques in that it can optimize the structural geometry of a withdrawal-weighted SAW filter in a direct manner by considering all the performance specifications simultaneously.


The treatment of idiopathic and diabetic gastroparesis with acute intravenous and chronic oral erythromycin.
The objective of this study was to investigate the effects of intravenous erythromycin and chronic oral dosing of erythromycin on gastric emptying in patients with idiopathic or diabetic gastroparesis. Symptoms were assessed on oral dosing and during long-term follow-up in an ambulatory setting at a University referral center. Fourteen patients (10 idiopathic and four diabetic gastroparesis) were studied. Four patients left during the 4-wk study; two due to rash, one with cramps and vomiting on erythromycin, and one due to other medical problems. Ten patients completed the 4-wk study and commenced long-term therapy. Five of these patients experienced enough symptomatic relief to continue oral erythromycin long-term, being followed for an average period of 8.4 months. After initial documentation of delayed gastric emptying, patients received 6 mg/kg intravenous erythromycin lactobionate before a second gastric emptying study. Erythromycin base was then given orally at a dose of 500 mg tid-ac and qhs, with a final gastric emptying study performed after 4 wk. During long-term follow-up, erythromycin dosage was adjusted to minimize symptoms. Radionuclide-labeled gastric emptying of a solid meal was studied at baseline, following intravenous erythromycin, and after 4 wk of oral treatment with erythromycin. Symptom scores were assessed at baseline, at 4 wk, and then at 8-wk intervals. The percentage of the solid meal retained in the stomach at 2 h decreased from 85% +/- 11% (SD) at baseline to 20% +/- 29% following intravenous erythromycin (p < 0.001), and to 48% +/- 21% after 4 wk of oral therapy (p < 0.01 vs. baseline). There was a reduction in total symptom scores and a significant reduction in global assessment scores (p = 0.03). We conclude that erythromycin has a strong gastric prokinetic effect in both idiopathic and diabetic gastroparesis, and may represent a useful new therapeutic approach to this problem.


Modification of PSf/SPSf Blended Porous Support for Improving the Reverse Osmosis Performance of Aromatic Polyamide Thin Film Composite Membranes.
In this study, modification of polysulfone (PSf)/sulfonated polysulfone (SPSf) blended porous ultrafiltration (UF) support membranes was proposed to improve the reverse osmosis (RO) performance of aromatic polyamide thin film composite (TFC) membranes. The synergistic effects of solvent, polymer concentration, and SPSf doping content in the casting solution were investigated systematically on the properties of both porous supports and RO membranes. SEM and AFM were combined to characterize the physical properties of the membranes, including surface pore natures (porosity, mean pore radius), surface morphology, and section structure. A contact angle meter was used to analyze the membrane surface hydrophilicity. Permeate experiments were carried out to evaluate the separation performances of the membranes. The results showed that the PSf/SPSf blended porous support modified with 6 wt % SPSf in the presence of DMF and 14 wt % PSf had higher porosity, bigger pore diameter, and a rougher and more hydrophilic surface, which was more beneficial for fabrication of a polyamide TFC membrane with favorable reverse osmosis performance. This modified PSf/SPSf support endowed the RO membrane with a more hydrophilic surface, higher water flux (about 1.2 times), as well as a slight increase in salt rejection than the nascent PSf support. In a word, this work provides a new facile method to improve the separation performance of polyamide TFC RO membranes via the modification of conventional PSf porous support with SPSf.


Haine v. Leves, 7 April 1987.
The Court ruled that where pupils coming from within a local community were segregated into single sex schools with differences in their curricula that resulted in a variation in educational qualification such that the school qualification of boys for tertiary education and employment was greater than that of girls, the Equal Opportunity Tribunal could conclude that the girls were being discriminated against under Section 31A of the Anti-Discrimination Act 1977.


Gastrointestinal paracoccidioidomycosis: an overview.
Paracoccidioidomycosis is the most prevalent mycosis in Latin America. Although the lungs are the primary site of infection, physicians often see patients because of disseminated disease. Imported paracoccidioidomycosis has been described in different regions of the world in patients who lived in endemic areas. Gastrointestinal disease owing to P. brasiliensis is rarely recognized in life because of nonspecific clinical manifestations. Gastrointestinal disease can present as part of progressive dissemination of infection or as a result of local complications from a silent healing process. This review will summarize the salient features of gastrointestinal paracoccidioidomycosis.


Dramatic response to low-dose erlotinib of epidermal growth factor receptor mutation-positive recurrent non-small cell lung cancer after severe cutaneous toxicity.
Erlotinib is increasingly being used for the treatment of non-small cell lung cancer. The recommended dose is 150 mg/day and no efficacy data is available for lower doses. We describe a case of dramatic tumor response to 50 mg erlotinib in a patient with EGFR mutation positive NSCLC who developed a severe rash on full dose erlotinib. Rash is known to correlate with response and survival in patients treated with erlotinib. Our case suggests that in the presence of rash, dose reductions to "subtherapeutic" levels remain effective and may prevent unnecessary early treatment termination.


Increased production of human granulocyte-macrophage colony stimulating factor (hGM-CSF) by the addition of stabilizing polymer in plant suspension cultures.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a glycoprotein that stimulates the production of granulocytes, macrophages, and white blood cells. Secretion of human GM-CSF from cell suspension cultures of genetically modified tobacco has been facilitated using natural mammalian leader sequences. At the mid-exponential growth phase (day 4 after the initiation of cell suspension culture), GM-CSF was detected in the medium at a maximum concentration of 180 microg l(-1). However, the secreted GM-CSF was unstable in the medium, and rapidly degraded after day 5. In order to stabilize the secreted GM-CSF, three stabilizing polymers were tested, polyethylene glycol, polyvinylpyrrolidone and gelatin. Gelatin was the most effective in stabilizing the secreted GM-CSF. Following the addition of 5% (w/v) gelatin, the maximum GM-CSF concentration reached 783 microg l(-1), a 4.6-fold increase over control.