Insertion-deletion polymorphism in the angiotensin-converting enzyme (ACE) gene among Sudanese, Somalis, Emiratis, and Omanis.
The angiotensin-converting enzyme (ACE) gene in humans contains an insertion-deletion polymorphism in its intron 16. Because of its involvement with the renin-angiotensin system, the insertion-deletion polymorphism of the ACE gene has been widely investigated in different populations and in case-control studies. However, similar studies for Arab populations are limited in number. Therefore we have investigated the frequencies of the *I and *D alleles of the ACE gene among Sudanese, Somalis, and Arab nationals of the United Arab Emirates and Oman using previously described methods. Our data indicate a preponderance of the *D allele among the Arab and African populations studied (Sudanese, 0.64; Somalis, 0.73; Emiratis, 0.61; and Omanis, 0.71).


Idiotypic analysis of anti-nucleosome monoclonal antibodies derived from lupus mice.
3F6 and 2E1 are anti-(H2A-H2B) monoclonal antibodies derived from a 12-month-old (NZBxNZW)F1 mouse that diverged from the same clonal precursor by somatic mutations. Rabbit anti-idiotypic antisera were prepared against these two monoclonal antibodies and used as probes to analyse the properties and expression of 3F6 and 2E1 idiotypes. Both idiotypes were conformational, distant from the antigen binding site and did not correlate with a VH- or VL-chain usage. 3F6 was preferentially bound by anti-3F6 idiotype but was weakly recognized by anti-2E1 idiotype suggesting, since 3F6 derives from 2E1, that 3F6 bore idiotypic determinants generated by somatic mutations. While none of the murine anti-DNA monoclonal antibodies tested expressed 2E1 or 3F6 idiotypes, 3F6 idiotype could be detected on approximately one-third of anti-(H2A-H2B) monoclonal antibodies derived from other lupus strains of mice, demonstrating the presence of cross-reactive idiotypes on autoantibodies directed against a nucleosome that could result from somatic mutations.


Galantamine-based hybrid molecules with acetylcholinesterase, butyrylcholinesterase and γ-secretase inhibition activities.
We previously designed novel peptides-containing galantamine analogues. These compounds we analyzed for their putative inhibitory effect towards acetylcholinesterase, butyrylcholinesterase and γ-secretase, three activities of which could be central to various neurodegenerative pathologies including Alzheimer's disease. These pharmacological agents were virtually equipotent on acetylcholinesterase activity but display drastically higher inhibitory activities towards butyrylcholinesterase with several compounds displaying an about 100-fold higher activity than that harboured by galantamine. Strikingly, two of the galantamine amides that displayed low activity towards acetylcholinesterase exhibited the highest inhibitory potency towards butyrylcholinesterase (106 to 133 times more active than galantamine). Interestingly, five compounds show a rather good γ-secretase inhibitory potency while they retain their ability to inhibit AChE and/or BuChE activity. Thus, we have been able to design novel compounds with significant inhibitory activity against several of the enzymes responsible for key dysfunctions taking place in several neurodegenerative diseases. These mixed inhibitors could therefore be envisioned as potential pharmacological tools aimed at circumventing the degenerative processes taking place in these major pathologies.


Environmental Lead Exposure and Influenza and Respiratory Syncytial Virus Diagnoses in Young Children: A Test-Negative Case-Control Study.
Experimental and epidemiological evidence suggests that environmental toxicants may influence susceptibility to influenza and respiratory syncytial virus (RSV). The objective of the present study was to estimate the association between blood lead concentrations and the odds of child influenza or RSV infection. A test-negative, case-control study was conducted among 617 children, <4 years of age, tested for influenza/RSV from 2012-2017 in Rochester, NY. There were 49 influenza cases (568 controls) and 123 RSV cases (494 controls). Blood lead concentrations reported in children's medical records were linked with influenza/RSV lab test results. Covariables were collected from medical records, birth certificates, and U.S. census data. In this sample, evidence of an association between blood lead levels and RSV or influenza diagnosis was not observed. Children with a lead level ≥1 μg/dL vs. <1 μg/dL had an adjusted odds ratio (aOR) and 95% confidence limit of 0.95 (0.60, 1.49) for RSV and 1.34 (0.65, 2.75) for influenza. In sex-specific analyses, boys with lead concentrations ≥1 μg/dL vs. <1 μg/dL had an aOR = 1.89 (1.25, 2.86) for influenza diagnosis, while the estimates were inconsistent for girls. These results are suggestive of sex-specific associations between blood lead levels and the risk of influenza, although the sample size was small.


Laser Polishing of Additive Manufactured Aluminium Parts by Modulated Laser Power.
In this study a new approach to laser polishing with periodic modulated laser power in the kilohertz regime is introduced. By varying the modulation frequency and modulation time, different periodic laser power curves with varying minimum, peak and average laser power can be created. The feasibility of the method is shown by polishing of vertical built AlSi10Mg L-PBF parts with an initial roughness of Ra = 12.22 µm. One polishing pass revealed a decreasing surface roughness with increasing energy density on the surface up to Ra = 0.145 µm. An increasing energy density results in a rising remelting depth between 50 and 255 µm and a rising relative porosity of 0.3% to 4.6%. Furthermore, the thermal process stability, analysed by the melt pool length in scanning direction, reveals a steadily increasing melt pool dimension due to component heating. Multiple laser polishing passes offers a further reduced surface roughness, especially at higher modulation frequencies and provides an improved orientation independent roughness homogeneity. The process stability regarding varying initial surface roughness revealed an almost constant relative roughness reduction rate with an achievable roughness variation after two polishing passes between Ra = 0.13-0.26 µm from an initial state of Ra = 8.0-19.2 µm.


Proximal and distal factors associated with dropout versus maintained participation in organized sport.
The purpose of this study was to investigate a large number of determinants of sport dropout among French adolescents, in order to reveal proximal and distal factors of dropout. 261 current and 106 dropout athletes (M = 14.6) participated to the study. The data were collected by a questionnaire assessing demographic information, athletes' perceptions on their experience, their parents, teammates and coach. t-tests revealed that current and former athletes were distinct on numerous variables. A discriminant function analysis showed three proximal predictors of sport dropout (perceived value of the activity, satisfaction, parents' investment). Subsequent regression analyses showed that perceived value was positively predicted by perceived competence, the value of the activity for teammates, coach's investment, and negatively by conflicts of interest and goal conflict with teammates; satisfaction was positively predicted by the coach's mastery climate, but negatively predicted by conflicts of interest and goal conflict with teammates and with the coach; parents investment was negatively predicted by the goal conflicts with them. This study permitted to discriminate between proximal and more distal psychological antecedents of the dropout behaviour. It brings information relative to the possible targets of interventions aiming at preventing dropout from organized sport. Key pointsGeographical, financial and time constraints did not predict dropout from organized sport.The value of the activity, the level of satisfaction of the athlete, and the perceived parental investment, were identified as proximal predictors of maintained participation.Athletes' perceptions about themselves (perceived competence, conflict of interest) or their coach (investment, climate, goal conflicts), peers (value, goal conflicts) or parents (goal conflicts), seem to act as distal factors.


Enhanced Oral Bioavailability of Etodolac by the Liquisolid Compact Technique: Optimisation, In-Vitro and In-Vivo Evaluation.
Poor dissolution of Etodolac is one of the major challenges in achieving the desired therapeutic effect in oral therapy. This study aimed to assess the potential of the liquisolid compact technique in increasing the rate of dissolution of Etodolac and thus its bioavailability. Liquisolid compacts were prepared using PEG 400, Avicel PH-200 and Aerosil 200 as non-volatile liquid, carrier and coating material, respectively. The optimisation was carried out by applying a 32 full factorial design using Design expert software 184.108.40.206 to examine the effects of independent variables (load factor and carrier: coating ratio) on dependent variables (angle of repose and % cumulative drug release at 30 min [Q <sub>30 min]). Assessment of bioavailability was based on a pharmacokinetic study on rabbits and pharmacodynamics evaluation on rats, respectively. The formulation M3 was identified as the optimised formulation based on the better flow (lower angle of repose) and a higher rate of dissolution (Q 30 min >95%). The higher dissolution rate could be due to conversion of Etodolac into an amorphous molecularly dispersed state, availability of larger surface area, enhancement of aqueous solubility and enhanced wetting of drug particles. Studies with DSC, XRD, and SEM verified the transformation of Etodolac from crystalline to amorphous state, a key factor responsible for improving the dissolution rate. The pharmacokinetic profile of M3 was prominent, demonstrating higher absorption of Etodolac in comparison to oral suspension and immediate-release conventional tablets in rabbits. Liquisolid formulation exhibited a 27% increment in paw thickness as compared to 57% and 46% increments for oral suspension and immediate-release conventional tablets, respectively, after 7 hrs in the carrageenan-induced paw model in rats. The results indicated the liquisolid compact technique to be a promising strategy to enhance the bioavailability of Etodolac.


Intrathecal infusion of bupivacaine and clonidine provides effective analgesia in a terminally ill child.
The intrathecal infusion of drugs to provide analgesia for terminally ill children with refractory pain is a rarely utilized but very effective technique. A number of pharmacological agents, most commonly opioids and local anesthetics, have been administered intrathecally for this purpose. However, tachyphylaxis and neuraxial opioid-related side effects can limit their utility. The alpha-2 agonist clonidine is commonly used to augment local anesthetic techniques for postsurgical pain in children and for the management of refractory cancer pain in adults, but there is only a single report of the use of clonidine intrathecally in a terminally ill child. We present the case of the youngest reported child to have received intrathecal analgesia for terminal care: a 3-year-old boy with advanced pelvic rhabdomyosarcoma, whose refractory pain was managed effectively with an intrathecal infusion of bupivacaine and preservative-free clonidine.


A mutation, in the iron-responsive element of H ferritin mRNA, causing autosomal dominant iron overload.
Ferritin, which is composed of H and L subunits, plays an important role in iron storage and in the control of intracellular iron distribution. Synthesis of both ferritin subunits is controlled by a common cytosolic protein, iron regulatory protein (IRP), which binds to the iron-responsive element (IRE) in the 5'-UTR of the H- and L-ferritin mRNAs. In the present study, we have identified a single point mutation (A49U) in the IRE motif of H-ferritin mRNA, in four of seven members of a Japanese family affected by dominantly inherited iron overload. Gel-shift mobility assay and Scatchard-plot analysis revealed that a mutated IRE probe had a higher binding affinity to IRP than did the wild-type probe. When mutated H subunit was overexpressed in COS-1 cells, suppression of H-subunit synthesis and of the increment of radiolabeled iron uptake were observed. These data suggest that the A49U mutation in the IRE of H-subunit is responsible for tissue iron deposition and is a novel cause of hereditary iron overload, most likely related to impairment of the ferroxidase activity generated by H subunit.


Fatal sand impaction of the spiral colon in a 1-month-old alpaca.
A 1-month-old cria (Lama pacos) was presented because of depression, anorexia, and diarrhea for 3 days. Although treated for enteritis (intravenous fluids and antibiotics), the cria's condition deteriorated. An abdominal radiograph revealed radiodense materials in the 3rd compartment and intestines. The cria died due to sand impaction of the spiral colon.


A mixed quantum-classical molecular dynamics study of anti-tetrol and syn-tetrol dissolved in liquid chloroform II: infrared emission spectra, vibrational excited-state lifetimes, and nonequilibrium hydrogen-bond dynamics.
The effect of vibrational excitation and relaxation of the hydroxyl stretch on the hydrogen-bond structure and dynamics of stereoselectively synthesized syn-tetrol and anti-tetrol dissolved in deuterated chloroform are investigated via a mixed quantum-classical molecular dynamics simulation. Emphasis is placed on the changes in hydrogen-bond structure upon photoexcitation and the nonequilibrium hydrogen-bond dynamics that follows the subsequent relaxation from the excited to the ground vibrational state. The propensity to form hydrogen bonds is shown to increase upon photoexcitation of the hydroxyl stretch, thereby leading to a sizable red-shift of the infrared emission spectra relative to the corresponding absorption spectra. The vibrational excited state lifetimes are calculated within the framework of Fermi's golden rule and the harmonic-Schofield quantum correction factor, and found to be sensitive reporters of the underlying hydrogen-bond structure. The energy released during the relaxation from the excited to the ground state is shown to break hydrogen bonds involving the relaxing hydroxyl. The spectral signature of this nonequilibrium relaxation process is analyzed in detail.


Extending the usefulness of the verbal memory test: The promise of machine learning.
The evaluation of verbal memory is a core component of neuropsychological assessment in a wide range of clinical and research settings. Leveraging story recall to assay neurocognitive function could be made more useful if it were possible to administer frequently (i.e., would allow for the collection of more patient data over time) and automatically assess the recalls with machine learning methods. In the present study, we evaluated a novel story recall test with 24 parallel forms that was deployed using smart devices in 94 psychiatric inpatients and 80 nonpatient adults. Machine learning and vector-based natural language processing methods were employed to automate test scoring, and performance using these methods was evaluated in their incremental validity, criterion validity (i.e., convergence with trained human raters), and parallel forms reliability. Our results suggest moderate to high consistency across the parallel forms, high convergence with human raters (r values ~ 0.89), and high incremental validity for discriminating between groups. While much work remains, the present findings are critical for implementing an automated, neuropsychological test deployable using remote technologies across multiple and frequent administrations.


Treatment of patients with HBV-related decompensated cirrhosis and liver transplanted patients.
Antiviral therapy using newer nucleos(t)ide analogs with lower resistance rates could suppress hepatitis B virus (HBV) replication, improve liver function in patients with compensated or decompensated cirrhosis, delay or obviate liver transplantation in some patients, and reduce the risk of HBV recurrence. Some form of HBV prophylaxis needs to be continued indefinitely posttransplant. However, in patients with a low-risk of HBV recurrence it is possible to discontinue hepatitis B immunoglobulins and maintain long-term nucleos(t)ide analog therapy. Currently, treatment of posttransplantation hepatitis B is a less important clinical problem than it was historically because effective antiviral therapies exist to rescue patients who failed initial prophylaxis.


Graphene quantum dots derived from carbon fibers.
Graphene quantum dots (GQDs), which are edge-bound nanometer-size graphene pieces, have fascinating optical and electronic properties. These have been synthesized either by nanolithography or from starting materials such as graphene oxide (GO) by the chemical breakdown of their extended planar structure, both of which are multistep tedious processes. Here, we report that during the acid treatment and chemical exfoliation of traditional pitch-based carbon fibers, that are both cheap and commercially available, the stacked graphitic submicrometer domains of the fibers are easily broken down, leading to the creation of GQDs with different size distribution in scalable amounts. The as-produced GQDs, in the size range of 1-4 nm, show two-dimensional morphology, most of which present zigzag edge structure, and are 1-3 atomic layers thick. The photoluminescence of the GQDs can be tailored through varying the size of the GQDs by changing process parameters. Due to the luminescence stability, nanosecond lifetime, biocompatibility, low toxicity, and high water solubility, these GQDs are demonstrated to be excellent probes for high contrast bioimaging and biosensing applications.


Corneal and scleral permeability of quinolones--a pharmacokinetics study.
To investigate the corneal and scleral permeability of nalidixic acid and synthesized fluoroquinolones and their in vivo pharmacokinetics in rabbits. The corneal and scleral permeability coefficients of ciprofloxacin, norfloxacin, cinoxacin, enoxacin, and ofloxacin were determined in rabbits using high performance liquid chromatography (HPLC). The aqueous humor levels of norfloxacin and ciprofloxacin were measured separately by topical instillation of 0.3% solutions of the two drugs onto rabbit eyes. Nalidixic acid had a higher corneal permeability coefficient (17.3 +/- 3.56 x 10(-6) cm/second) than all other drugs tested (p < 0.01). Corneal permeability coefficients in rabbits among ciprofloxacin, norfloxacin, cinoxacin, enoxacin, and ofloxacin were not significantly different (p > 0.1). Comparing the corneal and scleral permeability coefficients, only values for nalidixic acid were not significantly different (17.35 +/- 3.56 x l0(-6) cm/second versus 22.69 +/- 5.19 x 10(-6) cm/second, p > 0.05), while all other drugs had scleral permeability coefficients 8 to 10 times greater than corneal permeability coefficients. The mean aqueous humor concentration of norfloxacin and ciprofloxacin at 60 minutes to 180 minutes after instillation was around 0.3 microg/mL, a value higher than MIC90 of most bacteria.


Effects of Plasmodium berghei infection on arteether metabolism and disposition.
Arteether (AE) is primarily deethylated to dihydroqinghaosu (DQHS) in rats and humans. Conversion of AE to DQHS was impaired in microsomes from rats infected with Plasmodium berghei. The Km for AE was 175.1 +/- 49.1 and 124.4 +/- 115.1 mumol/l, and Vmax was 2.24 +/- 0.45 and 1.22 +/- 0.67 nmol AE formed/mg protein/min in control and infected microsomes (p < 0.05), respectively. Calculated intrinsic clearance (CLint = initial Vmax/Km) for AE was only 4% lower in infected microsomes. Apparent pharmacokinetic parameter estimates for AE using the isolated perfused rat liver demonstrated no differences (p > 0.05) in volume of distribution, clearance, and half-life between normal and infected animals. Malaria infection resulted in decreased biliary excretion of free AE and DQHS. The majority of AE is eliminated via biliary excretion of conjugated DQHS, which is approximately 500-fold higher than free DQHS and 75-fold higher than free AE on a molar basis.


[A Case of Bilateral Ureteral Stenosis Treated by Upper Urinary Tract Reconstruction Using an Ileal Ureter].
A 41-year-old female who suffered local recurrence of cervical cancer after receiving chemoradiotherapy underwent radical hysterectomy, radical vaginal resection, and pelvic and paraaortic lymph node dissection. After surgery, bilateral hydronephrosis due to right ureteral stenosis and left uretero-vaginal fistula occurred. We therefore placed a bilateral ureteral stent. Thereafter, we continued to replace the bilateral ureteral stent once every 3 months, but the replacement of the right ureteral stent became impossible three years after the initial placement. We thus performed bilateral upper urinary tract reconstruction using an ileal ureter with the aim of both eliminating the left ureteral vaginal fistula and resolving the right ureteral stricture.


The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition.
Much attention has been recently focused on the role of cancer stem cells (CSCs) in the initiation and progression of solid malignancies. Since CSCs are able to proliferate and self-renew extensively due to their ability to express anti-apoptotic and drug resistant proteins, thus sustaining tumor growth. Therefore, the strategy to eradicate CSCs might have significant clinical implications. The objectives of this study were to examine the molecular mechanisms by which epigallocathechin gallate (EGCG) inhibits stem cell characteristics of prostate CSCs, and synergizes with quercetin, a major polyphenol and flavonoid commonly detected in many fruits and vegetables. Our data indicate that human prostate cancer cell lines contain a small population of CD44+CD133+ cancer stem cells and their self-renewal capacity is inhibited by EGCG. Furthermore, EGCG inhibits the self-renewal capacity of CD44+alpha2beta1+CD133+ CSCs isolated from human primary prostate tumors, as measured by spheroid formation in suspension. EGCG induces apoptosis by activating capase-3/7 and inhibiting the expression of Bcl-2, survivin and XIAP in CSCs. Furthermore, EGCG inhibits epithelial-mesenchymal transition by inhibiting the expression of vimentin, slug, snail and nuclear beta-catenin, and the activity of LEF-1/TCF responsive reporter, and also retards CSC's migration and invasion, suggesting the blockade of signaling involved in early metastasis. Interestingly, quercetin synergizes with EGCG in inhibiting the self-renewal properties of prostate CSCs, inducing apoptosis, and blocking CSC's migration and invasion. These data suggest that EGCG either alone or in combination with quercetin can eliminate cancer stem cell-characteristics. Since carcinogenesis is a complex process, combination of bioactive dietary agents with complementary activities will be beneficial for prostate cancer prevention and/ortreatment.


Use of infrared thermography to detect injections and palmar digital neurectomy in horses.
Thermography is a non-contact, non-invasive technique that detects surface heat emitted as infrared radiation. Because skin temperature reflects the status of underlying tissue metabolism and blood circulation, abnormal thermal patterns can signify areas of superficial inflammation. The objective of this study was to determine if thermography could detect the injection of analgesic and neurolytic agents and surgical palmar digital neurectomy. Procedures evaluated include injection of the lumbar region, suspensory ligaments, tibial nerve, palmar digital nerves, and palmar digital neurectomy. Thermographic images were obtained before and after the procedures until a significant difference was no longer detected. Local injection of the lumbar region and the suspensory ligament produced detectable thermal patterns for two days, and tibial nerve infiltration with a neurolytic agent was significant for two days. Analgesia of the palmar nerves was significant for 24h with bupivicaine, compared to five days for ammonium chloride. Palmar digital neurectomy produced more variable thermal patterns. While sensitive enough to detect changes in heat patterns from control regions, thermography is not specific enough to discriminate between procedures and injury inducing an inflammatory response.


Treatment-resistant major depressive disorder: Canadian expert consensus on definition and assessment.
Treatment-resistant depression (TRD) is a debilitating chronic mental illness that confers increased morbidity and mortality, decreases the quality of life, impairs occupational, social, and offspring development, and translates into increased costs on the healthcare system. The goal of this study is to reach an agreement on the concept, definition, staging model, and assessment of TRD. This study involved a review of the literature and a modified Delphi process for consensus agreement. The Appraisal of Guidelines for Research & Evaluation II guidelines were followed for the literature appraisal. Literature was assessed for quality and strength of evidence using the grading, assessment, development, and evaluations system. Canadian national experts in depression were invited for the modified Delphi process based on their prior clinical and research expertize. Survey items were considered to have reached a consensus if 80% or more of the experts supported the statement. Fourteen Canadian experts were recruited for three rounds of surveys to reach a consensus on a total of 27 items. Experts agreed that a dimensional definition for treatment resistance was a useful concept to describe the heterogeneity of this illness. The use of staging models and clinical scales was recommended in evaluating depression. Risk factors and comorbidities were identified as potential predictors for treatment resistance. TRD is a meaningful concept both for clinical practice and research. An operational definition for TRD will allow for opportunities to improve the validity of predictors and therapeutic options for these patients.


Plants and Natural Products with Activity against Various Types of Coronaviruses: A Review with Focus on SARS-CoV-2.
COVID-19 is a pandemic disease caused by the SARS-CoV-2 virus, which is potentially fatal for vulnerable individuals. Disease management represents a challenge for many countries, given the shortage of medicines and hospital resources. The objective of this work was to review the medicinal plants, foods and natural products showing scientific evidence for host protection against various types of coronaviruses, with a focus on SARS-CoV-2. Natural products that mitigate the symptoms caused by various coronaviruses are also presented. Particular attention was placed on natural products that stabilize the Renin-Angiotensin-Aldosterone System (RAAS), which has been associated with the entry of the SARS-CoV-2 into human cells.


Survey of paediatricians' opinions on a regional paediatric telecardiology service.
The aim of this study is to evaluate consultant general paediatricians' opinions of a UK paediatric telecardiology service. A structured questionnaire was developed and sent to all consultant paediatricians working in a district general hospital in Northern Ireland. Paediatricians (n = 35) regarded the regional paediatric telecardiology service as very useful and of good value for money. Paediatricans in hospitals without access to telecardiology expressed a desire to join the network (86%, 12/14). More frequent use of the paediatric telecardiology service was associated with increased confidence in performing echocardiography and using the telemedicine equipment and a special interest in neonatology. The vast majority of paediatricians (32/35, 91%) believed that there should be a shared clinical responsibility for the patient following a teleconsultation. A total of 33/35 (94%) stated that the telephone costs of the consultation should be paid by the paediatrician but that the professional time of the cardiologist should be paid by the tertiary centre (29/35, 83%). Paediatricians have consistently positive experiences of a regional paediatric telecardiology service. They believe that clinical responsibility is shared, and there should not be any professional fee for telemedicine activities.


A Comprehensive Analysis of 2013 Dystrophinopathies in China: A Report From National Rare Disease Center.
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive neuromuscular disorders caused by mutations in DMD. A high-quality database of DMD/BMD is essential not only for clinical practice but also for fundamental research. Here, we aimed to build the largest Chinese national dystrophinopathy database using the National Rare Diseases Registry System of China. Peking Union Medical College Hospital (PUMCH) was the National Rare Diseases Center of China. This research involved 2013 patients with dystrophinopathies, whose diagnoses were confirmed; they were registered and followed up at PUMCH from March 2011 to December 2018. Family history, clinical signs, and treatment data were reported for patients with DMD and BMD at different rates. All six serum biochemical indexes could accurately distinguish between DMD and BMD patients. Copy number variations were the most frequent mutation type (79.2% in DMD and 84.3% in BMD), of which large deletions accounted for 88.4 and 88.6%, large duplications accounted for 11.6 and 11.4% in DMD and BMD, respectively. An exon deletion hotspot, located in exons 45-54, was observed in DMD, and intron 44 was the most frequent deletion starting point (26.5%). Duplication and single nucleotide variations appeared to be uniformly distributed among all exons. Eleven patients were identified to have ultrarare mutation types. Eleven other patients suffered from two separate mutations simultaneously, some of which may have taken place via dependent mechanisms. Thus, we have established the largest hospital-based Chinese dystrophinopathy database via the National Rare Diseases Registry System. This study provides valuable information for further diagnostic and therapeutic studies of dystrophinopathy.


Diagnostic tests for syphilis: New tests and new algorithms.
Syphilis is a sexually transmitted infection caused by Treponema pallidum. A total of 13,106 cases of primary and secondary syphilis were reported in the United States in 2011 and the rate of infection has increased in subgroups, particularly men who have sex with men. The disease is mainly diagnosed through clinical findings and serologic testing. However, no single serologic test of syphilis is sufficient. Hence, the serologic diagnosis of syphilis requires the detection of 2 types of antibodies (nontreponemal antibodies and treponemal antibodies). The paradigm in syphilis testing has recently shifted in many centers to screen with a treponemal antibody test, reflexing to a nontreponemal test if the treponemal antibody test is positive. This reverse of the traditional algorithm may not be widely recognized among clinicians.


Availability of tongue diagnosis system for assessing tongue coating thickness in patients with functional dyspepsia.
Tongue diagnosis is an important procedure in traditional Korean medicine (TKM). In particular, tongue coating thickness (TCT) is deemed to show the progression of the disease. However, conventional tongue diagnosis has limitations because of various external factors. Therefore, it is necessary to investigate the availability of tongue diagnosis system (TDS) in the assessment of TCT. This study has been designed as a prospective clinical trial involving 60 patients with functional dyspepsia. Tongue images will be obtained by TDS twice with a 30 min interval. The system will measure the percentage of TCT and classify it as either no coating, thin coating, or thick coating according to the existing diagnostic criteria. After finishing the collection of 60 patients' tongue images, TCT on the images will be simultaneously evaluated by the conventional method to establish the gold standard for assessing TCT by 5 well-trained clinicians. The evaluation will be repeated by the same clinicians after 2 weeks, but the order of the images will be changed. This trial is expected to provide clinical evidence for the availability of TDS as a diagnostic tool and to contribute to the standardization of the diagnosis system used in TKM. This trial is registered with ClinicalTrials.gov NCT01864837.


Interleukins 2 and 12 produce significant recovery of cytotoxic function in dibutyltin-exposed human natural killer cells.
Cytotoxic function of human natural killer (NK) cells is modulated by a variety of cytokines. Interleukins (IL) 2, 12, 15, and 18 and Interferon gamma (IFNgamma) are potent stimulators of NK cell cytotoxicity. Butyltins (BTs) are used in a variety of consumer products and industrial applications. Dibutyltin (DBT) is found in plastic products, beverages stored in PVC pipes during manufacturing, and poultry products. BTs appear to increase the risk of cancer and viral infections in exposed individuals. Recently, we have demonstrated that the ability of NK cells to kill tumor cells is greatly diminished after a 1-h exposure to dibutyltin. This inhibition of tumor killing function continues even after removal of the compound. There is no significant recovery of NK cytotoxic function even when the cells are allowed to recover for 6 days. In the current study we examine the effects of NK-stimulatory cytokines on the ability of NK cells to recover from the inhibitory effects of a 1-h DBT treatment. Highly purified NK cells (>95% CD16(+)) or a lymphocyte preparation containing both T lymphocytes and NK cells were treated with 5 microM DBT and then allowed to recover for 24 h, 48 h, 4 days, and 6 days in DBT-free medium containing either no cytokine or a maximally stimulatory dose of several NK-stimulatory cytokines. Tumor killing function was tested using a radioactive chromium release assay. As seen in our previous studies there is no recovery of NK cell cytotoxic function even after a 6-day recovery period when no cytokine is present in the medium. However, there is significant recovery of NK cytotoxic function when IL2, IL12, or the combination of IL2 plus IL12 is present in the medium during the recovery period. The other cytokines tested (IL15, IL18, and IFNgamma) were unable to increase the cytotoxicity of DBT-exposed NK cells.


Gata3 Silencing Is Involved in Neuronal Differentiation and Its Abnormal Expression Impedes Neural Activity in Adult Retinal Neurocytes.
GATA binding protein 3 (Gata3), a zinc-finger transcription factor, plays an important role in neural development. However, its expression and bioactivity in the retina remain unclear. In the present study, our data indicated that Gata3 maintains the precursor state of 661W cells, and Gata3 silencing induces cell differentiation. The expression of Nestin, a marker of precursor cells, was significantly decreased in parallel, whereas the expression of Map2, a marker of differentiated neurons, was significantly increased following the decrease in Gata3. Neurite outgrowth was increased by 2.78-fold in Gata3-silenced cells. Moreover, Gata3 expression generally paralleled that of Nestin in developing mouse retinas. Both Gata3 and Nestin were expressed in the retina at postnatal day 1 and silenced in the adult mouse retina. Exogenous Gata3 significantly inhibited the neural activity of primary retinal neurocytes (postnatal day 1) by decreasing synaptophysin levels, neurite outgrowth, and cell viability. Furthermore, in vivo, exogenous Gata3 significantly induced apoptosis and the contraction of retinal outlay filaments and decreased the a- and b-waves in adult mouse intravitreal injected with AAV-Re-Gata3-T2A-GFP. Thus, Gata3 silencing promotes neuronal differentiation and neurite outgrowth. Its abnormal expression impedes neural activity in adult retinal neurocytes. This study provides new insights into Gata3 bioactivity in retinal neurocytes.


Endometrioid ciliated-cell tumors of the ovary: a report of five cases.
Five patients with ovarian endometrioid tumors composed predominantly of ciliated cells are reported; two patients had bilateral neoplasms. Two unilateral, predominantly cystic ciliated-cell tumors from women in their 40s were associated with endometriosis: one was borderline and arose in an endometriotic cyst; the other was borderline with foci of carcinoma and was associated with ipsilateral ovarian and peritoneal endometriosis. Five predominantly adenofibromatous tumors in the three other women, all postmenopausal, were not associated with endometriosis. One woman with a borderline ciliated-cell adenofibroma had had a prior contralateral adnexectomy, another with a borderline ciliated-cell adenofibroma had a contralateral ciliated-cell adenofibroma, and the third woman had a ciliated-cell adenocarcinoma and a contralateral borderline ciliated-cell adenofibroma. In two of the latter three patients the fallopian tubes contained foci of ciliated-cell hyperplasia. All five ciliated-cell malignant tumors were stage I, were treated by operation alone, and had not recurred 21 to 64 (mean 39) months postoperatively. Ciliated-cell tumors of the ovary should be distinguished from serous and mixed serous and endometrioid cancers because of different pathological and possibly different clinical features. Criteria for separating endometrioid ciliated-cell tumors into benign, borderline, and malignant categories are presented; whether any of these neoplasms behaves in a clinically aggressive fashion has yet to be determined.


Experimental trajectory optimization of a flapping fin propulsor using an evolutionary strategy.
The experimental optimization of bio-inspired flapping fin trajectories are demonstrated for potential applications as a side or a rear propulsor of an autonomous underwater vehicle. The trajectories are scored based upon their difference from a force set-point and upon their efficiency and are parameterized by 10 variables inspired by fish swimming. The flapping fin is a generic rectangular rigid flat plate with a tapered edge. Optimization occurs as follows. First, a generation of trajectories is created. Second, the trajectories are executed by a spherical parallel manipulator, during which the forces are acquired. Third, the trajectories are scored and a new generation of trajectories is created using the covariance matrix adaptive evolutionary strategy. This loop repeats ad-infinitum until the search converges. Within the first set of searches, two trajectories for optimal side-force generation are found, one is fully three-dimensional while the other is artificially constrained to a line, and one trajectory for optimal thrust generation is found. All searches demonstrate good convergence properties and match the desired force set-point almost immediately. Additional generations primarily improve the efficiency of the maneuver. The two trajectories for generating side-force have a similar efficiency, which shows potential in utilizing a simple trajectory limited to a line. Comparison between the trajectories for generating side-force and thrust suggests that side-force generation is more efficient around Re ~1000, based on the average tip velocity and length of the fin. The second set of searches explores the behavior of the optimal trajectories for generating side-force at a lower force set-point and the third set of searches explores the sensitivity and repeatability of the optimization.


Accurate Determination of the Equilibrium Surface Tension Values with Area Perturbation Tests.
We demonstrate two robust protocols for determining the equilibrium surface tension (EST) values with area perturbation tests. The EST values should be indirectly determined from the dynamic surface tension (DST) values when surface tension (ST) values are at steady-state and stable against perturbations. The emerging bubble method (EBM) and the spinning bubble method (SBM) were chosen, because, with these methods, it is simple to introduce area perturbations while continuing dynamic tension measurements. Abrupt expansion or compression of an air bubble was used as a source of area perturbation for the EBM. For the SBM, changes in the rotation frequency of the sample solution were used to produce area perturbations. A Triton X-100 aqueous solution of a fixed concentration above its critical micelle concentration (CMC) was used as a model surfactant solution. The determined EST value of the model air/water interface from the EBM was 31.5 ± 0.1 mN·m-1 and that from the SBM was 30.8 ± 0.2 mN·m-1. The two protocols described in the article provide robust criteria for establishing the EST values.


RP 49356 and cromakalim relax airway smooth muscle in vitro by opening a sulphonylurea-sensitive K+ channel: a comparison with nifedipine.
RP 49356 is a novel compound which relaxes airway smooth muscle in vitro. Like cromakalim, RP 49356 reduced contractility in guinea pig isolated trachealis under basal conditions or when challenged with low (less than 20 mM) but not high K+. These effects were antagonized by the sulphonylureas glibenclamide and glipizide. This spectrum of action is typical of the class of compounds known as potassium channel openers (KCOs). Unlike RP 49356 and cromakalim, nifedipine had no effect on basal tone, relaxed tissues contracted with low or high K+ and was not antagonized by the sulphonylureas. These data suggest that the KCOs are not acting directly at the voltage-gated Ca++ channel in this tissue. RP 49356 and cromakalim were similar to nifedipine by being more potent at relaxing tissues precontracted with carbachol or histamine (spasmolytic effects) than they were at preventing initiation of the response to these spasmogens (antispasmogenic effects). Because the maintained phase of contraction in airway smooth muscle may be associated with some Ca++ influx, the data presented here suggests that, like nifedipine, the KCOs are more active smooth muscle relaxants under conditions of Ca++ influx. In summary, RP 49356, like cromakalim, is a compound which relaxes airway smooth muscle in vitro by opening a sulphonylurea-sensitive K+ channel which may be similar to the ATP-sensitive K+ channel found in other tissues.


Exploring nurses' experiences of value congruence and the perceived relationship with wellbeing and patient care and safety: a qualitative study.
Values are of high importance to the nursing profession. Value congruence is the extent to which an individual's values align with the values of their organisation. Value congruence has important implications for job satisfaction. This study explored nurse values, value congruence and potential implications for individual nurses and organisations in terms of wellbeing and patient care and safety. Fifteen nurses who worked in acute hospital settings within the UK participated in semi-structured telephone interviews. Thematic analysis was utilised to analyse the data. Four themes were identified: organisational values incongruent with the work environment; personal and professional value alignment; nurse and supervisor values in conflict; nurses' values at odds with the work environment. Perceived value incongruence was related to poorer wellbeing, increased burnout and poorer perceived patient care and safety. The barriers identified for nurses being able to work in line with their values are described. Value congruence is important for nurse wellbeing and patient care and safety. Improving the alignment between the values that organisations state they hold, and the values implied by the work environment may help improve patient care and safety and support nurses in practice.


Association of glomerulopathy with the 5'-end polymorphism of the aldose reductase gene and renal insufficiency in type 2 diabetic patients.
The expression of nephropathy in type 2 diabetes has several levels of abnormalities. To define the primary abnormalities of diabetic nephropathy, we conducted an autopsy study of 186 consecutive patients with type 2 diabetes to determine correlations among the aldose reductase gene, renal histopathologies, extracellular matrix, glomerular function, and clinical characteristics. Compared with cases of near-normal renal structure (n = 51) and atypical diabetic glomerulopathy (n = 75), patients with classic diabetic glomerulopathy (n = 60) had advanced glomerular disease, as reflected by elevated plasma creatinine levels (133.2 +/- 59.8 vs. 166.0 +/- 65.7 vs. 243.8 +/- 82.6 micromol/l; P < 0.001), glomerular matrix fractions (20.8 +/- 6.7 vs. 33.5 +/- 16.8 vs. 39.2 +/- 14.3%; P < 0.001), and risk of renal failure (odds ratio [OR] 1 vs. 3.5 vs. 21.4; P < 0.001). Compared with noncarriers of the aldose reductase z-2 allele (n = 92) and z-2 heterozygotes (n = 77), z-2 homozygotes (n = 17) had elevated plasma creatinine (164.1 +/- 73.7 vs. 190.6 +/- 60.9 vs. 241.1 +/- 86.2 micromol/l; P < 0.001) and an increased risk of classic diabetic glomerulopathy (OR 1 vs. 0.9 vs. 3.3; P = 0.026). Overexpression of transforming growth factor-beta1, mesangial cell transdifferentiation by expression of alpha-smooth muscle actin, and aberrant deposition of collagen type IV, fibronectin, and laminin were found in classic diabetic glomerulopathy. These data suggest genetic, biochemical, pathophysiological, and clinical correlations among the aldose reductase gene, extracellular matrix, classic diabetic glomerulopathy, and renal insufficiency. Gene mutation, cellular transdifferentiation, growth factor upregulation, extracellular matrix expansion, and glomerular filtration impairment are the primary abnormalities in type 2 diabetic patients with nephropathy.


Regulation of leukotriene synthesis by arachidonic acid in human polymorphonuclear leukocyte adhesive interactions is dependent on the presence of albumin.
We have previously demonstrated that the pretreatment of polymorphonuclear leukocytes (PMNs) with the chemotherapeutic drug, Suramin, increases both cell attachment and inhibits calcium ionophore A23187-stimulated leukotriene (LT) synthesis. Here, we examined the effects of extracellular arachidonic acid (AA) and albumin on attachment and LT synthesis in the interaction of PMNs with both collagen-coated surfaces and human umbilical vein endothelial cell (HUVEC) monolayers. Suramin decreased the release of radiolabelled AA and 5-lipoxygenase metabolites by [(14)C-AA]-prelabelled PMNs stimulated with A23187, with and without human serum albumin (HSA) in the culture medium. Addition of 1 microM AA together with calcium ionophore stimulated the release of endogenous AA to the same level as control and Suramin-pretreated cells, but attachment was unaffected and LT synthesis was still inhibited with Suramin treatment. Using 24 microM AA, regulation of LT synthesis was dependent on the presence of HSA in the medium. Without HSA, 24 microM AA induced detachment of PMNs and increased LT synthesis in Suramin-treated cells above the control level. In the presence of HSA, 24 microM AA did not influence PMN attachment or abolish Suramin-induced inhibition of LT synthesis. These results suggest that tight attachment of PMNs to a solid surface leads to decreased LT synthesis during subsequent stimulation of the cells by A23187 in the presence or absence of exogenous substrate.


Modernisation. The road to perfection.
The Pursuing Perfection programme, piloted in four areas, lays down joint improvement strategies for directors of social services and NHS trusts. The programme dares to think what a perfect service would be like, and how it could be achieved. It uses the 'no needless...' formulation to eliminate risk.


Determination of structure and composition of suberin from the roots of carrot, parsnip, rutabaga, turnip, red beet, and sweet potato by combined gas-liquid chromatography and mass spectrometry.
Suberin from the roots of carrots (Daucus carota), parsnip (Pastinaca sativa), rutabaga (Brassica napobrassica), turnip (Brassica rapa), red beet (Beta vulgaris), and sweet potato (Ipomoea batatas) was isolated by a combination of chemical and enzymatic techniques. Finely powdered suberin was depolymerized with 14% BF(3) in methanol, and soluble monomers (20-50% of suberin) were fractionated into phenolic (<10%) and aliphatic (13-35%) fractions. The aliphatic fractions consisted mainly of omega-hydroxyacids (29-43%), dicarboxylic acids (16-27%), fatty acids (4-18%), and fatty alcohols (3-6%). Each fraction was subjected to combined gas-liquid chromatography and mass spectrometry. Among the fatty acids very long chain acids (>C(20)) were the dominant components in all six plants. In the alcohol fraction C(18), C(20), C(22), and C(24) saturated primary alcohols were the major components. C(16) and C(18) dicarboxylic acids were the major dicarboxylic acids of the suberin of all six plants and in all cases octadec-9-ene-1, 18-dioic acid was the major component except in rutabaga where hexadecane-1, 16-dioic acid was the major dicarboxylic acid. The composition of the omega-hydroxyacid fraction was quite similar to that of the dicarboxylic acids; 18-hydroxy-octadec-9-enoic acid was the major component in all plants except rutabaga, where equal quantities of 16-hydroxyhexadecanoic acid and 18-hydroxyoctadec-9-enoic acid (42% each) were found. Compounds which would be derived from 18-hydroxyoctadec-9-enoic acid and octadec-9-ene-1, 18-dioic acid by epoxidation, and epoxidation followed by hydration of the epoxide, were also detected in most of the suberin samples. The monomer composition of the six plants showed general similarities but quite clear taxonomic differences.


The effectiveness of the door-in-the-face compliance strategy on friends and strangers.
The author examined the impact of the door-in-the-face procedure on concerns about self-presentation and hypothesized that (a) when a friend made door-in-the-face requests, the procedure would increase the participant's concern about self-presentation more than would a single request and (b) when a stranger made door-in-the-face requests, the procedure would not increase the participant's concern about self-presentation more than would a single request. Either friends or strangers presented requests to the participants. Half the requests were in a door-in-the-face format, and the other half were single requests. After receiving the request(s), the participants completed measures of self-presentation concerns and compliance with the request. The results supported the hypothesis.


Age-Related Changes in the Synaptic Density of Amyloid-β Protein Precursor and Secretases in the Human Cerebral Cortex.
Amyloid-β protein precursor (AβPP) is involved in synaptic formation and function. In the human cingulate cortex, AβPP was preferentially located in the presynaptic active zone as in rodents, indicating a preserved subsynaptic AβPP distribution across species and brain regions. Synaptic AβPP immunoreactivity was decreased with aging in cortical samples collected from autopsies of males (20-80 years), whereas the synaptic levels of α-secretase (ADAM10) and β-secretase (BACE1) did not significantly change. Decreased AβPP levels may be related to lower allostasis of synapses in the aged brain and their greater susceptibility to dysfunction characteristic of the onset of neurodegenerative disorders.


Maternal ABO blood group and stillbirth: a prospective cohort investigation.
To determine whether maternal ABO blood group is associated with risk of stillbirth. Prospective cohort. Risk of stillbirth among women of blood group A, B and AB was compared to that of women with group O by logistic regression and survival analysis. There were 1,018 stillbirths in 52,605 pregnancies (19.4 per thousand). Stillbirths occurred in 19.2/ 1,000 pregnancies in group O, 19.8/1,000 pregnancies in group A (race-adjusted odds ratio [OR] vs. group O of 1.1, 95% confidence interval [CI] 0.9-1.2), 19.4/1,000 to group B (race-adjusted OR vs. group O of 1.0, 95% CI 0.8-1.2), and 17.2/1,000 pregnancies in group AB (race-adjusted OR vs. group O of 0.9, 95% CI 0.6-1.2) women. Survival analysis, accounting for varying times at entry to prenatal care, produced similar results. Results were similar for singleton births, stillbirths < 24 weeks' and > or = 24 weeks' gestation, and antepartum and intrapartum stillbirths considered separately. Maternal ABO blood group was not associated with stillbirth.


Impairment of neocortical long-term potentiation in mice deficient of endothelial nitric oxide synthase.
The role of the possible retrograde messenger nitric oxide (NO) in the induction of long-term potentiation (LTP) was studied in supragranular layers of somatosensory cortical slices obtained from adult mice. High-frequency stimulation produced a slowly rising, long-lasting (50 min) and significant (P < 0.001) increase in the extracellular synaptic response by 23%. The induction of LTP was independent from activation of N-methyl-D-aspartate (NMDA) receptors, but prevented by bath application of NG-nitro-L-arginine methyl ester (L-NAME), indicating that one or several of the different NO synthases (NOS) produced NO within the postsynaptic neuron. No LTP could be induced in knockout mice lacking the endothelial NOS (eNOS) isoform. These data suggest that eNOS is involved in an NMDA receptor-independent form of LTP in the rodent cerebral cortex.


Factors affecting human heterocyclic amine intake and the metabolism of PhIP.
We are working to understand possible human health effects from exposure to heterocyclic amines that are formed in meat during cooking. Laboratory-cooked beef, pork, and chicken are capable of producing tens of nanograms of MeIQx, IFP, and PhIP per gram of meat and smaller amounts of other heteroyclic amines. Well-done restaurant-cooked beef, pork, and chicken may contain PhIP and IFP at concentrations as high as tens of nanograms per gram and MeIQx at levels up to 3 ng/g. Although well-done chicken breast prepared in the laboratory may contain large amounts of PhIP, a survey of flame-grilled meat samples cooked in private homes showed PhIP levels in beef steak and chicken breast are not significantly different (P=0.36). The extremely high PhIP levels reported in some studies of grilled chicken are not seen in home-cooked samples.Many studies suggest individuals may have varying susceptibility to carcinogens and that diet may influence metabolism, thus affecting cancer susceptibility. To understand the human metabolism of PhIP, we examined urinary metabolites of PhIP in volunteers following a single well-done meat exposure. Using solid-phase extraction and LC/MS/MS, we quantified four major PhIP metabolites in human urine. In addition to investigating individual variation, we examined the interaction of PhIP with a potentially chemopreventive food. In a preliminary study of the effect of broccoli on PhIP metabolism, we fed chicken to six volunteers before and after eating steamed broccoli daily for 3 days. Preliminary results suggest that broccoli, which contains isothiocyanates shown to induce Phases I and II metabolism in vitro, may affect both the rate of metabolite excretion and the metabolic products of a dietary carcinogen. This newly developed methodology will allow us to assess prevention strategies that reduce the possible risks associated with PhIP exposure.


Preparation of Cellulose/Graphene Oxide Composite Membranes and Their Application in Removing Organic Contaminants in Wastewater.
Cellulose/graphene oxide composite membranes (CGCMs) were prepared using a vacuum-filtration method. The CGCMs were then used as filters to remove organic pollutants from wastewater. It was found that the CGCM filters could efficiently and simultaneously achieve wastewater treatment and adsorbent separation. Their adsorption of Rhodamine B (RhB, an organic dye) varied with varying cellulose/graphene oxide mass ratios. The CGCM obtained at a cellulose/graphene oxide mass ratio of 8:1 exhibited the maximum removal efficiency for RhB. The maximum adsorption capacity of the CGCMs for RhB was found to be 86.4 mg/g. In addition, the CGCMs were easily regenerated and the regenerated CGCMs retained good abilities to remove contaminants, which could be significant for their application in wastewater treatment.


Recognize three different human telomeric G-quadruplex conformations by quinacrine.
Recognition of different human telomeric G-quadruplex structures has been a very important task for developing anti-cancer drug design. However, it also is a very challenging question since multiple conformational isomers of telomeric G-quadruplexes coexist under some conditions. Here, three different conformations including parallel, antiparallel, and mixed-type telomeric G-quadruplex structures have been well recognized by quinacrine (QNA) through monitoring its absorption, fluorescence, and fluorescence lifetime spectra. The multiple structures of H22 G-quadruplexes under physiological K(+) conditions could also be easily determined to coexist as mixed-type and antiparallel G-quadruplexes. The recognition mechanism based on the different binding affinity and binding sites has been further elucidated by association with the nuclear magnetic resonance (NMR) results.


The photoelectron spectrum of the isopropoxide anion: nonadiabatic effects due to conical intersections and the spin-orbit interaction.
The negative ion photoelectron spectrum of the isopropoxide anion is determined using the multimode vibronic coupling approach. The simulated spectrum is based on a two state quasidiabatic Hamiltonian for the isopropoxy radical, H(d), which includes all terms through second-order order in all internal coordinates and accurately represents the vicinity of the ab initio determined equilibrium geometry of the ground electronic state as well as the minimum energy crossing point (MECP) on the symmetry-allowed (2)A(")-(2)A(') accidental seam of conical intersection. H(d) is centered at the (2)A(")-(2)A(') MECP and is determined from ab initio gradients and derivative couplings using a normal equations based algorithm. Spin-orbit effects are included using a generalization of a procedure due to Child and Longuet-Higgins. The nonadiabatic interactions coupling the (2)A(") and (2)A(') states are very similar to those found in an Exe Jahn-Teller system although the requisite symmetry is absent. The simulated photoelectron spectrum for isopropoxide-h(7) is compared to a measured photoelectron spectrum and the results of a dispersed fluorescence experiment on the isopropoxy radical. The nominal A (2)A-X (2)A splitting of 68 cm(-1) from the dispersed fluorescence experiment is confirmed. This splitting is shown to be a consequence of the accidental Jahn-Teller symmetry and the spin-orbit interaction so that the standard designation of this spectral feature as the A-X splitting is not appropriate. This spectral feature is better thought of as the spin-orbit splitting of a nearly degenerate ground state. It is further shown that the intensities and line positions are such that the origin band of the nominal A (2)A state and that of the X (2)A state could not be distinguished with the resolution available in the photoelectron experiment. The photoelectron spectrum of the completely deuterated analog, isopropoxide-d(7), is also reported and discussed.


Inhalational diesel exhaust exposure in submariners: observational study.
An observational study was performed with a convenience sample of 38 submariners exposed to diesel exhaust for 9 hours, to assess the development of reactive airways dysfunction syndrome (RADS) after prophylactic corticosteroid treatment. Twenty-four subjects were available for baseline physical examinations, pulmonary function tests, and chest radiographs, and 16 more subjects were available for interviews; 30 subjects were available for 6-month follow-up surveys. Subjects were treated on the basis of presenting symptoms; 19 subjects were treated with a 10-day course of orally administered prednisone, accompanied by 30 days of inhaled fluticasone/salmeterol therapy. There were no cases of RADS diagnosed at 6-month follow-up evaluations. There were no cases of RADS diagnosed at 6-month follow-up evaluations in submariners with uncontrolled, isolated, heavy diesel exhaust exposure, despite many initial symptoms that portended the diagnosis. To our knowledge, this is the largest reported case study of corticosteroid treatment initiated with an expressed intention to prevent the development of RADS after an isolated diesel exhaust exposure. Although we cannot prove that early intervention with corticosteroids prevented RADS, we think that the implementation of prompt prophylactic treatment expedited symptom resolution and might have prevented RADS development, on the basis of previous historical control data. RADS resulting from diesel exhaust may be an important public health issue, and our hope is to promote increased recognition of the diagnosis, which often is not suspected upon initial presentation but is delayed by up to several years. Increasing awareness may prompt pursuit of more-aggressive interventions with acute and protracted corticosteroid treatment and execution of the necessary controlled trials to establish treatment efficacy in mitigating the severity and/or circumventing the development of RADS.


[Evaluation of bone mass and relevance ratio of osteoporosis among middle aged and elderly population in Beijing community].
To investigate the relevance ratio of osteoporosis and bone mass of middle aged and elderly people in Beijing communities, in order to understand occurrence and development trend of abnormality of bone mass in high-risk population from community. Based on the method of cross-sectional investigation, the information data of 1 540 middle-aged and elderly people from 10 communities were collected, including 415 males and 1 125 females, aged from 45 to 80 years old with the average of (63.02±7.15) years old; the height was (161.34±7.24) cm, the weight was (65.90±10.19) kg, body mass index was (25.29±3.32) kg /m2. Bone mineral density (BMD) of lumbar vertebrae (L1-L4) and both hips were measured by dual energy X ray absorptiometry (DEXA). The differences of bone mineral density and bone mass in different age groups were evaluated, and the relevance ratio of osteoporosis in different parts of the subjects was calculated. Elbow venous blood was collected on an empty stomach, and the gender differences of serum bone metabolic markers were detected and compared. The level of β-CTX was(0.27±0.12) ng /ml, procollanen type 1 N-terminal propeptide(P1NP) was(51.03± 22.36) ng /ml, 25(OH) D3 was (16.68±6.24) ng /ml, serum calcium was(2.34±0.09) mmol / L, blood phosphorus was (1.43± 0.37) mmol / L, and blood magnesium was (0.94±0.07) mmol / L, alkaline phosphatase was (79.28±20.48) U/ L, parathyroid hormone was (3.09±1.60) pmol / L, osteocalcin was (13.29±6.65) ng /ml. Except for blood magnesium, the other indexes had significant differences between different sex groups(P<0.05). Results of T value of bone mineral density and level of bone mass showed that bone mineral density of lumbar vertebrae and both hips fluctuated and decreased with the increase of age, and there were significant differences in level of bone mass among different age groups in women(P<0.05), and except lumbar vertebrae in males, there were significant differences in other parts of bone mass among different age groups (P<0.05). The relevance ratio of lumbar osteoporosis, left hip osteoporosis, and right hip osteoporosis was 27.89%, 14.80% and 14.47%, respectively. There are obvious differences in relevance ratio of osteoporosis and low bone mass among different sites. It is suggested that the clinical diagnosis of osteoporosis should be combined with bone mineral density and bone metabolic markers. With the increasing prevalence of osteoporosis among middle aged and elderly people in Beijing community, continuous follow-up research based on community primary health care units could promote early examination, early diagnosis, and early treatment of middle aged and elderly people at high risk of osteoporosis in community.


Aberrant celio-mesenteric supply of the splenic flexure: provoking a bleed.
Lower gastrointestinal hemorrhage presents a common indication for hospitalization and account for over 300,000 admissions per year in the United States. Multimodality imaging is often required to aid in localization of the hemorrhage prior to therapeutic intervention if endoscopic treatment fails. Imaging includes computer tomography angiography, red blood cell tagged scintigraphy and conventional angiography, with scintigraphy being the most sensitive followed by computer tomography angiography. Aberrant celio-mesenteric supply occurs in 2% of the population; however failure to identify this may result in failed endovascular therapy. Computer tomography angiography is sensitive for arterial hemorrhage and delineates the anatomy, allowing the treating physician to plan an endovascular approach. If at the time of conventional angiography, the active bleed is not visualized, but the site of bleeding has been identified on computer tomography angiography, provocative angiography can be utilized in order to stimulate bleeding and subsequent targeted treatment. We describe a case of lower gastrointestinal hemorrhage at the splenic flexure supplied by a celio-mesenteric branch in a patient and provocative angiography with tissue plasminogen activator utilized at the time of treatment to illicit the site of hemorrhage and subsequent treatment.


CT angiography of pulmonary embolism: diagnostic criteria and causes of misdiagnosis.
Computed tomographic (CT) pulmonary angiography is becoming the standard of care at many institutions for the evaluation of patients with suspected pulmonary embolism. This pathologic condition, whether acute or chronic, causes both partial and complete intraluminal filling defects, which should have a sharp interface with intravascular contrast material. In acute pulmonary embolism that manifests as complete arterial occlusion, the affected artery may be enlarged. Partial filling defects due to acute pulmonary embolism are often centrally located, but when eccentrically located they form acute angles with the vessel wall. Chronic pulmonary embolism can manifest as complete occlusive disease in vessels that are smaller than adjacent patent vessels. Other CT pulmonary angiographic findings in chronic pulmonary embolism include evidence of recanalization, webs or flaps, and partial filling defects that form obtuse angles with the vessel wall. Factors that cause misdiagnosis of pulmonary embolism may be patient related, technical, anatomic, or pathologic. The radiologist needs to determine the quality of a CT pulmonary angiographic study and whether pulmonary embolism is present. If the quality of the study is poor, the radiologist should identify which pulmonary arteries have been rendered indeterminate and whether additional imaging is necessary.


Occurrence of Cortical Arousal at Recovery from Respiratory Disturbances during Deep Propofol Sedation.
Abstract: Recent evidences suggest that non-arousal mechanisms can restore and stabilize breathing in sleeping patients with obstructive sleep apnea. This possibility can be examined under deep sedation which increases the cortical arousal threshold. We examined incidences of cortical arousal at termination of apneas and hypopneas in elderly patients receiving propofol sedation which increases the cortical arousal threshold. Ten elderly patients undergoing advanced endoscopic procedures under propofol-sedation were recruited. Standard polysomnographic measurements were performed to assess nature of breathing, consciousness, and occurrence of arousal at recovery from apneas and hypopneas. A total of 245 periodic apneas and hypopneas were identified during propofol-induced sleep state. Cortical arousal only occurred in 55 apneas and hypopneas (22.5%), and apneas and hypopneas without arousal and desaturation were most commonly observed (65.7%) regardless of the types of disordered breathing. Chi-square test indicated that incidence of no cortical arousal was significantly associated with occurrence of no desaturation. Higher dose of propofol was associated with a higher apnea hypopnea index (r = 0.673, p = 0.033). In conclusion, even under deep propofol sedation, apneas and hypopneas can be terminated without cortical arousal. However, extensive suppression of the arousal threshold can lead to critical hypoxemia suggesting careful respiratory monitoring.


Respectful disposition in early pregnancy loss.
This article discusses an issue rarely seen in the professional literature: the tangible ways nurses can respect a woman's needs following miscarriage by ensuring the safe handling and disposition of fetal tissue or remains. Concepts of personhood, place, and protection are important for nurses to understand within the context of a woman's response to miscarriage. Hospitals or clinics that foster a culture of respectful fetal disposition should have a system in place to bury tissue or fetal remains in a designated area; in fact, several states have enacted laws that regulate what hospitals and clinics must do, or what women must be offered, after a miscarriage or ectopic pregnancy. Barriers may exist to creating a culture of respectful disposition, including staff attitudes, perceived time and financial constraints, lack of knowledge, and inefficient communication between departments. Nurses can begin implementing change in this regard through conducting a needs assessment using guiding questions contained in this article. In addition, through communication, education, and implementation of respectful disposition, nurses can promote safe processes that will honor women's preferences and wishes for care following a miscarriage.


Age and ECOG Performance Status as Predictors of Survival of Patients with Upper Urinary Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy.
This study aimed to evaluate the impact of chronological and biological age on perioperative complications and survival after radical nephroureterectomy (RNU). Elderly patients with upper-tract urothelial carcinoma might be overtreated by RNU. We retrospectively analyzed patients undergoing RNU. To evaluate the perioperative risk, patients were divided into four groups (<75; 75-79; 80-84; ≥85 years). The endpoints are perioperative complications and survival (overall survival [OS]). We calculated a risk score including chronological and biological age (Eastern cooperative oncology group performance status). Statistical analysis was performed by Kruskal-Wallis, Mann-Whitney U, χ2, log-rank, and Breslow tests. 194 patients were included in the study. Median follow-up was 25.5 months. Elderly cohorts ≥2 presented a higher number of days in intensive care unit following RNU (p < 0.001). Complication rates increased from cohort 1-4 with rates of 48.8%; 55.2%; 92.0%; 85.7% (p < 0.001). Median survival was 115, 55, 28, and 20 months for cohorts 1, 2, 3, and 4, respectively. The combined risk score revealed a significant 5-year OS benefit for patients with score 0 (82.3%) compared to score 1 (46.0%) and score 2 (15.0%; p < 0.001). We evaluated the impact of chronological and biological age on perioperative complications and survival after RNU. A combined risk score of chronological and biological age correlates with survival after RNU.


Drug-induced lupus and autoimmune hepatitis secondary to infliximab for psoriasis.
We describe a case of previously unreported autoimmune hepatitis and lupus-like syndrome induced by infliximab treatment for chronic plaque psoriasis. The condition resolved after withdrawal of infliximab, with the liver injury having been reversed and minimal periportal fibrosis. In a two-part discussion we review the current literature on the pharmacology of infliximab and provide recommendations for management of infliximab side effects.


Fluence correction factor for graphite calorimetry in a clinical high-energy carbon-ion beam.
The aim of this work is to develop and adapt a formalism to determine absorbed dose to water from graphite calorimetry measurements in carbon-ion beams. Fluence correction factors, [Formula: see text], needed when using a graphite calorimeter to derive dose to water, were determined in a clinical high-energy carbon-ion beam. Measurements were performed in a 290 MeV/n carbon-ion beam with a field size of 11 × 11 cm2, without modulation. In order to sample the beam, a plane-parallel Roos ionization chamber was chosen for its small collecting volume in comparison with the field size. Experimental information on fluence corrections was obtained from depth-dose measurements in water. This procedure was repeated with graphite plates in front of the water phantom. Fluence corrections were also obtained with Monte Carlo simulations through the implementation of three methods based on (i) the fluence distributions differential in energy, (ii) a ratio of calculated doses in water and graphite at equivalent depths and (iii) simulations of the experimental setup. The [Formula: see text] term increased in depth from 1.00 at the entrance toward 1.02 at a depth near the Bragg peak, and the average difference between experimental and numerical simulations was about 0.13%. Compared to proton beams, there was no reduction of the [Formula: see text] due to alpha particles because the secondary particle spectrum is dominated by projectile fragmentation. By developing a practical dose conversion technique, this work contributes to improving the determination of absolute dose to water from graphite calorimetry in carbon-ion beams.


[The incidence, localization, sex and mean age in patients with renal carcinoma].
Retrospective analysis was made of the clinical case records of 97 nephrectomized patients with renal cancer at the University Urologic Clinic in Rostock, Germany. The Student-Fisher t-criterion was used for statistical processing of the results. The stage of the disease was determined in accordance with the histologic classification of pTNM, suggested in 1988 by the European Organization for Cancer Research and Treatment. Patients with malignant diseases of the urogenital tract accounted for 6.1 per cent of all patients treated at the Urologic Clinic. Malignant disease of the kidney alone comprised 1.7 per cent and of renal cancer--1.5 per cent. In 49 per cent of the patients renal cancer was localized in the left kidney, in 42 per cent--the right kidney, and 9 per cent both kidneys were involved. The male: female ratio was 2.2:1. Mean patient age was 57 years (males 58.1, females 55.9 years).


Predictors of survival and length of stay in burn patients older than 80 years of age: does age really matter?
Predictors of survival and length of stay (LOS) in the advanced elderly with burn injuries is not well studied. Because of progress in burn wound and critical care, we hypothesized that a contemporary analysis would show improved outcomes. Clinical data were collected on 45 consecutive patients older than 80 years of age that were treated for burn injury at our institution during the past 10 years. Regression analysis was used to identify predictors of LOS and survival. Overall rate of mortality was 29%, and no patient survived a burn more than 60% TBSA. The strongest predictor of survival was percent TBSA burn. LOS of survivors was dependent on presence of inhalation injury and total number of operations. The survival of patients older than 80 years of age with burn injury is better than reported. Modern burn care allows survival in many patients over 80 with less than 60% TBSA burns without significant other co-morbidities.


RGD Peptides-Conjugated Pluronic Triblock Copolymers Encapsulated with AP-2α Expression Plasmid for Targeting Gastric Cancer Therapy in Vitro and in Vivo.
Gastric cancer, a high-risk malignancy, is a genetic disease developing from a cooperation of multiple gene mutations and a multistep process. Gene therapy is a novel treatment method for treating gastric cancer. Here, we developed a novel Arg-Gly-Asp (RGD) peptides conjugated copolymers nanoparticles-based gene delivery system in order to actively targeting inhibit the growth of gastric cancer cells. These transcription factor (AP-2α) expression plasmids were also encapsulated into pluronic triblock copolymers nanoparticles which was constituted of poly(ethylene glycol)-block-poly(propylene glycol)- block-poly(ethylene glycol) (PEO-block-PPO-block-PEO, P123). The size, morphology and composition of prepared nanocomposites were further characterized by nuclear magnetic resonance (NMR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). In MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide) analysis, these nanocomposites have minor effects on the proliferation of GES-1 cells but significantly decreased the viability of MGC-803, suggesting they own low cytotoxicity but good antitumor activity. The following in vivo evaluation experiments confirmed that these nanocomposites could prevent the growth of gastric cancer cells in the tumor xenograft mice model. In conclusion, these unique RGD peptides conjugated P123 encapsulated AP-2α nanocomposites could selectively and continually kill gastric cancer cells by over-expression of AP-2α in vitro and in vivo; this exhibits huge promising applications in clinical gastric cancer therapy.


Effect of intracellular calcium on ATP-activated, GTP-dependent calcium channels in rat macrophages.
1. In order to study the effect of intracellular free Ca2+ concentration ([Ca2+]i) on the activity of ATP-activated, GTP-dependent Ca2+ channels in rat macrophages, experiments were performed using the inside-out configuration of the patch-clamp technique. 2. Channel activity was observed in the cell-attached mode when 100 microM ATP was added to the pipette solution containing 105 mM Ba2+, but it disappeared rapidly after patch excision. The activity could be restored by the application of 100 microM GTP or GTP gamma S onto the internal surface of the plasma membrane. 3. The properties of the GTP gamma S-evoked channels are identical to those of channels activated by extracellular application of ATP. The channels exhibited four current sublevels with conductances of about 3.5, 7, 10 and 15 pS when 105 mM Ba2+ was the only permeant cation. The extrapolated reversal potentials were similar for all the sublevels and averaged about +40 mV. 4. Elevation of [Ca2+]i within the range 0.01-1 microM resulted in a decrease in mean inward current. The half-maximal value of the mean current was about 0.08 microM. 5. This decreases in mean current resulted from a redistribution of sublevel occupancies: the 1st sublevel tended to be come more abundant with elevation of [Ca2+]i, while the relative weights of the high-conductance 3rd and 4th sublevels decreased. 6. The open-channel current fell with an increase in [Ca2+]i as quickly as the mean current did, indicating that the sublevel redistribution alone is sufficient to produce the revealed decrease in net inward current. 7. It is concluded that [Ca2+]i elevation does not fix the channel in a closed state but rather decreases the ability of the channel to operate in high-conductance states.


Relative and Quantitative Rhizosphere Microbiome Profiling Results in Distinct Abundance Patterns.
Next-generation sequencing is one of the most popular and cost-effective ways of characterizing microbiome in multiple samples. However, most of the currently available amplicon sequencing approaches are limited, as they result in relative abundance profiles of microbial taxa, which does not represent actual abundance in the environment. Here, we combined amplicon sequencing (16S rRNA gene for bacteria and ITS region for fungi) with real-time quantitative PCR (qPCR) to characterize the rhizosphere microbiome of wheat. We show that changes in the relative abundance of major microbial phyla do not necessarily follow the same pattern as the estimated quantitative abundance. Most of the bacterial phyla linked with the rhizosphere of plants grown in soil with no history of water stress showed enrichment patterns in their estimated absolute abundance, which was in contradiction with the trends observed in the relative abundance data. However, in the case of the fungal groups (except for Basidiomycota), such an enrichment pattern was not observed and the abundance of fungi remained relatively unchanged under different soil water stress history when estimated absolute abundance was considered. Comparing relative and estimated absolute abundances of dominant bacterial and fungal phyla, as well as their correlation with the functional processes in the rhizosphere, our results suggest that the estimated absolute abundance approach gives a different and more realistic perspective than the relative abundance approach. Such a quantification approach provides complementary information that helps to better understand the rhizosphere microbiomes and their associated ecological functional processes.


Providing healthcare to evacuees in the wake of a natural disaster: opportunities to improve disaster planning.
The impending landfall of Hurricane Katrina on the Mississippi Gulf Coast resulted in large numbers of evacuees into the Jackson, Mississippi area. Many evacuees with chronic medical problems had been directed to the Mississippi Coliseum in the downtown area near the University of Mississippi Medical Center. As the storm passed through Jackson, serious damage occurred to the municipal infrastructure. In this article, we asked how that experience has affected health planning for the care of sheltered populations. We reviewed the information accumulated in the course of operating a large medical clinic for evacuees at the Mississippi Coliseum. We also contacted representatives of disaster planning agencies and of healthcare planning organizations to determine changes that have occurred in strategic plans subsequent to Katrina. Using the resources of our academic health center, we were able to effectively deliver healthcare to sheltered evacuees. A model has been developed for future use from this experience. Much progress has been made toward preparation for care of the chronically-ill who may be displaced by future disasters. Hospitals and clinics on major evacuation routes for natural disasters can expect the sudden necessity to provide care to evacuees. Unless plans to care for chronically-ill individuals are incorporated into hospital disaster plans, local healthcare facilities may be unprepared to provide care. Many evacuees will have limited resources to pay for services. Academic medical centers have unique resources and capabilities to lead in the care plans for these populations.


Utilization of nucleoside diphosphate glucoses in developing cotton fibers.
The capacity for biosynthesis of hot alkali-insoluble products using uridine diphosphate (UDP)-glucose and guanosine diphosphate (GDP)-glucose as substrate has been studied in isolated cotton fibers harvested at various stages of development following anthesis. During the period of rapid elongation and primary wall synthesis (7-14 days postanthesis), incorporation of radioactivity from GDP-(14)C-glucose into hot alkali-insoluble product is high. This activity gradually declines and is not demonstrated in older fibers undergoing active deposition of secondary wall. With respect to all characteristics examined, the product from GDP-glucose resembles cellulose. Incorporation of UDP-(14)C-glucose into hot alkali-insoluble product was low in young fibers but increased to high levels in older fibers. This product was shown to be soluble in chloroform-methanol, and when chromatographed in lipid solvents it was separated into three components. Activity for the production of two of these three presumed glucolipids increased with increasing age of fibers.


Bioinspired Surfaces with Superwettability for Anti-Icing and Ice-Phobic Application: Concept, Mechanism, and Design.
Ice accumulation poses a series of severe issues in daily life. Inspired by the nature, superwettability surfaces have attracted great interests from fundamental research to anti-icing and ice-phobic applications. Here, recently published literature about the mechanism of ice prevention is reviewed, with a focus on the anti-icing and ice-phobic mechanisms, encompassing the behavior of condensate microdrops on the surface, wetting, ice nucleation, and freezing. Then, a detailed account of the innovative fabrication and fundamental research of anti-icing materials with special wettability is summarized with a focus on recent progresses including low-surface energy coatings and liquid-infused layered coatings. Finally, special attention is paid to a discussion about advantages and disadvantages of the technologies, as well as factors that affect the anti-icing and ice-phobic efficiency. Outlooks and the challenges for future development of the anti-icing and ice-phobic technology are presented and discussed.


Lactic Acid Bacteria Fermented Cordyceps militaris (GRC-SC11) Suppresses IgE Mediated Mast Cell Activation and Type I Hypersensitive Allergic Murine Model.
Cordyceps militaris (C. militaris) has various biomedical applications in traditional oriental medicine for different diseases including inflammatory and immune-dysregulated diseases. It is a reservoir of nutritional components such as cordycepin, polysaccharides, and antioxidants. To improve its bioactivity, we fermented C. militaris with a Pediococcus pentosaceus strain isolated from a salted small octopus (SC11). The current study aimed to evaluate whether P. pentosaceus (SC11) fermentation could enhance the anti-allergic potential of C. militaris cultured on germinated Rhynchosia nulubilis (GRC) against a type I hypersensitive reaction in in vitro and in vivo studies. Total antioxidant capacity and cordycepin content were significantly increased in GRC after SC11 fermentation. GRC-SC11 showed significantly enhanced anti-allergic responses by inhibiting immunoglobulin E (IgE)/antigen-induced degranulation in RBL-2H3 cells, compared to GRC. The results demonstrated the significant inhibition of phosphorylated spleen tyrosine kinase (Syk)/ p38/GRB2-associated binding protein 2 (Gab2)/c-jun in IgE/Ag-triggered RBL-2H3 cells. Furthermore, suppressed mRNA levels of interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α) in IgE/Ag-activated RBL-2H3 cells were observed. GRC-SC11 significantly ameliorated IgE-induced allergic reactions by suppressing the ear swelling, vascular permeability, and inflammatory cell infiltration in passive cutaneous anaphylaxis (PCA) BALB/c mice. In conclusion, GRC fermented with P.pentosaceus exerted enhanced anti-allergic effects, and increased the cordycepin content and antioxidants potential compared to GRC. It can be used as bio-functional food in the prevention and management of type I allergic diseases.


Metabolic Dysfunction Biomarkers as Predictors of Early Diabetes.
During the pathophysiological course of type 2 diabetes (T2D), several metabolic imbalances occur. There is increasing evidence that metabolic dysfunction far precedes clinical manifestations. Thus, knowing and understanding metabolic imbalances is crucial to unraveling new strategies and molecules (biomarkers) for the early-stage prediction of the disease's non-clinical phase. Lifestyle interventions must be made with considerable involvement of clinicians, and it should be considered that not all patients will respond in the same manner. Individuals with a high risk of diabetic progression will present compensatory metabolic mechanisms, translated into metabolic biomarkers that will therefore show potential predictive value to differentiate between progressors/non-progressors in T2D. Specific novel biomarkers are being proposed to entrap prediabetes and target progressors to achieve better outcomes. This study provides a review of the latest relevant biomarkers in prediabetes. A search for articles published between 2011 and 2021 was conducted; duplicates were removed, and inclusion criteria were applied. From the 29 studies considered, a survey of the most cited (relevant) biomarkers was conducted and further discussed in the two main identified fields: metabolomics, and miRNA studies.


Creating a surgical wait list management strategy for Saskatchewan.
In the summer of 2001, Saskatchewan Health asked Dr. Peter Glynn, Health Care Consultant, Dr. Mark Taylor, the Deputy Head of General Surgery at St. Boniface General Hospital in Winnipeg and Dr. Alan Hudson, a Toronto-based neurosurgeon and former CEO of the University Health Network, to advise on the creation of a provincial surgical wait list management strategy to address growing concerns about waiting times for many non-emergent surgical procedures. Although the work was focused on Saskatchewan, this is a common issue across the country.


Wide polytef (Gore-Tex) implants in lip augmentation and nasolabial groove correction.
To describe a new technique of polytef (Gore-Tex) implantation into the upper and lower lips and nasolabial grooves by using large implants as a method that achieves effective cosmetic improvement. A private cosmetic surgery center. Thirty-three (female) patients who desired fuller lips and 62 patients (52 female and 10 male) who requested less prominent cheek lip grooves. Significant patient satisfaction after 12 to 54 months. Conspicuous aesthetic effect that related to both lip and nasolabial groove correction was documented. All patients but 4 (2 in each group) were pleased with the final outcome of the treatment. In the opinion of the authors, the threading technique of polytef implantation creates inconspicuous improvement-both in lip augmentation and nasolabial groove correction. Large polytef implants that were inserted through a tunneling technique produced consistently good results. Implants (lip augmentation: width, < or = 10 mm, and thickness, 4 mm; nasolabial groove correction: width, 8 mm, and thickness, < or = 8 mm) were found to be safe, simple, and effective.


Epidemiology of bacterial infections in patients with liver cirrhosis. Experience in a Spanish tertiary health center.
Bacterial infections represent a serious complication of liver cirrhosis. Traditionally, Gram negative bacteria have been described as the microorganisms responsible for the majority of the infections. However, in the past few years, changes in the microbiological spectrum have been described, and multiresistant bacteria are observed more frequently. To assess the proportion of patients with infections caused by multiresistant bacteria admitted to our hospital, and to obtain information about their epidemiology, risk factors and clinical impact. We performed a retrospective evaluation of 294 cirrhotic patients admitted to our unit due to infection between June, 2011, and June, 2013. We isolated 310 microorganisms from 294 patients; 109 (35.2%) were Gram positive, 167 (53.9%), Gram negative, and 34, fungi (11%). As for the microbiological agents, the most frequent was Escherichia coli (98 isolations). The infection was community-acquired in 22.9% of cases, healthcareassociated in 38.1% and nosocomial in 39%. Worse liver infections and septic shock were more frequent among patients with multiresistant isolates (p=0.05); and intrahospital mortality was also higher among them (p=0.017). Previous hospital admission, antibiotic treatment 60 days before, nosocomial or healthcare-associated acquisition and bacterial isolation in control cultures were identified as possible risk factors for the development of multiresistant infection. The results of our study confirm that important changes have ocurred in the microbiological spectrum of bacterial infections in patients with liver cirrhosis. Multiresistant bacteria are associated with high morbidity and mortality, as well as failure of traditional antibiotic treatment. Successfull control of the infection requires an early identification of patients at risk.


Imidazolinones: potent inhibitors of acetohydroxyacid synthase.
The imidazolinones, a new chemical class of herbicides, were shown to be uncompetitive inhibitors of acetohydroxyacid synthase from corn. This is the first common enzyme in the biosynthetic pathway for valine, leucine, and isoleucine. The K(i) for the imidazolinones tested ranged from 2 to 12 micromolar. These results may explain the mechanism of action of these new herbicides.


TEL-AML1 regulation of survivin and apoptosis via miRNA-494 and miRNA-320a.
There is increasing evidence that miRNA and transcription factors interact in an instructive fashion in normal and malignant hematopoiesis. We explored the impact of TEL-AML1 (ETV6-RUNX1), the most common fusion protein in childhood leukemia, on miRNA expression and the leukemic phenotype. Using RNA interference, miRNA expression arrays, and quantitative polymerase chain reaction, we identified miRNA-494 and miRNA-320a to be up-regulated upon TEL-AML1 silencing independently of TEL expression. Chromatin immunoprecipitation analysis identified miRNA-494 as a direct miRNA target of the fusion protein TEL-AML1. Using bioinformatic analysis as well as functional luciferase experiments, we demonstrate that survivin is a target of the 2 miRNAs. miRNA-494 and miRNA-320a were introduced to the cells by transfection and survivin expression determined by Western blot analysis. These miRNAs blocked survivin expression and resulted in apoptosis in a similar manner as TEL-AML1 silencing by itself; this silencing was also shown to be Dicer-dependent. miRNAs-494 and -320a are expressed at lower levels in TEL-AML1+ leukemias compared with immunophenotype-matched nonTEL-AML1 acute lymphoblastic leukemia subtypes, and within TEL-AML1+ leukemias their expression is correlated to survivin levels. In summary our data suggest that TEL-AML1 might exert its antiapoptotic action at least in part by suppressing miRNA-494 and miRNA-320a, lowering their expression causing enhanced survivin expression.


Fourteen to 17-year-olds' experience of 'risky' drinking--a cross-sectional survey undertaken in south-east England.
In the UK, young people's alcohol consumption is considered an important social and health problem, and is the focus of government strategy and intervention. There is widespread concern that many young people are drinking in a 'risky' way. That is, they are often drinking large amounts of alcohol in a single session, in unsupervised locations. This small-scale, quantitative study used a shortened adaptation of the Adolescent Alcohol Expectancy Questionnaire (AEQ) to examine 14-17-year-olds' experience of 'risky' drinking. The results suggest that a major transition towards first ever drunkenness occurs between the ages of 14 and 15. Young people of this age are more likely to be getting very drunk in unsupervised, and potentially more harmful, locations. It is suggested that using this questionnaire could offer the potential to obtain a rapid and reliable indication of young people's propensity towards possible alcohol-related harm.


Bond strength of a composite resin to an adhesive luting cement.
This study evaluated the influence of surface treatment on the shear bond strength of a composite resin (CR), previously submitted to the application of a temporary cement (TC), to an adhesive luting cement. Eight-four CR cylinders (5 mm diameter and 3 mm high) were fabricated and embedded in acrylic resin. The sets were divided into 6 groups (G1 to G6) (n=12). Groups 2 to 6 received a coat of TC. After 24 h, TC was removed and the CR surfaces received the following treatments: G2: ethanol; G3: rotary brush and pumice; G4: air-abrasion; G5: air-abrasion and adhesive system; G6: air-abrasion, acid etching and adhesive system. G1 (control) did not receive TC or any surface treatment. The sets were adapted to a matrix and received an increment of an adhesive luting cement. The specimens were subjected to the shear bond strength test. ANOVA and Tukey's tests showed that G3 (8.53 MPa) and G4 (8.63 MPa) differed significantly (p=0.001) from G1 (13.34 MPa). The highest mean shear bond strength values were found in G5 (14.78 MPa) and G6 (15.86 MPa). Air-abrasion of CR surface associated with an adhesive system provided an effective bond of the CR to the adhesive luting cement, regardless the pre-treatment with the phosphoric acid.


Nanopore-based identification of individual nucleotides for direct RNA sequencing.
We describe a label-free ribobase identification method, which uses ionic current measurement to resolve ribonucleoside monophosphates or diphosphates in α-hemolysin protein nanopores containing amino-cyclodextrin adapters. The accuracy of base identification is further investigated through the use of a guanidino-modified adapter. On the basis of these findings, an exosequencing approach is envisioned in which a processive exoribonuclease (polynucleotide phosphorylase) presents sequentially cleaved ribonucleoside diphosphates to a nanopore.


On-resin assembly of a linkerless lanthanide(III)-based luminescence label and its application to the total synthesis of site-specifically labeled mechanosensitive channels.
A synthesis strategy for the on-resin assembly of luminescent lanthanide chelates from commercially available compounds was developed. Advantages of the approach include the absence of spacers between the metal ion and the attachment site, and the compatibility with typical chemical protein synthesis protection schemes. Methoxycoumarin-labeled lysine and tris(tert-butyl)-DOTA were consecutively coupled with high efficiency to a free amino group in otherwise fully protected peptide segments using standard peptide synthesis methods. Addition of stoichiometric amounts of Tb(3+) to the modified, cleaved, and purified peptides yielded the desired lanthanide chelate. Incorporation of this label into a chemically synthesized, full-length mechanosensitive channel of large conductance (MscL) of E. coli and subsequent reconstitution into vesicles resulted in a functional mechanosensitive channel of comparable conductance to the wild-type channel. However, this channel required increased suction to gate. Excitation of the antenna molecule methoxycoumarin at 336 nm resulted in an emission spectrum typical for Tb(3+) and a luminescence lifetime of 0.67 ms. The location of the probe close to the backbone of this protein may provide precise information about conformational changes during channel opening from LRET studies.