Diagnostic accuracy of positron emission tomography/computerized tomography for periprosthetic joint infection of hip: systematic review and meta-analysis.
American Academy of Orthopaedic Surgeons (AAOS) has provided the guidelines for diagnosing a patient with periprosthetic joint infection including the use of positron emission tomography/computed tomography (PET/CT). Systematic evidence focussing on periprosthetic joint infection (PJI) of hip is limited, which also contains limited number of studies. Hence, the current study aims to perform a pooled analysis of all studies that have assessed the diagnostic accuracy of PET/CT for PJI of hip. Searches were done in PubMed Central, EMBASE, MEDLINE, SCOPUS and Cochrane library until December 2022. Meta-analysis was carried out using random-effects model. With 95% confidence intervals (CIs), pooled sensitivity and specificity were reported. Twenty-six studies met the inclusion criteria. The pooled sensitivity of PET/CT was 89% (95% CI 84-93%), while the pooled specificity was 86% (95% CI 79-91%). The AUROC was 0.94 (95% CI 0.72-0.99). There was statistically significant heterogeneity (p < 0.001) with I2 value of 96%. The diagnostic odds ratio was 52 (95% CI 26-106). Likelihood ratio positive was 6.5 (95% CI 4.1-10.3) and negative was 0.13 (95% CI 0.08-0.19). Our study found that PET/CT was found to have higher level of accuracy in terms of sensitivity and specificity. Further large-scale research can help to find answers for such questions and provide final conclusive evidence on the inclusion of the imaging modality into the routine clinical practice guidelines for suspected periprosthetic joint infection patients.


Sierra SARS-CoV-2 sequence and antiviral resistance analysis program.
Although most laboratories are capable of employing established protocols to perform full-genome SARS-CoV-2 sequencing, many are unable to assess sequence quality, select appropriate mutation-detection thresholds, or report on the potential clinical significance of mutations in the targets of antiviral therapy METHODS: We describe the technical aspects and benchmark the performance of Sierra SARS-CoV-2, a program designed to perform these functions on user-submitted FASTQ and FASTA sequence files and lists of Spike mutations. Sierra SARS-CoV-2 indicates which sequences contain an unexpectedly large number of unusual mutations and which mutations are associated with reduced susceptibility to clinical stage mAbs, the RdRP inhibitor remdesivir, or the Mpro inhibitor nirmatrelvir RESULTS: To assess the performance of Sierra SARS-CoV-2 on FASTQ files, we applied it to 600 representative FASTQ sequences and compared the results to the COVID-19 EDGE program. To assess its performance on FASTA files, we applied it to nearly one million representative FASTA sequences and compared the results to the GISAID mutation annotation. To assess its performance on mutations lists, we applied it to 13,578 distinct Spike RBD mutation patterns and showed that exactly or partially matching annotations were available for 88% of patterns CONCLUSION: Sierra SARS-CoV-2 leverages previously published data to improve the quality control of submitted viral genomic data and to provide functional annotation on the impact of mutations in the targets of antiviral SARS-CoV-2 therapy. The program can be found at https://covdb.stanford.edu/sierra/sars2/ and its source code at https://github.com/hivdb/sierra-sars2.


Activation of canonical Wnt/β-catenin signaling inhibits H2O2-induced decreases in proliferation and differentiation of human periodontal ligament fibroblasts.
Human periodontal ligament fibroblasts (hPLFs) are exposed to oxidative stress during periodontal inflammation and dental treatments. It is hypothesized that hydrogen peroxide (H2O2)-mediated oxidative stress decreases survival and osteogenic differentiation of hPLFs, whereas these decreases are prevented by activation of the Wnt pathway. However, there has been a lack of reports that define the exact roles of canonical Wnt/β-catenin signaling in H2O2-exposed hPLFs. Treatment with H2O2 reduced viability and proliferation in hPLFs in a dose- and time-dependent manner and led to mitochondria-mediated apoptosis. Pretreatment with lithium chloride (LiCl) or Wnt1 inhibited the oxidative damage that occurred in H2O2-exposed hPLFs. However, knockout of β-catenin or treatment with DKK1 facilitated the H2O2-induced decreases in viability, mitochondrial membrane potential, and Bcl-2 induction. Osteoblastic differentiation of hPLFs was also inhibited by combined treatment with 100 μM H2O2, as evidenced by the decreases in alkaline phosphatase (ALP) activity and mineralization. H2O2-mediated inhibition of osteoblast differentiation in hPLFs was significantly attenuated in the presence of 500 ng/ml Wnt1 or 20 mM LiCl. In particular, H2O2 stimulated the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) at protein and mRNA levels in hPLFs, whereas the induction was almost completely suppressed in the presence of Wnt1 or LiCl. Furthermore, siRNA-mediated silencing of Nrf2 blocked H2O2-induced decreases in ALP activity and mineralization of hPLFs with the concomitant restoration of runt-related transcription factor 2 and osteocalcin mRNA expression and ALP activity. Collectively, these results suggest that activation of the Wnt/β-catenin pathway improves proliferation and mineralization in H2O2-exposed hPLFs by downregulating Nrf2.


Graphite carbon nitride-modified screen-printed electrode as a highly sensitive and selective sensor for detection of amaranth.
This work presented a particular electrochemical sensor for analysis of amaranth, an azo toxic dye. A graphite nitride carbon (g-C3N4) was used to modify an electro-treated screen-printed electrode (g-C3N4/SPE) for electroanalysis of amaranth. Physicochemical characteristics and analytical performance of g-C3N4/SPE were investigated by relevant equipment. The g-C3N4/SPE when comparing with bare SPE, possessed an impressive electrocatalytic performance towards the amaranth oxidation. As-developed sensor under the optimal circumstances exhibited an extended linear response range for different amaranth concentrations of 0.08 μM-340.0 μM, with a narrow practical limit of detection (LOD) of 0.02 μM, a limit of quantification (LOQ) of 0.08 μM, and an unparalleled sensitivity of 0.0702 μA/μM using differential pulse voltammetry (DPV). The applicability of as-fabricated sensor was verified by determining the amaranth in real samples, with acceptable recoveries.


Autosomal dominant inheritance in familial angiolipomatosis.
A patient with familial angiolipomatosis in whom an autosomal dominant mode of inheritance could be established is described. This patient also had coincidental autosomal dominant polycystic kidney disease.


Hybrid trans-apical device closure of left ventricular pseudoaneurysm under trans-oesophageal echocardiographic guidance.
Left ventricular pseudo aneurysm (LVPA) results from contained left ventricular free wall rupture following either myocardial infarction or cardiac surgery. Untreated LVPA carries approximately 30-45% risk of rupture in the first year. Conventional treatment for LVPA is surgery which carries a mortality of about 20%. Interventional closure of LVPA has been reported from trans-arterial and trans-apical routes. Here we report successful hybrid closure of a LVPA under trans-oesophageal echocardiogram (TEE) guidance.


Quantitative neuronal c-fos and c-jun expression in Alzheimer's disease.
Apoptosis, or programmed cell death, has been proposed as a mechanism of neuropathology in Alzheimer's disease (AD). Activation of immediate early genes (IEG) c-jun and c-fos appears to be required for the initiation of apoptosis. Furthermore, the expression of c-jun is induced in cultured neurons that undergo beta-amyloid-mediated apoptosis suggesting a direct role for c-jun in the apoptosis of AD neurons. Using immunohistochemical methods, we calculated the average number of neuronal profiles per unit area expressing c-Jun and c-Fos within hippocampal regions CA1, CA2/3, and CA4 in postmortem brain samples from AD patients and age-matched non-AD patients. There was an increase in c-Jun-positive and c-Fos-positive neuronal profile density in nearly all AD hippocampal regions examined. In cerebellum there was no evidence of apoptosis as determined by using TUNEL technique, and negligible c-Jun labeling.


Effect of calcium channel blockers on platelet GPIIb-IIIa as a calcium channel in liposomes: comparison with effects on the intact platelet.
The platelet membrane glycoprotein IIb-IIIa complex is essential for platelet aggregation and functions as a fibrinogen receptor on the activated platelet. When incorporated into phospholipid vesicles, this glycoprotein complex can function as an apparent calcium channel which facilitates the transit of calcium across a phospholipid barrier. In order to further evaluate this calcium channel, the effect of calcium channel blockers of the dihydropyridine (nifedipine and nicardipine), arylalkylamine (verapamil) and benzothiazepine (diltiazem) classes were evaluated on GPIIb-IIIa liposomes with encapsulated fura-2 (a fluorescent calcium indicator). Nicardipine, verapamil, and nifedipine significantly inhibited calcium influx into GPIIb-IIIa liposomes; however, this required 190 microM, 400 microM, and 140 microM drug, respectively. These concentrations are 10-1,000 fold greater than those clinically obtainable. In contrast, diltiazem at concentrations greater than 220 microM and amiloride at concentrations greater than 800 microM showed no inhibitory effects. When aspirinized platelets were activated with 30 micrograms/ml bovine fibrillar collagen, both nicardipine and diltiazem produced a decrease in both the initial rise and maximum cytoplasmic calcium concentration. Parallel experiments were performed to assess the effects of verapamil, nicardipine, and diltiazem on platelet aggregation in platelet rich plasma. Nicardipine, 190-380 microM, induced a prolongation of the lag phase, but no effect on the final degree of platelet aggregation to collagen. Similar inhibition of platelet aggregation was seen with diltiazem and verapamil although the effect of diltiazem was less pronounced particularly at higher concentrations of collagen. No effect was seen on aggregation with 32 microM ADP which is release independent, or on the primary wave of low dose ADP induced platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)


RTOG #89-06: a phase I study to evaluate intraoperative radiation therapy and the hypoxic cell sensitizer etanidazole in locally advanced malignancies.
To identify the maximum tolerated dose of the oxygen mimetic radiation sensitizer Etanidazole in the setting of surgery and intraoperative radiation therapy. 12 grams/meter2 was the maximum chosen target dose based on tolerance from other trials. 42 patients were entered in an escalating dose scheme, 5.5, 7.5, 9, 10.5, and 12.0 grams/meter2. Etanidazole was given via intravenous infusion over 15 minutes, followed within 20 to 30 minutes by intraoperative radiation therapy. Multiple tissue samples from tumor, tumor bed, and/or normal tissue were obtained with simultaneous plasma samples. Etanidazole concentrations in tissue and serum were determined in 33 of the 42 patients. The median time to maximum serum concentration was 25 minutes. Median time to maximum tissue concentration was 40 minutes. Tissue concentrations began falling approximately one hour after infusion. Acute drug toxicities were minimal. Toxicities reported during follow-up related to surgery and/or radiation, not to drug. The concentration of sensitizer in tumor/tumor bed tissues was ten-fold greater than in previous trials. A sensitizer enhancement ratio for the hypoxic cells of 2 to 2.5 is projected. On the basis of tissue biopsy information, intraoperative radiation therapy will be given 40 minutes after the start of the 15 minute infusion allowing time for maximum intracellular uptake into tumor cells. In view of these findings, a Phase III trial testing etanidazole with intraoperative radiation therapy will be conducted. The tolerable single dose level of 12 grams/meter2 has potential with other high-dose radiation settings such as brachytherapy or stereotactic radiosurgery.


Studies on in-use microbial contamination of sterile medicines at an animal hospital.
Eye drops, injection solutions and infusion fluids in-use were collected from the various wards of an animal hospital and tested for sterility. Medicines from the stationary wards showed a contamination frequency of 17.5%, whereas 62% of those from the ambulatory ward were contaminated. The veterinarians who, as regards the handling of medicines, often have to work under extraordinary conditions must be observant of the risks of handling and keeping sterile medicines in an inconvenient way. This is especially important in ambulatory practice.


[Effect of ionizing radiation on the functional state of Helix pomatia neurons. The systems of Na+ and K+ transport].
The influence of ionizing radiation (5.16 C/kg) on passive and active Na+ and K+ transfer within the giant neurons of edible snail (Helix pomatia) has been investigated. It has been shown that ionizing radiation increases passive permeability of membranes, inhibits active ion transport, changes the number and the affinity of functionally active Na+,K+-ATPase molecules. The authors discuss the mechanisms of action of ionizing radiation.


Double-Docking Technique for Femtosecond Laser-Assisted Deep Anterior Lamellar Keratoplasty: A Retrospective Consecutive Case Series Study of Advanced Keratoconus.
The aim of this study was to report the clinical outcomes and prognosis of femtosecond laser (FSL)-assisted double-docking deep anterior lamellar keratoplasty (DD-DALK) for advanced keratoconus (AK). Records of consecutive patients with keratoconus who underwent FSL-assisted DALK (DD-DALK) were reviewed. We analyzed 37 eyes from 37 patients who underwent DD-DALK. Sixty-eight percent of eyes had a successful big-bubble formation and 27% had a manual dissection to achieve the DALK deep dissection. Stromal scarring was associated with not achieving a big bubble. Intraoperative conversion to penetrating keratoplasty was conducted in 2 cases (5%). The best-corrected visual acuity improved from a median (± interquartile range) of 1.55 ±0.25 logMAR preoperatively to 0.2 ±0.2 logMAR ( P < 0.0001). The median postoperative spherical equivalent was -5.75 ±2.75 D with a median astigmatism of -3.5 ±1.3 D. BCVA, SE, and astigmatism were not statistically different between patients who underwent DD-DALK and patients who underwent manual DALK. Stromal scarring was associated with big-bubble (BB) formation failure ( P = 0.003). All patients with failed BB requiring manual dissection had anterior stromal scarring. DD-DALK is safe and reproducible. The success rate of BB formation is hampered by stromal scarring.


Sectionectomy of the liver.
Anatomic resection of the liver, which refers to the systemic elimination of the main tumor with micrometastases, preserves liver function and is highly recommended. Tumors located centrally or in the vicinity of major portal pedicles or hepatic veins, however, tend to require extensive hepatectomy. Anatomic sectionectomy of the liver might represent an alternative to such extensive resection. Preoperative simulation, external landmarks, selective devascularization, and intraoperative ultrasound are useful to achieve anatomic sectionectomy. Anatomic resection requires division of the relevant portal vein, hepatic artery, and bile duct. This may be achieved by individual isolation of the three elements or by mass isolation of all three in their surrounding fibrous sheath (Glisson's capsule). Both approaches are equally effective for extensive resections. When sectionectomy is performed, however, the isolation of individual vasculobiliary elements is sometimes difficult and dangerous compared with the isolation of the sectional portal pedicles. By identifying the portal pedicles to individual anatomic sections, it is possible to control the inflow to the section that is intended for resection. Anatomic sectionectomy is a safe alternative to extensive liver resection in selected patients, avoiding unnecessary sacrifice of functional liver parenchyma and increasing the opportunity to perform repeat resections in cases of recurrence.


Combinatorial Herbal Extracts Alleviate Alcohol-Induced Hepatic Disorders.
Plant-derived compounds can be useful for the management of liver disease. Traditionally, hepatic disorders have been treated with herbal extracts. Although many herbal extracts in Eastern medicine have been shown to possess hepatoprotective activities, single-origin herbal extracts primarily demonstrate either antioxidant or anti-inflammatory activities. The current study investigated the effects of combinatorial herbal extracts on alcohol-induced hepatic disorders in an ethanol-fed mouse model. Sixteen herbal combinations were evaluated as hepatoprotective formulations; the active constituents in these herbal extracts were daidzin, peonidin-3-glucoside, hesperidin, glycyrrhizin, and phosphatidylcholine. RNA sequencing analysis showed that exposure to ethanol altered hepatic gene expression profiles (compared to those of the non-alcohol-fed group), resulting in 79 differentially expressed genes. A majority of the differentially expressed genes in alcohol-induced hepatic disorders were associated with dysfunction of the normal cellular homeostasis in the liver; however, these genes were repressed by treatment with herbal extracts. Moreover, following treatment with herbal extracts, there were neither acute inflammatory responses in the liver tissue nor abnormalities in the cholesterol profile. These results suggest that combinatorial herbal extracts may alleviate alcohol-induced hepatic disorders by modulating the inflammatory response and lipid metabolism in the liver.


Isolation and characterization of a novel ε-caprolactam-degrading microbe, Acinetobacter calcoaceticus, from industrial wastewater by chemostat-enrichment.
For the isolation of a ε-caprolactam-degrading microbe from wastewaters of a factory producing caprolactam, we applied a chemostat-enrichment technique with a selective medium containing caprolactam as sole source of carbon and nitrogen. This allowed for the isolation of a novel caprolactam-degrading microbe, identified as Acinetobacter calcoaceticus. The strain had a critical tolerance of 19 g caprolactam l(-1) in minimal medium, which is higher than any previously reported caprolactam-degrading microbe. A. calcoaceticus also decreased the caprolactam content in medium by 65 % within 72 h despite the high caprolactam content (10 g l(-1)). This study highlights the potential use of A. calcoaceticus strain for the bioremediation of recalcitrant synthetic polymers, such as caprolactam.


Esthetic principles; concepts, and practices in pediatric and adolescent dentistry.
The foundation of all dental esthetics is health. A beautiful dentition only occurs in supporting structures free of disease and inflammatory responses. Beyond health, the desire for manipulation of the oral cavity for esthetics in pedodontics is guided by the expectations of the dentist and the parents. When treatment planning for young children and adolescents, it is imperative that the dentist helps to distinguish procedures performed for the health and functional needs of the child from techniques performed to meet cultural standards of esthetics.


Tetrodecadazinone, a novel tetrodecamycin-pyridazinone hybrid with anti-liver fibrosis activity from Streptomyces sp. HU051.
Tetrodecadazinone (1), a novel tetrodecamycin-pyridazinone hybrid possessing a new 1,2-dimethyl-1-(2-methylnonyl)decahydronaphthalene skeleton, and 4-hydroxydihydrotetrodecamycin (2) were separated from a culture of Streptomyces sp. HU051, together with a known compound, dihydrotetrodecamycin (3). Diverse spectroscopic approaches were applied to assign the structures of 1-3, and the structure of 1 was further confirmed by single crystal X-ray diffraction analysis. Compound 1 is the first example of a pyridazinone-containing natural product. Biosynthetically, 1 is proposed to be derived from a Michael addition reaction of a PKS-derived tetrodecamycin and a piperazic-acid-derived pyridazinone. Biological evaluation revealed 1 could reduce the expressions of extracellular matrix proteins (fibronectin and collagen I) and α-smooth muscle actin (α-SMA) in transforming growth factor-β (TGF-β1)-activated LX-2 cells. Preliminary mechanism study showed 1 exerted its anti-liver fibrosis effect by regulating TGF-β1/Smad2/3 signaling pathway.


Computer-regulated constant pressure ischemia in the rat: the animal model.
A system permitting computer control of partial ischemia in the normotensive rat brain was developed. Right carotid cannulation and bilateral subclavian artery occlusion made the input of blood to the brain dependent solely on left carotid artery flow. Perfusion pressure was controlled by partial compression of this artery with a balloon. The system can produce a range of partial ischemic states maintaining perfusion pressures from 4 to 20 mm Hg. The adequacy of the servo-control system was evaluated in greater detail at requested perfusion pressures of 7 and 12 mm Hg in 14 male Sprague-Dawley rats (300-450 g). Experimentally obtained cerebral perfusion pressures of 6.84 (SD = 0.25, n = 7) and 11.72 (SD = 0.89, n = 7) mm Hg, respectively, demonstrate the efficacy of the system. CBFs were concurrently measured at four separate bilaterally symmetric anatomic sites (cortex, hippocampus, thalamus, and substantia nigra). Significant intra- and interhemispheric differences were found to exist, with regional flows monitored ipsilaterally to the carotid balloon exceeding those of the opposite hemisphere. In summary, this acute model of cerebral ischemia permits control of perfusion pressure over the entire critical partial ischemic range.


Effect of fluoride agents on surface characteristics of NiTi wires. An ex vivo investigation.
To analyze the degree of corrosion of nickel titanium arch wires in patients with and without exposure to fluorides. This was an ex vivo study comprising of 60 subjects undergoing fixed orthodontic treatment. Group 1(controls) comprised of 30 sets of new unused NiTi wires and unused 11, 15 brackets, Group 2(patients) comprised of 30 sets of non fluoridated NiTi wires and 11, 15 brackets and Group 3(patients) had 30 sets of fluoridated NiTi wires and 11, 15 brackets. NiTi wires were used over 6 months of treatment(0.014″,0.016″, 16 × 22", each wire was used for 2 months and replaced with the next size). All wires were retrieved, stored and analyzed. At 6 months, brackets from 11 to 15 were debonded in both treatment groups. Archwires and brackets in 3 groups were subjected to SEM analysis at 500 and 1000X to observe differences. Additionally, EDX Spectroscopy was undertaken to evaluate surface elemental compositional differences in groups. Significant differences among groups were evident in brackets and archwires tested. Maximum degradation, cracks and dark spots were seen in wires and brackets exposed to fluoride agents. EDX spectroscopy revealed least Ni% in fluoridated wires and brackets. Increased leaching of metal ions was evident when wires and brackets are exposed to fluoride agents during treatment. Use of non fluoridated mouthwash and toothpastes may be considered in orthodontic patients without risk of caries to mitigate such effects.


Loading PEG-catalase into filamentous and spherical polymer nanocarriers.
Based on a unique phase alignment that occurs during formulation, we postulated that PEG-ylation of the cargo enzyme would enhance its encapsulation within diblock copolymer nanocarriers and thus resistance to proteases. A freeze-thaw modified double emulsion technique was utilized to encapsulate either the catalytically active enzyme catalase (MW approximately 250 kDa) or PEG-catalase in PEG-PLA polymer nanocarriers (PNC). Spectrophotometer measurement of substrate depletion was utilized to monitor enzyme activity. Isotope labeling of the enzyme was used in conjunction with activity measurements to determine PNC loading efficiency and PNC-enzyme resistance to proteases. This labeling also enabled blood clearance measurements of PNC-loaded and non-loaded enzymes in mice. Non-loaded PEG-catalase exhibited longer circulation times than catalase, but was equally susceptible to proteolysis. Modulation of the ratio of relatively hydrophilic to hydrophobic domains in the diblock PEG-PLA copolymer provided either filamentous or spherical PNC loaded with PEG-catalase. For both PNC geometries, encapsulation and resistance to proteases of the resultant PNC-loaded enzyme were more effective for PEG-catalase than catalase. Isotope tracing showed similar blood levels of PNC-loaded and free PEG-catalase in mice. PEGylation enhances active catalase loading within PNC and resistance to protease degradation, relative to unloaded PEG-catalase.


Insulin resistance and endogenous digoxin-like factor in obese hypertensive patients with glucose intolerance.
Hypertensive obese subjects with glucose intolerance have hyperinsulinaemia, insulin resistance and intracellular cation imbalance resulting in increased sodium content. The aim of our study was to assess in these patients plasma levels of endogenous digoxin-like factor (EDLF), an inhibitor of the sodium-pump mechanism. We studied 14 hypertensive and 12 normotensive subjects with obesity and glucose intolerance for fasting blood glucose, and plasma insulin, C-peptide and EDLF levels: the two groups were matched for age and BMI and were studied after a 2-week wash-out period from hypotensive drugs. Compared with normotensives, hypertensive subjects had higher plasma insulin levels, a greater immunoreactive insulin/C-peptide ratio, a lower glucose/insulin ratio and higher plasma EDLF levels. Our results confirm that among obese people with glucose intolerance, hypertensives are more hyperinsulinaemic and insulin-resistant than normotensives and indicate that the intracellular cation imbalance in these patients may be attributable, at least in part, to EDLF.


Effect of alumina femoral head on clinical results in cemented total hip arthroplasty: old versus current alumina.
The wear rate of polyethylene against alumina was demonstrated to be lower than against metal, and the results of early clinical studies of alumina-on-polyethylene combination were as good as expected, but the long-term results of alumina ceramic heads were not as good, as reported by several authors. The purpose of this study was to assess the clinical results over 10 years of cemented total hip arthroplasty (THA) with two types of alumina head: old and current alumina. We compared the clinical results of these two types of alumina used for cemented THA. The first type was old alumina (containing 7% yttria), and 77 hips with a 28-mm head (group I) were included. The second type was current alumina (highly purified alumina), and 50 hips with a 26-mm head (group II) and 88 hips with a 22-mm head (group III) were included. The mean follow-up was 17 years 4 months in group I, 12 years 3 months in group II, and 10 years in group III. The Kaplan-Meier survival analysis, with revision for any reason as the endpoint, predicted 10-year survival rates of 90.8%, 100%, and 97.5% for groups I, II, and III, respectively. The survival curves differed significantly only between groups I and II. The probabilities of 10-year survival of the pros-theses with radiological loosening as the endpoint were 77.2%, 91.6%, and 96.5%, respectively. The survival curves showed significant differences only between groups II and III. The old alumina showed a higher wear rate and rougher surface on the femoral head than did the current alumina in our previous study. The clinical results also indicated superiority of current alumina over old alumina. The difference in the size of the femoral head (26 vs. 22 mm) did not affect the clinical results.


Population modeling of bosutinib exposure-response in patients with newly diagnosed chronic phase chronic myeloid leukemia.
The BELA and BFORE trials compared bosutinib starting doses of 500 mg once daily (QD) and 400 mg QD, respectively, with imatinib in adults with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML). The B1871048 trial evaluated bosutinib 400 mg QD in Japanese patients with newly diagnosed CP-CML. This analysis assessed the impact of a lower bosutinib starting dose on key efficacy and safety outcomes. A pharmacokinetic model was used to estimate metrics of bosutinib exposure, and logistic regression was used to investigate relationships with efficacy (cumulative major molecular response [MMR] and cumulative complete cytogenetic response [CCyR]) and safety outcomes (eight prespecified adverse events). Totals of 573 and 574 patients were included in the efficacy and safety endpoint analyses, respectively. Cumulative MMR and CCyR were similar across studies. Log(Ctrough ) and log(Cavg ) were significant predictors of MMR and CCyR, and the probability of achieving MMR or CCyR increased 1.3-fold or 2.7-fold for every 1 unit increase in log(Ctrough ) or log(Cavg ), respectively. An exposure-response relationship was identified between time-to-event and risk of diarrhea, nausea, and vomiting. Significant relationships were also observed between time-to-event and log(Cavg ), Ctrough , and Cavg with diarrhea, nausea, and vomiting, respectively. A bosutinib exposure-response relationship with safety and efficacy was observed. Compared with 500 mg QD, a bosutinib starting dose of 400 mg QD improved tolerability in some patients with newly diagnosed CP-CML without compromising efficacy. gov identifiers: NCT00574873; NCT02130557; NCT03128411.


Sickness absence due to otoaudiological diagnoses and risk of disability pension: a nationwide Swedish prospective cohort study.
Hearing difficulties are a large public health problem. Knowledge is scarce regarding risk of disability pension among people who have been sickness absent due to these difficulties. A cohort including all 4,687,756 individuals living in Sweden in 2005, aged 20-64, and not on disability or old-age pension, was followed through 2009. Incidence rate ratios (RR) of disability pension with 95% confidence intervals (CI) were estimated using Cox proportional hazard models. In multivariable models, individuals who had a sick-leave spell due to otoaudiological diagnoses in 2005 had a 1.52-fold (95% CI: 1.43-1.62) increased risk of being granted a disability pension compared to individuals on sick leave due to other diagnoses. Hearing and tinnitus sick-leave diagnoses were associated with risk of disability pension: RR 3.38, 95% CI: 3.04-3.75, and 3.30, 95% CI: 2.95-3.68, respectively. No association was observed between sick leave due to vertigo diagnoses and disability pension whereas otological diagnoses and no sick leave were inversely associated with risk of disability pension compared to non-otoaudiological sick-leave diagnoses. Sick leave due to otoaudiological diagnoses was positively associated with risk of disability pension due to otoaudiological diagnoses and sick leave due to a tinnitus diagnosis was also associated with risk of disability pension due to mental diagnoses. The risk of disability pension among individuals with hearing or tinnitus sick-leave diagnoses was highest in the age group 35-44. Moreover, men had a slightly higher risk. This large cohort study suggests an increased risk of disability pension among those with sickness absence due to otoaudiological diagnoses, particularly hearing and tinnitus diagnoses, compared to those with sickness absence due to non-otoaudiological diagnoses.


Prognostic significance of serum resolvin D1 levels in patients with acute supratentorial intracerebral hemorrhage: A prospective longitudinal cohort study.
Resolvin D1 (RvD1) has anti-inflammatory properties and may be neuroprotective. This study was designed to assess usability of serum RvD1 as a prognostic biomarker after intracerebral hemorrhage (ICH). In this prospective, observational study of 135 patients and 135 controls, serum RvD1 levels were measured. Its relations to severity, early neurologic deterioration (END) and poststroke 6-month worse outcome (modified Rankin Scale scores of 3-6) were determined via multivariate analysis. Predictive effectiveness was evaluated based on area under receiver operating characteristic curve (AUC). Patients had markedly lower serum RvD1 levels than controls (median, 0.69 ng/ml versus 2.15 ng/ml). Serum RvD1 levels were independently correlated with the National Institutes of Health Stroke Scale (NIHSS) [β, -0.036; 95 % confidence interval (CI), -0.060--0.013; VIF, 2.633; t = -3.025; P = 0.003] and hematoma volume (β, -0.019; 95 % CI, -0.056--0.009; VIF, 1.688; t = -2.703; P = 0.008). Serum RvD1 levels substantially discriminated risks of END and worse outcome with AUCs at 0.762 (95 % CI, 0.681-0.831) and 0.783 (95 % CI, 0.704-0.850) respectively. A RvD1 cut-off value of 0.85 ng/ml was effective in predicting END with a sensitivity of 95.0 % and specificity of 48.4 % and its levels <0.77 ng/ml distinguished patients at risk of worse outcome with a sensitivity of 84.5 % and specificity of 63.6 %. Under restricted cubic spline, serum RvD1 levels were linearly related to risk of END and worse outcome (both P > 0.05). Serum RvD1 levels and NIHSS scores independently predicted END with odds ratio (OR) values of 0.082 (95 % CI, 0.010-0.687) and 1.280 (95 % CI, 1.084-1.513) respectively. Serum RvD1 levels (OR, 0.075; 95 % CI, 0.011-0.521), hematoma volume (OR, 1.084; 95 % CI, 1.035-1.135) and NIHSS scores (OR, 1.240; 95 % CI, 1.060-1.452) were independently associated with worse outcome. END prediction model containing serum RvD1 levels and NIHSS scores, and prognostic prediction model containing serum RvD1 levels, hematoma volumes and NIHSS scores displayed efficient predictive ability with AUCs at 0.828 (95 % CI, 0.754-0.888) and 0.873 (95 % CI, 0.805-0.924) respectively. Such two models were visually shown via building two nomograms. Using Hosmer-Lemeshow test, calibration curve and decision curve, the models were comparatively stable and had clinical benefit. There is a dramatical declination of serum RvD1 levels after ICH, which is tightly related to stroke severity and is independently predictive of poor clinical outcome, implying that serum RvD1 may be of clinical significance as a prognostic marker of ICH.


Retracted: Maternal traditional Chinese medicine exposure and risk of congenital malformations: A multicenter prospective cohort study.
The above article, published online on 19 April 2023 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal's Editor-in-Chief, Ganesh Acharya, and John Wiley & Sons Ltd. The retraction has been agreed due to flaws with the study design in collecting data on exposure to traditional Chinese medicine in pregnant women, which affects the validity of the data to support the conclusions of the study. How to cite this article: Peng, T, Yin, L-L, Xiong, Y, et al. Retracted: Maternal traditional Chinese medicine exposure and risk of congenital malformations: a multicenter prospective cohort study. Acta Obstet Gynecol Scand. 2023;102:735-743. doi:10.1111/aogs.14553.


Correlation between poly(U) misreading and poly(dT) translation efficiency in E coli cell-free systems.
A positive correlation between poly(U) misreading and efficiency of poly(dT) translation has been revealed in cell-free systems from wild-type E coli and streptomycin--resistant mutants with altered ribosomal protein S12. Different factors promoting misreading of poly(U) such as aminoglycoside antibiotics and Mg2+ ions also stimulate poly(dT) translation. The effect of the antibiotics on poly(U) translation efficiency and misreading as well as on poly(dT) decoding is characterised by the same order: neomycin greater than kanamycin greater than streptomycin. S12 mutants ribosomes are less erroneous in poly(U) translation and less efficient in poly(dT) decoding. The data obtained are in good agreement with the hypothesis of stereospecific stabilization of codon-anticodon complexes by the ribosome decoding centre.


Synovial sarcoma: characteristics, challenges, and evolving therapeutic strategies.
Synovial sarcoma (SS) is a rare and aggressive disease that accounts for 5%-10% of all soft tissue sarcomas. Although it can occur at any age, it typically affects younger adults and children, with a peak incidence in the fourth decade of life. In >95% of cases, the oncogenic driver is a translocation between chromosomes X and 18 that leads to the formation of the SS18::SSX fusion oncogenes. Early and accurate diagnosis is often a challenge; optimal outcomes are achieved by referral to a specialist center for diagnosis and management by a multidisciplinary team as soon as SS is suspected. Surgery with or without radiotherapy and/or chemotherapy can be effective in localized disease, especially in children. However, the prognosis in the advanced stages is poor, with treatment strategies that have relied heavily on traditional cytotoxic chemotherapies. Therefore, there is an unmet need for novel effective management strategies for advanced disease. An improved understanding of disease pathology and its molecular basis has paved the way for novel targeted agents and immunotherapies that are being investigated in clinical trials. This review provides an overview of the epidemiology and characteristics of SS in children and adults, as well as the patient journey from diagnosis to treatment. Current and future management strategies, focusing particularly on the potential of immunotherapies to improve clinical outcomes, are also summarized.


Jejunal intussusception due to malignant phyllodes tumor of the breast.
Phyllodes tumors are rare fibroepithelial neoplasms of the breast; classified as benign, borderline, or malignant based on the mitotic activity, cellular atypia, and stromal overgrowth. Wide surgical excision is the treatment of choice. The most common locations for metastasis are lung, bone, and liver; small intestinal metastasis is extremely rare. Here we present the first patient with jejunal metastases and intussusception due to malignant phyllodes tumor of the breast. Adjuvant treatment of malignant phyllodes tumor needs to be investigated.


CoCoPRED: coiled-coil protein structural feature prediction from amino acid sequence using deep neural networks.
Coiled-coil is composed of two or more helices that are wound around each other. It widely exists in proteins and has been discovered to play a variety of critical roles in biology processes. Generally, there are three types of structural features in coiled-coil: coiled-coil domain (CCD), oligomeric state and register. However, most of the existing computational tools only focus on one of them. Here, we describe a new deep learning model, CoCoPRED, which is based on convolutional layers, bidirectional long short-term memory, and attention mechanism. It has three networks, i.e. CCD network, oligomeric state network, and register network, corresponding to the three types of structural features in coiled-coil. This means CoCoPRED has the ability of fulfilling comprehensive prediction for coiled-coil proteins. Through the 5-fold cross-validation experiment, we demonstrate that CoCoPRED can achieve better performance than the state-of-the-art models on both CCD prediction and oligomeric state prediction. Further analysis suggests the CCD prediction may be a performance indicator of the oligomeric state prediction in CoCoPRED. The attention heads in CoCoPRED indicate that registers a, b and e are more crucial for the oligomeric state prediction. CoCoPRED is available at http://www.csbio.sjtu.edu.cn/bioinf/CoCoPRED. The datasets used in this research can also be downloaded from the website. Supplementary data are available at Bioinformatics online.


Circannual incidence of seizure evacuations from the Canadian Arctic.
Emerging evidence suggests that circadian rhythms affect seizure propensity in addition to, and possibly independent of, sleep-wake states. Subject to extreme seasonal changes in light and dark, the northerly Arctic can serve as a "natural experiment" to assess the real-life impact of environmental influences on seizure severity. Therefore, we evaluated the timing of seizure evacuations over 11.25 years in a well-defined region of the Canadian Arctic. Retrospective review of EEG database and patient records at the single "bottleneck" hospital to which all patients from the Kivalliq Region in Nunavut, Canada are evacuated for seizure emergencies. We calculated the mean resultant length (MRL) of circular data for circannual analysis, and conducted Rayleigh's test to assess for a statistical departure from circular uniformity. Screening 40,392 EEGs, we found 117 medical evacuations from 99 distinct individuals from September 2009 to November 2020. Most evacuations occurred month-wise in May (19%); week-wise within a 7-day period in February (5%), June (5%), or November (5%); and day-wise within a 24-hour period in June (3%) or November (3%). Maximal MRL clustering occurred in April no matter if analyzed by day (0.16333, p = 0.04), week (0.16296, p = 0.04), or month (0.1736, p = 0.03). A relative circannual increase in seizure evacuations between the winter and summer solstices may be related to increasing sleep loss when day length grows. Fewer evacuations between the summer and winter solstices may be related to decreased daylight and "catching up" on sleep when night length grows. Additional factors likely also play a role in circannual variation of seizure evacuations in the Arctic, which warrants further research.


Radical prostatectomy for stage D1 prostate cancer. Prognostic variables and results of treatment.
Surgical extirpation of the primary tumor together with the involved regional nodes has been considered ineffective treatment for locally disseminated prostatic carcinoma. We retrospectively reviewed our experience with 42 patients with Stage D1 disease who underwent radical prostatectomy and bilateral pelvic lymphadenectomy and who had a follow-up of one to thirteen years (mean 5 years). The following variables affecting survival and tumor progression were analyzed: (1) tumor grade and local extent; (2) number of positive lymph nodes, and (3) adjuvant therapy. The overall five- and ten-year survival was 79.5 per cent and 28 per cent compared with the expected survival of an age-matched control group of 88 per cent and 28 per cent, respectively. The degree of tumor differentiation had no effect on prognosis, but local tumor bulk and the number of involved lymph nodes significantly changed the disease progression and survival rate. Patients with low local tumor bulk and one positive node survived as long as the age-matched male population group. Our data suggest that radical prostatectomy may represent a valuable treatment in selected patients with Stage D1 prostate carcinoma.


Physical origin of selectivity in ionic channels of biological membranes.
This paper shows that the selectivity properties of monovalent cation channels found in biological membranes can originate simply from geometrical properties of the inner core of the channel without any critical contribution from electrostatic interactions between the permeating ions and charged or polar groups. By using well-known techniques of statistical mechanics, such as the Langevin equations and Kramer theory of reaction rates, a theoretical equation is provided relating the permeability ratio PB/PA between ions A and B to simple physical properties, such as channel geometry, thermodynamics of ion hydration, and electrostatic interactions between the ion and charged (or polar) groups. Diffusive corrections and recrossing rates are also considered and evaluated. It is shown that the selectivity found in usual K+, gramicidin, Na+, cyclic nucleotide gated, and end plate channels can be explained also in the absence of any charged or polar group. If these groups are present, they significantly change the permeability ratio only if the ion at the selectivity filter is in van der Waals contact with them, otherwise these groups simply affect the channel conductance, lowering the free energy barrier of the same amount for the two ions, thus explaining why single channel conductance, as it is experimentally observed, can be very different in channels sharing the same selectivity sequence. The proposed theory also provides an estimate of channel minimum radius for K+, gramicidin, Na+, and cyclic nucleotide gated channels.


Correction: Design of foldable, responsively drug-eluting polyacrylic intraocular lens bulk materials for prevention of postoperative complications.
Correction for 'Design of foldable, responsively drug-eluting polyacrylic intraocular lens bulk materials for prevention of postoperative complications' by Yueze Hong et al., J. Mater. Chem. B, 2022, DOI: https://doi.org/10.1039/d2tb01974d.


Field evaluation of commercial repellents against the floodwater mosquito Psorophora columbiae (Diptera: Culicidae) in St. Johns County, Florida.
Three plant-based repellents-REPEL LEMON Eucalyptus Insect Repellent Lotion (active ingredient [AI] 30% oil of eucalyptus), Bite Blocker Xtreme Sportsman Organic Insect Repellent ([AI] 3% soybean oil, 6% geranium oil, and 8% castor oil), and Bite Blocker BioUD Insect Repellent ([AI] 7.75% 2-undecanone)--were evaluated against OFF! ([AI] 15% N,N-diethyl-m-toluamide or N,N-diethyl-3-methyl-benzamide, also called DEET) at a field site in Elkton, FL, to determine the mean protection time provided against Psorophora columbiae (Dyar & Knab). These products provided different protection times against biting Ps. columbiae. REPEL provided the longest protection time (330 min) followed by Bite Blocker Xtreme Sportsman (163 min), Bite Blocker BioUD (140 min), and OFF! (130 min). This study provides the first information about plant-based insect repellent protection times against Ps. columbiae.


Transcriptome Analysis Reveals the Anti-Tumor Mechanism of Eucalyptol Treatment on Neuroblastoma Cell Line SH-SY5Y.
Eucalyptol (1.8-cineole), an active component in traditional Chinese medicine Artemisia argyi for moxibustion. Previous studies have shown that eucalyptol has anti-tumor effects on leukemia and colon cancer. Nonetheless, the effect and mechanism of eucalyptol on neuroblastoma remains unclear. In the present study, we intended to reveal the effect and mechanism of eucalyptol treatment on the neuroblastoma cell line SH-SY5Y through transcriptome analysis. In the group treated with eucalyptol, 566 brain genes were up-regulated, while 757 genes were down-regulated. GO function analysis showed that positive regulation of cell cycle was down-regulated in biological processes. Meanwhile, cancer-related pathways were identified in KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis, including pathways in cancer, PI3K-Akt signaling pathway, cAMP signaling pathway, TGF-beta signaling pathway, Hippo signaling pathway, p53 signaling pathway, and additional pathways. Furthermore, we found a key gene, such as MYC, by constructing a network of cancer related pathways with differentially expressed genes and transcription factor analysis. In conclusion, our research indicates that MYC might play a central role in the anit-tumor mechanisms of eucalyptol.


Adaptations for avian frugivory: assimilation efficiency and gut transit time of Manacus vitellinus and Pipra mentalis.
I examined the digestive physiology of two avian frugivores, the golden-collared manakin, Manacus vitellinus, and the red-capped manakin, Pipra mentalis, to discover how these birds extract energy from fruit. Using 14 species of fruit in the natural diet of manakins, I examined the assimilation of nutrients from fruit pulp, fruit passage rates, seed passage rates, and gut morphology. Fruits in the manakins' diets had high water content (average, 84%) and low nutrient concentrations (3 kJ/g wet pulp; 17 kJ/g dry pulp; 1% nitrogen/g dry pulp). Manacus and Pipra did not differ in the average assimilation of energy in fruit pulp (63%), although it varied from 37 to 84% depending on fruit species. Assimilation of total nonstructural carbohydrates in the fruit pulp was very high (86-98%) in both species. Gut evacuation was rapid; maximum transit time of a labeled fruit was 30 min. Seeds passed through the gut faster (Manacus: 15 min; Pipra: 12 min) than the accompanying fruit epidermis (both spp: 22 min). Manakins regurgitated large seeds (>5 mm diameter) in 7 to 9 min. Rapid gut passage time, high assimilation of nonstructural carbohydrates, and the selective regurgitation and rapid elimination of bulky seeds enable manakins to process a large volume of food per day. By increasing rates of fruit intake and gut passage, manakins can effectively increase total nutrient uptake. These adaptations of manakins are requisite for harvesting sufficient nutrients from fruit, due to its low nutrient density, high water content, and bulky seeds.


[Myxoma of the left atrium diagnosed by pathological examination of an embolism of the aortic bifurcation (author's transl)].
The case reported was a 69-year-old patient with a myxoma of the left atrium presenting as multiple emboli: acute ischaemia of the lower limbs preceded, three months before, by a spontaneously regressive right hemiplegia which, in view of the patient's age, was considered to be a simple manifestation of atherosclerosis. The diagnostic value of the echocardiogram in cases of systemic emboli of undetermined origin is stressed.


Visualization of Tunable Weyl Line in A-A Stacking Kagome Magnets.
Kagome magnets provide a fascinating platform for a plethora of topological quantum phenomena, in which the delicate interplay between frustrated crystal structure, magnetization, and spin-orbit coupling (SOC) can engender highly tunable topological states. Here, utilizing angle-resolved photoemission spectroscopy, the Weyl lines are directly visualized with strong out-of-plane dispersion in the A-A stacked kagome magnet GdMn6 Sn6 . Remarkably, the Weyl lines exhibit a strong magnetization-direction-tunable SOC gap and binding energy tunability after substituting Gd with Tb and Li, respectively. These results not only illustrate the magnetization direction and valence counting as efficient tuning knobs for realizing and controlling distinct 3D topological phases, but also demonstrate AMn6 Sn6 (A = rare earth, or Li, Mg, or Ca) as a versatile material family for exploring diverse emergent topological quantum responses.


A study on the intracellular transport of prothrombin, albumin and transferrin in rat.
The intracellular transport of prothrombin in rat has been studied and compared with the transport of albumin and transferrin. The proteins were immunoisolated from plasma samples after pulse labelling with [3H]leucine and the secretion kinetics were determined. The half-times for secretion (t1/2) were approx. 30, 53 and 75 min for albumin, prothrombin and transferrin, respectively, whereas the minimal transit time for prothrombin was approx. 30 min, and those for albumin and transferrin 15-20 min. After injection of vitamin K-1 into warfarin-treated rats, the accumulated prothrombin precursor was gamma-carboxylated and secreted with a t1/2 of 37 min. This indicates that the gamma-carboxylation of prothrombin in rough endoplasmic reticulum cannot account for the delay in the transport of prothrombin as compared to albumin. Comparison of the incorporation of [3H]leucine and [3H]glucosamine into plasma prothrombin and transferrin suggested that transferrin is secreted randomly from an intracellular pool, whereas prothrombin is transported in a more orderly sequence. Moreover, treatment of rough microsomes with 0.05% sodium deoxycholate indicated that prothrombin is more tightly associated with the membranes of rough endoplasmic reticulum than albumin and transferrin.


Low-prime perfusion circuit and autologous priming in CABG surgery on a Jehovah's Witness: a case report.
Cardiac surgery on Jehovah's Witnesses is a great challenge for the cardiothoracic surgery team and especially for the perfusionist. To reduce the risk of surgery in these patients, a very small extracorporeal circuit was designed to decrease the amount of priming volume and thereby the degree of hemodilution. A small bypass system was built, consisting of a 3/8-in. arterial line and a 3/8-in. venous line, a venous collapsible reservoir, a centrifugal pump, a hollow fiber oxygenator and a cell saver reservoir. The circuit priming volume was 650 ml. By using antegrade and retrograde autologous priming, the total amount of priming was reduced to +/-50 ml. Bypass time was 63 min with an average blood flow of 5300+/-114 ml/min and postmembrane pressures of 180+/-45 mmHg. Venous line pressure was monitored and kept between -8 and -20 mmHg with a mean arterial pressure (MAP) of 55+/-12.3 mmHg. The hematocrit before extracorporeal circulation (ECC) was 36%, per-ECC 35% and post-ECC 35%. On the fifth postoperative day, the hematocrit was 40%. The patient was discharged 7 days after surgery. A low-prime circuit, in combination with autologous priming, seems to be safe and effective in avoiding the use of banked blood.


Long-term clinical results after combined aortic and mitral valve replacement.
The results after 282 consecutive double (aortic & mitral) valve replacements (DVR) are compared with our previously reported experience after mitral (MVR, n = 810) and aortic valve replacement (AVR, n = 1753). All but one patient received Björk-Shiley valves. The follow-up which closed on August 1, 1985 was 99.3% and covered 16,869 patient-years (mean 6.3 years/patient). Autopsies were performed in 74% of all fatalities. Early mortality rates were identical in the three patient groups, and late mortality did not differ between MVR and DVR patients. The fraction of valve-related mortality was similar in all groups. Anticoagulant-related bleeding was equally common in all patient groups. The incidences of thromboembolism, reoperation and valve failure did not differ between MVR and DVR patients, but were significantly higher than among AVR patients. With the exception of a slightly increased incidence of prosthetic valve endocarditis, the results after DVR equal those after MVR. In cases with severe mitral valve disease but borderline aortic valve disease, primary DVR is clearly justified and eliminates the need for, and risks of, a secondary AVR.


Ageing of silorane-based and methacrylate-based composite resins: effects on translucency.
Verify if media and time of storage affect the translucency of a silorane-based composite (Filtek P90) compared to two methacrylate-based composites (Z350 and ROK), and compare two methods of translucency evaluation. Specimens were divided into two groups (n=7) according to the storage media (deionized water or red wine). With a spectrophotometer (SP60) in reflectance mode, the CIE L*a*b* parameters and opacity percentage readings were conducted at baseline, 24h, 30 days, and 180 days. Data were analyzed using two-way repeated measures ANOVA and Tukey (p<0.05). Pearson correlation measured the relationship between translucency parameter and opacity percentage. When stored in water, P90 showed an increase, whereas Z350 decreased in translucency. ROK did not exhibit any tendency over time. When stored in wine, the translucency of all materials decreased. A negative relationship was found between translucency parameter and opacity percentage. When stored in water, the a* values for P90 decreased, whereas Z350 and ROK showed values increasing over time. When stored in wine, the L* parameter tended to decrease over time, an effect that was less intense for P90. Moreover, the b* parameter for P90 decreased, whereas methacrylate-based composites increased over time. P90 was more stable in red wine than the other materials and became more translucent in water whether metacrilate-based materials became more opaque. Both media as well as storage time affected the translucency of the materials tested. Translucency could be measured with both methods tested. Silorane-based composites seemed to be more stable than methacrylate-based composites in red wine and became more translucent over time in water, which was different than methacrylate-based composites. More studies are needed to clarify silorane-based composites performance.


IL3 SNP rs40401 variant is a risk factor for rhinoconjunctivitis in Japanese women: the Kyushu Okinawa maternal and child health study.
No studies have investigated the relationship between IL3 single nucleotide polymorphism (SNP) rs40401 and allergic rhinitis. We performed a case-control study to examine this issue and to assess interactions between the SNP and smoking or older siblings in young adult Japanese women. Included were 393 women who met the criteria of the International Study of Asthma and Allergies in Childhood (ISAAC) for rhinoconjunctivitis. Controls were 767 women without rhinoconjunctivitis according to the ISAAC criteria who had not been diagnosed with allergic rhinitis by a doctor. Compared with women with the TT genotype of SNP rs40401, those with the CC genotype had a significantly increased risk of rhinoconjunctivitis: the adjusted OR was 1.52 (95% CI: 1.05-2.19). This positive relationship was significant under the additive model: the adjusted OR was 1.23 (95% CI: 1.02-1.47). The positive association fell just short of the significance level under the dominant or recessive model. There was no significant interaction between SNP rs40401 and smoking with respect to rhinoconjunctivitis. Compared with subjects with the TT or TC genotype of IL3 SNP rs40401 who had one or more older siblings, those with the CC genotype who had no older siblings had a 2.33-fold increased risk of rhinoconjunctivitis; nevertheless, the interaction was not significant. This is the first study to show a significant positive association between IL3 SNP rs40401 variant and the risk of rhinoconjunctivitis. We could not find evidence for interactions between SNP rs40401 and smoking or older siblings affecting rhinoconjunctivitis.


Fetal acoustic stimulation in early labor in patients screened with the admission test.
Fetal heart rate reactions to the fetal acoustic stimulation test were investigated in 952 women in early labor. All had cephalic presentations (greater than 33 weeks of gestation) and were screened with a 15-minute fetal heart rate recording (admission test) before the sound stimulation was applied. Three different types of responses were observed: type I, an accelerative response; type II, a biphasic response with acceleration(s) followed by a deceleration; type III, no response or a prolonged deceleration (greater than 60 beats/min and greater than 60 seconds). A type I response was recorded in 98.0% of the women after a reactive admission test result, in 90.2% after an equivocal admission test result, and in 42.9% after an ominous admission test result. Fetal distress in labor occurred in these three groups in 2.0%, 22.2%, and 35.7% of cases, respectively. The risk for fetal distress was high after an ominous admission test and a type III response on the fetal acoustic stimulation test (75.0%). The fetal acoustic stimulation test might be of value in labor and give additional information about fetal well-being in patients previously screened by the admission test. Testing time can be shortened after an equivocal admission test.


A new sensor for the rapid electrochemical detection of ractopamine in meats with high sensitivity.
In this research, g-C3N4/Cu@CoO/NC, which contained graphitic phase carbon nitride (g-C3N4) with a binary nanostructure and Cu@CoO/NC with a bimetallic MOF precursor, was constructed by a low-temperature pyrolysis process. The g-C3N4/Cu@CoO/NC was characterised by several techniques, including X-ray diffraction, scanning electron microscope, transmission electron microscope and X-ray photoelectron spectroscopy. Further, it was used to prepare an electrochemical sensor for the detection of ractopamine (RAC) in meat samples. The sensor showed excellent electrochemical oxidation characteristics for RAC detection, with a wide linear range (0.005 μmol/L to 32.73 μmol/L) and low detection limit (1.53 nmol/L). Meanwhile, the reproducibility, stability and interference of the g-C3N4/Cu@CoO/NC/GCE sensor were found to be excellent. Besides, the g-C3N4/Cu@CoO/NC/GCE sensor was well-used for the detection of RAC in pork, pig liver and lamb samples with recovery rates ranging from 96.5 % to 102.2 %.


[Expression and purification of T7 bacteriophage capsid protein P11 and preparation of monoclonal antibody against P11].
To express capsid tail protein P11 of T7 bacteriophage and produce mouse monoclonal antibody(mAb) against the protein. P11 protein was cloned and recombinant P11 protein was expressed as a fusion protein with an N-terminal 6-His tag. The purified protein was used to immunize BALB/c mouse. The specificity of mAb was analyzed by ELISA and Western blot. P11 protein was successfully expressed and purified. SDS-PAGE analysis showed that the molecular weight of the expressed protein was approximately 27 kd. One hybridoma cell (2G11) secreting mAb against P11 was developed. The isotype of the mAb was IgG(2b). ELISA detection showed that titers of mAb was 1:8. 1 x 10(5) in ascites.Western blot analysis proved mAb obtained could react specifically to the recombinant p11 protein. Recombinant P11 protein and mAbs were successfully prepared.


Community involvement in coastal infrastructure adaptation should balance necessary complexity and perceived effort.
Successful adaptation of coastal infrastructure requires public participation, and it is important to elicit accurate feedback from surveys and in-person interactions. But there remains a need for evidence about the efficacy of potential risk communication design metrics. This online experiment (n = 261) sought to understand the necessity of a multifaceted risk perception questionnaire to capture public input. Using six coastal infrastructure examples, risk perceptions were collected using a questionnaire highlighting multiple types of risk (intervention) or not (control). Public evaluations of risk did not differ in most cases. Moreover, the intervention imposed more cognitive strain on participants, which could unintentionally discourage public participation in the climate adaptation process. In this case, the single question provides the same input, with less effort. This finding is a reminder that effective risk communication for managing adaptation processes requires considering both the quality of public input and the effort required to provide it.


Discovering cell-active BCL6 inhibitors: effectively combining biochemical HTS with multiple biophysical techniques, X-ray crystallography and cell-based assays.
By suppressing gene transcription through the recruitment of corepressor proteins, B-cell lymphoma 6 (BCL6) protein controls a transcriptional network required for the formation and maintenance of B-cell germinal centres. As BCL6 deregulation is implicated in the development of Diffuse Large B-Cell Lymphoma, we sought to discover novel small molecule inhibitors that disrupt the BCL6-corepressor protein-protein interaction (PPI). Here we report our hit finding and compound optimisation strategies, which provide insight into the multi-faceted orthogonal approaches that are needed to tackle this challenging PPI with small molecule inhibitors. Using a 1536-well plate fluorescence polarisation high throughput screen we identified multiple hit series, which were followed up by hit confirmation using a thermal shift assay, surface plasmon resonance and ligand-observed NMR. We determined X-ray structures of BCL6 bound to compounds from nine different series, enabling a structure-based drug design approach to improve their weak biochemical potency. We developed a time-resolved fluorescence energy transfer biochemical assay and a nano bioluminescence resonance energy transfer cellular assay to monitor cellular activity during compound optimisation. This workflow led to the discovery of novel inhibitors with respective biochemical and cellular potencies (IC50s) in the sub-micromolar and low micromolar range.


On scales of measurement in Autism Spectrum Disorders (ASD) and beyond: where Smitty went wrong.
The author examined critically three beliefs of S.S. Stevens pertaining to his quadripartite system of scales of measurement: (1) There are four scales of measurement in common usage (2) These scales and the scientific disciplines that use them can be incrementally graded for levels of reliability and validity or accuracy such that: Nominal scale variables produce the lowest levels of reliability and accuracy; with successively improving levels for Ordinal, Equal Interval, and Equal Ratio scales; and (3) The scale upon which a variable is measured determines the type of statistical test that one is permitted to apply. It was shown that each of the three beliefs is fundamentally flawed.


Stochastic models and fluctuations in reversal time of ambiguous figures.
Five probability distributions for the description of temporal fluctuations in the perception of ambiguous figures were fitted to previously obtained experimental results and classified according to their efficiency in describing the data. The gamma, Wiener, and Capocelli-Riciardi distributions showed the highest efficiency, while the chi2 and Taylor-Aldridge distributions showed a very low effiency. Therefore the underlying process may be described either by a simple Poisson model or by a random-walk model. For the gamma distribution there was a strong correlation between the parameters, while for the Wiener distribution this correlation was lower.


Systemic microdystrophin gene delivery improves skeletal muscle structure and function in old dystrophic mdx mice.
Restoring dystrophin expression in the muscles of patients with Duchenne muscular dystrophy (DMD) may halt or reverse the degenerative wasting and weakness that causes premature death. However, the therapeutic efficacy of an intervention may be limited by the extent of disease progression prior to treatment. In this study, we considered the potential for ameliorating the pathology in a mouse model of advanced-stage muscular dystrophy by systemic administration of recombinant adeno-associated viral (rAAV6) vectors encoding a microdystrophin expression construct. The treatment of 20-month-old mdx mice restored body-wide expression of a dystrophin-based protein in striated musculature. In aged mice that received treatment, the resultant dystrophin expression was associated with improved hindlimb and respiratory muscle morphology and function, concomitant with reduced muscle fiber degeneration. The findings demonstrate that an established dystrophic state remains amenable to improvement with appropriate intervention and, by some measures, may even achieve benefits similar to those observed with intervention early in disease progression. The capacity to ameliorate the pathology in an animal model of advanced-stage muscular dystrophy suggests that interventions ultimately proven to exert a therapeutic effect in young patients may offer benefits to older patients or those with advanced conditions of progressive muscular dystrophy.


Benign mixed tumor of the palpebral lobe of the lacrimal gland. Clinical diagnosis and appropriate surgical management.
The treatment of suspected benign mixed tumor (pleomorphic adenoma) of the lacrimal gland consists of wide local surgical excision of the tumor and its capsule in their entirety. The tumor should be approached routinely via a lateral orbitotomy to provide maximal exposure and allow complete removal of the lesion. However, if clinical and radiographic evidence indicates a far anterior location implying an origin in the more superficial palpebral lobe, an anterior transcutaneous approach is advantageous and preferred. The authors report an adult case of an anteriorly located benign mixed tumor of the palpebral lobe of the lacrimal gland. The authors reviewed the characteristic clinical, echographic, and computed tomographic (CT) features, offered a differential diagnosis, and described surgical removal using a cryoprobe via an anterior lid approach. An awareness of the distinctive clinical and diagnostic features of benign mixed tumor of the palpebral lobe should help to avoid the complications that ensue from an incisional biopsy or piecemeal resection through the lid, and also to avoid the need for more extensive surgery for removal of residual or recurrent tumor.


Bacterial classification using genomic fingerprints obtained by virtual hybridization.
In silico genomic fingerprints were produced by virtual hybridization of 191 fully sequenced bacterial genomes using a set of 15,264 13-mer probes specially designed to produce universal whole genome fingerprints. A novel approach for constructing phylogenetic trees, based on comparative analysis of genomic fingerprints, was developed. The resultant bacterial phylogenetic tree had strong similarities to those produced from the alignment of conserved sequences. Notably, the trees derived from the alignment of other conserved COG genes divided the Bacillus and Corynebacterium genera into the same subgroups produced by the novel bacterial tree. A number of discrepancies between both techniques were observed for the grouping of some Lactobacillus species. However, a detailed analysis of the alignment of these genomes using other bioinformatics tools revealed that the grouping of these organisms in the novel tree was more satisfactory than the groupings from previous classifications, which used only a few conserved genes. All these data suggest that the bacterial taxonomy produced by genomic fingerprints is satisfactory, but sometimes different from classical taxonomies. Discrepancies probably arise because the fingerprinting technique analyzes genomic sequences and reveals more information than previously used approaches.


Amplification of N-myc oncogene in stage II and IVS neuroblastomas may be a prognostic indicator.
The amplification of N-myc oncogene is frequently observed in tumors of patients with advanced, poor prognostic stages of neuroblastoma (unfavorable stage group). However, there has been little documentation of the N-myc amplification in tumors of patients with stages II and IVS neuroblastoma (favorable stage group). In this communication, we present data on one patient in stage II and two in stage IVS. In these children, the primary tumors had an amplified N-myc and the clinical course was poor. In addition, from an analysis of the N-myc oncogene of 26 neuroblastomas, genomic amplification of more than three copies was observed in 4 of 11 (36%) in the favorable stage group, and in 9 of 15 (60%) in the unfavorable stage group. Death occurred only in those with an amplified N-myc, in both groups. The smaller copy number of N-myc amplification of stage IVS tumors as compared with those of stages III and IV, appeared to be characteristic. These findings suggest that N-myc amplification may be a reliable prognostic indicator even in the favorable stage group of neuroblastomas, and may be clinically useful as a guide for treating those with a poor prognosis in stages II and IVS.


Umbilical choline and related methylamines betaine and dimethylglycine in relation to birth weight.
Low birth weight (LBW) is associated with increased morbidity and mortality for the newborn and risk of chronic disease in adulthood. Choline plays an essential role in the integrity of cell membranes, methylation reactions, and memory development. We examined whether choline, betaine, and dimethylglycine (DMG) concentrations were associated with LBW in Dutch women. Blood was sampled from umbilical cords (UCs) at delivery in singleton pregnancies (n = 1,126). Maternal blood was sampled at 30-34 wk of gestational age (GA) (n = 366). We calculated birth weights standardized for GA and defined LBW as standardized birth weight ≤ 2,500 g. Maternal concentrations were lower as compared with UC concentrations and were not associated with birth weight. UC choline and betaine were inversely associated with birth weight (β = -60 (-89, -31) and β = -65 (-94, -36), respectively), whereas UC DMG was positively associated with birth weight (β = 35 (6.1, 63)). Odds ratios for LBW were 4.12 (1.15, 14.78), 5.68 (1.24, 25.91), and 0.48 (0.09, 2.65) for the highest UC choline, betaine, and DMG quartiles, respectively, as compared with the lowest quartiles. We observed an increased risk of LBW with increased umbilical choline and betaine in venous UC blood. These results might reflect a change in choline consumption or metabolism or a disturbed placental function.


Risk factors associated with mortality in patients infected with influenza A/H1N1 in Mexico.
Influenza virus pandemics vary dramatically in their severity and mortality. Thus, it is very important to identify populations with high risks of developing severe illness to reduce mortality in future pandemics. The purpose was to determine the mortality-associated risk factors in hospitalized Mexican patients infected with influenza A/H1N1. The risk factors associated with mortality were: male sex [odds ratio (OR) = 5.25, confidence interval (CI) = 1.22-28.95], medical attention delayed >3 days (OR = 9.9, CI = 1.51-64.52), anti-flu therapy delayed >3 days (OR = 10.0, CI = 1.07-93.43), admission to intensive care unit (ICU) (OR = 9.9, CI = 1.51-64.52) and creatinine levels >1.0 mg/dL when admitted to hospital (OR = 11.2, CI = 1.05-120.32). After adjusting for the effects of potentially confounding variables in a logistic regression model, delayed medical attention (OR = 13.91, CI = 1.09-41.42, p = 0.044) and ICU hospitalization (OR = 11.02, CI = 1.59-76.25, p = 0.015) were the only predictors of mortality. Early medical attention is essential for reducing the mortality risk in patients with influenza A/H1N1, while a requirement for ICU management increases the risk.


Structure of a protein G helix variant suggests the importance of helix propensity and helix dipole interactions in protein design.
Six helix surface positions of protein G (Gbeta1) were redesigned using a computational protein design algorithm, resulting in the five fold mutant Gbeta1m2. Gbeta1m2 is well folded with a circular dichroism spectrum nearly identical to that of Gbeta1, and a melting temperature of 91 degrees C, approximately 6 degrees C higher than that of Gbeta1. The crystal structure of Gbeta1m2 was solved to 2.0 A resolution by molecular replacement. The absence of hydrogen bond or salt bridge interactions between the designed residues in Gbeta1m2 suggests that the increased stability of Gbeta1m2 is due to increased helix propensity and more favorable helix dipole interactions.


AChE for DNA degradation.
DNA hydrolysis is a biochemical process often associated with different forms of cell death, including apoptosis. In a recent paper published in Cell Discovery, Du et al. report that synaptic acetylcholinesterase (AChE-S) shows an unexpected enzymatic activity as DNase switched on after cytotoxic insults.


Variation in apparent diffusion coefficient measurements among women with locally advanced cervical cancer.
ADC variability from mixed data sets acquired from women with locally advanced cervical cancer appears to be predominantly of biologic origin. Intra-histology ADC variance was similar when pooled across technical factors. Inter-histology pooling increased ADC variance. Normalization to urine ADC improved intra-histology variance and receiver-operator curve test performance.


Effects of deuterium oxide and temperature on heart rate in Drosophila melanogaster.
A non-intrusive optical technique has been developed to monitor heartbeat in late third-instar Drosophila larvae. Heartbeat in this insect is an oscillation that is not temperature compensated. Deuterium oxide lengthens the period of a number of high and low frequency oscillators and clocks in a variety of organisms. To determine whether deuterium affects heart rate, flies were raised on proteated and deuterated media and their heartbeat was monitored at four temperatures ranging from 18 to 33 degrees C. The rate of heartbeat increased linearly with increasing temperature, and decreased with increasing concentrations of deuterium. There was a significant interaction between temperature and deuterium: the higher the concentration of deuterium oxide the less temperature-sensitive was the heart rate. Raising temperatures also increased the amount of "noise" in the rhythm: signal-to-noise ratio, which characterizes the amount of power in a rhythmic signal, decreased with increasing temperatures. Deuterium oxide had no effect on signal-to-noise ratio.


Reversed-phase liquid chromatographic purification and isolation of a radio-iodinated selective probe for mu opioid receptors in the brain.
A Guard-PAK precolumn system was used for the reversed-phase liquid chromatography purification of a small, synthetic radiolabeled opioid peptide, FK 33-824 (D-Ala2, methyl-phe4, Met (O)ol5 enkephalin) (FK). This procedure involves trace enrichment of iodinated peptide onto the precolumn while iodination reagents are not retained. Radioactive contamination of high-performance liquid chromatography columns and injectors is thus avoided. Precolumn chromatography has sufficient resolving power to separate not only labeled from unlabeled peptide but also mono- from di-iodinated peptide. Purified 125I-labeled FK (estimated specific activity 85.9-153.7 Ci/mmol) showed high specific binding to mouse corpus striatum, neocortex, cingulate cortex, nucleus accumbens septi, diagonal band of Broca, nucleus medialis septi, area preopticus magnocellularis, and the nucleus of the caudate/putamen. Radioligand binding was inhibited by both antagonists (naloxone and naltrexone); and agonists D-Ala2, N-methyl-phe4, gly-ol5-enkephalin [DAGO]; FK; and beta-endorphin at all concentrations tested (1 x 10(-8) to 1 x 10(-4) M). Adrenocorticotropin hormone (ACTH) did not block ligand binding at any concentration tested. Distribution of mu opioid receptors was analyzed by light microscopic autoradiography. Sections incubated with 125I-labeled FK in the presence of agonists and antagonists demonstrated decreasing ligand binding with increasing doses of competitor. ACTH did not block ligand binding at any concentration tested. HPLC analyses of ligand which had been iodinated 1.5 half lives before the date of the experiment demonstrated a single peak similar to that of freshly iodinated ligand. Similar binding kinetics and autoradiographic labeling patterns were observed as compared to those obtained with freshly iodinated peptide.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of Luteolin on DNA damage mediated by a copper catalyzed Fenton reaction.
Luteolin has been reviewed as a flavonoid possessing potential cardioprotective, anti-inflammatory, anti-cancer activities. Having multiple biological effects, luteolin may act as either an antioxidant or a pro-oxidant. In this work, the protective role of copper(II)-chelation by luteolin on DNA damage via the Cu-Fenton reaction was studied. EPR and UV-vis spectroscopic data demonstrated that the luteolin, lacking 3-OH group, chelates to Cu(II) via the 5-OH and 4-CO groups, respectively. EPR spin trapping experiments using DMPO spin trap confirmed that the coordination of luteolin to Cu(II) significantly suppressed formation of hydroxyl and superoxide radicals (by 80%) in a Cu-Fenton system. Absorption titrations showed that the chelation of Cu(II) by luteolin slightly increased the mild intercalation strength of its interaction with DNA, as compared with free luteolin. Comparison with kaempferol and quercetin revealed, that the strength of the interaction between the free flavonoids/Cu-flavonoid complexes with DNA is only mildly affected by the presence/absence of 3-OH group. Due to the differences in the sensitivities of absorption titrations and viscometry, the latter confirmed weaker DNA intercalating efficiency of Cu-luteolin complex than does free luteolin. A dose dependent protective effect of luteolin against ROS-induced DNA damage was observed using gel electrophoresis. This effect was more pronounced compared to quercetin and kaempferol. In conclusion, the administration of luteolin to patients suffering from oxidative stress-related diseases with disturbed Cu-metabolism such as Alzheimer's diseases (antioxidant effect) and certain cancers (prooxidant effect) may have several health benefits.


Controversies in rheumatology: ultrasound for monitoring of RA-do we need it?
Clinical joint examination is the cornerstone for evaluation of patients with RA. However, since large discrepancies have been shown even between experienced rheumatologists in evaluation of joint inflammation, and tender joints may have limited value in reflecting inflammation, US has in recent decades been introduced in the clinical assessments of RA patients. US has high accordance with other imaging modalities and enables detection of clinically difficult pathologies and contributes to assessments of joints difficult to evaluate clinically. However, there is no general agreement on the optimal use of US in rheumatology, and the prevalence of machines as well as the level of experience differs greatly between countries. In addition, standardized use of US in treat-to-target follow-up of RA patients was found not to have any added value. Thus, how to use US in monitoring of RA patients is open for debate. The present article will discuss the pros and cons for using US in the clinical setting.


Prosociality and religion: History and experimentation.
Norenzayan et al. are praised for choosing to deal with significant questions in the understanding of religion. They are then criticized for refusing to define religion and for relying on problematic theoretical concepts. The authors discuss Abrahamic religions as the best-known prosocial religions, but the evidence shows that the case does not fit their conceptual framework. Finally, an extension of the authors' ideas about the meaning of priming effects is proposed.


Expanding the application of photoelectro-Fenton treatment to urban wastewater using the Fe(III)-EDDS complex.
This work reports the first investigation on the use of EDDS as chelating agent in photoelectro-Fenton (PEF) treatment of water at near-neutral pH. As a case study, the removal of the antidepressant fluoxetine was optimized, using an electrochemical cell composed of an IrO2-based anode an air-diffusion cathode for in-situ H2O2 production. Electrolytic trials at constant current were made in ultrapure water with different electrolytes, as well as in urban wastewater (secondary effluent) at pH 7.2. PEF with Fe(III)-EDDS (1:1) complex as catalyst outperformed electro-Fenton and PEF processes with uncomplexed Fe(II) or Fe(III). This can be explained by: (i) the larger solubilization of iron ions during the trials, favoring the production of •OH from Fenton-like reactions between H2O2 and Fe(II)-EDDS or Fe(III)-EDDS, and (ii) the occurrence of Fe(II) regeneration from Fe(III)-EDDS photoreduction, which was more efficient than conventional photo-Fenton reaction with uncomplexed Fe(III). The greatest drug concentration decays were achieved at low pH, using only 0.10 mM Fe(III)-EDDS, although complete removal in wastewater was feasible only with 0.20 mM Fe(III)-EDDS due to the greater formation of •OH. The effect of the applied current and anode nature was rather insignificant. A progressive destruction of the catalytic complex was unveiled, whereupon the mineralization mainly progressed thanks to the action of •OH adsorbed on the anode surface. Despite the incomplete mineralization using BDD as the anode, a remarkable toxicity decrease was determined. Fluoxetine degradation yielded F- and NO3- ions, along with several aromatic intermediates. These included two chloro-organics, as a result of the anodic oxidation of Cl- to active chlorine. A detailed mechanism for the Fe(III)-EDDS-catalyzed PEF treatment of fluoxetine in urban wastewater is finally proposed.


Structure-activity relationships of 2-, 4-, or 6-substituted estrogens as aromatase inhibitors.
Aromatase, which is responsible for the conversion of androgens to estrogens, is a potential therapeutic target for the selective lowering of estrogen levels in patients with estrogen-dependent breast cancer. To develop a novel class of aromatase inhibitors, we tested series of 2- and 4-substituted (halogeno, methyl, formyl, methoxy, nitro, and amino) estrones (7 and 9), as well as series of 6alpha- and 6beta-substituted (alkyl, phenalkyl, and alkoxy) estrones (13 and 14), and their estradiol analogs (8, 10, 11, and 12) as aromatase inhibitors. All of the inhibitors examined blocked the androstenedione aromatization in a competitive manner. Introduction of halogeno and methyl functions at C-2 of estrone as well as that of a phenalkyl or methyl function at the C-6alpha or C-6beta position markedly increased affinity to aromatase (apparent K(i) value=0.10-0.66 microM for the inhibitors versus 2.5 microM for estrone). 6alpha-Phenylestrone (13c) was the most powerful inhibitor among the estrogens studied, and its affinity was comparable to that of the androgen substrate androstenedione. Estradiol analogs were much weaker inhibitors than the corresponding estrone compounds in each series, indicating that the 17-carbonyl group plays a critical role in the formation of a thermodynamically stable enzyme-inhibitor complex.


Sucrose or honey at breakfast have no additional acute hyperglycaemic effect over an isoglucidic amount of bread in type 2 diabetic patients.
Exclusion of simple sugars from the diabetic diet is not always followed by patients and may not even be as crucial as was hitherto thought. We tested three types of mixed breakfasts (400 kcal, 50 g HCO) including an isoglucidic amount either of white bread (30 g), honey (20 g) or sucrose (15 g), at the critical morning period i.e. for breakfast, in a group of 21 Type 2 (non-insulin-dependent) diabetic patients (6 well- and 15 badly controlled). Mean plasma glucose and insulin levels were comparable on the three occasions: respectively with bread, sucrose and honey, peak glucose values were 18 mmol/l, 17.7 mmol/l and 17.5 mmol/l in the uncontrolled group versus 13.9 mmol/l, 12.8 mmol/l and 12.7 mmol/l in the well-controlled group. Peak insulin values were 33.6 mU/1,34.0 mU/l and 36.3 mU/l (p greater than 0.05) in uncontrolled patients against 57.5 mU/l, 54.8 mU/l and 52.5 mU/l in well-controlled subjects (p greater than 0.05). The mean increment in peak plasma glucose values for the three breakfasts was as follows: 6.9 mmol/l, 6.3 mmol/l and 6.2 mmol/l for the uncontrolled group against 7.2 mmol/l, 5.9 mmol/l and 6.2 mmol/l in well-controlled subjects; the mean increment in peak plasma insulin levels was 21.8 mU/l,22.0 mU/l and 24.2 mU/l in the controlled group versus 38.2 mU/l, 32.0 mU/l and 34.7 mU/l in the well-controlled subjects, all values being non-significantly different (p greater than 0.05). We conclude that, in acute conditions, simple sugars have no additional hyperglycaemic effect over an isoglucidic amount of bread in well-and in badly controlled Type 2 diabetic patients, even at breakfast.


Variation in the length of the lag phase following serum restimulation of mouse 3T3 cells.
We have investigated the length of the lag phase (time taken for the first cells to enter S phase) and the kinetics of entry into DNA synthesis after serum restimulation of Swiss mouse 3T3 cell cultures that were allowed to become quiescent under different conditions. Cells were allowed to reach quiescence as a confluent monolayer in medium containing 10% (v/v) calf serum. Alternatively, when serum was reduced to 1% (v/v), cultures became quiescent at about 30% confluency and there was little cell to cell contact. The results show that the lag, or prereplicative phase becomes longer as the time spent in the quiescent state increases. This is the case in both confluent and non-confluent cultures. The rate of entry of cells into the S phase, however, remains the same under all conditions.


The prediction of mercury bioavailability for common carp (Cyprinus carpio L.) using the DGT technique in the presence of chloride ions and humic acid.
The ability of the DGT technique to predict Hg2+ bioavailability for input tissues (skin, gills, and scales) of common carp in the presence of chloride ions and humic acid (HA) was evaluated. The mercury accumulation by the DGT units and input tissues of carp decreased with an increasing concentration of chloride ions (29-180 mg L-1) and HA (0-5 mg L-1). In the presence of chloride ions and HA, statistically significant correlations (Pearson's correlation coefficients 0.731-0.954) were determined between the rate of mercury accumulation by input tissues of carp and the rate of mercury accumulation by the DGT units. The laboratory experiments suggest the possibility of using the DGT technique for predicting the mercury bioaccumulation in natural aquatic ecosystems instead of commonly used input tissues of fish.


Comparative Assessment of Grit, Conscientiousness, and Self-Control in Applicants Interviewing for Residency Positions and Current Orthopaedic Surgery Residents.
The purpose of this study was to quantify grit, conscientiousness, and self-control in orthopaedic residency applicants and current orthopaedic surgery residents. As part of a continual reassessment of the selection process, this study will help to improve this process by assessing the introduction of these non-cognitive assessments. This is the first study to both evaluate and compare the applicants' scores to those of current residents. This introduction will allow selection of not only the current top performers but those who have the wherewithal (read grit) to sustain their efforts throughout their residency. A cross-sectional study composed of a confidential electronic survey consisting of a 17-item Grit scale, 10-item Self-control scale, and 9-item Conscientiousness scale was completed by medical school applicants and orthopaedic residents. Department of Orthopaedic Surgery, Hospital for Special Surgery. Fifty-six (100%) medical student applicants (mean age = 27) were invited to participate in our study following a full day of interviews. Forty-five residents (mean age = 31) were asked and 32 (72%) completed the same surveys 4 months later. There was a significant difference in grit for medical students (M = 4.19, SD = 0.34) and residents (M =3.86, SD = 0.48); t(86) = 3.76, p = 0.000. All grit subscales were also significantly different for medical students versus residents. Medical students (conscientiousness M = 4.60, SD = 0.41; self-control M = 3.51, SD = 0.30) and residents (conscientiousness M = 4.42, SD = 0.53; self-control M = 3.31, SD = 0.73) scored similarly in the conscientiousness t(86) = 1.75, p = 0.084 and self-control scales t(86) = 1.74, p = 0.086. Academic performance indicators such as the USMLE scores and residency ranking were also compared among medical student applicants. The similar and above average levels of conscientiousness and self-control demonstrate the persevering nature of the individual who elects to pursue an orthopaedic residency program. Although the grit levels were different between medical school student and residents, they were above average for both groups, again demonstrating the type of individual willing to pursue an orthopaedic residency program. This study was the first to demonstrate varying degrees of grit for high-performing students versus residents in a competitive program, which seems to suggest that grit can vary over time. Future studies will investigate the validity of these non-cognitive variables in predicting achievement prospectively in a residency program.


Lecithin can be detected by volume-selected proton MR spectroscopy using a 1.5 T whole body scanner: a potentially non-invasive method for the prenatal assessment of fetal lung maturity.
The prenatal determination of fetal lung maturity is currently assessed by chemical analysis of surfactant associated lipids from aminotic fluid obtained by amniocentesis. This is an invasive procedure with rare but occasionally serious morbidity. Magnetic resonance spectroscopy (MRS) is a non-invasive method for the in vivo localization and identification of molecules with known resonance peaks at specified chemical shifts. In this report we examine the in vitro MRS of a lecithin/saline solution as well as term and preterm amniotic fluid samples with the use of a 1.5 T whole body scanner and a flexible surface coil. We found that amniotic fluid at term demonstrates a resonance peak at 3.2 ppm which was the same as the chemical shift of lecithin in saline. The lecithin peak is not observed in preterm amniotic fluid. This demonstrates the feasibility of using MRS with a whole body scanner to detect lecithin, one of the markers for fetal lung maturity.


Female-to-Male Sexual Assault: The Role of the Perpetrator's Attractiveness and Attributed Emotional States on Victim Blame.
This study investigated the effect of the victim's gender and the perpetrator's attractiveness on the observer's blame on the male and female victims of coercive sexual contact. Two hundred and ninety-six participants (184 females) were enrolled in an experiment in which the victim's gender and the offender's attractiveness were manipulated using vignettes depicting cross-gender sexual assault. Participants rated emotions that the victims experienced in being assaulted and attributed victim blame. The results indicate that the male victim was blamed more than the female victim, especially when the female perpetrator was described as attractive. The female victim was perceived as having experienced more negative emotions and fewer positive emotions than the male victim. The effect of the victim's gender on victim blaming was mediated by both positive and negative emotions.


Efficacy of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine and 9-(1,3-dihydroxy-2-propoxymethyl)guanine for the treatment of murine cytomegalovirus infection in severe combined immunodeficiency mice.
Mice with severe combined immunodeficiency (SCID) inoculated intraperitoneally with murine cytomegalovirus (MCMV) develop a wasting syndrome at 3-4 days and die at 6-9 days after the infection. 9-(1,3-Dihydroxy-2-propoxymethyl)guanine (DHPG, ganciclovir) and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) were compared for their efficacy against MCMV-induced disease and mortality in SCID mice. Under all treatment conditions, i.e., administration of the test compounds for 5 consecutive days starting on the day of infection (day 0), for 5 consecutive days starting on day 4 after the infection, 2 periods of 3 consecutive days starting on day 0 and day 9 after infection, or as a single dose on day 3 before infection, HPMPC proved far superior to ganciclovir in delaying the onset of the disease and increasing the lifespan of the MCMV-infected mice.


Introduction to the modelling of venereal disease.
The continually rising trend in the incidence of venereal diseases, especially gonorrhoea, in a large number of countries, both developed and developing is causing considerable public health concern. There is a disquieting volume of human suffering involved, as well as large economic losses in treatment and hospitalization. The present paper reviews the existing state of development in the mathematical modelling of the relevant disease dynamics. The 'criss-cross' nature of the infections, which in heterosexual contacts switch between the male and female populations, together with the nonlinear form of the rate of spread normally occurring in infectious diseases, leads to special types of simultaneous nonlinear differential equations.


Strongyloides hyperinfection in an HIV-positive kidney transplant recipient: a case report.
Strongyloidiasis is caused by the helminth Strongyloides stercoralis and is well-recognised amongst transplant recipients. Serious complications, including Strongyloides hyperinfection which is a syndrome of accelerated autoinfection, or disseminated disease, can occur post-transplantation, resulting in significant morbidity and mortality. Here we present the first published case we are aware of, describing post-transplant Strongyloides hyperinfection in an HIV-positive kidney transplant patient. We discuss the diagnostic challenges and the role of pre-transplant screening. A 58-year-old African-American male, originally from the Caribbean, received a deceased donor kidney transplant for presumed focal segmental glomerulosclerosis. He was known to be HIV-positive, with a stable CD4 count, and an undetectable viral load. Five months post-transplant, he developed gastrointestinal symptoms and weight loss. He had a normal eosinophil count (0.1-0.2 × 109/L), negative serum cytomegalovirus DNA, and negative blood and stool cultures. His Strongyloides serology remained negative throughout. A diagnosis of Strongyloides hyperinfection was made by the histological examination of his duodenum and lung, which identified the parasites. He completed his course of treatment with Ivermectin but exhibited profound deconditioning and required a period of total parenteral nutrition. He was subsequently discharged after a prolonged hospital admission of 54 days. This case highlights the challenges in diagnosing Strongyloides infection and the need to maintain a high index of clinical suspicion. Non-invasive techniques for the diagnosis of Strongyloides may be insufficient. Routine pre-transplant serological strongyloidiasis screening is now performed at our centre.


Studies on quinazolinones as dual inhibitors of Pgp and MRP1 in multidrug resistance.
The syntheses and SAR studies of various quinazolinone compounds are described for the dual inhibition of Pgp and MRP1 in multidrug resistance.