Differential effects of trimetazidine on vascular smooth muscle cell and endothelial cell in response to carotid artery balloon injury in diabetic rats.
Treatment with trimetazidine (TMZ), 1-[2,3,4-trimethoxybenzyl] piperazine, dihydrochloride, improves cardiac function and ameliorates endothelial dysfunction. However, its potential efficacy against restenosis after balloon injury has not been addressed. We investigated the effect of TMZ on reducing the occurrence of restenosis in the carotid artery in response to balloon injury and explored potential mechanisms for the effects. Streptozotocin (40 mg/kg)-injected Sprague-Dawley rats and Otsuka Long-Evans Tokushima Fatty rats were used for type 1 and type 2 diabetes models, respectively. Both types of rats were divided into three groups: control and TMZ treatment 10 and 20mg/kg per day (n=10 per group). TMZ or normal saline was given orally from 2 weeks before to 2 weeks after carotid injury. Four weeks of TMZ treatment resulted in a significant and dose-dependent reduction in the intima-media ratio in diabetic rats. This effect was accompanied by decreased proliferation of vascular smooth muscle cells (VSMCs) and accelerated re-endothelialization after carotid balloon injury. In vitro study with VSMCs decreased proliferation and migration, while human umbilical vein endothelial cells (HUVECs) increased proliferation and decreased apoptosis after TMZ treatment. Antioxidative effects of TMZ were observed in both VSMCs and HUVECs. Reduction of restenosis by TMZ treatment involved changes in antioxidative and anti-inflammatory properties, which are cell-specific effects on either survival or apoptosis. The specific actions and physiological effects of TMZ may contribute to better understanding of the pathogenesis of atherosclerosis, which is a major complication of diabetes mellitus.


Fluorography--limitations on its use for the quantitative detection of 3H- and 14C-labeled proteins in polyacrylamide gels.
The suitability of fluorography for the detection of 3H- and 14C-labeled proteins on polyacrylamide gradient gels has been investigated. It was found that the absorbance of the fluorographic film image produced by a given level of radioactivity decreased as the acrylamide concentration in the gel increased. The use of Coomassie brilliant blue protein dyes to stain the gel prior to fluorography reduced the absorbance of the fluorographic image. It is concluded that quantitative fluorography can only be applied to unstained gels of a uniform acrylamide concentration.


Enriched rater training using Internet based technologies: a comparison to traditional rater training in a multi-site depression trial.
The evaluation and training of raters who conduct efficacy evaluations in clinical trials is an important methodological variable that is often overlooked. Few rater training programs focus on teaching and assessing applied clinical skills, and even fewer have been empirically examined for efficacy. The goal of this study was to develop a comprehensive, standardized, interactive rater training program using new technologies, and to compare the relative effectiveness of this approach to "traditional" rater training in a multi-center clinical trial. 12 sites from a 22 site multi-center study were randomly selected to participate (6=traditional, 6=enriched). Traditional training consisted of an overview of scoring conventions, watching and scoring videotapes with discussion, and observation of interviews in small groups with feedback. Enriched training consisted of an interactive web tutorial, and live, remote observation of trainees conducting interviews with real or standardized patients, via video- or teleconference. Outcome measures included a didactic exam on conceptual knowledge and blinded ratings of trainee's audiotaped interviews. A significant difference was found between enriched and traditional training on pre-to-post training improvement on didactic knowledge, t(27)=4.2, p<0.0001. Enriched trainees clinical skills also improved significantly more than traditional trainees, t(56)=2.1, p=0.035. All trainees found the applied training helpful, and wanted similar web tutorials with other scales. Results support the efficacy of enriched rater training in improving both conceptual knowledge and applied skills. Remote technologies enhance training efforts, and make training accessible and cost-effective. Future rater training efforts should be subject to empirical evaluation, and include training on applied skills.


Modification of the "Mustardé-Mathieu" and "Horton-Devine" urethroplasty in the management of hypospadias.
This paper reports on the method of repairing distal or mid-shaft hypospadias in 42 patients using a modification of the Mustardé-Mathieu and Horton-Devine techniques. A terminal meatus was achieved in all cases; there were two fistulae and one meatal stenosis.


Finding time for research.
If nurses wish to conduct research and there is no time, they can try these tools, and they probably will reclaim some time to do research. Make research activity a priority, find some collaborators, use opportunities to make one task meet multiple goals, and garner available resources to lighten the load.


Changes in early 'automatic' postural responses associated with the prior-planning and execution of a compensatory step.
There is growing interest in the perturbation-evoked stepping response as an important element in the movement repertoire to maintain upright stance. It is possible that there is an important relationship between the well-documented, early 'automatic' postural responses and subsequent stepping responses. In this study, we characterize changes in early 'automatic' postural responses associated with the prior-planning and execution of a compensatory (i.e. stabilizing) stepping response. Seven subjects were tested on a 'moveable' platform which could translate in the anterior-posterior direction. The subjects' responses were analyzed for two different tasks: (1) 'constrained' (keep feet in place), and (2) perturbation-cued 'reaction time' stepping (step when the platform moves). Only responses to forward platform translations were analyzed in this study. Responses for each of these tasks were evoked using two different perturbation magnitudes. The higher magnitude was sufficiently large to evoke stepping responses in a large proportion of the 'constrained' trials despite instructions not to step. We compared the magnitude of the early evoked postural reactions between trials when subjects had pre-planned a stepping response against trials characterized by either (1) no stepping or (2) unplanned stepping responses. The results revealed that the early 'automatic' responses in tibialis anterior were always present in all subjects and all tasks. However, the evoked 'automatic' responses were approximately 36% smaller (over the first 50 ms) when followed by a pre-planned stepping response ('reaction-time' task). This task-related difference was similar for both perturbation magnitudes i.e. it occurred regardless of whether the 'constrained' tasks involved feet-in-place responses (small perturbations) or stepping responses (large perturbations).(ABSTRACT TRUNCATED AT 250 WORDS)


Design and analysis of drug combination experiments.
In this paper we present and discuss a novel, simple and easy to implement parametric modeling approach to assess synergy. An extended three parameter log-logistic model is used to analyse the data and calculate confidence intervals of the interaction indices. In addition the model corrects for the bias due to plate-location effects. The analysis is performed with PROC NLMIXED and SAS-code is provided. The approach is illustrated using data coming from an oncology study in which the inhibition effect of a combination of two compounds is studied using 96-well plates and a fixed-ratio design.


Correction to: Sargramostim to treat patients with acute hypoxic respiratory failure due to COVID-19 (SARPAC): A structured summary of a study protocol for a randomised controlled trial.
An amendment to this paper has been published and can be accessed via the original article.


Renal disease in children with the acquired immunodeficiency syndrome.
Of 155 children with the acquired immunodeficiency syndrome (AIDS) whom we evaluated during a 6 1/2-year period, 12 were found to have proteinuria. Histologic studies of tissue from these 12 patients revealed a wide spectrum of renal disease: focal glomerulosclerosis in 5, mesangial hyperplasia in 5, segmental necrotizing glomerulonephritis in 1, and minimal change disease in 1. In addition, 6 had tubulointerstitial infiltrates, and 10 had glomerular dense deposits. All 10 renal specimens studied by electron microscopy contained endothelial tubuloreticular inclusions. The mean age (+/- SD) of the five patients with focal glomerulosclerosis when this condition was identified was 27 +/- 19 months. All five had severe renal failure within a year and died of other causes during the following year. The mean age of the five patients with mesangial hyperplasia was 38 +/- 31 months. Although none of them went on to have renal failure, four died within 8 +/- 7 months. Ten of the 12 patients with proteinuria died during the study period. Of the two surviving, one had mesangial hyperplasia and the other had minimal change disease. We conclude that children who acquire human immunodeficiency virus (HIV) infection during the perinatal period may have renal disease, most often focal glomerulosclerosis, as is the case in adults, or mesangial hyperplasia. Although 5 of the 12 children we studied had renal failure during the study period, none died of it. Further studies are needed to determine the correlations between clinical and pathological features and the pathophysiology of AIDS nephropathy in children.


A reentrant loop domain in the glutamate carrier EAAT1 participates in substrate binding and translocation.
To investigate the structural determinants underlying transport by the glutamate transporter EAAT1, we mutated each of 24 highly conserved residues (P392 to Q415) to cysteine. A majority of these substituted cysteines react with the sulfhydryl-modifying reagent MTSEA, suggesting that they reside in an aqueous environment. The impermeant reagents MTSES and MTSET react with residues at each end of the domain (A395C and A414C), supporting a model that places these residues near the extracellular surface. Substrates and inhibitors block the reaction between MTS derivatives and A395C, and the cosubstrate, sodium, slows reaction of MTSEA with Y405C and E406C. From these results, we propose that this domain forms a reentrant membrane loop at the cell surface and may comprise part of the translocation pore for substrates and cotransported ions.


Extended-duration thromboprophylaxis for abdominopelvic surgery: Development and evaluation of a risk-stratified patient decision aid to facilitate shared decision making.
Extended-duration thromboprophylaxis is used to decrease risk of venous thromboembolism (VTE) after surgery but may increase the risk of bleeding. The decision to complete a course of extended-duration thromboprophylaxis can be challenging. The objective of this study was to develop an acceptable patient decision aid (PtDA) to facilitate shared decision making for the use of extended-duration thromboprophylaxis following major abdominal surgery. An evidence-based, risk-stratified PtDA was created. The evidence on benefits and harms of a 28-day postoperative course of low-molecular-weight heparin (LMWH) versus in-hospital prophylaxis only were synthesized. Outcomes included minor bleeding, major bleeding, clinically significant VTE, and fatal VTE. Risks were calculated and reported by Caprini score. Alpha testing of the PtDA draft with various stakeholders was performed using a 10-question survey to assess acceptability of the PtDA with patients, thrombosis experts, and surgeons. The primary outcome was the acceptability of the PtDA. Acceptability testing was performed with 11 patients, 11 thrombosis experts, and 11 surgeons. Most responders felt the language on the PtDA was easy to follow (28/33, 85%), and that the information was well balanced between management options (9/11 [82%] patients; 17/21 [80%] clinicians). Most patients (9/11, 82%) and clinicians (18/22, 82%) believed it would be a useful clinical tool, and were satisfied with the overall quality of the PtDA (27/33, 82%). A risk-stratified, evidence-based PtDA was created to facilitate shared decision making for the use of extended-duration LMWH following major abdominal surgery. This clinical tool was acceptable with patients and physicians and is available at https://decisionaid.ohri.ca/decaids.html.


The impact of delayed heart rate recovery on prevalent hypertension.
Objectives: Delayed heart rate recovery (HRR) is considered an indicator of autonomic nervous dysfunction, which is a primary pathological mechanism of hypertension. The present study aimed to explore the independent association between delayed HRR and prevalent hypertension.Methods: In this cross-sectional study, 314 inpatients were recruited between January 2018 and December 2019. HRR was defined as the peak heart rate during exercise minus the 2nd-minute heart rate after exercise in the treadmill exercise test.Results: The mean HRR in the hypertension group was lower than that in the non-hypertension group (41 bpm vs. 46 bpm; P < 0.001). After full adjustment, each standard deviation increase in HRR was associated with a 35% decrease in the risk of prevalent hypertension (OR: 0.65, 95% CI: 0.48-0.87; P = 0.004). When the HRR was divided into quartiles, the risk in the top quartile was 26% of that in the bottom quartile (OR: 0.26, 95% CI: 0.12-0.56; P = 0.001). Furthermore, smooth curve fitting showed that the risk of prevalent hypertension decreased linearly with the increase in HRR.Conclusion: Delayed HRR was independently associated with prevalent hypertension. The association was linear and robust over the entire range of HRR. The present study suggested that delayed HRR could be used to optimize hypertension risk stratification.


The structure of the human NDUFV1 gene encoding the 51-kDa subunit of mitochondrial complex I.
The genomic organization of the human 51-kDa subunit gene (NDUFV1) on human Chromosome (Chr) 11q13 was determined. The NDUFV1 gene consists of 10 exons. Exon 1 encodes for the 20-amino-acids-long import sequence, and exon 1 through 10 codes for the 444-amino-acids-long mature protein. The protein sequence is highly conserved between human and bovine. Northern blotting analysis showed that the NDUFV1 gene expression varies widely among tissues and that in testis a unique mRNA species is present. In comparison with the other complex I flavoproteins, the expression of the 51-kDa gene in pancreatic tissue is high.


Novel effector monocytes against human RBC antigens invading rejected renal allografts.
A novel effector SPFC-MO may be involved in human renal allograft rejection, and the involvement of SPFC in rejected grafts may be reflected by the preoperative antidonor SPFC reactivity detected by the MLC-SPFC assay.


Automated interference refractometer: an algorithm for locating an irregular fringe pattern.
The interference refractometer is potentially a valuable instrument for the measurement of gas concentrations, but its usefulness has been limited by the necessity to locate visually a pattern of light and dark bands in order to obtain the reading. The instrument is therefore liable to human error and is unsuitable for continuous monitoring. An improved design has been patented, in which this location process is automated by the use of a microprocessor and an array of light-sensitive diodes. To implement this improvement it was necessary to design an algorithm which would reliably locate the pattern. This paper describes the approaches which were considered and the successful algorithm. Some examples are given to illustrate the power of the final algorithm to locate patterns even after severe distortion.


Substrates for energy metabolism in the heart: the role of the interstitial compartment.
Evidence is presented that, as in cardiomyocytes, vascular endothelial cells use fatty acids, in addition to glucose, as a respiratory fuel. Attention is focused on the cardiac interstitium, lined by vascular cells and cardiomyocytes, which may be enriched with metabolic products from these cells. Also, certain proteins are present in the interstitial fluid (Qi) such as plasma proteins and fatty acid binding protein (FABP). However, the concentration of FABP is so low in Qi that albumin is more important to shuttle long chain fatty acids in the interstitial fluid between cardiomyocytes and the vascular compartment. Under hypoxic conditions (hypo)xanthine, lactate and fatty acids may be expected to accumulate in the interstitium, as well as proteins from adjacent cells, such as xanthine oxidase from endothelial cells. This enzyme, acting upon the elevated level of (hypo)xanthine, giving rise to O2-., may be involved in the damage of the ischaemic heart. The significance of the interstitium in ischaemia and in fibrosis following long standing cardiac lipidosis is briefly discussed, as well as the possible mechanisms involved in fatty acid transport in the heart.


Assessment of the release of rehabilitated vervet monkeys into the Ntendeka Wilderness Area, KwaZulu-Natal, South Africa: a case study.
In South Africa, vervet monkeys (Chlorocebus aethiops) are frequently persecuted, resulting in large numbers of injured and/or orphaned animals. Rehabilitation centres aim to care for these monkeys and ultimately return them to the wild whenever possible. However, it is unknown whether rehabilitation is successful in its goal of creating wild-living, independent, self-sustaining troops due to limited published research in this area. This study describes the release and subsequent fate of a troop of rehabilitated vervet monkeys over a 6-month period. A troop of 16 monkeys was released into the Ntendeka Wilderness Area, a protected part of Ngome Forest, by the WATCH (Wild Animal Trauma Centre and Haven) rehabilitation centre in KwaZulu-Natal, South Africa. Monitoring data were evaluated with regard to survival, mortality, suitability of the release site, breeding, condition, troop composition, behaviour, group dynamics, ranging patterns and the effectiveness of monitoring tools. The release was considered to be a partial success in that the troop exhibited behaviour, group dynamics and ranging patterns similar to wild conspecifics. However, the survival rate was low and the troop was judged to be non-self-sustaining. The main problems identified were the limited lifetimes of radio collars, which resulted in missing animals and caused monitoring to be cut short, illegal hunting activities, predation and a small troop size with few adults. The authors recommend improvements that may increase success, such as retaining troops in release enclosures for longer periods, releasing a larger troop with more adults that more closely matches wild troop composition, selecting a release site at least 3 km from the nearest human settlement and the use of GPS collars to allow for a longer monitoring period encompassing all seasonal conditions. Furthermore, all primates for release should be medically screened so as to avoid potential negative impacts on wild populations.


Onset of overweight in Nuuk, Greenland: a retrospective cohort study of children from 1973 to 1992.
The purpose of the study was to examine the age at onset of overweight and obesity of 2-15-year-old children in Nuuk, Greenland, born between 1973 and 1992. The study was a retrospective cohort study. The data were retrieved from the children's individual health files containing information on height and weight, and the database contained a total of 12,002 measurements of BMI in 3,094 children (1,522 boys and 1,572 girls). The main outcome measure was age at onset of overweight-the age at which BMI was above an internationally recommended cutoff point for overweight. The study showed that an increasing proportion of children reached the overweight state and did so at an earlier age for later cohorts. This was seen for both boys and girls. Overweight was less prevalent among boys in all cohorts. For the 1973-1992 cohorts of children from Nuuk, Greenland, the age at onset of overweight was significantly decreased.


Professionalism and dental education: in search of a shared understanding.
Professionalism has profound historical origins; however, the current health care environment in the UK dental sphere is changing, which presents new professional dilemmas that require continued learning and debate. Professionalism is a key aspect of the education of dental students and the lifelong learning and development of dental practitioners. However, 'being' professional can be challenging because while it is recognised as a social good, there is much debate on what professionalism means and how best it can be learned and assessed. Since 2017, the UK Council for the Dental Teachers of Professionalism, consisting of educators from UK dental schools and dental therapy hygiene institutions, has been exploring and debating the role and place of professionalism, as well as sharing challenges and good practice within UK dental education. This paper includes a narrative overview of current thinking in the academic literature on professionalism to consider the use of a shared understanding of professionalism to facilitate conversations between various stakeholders.


Heart rate turbulence slope reduction in imminent ventricular tachyarrhythmia and its implications.
The aim of this study was to see whether heart rate turbulence (HRT) parameters change preceding imminent ventricular tachyarrhythmias (VT/VF). The Spontaneous Ventricular Tachyarrhythmia Database (Medtronic Version 1.0) consisting of 83 paired (control and pre-VT/VF) sets of 1,000 RR intervals recorded by the Medtronic Jewel Plus ICD was used. Sixty-one control records and 69 pre-VT/VF records had two or more ectopic beats, allowing calculation of six HRT indices: means and standard deviations (SD) of turbulence slope (TS), turbulence onset (TO), and turbulence timing (TT). The only index found to be different between control and pre-VT/VF records was SD of TS (4.2 +/- 3.0 control vs 3.1 +/- 1.9 pre-VT/VF, P < 0.05). Thirty-one datasets classified as having normal HRT in control demonstrated a decrease of both TS mean (P < 0.01) and SD (P < 0.01), and loss of correlation between TS mean and left ventricular ejection fraction (LVEF) preceding VT/VF (P < 0.0001 control, P = 0.8 pre-VT/VF). Both mean and SD of TS are reduced before VT/VF, but only in patients who have normal baseline HRT, and are capable of manifesting reduction. This may be why previous studies could not agree on pre-arrhythmia characteristics.


Conceptual/operational criteria of causality: relevance to systematic epidemiologic theory.
Emphasis has recently been placed on the possibility of developing "unified" criteria of causality applicable to both the infectious and chronic, non-infectious diseases. Yet, contemporary efforts are essentially compilations of criteria established over the past 140 years, without provision of the conceptual basis allowing such a unification. From hierarchical views of the natural history of infectious and neoplastic (i.e., chronic non-infectious) disease, it is possible to identify discipline and natural history-related concepts of causation from which it is possible to derive conceptual criteria of causality and complementary operational criteria of causality. These criteria are entirely relevant to the comprehension of disease as both product and process and applicable to both the infectious and neoplastic diseases.


Life satisfaction in young adults with cancer and the role of sociodemographic, medical, and psychosocial factors: Results of a longitudinal study.
Being diagnosed with and treated for cancer often has a strong impact on the life satisfaction (LS) of adolescents and young adults (AYAs). The current study investigated LS in AYA patients with cancer and determined associated factors. Young patients (those aged 18-39 years at the time of diagnosis) with all malignant cancer sites and with a diagnosis made within the last 4 years were assessed. LS was measured at 2 measuring time points using the Questions on Life Satisfaction (FLZ-M). Differences in the FLZ-M and the 10 subdomains (friends/acquaintances, leisure activities/hobbies, health, income/financial security, work/profession, housing situation, family life, children/family planning, partnership, and sexuality) between the 2 time points were calculated. Multiple regression analyses were conducted to determine factors associated with LS. A total of 514 patients (386 of whom were women) with a mean age at diagnosis of 29.6 years participated at both measurements. LS increased significantly in 5 domains with a small effect (Hedges g, 0.17) noted over time. The subdomains with the lowest LS were financial and professional situation, family planning, and sexuality. Significant associations with LS were found at baseline for sociodemographic, medical, and psychosocial variables (explained variance [R2 ]baseline = 0.41). At follow-up, psychosocial factors (positive social support, not having detrimental interactions, and lower perceived adjustment to the disease) remained most important for higher LS controlled for LS at baseline. Neither sociodemographic (except partnership) nor medical factors played a role (R2follow-up = 0.54). Of all the variables examined, social support was found to be the most decisive factor associated with LS at both time points. With regard to LS, social support and adjustment to illness should be given more consideration in the medical care of AYA patients with cancer.


Effect of material damping on bone remodelling.
This paper considers the effect of internal material damping on the stresses, strains, and surface and internal remodelling behaviour in a section of axisymmetrical bone with a force-fitted axially oriented medullary pin. The bone response to several loading situations is modelled using visco-elastic equations. An approximate method is developed to analyse the proposed mathematical model. By considering a numerical example, the effect of material damping on the remodelling stresses is quantified.


Isolation of a protein C activator from southern copperhead venom.
A protease from the venom of the Southern Copperhead snake (Agkistrodon contortrix contortrix) that activates protein C was purified to homogeneity by a combination of sulfopropyl (SP)-Sephadex C-50, Sephadex G-150 and Mono-S column chromatography. The purified enzyme is a glycoprotein, and migrated as a single band in sodium dodecylsulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 37,000 under non-reducing conditions. Upon reduction with 2-mercaptoethanol, the enzyme exhibited a Mr of 40,000. The purified enzyme prolonged the clotting time of human plasma in a dose- and temperature-dependent manner. Purified bovine protein C was completely activated within 10 minutes upon incubation with the purified protease at a 1:500 enzyme: substrate ratio. This reaction was markedly inhibited by calcium ions. The purified venom protein C activator had no effect on human fibrinogen.


[Potassium content analysis in healthy teeth in people of various ages].
Potassium level in permanent teeth has been designated by X-ray fluorescence and some relationships of the content of this element between individual groups of teeth according to the age and sex have been proved. Average K level in molar teeth of men and women was 272.1 +/- 50 (M-SE) ppm, in premolar teeth--297.6 +/- 7.1 ppm, in cuspid teeth--287.0 +/- 7.5 ppm and in incisive teeth--324.7 +/- 12.3 ppm. Irrespective of the age potassium level in permanent teeth in men and women doesn't essentially differ. In the remaining groups of teeth but molar teeth potassium level essentially increases with the age. The greatest growth of potassium with the age has been observed in incisive teeth.


Phospholipid Composition of Fingerlings of Atlantic Salmon Salmo salar during Growth and Development in Aquaculture: The Effect of Different Lighting and Feeding Regimes.
The effect of different feeding and lighting regimes (natural and continuous) on the phospholipid composition of Atlantic salmon fingerlings reared in commercial aquaculture in the summer-autumn period in North Ossetia-Alania was studied. Qualitative and quantitative determination of phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, lysophosphatidylcholine, sphingomyelin was performed by high-performance liquid chromatography. A decrease (September-November) in the content of the studied phospholipids in fingerlings decreased, which should be considered primarily as a biochemical adaptation of development and preparation of juveniles for the upcoming smoltification. The effects of lighting and feeding regime on phospholipid composition were found mainly in the fish reared under constant lighting and 24/7 feeding and the fish reared under natural light and feeding during daylight hours. However, the observed changes were not specific to a particular experimental group of fish in the framework of this study.


Adherence to practice guidelines for the management of febrile neutropenia in patients undergoing hematopoietic stem cell transplantation: An observational study in a referral center in Iran.
Patients undergoing hematopoietic stem cell transplantation (HSCT) are suspected to develop febrile neutropenia (FN) and severe infections. Therefore, appropriate prescription of antibiotics in these patients is crucial to reduce the rates of morbidity, mortality, and antimicrobial resistance. The present study aimed to evaluate the physicians' prescription and adherence to the FN clinical guidelines among patients undergoing HSCT. This prospective observational single-center study was conducted during a 15-month period in a tertiary referral hospital in Iran. The patients with at least one episode of FN following HSCT were included in the current study. The physicians' adherence to the Infectious Diseases Society of America (IDSA) and National Comprehensive Cancer Network (NCCN) clinical guidelines for the management of FN was evaluated using prescription data and medical record reviews. Two hundred and fifteen patients with 297 FN episodes were evaluated. The timing of antibiotics and the selection of the initial regimen were considered guideline-based therapy. However, antibiotic dosing and initial regimen modification were not followed in terms of the guideline recommendations in 58.1% of the patients. In particular, vancomycin was inappropriately given in 83.1% of patients. The overall adherence of physicians to the guidelines was 35.8%. Non-adherence to clinical guidelines is high particularly in initial regimen modification and administration of vancomycin, which affects hospital stay and patient's outcome. Implementation of guideline-review sessions to raise the awareness of the physicians and to improve the rational use of antimicrobial agents may be crucial.


Ophthalmological significance of HLA associated uveitis.
The association between HLA-A29 and birdshot chorioretinopathy is the strongest association between HLA and disease ever described. The determination of HLA-A29 is therefore of diagnostic significance. The association between HLA-B27 and acute anterior uveitis (AAU) is much weaker. However, it is evident that B27+ AAU is clinically different from B27-AAU. Half of the B27+AAU patients have or will have ankylosing spondylitis or Reiter's syndrome. The determination of HLA-B27 is therefore of clinical significance and should be determined in each case of AAU. The B27+ patients should be referred to a rheumatologist. The determination of HLA-Bw51 is of limited but significant diagnostic value for the diagnosis of Behçet's disease in countries around the Mediterranean Sea or Japan. In Northern Europe HLA-Bw51 determination will not give much practical information. The structure and function of HLA class I molecules is now known. It is probable that HLA-A29 and HLA-B27 molecules are directly involved in the pathogenesis of respectively birdshot chorioretinopathy and AAU.


Human muscle function following prolonged eccentric exercise.
4 subjects performed repeated eccentric contractions with leg extensors during prolonged downhill walking (-25% gradient) at 6.44 km.h-1 until collapse due to muscle weakness (range of exercise duration 29 to 40 min). During the exercise oxygen uptake rose progressively from approximately 45% of the previously determined VO2max at 10 min to approximately 65% at the end of the exercise. Following the exercise there was an immediate, significant, and sustained reduction in maximal voluntary isometric contraction, and short term (anaerobic) power output measured concentrically on an isokinetic ergometer. These reductions in muscle function persisted for 96 hours post exercise, and were reflected by significant reductions in the tension generated at low frequency (20 Hz) relative to higher frequency (50 Hz) percutaneous stimulation of the quadriceps. All four subjects showed an increase in plasma levels of creatine kinase post eccentric exercise. Performing concentric contractions by walking uphill for one hour at a significantly greater metabolic cost failed to induce comparable reductions in muscle function. These results provide evidence for the consequences of prolonged eccentric work upon dynamic function which complements earlier reports of structural, enzymatic, and static function changes.


Insurance expansions and adolescent use of substance use disorder treatment.
To provide evidence on the effects of expansions to private and public insurance programs on adolescent specialty substance use disorder (SUD) treatment use. The Treatment Episodes Data Set (TEDS), 1996 to 2017. A quasi-experimental difference-in-differences design using observational data. The TEDS provides administrative data on admissions to specialty SUD treatment. Expansions of laws that compel private insurers to cover SUD treatment services at parity with general health care increase adolescent admissions by 26% (P < .05). These increases are driven by nonintensive outpatient admissions, the most common treatment episodes, which rise by 30% (P < .05) postparity law. In contrast, increases in income eligibility for public insurance targeting those 6-18 years old are not statistically associated with SUD treatment. Private insurance expansions allow more adolescents to receive SUD treatment, while public insurance income eligibility expansions do not appear to influence adolescent SUD treatment.


Performance Metrics in Hand Surgery: Turning a Blind Eye Will Cost You.
The Medicare Access and Children's Health Insurance Program Reauthorization Act established the Quality Payment Program (QPP), which mandates that physicians who meet the threshold in volume of Medicare patients for whom they care participate in this program through either advanced Alternative Payment Models or the Merit-Based Incentive Payment System. Anticipating physicians' concerns regarding the burden of implementing the QPP, feedback from physicians became a critical component of the continued implementation process in 2018. The purpose of this review is to inform hand surgeons regarding the current QPP (early 2019) and for future observation periods.


Congenital toxoplasmosis: to screen or not to screen?
We have reviewed the present day quantifiable cost to society of the 73 cases of congenital toxoplasmosis which are estimated to occur annually in Scotland with the cost of preventing the disease by screening and treatment. Our analysis includes advances in laboratory techniques. The cost of screening would depend on its scale and if in-house or commercial tests are used. If only 2 specimens were screened, at booking and at delivery, the screening costs are estimated to be between 0.5-0.9 times the preventable costs. If a third specimen were tested in the second trimester, to maximise scope for remedial action during pregnancy, the screening costs are 0.7-1.2 times preventable costs. As likely screening costs in most of the schemes we consider are now less than the preventable costs, a screening programme should be adopted.


Measurement of lactate accumulation by in vivo proton NMR spectroscopy during global cerebral ischemia in rats.
In vivo 1H NMR spectral editing techniques were used to monitor cerebral lactate production during remotely controlled temporary forebrain ischemia in rats. The lactate/N-acetylaspartate (NAA) ratio correlated with survival after ischemia and subsequent reperfusion. The lactate/NAA ratio that predicted death after ischemia in rats was estimated to be approximately 1.3.


Association study of polymorphisms within matrix metalloproteinase 9 with bronchial asthma.
Matrix metalloproteinase 9 plays an important role in the development of bronchial asthma. We were interested in whether the polymorphisms -T1702A, -C1562T, R279Q and +C6T within the matrix metalloproteinase 9 (MMP-9) gene were associated with asthma in a population of 231 asthmatic children. However, we found no association. Thus MMP-9 might not be a major gene for asthma.


Atrial flutter. Tracing an elusive arrhythmia.
Seven bried case reports representing variations of atrial flutter point up important considerations bearing on diagnosis: situations predisposing individuals to atrial flutter with 1:1 atrioventricular conduction, the need for special care in placing ECG leads for continuous monitoring, the use of carotid sinus massage to unmask atrial flutter, the infrequent but not rare association of Wenckebach block, the possible presence of diffuse disease of the conduction system, the possibility of initiation of atrial tachyarrhythmia by a premature atrial impulse, and possible inherent limitations of routine ECGs.


Comment on the use of linear free-energy slopes as criteria for distinguishing hydride-ion from hydrogen-atom transfer in reactions of pyridine-nucleotide coenzymes.
For reductions by dihydropyridines, the slopes of plots of log k vs the standard reduction potential of the dihydropyridine are not direct indicators of whether the rate-determining step is hydride-ion or hydrogen-atom transfer. When there is no substituent effect on the reverse rate, those slopes are independent of mechanism and equal to about (30mV)-1.


Renal toxicity mediated by glucose degradation products in a rat model of advanced renal failure.
In peritoneal dialysis (PD) residual renal function contributes to improved patient survival and quality of life. Glucose degradation products (GDP) generated by heat sterilization of PD fluids do not only impair the peritoneal membrane, but also appear in the systemic circulation with the potential for organ toxicity. Here we show that in a rat model of advanced renal failure, GDP affect the structure and function of the remnant kidney. Sprague-Dawley rats were randomly assigned to a two stage subtotal nephrectomy (SNX) or sham operation and were left untreated for 3 weeks. The SNX + GDP group continuously received chemically defined GDP intravenously for 4 weeks; the SNX and the sham-operated rats remained without GDP. The complete follow-up for all groups was 7 weeks postoperatively. We analysed renal damage using urinary albumin excretion as well as a semiquantitative score for glomerulosclerosis and tubulointerstitial damage, as well as for immunohistochemical analyses. The SNX + GDP rats developed significantly more albuminuria and showed a significantly higher score of glomerulosclerosis index (GSI) and tubulointerstitial damage index (TII) as compared to SNX or control rats. In the SNX + GDP group the expression of carboxymethyllysine and methylglyoxal was significantly higher in the tubulointerstitium and the glomeruli compared to the SNX rats. Caspase 3 staining and TUNEL assay were more pronounced in the tubulointerstitium and the glomeruli of the SNX + GDP group. In SNX + GDP animals, the expression of the slit diaphragm protein nephrin, was significantly lower compared to SNX or control animals. In summary, our data suggests that GDP can significantly advance chronic kidney disease and argues that PD solutions containing high GDP might deteriorate residual renal function in PD.


Plasmon coupling between silver nanoparticles: Transition from the classical to the quantum regime.
We explore plasmon coupling between silver nanoparticles (AgNPs) as two AgNPs approach each other within a subnanometer distance. We prepare AgNP dimers with two 21-nm AgNPs separated by alkanedithiol linkers in high yield. Changing the length of the alkanedithiol linkers enables us to control the interparticle distance down to the subnanometer level on the molecular scale. We observe that the longitudinal plasmon coupling band, which is sensitive to the interaction between AgNPs, gradually redshifts as the interparticle distance decreases. This observation is fully consistent with the classical electromagnetic model. The redshift of the plasmon coupling, however, undergoes a drastic change when the interparticle distance reaches ∼1nm. The longitudinal plasmon coupling band vanishes and a new intense band appears at a shorter wavelength. This band redshifts as the nanogap further narrows, but crosses over to a blueshift at ∼0.7nm. A comparison of our observation with finite-difference time-domain simulations reveals that this band arises from quantum effects. Controlled assembly of AgNP dimers in combination with simulations allows us to observe the transition of the plasmon coupling from the classical to the quantum regime at the ensemble level.


Metallothionein, cadmium, copper and zinc levels of human and rat tissues.
Metallothionein (MT), zinc (Zn), copper (Cu) and cadmium (Cd) were determined in 10 tissues (brain, heart, kidney cortex, liver, lung, muscle, pancreas, small intestine, spleen and stomach) from human autopsies (10 male individuals, mean age 43 +/- 9 years, all smokers) and Wistar rats. The mean tissue concentrations of MT in the human samples varied between 3.8 and 495 micrograms/g wet weight in spleen and kidney cortex, respectively. In most tissues human MT levels were high as compared to rats; particularly in liver and kidney cortex human MT levels exceeded those of rats about 25- and 10-fold, respectively. Positive linear relationships were observed between Zn or Cu and MT in human liver and between Cd and MT in human kidney cortex.


Bovine luteinizing hormone. Circular dichroism and thermal difference spectra.
The circular dichroism of bovine luteinizing hormone in the far ultraviolet (200-240 nm) and near ultraviolet (240-320 nm) is reported as a function of pH, reduction and denaturation. The significance of side-chain ellipticity in the native and fully randomised hormone is critically examined, using denatured and reduced ribonuclease and insulin as bases for comparison. Disulphide groups make no measurable contribution to the side-chain ellipticity. Judged by the spectra of the subunits both isolated and recombined, those treatments which promote subunit disociation without causing chain unfolding, reversibly decrease the ellipticity in the near ultra-violet with minimal effect in the far ultraviolet. Thermal perturbation difference spectroscopy of bovine luteinizing hormone and its subunits shows that, in common with the ovine and porcine hormones, there are two tyrosine residues located at the interface between the subunits and inaccessible to water. Only two or three of the five water-accessible tyrosine residues are reactive to N-acetylimidazole.


Predicting polypharmacy in half a million adults in the Iranian population: comparison of machine learning algorithms.
Polypharmacy (PP) is increasingly common in Iran, and contributes to the substantial burden of drug-related morbidity, increasing the potential for drug interactions and potentially inappropriate medications. Machine learning algorithms (ML) can be employed as an alternative solution for the prediction of PP. Therefore, our study aimed to compare several ML algorithms to predict the PP using the health insurance claims data and choose the best-performing algorithm as a predictive tool for decision-making. This population-based cross-sectional study was performed between April 2021 and March 2022. After feature selection, information about 550 thousand patients were obtained from National Center for Health Insurance Research (NCHIR). Afterwards, several ML algorithms were trained to predict PP. Finally, to assess the models' performance, the metrics derived from the confusion matrix were calculated. The study sample comprised 554 133 adults with a median (IQR) age of 51 years (40 - 62) that nested in 27 cities within the Khuzestan province of Iran. Most of the patients were female (62.5%), married (63.5%), and employed (83.2%) during the last year. The prevalence of PP in all populations was about 36.0%. After performing the feature selection, out of 23 features, the number of prescriptions, Insurance coverage for prescription drugs, and hypertension were found as the top three predictors. Experimental results showed that Random Forest (RF) performed better than other ML algorithms with recall, specificity, accuracy, precision and F1-score of 63.92%, 89.92%, 79.99%, 63.92% and 63.92% respectively. It was found that ML provides a reasonable level of accuracy in predicting polypharmacy. Therefore, the prediction models based on ML, especially the RF algorithm, performed better than other methods for predicting PP in Iranian people in terms of the performance criteria.


Dermoid cyst of the maxilla.
Dermoid cysts of the jaw bones are very rare. A case of an intraosseous dermoid cyst of the maxilla of a 5-year-old-male is reported. The possible origins are described.


N-type anorectal malformations.
Three cases of N-type anorectal malformations have been encountered. Two girls with anorectal-vestibular fistulas (one with a normal anus and the other with mild stenosis) were typical of 15 other such cases in the literature. A boy with an anorectal-urethral fistula and covered anus had a lesser variant than most of the other 8 males in the literature. The frequently accompanying esophageal, renal, and skeletal anomalies were not present, nor did he have anterior urethral hypoplasia. The constellation of other major associated anomalies in the boys, but not in the girls, follows the pattern of other types of anorectal malformations and suggests an earlier and/or more severe teratogenic insult in the boys. Anterior perineal resection of the fistula is appropriate for girls with N-type fistulas and for those boys with normal anterior urethras. An additional urethroplasty is necessary for boys with anterior urethral hypoplasia. Our experience and that from the literature suggest that N-type anorectal malformations constitute a rare but real entity, akin to N-type tracheoesophageal fistulas. A plea is made that they be included in classifications of anorectal anomalies.


Experimental hypersensitivity pneumonitis in the mouse: histologic and immunologic features and their modulation with cyclosporin A.
A murine model of hypersensitivity pneumonitis (HP) was established with transnasally administered Thermoactinomyces vulgaris (Tv) bacilli. Bronchoalveolar lavage (BAL) of experimental animals revealed marked increase in the total cell, lymphocyte, and macrophage numbers; the findings were similar to those in human HP. The BAL lymphocytes were mostly Thy 1.2 positive. Lyt-1 positive cells predominated Lyt-2 positive cells. Anti-Tv IgG antibodies and delayed-type hypersensitivity footpad reactions against Tv were detected in animals with HP. Cyclosporin A (CyA), a potent immunosuppressive drug, had marked effects on the development of HP in this model. When CyA was administered throughout the course of Tv inoculations, the granulomatous pneumonitis was markedly suppressed, and an increase in BAL lymphocytes, Thy 1.2 positive cells, was suppressed. When CyA was administered only during the first half period of the Tv treatment, suppression of the disease was minimal; when CyA was administered in the latter half, both the HP lesions and the increase in BAL cell lymphocyte numbers were significantly suppressed. These results indicate that a series of transnasal administration of Tv in mice may provide a good model for human HP.


Actin filament- and Wiskott-Aldrich syndrome protein-binding sites on fructose-1,6-bisphosphate aldolase are functionally distinct from the active site.
The glycolytic enzyme fructose 1,6-(bis)phosphate aldolase (aldolase) is not only required for efficient utilization of glucose and fructose, but also for cytoskeletal functions like cytokinesis and cell motility. These differing roles are mediated by distinct and discrete binding interactions with aldolase's many binding partners, including actin filaments, Wiskott-Aldrich Syndrome protein (WASP), and Sorting Nexin 9 (SNX9). How these interactions are coordinated on the aldolase homotetramer of 160 kDa is unclear. In this study, the catalytic activity of wild-type aldolase is measured in the presence of actin filaments, and a WASP-derived peptide that binds to aldolase, or both. No appreciable changes in kcat or Km values are seen. Then, aldolase variants with substitutions targeting the tryptophan-binding pocket for WASP and SNX9 are created and perturbation of actin filament-, WASP peptide-, and SNX9 peptide-binding are assessed. Those that negatively impacted binding did not show an impact on aldolase catalysis. These results suggest that aldolase can engage in catalysis while simultaneously interacting with cytoskeletal machinery.


Novel clinical radiomic nomogram method for differentiating malignant from non-malignant pleural effusions.
To establish a clinical radiomics nomogram that differentiates malignant and non-malignant pleural effusions. A total of 146 patients with malignant pleural effusion (MPE) and 93 patients with non-MPE (NMPE) were included. The ROI image features of chest lesions were extracted using CT. Univariate analysis was performed, and least absolute shrinkage selection operator and multivariate logistic analysis were used to screen radiomics features and calculate the radiomics score. A nomogram was constructed by combining clinical factors with radiomics scores. ROC curve and decision curve analysis (DCA) were used to evaluate the prediction effect. After screening, 19 radiomics features and 2 clinical factors were selected as optimal predictors to establish a combined model and construct a nomogram. The AUC of the combined model was 0.968 (95% confidence interval [CI] = 0.944-0.986) in the training cohort and 0.873 (95% CI = 0.796-0.940) in the validation cohort. The AUC value of the combined model was significantly higher than those of the clinical and radiomics models (0.968 vs. 0.874 vs. 0.878, respectively). This was similar in the validation cohort (0.873, 0.764, and 0.808, respectively). DCA confirmed the clinical utility of the radiomics nomogram. CT-based radiomics showed better diagnostic accuracy and model fit than clinical and radiological features in distinguishing MPE from NMPE. The combination of both achieved better diagnostic performance. These findings support the clinical application of the nomogram in diagnosing MPE using chest CT.


Definition, clinical classification and initial diagnosis of pulmonary hypertension: Updated recommendations from the Cologne Consensus Conference 2018.
In the summer of 2016, delegates from the German Society of Cardiology (DGK), the German Respiratory Society (DGP), and the German Society of Pediatric Cardiology (DGPK) met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary hypertension (PH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines, aiming at their practical implementation, considering country-specific issues, and including new evidence, where available. To this end, a number of working groups was initiated, one of which was specifically dedicated to the definition, clinical classification and initial diagnosis of PH. While the European guidelines provide a detailed clinical classification and a structured approach for diagnostic testing, their application in routine care may be challenging, particularly given the changing phenotype of PH patients who are nowadays often elderly and may present with multiple potential causes of PH, as well as comorbid conditions. Specifically, the working group addresses the thoroughness of diagnostic testing, and the roles of echocardiography, exercise testing, and genetic testing in diagnosing PH. Furthermore, challenges in the diagnostic work-up of patients with various causes of PH including "PAH with comorbidities", CTEPH and coexisting conditions are highlighted, and a modified diagnostic algorithm is provided. The detailed results and recommendations of the working group on definition, clinical classification and initial diagnosis of PH, which were last updated in the spring of 2018, are summarized in this article.


[Long-term follow-up of actinic thoracic wall ulceration after radiation accident caused by an industrial radiation source].
The long-term outcome of a patient injured by an industrial x-irradiation-source is demonstrated and the problems of actinic chest wall damage as well as the development of plastic surgery technique within a 25 year period is discussed by means of this case report.


Synergistic effect of excellent carriers separation and efficient high level energy electron utilization on Bi3+-Ce2Ti2O7/ZnIn2S4 heterostructure for photocatalytic hydrogen production.
The separation of photogenerated carriers and the efficient utilization of high-level energy electrons (HLEEs) are the key processes for improving the performance of photocatalysts. Herein, Ce2Ti2O7/ZnIn2S4 (CTOZIS) and Bi3+-doped Ce2Ti2O7/ZnIn2S4 (BCTOZIS) photocatalyst were successfully synthesized through hydrothermal method. The photocatalytic hydrogen production of CTOZIS and BCTOZIS was 1233.7 μmol g-1 and 4168.5 μmol g-1 under visible light irradiation (λ ≥ 420 nm) within 5 h, which was 2.3 and 7.6 times than that of pure ZnIn2S4, respectively. X-ray photoelectron spectroscopy, photoluminescence spectroscopy and electrochemical characterization demonstrated that after Bi3+ doping, the electron-hole pairs recombination of BCTOZIS was inhibited, which may be ascribed to the establishment of a Z-scheme heterojunction and the presence of oxygen vacancy and Ce4+/Ce3+ redox center. The doping of Bi3+ resulted in the adjustment of the valence band position of Ce2Ti2O7 from 1.98 V to 1.92 V. This adjustment enabled direct transfer of HLEEs generated in Ce2Ti2O7 to the conduction band of ZnIn2S4 for hydrogen production with a wavelength below 423 nm. The synergistic effect of conventional Z-scheme electron transfer and the unique utilization of HLEEs boosted the photocatalytic performance of BCTOZIS. This study affords an innovative insight for designing visible-light-driven photocatalysts with high photocatalytic activity.


Mercury and antimony in wastewater: fate and treatment.
It is important to understand the fate of Hg and Sb within the wastewater treatment process so as to examine potential treatment options and to ensure compliance with regulatory standards. The fate of Hg and Sb was investigated for an activated sludge process treatment works in the UK. Relatively high crude values (Hg 0.092 μg/L, Sb 1.73 μg/L) were observed at the works, whilst low removal rates within the primary (Hg 52.2 %, Sb 16.3 %) and secondary treatment stages (Hg 29.5 %, Sb -28.9 %) resulted in final effluent concentrations of 0.031 μg/L for Hg and 2.04 μg/L for Sb. Removal of Hg was positively correlated with suspended solids (SS) and chemical oxygen demand (COD) removal, whilst Sb was negatively correlated. Elevated final effluent Sb concentrations compared with crude values were postulated and were suggested to result from Sb present in returned sludge liquors. Kepner Tregoe (KT) analysis was applied to identify suitable treatment technologies. For Hg, chemical techniques (specifically precipitation) were found to be the most suitable whilst for Sb, adsorption (using granulated ferric hydroxide) was deemed most appropriate. Operational solutions, such as lengthening hydraulic retention time, and treatment technologies deployed on sludge liquors were also reviewed but were not feasible for implementation at the works.


Studies on the constituents of Juglans species. I. Structural determination of (4S)- and (4R)-4-hydroxy-alpha-tetralone derivatives from the fruit of Juglans mandshurica MAXIM. var. sieboldiana MAKINO.
Four enantiomerically pure new alpha-tetralones, (4S)- and (4R)-5-hydroxy-4-methoxy-alpha-tetralones and (4S)- and (4R)-5,8-dihydroxy-4-methoxy-alpha-tetralones were isolated, together with five known ones, (4S)- and (4R)-4,8-dihydroxy-alpha-tetralones, (4S)-4,8-dihydroxy-5-methoxy-alpha-tetralone and (4S)- and (4R)-4-hydroxy-alpha-tetralones, from the fruit of Juglans mandshurica MAXIM. var. sieboldiana MAKINO. Their structures were established on the basis of spectral analysis. To the best of our knowledge, this is the first isolation of the (4R)-4-hydroxy-alpha-tetralone derivative from Juglans species.


Steroidal carbonitriles as potential aromatase inhibitors.
Estrogens, responsible for the growth of hormone-dependant breast cancer are biosynthesized from androgens involving aromatase enzyme in the last rate limiting step. Inhibition of aromatase is an efficient approach for the prevention and treatment of breast cancer. Novel 4-phenylthia derivatives (2, 3 and 7) have been synthesized as aromatase inhibitors. The synthesized compounds (2, 3 and 7) exhibited noticeable enzyme inhibiting activity. Kinetics study of these compounds (2, 3, and 7) showed negligible inhibition of the enzyme under conditions conducive for irreversible inhibition of the enzyme. Introduction of unsaturation at C-4, C-1 & 4 or C-4 & 6 (compounds 5, 9 and 11) was observed to not be an effective strategy for entrancing aromatase inhibiting activity in 17-oxo-16β-carbonitrile derivatives. The D-seco derivatives (13-15 and 17) having unsaturation at C-4, C-1 & 4 or C-4 & 6 along with carbonitrile function in ring-D showed complete loss of aromatase inhibiting activity.


Application of dispersive liquid-liquid microextraction for the determination of phosphatidylethanol in blood by liquid chromatography tandem mass spectrometry.
Phosphatidylethanol (PEth) is a phospholipid which requires for its metabolic formation the presence of relatively high ethanol levels. PEth is thus a promising marker to quentify ethanol abuse. Dispersive liquid-liquid microextraction has become a popular technique because it is fast, inexpensive, easy to operate and consumes low volume of organic solvent. In this method, the appropriate mixture of extraction solvent (230 μL dichloromethane) and disperser solvent (630 μL acetone) are injected into the sample by syringe, rapidly. The liquid chromatography method using a reversed phase-C8 column and a negative ion mode electrospray ionization tandem mass spectrometry detection instrument was developed for the determination of small amounts of PEth that might be present in blood samples, using phosphatidylbutanol (PBut) as an internal standard. The sensitivity of detection obtained with tandem MS was better than that of previous methods. Good linearity was obtained for a range of LOQ-10 μg/mL for PEth, whereas all of the deviations in precision and accuracy were less than 15% except for the LLOQ, where it should not exceed 20%. A set of 50 blood samples were analyzed by such method and whole blood concentrations of PEth 16:0/18:1 ranged from LLOQ to 1.71 μg/mL.


[Comparison of different means for tooth surface polishing after bracket debonding].
To observe the tooth surface after acid etching and removing of bonding adhesive by two means for polishing. Thirty extracted premolars for orthodontic purpose were used in this experiment. The brackets were adhered and debonded. Then the premolars were randomly divided into two groups. They were treated by traditional method and silicone particles, and observed by roughness instrument and scanning electronic microscope. The polishing-time and surface roughness value(Ra) were recorded. SPSS13.0 software package was used for paired t test. There was no significant difference in Ra and polishing-time between the two groups (P>0.05). Under SEM, the scratches on tooth surface polished by silicone particles were shallower and thinner. The silicone particles could provide good requirement for tooth polishing after bracket debonding clinically.


Single-molecule dynamic force spectroscopy of the fibronectin-heparin interaction.
The integrity of cohesive tissues strongly depends on the presence of the extracellular matrix, which provides support and anchorage for cells. The fibronectin protein and the heparin-like glycosaminoglycans are key components of this dynamic structural network. In this report, atomic force spectroscopy was used to gain insight into the compliance and the resistance of the fibronectin-heparin interaction. We found that this interaction can be described by an energetic barrier width of 3.1+/-0.2A and an off-rate of 0.2+/-0.1s(-1). These dissociation parameters are similar to those of other carbohydrate-protein interactions and to off-rate values reported for more complex interactions between cells and extracellular matrix components. Our results indicate that the function of the fibronectin-heparin interaction is supported by its capacity to sustain significant deformations and considerable external mechanical forces.


Antiproliferative property of n-hexane and chloroform extracts of Anisomeles malabarica (L). R. Br. in HPV16-positive human cervical cancer cells.
To find the efficacy of serial extracts of Anisomeles malabarica in inhibiting proliferation of and inducing apoptosis in human cervical cancer cells, SiHa and ME 180, that are HPV 16-positive. The whole plant was extracted in n-hexane, chloroform, ethyl acetate, n-butanol, methanol, and water. The cells were treated with the extracts at increasing concentrations to find the IC(50), adopting MTT ([3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]) assay. Acridine orange (AO) and ethidium bromide (EB) and Hoechst 33258 staining were adopted to assess the mode of cell death, Annexin V-Cy3 staining to evaluate one of the early apoptotic features, JC-1 staining to assess the mitochondrial membrane depolarization, comet assay for DNA fragmentation, and cell cycle analysis for the distribution of cells after treatment. n-Hexane and chloroform extracts were cytotoxic to the cervical cancer cells in dose- and duration-dependent manner. The cells that responded to the treatments revealed typical apoptotic features. Early features of apoptosis, phosphatidyl serine translocation and loss of mitochondrial trans-membrane potential, were observed in the treated cells, and comet assay revealed DNA damage. In the FACS analysis, the cells accumulated in the sub-G0/G1 phase of the cell cycle, except in n-hexane- and chloroform extract-treated SiHa cells at 24 h, which showed arrest in S- and G2/M phases. n-Hexane and chloroform extracts of A. malabarica inhibit proliferation of and induce death in HPV16-positive cervical cancer cells, mostly by apoptosis and to some extent by necrosis.


Estimation of nitrogen and phosphorus concentrations from water quality surrogates using machine learning in the Tri An Reservoir, Vietnam.
Surface water eutrophication due to excessive nutrients has become a major environmental problem around the world in the past few decades. Among these nutrients, nitrogen and phosphorus are two of the most important harmful cyanobacterial bloom (HCB) drivers. A reliable prediction of these parameters, therefore, is necessary for the management of rivers, lakes, and reservoirs. The aim of this study is to test the suitability of the powerful machine learning (ML) algorithm, random forest (RF), to provide information on water quality parameters for the Tri An Reservoir (TAR). Three species of nitrogen and phosphorus, including nitrite (N-NO2-), nitrate (N-NO3-), and phosphate (P-PO43-), were empirically estimated using the field observation dataset (2009-2014) of six surrogates of total suspended solids (TSS), total dissolved solids (TDS), turbidity, electrical conductivity (EC), chemical oxygen demand (COD), and biochemical oxygen demand (BOD5). Field data measurement showed that water quality in the TAR was eutrophic with an up-trend of N-NO3- and P-PO43- during the study period. The RF regression model was reliable for N-NO2-, N-NO3-, and P-PO43- prediction with a high R2 of 0.812-0.844 for the training phase (2009-2012) and 0.888-0.903 for the validation phase (2013-2014). The results of land use and land cover change (LUCC) revealed that deforestation and shifting agriculture in the upper region of the basin were the major factors increasing nutrient loading in the TAR. Among the meteorological parameters, rainfall pattern was found to be one of the most influential factors in eutrophication, followed by average sunshine hour. Our results are expected to provide an advanced assessment tool for predicting nutrient loading and for giving an early warning of HCB in the TAR.


High-order stimulated Raman scattering in a highly transient regime driven by a pair of ultrashort pulses.
We demonstrate efficient generation of high-order anti-Stokes Raman sidebands in a highly transient regime, using a pair of approximately 100-fs laser pulses tuned to Raman resonance with vibrational transitions in methane or hydrogen. The use of this technique looks promising for efficient subfemtosecond pulse generation.


Self-efficacy and psychosocial functioning in schizophrenia: a mediational analysis.
The construct of self-efficacy has been hypothesized to mediate the relationship between efforts at coping with psychiatric illness and functional outcome. This study examined whether self-efficacy mediated the relationships between psychosocial functioning and important predictors of functioning: premorbid functioning, negative symptoms, and cognitive functioning. Although self-efficacy was positively associated with psychosocial functioning, it did not mediate the relationships between functioning and the other established predictors. Rather, negative symptoms were the strongest predictor of functioning and mediated the relationship between self-efficacy and functioning. The findings suggest that negative symptoms, and not self-efficacy, are the most critical determinants of psychosocial functioning in schizophrenia, and that psychosocial treatment should focus on the amelioration of these symptoms.


Microwave-accelerated ruthenium-catalyzed olefin metathesis.
[reaction: see text]. Microwave heating is an efficient method for the acceleration of ring-closing metathesis reactions using ruthenium-based catalysts. The reaction can be rapidly conducted in either ionic liquids, such as 1-butyl-3-methylimidazolium tetrafluoroborate (bmim), or in a microwave transparent solvent (MTS) such as dichloromethane.


A new neuronal marker identified by phosphorylcholine-binding myeloma proteins.
The difficulty of working with the intact brain in vivo has led to the increasing use of nerve cell cultures in neurobiology. However, dissociated cells cannot be unambiguously identified by morphological criteria before the third week in culture, for it is not until then that the basic morphology and size of neurones become stable so that these and other cell types can be easily distinguished. However, cultured neurones can be identified by various cytochemical techniques based on (1) the detection of neurotransmitters or receptors for transmitters, (2) the presence of the Thy 1 antigen and the receptor for tetanus toxin, which are present on the membrane of most neurones, and (3) the presence in neurones of neurone-specific enolase (NSE), a cytoplasmic enzyme, which can only be identified on fixed specimens. Furthermore, other cell types in culture can also be specifically labelled. For instance, antisera to galactocerebroside bind selectively to oligodendrocytes, and antibodies to a neural tumour bind selectively to Schwann cells. We report here the selective interaction of phosphorylcholine-binding myeloma proteins (PC-BMP) with mouse neurones in culture and in suspension. Phosphorylcholine (PC) is found as part of lecithin and sphingomyelin molecules in variable amounts in eukaryotic and prokaryotic membranes, including plasma membranes.


Increased diffusion in the normal appearing white matter of brain tumor patients: is this just tumor infiltration?
Altered diffusion in the normal appearing white matter (NAWM) of glioma patients has been explained by tumor infiltration. The goal of the present study was to test this explanation indirectly by examining whether these alterations were also present in the contralateral NAWM of non-infiltrative tumors like meningiomas; and to search for other possible reasons for this abnormality. Twenty-seven patients with histologically verified glioma (grade II-IV), 22 meningioma patients and two groups of age- and sex-matched healthy controls underwent diffusion weighted imaging (DWI) on a 3T MR. All patients were examined before treatment. Apparent diffusion coefficient (ADC) values were calculated in the entire NAWM of the hemisphere contralateral to the tumor. ADC values of the NAWM were compared between groups with Mann-Whitney U-test and multiple linear regression. The relations of ADC in NAWM to glioma grade and to tumor volume were also investigated. ADC values of the contralateral NAWM were significantly higher in both glioma and meningioma patients compared to controls (P = 0.0006 and 0.0099, respectively). ADC value was higher in the NAWM of high grade gliomas than in low grade gliomas (P = 0.0181) and in healthy control subjects (P = 0.0003). ADC did not depend on tumor volume in any of the patient groups. Elevated ADC in the NAWM of both glioma and meningioma patients might indicate that the effect of infiltrating tumor cells is not the only reason for the alteration as it has been previously suggested. Although the role of mass effect was not proved, other mechanisms might also contribute to ADC elevation.


Proliferative responses of lymphocytes in Bovicola ovis-infested lambs.
Proliferative responses of peripheral blood and prescapular lymph node lymphocytes from 8 B. ovis-infested and 8 naive lambs to concanavalin A (Con A) and soluble antigen of B. ovis were examined in vitro. The numbers of lice and the extent of cockle were also assessed on each lamb. Prescapular lymph node lymphocytes from infested lambs showed significantly higher responses to B. ovis antigen than those from naive lambs. Only a marginal difference was observed between infested and naive lambs in the response of lymphocytes from peripheral blood. Proliferative responses to Con A by prescapular lymph node or blood cells were not significantly different between groups. The results indicated a relationship between the intensity of louse infestation and the proliferative response of prescapular lymph node lymphocytes to B. ovis antigen.


Tonic activity of submucosal neurons influences basal ion transport.
The influence of tonically active submucosal neurons on basal ion transport was studied using sheets of guinea pig ileum set up in flux chambers. Tetrodotoxin evoked an immediate and sustained decrease in short-circuit current that was sustained for 60 minutes compared with control tissues in which basal currents gradually decreased over time. Time-dependent changes in basal short-circuit currents in tissues treated with atropine were not significantly different from control tissues. The decrease in short-circuit current after tetrodotoxin resulted from a greater increase in net chloride absorption than sodium absorption. Changes in net sodium and chloride transport were due to an increase in the mucosal-to-serosal fluxes of these ions. The results suggest that tonic activity of submucosal neurons limits the absorptive capacity of the guinea pig ileum.


Influence of autolysis on rat gastric endocrine cells. Histochemical and electron microscopical study.
In the present study histochemical parameters of the rat gastric endocrine cells were followed up in the course of 24-h autolysis, and their ultrastructure was studied during autolysis lasting for 60 min. The autolysis occurred at 37 degrees C. In the light microscope, with the histochemical methods applied, only EC, ECL and G cells could be identified during the one-hour autolysis. With the autolysis proceeding for 6 and 12 h, only argyrophil method according to Grimelius (1968) enabled visualization of gastric argyrophilic cells. After 24 h of autolysis, none of the methods applied (not even the Grimelius method) proved to be adequate for successful demonstration of the gastric endocrine cells. In the course of 60-min autolysis, electron microscopic examination provided identification of the EC, ECL, AL, D1, and G cells with the characteristical ultrastructural appearance of granules. The granules of the endocrine cells (G cells included) were found to be considerably resistant to autolysis. The effect of 60-min autolysis did not induce granule "emiocytosis" or dissolution of granule content. Autolysis exceeding five minutes resulted in damage of the mitochondria of different degrees and in dilatation of the profiles of endoplasmic reticulum (particularly in G and AL cells). The results obtained in the present study demonstrate the feasibility of in vitro experimental stimulation since the endocrine granules have proved to be resistant to the effects of simultaneously developing autolysis.


Neither too little nor too much: Finding the ideal proportion of excipients using confocal Raman and chemometrics.
The applications of Raman imaging in pharmaceutical field are ever-increasing due its ability to obtain spatial and spectral information simultaneously, once it allows determine the chemical distribution of compounds. In this sense, it is used to study homogeneity, of paramount importance during the development of pharmaceutical formulations due to its relation to stability, safety and efficacy. Commonly, just surface is analyzed, but confocal Raman spectroscopy can also characterize the inner part of samples, allowing to determine phase separation in the early stages. In this sense, confocal 3D Raman microscopy was crucial to obtain the optimal proportion of Apifil®, Capryol® 90 and Transcutol® to promote controlled release of the local anesthetic butamben (BTB). 3D chemical maps were obtained by classical least squares (CLS) using pure compound spectra as S matrix, showing that chemical distribution throughout the material was different. Knowing that the composition of samples affects the homogeneity parameter, standard deviation and distributional homogeneity index (DHI) were used in mixture experimental design (DoE). From this analysis, it was revealed that a correct amount of Capryol® 90 enhances both miscibility and solubility. Furthermore, suitable miscibility was observed in two ratio proportions of excipients with a desirability of 0.783 and 0.742. These results unequivocally demonstrated that confocal Raman microscopy combined to DoE can bring pharmaceutical development to a higher level.


Aggregation-induced emission enhancement of gold nanoclusters triggered by sodium heparin and its application in the detection of sodium heparin and alkaline amino acids.
This work first reported that sodium heparin could cause the aggregation-induced emission enhancement (AIEE) effect of GSH-AuNCs (Glutathione functionalized gold nanoclusters). While it was interestingly found that the addition of alkaline amino acids would greatly weaken this effect. Thus, fluorescent system was designed for the quantitative detection of sodium heparin and alkaline amino acids. Negatively charged sodium heparin would connect with GSH-AuNCs through electrostatic attraction, leading to a significant AIEE effect. Then alkaline amino acids would competitively bind with sodium heparin, causing this effect to almost disappear. The reasons were as follows: (I) The hydrogen bonding between sodium heparin and alkaline amino acids was much stronger than electrostatic force, causing GSH-AuNCs to be competitively replaced. (II) Alkaline amino acids and GSH-AuNCs were both positively charged and repelled each other. The presence of alkaline amino acids would hinder the AIEE effect. (III) AIEE effect was confirmed to have a close relationship with the pH value which could be greatly affected by alkaline amino acids. (Ⅳ) Not only the hydrogen bonding, the electrostatic force also existed between the alkaline amino acids and sodium heparin. All the above reasons worked together to weaken the AIEE effect of GSH-AuNCs triggered by sodium heparin. Finally, both sodium heparin and alkaline amino acids were accurately detected, showing good correlation coefficients of 0.99 with the LODs of 0.0100 mg/mL (sodium heparin), 1.05 μM (histidine), 3.38 μM (arginine) and 6.16 μM (lysine), respectively.


Jdp2 downregulates Trp53 transcription to promote leukaemogenesis in the context of Trp53 heterozygosity.
We performed a genetic screen in mice to identify candidate genes that are associated with leukaemogenesis in the context of Trp53 heterozygosity. To do this we generated Trp53 heterozygous mice carrying the T2/Onc transposon and SB11 transposase alleles to allow transposon-mediated insertional mutagenesis to occur. From the resulting leukaemias/lymphomas that developed in these mice, we identified nine loci that are potentially associated with tumour formation in the context of Trp53 heterozygosity, including AB041803 and the Jun dimerization protein 2 (Jdp2). We show that Jdp2 transcriptionally regulates the Trp53 promoter, via an atypical AP-1 site, and that Jdp2 expression negatively regulates Trp53 expression levels. This study is the first to identify a genetic mechanism for tumour formation in the context of Trp53 heterozygosity.


Clinical studies of sweat rate reduction by an over-the-counter soft-solid antiperspirant and comparison with a prescription antiperspirant product in male panelists.
Individuals with axillary hyperhidrosis have much higher than average sweat rates and are often prescribed anhydrous aluminum chloride (AlCl(3)) solutions. Topical application of these solutions can be irritating to the skin, resulting in poor compliance and lower than desired efficacy. Demonstrate the efficacy of an over the counter "clinical strength" soft-solid antiperspirant using a night time application regimen and compare to a prescription aluminum chloride (6.5%) antiperspirant using male panelists. Gravimetric hot room efficacy testing (100 F and 35% Humidity) was performed comparing an over the counter soft-solid antiperspirant to placebo in a single test. Two separate gravimetric tests were placed comparing a prescription aluminum chloride (6.5%) antiperspirant to the same soft solid product using an intent to treat model. Skin irritation was assessed daily by a trained grader. Placebo testing resulted in 85% of panelists having a reduction in sweating rate greater than 50%. Comparison testing showed the over the counter soft solid reduced sweat rate by an average of 34% better than the prescription product while resulting significantly less skin irritation. Over the counter "clinical strength" soft-solid antiperspirants can be considered as an alternative treatment to aluminum chloride antiperspirants for the treatment of heavy sweating.


An analysis of early studies released by the Lung Imaging Database Consortium (LIDC).
To analyze radiologist lung nodule segmentations in the Lung Imaging Database Consortium (LIDC) database and to apply statistical tools to generate estimates of ground truth. This investigation expands on earlier work by considering a larger number of cases from the LIDC database, and results were generated on a per-nodule basis, as opposed to a per-case basis as was done previously. We analyzed nodule data drawn from the 41 most recent computed tomography exams released by the LIDC. We combined radiologist segmentations for a given nodule using different consensus schemes: union, intersection, and simultaneous truth and performance level estimation (STAPLE). We also generated three-dimensional models of the manual segmentations using discrete marching cubes to visualize features of the data. Using the union as the consensus scheme produced the greatest number of nodule-positive voxels while using the intersection produced the fewest. Considering only nodules for which all readers agreed on nodule presence, STAPLE computed sensitivity averages for readers one, two, three, and four were 0.91, 0.83, 0.90, and 0.77, respectively. Specificity averages were 0.97, 0.98, 0.97, and 0.97. Considering cases for which there was disagreement about nodule presence, sensitivity results become 0.67, 0.74, 0.60, and 0.37. Specificity results in this case are 0.95, 0.95, 0.95, and 0.98. STAPLE-generated pmaps exhibited probability values tightly grouped below the 0.25 and above the 0.75 probability levels. Three-dimensional models of manually segmented nodules revealed step-artefacts in the segmentation data. Radiologists often disagree about nodule presence. Ideally, knowing each reader's sensitivity and specificity a priori is preferred for optimal STAPLE results. Knowing these values and developing manual segmentation tools and imaging protocols that mitigate unwanted segmentation features (such as step artefacts) can result in more accurate estimates of ground truth. Furthermore, a computer-aided detection algorithm's performance is a function of the ground truth estimate by which it is scored.


Vitamin D3 supplementation does not modify cardiovascular risk profile of adults with inadequate vitamin D status.
The Nutrition Societies in Germany, Austria, and Switzerland recommend a daily intake of 20 µg vitamin D3 for adults when endogenous synthesis is absent. The current study aimed to elucidate whether this vitamin D3 dose impacts cardiovascular risk markers of adults during the winter months. The study was conducted in Halle (Saale), Germany (51o northern latitude) as a placebo-controlled, double-blinded, randomised trial (from January to April). A total of 105 apparently healthy subjects (male and female, 20-71 years old) were included. Subjects were randomly allocated to two groups. One group received a daily 20-µg vitamin D3 dose (n = 54), and the other group received a placebo (n = 51) for 12 weeks. Outcome measures included blood pressure, heart rate, concentrations of renin, aldosterone, serum lipids and vascular calcification markers, and haematologic variables such as pro-inflammatory monocytes. Blood pressure and systemic cardiovascular risk markers remained unchanged by vitamin D3 supplementation, although serum 25-hydroxyvitamin D3 increased from 38 ± 14 to 73 ± 16 nmol/L at week 12. The placebo and vitamin D groups did not differ in their final cardiovascular risk profile. Daily supplementation of 20 µg vitamin D3 during winter is unlikely to change cardiovascular risk profile.


RETRACTED: Auditory (dis-)fluency triggers sequential processing adjustments.
An increasing amount of studies indicates that experiencing increased task demands, triggered for example by conflicting stimulus features or low perceptual fluency, lead to processing adjustments. While these demand-triggered processing adjustments have been shown for different paradigms (e.g., response conflict tasks, perceptual disfluency, task switching, dual tasking), most of them are restricted to the visual modality. The present study investigated as to whether the challenge to understand speech signals in normal-hearing subjects would also lead to sequential processing adjustments if the processing fluency of the respective auditory signals changes from trial to trial. To that end, we used spoken number words (one to nine) that were either presented with high (clean speech) or low perceptual fluency (i.e., vocoded speech as used in cochlear implants-Experiment 1; speech embedded in multi-speaker babble noise as typically found in bars-Experiment 2). Participants had to judge the spoken number words as smaller or larger than five. Results show that the fluency effect (performance difference between high and low perceptual fluency) in both experiments was smaller following disfluent words. Thus, if it's hard to understand, you try harder.


Doppler umbilical velocimetry in the prediction of adverse outcome in pregnancies at risk for intrauterine growth retardation.
Perinatal indicators of fetal compromise were assessed according to the results of continuous-wave Doppler umbilical velocimetry for 172 patients at risk for intrauterine growth retardation (IUGR). Forty-three (25%) of the patients delivered an infant with a birth weight below the tenth percentile for gestational age. The last Doppler study before delivery was abnormal in 48.8% of the growth-retarded infants but in only 13.2% of the infants without evidence of IUGR. Furthermore, in the growth-retarded group, early delivery, reduced birth weight, decreased amniotic fluid at birth, admission to the neonatal intensive care unit, neonatal complications associated with IUGR, and a prolonged hospital stay were observed more frequently in those who had an abnormal ratio than in those with a normal ratio. The sensitivity of the systolic/diastolic ratio for an adverse perinatal outcome (operative delivery for fetal distress, neonatal morbidity associated with IUGR, and/or perinatal death) was significantly better for the infants with IUGR (66.7%) than for the infants without IUGR (27.8%; P less than .05). The predictive value of an abnormal ratio was also higher for the pregnancies complicated with IUGR (57.1%) than for those without IUGR (29.4%), but not to a statistically significant degree. These data suggest that Doppler umbilical velocimetry studies are valuable in identifying those growth-retarded fetuses at increased risk for an adverse perinatal outcome.


Surgical Outcomes for Transgender Men Undergoing Hysterectomy.
This study sought to assess surgical outcomes of hysterectomy performed for transgender individuals compared with hysterectomy for individuals with menstrual disorders. This retrospective cohort study was conducted using the American College of Surgeons National Surgical Quality Improvement Program database. Data of transgender individuals who underwent hysterectomy and individuals who underwent hysterectomy for menstrual disorders were extracted from the participant use data file (2015-2016). Transgender individuals were compared with individuals with menstrual disorders for surgical outcomes within 30 days of hysterectomy, by using appropriate statistical tests. A two-sided P value of less than 0.05 was considered statistically significant (Canadian Task Force Classification II-2). The study identified 89 cases of hysterectomy for transgender individuals and 4439 cases of hysterectomy for menstrual disorders. Compared with patients who underwent hysterectomy for menstrual disorders, transgender patients were more likely to be younger (mean ± SD 30.79 ± 9.68 years vs. 42.6 ± 7.04 years), have a normal body mass index (25.84% vs. 17.77%), be classified as American Society of Anesthesiologists class I (34.09% vs. 10.46%), and have outpatient surgery (76.40% vs. 53.55%) (P < 0.05). Overall incidence of postoperative complications was low for both groups. No significant difference in surgical outcomes was observed for re-admission, superficial or deep/organ space infections, wound dehiscence, sepsis, blood transfusion, deep vein thrombosis, pulmonary embolism, or death. Transgender patients who underwent hysterectomy on average required decreased operative time (120.4 ± 79.2 minutes vs. 131.2 ± 64.3 minutes) and decreased lengths of stay (0.82 ± 0.82 days vs. 1.35 ± 2.73 days). This study suggests that transgender patients undergoing hysterectomy were younger and healthier than patients undergoing hysterectomy for menstrual disorders. Surgical complications were low for both groups, and significant differences in surgical outcomes were not observed.


Enzyme-linked immunosorbent assay (ELISA) for IgG antibodies to thyroglobulin.
We used a computer programmed standard IgG curve for computer-assisted quantification of assay results for autoantibodies to thyroglobulin (Tg) by quantitative enzyme-linked immunosorbent assay (ELISA). Specific antibody levels in unknowns were quantified by comparison of their optical density readings with a standard curve of absorbance vs concentration obtained with dilutions of the reference serum. Anti-Tg antibodies were detected in 80% of the patients with chronic thyroiditis and 90% of those with Graves' disease. Anti-Tg antibodies were also detected in 14.3% of the healthy controls. The titer of anti-Tg antibodies detected by tanned red cell hemagglutination correlated well with that detected by ELISA, although, the sensitivity of the ELISA was higher. By our computer-assisted conversion method, the anti-Tg antibody can be readily and reliably quantified and low titer antibodies to Tg can be detected with adequate precision.


Expandable endodermal progenitors: new tools to explore endoderm and its derivatives.
In the two recent issues of Cell Stem Cell, Rossant and colleagues (Seguin et al., 2008) produced expandable endoderm from hESCs by constitutive expression of Sox transcription factors, while Brickman and associates (Morrison et al., 2008) used a reporter gene strategy to isolate replicating anterior definitive endoderm from mESCs.


Short-term variations in urinary estriol and renal function. Possible effects of extraneous conditions.
Variation in urinary excretion of estriol was found to be related to physical activity and climate conditions. Estriol content of sweat was studied but was found not to be of an order to explain the variation observed. Estriol clearance rate was significantly reduced even by moderate physical activity. Creatinine clearance was not affected to the same extent. Different explanations to the findings are discussed. The need for strictly standardized conditions during urine sampling for estriol assays in risk pregnancies is stressed.


Resolution of a giant atrial thrombus following anticoagulation therapy.
We report on a patient in whom a giant thrombus in the left atrium was detected by transthoracic echocardiography. Anticoagulant theraphy was started. After two months of therapy, repeat echocardiography showed complete resolution of the thrombus. This case indicates that large and presumably organised thrombi may be treated with anticoagulant therapy.


Expression of Ia molecules by astrocytes during acute experimental allergic encephalomyelitis in the Lewis rat.
One question in the pathogenesis of experimental allergic encephalomyelitis (EAE) is whether antigen-presenting cells exist in the central nervous system which help induce the development of the disease. Since EAE is a delayed-type hypersensitivity condition, and since T cells require major histocompatibility complex (MHC)-restricted antigen presentation, it is presumed that if antigen presentation occurs in CNS tissue, the presenting cell should express surface Ia molecules. Using immunofluorescent double labeling, the possibility that astrocytes express surface Ia during EAE evolution in the Lewis rat was examined. Very rare Ia-positive astrocytes were found (less than 0.1% of the astrocytes), but only in the spinal cords of clinically ill animals. In addition, endothelial cell Ia positivity was noted prior to the onset of clinical disease. The immunological significance of such low numbers of astrocytes expressing Ia during EAE is uncertain.


A controlled release bupivacaine-alginate construct: Effect on chondrocyte hypertrophy conversion.
Osteoarthritis is a degenerative disease of the joint, affecting over 30 million people in the US1. A key characteristic of OA is chondrocyte hypertrophy, characterized by chondrocyte changes to a more rounded and osteoblastic phenotype, characterized by increased IL-6 and IL-8 secretion2. While there are no cures for OA, treatments focus on mitigating pain and inflammation, the two main symptoms of OA. However, the analgesics, NSAIDS and corticosteroids commonly used, do not target regeneration and have negative side effects. Local anesthetics (LA) can be used as a pain management alternative but are usually short lasting and therefore, not suited for chronic conditions such as OA. Our engineered sustained release local anesthetic construct successfully delivers bupivacaine for an extended period of time3-5. This study is designed to evaluate the effect of the LA system on chondrocytes in an inflammatory OA-like environment. Chondrocytes were cultured with bolus, liposomal, or construct LA and either untreated or treated with TNF-α and IL-1α for 24 hrs, 48 hrs, or 96 hrs. Chondrocyte viability, interleukin-8 (IL-8), interleukin-6 (IL-6), collagenase activity and proteoglycan deposition were assessed. In the presence of the engineered construct, the chondrocytes retained viability and regenerative function. Moreover, the construct allowed for higher initial doses to be used, which promoted more regeneration and decreased inflammation without compromising cellular viability. The construct promotes a less hypertrophic chondrocyte environment while promoting a more anti-inflammatory environment. These two factors are consistent with a less OA progressive environment when using the engineered construct, compared to bolus LA.


In vivo gap analysis in various knee flexion angles during navigation-assisted total knee arthroplasty.
Achieving rectangular flexion and extension gaps is important during gap balancing technique in total knee arthroplasty (TKA). However, assessment of gaps throughout the range of knee motion is obscure. One hundred knees operated by TKA using a navigation-assisted gap balancing technique were evaluated. Intraoperatively, after achieving rectangular flexion and extension gaps, mediolateral gaps in each flexion angle (0°, 45°, 90°, 120°) were recorded. Patients were divided into 4 groups; Group I: no gap difference (n = 64), Group II: lax in midflexion (n = 20), Group III: lax in deep flexion (n = 8) and Group IV: lax in both midflexion and deep flexion (n = 8). This study demonstrated that significant proportion (36%) of TKA cases had laxity in midflexion (45°) even when rectangular extension (0°)-flexion (90°) gap was achieved.


Alcohol problems in several midwestern homosexual communities.
According to their scores on the Michigan Alcoholism Screening Test, close to one-third of the homosexual men surveyed in four urban areas of Kansas were alcoholics.


Complete Genome Sequence of Bacillus kochii Oregon-R-modENCODE Strain BDGP4, Isolated from Drosophila melanogaster Gut.
Bacillus kochii Oregon-R-modENCODE strain BDGP4 was isolated from the gut of Drosophila melanogaster for functional host microbial interaction studies. The complete genome comprised a single chromosomal circle of 4,557,232 bp with a G+C content of 37% and a single plasmid of 137,143 bp.


Laminin γ2 knockout mice rescued with the human protein exhibit enamel maturation defects.
The epithelial ameloblasts are separated from the maturing enamel by an atypical basement membrane (BM) that is enriched in laminin 332 (LM-332). This heterotrimeric protein (α3, ß3 and γ2 chains) provides structural integrity to BMs and influences various epithelial cell processes including cell adhesion and differentiation. Mouse models that lack expression of individual LM-332 chains die shortly after birth. The lethal phenotype of laminin γ2 knockout mice can be rescued by human laminin γ2 (LAMC2) expressed using a doxycycline-inducible (Tet-on) cytokeratin 14 promoter-rtTA. These otherwise normal-looking rescued mice exhibit white spot lesions on incisors. We therefore investigated the effect of rescue with human LAMC2 on enamel maturation and structuring of the atypical BM. The maturation stage enamel organ in transgenic mice was severely altered as compared to wild type controls, a structured BM was no longer discernible, dystrophic matrix appeared in the maturing enamel layer, and there was residual enamel matrix late into the maturation stage. Microtomographic scans revealed excessive wear of occlusal surfaces on molars, chipping of enamel on incisor tips, and hypomineralization of the enamel layer. No structural alterations were observed at other epithelial sites, such as skin, palate and tongue. These results indicate that while this humanized mouse model is capable of rescue in various epithelial tissues, it is unable to sustain structuring of a proper BM at the interface between ameloblasts and maturing enamel. This failure may be related to the atypical composition of the BM in the maturation stage and reaffirms that the atypical BM is essential for enamel maturation.


[Uterine artery score in patients with systemic lupus erythematous as a predictor of intrauterine growth restriction].
Because of its high prevalence in the female population and its high incidence in reproductive age, Systemic Lupus Erythematosus can complicate pregnancy causing miscarriage, fetal death, preeclampsia, fetal growth restriction (up to 25%) and preterm birth. Doppler ultrasonography measures the flow in the uterine arteries, which is reduced in patients with preeclampsia and FGR, and thus is an ideal method for identifying pregnant women with a high risk of developing an adverse perinatal outcome. Identify if Doppler ultrasound predicts FGR in patients with systemic lupus erythematosus. In this observational, transversal, prospective study carried out from June 1st, 2010 to November 30th, 2010, in patients who had already been diagnosed with SLE, a complete clinical history was registered, blood samples taken and Doppler of uterine arteries between 18 and 23 gestation weeks taken (measuring the pulsatility index) Of the 17 women in the study, 6 patients had a PI equal or greater than 1.45 (35.29%), of whom in 5 cases (29.41%), the product had FGR. Therefore the sensitivity of this test is 100%, with a specificity of 91%, a predictive positive value of 83% and a predictive negative value of 100%. With a p of 0.0010, which is considered extremely significant, and a confidence interval of 95%. There exists a high association between an abnormal PI and the development of FGR. Abnormal Doppler ultrasound of uterine arteries is useful for predicting FGR in pregnant women with SLE.