Comparison of the diurnal ocular hypotensive efficacy of travoprost and latanoprost over a 44-hour period in patients with elevated intraocular pressure.
Prostaglandin analogues are effective ocular hypotensive agents and are being used increasingly in the treatment of elevated intraocular pressure (IOP). These agents are typically dosed once daily. A pilot study was conducted to evaluate the duration of travoprost's IOP-lowering efficacy up to 84 hours after the final dose in patients with open-angle glaucoma. A follow-up study was conducted to compare diurnal IOP control with travoprost and latanoprost over a 44-hour period. In the open label pilot study, patients received 0.004% travoprost in both eyes at 8 pm daily for 2 weeks. After 2 weeks, IOP was measured before administration of the last daily dose, every 4 hours thereafter for 36 hours, and 60 and 84 hours after the last dose, with no additional ocular hypotensive medication given. In the controlled, double-masked, parallel-group, follow-up study, patients were randomized to self-administer 1 drop of the marketed doses of 0.004% travoprost or 0.005% latanoprost in both eyes at 8 pm daily for 2 weeks. At the end of this period, patients returned to the facility at approximately 8 pm for IOP measurement and administration of the final dose of study medication. IOP was then measured at 4-hour intervals for 44 hours after the last dose, with no additional ocular hypotensive medication given. The pilot study included 21 patients (67% female, 33% male; age range, 35-81 years) with open-angle glaucoma. IOP values were significantly below baseline at all time points up to 84 hours after the final dose of travoprost ( P<0.001). The follow-up study enrolled 35 patients, 1 of whom was excluded for missing data; thus, the intent-to-treat analysis included 34 patients (68% female, 32% male; age range, 36-72 years). At the unmedicated eligibility visit, mean IOP over 24 hours ranged from 21 to 26 mm Hg in each treatment group. After 2 weeks of treatment and 24 hours after the last dose, mean (SD) IOP was 13.1 (2.1) mm Hg (change from eligibility visit, -10.4 [2.7] mm Hg) in the travoprost group and 16.0 (3.1) mm Hg (change from eligibility visit, -7.1 [2.4] mm Hg) in the latanoprost group. The difference in change from baseline was statistically significant between treatment groups (P=0.006). Travoprost lowered IOP significantly at all time points throughout the 44-hour period after the last dose (mean IOP, <or=18 mm Hg; [P<0.001) and was statistically superior to latanoprost at 8 pm before the last dose (P=0.041) and 24 hours after the last dose (P=0.006). Latanoprost showed greater IOP-lowering efficacy compared with travoprost 4 hours after the last dose (P=0.040). IOP reductions were significantly different from zero at all time points with both treatments (P<0.001). The results of the pilot study suggest that travoprost produces reductions in IOP that may be sustained for up to 84 hours after dosing. The results of the follow-up study suggest that both prostaglandin analogues significantly lower IOP from baseline in patients with open-angle glaucoma and provide excellent diurnal IOP control throughout a 24-hour period.


Initial splanchnic extraction of ingested glucose in normal man.
Estimates of initial splanchnic uptake of ingested glucose and the concomitant suppression of endogenous glucose production were obtained in man by validated tracer techniques for non--steady-state turnover measurement. Nine normal volunteers (18--44 yr old) fasted overnight received intravenous infusions of tracer (3-3H-glucose or 1-14C-glucose) and a low (45 +/- 1 g) or high (96 +/- 5 g) oral load of glucose labeled with an alternative tracer (1-14C-glucose or 2-2H-glucose). A two-compartment model was used to derive rates of peripheral appearance (Ra) of glucose from all sources (total) and the Ra of ingested glucose. Ra (total glucose) and Ra (ingested glucose) were integrated from the first appearance of ingested glucose until the basal Ra (total glucose) or 116 +/- 6 (SEM) mg/min was reattained. The total amount of glucose reaching the systemic pool in this time was 95 +/- 4 g and 46 +/- 3 g with high and low doses, respectively. Of these quantities 86 +/- 4 g and 40 +/- 3 g originated in the oral glucose, representing 90% +/- 4% of the administered glucose. The remainder (11% +/- 2% of the total) represented endogenous production, suppressed by 66% +/- 6% relative to basal. Sequestration of ingested glucose and subsequent release did not take place during the study since identical results were obtained with ingested 1-14C-glucose or 2-3H-glucose. The latter label would have been lost if the glucose had entered the hexose--phosphate pool. Thus, in normal man approximately 90% of an ingested glucose load is absorbed and passes through the liver to appear in the systemic pool.


Intussusception associated with pneumatosis cystoides intestinalis in a male adolescent: A case report.
Pneumatosis cystoides intestinalis is an uncommon disease that rarely causes intussusception. We report the case of a 16-year-old male patient with intermittent abdominal pain who was diagnosed with intussusception. The patient had no history of raw food ingestion, fever, diarrhea, or hematochezia. Computed tomography revealed intussusception characterized by a crab-finger appearance, and pneumatosis cystoides intestinalis was diagnosed by colonoscopy. Treatment with hyperbaric enema and low-flow oxygen therapy resulted in a prominent improvement of the lesion. No recurrence was observed for > 1 year. Intermittent abdominal pain without diarrhea or hematochezia in male adolescents may represent pneumatosis cystoid-related intussusception, and the addition of low-flow oxygen therapy may help avoid surgery.


Group a streptococcal serotypes isolated from healthy schoolchildren in iran.
Serotypes of group A streptococci are still a major cause of pharyngitis and some post-infectious sequelae such as rheumatic fever. As part of the worldwide effort to clarify the epidemiological pattern of group A streptococci in different countries, the present study was conducted to assess the prevalence of Streptococcus pyogenes serotypes in Iran. A total of 1588 throat swabs were taken from healthy school children in the city of Gorgan during February and March 1999. Of those isolates, 175 resulted positive for group A streptococci. The distribution pattern was similar for girls and boys, with 10.8% and 11.2%, respectively. Urban school children showed a higher rate of colonization compared to those in rural areas. Serotyping was performed on 65 of the positive isolates using standard techniques, and only 21 (32%) were M-type isolates. Their profiles fell into four types with M1 predominating, which could reflect the presence of rheumatic fever in the region. However, when isolates were challenged for T-antigen types, nearly all were positive (94%). The pattern of T types was diverse (18 types), with the most common T types being T1 (26%), TB3264 (15%), TB\1-19 & B\25\1-19 (9.2%) and T2 & 2\28 (7.7%). When isolates were tested for opacity factor, only 23 (35%) were positive while 34 (52%) responded to the serum opacity reaction test. Although the number of isolates in this study was not sufficient to make any epidemiological conclusions, the scarcity of serotyping studies in Iran could render these data useful for future attempts to develop a streptococcal vaccine.


Evaluation of abnormal cervical cytology during pregnancy with colposcopy.
During a 6 1/2 year study period the authors used colposcopy to evaluate 174 pregnant patients with abnormal cervical cytology. The technique of colposcopy proved safe, accurate, and effective in determining the presence or absence of cervical cancer in the present patient's cervix. Colposcopy is mandatory for the evaluation of abnormal cervical cytology during pregancy.


Tunicamycin partially delays release of newly synthesized hyaluronate from Swarm rat chondrosarcoma chondrocytes.
Tunicamycin (5-100 micrograms/ml) inhibits total [3H]hyaluronate synthesis in cultures of Swarm rat chondrosarcoma chondrocytes by approx. 15%. In agreement with previous results (Lohmander, L.S., Fellini, S.K., Kimura, J.H., Stevens, R.L. and Hascall, V.C. (1983) J. Biol. Chem. 258, 12280-12286) the relative decrease in [3H]hyaluronate radioactivity in the culture medium was greater than in the cell layer. Treated cultures show a concentration-related decrease in the proportion of medium 35S-labelled proteoglycans forming 'natural aggregates'. Pulse-chase experiments in cultures pretreated with tunicamycin (100 micrograms/ml, 13 h) showed that 30-40% of the total [3H]hyaluronate synthesized is released more slowly from these chondrocytes than from control culture chondrocytes. Release of some hyaluronate molecules may be delayed by 6 h or more. After a 24 h chase period almost all the [3H]hyaluronate is released from the cells. The proportion of 35S-labelled proteoglycans present as aggregates in the 24 h chase medium (57%) remained depressed compared to controls (81%), although the monomers could form aggregates if exogenous hyaluronate was added. Hyaluronate synthesized in the presence of tunicamycin has the same hydrodynamic size as control culture hyaluronate, as assessed by its sedimentation profile in CsSO4 gradients and its chromatographic profile on a dissociative Sephacryl S-1000 column.


A "new" allele of esterase D in a retinoblastoma family.
We describe a new rare allele for esterase D (EsD) occurring in a Portuguese family with retinoblastoma in two generations.


Evaluating the Effect of Physician Fellowship Programs on Surgical Outcomes for Coronary Artery Bypass Grafting Procedures.
This study examined the relationship between fellowship training of thoracic surgeons and their patient outcomes following a coronary artery bypass graft (CABG) procedure. The study used data obtained from hospital discharges from Florida hospitals from 2006 to 2010 and linked them with the quality of the hospital wherein the physician completed his or her fellowship. Quality rankings were based on the hospital's national ranking among cardiovascular hospitals at the time when the fellowship was completed. A risk-adjusted analysis showed that completing a fellowship in a nationally ranked cardiovascular hospital and a longer time since fellowship and residency completion were associated with lower complication rates for CABG surgeries. This is the first study to incorporate hospital discharge data, external hospital quality rankings, and physician training characteristics to evaluate patient outcomes. Such knowledge could help shape the future direction of health care training and provide an objective, outcomes-based evaluation method for physician training programs.


[Teutschländer disease. A rare benign differential diagnosis of proliferative space-occupying lesions in the periarticular soft tissue].
The tumoral calcinosis (synonym: Teutschländer disease) is a very rare benign metabolic dysfunction of unknown etiology. It manifests principally as massive subcutaneous soft tissue deposits of calcium phosphate near the large joints and is also characterized by slow progressive growth. Causally, a disturbance of the calcium and phosphate metabolism/balance with, among others, autosomal dominant heredity is suspected. It appears frequently in the black African population in all age groups, but preferentially in the 1st and 2nd decades of life. Medical help is most frequently sought because of increasing tumor size causing displacement and consecutive pain as well as decreased joint play. We present here a case of Teutschländer disease in a 50-year-old woman on long-term hemodialysis and describe the clinical, radiological, and pathological signs of this rare disease. Subsequently, speculative etiology, differential diagnostic considerations as well as the therapeutic interventions for tumoral calcinosis are discussed taking into consideration the current literature.


Comparison of enzymes of tears, lacrimal gland fluid and lacrimal gland tissue in the rat.
A variety of enzymes were identified in rat tears and lacrimal gland fluid. The use of a tapered glass cannula in the opening of the excretory duct was found to be an useful method to collect samples of rat lacrimal gland fluid, i.e., the fluid directly originated from the main excretory duct of the lacrimal gland, uncontaminated by secretions from the Harderian gland and from desquamating conjunctival and corneal epithelial cells. Based upon comparison of the enzyme pattern in tears, lacrimal gland fluid and the lacrimal gland tissue, we concluded that the lacrimal gland is the primary tissue source for peroxidase (POD), amylase (AMY) and total protein in rat tears, while plasminogen activator and lactatedehydrogenase (LDH) may be present in tears primarily as secretion products from other ocular tissue sources. beta-hexosaminidase (beta-hex) is released from the lacrimal gland and from other ocular tissue sources as well.


Identification of novel factors involved in colonization and acid tolerance of Vibrio cholerae.
Despite over 100 years of study, the intestinal pathogen Vibrio cholerae still causes epidemic disease in areas of the world where there is poor sanitation. While cholera toxin and the toxin-coregulated pilus (TCP) are known to be essential for full virulence, the role that other factors play has remained ill-defined. Herein, we describe a large-scale signature-tagged mutagenesis (STM) screen utilizing 100 pools of 96 mutants each to identify factors involved in colonization of the infant mouse small intestine. A total of 164 mutants representing transposition events into 95 different open reading frames were shown to be recovered at greatly reduced numbers from the infant mouse model. Analysis of the sites of insertion revealed multiple independent mutations within the rfb gene cluster, needed for synthesis of lipopolysaccharide (LPS), and the tcp gene cluster, needed for synthesis of the TCP. More importantly, in addition to these previously known colonization factors, we identified many genes whose activity in colonization was not previously appreciated. These can be divided into a number of functional groups, which include production of factors involved in metabolic activities, regulation of cellular processes, transport, adaptation to stress and unknown functions. In addition, we describe the reiterative use of STM, whereby colonization-defective mutants were assembled into virulence-attenuated pools (VAPs), which were used to begin to reveal roles that the identified virulence factors play in the infection process. Nine new factors were shown to be crucial for the V. cholerae acid tolerance response, which has previously been hypothesized to be important for epidemic spread of cholera. Competition assays of these nine acid tolerance response (ATR)-defective mutants revealed that mutations in gshB, hepA and recO result in a 1000-fold reduction in colonization.


Moist and warm conditions in Eurasia during the last glacial of the Middle Pleistocene Transition.
The end of the Middle Pleistocene Transition (MPT, ~ 800-670 thousand years before present, ka) was characterised by the emergence of large glacial ice-sheets associated with anomalously warm North Atlantic sea surface temperatures enhancing moisture production. Still, the direction and intensity of moisture transport across Eurasia towards potential ice-sheets is poorly constrained. To reconstruct late MPT moisture production and dispersal, we combine records of upper ocean temperature and pollen-based Mediterranean forest cover, a tracer of westerlies and precipitation, from a subtropical drill-core collected off South-West Iberia, with records of East Asia summer monsoon (EASM) strength and West Pacific surface temperatures, and model simulations. Here we show that south-western European winter precipitation and EASM strength reached high levels during the Marine Isotope Stage 18 glacial. This anomalous situation was caused by nearly-continuous moisture supply from both oceans and its transport to higher latitudes through the westerlies, likely fuelling the accelerated expansion of northern hemisphere ice-sheets during the late MPT.


Developmental hemodynamic changes in rat embryos at 11 to 15 days of gestation: normal data of blood pressure and the effect of caffeine compared to data from chick embryo.
We attempted to measure arterial blood pressure of the rat embryo. The embryo was excised within the uterus and immersed in Hanks' solution at 37 degrees C. The uterus wall and yolk sac were opened to expose the umbilical vessels. The umbilical artery was punctured with a glass micro-pipette, and blood pressure was measured by using a servo-null micro-pressure system. The mean blood pressure was 0.27 +/- 0.05 mm Hg in the embryo at the 11th day of gestation (n = 7), 0.48 +/- 0.03 mm Hg in the 12-day embryos (n = 19), 1.3 +/- 0.08 mm Hg in the 13-day (n = 11), and 2.6 +/- 0.1 mm Hg in the 15-day embryos (n = 10). Heart rate was 84 +/- 11 in 11-day, 122 +/- 3 in 12-day, 192 +/- 7 in 13-day, and 198 +/- 5 in 15-day embryos. These parameters were stable within 10 min after the excision. A comparison of the data with those of the chick embryo of comparable developmental stages revealed that the blood pressure was lower in 11- and 12-day rat embryos than in the chick embryo of Hamburger-Hamilton stages 18 and 21, but this was reversed in the later stages. In the stage 21 chick embryo, intravenous administration of caffeine (60 +/- 9 mg/kg embryo weight) induced an increase in blood pressure by 11 +/- 3% (n = 8), but did not result in a significant increase in dorsal aortic blood flow (6 +/- 6%, n = 9) or in heart rate. In contrast, caffeine (62 +/- 3 mg/kg) increased the heart rate by 8 +/- 2% (n = 10) without changing the blood pressure in the rat embryo of day 12. The velocity of blood flow in the truncus was measured by a pulsed Doppler flowmeter. Caffeine injection increased the mean velocity by 21 +/- 8%). Herein we indicate that measurement of blood pressure in the rat embryo is feasible, but with some limitations, and that there may be qualitative hemodynamic differences between the rat and chick embryos.


Femtosecond laser assisted capsulotomy in the treatment of capsule contraction case report.
To present the surgical value of femtosecond laser capsulotomy in the treatment of capsular contraction. The clinical case of a 63-year-old male patient with single eye who, two months after cataract surgery without complications, presented a significant dislocation of the secondary intraocular lens due to a capsule contraction and epithelial metaplasia that covered the lens optics and caused low vision. The femtosecond laser-assisted capsulotomy proved to be effective and safe with minimal traction on the zonule and no IOL damage, in this patient with a follow-up of 29 months.


DNA repair deficiency as a therapeutic target in cancer.
Inhibitors of DNA repair proteins have been used in cancer therapy, mostly to potentiate the effects of cytotoxic agents. However, tumor cells frequently exhibit deficiencies in the signalling or repair of DNA damage. These deficiencies probably contribute to pathogenesis of the disease, but they also present an opportunity to target the tumor. Recently, inhibitors of poly(ADP-ribose) polymerase (PARP) have been shown to be highly selective for tumor cells with defects in the repair of double-strand DNA breaks (DSBs) by homologous recombination, particularly in the context of BRCA1 or BRCA2 mutation. It seems likely that other DNA repair processes can be targeted in a similar manner. These synthetic lethal approaches highlight how an understanding of DNA repair processes can be used in the development of novel cancer treatments.


Potential Role of CT Metrics in Chronic Obstructive Pulmonary Disease with Pulmonary Hypertension.
Recent imaging studies demonstrated the usefulness of quantitative computed tomographic (CT) analysis assessing pulmonary hypertension (PH) in patients with chronic obstructive lung disease (COPD-PH). The aim of this study was to investigate whether it would be also valuable for predicting and evaluating the effect of pulmonary vasodilators in patients with COPD-PH. We analyzed a correlation between the extent of cystic destruction (LAA%) and total cross-sectional areas of small pulmonary vessels less than 5 mm(2) (%CSA <5) in many CT slices from each of four COPD-PH patients before and after the initiation of pulmonary vasodilator. To evaluate those generalized data from patients with COPD, we evaluated multiple slices from 42 patients whose PH was not clinically suspicious. We also selected five PH patients with idiopathic interstitial pneumonia (IIP-PH) and analyzed serial changes of pulmonary artery enlargement (PA:A ratio). In 42 COPD patients without PH, LAA% had a statistically significant negative correlation with %CSA <5. However, three of four COPD-PH patients manifested no such correlation. In two patients, clinical findings were dramatically improved after the initiation of pulmonary vasodilator. Notably, LAA% and %CSA <5 in those patients correlated significantly after its treatment. In COPD-PH, the PA:A ratio was significantly decreased after the initiation of pulmonary vasodilator therapy (1.25 ± 0.13 vs. 1.13 ± 0.11, p = 0.019), but not in IIP-PH. Our study demonstrates that the use of quantitative CT analysis is a plausible and beneficial tool for predicting and evaluating the effect of pulmonary vasodilators in patients with COPD-PH.


Biological and immunological characterization of human luteinizing hormone: II. A comparison of the immunological and biological activities of pituitary extracts after electrofocusing using different standard preparations.
The profile of immunologically active human luteinizing hormone (hLH) was determined in aqueous pituitary extracts after electrofocusing using two radioimmunoassay systems and the estimates for each fraction were compared to those obtained by an in vitro bioassay method. Similar biological and immunological profiles were obtained in the pH 7.0-9.0 region, where most of the biological activity was present. Biological to immunological (B/I) ratios ranging from 0.6 to 1.7 (mean ratio 1.01; n = 21) were found in the major biologically active fractions of this pH region when a highly purified human pituitary LH preparation (68/40) was used as standard in both types of assays. The close proximity of these ratios to unity indicates a similar composition of biological and immunological activities in all these fractions in relation to that of the highly purified standard. However, marked discrepancies were observed in the pH region 3.0-7.0 where the B/I ratios ranged from 0.1 to 0.9, indicating the presence of immunological activity associated with relatively little biological activity. When impure human LH preparations of pituitary (69/104) and urinary (hMG 2nd IRP) origin were used as standards for the bioassay and radioimmunoassay of the hLH present in the major fractions of the pH region 7.0-9.0, significantly higher B/I ratios were obtained than with the use of the highly purified standard (68/40). These elevated B/I ratios are attributed to the presence in the impure standard preparations of immunological activity, which is associated with little or no biological activity. These observations may provide an explanation for the differences in B/I ratios which were reported for hLH in plasma, using different standard preparations.


Global vaccine action plan lessons learned I: Recommendations for the next decade.
The Global Vaccine Action Plan 2011-2020 (GVAP) was developed to realize the ambitions of the Decade of Vaccines - that all individuals and communities enjoy lives free from vaccine-preventable diseases. It included a comprehensive monitoring and evaluation/accountability framework to assess progress towards global targets with recommendations for corrective actions. While many of the GVAP targets are very unlikely to be met by the end of 2020, substantial progress has nevertheless been made, establishing a strong foundation for a successor global immunization strategy, the Immunization Agenda 2030 (IA2030). The Strategic Advisory Group of Experts on immunization has made a series of recommendations to ensure that the lessons learned from GVAP inform the development and implementation of IA2030.


Geometric Isomerisation of Bifunctional Alkenyl Fluoride Linchpins: Stereodivergence in Amide and Polyene Bioisostere Synthesis.
Amide groups are pervasive across the chemical space continuum, where their structural and pharmacological importance, juxtaposed with the hydrolytic vulnerabilities, continues to fuel bioisostere development. Alkenyl fluorides have a venerable history as effective mimics (Ψ[CF=CH]) owing to the planarity of the motif and intrinsic polarity of the C(sp2 )-F bond. However, emulating the s-cis to the s-trans isomerisation of a peptide bond with fluoro-alkene surrogates remains challenging, and current synthetic solutions only enable access to a single configuration. Through the design of an ambiphilic linchpin based on a fluorinated β-borylacrylate, it has been possible to leverage energy transfer catalysis to affect this unprecedented isomerisation process: this provides geometrically-programmable building blocks that can be functionalised at either terminus. Irradiation at λmax =402 nm with inexpensive thioxanthone as a photocatalyst enables rapid, effective isomerisation of tri- and tetra-substituted species (up to E/Z 98 : 2 in 1 h), providing a stereodivergent platform for small molecule amide and polyene isostere discovery. Application of the methodology in target synthesis and initial laser spectroscopic studies are disclosed together with crystallographic analyses of representative products.


Bioactive heterocyclic alkaloids with diterpene structure isolated from traditional Chinese medicines.
The diterpenoid alkaloids as one type of heterocyclic alkaloids have been found in many traditional herbal medicines, such as genus Consolida, Aconitum, and Delphinium (Ranunculaceae). Pharmacological researches have indicated that many diterpenoid alkaloids are the main bioactive components which have analgesic, anti-inflammatory, anti-microbial, anti-tumor, cardiotonic, and anti-arrhythmic activities. Studies focused on the determination, quantitation and pharmacological properties of these alkaloids have dramatically increased during the past few years. Up to now, newly discovered diterpenoid alkaloids with important biological activities have been isolated and synthesized. Considering their significant role and diffusely used in many disease treatments, we summarized the information of their analysis methods, bioactivity, metabolism and biotransformation in vivo as well as the pharmacological mechanisms. Based on above review, the further researches are suggested.


A component of lobular carcinoma in clinically lymph node-negative patients predicts for an increased likelihood of upstaging to pathologic stage III breast cancer.
Physical examination and diagnostic imaging are often less precise in determining the extent of disease in invasive lobular carcinoma (ILC) relative to nonlobular histologies. Anecdotally, surgical axillary evaluation frequently reveals positive lymph nodes in clinically N0 patients with ILC; however, few studies quantify the likelihood of finding unsuspected disease at the time of surgery. In this study, we evaluate whether the presence of lobular histology increases the incidence of surgical upstaging to pathologic stage IIIA or greater in patients with a clinically node-negative axilla and positive sentinel lymph node (SLN) biopsy. We examined patients from our institution between 1997 and 2009 treated specifically with mastectomy, SLN biopsy, and completion axillary lymph node dissection due to a positive SLN. For analysis, patients were grouped according to the presence of any lobular component on surgical pathology. The number of total positive lymph nodes, cancer stage, age, final tumor size, and ER/PR/HER2 status were assessed based on tumor histology. We evaluated 345 previously untreated women with clinical T0-T2 and N0 disease at the time of surgery. A total of 110 patients (32%) had a component of ILC on surgical pathology. In addition, 295 patients (85.5%) had ER + breast carcinoma, 243 (70.4%) had PR + disease, 56 (16.2%) were HER2 + , and 28 (8.1%) were triple negative. At the time of surgery, women with lobular disease were observed to have a greater number of positive lymph nodes (2.79 vs 2.26; P = .009) and were more frequently upstaged to at least pathologic stage IIIA compared with nonlobular patients (30.9% vs 17.4%; P = .007). In this cohort, patients with a component of lobular carcinoma were more often surgically upstaged to pathologic stage IIIA or higher, which is a classical indication for postmastectomy radiation therapy. Our findings suggest that ILC is often more extensive than it appears clinically and has significant implications for management of patients with lobular carcinoma after the discovery of a positive SLN.


Sudomotor dysfunction as a measure of small fiber neuropathy in type 1 diabetes.
This study evaluated whether measuring the electrochemical skin conductance (ESC), as an indirect measure of sudomotor function, may be also a reliable surrogate for early cardiovascular autonomic neuropathy (CAN). Longitudinal study included 37 type 1 diabetes (T1D) subjects (mean age 38±13years, duration 15±7years, HbA1c 7.9±1.1%, no known complications at baseline), and 40 age-matched healthy control (HC) subjects. Mean hands ESC (ESChands) and feet (ESCfeet) were measured with the SUDOSCAN (Impeto Medical, France). CAN was assessed with heart rate variability (HRV) studies (ANSAR Inc., PA), cardiovascular autonomic reflex tests (deep-breathing, Valsalva, postural test), and positron emission tomography with sympathetic analogue [11C]meta-hydroxyephedrine. Associations between measures of CAN and ESC were estimated using Spearman correlations. Longitudinal changes were analyzed using paired t-test. At baseline, there were no differences between T1D and HC in ESChands (69±14 vs. 69±13μS; P=0.84) or ESCfeet (82±8 vs. 78±9μS; P=0.12), while some indices of HRV and Valsalva ratio were significantly lower in T1D vs. HC. T1D subjects experienced a significant decline in both ESChands and ESCfeet at 12months (mean change -7.2±11.6µS, P=0.0006; -2.8±7.3µS, P=0.023 respectively). No significant correlations were consistently found between ESC and measures of CAN at baseline or at 12months. Comparing patients with T1D to controls, no differences in ESC were observed at baseline. The associations between ESC and established measures of CAN were inconsistent, which does not support ESC as a reliable surrogate for CAN. While both hands and feet ESC declined over time, the significance of this finding is unclear and warrants further reliability testing.


A risk prediction model for hepatocellular carcinoma after hepatitis B surface antigen seroclearance.
After hepatitis B surface antigen (HBsAg) seroclearance, the risk of hepatocellular carcinoma (HCC) remains, and the optimal surveillance strategy has yet to be determined. Herein, we aimed to evaluate incidence and risk factors for HCC and establish a novel prediction model for HCC development after HBsAg seroclearance. A total of 1,443 patients with chronic hepatitis B who achieved HBsAg seroclearance between 1991 and 2020 were retrospectively screened for study eligibility. The data from 831 of these patients were included in the final analysis. A prediction model was developed based on multivariable Cox models. Harrell's C-index and a time-dependent AUROC were used for discrimination. Bootstrap analysis was performed for internal validation. Overall, 40 patients (4.8%) developed HCC after HBsAg seroclearance during a follow-up of 4,644 person-years (0.86%/year). Age at HBsAg seroclearance, presence of cirrhosis, family history of HCC, and more-than-moderate alcohol consumption were independently predictive of HCC, and these 4 independent variables were used to develop the prediction model. The C-index of the model was 0.804. The time-dependent AUROCs of the score for HCC prediction at 5, 10, and 15 years were 0.799, 0.835, and 0.817, respectively. The score also showed good discrimination in the internal validation and sensitivity analysis. The novel prediction model based on age, cirrhosis, family history of HCC, and alcohol consumption enables reliable risk estimation of HCC after HBsAg seroclearance and may serve as a useful reference for decision-making in HCC surveillance for HBsAg-cleared patients. After spontaneous hepatitis B surface antigen (HBsAg) seroclearance, the risk of hepatocellular carcinoma (HCC) remains. Age at HBsAg seroclearance, presence of cirrhosis, family history of HCC, and more-than-moderate alcohol consumption were independently associated with HCC development after HBsAg seroclearance. The novel prediction model using these 4 variables enables reliable risk estimation of HCC and serves as a useful reference for decision-making in HCC surveillance and management for HBsAg-cleared patients.


Practical problems in assessing risk for coronary artery bypass grafting.
In order to put results of a surgical program in proper prospective, risk factors for the population being treated should be carefully assessed. This paper discusses the practical problems involved in determining the risk of surgical mortality for patients undergoing isolated coronary artery bypass grafting. A risk equation developed by the Collaborative Study in Coronary Artery Bypass was applied to a veterans hospital population. A simplified method of determining left ventricular function from clinical angiography reports was found to be a reasonable substitute for the more complex left ventricular scoring system used by the collaborative study. Results showed the veterans group to be at increased risk, primarily due to an older average age and higher incidence of left ventricular dysfunction.


Exploring leaf hydraulic traits to predict drought tolerance of Eucalyptus clones.
Ongoing changes in climate, and the consequent mortality of natural and cultivated forests across the globe, highlight the urgent need to understand the plant traits associated with greater tolerance to drought. Here, we aimed at assessing key foliar traits, with a focus on the hydraulic component, that could confer a differential ability to tolerate drought in three commercial hybrids of the most important Eucalyptus species utilized in tropical silviculture: E. urophyla, E. grandis and E. camaldulensis. All genotypes exhibited similar water potential when the 90% stomatal closure (Ψgs90) occurs with Ψgs90 always preceding the start of embolism events. The drought-tolerant hybrid showed a higher leaf resistance to embolism, but the leaf hydraulic efficiency was similar among all genotypes. Other traits presented by the drought-tolerant hybrid were a higher cell wall reinforcement, lower value of osmotic potential at full turgor and greater bulk modulus of elasticity. We also identified that the leaf capacitance after the turgor loss, the ratio between cell wall thickness (t) and lumen breadth (b) ratio (t/b)3, and the minimal conductance might be good proxies for screening drought-tolerant Eucalyptus genotypes. Our findings suggest that xylem resistance to embolism can be an important component of drought tolerance in Eucalyptus in addition to other traits aimed at delaying the development of high tensions in the xylem. Highlight Drought tolerance in tropical Eucalyptus hybrids encompasses a high leaf resistance to embolism and a suite of traits aimed at delaying the development of high tensions in the xylem.


Adipose-derived stem cell enrichment is counter-productive for the majority of women seeking primary aesthetic breast augmentation by autologous fat transfer: A systematic review.
Autologous lipotransfer (AL) is a popular method despite unpredictable retention rates. Higher retention rates have been reported when co-administering adipose-derived stem cells (ASCs), a process called cell-assisted lipotransfer (CAL). Our hypothesis is that CAL might indeed limit volume gain in most women seeking aesthetic breast augmentation because it doubles the amount of fat required without consistently improving the outcome. Electronic databases were searched for articles published between January 2008 and October 2019 in English and German. All original articles evaluating fat viability following autologous breast augmentation in vivo were included. Based on the reported retention rates, potential volume gains were estimated for CAL and AL. A total of 23 studies were selected. The AL retention rate varied from 39% to 76%, whereas CAL increased this rate at best by 24%. The body mass index (BMI) ranged from 18.8 to 23.4 (20.4±1.6) in the study population, whereas the BMI of women in the same age group is 28.7 (±8.4). We calculated that, starting from 200 ml of harvested fat and after two sessions of AL of 100 ml each, the volume retained would be at most 152 ml. In contrast, after one session of CAL of 100 ml, while the remaining 100 ml are used to isolate ASCs, a maximum of 95 ml of fat would remain. The volume gain after two sessions of AL is far superior to that after one session of CAL for the same volume of harvested fat. This is an important practical consideration for women with low BMI, as the extra fat required to isolate ASCs is not counterbalanced by an increase in the retention rate. Therefore, two sessions of AL may be preferable to maximize the volume gain.


Disulphide bonds are a requirement for adsorption of cephalosporins on the red cell membrane.
The authors studied the behavior of red cells (RBCs), treated with 2-aminoethylisothiouronium bromide (AET), against 100 serums containing cephalothin antibodies and 27 serums with cephapirin antibodies. None of the serums reacted with cephalosporin-coated RBCs that had been exposed previously to AET. The possibility of the Kell system acting as a receptor for cephalosporins was excluded. The authors discuss the significance of cysteine disulphide bonds and the tertiary or quaternary structure of red cell membrane proteins in the binding of cephalosporins to RBCs.


Survey of the use of catecholamines by French physicians.
The objective of the study was to perform a descriptive approach of the current use of catecholamines by French physicians. A questionnaire of 12 questions with 4 items established by a group of French intensivists. French physicians from 433 departments working in the following practicing areas: intensive care unit (ICU), emergency department, and pre-hospital setting. Responding physicians were asked about the catecholamine that they would select in various clinical settings. The response rate was 82%. Of the responding physicians, 277 (78%) worked in an ICU, 28 (8%) in an emergency department, and 21 (6%) in a pre-hospital setting. Dobutamine was chosen for patients with cardiogenic shock by 90% of the respondents. Norepinephrine was the first choice agent as vasopressor in patients with septic shock in 52% of the cases. Dopamine was selected in a clinical setting requiring an optimization of regional blood flow, as in the concept of high-risk surgical patients. Dopexamine was used as a second or third choice agent to improve regional blood flow and cardiac output. The indications of epinephrine for anaphylactic shock and cardio-circulatory arrest were obvious for more than 90% of responding physicians. A lack of standardization appears in the use of catecholamines by French physicians, particularly for improvement of regional circulation and management of high-risk surgical patients. Guidelines that define the place of each catecholamine in these settings are required to improve the quality of prescription.


Bringing emergency services to the event: the Champ Car experience.
Delivering emergency medical services at sporting events requires unique planning, equipment, personnel, and training. The Champ Car World Series is a top-level, open wheel racing series that uses both street and open terrain road courses for events held in several different countries. Medical services are available to both drivers and support staff through the use of on site medical personnel, specialized rescue vehicles, and a traveling medical center. This article describes the process of delivering high-quality, consistent medical care in a difficult racing environment.


Resveratrol causes COX-2- and p53-dependent apoptosis in head and neck squamous cell cancer cells.
Cyclooxygenase-2 (COX-2) content is increased in many types of tumor cells. We have investigated the mechanism by which resveratrol, a stilbene that is pro-apoptotic in many tumor cell lines, causes apoptosis in human head and neck squamous cell carcinoma UMSCC-22B cells by a mechanism involving cellular COX-2. UMSCC-22B cells treated with resveratrol for 24 h, with or without selected inhibitors, were examined: (1) for the presence of nuclear activated ERK1/2, p53 and COX-2, (2) for evidence of apoptosis, and (3) by chromatin immunoprecipitation to demonstrate p53 binding to the p21 promoter. Stilbene-induced apoptosis was concentration-dependent, and associated with ERK1/2 activation, serine-15 p53 phosphorylation and nuclear accumulation of these proteins. These effects were blocked by inhibition of either ERK1/2 or p53 activation. Resveratrol also caused p53 binding to the p21 promoter and increased abundance of COX-2 protein in UMSCC-22B cell nuclei. Resveratrol-induced nuclear COX-2 accumulation was dependent upon ERK1/2 activation, but not p53 activation. Activation of p53 and p53-dependent apoptosis were blocked by the COX-2 inhibitor, NS398, and by transfection of cells with COX-2-siRNA. In UMSCC-22B cells, resveratrol-induced apoptosis and induction of nuclear COX-2 accumulation share dependence on the ERK1/2 signal transduction pathway. Resveratrol-inducible nuclear accumulation of COX-2 is essential for p53 activation and p53-dependent apoptosis in these cancer cells.


Processing and characterization of egg shell derived nano-hydroxyapatite synthetic bone for Orthopaedic and Arthroscopy implants and substitutes in dentistry.
The present work is focused on the nano-Hydroxyapatite (nHAp) synthesis with two different Indian breed Aseel and Kadaknath eggshells. The alloplast implants were developed through the foam replica method with polyurethane 45-PPI as a porous template. The synthesized nHAp was characterized by Field Emission Scanning Electron Microscopy (FE-SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The FE-SEM images of the nHAp showed the one dimensional clustered nanoparticles and the X-ray diffraction spectrum confirms that the major phase was hydroxyapatite with a small trace of β-tricalcium phosphate. The maximum compression strength of the sample was 5.49 ± 0.12 MPa which is in the range of the compression strength of human trabecular bone. The thermal and degradability studies results confirmed that these are highly stable and provides necessary a resorption needed for new bone tissue formation. Besides, the antimicrobial activity against tested human microbiome are satisfactory and the cell viability towards MG 63 human osteoblast-like cells provides a potential pathway for developing the nHAp implants for bone tissue engineering.


Body mass index and prognosis in patients with head and neck cancer.
Body mass index (BMI) has been associated variably with head and neck cancer outcomes. We evaluated the association between BMI at either diagnosis or at early adulthood head and neck cancer outcomes. Patients with invasive head and neck squamous cell cancer at Princess Margaret Cancer Centre in Toronto, Canada, were surveyed on tobacco and alcohol exposure, performance status, comorbidities, and BMI at diagnosis. A subset also had data collected for BMI at early adulthood. With a median follow-up of 2.5 years, in 1279 analyzed patients, being overweight (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.4-0.8; p = .001) at diagnosis was associated with improved survival when compared with individuals with normal weight. In contrast, underweight patients at diagnosis were associated with a worse outcome (HR, 1.89; 95% CI, 1.2-3.1; p < .01). Being underweight at diagnosis was an independent, adverse prognostic factor, whereas being overweight conferred better prognosis. BMI in early adulthood was not associated strongly with head and neck cancer outcomes. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1226-1233, 2017.


On the heterogeneity of serum albumin: effect of sodium dodecyl sulphate on agarose chromatography of the protein.
The chromatographic behaviour of serum albumin changes if it is dissolved in an aqueous solution of sodium dodecyl sulphate (SDS) and is left at room temperature or is heated. Instead of emerging as one peak from an agarose column it emerges as more than one peak and the protein in each when rechromatographed elutes in more than one peak. Electropherograms made in the presence of SDS of the protein in these peaks show multiple banding from proteins migrating with a wide range of molecular weights. The chromatographic and electrophoretic behaviour of serum albumin in the presence of SDS suggests that the protein is not a simple monomer and alternative explanations for this behaviour are discussed.


RETRACTED: Vegetation analysis of Wadi Al-Jufair, a hyper-arid region in Najd, Saudi Arabia.
please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief and Author. Data processing errors have resulted in misleading conclusions. The scientific community in King Saud University has serious concerns regarding the results and the article will be resubmitted for publication after reprocessing of the data.


Pyrimidinoceptor potentiation by ATP in NG108-15 cells.
Regulation of inositol phospholipid hydrolysis by UTP and UDP in neuroblastoma x glioma hybrid cell line NG108-15 was potentiated in the presence of ATP. The effect of ATP was dose dependent and shifted the EC50 value for these uracil nucleotides up to three powers of magnitude, having no influence on the maximal value of the response. Adenine nucleotides (ADP, AMP, adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS), beta,gamma-methyleneadenosine 5'-triphosphate (betagammaMeATP), 3'-O-(4-benzoyl)benzoyl ATP (BzATP) and 3'-deoxyadenosine 5'-O-(1-thio)triphosphate (dATPalphaS)) as well as adenosine, had no influence on the pyrimidinoceptor response. The potentiation effect was abolished by excess of EDTA. The results were in agreement with the hypothesis of pyrimidinoceptor affinity regulation via extracellular phosphorylation of the receptor protein, initiated by ATP. This mechanism may have physiological implication for functioning of uracil nucleotides as endogenous signaling molecules.


High frequency of dental caries and calculus in dentitions from a British medieval town.
Dental pathology and tooth wear data can offer valuable insights into the diet and behaviour of past populations. This study aimed to investigate the presence of dietary continuity by examining different types of dental pathology and tooth wear in a medieval sample from the United Kingdom, comparing them to earlier and later samples from the same location. A comprehensive examination was conducted on 41 individuals (comprising 914 permanent teeth) retrieved from the medieval cemetery of St. Owens Church in Southgate Street, Gloucester, UK. The research focused on documenting and analysing various types of dental pathology and tooth wear, such as dental caries, calculus, and tooth chipping. The frequency of these specific pathologies and wear patterns was then compared to existing literature. Additionally, non-masticatory tooth wear was also evaluated as part of the study. The sample exhibits high levels of carious lesions and calculus (24 % and 74 % of teeth respectively). Anterior teeth also show an elevated chipping frequency, and along with occlusal notches on the maxillary central incisors suggest teeth were regularly used for non-masticatory purposes. Caries frequency is similar to sites from later periods and may relate to the early adoption of consuming refined carbohydrates. However, remains from the same area, but the earlier Roman period, also shows high rates of caries and calculus, suggesting a continuation of consuming certain cariogenic foods, or certain behavioural/environmental factors, may instead be responsible for these pathology and wear patterns.


Comparison of the efficacy of budesonide and fluticasone propionate aqueous nasal spray for once daily treatment of perennial allergic rhinitis.
Intranasal corticosteroids, such as budesonide and fluticasone propionate, are widely prescribed in the treatment of perennial allergic rhinitis. Once daily budesonide dry powder and fluticasone propionate aqueous suspension have been found to provide similar efficacy in controlling symptoms of perennial allergic rhinitis. The purpose of this study was to assess the efficacy and safety of treatment with once daily budesonide aqueous nasal spray. This study involved a multicenter, blinded, randomized, parallel-group, placebo-controlled trial of adults with perrenial allergic rhinitis. Patients (n = 273) recorded daily nasal symptoms for 8 to 14 days (baseline) and 6 weeks (treatment). Budesonide decreased combined symptoms to a significantly greater extent than did fluticasone (P =.03); both treatments significantly decreased mean combined nasal symptoms scores compared with placebo. Of the 3 nasal symptoms assessed (ie, nasal blockage, runny nose, and sneezing), nasal blockage was significantly (P =. 009) more decreased with budesonide compared with fluticasone. Both treatments also significantly improved runny nose and sneezing compared with placebo. Improvement in combined nasal symptom scores of the budesonide-treated group reached statistical significance within 36 hours compared with placebo (P =.01); in those patients treated with fluticasone, significant improvement compared with placebo was first observed within 60 hours. Adverse events were mild and transient. Once daily budesonide aqueous nasal spray, 256 microgram, was significantly better in controlling the symptoms of perrenial allergic rhinitis than once daily fluticasone propionate, 200 microgram, especially nasal blockage. Both treatments were superior to placebo. Budesonide may have a faster onset of action than fluticasone.


Adrenocorticotropin hormone, beta-endorphin and cortisol responses to oCRF in melancholic patients.
Several authors have reported attenuated adrenocorticotropin hormone (ACTH) responses to corticotropin releasing factor (CRF) administration in melancholic patients as compared with healthy controls. In order to explore the integrity of the hypothalamic-pituitary-adrenal (HPA)-axis in melancholics, we examined the following parameters in 98 subjects: the ACTH; beta-endorphin; and cortisol responses to ovine CRF (oCRF) (100 micrograms/i.v.); and the postdexamethasone cortisol values. We found significant lower CRF-induced ACTH responses in melancholic patients as opposed to healthy controls and minor depressives, while major depressives occupied an intermediate position. The psychopathological correlates of the blunted CRF-induced ACTH responses were feelings of worthlessness, self-reproach, or excessive guilt. The CRF-stimulated beta-endorphin and cortisol response did not differ between the study samples. Higher baseline plasma cortisol was associated with attenuated CRF-induced ACTH responses, but these effects were not pertinent to melancholia. There were no relationships between the disordered oCRF test results, and postdexamethasone cortisol values, age, body size, sex and severity of illness. The diagnostic power of the oCRF and the dexamethasone suppression test for melancholia is enhanced when both test results are combined.


Calsequestrin expression and calcium binding is increased in streptozotocin-induced diabetic rat skeletal muscle though not in cardiac muscle.
Altered mechanisms of Ca2+ transport may underlie the contractile dysfunctions that have been frequently reported to occur in diabetic cardiac and skeletal muscle tissues. Calsequestrin, a high-capacity Ca2+-binding protein, is involved in the regulation of the excitation-contraction-relaxation cycle of both skeletal and cardiac muscle fibres. We have investigated the expression of calsequestrin and Ca2+ binding in cardiac and skeletal muscle from streptozotocin-induced diabetic rat. Immunoblotting of microsomal membranes from normal and streptozotocin-induced diabetic muscle revealed no significant changes in heart, but an increase in the relative abundance of calsequestrin and calsequestrin-like proteins in skeletal muscle. In analogy, the overall Ca2+-binding capacity of sarcoplasmic reticulum vesicles from diabetic skeletal muscle was drastically increased. The expression of fast muscle marker proteins was not affected, indicating that no relevant fibre transformation occurred in streptozotocin-treated rat muscles. The up-regulation of the high-capacity Ca2+-binding element calsequestrin might represent a compensatory mechanism of diabetic skeletal muscle. An increased Ca2+-buffering capacity of the sarcoplasmic reticulum lumen might counteract elevated cytosolic Ca2+ levels in diabetes thereby preventing Ca2+-dependent myo-necrosis.


The effect of energy restriction on development and progression of chronic kidney disease: review of the current evidence.
Energy restriction (ER) has anti-ageing effects and probably protects from a range of chronic diseases including cancer, diabetes and chronic kidney disease (CKD). Specifically, ER has a positive impact on experimental kidney ageing, CKD (diabetic nephropathy, polycystic kidney disease) and acute kidney injury (nephrotoxic, ischaemia-reperfusion injury) through such mechanisms as increased autophagy, mitochondrial biogenesis and DNA repair, and decreased inflammation and oxidative stress. Key molecules contributing to ER-mediated kidney protection include adenosine monophosphate-activated protein kinase, sirtuin-1 and PPAR-γ coactivator 1α. However, CKD is a complex condition, and ER may potentially worsen CKD complications such as protein-energy wasting, bone-mineral disorders and impaired wound healing. ER mimetics are drugs, such as metformin and Na-glucose co-transporter-2 which mimic the action of ER. This review aims to provide comprehensive data regarding the effect of ER on CKD progression and outcomes.


Comparison between conventional indirect competitive enzyme-linked immunosorbent assay (icELISA) and simplified icELISA for small molecules.
A simplified indirect competitive enzyme-linked immunosorbent assay (icELISA) for small molecules was established by modifying the procedure of conventional icELISA. The key change was that the analyte, antibody, and enzyme-labeled second antibody in the simplified icELISA were added in one step, whereas in conventional icELISA these reagents were added in two separate steps. Three small chemicals, namely zeatin riboside, glycyrrhetinic acid, and chlorimuron-ethyl, were used to verify the new assay format and compare the results obtained from conventional icELISA and simplified icELISA. The results indicated that, under optimized conditions, the new assay offered several advantages over the conventional icELISA, which are simpler, less time consuming and higher sensitive although it requires more amount of reagents. The assay sensitivity (IC50) was improved for 1.2-1.4-fold. Four licorice roots samples were analyzed by conventional icELISA and simplified icELISA, as well as liquid chromatography (LC). There was no significant difference among the content obtained from the three methods for each sample. The correlation between data obtained from conventional icELISA and simplified icELISA analyses was 0.9888. The results suggest that the simplified icELISA be useful for high throughput screening of small molecules.


An automated C4b binding protein assay compared with an electroimmunoassay in a clinical material.
We have evaluated an automated, simplified, turbidimetric method for the measurement of the C4b binding protein (C4bBP). A comparison with a manually performed electroimmunoassay in plasma samples referred for coagulation analysis (n = 80) revealed a correlation coefficient of 0.88. Lipaemic plasma is not suitable for analysis, whereas moderately haemolytic or icteric plasma may be used with the present method. In young and middle-aged patients (n = 33) investigated 3 or more months after an episode with thrombosis of unknown reason, the mean C4bBP concentration was not significantly different from the mean found in healthy controls (n = 38). This result is in accordance with the hypothesis that C4bBP is an acute phase reactant. The results indicate that the turbidimetric assay may replace the electroimmunoassay in clinical work.


Testing groups of genomic locations for enrichment in disease loci using linkage scan data: a method for hypothesis testing.
Genes for complex disorders have proven hard to find using linkage analysis. The results rarely reach the desired level of significance and researchers often have failed to replicate positive findings. There is, however, a wealth of information from other scientific approaches which enables the formation of hypotheses on groups of genes or genomic regions likely to be enriched in disease loci. Examples include genes belonging to specific pathways or producing proteins interacting with known risk factors, genes that show altered expression levels in patients or even the group of top scoring locations in a linkage study. We show here that this hypothesis of enrichment for disease loci can be tested using genome-wide linkage data, provided that these data are independent from the data used to generate the hypothesis. Our method is based on the fact that non-parametric linkage analyses are expected to show increased scores at each one of the disease loci, although this increase might not rise above the noise of stochastic variation. By using a summary statistic and calculating its empirical significance, we show that enrichment hypotheses can be tested with power higher than the power of the linkage scan data to identify individual loci. Via simulated linkage scans for a number of different models, we gain insight in the interpretation of genome scan results and test the power of our proposed method. We present an application of the method to real data from a late-onset Alzheimer's disease linkage scan as a proof of principle.


Persistence of Ehrlichia phagocytophila infection in two age groups of lambs.
Tick-borne fever (TBF) is caused by the rickettsiae Ehrlichia phagocytophila and is a common disease in sheep in tick (Ixodes ricinus) infested areas in Norway. Earlier investigations have shown that some sheep could remain infected for several months after the primary infection. In this study, the persistence of E. phagocytophila after experimental infection was investigated in 2 age groups of lambs. Six lambs (1-2 weeks old) and 14 lambs (6-8 months old) were inoculated intravenously with an ovine strain of E. phagocytophila and thereafter examined clinically (including daily body temperature recording) and by haematological and serological (E. equi antibodies) methods for the next 4 months. At the end of this period, the lambs were examined for a TBF infection by blood smear investigation and blood inoculation studies. The infection was demonstrated in 19 (95%) of the 20 lambs.


Prevention of thromboxane B2-induced hepatocyte plasma membrane bleb formation by certain prostaglandins and a proteinase inhibitor.
Isolated hepatocytes incubated in the presence of thromboxane B2 developed many plasma membrane blebs which are a characteristic feature of toxic or ischaemic cell injury. When hepatocytes were incubated in the presence of both thromboxane B2 and the non-lysosomal proteinase inhibitor, leupeptin, were also well protected from the formation of blebs. This implies that thromboxane B2 is able to activate non-lysosomal proteinases which appear to attack certain cytoskeletal proteins. The data presented are consistent with thromboxane B2 acting as an intermediary in a proposed mechanism of cell injury and death in which elevated cytosolic free Ca2+ levels activate phospholipase A2 and the arachidonic acid cascade.


Early smoking initiation and nicotine dependence in a cohort of young adults.
We examined the extent to which nicotine dependence and daily smoking might vary by age at first cigarette. The potential confounding effects of sex, race and history of childhood behaviour problems were examined as well. A sample of 1200 was randomly selected from the subset of 21-30-year-old members of a large HMO in the Detroit SMSA; 1007 (84%) agreed to participate. Personal interviews were conducted in respondents' homes, using the NIMH-DIS to elicit information on DSM-III-R diagnoses, including nicotine dependence. Controlling for sex and race, persons who smoked their first cigarette at 14 to 16 years of age were 1.6 times more likely to become dependent than those who initiated smoking at an older age (P = 0.03). The association was unchanged when history of childhood behaviour problems was also controlled. Smoking initiation before age 14 was not associated with increased probability of dependence. Persons who initiated smoking before age 14 had a longer lag time to daily smoking and a lower likelihood of progressing to daily smoking, compared to persons who initiated smoking later on. The findings suggest that, among persons who have ever smoked, there might be two distinct groups in whom the chances of developing dependence are considerably reduced. The first comprises persons who delayed first use until age 17. The second comprises persons who smoked their first cigarette before age 14, a group in whom the progression to daily smoking might be markedly slower than in persons who initiated smoking when they were older.


Carotid-cavernous fistula. Demonstration of asymptomatic vascular "steal".
Abnormal distribution of cerebral vascular flow was studied in a patient who had a traumatic carotid-cavernous sinus fistula. Serial studies were performed using a method for determining relative cerebral vascular flow:99mtechnetium-diethylenetriamine pentaacetic acid (99mTc-DTPA) was injected intravenously and flow data were processed by a digital computer. Serial studies documented the occurrence of a vascular "steal" during temporary carotid occlusion; postoperative studies showed disappearance of the steal and obliteration of thiling arterial structures and capillary filling in the brain, and in demonstrating alteration in the cerebral circulation.


Alterations in the initial portion of the signal-averaged QRS complex in acute myocardial infarction with ventricular tachycardia.
This study was designed to examine 2 hypotheses: that acute myocardial infarction (AMI) alters early cardiac activation measured by signal-averaging; and that the magnitude of abnormality of early activation may be greater in patients with post-AMI ventricular tachycardia (VT). We examined the root-mean square voltage amplitude in 10-ms intervals over the first 80-ms of the signal-averaged QRS complex. Data from 42 healthy volunteers were compared with those from 52 patients with previous AMI (24 anterior) but no VT and 46 post-AMI patients (33 anterior AMI) with recurrent sustained VT. Patients with VT differed from other post-AMI patients because of lower left ventricular ejection fraction, more frequent aneurysm formation and higher levels of ventricular ectopic activity. A significant decrease in initial voltage amplitude occurred at 30 to 40 ms after the beginning of the QRS in both anterior and inferior AMI patients compared with the normal group. A further significant decrease in initial amplitude occurred in VT patients both after anterior and inferior AMI. These differences persisted for the remainder of the 80-ms interval. These changes were weakly related to QRS duration (r = 0.45), ejection fraction (r = 0.50) and poorly correlated with the presence of Q waves on 12-lead electrocardiogram (r = 0.21). Direct endocardial catheter recordings performed in VT patients confirmed abnormalities of local septal activation after anterior and inferior AMI.(ABSTRACT TRUNCATED AT 250 WORDS)


TRAIL and docosahexaenoic acid cooperate to induce HT-29 colon cancer cell death.
The resistance of some cancer cells to TRAIL-induced apoptosis is a major obstacle in successful clinical application of this cytokine. Combination treatment with agents capable of sensitising the cells to TRAIL effects is beneficial for new cancer treatment strategies. Docosahexaenoic acid (DHA) is under intense investigation for its ability to affect cancer cell growth and apoptosis. We demonstrated a modulation of TRAIL-induced apoptosis of HT-29 human colon cancer cells by DHA on the molecular (pro-caspase-3, -8, Bid, PARP cleavage) and cellular (cell viability and adhesion) level. To conclude, TRAIL and DHA were shown to cooperate in the induction of colon cancer cell apoptosis.


Increased autologous blood donation in rectal cancer by recombinant human erythropoietin (rhEPO)
A randomised, placebo-controlled trial was conducted to study whether the subcutaneous administration of recombinant human erythropoietin (rhEPO) increases the donated red cell blood volume in patients with rectal cancer. Patients with resectable rectal cancer and a haemoglobin (Hb) level > or = 12.5/ > 12 g/dl (males/females) were scheduled to receive pre-operatively either erythropoietin (200 U/kg body weight daily) (n = 28) or placebo (n = 26) subcutaneously for 11 days. During this period autologous blood was collected. No serious adverse events were attributed to erythropoietin. 20 of 28 patients treated with rhEPO were able to donate > or = 3 units (71%) compared with 11 of 26 control patients (42%). The mean cumulative volume of red cells donated was 29% higher in the patients who received rhEPO (571 versus 444 ml, P = 0.02). The change in the mean reticulocyte value from baseline to the last pre-operative value was significantly higher in the rhEPO group (10.4 to 61.6/1000 versus 11.0 to 20.1/1000, P = 0.0001). The fall in the mean haematocrit from baseline to the last pre-operative value was significantly lower in the rhEPO group (41.4 to 37.6% versus 41.8 to 34.8%, P = 0.0004). rhEPO increases the ability of cancer patients to donate autologous blood during a short pre-operative period and enhances the restoration of haematological values after the donation period.


The leukemias.
This article reviews the major leukemia disorders, discussing their definitions, incidence, manifestations, and general treatment and prognosis, with additional description of oral findings common among or particular to the disorders. It reviews management of the most frequent oral manifestations of leukemia and the cautions required to provide oral and maxillofacial surgical services to patients who have leukemia.


Skills or Pills: Randomized Trial Comparing Hypnotherapy to Medical Treatment in Children With Functional Nausea.
The potential effectiveness of gut-directed hypnotherapy (HT) is unknown for pediatric chronic nausea. This randomized controlled trial compared HT with standard medical treatment (SMT). One hundred children (ages, 8-18 y) with chronic nausea and fulfilling functional nausea (FN) or functional dyspepsia (FD) criteria were allocated randomly (1:1) to HT or SMT, with a 3-month intervention period. Outcomes were assessed at baseline, at the halfway point, after treatment, and at the 6- and 12-month follow-up evaluation. Children scored nausea symptoms in a 7-day diary. The primary outcome was treatment success, defined as a reduction in nausea of 50% or more, at the 12-month follow-up evaluation. Secondary outcomes included adequate relief of nausea. After treatment and at the 6-month follow-up evaluation, there was a trend toward higher treatment success in the HT group compared with the SMT group (45% vs 26%, P = .052; and 57% vs 40%, P = .099, respectively). At 12 months, treatment success was similar in both groups (60% in the HT group and 55% in the SMT group; P = .667). In the FN group, significantly higher success rates were found for HT, but no differences were found in patients with FD. Adequate relief was significantly higher in the HT group than in the SMT group at the 6-month follow-up evaluation (children: 81% vs 55%, P = .014; parents: 79% vs 53%; P = .016), but not at the 12-month follow-up evaluation. HT and SMT were effective in reducing nausea symptoms in children with FN and FD. In children with FN, HT was more effective than SMT during and after the first 6 months of treatment. Therefore, HT and SMT, applied separately or in combination, should be offered to children with FN as a treatment option (Clinical trials registration number: NTR5814).


Single-Benzene-Based Solvatochromic Chromophores: Color-Tunable and Bright Fluorescence in the Solid and Solution States.
The search for structurally simple chromophores with superior fluorescence brightness and a wide range of solvent compatibility is highly desirable. Herein, a new type of single-benzene-based solvatochromic chromophore with a symmetric bifunctional structure, in which azetidine and ethoxycarbonyl moieties serve as the electron-donating and -withdrawing groups, respectively, is reported. This chromophore exhibits an extraordinary wide range of solvent compatibility and preserves excellent fluorescence quantum yields from nonpolar n-hexane to polar methanol and even in water. Unusually, the symmetric structure of the chromophore shows a distinct color change from bright green to red with increasing solvent polarity and possesses large Stokes shifts (λ=132-207 nm) in the tested solvents. Moreover, this single-benzene-based chromophore displays good photochemical stability in both solution and solid states, and even exhibits reversible mechanochromic luminescence.


Cortical thickness abnormalities in patients with bipolar disorder: A systematic review and meta-analysis.
An increasing number of neuroimaging studies report alterations of cortical thickness (CT) related to the neuropathology of bipolar disorder (BD). We provide here a whole-brain vertex-wise meta-analysis, which may help improve the spatial precision of these identifications. A comprehensive meta-analysis was performed to investigate the differences in CT between patients with BD and healthy controls (HCs) by using a newly developed mask for CT analysis in seed-based d mapping (SDM) meta-analytic software. We used meta-regression to explore the effects of demographics and clinical characteristics on CT. This meta-review was conducted in accordance with PRISMA guideline. We identified 21 studies meeting criteria for the systematic review, of which 11 were eligible for meta-analysis. The meta-analysis comprising 649 BD patients and 818 HCs showed significant cortical thinning in the left insula extending to left Rolandic operculum and Heschl gyrus, the orbital part of left inferior frontal gyrus (IFG), the medial part of left superior frontal gyrus (SFG) as well as bilateral anterior cingulate cortex (ACC) in BD. In meta-regression analyses, mean patient age was negatively correlated with reduced CT in the left insula. All enrolled studies were cross-sectional; we could not explore the potential effects of medication and mood states due to the limited data. Our results suggest that BD patients have significantly thinner frontoinsular cortex than HCs, and the results may be helpful in revealing specific neuroimaging biomarkers of BD patients.


Source Areas as a Key Factor Contributing to the Recovery Time of Controlled Feral Pigeon (Columba livia var. domestica) Colonies in Low-Density Urban Locations.
Today, governments and administrations strive to minimise issues associated with Feral Pigeon (Columba livia var. domestica) colonies in urban areas. Scientific evidence has demonstrated that control measures are ineffective in the long term, and colonies recover rapidly. Most scientific research has occurred under high-density circumstances, primarily in large city centres. Moreover, very few studies have been conducted in residential zones or suburban areas where colony densities are lower, but where Feral Pigeons generate the same issues. In this study, we analysed the recovery time of Feral Pigeon colonies in 11 buildings in low-density urban areas where control campaigns were previously conducted to reduce their abundance. Recovery times were highly variable among the buildings (50−3072 days). Distance to the nearest uncontrolled colony of Feral Pigeons, i.e., a source area, was the primary factor that contributed to recovery time, which significantly increased with increasing distance to source colonies. Thus, buildings closest to the Pigeons' source areas (<500 m) were recolonised more rapidly than were buildings that were >500 m away from source areas. Our findings highlight the relevance of identifying an effective management unit for the implementation of control programmes to reduce immigration rates and increase long-term effects.


Well-Being Therapy and Lifestyle Intervention in Type 2 Diabetes: A Pilot Randomized Controlled Trial.
This pilot randomized controlled trial evaluates the preliminary efficacy of a 4-month well-being therapy (WBT) and lifestyle intervention among adults with type 2 diabetes and overweight/obesity. Fifty-eight patients were recruited from two outpatient clinics and randomized to receive the WBT-lifestyle intervention or the lifestyle intervention alone. Data were collected at baseline (T0), immediate postintervention (T1), 6-month follow-up (T2), and 12-month follow-up (T3). Primary efficacy outcomes included changes in weight, psychological distress, and well-being, whereas secondary efficacy outcomes included changes in lifestyle and physiological parameters. Compared with the lifestyle-alone intervention, the WBT-lifestyle intervention showed greater improvements in depression (p = .009, d = -0.6), hostility (p = .018, d = -0.6), and personal growth (p = .026, d = 0.5) at T1, in self-reported physical activity at T2 (p = .013, d = 0.7) and T3 (p = .040, d = 0.5), and in triglycerides (p = .019, d = -1.12) at T3. There were no differences between treatment groups in weight and other physiological parameters. These findings suggest that WBT may be a valuable addition to lifestyle interventions for improving short-term psychological outcomes and promoting long-term healthy changes in physical activity, with a potential impact on physiological outcomes.Trial Registration:ClinicalTrials.gov identifier: NCT03609463.


Helichrysum plicatum DC. subsp. plicatum extract as a preventive agent in experimentally induced urolithiasis model.
Since ancient times, various herbal preparations have been used in treatment of urolithiasis, which is basically formation of calcium oxalate stones in kidney. The aim of our study is to assess the effects of Helichrysum plicatum DC. subsp. plicatum (HP) as a preventive agent in experimentally induced urolithiasis model in rats. The efficacy of 125, 250, and 500 mg/kg HP extract was studied in 1% ethylene glycol and 1% ammonium chloride-induced urolithiasis for 21 days in rats. The weight difference and the levels of calcium, magnesium, phosphorus, urea nitrogen, creatinine and uric acid in both serum and 24h-urine were measured. The calcium oxalate (CaOx) and pH were defined in urine. Histo-pathological analyses in kidneys were also performed. The rats' weights were higher in HP groups than urolithiasis group. Urolithiasis caused a significant increase in both serum and urine biochemical parameters compared to healthy rats. HP extract decreased levels of these parameters. Urine CaOx level was high in urolithiasis rats, whereas it was decreased by HP extract. Histopathological examinations revealed extensive intratubular crystal depositions and degenerative tubular structures in urolithiasis group, but not in HP treatment groups. More studies will be necessary to elucidate the antiurolithiatic activity of HP. Nonetheless, having a beneficial effect in preventing and eliminating CaOx deposition into kidneys, HP extract may be a potential drug for urolithiasis treatment.


Fungal pathogens and COVID-19.
COVID-19 pandemic highlighted the complications of secondary fungal infections that occurred globally in severe cases of coronavirus disease managed in the intensive care units. Furthermore, varied underlying host factors, such as preexisting immunosuppression, the use of immunomodulatory agents, and invasive procedures predisposing lung tissues to fungal colonization and proliferation, caused increased susceptibility to fungal infections in COVID-19 patient populations. These invasive fungal infections directly impact the overall length of hospitalization and mortality. The most commonly reported fungal infections in patients with COVID-19 include aspergillosis, invasive candidiasis, and mucormycosis. An overall worldwide increase in the prevalence of candidiasis and aspergillosis was observed in COVID-19 patients , whereas outbreaks of mucormycosis were mainly recorded from India. Diagnostic challenges and limited antifungal treatment options make secondary fungal infections among COVID-19 patients more burdensome, which results in improper management and increased mortality.


The legacy of HfrH: mutations in the two-component system CreBC are responsible for the unusual phenotype of an Escherichia coli arcA mutant.
Strains derived from HfrH carrying the arcA2 null mutation exhibit a higher respiratory rate, enhanced glucose consumption, and a more-reduced intracellular redox state than arcA deletion mutants of a different lineage. The phenotype of the arcA2 mutants was due to the presence of a creC constitutive mutation introduced by P1 transduction.


A rabbit model of hypersensitivity to plicatic acid, the agent responsible for red cedar asthma.
We describe a rabbit model for the study of the immunogenicity and allergenicity of plicatic acid (PA), the small molecular weight compound in western red cedar responsible for occupational asthma in exposed workers. Specific anti-PA IgE as well as IgG antibodies could be raised, depending on the method of immunization. The sensitized rabbits reacted to antigenic challenge with PA-protein conjugates intravenously, with increases in respiratory frequency and pulmonary resistance. This animal model may be used for the further elucidation of the mechanism of occupational asthma induced by small molecular weight chemical compounds.


Study on the time taken for patients to achieve the ability to self-care their new stoma.
Stoma formation in colorectal surgery is a recognized independent cause of prolonged hospital stay. It has been shown that preoperative stoma education and siting leads to a reduction in the length of hospital stay. Despite this, the length of time to independent stoma management and the variables that affect this has not been well studied. We conducted a prospective case series to analyse this. A total of 107 consecutive colorectal surgery patients undergoing stoma formation at two separate large metropolitan hospitals, one private funded and the other government funded, were enrolled in a prospective case series. The primary outcome evaluated was independent management of stoma at discharge from hospital. Logistic regression analysis was performed to determine the factors associated with achieving independent stoma management at discharge. The median length of stay was 9 days (range: 4-71). In our study, 71% of patients achieved self-care at the time of discharge from hospital (76/107 patients). The median length of time taken to achieve independent management of a stoma was 7 days (interquartile range: 6-9). Factors associated with increased chance of independent management of stoma at discharge included younger age, male, preoperative siting and treatment in a public hospital. Our study supports that preoperative stoma education in combination with post-operative stoma education is superior to post-operative stoma education alone. Interestingly, treatment in a private hospital is associated with a higher likelihood of failure to achieve independent stoma management at discharge. This is unexpected and not explained by our data.


On the inter-monomer electron transfer in cytochrome bc1.
Cytochrome bc1 is a structural and functional homodimer. The catalytically-relevant inter-monomer electron transfer has been implicated by a number of experiments, including those based on analyses of the cross-dimer mutated derivatives. As some of the original data on these derivatives have recently been questioned, we extend kinetic analysis of these mutants to confirm the enzymatic origin of the observed activities and their relevance in exploration of conditions that expose electron transfer between the monomers. While obtained data consistently implicate rapid inter-monomer electron equilibration in cytochrome bc1, the mechanistic and physiological meaning of this equilibration is yet to be established.


Fatigue, Participation and Quality of Life in Adolescents and Young Adults with Acquired Brain Injury in an Outpatient Rehabilitation Cohort.
To study the association between fatigue and participation and QoL after acquired brain injury (ABI) in adolescents and young adults (AYAs). Cross-sectional study with AYAs aged 14-25 years, diagnosed with ABI. The PedsQL™ Multidimensional Fatigue Scale, Child & Adolescent Scale of Participation, and PedsQL™4.0 Generic Core Scales were administered. Sixty-four AYAs participated in the study, 47 with traumatic brain injury (TBI). Median age at admission was 17.6 yrs, 0.8 yrs since injury. High levels of fatigue (median 44.4 (IQR 34.7, 59.7)), limited participation (median 82.5 (IQR 68.8, 92.3)), and diminished QoL (median 63.0 (IQR 47.8, 78.3)) were reported. More fatigue was significantly associated with more participation restrictions (β 0.64, 95%CI 0.44, 0.85) and diminished QoL (β 0.87, 95%CI 0.72, 1.02). AYAs with ABI reported high levels of fatigue, limited participation and diminished quality of life with a significant association between fatigue and both participation and QoL. Targeting fatigue in rehabilitation treatment could potentially improve participation and QoL.


Relationship between conjugate lateral eye movements, brain organization, and cognitive style.
The relationship between individual differences in conjugate lateral eye movements (CLEMs) and inferential reasoning was investigated in two experiments. Subjects were given inference tasks in sentence and pictorial form and were later tested for recognition of correct inferences as well as literal recognition of the acquisition items. In Experiment 2, for example, subjects were given logical syllogisms during acquisition. Theoretically, right-eye movement/left-hemispheric (REM/LH) subjects should have excelled at this highly logical task but no significant differences between eye-movement groups were found. However, support for previous research showing the moderating effects of gender on hemispheric activation (measured by CLEMs) and hemispheric competence came from the memory data of Experiment 2. These data indicated that male REM/LH subjects recognized more acquisition sentences than the other eye movement/gender groups. It was suggested CLEMs and other measures of hemispheric activation and competence, coupled with data collected using complex cognitive tasks, can eventually lead to explanatory brain models of cognitive processing.


The impact of coronavirus disease 2019 (COVID-19) response on central-line-associated bloodstream infections and blood culture contamination rates at a tertiary-care center in the Greater Detroit area.
We conducted a comparative retrospective study to quantify the impact of coronavirus disease 2019 (COVID-19) on patient safety. We found a statistically significant increase in central-line-associated bloodstream infections and blood culture contamination rates during the pandemic. Increased length of stay and mortality were also observed during the COVID-19 pandemic.


Selective kainic acid lesions in cultured explants of rat hippocampus.
The influence of the excitotoxin kainic acid (KA) on cultivated explants of rat hippocampus was investigated. Addition of 3 microM KA to the culture medium over 24-48 h induced a destruction of the pyramidal cells in the CA3 region, whereas the CA1 pyramidal cells and the granule cells were left undamaged. Higher concentrations (10-100 microM) of KA destroyed also the latter cell groups. The selectivity of the KA lesion at 3 microM was further indicated by the fact that the acetylcholinesterase-positive neurons in the hippocampus were not destroyed through KA administration and that the stereoisomer dihydrokainic acid was ineffective in inducing lesions. Application of tetrodotoxin did not protect the CA3 pyramidal cells from KA lesion, whereas gamma-glutamylaminomethylsulphonic acid (GAMS) only offered a very small, statistically not significant, protection. Baclofen protected the cultures slightly from KA lesions but not when added together with GAMS. Possible mechanisms responsible for the KA lesions in these cultures are discussed.


Cycling between Molybdenum-Dinitrogen and -Nitride Complexes to Support the Reaction Pathway for Catalytic Formation of Ammonia from Dinitrogen.
Cycling between molybdenum(I)-dinitrogen and molybdenum(IV)-nitride complexes was investigated under ambient reaction conditions. A kinetic study of the second-order reaction rate for the conversion of the molybdenum-dinitrogen complex into the molybdenum-nitride complex indicates that the formation of the dinitrogen-bridged dimolybdenum complex is involved in the rate-determining step. DFT calculations indicate that the molybdenum-dinitrogen complex transforms into the molybdenum-nitride complex via direct cleavage of the nitrogen-nitrogen triple bond of the bridging dinitrogen ligand of the dinitrogen-bridged dimolybdenum complex. The corresponding reaction of the molybdenum-nitride complex transforming into the molybdenum-dinitrogen complex proceeds via the ligand exchange of ammonia for dinitrogen at the dinitrogen-bridged dimolybdenum complexes. A new modified reaction pathway has been proposed based on the findings of our experimental and theoretical results.


Measuring medium-sized muscular arteries using a novel broadband 15-MHz linear array probe.
We recently developed a wideband 15-MHz linear array probe (15 M) with a band width of 8 MHz (9-17 MHz). Both axial and lateral resolution of 15 M, evaluated using a phantom model, were better than those of the current 10-MHz linear probe. To compare interobserver variability in measurement of medium-sized muscular arteries acquired using a 7.5-MHz linear probe (7.5 M), a 10-MHz linear probe (10M) and 15 M, two observers independently acquired images of the brachial and radial arteries, and measured the diameter and intima-media thickness (IMT) of those arteries in 17 male volunteers. Intraobserver variability in determining percent flowmediated dilatation (%FMD) was assessed in the same subjects using 15 M. Coefficients of variation (CV) in arteries measured using 7.5 M, 10 M, and 15 M were 7.0%, 2.5%, and 1.5%, respectively, for the diameter of the brachial artery; 10.3%, 5.8%, and 3.2%, respectively, for the diameter of the radial artery; and 17.0%, 13.8%, and 8.5%, respectively, for IMT of the far wall of the brachial artery. The CV of measurement of %FMD was 4.6%. The new 15-MHz probe thus warrants use in evaluating morphology and function of muscular arteries of medium size.


Application of Operational Tolerance Signatures Are Limited by Variability and Type of Immunosuppression in Renal Transplant Recipients: A Cross-Sectional Study.
Renal transplant recipients (RTR) frequently develop complications relating to chronic immunosuppression. Identifying RTR who could safely reduce immunosuppression is therefore highly desirable. We hypothesized that "signatures" described in RTR who have stopped immunosuppression but maintained stable graft function ("operational tolerance") may enable identification of immunosuppressed RTR who are candidates for immunosuppression minimization. However, the effect of immunosuppression itself on these signatures and circulating B-cell populations is currently unknown. We undertook a cross-sectional study of 117 RTR to assess the effect of immunosuppression upon circulating B cell populations, humoral alloresponse and 2 previously published "signatures" of operational tolerance. Immunosuppression associated with alterations in both published "signatures." Azathioprine associated with a decrease in transitional and naive B-cell numbers and calcineurin inhibition associated with an increase in the number of circulating plasmablasts. However, only azathioprine use associated with the presence of donor-specific anti-HLA IgG antibodies. Calcineurin inhibition associated with an increase in total serum IgM but not IgG. Data were corrected for age, time since last transplant, and other immunosuppression. Current signatures of operational tolerance may be significantly affected by immunosuppressive regimen, which may hinder use in their current form in clinical practice. Calcineurin inhibition may prevent the development of long-lasting humoral alloresponses, whereas azathioprine therapy may be associated with donor specific antibody development.


A comparison of tripolar concentric ring electrode and spline Laplacians on a four-layer concentric spherical model.
We have simulated a four-layer concentric spherical head model. We calculated the spline and tripolar Laplacian estimates and compared them to the analytical Laplacian on the spherical surface. In the simulations we used five different dipole groups and two electrode configurations. The comparison shows that the tripolar Laplacian has higher correlation coefficient to the analytical Laplacian in the electrode configurations tested (19, standard 10/20 locations and 64 electrodes).


Values and preferences influencing willingness to change red and processed meat consumption in response to evidence-based information: a mixed methods study.
(1) to assess the extent to which omnivores are willing to stop or reduce their consumption of red and processed meat in response to evidence-based information regarding the possible reduction of cancer mortality and incidence achieved by dietary modification; (2) to identify sociodemographic categories associated with higher willingness to change meat consumption; (3) to understand the motives facilitating and hindering such a change. During an initial computer-assisted web interview, respondents were presented with scenarios containing the estimates of the absolute risk reduction in overall cancer incidence and mortality tailored to their declared level of red and processed meat consumption. Respondents were asked whether they would stop or reduce their average meat consumption based on the information provided. Their dietary choices were assessed at 6-month follow-up. Additionally, we conducted semi-structured interviews to better understand the rationale for dietary practices and the perception of health information. The study was conducted among students and staff of 3 universities in Krakow, Poland. Most of the 513 respondents were unwilling to change their consumption habits. We found gender to be a significant predictor of the willingness. Finally, we identified 4 themes reflecting key motives that determined meat consumption preferences: the importance of taste and texture, health consciousness, the habitual nature of cooking, and persistence of omnivorous habits. When faced with health information about the uncertain reduction in the risk of cancer mortality and incidence, the vast majority of study participants were unwilling to introduce changes in their consumption habits.


LncRNA TMPO-AS1 serves as a ceRNA to promote osteosarcoma tumorigenesis by regulating miR-199a-5p/WNT7B axis.
Osteosarcoma (OS) is a common kind of aggressive tumor in bone which was mostly identified in children and adolescents with extremely high risk of death. Accumulating research works have displayed that long noncoding RNAs (lncRNAs) exert an essential role in the development of multiple cancers. It has been reported that TMPO-AS1 is an oncogene in cancers; nonetheless, its molecular mechanism in OS is totally unclear. Our present study elucidated that a remarkable overexpression of TMPO-AS1 was found in OS tissues and cells. Moreover, TMPO-AS1 depletion restrained Wnt/β-catenin pathway and cell proliferation as well as facilitated cell apoptosis. Further molecular mechanism investigations showed that TMPO-AS1 can sponge to miR-199a-5p. Moreover, miR-199a-5p was at a low level at OS cells. Importantly, miR-199a-5p's overexpression was associated with the OS cells' decreased proliferation and increased apoptosis. In addition, WNT7B was confirmed as a downstream gene of miR-199a-5p. Also the WNT7B expression was reversely modulated by miR-199a-5p and positively modulated by TMPO-AS1. Rescue experiments suggested that downregulated WNT7B rescued miR-199a-5p inhibitor-mediated repression on OS progression, but the treatment of LiCl counteracted the effect of WNT7B downregulation. In a word, TMPO-AS1 serves as a competing endogenous RNA to boost osteosarcoma tumorigenesis by regulating miR-199a-5p/WNT7B axis, which provided an underlying therapeutic target for patients with OS.


Molecular determinants of single-channel conductance and ion selectivity in the Cys-loop family: insights from the 5-HT3 receptor.
The molecular determinants of the ionic selectivity and single-channel conductance of the Cys-loop family of transmitter-gated ion channels are beginning to be understood with increasing precision, in part, as a result of the recent availability of refined ultrastructural information for the archetype of the family, the nicotinic acetylcholine receptor (nAChR). Studies of another member of this family, the 5-HT(3) receptor, have now provided insight into the structure of its channel pore, the location of its gate and mechanisms of ion selectivity and translocation. The anomaly of the extremely low single-channel conductance of the homo-oligomeric 5-HT(3A) receptor has recently been solved, revealing that an intracellular domain of the protein is an important determinant of single-channel conductance. Such data are interpreted, in this article, in light of the most recent developments in structural characterization of the nAChR.


Open science.
The term 'open science' refers to a range of methods, tools, platforms and practices that aim to make scientific research more accessible, transparent, reproducible and reliable. This includes, for example, sharing code, data and research materials, embracing new publishing formats such as registered reports and preprints, pursuing replication studies and reanalyses, optimising statistical approaches to improve evidence assessment and re-evaluating institutional incentives. The ongoing shift towards open science practices is partly due to mounting evidence that studies across disciplines suffer from biases, underpowered designs and irreproducible or non-replicable results. It also stems from a general desire amongst many researchers to reduce hyper-competitivity in science and instead promote collaborative research that benefits science and society.


Chronic ethanol intake modulates vascular levels of endothelin-1 receptor and enhances the pressor response to endothelin-1 in anaesthetized rats.
The contribution of endothelin-1 (ET-1) to vascular hyper-reactivity associated with chronic ethanol intake, a major risk factor in several cardiovascular diseases, remains to be investigated. The biphasic haemodynamic responses to ET-1 (0.01-0.1 nmol kg(-1), i.v.) or to the selective ETB agonist, IRL1620 (0.001-1.0 nmol kg(-1), i.v.), with or without ETA or ETB antagonists (BQ123 (c(DTrp-Dasp-Pro-Dval-Leu)) at 1 and 2.5 mg kg(-1) and BQ788 (N-cis-2,6-dimethyl-piperidinocarbonyl-L-gamma-methylleucyl1-D-1methoxycarbonyltryptophanyl-D-norleucine) at 0.25 mg kg(-1), respectively) were tested in anaesthetized rats, after 2 weeks' chronic ethanol treatment. Hepatic parameters and ET receptor protein levels were also determined. The initial hypotensive responses to ET-1 or IRL1620 were unaffected by chronic ethanol intake, whereas the subsequent pressor effects induced by ET-1, but not by IRL1620, were potentiated. BQ123 at 2.5 but not 1 mg kg(-1) reduced the pressor responses to ET-1 in ethanol-treated rats. Conversely, BQ788 (0.25 mg kg(-1)) potentiated ET-1-induced increases in mean arterial blood pressure in control as well as in ethanol-treated rats. Interestingly, in the latter group, increases in heart rate, induced by ET-1 at a dose of 0.025 mg kg(-1) were enhanced following ETB receptor blockade. Finally, we observed higher levels of ETA receptor in the heart and mesenteric artery and a reduction of ETB receptor protein levels in the aorta and kidney from rats chronically treated with ethanol. Increased vascular reactivity to ET-1 and altered protein levels of ETA and ETB receptors could play a role in the pathogenesis of cardiovascular complications associated with chronic ethanol consumption.


Pseudomembranous colitis following low dose trimethoprim-sulfamethoxazole.
A 94-year-old man had pseudomembranous colitis while taking low dose trimethoprim-sulfamethoxazole for recurrent urinary tract infection. The suppressive effect of low dose trimethoprim-sulfamethoxazole on normal colonic flora appeared to be a factor in the development of pseudomembranous colitis in this patient.