The impact of changes in national prescribing conditions for statins on their public expenditure and utilization in the Czech Republic 1997-2013.
In the Czech Republic (CZ) extensive price regulation and prescribing conditions are common instruments often employed with new drugs. Since the introduction of statins onto the market in 1990s the originally strict conditions gradually relaxed while the prescription rates and public costs were rising. The aim was to analyze long-term utilization trends of statins, changes in their reimbursement prices and prescribing conditions, and the evolution of the market. From January 1997 to December 2013 statin use was measured in terms of defined daily doses per 1000 insured per day (DDD/TID). The prescription-based database of the General Health Insurance Company of the Czech Republic in 1997 covering 7825,216 inhabitants, i.e. 76% of CZ population, was used as the administrative data source. Also the overall expenditure, unit prices, and reimbursement criteria were analyzed. Between 1997 and 2013 the utilization of statins rose from 2 to 96 DDD/TID while the expenditure rose 5.5-fold. The rise of prescription for each molecule was always observed after the liberation of the prescribing criteria. In the study period reimbursement prices of simvastatin and atorvastatin gradually decreased to just 5% of their initial values. The rising consumption of statins in CZ clearly corresponds in time with the liberation of prescribing conditions allowing for prescription by general practitioners and with the introduction of generics accompanied by a swift and repeated reimbursement price cuts.


Characterization of gtf, a glucosyltransferase gene in the genomes of Pediococcus parvulus and Oenococcus oeni, two bacterial species commonly found in wine.
"Ropiness" is a bacterial alteration in wines, beers, and ciders, caused by beta-glucan-synthesizing pediococci. A single glucosyltransferase, Gtf, controls ropy polysaccharide synthesis. In this study, we show that the corresponding gtf gene is also present on the chromosomes of several strains of Oenococcus oeni isolated from nonropy wines. gtf is surrounded by mobile elements that may be implicated in its integration into the chromosome of O. oeni. gtf is expressed in all the gtf(+) strains, and beta-glucan is detected in the majority of these strains. Part of this beta-glucan accumulates around the cells forming a capsule, while the other part is liberated into the medium together with heteropolysaccharides. Most of the time, this polymer excretion does not lead to ropiness in a model medium. In addition, we show that wild or recombinant bacterial strains harboring a functional gtf gene (gtf(+)) are more resistant to several stresses occurring in wine (alcohol, pH, and SO(2)) and exhibit increased adhesion capacities compared to their gtf mutant variants.


Counting, accounting, and accountability: Helen Verran's relational empiricism.
Helen Verran uses the term 'relational empiricism' to describe situated empirical inquiry that is attentive to the relations that constitute its objects of study, including the investigator's own practices. Relational empiricism draws on and reconfigures Science and Technology Studies' traditional concerns with reflexivity and relationality, casting empirical inquiry as an important and non-innocent world-making practice. Through a reading of Verran's postcolonial projects in Nigeria and Australia, this article develops a concept of empirical and political 'accountability' to complement her relational empiricism. In Science and an African Logic, Verran provides accounts of the relations that materialize her empirical objects. These accounts work to decompose her original objects, generating new objects that are more promising for the specific postcolonial contexts of her work. The process of decomposition is part of remaining accountable for her research methods and accountable to the worlds she is working in and writing about. This is a practice of narrating relations and learning to tell better technoscientific stories. What counts as better, however, is not given, but is always contextual and at stake. In this way, Verran acts not as participant-observer, but as participant-storyteller, telling stories to facilitate epistemic flourishing within and as part of a historically located community of practice. The understanding of accountability that emerges from this discussion is designed as a contribution, both practical and evocative, to the theoretical toolkit of Science and Technology Studies scholars who are interested in thinking concretely about how we can be more accountable to the worlds we study.


[Analysis of international application of complementary and alternative medicine].
Traditional Chinese medicine (TCM) is an important part of complementary and alternative medicine (CAM) in the world medical market. The basis of globalization of TCM was to make sure the current situation of CAM and the role that TCM plays. It will improve the application and reputation of TCM by analyzing the global usage rate, sort of diseases, social-demographic characteristics of users and medical economics of CAM.


Propionibacterium acnes pneumonia in a patient with lymphoma.
A 57 year-old male with lymphocytic lymphoma developed symptoms of cough, fever and progressive dyspnea accompanied by a diffuse lower lung infiltrate. Open lung biopsy revealed multiple micro-abscesses surrounding small bronchioles which yielded a pure growth of Propionibacterium acnes.


The association between anti-Müllerian hormone and vitamin 25(OH)D serum levels and polycystic ovarian syndrome in adolescent females.
High anti-Müllerian hormone (AMH) levels and 25-hydroxyvitamin D [25(OH)D] deficiency have been associated with polycystic ovarian syndrome (PCOS) in adult women, and implicated in its pathogenesis. Herein we determined if the level of both AMH and 25(OH)D are altered in adolescent females with clinical features of PCOS. This is a cross-sectional study utilizing a retrospective chart review of 128 patients aged 12-20 referred to an academic adolescent gynecology and endocrinology clinic for an evaluation of suspected PCOS. Unadjusted comparisons of AMH and 25(OH)D distributions between subjects with and without PCOS were performed using the Wilcoxon Rank Sum test. Quantile regression was used to compare the median AMH and 25(OH)D between subject groups; adjusting for race, ethnicity, BMI, insurance type, age, and season when bloodwork was performed. Seventy-four subjects were classified as having PCOS by meeting ≥2 of the three Rotterdam diagnostic criteria, and 47 subjects met only one Rotterdam diagnostic criteria, and were used as the comparative non-PCOS group. There were statistically significant unadjusted differences in median levels of AMH and 25(OH)D. In the adjusted analyses, median AMH was significantly higher in the PCOS group compared to the non-PCOS group (+ 2.39 ng/mL, 95% CI 0.43, 4.35, p = 0.018); 25(OH)D was significantly lower in the PCOS group (- 9.01 ng/mL, 95% CI -14.49, - 3.53 p = 0.001). In our sample, adolescents in both groups had insufficient 25(OH)D level (22 ng/mL) and elevated BMI (32.2 kg/m2). Adolescents with PCOS display high levels of AMH and low 25(OH)D levels. Since traditional clinical markers of PCOS may be physiologic in adolescents, AMH and 25(OH)D may be used as surrogate markers of PCOS risk in adolescents.


Determination of insulin and insulin-like growth factors in the ovarian circulation.
Recent in vitro studies implicate the ovary as an extra-hepatic source of insulin-like growth factors (IGFs) with production regulated by gonadotropins and local steroids. Because previous studies have failed to show any significant variations in IGF levels in peripheral blood during the menstrual cycle, we measured the concentrations of IGF-I, IGF-II, and insulin in ovarian and peripheral venous blood samples obtained simultaneously from nine women undergoing abdominal hysterectomy to obtain more detailed data on the ovarian contribution. A significant decreased ovarian gradient was found for IGF-II but not for IGF-I or insulin. Although there was no significant ovarian vein insulin gradient, insulin levels were higher in follicular than in luteal phase ovarian samples. These data suggest that IGF-II may be locally regulated by the ovary. Both insulin and IGFs may regulate ovarian function in vivo.


Peritransplantation Use of Ruxolitinib in Myelofibrosis.
Ruxolitinib is an oral JAK1/2 inhibitor that is approved for use in patients with intermediate and high-risk myelofibrosis (MF) based on its proven spleen and symptom burden reduction. Its impact on hematopoietic stem cell transplantation (HSCT) outcomes is largely unknown, however. A significant number of patients proceeding to HSCT have been treated with ruxolitinib, and the specifics of its peritransplantation use vary widely in the published literature. Here we review the currently published data and experience to guide management of patients with MF on ruxolitinib proceeding to HSCT.


Mind the gap: race/ethnic and socioeconomic disparities in obesity.
Race/ethnic and socioeconomic status (SES) disparities in obesity are substantial and may widen in the future. We review nine potential mechanisms that recent research has used to explain obesity disparities. Those nine mechanisms fall into three broad groups-health behaviors, biological factors, and the social environment-which incorporate both proximate and upstream determinants of obesity disparities. Efforts to reduce the prevalence of obesity in the US population and to close race/ethnic and SES disparities in obesity will likely require the use of multifaceted interventions that target multiple mechanisms simultaneously. Unfortunately, relatively few of the mechanisms reviewed herein have been tested in an intervention framework.


Human cell variants resistant to rhodamine 6G.
Two variants have been isolated from the cultured human cell line VA2-B which are resistant in vivo to the mitochondrial-specific fluorescent dyes rhodamine 6G and rhodamine 123. Both mutants are cross-resistant to ethidium bromide but are sensitive to both colchicine and chloramphenicol. When either mutant is treated with low levels of rhodamine 6G, mitochondrial-associated fluorescence is significantly lower than in wild-type cells. Furthermore, when cell cultures are treated with high concentrations of either rhodamine 123 or 6G, and then washed free of the dye, mitochondrial-associated rhodamine fluorescence rapidly diminishes in the parental cell line. In hybrid cell fusions between resistant and sensitive cell lines, rhodamine resistance is gradually expressed, reaching maximal expression approximately 11 days after fusion. Cytoplasmic transmission of rhodamine resistance has not been clearly demonstrated in cytoplast-cell fusions, and thus resistance is probably due to a mutation of a nuclear, rather than mitochondrial DNA gene(s). These observations indicate that mitochondria of both rhodamine-resistant variants, unlike wild type, have a significantly decreased ability to bind and retain rhodamine, and thus their mitochondrial tramsmembrane electrical potential may be significantly reduced.


[Transient pseudohypoaldosteronism secondary to congenital malformation pathology of the urinary tract (valves of the posterior urethra): a report of a case with elements of a physiopathological nature].
A case of secondary transient pseudohypoaldosteronism (PHA) in a three-month-old infant who had arrived in emergency conditions is reported. Clinically the patient presented dehydration associated with salt loss, metabolic acidosis, severe hyperkalemia, markedly elevated levels both of plasma renin activity and aldosterone concentration. Biochemical and instrumental tests and clinical evolution have given reason to consider it as a case of transient PHA, secondary to an obstructive uropathy (PUV) with urinary infection. Secondary forms of PHA have frequently been documented in young infants with urinary tract infection associated with both obstructive and non obstructive uropathy. After medical or surgical therapy the abnormalities quickly disappear. This reported case suggests that the pediatrician-neonatologist dealing with a young infant with obstructive uropathy should not only consider the surgical treatment but also the medical one, in the light of the associated physiopathological aspects.


Mechanisms of Death in Low-Risk Patients After Transcatheter or Surgical Aortic Valve Replacement.
Death in high- and intermediate-risk patients after self-expanding transcatheter (TAVR) and surgical aortic valve replacement (surgery) differed in mechanisms and timing. In both risk groups, 1-year all-cause mortality was lower in TAVR than in surgery patients. The differences in mechanism and timing of death in low-risk patients has not been studied. This report explores the mechanisms of death during 3 time periods; 0 to 30 days (early), 31 to 120 days (recovery), and 121 to 365 days (late). We retrospectively examined the mechanisms and timing of death following TAVR or surgery in the randomized Evolut Low Risk Trial. Patients were enrolled between March 2016 and November 2018 from 86 designated TAVR centers. Mechanisms of death were categorized as due to technical reasons, failure to repair, complications linked to death, failure to recover or other. All-cause mortality at 1 year was 2.2% for TAVR and 2.8% for surgery, p = 0.44. Early deaths included 3 TAVR patients, all due to technical reasons, and 8 surgery patients (1 technical, 5 complications and 2 failed to recover). Recovery period deaths included 6 TAVR patients (4 complications, 1 failed to recover and 1 other), and 1 surgery patient from complications of valve endocarditis. Late period deaths included 6 TAVR patients and 9 surgery patients, primarily due to complications. In this low-risk study cohort, no patient died from failure to repair the valve; reduction in procedural complications in the TAVR and surgery groups remain opportunities for further improvement in outcomes. Clinical Trial Registrations (clinicaltrials.gov): NCT02701283 (Evolut Low Risk).


Atropine prevents the reflex tracheal relaxation arising from the stimulation of intestinal and skeletal muscle afferents in dogs.
Using cholinergic and beta-adrenergic antagonists, we characterized the efferent arms of two reflex arcs that relax tracheal smooth muscle in dogs. The reflex arcs investigated were activated by the capsaicin-induced stimulation of afferent endings in the intestine and in the hindlimb. We found that the reflex tracheal relaxations were due to a withdrawal of a tonic cholinergic input. Beta-adrenergic pathways played little role in causing these reflex responses.


Exploring the Potential Therapeutic Approach Using Ginsenosides for the Management of Neurodegenerative Disorders.
There is a need for an efficient and long-lasting treatment due to the population's increasing prevalence of neurodegenerative disorders. In an effort to generate fresh ideas and create novel therapeutic medications, scientists have recently started to investigate the biological functions of compounds derived from plants and herbs. Ginseng, famous Chinese herbal medicine, has therapeutic value by virtue of its compounds ginsenosides or panaxosides, which are triterpene saponins and steroid glycosides. Research revealed positive impacts on ameliorating various disease conditions and found it as a possible drug candidate. Several neuroprotection mechanisms followed by this compound are inhibition of cell apoptosis, oxidative stress, inflammatory, and tumor activity. It has been demonstrated that controlling these mechanisms enhances cognitive performance and safeguards the brain against neurodegenerative disorders. The main objective of this review is to give a description of the most recent studies on ginsenoside's possible therapeutic application in the treatment of neurodegenerative diseases. Using organic compounds like ginseng and its various components may create new avenues for innovative treatment approaches development for neurological diseases. However, further research is necessary to confirm the stability and effectiveness of ginsenosides for neurodegenerative disease.


Effects of prenatal vitamins A, E, and C on the hypoplastic hearts of fetal rats with diaphragmatic hernia.
Nitrofen induces heart hypoplasia together with congenital diaphragmatic hernia (CDH) in rats. Intracellular oxidative stress might be one of the mechanisms of action of the teratogen, and vitamin A has been shown to reverse in part these effects when administered simultaneously or shortly after it. This study aims at testing the hypothesis that vitamin A and other antioxidant vitamins, such as E and C, could improve myocardial development even when administered late in gestation, a likely useful period for prenatal medication. Time-mated Sprague-Dawley female rats were exposed to either vehicle (control) or 100 mg of nitrofen (experimental) on day 9.5 of gestation. In 3 additional groups, the animals were exposed to vitamin A (total 15000 IU), vitamin E (total 150 IU), or vitamin C (total 150 IU) on days 16, 17, and 18. The fetuses were recovered on day 21, and randomly selected hearts of those with CDH were processed for histologic studies (hematoxylin-eosin and periodic acid-Schiff stainings), DNA and protein contents, and ki-67 (proliferation) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling (apoptosis) studies. The differences among groups were assessed by analysis of variance with Bonferroni/Dunn post hoc tests and a threshold of significance of P < .05. Nitrofen induced heart hypoplasia in terms of decreased heart/body weight, cell mass (less DNA and protein), and proportion of proliferating cells with increased apoptosis. Vitamin C alleviated weight hypoplasia and the 3 vitamins were able to restore cell mass and to reestablish near-normal figures of proliferation and apoptosis. Antioxidant vitamins A, E, and C given late in gestation alleviate heart hypoplasia that accompanies CDH in the rat model. This timing suggests that the beneficial effects are exerted on the maturational phase of development.


Different cellular responses evoked by natural and stoichiometric synthetic chrysotile asbestos.
The carcinogenic potency of asbestos, including chrysotile, is well established. Several physico-chemical features of the fibers appear implied, such as fibrous habit, size, crystallinity, morphology, and surface active metal ions, where free radical generation may take place. In contrast to other asbestos forms, iron is not a stoichiometric component of chrysotile, but is only present together with other extraneous ions as a magnesium- and silicon-replacing contaminant. To determine the role played by contaminating ions and morphological features of the fibers, a stoichiometric chrysotile with constant structure and morphology was synthesized in hydrothermal conditions. Free radical generation and the effects of these fibers on human lung epithelial A549 cells have been compared to that elicited by a well known toxic natural chrysotile (UICC A, from Rhodesia). After a 24-h incubation, the natural, but not the synthetic, form exerted a cytotoxic effect, detected as leakage of lactate dehydrogenase. Homolytic rupture of a C-H bond and lipoperoxidation in A549 cells took place in the presence of the natural, but not of the synthetic, chrysotile. Antioxidant systems were also affected differently. The pentose phosphate pathway and its regulatory enzyme glucose 6-phosphate dehydrogenase were markedly inhibited only by the natural specimen, which also caused a depletion of intracellular reduced glutathione in A549 cells. These results suggest that metal ions, fiber size and state of the surface play a crucial role in the oxidative stress caused by chrysotile asbestos. Stoichiometric synthetic fibers may thus be proposed as a reference standard (negative control) for toxicological studies.


Leiomyoma of the hand.
Leiomyoma is most commonly found in the uterus and lower extremities of middle-aged women. Leiomyoma is uncommonly reported in the hand and is extremely uncommon in children. We present three cases of leiomyoma of the hand, including one case in the hand of a 10-year-old boy.


NRF-1 and HIF-1α contribute to modulation of human VDAC1 gene promoter during starvation and hypoxia in HeLa cells.
VDAC (Voltage Dependent Anion Channel) is a family of pore forming protein located in the outer mitochondrial membrane. Its channel property ensures metabolites exchange between mitochondria and the rest of the cell resulting in metabolism and bioenergetics regulation, and in cell death and life switch. VDAC1 is the best characterized and most abundant isoform, and is involved in many pathologies, as cancer or neurodegenerative diseases. However, little information is available about its gene expression regulation in normal and/or pathological conditions. In this work, we explored VDAC1 gene expression regulation in normal conditions and in the contest of some metabolic and energetic mitochondrial dysfunction and cell stress as example. The core of the putative promoter region was characterized in terms of transcription factors responsive elements both by bioinformatic studies and promoter activity experiments. In particular, we found an abundant presence of NRF-1 sites, together with other transcription factors binding sites involved in cell growth, proliferation, development, and we studied their prevalence in gene activity. Furthermore, upon depletion of nutrients or controlled hypoxia, as detected in various pathologies, we found that VDAC1 transcripts levels were significantly increased in a time related manner. VDAC1 promoter activity was also validated by gene reporter assays. According to PCR real-time experiments, it was confirmed that VDAC1 promoter activity is further stimulated when cells are exposed to stress. A bioinformatic survey suggested HIF-1α, besides NRF-1, as a most active TFBS. Their validation was obtained by TFBS mutagenesis and TF overexpression experiments. In conclusion, we experimentally demonstrated the involvement of both NRF-1 and HIF-1α in the regulation of VDAC1 promoter activation at basal level and in some peculiar cell stress conditions.


Structure and proposed DNA delivery mechanism of a marine roseophage.
Tailed bacteriophages (order, Caudovirales) account for the majority of all phages. However, the long flexible tail of siphophages hinders comprehensive investigation of the mechanism of viral gene delivery. Here, we report the atomic capsid and in-situ structures of the tail machine of the marine siphophage, vB_DshS-R4C (R4C), which infects Roseobacter. The R4C virion, comprising 12 distinct structural protein components, has a unique five-fold vertex of the icosahedral capsid that allows genome delivery. The specific position and interaction pattern of the tail tube proteins determine the atypical long rigid tail of R4C, and further provide negative charge distribution within the tail tube. A ratchet mechanism assists in DNA transmission, which is initiated by an absorption device that structurally resembles the phage-like particle, RcGTA. Overall, these results provide in-depth knowledge into the intact structure and underlining DNA delivery mechanism for the ecologically important siphophages.


Prevention of leakage of Di-(2-ethylhexyl)phthalate from blood bags by glow discharge treatment and its effect on aggregability of stored platelets.
Platelets storage in glow discharge treated PVC bags was studied. The amount of leaked di-(2-ethylhexyl) phthalate (DEHP) was 150-200 micrograms/ml/day in the nontreated PVC bags, but only 20-40 micrograms/ml in the treated bags after 48 h. The adhesion of silicone to PVC was much improved, and consequently, uniform coating with silicone became feasible. The decrease of the ability of platelets to aggregate was accelerated by DEHP. When stored platelets were resuspended in fresh plasma, the ability to aggregate was gradually restored. However, the degree of restoration of the ability of platelets which had been incubated with DEHP was low. When platelets were stored in the glow discharge treated and then silicone-coated PVC bags, their adhesion on the surface and the decrease of their function were prevented.


Closing the Mitochondrial Permeability Transition Pore in hiPSC-Derived Endothelial Cells Induces Glycocalyx Formation and Functional Maturation.
Human induced pluripotent stem cells (hiPSCs) are used to study organogenesis and model disease as well as being developed for regenerative medicine. Endothelial cells are among the many cell types differentiated from hiPSCs, but their maturation and stabilization fall short of that in adult endothelium. We examined whether shear stress alone or in combination with pericyte co-culture would induce flow alignment and maturation of hiPSC-derived endothelial cells (hiPSC-ECs) but found no effects comparable with those in primary microvascular ECs. In addition, hiPSC-ECs lacked a luminal glycocalyx, critical for vasculature homeostasis, shear stress sensing, and signaling. We noted, however, that hiPSC-ECs have dysfunctional mitochondrial permeability transition pores, resulting in reduced mitochondrial function and increased reactive oxygen species. Closure of these pores by cyclosporine A improved EC mitochondrial function but also restored the glycocalyx such that alignment to flow took place. These results indicated that mitochondrial maturation is required for proper hiPSC-EC functionality.


Clinical utility of cerebrospinal fluid biomarkers measured by LUMIPULSE® system.
Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) are well-established in research settings, but their use in routine clinical practice remains a largely unexploited potential. Here, we examined the relationship between CSF biomarkers, measured by a fully automated immunoassay platform, and brain β-amyloid (Aβ) deposition status confirmed by amyloid positron emission tomography (PET). One hundred ninety-nine CSF samples from clinically diagnosed AD patients enrolled in a clinical study and who underwent amyloid PET were used for the measurement of CSF biomarkers Aβ 1-40 (Aβ40), Aβ 1-42 (Aβ42), total tau (t-Tau), and phosphorylated tau-181 (p-Tau181) using the LUMIPULSE system. These biomarkers and their combinations were compared to amyloid PET classification (negative or positive) using visual read assessments. Several combinations were also analyzed with a multivariable logistic regression model. Aβ42, t-Tau, and p-Tau181, and the ratios of Aβ42 with other biomarkers had a good diagnostic agreement with amyloid PET imaging. The multivariable logistic regression analysis showed that amyloid PET status was associated with Aβ40 and Aβ42, but other factors, such as MMSE, sex, t-Tau, and p-Tau181, did not significantly add information to the model. CSF biomarkers measured with the LUMIPULSE system showed good agreement with amyloid PET imaging. The ratio of Aβ42 with the other analyzed biomarkers showed a higher correlation with amyloid PET than Aβ42 alone, suggesting that the combinations of biomarkers could be useful in the diagnostic assessment in clinical research and potentially in routine clinical practice.


A new dimension in vesicovaginal fistula management: an 8-year experience at Ramathibodi hospital.
Vesicovaginal fistula is mostly iatrogenic in origin and causes devastating medical, social, psychogenic and hygienic consequences. The aetiology has changed since the nineteenth century, becoming more associated with hysterectomy rather than other obstetric procedures, which were common in the past. We studied the causes, clinical presentations and management of vesicovaginal fistula in our institute during 1998 to 2005. From 1998 to 2005, 45 patients were treated in our hospital, of whom 35 were referred from other hospitals after failed surgery. All the medical records were reviewed. Fistulae, clinical presentation, clinical findings, means of treatment and clinical outcome as well as complications were noted. The most common cause of a fistula in our study was post laparoscopic hysterectomy that comprised 28 cases (62.2%). Transabdominal hysterectomy caused fistula in 10 cases (22.2%) and vaginal hysterectomy only four cases (8.8%). Most cases of vesicovaginal fistulae after laparoscopic hysterectomy presented with early urinary leakage, of which 35.7% presented within 1 week and 50% in the second week. Most of the patients after transabdominal hysterectomies (90%) had leakage in the second week. All patients were treated with surgical repair, 19 cases by a transvaginal approach and 26 cases by a transabdominal repair. Seventeen cases in the transvaginal group and 25 cases in the transabdominal group were dry after the first operation. The rest of both groups were dry after the second operation. After 38 months of follow-up, no complication or incontinence was noted. Vesicovaginal fistula is still a serious iatrogenic consequence and causes suffering in the physical, emotional and social functioning of patients. The study found that the condition is now more frequently associated with laparoscopic hysterectomy. Successful closure of the fistula requires an accurate and timely repair using procedures that exploit basic surgical principles. With the appropriate surgical expertise, all patients can be cured of this distressing condition.


Incidence and risk factors for osteonecrosis of the hip in renal transplant patients: a prospective single-centre study.
There is a lack of evidence about the risk factors associated with osteonecrosis of the femoral head (ONFH). To determine the incidence and risk factors for ONFH following renal transplantation (RT). In total, data of 681 RT patients (mean age at surgery, 49.5 ± 13.6 years; 249 women and 432 men) were evaluated to determine the incidence of ONFH. Hip magnetic resonance imaging (MRI) was performed six months after RT. The following potential predictors of ONFH were evaluated: (1) patient's condition at RT; laboratory test results including calcium (Ca), phosphorus (P), calcium-phosphorus product (Ca × P), and intact parathyroid hormone before RT; blood relationship between the patient and donor; and mismatching number of human leukocyte antigens (HLAs), especially HLA class I and class II and (2) dosages of steroids after RT, immunosuppressive regimen, and incidence of acute rejection. ONFH was observed in 30 hips (21 cases, 3.1%). We successfully matched 63 patients without ONFH. Multivariate logistic regression analysis, adjusted for cumulative dosages of steroids, revealed that mismatching number of HLA (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.10-2.36; p = 0.014), HLA class II (HR, 3.73; 95% CI, 1.46-9.56; p = 0.001), P before RT (HR, 1.62; 95% CI, 1.02-2.58; p = 0.041), and Ca × P before RT (HR, 1.06; 95% CI, 1.01-1.11; p = 0.024) were risk factors for ONFH. A greater number of HLA mismatches, HLA class II, serum P, and serum Ca × P were risk factors for ONFH after RT. Therefore, these factors should be evaluated in order to predict ONFH after RT.


Does This Patient Have Parkinson Disease or Essential Tremor?
In the elderly patient with tremor, the differential diagnosis is usually between essential tremor (ET) and Parkinson disease (PD). A careful history and examination are the keys to the diagnosis. Essential tremor is a bilateral action tremor of the upper limbs whereas PD begins unilaterally and is a rest tremor. A handwriting sample can usually distinguish PD from ET as the former is small (micrographic) but atremulous whereas writing in ET is tremulous but normal sized. In ET, there are no signs aside from tremor but in PD, the tremor is accompanied by bradykinesia and rigidity.


Two-photon fluorescence and fluorescence imaging of two styryl heterocyclic dyes combined with DNA.
Two new styryl heterocyclic two-photon (TP) materials, 4-[4-(N-methyl)styrene]-imidazo [4,5-f][1,10] phenanthroline-benzene iodated salt (probe-1) and 4,4-[4-(N-methyl)styrene]-benzene iodated salt (probe-2) were successfully synthesized and studied as potential fluorescent probes of DNA detection. The linear and nonlinear photophysical properties of two compounds in different solvents were investigated. The absorption, one- and two-photon fluorescent spectra of the free dye and dye-DNA complex were also examined to evaluate their photophysical properties. The binding constants of dye-DNA were obtained according to Scatchard equation with good values. The results showed that two probes could be used as fluorescent DNA probes by two-photon excitation, and TP fluorescent properties of probe-1 are superior to that of probe-2. The fluorescent method date indicated that the mechanisms of dye-DNA complex interaction may be groove binding for probe-1 and electrostatic interaction for probe-2, respectively. The MTT assay experiments showed two probes are low toxicity. Moreover, the TP fluorescence imaging of DNA detection in living cells at 800 nm indicated that the ability to locate in cell nuclei of probe-1 is better than that of probe-2.


Dual substrate limitation modeling and implications for mainstream deammonification.
Substrate limitation occurs frequently in wastewater treatment and knowledge about microbial behavior at limiting conditions is essential for the use of biokinetic models in system design and optimization. Monod kinetics are well-accepted for modeling growth rates when a single substrate is limiting, but several models exist for treating two or more limiting substrates simultaneously. In this study three dual limitation models (multiplicative, minimum, and Bertolazzi) were compared based on experiments using nitrite-oxidizing bacteria (limited by dissolved oxygen and nitrite) and ANaerobic AMMonia-OXidizing bacteria or Aanammox (limited by ammonium and nitrite) within mixed liquor from deammonification pilots. A deterministic likelihood-based parameter estimation followed by Bayesian inference was used to estimate model-specific parameters. The minimum model outperformed the other two by a slight margin in three separate analyses. 1) Parameters estimated using the minimum model were closest to parameters estimated from single limitation batch tests. 2) Among simulations based on each model's own estimated parameters, the minimum model best described the experimental observations. 3) Among simulations based on parameters estimated from single limitation, the minimum model best described the experimental observations. The dual substrate model selected among the three studied can effect a 75% process performance variation based on simulations of a full-scale mainstream deammonification system.


Cytochemical study of the lamellar bodies in the swimbladder of the toadfish Opsanus tau L.
The columnar epithelial cells of the gas gland in the swimbladder of the toadfish, Opsanus tau L., contain lamellar bodies that resemble the lamellar bodies found in epithelial cells of vertebrate lungs. Cytochemical assays indicate that swimbladder lamellar bodies are soluble in chloroform-methanol solution, react with tricomplex flocculation solution (indicating a phospholipid component), exhibit a positive reaction for cholesterol when exposed to digitonin, and contain acid phosphatase. The anterior chamber of the toadfish swimbladder is lined by an extracellular layer. Digitonin-cholesterol crystals are found in this layer when the swimbladder is treated with digitonin. A ruthenium red positive layer is also present in the anterior chamber of the toadfish swimbladder. The structure and cytochemistry of swimbladder lamellar bodies are compared with those of vertebrate lung lamellar bodies. Similarities between the extracellular layer in the swimbladder and the extracellular layer in lungs are also noted.


Crystallization and preliminary X-ray analysis of leukemia inhibitory factor.
Leukemia inhibitory factor (LIF) is a polyfunctional molecule with significant and diverse biological activities. LIF is a glycoprotein secreted by a number of different cell types in vitro. It is induced in fibroblasts, lymphocytes, monocytes and astrocytes by various inducers such as serum, TNF, interleukin-IP and EGF. Due to extensive and variable glycosylation the molecular weight can range from 38 to 67 kDA. The biological functions of LIF are mediated through a receptor and a signal transducer, gp130, which is also used by factors like interleukin-6 (IL-6), cilliary neurotropic factor (CNTF), and oncostatin M (OSM). Here, we report the crystallization of the non-glycosylated human-like LIF expressed in E. coli. The present crystals diffract to 2.0 A using synchrotron radiation. They belong to the monoclinic space group C2, and the cell dimensions are a = 61.5 A, b = 45.3 A, c = 77.7 A and beta = 112.3 degrees.


Author Correction: Cytotoxic unsaturated electrophilic compounds commonly target the ubiquitin proteasome system.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Magnetic resonance tomographic angiography in the investigation of hemifacial spasm.
Magnetic resonance angiography (MRA), combined with submillimeter magnetic resonance tomographic angiographic sections (MRTA) showed vascular compression of the 7th cranial nerve or its root exit zone (REZ) in the brain stem in 24 of 37 patients (64.86%) with hemifacial spasm. MRA alone was positive for REZ compression in only 19 (51.4%) cases, while conventional MRI was even less revealing, only 10 (27%) cases being positive.


Comparative effectiveness of school-based exercise interventions on physical fitness in children and adolescents: a systematic review and network meta-analysis.
Schools provide a favorable setting for health education, however, the most effective school-based exercise mode for improving physical fitness remains unclear. This network meta-analysis was designed to assess and rank the comparative efficacy of six exercise modalities on physical fitness indicators in a school-based setting. An online search of the Web of Science, PubMed, SPORTDiscus, and Scopus databases was conducted. Randomized and quasi-randomized controlled trials were considered. Outcomes included measures of anthropometry and body composition, muscular fitness, and cardiorespiratory fitness. Data were pooled with a random effects model using the frequentist framework. A total of 66 studies with 8,578 participants (48% girls) were included. High-intensity interval training was the most effective intervention reducing body mass index (mean difference (MD) = -0.60 kg·m-2, 95% confidence interval (95%CI) = -1.04 to -0.15, p = 0.009), elevating VO2max (MD = 3.59 mL·kg-1·min-1, 95% CI = 2.45 to 4.74, p < 0.001), and 20-meter sprint performance (MD = -0.35 s, 95% CI = -0.55 to -0.14, p = 0.001). Aerobic training had the highest probability of reducing waist circumference (standardized mean difference (SMD) = -0.60, 95% CI = -0.88 to -0.32, p < 0.001). Active video games emerged as a promising modality for improving countermovement jump (MD = 2.43 cm, 95% CI = 0.06 to 4.80, p = 0.041) and shuttle running performance (SMD = 0.86, 95% CI = 0.29 to 1.43, p = 0.003). Strength training was the best exercise mode for improving standing long jump performance (SMD = 1.03, 95% CI = 0.07 to 1.98, p = 0.035) while combined training was rated the first for decreasing body fat percent (MD = -2.56%, 95% CI = -4.73 to -0.40, p = 0.022) and increasing push-up repetitions (SMD = 3.59, 95% CI = 0.81 to 6.37, p = 0.012). School-based exercise interventions have multiple effects on physical fitness. The findings of this study will help to inform physical education teachers and coaches how best to deliver exercise programs in a school setting. Since the study was limited by the original research, the conclusions will require further verification using high-quality randomized controlled trials. PROSPERO, Identifier: CRD42023401963.


A Scandinavian tragedy.
This paper briefly reviews the logic surrounding the controversial banning of dental amalgam by the Norwegian government. The very small contribution from dentistry to environmental mercury pollution and the significant advantages of amalgam as a dental restorative are emphasised.


Effect of feed form and nutrient density on growth performance, blood parameters, and intestinal traits in broiler breeder pullets.
This study was conducted to evaluate the effect of feed form and nutrient density on growth performance, blood parameters, and intestinal traits of broiler breeder pullets during grower (7-19 wk) and pre-breeder (19 weeks to 5% production) periods. A total of 450 female broiler breeder pullets were used in a completely randomized design with a 3 × 2 factorial arrangement including 3 feed forms (mash, crumble, and pellet) and 2 nutrient densities (standard diet with the nutrient requirement of Ross 308 parent stock nutrition specification, and diluted diet by using sunflower hull to have 10% lower nutrient than the standard diet). Five replicates with 15 pullets per replicate were allocated to each of the 6 treatments. Blood samples were collected at 19 wk of age. Egg production reached 5% in the mid of 25 wk. Results showed that pullets fed crumble or pellet diets had greater body weight gain and a lower feed to gain ratio (F:G; P < 0.001). Diet dilution led to a decrease in body weight gain while increasing the F:G (P < 0.05). Pullets fed the pellet diets had shorter eating times than those fed crumble diets, whereas the longest eating time belonged to pullets fed mash diets (P < 0.001). Pullets fed pellet diet had a greater heterophil to lymphocyte (H/L) ratio than those fed crumble or mash diets (P = 0.007). Diluting the diet led to a decrease in the H/L ratio (P = 0.026). Neither feed form nor nutrient density had a significant effect on body weight uniformity, blood glucose and lipid concentrations, liver enzyme activities, and intestinal traits (P > 0.05). It can be concluded that pelleted or crumbled diets with lower nutrient density can be considered in broiler breeder's pullets feeding with no detrimental effect on their performance or health state.


Quantitative thin layer chromatographic multi-sulfonamide screening procedure: collaborative study.
A thin layer chromatographic procedure suitable for detection of multiple sulfonamides at 0.1 ppm was studied in an interlaboratory collaborative study. Sulfamethazine, sulfadimethoxine, and sulfaquinoxaline were variously analyzed in liver and muscle tissues from swine, turkey, and duck. The average recovery for all drugs across all tissues was 95%. The corresponding repeatability and reproducibility were 7.7% and 10.5%, respectively.


Characterization of key mechanisms in transmigration and invasion of mesenchymal stem cells.
For successful systemic stem cell therapy, mesenchymal stem cells (MSCs) must transmigrate across the endothelium and invade their target tissue. To date, most of the underlying mechanisms of transmigration and invasion remain to be elucidated. Improving our knowledge on these core processes might elevate the efficiency of stem cell therapy. Our aim was therefore to characterize key mechanisms involved in transmigration and invasion of MSCs. Co-cultivation experiments infer that MSCs integrate into the endothelial monolayer. However, the time course of adhesion, integration and transmigration depends on the endothelial phenotype and is most effective in venous vessels of the myocardium. Thus, a variable capacity for transmigration exists within the vasculature. Additionally, three-dimensional systems reveal that MSCs penetrate the endothelium and invade the surrounding tissue via plasmic podia. Furthermore, transmigration not only requires the interaction of vascular cell adhesion molecule-1 (VCAM-1) and very late antigen-4 (VLA-4) as verified by blocking experiments, but also triggers the clustering of beta1 integrins. In addition, in situ zymographies infer the activation of gelatinases at sites of MSC invasion into myocardial tissue. As evidenced by ELISA, MSCs secrete matrix metalloproteinase (MMP)-2 but not MMP-9. Finally, media containing additional cytokines accelerate the transmigration. Concluding, key players involved in transmigration and invasion of MSCs are the endothelial phenotype, VCAM-1/VLA-4, beta1 integrins, MMP-2 secretion and cytokines.


Radial artery pseudoaneurysm in a Maine Coon cat.
To report the diagnosis and treatment of a radial artery pseudoaneurysm in a cat. Clinical report. Maine Coon cat (8-year-old neutered male). Ultrasonographic and angiographic examination of a fluctuant, nonpainful, 3 cm × 1.5 cm subcutaneous swelling on the craniomedial distal aspect of the right radius that occurred 40 days after suspected cat bite trauma was consistent with a radial artery pseudoaneurysm. After ligation of the radial artery proximal to the lesion, the pseudoaneurysm was surgically excised. The excised tissue had hemorrhage and fibrin surrounded by a thick fibrous granulating capsule of variably mature fibroblasts and focal areas of inflammatory cells (lymphocytes, plasma cells, and macrophages) consistent with a pseudoaneurysm. Surgical excision resulted in resolution of clinical signs. Ultrasonography enabled prompt, noninvasive diagnosis of pseudoaneurysm. Angiography or computed tomography may be useful to aid diagnosis and assess the collateral blood supply to the manus before surgical treatment.


Study and isolation of human intestinal dendritic cell and macrophage subsets.
Dendritic cells and macrophages are the main antigen-presenting cells (APC). In the gut, they control the mechanisms of tolerance toward commensals and nutrients, at the time that they maintain their capacity to trigger immune responses against invading pathogens. Nevertheless, this balance is not perfect as it can get disrupted like in inflammatory bowel disease (where they drive an abnormal immune response against the microbiota) or in coeliac disease (where they trigger an immune response against dietary gluten). Therefore, the study of human intestinal APC subsets is crucial not just to get a deeper insight in the mechanisms of human intestinal homeostasis, but also to understand the pathogenesis of inflammatory bowel disease and coeliac disease. Nevertheless, their study is quite complicated as despite their relevance, their numbers are scare in the intestinal mucosa. Therefore, we hereby describe different approaches to study human intestinal dendritic cell and macrophage subsets in the human intestinal mucosa.


Within- and between-year variations of reproductive strategy and cost in a population of Siberian chipmunks.
Reproduction costs depend on the general life-history strategies employed by organisms for resource acquisition, the decision rules on resource allocation, and the resource availability. Although the predictability of resource availability is expected to influence the breeding strategy, the relationship between predictability and strategy has rarely been investigated at the population level. One reason is that, while the resource availability is commonly variable in space and time, their predictability is generally assumed constant. Here, we addressed the temporal variation of the breeding strategy and its associated survival cost in a hibernating population of Tamias sibiricus, in which food resources vary in their availability between years and in their predictability within years. Based on 11 years of mark-recapture data, we used multi-event modelling to investigate seasonal variations in reproduction costs of female chipmunks that breed twice a year (spring and summer). In summer, during which a large variety and quantity of resources is available (income breeding strategy), the proportion of breeding females was consistent across years and reproduction yielded no mortality cost. In contrast, in spring, the proportion of breeding females was positively correlated with the amount of resources available for hibernation (partial capital breeding strategy). Spring reproduction yielded no immediate cost, but induced a delayed mortality cost over the next winter if future unknown conditions were unfavorable. Our findings highlight complex temporal reproductive patterns in a short-lived species: not only does the modality of resource acquisition vary among seasons, but also the decision rule to breed and its associated cost.


Effect of different retraction and impression techniques on the marginal fit of crowns.
Periodontal conditions in restored teeth are strongly influenced by the marginal fit of the restoration which is closely related to the quality of the impression. However, the influence of the retraction and impression technique on the outcome of the impression has only sparsely been investigated. Thus, it was the objective of this study to compare the marginal fit in fixed restorations using two modes of gingival retraction and two different impression techniques in an animal model. To simulate clinical conditions, 6 teeth in each of 10 lower jaws of freshly slaughtered cows were prepared with subgingival finish lines. Two different retraction techniques were used to expose the finish line: retraction cords containing epinephrine (Surgident) and electro-surgery were applied contra-laterally at 3 teeth per quadrant. Two impressions per jaw were taken in a two-step putty-wash technique (TPW) and a one-step putty-wash technique (OPW), respectively. On the casts, measurement copings were fabricated and seated on the extracted original tooth. In each coping the marginal discrepancy was assessed at 8 reference marks. Since the data was normally distributed, results were subjected to parametric statistics (T-test; p=0.05). Overall marginal discrepancies ranged between 0 and 200 microm. There was a small but not significant difference between electro-surgery and the retraction cords whereas TPW produced significantly better results than OPW (p<0.05). Within the limits of the study it can be concluded that the use of gingival retraction cords as well as electro-surgery lead to acceptable results. The difference between TPW and OPW concerning the marginal discrepancies can be regarded as clinically insignificant.


Sinomenine attenuates septic-associated lung injury through the Nrf2-Keap1 and autophagy.
Our present study focused on assessing whether Sinomenine (SIN) could attenuate sepsis-induced acute lung injury (ALI). The mice were conditioned with SIN 1 h before intraperitoneal injection of lipopolysaccharide (LPS). Lung wet/dry (W/D) ratio, inflammatory level in bronchoalveolar lavage fluid (BALF), malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity and inflammatory cytokines production were detected. The expression of nuclear factor erythroid 2-like 2 (Nrf2) and autophagy-related proteins were detected by Western blot and immunohistochemical analyses. In addition, the RAW264.7 cells were treated with SIN 1 h before treatment with LPS. Inflammatory cytokines, iNOS and COX2 were detected. The expression of Nrf2 and autophagy-related proteins were explored by Western blot analysis. Experiments in vivo and in vitro discovered that LPS significantly increased the degree of injury, inflammatory cytokines production and oxidative stress. However, the increase was significantly inhibited by treatment of SIN. In addition, SIN was found to upregulate the expression of Nrf2 and autophagy-related proteins both in vivo and in vitro. Our data suggested that SIN could attenuate septic-associated ALI effectively, probably due to the inhibition of inflammation and oxidative stress through Nrf2 and autophagy pathways.


Up-regulation of Metabotropic glutamate receptor 3 (mGluR3) in rat fibrosis and cirrhosis model of persistent hypoxic condition.
Glutamate is the major excitatory neurotransmitter in the central nervous system, and evidence for peripheral glutamatergic fibers in mammals is still lacking. However, glutamate receptors have been identified in peripheral organs, including taste buds, myenteric plexus, and pancreatic islet cell. Protection against anoxic damage could also be explained by mechanisms mediated by postsynaptic mGluR2 or mGluR3, such as the inhibition of membrane excitability resulting from a reduction of cAMP formation by a G-protein-dependent modulation of ion channels. In addition, activation of mGluR3 present in glial cells may contribute to neuroprotection by enhancing the production of death. Thus, mGluR2/3 behaves potentially as a major defensive mechanism anoxia-tolerant species. There are a few reports for the regional pattern of hypoxic damage, which was inversely related to the expression of mGluR2/3. The aim of this study was to characterize the expression of mGluR3 in hypoxic liver in experimental model of rat liver. Proteomic analysis of protein extracts from CCl4-induced cirrhotic liver revealed the presence of the mGluR3. The presence of mGluR3 in the cirrhotic liver was confirmed by immunohistochemical analysis. There were a number of macrophages expressing mGluR3 mainly in the fibrous septa. After 2 weeks recovery, however, most of mGluR3 positive macrophages disappeared with collagen fibers. These results demonstrate that mGluR3 involved in the liver in response to persistent hypoxic status such as fibrotic/cirrhotic condition, and suggest that the expression of mGluR3 may be a key role functional metabolism and viability in the liver by interacting with the glutamate receptors in vivo.


Comparison of suppressive effects of a new anti-inflammatory compound, FR167653, on production of PGE2 and inflammatory cytokines, human monocytes, and alveolar macrophages in response to endotoxin.
FR167653 [1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8 (4-pyridyl) pyrazoro [5-1-c] [1,2,4] triazin-2-yl]-2-phenylethanedion sulfate monohydrate] was developed to inhibit proinflammatory cytokine production. However, the effects of FR167653 on prostanoid production are unclear. We investigated the effect of FR167653 on proinflammatory cytokine and prostaglandin (PG) production by lipopolysaccharide (LPS)-stimulated human peripheral blood monocytes and alveolar macrophages (AM) from the same individuals, and compared the effects in monocytes and AM. FR167653 inhibited interleukin-1beta and tumor necrosis factor alpha production. The effect on PGE2 production was assessed by four parameters. FR167653 inhibited PGE2 synthesis and LPS induction of cyclooxygenase activity. Western and Northern blot analyses revealed that LPS induction of cyclooxygenase-2 expression was attenuated by this compound. The suppression in monocytes was greater than that in AM. We concluded that the reduction of LPS-induced PGE2 synthesis by FR167653 was due to inhibition of cyclooxygenase-2 production. These results show that FR167653 may be therapeutically useful for inhibiting production of both inflammatory cytokines and PG production in inflammatory diseases.


Nationwide levels and distribution of endosulfan in air, soil, water, and sediment in South Korea.
We investigated the levels and distribution patterns of α- and β-endosulfan and endosulfan sulfate in air, soil, water, and sediment samples collected from the South Korean persistent organic pollutants (POPs) monitoring networks. In the air samples, the highest concentrations of the total (Σ3) endosulfan (50.3-611 pg/m3, mean: 274 pg/m3) were observed during summer. Spearman analysis revealed a good correlation between agricultural land area and atmospheric concentrations of Σ3 endosulfan except during winter. Regardless of the season, the ratio of the two isomers (α/β) was 3.6-4.9 in the air samples, higher than that observed in technical mixtures (2.0-2.3), possibly due to the higher volatility of α-endosulfan, compared to β-endosulfan. Concentrations of Σ3 endosulfan in the soil samples (n.d.-13.4 ng/g, mean: 0.8 ng/g) were not significantly different except at some stations adjacent to large areas of farmland. The average levels of Σ3 endosulfan in the water and sediment samples were 2.1 ng/L and 0.1 ng/g dw, respectively. In analyzing the four largest rivers, it was observed that a few water stations during spring and fall and sediment stations in fall had high concentrations of the two isomers and endosulfan sulfate, particularly around the Yeoungsan and Nakdong Rivers near large areas of agricultural land. Endosulfan sulfate was dominant at most water and sediment sampling stations. This study demonstrates that the endosulfan found in most environmental compartments most probably derives from agricultural areas despite its ban as a pesticide. On the other hand, given that it was also detected in industrial and urban areas, in which pesticide application does not occur, it can be conjectured that endosulfan is aerially transported at higher temperatures and continuously circulates within the environment.


Green synthesis of chitosan nanoparticles, optimization, characterization and antibacterial efficacy against multi drug resistant biofilm-forming Acinetobacter baumannii.
Chitosan nanoparticles (CNPs) are promising versatile cationic polymeric nanoparticles, which have received growing interest over last few decades. The biocompatibility, biodegradability, environmental safety and non-toxicity of the chitosan nanoparticles makes it preferred for a wide range of biological applications including agriculture, medical and pharmaceutical fields. In this study, CNPs were biosynthesized by aqueous extract of Eucalyptus globulus Labill fresh leaves as bio-reductant. Box-Behnken design in 29 experimental runs was used for optimization of different factors affecting the production of CNPs. The maximum yield of CNPs was 9.91 mg/mL at pH of 4.5, chitosan concentration of 1%, incubation time of 60 min and temperature of 50 °C. The crystallinity, particle size and morphology of the biosynthesized CNPs were characterized. The CNPs possess a positively charged surface of 31.1 mV. The SEM images of the CNPs confirms the formation of spherical form with smooth surface. The TEM images show CNPs were spherical in shape and their size range was between 6.92 and 10.10 nm. X-ray diffraction indicates the high degree of CNPs crystallinity. FTIR analysis revealed various functional groups of organic compounds including NH, NH2, C-H, C-O, C-N, O-H, C-C, C-OH and C-O-C. The thermogravimetric analysis results revealed that CNPs are thermally stable. The antibacterial activity of CNPs was determined against pathogenic multidrug-resistant bacteria, Acinetobacter baumannii. The diameters of the inhibition zones were 12, 16 and 30 mm using the concentrations of 12.5, 25 and 50 mg/mL; respectively. When compared to previous studies, the biosynthesized CNPs produced using an aqueous extract of fresh Eucalyptus globulus Labill leaves have the smallest particle sizes (with a size range between 6.92 and 10.10 nm). Consequently, it is a promising candidate for a diverse range of medical applications and pharmaceutical industries.


Fractional flow reserve derived from coronary computed tomography angiography reclassification rate using value distal to lesion compared to lowest value.
A standardised approach to the interpretation of FFRCT data is currently lacking. We evaluated the rate of reclassification of FFRCT positivity using the FFRCT value distal to an anatomical stenoses compared to the lowest FFRCT value. Patients who underwent coronary CTA and FFRCT analysis were eligible. FFRCT value of ≤ 0.80 was considered positive. Positive FFRCT distal to stenosis was defined as those with a stenoses of ≥ 25% with an associated FFRCT value of ≤ 0.80 within 2cm distal to the lesion. Outcome data on subsequent invasive coronary angiography (ICA) and coronary revascularisation were collected with a minimum follow-up of 60 days to account for delay between referral for invasive testing and/or revascularisation and receiving the procedure. 192 patients (mean age 60.7 ± 10.6 years, 67.5% men) were included. FFRCT was positive for lowest FFRCT value in 55.7% of patients. Positive FFRCT value distal to stenosis was found in 31.3%. The overall reclassification rate of those positive for lowest FFRCT value to negative for FFRCT value distal to stenosis was 43.9% (p < 0.01). The reclassification rates were most pronounced for those with intermediate stenoses - 67% for those with < 50% stenoses, p < 0.01; 49% for 50-69% stenoses, p < 0.01. Amongst those who underwent ICA, the rate of revascularization was significant higher for those with positive FFRCT distal to stenosis compared to those positive for lowest FFRCT value (revascularization/ICA = 0.53 vs 0.44, p < 0.01). Using FFRCT values distal to a anatomical stenoses, 44% of patients positive for lowest FFRCT value were reclassified as negative for FFRCT value distal to stenosis. Those who underwent ICA, the rate of revascularisation was higher amongst those with positive FFRCT distal to stenosis compared to those positive for lowest FFRCT value.


Axonemal dynein expression in human fetal tracheal epithelium.
Ciliogenesis in human fetal airway epithelium occurs from 11 to 24 gestational weeks. Using genetic and antigenic markers specific for human axonemal dynein heavy chain 9, we characterized temporal aspects of axonemal dynein expression associated with large airway epithelial ciliogenesis during human fetal development. Late in the first trimester, an undifferentiated columnar epithelium is characteristic of the large airways, and immunocytochemical studies exhibited focal localization of axonemal dynein antigen on luminal epithelial cell borders at sites consistent with emergent ciliary beds. From 12 to 22 wk, immunocytochemical labeling of new ciliary beds was prominent, and localization within the cytoplasm of epithelial cells suggested avid synthesis of axonemal dynein in advance of ciliogenic events. Quantitative RT-PCR of tracheal RNA and in situ hybridization studies compared favorably with immunocytochemical findings with the earliest expression of axonemal dynein at 9-10 wk gestation. These studies have documented that axonemal dynein is expressed early in human fetal life during airway epithelial maturation and well before histological or ultrastructural evidence of ciliogenesis is apparent.


[Genetic structure of the native populations of the northeastern USSR. II. Phenotype frequencies of the polymorphic systems in generations of the coast Chukchi].
Reliable differences between phenotype frequencies in generations for six of ten polymorphic systems were received. Unequal selective value of separate phenotypes at different stages of ontogeny is supposed, which results in heterogeneity of generations in a population. A possible significance of ecological factors in the formation of the genotypic structure of a population is discussed.


Quercetin metabolites inhibit MMP-2 expression in A549 lung cancer cells by PPAR-γ associated mechanisms.
Our previous study demonstrated that quercetin-metabolite-enriched plasma (QP) but not quercetin itself upregulates peroxisome proliferator-activated receptor gamma (PPAR-γ) expression to induce G2/M arrest in A549 cells. In the present study, we incubated A549 cells with QP as well as quercetin-3-glucuronide (Q3G) and quercetin-3'-sulfate (Q3'S), two major metabolites of quercetin, to investigate the effects of quercetin metabolites on cell invasion and migration, the possible mechanisms and the role of PPAR-γ. We also compared the effects of QP with those of quercetin and troglitazone (TGZ), a PPAR-γ ligand. The results showed that QP significantly suppressed cell invasion and migration, as well as matrix metalloproteinases (MMPs)-2 activity and expression in a dose-dependent manner. The effects of 10% QP on those parameters were similar to those of 10μM quercetin and 20μM TGZ. However, QP and TGZ rather than quercetin itself increased the expressions of nm23-H1 and tissue inhibitor of metalloproteinase (TIMP-2). Furthermore, we demonstrated that Q3G and Q3'S also inhibited the protein expression of MMP-2. GW9662, a PPAR-γ antagonist, significantly diminished such an effect of Q3G and Q3'S. Silencing PPAR-γ expression in A549 cells also significantly diminished the suppression effect of Q3G and Q3'S on MMP-2 expression. Taken together, our study demonstrated that QP inhibited cell invasion and migration through nm23-H1/TIMP-2/MMP-2 associated mechanisms. The upregulation of PPAR-γ by quercetin metabolites such as Q3G and Q3'S could play an important role in the effects of QP.


Effect of the protein synthesis inhibitor cycloheximide on RNA synthesis in radish seedlings.
The effect of cycloheximide on rRNA and poly (A) (+) RNA synthesis is studied in radish seedlings. When used at a concentration of 50 microng/ml cycloheximide selectively blocks rRNA synthesis without altering poly (A) (+) RNA synthesis. Processing of the 2.3 X 10(6) dalton pre-rRNA is severely impaired. This observation should help in studies of mRNA metabolism in plants. When the concentration of cycloheximide is lowered, it is possible to completely block protein synthesis without preventing RNA synthesis. This implies that the effect of cycloheximide on RNA synthesis is probably more complex than usually assumed.


Interventions for improving adherence to treatment for latent tuberculosis infection: a systematic review.
Latent tuberculosis infection (LTBI) control relies on high initiation and completion rates of preventive treatment to preclude progression to tuberculosis disease. Specific interventions may improve initiation and completion rates. The objective was to systematically review data on determinants of initiation, adherence and completion of LTBI treatment, and on interventions to improve initiation and completion. A systematic review of the literature (PubMed, Embase) published up to February 2014 was performed. Relevant prospective intervention studies were assessed using GRADE. Sixty-two articles reporting on determinants of treatment initiation and completion were included and 23 articles on interventions. Determinants of LTBI treatment completion include shorter treatment regimen and directly observed treatment (DOT, positive association), adverse events and alcohol use (negative association), and specific populations with LTBI (both positive and negative associations). A positive effect on completion was noted in intervention studies that used short regimens and social interventions; mixed results were found for intervention studies that used DOT or incentives. LTBI treatment completion can be improved by using shorter regimens and social interventions. Specific needs of the different populations with LTBI should be addressed taking into consideration the setting and condition in which the LTBI treatment programme is implemented.


Isolation and characterization of the human genomic locus coding for the putative metastasis control gene nm23-H1.
Nm23-H1 gene expression is inversely correlated with tumor metastatic potential in certain tumors, including melanomas, breast carcinomas, and hepatocellular carcinomas. Using nm23-H1 c-DNA primer and genomic polymerase chain reaction (PCR) amplification, we purified three PCR fragments (one of 4kb and two of 2 kb) covering the whole human genomic locus of the gene (8.460bp). We recombined the PCR products into pUC18 and produced a restriction map to perform subcloning. Complete sequencing of genomic PCR fragments, including the whole coding region of nm23-H1, revealed that the gene consists of five exons and four introns spanning 8.5kb. A sequence homology analysis between human nm23-H1 and the homolog gene of the rat (NDP-K beta) shows that exon-intron boundaries are well conserved between these two species.


Levels of expression of lipoxygenases and cyclooxygenase-2 in human breast cancer.
Lipoxygenases and cyclooxygenase are key mediators of arachidonic acid metabolism. The eicosanoids metabolites from these oxygynases have been shown to regulate the growth and death of cancer cells. This study determined the level of expression of 5-, 12-, 15-lipoxygenase and cyclooxygenase-2 expression in a cohort of breast cancer patients and their correlation with clinical outcomes. Compared with normal breast tissues, tumour tissues exhibited a significantly higher levels of 12-lipoxygenase and cyclooxygenase-2 (P<0.05), and significantly lower level of 15-lipoxygenase (P=0.05). Lobular carcinomas had a higher level of cyclooxygenase-2 and lower level of 15-lipoxygenase than ductal carcinomas. The lowest level of 15-lipoxygenase was seen in TNM3 and TNM4 tumours and from patients who died of breast cancer. Levels of 12- and 5-lipoxygenases were also particularly high in tumours from patients who died of breast cancer. This study shows that human breast tumours aberrantly express lipoxygenases and cyclooxygenase-2 and that decreased level of 15-lipoxygenase and raised level of cyclooxygenase-2 and 12-lipoxygenase has prognostic value in patients with breast cancer.


Investigation of the properties of nanostructured Li-doped NiO films using the modified spray pyrolysis method.
The lithium-doped nickel oxide (L-NiO) films were synthetized using the modified spray pyrolysis method with a two-step grown process. By observing the spectra of X-ray photoemission spectroscopy of L-NiO films, the intensity of Ni 2p3/2 peak of Ni3+ bonding state increases with increasing Li concentration that causes the decrease of transparency and resistivity. The L-NiO films with optimum characteristics were obtained at Li = 8 at%, where a p-type resistivity of 4.1 × 10-1 Ω cm and optical transparency above 76% in the visible region are achieved.


Living with AIDS in Uganda: a qualitative study of patients' and families' experiences following referral to hospice.
Globally, the majority of people with HIV/AIDS live in sub-Saharan Africa. While the increasing availability of antiretroviral therapy is improving the outlook for many, its effects are yet to reach all of those in need and patients still present with advanced disease. This paper reports findings from qualitative interviews with patients living with AIDS and their caregivers who were receiving palliative care from Hospice Africa Uganda (HAU). We aimed to understand what motivated patients and their families to seek formal healthcare, whether there were any barriers to help- seeking and how the help and support provided to them by HAU was perceived. We invited patients with AIDS and their relatives who were newly referred to HAU to participate in qualitative interviews. Patients and carers were interviewed in their homes approximately four weeks after the patient's enrolment at HAU. Interviews were translated, transcribed and analysed using narrative and thematic approaches. Interviews were completed with 22 patients (10 women and 12 men) and 20 family caregivers, nominated by patients. Interviews revealed the extent of suffering patients endured and the strain that family caregivers experienced before help was sought or accessed. Patients reported a wide range of severe physical symptoms. Patients and their relatives reported worries about the disclosure of the AIDS diagnosis and fear of stigma. Profound poverty framed all accounts. Poverty and stigma were, depending on the patient and family situation, both motivators and barriers to help seeking behaviour. Hospice services were perceived to provide essential relief of pain and symptoms, as well as providing rehabilitative support and a sense of caring. The hospice was perceived relieve utter destitution, although it was unable to meet all the expectations that patients had. Hospice care was highly valued and perceived to effectively manage problems such as pain and other symptoms and to provide rehabilitation. Participants noted a strong sense of being "cared for". However, poverty and a sense of stigma were widespread. Further research is needed to understand how poverty and stigma can be effectively managed in hospice care for patients for advanced AIDS and their families.


A case-control study of robot-assisted type III radical hysterectomy with pelvic lymph node dissection compared with open radical hysterectomy.
The purpose of this study was to compare robotically assisted hysterectomy (RAH) with open (ORH) type III radical hysterectomy in the treatment of early-stage cervical cancer. The outcomes of 51 consecutive patients who underwent RAH were compared with the outcomes of 49 patients who underwent ORH. There were no differences with regard to patient demographics. There were significant differences between the groups with regard to operative blood loss (P < .0001), operative time (P = .0002), and lymph node retrieval (P = .0003), all of which were in favor of the RAH cohort. All patients with RAH were discharged on postoperative day 1, compared with a 3.2-day average hospitalization for the cohort with ORH. The incidence of postoperative complications was 7.8% and 16.3% for the RAH and ORH cohorts, respectively (P = .35). Robotic type III radical hysterectomy with pelvic node dissection is feasible and may be preferable over open radical hysterectomy in patients with early-stage cervical cancer. Further study will determine procedure generalizability and long-term oncologic outcomes.


On the influence of interface charging dynamics and stressing conditions in strained silicon devices.
The performance of strained silicon devices based on the deposition of a top silicon nitride layer with high stress have been thoroughly analyzed by means of simulations and experimental results. Results clearly indicate that the electro-optic static response is basically governed by carrier effects. A first evidence is the appearance of a variable optical absorption with the applied voltage that should not occur in case of having a purely electro-optic Pockels effect. However, hysteresis and saturation effects are also observed. We demonstrate that such effects are mainly due to the carrier trapping dynamics at the interface between the silicon and the silicon nitride and their influence on the silicon nitride charge. This theory is further confirmed by analyzing identical devices but with the silicon nitride cladding layer optimized to have intrinsic stresses of opposite sign and magnitude. The latter is achieved by a post annealing process which produces a defect healing and consequently a reduction of the silicon nitride charge. Raman measurements are also carried out to confirm the obtained results.


Maturation of human fetal responses to airborne sound in low- and high-risk fetuses.
The purpose of the study was to characterize the onset and maturation of airborne sound-elicited responses in low- and high-risk preterm fetuses. In Study 1, a total of 91 low-risk fetuses at 27, 30, 33, and 36 weeks GA received three sound trials at 90, 100, 105 and 110 dB and three no-stimulus control trials. The onset of cardiac acceleration and body movement responses occurred at 30 weeks GA. Maturation of the cardiac response was observed with a decrease in threshold from 105-110 dB at 33 weeks GA to 100-105 dB at 36 weeks GA. In Study 2, the procedure was similar except that the 43 high-risk fetuses at 27, 30 and 33 weeks GA did not receive sounds at 90 dB. For the high-risk fetuses, the onset of cardiac and motor responses also occurred at 30 weeks GA. At 33 weeks GA, those high-risk fetuses subsequently born at term showed an increased magnitude of the cardiac acceleration response compared to low-risk fetuses. The results indicate that both low- and high-risk fetuses begin responding to sounds at the same gestational age. Differential responses observed over gestation in the high-risk group most likely indicate differential functional development of the auditory-response system.


Predicted intake of trace elements and minerals via household drinking water by 6-year-old children from Krakow, Poland. Part 3: aluminium.
In order to assess aluminium intake via drinking water by children, approximately 400 households in urban, peripheral, and rural areas were investigated. The study comprised about 200 children (5-7 years old) in the period between 2000 and 2001. The samples of drinking water were collected by a double sampling method (morning and evening). Aluminium was measured by graphite furnace-atomic absorption spectroscopy (GF-AAS). Geometric means (microg l(-1), confidence interval) were for evening samples: urban 72.5 (13.2-398), peripheral 6.3 (0.5-86.7), and rural 16.6 (0.5-593). For most households the aluminium concentration in the morning samples was lowered by about 40% due to deposition of aluminium-containing compounds during standing overnight. These deposits can be later taken up into the water. The European Commission aluminium limit of 200 microg l(-1) for drinking water was exceeded for 7.7, 0 and 13.2% of households from urban, peripheral, and rural areas, respectively. The predicted contribution of drinking water to aluminium intake by 6-year-old children was 3.81 microg day(-1) kg body weight(-1) or 2.7% of the provisional tolerable weakly intake (PTWI. 1 mg kg(-1) body weight) for urban sites and less for the others. For those cases exceeding the aluminium limit, the predicted aluminium intake via water consumption was 18.4-42.1 microg day(-1) kg body weight(-1) and contributed 12.8-29.5% of the provisional tolerable weakly intake. In urban areas the aluminium concentration was enhanced due to water treatment; while in rural sites it was due to contamination from cement-made wells. The high prevalence of cement wells in rural areas suggests that drinking water from individual sources should be included in a safety control system. The quality of materials for the construction of wells and containers for drinking water storage should be also improved. In order to limit aluminium intake from drinking water, this study also supports the suggestion of discarding overnight standing water before it is taken for consumption, especially for use by children.


Relating side-chain mobility in proteins to rotameric transitions: insights from molecular dynamics simulations and NMR.
The dynamic aspect of proteins is fundamental to understanding protein stability and function. One of the goals of NMR studies of side-chain dynamics in proteins is to relate spin relaxation rates to discrete conformational states and the timescales of interconversion between those states. Reported here is a physical analysis of side-chain dynamics that occur on a timescale commensurate with monitoring by 2H spin relaxation within methyl groups. Motivated by observations made from tens-of-nanoseconds long MD simulations on the small protein eglin c in explicit solvent, we propose a simple molecular mechanics-based model for the motions of side-chain methyl groups. By using a Boltzmann distribution within rotamers, and by considering the transitions between different rotamer states, the model semi-quantitatively correlates the population of rotamer states with 'model-free' order parameters typically fitted from NMR relaxation experiments. Two easy-to-use, analytical expressions are given for converting S2 (axis') values (order parameter for C-CH3 bond) into side-chain rotamer populations. These predict that S2 (axis') values below 0.8 result from population of more than one rotameric state. The relations are shown to predict rotameric sampling with reasonable accuracy on the ps-ns timescale for eglin c and are validated for longer timescales on ubiquitin, for which side-chain residual dipolar coupling (RDC) data have been collected.


Early activation of the proto-oncogene c-fgr during Epstein-Barr virus immortalization.
In an attempt to clarify the chronological relationships between Epstein-Barr virus (EBV) infection, B cell immortalization and c-fgr activation, we evaluated for the presence of EBV-determined nuclear antigen (EBNA), cellular DNA synthesis and expression of c-fgr-specific RNA following infection of human peripheral blood lymphocytes with B95-8 EBV. High expression of c-fgr was observed prior to EBNA detection and cellular DNA synthesis in EBV-infected cells. These results suggest that activation of c-fgr is an essential event during the early phase of EBV immortalization.


Complete retroperitoneal laparoscopic nephroureterectomy with bladder cuff excision for upper tract urothelial carcinoma without patient repositioning: a single-center experience.
This study was performed to evaluate the outcome of complete retroperitoneal laparoscopic nephroureterectomy with bladder cuff excision (RLNU-BCE), which is performed to treat urothelial carcinomas in the renal pelvis or in the ureter higher than the crossing of the common iliac artery without patient repositioning. We retrospectively analyzed the clinical data of 48 patients with upper tract urothelial carcinoma who underwent complete RLNU-BCE in our institution from May 2017 to September 2019. RLNU-BCE was successfully performed in all 48 patients. The median operation time was 110 minutes [interquartile range (IQR), 100-130 minutes], and the median postoperative anesthesia recovery time was 10 minutes (IQR, 7-15 minutes). The median postoperative hospitalization period was 5 days (IQR, 4-6 days). Pathologic examination revealed that the margin of all resected specimens was negative. After a median follow-up of 13 months (IQR, 7-20 months), no local recurrence or distant metastasis was found. No complications occurred during follow-up. Based on our experience with this technique, RLNU-BCE deserves application and promotion in clinical practice. Long-term comparative studies are required to confirm its superiority over other techniques.


Hierarchically arranged helical fibre actuators driven by solvents and vapours.
Mechanical responsiveness in many plants is produced by helical organizations of cellulose microfibrils. However, simple mimicry of these naturally occurring helical structures does not produce artificial materials with the desired tunable actuations. Here, we show that actuating fibres that respond to solvent and vapour stimuli can be created through the hierarchical and helical assembly of aligned carbon nanotubes. Primary fibres consisting of helical assemblies of multiwalled carbon nanotubes are twisted together to form the helical actuating fibres. The nanoscale gaps between the nanotubes and micrometre-scale gaps among the primary fibres contribute to the rapid response and large actuation stroke of the actuating fibres. The compact coils allow the actuating fibre to rotate reversibly. We show that these fibres, which are lightweight, flexible and strong, are suitable for a variety of applications such as energy-harvesting generators, deformable sensing springs and smart textiles.


Comparison of two interferon-gamma release assays (QuantiFERON-TB Gold In-Tube and T-SPOT.TB) in testing for latent tuberculosis infection among HIV-infected adults.
There is currently no 'gold standard' for diagnosis of latent tuberculosis infection (LTBI), and both the tuberculin skin test and interferon-gamma release assays (IGRAs) are used for diagnosis; the latter have a higher sensitivity than tuberculin skin tests for diagnosis of LTBI in HIV-infected individuals with lower CD4 counts. No evidence base exists for selection of IGRA methodology to identify LTBI among human immunodeficiency virus-infected patients in the UK. We prospectively evaluated two commercially available IGRA methods (QuantiFERON-TB Gold In Tube [QFG] and T-SPOT.TB) for testing LTBI among HIV-infected patients potentially nosocomially exposed to an HIV-infected patient with 'smear-positive' pulmonary tuberculosis. Among the exposed patients median CD4 count was 550 cells/µL; 105 (90%) of 117 were receiving antiretroviral therapy, of who 104 (99%) had an undetectable plasma HIV load. IGRAs were positive in 12 patients (10.3%); QFG positive in 11 (9.4%) and T-SPOT.TB positive in six (5.1%); both IGRAs were positive in five patients (4.3%). There was one indeterminate QFG and one borderline T-SPOT.TB result. Concordance between the two IGRAs was moderate (κ = 0.56, 95% confidence interval = 0.27-0.85). IGRAs were positive in only 4 (29%) of 14 patients with previous culture-proven tuberculosis. No patient developed tuberculosis during 20 months of follow-up.


Incidence, risk factors and prognosis of acute kidney injury in patients treated with immune checkpoint inhibitors: a retrospective study.
Immune checkpoint inhibitors (ICIs) change the prognosis of many cancer patients. With the increasing use of ICIs, immune-related adverse events are occurring, including acute kidney injury (AKI). This study aimed to assess the incidence of AKI during ICI treatment and its risk factors and impact on mortality. Patients treated with ICIs at the First Medical Center of the Chinese PLA General Hospital from January 1, 2014, to December 30, 2019, were consecutively enrolled, and risk factors affecting AKI development in patients treated with ICIs were analyzed using univariate and multivariate logistic regression. Medical record surveys and telephone inquiry were used for follow-up, and Kaplan-Meier survival analysis and Cox regression were used to analyze independent risk factors for death. Among 1615 patients, 114 (7.1%) had AKI. Multivariate logistic regression analysis showed that anemia, Alb < 30 g/L, antibiotic use, diuretic use, NSAID use and proton pump inhibitor use were independent risk factors for AKI development in patients treated with ICIs. Stage 2 or 3 AKI was an independent risk factor for nonrecovery of renal function after AKI onset. Multivariate Cox regression analysis showed that anemia, Alb < 30 g/L, AKI occurrence, and diuretic use were independent risk factors for death in patients treated with ICIs, while high baseline BMI, other tumor types, ACEI/ARB use, and chemotherapy use were protective factors for patient death. AKI occurs in 7.1% of patients treated with ICIs. Anemia, Alb < 30 g/L, and combined medication use are independent risk factors for AKI in patients treated with ICIs. Anemia, Alb < 30 g/L, AKI occurrence, and diuretic use were independent risk factors for death in patients treated with ICIs.


Colloidal silica--aluminum modified--PVP density gradient centrifugation: centrifuge tube wall cell adherence, aggregation, separation properties and comparison to BSA and Ficoll.
A method is described for the inexpensive and easy preparation of colloidal silica--aluminum modified--polyvinylpyrrolidone (CS-AM-PVP) density gradient centrifugation medium. Using density gradient centrifugation, several cell separation and biochemical characteristics were studied: centrifuge tube wall cell adherence, mouse spleen cell density distribution, rebanding properties, mitogen response and cell aggregation. Cell adherence to the centrifuge tube wall using density gradients of CS-AM-PVP was compared with density gradients of bovine serum albumin and Ficoll. Few cells adhered to the centrifuge tube wall when CS-AM-PVP was used as a gradient medium; whereas, significant cell adherence to the centrifuge tube cell wall occurred when bovine serum albumin or Ficoll was used as a gradient medium. The CS-AM-PVP gradient medium did not inhibit the response to mitogens of mouse spleen cells which had been separated into density subpopulations in a discontinuous CS-AM-PVP density gradient, caused a minimum amount of cell aggregation, and was found to be non-toxic.


A plastic surgery literature review to assist in the management of patients seeking elective esthetic dental treatments.
This article reviews plastic surgery literature to help identify and manage the risk presented by patients interested in elective esthetic dentistry whose physiologic profile would compromise the success of the procedure. A questionnaire, designed to help identify patients with problematic physiologic profiles, is presented. In addition, risk management techniques adapted from the plastic surgery literature are reviewed.


Medical Nutrition Therapy Provided by Dietitians is Effective and Saves Healthcare Costs in the Management of Adults with Dyslipidemia.
Referral to nutrition care providers in the USA such as registered dietitian nutritionists (RDNs) for medical nutrition therapy (MNT) remains low. We summarize research on the effectiveness of MNT provided by dietitians versus usual care in the management of adults with dyslipidemia. Improvements in lipids/lipoproteins were examined. If reported, blood pressure (BP), fasting blood glucose (FBG) glycated hemoglobin (A1c), body mass index (BMI), and cost outcomes were also examined. The synthesis of three systematic reviews included thirty randomized controlled trials. Multiple MNT visits (3-6) provided by dietitians, compared with usual care, resulted in significant improvements in total cholesterol (mean range: - 4.64 to - 20.84 mg/dl), low-density lipoprotein cholesterol (mean range: - 1.55 to - 11.56 mg/dl), triglycerides (mean range: - 15.9 to - 32.55 mg/dl), SBP (mean range: - 4.7 to - 8.76 mm Hg), BMI (mean: - 0.4 kg/m2), and A1c (- 0.38%). Cost savings from MNT were attributed to a decrease in medication costs and improved quality of life years (QALY). Multiple MNT visits provided by dietitians compared with usual care improved lipids/lipoproteins, BP, A1c, weight status, and QALY with significant cost savings in adults with dyslipidemia and justify a universal nutrition policy for equitable access to MNT.


New Genetic Constructs for Generation of Stable Therapeutic Antibodies to Organophosphorus Toxins in Methylotrophic Yeasts Pichia Pastoris.
We propose a new method of obtaining of stable Fab-fragments of antibodies in Pichia pastoris expression system. Recently, we obtained Fab-fragments of antibodies neutralizing organophosphorus toxins. However, high yield of the target products was not attained because of high level of proteolytic degradation. In the present study, we identified sites of proteolytic degradation in Fab-fragments and endogenous proteases performing degradation, which allowed obtaining optimized genetic constructs for expression of antibody heavy chains (IgGγ1) and kappa and lambda isotypes of light chains. Co-transformation of these vectors allowed obtaining Fab-fragments of antibodies to organophosphorus toxins without proteolytic degradation of the product.


Significance of the C-terminal globular domain and the extra tail of the calmodulin-like protein (Pinctada fucata) in subcellular localization and protein-protein interaction.
Calmodulin (CaM) plays a very important role in many physiological processes and is highly conserved in different species. In a previous study, we successfully cloned CaM and a novel calmodulin-like protein (CaLP) with an extra C-terminal sequence from the pearl oyster Pinctada fucata and then expressed in Escherichia coli. In this research, we used fluorescence confocal microscopy to analyze the protein-protein interaction between CaM/CaLP and p21Cip1, which is cloned from mammalian cells, to show the different characteristics of these two proteins in vivo. The fluorescence confocal microscopy showed that the C-terminal globular domain together with the extra tail of CaLP is very important in CaLP's sequestration in cytoplasm. The most interesting phenomenon is that transfection of p21Cip1 can stimulate translocation of CaLP from the cytoplasm to the nucleus, but this is not the case for CaM. Fluorescence confocal microscopy and co-immunoprecipitation on different mutants of CaLP with p21Cip1 indicated that the C-terminal globular domain of CaLP is responsible for the trafficking of CaLP from cytoplasm to nucleus.


[Choice of antibacterial therapy with the use of a computerized consultation system].
The principle for a consulting system ensuring selection of a "theoretically optimal" antibiotic or antibacterial drug combination for the treatment of severe pyo-septic conditions in critically ill patients is described. The system is an addition to an automated case history, which ensures its efficacy. The algorithms are based on the analysis of the literary data and the results of many years of studying microorganisms in infectious foci.


Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning.
The production of reactive oxygen species by the mitochondrial complex II (succinate:ubiquinone oxidoreductase) recently has gained broad scientific interest. Depending on the (patho)physiological situation, ROS produced or triggered by complex II can have either beneficial or deleterious effects. This ambivalence can be explained mechanistically by the diverse role of complex II on mitochondrial ROS production: it can be a source as well as a suppressor or enhancer of ROS generation by other respiratory chain complexes. Since complex II directly links the respiratory chain to the tricarboxylic acid (TCA) cycle, the TCA-cycle intermediates - especially oxaloacetate that acts as a high affinity endogenous inhibitor - have major impact on complex II-related ROS release. The review relates the diverse effects of complex II activity on the mitochondrial ROS production that have been observed during cardioprotective ischemic or pharmacological preconditioning and the oxidative burst that occurs during ischemia/reperfusion. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease.


Ocular motor characteristics of different subtypes of spinocerebellar ataxia: distinguishing features.
Because of frequent involvement of the cerebellum and brainstem, ocular motor abnormalities are key features of spinocerebellar ataxias and may aid in differential diagnosis. Our objective for this study was to distinguish the subtypes by ophthalmologic features after head-shaking and positional maneuvers, which are not yet recognized as differential diagnostic tools in most common forms of spinocerebellar ataxias. Of the 302 patients with a diagnosis of cerebellar ataxia in 3 Korean University Hospitals from June 2011 to June 2012, 48 patients with spinocerebellar ataxia types 1, 2, 3, 6, 7, or 8 or with undetermined spinocerebellar ataxias were enrolled. All patients underwent a video-oculographic recording of fixation abnormalities, gaze-evoked nystagmus, positional and head-shaking nystagmus, and dysmetric saccades. Logistic regression analysis controlling for disease duration revealed that spontaneous and positional downbeat nystagmus and perverted head-shaking nystagmus were strong predictors for spinocerebellar ataxia 6, whereas saccadic intrusions and oscillations were identified as positive indicators of spinocerebellar ataxia 3. In contrast, the presence of gaze-evoked nystagmus and dysmetric saccades was a negative predictor of spinocerebellar ataxia 2. Positional maneuvers and horizontal head shaking occasionally induced or augmented saccadic intrusions/oscillations in patients with spinocerebellar ataxia types 1, 2, and 3 and undetermined spinocerebellar ataxia. The results indicated that perverted head-shaking nystagmus may be the most sensitive parameter for SCA6, whereas saccadic intrusions/oscillations are the most sensitive for spinocerebellar ataxia 3. In contrast, a paucity of gaze-evoked nystagmus and dysmetric saccades is more indicative of spinocerebellar ataxia 2. Head-shaking and positional maneuvers aid in defining ocular motor characteristics in spinocerebellar ataxias. © 2013 Movement Disorder Society.


A prospective non-fatal injuries assessment: A multivariate analysis in medical-legal examinations.
To prospectively determine injury recovery time in the medical-legal examinations of non-fatal injuries and their associated factors, carried out by the National Institute of Legal Medicine and Forensic Sciences of Colombia to create a multivariate analysis. A prospective medical-legal assessment of non-fatal injuries was carried out on 281 individuals with complete follow-up, in which the observational unit of analysis was the most serious injury. Variables, such as sex, circumstances of the injury, the mechanism that caused the injury, medical certificate of incapacity to work, among others were related to the injury recovery time, measured in days. The Kruskal Wallis (K-W) ANOVA and a multivariate analysis using the ordinal regression model were applied. In the multivariate analysis, the factors most associated with longer recovery time were the extent of joint damage (CR95%:1.47-5.94,p = 0.0001) and bone damage (CR95%:2.92-7.42,p < 0.001). In terms of circumstances of the injury, traffic accidents (CR95%:1.03-2.96,p < 0.001), medical-legal impairments (CR95%:0.34-2.19,p = 0.007), and complications of the primary injury (CR95%: 1.18-2.57,p < 0.001) had the greatest impact on recovery time. Others factors that significantly impacted injury recovery time are surgical treatments (IC95%: 0.33-3.26,p = 0.0164) and delayed treatment (CR95%:1.41-4.72,p < 0.001). A direct correlation (significant and moderately strong) was found between the recovery time of the injury and the days of incapacity for work (r = 0.802, p < 0.001). This prospective analysis determined which variables were most strongly related to the medical-legal assessment of non-fatal injuries and the recovery time of said injuries. Further studies aimed at improving the strategies to help individuals complete the legal process are required.