[Laparoscopic adjustable gastric banding for morbid obesity: clinical and radiographic follow-up].
To evaluate the role of imaging for follow-up after treatment of morbid obesity by laparoscopic adjustable gastric banding (LAGB). Since 1996, more than 1,000 patients underwent gastric banding using 5 different types of devices. Our experience is based on a retrospective study (from September 1996 to September 2002) concerning 663 consecutive patients who underwent LAGB: 114 Lapband system (LB) and 549 Swedish adjustable gastric banding (SAGB). Upper gastrointestinal series were performed within 24-48 hours after surgery in all patients. Radiological examination was also used to detect complications and to adjust gastric band. The five types of gastric band are easily identified on plain films. Early and late complications are illustrated: pouch dilatation, slippage, band migration, rotation of the port, and system disconnection. Radiological criteria for adjustment of gastric band are explained on the basis of barium studies performed before and after any modification of the stoma size. In patients treated with LAGB for morbid obesity, radiology plays an important role in evaluating early and late complications.


Effect of substrate interferences from high-density polyethylene on association of simulated ignitable liquid residues with the corresponding liquid.
The effect of substrate interferences from high-density polyethylene (HDPE) on the ability to associate an ignitable liquid residue with the corresponding liquid standard, using statistical procedures, is demonstrated. Gasoline, kerosene, and lighter fluid, at three different evaporation levels, were spiked onto HDPE and subsequently burned to generate simulated ignitable liquid residues (ILRs). Samples were extracted using a passive headspace procedure and analyzed by gas chromatography-mass spectrometry. The total ion chromatograms were subjected to data pretreatment procedures prior to principal components analysis and Pearson product moment correlation. Using the combination of these statistical procedures, simulated ILRs were successfully associated with the corresponding liquid type, despite the presence of compounds inherent to the HDPE substrate, as well as those resulting from pyrolysis of the substrate.


Isolation of Campylobacter spp. from semen samples of commercial broiler breeder roosters.
Pooled semen samples from 12 groups of mature commercial broiler breeder roosters were analyzed for the presence of Campylobacter. Each of the 12 groups was comprised of eight individuals and was sampled weekly for five consecutive weeks. Once a day, roosters were allowed to have a restricted amount of feed after the semen samples were collected by abdominal massage. This feeding schedule reduced the amount of fecal contamination in and around the vent as well as in the semen sample. For replications 1, 2, and 3, the numbers of Campylobacter-positive groups were 8, 5, and 5, respectively, out of 12. For replications 4 and 5, 6 of 8 and 6 of 11 groups were positive, respectively. Only two groups were positive for Campylobacter at all sampling times, two groups were negative each time, and eight groups produced variable results. Also, fecal droppings, external swabs of the genitalia, and semen samples were taken from individual roosters between 49 to 65 wk of age. Of the total 275 semen samples collected, 9.47% contained naturally occurring Campylobacter, whereas 9.6% of 114 fecal droppings and 7.9% of the 114 genital swabs were positive. Levels of the organism present in the fecal samples ranged from 1.0 to 4.2 log colony-forming units (CFU)/g with an average of 2.9 log CFU/g feces. For semen, the levels ranged from as low as enrichment recovery only to as high as 3.1 log CFU/ml of semen with an average of 1.2 log CFU/ml. For swabs of genitalia, the levels of Campylobacter were so low that recovery was achieved only through enrichment. These data suggest that rooster semen may serve as a vehicle for transmission of Campylobacter to the reproductive tract of the hen and subsequently to the fertile egg.


Regulation of Btk function by a major autophosphorylation site within the SH3 domain.
Bruton's tyrosine kinase (Btk) plays a crucial role in B cell development. Overexpression of Btk with a Src family kinase increases tyrosine phosphorylation and catalytic activity of Btk. This occurs by transphosphorylation at Y551 in the Btk catalytic domain and the enhancement of Btk autophosphorylation at a second site. A gain-of-function mutant called Btk* containing E41 to K change within the pleckstrin homology domain induces fibroblast transformation. Btk* enhances the transphosphorylation of Y551 by endogenous Src family tyrosine kinases and autophosphorylation at the second site. We mapped the major Btk autophosphorylation site to Y223 within the SH3 domain. Mutation of Y223 to F blocks Btk autophosphorylation and dramatically potentiates the transforming activity of Btk* in fibroblasts. The location of Y223 in a potential ligand-binding pocket suggests that autophosphorylation regulates SH3-mediated signaling by Btk.


American Society of Emergency Radiology Multicenter Blunt Splenic Trauma Study: CT and Clinical Findings.
Background Treatment of blunt splenic trauma (BST) continues to evolve with improved imaging for detection of splenic vascular injuries. Purpose To report on treatments for BST from 11 trauma centers, the frequency and clinical impact of splenic vascular injuries, and factors influencing treatment. Materials and Methods Patients were retrospectively identified as having BST between January 2011 and December 2018, and clinical, imaging, and outcome data were recorded. Patient data were summarized descriptively, both overall and stratified by initial treatment received (nonoperative management [NOM], angiography, or surgery). Regression analyses were used to examine the primary outcomes of interest, which were initial treatment received and length of stay (LOS). Results This study evaluated 1373 patients (mean age, 42 years ± 18; 845 men). Initial treatments included NOM in 849 patients, interventional radiology (IR) in 240 patients, and surgery in 284 patients. Rates from CT reporting were 22% (304 of 1373) for active splenic hemorrhage (ASH) and 20% (276 of 1373) for contained vascular injury (CVI). IR management of high-grade injuries increased 15.6%, from 28.6% (eight of 28) to 44.2% (57 of 129) (2011-2012 vs 2017-2018). Patients who were treated invasively had a higher injury severity score (odds ratio [OR], 1.04; 95% CI: 1.02, 1.05; P < .001), lower temperature (OR, 0.97; 95% CI: 0.97, 1.00; P = .03), and a lower hematocrit (OR, 0.96; 95% CI: 0.93, 0.99; P = .003) and were more likely to show ASH (OR, 8.05; 95% CI: 5.35, 12.26; P < .001) or CVI (OR, 2.70; 95% CI: 1.64, 4.44; P < .001) on CT images, have spleen-only injures (OR, 2.35; 95% CI: 1.45, 3.8; P < .001), and have been administered blood product for fewer than 24 hours (OR, 2.35; 95% CI: 1.58, 3.51; P < .001) compared with those chosen for NOM, after adjusting for key demographic and clinical variables. After adjustment, factors associated with a shorter LOS were female sex (OR, 0.84; 95% CI: 0.73, 0.96; P = .009), spleen-only injury (OR, 0.72; 95% CI: 0.6, 0.86; P < .001), higher admission hematocrit (OR, 0.98; 95% CI: 0.6, 0.86; P < .001), and presence of ASH at CT (OR, 0.74; 95% CI: 0.62, 0.88; P < .001). Conclusion Contained vascular injury and active splenic hemorrhage (ASH) were frequently reported, and rates of interventional radiologic management increased during the study period. ASH was associated with a shorter length of stay, and patients with ASH had eight times the odds of undergoing invasive treatment compared with undergoing nonoperative management. © RSNA, 2021 See also the editorial by Patlas in this issue.


Hereditary deafness and phenotyping in humans.
Hereditary deafness has proved to be extremely heterogeneous genetically with more than 40 genes mapped or cloned for non-syndromic dominant deafness and 30 for autosomal recessive non-syndromic deafness. In spite of significant advances in the understanding of the molecular basis of hearing loss, identifying the precise genetic cause in an individual remains difficult. Consequently, it is important to exclude syndromic causes of deafness by clinical and special investigation and to use all available phenotypic clues for diagnosis. A clinical approach to the aetiological investigation of individuals with hearing loss is suggested, which includes ophthalmology review, renal ultrasound scan and neuro-imaging of petrous temporal bone. Molecular screening of the GJB2 (Connexin 26) gene should be undertaken in all cases of non-syndromic deafness where the cause cannot be identified, since it is a common cause of recessive hearing impairment, the screening is straightforward, and the phenotype unremarkable. By the same token, mitochondrial inheritance of hearing loss should be considered in all multigeneration families, particularly if there is a history of exposure to aminoglycoside antibiotics, since genetic testing of specific mitochondrial genes is technically feasible. Most forms of non-syndromic autosomal recessive hearing impairment cause a prelingual hearing loss, which is generally severe to profound and not associated with abnormal radiology. Exceptions to this include DFNB2 (MYO7A), DFNB8/10 (TMPRSS3) and DFNB16 (STRC) where age of onset may sometimes be later on in childhood, DFNB4 (SLC26A4) where there may be dilated vestibular aqueducts and endolymphatic sacs, and DFNB9 (OTOF) where there may also be an associated auditory neuropathy. Unusual phenotypes in autosomal dominant forms of deafness, include low frequency hearing loss in DFNA1 (HDIA1) and DFNA6/14/38 (WFS1), mid-frequency hearing loss in DFNA8/12 (TECTA), DFNA13 (COL11A2) and vestibular symptoms and signs in DFNA9 (COCH) and sometimes in DFNA11 (MYO7A). Continued clinical evaluation of types and course of hearing loss and correlation with genotype is important for the intelligent application of molecular testing in the next few years.


Thyrotropin-releasing hormone (TRH) and phorbol myristate acetate decrease TRH receptor messenger RNA in rat pituitary GH3 cells: evidence that protein kinase-C mediates the TRH effect.
In a previous report we showed that TRH-induced down-regulation of the density of its receptors (TRH-Rs) on rat pituitary tumor (GH3) cells was preceded by a decrease in the activity of the mRNA for the TRH-R, as assayed in Xenopus oocytes. Here we report the effects of TRH, elevation of cytoplasmic free Ca2+ concentration, phorbol myristate acetate (PMA), and H-7 [1-(5-isoquinolinesulfonyl)2-methylpiperazine dihydrochloride], an inhibitor of protein kinases, on the levels of TRH-R mRNA, which were measured by Northern analysis and in nuclease protection assays using probes made from mouse pituitary TRH-R cDNA, in GH3 cells. These agents were studied to gain insight into the mechanism of the TRH effect, because signal transduction by TRH involves generation of inositol 1,4,5-trisphosphate and elevation of cytoplasmic free Ca2+ concentration, which leads to activation of Ca2+/calmodulin-dependent protein kinase, and of 1,2-diacylglycerol, which leads to activation of protein kinase-C. TRH (1 microM TRH, a maximally effective dose) caused a marked transient decrease in TRH-R mRNA that attained a nadir of 20-45% of control by 3-6 h, increased after 9 h, but was still below control levels after 24 h. Elevation of the cytoplasmic free Ca2+ concentration had no effect on TRH-R mRNA. A maximally effective dose of PMA (1 microM) caused decreases in TRH-R mRNA that were similar in magnitude and time course to those induced by 1 microM TRH. H-7 (20 microM) blocked the effects of TRH and PMA to lower TRH-R mRNA to similar extents.(ABSTRACT TRUNCATED AT 250 WORDS)


Ubiquitin: a small protein folding paradigm.
For the past twenty years, the small, 76-residue protein ubiquitin has been used as a model system to study protein structure, stability, folding and dynamics. In this time, ubiquitin has become a paradigm for both the experimental and computational folding communities. The folding energy landscape is now uniquely characterised with a plethora of information available on not only the native and denatured states, but partially structured states, alternatively folded states and locally unfolded states, in addition to the transition state ensemble. This Perspective focuses on the experimental characterisation of ubiquitin using a comprehensive range of biophysical techniques.


Association of Lithium Use and a Higher Serum Concentration of Lithium With the Risk of Declining Renal Function in Older Adults: A Population-Based Cohort Study.
Lithium is an important mood disorder treatment; however, the renal risks of its use in older adults are unclear. We wished to determine in older adults (1) whether lithium is associated with increased risk of renal decline compared to valproate and (2) whether this association differs with higher vs lower baseline serum lithium concentrations. We conducted a population-based cohort study using linked health care databases (Ontario, Canada). The cohort consisted of older adults (mean age 71 years) accrued 2007-2015; 3,113 lithium users were propensity-score matched 1:1 to 3,113 valproate users. Users with higher (> 0.7 mmol/L) or lower concentration of serum lithium were further examined. The primary outcome was ≥ 30% loss in estimated glomerular filtration rate from baseline. Matched lithium users and valproate users demonstrated similar indicators of baseline health over a median (maximum) follow-up of 3.1 (8.3) years. Lithium was associated with increased risk of renal function loss compared to valproate (674/3,113 [21.7%] vs 584/3,113 [18.8%]; 6.5 vs 5.7 events per 100 person years; hazard ratio = 1.14 [95% CI = 1.02-1.27]). When baseline serum lithium concentrations were > 0.7 mmol/L, the risk of renal decline compared to valproate use was 1.26 (95% CI = 1.06-1.49); when baseline lithium concentrations were ≤ 0.7 mmol/L, the risk was 1.06 (95% CI = 0.92-1.22). In older adults, lithium use is associated with a statistically significant increased risk of renal decline compared to valproate use, although the decline is less than previously reported. Further studies should confirm whether this effect is primarily in patients with higher serum lithium concentrations.


Recurrent Hypothenar Hammer Syndrome: A Case Report.
Hypothenar hammer syndrome (HHS) is a rare cause of digital ischemia and pain caused from repetitive trauma to the palm. Often related to occupational practices, thrombosis and embolization can occur. Treatment is often surgical and involves excision with or without reconstruction. We describe a 55 year-old, male pipe fitter previously diagnosed and treated for HHS with excision and repair using a reversed interpositional vein graft in the mid-1980's. He continued to work in the profession, which he regularly used his palm as a hammer and returned approximately 30 years later with recurrent symptoms of cold intolerance and pain. Angiography confirmed occlusion of the ulnar artery with emboli present distally. The patient was again treated with excision and reconstruction. HHS is an uncommon cause of digital ischemia. Its recurrence is even more rare. To our knowledge, this is the first described case of diagnosed and treated recurrent HHS.


Wound healing after laser skin resurfacing: the effect of a silver sulfadiazine-hyaluronic acid-containing cream under an occlusive dressing.
Occlusive dressings promote wound healing after laser skin resurfacing. Our goal was to evaluate whether a cream containing hyaluronic acid-silver sulfadiazine could improve this process. Ten guinea pigs received laser resurfacing on the skin of their backs. Polyurethane foam film adhesive dressing was applied. A cream containing hyaluronic acid-silver sulfadiazine was applied under the dressing over half of the wound. Skin biopsies were taken at days 2, 4, 7 and 9 and examined by a pathologist blinded to the study. Re-epithelialization appeared to occur faster in the cream-treated areas, together with a lower level of acute inflammation in the early phase of the healing process. The cream containing silver sulfadiazine/hyaluronic acid seems to improve wound healing after laser skin resurfacing in guinea pigs. The clinical application of this finding on humans should be assessed.


Colonization of Bacillus spp. on seeds and in plant rhizoplane.
Seed coating, dipping and Scanning Electron Microscopy (SEM) were employed to study bacterial and fungal colonization of the seeds and rhizoplane of maize (Zea mays L.) during the early stages of growth. Isolation of Bacillus spp. entailed screening soil bacteria with potential growth stimulation and plant pathogen suppressive abilities isolated from the rhizospheres and rhizoplanes of vegetable crops. The bacterial colonization of the spermosphere was 90%. When the coated seeds were fully germinated, bacteria moved to the emerging radicle. Virtually no bacteria occurred on the root tip both for the treated and untreated. However, colonization was 20% in the basal portion of the roots close to the seed-root junction. SEM observations showed that the bacterial cells were arranged linearly and laterally on the growing root axis. This phenomenon was more noticeable in the seedlings dipped in the bacterial culture on the 3rd day after germination. The results indicate that attachment to the seed coat and the rhizoplane by the plant growth-promoting rhizobacterium (PGPR) is an important factor in the successful colonization of the rhizoplane. The significance of the work is to ascertain that the inoculated Bacillus spp. adhered to and established in the rhizoplane of maize. It can therefore be used as a PGPR and as a biocontrol agent.


The Long-term Outcomes of Glaucoma Drainage Device in Pediatric Glaucoma.
To evaluate the long-term outcomes and safety of glaucoma drainage device (GDD) in pediatric patients. Retrospective, noncomparative study including all patients below 18 years old who underwent Baerveldt or Molteno GDD implantation by a single surgeon. Mitomycin-C was used in most cases. Success was defined as postoperative intraocular pressure (IOP) between 6 and 22 mm Hg and a 20% reduction in IOP. Sixty-nine eyes of 52 patients were analyzed. Mean follow-up length was 45.7±25.2 months (range, 6 to 101 mo). At last postoperative visit, mean IOP and median number of antiglaucoma medications had been significantly reduced from baseline. Cumulative probability of qualified success was 95.6% at 1 year and declined to 71.3% at 5 years and 39.7% at 8 years. Multivariate analysis showed that non-white patients and previous history of cyclophotocoagulation had higher risks of failure at 5 years. Hypotony was the most common complication (39.1%) in the first 6 months postoperatively. Bleb encapsulation occurred in 16.4% of patients. Endophthalmitis occurred in 5.8% of cases and necessitated removal of the GDD. GDD surgery can work adequately in children in the long term. A relatively high complications rate should be expected, but in most cases these can be managed successfully. Early recognition of complications is necessary to ensure a good outcome.


The practice of dialysis in the developing countries.
There are few organized data on the practice of dialysis in developing countries, mostly because of a lack of renal registries. The economic, human, and technical resources required for long-term dialysis make it a major economical and political challenge. Most countries do not have not well-formed policies for treatment of end-stage renal disease. The dialysis facilities are grossly inadequate, and there are no reimbursement schemes to fund long-term dialysis. Hemodialysis units are mostly in the private sector and consist of small numbers of refurbished machines. Water treatment is frequently suboptimal, and this problem has led to a number of complications. Hepatitis B and C infections are widespread in dialysis units. Continuous ambulatory peritoneal dialysis (CAPD) seems to be the ideal dialysis option for patients living in remote areas, but high costs preclude its widespread usage. The Mexican experience suggests that even after it becomes affordable, CAPD needs to be used judiciously. Inadequate dialysis, infections, and malnutrition account for the high mortality among the dialysis population in developing countries. Acute peritoneal dialysis using rigid stylet-based catheters is the main form of dialysis in remote areas. Pediatric dialysis units are almost nonexistent. A significant lack of resources exists in developing countries, making the provision of highly technical and expensive care like dialysis a challenge.


Area MST and heading perception in macaque monkeys.
The macaque medial superior temporal area (MST) is proposed to be specialized for analyzing complex 'optic flow' information. Such space-varying motion patterns provide a rich source of information about self motion, scene structure and object shape. We report the performance of rhesus macaques on a two-alternative 'heading' task, in which they reported whether horizontally varying, simulated trajectories were to left or right of center. Monkeys were sensitive to small heading angles; thresholds averaged 1.5-3 degrees. Heading estimates were stable in the face of changing stimulus location and smooth pursuit eye movements. In addition, we tested the role of area MST in heading judgements by electrically activating columns of neurons in this area while the monkeys performed the heading task. Activation of MST frequently affected performance, usually causing choice biases. These induced biases were often large and usually concordant with the preference of the neurons being activated. In addition, the induced biases were often larger in the presence of smooth pursuit eye movements. These results favor the hypothesis that MST is involved in recovering self-motion direction from optic flow cues and in the process by which heading perception is compensated for ongoing eye movements.


Modified plant plasma membrane H(+)-ATPase with improved transport coupling efficiency identified by mutant selection in yeast.
Transport across the plasma membrane is driven by an electrochemical gradient of H+ ions generated by the plasma membrane proton pump (H(+)-ATPase). Random mutants of Arabidopsis H(+)-ATPase AHA1 were isolated by phenotypic selection of growth of transformed yeast cells in the absence of endogenous yeast H(+)-ATPase (PMA1). A Trp-874-Leu substitution as well as a Trp-874 to Lys-935 deletion in the hydrophilic C-terminal domain of AHA1 conferred growth of yeast cells devoid of PMA1. A Trp-874-Phe substitution in AHA1 was produced gy site-directed mutagenesis. The modified enzymes hydrolyzed ATP at 200-500% of wild-type level, had a sixfold increase in affinity for ATP (from 1.2 to 0.2 mM; pH 7.0), and had the acidic pH optimum shifted towards neutral pH. AHA1 did not contribute significantly to H+ extrusion by transformed yeast cells. The different specifies of aha1, however, displayed marked differences in initial rates of net H+ extrusion and in their ability to sustain an electrochemical H+ gradient. These results provide evidence that Trp-874 plays an important role in auto-inhibition of the plant H(+)-ATPase and may be involved in controlling the degree of coupling between ATP hydrolysis and H+ pumping. Finally, these results demonstrate the usefulness of yeast as a generalized screening tool for isolating regulatory mutants of plant transporters.


Rational design of the carbon doping of hexagonal boron nitride for oxygen activation and oxidative desulfurization.
The doping of hexagonal boron nitride (h-BN) materials has a great influence on their catalytic oxidation performance, but the mechanism of doping has still not been studied in depth to date. Herein, carbon-doped h-BN materials were systematically investigated. Three different doping modes were established, and their performance for O2 activation and oxidative desulfurization (ODS) were explored. DFT calculation showed that not all carbon-doped forms of the h-BN surface could activate O2. Specifically, two of the dispersed doping forms could activate O2, whereas the π-doping form could not activate O2, and thus the ODS reaction could not be carried out. For the two dispersed doping forms, the O2 adsorption on the CB-doped h-BN surface (C-doped in B position) was too strong, which hampered its ODS performance; whereas the O2 adsorption on the CN-doped h-BN surface (C-doped in the N position) was moderate, resulting in good catalytic activity for ODS. Therefore, to design effective BN-based catalysts by C doping, it is suggested that the C dopant should be dispersed to substitute the N atom of h-BN, and CN-doped h-BN will play an important role in ODS with moderate O2 activation. This study can be used as a reference for the catalytic oxidation of boron nitride.


mRNA decay rates in late-developing Dictyostelium discoideum cells are heterogeneous, and cyclic AMP does not act directly to stabilize cell-type-specific mRNAs.
We reevaluated the use of 32PO4 pulse-chases for analyzing mRNA decay rates in late-developing Dictyostelium cells. We found that completely effective PO4 chases could not be obtained in developing cells and that, as a consequence, the decay rates exhibited by some mRNAs were influenced by the rates at which they were transcribed. In developing cells disaggregated in the presence of cyclic AMP, the poly(A)+ mRNA population turned over with an apparent half-life of 4 h, individual mRNA decay rates were heterogeneous, and some prestalk and prespore mRNAs appeared to decay with biphasic kinetics. In cells disaggregated in the absence of cyclic AMP, all prestalk and prespore mRNAs decayed with biphasic kinetics. During the first 1 to 1.5 h after disaggregation in the absence of cyclic AMP, the cell-type-specific mRNAs were selectively degraded, decaying with half-lives of 20 to 30 min; thereafter, the residual prestalk and prespore mRNA molecules decayed at rates that were similar to those measured in the presence of cyclic AMP. This short-term labilization of cell-type-specific mRNAs was observed even for those species not requiring cyclic AMP for their accumulation in developing cells. The observation that cell-type specific mRNAs can decay at similar rates in disaggregated cells with or without cyclic AMP indicates that this compound does not act directly to stabilize prestalk and prespore mRNAs during development and that its primary role in the maintenance of cyclic-AMP-dependent mRNAs is likely to be transcriptional.


OutbreakFinder: a visualization tool for rapid detection of bacterial strain clusters based on optimized multidimensional scaling.
With the evolution of next generation sequencing (NGS) technologies, whole-genome sequencing of bacterial isolates is increasingly employed to investigate epidemiology. Phylogenetic analysis is the common method for using NGS data, usually for comparing closeness between bacterial isolates to detect probable outbreaks. However, interpreting a phylogenetic tree is not easy without training in evolutionary biology. Therefore, developing an easy-to-use tool that can assist people who wish to use a phylogenetic tree to investigate epidemiological relatedness is crucial. In this paper, we present a tool called OutbreakFinder that can accept a distance matrix in csv format; alignment files from Lyve-SET, Parsnp, and ClustalOmega; and a tree file in Newick format as inputs to compute a cluster-labeled two-dimensional plot based on multidimensional-scaling dimension reduction coupled with affinity propagation clustering. OutbreakFinder can be downloaded for free at https://github.com/skypes/Newton-method-MDS.


Molecular design and evaluation of biodegradable polymers using a statistical approach.
The challenging paradigm of bioresorbable polymers, whether in drug delivery or tissue engineering, states that a fine-tuning of the interplay between polymer properties (e.g., thermal, degradation), and the degree of cell/tissue replacement and remodeling is required. In this paper we describe how changes in the molecular architecture of a series of terpolymers allow for the design of polymers with varying glass transition temperatures and degradation rates. The effect of each component in the terpolymers is quantified via design of experiment (DoE) analysis. A linear relationship between terpolymer components and resulting Tg (ranging from 34 to 86 °C) was demonstrated. These findings were further supported with mass-per-flexible-bond analysis. The effect of terpolymer composition on the in vitro degradation of these polymers revealed molecular weight loss ranging from 20 to 60 % within the first 24 h. DoE modeling further illustrated the linear (but reciprocal) relationship between structure elements and degradation for these polymers. Thus, we describe a simple technique to provide insight into the structure property relationship of degradable polymers, specifically applied using a new family of tyrosine-derived polycarbonates, allowing for optimal design of materials for specific applications.


How effective is a brief educational intervention on prescribing first-line antibiotics in acute cystitis? A quasi-experimental study among general practitioners in Croatia.
To assess the effectiveness of a brief educational intervention on prescribing first-line antibiotics in acute cystitis. This quasi-experimental before-after study was conducted over a period of eight months. We collected prescribing data related to urinary tract infections four months before the educational intervention and four months after it. Aggregate data on office visits, diagnoses, and issued prescriptions were collected from each practice's electronic medical records based on monthly reports. Overall, 3581 prescriptions were issued: 1717 before and 1864 after the intervention. The total number of prescriptions increased by 8.5%. The use of first-line antibiotics increased by 21.2%, the use of fluoroquinolones decreased by 6.6%, while the use of beta-lactams remained unchanged. After the intervention, nitrofurantoin was the most prescribed first-line antibiotic. The proportion of women who were prescribed first-line antibiotic did not reach the acceptable range (80%-100%) according to the European Surveillance of Antimicrobial Consumption quality indicators. The proportion of fluoroquinolones (17.9%) use was well above the acceptable range (0%-5%). A brief educational intervention proved to be a useful method in adopting better prescribing habits. Of particular importance is the considerable increase in the use of nitrofurantoin due to its reliable efficacy against multidrug-resistant urinary pathogens.


Anatomo-pathological studies on alcoholic dementia: a review and up to date research.
Neuropathological studies of cerebral disorders in alcoholics which started by means of macroscopic observation have issued many important articles until now. However, we can not yet stretch out the essential core of alcoholic dementia. Plenty of animal experiments also suggest some possibility fo neurotoxicity by ethanol but do not offer a definitive resolution. Moreover, there is the strict criticism concerning neuropathological evidence on alcoholic dementia. Nevertheless, we know that there are some alcoholics who have no evidence of Wernicke-Korsakoff syndrome, but manifest persistent cerebral impairment after long-term heavy drinking. Under such circumstances it might be necessary to consider and study cerebral disorders in alcoholics, particularly relating to subcortical lesions. Pathomorphological investigations in our laboratory have put forward some significant findings.


Regulation of Nociceptive Plasticity Threshold and DARPP-32 Phosphorylation in Spinal Dorsal Horn Neurons by Convergent Dopamine and Glutamate Inputs.
Dopamine can influence NMDA receptor function and regulate glutamate-triggered long-term changes in synaptic strength in several regions of the CNS. In spinal cord, regulation of the threshold of synaptic plasticity may determine the proneness to undergo sensitization and hyperresponsiveness to noxious input. In the current study, we increased endogenous dopamine levels in the dorsal horn by using re-uptake inhibitor GBR 12935. During the so-induced hyperdopaminergic transmission, conditioning low-frequency (1 Hz) stimulation (LFS) to the sciatic nerve induced long-term potentiation (LTP) of C-fiber-evoked potentials in dorsal horn neurons. The magnitude of LTP was attenuated by blockade of either dopamine D1-like receptors (D1LRs) by with SCH 23390 or NMDA receptor subunit NR2B with antagonist Ro25-6981. Conditioning LFS during GBR 12935 administration increased phosphorylation of dopamine- and cAMP-regulated phosphoprotein of Mr 32kDa (DARPP-32) at threonine 34 residue in synaptosomal (P3) fraction of dorsal horn homogenates, as assessed by Western blot analysis, which was partially prevented by NR2B blockade prior to conditioning stimulation. Conditioning LFS also was followed by higher co-localization of phosphorylated form of NR2B at tyrosine 1472 and pDARPP-32Thr34- with postsynaptic marker PSD-95 in transverse L5 dorsal horn sections. Such increase could be significantly attenuated by D1LR blockade with SCH 23390. The current results support that coincidental endogenous recruitment of D1LRs and NR2B in dorsal horn synapses plays a role in regulating afferent-induced nociceptive plasticity. Parallel increases in DARPP-32 phosphorylation upon LTP induction suggests a role for this phosphoprotein as intracellular detector of convergent D1L- and NMDA receptor activation.


Islam is the solution: Jordanian Islamists and the dilemma of the 'modern woman'.
During the past decade, the issue of gender relations and women's conduct and dress has been occupying an increasingly prominent place in the discourse of Islamist movements. This article attempts to situate Arab Islamists' preoccupation with women within the legacy of colonialism and social transformations relating to gender and class. With regard to Jordan, the author links the urgency of the issue with social transformations at the level of gender and class during recent decades, and points out that the key to understanding the prominence of the 'woman question' in Islamist thinking is the fact that the social groups which comprise the traditional constituency of the Islamists are finally experiencing for themselves the socially disruptive implications of new patterns in women's work, education and visibility. In short, the issue of women's modesty and conduct, which was more abstract as recent as one generation ago (when only upper middle and upper class women were visible in the public domain), acquires concreteness and urgency in the rapidly changing social environment. The article also tries to show how the Islamists' framing of the issue in cultural terms has a primal appeal, especially to those social groups most alienated from the insular world of the westernized elite and in search of 'authentic' ways of living in the modern world.


Education-based stigma and discrimination among young adults not in 4-year college.
Lower levels of education are strongly associated with negative health outcomes. The current study examined the degree to which those without a history of 4-year college attendance experience social stigmatization of their educational status and if these experiences are associated with mental health symptoms. Data was obtained from 488 emerging adults who never attended 4-year college using Qualtrics Panels. 79.4% of participants agreed to one of the six statements that not attending 4-year college is stigmatized, and 71.8% endorsed experiencing at least one form of discrimination. Higher levels of education-related stigma and more frequent experiences of education-related discrimination was associated with greater past-month anxiety and depression symptoms. These findings could serve to increase awareness regarding the unique and significant discrimination faced by young adults who do not attend 4-year college and identify specific areas of intervention that can help these young adults cope with the effects of stigma and discrimination.


Association of TLR polymorphisms with development of tuberculosis in Indonesian females.
Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is a major cause of morbidity and mortality worldwide. Many candidate genes have been investigated for a possible association with TB. Toll-like receptors (TLRs) are known to play important roles in human innate immune systems. Polymorphisms in and functions of TLRs have been investigated to identify associations with specific infectious diseases, including TB. Here, we examined whether single-nucleotide polymorphisms (SNPs) in TLRs and genes in TLR signaling were associated with TB susceptibility in Indonesian and Vietnamese populations. A statistically significant association was observed between TB susceptibility in a classified Indonesian female group and rs352139, an SNP located in the intron of TLR9, using the genotype (P = 2.76E-04) and recessive (AA vs AG+GG, P = 2.48E-04, odds ratio = 1.827, 95% confidence interval = 1.321-2.526) models. Meta-analysis of the Indonesian and Vietnamese populations showed that rs352139 was significantly associated with TB in the recessive model. This finding indicated that a TLR9 polymorphism might have an important role in the susceptibility to M. tuberculosis in Asian populations.


An asymmetric Ugi three-component reaction induced by chiral cyclic imines: synthesis of morpholin- or piperazine-keto-carboxamide derivatives.
A series of chiral 5,6-dihydro-1,4-oxazin-2-one substrates, as preformed cyclic aldimines and ketoimines, were employed to develop a new asymmetric Ugi three-component reaction for the first time. The Ugi reaction of the imines, isocyanides, and carboxylic acids opens an efficient access to novel morpholin-2-one-3-carboxamide compounds. The chiral imines showed promising stereoinduction for the new chiral center of the Ugi products, and predominant trans-isomers were obtained in the most cases. Addition of some Lewis acids or proton acids could improve the diastereoselectivity further but usually led to a drop in total yield. The Ugi-3CR could be extended to the stereoselective synthesis of ketopiperazine-2-carboxamide derivatives.


Myosins FaMyo2B and Famyo2 Affect Asexual and Sexual Development, Reduces Pathogenicity, and FaMyo2B Acts Jointly with the Myosin Passenger Protein FaSmy1 to Affect Resistance to Phenamacril in Fusarium asiaticum.
We previously reported that mutations occurred in the gene myosin5 were responsible for resistance to the fungicide phenamacril in Fusarium graminearum. Here, we determined whether there is a functional link between phenamacril resistance and the myosin proteins FaMyo2B and Famyo2 in Fusarium asiaticum, which is the major causal agent of Fusarium head blight in China. We found that FaMyo2B acts jointly with FaSmy1 to affect resistance to phenamacril in F. asiaticum. We also found that FaMyo2B disruption mutant and Famyo2 deletion mutant were defective in hyphal branching, conidiation, and sexual reproduction. ΔFamyo2 also had an enhanced sensitivity to cell wall damaging agents and an abnormal distribution of septa and nuclei. In addition, the FaMyo2B and Famyo2 mutants had reduced pathogenicity on wheat coleoptiles and flowering wheat heads. Taken together, these results reveal that FaMyo2B and Famyo2 are required for several F. asiaticum developmental processes and activities, which help us better understand the resistance mechanism and find the most effective approach to control FHB.


Inhibition of in vitro and ex vivo translation by a transplatin-modified oligo(2'-O-methylribonucleotide) directed against the HIV-1 gag-pol frameshift signal.
A 2'-O-methylribooligonucleotide containing a G1.U.G3 triad modified by trans-diamminedichloro-platinum(II) was targeted to the RNA region responsible for the gag-pol frameshifting during translation of the HIV-1 mRNA. The binding of the platinated oligonucleotide to its target RNA induced a rearrangement of the (G1, G3)-intrastrand crosslink, leading to the formation of an intermolecular oligonucleotide-RNA G-A crosslink. This resulted in the selective arrest of translation of a luciferase gene placed downstream of the HIV-1 frameshift signal both in a cell-free extract (rabbit reticulocyte lysate) and in RNA-transfected cells. A specific inhibition of luciferase activity was still observed when the oligonucleotide-RNA complex was not pre-formed prior to either translation or transfection. Moreover, a selective inhibition was also observed when the oligonucleotide and the plasmid DNA encoding the luciferase and bearing the RNA gag- pol frameshifting signal were co-transfected in NIH 3T3 cultured cells. Therefore the intra-strand-->interstrand conversion of the platinum crosslink kinetically competes with the translation machinery and blocks the polypeptide elongation. These transplatin-modified oligonucleotides which operate within a live cell on a 'real-time' basis and do not need an external triggering signal constitute a promising new class of selective reactive probes.


Significance of MR/OPN/HMGB1 axis in NAFLD-associated hepatic fibrogenesis.
The activation of hepatic stellate cells (HSCs) plays a central role in liver fibrosis, however non-alcoholic fatty liver disease (NAFLD) associated liver fibrogenesis have been poorly understood. We aimed to determine the significance of mineralocorticoid receptor (MR)/osteopontin (OPN)/high-mobility group box-1 (HMGB1) axis in this setting. Liver specimens were collected from NAFLD patients and murine NAFLD models established with 12-week high fat diet (HFD) for analysis of both upstream signals of MR and intrahepatic MR/OPN/HMGB1 axis. The in vitro cell model of NAFLD-associated liver fibrogenesis was established by treating LX-2 (a cell line of human HSCs) with free fatty acids (FFA). The effects of MR signaling were evaluated using with ALD (MR activator) or eplerenone (Ep, MR antagonist). Moreover, the in vitro loss- and gain- of function approaches were applied to confirm the upstream and downstream relationships of mediators contained in the intracellular MR/OPN/HMGB1 axis of LX-2. In NAFLD condition, both human and mouse liver tissue samples demonstrated a significant up-regulation of MR/OPN/HMGB1 axis simultaneously with enhanced expression of pro-fibrogenic markers, including ACTA2, TIMP1, TGFB1 and COL1A1. Besides, enhanced production of serum aldosterone (ALD) was also observed in mouse NAFLD models. Moreover, the in vitro data demonstrated MR play an essential role in FFA-induced HSCs fibrogenesis. Meanwhile, MR acts as the upstream effector mediator of OPN and shares downstream HMGB1 with OPN. The MR/OPN/HMGB1 axis could be therapeutically targeted to treat NAFLD associated hepatic fibrogenesis.


Urinary single-cell sequencing captures kidney injury and repair processes in human acute kidney injury.
Acute kidney injury (AKI) is a major health issue, the outcome of which depends primarily on damage and reparative processes of tubular epithelial cells. Mechanisms underlying AKI remain incompletely understood, specific therapies are lacking and monitoring the course of AKI in clinical routine is confined to measuring urine output and plasma levels of filtration markers. Here we demonstrate feasibility and potential of a novel approach to assess the cellular and molecular dynamics of AKI by establishing a robust urine-to-single cell RNA sequencing (scRNAseq) pipeline for excreted kidney cells via flow cytometry sorting. We analyzed 42,608 single cell transcriptomes of 40 urine samples from 32 patients with AKI and compared our data with reference material from human AKI post-mortem biopsies and published mouse data. We demonstrate that tubular epithelial cells transcriptomes mirror kidney pathology and reflect distinct injury and repair processes, including oxidative stress, inflammation, and tissue rearrangement. We also describe an AKI-specific abundant urinary excretion of adaptive progenitor-like cells. Thus, single cell transcriptomics of kidney cells excreted in urine provides noninvasive, unprecedented insight into cellular processes underlying AKI, thereby opening novel opportunities for target identification, AKI sub-categorization, and monitoring of natural disease course and interventions.


Programme and policy issues related to promoting positive early nutritional influences to prevent obesity, diabetes and cardiovascular disease in later life: a developing countries view.
Public health policy differs from programme insofar as the former is the expression of goals at a higher decision-making level (international, regional, national or provincial) and the latter involves the execution of intervention measures at the community or individual level. It has recently become fashionable to speak of "evidence-based" policy. There is now ample evidence to suggest that early nutritional influences on chronic disease risk in later life are contributing to the acceleration of the overall worldwide epidemic of obesity and non-transmissible diseases. In developing countries, in which 80% of the world's population resides, the opportunities for preventive policy must be balanced against needs, cost and effectiveness considerations and the intrinsic limitations of policy execution. Not everyone in the population is at risk of suffering from any given negative condition of interest, nor will everyone at risk benefit from any given intervention. Hence, decisions must be made between universal or targeted policies, seeking maximal cost-efficiency, but without sowing the seeds of either discrimination or stigmatization with a non-universal application of benefits. Moreover, although large segments of the covered population may benefit from a public health measure, it may produce adverse and harmful effects on another segment. It is ethically incumbent on policy makers to minimize unintended consequences of public health measures. With respect to the particular case of mothers, fetuses and infants and long-term health, only a limited number of processes are amenable to intervention measures that could be codified in policy and executed as programmes.


Increased production of matrix metalloproteinases in enriched astrocyte and mixed hippocampal cultures treated with beta-amyloid peptides.
Growing evidence supports the notion of a functional relationship between the presence of the beta-amyloid (A beta) peptide and the production of inflammatory mediators in and around neuritic plaques of Alzheimer's disease. Tissue remodeling enzymes that are critical in peripheral inflammatory responses are the matrix metalloproteinases (MMPs), enzymes produced by neurons and glia. Thus, it was of interest to determine whether A beta may alter the expression of MMPs in glial and neuronal cultures. It was demonstrated that A beta (1-40) is a potent stimulator of MMP-9 and MMP-2 activity in addition to inducing the expression of a lower molecular weight, unidentified gelatinase activity in mixed hippocampal and astrocyte cultures. Shorter fragments of A beta were less effective in stimulating the production of these enzymes. The lower molecular weight activity was observed only in response to A beta, and not after treatment with various cytokines. In addition, both cultures express MMP-3 (stromelysin-1) in response to A beta peptides. These results suggest that MMPs may play a role in the development or progression of neuritic plaques, i.e., abnormal neurite outgrowth.


Years of Life Lost (YLLs) Due to Suicide and Homicide in Ilam Province: Iran, 2014-2018.
To provide detailed of suicide and homicide mortality and calculate of years of life lost (YLLs) in Ilam province Iran, during 2014-2018. In this cross-sectional study, all deaths due to suicide and homicide were enrolled to estimate YLLs, in Ilam province between 2014-2018. The source of data was legal medicine organization (LMO). All analysis was performed at 0.05 significant levels using statistical software package STATA for Windows version 11.2 and SPSS 21 software. The total YLLs of suicide and homicide were 15685 and 5317, respectively. 522 per 100,000 populations were suicide and 117 for homicide. The YLL and 95% confidence interval form suicide was 34.4 (32.8-36.1) for both sexes that 33.7 (31.6-35.8) for men, and 35.5 (32.7-38.3) for women. In this study period, YLLs rate began to increase over the years in both injury-related in 2016. Results of this study disclosed the most prominent contribution of men and peoples aged 15-29 to the YLLs. Also our results indicate a recent increase in suicide and homicide YLLs for both genders.


Limiting dilution analysis of the B cell compartment in human bone marrow.
Mononuclear cells (MNC) obtained from adult rib specimen were investigated for their capacity to produce immunoglobulin (Ig) in vitro. Using limiting dilution analysis 3 populations of B lineage cells could be distinguished. The first produces Ig in culture without any intentional activation. These cells are strictly nonproliferating and sustain extraordinary secretory rates of 5 X 10(7)-10 X 10(7) molecules IgG, IgA or IgM/cell/h for at least 2 weeks. They occur at frequencies of 1 X 10(-4)-10 X 10(-4) (marrow MNC) or represent 1-5% of marrow B cells. Following exposure to infectious Epstein-Barr virus (EBV), these cells do not (a) proliferate, (b) express EBV-determined nuclear antigens (EBNA), (c) enhance their secretory rates or (d) show secretory activity for prolonged time. These cells are therefore EBV resistant. If these cells produced their antibody at similar rates in vivo, then their frequencies would suggest that they could provide up to 2/3 of daily synthetic rates for IgG and IgA and 20-30% of the daily IgM production. The second population of marrow B cells is exclusively committed to IgM production. Following exposure to EBV these cells proliferate, express EBNA and begin to secrete IgM. The third population represents 90% of marrow B cells. In our hands, these cells are unable to produce Ig in vitro.


Effect of etorphine on adrenergic neurotransmission in the rat and guinea pig heart.
The effect of etorphine (ET) on nerve stimulation-mediated release of norepinephrine (NE) was investigated in isolated rat and guinea pig hearts. Hearts were perfused with Krebs bicarbonate solution via the aorta and the overflow of NE was measured after stimulation of the heart. ET (0.001-0.1 mumol/l) caused a dose-dependent inhibition of NE release in both preparations. Inhibition of NE release from guinea pig hearts ranged from 13% at 0.001 mumol/l to 24% at 0.1 mumol/l. The same concentrations of ET decreased NE release by 10 and 36% in the rat heart. The inhibitory effect of ET was blocked by naloxone. It is concluded that presynaptic opioid receptors located on the adrenergic neuronal terminals may be involved in the regulation of adrenergic neurotransmission in the rat and guinea pig heart.


Numerical simulations of phase contrast velocity mapping of complex flows in an anatomically realistic bypass graft geometry.
Combined in vitro experiments and numerical simulations were performed to study flow artifacts in phase contrast (PC) velocity mapping of steady flow through an anatomically realistic aortocoronary bypass graft model. The geometry was obtained through imaging and computational reconstruction of a left anterior descending (LAD) coronary artery of a porcine heart. Simulated images of through-plane velocity were obtained at selected slices of the geometry. These were then compared and contrasted with velocity images of corresponding sites that were obtained from in vitro experiments. The shift and distortion of the measured velocity profile was well predicted by the simulation, while trajectories obtained from particle tracking were shown to be useful in understanding the origins of the flow artifacts that were observed.


The Drosophila gene Bearded encodes a novel small protein and shares 3' UTR sequence motifs with multiple Enhancer of split complex genes.
Gain-of-function alleles of the Drosophila gene Bearded (Brd) cause sensory organ multiplication and loss phenotypes indistinguishable at the cellular level from those caused by loss-of-function mutations in the genes of the Notch pathway (Leviten, M. W. and Posakony, J. W. (1996). Dev. Biol. 176, 264-283). We have carried out a molecular analysis of the structure and expression of both wild-type and mutant Brd transcription units. We find that the Brd transcript is truncated and accumulates to substantially higher levels in the gain-of-function mutants, due to the insertion of a transposable element of the blood family in the Brd 3' untranslated region (UTR). The wild-type Brd 3' UTR includes three copies of a 9-nucleotide sequence (CAGCTTTAA) that we refer to as the 'Brd box'. Moreover, the 3' UTRs of Brd and of the m4 transcription unit of the Enhancer of split gene complex [E(spl)-C] exhibit an unusually high degree of sequence identity that includes not only Brd box sequences but also a second motif we refer to as the 'GY box' (GTCTTCC). We find that both the Brd box and the GY box are also present in the 3' UTRs of several basic helix-loop-helix repressor-encoding genes of the E(spl)-C, often in multiple copies, suggesting that a novel mode of post-transcriptional regulation applies to Brd and many E(spl)-C genes. The fact that the more abundant Brd mutant mRNA lacks the GY box and two of the Brd boxes present in wild-type Brd mRNA suggests that either or both of these elements may confer instability on transcripts that contain them. Finally, we find that Brd encodes a novel small protein of only 81 amino acids that is predicted to include a basic amphipathic alpha-helix. The deduced Brd protein shows sequence similarity to the E(spl)m4 protein, which is likewise expected to include a basic amphipathic alpha-helix, suggesting that the two proteins have related biochemical functions.


What Do Primary Care Providers and Nurses Need to Know About Managing Chronic Pain?
Pain is the leading reason Americans seek health care access. Worldwide, more than 1.5 billion people are suffering from chronic pain. Unfortunately, providers are not equipped to manage patients with chronic pain as many advanced programs provide little to no education on pain management. Additionally, there are limited research articles on managing chronic pain, let alone regarding alternative treatment options for chronic pain. The patient presented in this case study is a 66-year-old woman who presents for a follow up regarding chronic pain. The case study outlines the success a patient found using alternative options other than opioid medication with lifestyle changes and a newer medication called low-dose Naltrexone (LDN). The purpose of this case study is to present a patient who has found success in managing chronic pain through alternative treatments and help the provider be able to educate patients on the importance of lifestyle changes to increase the prescribing and compliance of alternative treatment options.


Consumer behavior in the setting of over-the-counter statin availability: lessons from the consumer use study of OTC Mevacor.
Despite the proven benefits of statins, large numbers of patients meeting guideline criteria for therapy are not receiving these drugs. It has been suggested that over-the-counter (OTC) availability of statins would allow more consumers to use statins and achieve cardiovascular risk reduction. However, concerns have been raised as to the consumers' ability to self-manage hyperlipidemia and use statins safely. The Consumer Use Study of OTC Mevacor (CUSTOM) was designed to define consumer behaviors in the setting of OTC statin availability. The study was conducted in a simulated OTC setting and allowed consumers to purchase once-daily lovastatin 20 mg. The CUSTOM dataset includes >3,300 consumers who evaluated OTC lovastatin for potential purchase at study sites and follow-up information on purchasers for up to 6 months of self-managed therapy. These data have been analyzed to address consumers' knowledge of their cholesterol concentrations as well as their ability to make OTC use decisions based on their cardiovascular risk, avoid drug-drug interactions, self-manage their cholesterol treatment after deciding to use the OTC product, and maintain interactions with physicians while using lovastatin OTC. The results showed that most study participants appropriately self-selected OTC statin therapy and managed their treatment. Use of OTC statins by consumers needing more intensive statin therapy or facing the risk of potential drug-drug interactions remains an area of concern but occurred infrequently in CUSTOM. These data are important for making an informed risk-benefit decision concerning OTC statin availability.


A Hemodynamically Significant Patent Ductus Arteriosus Does Not Affect Cerebral or Renal Tissue Oxygenation in Preterm Infants.
Patent ductus arteriosus (PDA) is common in preterm infants and is associated with significant morbidity. To determine whether the PDA is hemodynamically significant (HSDA), several echocardiographic parameters have been suggested, including retrograde diastolic blood flow in the descending aorta (Dao). To assess the impact of an HSDA, including retrograde diastolic flow in the Dao, on regional tissue oxygen saturation (rSO2) and extraction measured by near-infrared spectroscopy (NIRS). This is a prospective observational cohort study in which we included preterm infants (GA <32 weeks) who underwent echocardiographic screening because of clinical signs of an HSDA within 2 weeks after birth. We measured cerebral and renal rSO2 on the day of echocardiography. HSDA was diagnosed if left-to-right shunting through the PDA was accompanied by left atrial-to-aortic root ratio >1.4 and/or left pulmonary artery end-diastolic flow velocity >0.2 m/s and/or retrograde diastolic blood flow in the Dao. Forty-nine infants were included, with a median GA of 27.6 weeks (IQR: 26.1-29.0), birth weight of 980 g (IQR: 800-1,200), and postnatal age of 77 h (IQR: 70-107). Infants with a closed duct (n = 11), a non-HSDA (n = 18), and an HSDA (n = 20) had similar cerebral and renal NIRS measurements. Retrograde diastolic blood flow in the Dao, present in 11 infants with PDA, also did not affect cerebral and renal NIRS measurements. In preterm infants with clinical signs of an HSDA within 2 weeks after birth, cerebral and renal oxygen saturation and extraction are not affected by an HSDA or by retrograde diastolic blood flow in the Dao.


Percutaneous pulsed radiofrequency applied to the L-2 dorsal root ganglion for treatment of chronic low-back pain: 3-year experience.
The authors assessed the effectiveness of percutaneous pulsed radiofrequency treatment for providing pain relief in patients with chronic low-back pain with or without lower-limb pain. Data were obtained in 127 patients who had chronic low-back pain with or without lower-limb pain due to a herniated intervertebral disc or previous failed back surgery and who underwent pulsed radiofrequency treatment. Their conditions were proven by clinical features, physical examination, and imaging studies. Low-back pain was treated with pulsed radiofrequency applied to the L-2 dorsal root ganglion (DRG) and lower-limb pain was treated with pulsed radiofrequency applied to the L3-S1 DRG. Patients underwent uni- or bilateral treatment depending on whether their low-back pain was unilateral or bilateral. A visual analog scale was used to assess pain. The patients were followed up for 3 years postoperatively. In patients without lower-limb pain (Group A), 27 (55.10%) of 49 patients had initial improvement >or= 50% at 3-month follow-up. At 1-year follow-up, 20 (44.44%) of 45 patients in Group A had pain relief >or= 50%. An analysis of patients with pain relief >or= 50% for at least 1 month showed that the greatest effect was at 3 months after treatment. In patients with low-back pain and lower-limb pain (Group B), 37 (47.44%) of 78 patients had initial improvement >or= 50% at 3-month follow-up. At 1-year follow-up, 34 (45.95%) of 74 patients had pain relief effect >or= 50%. An analysis of patients in Group B with pain relief >or= 50% for at least 1 month showed that the greatest effect was at 1 month after treatment. The results of this prospective analysis showed that treatment with pulsed radiofrequency applied at the L-2 DRG is safe and effective for treating for chronic low-back pain. Satisfactory pain relief was obtained in the majority of patients in Group A with the effect persisting for at least 3 months. The results indicate that pulsed radiofrequency provided intermediate-term relief of low-back pain. Further studies with long-term follow-up are necessary.


Induction of T cell CD7 gene transcription by nonmitogenic ionomycin-induced transmembrane calcium flux.
The CD7 molecule is a 40-kDa member of the Ig superfamily that has structural homology to the murine Thy-1 molecule and is acquired early in human T cell ontogeny. Previous studies have demonstrated that expression of the CD7 molecule is markedly up-regulated during T cell activation. In this study, we have studied the signals required for CD7 up-regulation on human T cells. We found that nonmitogenic amounts of ionomycin selectively and maximally up-regulated T cell CD7 on mature (peripheral blood) T cells after 24 h. Whereas CD7 expression was increased 78 +/- 25% by 0.5 microM ionomycin, expression of CD25 (IL-2R alpha), class II MHC, 4F2, transferrin receptor, CD2, CD3, CD4, CD5, and CD8 molecules was not increased. Ionomycin-induced CD7 surface expression was associated with peak increases in CD7 mRNA after 4 to 6 h. Transcriptional analysis and CD7 mRNA half-life determination revealed the increase in CD7 mRNA was the result of increased CD7 gene transcription 1 h after ionomycin stimulation and was not due to prolongation of CD7 mRNA half-life. The up-regulation of surface CD7 expression by ionomycin was dependent on extracellular calcium and did not require the activation of T cell tyrosine protein kinase. Mitogenic CD2 and CD3 mAb as well as stimulation of T cells by PHA also up-regulated CD7 expression. CD7 up-regulation by ionomycin was transient (24 to 72 h) and inhibitable by cyclosporin A, whereas CD7 up-regulation by PHA was sustained over 5 to 7 days and was significantly less inhibitable by cyclosporin A. These data demonstrate that induction of a transmembrane calcium flux generates signals that lead to CD7 gene transcription.


Functional differences in echolocation call design in an adaptive radiation of bats.
All organisms have specialized systems to sense their environment. Most bat species use echolocation for navigation and foraging, but which and how ecological factors shaped echolocation call diversity remains unclear for the most diverse clades, including the adaptive radiation of neotropical leaf-nosed bats (Phyllostomidae). This is because phyllostomids emit low-intensity echolocation calls and many inhabit dense forests, leading to low representation in acoustic surveys. We present a field-collected, echolocation call dataset spanning 35 species and all phyllostomid dietary guilds. We analyze these data under a phylogenetic framework to test the hypothesis that echolocation call design and parameters are specialized for the acoustic demands of different diets, and investigate the contributions of phylogeny and body size to echolocation call diversity. We further link call parameters to dietary ecology by contrasting minimum detectable prey size estimates (MDPSE) across species. We find phylogeny and body size explain a substantial proportion of echolocation call parameter diversity, but most species can be correctly assigned to taxonomic (61%) or functional (77%) dietary guilds based on call parameters. This suggests a degree of acoustic ecological specialization, albeit with interspecific similarities in call structure. Theoretical MDPSE are greatest for omnivores and smallest for insectivores. Omnivores significantly differ from other dietary guilds in MDPSE when phylogeny is not considered, but there are no differences among taxonomic dietary guilds within a phylogenetic context. Similarly, predators of non-mobile/non-evasive prey and predators of mobile/evasive prey differ in estimated MDPSE when phylogeny is not considered. Phyllostomid echolocation call structure may be primarily specialized for overcoming acoustic challenges of foraging in dense habitats, and then secondarily specialized for the detection of food items according to functional dietary guilds. Our results give insight into the possible ecological mechanisms shaping the diversity of sensory systems, and their reciprocal influence on resource use.


Uptake of extracellular Ca2+ is a requirement for production of interferon-gamma by cord blood mononuclear cells.
We studied the response of adult peripheral and cord blood mononuclear cells (MNCs) to graded concentrations of phytohemagglutinin (PHA) to characterize the requirements for proliferation and interferon-gamma (IFN-gamma) production. As the concentration of PHA was decreased, the proliferative response of both adult and cord blood MNCs decreased in parallel. At high concentrations of PHA (a: 120) cord blood MNCs display normal high proliferation but IFN-gamma production was greatly diminished compared with adult MNCs. Addition of the calcium ionophore, A23187, to PHA-stimulated adult MNCs had no effect on proliferation or IFN-gamma production at any of the concentrations of PHA tested. Furthermore, A23187 alone had no effect on proliferation or IFN-gamma secretion. Similarly, the addition of A23187 to PHA-stimulated cord-blood MNCs had no effect on proliferation. However, when A23187 was added to high dose (1:120) PHA-stimulated cord blood MNCs IFN-gamma production increased to levels comparable with adult PHA-stimulated MNCs. A similar pattern of response was seen when exogenous calcium chloride was added in place of A23187.


Self-recognition in pigeons revisited.
Recognition of a self-image in a mirror is investigated using the mark test during which a mark is placed onto a point on the body that is not directly visible, and the presence or absence of self-directed behaviors is evaluated for the mirror-observing subjects. Great apes, dolphins, possibly elephants, and magpies have all passed the mark test, that is, displayed self-directed behaviors, whereas monkeys, crows, and other animals have failed the test even though they were able to use a mirror to find a not-directly-visible object. Self-directed behavior and mirror use are prerequisites of a successful mark test, and the absence of these behaviors may lead to false negative results. Epstein, Lanza, and Skinner (1981) reported self-directed behavior of pigeons in front of a mirror after explicit training of self-directed pecking and of pecking an object with the aid of a mirror, but certain other researchers could not confirm the results. The aim of the present study was to conduct the mark test with two pigeons that had received extensive training of the prerequisite behaviors. Crucial points of the training were identical topography (pecking) and the same reinforcement (food) in the prerequisite behaviors as well as sufficient training of these behaviors. After training for the prerequisite behaviors, both pigeons spontaneously integrated the learned self-directed and mirror-use behavior and displayed self-directed behavior in a mark test. This indicates that pigeons display mirror self-recognition after training of suitable ontogenetic contingency.


Aspects of the structure, function, and applications of superoxide dismutase.
The current status of superoxide dismutase (SOD) is that it is an enzyme with diverse ramifications. This review attempts an understanding of SOD as a structural, functional, and biological entity. Accordingly, the review is in three parts. The first part discusses SOD in terms of protein structure, proceeding from primary to secondary and three-dimensional structure for the three forms of SOD: copper/zinc SOD, manganese SOD, and iron SOD. This is the order of structural knowledge of the enzyme. Iron SOD is an enzyme of prokaryotes and some higher plants. Manganese SOD is an enzyme of prokaryotes and eukaryotes. Copper/zinc SOD is an enzyme of eukaryotes and certain prokaryotes. The evolutionary relationships of the three forms of SOD, the status of the copper/zinc SOD gene in prokaryotes, and the cloning and sequencing of SOD genes are discussed. The second part of the review deals with the catalytic mechanism of SOD in the three forms of the enzyme. Structural and mechanistic conclusions from various spectroscopic studies are critically considered. A detailed picture is given of the active site of copper/zinc SOD. The third part is a review of SOD in the general context of oxygen toxicity. After consideration of the question of superoxide toxicity and superoxide pathology, several areas in which SOD has been investigated or used as a tool in a biochemical, pharmacological, or clinical context are discussed, including population genetics; trisomy 21; development and senescence; the nutritional copper, zinc, and manganese status; hemolysis and anemia; oxygen toxicity in the lung and nervous system; inflammation, autoimmune disease and chromosome breakage, ischemia and degenerative changes; radiation damage; and malignancy. A comprehensive picture is given of measurements of SOD activity in disease states, and the question of superoxide-related disease is considered at several points.


Managing impossible missions: ethical quandaries and ethical solutions.
Healthcare financial managers are confronted daily with ethical and practical conflicts, particularly with regard to meeting the conflicting and unduly restrictive laws and regulations with which their organizations must comply. Sometimes the right course of action is not clear, as an examination of the 72-hour rule, safe harbor provisions, and legal interpretations of the False Claims Act reveals. Healthcare financial managers have an ethical duty, based on healthcare codes of ethics and ethical theories, to oppose laws and regulations that put their organizations in untenable legal and ethical situations.


Population homeostasis in sub-Saharan Africa.
Global population growth remains one of the major challenges of the twenty-first century. This is particularly true for African countries which have been undergoing their demographic transitions. To investigate whether predicted increasing population density and urbanization can help to stabilize African population, we construct a database for 84 georeferenced Demographic and Health Survey (DHS) samples including 947,191 individuals in sub-Saharan Africa and match each location with gridded population density from NASA. We apply a proportional hazard model to evaluate the quantitative impact of local population density on the transitions from childlessness to motherhood, and from celibacy to marriage. Moving from the 5th to the 95th percentile of population density increases the median age at first birth by 2.2 years. This roughly decreases completed fertility by half a child. The same increase in population density increases the median age at first marriage by 3.3 years. These findings contribute to the understanding of why fertility has not dropped in Africa as fast as expected. One part of the answer is that population density remains low. Yet the total effect of increased density on fertility remains limited and counting on it to stabilize the population would be unrealistic.


Population Genomics of Microbial Biostalactites: Non-recombinogenic Genome Islands and Microdiversification by Transposons.
Intrapopulation genetic variability in prokaryotes is receiving increasing attention thanks to improving sequencing methods; however, the ability to distinguish intrapopulation variability from species clusters or initial stages of gene flow barrier development remains insufficient. To overcome this limitation, we took advantage of the lifestyle of Ferrovum myxofaciens, a species that may represent 99% of prokaryotic microbiome of biostalactites growing at acid mine drainage springs. We gained four complete and one draft metagenome-assembled F. myxofaciens genomes using Oxford Nanopore and Illumina sequencing and mapped the reads from each sample on the reference genomes to assess the intrapopulation variability. We observed two phenomena associated with intrapopulation variability: hypervariable regions affected by mobilome expansion called "scrapyards," and variability in gene disruptions caused by transposons within each population. Both phenomena were previously described in prokaryotes. However, we present here for the first time scrapyard regression and the development of a new one. Nearly complete loss of intrapopulation short sequence variability in the old scrapyard and high variability in the new one suggest that localized gene flow suppression is necessary for scrapyard formation. Concerning the variable gene disruptions, up to 9 out of 41 occurrences per sample were located in highly conserved diguanylate cyclases/phosphodiesterases. We propose that microdiversification of life strategies may be an adaptive outcome of random diguanylate cyclase elimination. The mine biostalactites thus proved as a unique model system for describing genomic intrapopulation processes, as they offer easily sampleable units enriched in a single microbial species.


A robust method for quantification of volatile compounds within and between vintages using headspace-solid-phase micro-extraction coupled with GC-MS--application on Semillon wines.
A headspace-solid-phase micro-extraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) method has been developed to quantify a range of volatile compounds in Hunter Valley Semillon wines. The fibre selected for the method was a 50/30 microm divinylbenzene/carboxen/polydimethylsiloxane fibre, a three-phase fibre that allows extraction and desorption of a wide range of volatile compounds of different chemical functionalities and polarities. Four internal standards, methyl isobutyl ketone, n-dodecane, 4-methyl-2-pentanol and ethyl nonanoate were used to monitor the SPME fibre extraction efficiency and integrity. Fibre integrity was monitored by plotting the ratio of the peak area for each internal standard divided by the sum of the peak area for all internal standards as a function of analysis number. The advantage of using four internal standards for better quality control of the fibre integrity is described. The identity of twenty-one volatile compounds was ascertained by comparison of their chemical characteristics (retention indices, mass spectra) with reference compounds using two columns of different polarities. Quantification was achieved using calibration curves constructed for each compound with linear regression equations having correlation coefficients (R(2)) ranging from 0.9717 to 0.9999. The method was applied to two Semillon wines (recent vintage and aged) representative of the Hunter Valley styles. As is typical of white wines, 3-methyl-1-butanol was quantified as the most concentrated volatile compound (83 and 66 mg L(-1) for the 2006 and the 1996 wines, respectively). The study highlights the use of well-defined procedures to ensure integrity of quantitative data where several fibres may be required during an extended study over one or more vintages.


Trends in dental hygiene applicant pool size and characteristics of students upon entry over three decades.
A survey was conducted to determine trends that have occurred in the dental hygiene applicant pool and characteristics of entering dental hygiene students between 1957 and 1987. A two page, 46-item questionnaire with a cover letter and stamped pre-addressed envelope was mailed to each dental hygiene program director in the United States. A second mailing was sent one month later to directors who had not responded to the first mailing. A total of 106 usable questionnaires were returned, for a 54 percent response rate for 1987 programs. Response rates for programs existing in 1977, 1967, and 1957 were 51 percent, 45 percent, and 45 percent, respectively. For associate degree/certificate and baccalaureate degree programs, results suggest trends toward (1) a dramatic decline in dental hygiene applicants over the past ten years, (2) a decrease in dental hygiene class size, (3) an increase in age of applicants and length of education prior to acceptance into dental hygiene programs, and (4) a slight decrease in applicants' overall grade point average and science grade point average in the past decade. In addition, findings indicate that dental hygiene remains predominantly a Caucasian woman's profession. Implications of these findings for recruitment efforts and the numbers of dental hygienists for the future are discussed.


[Use of Finapres during warming for postoperative patients].
We used Finapres during rewarming after extracorporeal circulation in 16 patients who underwent cardiac surgery. In patients with passive rewarming there were no differences in blood pressure measured with a Finapres and that by an invasive monitor. On the other hand, in patients rewarmed with the aid of nitroglycerin, there were statistically significant differences between blood pressures measured with indirect and direct methods.


[Equity promotion in Maccabi Healthcare Services: from the Equality Report to an organizational action plan].
Maccabi Healthcare Services (MHS), the second largest HMO in Israel, has chosen to implement a multi-annual strategy to promote equality and equity in healthcare. Within the strategy's framework, MHS will maintain an ongoing process of studying the variability of its members characteristics for the purpose of adjusting service provision and improving health outcomes. MHS has recently published its first Equality Report, dedicated to defining the observed associations between its members demographic and socioeconomic characteristics and their health measures. The report identifies those sub-groups belonging to Israel's geographic and social peripheries that require focused interventions. Based on the report's recommendations, MHS has decided to designate promotion of equality as its strategic objective, a filter through which every policy decision will be reviewed. In addition it was decided to: 1. develop an organizational methodology to produce an index to assess reductions in disparities over time; 2. adjust MHS services to member's ethnic and cultural needs; 3. strengthen perceptions of community orientation based in primary care; 4. target resources to "social peripheries", beginning in 2010; 5. improve service accessibility and availability in geographically peripheral areas; 6. reduce economic barriers to healthcare. This article details the disparities as analyzed in the report in addition to the specific policy decisions made in their wake.


Therapeutic Approaches Targeting Nucleolus in Cancer.
The nucleolus is a distinct sub-cellular compartment structure in the nucleus. First observed more than 200 years ago, the nucleolus is detectable by microscopy in eukaryotic cells and visible during the interphase as a sub-nuclear structure immersed in the nucleoplasm, from which it is not separated from any membrane. A huge number of studies, spanning over a century, have identified ribosome biogenesis as the main function of the nucleolus. Recently, novel functions, independent from ribosome biogenesis, have been proposed by several proteomic, genomic, and functional studies. Several works have confirmed the non-canonical role for nucleoli in regulating important cellular processes including genome stability, cell-cycle control, the cellular senescence, stress responses, and biogenesis of ribonucleoprotein particles (RNPs). Many authors have shown that both canonical and non-canonical functions of the nucleolus are associated with several cancer-related processes. The association between the nucleolus and cancer, first proposed by cytological and histopathological studies showing that the number and shape of nucleoli are commonly altered in almost any type of cancer, has been confirmed at the molecular level by several authors who demonstrated that numerous mechanisms occurring in the nucleolus are altered in tumors. Recently, therapeutic approaches targeting the nucleolus in cancer have started to be considered as an emerging "hallmark" of cancer and several therapeutic interventions have been developed. This review proposes an up-to-date overview of available strategies targeting the nucleolus, focusing on novel targeted therapeutic approaches. Finally, a target-based classification of currently available treatment will be proposed.


Chronic restraint stress inhibits hair growth via substance P mediated by reactive oxygen species in mice.
Solid evidence has demonstrated that psychoemotional stress induced alteration of hair cycle through neuropeptide substance P (SP) mediated immune response, the role of reactive oxygen species (ROS) in brain-skin-axis regulation system remains unknown. The present study aims to investigate possible mechanisms of ROS in regulation of SP-mast cell signal pathway in chronic restraint stress (CRS, a model of chronic psychoemotional stress) which induced abnormal of hair cycle. Our results have demonstrated that CRS actually altered hair cycle by inhibiting hair follicle growth in vivo, prolonging the telogen stage and delaying subsequent anagen and catagen stage. Up-regulation of SP protein expression in cutaneous peripheral nerve fibers and activation of mast cell were observed accompanied with increase of lipid peroxidation levels and reduction of the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in CRS mice skin. In addition, SP receptor antagonist (RP67580) reduced mast cell activations and lipid peroxidation levels as well as increased GSH-Px activity and normalized hair cycle. Furthermore, antioxidant Tempol (a free radical scavenger) also restored hair cycle, reduced SP protein expression and mast cell activation. Our study provides the first solid evidence for how ROS play a role in regulation of psychoemotional stress induced SP-Mast cell pathway which may provide a convincing rationale for antioxidant application in clinical treatment with psychological stress induced hair loss.


Skin wound healing in different aged Xenopus laevis.
Xenopus froglets can perfectly heal skin wounds without scarring. To explore whether this capacity is maintained as development proceeds, we examined the cellular responses during the repair of skin injury in 8- and 15-month-old Xenopus laevis. The morphology and sequence of healing phases (i.e., inflammation, new tissue formation, and remodeling) were independent of age, while the timing was delayed in older frogs. At the beginning of postinjury, wound re-epithelialization occurred in form of a thin epithelium followed by a multilayered epidermis containing cells with apoptotic patterns and keratinocytes stained by anti-inducible nitric oxide synthase (iNOS) antibody. The inflammatory response, early activated by recruitment of blood cells immunoreactive to anti-tumor necrosis factor (TNF)-α, iNOS, transforming growth factor (TGF)-β1, and matrix metalloproteinase (MMP)-9, persisted over time. The dermis repaired by a granulation tissue with extensive angiogenesis, inflammatory cells, fibroblasts, and anti-α-SMA positive myofibroblasts. As the healing progressed, wounded areas displayed vascular regression, decrease in cellularity, and rearrangement of provisional matrix. The epidermis restored to a prewound morphology while granulation tissue was replaced by a fibrous tissue in a scar-like pattern. The quantitative PCR analysis demonstrated an up-regulated expression of Xenopus suppressor of cytokine signaling 3 (XSOCS-3) and Xenopus transforming growth factor-β2 (XTGF-β2) soon after wounding and peak levels were detected when granulation tissue was well developed with a large number of inflammatory cells. The findings indicate that X. laevis skin wound healing occurred by a combination of regeneration (in epidermis) and repair (in dermis) and, in contrast to froglet scarless wound healing, the growth to a more mature adult stage is associated with a decrease in regenerative capacity with scar-like tissue formation.


Effect of regional inhomogeneity on collateral airway resistance.
We studied the interaction of transpulmonary pressure (Pao) and the pressure in an isolated sublobar lung segment (Ps) on collateral resistance (Rcoll) in excised dog lungs. A double-lumen catheter was advanced through the trachea and wedged in a peripheral airway. Gas flowed through the outer lumen of the catheter (Vcoll) to enter the segment while Ps was measured by the inner lumen. Collateral resistance was calculated as Rcoll = (Ps - Pao)/Vcoll. At constant Ps, raising Pao sharply decreased Rcoll, but at constant Pao, raising Ps increased Rcoll. Replotting these data showed that Rcoll was related to the pressure difference between the segment and the remainder of the lobe (Ps - Pao), such that raising Ps - Pao caused no change in Rcoll at lower Pao but increased Rcoll at higher Pao. Similar findings occurred in the lungs of closed-chest anesthetized dogs. We propose that this technique measures the sum of resistances of airways and collateral channels found in the segment body (Rs) and of those passing through the segment-lobar parenchymal interface (Ri). Raising Ps - Pao decreases Rs because of the volume dependency of airway resistance and increases Ri due to tissue distortion at the interface occurring as a result of inhomogeneous segment inflation. The net change in measured Rcoll depends on which of its components change in greatest magnitude. This effect varies with Pao due to the hyperbolic relationship of Pao with airway and collateral resistance.


Population mobility and multi-partner sex in Botswana: implications for the spread of HIV/AIDS.
For cultural and economic reasons, Botswana has one of the most mobile populations in the world. People move around the country frequently for employment opportunities and because of the nature of the settlement patterns. Also, there is extensive multi-partner sexual activity in the country. This study analyses the relationship between population mobility and multi-partner sex and their implications for the spread of HIV and AIDS in Botswana. The unit of analysis is a sample of 292 mobile working in rural and urban settings in four selected districts of the country.


Enhancing chemosensitivity in oral squamous cell carcinoma by lentivirus vector-mediated RNA interference targeting EGFR and MRP2.
Oral cancer is the eighth most common type of cancer among men worldwide, with an age-standardized rate of 6.3 per 100,000, and is the fourth leading cause of cancer-associated mortality among men in Taiwan. Cisplatin and 5-fluorouracil (5-FU) are two of the most frequently utilized chemotherapy drugs for the treatment of oral cancer. Although oral cancer patients initially benefit from chemotherapy with these drugs, they may develop resistance to them, which worsens their prognosis and reduces survival rates. It has been reported that increased levels of epidermal growth factor receptor (EGFR) and multidrug resistance-associated protein 2 (MRP2) induce drug resistance in numerous types of human cancer. Therefore, the present study employed lentivirus vector-mediated RNA interference (RNAi) in order to target the genes encoding EGFR and MRP2 in the oral squamous cell carcinoma cell line OC2. It was observed that RNAi-mediated downregulation of EGFR or MRP2 increased the sensitivity to 5-FU and cisplatin in OC2 cells. Downregulation of EGFR resulted in significant suppression of OC2 tumor growth following 5-FU administration. However, simultaneous downregulation of the two genes did not further suppress the tumor growth, indicating that MRP2 does not have a significant role in the chemosensitivity of EGFR-downregulated cells to 5-FU. In contrast, downregulation of MRP2 was demonstrated to significantly enhance the therapeutic effects of cisplatin in EGFR-downregulated OC2 tumors. The observation that the expression of MRP2 was positively correlated with the level of cisplatin resistance in cells suggests that RNAi-mediated downregulation of MRP2 may be applicable as a therapeutic approach toward reversing MRP2-dependent cisplatin resistance in oral cancer.


Pulmonary toxicity and metabolic activation of dauricine in CD-1 mice.
Dauricine is the major bioactive component isolated from the roots of Menispermum dauricum D.C. and has shown promising pharmacological activities with a great potential for clinic use. However, the adverse effects and toxicity of the alkaloid are unfortunately ignored. The objective of the current study was to evaluate the toxicity of dauricine in vitro and in vivo. Mice (CD-1) were treated intraperitoneally with dauricine at various doses, and sera and lung lavage fluids were collected after 24 h of treatment. No changes in serum aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen were noticed, whereas a dose-dependent increase in lactate dehydrogenase activity was observed in lung lavage fluids. Ethidium-based staining studies showed that remarkable cells lost membrane integrity in the lungs of the animals treated with dauricine at 150 mg/kg. Histopathological evaluation of lungs of mice showed that dauricine at the same dose caused significant alveolar edema and hemorrhage. Exposure to dauricine at 40 muM for 24 h resulted in up to 60% cell death in human lung cell lines BEAS-2B, WI-38, and A549. Ketoconazole showed protective effect on the pulmonary injury in mice given dauricine. A quinone methide metabolite of dauricine was identified in mouse lung microsomal incubations, and the presence of ketoconazole in the microsomal incubations suppressed the formation of the quinone methide metabolite. In conclusion, dauricine produced pulmonary injury in CD-1 mice. The pulmonary toxicity appears to depend on the metabolism of dauricine mediated by CYP3A. The electrophilic quinone methide metabolite probably plays an important role in the pulmonary toxicity induced by dauricine.


Germination and Outgrowth of Bacillus subtilis Spores in the Presence of Selected Antioxidants.
Germination and outgrowth of Bacillus subtilis spores was investigated using laboratory media containing butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tertiary butylhydroquinone (TBHQ) and propyl gallate (PG). Although all antioxidants inhibited or retarded germination initiation and outgrowth, only BHA and TBHQ were effective at relatively low concentrations (150 and 100 ppm, respectively). Furthermore, BHA and TBHQ (150 ppm) were also shown to reduce spore growth by approximately 1 and 4 log10 within 72 and 6 h, respectively. The difference in the number of survivors between thermally (10 min at 80°C) and BHA (150 ppm)-treated germinated spores indicated that the antioxidant was effective against only a certain portion of the total heat-sensitive spore population. Sporostasis caused by BHA appeared reversible by the addition of Tween 80.


Thromboprophylaxis, bleeding and post-operative prosthetic joint infection in total hip and knee arthroplasty: a comprehensive literature review.
Concerns regarding risk versus benefit, that is, the possible impact of surgical-site bleeding on post-operative joint infections, have contributed to a continuing debate over recommendations for venous thromboembolism (VTE) prophylaxis in post-surgical orthopedic patients undergoing total hip and knee arthroplasty (THA/TKA). A comprehensive literature search using MEDLINE covering the period 2004-2009 was conducted, and published studies that focused on THA and TKA and contained data applicable to thromboprophylaxis, post-surgical wound infection and bleeding are reviewed in this paper. The search strategy included various combinations of terms related to lower limb joint arthroplasty, anticoagulant drugs, post-operative bleeding and prosthetic joint infection (wound infection). Methodological constraints included failure in some studies to define an infection, variations among the studies in the definitions of bleeding and differences in the follow-up time for capturing infection and bleeding events. Despite this, this comprehensive review identified observational, 'real-world' data that can contribute in important ways to the existing evidence base. There are insufficient data to either confirm or refute the hypothesis that post-operative bleeding is a mediating pathophysiologic factor linking pharmacologic VTE prophylaxis to an increased risk for wound infection. Studies specifically designed to examine the interrelationship between thromboprophylaxis, bleeding and wound infections following THA/TKA are warranted.


Possible Therapeutic Doses of Cannabinoid Type 1 Receptor Antagonist Reverses Key Alterations in Fragile X Syndrome Mouse Model.
Fragile X syndrome (FXS) is the most common monogenetic cause of intellectual disability. The cognitive deficits in the mouse model for this disorder, the Fragile X Mental Retardation 1 (Fmr1) knockout (KO) mouse, have been restored by different pharmacological approaches, among those the blockade of cannabinoid type 1 (CB1) receptor. In this regard, our previous study showed that the CB1 receptor antagonist/inverse agonist rimonabant normalized a number of core features in the Fmr1 knockout mouse. Rimonabant was commercialized at high doses for its anti-obesity properties, and withdrawn from the market on the bases of mood-related adverse effects. In this study we show, by using electrophysiological approaches, that low dosages of rimonabant (0.1 mg/kg) manage to normalize metabotropic glutamate receptor dependent long-term depression (mGluR-LTD). In addition, low doses of rimonabant (from 0.01 mg/kg) equally normalized the cognitive deficit in the mouse model of FXS. These doses of rimonabant were from 30 to 300 times lower than those required to reduce body weight in rodents and to presumably produce adverse effects in humans. Furthermore, NESS0327, a CB1 receptor neutral antagonist, was also effective in preventing the novel object-recognition memory deficit in Fmr1 KO mice. These data further support targeting CB1 receptors as a relevant therapy for FXS.


Claisen rearrangements of equilibrating allylic azides.
Equilibrating mixtures of allylic azide-containing allylic alcohols or allylic 2-tolylsulfonylacetic esters undergo Johnson-Claisen or Ireland-Claisen rearrangement reactions to give unsaturated γ-azidoesters and -acids, respectively. Decarboxylation of the acids under basic conditions gives azidosulfones, with moderate to high diastereoselectivity.


The effects of cigarette smoking and nicotine on the therapeutic potential of mesenchymal stem cells.
Due to their immunoregulatory properties and capacity for multi-lineage differentiation, mesenchymal stem cells (MSCs) have been used as new therapeutic agents in regenerative medicine. Numerous lifestyle habits and behavioral risk factors may modulate metabolic and cell growth signaling pathways in MSCs, affecting their phenotype and function. Accordingly, identification of these factors and minimization of their influence on viability and function of transplanted MSCs may greatly contribute to their better therapeutic efficacy. A large number of experimental and clinical studies have demonstrated the detrimental effects of cigarette smoke and nicotine on proliferation, homing, chondrogenic and osteogenic differentiation of MSCs. Cigarette smoke down-regulates expression of chemokine receptors and modulates activity of anti-oxidative enzymes in MSCs, while nicotine impairs synthesis of transcriptional factors that regulate the cell cycle, metabolism, migration, chondrogenesis and osteogenesis. In this review article, we summarize current knowledge about molecular mechanisms that are responsible for cigarette smoke and nicotine-dependent modulation of MSCs' therapeutic potential.


Update on outcomes research databases in prostate cancer 2006.
The purpose of this review is to summarize single-institution prostate-cancer-outcomes databases (which are most commonly derived from large academic medical centers, Veterans Affairs medical centers, and military hospitals) to summarize the design and development of three well characterized outcomes databases that combine data from multiple sites (Carcinoma of the Prostate Strategic Urological Research Endeavor, Center for Prostate Disease Research, and the Shared Equal Access Regional Cancer Hospital database) and to use the examples of obesity and prostate-specific antigen changes over time to highlight the importance of these databases in prostate-cancer outcomes. Multiple databases have demonstrated that obese men are at greater risk of biochemical progression following radical prostatectomy. In addition, objective data have shown that it is more difficult to operate on obese men leading to greater risk of positive surgical margins, which may contribute to poorer outcomes. Several databases have shown that a rapidly increasing prostate-specific antigen, measured either before diagnosis or after failed primary therapy, is associated with increased risk of prostate-cancer-specific mortality. Outcomes databases are extremely useful tools. They have lead to dramatic improvements of our understanding of prostate cancer. The challenge is to use this information from past patients to help us better manage our current and future patients.